Low castes have poor access to visceral leishmaniasis treatment in Bihar,India

Objectives Bihar, the poorest state in India, concentrates most of the visceral leishmaniasis (VL) cases in the country. A large proportion of the poor rural communities where VL is endemic are marginalized by their socio‐economic status, intrinsically related to the caste system. In this study, we evaluated whether people from low socio‐economic strata had difficulties accessing VL treatment in Bihar. As a secondary outcome, we evaluated whether people delaying their VL treatment had poorer clinical indicators at admission. Methods Data on 2187 patients with VL treated by Médecins Sans Frontières (MSF) in Vaishali district from July 2007 to December 2008 were analysed. Patients who reported having onset of symptoms ≥8 weeks before admission were defined as ‘late presenters’. Logistic regression models were used to evaluate whether low castes had higher risk to be ‘late presenters’ compared to the rest of castes and whether ‘late presenters’ had poorer indicators at admission (i.e. haemoglobin level, spleen size). Results After adjusting for age, gender and distance to VL treatment facility, Mushars (the lowest caste in Bihar) had twice the odds to be ‘late presenters’ compared to the rest of castes (OR 2.05, 95% CI: 1.24–2.38). Subjects that had VL symptoms for ≥8 weeks had a larger spleen and lower haemoglobin level than those that were treated earlier. Conclusion Low castes have poor access to VL treatment in Bihar, and late presenters have poorer clinical indicators at admission. These findings have implications at individual and community levels and should stimulate targeted VL control programmes to ensure that marginalized communities in Bihar are properly treated.     

Serological markers for leishmania donovani infection in Nepal: Agreement between direct agglutination test and rK39 ELISA

Visceral leishmaniasis (VL) is an important vector-borne disease caused by Leishmania donovani in the Indian subcontinent. The actual incidence and role of asymptomatic infections in the region are not wellknown. We used the direct agglutination test (DAT) and the rK39 ELISA as L. donovani infection markers in 10 VL endemic villages in Nepal. DAT titre distribution showed two subgroups in the population (infected and non-infected individuals), while rK39 did not. The agreement between both tests was moderate (j = 0.53; 95% CI 0.49–0.57). More research is needed to develop validated markers for Leishmania infection.     

Sensitivity and specificity of the Leishmania OligoC‐TesT and NASBA‐oligochromatography for diagnosis of visceral leishmaniasis in Kenya

Objective To estimate the sensitivity and specificity of the OligoC‐TesT and nucleic acid sequence‐based amplification coupled to oligochromatography (NASBA‐OC) for molecular detection of Leishmania in blood from patients with confirmed visceral leishmaniasis (VL) and healthy endemic controls from Kenya. Methods Blood specimens of 84 patients with confirmed VL and 98 endemic healthy controls from Baringo district in Kenya were submitted to both assays. Results The Leishmania OligoC‐TesT showed a sensitivity of 96.4% (95% confidence interval [CI]: 90–98.8%) and a specificity of 88.8% (95% CI: 81–93.6%), while the sensitivity and specificity of the NASBA‐OC were 79.8% (95% CI: 67–87%) and 100% (95% CI: 96.3–100%), respectively. Conclusion Our findings indicate high sensitivity of the Leishmania OligoC‐TesT on blood while the NASBA‐OC is a better marker for active disease.     

Latent class analysis of diagnostic tests for visceral leishmaniasis in Brazil

Objective To estimate the sensitivities and specificities of different diagnostic tests for visceral leishmaniasis (VL) using latent class analysis (LCA). Methods This study was performed using data from a prospective study conducted in four Brazilian states from May 2004 to May 2007. Five diagnostic tests for VL were evaluated in 285 VL cases and 119 non‐cases: microscopy, indirect fluorescence antibody test (IFAT), enzyme‐linked immunosorbent assay using recombinant K39 antigen (rK39‐ELISA), direct agglutination test (DAT) and the rK39 rapid test. Results Microscopy showed sensitivity of 77.0% (CI: 71.5–81.5) and specificity of 99.0% (CI: 94.0–99.7). The IFAT and the DAT showed similar sensitivities, 88.3% (CI: 84.0–92.0) and 88.5% (CI: 84.1–92.0), respectively, but the DAT had a higher specificity (95.4%, CI: 89.2–98.1) than did the IFAT (83.0%, CI: 75.0–88.2). The rK39‐ELISA and the rK39 rapid test showed sensitivities of 99.0% (CI: 96.3–99.6) and 94.0% (CI: 90.1–96.3), and specificities of 82.5% (CI: 75.0–88.3) and 100% (CI: 97.0–100.0%), respectively. Conclusions Considering the lack of an adequate reference standard, LCA proved to be a useful tool in validating diagnostic methods for VL. The DAT and the rK39 rapid test showed better performance. Thus, clinically suspected cases of VL in a Brazilian endemic area could be treated based on the positivity of one of these tests.     

Drug regimens for visceral leishmaniasis in Mediterranean countries

Until the early 1990s, pentavalent antimony was the only documented first-line drug employed for the treatment of zoonotic visceral leishmaniasis (VL) in the Mediterranean, with reported cure rates exceeding 95% in immunocompetent patients. The emergence of antimony resistance in other endemic settings and the increase in drug options have stimulated re-evaluation of the current therapeutic approaches and outcomes in Mediterranean countries. A scientific consortium ('LeishMed' network) collected updated information from collaborating clinical health centres of 11 endemic countries of Southern Europe, Northern Africa and the Middle East. In contrast with the previous situation, VL is now treated differently in the region, basically through three approaches: (1) In Northern Africa and in part of the Middle East, pentavalent antimony is still the mainstay for therapy, with no alternative drug options for treating relapses; (2) In some European countries and Israel, both pentavalent antimony and lipid-associated amphotericin B (AmB) formulations are used as first-line drugs, although in different patients' categories; (3) In other countries of Europe, mainly liposomal AmB is employed. Importantly, cure rates exhibited by different drugs, including antimonials in areas where they are still in routine use, are similarly high (>/=95%) in immunocompetent patients. Our findings show that antimony resistance is not an emerging problem in the Mediterranean. A country's wealth affects the treatment choice, which represents a balance between drug efficacy, toxicity and cost, and costs associated with patient's care.     

Molecular epidemiology of cutaneous leishmaniasis and heterogeneity of Leishmania major strains in Iran

Objective To determine the geographical distribution of Leishmania species causing cutaneous leishmaniasis (CL) and to study the genetic heterogeneity of Leishmania major isolates from different endemic areas of Iran. Methods A total of 341 isolates from lesions of patients living in 11 provinces of Iran were grown in culture medium and inoculated to BALB/c mice to detect possible visceralisation. The species were identified by isoenzyme analysis using a battery of six enzymes and kinetoplast (k) DNA‐PCR technique. Genetic variation among L. major isolates was analysed by random amplified polymorphic DNA (RAPD) technique. Results Of the total 341 isolates, 283 isolates were L. major and 58 isolates were Leishmania tropica. In rural areas, the causative agent of CL was mainly L. major (95%L. major vs. 5%L. tropica), in urban areas it was L. tropica (65%L. tropica vs. 35%L. major). All isolates of L. major and 8.6% of L. tropica isolates showed visceralisation in BALB/c mice. There is considerable genetic diversity between L. major strains from different endemic areas and even between some isolates of the same endemic area. Conclusion Leishmania major is the most frequent species in the endemic areas of CL in eleven provinces of Iran, and genetic diversity is a common feature of L. major in the country.     

Clinical characteristics and treatment outcome of patients with visceral leishmaniasis and HIV co‐infection in northwest Ethiopia

Objectives To describe the clinical presentation of patients with visceral leishmaniasis (VL) with and without human immunodeficiency virus (HIV) co‐infection and factors associated with poor outcome in northwest Ethiopia. Method Retrospective review of 241 patients with VL (92 with and 149 without HIV co‐infection). Results HIV co‐infection was present in 92 (38%) of the patients. Clinical presentation of VL was indistinguishable between patients with and without HIV co‐infection. Co‐infected patients had a poorer outcome i.e. either death or treatment failure (31.5%vs. 5.6%, P < 0.001). The presence of tuberculosis or sepsis syndrome among patients with VL and HIV co‐infected independently predicted death or treatment failure [odds ratio 4.5 (95% CI 1.47–13.92, P = 0.009) and 9.1 (95% CI 2.16–37.97, P = 0.003), respectively]. Despite having similar clinical presentation at the time of diagnosis, VL and HIV co‐infected patients had a higher mortality and treatment failure than immunocompetent patients. Conclusion The frequency of HIV co‐infection among patients with VL is high in the study area, and this co‐infection was associated with death or treatment failure. The clinical management of VL in HIV co‐infected patients is a major challenge that requires new treatment approaches to improve its outcome.