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Diagnosing Neglected Tropical Diseases in HIV Coinfection

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Diagnosing Neglected Tropical Diseases in HIV Coinfection Journal name: Human Parasitic Diseases Journal type: Review Year: 2015 Volume: 7 Diagnosing Neglected Tropical Diseases in HIV Running head verso: Lindoso et al Coinfection Running head recto: Neglected tropical diseases in HIV coinfection José A.L. Lindoso1,2, Ana C.S. Lima3, Mirella A. Cunha1,4 and Claudia M.C. Gomes3 1Instituto de Infectologia, Emilio Ribas, São Paulo, 2Laboratório de Soroepidemiologia (LIM-38 HC), Instituto de Medicina Tropical de São Paulo, Universidade de São Paulo, 3Laboratório de Patologia de Moléstias Infecciosas (LIM-50 HC), Faculdade de Medicina, Universidade de São Paulo, 4Departamento de Moléstias Infecciosas e Parasitárias, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil. ABSTRACT: Neglected tropical diseases (NTDs) and human immunodeficiency virus (HIV) coinfection are overlapping conditions around the world, mainly in tropical regions, affecting people living in absolute poverty (about US$1.00 a day). Malaria, Chagas disease, and leishmaniasis are the main NTDs affected by HIV infection, in terms of clinical manifestation, diagnostics, and outcome after treatment. Unusual manifestation and reactivation of NTDs are more common in coinfected patients. Traditional serological methods used in the diagnostics of NTDs show low sensitivity, and parasitologi- cal methods possess higher sensitivity. In this article, we discuss about the clinical presentation and laboratory diagnostics in the context of NTD and HIV coinfection. KEYWORDS: neglected tropical disease, HIV infection, clinical presentation, diagnostic and laboratorial methods CITATION: Lindoso et al. Diagnosing Neglected Tropical Diseases in HIV Coinfection. COPYRIGHT: © the authors, publisher and licensee Libertas Academica Limited. Human Parasitic Diseases 2015:7 11–18 doi:10.4137/HPD.S19569. This is an open-access article distributed under the terms of the Creative Commons CC-BY-NC 3.0 License. TYPE: Review CORRESPONDENCE: [email protected] RECEIVED: May 6, 2015. RESUBMITTED: July 7, 2015. ACCEPTED FOR PUBLICATION: July 9, 2015. Paper subject to independent expert blind peer review. All editorial decisions made by independent academic editor. Upon submission manuscript was subject to anti- ACADEMIC EDITOR: Ashley Croft, Editor in Chief plagiarism scanning. Prior to publication all authors have given signed confirmation of PEER REVIEW: Three peer reviewers contributed to the peer review report. Reviewers’ agreement to article publication and compliance with all applicable ethical and legal reports totaled 216 words, excluding any confidential comments to the academic editor. requirements, including the accuracy of author and contributor information, disclosure of competing interests and funding sources, compliance with ethical requirements relating FUNDING: The authors gratefully acknowledge the following grants: Sao Paulo to human and animal study participants, and compliance with any copyright requirements Research Foundation (FAPESP) grant 2012/14689-8 to JALL and grant 2012/08338-8 of third parties. This journal is a member of the Committee on Publication Ethics (COPE). to CMCG and ACSL. The authors confirm that the funder had no influence over the Provenance: the authors were invited to submit this paper. study design, content of the article, or selection of this journal. Published by Libertas Academica. Learn more about this journal. COMPETING INTERESTS: Authors disclose no potential conflicts of interest. Introduction is not possible for leishmaniasis and Chagas disease but pos- Neglected tropical diseases (NTDs) occur in some parts of sible for malaria, despite high error rates.10 Other diagnostic the world, mainly in subtropical and tropical areas. Leish- methods have improved aggregate sensitivity and specificity maniasis, malaria, and Chagas disease are considered NTDs, relative to conventional techniques. In this scenario, the poly- occurring mainly in tropical regions and affecting people liv- merase chain reaction (PCR) has contributed to improving ing under absolute poverty (on about US$1.00 a day).1,2 Addi- the sensitivity and specificity of the diagnosis of these diseases tionally, HIV infections have increased in these regions, and throughout the world and, therefore, it has been increasingly naturally, overlapping between NTDs and HIV has taken used.11–14 In this article, we discuss the clinical manifestations place. Malaria, leishmaniasis, and Chagas disease are affected and laboratory diagnosis of NTDs (malaria, leishmaniasis, by coinfection with HIV, mainly in terms of clinical expres- and Chagas disease) in relation to HIV infection. sion, therapeutic failure, and diagnosis.3 Of note, diagnosis of NTDs in HIV coinfection has been observed to be particu- HIV Infection larly difficult, due to the decrease in sensitivity of traditional The number of people who are newly infected with this virus immunological methods and the unusual manifestations of continues to decline in most parts of the world. Yet, there leishmaniasis, malaria, and Chagas disease.3 The gold standard were 2.1 million new HIV infections and 1.5 million acquired diagnostic method for malaria, leishmaniasis, and acute Cha- immune deficiency syndrome (AIDS)-related deaths in 2013, gas disease is direct demonstration of the parasite by micros- with the major proportion of these individuals living in sub- copy techniques.4–6 This diagnostic method is inexpensive and Saharan Africa.15 A Joint United Nations Programme on HIV can be conducted under field conditions, as it requires little and AIDS (UNAIDS) report shows that 19 million of the structure. Once the parasite is seen, diagnosis can be made 35 million people living with HIV today do not know that accurately. However, false-negative results are the inherent they have the virus.16 The vast majority of people living with problem in the direct demonstration of parasites by micros- HIV are in low- and middle-income countries. According to copy. Causes of false-negative diagnosis may be low parasite the World Health Organization (WHO), sub-Saharan Africa load, lack of a well-trained expert to identify the parasites, and is the most affected region, with 24.7 million people living delayed diagnosis.7–9 Another limitation of microscopic meth- with HIV in 2013.15 Seventy-one percent of all people living ods is the identification of species of the causal agent, which with HIV in the world live in this region. Even today, despite HUMAN PARASITIC DISEASES 2015:7 11 Lindoso et al advances in our scientific understanding of HIV and its pre- been increasingly frequent reports of severe malaria caused by vention and treatment, most people living with HIV or at risk P. vivax in different regions. The main signs of severity were for HIV do not have access to prevention, care, and treatment, severe thrombocytopenia, severe anemia, hepatic dysfunction, and there is still no cure for the disease.16 However, effective metabolic acidosis, and renal dysfunction. Mortality due to treatment with antiretroviral drugs can control the virus so P. vivax infection is reported to be around 0.1%.25,26 that individuals with HIV can enjoy healthy lives and reduce The interplay between HIV infection and malaria varies the risk of transmitting the virus to others. The HIV epi- according to this dynamics of malaria transmission. In theory, demic not only affects the health of individuals, it also affects in areas with a high prevalence of HIV infection and a low households, communities, and the development and economic occurrence of malaria, the effect of HIV infection on malaria growth of nations.15 Many of the countries most affected by is more noted, as there higher proportion of symptomatic HIV also suffer from other infectious diseases such as NTDs. cases is found among adults. In regions of unstable malaria, Due to the spread of HIV infection and overlap with NTD the concept that HIV infection could increase morbidity and transmission, the burden of tropical diseases in these HIV- mortality attributable to malaria is well established, especially infected individuals is increasing around the world. in patients with severe immunosuppression3,24 Some reports have shown that the occurrence of severity Malaria and mortality due to malaria in areas of stable transmission is According to the 2014 World Malaria Report, 198 million also affected by HIV infection. A study conducted in Maputo, cases of malaria occurred globally in 2013 and the disease Mozambique, an endemic area for malaria, demonstrated an led to 584,000 deaths.16 As Plasmodium falciparum malaria increase of severity and mortality due to malaria in coinfected and HIV have similar global distribution, with the majority patients, compared to patients without HIV.17 Another study of people affected living in sub-Saharan Africa, the Indian carried out in Zambia, an area with high malaria transmis- subcontinent, and Southeast Asia, interactions between the sion, found that HIV-1 infection was a highly significant risk two diseases pose major public health problems.17 Because factor for adults with severe malaria, compared to controls the control of malaria parasitemia is mediated by the immune with uncomplicated malaria and asymptomatic controls.27 system, in theory, severely immunosuppressed HIV-infected Regarding women of childbearing age, in regions of stable patients should have more parasitemia episodes and clinical malaria, the immunity developed by women over the years manifestations.18 Furthermore, malaria infections have been is impaired by pregnancy.
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