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      A review of visceral leishmaniasis during the conflict in South Sudan and the consequences for East African countries

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          Abstract

          Background

          Visceral leishmaniasis (VL), caused predominantly by Leishmania donovani and transmitted by both Phlebotomus orientalis and Phlebotomus martini, is highly endemic in East Africa where approximately 30 thousands VL cases are reported annually. The largest numbers of cases are found in Sudan - where Phlebotomus orientalis proliferate in Acacia forests especially on Sudan’s eastern border with Ethiopia, followed by South Sudan, Ethiopia, Somalia, Kenya and Uganda. Long-standing civil war and unrest is a dominant determinant of VL in East African countries. Here we attempt to identify the correlation between VL epidemics and civil unrest.

          Objective and methodology

          In this review, literature published between 1955 and 2016 have been gathered from MSF, UNICEF, OCHA, UNHCR, PubMed and Google Scholar to analyse the correlation between conflict and human suffering from VL, which is especially apparent in South Sudan.

          Findings

          Waves of forced migration as a consequence of civil wars between 1983 and 2005 have resulted in massive and lethal epidemics in southern Sudan. Following a comprehensive peace agreement, but especially with increased allocation of resources for disease treatment and prevention in 2011, cases of VL declined reaching the lowest levels after South Sudan declared independence. However, in the latest epidemic that began in 2014 after the onset of a civil war in South Sudan, more than 1.5 million displaced refugees have migrated internally to states highly endemic for VL, while 800,000 have fled to neighboring countries.

          Conclusion

          We find a strong relationship between civil unrest and VL epidemics which tend to occur among immunologically naïve migrants entering VL-endemic areas and when Leishmania-infected individuals migrate to new areas and establish additional foci of disease. Further complicating factors in East Africa’s VL epidemics include severe lack of access to diagnosis and treatment, HIV/AIDS co-infection, food insecurity and malnutrition. Moreover, cases of post-kala-azar dermal leishmaniasis (PKDL) can serve as important reservoirs of anthroponotic Leishmania parasites.

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          Most cited references84

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

          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.

            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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              Neglected tropical diseases and mental health: a perspective on comorbidity.

              Mental health conditions will be the largest contributor to the global health burden by 2030. Our review suggests that neglected tropical diseases (NTDs) predispose individuals to poor mental health. Factors predisposing to poor mental health include stigma and discrimination, exclusion from participating fully in society, reduced access to health and social services, lack of educational opportunities, exclusion from income-generation and employment opportunities, and restrictions in exercising civil and political rights. These characteristics are all features of NTDs, but the mental health of these sufferers has been ignored. This review raises an issue of concern and highlights the opportunities for research by psychiatrists and psychologists on NTDs. Copyright © 2012 Elsevier Ltd. All rights reserved.
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                Author and article information

                Contributors
                waleed-alsalem@hotmail.com
                Jennifer.R.Herricks@rice.edu
                hotez@bcm.edu
                Journal
                Parasit Vectors
                Parasit Vectors
                Parasites & Vectors
                BioMed Central (London )
                1756-3305
                22 August 2016
                22 August 2016
                2016
                : 9
                : 1
                : 460
                Affiliations
                [1 ]Ministry of Health, Riyadh, Saudi Arabia
                [2 ]Department of Pediatrics and Molecular Virology and Microbiology, National School of Tropical Medicine, Baylor College of Medicine, Houston, TX USA
                [3 ]James A. Baker III Institute for Public Policy, Rice University, Houston, TX USA
                [4 ]Sabin Vaccine Institute and Texas Children’s Hospital Center for Vaccine Development, Houston, TX USA
                [5 ]Department of Biology, Baylor University, Waco, TX USA
                Article
                1743
                10.1186/s13071-016-1743-7
                4994383
                27549162
                270d450f-a6ed-47a0-9318-511b9dfb3532
                © The Author(s). 2016

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 22 February 2016
                : 8 August 2016
                Funding
                Funded by: Clare Glassell for the Disease and Poverty Program at Rice Universitys Baker Institute for Public Policy, Center for Health and Biosciences.
                Categories
                Review
                Custom metadata
                © The Author(s) 2016

                Parasitology
                visceral leishmaniasis,east africa,south sudan,refugees,civil war,conflict zone,leishmania donovani,phlebotomus orientalis

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