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Background: Cholera epidemics occur frequently in low-income countries affected by concurrent humanitarian crises. Evaluations of these epidemic response remains largely unpublished and there is a need to generate evidence on response efforts to inform future programmes. This review of MSF cholera epidemic responses aimed to describe the main characteristics of the cholera epidemics and related responses in these three countries, to identify challenges to different intervention strategies based on available data; and to make recommendations for epidemic prevention and control practice and policy. Methods: Case studies from the Democratic Republic of Congo, Malawi and Mozambique were purposively selected by MSF for this review due to the documented burden of cholera in each country, frequency of cholera outbreaks, and risk of humanitarian crises. Data were extracted on the characteristics of the epidemics; time between alert and response; and, the delivery of health and water, sanitation and hygiene interventions. A Theory of Change for cholera response programmes was built to assess factors that affected implementation of the responses. Results and conclusions: 20 epidemic response reports were identified, 15 in DRC, one in Malawi and four in Mozambique. All contexts experienced concurrent humanitarian crises, either armed conflict or natural disasters. Across the settings, median time between the date of alert and date of the start of the response by MSF was 23 days (IQR 14–41). Almost all responses targeted interventions community-wide, and all responses implemented in-patient treatment of suspected cholera cases in either established health care facilities (HCFs) or temporary cholera treatment units (CTUs). In three responses, interventions were delivered as case-area targeted interventions (CATI) and four responses targeted households of admitted suspected cholera cases. CATI or delivery of interventions to households of admitted suspected cases occurred from 2017 onwards only. Overall, 74 factors affecting implementation were identified including delayed supplies of materials, insufficient quantities of materials and limited or lack of coordination with local government or other agencies. Based on this review, the following recommendations are made to improve cholera prevention and control efforts: explore improved models for epidemic preparedness, including rapid mobilisation of supplies and deployment of trained staff; invest in and strengthen partnerships with national and local government and other agencies; and to standardise reporting templates that allow for rigorous and structured evaluations within and across countries to provide consistent and accessible data. [ABSTRACT FROM AUTHOR]

Background: Cholera remains a leading cause of infectious disease outbreaks globally, and a major public health threat in complex emergencies. Hygiene kits distributed to cholera case-households have previously shown an effect in reducing cholera incidence and are recommended by Médecins Sans Frontières (MSF) for distribution to admitted patients and accompanying household members upon admission to health care facilities (HCFs). Methods: This process evaluation documented the implementation, participant response and context of hygiene kit distribution by MSF during a 2018 cholera outbreak in Kasaï-Oriental, Democratic Republic of Congo (DRC). The study population comprised key informant interviews with seven MSF staff, 17 staff from other organisations and a random sample of 27 hygiene kit recipients. Structured observations were conducted of hygiene kit demonstrations and health promotion, and programme reports were analysed to triangulate data. Results and conclusions: Between Week (W) 28–48 of the 2018 cholera outbreak in Kasaï-Oriental, there were 667 suspected cholera cases with a 5% case fatality rate (CFR). Across seven HCFs supported by MSF, 196 patients were admitted with suspected cholera between W43-W47 and hygiene kit were provided to patients upon admission and health promotion at the HCF was conducted to accompanying household contacts 5–6 times per day. Distribution of hygiene kits was limited and only 52% of admitted suspected cholera cases received a hygiene kit. The delay of the overall response, delayed supply and insufficient quantities of hygiene kits available limited the coverage and utility of the hygiene kits, and may have diminished the effectiveness of the intervention. The integration of a WASH intervention for cholera control at the point of patient admission is a growing trend and promising intervention for case-targeted cholera responses. However, the barriers identified in this study warrant consideration in subsequent cholera responses and further research is required to identify ways to improve implementation and delivery of this intervention. [ABSTRACT FROM AUTHOR]

Background: Provision of Emergency Obstetric and Neonatal Care (EmONC) reduces maternal mortality and should include three components: Basic Emergency Obstetric and Neonatal Care (BEmONC) offered at primary care level, Comprehensive EmONC (CEmONC) at secondary level and a good referral system in-between. In a conflict-affected province of Afghanistan (Khost), we assessed the performance of an Médecins Sans Frontières (MSF) run CEmONC hospital without a primary care and referral system. Performance was assessed in terms of hospital utilisation for obstetric emergencies and quality of obstetric care. Methods: A cross-sectional study using routine programme data (2013-2014). Results: Of 29,876 admissions, 99% were self-referred, 0.4% referred by traditional birth attendants and 0.3% by health facilities. Geographic origins involved clustering around the hospital vicinity and the provincial road axis. While there was a steady increase in hospital caseload, the number and proportion of women with Direct Obstetric Complications (DOC) progressively dropped from 21% to 8% over 2 years. Admissions for normal deliveries continuously increased. In-hospital maternal deaths were 0.03%, neonatal deaths 1% and DOC case-fatality rate 0. 2% (all within acceptable limits). Conclusions: Despite a high and ever increasing caseload, good quality Comprehensive EmONC could be offered in a conflict-affected setting in rural Afghanistan. However, the primary emergency role of the hospital is challenged by diversion of resources to normal deliveries that should happen at primary level. Strengthening Basic EmONC facilities and establishing an efficient referral system are essential to improve access for emergency cases and increase the potential impact on maternal mortality. [ABSTRACT FROM AUTHOR]

Background: The South African Triage Scale (SATS) was developed to facilitate patient triage in emergency departments (EDs) and is used by Médecins Sans Frontières (MSF) in low-resource environments. The aim was to determine if SATS data, reason for admission, and patient age can be used to develop and validate a model predicting the in-hospital risk of death in emergency surgical centers and to compare the model's discriminative power with that of the four SATS categories alone.Methods: We used data from a cohort hospitalized at the Nap Kenbe Surgical Hospital in Haiti from January 2013 to June 2015. We based our analysis on a multivariate logistic regression of the probability of death. Age cutoff, reason for admission categorized into nine groups according to MSF classifications, and SATS triage category (red, orange, yellow, and green) were used as candidate parameters for the analysis of factors associated with mortality. Stepwise backward elimination was performed for the selection of risk factors with retention of predictors with P < 0.05, and bootstrapping was used for internal validation. The likelihood ratio test was used to compare the combined and restricted models. These models were also applied to data from a cohort of patients from the Kunduz Trauma Center, Afghanistan, to validate mortality prediction in an external trauma patients population.Results: A total of 7618 consecutive hospitalized patients from the Nap Kenbe Hospital were analyzed. Variables independently associated with in-hospital mortality were age > 45 and < = 65 years (odds ratio, 2.04), age > 65 years (odds ratio, 5.15) and the red (odds ratio, 65.08), orange (odds ratio, 3.5), and non-trauma (odds ratio, 3.15) categories. The combined model had an area under the receiver operating characteristic curve (AUROC) of 0.8723 and an AUROC corrected for optimism of 0.8601. The AUROC of the model run on the external data-set was 0.8340. The likelihood ratio test was highly significant in favor of the combined model for both the original and external data-sets.Conclusions: SATS category, patient age, and reason for admission can be used to predict in-hospital mortality. This predictive model had good discriminative ability to identify ED patients at a high risk of death and performed better than the SATS alone. [ABSTRACT FROM AUTHOR]

Background: In Cambodia, elimination of artemisinin resistance through direct elimination of the Plasmodium falciparum parasite may be the only strategy. Prevalence and incidence at district and village levels were assessed in Chey Saen district, Preah Vihear province, North of Cambodia. Molecular and clinical indicators for artemisinin resistance were documented. Methods: A cross sectional prevalence survey was conducted at village level in the district of Chey Saen from September to October 2014. Plasmodium spp. was assessed with high volume quantitative real-time polymerase chain reaction (qPCR). Plasmodium falciparum-positive samples were screened for mutations in the k13-propeller domain gene. Treatment effectiveness was established after 28 days (D28) using the same qPCR technique. Data from the provincial surveillance system targeting symptomatic cases, supported by Médecins Sans Frontières (MSF), were used to assess incidence. Results: District P. falciparum prevalence was of 0.74 % [0.41; 1.21]; village prevalence ranged from 0 to 4.6 % [1.4; 10.5]. The annual incidence of P. falciparum was 16.8 cases per 1000 inhabitants in the district; village incidence ranged from 1.3 to 54.9 for 1000 inhabitants. Two geographical clusters with high number of cases were identified by both approaches. The marker for artemisinin resistance was found in six samples out of the 11 tested (55 %). 34.9 % of qPCR blood analysis of symptomatic patients were still positive at D28. Conclusions: The overall low prevalence of P. falciparum was confirmed in Chey Saen district in Cambodia, while there were important variations between villages. Symptomatic cases had a different pattern and were likely acquired outside the villages. It illustrates the importance of prevalence surveys in targeting interventions for elimination. Mutations in the k13-propeller domain gene (C580Y), conferring artemisinin resistance, were highly prevalent in both symptomatic and asymptomatic cases (realizing the absolute figures remain low). Asymptomatic individuals could be an additional reservoir for artemisinin resistance. The low effectiveness of dihydroartemisinin-piperaquine (DHA-PPQ) for symptomatic cases indicates that PPQ is no longer able to complement the reduced potency of DHA to treat falciparum malaria and highlights the need for an alternative first-line treatment. [ABSTRACT FROM AUTHOR]

Background: Death among premature neonates contributes significantly to neonatal mortality which in turn represents approximately 40 % of paediatric mortality. Care for premature neonates is usually provided at the tertiary care level, and premature infants in rural areas often remain bereft of care. Here, we describe the characteristics and outcomes of premature neonates admitted to neonatal services in a district hospital in rural Burundi that also provided comprehensive emergency obstetric care. These services included a Neonatal Intensive Care Unit (NICU) and Kangaroo Mother Care (KMC) ward, and did not rely on high-tech interventions or specialist medical staff. Methods: A retrospective descriptive study, using routine programme data of neonates (born at <32 weeks and 32-36 weeks of gestation), admitted to the NICU and/or KMC at Kabezi District Hospital. Results: 437 premature babies were admitted to the neonatal services; of these, 134 (31 %) were born at <32 weeks, and 236 (54 %) at 32-36 weeks. There were 67 (15 %) with an unknown gestational age but with a clinical diagnosis of prematurity. Survival rates at hospital discharge were 62 % for the <32 weeks and 87 % for the 32-36 weeks groups; compared to respectively 30 and 50 % in the literature on neonates in low- and middle-income countries. Cause of death was categorised, non-specifically, as "Conditions associated with prematurity/low birth weight" for 90 % of the <32 weeks and 40 % of the 32-36 weeks of gestation groups. Conclusions: Our study shows for the first time that providing neonatal care for premature babies is feasible at a district level in a resource-limited setting in Africa. High survival rates were observed, even in the absence of hightech equipment or specialist neonatal physician staff. We suggest that these results were achieved through staff training, standardised protocols, simple but essential equipment, provision of complementary NICU and KMC units, and integration of the neonatal services with emergency obstetric care. This approach has the potential to considerably reduce overall neonatal mortality. [ABSTRACT FROM AUTHOR]

Background: The ChinaÂ's 1-3-7 strategy was initiated and extensively adopted in different types of counties (geographic regions) for reporting of malaria cases within 1 day, their confirmation and investigation within 3 days, and the appropriate public health response to prevent further transmission within 7 days. Assessing the level of compliance to the 1-3-7 strategy at the county level is a first step towards determining whether the surveillance and response strategy is happening according to plan. This study assessed if the time-bound targets of the 1-3-7 strategy were being sustained over time. Such information would be useful to improve implementation of the 1-3-7 strategy in China. Methods: This cross-sectional study involved country-wide programmatic data for the period January 1st 2013 to June 30th 2014. Data variables were extracted from the national malaria information system and included socio-demographic information, type of county, date of diagnosis, date of reporting, date of case investigation, case classification (indigenous, or imported, or unknown), focus investigation, date of reactive case detection (RACD), and date of indoor residual spraying (IRS). Summary statistics and proportions were used and comparisons between groups were assessed using the chi-square test. Level of significance was set at a P-value ≤ 0.05. Results: Of a total of 5,688 malaria cases from 731 counties, there were 55 (1%) indigenous cases (only in Type 1 and Type 2 counties) and 5,633 (99%) imported cases from all types of counties. There was no delay in reporting malaria cases by type of county. In terms of case investigation, 97.5% cases were investigated within 3 days with the proportion of delays (1.5%) in type 2 counties, being significantly lower than type 1 counties (4.1%). Regarding active foci, 96.4% were treated by RACD and/or IRS. Conclusions: The performance of 1-3-7 strategy was encouraging but identified some challenges that if addressed can further improve implementation. [ABSTRACT FROM AUTHOR]

Background We have conducted 23 operational research (OR) courses since 2009, based on 'The Union/ Médecins Sans Frontières (MSF)' model, now popularly known as SORT-IT (Structured Operational Research and Training Initiative) model - wherein participants are mentored through the whole research process from protocol development (module 1) to data analysis (module 2) to publication (module 3) over a period of 9-12 months. We have faced a number of challenges including shortage of time, especially for data analysis and interpretation, and a heavy mentorship burden on limited numbers of experienced facilitators. To address these challenges, we have made several modifications to the structure of the OR course. In this article, we describe the revised structure and our experience (successes and challenges) of implementing it in Asia in 2013. Findings The key changes introduced included extending the duration of the course modules (by a day each in module 1 and 2 and by three days in module 3), increasing the numbers of facilitators and standardizing milestones related to data entry and analysis. We successfully implemented this revised structure in the second Asian OR Course held in Nepal in 2013. Eleven of twelve participants successfully completed all the milestones and submitted 13 scientific manuscripts (two participants completed two projects) to international peer-reviewed journals. Though, this posed two challenges - increased costs and increased time away for faculty and participants. Conclusions The revised structure of 'The Union/MSF' model of OR capacity building addressed previous issues of insufficient time and overburdened mentors and we intend to continue with this model for future courses. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background User fees have been shown to constitute a major barrier to the utilisation of health-care, particularly in low-income countries such as the Democratic Republic of Congo (DRC). Importantly, such barriers can lead to the exclusion of vulnerable individuals from healthcare. In 2008, a donor-funded primary health-care programme began implementing user fee subsidisation in 20 health zones of the DRC. In this study, we quantified the short and long-term effects of this policy on health-care utilisation. Methods Sixteen health zones were included for analysis. Using routinely collected health-care utilisation data before and after policy implementation, interrupted time series regression was applied to quantify the temporal impact of the user fee policy in the studied health zones. Payment of salary supplements to health-care workers and provision of free drugs - the other components of the programme - were controlled for where possible. Results Fourteen (88%) health zones showed an immediate positive effect in health-care utilisation rates (overall median increase of 19%, interquartile range 11 to 43) one month after the policy was introduced, and the effect was significant in seven zones (P <0.05). This initial effect was sustained or increased at 24 months in five health zones but was only significant in one health zone at P <0.05. Utilisation reduced over time in the remaining health zones (overall median increase of 4%, interquartile range -10 to 33). The modelled mean healthcare utilisation rate initially increased significantly from 43 consultations/1000 population to 51 consultations/1000 population during the first month following implementation (P <0.01). However, the on-going effect was not significant (P =0.69). Conclusions Our research brings mixed findings on the effectiveness of user fee subsidisation as a strategy to increase the utilisation of services. Future work should focus on feasibility issues associated with the removal or reduction of user fees and how to sustain its effects on utilisation in the longer term. [ABSTRACT FROM AUTHOR]

Background: Intensified efforts are urgently needed to contain and eliminate artemisinin-resistant Plasmodium falciparum in the Greater Mekong subregion. Médecins Sans Frontières plans to support the Ministry of Health in eliminating P. falciparum in an area with artemisinin resistance in the north-east of Cambodia. As a first step, the prevalence of Plasmodium spp. and the presence of mutations associated with artemisinin resistance were evaluated in two districts of Preah Vihear Province. Methods: A cross-sectional population-based study using a two-stage cluster sampling was conducted in the rural districts of Chhaeb and Chey Saen, from September to October 2013. In each district, 30 clusters of 10 households were randomly selected. In total, blood samples were collected for 1,275 participants in Chhaeb and 1,224 in Chey Saen. Prevalence of Plasmodium spp. was assessed by PCR on dried blood spots. Plasmodium falciparum positive samples were screened for mutations in the K13-propeller domain gene (PF3D7_1343700). Result: The prevalence of Plasmodium spp. was estimated at 1.49% (95% CI 0.71-3.11%) in Chhaeb and 2.61% (95% CI 1.45-4.66%) in Chey Saen. Twenty-seven samples were positive for P. falciparum, giving a prevalence of 0.16% (95% CI 0.04-0.65) in Chhaeb and 2.04% (95% CI 1.04-3.99%) in Chey Saen. Only 4.0% of the participants testing positive presented with fever or history of fever. K13-propeller domain mutant type alleles (C580Y and Y493H) were found, only in Chey Saen district, in seven out of 11 P. falciparum positive samples with enough genetic material to allow testing. Conclusion: The overall prevalence of P. falciparum was low in both districts but parasites presenting mutations in the K13-propeller domain gene, strongly associated with artemisinin-resistance, are circulating in Chey Saen.The prevalence might be underestimated because of the absentees - mainly forest workers - and the workers of private companies who were not included in the study. These results confirm the need to urgently develop and implement targeted interventions to contain and eliminate P. falciparum malaria in this district before it spreads to other areas. [ABSTRACT FROM AUTHOR]

Background: During HIV infection and/or antiretroviral therapy (ART), monocytes and macrophages exhibit a wide range of dysfunctions which contribute significantly to HIV pathogenesis and therapy-associated complications. Nevertheless, the molecular components which contribute to these dysfunctions remain elusive. We therefore applied a parallel approach of genome-wide microarray analysis and focused gene expression profiling on monocytes from patients in different stages of HIV infection and/or ART to further characterise these dysfunctions. Results: Processes involved in apoptosis, cell cycle, lipid metabolism, proteasome function, protein trafficking and transcriptional regulation were identified as areas of monocyte dysfunction during HIV infection. Individual genes potentially contributing to these monocyte dysfunctions included several novel factors. One of these is the adipocytokine NAMPT/visfatin, which we show to be capable of inhibiting HIV at an early step in its life cycle. Roughly half of all genes identified were restored to control levels under ART, while the others represented a persistent dysregulation. Additionally, several candidate biomarkers (in particular CCL1 and CYP2C19) for the development of the abacavir hypersensitivity reaction were suggested. Conclusions: Previously described areas of monocyte dysfunction during HIV infection were confirmed, and novel themes were identified. Furthermore, individual genes associated with these dysfunctions and with ART-associated disorders were pinpointed. These genes form a useful basis for further functional studies concerning the contribution of monocytes/macrophages to HIV pathogenesis. One such gene, NAMPT/visfatin, represents a possible novel restriction factor for HIV. [ABSTRACT FROM AUTHOR]

Recent systematic reviews have highlighted a paucity of rigorous evidence to guide water, sanitation and hygiene (WASH) interventions in humanitarian crises. In June 2017, the Research for Health in Humanitarian Crises (R2HC) programme of Elrha, convened a meeting of representatives from international response agencies, research institutions and donor organisations active in the field of humanitarian WASH to identify research priorities, discuss challenges conducting research and to establish next steps. Topics including cholera transmission, menstrual hygiene management, and acute undernutrition were identified as research priorities. Several international response agencies have existing research programmes; however, a more cohesive and coordinated effort in the WASH sector would likely advance this field of research. This report shares the conclusions of that meeting and proposes a research agenda with the aim of strengthening humanitarian WASH policy and practice. [ABSTRACT FROM AUTHOR]

Background: The China's 1-3-7 strategy was initiated and extensively adopted in different types of counties (geographic regions) for reporting of malaria cases within 1 day, their confirmation and investigation within 3 days, and the appropriate public health response to prevent further transmission within 7 days. Assessing the level of compliance to the 1-3-7 strategy at the county level is a first step towards determining whether the surveillance and response strategy is happening according to plan. This study assessed if the time-bound targets of the 1-3-7 strategy were being sustained over time. Such information would be useful to improve implementation of the 1-3-7 strategy in China., Methods: This cross-sectional study involved country-wide programmatic data for the period January 1st 2013 to June 30th 2014. Data variables were extracted from the national malaria information system and included socio-demographic information, type of county, date of diagnosis, date of reporting, date of case investigation, case classification (indigenous, or imported, or unknown), focus investigation, date of reactive case detection (RACD), and date of indoor residual spraying (IRS). Summary statistics and proportions were used and comparisons between groups were assessed using the chi-square test. Level of significance was set at a P-value ≤ 0.05., Results: Of a total of 5,688 malaria cases from 731 counties, there were 55 (1 %) indigenous cases (only in Type 1 and Type 2 counties) and 5,633 (99 %) imported cases from all types of counties. There was no delay in reporting malaria cases by type of county. In terms of case investigation, 97.5 % cases were investigated within 3 days with the proportion of delays (1.5 %) in type 2 counties, being significantly lower than type 1 counties (4.1 %). Regarding active foci, 96.4 % were treated by RACD and/or IRS., Conclusions: The performance of 1-3-7 strategy was encouraging but identified some challenges that if addressed can further improve implementation.

Background: Research involving gene expression profiling and clinical applications, such as diagnostics and prognostics, often require a DNA array platform that is flexibly customisable and cost-effective, but at the same time is highly sensitive and capable of accurately and reproducibly quantifying the transcriptional expression of a vast number of genes over the whole transcriptome dynamic range using low amounts of RNA sample. Hereto, a set of easy-to-implement practical optimisations to the design of cDNA-based nylon macroarrays as well as sample (33)P-labeling, hybridisation protocols and phosphor screen image processing were analysed for macroarray performance., Results: The here proposed custom macroarray platform had an absolute sensitivity as low as 50,000 transcripts and a linear range of over 5 log-orders. Its quality of identifying differentially expressed genes was at least comparable to commercially available microchips. Interestingly, the quantitative accuracy was found to correlate significantly with corresponding reversed transcriptase - quantitative PCR values, the gold standard gene expression measure (Pearson's correlation test p < 0.0001). Furthermore, the assay has low cost and input RNA requirements (0.5 μg and less) and has a sound reproducibility., Conclusions: Results presented here, demonstrate for the first time that self-made cDNA-based nylon macroarrays can produce highly reliable gene expression data with high sensitivity and covering the entire mammalian dynamic range of mRNA abundances. Starting off from minimal amounts of unamplified total RNA per sample, a reasonable amount of samples can be assayed simultaneously for the quantitative expression of hundreds of genes in an easily customisable and cost-effective manner.