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THE LASSA FEVER STORY Abdulrazaq G. Habib Infectious & Tropical Diseases Unit College of Health Sciences Bayero University & Aminu Kano Teaching Hospital Kano, Nigeria (Member WHO-Nigerian Immunization Technical Advisory Group) Bayero University Kano Nigeria President www.nigerianidsociety.com Fauci A (2001). Global emerging and reemerging infectious diseases Lassa 5/24/2017 3 Lassa fever • • • • • • • 12 Jan 1969- 1st recognised case an American missionary nurse in Lassa, NE- Nigeria 25 Jan 1969- Air lifted to Evangel. Hospital Jos, N. Nigeria 26 Jan 1969- Pt was cared by two american nurses but died that day One of the two caring nurses fell sick after an 8d IP and died after an illness lasting 11d 20 Feb 1969- Head Nurse of the hospital where autopsy for 1st case was done fell sick Pt evacuated to USA by air on a commercial Boeing 707, separated with curtain only Pt recovered after severe protracted illness at ICU of Columbia University NY Lassa fever • A virus was isolated and later named Lassa at Yale Arbovirus Research (YAR) Unit • 9 Jun 1969- One of YAR virologists fell ill and survived only as a result of an immune plasma transfusion donated by the surviving third case • 30 Nov 1969- A Laboratory technician at YAR fell ill and died • Jan-Feb 1970- a devastating hospital outbreak at Vom and Jos: Outbreak affected 28 patients with 12 deaths, including the American doctor who first identified the disease and did autopsies General Facts • Viral hemorrhagic fever caused by the Arenavirus Lassa • Transmitted from rodents to humans • Discovered in Nigeria, 1969 • Endemic in portions of West Africa • Seasonal clustering: Late rainy and early dry season • Affects all age groups and both sexes Arenaviridae • Name derived from “arenosus” (Latin “sandy”) describing appearance of virions on examination by electron microscopy • Enveloped virus, round or pleomorphic, 50-300 nm in diameter • Single-stranded genome divided into 2 RNA segments: small (~3.4 kb) and large (~7.1 kb) • 2 genes on each segment, arranged in unique “ambisense” orientation, encoding 5 proteins • Inactivated by: – – – – o heating to 56 F pH<5.5 or >8.5 UV/gamma irradiation detergents Arenaviridae • Arenaviruses associated with human disease Virus Lassa Junin Machupo Guanarito Sabia LCMV Origin of Name Town, Nigeria Town, Argentina River, Bolivia Area, Venezuela Town, Brazil Clinical disease Year 1969 1957 1962 1989 1990 1933 Distribution West Africa South America South America South America South America Worldwide Lassa Virus Image source: C.S. Goldsmith and M. Bowen (CDC). Epidemiology • Endemic in areas of West Africa, including Nigeria, Liberia, Sierra Leone, and Guinea • Estimated 300,000-500,000 infections/year, with 5000 deaths • Rodent-to-human transmission (the “multimammate rat”, Mastomys species-complex) • Secondary human-to-human transmission with the potential for nosocomial outbreaks with high case-fatality • CDC undertook serological studies in Sierra Leone • 2.2 cases/1000 inhabitants • Some areas had seroprevalence of 52% • Most infections benign • 200,000-300,000 cases p.a. • 5,000-10,000 deaths p.a. 5/24/2017 11 LASSA FEVER IN WEST AFRICA Fichet-Calvet & Rogers 2009 5/24/2017 13 States that reported Lassa fever 2007/2008 Lassa fever 2007/08 Current Nigerian epidemic: Kano • • • • • • • • • Started Nov 2015 Two patients admitted 3rd / 4th December Diagnosis came out Lassa Fever 112 people had contacted them, 75% HCW 4 had symptoms, positive sera and on Ribavirin Unguwa Uku, Tiga and Bunkure 38 being monitored now Rijiyar Lemo? (A case in 2012?) 5/24/2017 15 5/24/2017 16 5/24/2017 17 • 2015 Wk 42: 337 cases, 13 lab confirmed, 7 dead, CFR2.08% • 2014: 974 cases 95 lab confirmed, 33 dead, CFR 3.39% • Taraba, Rivers 5/24/2017 18 Epidemiology in Nigeria • Many cases of Lassa fever are un accounted • Poor lab support • Inadequate surveillance systems 5/24/2017 19 Tarauni Kura Bebeji Bunkure Fagge Dala Gwale Kumbotso KMC Gwarzo Shanono T/Wada Rano Total Description New Cases New Confirmed New Probable New Suspected Cumulative Cases Total Confirmed Total Probable Total Suspected Total Total No. currently in isolation Deaths Newly Reported on 18th Jan 2016 Total Deaths in Confirmed cases Total Deaths in Probable cases Total Deaths in suspected cases Total Deaths Contacts New Contacts listed on 18th Jan 2016 Cumulative contacts listed Contacts currently under follow up Contacts seen on 18th Jan 2016 Contacts who completed 21 days FU Contacts lost to follow Up Contact Dropped after negative result Laboratory Specimen collected on 18th Jan 2016 Specimen Pending testing Total Specimen tested Garun Mallam KANO DATA AS AT 18th JANUARY 2016 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 2 0 5 7 0 0 0 1 1 0 0 0 1 1 1 0 0 1 1 0 0 0 1 1 0 0 0 0 0 0 0 0 1 1 0 0 0 0 0 0 0 0 1 1 0 0 0 0 0 0 0 0 0 0 0 0 0 1 1 0 0 0 1 1 0 0 0 1 1 0 2 0 14 16 1 0 2 0 1 3 0 0 0 1 1 0 0 0 0 0 0 0 0 1 1 0 0 0 1 1 0 0 0 0 0 0 0 0 1 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 1 0 0 0 0 0 0 0 2 0 7 9 0 45 0 0 45 0 0 0 115 11 4 78 7 26 0 29 0 0 24 0 5 0 34 11 0 23 11 0 0 7 0 0 7 0 0 0 4 4 0 0 4 0 0 14 14 7 0 7 0 0 12 12 11 0 1 0 0 7 7 3 0 4 0 0 2 1 1 1 0 0 0 4 0 0 4 0 0 0 6 0 0 6 0 0 0 0 0 0 0 0 0 0 27 27 0 0 27 0 0 306 87 26 188 61 31 0 0 6 0 0 1 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 0 1 8 Known Distribution of Mastomys MASTOMYS DISTRIBUTION LASSA 1969 Reservoir 5/24/2017 22 Rodent Reservoir • Mastomys species complex • Taxonomy still unclear – M. huberti: more common in peridomestic habitat – M. erytholeucus: more common in brush habitat – Others 5/24/2017 24 Transmission • Rodent-to-human: – Inhalation of aerosolized virus – Ingestion of food or materials contaminated by infected rodent excreta – Catching and preparing Mastomys as a food source Transmission • Human-to-human: – Direct contact with blood, tissues, secretions or excretions of infected humans – Needle stick or cut – Inhalation of aerosolized virus Pathogenesis • Endothelial cell damage/capillary leak • Platelet dysfunction • Suppressed cardiac function • Cytokines and other soluble mediators of shock and inflammation Clinical Aspects • Incubation period of 5-21 days • Gradual onset of fever, headache, malaise and other non-specific signs and symptoms • Pharyngitis, myalgias, retro-sternal pain, cough and gastrointestinal symptoms typically seen • A minority present with classic symptoms of bleeding, neck/facial swelling and shock • Case fatality of hospitalized cases: 15-20% • Particularly severe in pregnant women and their offspring • Deafness a common sequela Clinical Signs and Symptoms Fever Headache Arthralgias/Myalgias Retro-sternal Pain Weakness Dizziness Sore throat/Pharyngitis Cough Vomiting Abdominal Pain/Tenderness Diarrhea Conjunctivitis/Sub-conjunctival Hemorrhage Chills Deafness Lymphadenopgathy Bleeding Confusion Swollen Neck or Face 0 10 20 30 40 50 Percent 60 70 80 90 100 Lassa Fever in Pregnancy • Increased maternal mortality in third trimester (>30%) • Increased fetal and neonatal mortality (>85%) • Increased level of viremia in pregnant women • Placental infection • Evacuation of uterus improves mother’s chance of survival Sensorineural Hearing Deficit in Lassa Fever • Typically appears during early convalescence • Not related to severity of acute illness • Occurs in one-third of cases • May be bilateral or unilateral • May persist for life in up to one-third of those affected Lassa Fever in Children and Infants • Significant cause of pediatric hospitalizations in some areas of West Africa • Signs and symptoms most often similar to adults • “Swollen Baby Syndrome” - Edema/Anasarca - Abdominal distension - Bleeding - Poor prognosis Differential Diagnosis of Lassa Fever • Malaria • Bacterial sepsis • Typhoid fever • Bacterial meningitis • Streptococcal pharyngitis • Arboviral infection • Leptospirosis • Enterovirus infection • Anicteric hepatitis • Bacterial or viral conjuctivitis Diagnostics • Clinical diagnosis often difficult • ELISA (Enzyme-linked immunosorbent assays) for antigen, IgM, and IgG • As research tools: – Virus isolation – Immunohistochemistry (for post-mortem diagnosis) – RT-PCR (Reverse transcription-polymerase chain reaction) Treatment • General support Fluids and electrolytes Antipyretics Oxygen Intensive care (Antibiotics) • Ribavirin • Infection control Barrier nursing • Report! 5/24/2017 35 Treatment • Supportive measures • Ribavirin – Most effective when started within the first 6 days of illness – Major toxicity: mild hemolysis and suppression of erythropoesis. Both reversible – Presently contraindicated in pregnancy, although may be warranted if mother’s life at risk – Does not appear to reduce incidence or severity of deafness Ribavirin dose • • • • Loading dose 2g 1g 6 hourly x 4d 500mg 6 hourly days 5-10 30mg/kg, 15mg/kg, 7mg/kg 5/24/2017 37 Side effects • Fatigue, headache, alopecia, fever, anxiety, N. V, D, impaired concentration • Haemolytic anaemia • Neutropenia • Thrombocytopenia • Embryocide • Suicide ideation • Pregnancy benefits Vs risks 5/24/2017 • Hypersensitivity 38 Associated with Poor Prognosis in Lassa Fever • High viremia • Serum AST level >150 IU/L • Bleeding • Encephalitis • Edema • Third trimester of pregnancy Nosocomial Lassa fever in Nigeria Fisher-Hoch SP, Tomori O, Nasidi A et al. BMJ 1995; 311: 857-9 • • • • • • • • • Two hospital outbreaks in Imo state 34 patients 6 nurses; 2 surgeons; 1 physician Diagnosis: All clinically consistent; 11 serological; 5 virus isolation Attack rate = 55% 22 deaths (65%) Likely cause: Parenteral drug rounds and sharing of needles Inference: Elucidates the high price of poor medical practice Key points: High priority must be given to education of medical staff, equiping hospitals, promoting infection control practices and use of guidelines for safe operation of clinics and hospitals in developing countries. Prevention • • • • • • • • Early patient identification Barrier nursing Universal precautions PPE Waste disposal Rodent control Rodent hunting/ eating No vaccine 5/24/2017 41 5/24/2017 42 Prevention and Control • Village-based programs for rodent control and avoidance • Hospital training programs to avoid nosocomial spread: barrier nursing manual • Diagnostic technology transfer • Specific antiviral chemotherapy (ribavirin) Rodent Control • Proper storage of food in rodent-proof containers • Cleaning around homes • Trapping and killing rodents with proper and safe disposal of carcasses • Avoid rodents as a food source Negative Pressure Isolation Room Natural Ventilation Cohorting Room 1 meter Use PPE on patient contact Put on and Remove PPE PAPRs are available Ongoing Lassa Fever Research in Guinea, West Africa • Natural history of disease – Where it came from – How clinical course progresses – Whom it affects • Diagnosis: Clinical/Laboratory • Immunopathogenesis • Treatment • Rodent population dynamics • Prevention and control Collaboration between CDC/SPB and the Guinean Institute for Research and Applied Biology Infections as Strategic and Security issue: Daniel Defoe’s Journal – A Visitation of The Plague ‘It was indeed, that man withered like grass and that his brief earthly existence became a fleeting shadow. Contagion was rife in all our streets and so baleful were its effects, that the church yards were not sufficiently capacious to receive the dead. It seemed for a while as though the brand of an avenging angel had been unloosed in judgement ….’ ‘..panic spread over the city of London. Trapped by poverty, a gullible populace became prey to an army of astrologers, charlatans and quack doctors who offered false promises of hope in the face of impending horror’ Distribution of Reported Epidemics in Nigeria from 2003 – 2007 and Jan 2008 KEY Cholera/Gastro Enteritis 2003 2004 2005 2006 2007 CSM NE Measles Yellow Fever 2007/2008 2004 2005 Lassa Fever 2003 2003 2003 2006 2004 2004 2005 2005 2006 2006 2007/2008 2007/2008 NE: No Epidemics reported 2007 AI Human 2007 “Humanity has but three great enemies: fever, famine and war; of these by far the greatest, by far the most terrible, is fever” William Osler Thank you