Sujeet Raina, D.M. Mahesh, Rashmi Kaul, Kaushal S. Satinder, Dilip Gupta, Ashok Sharma & Surinder Thakur

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J Vector Borne Dis 46, December 2009, pp. 303–306A new focus of visceral leishmaniasis in the Himalayas, IndiaSujeet Rainaa, D.M. Mahesha, Rashmi Kaulb, Kaushal S. Satindera, Dilip Guptaa,Ashok Sharmaa & Surinder ThakuraaDepartment of Medicine, bDepartment of Pathology, Indira Gandhi Medical College, Shimla, IndiaKey words Himalayas – India – visceral leishmanisisVisceral leishmaniasis (VL), commonly known askala-azar in Indian subcontinent is a major publichealth problem and >90% of cases are from India,Bangladesh, southern Sudan, Nepal and north-eastBrazil. VL affects more than 1,00,000 persons everyyear in India and occurs epidemically and endemi-cally in well-defined areas in the eastern parts of thecountry, mainly Bihar, West Bengal, the eastern dis-tricts of Uttar Pradesh, Assam and the foothills ofSikkim1. Despite its widespread geographic distri-bution, leishmaniasis in humans is often focal withinan endemic area, leading to ‘hotspots’ of diseasetransmission2.Visceral leishmaniasis is a disease of low altitude; itdoes not occur in altitudes over 2000 ft (600 m)3.However, cases have been reported from natives ofsub- Himalayan region, India. The existence of apocket of the disease and vector in the Kumaon(350–900 m above mean sea level) and Garhwal(1500–2500 m above mean sea level) region ofthe non-endemic north Indian hilly state ofUttarakhand has already been established recently1,4.Few sporadic cases have been reported fromHimachal Pradesh  in the past but details aboutaltitude are not available5,6. In an another report fromthis state two cases of VL were diagnosed in nativesliving at an altitude of 2300 and 3000 m respectively7.However, the incidence of the disease is still increas-ing, and 18 cases of VL have since been recordedfrom January 2003 to December 2007. In thisreport, we present results of epidemiological,clinical investigative and therapeutic features of thesecases identified in this new focus. The possible modeof its introduction in the region is postulated.The study was conducted in the Department of Medi-cine, Indira Gandhi Medical College, Shimla(Himachal Pradesh), India. Eighteen cases were di-agnosed over a five year period from January 2003to December 2007. The patients of our study werediagnosed as VL by clinical findings and confirmedby demonstration of amastigotes (Leishmaniadonovani bodies) in bone marrow smears of 15 pa-tients and in splenic smears of three cases. None ofour patients reported to have been out of the state ordistrict during the three years preceding onset ofsymptoms. All the patients lived in a rural area andwere engaged in cattle rearing and agricultural andhorticultural activities, four were state governmentemployees and one was a student. All the patientsexcept one lived in a sub-alpine valley along the Satlujriver that leads to the mountain deserts of the tribaldistrict of Kinnaur and adjacent area of Shimla andKullu districts (Fig. 1).Eight patients belonged to Kinnaur district, sevenwere from Rampur subdivision of Shimla district andtwo patients were from Nirmand subdivision of Kulludistrict. One patient belonged to Beas river valleyarea in Hamirpur district. The altitude of these areasranges between 924 and 2960 m above the mean sealevel. The terrain of the Kinnaur district is dry andsandy with loose rocks. The minimum temperaturein the winter at the district headquarters is –7°C andmaximum is 13°C. The minimum temperature in thesummer at the district headquarters is 8°C and maxi-mum is 25°C . The average temperature is 1.5°C and J  VECTOR  BORNE  DIS  46, DECEMBER 2009 30416.2°C in December and June, respectively. Theannual average rainfall is 28.1 mm and the snowfallranges from 64 to 1399 mm. In Kullu district, themaximum temperature is 38.8°C and minimum is5.2°C in winter. The average rainfall in the Kullu Val-ley is 80 cm. Heavy frost occurs during December toFebruary. Snowfall generally occurs during Decem-ber and January. In Rampur area of Shimla district,the rainfall as well as temperature is slightly higherand the area does not get snowfall8.Of the 18 VL cases, 15 were males and three werefemales. The median age was 34 yr, with the oldestpatient being a 65 yr old man and the youngest an18 yr old girl. All the patients reported fever. Theduration between the onset of fever till diagnosisvaried from six weeks to one year with the medianperiod being three months. Other clinical features re-ported were weight loss in all the patients, epistaxisin five and diarrhoea in three. Splenomegaly wasfound in all the cases and massive splenomegaly wasnoted in 14 cases. Hepatomegaly was detected in11 patients. Lymphadenopathy was seen in eightcases. Significant axillary lymphadenopathy wasnoted in seven patients, cervical lymphadenopathyin three and retroperitoneal in two patients.Amastigotes (Leishmanaia bodies) were isolated onFNAC from lymphnodes in two patients. Three pa-tients had pedaledema and ascites was present in two.None of the patients had jaundice or hyperpigmen-tation. Eight patients were also evaluated for theirHIV status and all were found negative. All the pa-tients were anaemic. Dimorphic anaemia was thecommonest type of anaemia. Leucopenia was presentin seven patients and thrombocytopenia in six pa-tients. The differential leucocyte count revealed rela-tive lymphocytosis in eight patients. ESR was raisedin 14 patients. Five patients had hypoalbuminemia.Fig. 1: Study area showing geographic distribution of patients. Figures in parentheses depict number of patients from thatlocation.N 305 RAINA  ET AL: VISCERAL LEISHMANIASIS IN HIMALAYASSerum transaminases were raised in six patientsthough bilirubin was normal in all the patients. Renalfunctions were deranged in two patients. All patientswere administered sodium stibogluconate at a doseof 20 mg/kg/day for 4 wk. Clinical cure was achievedin 14 out of 18 cases. Four patients died during thetreatment in the hospital. The parameters for afavourable therapeutic response were disappearanceof symptoms and resolution of splenic size and lackof recurrence of symptoms during six months of fol-low-up.The clinical picture in our cases is generally similarto that already established in Indian patients but cer-tain clinical features need emphasis because of un-common manifestations. Leishmanial lymphadeno-pathy, an interesting feature noticed in our cases hasbeen stressed as an extremely rare feature in Indiankala-azar. Most of our cases were relatively fairskinned, and none of them had hyperpigmentation.The present report of a visceral leishmaniasis focusin a previously non-endemic area raises few basicquestions about the understanding of kala-azar epi-demiology in this area. The fact that all our patientshad contracted the disease indigenously is sugges-tive of a local vector and probably a zoonotic reser-voir. Six species of Phlebotomus and 15 species ofSergentomyia have been found in the northern moun-tain ranges of the Himalayas (Himachal Pradesh issituated in these ranges), with their distribution lim-ited to particular ecoclimatic zones9. Survey ofsandflies in the Himalayan region has established thepresence of Phlebotomus argentipes, P. longiductusand P. major (Diptera: Psychodidae) in this area9,10.A new focus of localised cutaneous leishmaniasis andvector has already been established along the Satlujriver valley in the mountainous region of non-endemicnorth-west Himachal Pradesh very recently. The char-acterization of Leishmania strains by polymerasechain reaction-restriction fragment length polymor-phism (PCR-RFLP) of the ribosomal gene region of10 biopsy specimens revealed presence of both L.tropica and L. donovani in these patients of localisedcutaneous leishmaniasis8. Similar characterization ofthe Leishmania species by PCR is required in pa-tients of VL.Identification of the sandflies collected from theperidomestic environment of the patients of localisedcutaneous leishmaniasis, revealed the presence of P.longiductus, P. major and P. kandelaki in this belt8.Their role as a vector for transmission of VL, in thisparticular region needs to be delineated by demon-strating similar strains of Leishmania in both the vec-tor and the human host. Also lymphadenopathy, acommon feature in this focus raises the possibility ofa new vector or a variant of the disease. More epide-miological work is required in this naïve area.The recent emergence of VL in this area of HimachalPradesh appears to be due to construction activities,horticulture development, and establishment of newresidential colonies leading to destruction of forestsand intrusion into the sylvatic cycle. With the pres-ence of major River Sutlej and few other small rivu-lets the hydroelectric potential of this area has beenexploited in last 20 years. This has resulted in con-struction of at least three major and few minor hy-droelectric power projects. The labourers employedare mainly from the known endemic areas of Bihar,Jharkhand, Uttar Pradesh and Nepal. It is still notclear whether the parasite has come from sylvaticcycle or introduced by migrant population. The cattlekept close to the houses by people in rural areas arealso known to attract both anthropophilic, as well aszoophilic vectors11. Moreover, adaptation of the vec-tor, as well as the parasite, to strange, often bizarrehabitats is well-known. Two studies have indicatedpotential changes in the geographical distribution ofthe vectors. Modelling studies in south-west Asiahave indicated potential range expansion of P.papatasi with global warming12. In Italy, VL causedby L. infantum is prevalent in the milder parts, whereit is transmitted by P. perniciosus. Low temperatureappears to be one of the main factors preventing itsspread into northern Europe13. Indian kala-azar is acomplete anthroponosis. There is no known animalreservoir involved in its transmission. However, kala-azar in several other parts of the world is a zoonosis, J  VECTOR  BORNE  DIS  46, DECEMBER 2009 306involving canine reservoirs, principally dogs, foxesand jackals4. Epidemiological work is required in thisarea to substantiate the presence or absence of anyzoonotic reservoir.Although the clinical presentation was more or lessclassical, the first diagnosis was other than kala-azarin most of the cases. The correct initial diagnosis wasmade more often with greater awareness and experi-ence of the occurrence of this disease in this area.Initial failure to suspect kala-azar in this area mightcause a diagnostic delay. It is important to mentionthat 14 patients responded to sodium stibogluconatetreatment and had a favourable therapeutic responsewithout recurrence of symptoms during 6 months offollow-up. References1. Verma SK, Ahmed S, Shirazi N, Kusum A, Kaushik RM,Barthwal SP. Sodium stibogluconate-sensitive visceralleishmaniasis in the non-endemic hilly region ofUttarakhand, India. Trans R Soc Trop Med Hyg 2007;101: 730–2.2. Desjeux P. The increase in risk factors for leishmaniasisworldwide.  Trans R Soc Trop Med Hyg 2001; 95:239–43.3. Park K. Leishmaniasis. In: Park K, editor. Park’s Text-book of Preventive and Social Medicine. VI edn. Jabalpur,India:  Banarsidas Bhanot 2007; p. 256–8.4. Singh S, Biswas A, Wig N, Aggarwal P, Sood R, Wali JP.Corresponding author: Dr Sujeet Raina, Fire Officers Building, Stokes Place, Shimla–171 002, India.E-mail: sujeetrashmishera@yahoo.co.inReceived: 17 November 2008         Accepted in revised form: 11 October 2009A new focus of visceral leishmaniasis in sub-Himalayan(Kumaon) region of northern India. J Commun Dis 1999;31: 73–7.5. Naik SR, Rao PN, Datta DV, Mehta SK, Mahajan RC,Mehta S, et al. Kala-azar in north-western India: a study of24 patients. Trans R Soc Trop Med Hyg 1979; 73: 61–5.6. Dutta U, Rajwanshi A, Rayat CS, Sakhuja V, Sehgal S.Kala-azar in Himachal Pradesh: a new pocket. J AssocPhysic India 1984; 32: 1072–3.7. Mahajan SK, Machhan P, Kanga A, Thakur S, SharmaA, Prasher BS, et al. Kala-azar at high altitude. J CommunDis 2004; 36: 117–20.8. Sharma NL, Mahajan VK, Kanga A, Sood A, Katoch VM,Mauricio I, et al. Localized cutaneous leishmaniasis dueto Leishmania donovani and Leishmania tropica: prelimi-nary findings of the study of 161 new cases from a newendemic focus in Himachal Pradesh, India. Am J TropMed Hyg 2005; 72: 819–24.9. Kaul SM, Jain DC. Distribution of phlebotomine sandflies(Diptera: Psychodidae) according to the physiographicdivisions of India. J Commun Dis 1995; 27: 155–63.10. Kulkarni SM, Bhat HR, Modi GB. Survey of phlebotomidsandflies from the Himalayan region, India (Diptera:Phlebotomidae). Indian J Med Res 1978; 67: 583–8.11. Control of leishmaniasis. Geneva: World Health Organi-zation.  WHO Tech Rep Ser 1990; 793: 66–94.12. Cross ER, Hyams KC. The potential effect of global warm-ing on the geographical and seasonal distribution of Phle-botomus papatasi in Southwest Asia. Environ HealthPerspect 1996; 104: 724–7.13. Kuhn KG. Global warming and leishmaniasis in Italy.Bull Trop Med Int Health 1999; 7:1–2.

A new focus of visceral leishmaniasis in the Himalayas, India

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