Knowledge, attitude and practices towards visceral leishmaniasis among HIV patients: A cross-sectional study from Bihar, India.

BACKGROUND: In the Indian state of Bihar, visceral leishmaniasis (VL) is a major public health issue that has been aggravated by the rising incidence of new Human immunodeficiency virus (HIV) infections. In endemic areas, the risk of VL infections in patients living with HIV (PLHIV) is higher. It is important to investigate the disease-related knowledge, attitude, and practices (KAP) of PLHIV in Bihar in order to monitor HIV/VL co-infection. Adequate knowledge, a positive attitude, and good practices for VL control are essential to stamp out the disease. This study investigated the KAP towards VL in HIV patients attending antiretroviral therapy (ART) clinic at ICMR-RMRIMS, Patna. METHODS: A questionnaire based cross-sectional study was performed among 120 HIV patients aged ≥18 years, to evaluate their KAP regarding visceral leishmaniasis. For the KAP indicators, each correct answer received a score of 1, while unsure and incorrect responses received a score of 0. Descriptive statistics and logistic regression were used for the analysis. Data analysis was performed using Statistical Package for the Social Sciences (SPSS) version 27. RESULTS: The study population had a male (68.30%) preponderance with a mean age of 37.03 years ± 9.80 years of standard deviation. The majority (93.30%) of the study participants had previously heard about VL. Only 32.10% of those who had heard about VL knew that the disease was transmitted by the sandfly. Most (80.40%) of the study respondents were ignorant of the sandfly breeding grounds. The vast majority (75.90%) had no idea how to recognize sandflies and were unaware of their biting time, leishmaniasis transmission season, and preventive practices. Although PLHIV are vulnerable to VL, only 27.70% of them agreed that VL is a fatal disease if untreated, and 42.90% believed they wear not at risk of developing the disease. Regarding the control methods of sandflies, 28.60% of participants did not use any methods to avoid sandfly bites. The multivariable analysis revealed that occupation and family history were the two independent predictor variables of the knowledge index. Age and gender were significantly associated with attitude towards VL. Participants working as laborers had significantly lesser odds (AOR: 0.248, 95% CI: 0.073-0.844) to follow good preventive practices. There were significantly higher odds of having good practice among participants aged 18-40 years (AOR: 6.866, 95% CI: 1.694-27.834) and those residing in urban areas (AOR: 4.159, 95% CI: 1.317-13.139) than their peers. Overall, 27.7% of respondents were knowledgeable, 41.1% had a positive mindset, and 33.9% had strong VL preventive habits, according to the study. CONCLUSION: The study determined a remarkable gap in the knowledge attitude and practices towards VL among PLHIV. This underscores the need of augmented health education initiatives for PLHIV in endemic areas for good VL awareness and preventive practices.

Assessment of a recombinant protein from Leishmania infantum as a novel tool for Visceral Leishmaniasis (VL) diagnosis in VL/HIV co-infection cases.

Visceral Leishmaniasis and HIV-AIDS coinfection (VL/HIV) is considered a life-threatening pathology when undiagnosed and untreated, due to the immunosuppression caused by both diseases. Serological tests largely used for the VL diagnosis include the direct agglutination test (DAT), ELISA and immunochromatographic (ICT) assays. For VL diagnosis in HIV infections, different studies have shown that the use of the DAT assay facilitates the VL diagnosis in co-infected patients, since the performance of the most widely used ELISA and ICT tests, based on the recombinant protein rK39, are much less efficient in HIV co-infections. In this scenario, alternative recombinant antigens may help the development of new serological diagnostic methods which may improve the VL diagnosis for the co-infection cases. This work aimed to evaluate the use of the recombinant Lci2 antigen, related to, but antigenically more diverse than rK39, for VL diagnosis in co-infected sera through ELISA assays. A direct comparison between recombinant Lci2 and rK39 was thus carried out. The two proteins were first tested using indirect ELISA with sera from VL afflicted individuals and healthy controls, with similar performances. They were then tested with two different sets of VL/HIV co-infected cases and a significant drop in performance, for one of these groups, was observed for rK39 (32% sensitivity), but not for Lci2 (98% sensitivity). In fact, an almost perfect agreement (Kappa: 0.93) between the Lci2 ELISA and DAT was observed for the coinfected VL/HIV patients. Lci2 then has the potential to be used as a new tool for the VL diagnosis of VL/HIV co-infections.

Prevalence estimates of human immunodeficiency virus (HIV) infection among visceral leishmaniasis infected people in Northwest Ethiopia: a systematic review and meta-analysis.

BACKGROUND: In Ethiopia, by the end of 2018, an estimated 690,000 people are infected with HIV and the annual cases of Visceral Leishmaniasis (VL) is estimated to be between 4000 and 5000 with over 3.2 million people are at risk. Northwest Ethiopia accounts for over 60% cases of VL in the country. Prevalence of HIV infection among VL infected people in Ethiopia has not yet been synthesized. Therefore, we aimed to estimate the pooled prevalence of HIV infection among VL infected people in Northwest Ethiopia with the hope that it would guide the development of a more robust and cost-effective intervention strategies. METHODS: In this systematic review and meta-analysis, we searched six international databases: PubMed, Ovid MEDLINE®, Embase, Scopus, Google Scholar, and ProQuest Dissertations & Theses. We also searched reference lists of included studies and Ethiopian universities electronic thesis and dissertation repositories. The search was performed until June 30,2019. Funnel plot symmetry visualization confirmed by Egger's regression asymmetry test and Begg rank correlation methods was used to assess publication bias. Pooled prevalence estimate was calculated using Der Simonian and Laird's random Effects model. We went further to perform univariate meta-regression and subgroup analysis to identify a possible sources of heterogeneity among the studies. STATA software (version 14, Texas, USA) was used for analysis. RESULTS: From 1286 citations identified by our search, 19 relevant studies with 5355 VL infected individuals were included in this meta-analysis. The pooled prevalence of HIV infection among VL infected individuals in Northwest Ethiopia was 24% (95%CI: 17-30%). The result of sensitivity analysis demonstrated that the pooled prevalence estimate was robust and not one-study dependent. The pooled prevalence estimate of HIV infection among VL infected people in Northwest Ethiopia ranged from 20.88% (95%CI: 15.91-25.86) to 24.86% (95%CI: 18.57-31.14) after a single study was deleted. CONCLUSIONS: The burden of HIV infection in people infected with VL in Northwest Ethiopia is considerably high. Integrating HIV/AIDS surveillance among VL infected people would improve case detection as well as prevention and control of disease spread.

Co-circulation of Toscana virus and Leishmania infantum in a focus of zoonotic visceral leishmaniasis from Central Tunisia.

In the Mediterranean basin, sand flies are vectors of Leishmania parasites and phleboviruses affecting humans and animals. In this study, we aimed to investigate phlebovirus and Leishmania parasites circulating in a focus of zoonotic visceral leishmaniasis (ZVL) located in a highly irrigated area within the arid Central Tunisia, known mainly to be endemic for zoonotic cutaenous leishmaniasis (ZCL) caused Leishmania major and transmitted by Phlebotomus papatasi. Sand flies were collected using CDC light traps in the village of Saddaguia, an emergent focus of ZVL located in Central Tunisia during September-October 2014, 2015, and 2016. Pools of live female sand flies were screened for phleboviruses and Leishmania by nested PCR in the polymerase gene and kinetoplast minicircle DNA, respectively. Dead sand flies were identified morphologically to species level. Sand flies of the subgenus Larroussius mainly Phlebotomus perfiliewi, Phlebotomus perniciosus, and Phlebotomus longicuspis were predominant in this ZVL focus compared to P. papatasi. A total of 1932, 1740, and 444 sand flies were tested in 2014, 2015 and 2016, respectively. Pathogen screening performed on 4116 sand flies distributed in 148 pools revealed the presence of Leishmania infantum and Toscana virus. The minimum infection rates of sand flies with TOSV in 2014, 2015, and 2016 were 0.05%, 011%, and 0.22%, respectively. The minimum infection rates of sand flies with L. infantum in 2014, 2015, and 2016 were 0.25%, 012%, and 0.79%, respectively. No L. major was detected during the 3-years investigation in this ZVL focus. Our results showed clearly the endemic co-circulation of TOSV and L. infantum in this emergent ZVL focus. However, no co-infection of TOSV and L. infantum was detected in any of the sand fly pools investigated during the three years period. TOSV was isolated from positive pools in 2015. Phylogenetic analysis showed that the Tunisian strains of TOSV belonged to the sublineage A. Based on the present findings, our results provided strong evidence that TOSV and L. infantum are transmitted by the same predominant sand fly species of the subgenus Larroussius, and subsequently, humans and dogs could be co-infected through co-infected or successive infected bites. Our results showed clearly that the development of irrigation in arid areas contributed significantly to the establishment of stable transmission cycles of L. infantum and TOSV and subsequently to the emergence of a ZVL focus within this arid bio-geographical area characterized by the presence of multiple foci of ZCL located outside the study site. Thus, more studies are needed to better understand the impact of RNA viruses shared by vectors and reservoir hosts of L. infantum on the development of zoonotic visceral leishmaniasis.

Immunoprophylactic Potential of a New Recombinant Leishmania infantum Antigen for Canine Visceral Leishmaniasis: An In Vitro Finding.

The development and application of safe and effective immunoprophylactic/immunotherapeutic agents against canine visceral leishmaniasis (CanL) have been pointed out as the only means for the real control of the disease. Thus, this study aimed to evaluate the in vitro cellular immune response of dogs, elicited by the new recombinant proteins of Leishmania infantum, Lci10 and Lci13, in order to investigate their potential for vaccinology. Twenty-four dogs were submitted to clinical, parasitological, serological and molecular tests, and then separated into two study groups: 12 infected (InD) and 12 non-infected dogs (NInD), and six of each group were directed for Lci10 and Lci13 evaluation. Peripheral blood mononuclear cells (PBMC) were cultured and stimulated with Lci10 (10 µg/ml) or Lci13 (5 µg/ml), and with L. infantum soluble antigen (LSA) (25 µg/ml) or no stimulus (NS) as controls. Afterwards, the mRNA levels of different cytokines were quantified through qPCR, and Nitric Oxide (NO) production was assessed in the culture supernatants. Significant differences were considered when p ≤ 0.05. The comparative analysis revealed that, in the NInD group, Lci13 promoted a significant increase in the expression of IFN-γ in relation to LSA (p = 0.0362), and the expression of this cytokine in NInD was significantly higher than that presented in the InD (p = 0.0028). A negative expression for TGF-ß was obtained in both groups. Lci13 also induced a greater production of NO in relation to the NS sample in the NInD group. No significant differences were observed after stimulation with Lci10. In conclusion, the results suggest a protective role of Lci13 for uninfected animals, thus with a potential for immunoprophylaxis. The results will help to direct the antigen Lci13 for further studies (pre-clinical trials), in order to determine its immunogenicity and reactogenicity effects, as a way to consolidate its real applicability for vaccinology against CanL.

Serum proteome of dogs at subclinical and clinical onset of canine leishmaniosis.

The objective of this study was to identify changes in serum proteome in dogs that may occur after an experimental infection at subclinical and clinical stages of canine leishmaniosis (CanL). For this purpose, canine pre- and post-infection with Leishmania infantum serum proteomes in the same dogs were analysed by a high-throughput label-based quantitative LC-MS/MS proteomic approach. A total of 169 proteins were identified, and 74 of them including complement C8 alpha chain, adiponectin, transferrin, sphingomyelin phosphodiesterase acid-like 3A and immunoglobulins showed different modulation between the different stages of CanL. These proteins could be considered as potential serum biomarkers of early diagnostic or disease progression in CanL. Additionally, biological pathways modulated during CanL such as blood coagulation or gonadotropin-releasing hormone receptor were revealed, which could help to understand the pathological mechanisms of the disease.

Visceral Leishmaniasis in Hospitalized HIV-Infected Patients in Pernambuco, Brazil.

Common in four continents, visceral leishmaniasis (VL) is an important but neglected disease. Human immunodeficiency virus (HIV) infection increases the risk of developing VL in people from leishmaniasis-endemic areas, with worse prognosis when there is coinfection. We conducted a cross-sectional study to determine the prevalence of HIV/VL coinfection in patients admitted in three referral hospitals for HIV/acquired immunodeficiency syndrome (AIDS) in Pernambuco, Brazil, and to compare epidemiological, clinical, and laboratory characteristics among HIV/VL coinfected and HIV mono-infected individuals. The sample consisted of HIV patients aged 18 years or more, in a period of data collection of 6 months. We performed four Leishmania tests-polymerase chain reaction (PCR), direct agglutination test, rK39, and latex agglutination test-and individuals with at least one positive test were considered coinfected. The HIV/VL coinfection prevalence we found was 16.9%. We observed large variation in prevalence according to the Leishmania test used, with low coincidence of positive tests. The most frequent symptoms found were weight loss (75.6%), fever (67.6%), and cough (55.3%). When we compared HIV/VL coinfected and HIV mono-infected groups we did not observe statistically significant differences. Low educational level (P = 0.004) and pallor (P = 0.009) were more frequent in the coinfected group. Serum albumin level was higher in coinfected individuals (P = 0.009). It is important to follow-up these individuals to understand the dynamics of VL in people living with HIV. New tests are necessary, ideally differentiating active from latent infection. Testing for VL in people with HIV is important and should be considered as part of the initial investigation in these individuals.

Linfohistiocitosis hemofagocítica secundaria a leishmaniasis viscera / Visceral leishmania-associated hemophagocytic lymphohistiocytosis

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Visceral leishmaniasis in a Brazilian endemic area: an overview of occurrence, HIV coinfection and lethality.

The Brazilian municipality of Rondonópolis, Mato Grosso State, represents an important visceral leishmaniasis (VL) endemic area. This study described epidemiological and clinical aspects of the occurrence, VL/HIV coinfection and lethality related to VL in Rondonópolis. Data from autochthonous cases reported between 2011 and 2016 were obtained from official information systems. During this period, 81 autochthonous cases were reported, with decreasing incidence through 2016. Contrastingly, the lethality rate was 8.6% overall, but varied widely, reaching a peak (20%) in 2016. Almost 10% of patients had VL/HIVcoinfection. The occurrence of VL prevailed among men (56.8%), brown-skinned (49.4%), urban residents (92.6%), aged 0-4 years (33.3%). Housewives or retired (29.6%) were the most affected occupational groups. Lower age was the main difference among the total VL cases and those who were coinfected or died. Clinically, fever, weakness and splenomegaly were more frequent among all VL cases and VL/HIV coinfected individuals. Bacterial infections (p=0.001) and bleeding (p<0.001) were associated with death due to VL. Pentavalent antimonial and liposomal amphotericin B were the first choices for treatment among all VL cases (71.6%) and those who died (71.4%), respectively. VL/HIV patients were equally treated with both drugs. These findings may support control measures and demonstrate the need for further investigations.

Is Visceral Leishmaniasis the same in HIV-coinfected adults?

INTRODUCTION: Visceral Leishmaniasis is the most severe form of disease caused by the Leishmania donovani complex, with significant morbidity and mortality in developing countries. Worse outcomes occur among HIV-positive individuals coinfected with Leishmania. It is unclear, however, if there are significant differences on presentation between Visceral Leishmaniasis patients with or without HIV coinfection. METHODS: We reviewed medical records from adult patients with Visceral Leishmaniasis treated at a reference healthcare center in Fortaleza - Ceará, Brazil, from July 2010 to December 2013. Data from HIV-coinfected patients have been abstracted and compared to non-HIV controls diagnosed with Visceral Leishmaniasis in the same period. RESULTS: Eighty one HIV-infected patients and 365 controls were enrolled. The diagnosis in HIV patients took significantly longer, with higher recurrence and death rates. Kala-azar's classical triad (fever, constitutional symptoms and splenomegaly) was less frequently observed in Visceral Leishmaniasis-HIV patients, as well as jaundice and edema, while diarrhea was more frequent. Laboratory features included lower levels of hemoglobin, lymphocyte counts and liver enzymes, as well as higher counts of blood platelets and eosinophils. HIV-infected patients were diagnosed mainly through amastigote detection on bone marrow aspirates and treated more often with amphotericin B formulations, whereas in controls, rK39 was the main diagnostic tool and pentavalent antimony was primarily used for treatment. CONCLUSIONS: Clinical and laboratory presentation of Visceral Leishmaniasis in HIV-coinfected patients may differ from classic kala-azar, and these differences may be, in part, responsible for the delay in diagnosing and treating leishmaniasis, which might lead to worse outcomes.

Is Visceral Leishmaniasis the same in HIV-coinfected adults?

ABSTRACT Introduction: Visceral Leishmaniasis is the most severe form of disease caused by the Leishmania donovani complex, with significant morbidity and mortality in developing countries. Worse outcomes occur among HIV-positive individuals coinfected with Leishmania. It is unclear, however, if there are significant differences on presentation between Visceral Leishmaniasis patients with or without HIV coinfection. Methods: We reviewed medical records from adult patients with Visceral Leishmaniasis treated at a reference healthcare center in Fortaleza - Ceará, Brazil, from July 2010 to December 2013. Data from HIV-coinfected patients have been abstracted and compared to non-HIV controls diagnosed with Visceral Leishmaniasis in the same period. Results: Eighty one HIV-infected patients and 365 controls were enrolled. The diagnosis in HIV patients took significantly longer, with higher recurrence and death rates. Kala-azar's classical triad (fever, constitutional symptoms and splenomegaly) was less frequently observed in Visceral Leishmaniasis-HIV patients, as well as jaundice and edema, while diarrhea was more frequent. Laboratory features included lower levels of hemoglobin, lymphocyte counts and liver enzymes, as well as higher counts of blood platelets and eosinophils. HIV-infected patients were diagnosed mainly through amastigote detection on bone marrow aspirates and treated more often with amphotericin B formulations, whereas in controls, rK39 was the main diagnostic tool and pentavalent antimony was primarily used for treatment. Conclusions: Clinical and laboratory presentation of Visceral Leishmaniasis in HIV-coinfected patients may differ from classic kala-azar, and these differences may be, in part, responsible for the delay in diagnosing and treating leishmaniasis, which might lead to worse outcomes.

Long-term Clinical Outcomes in Visceral Leishmaniasis/Human Immunodeficiency Virus-Coinfected Patients During and After Pentamidine Secondary Prophylaxis in Ethiopia: A Single-Arm Clinical Trial.

Background: We have conducted a single-arm trial evaluating monthly pentamidine secondary prophylaxis (PSP) to prevent visceral leishmaniasis (VL) relapse in Ethiopian human immunodeficiency virus-infected patients. Outcomes at 12 months of PSP have been previously reported, supporting PSP effectiveness and safety. However, remaining relapse-free after PSP discontinuation is vital. We now report outcomes and associated factors for a period of up to 2.5 years after initiating PSP, including 1-year follow-up after PSP discontinuation. Methods: The trial had 3 phases: (1) 12 months of PSP; (2) a 6-month PSP extension period if CD4 count was ≤200 cells/µL at month 12; and (3) 12-month follow-up after stopping PSP. The probability of relapse and risk factors were calculated using Kaplan-Meier methods and Cox regression analysis. Results: For the 74 patients included, final study outcomes were as follows: 39 (53%) relapse-free, 20 (27%) relapsed, 5 (7%) deaths, 10 (14%) lost to follow-up. The 2-year risk of relapse was 36.9% (95% confidence interval, 23.4%-55.0%) and was highest for those with a history of VL relapse and low baseline CD4 count. Forty-five patients were relapse-free and in follow-up at month 12 of PSP. This included 28 patients with month 12 CD4 counts >200 cells/µL, remaining relapse-free after PSP discontinuation. Among the 17 with month 12 CD4 count <200 cells/µL, 1 relapsed and 3 were lost during the PSP extension period. During 1-year post-PSP follow-up, 2 patients relapsed and 1 was lost to follow-up. No PSP-related serious adverse events were reported during the PSP-extension/post-PSP follow-up period. Conclusions: It seems safe to discontinue PSP at month 12 CD4 counts of >200 cells/µL. The management of those failing to reach this level remains to be defined. Clinical Trials Registration: NCT01360762.

Visceral leishmaniosis in immunocompromised host: an update and literature review.

Visceral leishmaniasis (VL) is a chronic infectious disease endemic in tropical and sub-tropical areas including the Mediterranean basin, caused by a group of protozoan parasites of the genus Leishmania and transmitted by phlebotomine sandflies. Immunocompromised patients, in particular HIV positive, are considered at risk of VL. They report atypical signs and poor response to treatment due to impairment of T-helper and regulatory cells activity. Laboratory diagnosis is based on microscopy on bone marrow or spleen aspirates. Value of serology remains high in term of sensibility, but a positive test must be confirmed by microscopy or molecular tests. Treatment is based on Liposomal amphotericin B whose administration is associated to lower incidence of side effects, in respect to antimonials and other formulations of AmB. Use of Miltefosine needs further investigation when L. infantum is the causative agent. Frequent relapses are observed in co-infected HIV who can benefit of a second cycle.

Prevalence of Human Immunodeficiency Virus and associated factors among Visceral Leishmaniasis infected patients in Northwest Ethiopia: a facility based cross-sectional study.

BACKGROUND: Visceral Leishmaniasis coinfection with HIV/AIDS has emerged as a series of disease pattern. It most often results in unfavorable responses to treatment, frequent relapses, and deaths. Scarce data is available regarding the prevalence of HIV and associated factors among Visceral Leishmaniasis coinfected patients. This study sought to determine the prevalence of HIV and associated factors among Visceral Leishmaniasis infected patients. METHODS: Facility based cross-sectional study was conducted from October, 2015 to August, 2016 in Northwest Ethiopia. Cluster sampling technique was used to select 462 Visceral Leishmaniasis infected patients. Serologic and parasitological test results have been used to diagnose Visceral Leishmaniasis. The HIV diagnosis was based on the national algorithm with two serial positive rapid test results. In case of discrepancy between the two tests, Uni-Gold TM was used as a tie breaker. Structured questionnaire was used to collect independent variables. Data was entered by using Excel and analyzed by using SPSS version 20. Descriptive statistics and logistic regression model was used to analyze the data. RESULTS: A total of 462 study participants were included in the study with a response rate of 92.4%. HIV and Visceral Leishmaniasis coinfection was found to be 17.75% with 95% CI; 14.30-21.40. Age ≥ 30 years (AOR = 22.58, 95% CI 11.34, 45.01), urban residents (AOR = 2.02, 95% CI 1.16, 4.17) and daily laborer workers (AOR = 4.99, 95% CI 2.33, 10.68) were significantly associated with HIV and Visceral Leishmaniasis coinfection. CONCLUSION: HIV and Visceral Leishmaniasis coinfection in the Northwest Ethiopia was found to be low. Age, residence and employment were independently associated with HIV-VL coinfection in the Northwest Ethiopia. It is better to design interventions to prevent and control HIV-VL coinfection for productive age groups (age ≥ 30) and daily laborers.

Visceral leishmaniasis and HIV coinfection in Latin America.

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.

High parasitological failure rate of visceral leishmaniasis to sodium stibogluconate among HIV co-infected adults in Ethiopia.

BACKGROUND: Antimonials are still being used for visceral leishmaniasis (VL) treatment among HIV co-infected patients in East-Africa due to the shortage of alternative safer drugs like liposomal amphotericin B. Besides tolerability, emergence of resistance to antimonials is a major concern. OBJECTIVES: This study was aimed at assessing the clinical outcome of VL-HIV co-infected patients when treated with sodium stibogluconate (SSG). METHODS: Retrospective patient record analysis of VL-HIV co-infected patients treated at a clinical trial site in north-west Ethiopia was done. Patients with parasitologically confirmed VL and HIV co-infection treated with SSG were included. The dose of SSG used was 20 mg Sb5 (pentavalent antimony)/kg and maximum of 850 mg Sb5 for 30 days. The clinical outcomes were defined based on the tissue aspiration results as cure or failure, and additionally the safety and mortality rates were computed. RESULTS: The study included 57 patients treated with SSG and by the end of treatment only 43.9% of patients were cured. The parasitological treatment failure and the case fatality rate were 31.6% and 14.0% respectively. SSG was discontinued temporarily or permanently for 12 (21.1%) cases due to safety issues. High baseline parasite load (graded more than 4+) was significantly associated with treatment failure (odds ratio = 8.9, 95% confidence interval = .5-51.7). CONCLUSION: SSG is not only unsafe, but also has low effectiveness for VL-HIV patients. Safe and effective alternative medications are very urgently needed. Drug sensitivity surveillance should be introduced in the region.

Emergence of co-infection of visceral leishmaniasis in HIV-positive patients in northeast Iran: a preliminary study.

Visceral leishmaniasis (VL) serosurvey was carried out on 49 HIV/AIDS patients among 500 asymptomatic HIV/infected patients who registered in the Khorasan Razavi Province during the last 14 years. HIV infections were detected by ELISA and confirmed using western blot assay at the AIDS centre of the Khorasan Razavi Province. All collected sera were screened using the direct agglutination test (DAT). The sera with anti-Leishmania infantum antibodies at a titre of 1:100 were considered positive for VL infection and serum titration was performed from 1:100 to 1:102,400. Nine (18.4%) patients were sero-positive according to DAT. The distribution of sera titrations were as follows: 1:100 (n = 6) 1:1600 (n = 1); 1:25,600 (n = 1) and 1:102,400 (n = 1). All sero-positive cases showed clinical signs and symptoms. The most predominant signs and symptoms of co-infection of visceral leishmaniasis in HIV-positive patients were pneumonia (n = 2), hepatosplenomegaly (n = 2), lymphadenopathy (n = 2), anaemia (n = 1), prolonged fever (n = 1) and cachexia (n = 1). Our finding shows that VL (or kala-azar) is an opportunistic disease in HIV-positive patients that may be occurred in VL endemic areas of Iran.

FDG-PET/CT findings during immune reconstitution in an HIV-1 patient infected with visceral leishmaniasis.

Visceral leishmaniasis can rarely be unmasked by immune reconstitution in human immunodeficiency virus (HIV)-1-infected patients. We report the first case of immune reconstitution associated with leishmaniasis in an HIV patient to be imaged with [(18)F]fluorodeoxyglucose positron emission tomography (FDG/PET), at both baseline and after therapy.

Ultrasensitive real-time PCR for the clinical management of visceral leishmaniasis in HIV-Infected patients.

Molecular methods have been proposed as an alternative tool for the diagnosis of visceral leishmaniasis (VL), but no data are available regarding use for monitoring clinical outcome. A prospective cohort study of human immunodeficiency virus-(HIV) and VL-coinfected patients was conducted in a university-affiliated hospital in Barcelona, Spain. Leishmania parasite load was monitored using a real-time polymerase chain reaction (PCR) at baseline and every 3 months. Cutoff values for PCR were determined using receiver operating characteristic (ROC) curves. Overall, 37 episodes were analyzed, and 25 of these episodes were considered as relapsing episodes. A significant decrease of parasite load measured 3 months after treatment could predict the clinical evolution of VL. A parasite load over 0.9 parasites/mL measured 12 months after treatment could predicts relapse with a sensitivity of 100% and a specificity of 90.9%. Monitoring parasite load by an ultrasensitive quantitative Leishmania PCR is useful to predict the risk of relapse after a VL episode in HIV-infected patients.

Serum chemokine profiles in visceral leishmaniasis, HIV and HIV/ visceral leishmaniasis co-infected Ethiopian patients.

BACKGROUND: The search for a correlation between chemokine levels in plasma or serum and protection from HIV infection or progression to AIDS has been attempted by a number of workers. Chemokines are also suggested to play a role in immunity to Leishmania and Leishmania co-infection with HIV. OBJECTIVE: To assess plasma level of alpha chemokine (CXCL12, formerly known as SDF-1alpha) and beta chemokines (CCL3, CCL4 and CCL5, formerly known as MIP-1alpha, MIP-1beta and RANTES, respectively) in HIV Visceral Leishmaniasis (VL) and HIV/VL coinfection. METHODS: Frozen serum samples from a cross sectional study were used. The samples (n = 80) were comprised of healthy controls (n = 20), HIV patients (n = 20); Visceral Leishmaniasis (VL) patients (n = 22), and HIV/VL coinfected patients (n = 18). Chemokine levels of MIP-1alpha, MIP-1beta, RANTES, and SDF-1alpha of the serum samples were determined using ELISA. RESULTS: MIP-1alpha and MIP-1beta expression were significantly elevated in Leishmania infected (p < 0.001) and in HIV/ VL co-infected individuals (p < 0.001) as compared to the control groups, while no significant difference was seen between HIV infected patients p > 0.05, implying that VL alone might modulate the production of these two chemokines in the case of co-infection In RANTES, however, its expression was significantly higher in HIV patients compared to controls (p = 0.002). Further assessment of serum RANTES concentration in HIV patients has shown a tendency of negative association with viral load. Higher amount of the alpha chemokine, SDF-1alpha, was detected in the HIV patients (p = 0.001) than the control group. Also a trend of positive association between SDF-1alpha and CD4 count was observed CONCLUSION: From our data we can speculate that RANTES and SDF-1alpha might be involved in the regulation of HIV; and MIP-1alpha and MIP-1beta in VL. Therefore, enhancing or suppressing the production of these chemokines might help in therapeutic intervention of VL or HIV.