Leishmania–HIV co-infection: An emerging problem in India : AIDS

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Correspondence

Leishmania–HIV co-infection: An emerging problem in India

Redhu, Naresh S; Dey, Ayan; Balooni, Veena; Singh, Sarman

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AIDS 20(8):p 1213-1215, May 12, 2006. | DOI: 10.1097/01.aids.0000226971.42622.4e
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Leishmaniasis is emerging as third most frequent opportunistic infection in AIDS patients in various parts of the world particularly in Leishmania endemic countries where in 25–70% of adult cases of visceral leishmaniasis or kala-azar are found to be HIV co-infected [1]. The Leishmania–HIV co-infection has serious implications for patient management as the visceral strains can manifest in atypical forms localizing to mucus membranes and skin while dermotrophic strains can cause visceral disease [2,3].

So far, 33 countries have reported HIV–Leishmania co-infections. Of the first 1700 co-infections reported to the World Health Organization until 1998, 1440 cases were from south-western Europe, mainly Spain (835) followed by Italy (229); France (259); and Portugal (117) [4]. In the Americas, most co-infections are reported from Brazil [5]. In Africa, the number of cases is expected to rise but the actual figures are not available [6].

In Asia, it is likely that a number of cases are missed due to the poor reporting system and lack of diagnostic facilities. In India, the first co-infection was reported in 1999 from the sub-Himalayan (Kumaon) region [7]. Later five more reports of Leishmania–HIV co-infection were published [2,8–11].

Our study population comprised 100 patients with clinical suspicion of kala-azar seen or hospitalized in the last 4 years at the All India Institute of Medical Sciences, New Delhi, a tertiary care hospital. The diagnosis of leishmaniasis was made by demonstrating Leishman-Donovan (LD) bodies in the tissue of relevance followed by antibody detection using recombinant antigens from Leishmania chagasi, rK39 [12] and another from Leishmania donovani, rKE-16 [13]. The tests were performed with appropriate negative and positive controls. Positive samples were tested for HIV using standard methods and confirmed by western blot (BioRad, Maines-La-Coquette, France). The samples positive for LD bodies and anti-Leishmanial antibodies by both the antigens in qualitative screening tests were further analysed by rKE-16 quantitative ELISA using a twofold serial dilution in phosphate-buffered saline (from 1: 100 to 1: 4096000) to determine the end-point titers, as published previously [13].

Of 100 patients with clinical suspicion of leishmaniasis, 25 were confirmed by parasitology and serology to have leishmaniasis. Of the 25 patients, 19 (76%) were male and six (24%) were female. The age of patients ranged from 2.5 years to 61 years with overall mean of 25 ± 17.3 years. Of these only six (24%) were found to be HIV–Leishmania co-infected. One patient had triple infection of Leishmania, Mycobacterium tuberculosis and HIV. The anti-leishmania antibody end-point titers were found to be significantly lower in co-infected cases (P < 0.017) than the HIV uninfected patients (Fig. 1).

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Fig. 1:
Mean anti-rKE-16 anti- Leishmania antibody end-point titers in Leishmaniasis patients with HIV (n = 6) and without HIV co-infection (n = 19).

Visceral leishmaniasis is characterized by a strong humoral response in otherwise immunocompetent patients [12]. This phenomenon has been exploited to devise various non-parasitological non-specific diagnostic methods, such as aldehyde test, Sia test and albumin: globulin ratio determination [14]. In the past three decades some specific antibody detection methods have been developed which were used in this study. In 19 HIV-negative patients the anti-Leishmania antibody titres were found to be very high (upto 4 × 106), as reported earlier [12]. However, the antibody response in six co-infected patients was significantly (P < 0.017) low (Fig. 1). Similar findings have been reported by Medrona et al. from Spain [15]. In our patients, four of the six (66.6%) Leishmania–HIV co-infected patients showed end-point titers below 1: 10 × 104 dilutions, whereas in all HIV-negative patients, the antibody titers were higher than 1: 10 × 105.

Geographically, of six cases four were from Bihar (Eastern India), an old endemic state, and two were from Uttaranchal (North India). The latter has recently been found to be a new focus of leishmaniasis [7].

Both HIV and Leishmania spp. are obligate intracellular parasites. It is reported that like HIV, Leishmania infection causes depletion of T-helper cells [16]. HIV-related immunosuppression increases the risk of reactivating leishmaniasis by 100–1000 times in endemic areas and enhances the chances of drug resistant leishmaniasis [17].

The present study presents two major observations. First, HIV–Leishmania coinfection is an emerging problem in India and more awareness is required. Second, humoral response to Leishmania is severely compromised in HIV co-infected patients. Therefore, one may think of separate test cut-off values for making the diagnosis of leishmaniasis in HIV infected patients. It will also be advisable for manufactures of diagnostic kits and tests to mention this limitation and prepare appropriate test guidelines.

References

1. Guerin PJ, Olliaro P, Sundar S, Boelaert M, Croft SL, Desjeux P, et al. Visceral leishmaniasis: current status of control, diagnosis, and treatment, and a proposed research and development agenda. Lancet Infect Dis 2002; 2:494–501.
2. Singh S. Mucosal Leishmaniasis in an Indian AIDS patient. Lancet Infect Dis 2004; 4:660–661.
3. Pratlong F, Dedet JP, Marty P, Portus M, Deniau M, Dereure J, et al. Leishmania–human immunodeficiency virus coinfection in the Mediterranean basin: isoenzymatic characterization of 100 isolates of the Leishmania infantum complex. J Infect Dis 1995; 172:323–326.
4. Desjeux P, Meert JP, Piot B, Alwar J, Medrano FJ, Portus M, et al. Leishmania/HIV co-infection, South Western Europe 1990–98. Document WHO/LEISH/2000. 42, Geneva: World Health Organization.
5. Rabello A, Orsini M, Disch J. Leishmania/HIV coinfection in Brazil: an appraisal. Ann Trop Med Parasitol 2002; 97:17–28.
6. Paredes R, Munoz J, Diaz I, Domingo P, Gurgui M, Clotet B. Leishmaniasis in HIV infection. J Post Grad Med 2003; 49:39–49.
7. Singh S, Biswas A, Wig N, Aggarwal P, Sood R, Wali JP. A new focus of visceral leishmaniasis in sub-Himalayan (Kumaon) region of northern India. J Commun Dis 1999; 31:73–77.
8. Singh S, Kumar J, Singh R, Dwivedi SN. Hepatitis B and C viral infections in Indian kala-azar patients receiving injectable anti-leishmanial drugs: a community- based study. Int J Infect Dis 2000; 4:203–208.
9. Singh S, Dwivedi SN, Sood R, Wali JP, Hepatitis B. C and human immunodeficiency virus infections in multiply injected kala-azar patients in Delhi. Scand J infect Dis 2000; 32:3–6.
10. Sinha PK, Rabidas VN, Pandey K, Verma N, Gupta AK, Ranjan A, et al. Visceral Leishmaniasis and HIV Co-infection in Bihar, India [Letter]. J Acquir Immune Defic Syndr 2003; 32:115–116.
11. Pandey K, Sinha PK, Ravidas VN, Kumar N, Verma N, Lal CS, et al. Nexus of infection with Human Immunodeficiency Virus, pulmonary tuberculosis and visceral Leishmaniasis: A case report from Bihar, India. Am J Trop Med Hyg 2005; 72:30–32.
12. Singh S, Kumari V, Singh N. Predicting kala-azar disease manifestations in asymptomatic patients with latent Leishmania donovani infection by detection of antibody against recombinant K39 antigen. Clin Diagn Lab Immunol 2002; 9:568–572.
13. Sivakumar R, Sharma P, Chang KP, Singh S. Cloning, expression, and purification of a novel recombinant antigen from Leishmania donovani. Protein Expr Purif 2006; 46:156–165.
14. Singh S, Sivakumar R. Recent advances in the diagnosis of leishmaniasis. J Postgrad Med 2003; 49:55–60.
15. Medrano FJ, Canãvate C, Leal M, Rey C, Lissen E, Alvar J. The role of serology in the diagnosis and prognosis of visceral Leishmaniasis in patients co-infected with HIV-1. Am J Trop Med Hyg 1998; 59:155–162.
16. Mosier D, Sieburg H. Macrophage-tropic HIV: critical for AIDS pathogenesis? Immunol Today 1994; 15:332–339.
17. Aranka A. Treating HIV/AIDS and Leishmaniasis co infection in Ethiopia. JAMC 2005; 11:172.
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