Background and ObjectivesVisceral leishmaniasis (VL) is a common complication in AIDS patients living in Leishmania-endemic areas. Although antiretroviral therapy has changed the clinical course of HIV infection and its associated illnesses, the prevention of VL relapses remains a challenge for the care of HIV and Leishmania co-infected patients. This work is a systematic review of previous studies that have described predictors of VL relapse in HIV-infected patients.Review MethodsWe searched the electronic databases of MEDLINE, LILACS, and the Cochrane Central Register of Controlled Trials. Studies were selected if they included HIV-infected individuals with a VL diagnosis and patient follow-up after the leishmaniasis treatment with an analysis of the clearly defined outcome of prediction of relapse.ResultsEighteen out 178 studies satisfied the specified inclusion criteria. Most patients were males between 30 and 40 years of age, and HIV transmission was primarily via intravenous drug use. Previous VL episodes were identified as risk factors for relapse in 3 studies. Two studies found that baseline CD4+ T cell count above 100 cells/mL was associated with a decreased relapse rate. The observation of an increase in CD4+ T cells at patient follow-up was associated with protection from relapse in 5 of 7 studies. Meta-analysis of all studies assessing secondary prophylaxis showed significant reduction of VL relapse rate following prophylaxis. None of the five observational studies evaluating the impact of highly active antiretroviral therapy use found a reduction in the risk of VL relapse upon patient follow-up.ConclusionSome predictors of VL relapse could be identified: a) the absence of an increase in CD4+ cells at follow-up; b) lack of secondary prophylaxis; and c) previous history of VL relapse. CD4+ counts below 100 cells/mL at the time of primary VL diagnosis may also be a predictive factor for VL relapse.

ObjectiveWe conducted a systematic literature review with indirect comparison of studies evaluating therapeutic efficacy and toxicity associated to visceral leishmaniasis (VL) therapy among HIV infected individuals.Main outcome measurementsThe outcomes of interest were clinical and parasitological cure, mortality, and adverse events.MethodsPRISMA guidelines for systematic reviews and Cochrane manual were followed. Sources were MEDLINE, LILACS, EMBASE, Web of Knowledge databases and manual search of references from evaluated studies. We included all studies reporting outcomes after VL treatment, regardless of their design. Study quality was evaluated systematically by using the Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomized studies in meta-analyses. Comprehensive Meta-Analysis software v.2.2.048 was used to perform one-group meta-analysis of study arms with the same drug to estimate global rates of success and adverse events with each drug. These estimates were used, when possible, to indirectly compare treatment options, adjusted for CD4 count. Direct comparison was pooled when available.ResultsSeventeen studies reporting five treatment regimens and outcome of 920 VL episodes occurring in HIV infected individuals were included. The main outstanding difference in outcome among the treatment regimens was observed in mortality rate: it was around 3 times higher with high-dose antimony use (18.4%, CI 95% 13.3–25%), indirectly compared to lipid formulations of amphotericin B treatment (6.1%, CI 95% 3.9–9.4%). It was observed, also by indirect comparison, higher rates of clinical improvement in study arms using amphotericin B than in study arms using pentavalent antimonial therapy (Sbv). The parasitological cure, an outcome that presented some degree of risk of selection and verification bias, had rates that varied widely within the same treatment arm, with high heterogeneity, hampering any formal comparison among drugs. One direct comparison of amphotericin and antimoniate was possible combining results of two studies and confirming the superiority of amphotericin.ConclusionsAvailable evidence suggests that amphotericin is superior to antimony treatment. Death rate using antimoniate high dose is unacceptably high. Randomized controlled trials are necessary to compare different formulations and doses of amphotericin, alternative therapies and drug combinations.

BackgroundHuman visceral leishmaniasis (VL), a potentially fatal disease, has emerged as an important opportunistic condition in HIV infected patients. In immunocompromised patients, serological investigation is considered not an accurate diagnostic method for VL diagnosis and molecular techniques seem especially promising.ObjectiveThis work is a comprehensive systematic review and meta-analysis to evaluate the accuracy of serologic and molecular tests for VL diagnosis specifically in HIV-infected patients.MethodsTwo independent reviewers searched PubMed and LILACS databases. The quality of studies was assessed by QUADAS score. Sensitivity and specificity were pooled separately and compared with overall accuracy measures: diagnostic odds ratio (DOR) and symmetric summary receiver operating characteristic (sROC).ResultsThirty three studies recruiting 1,489 patients were included. The following tests were evaluated: Immunofluorescence Antibody Test (IFAT), Enzyme linked immunosorbent assay (ELISA), immunoblotting (Blot), direct agglutination test (DAT) and polimerase chain reaction (PCR) in whole blood and bone marrow. Most studies were carried out in Europe. Serological tests varied widely in performance, but with overall limited sensitivity. IFAT had poor sensitivity ranging from 11% to 82%. DOR (95% confidence interval) was higher for DAT 36.01 (9.95–130.29) and Blot 27.51 (9.27–81.66) than for IFAT 7.43 (3.08–1791) and ELISA 3.06 (0.71–13.10). PCR in whole blood had the highest DOR: 400.35 (58.47–2741.42). The accuracy of PCR based on Q-point was 0.95; 95%CI 0.92–0.97, which means good overall performance.ConclusionBased mainly on evidence gained by infection with Leishmania infantum chagasi, serological tests should not be used to rule out a diagnosis of VL among the HIV-infected, but a positive test at even low titers has diagnostic value when combined with the clinical case definition. Considering the available evidence, tests based on DNA detection are highly sensitive and may contribute to a diagnostic workup.

Visceral leishmaniasis (VL) is an endemic zoonotic disease in Latin America caused by Leishmania (Leishmania) infantum, which is transmitted by sand flies from the genus Lutzomyia. VL occurs in 12 countries of Latin America, with 96% of cases reported in Brazil. Recently, an increase in VL, primarily affecting children and young adults, has been observed in urban areas of Latin America. The area in which this spread of VL is occurring overlaps regions with individuals living with HIV, the number of whom is estimated to be 1.4 million people by the World Health Organization. This overlap is suggested to be a leading cause of the increased number of reported VL-HIV coinfections. The clinical progression of HIV and L. infantum infections are both highly dependent on the specific immune response of an individual. Furthermore, the impact on the immune system caused by either pathogen and by VL-HIV coinfection can contribute to an accelerated progression of the diseases. Clinical presentation of VL in HIV positive patients is similar to patients without HIV, with symptoms characterized by fever, splenomegaly, and hepatomegaly, but diarrhea appears to be more common in coinfected patients. In addition, VL relapses are higher in coinfected patients, affecting 10% to 56.5% of cases and with a lethality ranging from 8.7% to 23.5% in Latin America, depending on the study. With regards to the diagnosis of VL, parasitological tests of bone marrow aspirates have proven to be the most sensitive test in HIV-infected patients. Serologic tests have demonstrated a variable sensitivity according to the method and antigens used, with the standard tests used for diagnosing VL in Latin America displaying lower sensitivity. For this review, few articles were identified that related to VL-HIV coinfections and originated from Latin America, highlighting the need for improving research within the regions most greatly affected. We strongly support the formation of a Latin American network for coinfections of Leishmania and HIV to improve the consistency of research on the current situation of VL-HIV coinfections. Such a network would improve the collection of vital data and samples for better understanding of the clinical manifestations and immunopathogenic aspects of VL in immunosuppressed patients. Ultimately, a concerted effort would improve trials for new diagnostic methodologies and therapeutics, which could accelerate the implementation of more specific and effective diagnosis as well as public policies for treatments to reduce the impact of VL-HIV coinfections on the Latin American population.

Visceral leishmaniasis (VL) is a rare disease in solid-organ transplant (SOT) recipients. Therefore, little is known about the risk factors and disease behavior in the transplant setting. This multicenter, matched case-control study (1:2 ratio) was designed to determine the risk factors, clinical features and outcomes of VL among this population. Control and case subjects were matched by center, transplant type and timing. Thirty-six VL cases were identified among 25 139 SOT recipients (0.1%). VL occurred 5.7-fold more frequently in Brazil than in Spain, presenting a median time of 11 months after transplantation. High-dose prednisone in the preceding 6 months was associated with VL. Patients were diagnosed over 1 month after symptom onset in 25% of cases. Thirty-one patients (86%) were febrile upon diagnosis, 81% exhibited visceromegaly and 47% showed pancytopenia. Concomitant infection was common. Parasites were identified in 89% of patients; the remaining patients were diagnosed by serology. The majority of the patients received amphotericin B. Relapses occurred in 25.7% of cases, and the crude mortality rate was 2.8%. VL after SOT is related to the VL prevalence in the general population. Delayed diagnosis frequently occurs. Liposomal amphotericin is the most commonly used therapy; mortality is low, although relapses are common. Clinical Microbiology and Infection

Abstract. The aim of this study was to evaluate the accuracy of invasive and non-invasive tests for diagnosis of visceral leishmaniasis (VL) in a large series of human immunodeficiency virus (HIV)-infected patients. In this delayedtype cross-sectional study, 113 HIV-infected symptomatic patients were evaluated by an adjudication committee after clinical follow-up to establish the presence or absence of VL as the target condition (reference test). The index tests were recombinant K39 antigen-based immunochromatographic test (rK39), indirect fluorescent antibody test (IFAT), prototype kit of direct agglutination test (DAT-LPC), and real-time polymerase chain reaction (qPCR) in peripheral blood. Compared with parasitological test and adjudication committee diagnosis or latent class model analyses, IFAT and rk39 dipstick test presented the lowest sensitivity. DAT-LPC exhibited good overall performance, and there was no statistical difference between DAT-LPC and qPCR diagnosis accuracy. Real-time PCR emerges as a less invasive alternative to parasitological examination for confirmation of cases not identified by DAT.

Highlights The performance of SARS-CoV-2 serological tests until the 14th day of symptoms is markedly low, and its use is not recommended at this stage. The performance of SARS-CoV-2 serological tests increases with the duration of symptoms and the clinical severity of the disease. In general, IgM and IgA antibodies were not earlier or more sensitive markers for the SARS-CoV-2 diagnosis, reaching their highest positivity rate after 14 days of the onset of symptoms. LFIA tests are more specific than ELISA tests for SARs-Cov-2 diagnostic. Infectious diseases prevalent in tropical regions, such as HIV, leishmaniasis, arbovirus and malaria may be related to false-positive results in the SARS-CoV-2 tests.

BackgroundVisceral leishmaniasis (VL) is an emerging condition affecting HIV-infected patients living in Latin America, particularly in Brazil. Leishmania-HIV coinfection represents a challenging diagnosis because the clinical picture of VL is similar to that of other disseminated opportunistic diseases. Additionally, coinfection is related to treatment failure, relapse and high mortality.ObjectiveTo assess the clinical-laboratory profile and outcomes of VL-HIV-coinfected patients using a group of non HIV-infected patients diagnosed with VL during the same period as a comparator.MethodsThe study was conducted at a reference center for infectious diseases in Brazil. All patients with suspected VL were evaluated in an ongoing cohort study. Confirmed cases were divided into two groups: with and without HIV coinfection. Patients were treated according to the current guidelines of the Ministry of Health of Brazil, which considers antimony as the first-choice therapy for non HIV-infected patients and recommends amphotericin B for HIV-infected patients. After treatment, all patients with CD4 counts below 350 cells/mm3 received secondary prophylaxis with amphotericin B.ResultsBetween 2011 and 2013, 168 patients with suspected VL were evaluated, of whom 90 were confirmed to have VL. In total, 51% were HIV coinfected patients (46 patients). HIV-infected patients had a lower rate of fever and splenomegaly compared with immunocompetent patients. The VL relapse rate in 6 months was 37% among HIV-infected patients, despite receiving secondary prophylaxis. The overall case-fatality rate was 6.6% (4 deaths in the HIV-infected group versus 2 deaths in the non HIV-infected group). The main risk factors for a poor outcome at 6 months after the end of treatment were HIV infection, bleeding and a previous VL episode.ConclusionAlthough VL mortality rates among HIV-infected individuals are close to those observed among immunocompetent patients treated with amphotericin B, HIV coinfection is related to a low clinical response and high relapse rates within 6 months.