| Abstract|| |
Rickettsial infections are caused by bacteria of the Rickettsiae family. Several reports in the past decade indicated the presence of disease in various parts of India. We reviewed the rickettsial outbreaks to describe the epidemiology, clinical features, laboratory investigations, entomological investigations, risk factors and treatment. We searched the literature about rickettsial diseases outbreaks in India using web databases. We included research papers about the investigation of rickettsial disease outbreaks during 2000-2011. We included 11 outbreaks from seven Indian states of which four were in a community setting rest were hospital based. There were more than 900 cases and forty two deaths with case fatality ratios 5%-17%. The clinical manifestations were fever, eschar, headache, myalgia, cough and lymphadenopathy. The laboratory diagnosis in 9 outbreaks was based on Weil Felix test either singly (n = 5) or in combination with Micro-immunofluorescence (n = 2) or ELISA (n = 2). Only IgM ELISA was used in 2 outbreaks. Only one of the outbreaks was due to Indian Tick Typhus while the remaining 10 were due to Scrub Typhus. Risk factor and entomological investigations were conducted in few studies. The review of rickettsial outbreaks in the last decade indicates its continued presence in several parts of the India. We recommend use of uniform case definition, capacity building for laboratory confirmation and entomology surveys. Doctors practicing in areas prone to these diseases need to be sensitized to have high index of suspicion while evaluating patients with fever and community should be educated to seek early treatment.
Keywords: India, outbreak, rickettsial
|How to cite this article:|
Dasari V, Kaur P, Murhekar MV. Rickettsial disease outbreaks in India: A review. Ann Trop Med Public Health 2014;7:249-54
| Background|| |
Rickettsial infections are caused by bacteria of the rickettsiae family. They are transmitted to humans by arthropods like ticks, fleas, mites, and lice.  Rickettsial infections have in the past taken more lives than all of the wars fought to date, combined.  Treatment of rickettsial infections is easy, inexpensive and mostly successful. However, these diseases often remain undiagnosed and the lack of treatment leads to fatality rates as high as 35%.  Signs and symptoms of these infections are generally nonspecific such as fever, headache, myalgia, and rash, and laboratory tests do not reveal anything until about two weeks after the onset of the disease. Knowledge of geographical distribution, evidence of exposure to vector, clinical features including eschar(s), and a high index of suspicion are important for early diagnoses. 
Rickettsial infections have been reported in India for several decades. During the World War II era, there were many deaths due to scrub typhus in this region. , It was thought that these infections declined over time; however several reports in the past decade indicate the presence of disease in various parts of India, such as the Himalayan region, the northeast, and the south. ,,, These diseases have been responsible for causing outbreaks. We reviewed the rickettsial outbreaks investigated since 2000 to describe the epidemiology of the disease in terms of time, place, and person. We described clinical features, laboratory investigations, entomological investigations, risk factors, and treatment during the outbreaks.
| Materials and Methods|| |
We searched the published literature about rickettsial diseases outbreaks in India between the years 2000 and 2011. We searched PubMed, IndMedica, Google Scholar and Medline databases using the following search terms: Rickettsi * , rickettsi * disease, typhus, scrub typhus, epidemic typhus, endemic typhus, spotted fever, rickettsi * infection, tropic * disease * , rickettsi * india, tick typhus, child * typhus, child * rickettsi * , child * rickettsi * India, the weil-felix, immunofluorescence, microimmunofluorescence, Orientia tsutsugamushi, Rickettsia prowazeki, Rickettsia typhi, Rickettsia conorii, and Coxiella burnetii. We also reviewed the rickettsial outbreaks investigated by the trainees of the Field Epidemiology Training Programme (FETP) of the National Institute of Epidemiology, Chennai.
We included research papers about the investigation of rickettsial disease outbreaks from 2000-2011. We excluded the studies that were about estimation of disease burden assessed through serological surveys, case studies, description of the organism, or unusual presentation of the disease.
Data collection method
Using a standardized abstraction form, we abstracted information about the time, place and person distribution of the disease. We collected information about the month, year, and place of the outbreak; the setting (community- or hospital-based study); the clinical case definition used for case search; clinical features; and laboratory tests. We also abstracted information about the entomological investigations conducted, as well as risk factors associated with the disease.
| Results|| |
We identified 11 reports of rickettsial outbreak investigations conducted between 2000-11. ,,,,,,,,,, The Indian tick typhus outbreak that occurred in Kangra in 2007 was reported in one published paper and one unpublished report. We used the data from the published paper by Kumar et al. about the epidemiology of the disease and included the data regarding the risk factors for the disease from the unpublished report by Sood et al. , Four reports described the investigation of the outbreak conducted in a community setting, while the remaining seven reports described the outbreak based on the patients attending a health care facility. ,,,,,,,,,, Two reports included the cases admitted in the health facility over a period of more than one year [Table 1]. ,
|Table 1: Case defi nition, epidemiological characteristics, and laboratory tests in the 11 rickettsial disease outbreaks (2000-2011), India|
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Time and place distribution: Of the 11 outbreaks, four were reported from Himachal Pradesh (Kangra, Shimla, Solan, and Sirmapur districts), two from Manipur (Bishnupur and Senapti districts), and one each from Jammu and Kashmir (Rajouri district), Tamil Nadu (Vellore), Pondicherry, West Bengal (Darjeeling), and Meghalaya (Shillong). In north Indian states, the outbreaks were reported during the rainy season and winter months (May-Jan); in Tamil Nadu and Pondicherry, the outbreaks were reported during September/October-February, which are relatively cooler months [Table 1]. ,,,,,,,,,,
Ten of the outbreaks investigated mentioned the criteria used for inclusion of patients in the specific studies, while no specific case definition was mentioned in one investigation. Three studies included laboratory positivity as a criterion in the case definitions. ,, The other studies used case definitions based on clinical presentation, such as fever of unknown origin, acute febrile illness, fever with or without eschar, as well as other symptoms including rash, lymphadenopathy, etc. [Table 1].
Age and gender of cases
More than 900 cases were reported from the 11 outbreaks (range: 8-357). Most of the cases occurred among the middle and older aged individuals. The outbreak in Meghalaya occurred among children with a mean age of case patients as nine years.  The outbreak in the Kangra district had 60% of fever cases detected during the community survey in the age group of 5-26 years.  Forty-two deaths were reported in five outbreaks, with case fatality ratios ranging between 5-17% [Table 1]. ,,,,
The common clinical manifestations of the case-patients included fever (100% in all outbreaks), chills and rigors (71-88% in two outbreaks), headache (25%-100%, in five outbreaks), myalgia (10-52% in five outbreaks), cough (10-44% in five outbreaks) and lymphadenopathy (13%-45% in seven outbreaks). Eschar was observed in most (10/11) of the outbreaks. Abnormal renal function and liver function tests were reported in four and five outbreaks, respectively. ,,,,,,,,,, Most of the cases were treated with doxycycline or azithromycin [Table 2].
|Table 2: Clinical features, liver and renal function test abnormalities in 10 rickettsial disease outbreaks (2000-2011), India|
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The laboratory diagnosis in 9 outbreaks was based on the Weil-Felix test, either singly (n = 5) or in combination with micro-immunofluorescence (MIF) (n = 2)_or enzyme-linked immune assay (ELISA) (n = 2). In the remaining two outbreaks, IgM ELISA alone was used for the diagnosis. Only one of the outbreaks was due to Indian tick typhus, while the remaining 10 were due to scrub typhus [Table 1].
Three studies provided information regarding the risk factors of the disease. In an outbreak in Himachal Pradesh, an analytical study was not done, but the authors described that majority of the patients were those frequenting forest for grass cutting and wood collection.  An analytical study done during the outbreak in Bishenpur indicated that the practice of defecating or urinating in the jungle or bushy areas in a squatting position was a risk factor.  Changing clothes weekly or less frequently, tall grass in the neighborhood, travel to the forest, bathing infrequency (less than thrice weekly), handling of tick-infested animals, household contact with fever cases were the risk factors during the analytical study done in an outbreak in Himachal Pradesh. 
Entomological investigations were conducted in three outbreaks. As a part of these investigations, rodents in domestic and peridomestic areas were trapped and ectoparasites on these rodents were collected and identified using standard procedures. Kumar et al.  conducted an entomological investigation that revealed the presence of ixodid ticks on domestic animals in the affected area. The authors reported presence of Rhipicephalus sanguineus, which is the proven vector of Indian tick typhus. 
Kumar et al.  used traps for rodents. Mite incidence rate among rodents was 1.84%. Mite species were Leptotrombidium deliense and Gahrliepia. The chigger index ranged from 1-23 in different villages. The overall tick infestation rate was 29 per rodent. Immature stages of Haemaphysalis leachi, Rhipicephalus species and Ixodes species were retrieved. 
Tilak et al. (2011) conducted an entomological survey by analyzing ectoparasite diversity, the efficacy of rodent trapping, and the relative abundances of different species of mammals and parasitization of small mammals. They found 66% of trapped rodents to be infested with ectoparasites, of which 56.25% tested positive for mite infestation and 25% tested positive for mites and ticks together. 
| Discussion|| |
The review of published rickettsial outbreaks in the last decade indicates its continued presence, particularly scrub and tick typhus, in several parts of the India. The outbreaks were reported from seven Indian states. Howeve,r the published literature is less likely to reflect the actual scenario of the disease in the country mainly due to its underreporting. Nevertheless, the findings of our review highlight certain issues about the epidemiology and control of the disease in India.
Rickettsial infections are difficult to diagnose and require consideration of clinical presentation, various environmental factors, and even the response to antibiotics. The common clinical presentation reported during the outbreaks reviewed included fever (>1 week) with chills and rigor, headache, vomiting, cough, conjunctival congestion and eschar. Rashes were a rare symptom. Abnormal kidney and liver function were the most common biochemical abnormalities observed. It is necessary to increase awareness among doctors in endemic areas to consider these clinical features for suspecting rickettsial infections, as these infections are often the last to be suspected. 
The case definitions used in these investigations included a combination of various clinical presentations, with or without laboratory confirmation. Various levels of definitions need to be developed in endemic areas depending on the common clinical presentations in order to capture majority of the cases during a given outbreak. In our review, several investigations included only those patients who reported to the hospital. However, an unexpected increase in such cases in the hospitals should lead to enhanced surveillance. The clustering of cases with symptoms such as fever, headache, myalgia, vomiting and cough in endemic areas should raise the suspicion of rickettsial outbreaks. Though eschar is specific feature of rickettsial infection, it was present in variable proportion of cases. Hence, its inclusion in the case definition should be based on the local disease presentation.
Confirmation of suspected cases by appropriate laboratory tests is key for documenting the infection. Most of the outbreaks reviewed were confirmed by the Weil-Felix test. Unfortunately, the laboratory tests that are more specific and sensitive than the commonly used Weil-Felix test are too expensive and are available in very few laboratories in India. The specific gold standard test for rickettsial infections is the microimmunofluorescence test, namely immunofluorescence assay (IFA).  However, this test is not widely available. Other confirmatory tests such as the indirect immunoperoxidase (IP) test, ELISA, and the isolation of the organisms in animals or cell culture are also not available in most of the settings in India.  Evaluations done by Prakash et al. (2006) showed that the Weil-Felix test had a specificity of over 98& and a sensitivity of about 43%.  Though this test is a retro-confirmatory test, done to confirm the presence of the infection two weeks after the onset of the disease rather than to diagnose it in its early stages, it documented the presence of the disease in several areas. , Rapid diagnostic tests and polymerase chain reaction (PCR) tests available in developed countries are still not widely used due to cost and other barriers. 
Entomological investigations and analytical studies to understand the risk factors associated with the illness provided useful clues for designing specific interventions. Entomological investigations were conducted in only in three of the 11 outbreaks reviewed and were limited to identifying and characterizing the ectoparasites. The absence of entomological data leads to an incomplete field investigation regarding transmission of the disease. Risk factors described during three outbreaks suggested recent exposure to the environment to be associated with the clinical illness. Interventions for controlling the disease should be aimed at reducing the environmental exposure and making the living and working environments safer. Measures such as clearing of bushes, keeping wood and animals away, controlling rodents, de-ticking animals, and promotion of protective measures would likely reduce the risk of the disease in endemic areas.
Our review highlights that rickettsial diseases occur as outbreaks in several parts of India. We observed lack of uniform case definition, lack of confirmatory laboratory tests, lack of analytical studies, and entomological surveys in the majority of the outbreaks. It is necessary to develop and disseminate uniform case definition, strengthen the surveillance, and develop the capacity for laboratory confirmation and entomology surveys. Doctors practicing in areas prone to these diseases need to be sensitized to have high index of suspicion while evaluating patients with fever. Health promotion programs should focus on behavioral interventions for controlling the disease, like avoiding defecation/urination in jungle/bushy areas, frequent bathing, and sitting and lying on the floor only when using a mat or cover. Educating the community about the common symptoms of the disease and encouraging people to seek early treatment from the public health facilities is the mainstay of controlling the outbreaks and preventing mortality.
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Dr Prabhdeep Kaur
National Institute of Epidemiology, Indian Council of Medical Research (ICMR), # R-127, 3rd Avenue, Tamil Nadu Housing Board, Ayapakkam, Chennai, Tamil Nadu
Source of Support: None, Conflict of Interest: None
[Table 1], [Table 2]