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PLAGUE PLAGUE Causative Agent Yersinia pestis Causative Agent Yersinia pestis Incubation Period 2-6 days Incubation Period 2-6 days Period Infectious Throughout duration of illness (pneumonic plague is the most important infectious Infectious Period form). Throughout duration of illness (pneumonic plague is the most important infectious form). Transmission Transmitted from rats by flea bites, by handling infected animal tissues, or airborne Transmission by aerosol from animals or humans with pneumonic plague. Transmitted from rats by flea bites, by handling infected animal tissues, or airborne by aerosol from animals or humans with pneumonic plague. Epidemiology There are natural foci of plague infection of rodents in many parts of the world. Epidemiology Wild rodent plague is present in central, eastern and southern Africa, South There are the natural foci part of plague infection of rodents in many of theInworld. America, western of North America and in large areasparts of Asia. some Wild rodent between plague iswild present in central, andresulting southernin sporadic Africa, South areas, contact and domestic rats iseastern common, cases America, the western part of North America and in large areas of Asia. In some of human plague and occasional outbreaks. areas, contact between wild and domestic rats is common, resulting in sporadic cases of plague occasional In human Southeast Asia,and Myanmar andoutbreaks. Vietnam report the highest number of cases. In Southeast Asia, Myanmar and Vietnam report the highest number of cases. Clinical Features Plague should be suspected in anyone with fever and painful lymphadenopathy who Clinical has been Features to an endemic country. Plague should be suspected in anyone with fever and painful lymphadenopathy who has been an endemic There aretothree principalcountry. clinical presentations: Bubonic plague: initial fever, headache, myalgia followed by painful acute There are threelymphadenopathy principal clinical presentations: regional (pathognomonic bubo), typically involving the fever, regions. headache, myalgia followed byprogression painful acute Bubonic inguinal, plague: axillary initial or cervical If left untreated, rapid to regional lymphadenopathy (pathognomonic bubo),(fatality typically the septicaemia and secondary plague pneumonia occurs 50 -involving 60%). axillary or occurs cervicalwhen regions. If leftinvades untreated, rapid progression to inguinal, Septicaemic plague: Y. pestis the bloodstream. It can septicaemia and plague secondary plaguewithout pneumonia occurs lymphadenopathy (fatality 50 - 60%).(primary follow bubonic or occurs detectable when Y. pestis invades the shock, bloodstream. It can Septicaemic septicaemic plague: plague).occurs Complications include septic disseminated follow bubonic plague or occurs without detectable lymphadenopathy (primary intravascular coagulation, meningitis and multiorgan failure. plague). Complications shock, septicaemic Pneumonic plague: the least common butinclude the mostseptic dangerous and disseminated fatal form of intravascular coagulation, meningitis and multiorgan the disease. It can develop as a complication of failure. septicaemic plague or be theinhalation least common but the most form of Pneumonic plague:by acquired directly of aerosols fromdangerous a human and or fatal animal with the disease.plague. It can The develop a complication of septicaemic plague orand be pneumonic signsasinclude severe pneumonia, fever, dyspnoea acquired directly by inhalation of aerosols from a human or animal with pneumonic plague. The signs include severe pneumonia, fever, dyspnoea and 87 87 often haemoptysis. Patients who do not receive treatment within 18 hours of onset of respiratory symptoms are unlikely to survive. often haemoptysis. Patients who do not receive treatment within 18 hours of Investigations onset of respiratory symptoms are unlikely to survive. Blood, bubo aspirate, sputum/throat swab, necropsy material can be sent for isolation of Y. pestis. Investigations Acute convalescent serology for fourfold rise in titre. A single is Blood,and bubo aspirate, sputum/throat swab, necropsy material cantitre be >1:16 sent for suggestive. isolation of Y. pestis. Informand the convalescent laboratory beforehand so fourfold that arrangements can made to >1:16 forward Acute serology for rise in titre. A be single titre is samples if necessary to the Department of Pathology, Singapore General suggestive. Hospital, other designated sites.so that arrangements can be made to forward Inform theorlaboratory beforehand samples if necessary to the Department of Pathology, Singapore General Hospital, or other designated sites. Notification A legally notifiable disease in Singapore. Notify Ministry of Health (Form MD 131 or electronically via CD-LENS) not later than 24 hours from the time of diagnosis. Notification Call MOHnotifiable Communicable Surveillance team at:of 98171463 immediately A legally disease Diseases in Singapore. Notify Ministry Health (Form MD 131 on suspicion. or electronically via CD-LENS) not later than 24 hours from the time of diagnosis. Call MOH Communicable Diseases Surveillance team at: 98171463 immediately on suspicion. Management All cases must be managed at the Communicable Disease Centre (CDC). Management Gentamicin, chloramphenicol or tetracycline are (CDC). highly effective if All cases muststreptomycin, be managed at the Communicable Disease Centre used within hours of presentation. Gentamicin, streptomycin, chloramphenicol or tetracycline are highly effective if used within hours of presentation. Infection Control Patients with uncomplicated infection who are promptly treated present no healthControl hazard to others. Infection Those with and other infection signs of who pneumonia must be placed in strict Patients withcough uncomplicated are promptly treated present no respiratory health hazardisolation to others.for at least 48 hours after the institution of antibiotic therapywith or until the sputum culture is negative. Those cough and other signs of pneumonia must be placed in strict Bubo aspirate and blood handled and aerosolization of respiratory isolation for atmust leastbe48 hours with after gloves the institution of antibiotic these materials be avoided. therapy or until should the sputum culture is negative. Laboratory workers must be alerted to exercise standard Bubo aspirate and blood must be handled with precautions gloves and although aerosolization of bacteriological that safeguard against skin contact and aerosolization these materials techniques should be avoided. should be adequate. Laboratory workers must be alerted to exercise precautions although standard bacteriological techniques that safeguard against skin contact and aerosolization should be adequate. Prevention and Control All cases will be isolated at CDC, Tan Tock Seng Hospital. Case investigations Prevention and Controlwill be carried out and contact tracing will be intensified. In event death, proper disposal the body important. Allthe cases willofbe isolated at CDC, TanofTock SengisHospital. Cases and close contacts, their personal Case investigations will beincluding carried out andclothing contact and tracing will bebelongings, intensified.will disinfected insecticide dusting.of the body is important. be In the event ofwith death, proper disposal Cases and close contacts, including their clothing and personal belongings, will be disinfected with insecticide dusting. 88 88 Anti-flea measures and rodent trapping will be increased at the focus of transmission. Anti-flea and rodent trapping willwill be be increased focus of The publicmeasures and the World Health Organisation informedatof the all suspected transmission. and confirmed cases. be informed of infestation all suspected The public and will the be World advisedHealth to stepOrganisation up measureswill to prevent rodent in andpremises confirmed cases. the and to avoid contact with rodents (either live or dead). The public will be advised to step up measures to prevent rodent infestation in the premises and to avoid contact with rodents (either live or dead). Chemoprophylaxis Consider antibiotic prophylaxis for the following: Chemoprophylaxis Persons exposed to patients with pneumonic plague. antibiotic prophylaxis following: Consider Persons exposed to bites for of the wild rodent fleas during an outbreak or to tissues/fluids Persons exposed patients with pneumonic of atoplague-infected animal. plague. Persons travelling exposed to to highly bites endemic of wild area rodent fleasduration. during an outbreak or to for short tissues/fluids of a plague-infected animal. For Persons to highly endemic area for (100mg short duration. adults, travelling doxycycline is the best choice orally bd for 7 days). Trimethoprim-sulfamethoxazole is a suitable alternative. For adults, doxycycline is the best choice (100mg orally bd for 7 days). Trimethoprim-sulfamethoxazole Indications for vaccine usage is a suitable alternative. A formalin-killed plague vaccine has been used for the following groups: Indications fortovaccine usage Travellers endemic or hyperendemic areas. A formalin-killed plague been the following groups: Individuals who mustvaccine live andhas work inused closefor contact with rodents. Travellers toworkers endemic or hyperendemic areas. Laboratory who must handle live cultures of Y. pestis. Individuals who must live and in close contact Military personnel deployed inwork plague-endemic areas.with rodents. Laboratory workers who must handle live cultures of Y. pestis. Military personnel deployed in plague-endemic This vaccine is not routinely available in Singapore. areas. This vaccine is not routinely available in Singapore. References 1. Perry RD, Fetherston JD. Yersinia pestis-etiologic agent of plague. Clin Microbiol Rev 1997; 10:35- 2. 1. CDC (Atlanta). Information on plague. Available at: Perry RD, Fetherston JD. Yersinia pestis-etiologic agent of plague. Clin Microbiol Rev 1997; 10:35http://www.cdc.gov/ncidod/dvbid/plague/info.htm. Accessed Aug 2010. 66 Plague as a biological weapon: medical & public health management. JAMA 2000; 283:2281-90 CDC (Atlanta). Information on plague. Available at: http://www.cdc.gov/ncidod/dvbid/plague/info.htm. Accessed Aug 2010. Plague as a biological weapon: medical & public health management. JAMA 2000; 283:2281-90 66 References 3. 2. 3. 89 89 PNEUMOCOCCAL DISEASE (INVASIVE) Causative agent PNEUMOCOCCAL DISEASE (INVASIVE) Streptococcus pneumoniae (also known as pneumococcus) Causative agent Streptococcus pneumoniae (also known as pneumococcus) Incubation Period Not well defined as colonization usually precedes invasive disease; may be as short Incubation Period as 1 to 3 days. Not well defined as colonization usually precedes invasive disease; may be as short as 1 to 3 days. Infectious Period Presumably as long as pneumococci are carried in oro-nasal secretions in Infectious Period asymptomatic individuals (colonization usually lasts weeks to months); with Presumably as long as pneumococci carried in oro-nasal in nonpenicillin treatment, persons infectedare with susceptible strainssecretions are rendered asymptomatic individuals (colonization usually lasts weeks to months); with infectious within 24-48 hours. penicillin treatment, persons infected with susceptible strains are rendered noninfectious within 24-48 hours. Transmission Respiratory droplets and direct contact with respiratory secretions of an infected Transmission person (usually requires frequent or prolonged close contact). Respiratory droplets and direct contact with respiratory secretions of an infected person (usually requires frequent or prolonged close contact). Epidemiology S. pneumoniae is one of the most common causes of invasive infections such as Epidemiology bacteraemia, meningitis and bacteraemic pneumonia, and bacterial mucosal S. pneumoniae is one of the causes of pneumococcal invasive infections such 23 as infections such as sinusitis andmost otitiscommon media. Of the 91 serotypes, bacteraemia, and ofbacteraemic pneumonia, disease and bacterial mucosal account for themeningitis vast majority invasive pneumococcal (IPD) in humans. infections such emergence as sinusitis of and otitis media. resistance Of the 91 to pneumococcal serotypes, 23 The worldwide pneumococcal antibiotics, including betaaccount the vast majority of invasive pneumococcal disease (IPD) has in humans. lactams, for macrolides, tetracycline, cotrimoxazole and fluoroquinolones been a The worldwide emergence of pneumococcal resistance to antibiotics, including betaconsiderable concern. lactams, macrolides, tetracycline, cotrimoxazole and fluoroquinolones has been a considerable concern. infection is defined as the isolation of S. pneumoniae from Invasive pneumococcal normally sterile sites such as blood, pleural fluid and cerebrospinal fluid (CSF). Invasive pneumococcal infection is defined as the isolation pneumoniae from Pneumococcal pneumonia is considered an invasive disease of butS.would be excluded normally sterile sitesfluid suchcultures as blood, andmedia cerebrospinal fluid (CSF). if blood or pleural arepleural sterile.fluid Otitis is not considered an Pneumococcal pneumonia disease but would be excluded invasive disease, but may is beconsidered included ifanS.invasive pneumoniae is isolated from normally if blood or pleural fluid cultures are sterile. Otitis media is not considered an sterile middle ear fluid. invasive disease, but may be included if S. pneumoniae is isolated from normally sterile middle ear In Singapore, the fluid. mean annual hospitalisation rate for IPD from 2000-2008 was 8.9 per 100,000 population (about 380 cases per year). A total of 157 deaths from IPD In Singapore, mean hospitalisation rate under for IPD 2000-2008 was 8.9 were reported the during thisannual period, of which 5 were thefrom age of 5 years. In 2009, per population casesOfper year). A met totalthe of 157 deaths there100,000 were 251 reported(about cases 380 of IPD. these, 124 criteria for from IPD. IPD The were reported during of which 5 were thethe ageelderly of 5 years. In 2009, highest incidence ratethis wasperiod, in children < 5 years of under age and aged 65 years there were 251 reported serotypes cases of IPD. Of these, 124 met for IPD. The and above. In children, 14, 6B, 23F, 19F, 6A the andcriteria 19A were the most highest rate wasand in children < 5for years the elderly aged years commonincidence strains isolated, accounted 89%ofofage all and invasive diseases in 65 children and above.old. In However, children, serotypes 6B, 23F, 19F, 6Awas andmore 19A spread were the <5 years in adults,14, isolate distribution outmost and common strains isolated, and accounted for 89% of all invasive diseases in children <5 years old. However, in adults, isolate distribution was more spread out and 90 90 common ones were 14, 3, 6B, 8 and 19F which accounted for 51% of all invasive diseases. Mean case fatality rates for IPD in single-centre series were 6.1% in common onesrising were 14, 3, 6B,in 8children and 19F with whichpneumococcal accounted formeningitis; 51% of all while invasive children but to 30% in diseases. case fatality rates for IPD in single-centre series were 6.1% in adults, thisMean was 21.4%. children but rising to 30% in children with pneumococcal meningitis; while in adults, this was 21.4%. A pneumococcal polysaccharide vaccine (23-valent or serotype) has been available locally since 1988. It was recommended for children >2 years old with risk factors A pneumococcal (23-valent or serotype) available for IPD and adultspolysaccharide >65 years old, vaccine but its immunogenicity was fair has and been its uptake was locally sinceHowever, 1988. It itwas recommended for children >2 years old with risk very poor. would cover 82.8% of IPD serotypes in adults. A factors highly for IPD and adults >65 years old, but its vaccine immunogenicity was fairlicensed and its uptake immunogenic pneumococcal conjugate (7-valent) was locallywas for very poor. wouldold cover 82.8% IPD serotypes in adults. A highly children 6 However, weeks to 9it years since 2002ofbut became commercially available immunogenic pneumococcal vaccine (7-valent) was licensed for locally only since late 2005, conjugate with uptake primarily in children <5years locally within the th children 6 weeks to 9 years old since 2002 but became commercially available private sector. In November 2009, it became the 10 vaccine-preventable disease to locally onlyinsince late 2005, with uptake primarily Programme. in children <5years within the be included the National Childhood Immunization private sector. In November 2009, it became the 10 th vaccine-preventable disease to be included in the National Childhood Immunization Programme. Clinical Features Typically between 40-50% of children and 20-30% of adults carry Clinical Features asymptomatically in their nasopharynx. pneumococci Typicallyisbetween 40-50% by of children and 20-30% of adults Infection often preceded a respiratory viral illness beforecarry local disease pneumococci asymptomatically in their nasopharynx. (from congestion and concentration of virulent pneumococci) or invasion Infection often preceded by adisease respiratory viral illness before local disease leading toissystemic or invasive (from congestion and concentration of virulent pneumococci) or invasion Can infect any organ. leading systemic include or invasive disease Mucosaltoinfections acute otitis media, bacterial sinusitis, Can infect any organ. conjunctivitis. Mucosal infections include acute otitis media, bacterial sinusitis, Otitis media may be complicated by mastoiditis and intracranial conjunctivitis. extension with abscess formation. Otitis media be complicated by mastoiditis and intracranial Sinusitis maymay be complicated by periorbital or orbital cellulitis, with extension with abscess formation. resultant intracranial extension. Sinusitis mayor beinvasive complicated by periorbital or orbital cellulitis, with Common deep-seated infections include primary bacteraemia, resultant intracranial extension. pneumonia without bacteraemia is pneumonia (with or without bacteraemia; Common deep-seated or invasive infections primary bacteraemia, not traditionally classified as “invasive”), andinclude meningitis. pneumonia (with or without without effusions bacteraemia Pneumonias may bebacteraemia; complicatedpneumonia by parapneumonic andis not traditionally classified as “invasive”), and meningitis. empyemas. Meningitis Pneumoniasismay be complicated by parapneumonic effusions and infrequently associated with development of subdural empyemas. empyemas, intracranial abscesses and vasculitic/ thrombotic Meningitis phenomena.is infrequently associated with development of subdural empyemas, intracranial and vasculitic/ Less commonly, it can also causeabscesses osteomyelitis, pyogenic thrombotic arthritis, phenomena. endocarditis, myocarditis, pericarditis, bacterial peritonitis, endophthalmitis Less commonly, it can also cause osteomyelitis, pyogenic arthritis, and salpingitis. endocarditis, myocarditis, pericarditis, peritonitis, endophthalmitis In some patients (especially those who bacterial are immunocompromised), and salpingitis. pneumococcal infections may be fulminant and present with overwhelming In some patients (especially those who are immunocompromised), sepsis and multi-organ failure. pneumococcal infections may be fulminant and present with overwhelming sepsis and multi-organ failure. 91 91 Risk Factors: Risk Factors: Age (<5 years and >65 years) Age (<5 years and >65(though years) not evident in local series) Racial predisposition Racial predisposition (though evident inheart, local series) Chronic illnesses (chronic not respiratory, renal and liver disease, Chronic illnesses alcoholism, diabetes)(chronic respiratory, heart, renal and liver disease, alcoholism, diabetes) Cochlear implants Cochlear implants Cerebrospinal fluid leaks Cerebrospinal leaks asplenia/ splenic dysfunction (including sickle cell Functional or fluid anatomic Functional disease) or anatomic asplenia/ splenic dysfunction (including sickle cell disease) Immunocompromised—either congenital, acquired (e.g. HIV infection) or Immunocompromised—either congenital, acquired (e.g. HIV infection) or iatrogenic via immunosuppression. iatrogenic via immunosuppression. Investigations Investigations Microbiological confirmation by culture remains the gold standard for Microbiological confirmation by culture remains gold standard for diagnosis and allows for sensitivity testing as well as the subsequent serotyping; diagnosis for blood sensitivity as well subsequent serotyping; however and the allows yield in maytesting be low for asdifferent pneumococcal however the yield in blood low may(around be low forindifferent pneumococcal syndromes—high in meningitis, 25%) pneumonia. syndromes—high in meningitis, low (around 25%) in pneumonia. The volume of inoculum (usually blood, uncommonly pleural fluid or The of inoculum (usually blood, pleural positive fluid or CSF)volume is important, and blood cultures (if uncommonly positive) are usually CSF) is important, and blood cultures (if positive) are usually positive within 18 hours of inoculation hours ofagglutination inoculation testing of infected body fluids (e.g. CSF, Gramwithin stains18and latex Gram stains and latex agglutination testingalways of infected body fluids (e.g. CSF, pleural, peritoneal or joint fluid) should be performed and may be pleural, jointstreptococci fluid) should always performed and may be helpful, peritoneal although or other may also be appear as Gram-positive helpful, streptococci appear as Gram-positive diplococcialthough and latexother agglutination testingmay lacksalso sensitivity. diplococci and latex agglutination testing lacks sensitivity. Urinary pneumococcal cell wall polysaccharide (antigen) testing is currently Urinary cell result wall polysaccharide (antigen) testing is currently availablepneumococcal and a positive is strongly suggestive of pneumococcal available and a positive result is strongly disease/ pneumonia in adults, although it can suggestive be positiveofin pneumococcal the setting of disease/ pneumonia incarriage adults, although can beinpositive the hence setting the of acute nasopharyngeal (as often itoccurs children)in and acute nasopharyngeal carriage (as often occurs in children) and hence the specificity is much poorer in children. specificity is much poorer in children.tomography, ultrasound, and nuclear or Imaging (e.g. X-ray, computerised Imaging (e.g. X-ray,imaging) computerised nuclearwith or magnetic resonance assiststomography, in localisingultrasound, infection inand patients magnetic resonance imaging) and assists in localising infection in patients with appropriate clinical symptoms signs appropriate clinical symptoms and signs Notification Notification A legally notifiable disease in Singapore. Notify Ministry of Health (Form MD 131 A notifiable in Singapore. Notify of the Health MD 131 or legally electronically via disease CD-LENS) not later than 72 Ministry hours from time(Form of diagnosis. or electronically via CD-LENS) not later than 72 hours from the time of diagnosis. Management Management Appropriate resuscitation, oxygenation and invasive or supportive care as Appropriate invasive or supportive care as required; the resuscitation, importance of oxygenation this cannot beand overemphasized. required; the importance of this cannot be overemphasized. 92 92 Initial choice of empirical antibiotics should be guided by local ageappropriate guidelines for respective clinical syndromes (by institution or college).choice of empirical antibiotics should be guided by local age Initial Once confirmed microbiologically, appropriate, targeted antibiotic treatment appropriate guidelines for respective clinical syndromes (by institution or should be guided by susceptibility testing after the initial empirical regime. college). OncePenicillins by 1st and appropriate, 2nd generation cephalosporins) are the confirmed(followed microbiologically, targeted antibiotic treatment preferred choice of antimicrobials; however, on the regime. site of should be guided by susceptibility testing after thedepending initial empirical infection, much higherbydoses may be generation required, orcephalosporins) 3rd generation are the Penicillins (followed 1st and 2nd cephalosporins be used (e.g. meningitis). preferred choicemay of antimicrobials; however, depending on the site of Where pneumococci aredoses resistant treatment may be infection, much higher mayto bebeta-lactams, required, or 3rd generation individualized cephalosporinswith mayvancomycin, be used (e.g. quinolones meningitis).or tetracyclines as appropriate. Where pneumococci are resistant to beta-lactams, treatment may be Source control (e.g.with drainage of infections in closed spaces like empyemas or individualized vancomycin, quinolones or tetracyclines as cerebral abscesses) are often critical to success or failure of antibiotic appropriate. treatment. Source control (e.g. drainage of infections in closed spaces like empyemas or Adjunct therapies to betoconsidered dexamethasone in cerebral abscesses)may are also oftenneed critical success ore.g. failure of antibiotic pneumococcal meningitis, activated protein C in severe pneumococcal sepsis. treatment. Adjunct therapies may also need to be considered e.g. dexamethasone in pneumococcal meningitis, activated protein C in severe pneumococcal sepsis. Prevention and Control All children <2 years old should receive pneumococcal conjugate vaccine as Prevention and Control recommended under the National Childhood Immunization Program. children Children<2 <1years year old primary doses conjugate at 3 months and 5 as All old should shouldreceive receive2pneumococcal vaccine months followed by National a boosterChildhood at 1-2 years. recommended under the Immunization Program. >1 year old should receive 2age appropriate of Children <1 primary doses doses at 3 months and 5 pneumococcal conjugate vaccine and also depending on whether they months followed by a booster at 1-2 years. have risk >1 factors Children year for oldIPD. should receive age appropriate doses of All adults ≥65 yearsconjugate old, and vaccine personsand 2 toalso 64 depending years with on riskwhether factors they for IPD pneumococcal (as above) should receive 23-valent pneumococcal polysaccharide vaccine as have risk factors for IPD. recommended MOH. All adults ≥65 by years old, and persons 2 to 64 years with risk factors for IPD All above) childhood vaccinations should be notified to the National Immunisation (as should receive 23-valent pneumococcal polysaccharide vaccine as Registry, Health Promotion Board. All post vaccination adverse reactions recommended by MOH. should also bevaccinations notified to the Pharmacovigilance Health Sciences All childhood should be notified to theBranch, National Immunisation Authority. Registry, Health Promotion Board. All post vaccination adverse reactions should also be notified to the Pharmacovigilance Branch, Health Sciences Authority. 93 93 References References 1. O’Brien KL, Wolfson LJ, Watt JP et al. Burden of disease caused by Streptococcus pneumoniae in 2. 1. 3. 2. 4. 3. 5. 4. 6. 5. 7. 6. 8. 7. 8. children younger than 5 years: global estimates. Lancet 2009; 374:893-902 van der Poll Opal SM. prevention O’Brien KL,T, Wolfson LJ, Pathogenesis, Watt JP et al. treatment Burden ofand disease caused of bypneumococcal Streptococcuspneumonia. pneumoniae in Lancet 374:1543-56 children2009; younger than 5 years: global estimates. Lancet 2009; 374:893-902 Lowder S, Chan L F, Cutter J et al. A national studyand of the epidemiology of pneumococcal disease van Poll T,F Opal SM. Pathogenesis, treatment prevention of pneumococcal pneumonia. among 2009; hospitalised patients in Singapore: 1995 to 2004. Singapore Med J 2007; 48:824-9 Lancet 374:1543-56 Chong MokJ et YH Invasive pneumococcal disease inofSingapore children. Low S, CY, ChanThoon F L F,KC, Cutter al.etAal. national study of the epidemiology pneumococcal disease Vaccine 2008; 26:3427-31 among hospitalised patients in Singapore: 1995 to 2004. Singapore Med J 2007; 48:824-9 Hsu LY, LuiThoon SW, Lee et al. Adult and peri-pneumococcal Chong CY, KC,JL Mok YH et al.invasive Invasivepneumococcal pneumococcaldisease diseaseprein Singapore children. connjugate vaccine introduction in a tertiary hospital in Singapore. J Med Microbiol 2009; 58:101-4 Vaccine 2008; 26:3427-31 Musher Streptococcus In Mandell GL, Bennet JE, Dolin R (eds). Principles and Hsu LY,DM. Lui SW, Lee JL et pneumoniae. al. Adult invasive pneumococcal disease pre- and peri-pneumococcal Practice of Infectious Diseases. 7th Philadelphia, Churchill JLivingstone; 2010:2623-42. connjugate vaccine introduction in aed. tertiary hospital PA: in Singapore. Med Microbiol 2009; 58:101-4 Ministry of Health. Vaccination against pneumococcal disease. Bulletin 2010;and 36: Musher DM. Streptococcus pneumoniae. In Mandell GL, BennetEpidemiol JE, DolinNews R (eds). Principles 7-15. Practice of Infectious Diseases. 7th ed. Philadelphia, PA: Churchill Livingstone; 2010:2623-42. Ministry of of Health. Health. Vaccination Laboratory-based surveillance system of invasive pneumococcal diseases in 36: Ministry against pneumococcal disease. Epidemiol News Bulletin 2010; Singapore: a nationwide monitoring of vaccine serotype coverage. Epidemiol News Bulletin 7-15. 2010;36: 40-5. Ministry of Health. Laboratory-based surveillance system of invasive pneumococcal diseases in Singapore: a nationwide monitoring of vaccine serotype coverage. Epidemiol News Bulletin 2010;36: 40-5. 94 94 POLIOMYELITIS POLIOMYELITIS Causative Agent Poliovirus, types 1, 2 and 3 Causative Agent Poliovirus, 1, 2 and 3 Incubationtypes Period 7-14 days (Range 5-35 days) Incubation Period 7-14 days (Range Infectious Period5-35 days) A few days before and after onset of illness. Infectious Period A few days before and after onset of illness. Transmission Faeco-oral or respiratory transmission. Transmission Faeco-oral or respiratory transmission. Epidemiology The last indigenous case of poliomyelitis notified in Singapore was in 1973. Epidemiology The last indigenous casehave of poliomyelitis notified Singapore was infrom 1973.estimated Globally, polio cases decreased by over in 99% since 1988, 350,000 cases then to 1997 reported cases in 2006. In 2008, only four countries Globally, polio cases haveIndia, decreased by Nigeria over 99% from estimated remain endemic (northern northern and since border1988, between Afghanistan 350,000 cases then to 1997 reported cases in 2006. In 2008, only four countries and Pakistan). remain endemic (northern India, northern Nigeria and border between Afghanistan and Pakistan). Clinical Features Disease manifestation can range from subclinical infection to severe paralysis Clinical Features and death. Disease manifestation range from subclinical paralysis The infection should becan suspected in someone withinfection a historytoofsevere an incomplete and death. immunisation against polio or recent travel to an endemic country. be polio suspected in someone with a history of an incomplete The Threeinfection forms ofshould paralytic may be seen: immunisation against polio or recent travel to an endemic country. 1. Spinal Paralytic Polio Three forms of paralytic may beillness seen: with fever, muscle pain, headache, This is preceded bypolio a “minor” 1. Spinal nausea,Paralytic vomitingPolio and stiff neck/back and less frequently, signs of aseptic This is preceded by a “minor” illness muscle headache, meningitis. The minor illness lasts 1-3with daysfever, followed by apain, symptom-free nausea, vomiting and stiff neck/back and less frequently, signs of aseptic period of 1-5 days before the onset of “major” illness of paralysis. meningitis. The minor illness lasts 1-3 days followed by a symptom-free Paralysis which varies from single muscle involvement to quadriplegia, is period of 1-5 days and before the onset of with “major” of paralysis. usually asymmetric typically flaccid loss illness of tendon reflexes. Paralysis which varies from single muscle involvement to quadriplegia, is There is no accompanying sensory loss. usually asymmetric and typically flaccid with loss of tendon reflexes. 2. Bulbar Paralytic Polio There is noofaccompanying sensory loss.and larynx resulting in dysphagia, Paralysis the soft palate, pharynx 2. nasal Bulbarspeech Paralytic and Polio dyspnoea. Paralysis of the soft palate, pharynx and larynx resulting in dysphagia, 3. Polioencephalitis nasal speech is andmanifested dyspnoea.by confusion and change in sensorium. This is Encephalitis 3. an Polioencephalitis uncommon form of polio seen in infants. Seizures are common and Encephalitis manifested by as confusion changeparalysis. in sensorium. This is there may be is spastic paralysis opposedand to flaccid an uncommon form of polio seen in infants. Seizures are common and there may be spastic paralysis as opposed to flaccid paralysis. 95 95 The most common differential diagnoses are those causing acute flaccid paralysis including transverse myelitis, Guillain-Barré Syndrome, enterovirus Westcommon Nile virusdifferential infections. diagnoses are those causing acute flaccid 71 Theand most paralysis including transverse myelitis, Guillain-Barré Syndrome, enterovirus Investigations 71 and West Nile virus infections. CSF findings consistent with any viral meningitis. CSF protein is minimally elevated (unlike in Guillain-Barre syndrome). Investigations Polioviruses usually be frommeningitis. the throat CSF swabprotein in the first week of CSF findingscan consistent withisolated any viral is minimally illness and stool in cultures may remain positive for several weeks. elevated (unlike Guillain-Barre syndrome). In the absence a virusbeisolate, diagnosis is confirmed a four-fold Polioviruses canofusually isolatedthe from the throat swab in thebyfirst week of increase in stool antibody titre may of theremain acute and convalescent sera. illness and cultures positive for several weeks. In the absence of a virus isolate, the diagnosis is confirmed by a four-fold Notification increase in antibody titre of the acute and convalescent sera. A legally notifiable disease in Singapore. Notify Ministry of Health (Form MD 131 or electronically via CD-LENS) not later than 72 hours from the time of diagnosis. Notification A legally notifiable disease in Singapore. Notify Ministry of Health (Form MD 131 Management or electronically via CD-LENS) not later than 72 hours from the time of diagnosis. Refer all confirmed cases to the Communicable Disease Centre (CDC), Tan Tock Seng Hospital, for isolation and management. Specific anti-viral therapy is not Management available. Management is therefore supportive andDisease symptomatic. Refer all confirmed cases to the Communicable Centre (CDC), Tan Tock Seng Hospital, for isolation and management. Specific anti-viral therapy is not PreventionManagement and Controlis therefore supportive and symptomatic. available. Case investigation and contact tracing will be carried out to identify unrecognised and unreported cases. Contacts below 12 years old without Prevention and Control complete immunisation be referred the nearest Polyclinic School Case investigation and will contact tracing towill be carried out toor identify Health Clinic for unrecognised andvaccination. unreported cases. Contacts below 12 years old without complete All infants are routinely as part of the immunisation willvaccinated be referredagainst to the poliomyelitis nearest Polyclinic or School Childhood Immunisation Programme in Singapore. Health Clinic for vaccination. Bothinfants IPV (inactivated polio vaccinated vaccine) and OPV (live, attenuatedas vaccine) All are routinely against poliomyelitis part of have the been used Immunisation for more thanProgramme 30 years inincontrolling Childhood Singapore.paralytic poliomyelitis. IPV be used for immunocompromised children including travellers. should Both IPV (inactivated polio vaccine) and OPV and (live,adults attenuated vaccine) have Notify all childhood vaccinations to the National Immunisation Registry, been used for more than 30 years in controlling paralytic poliomyelitis.Health IPV Promotion and post-vaccination adverse reactions travellers. to the should be usedBoard, for immunocompromised children and adults including HealthtoSciences Authority. Pharmacovigilance Notify all childhoodBranch, vaccinations the National Immunisation Registry, Health Promotion Board, and post-vaccination adverse reactions to the References Pharmacovigilance Branch, Health Sciences Authority. 1. Chew SK. Certification of poliomyelitis eradication in the World Health Organisation Western Pacific Region. Epidemiological News Bulletin 1997; 23:70-1 References 2. WHO. Poliomyelitis 2008. Available at http://www.who.int/mediacentre/factsheets/fs114/en/index.html. 1. Accessed Chew SK. Certification of poliomyelitis eradication in the World Health Organisation Western August 2010. Pacific Wild Region. Epidemiological NewsaBulletin 3. WHO. poliovirus isolation from Nigerian1997; child23:70-1 with acute flaccid paralysis seeking medical 2. WHO. Poliomyelitis 2008. Available at http://www.who.int/mediacentre/factsheets/fs114/en/index.html. care in Singapore. Weekly Epidemiological Record 2006; 81:285-6. 2010.Cutter J et al. Evaluation on the effectiveness of the National Childhood 4. Accessed Liew F, August Ang LW, 3. WHO. Wild poliovirus isolation from a 1982-2007. Nigerian child with acute flaccid paralysis seeking medical Immunisation Programme in Singapore, Ann Acad Med Singapore 2010; 39:532-41. care in Singapore. Weekly Epidemiological Record 2006; 81:285-6. 4. Liew F, Ang LW, Cutter J et al. Evaluation on the effectiveness of the National Childhood Immunisation Programme in Singapore, 1982-2007. Ann Acad Med Singapore 2010; 39:532-41. 96 96 RABIES RABIES Causative Agent Rabies virus Causative Agent Rabies virusPeriod Incubation 20 - 90 days (range 4 days - 19 years) Incubation Period 20 - 90 daysPeriod (range 4 days - 19 years) Infectious Throughout duration of clinical illness Infectious Period Throughout duration of clinical illness Transmission From saliva of infected animals via bites. Rarely, contamination of mucous Transmission membranes by infectious material, aerosol transmission and organ transplantation. From saliva of infected animals via bites. Rarely, contamination of mucous membranes by infectious material, aerosol transmission and organ transplantation. Epidemiology Although reservoir is present in many mammalian species, dog bites account for the Epidemiology majority of human infections. Rabies has not been reported locally since 1953. but Although reservoir in is present in many mammalian species, dog bites account for the remains prevalent many parts of the region and the world. Recent decrease in majority of human infections. Rabies has not been reported locally since 1953. human rabies cases has been due to improved post-exposure treatment as wellbut as remains prevalent in inmany parts of the via region the world.ofRecent decrease in elimination of rabies animal reservoirs oraland immunisation wildlife. human rabies cases has been due to improved post-exposure treatment as well as elimination of rabies in animal reservoirs via oral immunisation of wildlife. Clinical Features The first symptoms of rabies usually begin when the virus enters the CNS. A Clinical Featuresprodrome of 2-10 days includes fever, malaise, fatigue, anorexia, non-specific cough, The firstsore symptoms of rabies usually begin when the virus enters the The CNS. A throat, abdominal pain, nausea, vomiting or diarrhoea. first of 2-10 days includes fever, malaise, fatigue, anorexia, non-specific prodrome rabies-specific symptom is pain or paraesthesia referred to the site of the cough, sore throat, abdominal pain, nausea, vomiting or diarrhoea. The first exposure. rabies-specific symptom is pain or paraesthesia to the site rabies) of the The acute neurological period manifests as either a referred hyperactive (furious exposure. in 80% or a paralytic (dumb rabies) form in 20%. Autonomic instability is often manifests as either aand hyperactive (furious rabies) prominent The acute neurological period (hyperthermia, salivation, hypertension tachycardia). in 80% or a paralytic (dumb in 20%. Autonomic instability is often The neurological phase lasts rabies) 2-7 daysform before development of coma then death. prominent (hyperthermia, salivation, hypertension and tachycardia). The neurological phase lasts 2-7 days before development of coma then death. Investigations No tests are available to diagnose human rabies during the incubation period. Investigations No tests areof available diagnose human rabies during the incubation period. After onset clinical to disease, diagnostic methods include: Direct fluorescent antibody staining of skin biopsy from nape of neck (50%). AfterRabies onset of clinical disease, diagnostic methods include: neutralising antibodies in serum or CSF. Rabies Direct fluorescent antibody stainingCSF, of skin biopsy from nape of neck (low). (50%). virus isolation from saliva, urine and tracheal secretions Rabies Rabies RT-PCR neutralising antibodies serum ortissue. CSF. in saliva, CSF,inurine and Cortical Rabies virus brainisolation biopsy. from saliva, CSF, urine and tracheal secretions (low). Rabies RT-PCR in saliva, CSF, urineoverseas and tissue. Specimens may need to be sent for tests. Cortical brain biopsy. Specimens may need to be sent overseas for tests. 97 97 Post-mortem brain examination for Negri bodies and fluorescent staining for rabies antibodies. Post-mortem brain examination for Negri bodies and fluorescent staining for rabies antibodies. Notification Notify all suspected and confirmed cases immediately. Call MOH Communicable Notification Diseases Surveillance team at 98171463 and the Agri-Food and Veterinary Notify all of suspected and confirmed casesinvestigation. immediately. Call MOH Communicable Authority Singapore (AVA) for further Diseases Surveillance team at 98171463 and the Agri-Food and Veterinary Authority of Singapore (AVA) for further investigation. Management There is no specific treatment for clinical human rabies. Intensive supportive Management care in the ICU is often used although mortality is virtually 100%. is no treatment for clinical rabies. byIntensive supportive There Standard andspecific respiratory precautions shouldhuman be observed healthcare workers care in the ICU is often used although mortality is virtually 100%. caring for such patients. Pre-exposure immunisation of medical staff is generally Standard and precautions should observedisbynot healthcare workers not respiratory required. Routine delivery of be healthcare an indication of caring for such patients. Pre-exposure immunisation of medical is post-exposure prophylaxis unless the healthcare worker is reasonably staff certain generally not required. Routine delivery of healthcare is not an indication of that he or she was bitten or mucous membranes or non-intact skin was exposed post-exposure prophylaxis unless the healthcare worker is reasonably certain to potentially infectious saliva or neural tissue. that he or she was bitten or mucous membranes or non-intact skin was exposed to potentially infectious saliva or neural tissue. Prevention and Control In rabies-free Singapore, the AVA exercises strict control on importation and Prevention andofControl quarantine dogs, cats and wild animals and intensive control of stray dog and In rabies-free cat population.Singapore, the AVA exercises strict control on importation and quarantine and wild animals suspected and intensive controlrabies, of stray dog and In the case of of dogs, humancats exposure to animals of having immediate cat population. attempts should be made to identify, capture or kill the animal involved. The In the case ofAVA, humanwill exposure animals of having rabies,forimmediate veterinarian, removetothe brain suspected of the animal to examine presence attempts shouldantigen be made to identify, capture or kill the animal involved. The of rabies virus by immunofluorescence. veterinarian, AVA, will remove the brain of the animal to examine for presence of rabies virus antigen by immunofluorescence. Pre-Exposure Vaccination For travellers visiting rabies endemic countries (Central and South America, Pre-Exposure Vaccination Africa, Indian subcontinent and Southeast Asia), pre-exposure vaccination may be For recommended travellers visiting rabies endemic countries (Central and South America, depending on intended activity, duration of stay, local Africa, Indian subcontinent and Southeast Asia), pre-exposure vaccination incidence of rabies and availability of appropriate anti-rabies biologicals. may be recommended depending onsimplifies intended but activity, duration of the stay, Pre-exposure vaccination greatly does not eliminate needlocal for incidence of rabies and availability of appropriate anti-rabies biologicals. post-exposure treatment. Pre-exposure Pre-exposure vaccination butgiven doeson notdays eliminate the 21 need vaccination greatly consistssimplifies of 3 doses 0, 7 and or for 28 post-exposure treatment. days. The Pre-exposure vaccination 3 doses is given days 0, 7 virus and 21vaccine or 28 human diploid cell consists vaccine of(HDCV) an on inactivated days. available in Singapore. The human diploid cell vaccine (HDCV) is an inactivated virus vaccine available inTreatment Singapore. Post-Exposure The most effective mechanism of protection against rabies is to wash and flush Post-Exposure Treatment a wound or point of contact with soap and water, followed by application of ethanol, The mosttincture effective mechanism of protection or aqueous solution of iodine.against rabies is to wash and flush a wound or point of contact with soap and water, followed by application of ethanol, tincture or aqueous solution of iodine. 98 98 Suturing should be postponed and where indicated, anti-tetanus toxoid and antimicrobials should be administered. Suturing should and be postponed and where Rabies vaccine immunoglobulin shouldindicated, be given anti-tetanus as soon as toxoid possibleand if antimicrobials should be administered. indicated (see table below). Post-exposure vaccination consists of 5 doses given on Rabies immunoglobulin be given keeps as soon as possible if daysvaccine 0, 3, 7, and 14 and 28. Tan Tockshould Seng Hospital, a stock of rabies indicatedand (see table rabies below).immunoglobulin. Post-exposure vaccination consists of 5 doses given vaccine human on days 0, 3, 7, 14 and 28. Tan Tock Seng Hospital, keeps a stock of rabies vaccine and human rabies immunoglobulin. Guide for Post-Exposure Treatment Guide for Post-Exposure Type of contactTreatment with a suspect Category Category I I II II III III a a b cb c or confirmed rabid domestic a or wild animal,with or animal Type of contact a suspect unavailable observation or confirmedfor rabid domestic or wild a animal, or animal Touching or feeding of unavailable for observation animals. Licks on intact skin. of Touching or feeding Nibbling of uncovered skin. animals. Minoron scratches or abrasion Licks intact skin. without bleeding. Nibbling of uncovered skin. Licks on broken or skin. Minor scratches abrasion without bleeding. Licks on broken skin. Single or multiple transdermal bites or scratches. Contamination of mucous Single or multiple transdermal membrane with saliva (i.e. bites or scratches. licks). Contamination of mucous membrane with saliva (i.e. licks). Recommended treatment Recommended None, if reliabletreatment case history is available. None, if reliable case history is Administer vaccine immediately. b available. Stop treatment if animal remains healthy throughout an observation period bc of 10 Administer vaccine immediately. days or if animal is euthanised and Stop treatment if animal remains healthy found to be an negative for rabies byc of 10 throughout observation period appropriate laboratory techniques. days or if animal is euthanised and Administer immunoglobulin found to be rabies negative for rabies by and vaccine immediately Stop treatment if appropriate laboratoryb. techniques. animal remains healthy throughout an Administer rabies immunoglobulin and b 10 days or if the observation period c of vaccine immediately . Stop treatment if is euthanised andthroughout found to bean animal remains healthy c appropriate negative for period rabies by observation of 10 days or if the laboratory techniques.and found to be animal is euthanised negative for rabies by appropriate techniques. Source: Rabies pre- and post-exposurelaboratory prophylaxis in humans (revised 15 June 2010). Dept of Neglected Tropical Diseases. Neglected Zoonotic Diseases team. WHO, Geneva. to rodents, rabbits and hares seldom, (revised if ever, requires Source: Rabies Exposure pre- and post-exposure prophylaxis in humans 15 June specific anti-rabies treatment. 2010). Dept of Neglected Tropical Diseases. Neglected Zoonotic Diseases team. If an apparently healthy dog or cat inrabbits or from low-risk area ifis ever, placed under WHO, Geneva. Exposure to rodents, anda hares seldom, requires observation, it may treatment. be justified to delay specific treatment. specific anti-rabies This period applies onlyintoordogs cats. Except the case of If an observation apparently healthy dog or cat fromand a low-risk area isinplaced under threatened species, other specific domestictreatment. and wild animals suspected as observation,oritendangered may be justified to delay rabid should be period euthanised their tissues using This observation appliesand only to dogs andexamined cats. Except in appropriate the case of laboratory techniques. threatened or endangered species, other domestic and wild animals suspected as rabid should be euthanised and their tissues examined using appropriate laboratory techniques. 99 99 References 1. 2. 3. 4. 5. 6. Rupprecht CE, Hanlon CA, Hemachudha T. Rabies re-examined. Lancet Infect Dis. 2002; 2:327-43 Whitley RJ, Gnann JW. Viral encephalitis: familiar infections and emerging pathogens. Lancet 2002; 359:507-13 WHO Rabies Fact Sheet No 99 December 2008. Available at http://www.who.int/mediacentre/factsheets/fs099/en/index.html. Accessed August 2010 Committee on Epidemic Diseases. An imported case of human rabies in Singapore. Epidemiological News Bulletin 1999; 25:71 Warrell MJ, Warrell DA. Rabies and other Lyssavirus diseases. Lancet 2004; 363:959-69 CDC (Atlanta). Human Rabies Prevention. Recommendations of the Advisory Committee on Immunization Practices 2008 100 RUBELLA Causative Agent Rubella virus RUBELLA Causative Agent Incubation Period Rubella virus 2 - 3 weeks Incubation Period Infectious Period 2 - 3 weeks Few days before until seven days after onset of rash. Infants with congenital rubella syndrome may shed the virus from their body secretions for 1 year or more after Infectious Period birth. Few days before until seven days after onset of rash. Infants with congenital rubella syndrome may shed the virus from their body secretions for 1 year or more after Transmission birth. Respiratory droplets and direct contact with nasopharyngeal secretions. Transmission Epidemiology Respiratory droplets and direct contact with nasopharyngeal secretions. Rubella immunisation was introduced in Nov 1976 for female primary school leavers at 11+ years of age. However as rubella outbreaks continued to occur in Epidemiology susceptible populations especially national servicemen (NS men), the vaccination Rubella immunisation was introduced in Nov 1976 for female primary school was extended to cover male primary school leavers in 1982. NS men were also leavers at 11+ years of age. However as rubella outbreaks continued to occur in routinely vaccinated to eliminate rubella in army camps. The programme was further susceptible populations especially national servicemen (NS men), the vaccination expanded to include children 1-2 years of age using the trivalent measles, mumps, was extended to cover male primary school leavers in 1982. NS men were also rubella (MMR) vaccine in Jan 1990. The 2nd dose of MMR was introduced in 1997 routinely vaccinated to eliminate rubella in army camps. The programme was further for secondary and junior college students in a catch-up measles vaccination expanded to include children 1-2 years of age using the trivalent measles, mumps, programme and to all primary school leavers in 1998. Since 2008, the 2nd dose of rubella (MMR) vaccine in Jan 1990. The 2nd dose of MMR was introduced in 1997 MMR vaccine is now given at 6-7 years of age (primary 1) under the revised for secondary and junior college students in a catch-up measles vaccination National Childhood Immunisation Programme. programme and to all primary school leavers in 1998. Since 2008, the 2nd dose of MMRrubella vaccine is now peaked given atin 6-7 agenotifications. (primary 1) With underthe thecatch-up revised The incidence 1996years withof487 National vaccination Childhood Immunisation measles program, the Programme. number of rubella cases has gradually declined from 10.9 cases per 100,000 population in 1999 to 3.6 per 100,000 in 2009. The The rubella incidence peaked in 1996 with 487 notifications. With the catch-up incidence of congenital rubella is about 0-2 cases per year since 1995. measles vaccination program, the number of rubella cases has gradually declined from 10.9 cases per 100,000 population in 1999 to 3.6 per 100,000 in 2009. The incidence of congenitalstudy rubella about 0-2 cases perinyear since In a serosurveillance ofisrubella conducted 1998, it 1995. was found that the overall immunity of the population to rubella was 80.2% with the lowest immunity in the 10-14 year age group (65.5%). Another survey in 2004 showed that 15.8% of In a serosurveillance study of rubella conducted in 1998, it was found that the women aged 18 to 44 years were non-immune to rubella (a relatively high level overall immunity of the population to rubella was 80.2% with the lowest immunity compared to women of reproductive age in other developed countries). in the 10-14 year age group (65.5%). Another survey in 2004 showed that 15.8% of women aged 18 to 44 years were non-immune to rubella (a relatively high level It is important to ensure that at least 95% of the children are immunised at 1-2 years compared to women of reproductive age in other developed countries). of age. Congenital rubella can only be completely eliminated if every woman in the It is important to ensure that at least 95% of the children are immunised at 1-2 years of age. Congenital rubella can only be completely eliminated if every woman in the 101 101 15-44 year age group is immunised against the disease. Women should be advised to be vaccinated before they are married and prior to conception. 15-44 year age group is immunised against the disease. Women should be advised to be vaccinated before they are married and prior to conception. Clinical Features Many cases are subclinical. Clinical Features Infection usually starts with a mild prodrome and appearance of tender Many casespost-auricular are subclinical. occipital, and cervical lymphadenopathy which precedes the appearance Infection usually starts with a mild prodrome and appearance of tender of the rash. occipital, post-auricular and cervical lymphadenopathy precedes the Prodromal symptoms include low grade fever, headache,which malaise, anorexia, appearance of the rash. mild conjunctivitis, coryza, sore throat, cough and lymphadenopathy. The Prodromal symptoms include low grade malaise, anorexia, symptoms last 1 - 5 days and subside rapidlyfever, after headache, the rash appears. mildenanthem conjunctivitis, coryza, sore throat, and lymphadenopathy. An consisting of reddish spots oncough the soft palate may be observedThe in symptoms last period 1 - 5 days and rapidly appears. the prodromal or on thesubside first day of theafter rashthe butrash is not diagnostic. An enanthem consisting reddish spots ondirection the soft and palate may be observed The rash progresses in aofcephalo-caudal usually subsides in in3 the prodromal or the on the first daythe of the rashisbut is not diagnostic. days. By theperiod end of first day, body covered with red, discrete maculopapules. The rash progresses in athird cephalo-caudal andwithout usuallyany subsides By the day, the rashdirection disappears stainingin or3 days. By the end of the first day, the body is covered with red, discrete desquamation. maculopapules. Byslightly the third day, the rash disappears without any staining or The spleen may be enlarged. desquamation. Fever if present is usually low grade and lasts 1 - 3 days. The spleen maysuch be slightly enlarged.and arthritis, which are more common in Complications as arthralgia adults, Fever ifclear present is usually lowdays. gradeEncephalitis and lasts 1 -and 3 days. in about 5 - 10 thrombocytopaenia are rare complications. Complications such as arthralgia and arthritis, which are more common in adults, clear aboutinfection 5 - 10 days. and thrombocytopaenia are rare The risk of in foetal and Encephalitis congenital anomalies depends on stage of complications. pregnancy at which infection occurs (lower risk after 20 weeks). The risk of foetal infection and congenital anomalies depends on stage of pregnancy at which infection occurs (lower risk after 20 weeks). Differential diagnoses include: Exanthem subitum (Roseola infantum) Differential diagnoses include: Drug rash Exanthem mononucleosis subitum (Roseola infantum) Infectious Drug rash infections Enteroviral Infectious mononucleosis Mild measles Enteroviral Scarlet feverinfections Mild measles Scarlet fever Investigations Indicate on the request form a brief clinical history, as the assays used for Investigations immunity screening and for diagnosing recent infection may differ. Indicate on the request form brief clinical ahistory, the in assays used for Rubella can be diagnosed by ademonstrating fourfoldasrise IgG antibody immunity screening diagnosingsamples recent infection may differ. titres between acute and for convalescent and by detecting rubella-specific IgM Rubella can be diagnosed by demonstrating a fourfold rise in IgG antibody antibody. between acute convalescent samples and bybydetecting titres Rubella-specific IgMand antibody is usually detectable five daysrubella-specific after onset of IgM antibody. illness and remains detectable for at least one month but commonly for two Rubella-specific IgM antibody is usually detectable by five days after onset of months. illness and remains detectable for at least one month but commonly for two months. 102 102 Caution is advised in interpretation of rubella IgM antibody tests since false positive results are not uncommon. They may arise during other virus infections Caution is advised interpretation of rubella IgM antibody tests since false such as those due to in parvovirus B19, CMV or EBV. positive results are not uncommon. They may arise during other virus infections such as those due to parvovirus B19, CMV or EBV. Notification A legally notifiable disease in Singapore. Notify Ministry of Health (Form MD 131 Notification or electronically via CD-LENS) not later than 72 hours from the time of diagnosis. A legally notifiable disease in Singapore. Notify Ministry of Health (Form MD 131 or electronically via CD-LENS) not later than 72 hours from the time of diagnosis. Management Patient is managed symptomatically. Management If infection occurs in early pregnancy, the patient should be referred to a Patient is managed gynaecologist or ansymptomatically. infectious disease physician who can provide advice and If infection occurs in early risks pregnancy, the patient should beandreferred to a counselling on the possible of congenital malformation appropriate gynaecologist anpoint infectious disease physician who can provide advice and management atorthat in pregnancy. on be theisolated possiblefrom risks of congenital malformation and precautions) appropriate counselling Patients should non-immune persons (with droplet management at that point in pregnancy. for seven days after onset of rash. Patients should be isolated from non-immune persons (with droplet precautions) for seven days after onset of rash. Prevention and Control Combined measles/ mumps/rubella (MMR) vaccine is given to all pre-school Prevention Control childrenand at the age 12-15 months and primary school entrants at the age of 6-7 years Combined measles/ mumps/rubella (MMR) vaccine is given Programme to all pre-school as part of the National Childhood Immunisation (see children at2). the age 12-15 months and primary school entrants at the age of 6-7 Appendix part of the National Childhood (see years Rubellaasvaccination is also routinely offeredImmunisation at polyclinicsProgramme to non-immune Appendix 2). and mothers who have just delivered their first babies. married women Rubella vaccination is alsoatroutinely at polyclinics to non-immune All unimmunised children nurseries,offered kindergartens and schools where an married and mothers who have just delivered their first babies. outbreakwomen is occurring should be immunised. All at nurseries, kindergartens schools where an The unimmunised vaccine shouldchildren be avoided in pregnancy and womenand who received rubella outbreakshould is occurring shouldtobe immunised. vaccine be advised avoid pregnancy for one month after vaccination. The vaccine be avoided in pregnancycongenital and women who received rubella observedshould risk for vaccine-associated rubella is zero but the vaccine should beasadvised avoid pregnancy one month after vaccination. theoretical risk is high asto2%. The currentlyfor recognised theoretical risk does The observed automatic risk for vaccine-associated congenital ifrubella is zerohasbutbeen the not mandate termination of pregnancy a woman theoretical riskvaccinated is as highwith as 2%. Thevaccine. currently recognised theoretical risk does inadvertently rubella mandate automatic termination pregnancy a woman has been not All childhood immunisations should beofnotified to theifNational Immunisation inadvertently vaccinated withBoard. rubella Post-vaccination vaccine. Registry, Health Promotion adverse reactions should All should be notified the National alsochildhood be notifiedimmunisations to the Pharmacovigilance Branch, to Health Sciences Immunisation Authority. Registry, Health Promotion Board. Post-vaccination adverse reactions should also be notified to the Pharmacovigilance Branch, Health Sciences Authority. References 1. Committee on Epidemic Disease. Serosurveillance of rubella in Singapore. Epidemiological News 2. 1. Ang LW, Chua LT, James L et al. Epidemiological surveillance and control of rubella in Singapore, Committee on Epidemic Disease. Serosurveillance of rubella in Singapore. Epidemiological News 1991-2007. Ann Acad Med Singapore 2010; 39; 95-101 Bulletin 2001; 27:1-3 Ang LW, Chua LT, James L et al. Epidemiological surveillance and control of rubella in Singapore, 1991-2007. Ann Acad Med Singapore 2010; 39; 95-101 Bulletin 2001; 27:1-3 References 2. 103 103 SEVERE ACUTE RESPIRATORY SYNDROME (SARS) SEVERE ACUTE RESPIRATORY SYNDROME (SARS) Causative Agent SARS-associated coronavirus (SARS-CoV) Causative Agent SARS-associated coronavirus (SARS-CoV) Incubation Period Typically 2-7 days but may be prolonged up to 10-14 days Incubation Period Typically 2-7 days but may be prolonged up to 10-14 days Infectious Period Throughout the symptomatic phase of the disease. Infectious Period Throughout the may symptomatic phaseviral of the disease.in the stool for up to 6 weeks after Although there be persistent shedding recovery from clinical illness, transmission of the disease has not been documented Although there maynor be convalescent persistent viral shedding in the stool for up to 6 weeks after from asymptomatic individuals. recovery from clinical illness, transmission of the disease has not been documented from asymptomatic nor convalescent individuals. Transmission Respiratory droplets and less often by direct contact with objects contaminated by Transmission respiratory secretions. Oral-faecal and airborne transmission may occur under Respiratory droplets and less often by direct contact with objects contaminated by special circumstances. respiratory secretions. Oral-faecal and airborne transmission may occur under special circumstances. Epidemiology The first outbreak of this new infectious disease occurred in Guangdong, China in Epidemiology November 2002, but soon spread to several Asian countries and Canada by March The outbreak of this newoninfectious occurred in China in 2003, although twoGuangdong, cases attributed to 2003.first The outbreak ended 5th July disease November 2002, but soon spread to several Asian countries and Canada by March laboratory transmission were reported from Singapore and Taiwan in September and 2003, although twooutbreak cases attributed to 2003. The 2003, outbreak ended onAnother 5th Julylaboratory December respectively. associated occurred in laboratory transmission were reported from Singapore and Taiwan in September and China in April 2004. December 2003, respectively. Another laboratory associated outbreak occurred in The majority transmission occurred in hospitals and other institutional healthcare China in Aprilof2004. settings. The majority of transmission occurred in hospitals and other institutional healthcare settings. By the end of the worldwide outbreak in July 2003, a total of 8096 cases were reported, with 774 deaths and a case-fatality rate of 9.6 percent. By the end of the worldwide outbreak in July 2003, a total of 8096 cases were reported, March with 774 deaths a case-fatality ratecases, of 9.6with percent. Between and May and 2003, a total of 238 33 deaths, were reported in Singapore. 41% of the cases were healthcare workers, and 68% were females. The Betweenage March Maycases 2003, a total of 238 with 33 deaths, were reported median of alland SARS was 36 (range 4 tocases, 90) years. in Singapore. 41% of the cases were healthcare workers, and 68% were females. The median age of all SARS cases was 36 (range 4 to 90) years. 104 104 Clinical Features The clinical presentation is non-specific and resembles other influenza-like Clinical Features illnesses. clinical presentation non-specific influenza-like The prodrome is prolongedis lasting from 3and to 7resembles days and other is characterised by illnesses. fever, malaise, headache and myalgia. Respiratory symptoms and diarrhoea, if present, The prodrome is occur prolonged from to 7 of days and is characterised by typically a few lasting days after the3onset fever. malaise, headache and myalgia. Respiratory diarrhoea, if fever, Physical examination is not helpful except as a gaugesymptoms of severityand of illness. present, typically occur vary a fewfrom daysmild after infection the onset (80%) of fever. Clinical manifestations to severe disease (20%) with Physical examination not death. helpful except as a gauge of severity of illness. respiratory failureisand Death Clinical manifestations vary from mild infection (80%) to multiorgan severe disease (20%) is usually caused by combination of respiratory and failure. with respiratory failure and death. The clinical course is marked by deterioration in the second week of illness and Death is usually caused by combination of respiratory and multiorgan failure.and recovery by the third week in the majority of cases. Children have a shorter The clinical is marked by deterioration in the second week of illness and milder coursecourse of illness. byevidence the third at week in the of cases. Children have a shorter and recovery There is no present of majority intra-partum infection. milder course of illness. There is no evidence at present of intra-partum infection. Investigations Chest X-ray. This may be normal early in the course of the disease. However, Investigations the more distinct radiographic features include: Chesta predominantly X-ray. This may be normal early inofthe course of the disease. However, peripheral location air-space opacity; distinctfrom radiographic include: the more progression unifocal features to multifocal or bilateral lung involvement aduring predominantly location of air-space opacity; treatment;peripheral and progression from unifocal to multifocal bilateral lung involvement lack of cavitation, lymphadenopathy andorpleural effusion. during treatment; and lack of cavitation, lymphadenopathy and pleural effusion. Case Definitions At the time of and in the immediate aftermath of the SARS epidemic, both the CaseWorld Definitions Health Organization (WHO) and the US CDC issued case definitions for At the time of and in the immediate aftermath of the SARS epidemic, both the SARS. Health Organization (WHO) and the US CDCifissued caseindefinitions for World According to the WHO, a case of SARS is notifiable it occurs an individual SARS. with laboratory confirmation of infection who either meets the clinical case According to has the WHO, case SARS iswith notifiable if it occurs in an individual definition or workeda in a of laboratory live SARS coronavirus or with with laboratory confirmation infection who either meets the clinical case clinical specimens infected withofSARS coronavirus. has definition worked inused a laboratory withincludes: live SARS coronavirus or with definition The clinicalorcase by the WHO clinical specimens infected with SARSfever; coronavirus. A history of fever or documented and The One clinical case definition by the WHO includes: or more symptomsused of lower respiratory tract illness (cough, difficulty A history of fever or documented fever; in breathing, shortness of breath); and and One or more symptoms oflung lowerinfiltrates respiratory tract illness difficulty Radiographic evidence of consistent with(cough, pneumonia or in breathing, shortness of syndrome breath); and acute respiratory distress (ARDS) or autopsy findings consistent with Radiographic evidence of lung infiltrates consistent with pneumonia or the pathology of pneumonia or ARDS without an identifiable cause; acute and respiratory distress syndrome (ARDS) or autopsy findings consistent the pathology of pneumonia or ARDS with No alternative diagnosis fully explaining thewithout illness.an identifiable cause; and Laboratory diagnostic tests that are required include one or both of the No alternative diagnosis fully explaining the illness. following: Laboratory diagnostic tests that are required include one or both of the following: 105 105 Detection of virus (reverse transcriptase PCR) assay detecting viral RNA present in two separate samples, or virus culture from any clinical specimen. Detection of virustwo (reverse transcriptase PCR) from assayeither detecting RNA These samples can be obtained two viral separate present in nasopharyngeal two separate samples, or virus culture sites (e.g. and stool) or from the from same any site,clinical but at different specimen. two samples can be obtained from either two separate times (e.g. These sequential nasopharyngeal aspirates); and/or (e.g. nasopharyngeal andinstool) or from same site,negative but at different sites Detection of antibody (a rise antibody titre,the either from to times (e.g. nasopharyngeal and/or immunosorbent positive or sequential at least a four-fold increase)aspirates); by enzyme-linked assay Detection of antibody (a rise in antibody titre, either from negative to (ELISA) and/or immunofluorescent assay (IFA). positive at leastsensitive a four-fold by enzyme-linked immunosorbent These areorhighly andincrease) specific but positive only from the second assay (ELISA) immunofluorescent assay (IFA). week of illness and/or onwards. These are highly sensitive and specific but positive only from the second week of illness onwards. Notification A legally notifiable disease in Singapore. Notify Ministry of Health (Form MD 131 Notification or electronically via CD-LENS) not later than 24 hours from the time of diagnosis. A legallyMOH notifiable disease inon Singapore. Notify Health (Form MD 131 Notify immediately suspicion. CallMinistry MOH of Communicable Diseases or electronically Surveillance teamvia at:CD-LENS) 98171463 not later than 24 hours from the time of diagnosis. Notify MOH immediately on suspicion. Call MOH Communicable Diseases Surveillance team at: 98171463 Management All suspected and probable/confirmed cases of SARS will be isolated and Management treated at the Communicable Disease Centre (CDC). Symptomatic All suspectedand andsupportive probable/confirmed of SARS will be isolated and treatment forcases all cases. treated at the Communicable Diseaseduring Centrethe (CDC). Ribavirin which was used initially pandemic has been shown to be ineffective Symptomatic treatment for all cases. in and vitrosupportive towards SARS coronavirus and is associated with significant toxicities. Ribavirin which was used initially during the pandemic has been shown to be ineffective in vitro towards SARS coronavirus significant Some centres recommend a short courseandofis associated moderate with to high dose toxicities. corticosteroids. Some centres a short using course of moderate dose There may be arecommend role for treatment protease inhibitor to likehigh lopinavir, corticosteroids. immunoglobulins and interferon based on prior experience. There may be a role for treatment using protease inhibitor like lopinavir, immunoglobulins and interferon based on prior experience. Infection Control Patients with SARS should ideally be nursed in negative pressure isolation Infection rooms.Control Patients with SARSand should ideally nursed in negative Respiratory (droplet airborne) andbe contact precautions are pressure required. isolation rooms. Procedures which may aerosolize the virus (viz. nebulizer therapy) should be avoided Respiratory (droplet and airborne) and contact precautions are required. if possible. Movement Procedures of which may(viz. aerosolize nebulizer therapy) should be patients for scansthe or virus other (viz. procedures) within the hospital avoided if possible. should be kept to a minimum. Movement of patients (viz. for scans or other procedures) within the hospital should be kept to a minimum. Prevention and Control Public health measures to limit transmission include: Prevention and Control Shortening the time from symptom-onset to isolation of patients (viz. early Public health measures to limit transmission include: case detection) Shorteningcontact the time from symptom-onset to isolation of patients (viz. early Effective tracing case detection) Effective contact tracing 106 106 Quarantine of exposed persons Surveillance of fever clusters and atypical pneumonia cases combination Quarantineof ofclinical exposedand persons A relevant epidemiological features should raise suspicions Surveillance of fever clusters atypical cases of SARS. However, it isand quite likelypneumonia that a de novo case will be missed A combination of clinical and relevant epidemiological features should raise initially, and success of current preventive policies will be gauged by the suspicions of SARS. However, size of the consequent outbreak.it is quite likely that a de novo case will be missed are initially, and success of current preventive policies bestage. gauged by the Efforts underway to prepare a vaccine but are still at anwill early size of the consequent outbreak. Efforts are underway to prepare a vaccine but are still at an early stage. References 1. SARS Reference. http://www.sarsreference.com. Accessed Aug 2010 2. CDC (Atlanta) http://www.cdc.gov/ncidod/sars. Accessed Aug 2010 References 3. SARS WHO http://www.who.int/csr/sars/en/index.html. Accessed Aug Aug 2010 2010 1. Reference. http://www.sarsreference.com. Accessed 4. CDC Peiris (Atlanta) JS, Yuenhttp://www.cdc.gov/ncidod/sars. KY, et al. The severe acute respiratory syndrome. N Engl J Med 2003; 349: 2431-41 2. Accessed Aug 2010 5. JA, Low DE, Hefland RF. Combining clinical and epidemiologic features for early 3. Jernigan WHO http://www.who.int/csr/sars/en/index.html. Accessed Aug 2010 of SARS. Dis 2004; 10: 327-33 4. recognition Peiris JS, Yuen KY, etEmerg al. TheInfect severe acute respiratory syndrome. N Engl J Med 2003; 349: 2431-41 6. G, Choo P, Leo YS al. SARS clinical transmission and hospital containment. Emerg 5. Gopalakrishna Jernigan JA, Low DE, Hefland RF. et Combining and epidemiologic features for early Infect Dis. 2004; 10:395-400 recognition of SARS. Emerg Infect Dis 2004; 10: 327-33 7. Gopalakrishna Lim PL, KurupG, A,Choo Gopalakrishna Laboratory-acquired acute respiratory Emerg syndrome. 6. P, Leo YSGetetal.al.SARS transmission andsevere hospital containment. N EngDis. J Med. 2004; 350:1740-5 Infect 2004; 10:395-400 8. definitions forGopalakrishna the 4 diseases G requiring notification to WHOsevere in allacute circumstances under the IHR 7. Case Lim PL, Kurup A, et al. Laboratory-acquired respiratory syndrome. (2005). Rec 2009; 84:52 N Eng JWkly Med. Epidemiol 2004; 350:1740-5 9. Pharmacologic of SARS:notification current knowledge recommendations. Annthe Acad 8. Tai CaseDY. definitions for the 4treatment diseases requiring to WHOand in all circumstances under IHR Med Singapore. 2007;36:438-43. (2005). Wkly Epidemiol Rec 2009; 84:52 10. Tai Stockman L.J., Bellamy R., Garnerof P.SARS: SARS:current systematic review of effects. PLoS 9. DY. Pharmacologic treatment knowledge andtreatment recommendations. Ann Acad Med 3. e343.2006 Med Singapore. 2007;36:438-43. 11. Stockman Goh KT, Cutter J, Heng BH et al. Epidemiology and control of SARS in Singapore. Acad Med 10. L.J., Bellamy R., Garner P. SARS: systematic review of treatment effects.Ann PLoS Singapore 2006;35:301-6. Med 3. e343.2006 11. Goh KT, Cutter J, Heng BH et al. Epidemiology and control of SARS in Singapore. Ann Acad Med Singapore 2006;35:301-6. 107 107 SEXUALLY-TRANSMITTED INFECTIONS Causative AgentsSEXUALLY-TRANSMITTED INFECTIONS In 2009, the top 5 sexually-transmitted infections (STIs) diagnosed in Singapore Causative Agentstrachomatis (infection of the urethra, cervix, pharynx and rectum), were: Chlamydia In 2009, the top 5 sexually-transmitted infections (STIs) diagnosed in Singapore Neisseria gonorrhoeae (infection of the urethra, cervix, pharynx and rectum), nonwere: Chlamydia trachomatis of the urethra, cervix, pharynx gonococcal urethritis (NGU),(infection herpes simplex virus (HSV): types 1 and rectum), 2 (anoNeisseria gonorrhoeae (infection of the urethra, cervix, (ano-genital pharynx and warts). rectum),Other nongenital herpes), and human papilloma virus (HPV) gonococcal urethritis herpespallidum simplex (syphilis), virus (HSV): types 1 andvaginalis 2 (anoimportant STIs are (NGU), Treponema Trichomonas genital herpes), and human humanimmunodeficiency papilloma virus virus (HPV) (ano-genital (trichomoniasis), infection (HIV). warts). Other important STIs are Treponema pallidum (syphilis), Trichomonas vaginalis (trichomoniasis), and human immunodeficiency virus infection (HIV). Incubation Period Chlamydia : 5 - 14 days Incubation Period Gonorrhoea : 3 - 5 days Chlamydia herpes Ano-genital : 25 - 14 days Gonorrhoea warts 3 -65months days (mean 3 months) Ano-genital : 1Ano-genital herpes 2 - -14 Syphilis : 10 90days days (mean 21 days) Ano-genital warts 6 months Trichomoniasis : a1-few days (mean 3 months) Syphilis : 10 - 90ofdays (mean days) HIV mean 1 month to 21 acute HIV infection, Trichomoniasis : amean few of days 5 to 8 years to AIDS if untreated HIV : mean of 1 month to acute HIV infection, mean of 5 to 8 years to AIDS if untreated Infectious Period Gonorrhoea, chlamydia : active infection, symptomatic or asymptomatic Infectious Ano-genitalPeriod herpes : presence of vesicles and erosions; asymptomatic Gonorrhoea, chlamydia : active shedding infection, is symptomatic or asymptomatic viral also an important route of Ano-genital herpes : presence of vesicles and erosions; asymptomatic transmission viral is also an important Ano-genital warts : highershedding with presence of active lesions; route of transmissioninfections common subclinical Ano-genital warts : higher presence of active stages lesions; Syphilis during with primary and secondary subclinical infections commonor asymptomatic Trichomoniasis : active infection, symptomatic Syphilis during primary stagesif untreated HIV infection : infectious from and earlysecondary on till demise Trichomoniasis : active infection, symptomatic or asymptomatic HIV infection : infectious from early on till demise if untreated Clinical Features STI may present with: Clinical Features genital discharges (gonorrhoea, chlamydia, trichomoniasis) STI presentulcers with: (herpes, syphilis) may ano-genital ano-genital genital discharges (gonorrhoea, chlamydia, trichomoniasis) growths (warts, molluscum contagiosum) ano-genital ulcersscabies) (herpes, syphilis) rashes (syphilis, ano-genital growths (warts, contagiosum) pelvic inflammatory diseasemolluscum (gonorrhoea, chlamydia) rashes (syphilis, scabies) epididymo-orchitis (gonorrhoea, chlamydia) pelvicinfection inflammatory diseasein(gonorrhoea, HIV may present several wayschlamydia) depending on the organ systems affected epididymo-orchitis (see chapter(gonorrhoea, on HIV). chlamydia) HIV infection may present in several ways depending on the organ systems affected (see chapter on HIV). 108 108 Many STIs may be asymptomatic and can be detected only if the appropriate laboratory screening tests are performed (see references). Many STIs may be asymptomatic and can be detected only if the appropriate laboratory screening tests are Investigations and Guide to performed Diagnosis (see references). Ano-genital Herpes (First episode/ Recurrent) Investigations Guideor to erosions Diagnosisin the ano-genital area (may be severe with Typicaland vesicles Ano-genital Herpes (First episode/ Recurrent) initial episode). Typical vesicles or isolation, erosions in the immunofluorescence ano-genital area (may(DIF), be severe Confirmed by viral direct PCR, with EIA initial episode). serological test against glycoprotein gG1 (HSV-1) & gG2 or type-specific (HSV-2) ConfirmedforbyHSV viral (serology isolation, is direct (DIF), PCR, as EIA not immunofluorescence useful for first episode infection it or type-specific test for against glycoprotein gG1 following (HSV-1) &a gG2 takes between 6serological and 8 weeks serological detection first (HSV-2) for HSV (serology is not useful for first episode infection as it episode). takes between 6 and 8 weeks for serological detection following a first episode). Chlamydia Genital Infection—(A laboratory diagnosed infectious disease) Nucleic acid amplification test (NAAT) (e.g. PCR) positive for C. diagnosed Chlamydia Genital Infection—(A trachomatis from ano-genital laboratory specimen or urine; or infectious disease) Nucleic detection acid amplification (NAAT) for (e.g. positive foranoC. Antigen (e.g. EIA, test IF) positive C. PCR) trachomatis from trachomatis from ano-genital specimen or urine; or genital specimen. Antigen detection EIA, IF)aspositive for distinguish C. trachomatis from anoChlamydia serology(e.g. is not useful it does not between past or genital specimen. current infection; there is also cross-reactivity with other chlamydial species. Chlamydia serology is not useful as it does not distinguish between past or current infection; there is also cross-reactivity with other chlamydial species. Gonorrhoea Purulent genital discharge (associated with dysuria in males), history of Gonorrhoea recent unprotected sexual intercourse; or Purulent genitalsmear discharge dysuria with in males), history of Gram-stained from(associated genital with discharges Gram-negative recent unprotected sexualorintercourse; or intracellular diplococci; Positive Gram-stained frommedia genital with culture smear on selective for N.discharges gonorrhoeae; or Gram-negative intracellular diplococci; or Urine nucleic acid amplification test (NAAT) (e.g. PCR) positive for N. Positive culture on selective media for N. gonorrhoeae; or gonorrhoeae. Urine nucleic acid amplification (NAAT) PCR)&positive for N. Gonorrhoea serology is not useful test due to lack of (e.g. sensitivity specificity. gonorrhoeae. Gonorrhoea serology not useful due to lack of sensitivity & specificity. Non-Gonococcal Urethritisis(NGU) Mucopurulent or whitish discharge from urethra associated with dysuria or Non-Gonococcal Urethritis (NGU) urethral discomfort/itch in males, history of recent unprotected sexual intercourse; Mucopurulent or or whitish discharge from urethra associated with dysuria or urethral discomfort/itch in males, history of count recent(5unprotected sexual Gram-stained smear showing increased pus cell or more WBC per intercourse; or high-power field) in absence of Gram-negative intracellular diplococci; or Gram-stained increased pus urine cell count Visible threadssmear in theshowing first glass of a 2 glass test. (5 or more WBC per high-power field) in absence of Gram-negative intracellular diplococci; or VisibleSyphilis threads in the first glass of a 2 glass urine test. Infectious Presence of primary chancre usually solitary, indurated, non-tender (but the Infectious Syphilis ulcer may also be atypical), inguinal lymphadenopathy; or Presence of primary chancre usually solitary, indurated, non-tender (but the ulcer may also be atypical), inguinal lymphadenopathy; or 109 109 Presence of clinical features of secondary syphilis e.g. rash especially on palms and soles, ano-genital patches and growths, generalized Presence of clinicalpatchy features secondary syphilis lymphadenopathy, hairofloss; confirmed by: e.g. rash especially on palms and soles, dark-field ano-genitalmicroscopic patches examination and growths, generalized Positive of exudate from lymphadenopathy, patchy hair loss; confirmed by: primary or secondary ano-genital lesions for spirochaetes; or Positive dark-field Reactive blood testsmicroscopic for syphilis:examination of exudate from primary or secondary ano-genital lesions for spirochaetes; or 1. Non-specific treponemal tests (RPR/VDRL) Specific Reactivetreponemal blood tests tests for syphilis: 2. (TPPA/TPHA, LIA, Syphilis EIA) 1. Non-specific treponemal tests (RPR/VDRL) 2. Syphilis Specific treponemal tests (TPPA/TPHA, LIA, Syphilis EIA) Non-Infectious Presence of clinical features of tertiary syphilis (viz. cardiovascular Non-Infectious Syphilis syphilis, central nervous system syphilis); or Asymptomatic Presence of clinical of tertiary syphilis (viz. cardiovascular infectionfeatures with reactive blood tests for syphilis syphilis, central nervous system syphilis); or Note - persistence of reactive serology in patients with treated syphilis may be Asymptomatic with scar reactive blood tests for syphilis indicative ofinfection a serological Note - persistence of reactive serology in patients with treated syphilis may be indicative of a serological scar Congenital Syphilis Presence of clinical features of active disease (e.g. muco-cutaneous signs, Congenital Syphilishepatosplenomegaly) and confirmed by reactive blood tests bone changes, for Presence of clinical features of active disease (e.g. muco-cutaneous signs, syphilis. bone changes, hepatosplenomegaly) by reactive Asymptomatic infection in infant bornand to confirmed infected mother with: blood tests for syphilis. Detectable LIA IgM in infant; or Asymptomatic infection in titre infant to fourfold infected or mother with: RPR/VDRL inborn infant greater than in mother; or Detectable LIA IgM in infant; or titre in infant fourfold RPR/VDRL titres show serial rise; oror greater than in mother; or Reactive CSF-VDRL or abnormal CSF FEME in infant. RPR/VDRL titres show serial rise; or Reactive CSF-VDRL or abnormal CSF FEME in infant. Trichomoniasis Diagnosed by direct wet-mount microscopy and culture. Serology is not Trichomoniasis useful. Diagnosed by direct wet-mount microscopy and culture. Serology is not useful. There are no clear guidelines for screening with serology. Mycoplasma: There clearasguidelines for screening with serology. Mycoplasma: Candida: Serology is are not no useful it is not indicative of a genital cause/disease. Candida: Serology is not useful as it is not indicative of a genital cause/disease. Management All patients with a STI should be screened for syphilis, hepatitis B and HIV Management infection. All patients with a STIrecommended should be screened for syphilis, B and HIV Patients should receive antimicrobials in thehepatitis correct dosages (see infection. references). Test-of-cure is important to assess treatment efficacy particularly for Patients should and receive recommended antimicrobials in the correct dosages (see gonorrhoea syphilis. references). Test-of-cure is important to assess treatment efficacy particularly for gonorrhoea and syphilis. 110 110 Chlamydia: Doxycycline 100mg bid x 7days (avoid if pregnant) Chlamydia: Erythromycin 500mg qid x 7 days Doxycycline bid x 7days Erythromycin100mg ethylsuccinate 800 (avoid mg qidifx pregnant) 7days Azithromycin Erythromycin 500mg x 7(useful days if adherence is an anticipated problem) 1gm x 1qid dose Erythromycin ethylsuccinate 800 mg qid x 7days Gonorrhoea: Azithromycin 1gm x 1 dose (useful if adherence is an anticipated problem) All patients with gonorrhoea should be given concurrent treatment for Gonorrhoea: chlamydia. All patients with are gonorrhoea should bedue given concurrent treatment Fluoroquinolones not recommended to high prevalence (80%) for of chlamydia.in N. gonorrhoeae. resistance Fluoroquinolones not recommended due to high of Repeat smears andarecultures should be performed onprevalence or around (80%) the 14th resistance in N.day. gonorrhoeae. post-treatment Repeat smears culturesallergy, should IM be performed on orcan around the 14th For those withand penicillin spectinomycin be used. Or post-treatment day. testing and desensitization. Specialist consultation consider allergy recommended. For those with penicillin allergy, IM spectinomycin can be used. Or consider allergy testing and desensitization. Specialist consultation Uncomplicated (pharynx/urethra/rectum/cervix): recommended. IM Ceftriaxone 250mg x 1 dose; or (pharynx/urethra/rectum/cervix): Uncomplicated Cefixime 400mg x 1 dose IM Ceftriaxone 250mg Infections x 1 dose; or Severe orDisseminated Gonococcal (DGI): IV Cefixime 400mg 1-2g x 1 dose Ceftriaxone daily. Duration depending on site of Severe or Disseminated Gonococcal infection and response Infections (DGI): IV Ceftriaxone 1-2g daily. Duration depending on site of infection and response Syphilis: Cases of syphilis should be treated with intramuscular benzathine penicillin. Syphilis: They should have serological tests repeated at 3 months, and then every 6 months Cases offor syphilis should be treated intramuscularshould benzathine 2 years. Suspected caseswith of neurosyphilis have penicillin. a lumbar They should have serological tests repeated at 3 months, and then every 6 puncture performed. months 2 years. Suspected of neurosyphilis have asyphilis, lumbar For late for latent syphilis, syphiliscases of unknown duration,should congenital puncture performed. neurosyphilis or syphilis in pregnancy, the treatment recommendations are different For late latent syphilis, syphilis of should unknown and relevant expert advice be duration, sought. congenital syphilis, neurosyphilis or syphilisSyphilis: in pregnancy, the treatment recommendations are Primary and Secondary different and relevant expert advice should be million sought. units x 1 dose. (Some IM Benzathine Penicillin G 2.4 Primary and Secondary authoritiesSyphilis: use 2 doses for secondary syphilis); or IM Aqueous Benzathine Penicillin G 2.4 million units units x 1 dose. IM Procaine Penicillin G 600,000 daily(Some x 10 authorities use 2 doses for secondary syphilis); or days IM Aqueous Penicillinallergic patients: Procaine Penicillin G 600,000 units daily x 10 days Doxycycline 100mg bid x 14 days; or Penicillinallergic patients: 500mg qid x 14 days; or Erythromycin Doxycycline 100mg x 14 days; or Azithromycin 500mgbid daily x 10 days Erythromycin 500mg qid x 14 days; or Azithromycin 500mg daily x 10 days 111 111 Cases of first-episode genital herpes should be treated with acyclovir or related medications. Recurrent genital herpes may be treated with either episodic or Cases of first-episode genital herpes should be treated with acyclovir or related suppressive anti-viral regimens (see references). medications. warts Recurrent herpes may be or treated with either or Ano-genital can genital be treated medically surgically; they episodic should be suppressive anti-viral regimens (see references). followed up till all visible warts are cleared. Regular PAP smears are Ano-genital can be treated medically or surgically; they should be recommendedwarts for female patients. followed up till all visible warts aremetronidazole cleared. Regular PAP smears are Cases of trichomoniasis are treated with (see references). recommended for female patients. Cases of trichomoniasis are treated with metronidazole (see references). Notification Chlamydia, gonorrhoea, syphilis (infectious, non-infectious and congenital), Notification NGU, genital herpes (first episode and recurrent) should be notified to the DSC clinic Chlamydia, syphilis andCD-LENS. congenital), by fax gonorrhoea, (62994335) using form(infectious, MD 131 ornon-infectious electronically via NGU, genital herpeson (first recurrent) should be notified to the DSC Provide information typeepisode of HSVand detected where available. clinic bynotifications fax (62994335) using form MDherpes 131 orare electronically via CD-LENS. Repeat of recurrent genital not necessary. Provide information on typeand of HSV detected whereneed available. The name, NRIC, address telephone number not be completed, but initials, Repeat notifications of recurrent genital herpes arestatus not necessary. sex, date of birth, ethnicity and residential should be provided. The name, NRIC, address and telephone number need not be completed, but initials, and sex, Control date of birth, ethnicity and residential status should be provided. Prevention Patients with STI should be given information about their current infection. Prevention and future Control To prevent infections, information on safer sex should be given too e.g. correct Patientsand withconsistent STI should be given condom use.information about their current infection. To prevent future infections, tracing information onbe safer sex should be givenand too treat e.g. Partner management/contact should conducted to diagnose correct andinconsistent condom use. complications and further transmission. infections sex partners, to prevent Partner management/contact should be conducted to diagnose andB treat Antenatal mothers should betracing routinely screened for syphilis, hepatitis and infections in sex partners, to prevent complications and further transmission. HIV infection. Antenatal should be routinely syphilis, hepatitis and Hepatitis Bmothers vaccination should be givenscreened to thosefor who are negative forBHBV HIV infection. markers. Hepatitis B vaccination should be givenwith to those whoeducational are negative for HBV Brothel-based sex workers are provided STI/HIV information markers. and taught negotiation skills to achieve 100% condom use; they are screened Brothel-based sex workers are provided with STI/HIV routinely for syphilis, gonorrhoea, chlamydia, HIV andeducational hepatitis Binformation infections. and taughtSTI/HIV negotiation skills toforachieve condom use; they are screened Targeted education at risk100% groups e.g. youth, MSM, military routinely gonorrhoea, HIV and hepatitis personnel,for andsyphilis, clients of sex workerschlamydia, should be conducted regularly.B infections. STI/HIV education for early at risk groups e.g. MSM, military Targeted Patients are encouraged to seek treatment, not toyouth, self-medicate and to personnel, and clients ofmedications. sex workers should be conducted regularly. complete all prescribed Patients are encouraged to seek may earlyresult treatment, to self-medicate and to Self-medication with antibiotics in the not emergence of drug-resistant complete all prescribed medications. strains. Medical practitioners should not dispense antibiotic chemoprophylaxis as Self-medication antibiotics may result in thethis emergence drug-resistant there is no onewith universally effective antibiotic, may alsoofresult in a false strains. should not dispense antibiotic chemoprophylaxis sense ofMedical security practitioners and may be dangerous. as there is no one universally effective antibiotic, this may also result in a false sense of security and may be dangerous. 112 112 References 1. DSC clinic website: http://www.dsc-sexualhealth.com.sg. Accessed Dec 2010. References 2. STI Management Guidelines - Department of STI Control, National Skin Centre, 2007 3. Clinical Guidelines on genital Accessed ulcers Dec & 2010. discharges, May 1. MOH DSC clinic website:Practice http://www.dsc-sexualhealth.com.sg. Accessed 2010. 2. http://www.moh.gov.sg/mohcorp/publications.aspx?id=22326. STI Management Guidelines - Department of STI Control, National Skin Dec Centre, 2007 3. MOH Clinical Practice Guidelines on genital ulcers & discharges, http://www.moh.gov.sg/mohcorp/publications.aspx?id=22326. Accessed Dec 2010. 113 113 May 2009: 2009: SHIGELLOSIS (BACILLARY DYSENTERY) Causative AgentsSHIGELLOSIS (BACILLARY DYSENTERY) Shigella sonnei, S. flexneri, S. boydii and S. dysenteriae. Causative Agents Shigella sonnei, S. flexneri, S. boydii and S. dysenteriae. Incubation Period Usually 1 - 3 days. Up to 1 week for S. dysenteriae type 1 Incubation Period Usually 1 -Period 3 days. Up to 1 week for S. dysenteriae type 1 Infectious Throughout duration of acute illness and until the organism is no longer present in Infectious Periodwithin 4 weeks after illness. the stool, usually Throughout duration of acute illness and until the organism is no longer present in the stool, usually within 4 weeks after illness. Transmission Direct or indirect faecal-oral transmission from a symptomatic person or shortTransmission term asymptomatic carrier. Also via faecally-contaminated water, milk or food. Transmission Direct or indirect faecal-oral transmission from a symptomatic person or shortby house flies has also been documented. termfew asymptomatic Alsocan viacause faecally-contaminated water, milk or food. As as 10-100 carrier. organisms infection, enabling person-to-person Transmissionwhere by house flies conditions has also been transmission hygiene aredocumented. compromised. As few as have 10-100 organisms can cause men; infection, person-to-person Outbreaks occurred in homosexual underenabling conditions of crowding; transmission where hygiene are compromised. and where personal hygieneconditions is poor such as in day care centres, jails, mental institutions Outbreaks have occurredrefugee in homosexual and crowded camps. men; under conditions of crowding; and where personal hygiene is poor such as in day care centres, jails, mental institutions and crowded refugee camps. Epidemiology Endemic throughout the world with the greatest burden of disease occurring in Epidemiology developing countries afflicting children less than five years of age particularly. S. Endemic throughout world of with the greatest burden countries. of disease occurring in sonnei accounts for thethe majority shigellosis in developed developing countries afflicting children less than five years of age particularly. S. sonnei accountsa for of shigellosis developedwere countries. In Singapore, totaltheofmajority 29 sporadic cases of in shigellosis reported in 2008, as compared to 13 cases in 2007. The serotypes involved were Shigella sonnei In Singapore, a total of 29 sporadic cases shigellosis reported in 2008, as (75.9%), Shigella dysenteriae (13.8%), and of Shigella boydiiwere (10.3%). Of the reported compared to 13local cases in 2007. The serotypes involved cases, 17 were residents comprising 12 indigenous andwere five Shigella imported sonnei cases. (75.9%), Shigella dysenteriae (13.8%), and Shigella boydiilocally. (10.3%). the reported There were two non-residents that acquired the infection TheOfremaining 10 cases, comprised 17 were local comprising 12 indigenous andmedical five imported cases. cases oneresidents tourist and nine foreigners seeking treatment in There were The two non-residents acquired the the infection locally. remaining(1), 10 Singapore. five imported that cases acquired infection fromThe Bangladesh cases comprised oneKong tourist foreigners seeking medical treatment in Cambodia (1), Hong (1), and Indianine (1) and Nepal (1). Singapore. The five imported cases acquired the infection from Bangladesh (1), Cambodia Hong Kong (1), India (1) and Nepal (1).(esp. in Asia), nalidixic acid, Increasing (1), antibiotic resistance to flouroquinolones TMP/SMX, ampicillin and tetracycline, has been reported. Increasing antibiotic resistance to flouroquinolones (esp. in Asia), nalidixic acid, TMP/SMX, ampicillin and tetracycline, been reported. S. dysenteriae type 1 (SD1) serotype is has responsible for epidemics and for the most severe clinical illness of Shigella species. Only SD1 elaborates true Shiga toxin—a S. dysenteriae 1 (SD1)that serotype is responsible epidemicsUremic and forSyndrome the most neurotoxin andtype enterotoxin is associated with thefor Haemolytic severe clinical illness of Shigella species. Only SD1 elaborates true Shiga toxin—a neurotoxin and enterotoxin that is associated with the Haemolytic Uremic Syndrome 114 114 (HUS). All Shigella species secrete enterotoxins responsible for the watery diarrhoea. (HUS). All Shigella species secrete enterotoxins responsible for the watery diarrhoea.Features Clinical Causes a spectrum of illness from watery diarrhoea to classical dysentery. Clinical Features Causes a spectrum of illnessseverity from watery to classical dysentery. The spectrum of disease variesdiarrhoea according to the host’s immunity and serogroup of the infecting organism. S. sonnei commonly causes mild disease, which The spectrum severity varies to the host’s immunity and may be limited of to disease watery diarrhoea, while according S. dysenteriae or S. flexneri commonly serogroup of the infecting organism. S. sonneihealthy commonly mild disease, which causes dysenteric symptoms. In a normal host,causes the course of disease is may be limited to watery diarrhoea, S. dysenteriae S. untreated. flexneri commonly generally self-limited, lasting no morewhile than seven days whenorleft causes dysenteric symptoms. In a normal healthy host, the course of disease is generally self-limited, lasting no more than seven days when left untreated. Diarrhoea: Sudden onset; initial voluminous watery stool (small intestine phase); subsequently containing blood and mucus (colonic phase); fluid depletion Diarrhoea:typically Sudden uncommon. onset; initial voluminous watery stool (small intestine phase); Fever subsequently containing blood and mucus (colonic phase); fluid typically uncommon. depletion Nausea. Occasionally vomiting Fever Abdominal cramps Nausea. Occasionally Tenesmus (common) vomiting Abdominal cramps Stools usually contain blood and mucous (dysentery) Tenesmus (common) Painful rectal examination by proctoscopy and the rectum may be hyperaemic Stools usually contain blood and mucous (dysentery) or ulcerated. Painful rectal examination by proctoscopy and the rectum may be hyperaemic or ulcerated. Complications Intestinal: Complications Proctitis/rectal prolapse Intestinal: Toxic megacolon Proctitis/rectal prolapse Intestinal obstruction Toxic megacolon Colonic perforation Intestinal obstruction Protein losing enteropathy Colonic perforation Systemic: Protein losing enteropathy Reactive arthritis: May follow after S. flexneri infection. Can be seen Systemic:alone or in association with conjunctivitis and urethritis (formerly Reactive May followHLA-B27 after S. flexneri infection. Can be seen known as arthritis: Reiter’s syndrome). associated. alone or in association with inconjunctivitis and urethritis Haemolytic-uremic syndrome Shiga toxin producing strains.(formerly known as Reiter’s syndrome). HLA-B27 associated. Neurological (seizure, headache, encephalopathy, lethargy, confusion) Haemolytic-uremic syndrome in Shiga toxin producing strains. Neurological (seizure, headache, encephalopathy, lethargy, confusion) Investigations Stool leukocytes and culture (select portion with blood or mucus) or rectal swab Investigations (if the patient is unable to provide a stool specimen). Shigella is a fastidious Stool leukocytes and culture (select portion with blood or mucus) or rectal swab organism; and requires prompt handling. Antibiotics susceptibility testing is (if the patient is unable to provide a stool specimen). Shigella is a fastidious needed for all specimens. organism; and requires prompt handling. Antibiotics susceptibility testing is needed for all specimens. 115 115 Blood cultures are usually negative Blood cultures are usually negative Notification If two or more cases are recognised in an institution, this should be reported to the Notification Ministry of Health (Form MD 131 or electronically via CD-LENS). Shigellosis is no If two aornotifiable more cases are recognised in an institution, this should be reported to the longer disease. Ministry of Health (Form MD 131 or electronically via CD-LENS). Shigellosis is no longer a notifiable disease. Management Mild infections are usually self-limited and most patients recover without Management antibiotic treatment. Mild infections are usually patients without Anyone whose stool cultures self-limited are positiveand for most Shigella shouldrecover be treated for antibiotic treatment. public health reasons. Antibiotics Anyone whose stool positive for Shigella should be treated for shorten thecultures durationare of fever, diarrhoea and shedding of Shigella in public stool. health reasons. Antibiotics shorten the duration of fever, diarrhoea and shedding of Shigella in Treatment regimens include: stool. Ciprofloxacin 500 mg bd x 5 days (Recommended) Treatment regimens include: Azithromycin 500 mg day1, then 250mg daily x 4 days (Alternative) Ciprofloxacin x 5 for days (Recommended) IV Ceftriaxone500 1-2mg gmbd daily hospitalized patients Azithromycin 500make mg day1, then 250mg x 4 days Anti-diarrhoeal agents can the illness worse daily and should be (Alternative) avoided. IV Ceftriaxone 1-2 gm daily for hospitalized patients Anti-diarrhoeal Infection control agents can make the illness worse and should be avoided. Contact precautions should be observed when nursing a patient with shigellosis. Infection control This involves strict hand-washing before and after handling the patient as well as Contact precautions be observed nursing a patient withhandling shigellosis. wearing of personal should protective garments when e.g. plastic aprons. Proper and This involves strict before and after handling patient as well as disposal of stool is hand-washing important as the organism is present in the large amounts in the wearing stool. of personal protective garments e.g. plastic aprons. Proper handling and disposal of stool is important as the organism is present in large amounts in the stool. Food handlers infected with Shigella must be treated with antibiotics and should not be involved in preparation of food as long as their stool cultures are positive; Food handlers infected Shigellagenerally must be requires treated with antibiotics andofshould not conversion of the stool with to negative at least 48 hours antibiotic be involved in preparation food as long as their stool cultures are positive; treatment. Health care and dayofcare centre workers should always be treated as well. conversion of the stool to negative generally requires at least 48 hours of antibiotic treatment. care and day care centre workers should always be treated as well. PreventionHealth and Control The Ministry of Health will carry out epidemiological investigations to trace the Prevention and Control source of infection when an outbreak is suspected. The Ministry Health will carry outscreened epidemiological investigations to trace Contacts and of food handlers will be for Shigella and those found tothe be source ofwill infection when an outbreak is suspected. infected be treated. Contacts and food of handlers willand be screened for Shigella and those to be A high standard personal food hygiene is important in found preventing infected will be treated. transmission. A high standard of personal and food hygiene is important in preventing transmission. 116 116 References 1. Thielman NM, Guerrant RL. Acute infectious diarrhoea. N Engl J Med 2004; 350:38-47 References 2. Christopher PR, David KV, John SM et al. Antibiotic therapy for Shigella dysentery. Cochrane Database Syst 2010RL. AugAcute 4;(8):CD006784. AvailableNat: 1. Thielman NM,Rev. Guerrant infectious diarrhoea. Engl J Med 2004; 350:38-47 http://info.onlinelibrary.wiley.com/userfiles/ccoch/file/CD006784.pdf. Accessed Dec Cochrane 2010. 2. Christopher PR, David KV, John SM et al. Antibiotic therapy for Shigella dysentery. Database Syst Rev. 2010 Aug 4;(8):CD006784. Available at: http://info.onlinelibrary.wiley.com/userfiles/ccoch/file/CD006784.pdf. Accessed Dec 2010. 117 117 SMALLPOX SMALLPOX Causative Agent Variola virus, a species of Orthopoxvirus Causative Agent Variola virus, a species of Orthopoxvirus Incubation Period 12-14 days (range 7-17 days) Incubation Period 12-14 days Period (range 7-17 days) Infectious From fever onset (usually 2–4 days before rash) until last scab has separated; about Infectious Period three weeks. From fever onset (usually 2–4 days before rash) until last scab has separated; about three weeks. Transmission Aerosols/droplets from nasopharyngeal lesions and contact with contaminated Transmission articles. Aerosols/droplets from nasopharyngeal lesions and contact with contaminated articles. Epidemiology Last naturally acquired human case in the world occurred in Somalia in 1977; global Epidemiology eradication was certified two years later. Last naturally acquired human case in the world occurred in Somalia in 1977; global eradication two years major later. and the variola minor. There are atwas leastcertified 2 strains, variola There are at least 2 strains, variola major andwith the variola minor.rate up to 30-50% in Variola major: the more severe form case fatality susceptible populations. major: the more severe form with with case more fatalitydiminutive rate up topox 30-50% in Variola minor: milder form of the disease lesions; susceptible case fatalitypopulations. rate of 1-2% in susceptible populations. Variola minor: milder form of the disease with more diminutive pox lesions; case Features fatality rate of 1-2% in susceptible populations. Clinical Characteristic rash appears 2-4 days after non-specific, flu-like prodrome (fever Clinical Features and headache). Characteristic rash after of non-specific, prodrome (fever Maculopapular rashappears begins2-4 ondays mucosa mouth andflu-like pharynx, face, hands, and headache). forearms and spreads to legs and centrally to trunk; lesions are more Maculopapular rashface begins on mucosathan of mouth and pharynx, face, hands, predominant on the and extremities on the trunk (centrifugal). forearmsprogress and spreads to legs onand lesions are more Lesions synchronously any centrally given parttoof trunk; the body from macules to predominant on thetoface and extremities thanscabs. on the trunk (centrifugal). papules to vesicles pustules and to crusty Two Lesions any given partbeen of the body from macules to rareprogress forms ofsynchronously invariably fatalonsmallpox have reported: papules to vesicles to pustules and to crusty scabs. Purpura variolosa or hemorrhagic type smallpox Two raretype forms of invariably fatal smallpox have been reported: Flat smallpox Purpura variolosa or hemorrhagic type smallpox Flatdiagnosis type smallpox Differential Chickenpox, monkeypox, disseminated herpes zoster. Differential Clues todiagnosis distinguish smallpox from chickenpox: Chickenpox, disseminatedinherpes zoster.of development Smallpoxmonkeypox, lesions are synchronous their stage Clues to distinguish smallpox from chickenpox: Smallpox lesions are synchronous in their stage of development 118 118 Smallpox has many more lesions on the face and extremities than trunk (centrifugal spread) are more common on the palms soles Smallpox lesions has many lesions on faceand and extremities than trunk (centrifugal Smallpox lesions are more deeply imbedded in the dermis compared with spread) the superficial lesions of chickenpox Smallpox lesions are more common on palms and soles Smallpox lesions are more deeply imbedded in the dermis compared with Investigations the superficial lesions of chickenpox Electron microscopy, PCR, viral isolation (culture of pharyngeal swab or lesions). Investigations Guarnieri bodies on Giemsa modified silver(culture stain. of pharyngeal swab or Electron microscopy, PCR,orviral isolation lesions). Management Guarnieri bodies on Giemsa or modified silver stain. Supportive care. Antibiotics may be used for secondary bacterial infection. Management Supportive care. Prophylaxis Antibiotics may be used for secondary bacterial infection. Vaccination within 3 days of exposure may significantly ameliorate or prevent smallpox. Vaccination 4 to 7 days after exposure likely still offers some protection Prophylaxis or modification of disease severity. Vaccination within 3 days of exposure may significantly ameliorate or prevent smallpox. Vaccination 4 to 7 days after exposure likely still offers some protection Notification or modification of disease severity. Notify MOH immediately on suspicion. Call MOH Communicable Diseases Surveillance Notification team at: 98171463 Notify MOH immediately on suspicion. Call MOH Communicable Diseases Isolation Precautions Surveillance team at: 98171463 Airborne and contact precautions. Isolate patients in negative pressure isolation room.Precautions Isolation Patients be considered infectious all scabs separate and should be Airborneshould and contact precautions. Isolateuntil patients in negative pressure isolation isolated during this period. room. Droplet airborne precaution for a minimum 17 days following exposure Patients and should be considered infectious until allofscabs separate and should be for all persons in direct contact with the index case. isolated during this period. Droplet and airborne precaution for a minimum of 17 days following exposure for all persons in direct contact with the index case. References 1. Henderson DA, Inglesby TV et al. Smallpox as a biological weapon: medical and public health management. Working group on Civilian Biodefense. JAMA 1999; 281: 2127-37 References 2. Committee on Epidemic Diseases. Clinical guidelines on anthrax, botulism, plague and smallpox. 1. Epidemiological Henderson DA, Inglesby TV et2001; al. Smallpox News Bulletin. 27:61-68as a biological weapon: medical and public health management.(Atlanta), Working group on Civilian Biodefense. JAMA 1999; 281: 2127-37 3. CDC Smallpox overview. 2004. Available from 2. http://emergency.cdc.gov/agent/smallpox/overview/disease-facts.asp. Committee on Epidemic Diseases. Clinical guidelines on anthrax, botulism, and smallpox. Accessedplague Dec 2010. Epidemiological Bulletin. 2001;from 27:61-68 4. WHO. Smallpox.News 2010. Available http://www.who.int/mediacentre/factsheets/smallpox/en. 3. CDC Smallpox overview. 2004. Available from Accessed Dec(Atlanta), 2010. http://emergency.cdc.gov/agent/smallpox/overview/disease-facts.asp. Accessed Dec 2010. 4. WHO. Smallpox. 2010. Available from http://www.who.int/mediacentre/factsheets/smallpox/en. Accessed Dec 2010. 119 119 TUBERCULOSIS (TB) TUBERCULOSIS (TB) Causative Agent Mycobacterium tuberculosis (rarely M. bovis). Causative Agent Mycobacterium tuberculosis (rarely M. bovis). Incubation Period Weeks to years Incubation Period Weeks years Initial toinfection usually goes unnoticed—latent TB infection (LTBI). Approximately 10% of those with LTBI will eventually progress to active disease, Initial unnoticed—latent TB following infection infection. (LTBI). and halfinfection will dousually so in goes the first 2 to 3 years Approximately 10% of those with LTBI will eventually progress to active disease, Immunocompromised patients (e.g. HIV infection, diabetes mellitus) are at higher and for half will do so TB. in the first 2 to 3 years following infection. risk developing active Immunocompromised patients (e.g. HIV infection, diabetes mellitus) are at higher risk for developing Infectious Period active TB. Sputum bacteriologically positive, drug-susceptible pulmonary TB is considered Infectious Period non-infectious after two weeks of effective therapy. (Multi-drug resistant TB may Sputuma bacteriologically positive,therapy drug-susceptible TB is considered require longer period of effective before casespulmonary become non-infectious). non-infectious after two weeks of effective therapy. (Multi-drug resistant TB may require a longer period of effective therapyTB) before cases become non-infectious). Non-pulmonary TB (except for laryngeal is not infectious. . Non-pulmonary TB (except for laryngeal TB) is not infectious. Transmission .Airborne. Rarely through unpasteurized milk (M. bovis). Transmission Airborne. Rarely through unpasteurized milk (M. bovis). Epidemiology The TB incidence in the local Singapore population (i.e. citizens and permanent Epidemiology residents) rose for the first time in ten years to 40 per 100,000 in 2008 and 39 per The 100,000 TB incidence in thePrior localtoSingapore and permanent in 2009. this, the population TB rate of(i.e. thecitizens local population had residents)steadily rose forfrom the first time in ten years to 40 perper 100,000 in 2008 and TB 39 declined 57 per 100,000 in 1998 to 35 100,000 in 2007. per 100,000 in 2009. Prior to this, the TB rate of the local population had continued to be a disease of older males. The TB incidence rate among Malays declined from 57 per in 1998 35 per 100,000 in 2007. TB remainedsteadily the highest among the100,000 three main ethnictogroups. continued to be a disease of older males. The TB incidence rateextrapulmonary among Malays The majority (83.6%) had pulmonary TB. The two commonest remained the highest among the three main ethnic groups. sites were the pleura and the lymphatic system. (83.6%) had pulmonary TB. Theintwo commonest The The majority number of TB cases among foreigners Singapore has extrapulmonary increased since sites were the pleura and the lymphatic system. 2005. In 2009, long-term immigration pass holders comprised 20.8% and short term The number of TB casesofamong foreigners in in Singapore has increased since pass holders 21.9% all notified TB cases the country. 2005. In 2009, long-term immigration pass holders comprised and short In 2009, the proportion of primary drug resistance among new20.8% pulmonary TB term pass holders 21.9% of all notified TB cases in the country. cases in Singapore residents examined was 6.6%. Streptomycin resistance was In the proportion of primary drug resistance among newresistant pulmonary TB the2009, most commonly encountered. The proportion of multi-drug (MDR) cases in Singapore residents examined was 6.6%. Streptomycin resistance was tuberculosis among new pulmonary TB cases in Singapore residents examined the most commonly encountered. multi-drug resistant has remained very low, at 0.3%.The Theproportion MDRTB of rate is, however, 10 or(MDR) more tuberculosis pulmonary TB cases in Singapore residents examined times higher among among new foreigners reported with TB in Singapore, i.e. 3% among has remained very low, at 0.3%. The MDRTB rate is, however, 10 or more times higher among foreigners reported with TB in Singapore, i.e. 3% among 120 120 Indonesians and those from the People’s Republic of China, 4% among Vietnamese and 6% among Burmese. Indonesians and those from the People’s Republic of China, 4% among Vietnamese and 6% among Burmese. Clinical Features Pulmonary TB: Common symptoms are prolonged cough (> 3 weeks), chest Clinical pain Features and haemoptysis. Patients with miliary TB may have minimal respiratory Pulmonary TB:present Common are prolonged cough (> 3 weeks), chest symptoms and withsymptoms systemic complaints. pain and haemoptysis. Patients with miliary TB may have minimal Extrapulmonary TB: Lymphadenitis (especially cervical), pleuralrespiratory effusion, symptoms and present with systemic complaints. osteomyelitis, meningitis or gastrointestinal involvement. TB:associated Lymphadenitis cervical), Extrapulmonary Patients often have fever, (especially night sweats, loss of pleural appetite,effusion, loss of osteomyelitis, meningitis or gastrointestinal involvement. weight and fatigue. oftenforhave fever, night sweats, loss lossoral of Patients Risk factors HIVassociated and examination for physical signsofofappetite, HIV (e.g. weight and fatigue. candidiasis) should be sought. Risk factors for HIV and examination for physical signs of HIV (e.g. oral candidiasis) should be sought. Investigations Chest X-Ray. All persons with chest X-ray findings suggestive of TB should Investigations have sputum specimens submitted for microbiological examination. X-Ray. persons with X-ray findings suggestive TB should Chest Acid fast bacilliAll (AFB) smear andchest TB culture of sputum and otherofpathological have sputum specimens submitted for microbiological examination. specimens such as pleural fluid, CSF, urine and pus. All patients suspected of Acid bacilli (AFB) TB culture sputum and other pathological havingfastpulmonary TB smear shouldand have at leastoftwo, preferably three, sputum specimens such as pleural fluid, CSF, urine and pus. All patients suspected of obtained for microscopic examination and TB culture (with drug having pulmonary TB should have at least two, preferably three, sputum susceptibility testing), with at least one early morning specimen where possible. specimens obtained for microscopic examination TB culture (with Nucleic acid amplification tests (NAATs) do notand obviate the need fordrug TB susceptibility testing), with at least one early morning specimen where possible. culture as these tests do not provide information on the drug susceptibility Nucleic amplification (NAATs) do not obviate the for need for TB pattern ofacid the organism. The tests NAATs are not sufficiently sensitive a negative culture these TB testsindo not provide sputum information on the drug susceptibility result toas exclude smear-negative samples of theshould organism. The NAATs arepatients. not sufficiently sensitive for a negative pattern HIV testing be performed for all result to exclude TB in smear-negative sputum samples Screening for diabetes mellitus is strongly recommended. HIV testing should be performed for all patients. Screening for diabetes mellitus is strongly recommended. Notification Healthcare providers are required to notify suspected and confirmed cases to the Notification Director, TB Control Unit, c/o STEP Registry (Form MD 532 or electronically via Healthcare providers CD-LENS) withinare 72 required hours. to notify suspected and confirmed cases to the Director, TB Control Unit, STEP Registry MD or 532via or CD-LENS, electronically Attending physicians shouldc/oalso submit Form(Form MD 117, to via CD-LENS) 72 hours. update treatmentwithin progress and changes at each visit, preferably monthly until a Attending physicians should also submit Form MD 117, or via CD-LENS, to final outcome is reached. update treatment progress and changes at each visit, preferably monthly until a final outcome is reached. Management Any physician treating a patient for TB is assuming an important public health Management responsibility; he must not only prescribe an appropriate regimen but also be Any physician treating a patient for TB is assuming an important public health responsibility; he must not only prescribe an appropriate regimen but also be 121 121 capable of assessing adherence of the patient to the regimen, and addressing poor adherence when it occurs. of assessing the patient regimen, drugs: and addressing capable Initial drug therapy foradherence new casesofshould consisttoofthe 4 first-line isoniazid poor adherence whenpyrazinamide it occurs. (INH), rifampicin, and ethambutol or streptomycin. Initiating treatment Initial drugusing therapy for new cases should consist of not 4 first-line drugs: isoniazid a quinolone as a first-line drug is a standard practice. In (INH), rifampicin, pyrazinamide TB and cases, ethambutol or streptomycin. Initiating uncomplicated, drug-susceptible 6 months of drug therapy is treatment using a quinolone as a first-line is as notthis a standard practice. In sufficient. Monotherapy should never bedrug given will generate druguncomplicated, drug-susceptible TB cases, 6 months of regimen. drug therapy is resistant TB. A single drug should never be added to a failing sufficient. should never be given as this drug The treating Monotherapy physician should be alert to the TB culture andwill druggenerate susceptibility resistant TB. Amay single should never to a There failingshould regimen. results which takedrug several weeks to be be added available. be an index The treating physician should be alert to the TB culture drug susceptibility of suspicion for the possibility of drug-resistant TB and in patients who were results which may take weeks to be available. There should of be MDRTB an index previously treated, whoseveral fail treatment, who are known contacts of suspicion for the possibility of drug-resistant TB in patients who were cases, or who come from countries with high prevalence of TB drug resistance. previously treated, who of failadverse treatment, who and are prolonged known contacts Non-adherence because reactions therapyofisMDRTB a major cases, or who come from countries with hightreatment prevalence of TBand drug resistance. problem. Non-adherence leads to possible failure acquired drug resistance. Non-adherence because of adverse reactions and prolonged therapy is a major problem. observed Non-adherence to possible treatment for failure and patients, acquired as drug Directly therapyleads (DOT) is recommended all TB it resistance. allows for closer monitoring, thus ensuring adherence to treatment, preventing Directly observedoftherapy (DOT) isDOT recommended foratall it the development drug resistance. is available theTB TBpatients, Control as Unit allows closer monitoring, thus ensuring adherence to treatment, preventing (TBCU)for and polyclinics. of be drug resistance. DOT isleave available the TB Unit the All development patients should issued with medical for atatleast two Control weeks, after (TBCU) andmay polyclinics. which they be considered non-infectious. All patientsappointments should be issued withbemedical leave for at least two intervals weeks, after Follow-up should at no longer than monthly for which they be considered non-infectious. patients on may TB treatment. Patients should be asked about clinical response to treatment, Follow-up adherence appointments should be no longer for to therapy andat any adversethan drugmonthly effects, intervals particularly patients onPatients TB treatment. Patients should be suggestive asked aboutofclinical response to hepatitis. with signs or symptoms hepatitis such as treatment,nausea, adherence to appetite, therapy abdominal and any adverse drugteaeffects, particularly jaundice, loss of discomfort, coloured urine and hepatitis. Patientsshould with be signs or symptoms suggestive of hepatitis easy fatiguability further evaluated with liver function studies.such as jaundice, nausea, loss of appetite, abdominal discomfort, tea coloured and Response to treatment is best monitored bacteriologically with repeaturine sputum easy fatiguability be further with of liver functionphase) studies. examination at theshould very least at twoevaluated months (end intensive and at the Response to treatment bestdomonitored with repeat end of treatment. Those iswho not convertbacteriologically their sputum cultures at two sputum months examination at the veryofleast at twoduration monthsbeyond (end ofsix intensive may require extension treatment months.phase) and at the of treatment. who do not convert their sputumresponse, cultures atand two adverse months end A record of allThose medications given, bacteriological may require extension of treatment duration beyond six months. reactions should be maintained for all patients. Sputum A record of all medications given, bacteriological adverse smear-positive cases, relapsed cases and thoseresponse, with riskand factors for reactions should maintained for alltopatients. drug-resistant TBbeshould be referred the TBCU. Non-compliance Sputum smear-positive cases, relapsed and those with risk factorscases for to TB treatment should cases be detected promptly, and these drug-resistant TB should be referred to the TBCU. should be referred to TBCU. Non-compliance to TB treatment should be detected promptly, and these cases should be referred to TBCU. Prevention and Control In an endemic area, BCG vaccination at birth helps to reduce the incidence of Prevention Control miliary and TB and TB meningitis in childhood. In an endemic area, BCG vaccination at birth helps to reduce the incidence of miliary TB and TB meningitis in childhood. 122 122 Early recognition and early appropriate treatment of TB cases. Suspect TB in any person with unexplained cough for three or more weeks. In Early recognition and early appropriate treatment of TB cases. Suspect hospitals and other institutions, isolation of smear-positive patients TB for in at any person with unexplained cough for three or more weeks. least 2 weeks after initiation of appropriate drug therapy will help reduce transmission. In hospitals and other institutions, isolation of smear-positive patients for at 2 weeks after initiation of appropriate drug bacteriologically therapy will helppositive) reduce least Screening of close contacts of infectious (i.e. sputum transmission. TB cases for latent TB infection (LTBI) and preventive therapy. This is Screening contacts of infectious performed of byclose the TBCU Contact Clinic. (i.e. sputum bacteriologically positive) TB caseso forThe latent TB infection (LTBI)test andis the preventive This is tuberculin skin (Mantoux) standardtherapy. method of LTBI performed byscreening. the TBCU Contact Criteria Clinic. for a positive reaction depend on the patient’s o The tuberculin skin test is the standard method of LTBI health status and TB(Mantoux) risk. for a positive dependshould on thebepatient’s o screening. All screenedCriteria close contacts found reaction to have LTBI offered health status and TB risk. treatment, regardless of age and BCG vaccination status. Before o All screened close contacts found LTBI should be history, offered initiating treatment, active TB musttobehave ruled out by patient treatment, regardless of age andX-ray. BCG vaccination status. Before physical examination, and chest initiating treatment, active TB must ruledfor outLTBI. by patient o Isoniazid (INH) is the treatment of be choice Forhistory, adults, physical examination, and chest the recommended duration ofX-ray. treatment is at least six, and o Isoniazid is the treatment of choice for LTBI. For adults, preferably,(INH) nine months. the recommended duration of treatment is at least six, and preferably, nine months. Air Travel According to WHO guidelines, people with infectious or potentially infectious Air Travel TB should not travel by commercial air transportation on a flight of any According to WHO infectiousinfection or potentially infectious duration, until there isguidelines, no longer people a risk ofwith transmitting to others. TB should should not travel by all commercial air infectious transportation on a flight of any Physicians inform patients with or potentially infectious duration, untilpose therea isrisk no of longer a risktoofothers, transmitting infection to that others. TB that they infection and advise them they must Physicians should with infectious infectious not travel by any inform public all air patients transportation as long or as potentially they are considered TB that they pose a riskinfectious. of infection to others, and advise them that they must infectious or potentially not travel by any public air transportation as long as they are considered infectious or potentially infectious. References 1. Ministry of Health. Communicable Diseases Surveillance in Singapore 2009. 1. 3. 2. 2003; 52RR(11): 1-77. Ministry of Health. Communicable Diseases Surveillance in Singapore 2009. Small PM, Fujiwara PI. Management of tuberculosis in the United States. N MMWR Engl J Med 2001; 345: US Centers for Disease Control and Prevention. Treatment of tuberculosis. Recomm Rep 189-200. 2003; 52RR(11): 1-77. Tuberculosis Coalition for Technical Assistance. International Standards of Tuberculosis Care Small PM, Fujiwara PI. Management of tuberculosis in the United States. N Engl J Med 2001; 345: (ISTC), second edition.. The Hague, Tuberculosis Coalitions for Technical Assistance, 2009. 189-200. Ministry of Health. pulmonaryInternational tuberculosisStandards in Singapore, 2000 to 2006. Tuberculosis CoalitionMultidrug-resistant for Technical Assistance. of Tuberculosis Care Epidemiological News Bulletin 2007;Tuberculosis 33:50-5. Coalitions for Technical Assistance, 2009. (ISTC), second edition.. The Hague, Fern RH, Brian HN, Amiesha SP. Identification and management of latent tuberculosis infection. Ministry of Health. Multidrug-resistant pulmonary tuberculosis in Singapore, 2000 to 2006. American FamilyNews Physician, May 15 2009. Available at: Epidemiological Bulletin 2007; 33:50-5. http://www.aafp.org/afp/2009/0515/p879.html#afp20090515p879-b14. Accessed Dec 2010. Fern RH, Brian HN, Amiesha SP. Identification and management of latent tuberculosis infection. rd World Health Organization. Tuberculosis air travel–Guidelines for prevention and Control, 3 American Family Physician, May 15 2009.and Available at: edition 2008. http://www.aafp.org/afp/2009/0515/p879.html#afp20090515p879-b14. Accessed Dec 2010. 2. US Centers for Disease Control and Prevention. Treatment of tuberculosis. MMWR Recomm Rep References 4. 3. 5. 4. 6. 5. 6. 7. 7. World Health Organization. Tuberculosis and air travel–Guidelines for prevention and Control, 3rd edition 2008. 123 123 TULAREMIA Causative Agent TULAREMIA Francisella tularensis Causative Agent Incubation tularensis Period Francisella 3 - 5 days (range 1 to 14 days) Incubation Period Infectious Period1 to 14 days) 3 - 5 days (range No human-to-human transmission Infectious Period Transmission No human-to-human transmission Humans can become incidentally infected through diverse routes of exposures: bites of infective arthropods (primarily ticks and mosquitoes); handling infectious animal Transmission tissue or can fluids; ingestion of contaminated water, diverse or inadequately meat of Humans become incidentally infected through routes of cooked exposures: bites infected animals; and (primarily inhalationticks of and dustmosquitoes); from contaminated soil. Laboratory of infective arthropods handling infectious animal infections occuringestion throughofaccidental inoculation by inhaling aerosolized tissue or fluids; contaminated water, or or inadequately cooked meat of organisms.animals; and inhalation of dust from contaminated soil. Laboratory infected infections occur through accidental inoculation or by inhaling aerosolized Inoculation or inhalation of as few as 10 organisms is needed to cause disease and is organisms. one of the most infectious pathogenic bacteria known. Inoculation or inhalation of as few as 10 organisms is needed to cause disease and is The of primary concern for intentional by the organism is through inhalation one the most infectious pathogenicinfection bacteria known. after aerosol dissemination of bacteria. The primary concern for intentional infection by the organism is through inhalation Epidemiology after aerosol dissemination of bacteria. The majority of infections in humans and animals are caused by the two species: F. tularensis subspecies tularensis (most virulent) and F. tularensis subspecies Epidemiology holarctica andofrarely subspecies philomiragia and novicida. The majority infections in humans and animals are caused by the two species: F. tularensis subspecies tularensis (most virulent) and F. tularensis subspecies The diseaseand occurs throughout much North America and Eurasia. F. holarctica rarelynaturally subspecies philomiragia andofnovicida. tularensis is found in widely diverse animal hosts and habitats and can be recovered water, soil, and vegetation. A variety of small mammals, from contaminated The disease occurs naturally throughout much of North America and Eurasia. F. andhabitats hares, and are natural reservoirs including mice, water rats, squirrels, animal rabbits, hosts and can be recovered tularensis voles, is found in widely diverse of infection. from contaminated water, soil, and vegetation. A variety of small mammals, including voles, mice, water rats, squirrels, rabbits, and hares, are natural reservoirs Tularemia of infection.is almost entirely a rural disease, though exposure in urban or suburban settings does occur. Certain activities, such as hunting, trapping, butchering, and with transmission risk.though exposure in urban or suburban farming, areisassociated Tularemia almost entirely a rural disease, settings does occur. Certain activities, such as hunting, trapping, butchering, and The agent tularemia is transmission not indigenous arefor associated with risk.in Singapore. Bioterrorism should be farming, suspected should this disease be diagnosed in Singapore in persons without a relevant travel The agent for history. tularemia is not indigenous in Singapore. Bioterrorism should be suspected should this disease be diagnosed in Singapore in persons without a relevant travel history. 124 124 Clinical Features Clinical forms vary in presentation and severity depending on virulence of the Clinical Features infecting organism, dose and site of inoculation. Clinical forms vary in presentation and severity depending on virulence of the infecting organism, dose and site of inoculation. Main forms of disease: Pneumonia: Main forms of disease: Pleuropneumonitis with hilar lymphadenitis (through airborne or Pneumonia: haematogenous routes). Pleuropneumonitis with lymphadenitis (through airborne or Occurs more often in thehilar elderly and has a higher mortality rate. haematogenous routes).of tularemic pneumonia include patchy Radiographic features unilateral Occurs more often in infiltrates, the elderlylobar and has a higher mortality rate. or bilateral or segmental opacities, hilar adenopathy, Radiographicpleural features of tularemic pneumonia include patchy a effusions, cavitary lesions and occasionally unilateral or bilateral infiltrates, lobar or segmental opacities, hilar miliary pattern. adenopathy, pleural effusions, cavitary lesions and occasionally a Ulceroglandular (60-80%): miliary pattern. Patients typically present with fever and a single erythematous Ulceroglandular (60-80%):lesion with a central eschar accompanied by tender papuloulcerative regional Patients typically present with fever and a single erythematous lymphadenopathy. papuloulcerative lesionrecent with ahandling central eschar accompanied by tender Patients usually report of an animal, an animal bite regional lymphadenopathy. (especially cat bites), or exposure to potential vectors, particularly ticks. Patients usually report recent handling of an animal, an animal bite (especially cat bites), or exposure to potential vectors, particularly Oculoglandular (1-2%): ticks. Chemosis /conjunctivitis with regional lymphadenitis (through Oculoglandular (1-2%): inoculation of conjunctiva). Chemosis /conjunctivitis with regional lymphadenitis (through Oropharyngeal (1-4%): inoculationpharyngitis/tonsillitis of conjunctiva). Exudative with cervical adenitis (through Oropharyngeal (1-4%): inoculation of oropharyngeal mucosa). Exudative should pharyngitis/tonsillitis with cervical adenitis (through Diagnosis be considered in patients with pharyngitis inoculation oftooropharyngeal unresponsive penicillin. mucosa). Diagnosis Glandular (3-15%):should be considered in patients with pharyngitis unresponsive Enlargement to of penicillin. a single or multiple lymph nodes without an Glandularidentifiable (3-15%): skin lesion. Enlargement of a single or multiple lymph nodes without an Typhoidal: identifiable tularemia skin lesion.with or without pneumonia is an uncommon Typhoidal Typhoidal: presentation. Typhoidalillness tularemia with or without pneumonia is an uncommon Systemic with non-localizing fever. presentation. ofSystemic withabrupt, non-localizing fever. Onset illness isillness usually with fever (38°- 40°C), headache, chills, coryza and sore throat. Pulse-temperature dissociation has been noted in as Onset illness is usually abrupt, with fever (38°- 40°C), headache, chills, many asof42% of patients. dissociation hastightness been noted in as sore throat. Pulse-temperature frequently coryza A dry orand slightly productive cough and substernal pain or many as 42% patients. occur with or of without objective signs of pneumonia, such as purulent sputum, dyspnoea, A dry or slightly productive cough substernal pain or tightness frequently or haemoptysis. tachypnoea, pleuritic pain,and occur with or without objective signs of pneumonia, such as purulent sputum, dyspnoea, tachypnoea, pleuritic pain, or haemoptysis. 125 125 Nausea, vomiting, and diarrhoea sometimes occur. Sweats, fever and chills, progressive weakness, malaise, anorexia, and weight loss characterize the Nausea, vomiting, illness. and diarrhoea sometimes occur. Sweats, fever and chills, continuing malaise, anorexia, and weight loss characterize the progressive Any form of weakness, tularemia may be complicated by hematogenous spread, resulting illness. continuing in secondary pleuro-pneumonia, sepsis and rarely, meningitis. Any form of tularemia may be complicated by hematogenous spread, resulting in secondary pleuro-pneumonia, sepsis and rarely, meningitis. Investigations The laboratory needs to be notified for special diagnostic and safety procedures. Investigations Direct examination of secretions, exudates and biopsy specimens using Gram The stain, laboratory to be notified fororspecial diagnostic and safety procedures. directneeds fluorescent antibody immunochemical stains. Culture Direct examination of secretions, exudates and biopsy specimens usingsputum Gram of F. tularensis from clinical specimens (pharyngeal washings, stain, direct fluorescent antibody or immunochemical stains. or fasting gastric aspirates). Serology Culture ofwith F. tularensis clinicalofspecimens (pharyngeal washings, sputum a fourfold from titre change serum antibodies against F. tularensis. or fasting gastric aspirates). Serology with a fourfold titre change of serum antibodies against F. tularensis. Management In contained casualty setting: Management Drugs of choice: In contained casualty setting: IM streptomycin 1gm 12 hourly for 10 days; or Drugs choice:gentamicin 5mg/kg once daily for 10 days of IV/IM IM streptomycin 1gm 12 hourly for 10 days; or Alternatives: IV IV/IM gentamicin daily 10 days; days or doxycycline 1005mg/kg mg 12 once hourly for for 14-21 Alternatives: IV ciprofloxacin 400 mg 12 hourly for 10 days IV doxycycline 100 mg 12 hourly for 14-21 days; or casualty IV ciprofloxacin In mass setting: 400 mg 12 hourly for 10 days Drugs of choice: In mass setting: casualty Doxycycline 100 mg orally 12 hourly for 14-21 days; or Drugs choice: of Ciprofloxacin 500 mg orally 12 hourly for 10 days Doxycycline 100 mg orally 12 hourly for 14-21 days; or Ciprofloxacin 500 mg orally 12 hourly for 10 days Chemoprophylaxis Exposed persons can be prophylactically treated with 14 days of oral doxycycline or Chemoprophylaxis ciprofloxacin. If unexplained fever or flu-like illness develops within 14 days of canasbeforprophylactically treated with 14 days of oral doxycycline or Exposed exposure,persons then treat infection. ciprofloxacin. If unexplained fever or flu-like illness develops within 14 days of exposure, then treat as for infection. Notification Notify MOH immediately on suspicion. Call MOH Communicable Diseases Notification Surveillance team at: 98171463 Notify MOH immediately on suspicion. Call MOH Communicable Diseases Surveillance team at: 98171463 Vaccine Currently no vaccine is available locally. In the United States, a live attenuated Vaccine vaccine has been used by laboratory staff working routinely with the bacterium. Currently no vaccine is available locally. In the United States, a live attenuated vaccine has been used by laboratory staff working routinely with the bacterium. 126 126 Isolation Precautions Standard precautions are recommended. Respiratory isolation is not necessary given Isolation lack ofPrecautions human-to-human transmission. Bodies of patients who die of tularemia the are standard recommended. Respiratory isolation is notlikely necessary given Standard should beprecautions handled using precautions. Autopsy procedures to produce lack of human-to-human transmission. Bodies of patients who die of tularemia the aerosols or droplets should be avoided. should be handled using standard precautions. Autopsy procedures likely to produce aerosols or droplets should be avoided. References 1. Dennis DT, Ingleshy TV, Henderson DA et al. Tularemia as a biological weapon: medical and 2. 1. 3. Ellis J, Oyston PC, Green M, et al. Tularemia. Microbiol 2002;15:631-46 Dennis DT, Ingleshy TV, Henderson DA et al. Clin Tularemia as a Rev. biological weapon: medical and CDC (Atlanta) informational website: http://www.bt.cdc.gov/agent/tularemia. Accessed Dec 2010. public health management. JAMA. 2001; 285:2763-73 Ellis J, Oyston PC, Green M, et al. Tularemia. Clin Microbiol Rev. 2002;15:631-46 CDC (Atlanta) informational website: http://www.bt.cdc.gov/agent/tularemia. Accessed Dec 2010. public health management. JAMA. 2001; 285:2763-73 References 2. 3. 127 127 TYPHOID AND PARATYPHOID FEVER Causative Agents TYPHOID AND PARATYPHOID FEVER Salmonella typhi (Typhoid fever) Salmonella paratyphi A, B and C (Paratyphoid fever). Causative Agents Salmonella typhi (Typhoid fever) Salmonella paratyphi Incubation Period A, B and C (Paratyphoid fever). 1 - 3 weeks Incubation Period 1 - 3 weeksPeriod Infectious During acute infection and until stool and urine clearance. Infectious Period During acute infection and until stool and urine clearance. Transmission Faeco-oral route through contaminated food or water. Transmission through sexual Transmission contact, especially among men who have sex with men have been documented. Faeco-oral through contaminated foodthe or water. through sexual There is noroute animal reservoir so ultimately diseaseTransmission always involves human-tocontact,spread. especially among men who have sex with men have been documented. human There is no animal reservoir so ultimately the disease always involves human-tohuman spread. Epidemiology During the period 2005-2009, there were 349 reported cases of typhoid (94% Epidemiology imported) and 139 reported cases of paratyphoid (88.5% imported). The disease is During the period 2005-2009, were 349 reported cases of typhoid (94% endemic in Southeast Asia and thethere Indian subcontinent. imported) and 139 reported cases of paratyphoid (88.5% imported). The disease is endemic Features in Southeast Asia and the Indian subcontinent. Clinical Typhoid fever Clinical Features 1st week of illness: Rising, “stepwise” fever, bacteraemia and diarrhoea Typhoid (78%fever of children) or constipation (more frequent in adults). st week “stepwise” fever, weekof ofillness: illness: Rising, Abdominal pain and rashbacteraemia (rose spots) and diarrhoea 21nd rd of children) constipation (more frequent in adults). week of illness:orHepatosplenomegaly, intestinal bleeding and 3(78% perforation 2nd week of illness: Abdominal pain and rash (rose spots) 3rd week of illness: Hepatosplenomegaly, intestinal bleeding and perforation(rare if diagnosed and treated early) Complications Intestinal haemorrhage or perforation (rare if diagnosed and treated early) Complications Toxic myocarditis Intestinal haemorrhage perforation Confusion, convulsions,orencephalitis Toxic myocarditis Haemolytic anaemia (especially in G6PD deficiency) Confusion, convulsions, encephalitis Renal failure Haemolyticinanaemia (especially in G6PD deficiency) Abscesses liver, spleen, bone etc. Renal failure Abscesses in liver, spleen, bone etc. Paratyphoid fever Maybe clinically mild or asymptomatic Paratyphoid fever Maybe clinically mild or asymptomatic 128 128 Nausea, vomiting, fever, diarrhoea, and cramping—usually occur within 8 to 72 hours of ingesting contaminated food or water Nausea, fever, diarrhoea, and cramping—usually occur within 8 Less thanvomiting, 5% of non-typhoidal salmonella gastroenteritis develop to 72 hours of ingesting contaminated food or manifestations water bacteraemia and may result in extra-intestinal including endocarditis, Less than 5%mycotic of non-typhoidal gastroenteritis develop aneurysmsalmonella and osteomyelitis. bacteraemia and may result in extra-intestinal manifestations including endocarditis, mycotic aneurysm and osteomyelitis. Investigations Blood test frequently show anaemia, elevated hepatic transaminases and either Investigations leucopoenia or leucocytosis. testoffrequently elevated hepatic transaminases and either Blood Isolation organism show is the anaemia, gold standard for diagnosis. leucopoenia or leucocytosis. Blood culture usually positive for 1st two weeks only. Stool Isolation organism the goldfrom standard 4thdiagnosis. weeks. andof urine cultureispositive 2 nd tofor culture positive for 1st two weeks only. Blood The yield fromusually bone marrow culture is high and is usually positive even after Stool and urine positive from 2 nd to 4th weeks. antibiotics have culture been initiated. The The Widal yield from marrowin culture is high is usually positive evenforafter test isbone unreliable itself, but may and provide additional support the antibiotics have been initiated. diagnosis when the clinical picture is suggestive. The Widal test is unreliable in itself, but may provide additional support for the diagnosis when the clinical picture is suggestive. Notification A legally notifiable disease in Singapore. Notify Ministry of Health (Form MD 131 Notification or electronically via CD-LENS) not later than 24 hours from the time of diagnosis. A legally notifiable disease in Singapore. Notify Ministry of Health (Form MD 131 or electronically via CD-LENS) not later than 24 hours from the time of diagnosis. Management Typhoid Management Patients should be hospitalised during antibiotic treatment. Typhoid Rehydration and other supportive care. Current Patients drugs shouldofbechoice: hospitalised during antibiotic treatment. Rehydration and other supportive PO Ciprofloxacin 500 mg bd care. x 7-10 days (if sensitive to ciprofloxacin and Current drugs of choice: nalidixic acid) PO Ciprofloxacin 500once mg daily bd x 7-10 daysdays (if sensitive to ciprofloxacin and IV Ceftriaxone 2-3g x 10-14 nalidixic acid) Alternative: PO Azithromycin 1g once then 500mg once daily x 5-7 days IV Ceftriaxone 2-3g once daily x 10-14 days N.B. 70-90 % of isolates in some parts of Nepal, India and Vietnam are Alternative: Azithromycin nalidixic acidPO resistant strains. 1g once then 500mg once daily x 5-7 days N.B. 70-90 % of isolates some parts of Nepal, are Dexamethasone 3mg/kg thenin1mg/kg 6 hourly x 8 India dosesand forVietnam severe typhoid nalidixic acid resistant strains. fever (as suggested by delirium, shock and altered mental status) decreases Dexamethasone 3mg/kg then 1mg/kg 6 hourly x 8 doses for severe typhoid mortality. fever (as suggested bynewer delirium, shock (10-25% and altered status) decreases Relapse rate 1-6% with antibiotics withmental chloramphenicol) mortality. One to four percent of adults become chronic carriers despite antibiotics. Follow-up Relapse ratestool 1-6% with newer antibioticsstool (10-25% with after chloramphenicol) evaluation to document clearance treatment: One Three to fourconsecutive percent of adults antibiotics. stool become sampleschronic taken atcarriers weeklydespite intervals no sooner than Follow-up stoolafter evaluation to document stool treatment. clearance after treatment: two weeks completion of antibiotic Three consecutive stool samples taken at weekly intervals no sooner than two weeks after completion of antibiotic treatment. 129 129 Chronic carriers (positive stool samples after 6 months): give prolonged course of ciprofloxacin (750 bd orally for 1 month) and perform abdominal ultrasound; Chronic carriers (positive stool after if6 gallstones months): give prolonged cholecystectomy maysamples be necessary are present and course of ciprofloxacin (750 bd orally for 1 month) and perform abdominal prolonged antibiotic treatment fails. ultrasound; cholecystectomy may be necessary if gallstones are present and prolonged antibiotic treatment fails. Prevention and Control Public health measures: education on good personal and food hygiene. Prevention and Control Vaccination for travellers: (see section on travel vaccination in Appendix 3). Public health measures: education on good personal and food hygiene. for Follow up stool examinations recommended for all cases and mandatory Vaccination for travellers: (see section on travel vaccination in Appendix 3). food handlers. Follow up stoolrequire examinations recommended for (three all cases and mandatory for Food handlers further stool examination consecutive daily stool food handlers. samples) at three and six months post treatment. Carriers Food handlers require further stooland examination (threenot consecutive daily stool (convalescent, temporary chronic) must work as food handlers. samples) at three and six months post treatment. Carriers (convalescent, temporary and chronic) must not work as food handlers. References 1. Teoh YL, Goh KT, Neo KS et al. A nationwide outbreak of coconut-associated paratyphoid A fever 2. 1. 3. Parry CM,Goh HienKT, TT,Neo Dougan et A al.nationwide Typhoid fever. N Engl Med 2002; 347: 1770-82. Teoh YL, KS etGal. outbreak of Jcoconut-associated paratyphoid A fever Slinger R, Desjardins McCarthy AE1997; et al.26:544-8. Suboptimal clinical response to ciprofloxacin in in Singapore. Ann AcadM,Med Singapore patients with enteric fever due spp. N with reduced susceptibility: a Parry CM, Hien TT, Dougan G ettoal.Salmonella Typhoid fever. Engl J Med fluoroquinolone 2002; 347: 1770-82. case series. BMC InfectM, DisMcCarthy 2004; 20:4-36. Slinger R, Desjardins AE et al. Suboptimal clinical response to ciprofloxacin in Effa EE,with Bukirwa Azithromycin for treating typhoid and paratyphoid fevera patients entericH.fever due to Salmonella spp. uncomplicated with reduced fluoroquinolone susceptibility: (enteric fever). Cochrane Database Syst Rev. 2008;(4):CD006083. case series. BMC Infect Dis 2004; 20:4-36. Connor SchwartzH. E. Typhoid and paratyphoid fever in travellers. Lancet 2005; 5:623-8 Effa EE,B,Bukirwa Azithromycin for treating uncomplicated typhoidInfect and Dis paratyphoid fever Bhan M,fever). Bahl R,Cochrane Bhatnager S. Typhoid fever. Lancet 2005; 366: 749-62. (enteric Database Systand Rev.paratyphoid 2008;(4):CD006083. Ty AU, B, Ang GY, Ang et al.and Changing epidemiology of entericLancet fevers Infect in Singapore. Ann Acad Connor Schwartz E. LW Typhoid paratyphoid fever in travellers. Dis 2005; 5:623-8 Med Bhan2010;39:889-96. M, Bahl R, Bhatnager S. Typhoid and paratyphoid fever. Lancet 2005; 366: 749-62. in Singapore. Ann Acad Med Singapore 1997; 26:544-8. References 2. 3. 4. 5. 4. 6. 7. 5. 6. 7. Ty AU, Ang GY, Ang LW et al. Changing epidemiology of enteric fevers in Singapore. Ann Acad Med 2010;39:889-96. 130 130