|Year : 2020 | Volume
| Issue : 1 | Page : 5-10
Rickettsial disease existence in India: resurgence in outbreaks with the advent of 20th century
Abha Sharma, Bibhabati Mishra
Department of Microbiology, G B Pant Institute of Postgraduate Medical Education and Research, New Delhi, India
|Date of Submission||22-Jul-2019|
|Date of Acceptance||27-Sep-2019|
|Date of Web Publication||23-Jan-2020|
Dr. Abha Sharma
G B Pant Institute of Postgraduate Medical Education and Research, New Delhi
Source of Support: None, Conflict of Interest: None
Rickettsial infections are both one of the oldest and recently recognized reemerging zoonotic infections. Misdiagnosis and underreporting of rickettsial infections are significant public health problems leading to extensive investigations in patients with fever of unknown origin, thus contributing to economic burden on families. We review the situation of rickettsial outbreaks in India with the advent of the 20th century. We did a PubMed and Google search for literature available for rickettsial outbreaks in India. Literature was searched for outbreaks that were reported before the year 2000 and after the year 2000. The data were compiled and tabulated for comparative and descriptive analysis of the clinicoepidemiological profile, diagnosis, and existence of rickettsial infections in India. Rickettsial infections are reemerging and are reported from almost all parts of India such as Himachal Pradesh, Rajasthan, Jammu and Kashmir, Uttaranchal, Maharashtra, Tamil Nadu, Karnataka, Kerala, Assam, Mizoram, and West Bengal. Nonspecific clinical presentation and nonavailability of sensitive and specific diagnostic test make it difficult to document the diagnosis of these infections in India. Recently, molecular biological methods such as polymerase chain reaction and loop-mediated isothermal amplification have been developed but available only at reference laboratories.
Keywords: India, outbreaks, rickettsial diseases
|How to cite this article:|
Sharma A, Mishra B. Rickettsial disease existence in India: resurgence in outbreaks with the advent of 20th century. Indian J Health Sci Biomed Res 2020;13:5-10
|How to cite this URL:|
Sharma A, Mishra B. Rickettsial disease existence in India: resurgence in outbreaks with the advent of 20th century. Indian J Health Sci Biomed Res [serial online] 2020 [cited 2020 Jun 1];13:5-10. Available from: http://www.ijournalhs.org/text.asp?2020/13/1/5/276416
| Introduction|| |
Most covert reemerging infection of the present times, rickettsial diseases have been prevalent worldwide. In India, several cases have been reported from Delhi, Himachal Pradesh, Jammu and Kashmir, Uttarakhand, Rajasthan, Tamil Nadu, and Maharashtra. In the early years, cases have mainly been reported from soldiers in the Assam and Burma fronts during the Second World War when it was a problem second only to malaria. Thereafter, very little data about rickettsial diseases have been available from India. Since the past decade, increasing number of cases are being reported, and scrub typhus and Indian tick typhus are the common rickettsial infections reported from India so far. In fact, it has been established that rickettsial diseases are a reemerging zoonotic bacterial infection in the Indian subcontinent. However, all cases reported so far from India are an underestimate because of several reasons such as difficulty in diagnosing the infections due to lack of proper diagnostic tests, low index of clinical suspicion due to nonspecific signs and symptoms, and lack of awareness among health-care workers. Treatment is more cost-effective than definitive laboratory diagnosis; irrational antibiotics are prescribed to pyrexia of unknown origin (PUO) cases in endemic areas. This has led to overtreatment in comparison to underdiagnosis.
Rickettsiae are obligate intracellular organisms which are difficult to culture. The awareness of clinicians about this reemerging infection in India, which has long been a neglected infectious disease, is essential for early diagnosis and management of PUO cases and therefore with this aim, we reviewed the situation of rickettsial infections in India before and after the 20th century, clinical-epidemiological profile, diagnosis, and prevention for better public health understanding.
| Existence of Rickettsial Infections in India|| |
Before the 20th century, rickettsial diseases (typhus and spotted fever group) were thought to be rarely reported in India [Table 1]. Most of the cases were reported from soldiers in Assam, West Bengal, during World War II. Few data were available about the prevalence of rickettsial infections in the country. In fact, the tests available for diagnosing the infection were actually done only at a few centers. Scrub typhus was an endemic disease in several parts of India in the 1960s and 1970s. After that, the disease was thought to be eradicated as a result of widespread use of insecticides, empirical use of new antibiotics such as tetracyclines and chloramphenicol for treating PUO. After two decades, in 1990, cases were reported from soldiers in the army at Pakistan border of India. However, since the year 2000 [Table 2], rickettsial infections have reemerged and increasing number of outbreaks have been reported. The increase in the outbreaks reported after 20th century may be due to human behavioral changes, unplanned urbanization, deforestation, and rapid transport leading to the displacement of vectors as well as the rodents from one place to another. It is clear from the data available that among the major groups of rickettsioses, commonly reported diseases in India are scrub typhus, murine flea-borne typhus, and Indian tick typhus in most of the regions of India.,,, The geographical distribution of rickettsial infections that are common in India is given in [Table 3]. Endemic typhus, Indian tick typhus, and scrub typhus are reported in most of the outbreaks.,,,,, The most common rickettsial disease in India is scrub typhus and is prevalent in many parts of India. Some newly discovered or less recognized rickettsial infections such as flea-borne spotted fever caused by unidentified rickettsial species (R14 strain) which has genetic identity with rickettsia species of flea origin from Egypt and Thai-Myanmar border have also been reported from Western Himalayan region of India.
| Clinico-Epidemiological Profile of Rickettsial Infections|| |
Rickettsial infections are a reemerging bacterial zoonotic infection. Human beings are accidentally involved in the transmission chain between vectors (ticks/flea/mites) and animals (rodents/cats). Most of the cases in the outbreaks reported have a history of animal contact (dog/cattle) or insect bite. Most of the outbreaks in Karnataka, Tamil Nadu, Andhra Pradesh, and other places have reported patients from rural areas. Although rickettsial diseases are common in rural areas, but its presence has been documented in urban areas such as Delhi and Bengaluru and other towns in India, where mites and other vectors may be present in vegetations near residences. Seasonal trend has been reported in most of the cases. Outbreaks were observed soon after the rainy season (August–November).,,,, It is because of the vector breeding habits, especially mites. The egg hatches to larva due to increased humidity postmonsoon. Moreover, it is the larval stage that transmits the disease. Outbreaks in India have reported cases that are more prevalent in male gender.,,,, [20, Infection is most commonly found in children.,, The clinical presentation of rickettsial infections ranges from mild febrile illness to life-threatening conditions if there is delay in diagnosis and management. In most of the outbreaks that have been reported, patients presented with acute febrile illness with nonspecific signs and symptoms.,, One of the pathognomonic sign of scrub typhus is eschar formation present in 50%–80% cases.,, However, in some outbreaks, no eschar was found in the cases.,,, Presence of rash is considered hallmark of rickettsial disease, but it is not seen in all the patients. It becomes apparent after 3–5 days of fever. Vomiting, headache, abdominal pain, breathlessness, and lymphadenopathy are other signs and symptoms associated with fever in many cases.,
| Diagnosis of Rickettsial Diseases in the Indian Scenario|| |
In the earlier times, diagnosis was mainly clinical based on the presence of eschar and rash and history of outdoor activities. The clinical signs and symptoms including eschar formation are not diagnostic of rickettsial diseases. Epidemiological parameters such as geographical distribution, occupation, animal contact, travel history to forest, and endemic areas may help in making a presumptive diagnosis so as to initiate timely management. Hence, it is important for the clinicians to be aware of all these parameters and be sensitized to have a high index of suspicion while managing patients of PUO. However, all suspected cases need to be confirmed by laboratory tests to document the infection. Laboratory diagnosis is done by serology, isolation of organism, and molecular assays [Table 4].
|Table 4: Comparative analysis of diagnostic tests available for rickettsial diseases|
Click here to view
The Weil–Felix test discovered in 1916 is the most commonly used laboratory test in India for diagnosing rickettsial diseases in most of the outbreaks. Weil–Felix is an antibody detection test with low sensitivity and specificity. It detects antibodies to various Proteus spp. antigens that crossreact with rickettsiae. The sensitivity and specificity of this test are 43% and 98%, respectively, as evaluated by some studies., This test confirms the presence of infection 2 weeks after the onset of disease. It is an inexpensive test and therefore an important diagnostic tool for developing countries such as India, where other specific serologic tests such as indirect immunofluorescence assay (IFA), ELISA (IgM capture), and rapid immunochromatographic test (ICT) are expensive and available only in few laboratories in India. A study conducted by Kulkarni et al. compared the performance of serodiagnostic assays and found that ELISA-IgM assay has 95% sensitivity and 95.2% specificity in IFA-positive patients, while Weil–Felix test has 77% sensitivity and 81.6% specificity in IFA-positive patients. ELISA IgM is similar to IFA and better than Weil–Felix and may be used as a low-cost alternative test to IFA in developing countries with poor resources. The gold standard test is IFA but not easily available in our country. Only reference laboratories perform this test. It is the most sensitive and specific test. Four-fold rise in titer is demonstrated in paired sera to confirm the diagnosis of rickettsial infection. Rapid ICT is available for the diagnosis of scrub typhus only but not widely used due to poor sensitivity. Studies,, have shown 98%–100% specificity but 28%–49% sensitivity. ICT is a screening test and should be more sensitive, and therefore, in India, it is not recommended for the diagnosis of rickettsial diseases. Rapid ICT has been used to diagnose rickettsial infection in several outbreaks reported since 2012–2016 in Mizoram.
Isolation of the organism
Rickettsiae can grow in variety of cell lines such as human fibroblasts, endothelial and epithelial cells (HeLa), other mammals (VeRo, L929), amphibians (XTC-2), avian hosts (chick embryo fibroblast), and arthropods (tick-derived DAE100, mosquito-derived Aa23, and C6/36 cell lines). However, cell lines are not easily available in most Indian settings. Rickettsiae are highly infectious agents, and biosafety level III facilities are required in the laboratories where culture is done. Hence, it is done only in reference laboratories for the research purpose.
Polymerase chain reaction (PCR) was first shown useful for scrub typhus in 1990. It can be done up to 10 days of fever after which serology is better for making a diagnosis. Common target genes are htrA (47-kDa periplasmic serine protease), 56-kDa type-specific antigen, rrs (16SrRNA), and GroEL (heat shock protein Hsp60). Real-time PCR formats are also there but very expensive so not used widely in India for diagnosis. Molecular assays are also available only in reference laboratories such as culture. Some outbreaks, in Himachal Pradesh and Vellore have used PCR and IFA along with Weil–Felix test to confirm their diagnosis. Studies have shown that loop-mediated isothermal amplification (LAMP ) assays are affordable, sensitive, specific, user-friendly, and rapid.,
| Conclusion|| |
Rickettsial diseases occur as outbreaks in almost all parts of India. Resurgence of cases reported with the advent of the new millennium highlights the need for generation of awareness among the clinicians, especially those working at the periphery to consider rickettsial infections as one of the important cause of PUO. It should be higher in the list of differential diagnosis of PUO with a high index of suspicion in patients with fever, rash, history of travel, or animal contact. Standard treatment guidelines should be followed for timely diagnosis and management of cases. A uniform case definition needs to be followed, surveillance activities need to be strengthened and capacity for laboratory confirmation should be developed in the country. Focus needs to be on prevention of the disease by bringing behavioral changes in the public such as avoiding defecation/urination in open areas and forests. Use mat while sitting/lying on floor to prevent the vector bites. Wear full covered clothes when visiting vector-infested areas. The community needs to be educated about the signs and symptoms of infection so that they seek prompt medical help to decrease mortality.
Financial support and sponsorship
Conflicts of interest
| References|| |
Rathi N, Rathi A. Rickettsial infections: Indian perspective. Indian Pediatr 2010;47:157-64.
Varghese GK. Rickettsial diseases in India: Not as uncommon as believed. J Assoc Physicians India 2014;62:9-10.
Kalal BS, Puranik P, Nagaraj S, Rego S, Shet A. Scrub typhus and spotted fever among hospitalised children in South India: Clinical profile and serological epidemiology. Indian J Med Microbiol 2016;34:293-8.
] [Full text]
Rathi N. Rickettsial diseases in India-a long way ahead. Pediatr Infect Dis 2015;7:61-3.
Lalchchandama K. Rickettsiosis as a critical emerging infectious disease in India. Sci Vis 2017;17:250-9.
Thomas R, Puranik P, Kalal B, Britto C, Kamalesh S, Rego S, et al.
Five-year analysis of rickettsial fevers in children in South India: Clinical manifestations and complications. J Infect Dev Ctries 2016;10:657-61.
Laskar AR, Suri S, Acharya AS. Scrub typhus: Re-emerging public health problem in India. J Commun Dis 2015;47:19-25.
Subbalaxmi MV, Madisetty MK, Prasad AK, Teja VD, Swaroopa K, Chandra N et al
. Journal of the association of physicians of India 2014;62:490-96.
Mahajan SK, Rolain JM, Kashyap R, Bakshi D, Sharma V, Prasher BS, et al.
Scrub typhus in Himalayas. Emerg Infect Dis 2006;12:1590-2.
Chrispal A, Boorugu H, Gopinath KG, Prakash JA, Chandy S, Abraham OC, et al.
Scrub typhus: An unrecognized threat in South India – Clinical profile and predictors of mortality. Trop Doct 2010;40:129-33.
Rahi M, Gupte MD, Bhargava A, Varghese GM, Arora R. DHR-ICMR guidelines for diagnosis and management of rickettsial diseases in India. Indian J Med Res 2015;141:417-22.
] [Full text]
Kumar K, Jain SK, Kumar A. Outbreak Indian tick typhus amongst residents of Deol village, district Kangra Himachal Pradesh. Int J Med Public Health 2011;1:67-71. [Full text]
Dedwal A, Bhardwaj R, Pol S, Bhamre S, Tambe M, Chandanwale A. An outbreak of typhus fever from Western India. Clin Infect Dis 2018;2:2.
Chahota R, Thakur SD, Sharma M, Mitta S. Detection of flea – Borne Rickettsia species in the Western Himalayan region of India. Indian J Med Microbiol 2015;33:422-5.
] [Full text]
Sastry AS, Bhat S. Essentials of Medical Microbiology. Rickettsiae, Coxiella and Bartonella. 2nd ed., Ch. 38. New Delhi: Jaypee Brothers and Medical Publishers; 2019. p. 403-12.
Mittal V, Gupta N, Bhattacharya D, Kumar K, Ichhpujani RL, Singh S, et al.
Serological evidence of rickettsial infections in Delhi. Indian J Med Res 2012;135:538-41. [Full text]
Palanivel S, Nedunchelian K, Poorazhagi V, Raghunadan R, Ramachandran P. Clinical profile of scrub typhus in children. Indian J Pediatr 2012;79:1459-62.
Mathai E, Rolain JM, Verghese GM, Abraham OC, Mathai D, Mathai M, et al.
Outbreak of scrub typhus in Southern India during the cooler months. Ann N
Y Acad Sci 2003;990:359-64.
Xu G, Walker DH, Jupiter D, Melby PC, Arcari CM. A review of the global epidemiology of scrub typhus. PLoS Negl Trop Dis 2017;11:e0006062.
Mahajan SK, Rolain JM, Sankhyan N, Kaushal RK, Raoult D. Pediatric scrub typhus in Indian Himalayas. Indian J Pediatr 2008;75:947-9.
Dass R, Deka NM, Duwarah SG, Barman H, Hoque R, Mili D, et al
. Characteristics of pediatric scrub typhus during an outbreak in the North Eastern region of India: Peculiarities in clinical presentation, laboratory findings and complications. Indian J Pediatr 2011;78:1365-70.
Kumar S, Kumar M, Aggarwal B, Kumari R. Scrub typhus in children: Clinical profile and complications at a tertiary care teaching hospital in Uttarakhand. Indian J Child Health 2017;4:188-92.
Kumar Bhat N, Dhar M, Mittal G, Shirazi N, Rawat A, Prakash Kalra B, et al.
Scrub typhus in children at a tertiary hospital in North India: Clinical profile and complications. Iran J Pediatr 2014;24:387-92.
Digra SK, Saini GS, Singh V, Sharma SD, Kaul R. Scrub typhus in children: Jammu experience. JK Sci 2010;12:95-7.
Krishna MR, Vasuki B, Nagaraju K. Scrub typhus: Audit of an outbreak. Indian J Pediatr 2015;82:537-40.
Lee CS, Min IS, Hwang JH, Kwon KS, Lee HB. Clinical significance of hypoalbuminemia in outcome of patients with scrub typhus. BMC Infect Dis 2010;10:216.
Vivekanandan M, Mani A, Priya YS, Singh AP, Jayakumar S, Purty S. Outbreak of scrub typhus in Pondicherry. J Assoc Physicians India 2010;58:24-8.
Kamarasu K, Malathi M, Rajagopal V, Subramani K, Jagadeeshramasamy D, Mathai E. Serological evidence for wide distribution of spotted fevers and typhus fever in Tamil Nadu. Indian J Med Res 2007;126:128-30.
] [Full text]
Kumar M, Krishnamurthy S, Delhikumar CG, Narayanan P, Biswal N, Srinivasan S. Scrub typhus in children at a tertiary hospital in Southern India: Clinical profile and complications. J Infect Public Health 2012;5:82-8.
Chogle AR. Diagnosis and treatment of scrub typhus – The Indian scenario. J Assoc Physicians India 2010;58:11-2.
Dasari V, Kaur P, Murhekar M. Rickettsial disease outbreaks in India: A review. Ann Trop Med Public Health 2014;7:249-54. [Full text]
Prakash JA, Abraham OC, Mathai E. Evaluation of tests for serological diagnosis of scrub typhus. Trop Doct 2006;36:212-3.
Kulkarni T, Benakatti G, Bidari L. Prospective study with rapid and low cost serodiagnostic assay for rickettsial infection in children of Vijaya Pura district, Northern Karnataka, India. Int J Contemp Pediatr 2018;5:1244-8.
Ghosh S, Nagar G. Problem of ticks and tick-borne diseases in India with special emphasis on progress in tick control research: A review. J Vector Borne Dis 2014;51:259-70.
] [Full text]
Pote K, Narang R, Deshmukh P. Diagnostic performance of serological tests to detect antibodies against acute scrub typhus infection in central India. Indian J Med Microbiol 2018;36:108-12.
] [Full text]
Lee KD, Moon C, Oh WS, Sohn KM, Kim BN. Diagnosis of scrub typhus: Introduction of the immunochromatographic test in Korea. Korean J Intern Med 2014;29:253-5.
Kim YJ, Park S, Premaratna R, Selvaraj S, Park SJ, Kim S, et al.
Clinical evaluation of rapid diagnostic test kit for scrub typhus with improved performance. J Korean Med Sci 2016;31:1190-6.
Lalrinkima H, Lalremruata R, Lalchhandama C, Khiangte L, Siamthara FH, Lalnunpuia C, et al.
Scrub typhus in Mizoram, India. J Vector Borne Dis 2017;54:369-71.
] [Full text]
Ammerman NC, Beier-Sexton M, Azad AF. Laboratory maintenance of Rickettsia Rickettsii. Curr Protoc Microbiol 2008;Chapter 3:Unit 3A.5.
Batra HV. Spotted fevers and typhus fever in Tamil Nadu. Indian J Med Res 2007;126:101-3.
] [Full text]
Paris DH, Dumler JS. State of the art of diagnosis of rickettsialdiseases: The use of blood specimens for diagnosis of scrub typhus, spotted fever group rickettsiosis, and murine typhus. Curr Opin Infect Dis 2016;29:433-9.
Varghese GM, Trowbridge P, Janardhanan J, Thomas K, Peter JV, Mathews P, et al.
Clinical profile and improving mortality trend of scrub typhus in South India. Int J Infect Dis 2014;23:39-43.
Pan L, Zhang L, Wang G, Liu Q. Rapid, simple, and sensitive detection of the ompB gene of spotted fever group Rickettsiae
by loop-mediated isothermal amplification. BMC Infect Dis 2012;12:254.
Dittrich S, Castonguay-Vanier J, Moore CE, Thongyoo N, Newton PN, Paris DH. Loop-mediated isothermal amplification for Rickettsia typhi
(the causal agent of murine typhus): Problems with diagnosis at the limit of detection. J Clin Microbiol 2014;52:832-8.
[Table 1], [Table 2], [Table 3], [Table 4]