Access to leishmaniasis care in Africa

[eng] Leishmaniasis is a group of diseases caused by an obligate protozoan Leishmania and transmitted by sand flies. As a neglected tropical disease (NTD), leishmaniasis disproportionately affects the poorest populations and those living in rural, remote areas or conflict zones with limited or no access to health care. Manifesting in cutaneous, mucocutaneous or visceral symptoms, the diseases’ complexity and diversity across regions contribute to the challenges in the control efforts. Visceral leishmaniasis (VL) is fatal without treatment, and the indelible scars left by cutaneous leishmaniasis (CL) may have important psycho-social impact. Eastern Africa region currently bears most of the world’s VL burden. However, underestimation of true disease burden is likely, as the paucity of data from unstable contexts may contribute to inaccurate disease estimates. Both VL and CL are known to have limited geographic distribution but may show high variability inter- and intra-countries. Population movement due to conflict or drought, combined with weak or poorly functioning health system have led to epidemics and spread in new areas. Without vaccine or effective vector control, the pillar of control strategy in Africa remains diagnosis and treatment. Access to adequate, quality diagnostic and treatment services in Africa is challenging. The rk39 rapid test is less accurate and treatment options are limited. A 17-day combination of antimonial and paromomycin is the first line treatment for VL in the region, requiring prolonged hospitalisation and increased economic burden for the patients and their households. Despite the progress in tackling NTDs, access to care for leishmaniasis is often taken for granted. Especially in Africa, access remains problematic and the current body of literature shows critical evidence gaps. Low coverage of the health services, accessibility and availability of quality care, limited diagnostic and therapeutic options along with inefficient procurement and supply remain significant challenges in the region. Delay in seeking treatment not only increase morbidity and mortality but also sustain transmission. The hypothesis informing the project is that access to care for leishmaniasis in Africa is still inadequate. The general objectives of this thesis are to improve our understanding on access to care in Africa, by documenting availability, affordability and accessibility of care, explore novel ways of enhancing such care, and provide insights into specific elements of access to formulate coherent policy recommendations for leishmaniasis in eastern Africa. Three specific objectives were formulated: the first is to update the disease burden, second to examine access issues ‘upstream' i.e. the R&D process and third, assess access issues ‘downstream’.[spa] La leishmaniasis es un grupo de enfermedades causadas por un protozoo (Leishmania) y transmitidas por flebótomos. Como enfermedad tropical desatendida (NTD, por sus siglas en inglés), la leishmaniasis afecta de manera desproporcionada a las poblaciones más pobres y a las personas que viven en zonas rurales, remotas o en zonas de conflicto con acceso limitado o nulo a la atención médica. Las distintas formas clínicas (cutánea, visceral), la complejidad y la distribución de la leishmaniasis en distintas regiones son algunos de los desafíos para controlar la enfermedad. La leishmaniasis visceral (LV) es mortal si el paciente no recibe tratamiento a tiempo, y las cicatrices dejadas por la leishmaniasis cutánea (LC) pueden tener un importante impacto psicosocial. Actualmente la mayor carga de LV se concentra en la región de África oriental aunque las cifras disponibles son probablemente una subestimación del número real de casos debido a la falta de datos fiables. Se sabe que tanto la LV como la LC tienen una distribución geográfica limitada, pero pueden mostrar una alta variabilidad tanto entre países como entre zonas en un mismo país. Los movimientos poblacionales debidos a conflictos o sequías, combinado con un sistema de salud débil o con un funcionamiento deficiente, provocan la expansión de la enfermedad a nuevas áreas y la aparición de epidemias. Al no existir una vacuna ni un control efectivo de vectores, el control de la leishmaniasis en África se sigue basando en el diagnóstico y el tratamiento de los casos. La hipótesis inicial de este proyecto es que es que el acceso al cuidado de la leishmaniasis en África sigue siendo inadecuado. Los objetivos generales de esta tesis son mejorar el conocimiento sobre el acceso a la atención de los casos de leihmaniasis en África, documentando la disponibilidad, la asequibilidad y la accesibilidad de los servicios sanitarios, explorar nuevas formas de mejorar dicha atención y formular recomendaciones de políticas de acceso al cuidado de la leishmaniasis en África oriental. Los tres objetivos específicos son: actualizar los datos sobre carga de enfermedad así como estudiar los problemas de acceso tanto a nivel de I+D como sobre el terreno

Are public-private partnerships the solution to tackle neglected tropical diseases? A systematic review of the literature

Pharmaceutical companies are reluctant to invest in research and development (R&D) of products for neglected tropical diseases (NTDs) mainly due to the low ability-to-pay of health insurance systems and of potential consumers. The available preventive and curative interventions for NTDs mostly rely on old technologies and products that are often not adequate. Moreover, NTDs mostly affect populations living in remote rural areas and conflict zones, thereby hampering access to healthcare. The challenges posed by NTDs have led to the proliferation of a variety of public-private partnerships (PPPs) in the last decades. We conducted a systematic review to assess the functioning and impact of these partnerships on the development of and access to better technologies for NTDs. Our systematic review revealed a clear lack of empirical assessment of PPPs: we could not find any impact evaluation analyses, while these are crucial to realize the full potential of PPPs and to progress further towards NTDs elimination

Changing epidemiology of dengue in South-East Asia

ABSTRACT The burden of dengue and its potential threat to global health are now globally recognized, with 2.5 billion people at risk worldwide. The pathogenesis of severe dengue is particularly intriguing with the involvement of different immune factors. Also, the epidemiology of dengue in South-East Asia is undergoing a change in the human host, the dengue virus and the vector bionomics. Shift in affected age groups, sex differences and expansion to rural areas are evident, while the virulence and genotype of the virus determine the severity and time interval between sequential infections. The Aedes mosquito, a potent and adaptive vector, has evolved in longevity and survival, affected by seasonality and climate variability, socio-cultural and economic factors of human habitation and development. This review provides insights into the changing epidemiology and its factors in South-East Asia, one of the most important epicentres of dengue in the world, highlighting the major factors influencing these rapid changes. Addressing the changes may help mitigate the challenges in the current dengue control and prevention efforts

Community-based management of severe acute malnutrition in India: new evidence from Bihar.

BACKGROUND: An estimated one-third of the world's children who are wasted live in India. In Bihar state, of children -2 SDs and MUAC >110 mm. These variables changed in July 2010 to admission on the basis of an MUAC <115 mm and discharge at an MUAC ≥120 mm. Uncomplicated SAM cases were treated as outpatients in the community by using a WHO-standard, ready-to-use, therapeutic lipid-based paste produced in India; complicated cases were treated as inpatients by using F75/F100 WHO-standard milk until they could complete treatment in the community. RESULTS: A total of 8274 children were admitted including 5149 girls (62.2%), 6613 children aged 6-23 mo (79.9%), and 87.3% children who belonged to Scheduled Caste, Scheduled Tribe, or Other Backward Caste families or households. Of 3873 children admitted under the old criteria, 41 children (1.1%) died, 2069 children (53.4%) were discharged as cured, and 1485 children (38.3%) defaulted. Of 4401 children admitted under the new criteria, 36 children (0.8%) died, 2526 children (57.4%) were discharged as cured, and 1591 children (36.2%) defaulted. For children discharged as cured, the mean (±SD) weight gain and length of stay were 4.7 ± 3.1 and 5.1 ± 3.7 g · kg(-1) · d(-1) and 8.7 ± 6.1 and 7.3 ± 5.6 wk under the old and new criteria, respectively (P < 0.01). After adjustment, significant risk factors for default were as follows: no community referral for admission, more severe wasting on admission, younger age, and a long commute for treatment. CONCLUSIONS: To our knowledge, this is the first conventional CMAM program in India and has achieved low mortality and high cure rates in nondefaulting children. The new admission criteria lower the threshold for severity with the result that more children are included who are at lower risk of death and have a smaller WHZ deficit to correct than do children identified by the old criteria. This study was registered as a retrospective observational analysis of routine program data at http://www.isrctn.com as ISRCTN13980582

Simple and Effective Multi-Paragraph Reading Comprehension

We consider the problem of adapting neural paragraph-level question answering models to the case where entire documents are given as input. Our proposed solution trains models to produce well calibrated confidence scores for their results on individual paragraphs. We sample multiple paragraphs from the documents during training, and use a shared-normalization training objective that encourages the model to produce globally correct output. We combine this method with a state-of-the-art pipeline for training models on document QA data. Experiments demonstrate strong performance on several document QA datasets. Overall, we are able to achieve a score of 71.3 F1 on the web portion of TriviaQA, a large improvement from the 56.7 F1 of the previous best system.Comment: 11 pages, updated a referenc

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

Visceral leishmaniasis and HIV co-infection in Bihar, India: long-term effectiveness and treatment outcomes with liposomal amphotericin B (AmBisome).

BACKGROUND: Visceral Leishmaniasis (VL; also known as kala-azar) is an ultimately fatal disease endemic in the Indian state of Bihar, while HIV/AIDS is an emerging disease in this region. A 2011 observational cohort study conducted in Bihar involving 55 VL/HIV co-infected patients treated with 20-25 mg/kg intravenous liposomal amphotericin B (AmBisome) estimated an 85.5% probability of survival and a 26.5% probability of VL relapse within 2 years. Here we report the long-term field outcomes of a larger cohort of co-infected patients treated with this regimen between 2007 and 2012. METHODS AND PRINCIPAL FINDINGS: Intravenous AmBisome (20-25 mg/kg) was administered to 159 VL/HIV co-infected patients (both primary infections and relapses) in four or five doses of 5 mg/kg over 4-10 days. Initial cure of VL at discharge was defined as improved symptoms, cessation of fever, improvement of appetite and recession of spleen enlargement. Test of cure was not routinely performed. Antiretroviral treatment (ART) was initiated in 23 (14.5%), 39 (24.5%) and 61 (38.4%) before, during and after admission respectively. Initial cure was achieved in all discharged patients. A total of 36 patients died during follow-up, including six who died shortly after admission. Death occurred at a median of 11 weeks (IQR 4-51) after starting VL treatment. Estimated mortality risk was 14.3% at six months, 22.4% at two years and 29.7% at four years after treatment. Among the 153 patients discharged from the hospital, 26 cases of VL relapse were diagnosed during follow-up, occurring at a median of 10 months (IQR 7-14) after discharge. After accounting for competing risks, the estimated risk of relapse was 16.1% at one year, 20.4% at two years and 25.9% at four years. Low hemoglobin level and concurrent infection with tuberculosis were independent risk factors for mortality, while ART initiated shortly after admission for VL treatment was associated with a 64-66% reduced risk of mortality and 75% reduced risk of relapse. SIGNIFICANCE: This is the largest cohort of HIV-VL co-infected patients reported from the Indian subcontinent. Even after initial cure following treatment with AmBisome, these patients appear to have much higher rates of VL relapse and mortality than patients not known to be HIV-positive, although relapse rates appear to stabilize after 2 years. These results extend the earlier findings that co-infected patients are at increased risk of death and require a multidisciplinary approach for long-term management

"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

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

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

BackgroundBreastfeeding (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 (&lt;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 &lt;6 m in this setting.MethodsWe 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.ResultsParticipants 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.ConclusionThis 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 &lt;6 m and their CGs in the community