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Scrub typhus: A serious public health issue in Nepal

Published:April 04, 2020DOI:https://doi.org/10.1016/j.cegh.2020.02.006

      Abstract

      The agro-climatic conditions, socio-economic situation, poor sanitation, low hygiene and health standards in Nepal are major contributing factors to the emergence of scrub typhus in Nepal. These outbreaks, along with poor diagnostic facilities, can lead to severe economic losses in a resource-limited country like Nepal. Diseases like avian influenza, leptospirosis, brucellosis, tuberculosis and rabies, that cause heavy socio-economic burden, have received huge attention of Government of Nepal and hence are among the top ten priority diseases. However, until now, scrub typhus is not considered a priority disease in Nepal, despite having severe outbreaks time to time. In order to diagnose and treat scrub typhus infection, low budget diagnostic tests such as Weil Felix are less efficient and poor in screening, and highly advanced & efficient tests are less likely to be available and are expensive. Nepal needs to explore appropriate and applicable test settings in primary health centers and referral laboratories in the country. Moreover, focus should be made on effective surveillance programs and public awareness campaigns, mice/rat control strategies, and improving sanitation, public health and hygiene measures for the people at most risk. In addition, health workers and professionals should be trained on early case detection, personal protection, proactive rodent control strategies, habitat destruction and good sanitation and hygiene practices.

      Keywords

      Scrub typhus, also known as bush typhus, is an acute, endemic, febrile, zoonotic rickettsial infectious disease. Scrub typhus is caused by Orientia tsutsugamushi, an obligatory intracellular gram negative proteo-bacterium
      • Taylor A.J.
      • Paris D.H.
      • Newton P.N.
      A systematic review of mortality from untreated scrub typhus (Orientia tsutsugamushi)..
      transmitted by the blood sucking larvae, chigger, of arthropod (Trombiculadae family) mites. These mites are highly prevalent in certain regions of Nepal and are endemic to neighboring countries like Pakistan, India, Indonesia, Maldives, Myanmar, Sri Lanka, Thailand and other islands in the region.
      • Chakraborty S.
      • Sarma N.
      Scrub typhus: an emerging threat.
      The onset of disease condition is characterized by the fever of unknown origin (FUO), headache, body aches (Myalgia), rashes, cough and gastro-intestinal problems. Usually the eschar or scab is developed at the site of chigger bite. However, detection of eschar is rare in South-East Asian patients and is usually reported with less severe form of illness often without the eschar or rash.
      • Peter J.V.
      • Sudarsan T.I.
      • Prakash J.A.J.
      • Varghese G.M.
      Severe scrub typhus infection: clinical features, diagnostic challenges and management.
      The other symptoms may include lymphadenopathy and hypo-tension.
      • Chakraborty S.
      • Sarma N.
      Scrub typhus: an emerging threat.
      ,
      • Peter J.V.
      • Sudarsan T.I.
      • Prakash J.A.J.
      • Varghese G.M.
      Severe scrub typhus infection: clinical features, diagnostic challenges and management.
      In Nepal, the vast majority (approximately 80%) of the population lives in rural areas with agriculture as their mainstay of household economy.
      • Central Bureau of Statistics
      National population and housing census 2011 (national report).
      While involving in agricultural activities as well as household chores, they daily come in direct contact with rodents, ticks, and mites.
      • Chakraborty S.
      • Sarma N.
      Scrub typhus: an emerging threat.
      ,
      • UNDP
      Nepal Country Report Global (GLOBAL ASSESSMENT of RISK). Assessment.
      • Acharya N.
      • Acharya K.P.
      • Dhakal I.P.
      Cross-sectional sero-prevalence of tularemia among murine rodents of Nepal.
      • Gautam R.
      • Parajuli K.
      • Sherchand J.B.
      Epidemiology, risk factors and seasonal variation of scrub typhus fever in central Nepal.
      Likewise in urban areas, where waste disposal is a major issue,

      Muzzini E, Aparicio G, Muzzini A. Urban Growth and Spatial Transition in Nepal an Initial Assessment Countries and Regions.

      • Acharya K.P.
      • Wilson R.T.
      Antimicrobial resistance in Nepal.
      • Acharya K.P.
      • Subramanya S.H.
      • Lopes B.S.
      Combatting antimicrobial resistance in Nepal: the need for precision surveillance programmes and multi-sectoral partnership.
      also provides flourishing environment for rodents and pests especially rats, mice and mice.
      • Karkey A.
      • Aryjal A.
      • Basnyat B.
      • Baker S.
      Kathmandu, Nepal: still an enteric fever capital of the world.
      The seasonal flooding in Nepal predisposes to the poor sanitary and hygienic conditions and increases the number of rodents that eventually increase the risk of disease transmission. In addition, during the wetter months of the year more chiggers are attached to a rodent which may cause scrub typhus burdens in rainy seasons.
      • Gautam R.
      • Parajuli K.
      • Sherchand J.B.
      Epidemiology, risk factors and seasonal variation of scrub typhus fever in central Nepal.
      ,
      • Gurung S.
      • Pradhan J.
      • Bhutia P.Y.
      Outbreak of scrub typhus in the North East Himalayan region-Sikkim: an emerging threat.
      The recurrent outbreaks of scrub typhus in Nepal could have been thus, substantiated by occupational status, poor sewage and agro-climatic condition of the country.
      Acute febrile illness is the most common problem in Nepal and most of the cases FUO are often misdiagnosed.
      • Blacksell S.D.
      • Sharma N.P.
      • Phumratanaprapin W.
      • et al.
      Serological and blood culture investigations of Nepalese fever patients.
      • Upadhyaya B.P.
      • Shakya G.
      • Adhikari S.
      • et al.
      Scrub typhus: an emerging neglected tropical disease in Nepal.
      • Murdoch D.R.
      • Woods C.W.
      • Zimmerman M.D.
      • et al.
      The etiology of febrile illness in adults presenting to Patan hospital in Kathmandu, Nepal.
      These febrile illness cases, characterized by high body temperature, are suspected to be salmonella enterica serovar typhi and paratyphi-A
      • Blacksell S.D.
      • Sharma N.P.
      • Phumratanaprapin W.
      • et al.
      Serological and blood culture investigations of Nepalese fever patients.
      ,
      • Murdoch D.R.
      • Woods C.W.
      • Zimmerman M.D.
      • et al.
      The etiology of febrile illness in adults presenting to Patan hospital in Kathmandu, Nepal.
      and treated as per
      • Blacksell S.D.
      • Sharma N.P.
      • Phumratanaprapin W.
      • et al.
      Serological and blood culture investigations of Nepalese fever patients.
      ,
      • Sharma P.K.
      • Ramakrishnan R.
      • Hutin Y.J.F.
      • et al.
      Scrub typhus in Darjeeling, India: opportunities for simple, practical prevention measures.
      Most of the cases of febrile illness are mostly treated based on the clinical suspicion rather than the epidemiological studies and identification of causative pathogens.
      • Blacksell S.D.
      • Sharma N.P.
      • Phumratanaprapin W.
      • et al.
      Serological and blood culture investigations of Nepalese fever patients.
      ,
      • Basnyat B.
      Typhoid versus typhus fever in post-earthquake Nepal.
      • Karki K.B.
      • Acharya B.P.
      • Dhimal M.
      • et al.
      Descriptive Epidemiology of Scrub Typhus in Nepal, 2017 Nepal Health Research Council (NHRC) Descriptive Epidemiology of Scrub Typhus in Nepal, 2017 Authors.
      • Koirala K.D.
      • Chappuis F.
      • Verdonck K.
      • Rijal S.
      • Boelaert M.
      Persistent febrile illnesses in Nepal: a systematic review.
      • Pokharel S.
      • Karki M.
      • Acharya B.
      • Marasini B.
      • Arjyal A.
      Outbreak of acute undifferentiated febrile illness in Kathmandu, Nepal: clinical and epidemiological investigation.
      Chances exist that the possible reason behind those febrile illnesses could be rickettsial infection of spotted fever group or typhus group type (scrub typhus) or mixed infection of both. These two forms of rickettsial infection (spotted fever group and scrub typhus) have varying degree of clinical manifestations. Though both rickettsial infections have different geographical distribution, seasonal patterns, and clinical indications, they share some clinical features. A study by Kalal et al., with ELISA shows that skin rash and leukocytosis was more associated with spotted fever group and thrombocytopenia with scrub typhus infection.
      • Kalal B.S.
      • Puranik P.
      • Nagaraj S.
      • Rego S.
      • Shet A.
      Scrub typhus and spotted fever among hospitalised children in South India: clinical profile and serological epidemiology.
      Therefore, unidentified fever or FUO, without neglecting potential diseases with similar symptoms, must be distinguished with an appropriate diagnostic test.
      Scrub typhus was first reported in Nepal in 1981 as a cause of FUO.
      • Brown G.W.
      • Shirai A.
      • Gan E.
      • Bernthal P.
      Antibodies to typhus in eastern Nepal.
      Serological investigation of scrub typhus was carried out in 2004, in Patan Hospital (one of the largest hospitals in Nepal) in a small number of febrile patients (876) admitted to the same hospital.
      • Murdoch D.R.
      • Woods C.W.
      • Zimmerman M.D.
      • et al.
      The etiology of febrile illness in adults presenting to Patan hospital in Kathmandu, Nepal.
      Very few attempts were made before 2014 to determine the prevalence of scrub typhus in Nepal.
      • Karki K.B.
      • Acharya B.P.
      • Dhimal M.
      • et al.
      Descriptive Epidemiology of Scrub Typhus in Nepal, 2017 Nepal Health Research Council (NHRC) Descriptive Epidemiology of Scrub Typhus in Nepal, 2017 Authors.
      In 2015, the number of recurrent outbreaks of scrub typhus increased in Nepal in the people living in temporary shelters following a devastating 7.8-magnitude earthquake and the subsequent aftershocks with history of increased rodent infestation in the environment.
      • Basnyat B.
      Typhoid versus typhus fever in post-earthquake Nepal.
      ,
      • Nayak N.
      Scrub typhus in Nepal.
      Since then, several episodes of outbreak of scrub typhus have been reported (Table 1).
      Table 1Studies/reports on scrub typhus in Nepal.
      AuthorStudy YearLocationTest UsedPrevalence %Type of study
      Murdoch et al.,
      • Murdoch D.R.
      • Woods C.W.
      • Zimmerman M.D.
      • et al.
      The etiology of febrile illness in adults presenting to Patan hospital in Kathmandu, Nepal.
      2001Different Hospitals of KathmanduINDx Multitest dipstick-SDLST3.2% (28/876)Prospective
      Blacksell et al.,
      • Blacksell S.D.
      • Sharma N.P.
      • Phumratanaprapin W.
      • et al.
      Serological and blood culture investigations of Nepalese fever patients.
      2002-2004Different Hospitals of Kathmandu22.33% (23/103)Retrospective
      Upadhyay et al.,
      • Upadhyaya B.P.
      • Shakya G.
      • Adhikari S.
      • et al.
      Scrub typhus: an emerging neglected tropical disease in Nepal.
      2015DhadingELISA35.3% (36/102)Prospective
      KailaliELISA60.4% (32/53)
      KanchanpurELISA54.2% (13/24)
      RamechhapELISA81.3% (13/16)
      KhotangELISA61.5% (8/13)
      Thapa et al.,
      • Thapa S.
      • Sapkota L.B.
      • Hamal P.
      Threat of scrub typhus in post-earthquake Nepal.
      2016Patient admitted to Chitwan Medical CollegeELISA44.1% (181/410)Prospective
      Upadhyay et al.,
      • Upadhyaya B.P.
      • Shakya G.
      • Adhikari S.
      • et al.
      Scrub typhus: an emerging neglected tropical disease in Nepal.
      201530 districts of NepalELISA52.4% (175/434)Prospective
      PCR29.4% (5/17)
      IFA70.6% (12/17)
      Bastola and Pant
      • Bastola A.
      • Pant N.
      An outbreak of scrub typhus in Nepal following the 2015 Gorkha earthquake.
      2015Patients admitted to the Sukraraj Tropical and Infectious Disease Hospital, KtmELISA23 casesProspective
      Epidemiology and Disease Control Division (EDCD), Nepal
      2016Eastern NepalELISA6 casesRetrospective
      All over the NepalELISA>400 casesRetrospective
      Epidemiology and Disease Control Division (EDCD), Nepal
      201625 districts of NepalELISA

      IFA
      >500 casesRetrospective
      Nepal Health Research Council (NHRC)
      • Karki K.B.
      • Acharya B.P.
      • Dhimal M.
      • et al.
      Descriptive Epidemiology of Scrub Typhus in Nepal, 2017 Nepal Health Research Council (NHRC) Descriptive Epidemiology of Scrub Typhus in Nepal, 2017 Authors.
      2016From Rodents populationPCR22.2% (2/9)Prospective
      Nepal Health Research Council (NHRC)
      • Karki K.B.
      • Acharya B.P.
      • Dhimal M.
      • et al.
      Descriptive Epidemiology of Scrub Typhus in Nepal, 2017 Nepal Health Research Council (NHRC) Descriptive Epidemiology of Scrub Typhus in Nepal, 2017 Authors.
      2016Chiggers mite samplesPCR33.3% (1/3)Prospective
      Nepal Health Research Council (NHRC)
      • Karki K.B.
      • Acharya B.P.
      • Dhimal M.
      • et al.
      Descriptive Epidemiology of Scrub Typhus in Nepal, 2017 Nepal Health Research Council (NHRC) Descriptive Epidemiology of Scrub Typhus in Nepal, 2017 Authors.
      2016National Public Health Laboratory, KathmanduELISA60.0% (30/50)Prospective
      IFA52.0% (26/50)Prospective
      Nepal Health Research Council (NHRC)
      • Karki K.B.
      • Acharya B.P.
      • Dhimal M.
      • et al.
      Descriptive Epidemiology of Scrub Typhus in Nepal, 2017 Nepal Health Research Council (NHRC) Descriptive Epidemiology of Scrub Typhus in Nepal, 2017 Authors.
      2016ChitwanIFA27.3% (3/11)Prospective
      Pathak et al.,
      • Pathak S.
      • Chaudhary N.
      • Dhakal P.
      • et al.
      Clinical profile, complications and outcome of scrub typhus in children: a hospital based observational study in central Nepal.
      2016-2017ChitwanELISA24.4% (76/312)Prospective
      Shah et al.,
      • Kumar Sah R.
      • Chapagain R.H.
      • Shrestha S.M.
      • Kumar Rai G.
      Clinico-laboratory profile and therapeutic outcome of serologically confirmed scrub typhus in children in tertiary care Children's hospital of Nepal.
      2016-2018Kanti Children HospitalSerological tests2016: 37.1%

      2017: 61.3%

      2018: 1.6%
      Retrospective
      This all has been speculated most likely to be due to creation of favorable niche due to aftermath and debris created by the earthquake, overcrowding in temporary makeshift camps, poor sanitation and health hygiene, large scale human and rat/mice habitat destruction, and population dislocation that resulted in rats abandoning their underground habitat,
      • Karki K.B.
      • Acharya B.P.
      • Dhimal M.
      • et al.
      Descriptive Epidemiology of Scrub Typhus in Nepal, 2017 Nepal Health Research Council (NHRC) Descriptive Epidemiology of Scrub Typhus in Nepal, 2017 Authors.
      ,
      • Nayak N.
      Scrub typhus in Nepal.
      • Thapa S.
      • Sapkota L.B.
      • Hamal P.
      Threat of scrub typhus in post-earthquake Nepal.
      • Bastola A.
      • Pant N.
      An outbreak of scrub typhus in Nepal following the 2015 Gorkha earthquake.
      coming in close proximity of human dwellings and thus, breeding sites of vectors and reservoirs, and altered epidemiological behavior of vectors/reservoirs.
      The outbreaks alarmed health authority and hence Epidemiology and Disease Control Division (EDCD) developed an interim guideline on Prevention and Control of Scrub Typhus in Nepal.
      However, the public have poorly opted and implemented these guidelines as evidenced by recent rise on the cases of scrub typhus in Nepal. A number of tests have been developed for diagnosis of this condition. Weil Felix test and ELISA test are among these most frequently used tests in Nepal.
      • Sedhain A.
      • Bhattarai G.R.
      Clinical presentation of scrub typhus during a major outbreak in central Nepal.
      Weil-Felix is less sensitive test characterized by low efficiency, which can be referred in primary health centers and hospitals. However, more simple and rapid tests like dipstick can be arranged in primary hospital which is more efficient, sensitive and specific than Weil-Felix test. In the reference laboratory, tests like IgM ELISA and gold standard tests like Immuno-fluorescent Assay (IFA) and Indirect Immuno-peroxidase assay (IIPA) could be conducted. Real time PCR (RT-PCR) which is highly specific, if feasible could be employed to antigen detection. But, high technical savviness and expenses,
      • Koh G.C.K.W.
      • Maude R.J.
      • Paris D.H.
      • Newton P.N.
      • Blacksell S.D.
      Review: diagnosis of scrub typhus.
      hinders its application in Nepalese condition.
      Currently, scrub typhus is not considered a priority disease in Nepal. Diseases like avian influenza, leptospirosis, brucellosis, rabies and other similar zoonotic infection that cause heavy socio-economic burden, have received attention of Government of Nepal and hence are among the top ten priority zoonotic diseases.
      • Ministry of Health D.
      Annual report 2072/73 (2015/2016).
      • Acharya K.P.
      • Karki S.
      • Shrestha K.
      • Kaphle K.
      One health approach in Nepal: scope, opportunities and challenges.
      Almost all health sector budget, allocated for the disease control and prevention, is used up for the prevention and control of these prioritized diseases. With the availability of limited budget and resource allocation in health sector, the government is unable to spend financial resources for prevention and control of every disease with equal emphasis.
      Putting the facts together, medical and para-medical staff training and education, availability of cost effective diagnostic methods and an effective program to assure prompt treatment, should be initiated as there is always an ever existing danger of disease re-emergence. The situation could also be handled in a better way by proactive management strategies for mice/rat control and improving sanitation, public health and hygiene conditions for the people at most risk. Last but not least, primary health workers and medical professionals should be trained on early case detection, personal protection, proactive rodent control strategies, habitat destruction and good sanitation/hygiene practices. Thus, a nationwide study is needed to identify the niche and track scrub typhus, an important issue of high public health concern while emphasizing on its future epidemiological characterization and ecological studies in Nepal.

      Declaration of competing interest

      No competing interest.

      Acknowledgements

      The author is thankful to the Dr. Prerana Sedhain Bhattarai, Dr. Krishna Kaphle for their inputs and valuable suggestions. Thanks are also due to two reviewers for their constructive comments without which this paper would not have been in the present shape.

      List of abbreviations

      FUO
      Fever of unknown origin
      ELISA
      Enzyme linked immuno sorbent Assay
      IFA
      Immuno-fluorescence Assay
      IIPA
      Indirect Immuno-peroxidase assay
      EDCD
      Epidemiology and Disease Control Division
      RT-PCR
      Real time polymerase chain reaction
      NHRC
      Nepal Health Research Council

      Ethics approval and consent to participate

      Not applicable (NA).

      Consent for publication

      Not applicable (NA).

      Availability of data and material

      All data generated or analyzed during this article preparation from published articles are referenced in author & ref. column of table.

      Funding

      No funding was available.

      Authors' contributions

      KPA designed study, KPA and NA did literature review and prepared the manuscript, KPA, NA and MT extensively revised the manuscript, read and approved the final manuscript.

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