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Leishmaniasis is a poverty-related disease with two main clinical forms: visceral leishmaniasis and cutaneous leishmaniasis. An estimated 0·7–1 million new cases of leishmaniasis per year are reported from nearly 100 endemic countries. The number of reported visceral leishmaniasis cases has decreased substantially in the past decade as a result of better access to diagnosis and treatment and more intense vector control within an elimination initiative in Asia, although natural cycles in transmission intensity might play a role. In east Africa however, the case numbers of this fatal disease continue to be sustained. Increased conflict in endemic areas of cutaneous leishmaniasis and forced displacement has resulted in a surge in these endemic areas as well as clinics across the world. WHO lists leishmaniasis as one of the neglected tropical diseases for which the development of new treatments is a priority. Major evidence gaps remain, and new tools are needed before leishmaniasis can be definitively controlled.

Human visceral leishmaniasis (VL) continues to be a life-threatening neglected tropical disease, with close to 200 million people at risk of infection globally. Epidemics and resurgence of VL are associated with negligence by the policy makers, economic decline and population movements. Control of the disease is hampered by the lack of proficient vaccination, rapid diagnosis in a field setting and severe side effects of current drug therapies. The diagnosis of VL relied largely on invasive techniques of detecting parasites in splenic and bone marrow aspirates. rK39 and PCR, despite problems related to varying sensitivities and specificities and field adaptability, respectively, are considered the best options for VL diagnosis today. No single therapy of VL currently offers satisfactory efficacy along with safety. The field of VL research only recently shifted toward actively identifying new drugs for safe and affordable treatment. Oral miltefosine and safe AmBisome along with better use of amphotericin B have been rapidly implemented in the last decade. A combination therapy will substantially reduce the required dose and duration of drug administration and reduce the chance of the development of resistance. In addition, identification of asymptomatic cases, vector control and treatment of post-kala-azar dermal leishmaniasis would allow new perspectives in VL control and management.

Deltamethrin-impregnated dog collars reduce sandfly bite rates on dogs, and are effective in killing sandflies that attempt to feed. Because domestic dogs are the principal reservoir hosts of zoonotic visceral leishmaniasis, we tested whether community-wide application of dog collars could protect children against infection with Leishmania infantum, the parasite that causes the disease. 18 villages were paired, matched by preintervention child prevalence of L infantum infection. Within pairs, villages were randomly assigned to either control or intervention. All domestic dogs in intervention villages were provided with collars for the transmission season. The main outcome measure was incidence of L infantum infection after 1 year measured by seroconversion. Secondary outcomes were leishmanin skin test (LST) conversion and seroconversion in dogs. The seroconversion rate in children was 1.49% (17/1141) in the intervention villages and 2.41% (26/1078) in control villages (odds ratio 0.57, 95% CI 0.36-0.90, p=0.017). LST conversion was also lowered, but not significantly (odds ratio 0.66, 0.41-1.08, p=0.096). The seroconversion rate in dogs in intervention villages was also significantly reduced (0.46, 0.30-0.70, p=0.0003). Community-wide application of deltamethrin-impregnated dog collars not only protects domestic dogs from L infantum infections, but might also reduce the risk of L infantum infection in children. These dog collars could have a role in control of visceral leishmaniasis and replace controversial dog culling programmes in some countries. However, the effectiveness of dog collars will depend on the importance of wild versus domestic canids as reservoir hosts of L infantum.

Human visceral leishmaniasis (VL), a potentially fatal disease, is most prevalent in the Indian subcontinent, East Africa and South America. Definite diagnosis and effective treatment are the primary needs for the control of VL. Diagnosis of VL has typically relied on microscopic examination of bone marrow/splenic aspirate, but serology and molecular methods are now better alternatives. The conventional drugs for treatment of VL have limitations including unresponsiveness, relapse, specific toxicities and parenteral administration lasting for long durations. Moreover, they are less effective in HIV-VL-coinfected patients. Registration of miltefosine and paromomycin, and preferential pricing of AmBisome has offered more choices for monotherapy and combination therapy for VL. Combination therapy will increase treatment efficacy and prevent the development of resistance. In addition, active case finding and vector control strategies will also have a positive impact in the control of VL. This article critically addresses the currently available diagnostic and treatment regimens for the control of VL.

Background Treatment options for Visceral Leishmaniasis (VL) in East Africa are far from satisfactory due to cost, toxicity, prolonged treatment duration or emergence of parasite resistance. Hence there is a need to explore alternative treatment protocols such as miltefosine alone or in combinations including miltefosine, sodium stibogluconate (SSG) or liposomal amphotericin B. The aim of this trial is to identify regimen(s) which are sufficiently promising for future trials in East Africa. Methods/Design A phase II randomized, parallel arm, open-labelled trial is being conducted to assess the efficacy of each of the three regimens: liposomal amphotericin B with SSG, Liposomal amphotericin B with miltefosine and miltefosine alone. The primary endpoint is cure at day 28 with secondary endpoint at day 210 (6 months). Initial cure is a single composite measure based on parasitologic evaluation (bone marrow, spleen or lymph node aspirate) and clinical assessment. Repeated interim analyses have been planned after recruitment of 15 patients in each arm with a maximum sample size of 63 for each. These will follow group-sequential methods (the triangular test) to identify when a regimen is inadequate (<75% efficacy) or adequate (>90% efficacy). We describe a method to ensure consistency of the sequential analysis of day 28 cure with the non-sequential analysis of day 210 cure. Discussion A regimen with adequate efficacy would be a candidate for treatment of VL with reasonable costs. The design allows repeated testing throughout the trial recruitment period while maintaining good statistical properties (Type I & II error rates) and reducing the expected sample sizes. Trial Registration ClinicalTrials.gov: NCT01067443

Background Visceral leishmaniasis (VL) is a parasitic disease transmitted by sandflies and is fatal if left untreated. Phase II trials of new treatment regimens for VL are primarily carried out to evaluate safety and efficacy, while pharmacokinetic data are also important to inform future combination treatment regimens. The efficacy of VL treatments is evaluated at two time points, initial cure , when treatment is completed and definitive cure , commonly 6 months post end of treatment, to allow for slow response to treatment and detection of relapses. This paper investigates a generalization of the triangular design to impose a minimum sample size for pharmacokinetic or other analyses, and methods to estimate efficacy at extended follow-up accounting for the sequential design and changes in cure status during extended follow-up. Methods We provided R functions that generalize the triangular design to impose a minimum sample size before allowing stopping for efficacy. For estimation of efficacy at a second, extended, follow-up time, the performance of a shrinkage estimator (SHE), a probability tree estimator (PTE) and the maximum likelihood estimator (MLE) for estimation was assessed by simulation. Results The SHE and PTE are viable approaches to estimate an extended follow-up although the SHE performed better than the PTE: the bias and root mean square error were lower and coverage probabilities higher. Conclusions Generalization of the triangular design is simple to implement for adaptations to meet requirements for pharmacokinetic analyses. Using the simple MLE approach to estimate efficacy at extended follow-up will lead to biased results, generally over-estimating treatment success. The SHE is recommended in trials of two or more treatments. The PTE is an acceptable alternative for one-arm trials or where use of the SHE is not possible due to computational complexity. Trial registration NCT01067443 , February 2010.

Visceral leishmaniasis (VL), caused by the Leishmania donovani complex, is a vector-borne systemic disease, with a worldwide distribution causing high morbidity and mortality in the developing world. VL patients may be asymptomatic or they may present symptoms and findings of a systemic infection. The positive predictive value of clinical diagnosis in patients with typical symptoms is usually high, but more often, the signs and symptoms are inconclusive and mistaken with other co-endemic diseases. The fact that HIV co-infections often produce atypical presentations and the heterogeneity of Leishmania species, which is common in many endemic regions, also complicate the diagnosis. Despite that, some of the parasitological methods are still considered to be the reference standard for VL diagnosis due to their specificity. The development of serological and molecular tests has further enhanced the diagnostic approach of VL. Recombinant antigens have improved the performance of serodiagnostic tests, with DAT and the rK39 antigen based immunochromatographic test being the most appropriate methods for the serological diagnosis of VL. Molecular techniques, despite the fact that their implementation is often difficult and infeasible, have become increasingly relevant due to remarkable sensitivity and specificity, and to the variability of tested samples. Quantitative polymerase chain reaction (qPCR) has been shown to be superior than conventional PCR for the differentiation between active VL and asymptomatic infections, such as for the detection of VL-HIV coinfection. This review summarizes the available methods with their applications in the diagnosis of VL, and focuses on the recent developments in VL diagnostics.

In Brazil, Leishmania (Leishmania) infantum causes canine visceral leishmaniasis; the primary vector is the Lutzomyia longipalpis sand fly. We describe a case of canine visceral leishmaniasis caused by Leishmania (Viannia) lainsoni in a dog from Barra Mansa municipality, Rio de Janeiro state. Better specificity of serologic diagnostic techniques is needed for diagnoses.

Cutaneous leishmaniasis (CL) is endemic to Israel. Previously, CL caused by Leishmania infantum had been reported in Israel only once (in 2016). We report 8 L. infantum CL cases; 7 occurred during 2020-2021. None of the patients had systemic disease. L. infantum CL may be an emerging infection in Israel.

Every year there are an estimated 500,000 new cases of visceral leishmaniasis (VL) and more than 50,000 deaths from the disease, a death toll that is surpassed among the parasitic diseases only by malaria. The epidemiology, clinical presentation and pathogenesis of VL are reviewed, along with the current control strategies and research challenges. Visceral leishmaniasis (VL) is a systemic protozoan disease that is transmitted by phlebotomine sandflies. Poor and neglected populations in East Africa and the Indian sub-continent are particularly affected. Early and accurate diagnosis and treatment remain key components of VL control. In addition to improved diagnostic tests, accurate and simple tests are needed to identify treatment failures. Miltefosine, paromomycin and liposomal amphotericin B are gradually replacing pentavalent antimonials and conventional amphotericin B as the preferred treatments in some regions, but in other areas these drugs are still being evaluated in both mono- and combination therapies. New diagnostic tools and new treatment strategies will only have an impact if they are made widely available to patients.