Visceral leishmaniasis in Northeast Brazil: What is the impact of HIV on this protozoan infection?
ABSTRACT: BACKGROUND:The aim of this study was to compare cases of Visceral Leishmaniasis (VL) with and without HIV in a state in northeastern Brazil. METHODOLOGY:We performed a comparative study in the state's referral hospital for infectious/parasitic diseases located in Northeast Brazil between January 2007 and July 2017. The data obtained using this protocol were analyzed with SPSS. PRINCIPAL FINDINGS:In total, 252 patients were evaluated, including 126 with coincident VL/HIV and 126 with VL alone. Both groups primarily consisted of male patients. The most commonly affected ages were 30-39 years in the coinfected group and 19-29 years in the VL group (p < 0.001). Fever and anorexia (p = 0.001), which were more common in those with VL alone, were frequently observed, while diarrhea, vomiting, bleeding and dyspnea were more common in patients with VL/HIV coinfection (p<0.005). According to the hemogram results, leukocyte levels were lower in the VL group (p < 0.0001). Additionally, AST (aspartate aminotransferase) and ALT (alanine aminotransferase) levels differed between the groups, with higher levels in patients with VL (p < 0.001). On average, HIV was diagnosed 2.6 years before VL (p < 0.001), and VL relapse was observed only in the coinfection group (36.5% of cases). Fever (? = +0.17; p = 0.032) in the first VL/HIV episode was identified as a risk factor for relapse (R2 = 0.18). More deaths occurred in the VL/HIV group (11.1%) than in the VL group (2.4%). CONCLUSION/SIGNIFICANCE:VL/HIV was found to be prevalent among young adults, although the median patient age was higher in the VL/HIV group. The classic symptomatology of VL was more common in patients not coinfected with HIV; therefore, attention is needed in patients with HIV who present with any symptoms that suggest the presence of VL, especially in endemic areas. No cases of VL relapse occurred in patients without HIV, and death was more common in the VL/HIV co-infected group.
Project description:The urbanization of visceral leishmaniasis (VL) and the concurrent movement of the HIV infection to rural areas in Brazil are possible mechanisms associated with an increased number of Leishmania/HIV coinfected people. This study aimed to describe the clinical and epidemiological profile of VL/HIV coinfected patients and compare this profile to non-coinfected VL patients.Cases of VL/HIV coinfection were obtained through a probabilistic record linkage of databases of VL and AIDS cases from the Brazilian Ministry of Health.We retrieved 760 cases of VL/HIV coinfection, most prevalent in adult males, with incidence ranging from 0.01 to 0.07 cases, per 100.000 population, in 2001 and 2010, respectively. Case-fatality rates were 27.3% in 2001 and 23.2% in 2010. Weakness, weight loss, cough, other associated infections and haemorrhagic phenomena were more commonly found among coinfected patients, which had a fatality rate three times higher as compared to the non-coinfected group. The relapse proportion was two times greater among coinfected (6.3%) than non-coinfected (3.1%).The results found herein contribute to the increase of knowledge of the epidemiological situation of VL/HIV coinfection in Brazil and reinforce the necessity of implementing specific strategies to improve early case detection and efficacious and less toxic treatment in order to achieve lower case-fatality rates.
Project description:BACKGROUND: Visceral 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. OBJECTIVE: To 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. METHODS: The 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. RESULTS: Between 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. CONCLUSION: Although 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.
Project description:Patients with visceral leishmaniasis (VL)-human immunodeficiency virus (HIV) coinfection experience increased drug toxicity and treatment failure rates compared to VL patients, with more frequent VL relapse and death. In the era of VL elimination strategies, HIV coinfection is progressively becoming a key challenge, because HIV-coinfected patients respond poorly to conventional VL treatment and play an important role in parasite transmission. With limited chemotherapeutic options and a paucity of novel anti-parasitic drugs, new interventions that target host immunity may offer an effective alternative. In this review, we first summarize current views on how VL immunopathology is significantly affected by HIV coinfection. We then review current clinical and promising preclinical immunomodulatory interventions in the field of VL and discuss how these may operate in the context of a concurrent HIV infection. Caveats are formulated as these interventions may unpredictably impact the delicate balance between boosting of beneficial VL-specific responses and deleterious immune activation/hyperinflammation, activation of latent provirus or increased HIV-susceptibility of target cells. Evidence is lacking to prioritize a target molecule and a more detailed account of the immunological status induced by the coinfection as well as surrogate markers of cure and protection are still required. We do, however, argue that virologically suppressed VL patients with a recovered immune system, in whom effective antiretroviral therapy alone is not able to restore protective immunity, can be considered a relevant target group for an immunomodulatory intervention. Finally, we provide perspectives on the translation of novel theories on synergistic immune cell cross-talk into an effective treatment strategy for VL-HIV-coinfected patients.
Project description:East Africa, where Leishmania donovani is prevalent, faces the highest burden world-wide of visceral leishmaniasis (VL) and human immunodeficiency virus (HIV) coinfection. However, data on the risk and predictors of VL relapse are scarce. Such information is vital to target medical follow-up and interventions to those at highest risk.We conducted a retrospective cohort study at a Médecins Sans Frontières-supported health center in northwest Ethiopia. We included adult VL-HIV coinfected patients treated for VL and discharged cured between February 2008 and February 2013. The risk of relapse was calculated using Kaplan-Meier methods, and predictors were determined using Cox regression models.Of the 146 patients included, 140 (96%) were male and the median age was 31 years. At the index VL diagnosis, 110 (75%) had primary VL, 57 (40%) were on antiretroviral therapy (ART), and the median CD4 count was 149 cells/µL. The median follow-up time after cure was 11 months, during which 44 (30%) patients relapsed. The risk of relapse was 15% at 6 months, 26% at 12 months, and 35% at 24 months. Predictors of relapse were: not being on ART at VL diagnosis, ART not initiated during VL treatment, and high tissue parasite load (parasite grade 6+) at VL diagnosis.The risk of VL relapse in coinfected patients was high, particularly in those not on ART or presenting with a high tissue parasite load. These patients should be preferentially targeted for secondary prophylaxis and/or regular medical follow-up. Timely ART initiation in all coinfected patients is crucial.
Project description:There are considerable numbers of patients coinfected with human immunodeficiency virus (HIV) and visceral leishmaniasis (VL) in the VL-endemic areas of Bihar, India. These patients are at higher risk of relapse and death, but there are still no evidence-based guidelines on how to treat them. In this study, we report on treatment outcomes of coinfected patients up to 18 months following treatment with a combination regimen.This retrospective analysis included all patients with confirmed HIV-VL coinfection receiving combination treatment for VL at a Médecins Sans Frontières treatment center between July 2012 and September 2014. Patients were treated with 30 mg/kg body weight intravenous liposomal amphotericin B (AmBisome) divided as 6 equal dose infusions combined with 14 days of 100 mg/day oral miltefosine (Impavido). All patients were encouraged to start or continue on antiretroviral therapy (ART).102 patients (76% males, 57% with known HIV infection, 54% with a prior episode of VL) were followed-up for a median of 11 months (interquartile range: 4-18). Cumulative incidence of all-cause mortality and VL relapse at 6, 12, and 18 months was 11.7%, 14.5%, 16.6% and 2.5%, 6.0%,13.9%, respectively. Cumulative incidence of poor outcome at 6, 12, and 18 months was 13.9%, 18.4%, and 27.2%, respectively. Not initiating ART and concurrent tuberculosis were independent risk factors for mortality, whereas no factors were associated with relapse.In this Bihar-based study, combination therapy appeared to be well tolerated, safe, and effective and may be considered as an option for treatment of VL in HIV coinfected patients.
Project description:Diagnosis of human immunodeficiency virus (HIV) infection with visceral leishmaniasis (VL) coinfection is challenging. Specific diagnosis of VL in HIV-coinfected patients was evaluated by molecular methods in desquamated buccal swab samples, demonstrating 86.3% sensitivity and 98.3% specificity in controls. This test holds significant potential for development as a noninvasive diagnostic tool for VL in HIV-coinfected patients.
Project description:Visceral leishmaniasis is hypoendemic in Mediterranean countries, where it is caused by the flagellate protozoan Leishmania infantum. VL cases in this area account for 5%-6% of the global burden. Cases of Leishmania/HIV coinfection have been reported in the Mediterranean region, mainly in France, Italy, Portugal, and Spain. Since highly active antiretroviral therapy was introduced in 1997, a marked decrease in the number of coinfected cases in this region has been reported. The development of new diagnostic methods to accurately identify level of parasitemia and the risk of relapse is one of the main challenges in improving the treatment of coinfected patients. Clinical trials in the Mediterranean region are needed to determine the most adequate therapeutic options for Leishmania/HIV patients as well as the indications and regimes for secondary prophylaxis. This article reviews the epidemiological, diagnostic, clinical, and therapeutic aspects of Leishmania/HIV coinfection in the Mediterranean region.
Project description:BACKGROUND:The WHO established targets for 2030 to globally reduce new viral hepatitis B and C infections by 90% and deaths by 65% and recommends searching for coinfections that increase the progression of chronic liver infections towards cirrhosis and hepatocellular carcinoma. AIMS AND METHODOLOGY:This study aimed to add information concerning the influence of human T-lymphotropic virus type 1 (HTLV-1) and type 2 (HTLV-2) infections in hepatitis B and C, since in Brazil, these human retroviruses are endemic but neglected. Serum samples from 1,910 patients with hepatitis B and 1,315 with hepatitis C from São Paulo, southeast Brazil, that were previously tested and grouped for HIV and HTLV-1/-2 coinfections were analyzed for hepatitis B virus (HBV) and hepatitis C virus (HCV) loads measurements and subsequent clearance using data from laboratory records. KEY RESULTS:Briefly, the lowest HBV viral load (VL) was detected in HBV/HTLV-2 coinfected patients, regardless of whether they were infected with HIV (all comparisons p<0.05). In contrast, higher HCV VL was detected in HCV/HIV, HCV/HIV/HTLV-1/-2 coinfected patients (all p<0.05), and the lowest HCV VL was detected in HCV/HTLV-2 coinfected patients. Curiously, 61.1% of the patients with HBV/HTLV-2 coinfection had an undetectable HBV VL at the beginning of the study versus 21.4% in the patients with HBV/HTLV-1 coinfection. Although the percentages of undetectable HCV loads in HCV/HTLV-1 and HCV/HTLV-2 coinfected patients were quite similar, during follow-up, more HCV clearance was detected in patients with HCV/HTLV-2 coinfection [OR 2.65; 95% IC (1.17-5.99)]. MAJOR CONCLUSIONS:HTLV-2 positively impacts HBV and HCV viral loads and HCV clearance, while HIV and/or HTLV-1 negatively impacts HCV viral load. Thus, the search for HTLV-1/-2 in viral hepatitis B and C infected patients has virological prognostic value, which is a strong reason to suggest including HTLV serology in the follow-up of patients.
Project description:HIV increases the risk of liver disease as do two common coinfections, hepatitis B and C viruses (HBV and HCV). However, whether combination antiretroviral therapy (cART) reverses or exacerbates hepatic fibrosis remains unclear.This was an observational retrospective study. cART-naïve HIV-infected subjects without a history of substance abuse (including alcohol) had liver disease stage determined by aspartate aminotransferase-to-platelet ratio indices (APRIs) and fibrosis-4 (FIB-4) before and 24 and 48 weeks after cART. All the data were retrieved from previously established cohorts. Values before and after cART were compared using Wilcoxon test for paired samples. Regression analyses were used to determine factors associated with moderate-to-severe liver disease.Of the 1105 HIV-infected subjects, 120 were HBV coinfected and 64 were HCV coinfected. About 20% of HIV monoinfected participants had APRI and FIB-4 scores consistent with moderate-to-significant fibrosis compared to ?36% of HIV-HBV coinfected and 67% to 77% of HIV-HCV coinfected participants. In adjusted analyses compared with HIV monoinfection, HBV coinfection was associated with 1.18-fold higher APRI (P?<?0.001) and a 1.12-fold higher FIB-4 (P?=?0.007) prior to cART; while HCV coinfection was associated with 1.94-fold higher APRI (P?<?0.001) and a 1.43-fold higher FIB-4 (P?<?0.001). After 48 weeks of cART, both fibrosis scores decreased in all subjects; however, HCV coinfection was still associated with higher fibrosis scores at week 48 compared to HIV monoinfection.cART was associated with improvement in hepatic fibrosis scores in the majority of HIV-hepatitis coinfected and HIV-monoinfected Chinese participants.
Project description: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.