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      Visceral Leishmaniasis and HIV Coinfection in East Africa

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          Abstract

          Visceral Leishmaniasis (VL) is an important protozoan opportunistic disease in HIV patients in endemic areas. East Africa is second to the Indian subcontinent in the global VL caseload and first in VL-HIV coinfection rate. Because of the alteration in the disease course, the diagnostic challenges, and the poor treatment responses, VL with HIV coinfection has become a very serious challenge in East Africa today. Field experience with the use of liposomal amphotericin B in combination with miltefosine, followed by secondary prophylaxis and antiretroviral drugs, looks promising. However, this needs to be confirmed through clinical trials. Better diagnostic and follow-up methods for relapse and prediction of relapse should also be looked for. Basic research to understand the immunological interaction of the two infections may ultimately help to improve the management of the coinfection.

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          The relationship between leishmaniasis and AIDS: the second 10 years.

          Jorge Alvar, Pilar Aparicio, Abraham Aseffa … (2008)
          To date, most Leishmania and human immunodeficiency virus (HIV) coinfection cases reported to WHO come from Southern Europe. Up to the year 2001, nearly 2,000 cases of coinfection were identified, of which 90% were from Spain, Italy, France, and Portugal. However, these figures are misleading because they do not account for the large proportion of cases in many African and Asian countries that are missed due to a lack of diagnostic facilities and poor reporting systems. Most cases of coinfection in the Americas are reported in Brazil, where the incidence of leishmaniasis has spread in recent years due to overlap with major areas of HIV transmission. In some areas of Africa, the number of coinfection cases has increased dramatically due to social phenomena such as mass migration and wars. In northwest Ethiopia, up to 30% of all visceral leishmaniasis patients are also infected with HIV. In Asia, coinfections are increasingly being reported in India, which also has the highest global burden of leishmaniasis and a high rate of resistance to antimonial drugs. Based on the previous experience of 20 years of coinfection in Europe, this review focuses on the management of Leishmania-HIV-coinfected patients in low-income countries where leishmaniasis is endemic.
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            Post-kala-azar dermal leishmaniasis.

            E Zijlstra, A. M. Musa, E A G Khalil … (2003)
            Post-kala-azar dermal leishmaniasis (PKDL) is a complication of visceral leishmaniasis (VL); it is characterised by a macular, maculopapular, and nodular rash in a patient who has recovered from VL and who is otherwise well. The rash usually starts around the mouth from where it spreads to other parts of the body depending on severity. It is mainly seen in Sudan and India where it follows treated VL in 50% and 5-10% of cases, respectively. Thus, it is largely restricted to areas where Leishmania donovani is the causative parasite. The interval at which PKDL follows VL is 0-6 months in Sudan and 2-3 years in India. PKDL probably has an important role in interepidemic periods of VL, acting as a reservoir for parasites. There is increasing evidence that the pathogenesis is largely immunologically mediated; high concentrations of interleukin 10 in the peripheral blood of VL patients predict the development of PKDL. During VL, interferon gamma is not produced by peripheral blood mononuclear cells (PBMC). After treatment of VL, PBMC start producing interferon gamma, which coincides with the appearance of PKDL lesions due to interferon-gamma-producing cells causing skin inflammation as a reaction to persisting parasites in the skin. Diagnosis is mainly clinical, but parasites can be seen by microscopy in smears with limited sensitivity. PCR and monoclonal antibodies may detect parasites in more than 80% of cases. Serological tests and the leishmanin skin test are of limited value. Treatment is always needed in Indian PKDL; in Sudan most cases will self cure but severe and chronic cases are treated. Sodium stibogluconate is given at 20 mg/kg for 2 months in Sudan and for 4 months in India. Liposomal amphotericine B seems effective; newer compounds such as miltefosine that can be administered orally or topically are of major potential interest. Although research has brought many new insights in pathogenesis and management of PKDL, several issues in particular in relation to control remain unsolved and deserve urgent attention.
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              A meta-analysis of the diagnostic performance of the direct agglutination test and rK39 dipstick for visceral leishmaniasis.

              François Chappuis, Marleen Boelaert, Luis Soto … (2006)
              To compare the performance of the direct agglutination test and rK39 dipstick for the diagnosis of visceral leishmaniasis. Medline, citation tracking, January 1986 to December 2004. Selection criteria Original studies evaluating the direct agglutination test or the rK39 dipstick with clinical visceral leishmaniasis as target condition; adequate reference classification; and absolute numbers of true positive, true negative, false positive, and false negative observations available or derivable from the data presented. 30 studies evaluating the direct agglutination test and 13 studies evaluating the rK39 dipstick met the inclusion criteria. The combined sensitivity estimates of the direct agglutination test and the rK39 dipstick were 94.8% (95% confidence interval 92.7% to 96.4%) and 93.9% (87.7% to 97.1%), respectively. Sensitivity seemed higher and more homogenous in the studies carried out in South Asia. Specificity estimates were influenced by the type of controls. In phase III studies carried out on patients with clinically suspected disease, the estimated specificity of the direct agglutination test was 85.9% (72.3% to 93.4%) and of the rK39 dipstick was 90.6% (66.8% to 97.9%). The diagnostic performance of the direct agglutination test and the rK39 dipstick for visceral leishmaniasis is good to excellent and seem comparable.
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                Author and article information

                Contributors
                Jesus G. Valenzuela: Role: Editor
                Journal
                Journal ID (nlm-ta): PLoS Negl Trop Dis
                Journal ID (iso-abbrev): PLoS Negl Trop Dis
                Journal ID (publisher-id): plos
                Journal ID (pmc): plosntds
                Title: PLoS Neglected Tropical Diseases
                Publisher: Public Library of Science (San Francisco, USA )
                ISSN (Print): 1935-2727
                ISSN (Electronic): 1935-2735
                Publication date Collection: June 2014
                Publication date (Electronic): 26 June 2014
                Volume: 8
                Issue: 6
                Electronic Location Identifier: e2869
                Affiliations
                [1 ]Department of Clinical Sciences, Institute of Tropical Medicine, Antwerp, Belgium
                [2 ]Department of Internal Medicine, University of Gondar, Gondar, Ethiopia
                [3 ]Public Health Department, Médecins Sans Frontières, Amsterdam, the Netherlands
                [4 ]Department of Public Health, Institute of Tropical Medicine, Antwerp, Belgium
                [5 ]School of Medicine, Addis Ababa University, Addis Ababa, Ethiopia
                National Institute of Allergy and Infectious Diseases, United States of America
                Author notes

                The authors have declared that no competing interests exist.

                Article
                Publisher ID: PNTD-D-13-01909
                DOI: 10.1371/journal.pntd.0002869
                PMC ID: 4072530
                PubMed ID: 24968313
                SO-VID: 41e8890f-0ce4-4ba9-a06c-658c74fc1f11
                Copyright statement: Copyright @ 2014
                License:

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                Page count
                Pages: 10
                Funding
                ED has received individual PhD scholarship from Belgian development cooperation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Subject: Review
                Subject: Biology and Life Sciences
                Subject: Veterinary Science
                Subject: Veterinary Diseases
                Subject: Zoonoses
                Subject: Leishmaniasis
                Subject: Medicine and Health Sciences
                Subject: Epidemiology
                Subject: Clinical Epidemiology
                Subject: Infectious Disease Epidemiology
                Subject: Infectious Diseases
                Subject: Tropical Diseases
                Subject: Neglected Tropical Diseases

                ScienceOpen disciplines: Infectious disease & Microbiology
                Data availability:
                ScienceOpen disciplines: Infectious disease & Microbiology

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