Recent Trends in Emerging and Re-emerging Microbial Infections: An Update on Scrub Typhus  

Venkataramana Kandi
Department of Microbiology, Prathima Institute of Medical sciences, Karimnagar, Telangana, India
Author    Correspondence author
International Journal of Molecular Medical Science, 2015, Vol. 5, No. 3   doi: 10.5376/ijmms.2015.05.0003
Received: 21 May, 2015    Accepted: 03 Jun., 2015    Published: 18 Jun., 2015
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This is an open access article published under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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Venkataramana Kandi, 2015, Recent Trends in Emerging and Re-emerging Microbial Infections: An Update on Scrub Typhus, International Journal of Molecular Medical Science, Vol.5, No.3, 1-6 (doi: 10.5376/ijmms.2015.05.0003)

Abstract

In the era of emerging and re-emerging infectious diseases which has seen many endemics, epidemics and pandemics throughout the world attributed to viral, parasitic and bacterial microbes, preparedness assumes significance. Changing microbial behaviour due to genetic variations as seen in Influenza virus is responsible for emergence of newer strains which are antigenically different from the existing ones is responsible for infections that cause severe morbidity and mortality. Other microbial species including the Dengue virus, Chikungunya virus, Crimean Congo haemorrhagic fever virus transmitted to human through vectors, Listeria monocytogenes, Leptospira spp, Legionella pneumophila cause frequent endemics and epidemics worldwide. Emergence of multi-drug resistant species of Mycobacterium tuberculosis has already thrown a challenge for the control and eradication programmes against tuberculosis. Other bacterial species resistant to many antimicrobials currently being used owing to the genetic variations cause infections in human that are very difficult to treat. Scrub typhus is a unique disease caused by Orientia tsutsugamushi, an intracellular bacterium transmitted by the bite of chiggers (larval forms of mites) and is usually present endemically whose clinical features are very similar to other prevalent infectious diseases in the same geographical areas. The need of the hour is to have a good knowledge of microbial infections in respective geographic regions and predicting emerging and re-emerging infectious diseases which could contribute to better patient management.

Keywords
Emerging infections; Re-emerging infections; Scrub Typhus; Orientia tsutsugamushi

Introduction
Emerging infectious diseases (EIDs) are diseases of infectious origin whose incidence in humans has increased within the recent past or threatens to increase in the near future. Emerging infections are those which are either new or previously undefined diseases as well as old diseases with new features. Infectious diseases which are newly introduced to a particular geographic location or a new population (e.g. it may present in young adults where previously it was only seen in the elderly), those showing newer clinical features and resistance patterns to available antimicrobial agents should be considered as emerging and re-emerging diseases. Other characteristics of an emergent infectious disease include rapid increase in the incidence and spread of the disease, reappearance of a disease which was once endemic but had since been eradicated or controlled new recognition of an infectious agent in the population or realization that an established clinical condition has an infectious origin. Over 30 new infectious agents have been detected worldwide in the last three decades and 60 per cent of these are of zoonotic origin with more than two-thirds of these have initially originated in the wildlife (WHO, 2005; Dikid et al., 2013).
Emerging infectious diseases account for 26 per cent of annual deaths worldwide. Nearly 30 per cent of 1.49 billion disability-adjusted life years (DALYs) are lost every year to diseases of infectious origin (Fauci et al., 2001). The burden of morbidity and mortality associated with infectious diseases falls most heavily on people in developing countries, and particularly on infants and children (about three million children die each year from malaria and diarrhoeal diseases alone) (Taylor et al., 2001).
Patho-physiology of Scrub typhus
Among the many emerging bacterial infections, the causative of scrub typhus/bush typhus, Orientia tsutsugamushi is responsible for re-emerging zoonotic disease. Previously called as Rickettsia tsutsugamushi, O tsutsugamushi is a gram-negative bacillus. It is an intracellular parasite belonging to the family Rickettsiaceae and was first isolated and identified in 1930 in Japan. Scrub typhus is transmitted by some species of trombiculid mites/Chiggers (Leptotrombidium deliense) and produces a characteristic skin lesion identified as black eschar. Adult mite does not feed on man and only feeds on the serum of warm blooded animals. The Larval form/ Chiggers which are very small and seen only with the help of a magnifying glass actually bite Figure 1.

Figure 1 The Mite life cycle (Extracted from http://www.infectionlandscapes.org/2011/06/typhus.html)


Humans are accidental hosts and symptoms appear after an incubation period is six to twenty-one days after the bite of chiggers which is usually painless and not noticed by the patients. Clinical presentation of patients suspected to be suffering from scrub typhus may include fever with chills, headache, muscle pain, cough, and gastrointestinal symptom. Other clinical signs that may appear in patients are centrifugal macular rash on the trunk, ocular pain, conjunctival inflammation, delirium, eschar, splenomegaly and lymphadenopathies (http://emedicine.medscape.com/ article/971797-overview#a0156).

Complications of scrub typhus include haemorrhage, disseminated intravascular coagulation (DIC), multiple organ dysfunction syndrome (MODS), shock, central nervous system (CNS) involvement, renal impairment and acute respiratory distress syndrome (ARDS). Leucopoenia and abnormal liver function tests (>90%) are commonly seen in the early phase of the illness. Pneumonitis, encephalitis, and myocarditis may occur in the late phase of illness (http://emedicine.medscape.com/article/971797-overview#a0156).

Clinical symptoms of scrub typhus overlap with other endemic infectious diseases like dengue fever, malaria, chikungunya, leptospirosis, Paratyphoid, other viral fevers and pyrexia of unknown origin (P.U.O). Infections are usually confined to the areas where the insect vector is prevalent and a strong clinical suspicion should be made among the people who give a recent travel history to such regions. A recent report of patient suffering from acute respiratory distress syndrome after being infected with Orientia tsutsugamushi reveals the necessity to investigate further on the modes of transmission to human (inhalation/aerosols) and the life-threatening nature of the disease in case of delay in suspicion and diagnosis (Angelakis et al., 2015).
Epidemiology of Scrub Typhus
Endemic regions for scrub typhus include Asia, Australia, Korea, Japan, Thailand, Myanmar China, India and Pakistan (Suputtamongkol et al., 2009; Matsumura and Shimizu, 2009; Liu et al., 2009). Epidemic scrub typhus involving American soldiers working in Vietnam during World War II has also been reported. In India scrub typhus has been reported to be prevalent in Southern India (Rajasthan, AP, Pondicherry, Tamil Nadu, Goa) and Northern India (Himalayan region of India) and north-western India (Sachdeva et al., 2014; Sinha et al., 2014) (Table 1 and Figure 2).

Table 1 Classification, primary vector, and reservoir occurrence of rickettsiae known to cause disease in humans (Extracted from CDC)

  

Figure 2 Map revealing the Geographic triangular area where scrub typhus is prevalent (Extracted from CDC)


Laboratory Diagnosis of Scrub Typhus
Laboratory diagnosis of scrub typhus can be performed using both conventional and molecular methods. Traditional methods for diagnosis include Weil-Felix test, indirect immunofluorescence, indirect immunoperoxidase (IIP), immunochromatography, enzyme linked immunosorbant assay (ELISA) and culture. Interpretation of results of ELISA for the detection of antibodies should be cautiously as even healthy individuals (18%) also react positively (Chung et al., 2012). A four-fold rise in titre should be considered as diagnostic in patients showing clinical symptoms. Real-time quantitative polymerase chain reaction method (rt-PCR) has been evaluated for the diagnosis of rickettsial infections (Jiang et al., 2004).
Orientia stutsugamushi does not grow in routine culture media used in clinical laboratories. Cell culture technique is applied using monolayer of L929 cell lines for growing them in laboratory (Angelakis et al., 2012).
Discussion
Considering the fact that there is no vaccine available for protection against scrub typhus disease, prevention of infection remains only the best alternative (Chattopadhyay et al., 2007; Valbuena et al., 2012). People residing in the endemic regions of the vector should be educated about protecting themselves form insect bites by wearing protective clothes, using insect repellents, reducing visits to the forest areas infested with trombiculid mites and chiggers. Previous studies have also evaluated the anti-chigger effects of some oil extracts from plants (Rodkvamtook et al., 2012). Screening international and national travellers returning from potentially endemic places would contribute to early diagnosis of scrub typhus thereby reducing the morbidity and mortality (Jensenius et al., 2009). Resistance reports recently of Orientia tsutsugamushi against quinolone group drugs should be considered as a cause of serious concern (Tantibhedhyangkul et al., 2010).
Management of scrub typhus includes initiation of antibiotics following strong clinical suspicion supported with positive laboratory reports. Doxycycline is considered as the drug of choice which can be given as single dose weekly for six weeks. In case of prophylactic treatment while visiting the endemic areas the first dose should be taken before one week. Other antimicrobial agents belonging to macrolide group (azithromycin, clarithromycin, roxithromycin and telithromycin), rifampicin and chloramphenicol are also are effective against Orientia tsutsugamushi (Olson et al., 1980).
Conclusion
In conclusion it is very important both for the clinician and laboratory medicine personnel to have a better understanding of the infections prevalent in a particular geographical region and the characteristics of emerging and re-emerging infections. Timely clinical suspicion supported by use of appropriate diagnostic techniques would be instrumental in better management of patients.
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