Characteristics and treatment outcomes of malnutrition among infants aged less than 6 months in North-East Nigeria (2019-2022).

Recommendations for the management of malnutrition among infants aged less than 6 months (<6 m) are based on limited evidence. This study aimed to describe the characteristics, treatment outcomes and outcome-associated factors among malnourished infants <6 m admitted at Médecins Sans Frontières (MSF) inpatient and ambulatory therapeutic feeding centres (ITFC and ATFC) in North-East Nigeria, 2019-2022. We conducted a descriptive analysis of the cohorts and logistic regression to measure the association between two selected outcomes-inpatient mortality and defaulting from the ambulatory programme-and possible factors associated. In total, 940 infants <6 m were admitted at ITFC. Most of them presented severe acute malnutrition and comorbidities, with diarrhoea being the most frequent. On discharge, 13.3% (n = 125) of infants were cured, 72.9% (n = 684) stabilized (referred to ATFC), 6.5% (n = 61) left against medical advice and 4.2% (n = 39) died. The median length of hospital stay was 10 days [IQR 7-14]. A hospital stay shorter than 10 days was significantly associated with inpatient mortality (aOR = 12.51, 95% confidence interval [CI] = 3.72-42.11, p ≤ 0.01). Among 561 infants followed up at the ATFC, only 2.8% reported comorbidities. On discharge, 80.9% (n = 429) were cured, 16.2% (n = 86) defaulted and 1.1% (n = 6) died. Male sex (aOR = 1.94, 95% CI = 1.15-3.27, p = 0.01), internally displaced status (aOR = 1.70, 95% CI = 1.05-2.79, p = 0.03) and <-3 WLZ (aOR = 1.95, 95% CI = 1.05-3.63, p = 0.03) were significantly associated with programme defaulting. Stabilization and recovery rates among malnourished infants <6 m in the studied project align with acceptable standards in this humanitarian setting. Notable defaulting rates from outpatient care should be further explored.

Whole-genome sequencing for surveillance of antimicrobial resistance in Ecuador: present and future implications.

Whole-genome sequencing is becoming the gold standard for pathogen characterization and offers considerable advantages for understanding the evolution and dissemination of new determinants of antimicrobial resistance. Despite the benefits of whole-genome sequencing for pathogen characterization, implementation costs and lack of expertise may limit its use by public health laboratories. This article reviews the advantages of whole-genome sequencing for pathogen characterization and the current status of the use of whole-genome sequencing for antimicrobial resistance surveillance in Ecuador. A roadmap is suggested for including whole-genome sequencing for pathogen characterization based on the needs of the health reference institutions through alliances with Ecuadorian universities. Establishing a partnership between public health institutions and academia would be valuable for clinicians, policy-makers, and epidemiologists who could then take reasonable measures in those areas and establish a basis for adapting One Health strategies to tackle antimicrobial resistance in Ecuador.

La secuenciación del genoma completo, que está pasando a ser el estándar de referencia para la caracterización de agentes patógenos, ofrece ventajas considerables para comprender la evolución y la diseminación de los nuevos determinantes de la resistencia a los antimicrobianos. Sin embargo, a pesar de los beneficios que genera, los costos de ejecución y la falta de experiencia pueden limitar su uso por parte de los laboratorios de salud pública. En este artículo se evalúan las ventajas de la secuenciación del genoma completo para la caracterización de agentes patógenos y el estado actual del uso de la secuenciación del genoma completo en la vigilancia de la resistencia a los antimicrobianos en Ecuador. Se propone una hoja de ruta para incluir la secuenciación del genoma completo para la caracterización de agentes patógenos según las necesidades de las instituciones de salud de referencia, lo que se haría por medio de alianzas con universidades ecuatorianas. Establecer una asociación entre las instituciones de salud pública y los círculos académicos sería sumamente valioso para los médicos, los responsables de las políticas y los epidemiólogos, que podrían adoptar medidas razonables en sus ámbitos y sentar una base para adaptar las estrategias de "Una salud" a fin de abordar la resistencia a los antimicrobianos en Ecuador.

O sequenciamento do genoma completo está se tornando o padrão ouro para a caracterização de patógenos e oferece vantagens consideráveis para a compreensão da evolução e disseminação de novos determinantes de resistência aos antimicrobianos. Apesar dos benefícios do sequenciamento do genoma completo para a caracterização de patógenos, os custos de implementação e a falta de especialização podem limitar seu uso pelos laboratórios de saúde pública. Este artigo analisa as vantagens do sequenciamento do genoma completo para a caracterização de patógenos e a situação atual do uso desta técnica para a vigilância da resistência aos antimicrobianos no Equador. Sugere-se um roteiro para incluir o sequenciamento de genomas completos para caracterização de patógenos com base nas necessidades das instituições de saúde de referência, por meio de alianças com universidades equatorianas. A criação de uma parceria entre instituições de saúde pública e entidades acadêmicas seria valiosa para clínicos, formuladores de políticas e epidemiologistas, que poderiam, assim, tomar medidas razoáveis nessas áreas e estabelecer uma base para adaptar estratégias de Saúde Única para combater a resistência aos antimicrobianos no Equador.

Colistin resistance in Escherichia coli and Klebsiella pneumoniae in humans and backyard animals in Ecuador.

Objective: Colistin is an antibiotic of last resort for treating serious Gram-negative bacterial infections. However, the misuse of colistin, especially as an animal growth promoter, has contributed to increasing antimicrobial resistance, mediated mainly through plasmid transfer of the mcr-1 gene. This study assessed the prevalence of phenotypic and molecular colistin resistance in Escherichia coli and Klebsiella pneumoniae in Ecuador in healthy humans and their chickens and pigs. Methods: Fecal samples were collected from humans and their chickens and pigs in two rural coastal and Amazon regions between April and August 2020. Gram-negative bacteria were isolated and identified using conventional techniques. Phenotypic resistance was determined using the broth microdilution technique, and the mcr-1 gene was detected using conventional polymerase chain reaction. Results: A total of 438 fecal samples were obtained from 137 humans, 147 pigs and 154 chickens. The prevalence of E. coli isolates was 86.3% (378/438) and K. pneumoniae, 37.4% (164/438). Overall, the mcr-1 gene was found in 90% (340/378) of E. coli isolates, with higher prevalences found in isolates from coastal regions (96.5%, 191/198), humans (95.6%, 111/116) and chickens (91.8%, 123/134); for K. pneumoniae, the gene was found in 19.5% (32/164) of isolates, with equal distribution between regions and hosts. Only four isolates, two E. coli and two K. pneumoniae, showed phenotypic resistance: mcr-1 was present in both E. coli strains but absent in the K. pneumoniae strains. Conclusions: Despite a low prevalence of phenotypic resistance to colistin, the high prevalence of the mcr-1 gene in E. coli is of concern. Ecuador's ban on using colistin in animal husbandry must be enforced, and continual monitoring of the situation should be implemented.

Visceral Leishmaniasis, Northern Somalia, 2013-2019.

We identified visceral leishmaniasis caused by Leishmania donovani in a previously unknown focus in northern Somalia. Clinical and epidemiologic characteristics of 118 cases during 2013-2019 in Bosaso, the region's commercial capital, have raised suspicion of visceral leishmaniasis endemicity status there.

Combination Treatment for Visceral Leishmaniasis Patients Coinfected with Human Immunodeficiency Virus in India.

BACKGROUND: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.

HIV and visceral leishmaniasis coinfection in Bihar, India: an underrecognized and underdiagnosed threat against elimination.

Although human immunodeficiency virus (HIV) and visceral leishmaniasis coinfection is recognized as a major public health challenge in Africa, data regarding the prevalence in India are very limited. Consecutive HIV screening of 2077 patients aged ≥14 years with confirmed visceral leishmaniasis in Bihar, eastern India, found that 5.6% were HIV positive, including 2.4% with newly diagnosed HIV infection.

Rapid tests for the diagnosis of visceral leishmaniasis in patients with suspected disease.

BACKGROUND: The diagnosis of visceral leishmaniasis (VL) in patients with fever and a large spleen relies on showing Leishmania parasites in tissue samples and on serological tests. Parasitological techniques are invasive, require sophisticated laboratories, consume time, or lack accuracy. Recently, rapid diagnostic tests that are easy to perform have become available. OBJECTIVES: To determine the diagnostic accuracy of rapid tests for diagnosing VL in patients with suspected disease presenting at health services in endemic areas. SEARCH METHODS: We searched MEDLINE, EMBASE, LILACS, CIDG SR, CENTRAL, SCI-expanded, Medion, Arif, CCT, and the WHO trials register on 3 December 2013, without applying language or date limits. SELECTION CRITERIA: This review includes original, phase III, diagnostic accuracy studies of rapid tests in patients clinically suspected to have VL. As reference standards, we accepted: (1) direct smear or culture of spleen aspirate; (2) composite reference standard based on one or more of the following: parasitology, serology, or response to treatment; and (3) latent class analysis. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed quality of included studies using the QUADAS-2 tool. Discrepancies were resolved by a third author. We carried out a meta-analysis to estimate sensitivity and specificity of rapid tests, using a bivariate normal model with a complementary log-log link function. We analysed each index test separately. As possible sources of heterogeneity, we explored: geographical area, commercial brand of index test, type of reference standard, disease prevalence, study size, and risk of bias (QUADAS-2). We also undertook a sensitivity analysis to assess the influence of imperfect reference standards. MAIN RESULTS: Twenty-four studies containing information about five index tests (rK39 immunochromatographic test (ICT), KAtex latex agglutination test in urine, FAST agglutination test, rK26 ICT, and rKE16 ICT) recruiting 4271 participants (2605 with VL) were included. We carried out a meta-analysis for the rK39 ICT (including 18 studies; 3622 participants) and the latex agglutination test (six studies; 1374 participants). The results showed considerable heterogeneity. For the rK39 ICT, the overall sensitivity was 91.9% (95% confidence interval (95% CI) 84.8 to 96.5) and the specificity 92.4% (95% CI 85.6 to 96.8). The sensitivity was lower in East Africa (85.3%; 95% CI 74.5 to 93.2) than in the Indian subcontinent (97.0%; 95% CI 90.0 to 99.5). For the latex agglutination test, overall sensitivity was 63.6% (95% CI 40.9 to 85.6) and specificity 92.9% (95% CI 76.7 to 99.2). AUTHORS' CONCLUSIONS: The rK39 ICT shows high sensitivity and specificity for the diagnosis of visceral leishmaniasis in patients with febrile splenomegaly and no previous history of the disease, but the sensitivity is notably lower in east Africa than in the Indian subcontinent. Other rapid tests lack accuracy, validation, or both.

Providing emergency care and assessing a patient triage system in a referral hospital in Somaliland: a cross-sectional study.

BACKGROUND: In resource-poor settings, where health systems are frequently stretched to their capacity, access to emergency care is often limited. Triage systems have been proposed as a tool to ensure efficiency and optimal use of emergency resources in such contexts. However, evidence on the practice of emergency care and the implementation of triage systems in such settings, is scarce. This study aimed to assess emergency care provision in the Burao district hospital in Somaliland, including the application of the South African Triage Scale (SATS) tool. METHODS: A cross-sectional descriptive study was undertaken. Routine programme data of all patients presenting at the Emergency Department (ED) of Burao Hospital during its first year of service (January to December 2012) were analysed. The American College of Surgeons Committee on Trauma (ACSCOT) indicators were used as SATS targets for high priority emergency cases ("high acuity" proportion), overtriage and undertriage (with thresholds of >25%, <50% and <10%, respectively). RESULTS: In 2012, among 7212 patients presented to the ED, 41% were female, and 18% were aged less than five. Only 21% of these patients sought care at the ED within 24 hours of developing symptoms. The high acuity proportion was 22.3%, while the overtriage (40%) and undertriage (9%) rates were below the pre-set thresholds. The overall mortality rate was 1.3% and the abandon rate 2.0%. The outcomes of patients corresponds well with the color code assigned using SATS. CONCLUSION: This is the first study assessing the implementation of SATS in a post-conflict and resource-limited African setting showing that most indicators met the expected standards. In particular, specific attention is needed to improve the relatively low rate of true emergency cases, delays in patient presentation and in timely provision of care within the ED. This study also highlights the need for development of emergency care thresholds that are more adapted to resource-poor contexts. These issues are discussed.

Field evaluation of validity and feasibility of Pan-Lassa rapid diagnostic test for Lassa fever in Abakaliki, Nigeria: a prospective diagnostic accuracy study.

BACKGROUND: Lassa fever is a viral haemorrhagic fever with few options for diagnosis and treatment; it is also under-researched with knowledge gaps on its epidemiology. A point-of-care bedside test diagnosing Lassa fever, adhering to REASSURED criteria, is not currently available but is urgently needed in west African regions with high Lassa fever burden. We aimed to assess the validity and feasibility of a rapid diagnostic test (RDT) to confirm Lassa fever in people in Nigeria. METHODS: We estimated the diagnostic performance of the ReLASV Pan-Lassa RDT (Zalgen Labs, Frederick, MD, USA) as a research-use-only test, compared to RT-PCR as a reference standard, in 217 participants at a federal tertiary hospital in Abakaliki, Nigeria. We recruited participants between Feb 17, 2022, and April 17, 2023. The RDT was performed using capillary blood at the patient bedside and using plasma at the laboratory. The performance of the test, based on REASSURED criteria, was assessed for user friendliness, rapidity and robustness, sensitivity, and specificity. FINDINGS: Participants were aged between 0 and 85 years, with a median age of 33·0 years (IQR 22·0-44·3), and 24 participants were younger than 18 years. 107 (50%) participants were women and 109 (50%) were men; one participant had missing sex data. Although the specificity of the Pan-Lassa RDT was high (>90%), sensitivity at bedside using capillary blood was estimated as 4% (95% CI 1-14) at 15 min and 10% (3-22) at 25 min, far below the target of 90%. The laboratory-based RDT using plasma showed better sensitivity (46% [32-61] at 15 min and 50% [36-64] at 25 min) but did not reach the target sensitivity. Among the 52 PCR-positive participants with Lassa fever, positive RDT results were associated with lower cycle threshold values (glycoprotein precursor [GPC] gene mean 30·3 [SD 4·3], Large [L] gene mean 32·3 [3·7] vs GPC gene mean 24·5 [3·9], L gene mean 28·0 [3·6]). Personnel conducting the bedside test procedure reported being hindered by the inconvenient use of full personal protective equipment and long waiting procedures before a result could be read. INTERPRETATION: The Pan-Lassa RDT is not currently recommended as a diagnostic or screening tool for suspected Lassa fever cases. Marked improvement in sensitivity and user friendliness is needed for the RDT to be adopted clinically. There remains an urgent need for better Lassa fever diagnostics to promote safety of in-hospital care and better disease outcomes in low-resource settings. FUNDING: Médecins Sans Frontières.

Emerging and re-emerging arboviral diseases in Southeast Asia.

Arthropod-borne viruses (arboviruses) have become significant public health problems, with the emergence and re-emergence of arboviral diseases nearly worldwide. The most populated Southeast Asia region is particularly vulnerable. The arboviral diseases such as dengue (DEN), Japanese encephalitis (JE), West Nile virus (WNV), chikungunya fever (CHIK), hemorrhagic fevers such as Crimean-Congo hemorrhagic (CCHF) fever, Kyasanur forest disease virus (KFDV), etc. are on the rise and have spread unprecedentedly, causing considerable burden of disease. The emergence/re-emergence of these diseases is associated with complex factors, such as viral recombination and mutation, leading to more virulent and adaptive strains, urbanization and human activities creating more permissive environment for vector-host interaction, and increased air travel and commerce. Climate is a major factor in determining the geographic and temporal distribution of arthropods, the characteristics of arthropod life cycles, the consequent dispersal patterns of associated arboviruses, the evolution of arboviruses; and the efficiency with which they are transmitted from arthropods to vertebrate hosts. The present and future arboviral threats must be mitigated by priority actions such as improving surveillance and outbreak response, establishing collaboration and communication intersectorally, and strengthening the prevention and control programmes along with improving biosafety aspects with regards to highly infectious nature of these arboviral diseases. Evidence from research needs to be generated and priority areas for research defined.

Promoting and supporting breastfeeding in a protracted emergency setting-Caregivers' and health workers' perceptions from North-East Nigeria.

Background: Breastfeeding (BF) should be protected, promoted, and supported for all infants in humanitarian settings. The re-establishment of exclusive BF is also a central part of the management of acutely malnourished infants under 6 months (<6 m). Médecins Sans Frontières (MSF) runs a nutrition project in Maiduguri, a protracted emergency setting in North-East Nigeria. This study aimed to explore caregivers' (CGs) and health workers' (HWs) perceptions of BF practice, promotion, and support among CGs with infants <6 m in this setting. Methods: We conducted a qualitative study using in-depth interviews and focus group discussions combined with non-participant observations. Participants included CGs of young infants enrolled in MSF nutritional programs or who attended health promotion activities in a displacement camp. MSF HWs were involved at different levels in BF promotion and support. Data were collected involving a local translator and analyzed using reflexive thematic analysis directly from audio recordings. Results: Participants described how feeding practices are shaped by family, community, and traditional beliefs. The perception of breastmilk insufficiency was common and led to early supplementary feeding with inexpensive but unsuitable products. Participants often linked insufficient breastmilk production with poor maternal nutrition and stress, in a context shaped by conflict and food insecurity. BF promotion was generally well received but could be improved if tailored to address specific barriers to exclusive BF. Interviewed CGs positively valued BF support received as part of the comprehensive treatment for infant malnutrition. One of the main challenges identified was the length of stay at the facility. Some participants perceived that improvements in BF were at risk of being lost after discharge if CGs lacked an enabling environment for BF. Conclusion: This study corroborates the strong influence of household and contextual factors on the practice, promotion, and support of BF. Despite identified challenges, the provision of BF support contributes to improvements in BF practice and was positively perceived by CGs in the studied setting. Greater attention should be directed toward providing support and follow-up for infants <6 m and their CGs in the community.

Genomic insights of mcr-1 harboring Escherichia coli by geographical region and a One-Health perspective.

The importance of the One Health concept in attempting to deal with the increasing levels of multidrug-resistant bacteria in both human and animal health is a challenge for the scientific community, policymakers, and the industry. The discovery of the plasmid-borne mobile colistin resistance (mcr) in 2015 poses a significant threat because of the ability of these plasmids to move between different bacterial species through horizontal gene transfer. In light of these findings, the World Health Organization (WHO) recommends that countries implement surveillance strategies to detect the presence of plasmid-mediated colistin-resistant microorganisms and take suitable measures to control and prevent their dissemination. Seven years later, ten different variants of the mcr gene (mcr-1 to mcr-10) have been detected worldwide in bacteria isolated from humans, animals, foods, the environment, and farms. However, the possible transmission mechanisms of the mcr gene among isolates from different geographical origins and sources are largely unknown. This article presents an analysis of whole-genome sequences of Escherichia coli that harbor mcr-1 gene from different origins (human, animal, food, or environment) and geographical location, to identify specific patterns related to virulence genes, plasmid content and antibiotic resistance genes, as well as their phylogeny and their distribution with their origin. In general, E. coli isolates that harbor mcr-1 showed a wide plethora of ARGs. Regarding the plasmid content, the highest concentration of plasmids was found in animal samples. In turn, Asia was the continent that led with the largest diversity and occurrence of these plasmids. Finally, about virulence genes, terC, gad, and traT represent the most frequent virulence genes detected. These findings highlight the relevance of analyzing the environmental settings as an integrative part of the surveillance programs to understand the origins and dissemination of antimicrobial resistance.

Prevalence of MDR bacteria in an acute trauma hospital in Port-au-Prince, Haiti: a retrospective analysis from 2012 to 2018.

BACKGROUND: Antibiotic resistance (ABR) is recognized as an increasing threat to global health. Haiti declared ABR an emerging public health threat in 2018, however, the current surveillance system is limited. We described the microbiological data from a Médecins Sans Frontières trauma hospital, to increase knowledge on ABR in Haiti for similar facilities. METHODS: A retrospective cross-sectional analysis of routine microbiological data of samples taken from patients admitted to the inpatient ward or followed up in the outpatient clinic of the trauma hospital from March 2012 to December 2018. Resistance trends were analysed per isolate and compared over the 7 year period. RESULTS: Among 1742 isolates, the most common samples were pus (53.4%), wound swabs (30.5%) and blood (6.9%). The most frequently detected bacteria from these sample types were Staphylococcus aureus (21.9%), Pseudomonas aeruginosa (20.9%) and Klebsiella pneumoniae (16.7%). MDR bacteria (32.0%), ESBL-producing bacteria (39.1%), MRSA (24.1%) and carbapenem-resistant Enterobacteriaceae (CRE) species (2.6%) were all detected. Between 2012 and 2018 the number of ESBL isolates significantly increased from 3.2% to 42.9% (P = 0.0001), and resistance to clindamycin in MSSA isolates rose from 3.7% to 29.6% (P = 0.003). Two critical WHO priority pathogens (ESBL-producing CRE and carbapenem-resistant P. aeruginosa) were also detected. CONCLUSIONS: Over a 7 year period, a high prevalence of MDR bacteria was observed, while ESBL-producing bacteria showed a significantly increasing trend. ABR surveillance is important to inform clinical decisions, treatment guidelines and infection prevention and control practices.

Partnerships for better neglected disease drug discovery and development: how have we fared?

Introduction: In the field of neglected disease, mushrooming partnerships have changed the landscape in the last decades. With high diversity in participants, type, scope, and operational models, partnership becomes the ultimate choice for drug discovery and development. This paper aims to reflect on this phenomenon based on experiences and lessons learned, providing insights for the future.Areas covered: Lack of safe and effective drugs for neglected diseases stems from market and public policy failure. Combining resources, skills, and expertise justifies working collaboratively in the R&D quest. The advancement of public-private partnerships (PPP), including product development partnership (PDP) for neglected diseases, is described, herein, including the rationale behind their conception, evolution, expansion, and alternative approaches. The author also discusses the appeals and the pitfalls of partnership in this field.Expert opinion: The progressive partnerships in drug discovery and development for neglected diseases need to be encouraged, especially in alignment with an open science culture. Experiences in partnerships vary with bias for successful ones, rendering more rigorous evaluation and research necessary. Eventually, the focus of improving partnership should not only be on addressing discovery bottlenecks, but also safeguarding access and delivery. Expanding focus to include vaccines and diagnostics is necessary.

Understanding the economic impact of leishmaniasis on households in endemic countries: a systematic review.

INTRODUCTION: Leishmaniasis is a poverty-related disease that causes a significant socioeconomic burden to affected households. Visceral leishmaniasis is fatal if untreated, yet illness costs may lead to delays in accessing care. Skin manifestations of leishmaniasis cause a psychological burden and even longer treatment trajectories. The objective of this review is to evaluate illness costs associated with leishmaniasis across different settings (Asia, Africa, and Latin America) and the consequences to households. Areas covered: Through a systematic review of cost-of-illness studies, we documented the distribution of costs, the health-seeking behavior, and the consequences of leishmaniasis. We discuss the value of cost-of-illness studies for leishmaniasis. Expert commentary: Despite the free provision of diagnostics and treatment in the public health care sector, out-of-pocket payments remain substantial. There has been progress in addressing the economic burden of leishmaniasis, particularly through the elimination initiative in the Indian subcontinent. Though the illness cost is decreasing due to shorter treatment regimens and better access to care, the situation remains challenging in Africa. Improvement of control tools is critical. There is a need to update cost estimates to inform policy-making and ensure sustainable solutions to reduce financial barriers to leishmaniasis care, especially in pursuing universal health coverage.

Exploring global and country-level barriers to an effective supply of leishmaniasis medicines and diagnostics in eastern Africa: a qualitative study.

OBJECTIVES: To understand stakeholders' perceptions of the access barriers to quality-assured diagnostics and medicines for leishmaniasis in the high-burden region of eastern Africa, and to identify key bottlenecks to improve the supply of commodities for neglected tropical diseases. DESIGN: Desk reviews and qualitative in-depth interview study with purposive sampling. METHODS: A landscape analysis through literature and desk review was performed. Next, 29 representatives from international organisations, non-governmental agencies, national control programmes from six countries (Ethiopia, Kenya, Somalia, South Sudan, Sudan and Uganda) and manufacturers were interviewed between May and July 2018. Participants were selected purposively and expanded through a snowballing technique.Data analysis was aided by NVivo, applying the framework method as a part of the thematic content analysis approach. RESULTS: The barriers along the visceral leishmaniasis (VL) supply chain were identified as emerging themes, grouped across supply chain activities and health systems component(s). Stakeholders expressed the perception of progress, but bottlenecks persist. VL medicines, in general, lack multisource production capacity and with small market volume, expansion of suppliers is difficult. Procurement is plagued by forecasting difficulties, complex regulatory policies and procedures, and distribution challenges. Weak communication and coordination across different levels resulted in shortages and loss of trust among different actors. Cross-cutting issues spanned from limited political and resource commitment due to low awareness and limited in-country capacity. However, study respondents were optimistic to pursue several remedies, most importantly to build bridges between supply and demand sides through continued dialogue and collaborations. Diagnostics supply has mostly been overlooked; thus, improved investment in this area is needed. CONCLUSIONS: Addressing supply barriers in eastern Africa requires consistent, specific efforts at the global and national levels, progressing from current partnerships and agreements. Priority actions include pooled procurement, improved forecast, and increased commitment and resources. Sustainability remains an elusive goal, yet to be integrated into discussions moving forward.

Field effectiveness of new visceral leishmaniasis regimens after 1 year following treatment within public health facilities in Bihar, India.

BACKGROUND: An earlier open label, prospective, non-randomized, non-comparative, multi-centric study conducted within public health facilities in Bihar, India (CTRI/2012/08/002891) measured the field effectiveness of three new treatment regimens for visceral leishmaniasis (VL): single dose AmBisome (SDA), and combination therapies of AmBisome and miltefosine (AmB+Milt) and miltefosine and paromomycin (Milt+PM) up to 6 months follow-up. The National Vector Borne Disease Control Program (NVBDCP) recommended an extended follow up at 12 months post-treatment of the original study cohort to quantify late relapses. METHODS: The 1,761 patients enrolled in the original study with the three new regimens were contacted and traced between 10 and 36 months following completion of treatment to determine their health status and any occurrence of VL relapse. RESULTS: Of 1,761 patients enrolled in the original study, 1,368 were traced at the extended follow-up visit: 711 (80.5%), 295 (83.2%) and 362 (71.5%) patients treated with SDA, AmB+Milt and Milt+PM respectively. Of those traced, a total of 75 patients were reported to have relapsed by the extended follow-up; 45 (6.3%) in the SDA, 25 (8.5%) in the AmB+Milt and 5 (1.4%) in the Milt+PM arms. Of the 75 relapse cases, 55 had already been identified in the 6-months follow-up and 20 were identified as new cases of relapse at extended follow-up; 7 in the SDA, 10 in the AmB+Milt and 3 in the Milt+PM arms. CONCLUSION: Extending follow-up beyond the standard 6 months identified additional relapses, suggesting that 12-month sentinel follow-up may be useful as a programmatic tool to better identify and quantify relapses. With limited drug options, there remains an urgent need to develop effective new chemical entities (NCEs) for VL.

Why miltefosine-a life-saving drug for leishmaniasis-is unavailable to people who need it the most.

Miltefosine, the only oral drug approved for the treatment of leishmaniasis-a parasitic disease transmitted by sandflies-is considered as a success story of research and development (R&D) by a public-private partnership (PPP). It epitomises the multiple market failures faced by a neglected disease drug: patients with low ability to pay, neglect by authorities and uncertain market size. Originally developed as an anticancer agent in the 1990s, the drug was registered in India in 2002 to treat the fatal visceral leishmaniasis. At the time, miltefosine was considered a breakthrough in the treatment, making it feasible to eliminate a regional disease. Today, access to miltefosine remains far from secure. The initial PPP agreement which includes access to the public sector is not enforced. The reality on the ground has been challenging: shortages due to inefficient supply chains, and use of a substandard product which led to a high number of treatment failures and deaths. Miltefosine received orphan drug status in the USA; when it was registered there in 2014, a priority review voucher (PRV) was awarded. The PRV, meant to facilitate drug development for neglected disease, was subsequently sold to another company for US$125 million without, to date, any apparent impact on drug access. At the heart of these concerns are questions on how to protect societal benefit of a drug developed with public investment, while clinicians worldwide struggle with its lack of affordability, limited availability and sustainability of access. This article analyses the reasons behind the postregistration access failure of miltefosine and provides the lessons learnt.

Uncharted territory of the epidemiological burden of cutaneous leishmaniasis in sub-Saharan Africa-A systematic review.

INTRODUCTION: Cutaneous leishmaniasis (CL) is the most frequent form of leishmaniasis, with 0.7 to 1.2 million cases per year globally. However, the burden of CL is poorly documented in some regions. We carried out this review to synthesize knowledge on the epidemiological burden of CL in sub-Saharan Africa. METHODS: We systematically searched PubMed, CABI Global health, Africa Index Medicus databases for publications on CL and its burden. There were no restrictions on language/publication date. Case series with less than ten patients, species identification studies, reviews, non-human, and non-CL focused studies were excluded. Findings were extracted and described. The review was conducted following PRISMA guidelines; the protocol was registered in PROSPERO (42016036272). RESULTS: From 289 identified records, 54 met eligibility criteria and were included in the synthesis. CL was reported from 13 of the 48 sub-Saharan African countries (3 eastern, nine western and one from southern Africa). More than half of the records (30/54; 56%) were from western Africa, notably Senegal, Burkina Faso and Mali. All studies were observational: 29 were descriptive case series (total 13,257 cases), and 24 followed a cross-sectional design. The majority (78%) of the studies were carried out before the year 2000. Forty-two studies mentioned the parasite species, but was either assumed or attributed on the historical account. Regional differences in clinical manifestations were reported. We found high variability across methodologies, leading to difficulties to compare or combine data. The prevalence in hospital settings among suspected cases ranged between 0.1 and 14.2%. At the community level, CL prevalence varied widely between studies. Outbreaks of thousands of cases occurred in Ethiopia, Ghana, and Sudan. Polymorphism of CL in HIV-infected people is a concern. Key information gaps in CL burden here include population-based CL prevalence/incidence, risk factors, and its socio-economic burden. CONCLUSION: The evidence on CL epidemiology in sub-Saharan Africa is scanty. The CL frequency and severity are poorly identified. There is a need for population-based studies to define the CL burden better. Endemic countries should consider research and action to improve burden estimation and essential control measures including diagnosis and treatment capacity.

"Kala-Azar is a Dishonest Disease": Community Perspectives on Access Barriers to Visceral Leishmaniasis (Kala-Azar) Diagnosis and Care in Southern Gadarif, Sudan.

Early diagnosis and treatment is the principal strategy to control visceral leishmaniasis (VL), or kala-azar in East Africa. As VL strikes remote rural, sparsely populated areas, kala-azar care might not be accessed optimally or timely. We conducted a qualitative study to explore access barriers in a longstanding kala-azar endemic area in southern Gadarif, Sudan. Former kala-azar patients or caretakers, community leaders, and health-care providers were purposively sampled and thematic data analysis was used. Our study participants revealed the multitude of difficulties faced when seeking care. The disease is well known in the area, yet misconceptions about causes and transmission persist. The care-seeking itineraries were not always straightforward: "shopping around" for treatments are common, partly linked to difficulties in diagnosing kala-azar. Kala-azar is perceived to be "hiding," requiring multiple tests and other diseases must be treated first. Negative perceptions on quality of care in the public hospitals prevail, with the unavailability of drugs or staff as the main concern. Delay to seek care remains predominantly linked to economic constraint: albeit treatment is for free, patients have to pay out of pocket for everything else, pushing families further into poverty. Despite increased efforts to tackle the disease over the years, access to quality kala-azar care in this rural Sudanese context remains problematic. The barriers explored in this study are a compelling reminder of the need to boost efforts to address these barriers.