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Recent trends in emerging and re-emerging microbial infections: an update
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on Scrub Typhus
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Abstract
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In the era of emerging and re-emerging infectious diseases which has seen many endemics,
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epidemics and pandemics throughout the world attributed to viral, parasitic and bacterial
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microbes, preparedness assumes significance. Changing microbial behaviour due to genetic
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variations as seen in Influenza virus is responsible for emergence of newer strains which are
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antigenically different from the existing ones is responsible for infections that cause severe
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morbidity and mortality. Other microbial species including the Dengue virus, Chikungunya
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virus, Crimean Congo haemorrhagic fever virus transmitted to human through vectors,
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Listeria monocytogenes, Leptospira spp, Legionella pneumophila cause frequent endemics
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and epidemics worldwide. Emergence of multi-drug resistant species of Mycobacterium
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tuberculosis has already thrown a challenge for the control and eradication programmes
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against tuberculosis. Other bacterial species resistant to many antimicrobials currently being
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used owing to the genetic variations cause infections in human that are very difficult to treat.
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Scrub typhus is a unique disease caused by Orientia tsutsugamushi, an intracellular bacterium
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transmitted by the bite of chiggers (larval forms of mites) and is usually present endemically
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whose clinical features are very similar to other prevalent infectious diseases in the same
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geographical areas. The need of the hour is to have a good knowledge of microbial infections
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in respective geographic regions and predicting emerging and re-emerging infectious diseases
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which could contribute to better patient management.
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Key Words: Emerging infections, re-emerging infections, Scrub Typhus, Orientia
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tsutsugamushi
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Introduction
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Emerging infectious diseases (EIDs) are diseases of infectious origin whose incidence in
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humans has increased within the recent past or threatens to increase in the near future.
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Emerging infections are those which are either new or previously undefined diseases as well
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as old diseases with new features. Infectious diseases which are newly introduced to a
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particular geographic location or a new population (e.g. it may present in young adults where
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previously it was only seen in the elderly), those showing newer clinical features and
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resistance patterns to available antimicrobial agents should be considered as emerging and re1
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emerging diseases. Other characteristics of an emergent infectious disease include rapid
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increase in the incidence and spread of the disease, reappearance of a disease which was once
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endemic but had since been eradicated or controlled new recognition of an infectious agent in
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the population or realization that an established clinical condition has an infectious origin.
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Over 30 new infectious agents have been detected worldwide in the last three decades and 60
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per cent of these are of zoonotic origin with more than two-thirds of these have initially
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originated in the wildlife [1, 2].
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Emerging infectious diseases account for 26 per cent of annual deaths worldwide. Nearly 30
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per cent of 1.49 billion disability-adjusted life years (DALYs) are lost every year to diseases
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of infectious origin [3]. The burden of morbidity and mortality associated with infectious
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diseases falls most heavily on people in developing countries, and particularly on infants and
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children (about three million children die each year from malaria and diarrhoeal diseases
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alone) [4].
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Patho-physiology of Scrub typhus
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Among the many emerging bacterial infections, the causative of scrub typhus/bush typhus,
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Orientia tsutsugamushi is responsible for re-emerging zoonotic disease. Previously called as
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Rickettsia tsutsugamushi, O tsutsugamushi is a gram-negative bacillus. It is an intracellular
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parasite belonging to the family Rickettsiaceae and was first isolated and identified in 1930 in
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Japan. Scrub typhus is transmitted by some species of trombiculid mites /Chiggers
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(Leptotrombidium deliense) and produces a characteristic skin lesion identified as black
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eschar. Adult mite does not feed on man and only feeds on the serum of warm blooded
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animals. The Larval form/ Chiggers which are very small and seen only with the help of a
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magnifying glass actually bite.
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Humans are accidental hosts and symptoms appear after an incubation period is six to twenty-
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one days after the bite of chiggers which is usually painless and not noticed by the patients.
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Clinical presentation of patients suspected to be suffering from scrub typhus may include
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fever with chills, headache, muscle pain, cough, and gastrointestinal symptom. Other clinical
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signs that may appear in patients are centrifugal macular rash on the trunk, ocular pain,
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conjunctival inflammation, delirium, eschar, splenomegaly and lymphadenopathies [5].
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Complications of scrub typhus include haemorrhage, disseminated intravascular coagulation
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(DIC), multiple organ dysfunction syndrome (MODS), shock, central nervous system (CNS)
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involvement, renal impairment and acute respiratory distress syndrome (ARDS).
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Leucopoenia and abnormal liver function tests (>90%) are commonly seen in the early phase
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of the illness. Pneumonitis, encephalitis, and myocarditis may occur in the late phase of
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illness [5].
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Clinical symptoms of scrub typhus overlap with other endemic infectious diseases like
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dengue fever, malaria, chikungunya, leptospirosis, Paratyphoid, other viral fevers and pyrexia
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of unknown origin (P.U.O). Infections are usually confined to the areas where the insect
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vector is prevalent and a strong clinical suspicion should be made among the people who give
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a recent travel history to such regions. A recent report of patient suffering from acute
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respiratory distress syndrome after being infected with Orientia tsutsugamushi reveals the
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necessity to investigate further on the modes of transmission to human (inhalation/aerosols)
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and the life-threatening nature of the disease in case of delay in suspicion and diagnosis [6].
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Epidemiology of Scrub Typhus
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Endemic regions for scrub typhus include Asia, Australia, Korea, Japan, Thailand, Myanmar
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China, India and Pakistan [7, 8 and 9]. Epidemic scrub typhus involving American soldiers
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working in Vietnam during World War II has also been reported. In India scrub typhus has
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been reported to be prevalent in Southern India (Rajasthan, AP, Pondicherry, Tamil Nadu,
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Goa) and Northern India (Himalayan region of India) and north-western India [10, 11].
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Laboratory Diagnosis of Scrub Typhus
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Laboratory diagnosis of scrub typhus can be performed using both conventional and
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molecular methods. Traditional methods for diagnosis include Weil-Felix test, indirect
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immunofluorescence, indirect immunoperoxidase (IIP), immunochromatography, enzyme
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linked immunosorbant assay (ELISA) and culture. Interpretation of results of ELISA for the
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detection of antibodies should be cautiously as even healthy individuals (18%) also react
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positively [12]. A four-fold rise in titre should be considered as diagnostic in patients
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showing clinical symptoms. Real-time quantitative polymerase chain reaction method (rt-
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PCR) has been evaluated for the diagnosis of rickettsial infections [13]. Orientia
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stutsugamushi does not grow in routine culture media used in clinical laboratories. Cell
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culture technique is applied using monolayer of L929 cell lines for growing them in
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laboratory [14].
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Discussion
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Considering the fact that there is no vaccine available for protection against scrub typhus
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disease, prevention of infection remains only the best alternative [15, 16]. People residing in
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the endemic regions of the vector should be educated about protecting themselves form insect
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bites by wearing protective clothes, using insect repellents, reducing visits to the forest areas
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infested with trombiculid mites and chiggers. Previous studies have also evaluated the anti-
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chigger effects of some oil extracts from plants [17].Screening international and national
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travellers returning from potentially endemic places would contribute to early diagnosis of
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scrub typhus thereby reducing the morbidity and mortality [18]. Resistance reports recently
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of Orientia tsutsugamushi against quinolone group drugs should be considered as a cause of
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serious concern [19].
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Management of scrub typhus includes initiation of antibiotics following strong clinical
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suspicion supported with positive laboratory reports. Doxycycline is considered as the drug
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of choice which can be given as single dose weekly for six weeks. I case of prophylactic
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treatment while visiting the endemic areas the first dose should be taken before one week.
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Other antimicrobial agents belonging to macrolide group (azithromycin, clarithromycin,
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roxithromycin and telithromycin), rifampicin and chloramphenicol are also are effective
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against Orientia tsutsugamushi [20].
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Conclusion
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In conclusion it is very important both for the clinician and laboratory medicine personnel to
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have a better understanding of the infections prevalent in a particular geographical region and
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the characteristics of emerging and re-emerging infections. Timely clinical suspicion
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supported by use of appropriate diagnostic techniques would be instrumental in better
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management of patients.
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