Publications by authors named "Temmy Sunyoto"

21 Publications

  • Page 1 of 1

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

JAC Antimicrob Resist 2021 Sep 6;3(3):dlab140. Epub 2021 Sep 6.

MSFOCB Operations Department Cell 3, Brussels, Belgium.

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 (21.9%) (20.9%) and (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% ( = 0.0001), and resistance to clindamycin in MSSA isolates rose from 3.7% to 29.6% ( = 0.003). Two critical WHO priority pathogens (ESBL-producing CRE and carbapenem-resistant ) 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.
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http://dx.doi.org/10.1093/jacamr/dlab140DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8419367PMC
September 2021

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

Authors:
Temmy Sunyoto

Expert Opin Drug Discov 2020 05 10;15(5):531-537. Epub 2020 Mar 10.

Public Health Department, Institute of Tropical Medicine, Antwerpen, Belgium.

: 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.: 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.: 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.
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http://dx.doi.org/10.1080/17460441.2020.1736550DOI Listing
May 2020

Visceral Leishmaniasis, Northern Somalia, 2013-2019.

Emerg Infect Dis 2020 01;26(1):153-154

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.
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http://dx.doi.org/10.3201/eid2601.181851DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6924893PMC
January 2020

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

PLoS Negl Trop Dis 2019 09 26;13(9):e0007726. Epub 2019 Sep 26.

Drugs for Neglected Diseases initiative (DNDi), Geneva, Switzerland.

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.
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http://dx.doi.org/10.1371/journal.pntd.0007726DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6782108PMC
September 2019

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

BMJ Open 2019 05 30;9(5):e029141. Epub 2019 May 30.

Public Health Department, Institute of Tropical Medicine, Antwerpen, Belgium.

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.
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http://dx.doi.org/10.1136/bmjopen-2019-029141DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6549606PMC
May 2019

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

Expert Rev Anti Infect Ther 2019 01 12;17(1):57-69. Epub 2018 Dec 12.

b Early Detection and Prevention Section , International Agency for Research on Cancer , Lyon , France.

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.
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http://dx.doi.org/10.1080/14787210.2019.1555471DOI Listing
January 2019

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

PLoS Negl Trop Dis 2018 10 25;12(10):e0006914. Epub 2018 Oct 25.

Department of Public Health, Institute of Tropical Medicine, Antwerp, Belgium.

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.
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http://dx.doi.org/10.1371/journal.pntd.0006914DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6219817PMC
October 2018

Field safety and effectiveness of new visceral leishmaniasis treatment regimens within public health facilities in Bihar, India.

PLoS Negl Trop Dis 2018 10 22;12(10):e0006830. Epub 2018 Oct 22.

Drugs for Neglected Diseases initiative (DNDi), Geneva, Switzerland.

Background: In 2010, WHO recommended the use of new short-course treatment regimens in kala-azar elimination efforts for the Indian subcontinent. Although phase 3 studies have shown excellent results, there remains a lack of evidence on a wider treatment population and the safety and effectiveness of these regimens under field conditions.

Methods: This was an open label, prospective, non-randomized, non-comparative, multi-centric trial conducted within public health facilities in two highly endemic districts and a specialist referral centre in Bihar, India. Three treatment regimens were tested: single dose AmBisome (SDA), concomitant miltefosine and paromomycin (Milt+PM), and concomitant AmBisome and miltefosine (AmB+Milt). Patients with complicated disease or significant co-morbidities were treated in the SDA arm. Sample sizes were set at a minimum of 300 per arm, taking into account inter-site variation and an estimated failure risk of 5% with 5% precision. Outcomes of drug effectiveness and safety were measured at 6 months. The trial was prospectively registered with the Clinical Trials Registry India: CTRI/2012/08/002891.

Results: Out of 1,761 patients recruited, 50.6% (n = 891) received SDA, 20.3% (n = 358) AmB+Milt and 29.1% (n = 512) Milt+PM. In the ITT analysis, the final cure rates were SDA 91.4% (95% CI 89.3-93.1), AmB+Milt 88.8% (95% CI 85.1-91.9) and Milt+PM 96.9% (95% CI 95.0-98.2). In the complete case analysis, cure rates were SDA 95.5% (95% CI 93.9-96.8), AmB+Milt 95.5% (95% CI 92.7-97.5) and Milt+PM 99.6% (95% CI 98.6-99.9). All three regimens were safe, with 5 severe adverse events in the SDA arm, two of which were considered to be drug related.

Conclusion: All regimens showed acceptable outcomes and safety profiles in a range of patients under field conditions. Phase IV field-based studies, although extremely rare for neglected tropical diseases, are good practice and an important step in validating the results of more restrictive hospital-based studies before widespread implementation, and in this case contributed to national level policy change in India.

Trial Registration: Clinical trial is registered at Clinical trial registry of India (CTRI/2012/08/002891, Registered on 16/08/2012, Trial Registered Prospectively).
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http://dx.doi.org/10.1371/journal.pntd.0006830DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6197645PMC
October 2018

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

BMJ Glob Health 2018 3;3(3):e000709. Epub 2018 May 3.

Department of Public Health, Institute of Tropical Medicine (ITM), Antwerp, Belgium.

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.
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http://dx.doi.org/10.1136/bmjgh-2018-000709DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5935166PMC
May 2018

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

Am J Trop Med Hyg 2018 04 22;98(4):1091-1101. Epub 2018 Feb 22.

Institute of Tropical Medicine, Antwerp, Belgium.

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.
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http://dx.doi.org/10.4269/ajtmh.17-0872DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5928836PMC
April 2018

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

Health Policy 2017 Jul 19;121(7):745-754. Epub 2017 May 19.

ISGlobal, Barcelona Centre for International Health Research (CRESIB), Hospital Clínic, Universitat de Barcelona, Barcelona, Spain; Health Economics Group, Department of Infectious Disease Epidemiology, School of Public Health, Imperial College London, London, UK. Electronic address:

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.
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http://dx.doi.org/10.1016/j.healthpol.2017.05.005DOI Listing
July 2017

Visceral leishmaniasis in Somalia: A review of epidemiology and access to care.

PLoS Negl Trop Dis 2017 03 9;11(3):e0005231. Epub 2017 Mar 9.

Institute of Tropical Medicine, Antwerp, Belgium.

Somalia, ravaged by conflict since 1991, has areas endemic for visceral leishmaniasis (VL), a deadly parasitic disease affecting the rural poor, internally displaced, and pastoralists. Very little is known about VL burden in Somalia, where the protracted crisis hampers access to health care. We reviewed evidence about VL epidemiology in Somalia and appraised control options within the context of this fragile state's health system. VL has been reported in Somalia since 1934 and has persisted ever since in foci in the southern parts of the country. The only feasible VL control option is early diagnosis and treatment, currently mostly provided by nonstate actors. The availability of VL care in Somalia is limited and insufficient at best, both in coverage and quality. Precarious security remains a major obstacle to reach VL patients in the endemic areas, and the true VL burden and its impact remain unknown. Locally adjusted, innovative approaches in VL care provision should be explored, without undermining ongoing health system development in Somalia. Ensuring VL care is accessible is a moral imperative, and the limitations of the current VL diagnostic and treatment tools in Somalia and other endemic settings affected by conflict should be overcome.
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http://dx.doi.org/10.1371/journal.pntd.0005231DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5344316PMC
March 2017

Reply to R Dasgupta et al.

Am J Clin Nutr 2015 Nov;102(5):1298-9

From Médecins Sans Frontières (MSF), New Delhi, India (RM, EM, TS, PM, and GD; SB, e-mail: and MSF, Barcelona, Spain (NS).

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http://dx.doi.org/10.3945/ajcn.115.117267DOI Listing
November 2015

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

Clin Infect Dis 2015 Oct 30;61(8):1255-62. Epub 2015 Jun 30.

Médecins Sans Frontières, New Delhi Institute of Tropical Medicine, Antwerp, Belgium.

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.
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http://dx.doi.org/10.1093/cid/civ530DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4583582PMC
October 2015

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

Am J Clin Nutr 2015 Apr 25;101(4):847-59. Epub 2015 Feb 25.

From Médecins Sans Frontières (MSF), New Delhi, India (SB, RM, EM, TS, CS, MT, KK, PM, and AJ); MSF, Barcelona, Spain (NS); and the Department of Pediatrics, Darbhangha Medical College Hospital, Darbhangha, India (KNM).

Background: An estimated one-third of the world's children who are wasted live in India. In Bihar state, of children <5 y old, 27.1% are wasted and 8.3% have severe acute malnutrition (SAM). In 2009, Médecins Sans Frontières (MSF) initiated a community-based management of acute malnutrition (CMAM) program for children aged 6-59 mo with SAM.

Objective: In this report, we describe the characteristics and outcomes of 8274 children treated between February 2009 and September 2011.

Design: Between February 2009 and June 2010, the program admitted children with a weight-for-height z score (WHZ) <-3 SD and/or midupper arm circumference (MUAC) <110 mm and discharged those who reached a WHZ >-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.
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http://dx.doi.org/10.3945/ajcn.114.093294DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4381773PMC
April 2015

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

BMC Health Serv Res 2014 Nov 6;14:531. Epub 2014 Nov 6.

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.
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http://dx.doi.org/10.1186/s12913-014-0531-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4229595PMC
November 2014

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

PLoS Negl Trop Dis 2014 Aug 7;8(8):e3053. Epub 2014 Aug 7.

Institute of Tropical Medicine, Antwerp, Belgium.

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.
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http://dx.doi.org/10.1371/journal.pntd.0003053DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4125300PMC
August 2014

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

Cochrane Database Syst Rev 2014 Jun 20(6):CD009135. Epub 2014 Jun 20.

Institute of Tropical Medicine, Antwerp, Belgium.

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.
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http://dx.doi.org/10.1002/14651858.CD009135.pub2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4468926PMC
June 2014

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

Clin Infect Dis 2014 Aug 10;59(4):552-5. Epub 2014 May 10.

Médecins Sans Frontières, Barcelona, Spain.

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.
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http://dx.doi.org/10.1093/cid/ciu333DOI Listing
August 2014

Emerging and re-emerging arboviral diseases in Southeast Asia.

J Vector Borne Dis 2013 Apr-Jun;50(2):77-84

Department of Communicable Diseases, World Health Organization/South East Asia Regional Office, New Delhi, India.

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.
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February 2014

Changing epidemiology of dengue in South-East Asia.

WHO South East Asia J Public Health 2013 Jan-Mar;2(1):23-27

Department of Communicable Diseases, World Health Organization/South East Asia Regional Office (SEARO); Medical Coordinator, MSF Spain, New Delhi, India.

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.
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http://dx.doi.org/10.4103/2224-3151.115830DOI Listing
June 2017
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