In 2015, I was in the Democratic Republic of the Congo (DRC), working as a pediatrician with Médecins Sans Frontières (MSF). As had been the case in my two previous assignments with MSF, I encountered many interesting and challenging cases—cases that I had never experienced prior to working in resource limited settings. Contrary to when I work in the USA and have access to extensive laboratory exams and diagnostic testing, in our hospital in the DRC, no such tools were available, and thus I needed to use a whole new level of clinical skills and deductive reasoning. To make clinical management even more challenging, I rarely saw these types of cases written about or published in the medical literature. I was discouraged that although these clinical examples were perfect fodder for medical case discussions, they did not have the ‘components’ required for a traditional case report. In frustration, I wrote the following:
‘The reason why we, those working in “resource limited settings”, do not often attempt to publish case reports is because we don’t often find an answer. We think that published articles and case reports should be neat and clean. That students or colleagues should be able to read a mystery case, try to solve the puzzle, and at the end be rewarded with an answer brought about by some obscure lab or radiology report. But that’s not what happens. The world of medicine in resource limited settings isn’t neat and clean. It’s frustrating and messy. Mystifying and sad. You can come up with a million differentials but ultimately the child, because of, or in despite of, your chosen treatment, makes it. Or doesn’t make it. And you never get an answer. You don’t learn. And you can try to look in the literature, but the research will talk about IGF1 and MRI and calcium. I can’t even get a cal.ci.um. And so, the mystery disease leads to a mystery death and you are left feeling powerless. And there is not even a take home message.’
I am excited that now with the Oxford Medical Case Reports collaboration, there is a platform to start regaining some power, to start creating a take-home message. There is a platform for collaboration amongst all of us medical professionals working in resource limited settings—a platform to share these unique cases to perhaps discover that they are not so unique at all. They are just not published.
Contributors:van Lenthe, M, van der Meulen, R, Okell, L, Piriou, E, Lassovski, M, Bakula, E, Badio, C, Roper, C, Bousema, T, Ouabo, A, Cibenda, D, Grignard, L, Lanke, Kjerstin, Rao, B, MSF OCA and MSF London
Sulfadoxine–pyrimethamine (SP) is a cornerstone of malaria chemoprophylaxis and is considered for programmes in the Democratic Republic of Congo (DRC). However, SP efficacy is threatened by drug resistance, that is conferred by mutations in the dhfr and dhps genes. The World Health Organization has specified that intermittent preventive treatment for infants (IPTi) with SP should be implemented only if the prevalence of the dhps K540E mutation is under 50%. There are limited current data on the prevalence of resistance-conferring mutations available from Eastern DRC. The current study aimed to address this knowledge gap.
Dried blood-spot samples were collected from clinically suspected malaria patients [outpatient department (OPD)] and pregnant women attending antenatal care (ANC) in four sites in North and South Kivu, DRC. Quantitative PCR (qPCR) was performed on samples from individuals with positive and with negative rapid diagnostic test (RDT) results. Dhps K450E and A581G and dhfr I164L were assessed by nested PCR followed by allele-specific primer extension and detection by multiplex bead-based assays.
Across populations, Plasmodium falciparum parasite prevalence was 47.9% (1160/2421) by RDT and 71.7 (1763/2421) by qPCR. Median parasite density measured by qPCR in RDT-negative qPCR-positive samples was very low with a median of 2.3 parasites/µL (IQR 0.5–25.2). Resistance genotyping was successfully performed in RDT-positive samples and RDT-negative/qPCR-positive samples with success rates of 86.2% (937/1086) and 55.5% (361/651), respectively. The presence of dhps K540E was high across sites (50.3–87.9%), with strong evidence for differences between sites (p < 0.001). Dhps A581G mutants were less prevalent (12.7–47.2%). The dhfr I164L mutation was found in one sample.
The prevalence of the SP resistance marker dhps K540E exceeds 50% in all four study sites in North and South Kivu, DRC. K540E mutations regularly co-occurred with mutations in dhps A581G but not with the dhfr I164L mutation. The current results do not support implementation of IPTi with SP in the study area.
Contributors:Elder, K, Saitta, B, Tanja, D, Elder, G, Close, R, Scourse, R, Kahn, P, Scheele, S, Miriam, A, Erickson, E, Ducomble, T, MSF Access Campaign / MSF USA
Vaccination is an effective intervention to reduce disease, disability, death
and health inequities worldwide. Over
the last two decades, vaccines have
become more accessible in low-income
countries; however, significant gaps
remain, particularly in humanitarian
emergencies, where populations face
increased risks of many diseases. In
2013, the World Health Organization
(WHO) published Vaccination in acute
humanitarian emergencies: a framework
for decision-making, to provide guidance
on which vaccines to prioritize during
obstacles, especially high prices for new
vaccines, hinder implementation of this
framework and of critical vaccination
activities in emergency settings.
In response to these challenges,
global health stakeholders held a series
of consultations in 2016 and proposed
a WHO-based mechanism, the Humanitarian Mechanism, for the rapid
procurement of affordable vaccines during emergencies, to be used by nongovernmental organizations (NGOs), civil
society organizations, United Nations
(UN) agencies and governments.
Here we present the background of
the creation of the mechanism from the
perspective of Médecins Sans Frontières
(MSF), including a description of our
past challenges in accessing affordable
pneumococcal conjugate vaccine (PCV;
Box 1), a critical vaccine during many
emergencies. We then describe how the
mechanism has so far facilitated access
to more affordable PCV and outline
steps that could increase its potential
for saving lives.
Contributors:Jeufack, H, Neufeld, N, Alem, A, Sauer, S, Odhiambo, J, Boum, Y, Shuchman, M, Volmink, J
Collaborations are often a cornerstone of global health research. Power dynamics can shape if and how local researchers are included in manuscripts. This article investigates how international collaborations affect the representation of local authors, overall and in first and last author positions, in African health research.
We extracted papers on 'health' in sub-Saharan Africa indexed in PubMed and published between 2014 and 2016. The author's affiliation was used to classify the individual as from the country of the paper's focus, from another African country, from Europe, from the USA/Canada or from another locale. Authors classified as from the USA/Canada were further subclassified if the author was from a top US university. In primary analyses, individuals with multiple affiliations were presumed to be from a high-income country if they contained any affiliation from a high-income country. In sensitivity analyses, these individuals were presumed to be from an African country if they contained any affiliation an African country. Differences in paper characteristics and representation of local coauthors are compared by collaborative type using χ² tests.
Of the 7100 articles identified, 68.3% included collaborators from the USA, Canada, Europe and/or another African country. 54.0% of all 43 429 authors and 52.9% of 7100 first authors were from the country of the paper's focus. Representation dropped if any collaborators were from USA, Canada or Europe with the lowest representation for collaborators from top US universities-for these papers, 41.3% of all authors and 23.0% of first authors were from country of paper's focus. Local representation was highest with collaborators from another African country. 13.5% of all papers had no local coauthors.
Individuals, institutions and funders from high-income countries should challenge persistent power differentials in global health research. South-South collaborations can help African researchers expand technical expertise while maintaining presence on the resulting research.
Contributors:Maataoui1, M, Et al
We regret that this article is behind a paywall.
Contributors:Hacking, D, Cassidy, T, Mgengwana-Mbakaza, Z, Boulle, A, Mathys, R, Runeyi, P, Duran, L
Background: Youths in South Africa are poor utilizers of HIV health services. Medecins Sans Frontieres has been piloting youth-adapted services at a youth clinic in Khayelitsha, including a peer virtual mentorship program over mobile phones, piloted from March 2015 to May 2016.
Objective: The objective of this study was to evaluate the effect of the peer mentorship program on youth engagement with HIV services and explore the acceptability of the program to both mentors and mentees.
Methods: Antiretroviral initiation, retention in care (RIC), and viral load suppression were compared between youths engaged in the virtual mentorship program and two matched controls. In-depth interviews were also conducted for 5 mentors and 5 mentees to explore acceptability and impact of the program.
Results: A total of 40 youths were recruited into the virtual mentorship program over the study period. Of these, data were obtained for 35 and 2 matched controls were randomly sampled for each. There was no difference in baseline demographics (eg, age, gender, and CD4 count). Mentees had increased antiretroviral initiation (28/35, 80% vs 30/70, 42% in matched controls) and viral load completion (28/35, 80% vs 32/70, 45%); however, no differences were found in viral load suppression or RIC at 6 or 12 months. Mentors reported being motivated to participate in the program because of previous personal struggles with HIV and a desire to help their peers. Mentees reported fears of disclosure and lack of acceptance of their status as barrier to accessing services, but they felt free to talk to their mentors, valued the mentorship program, and indicated a preference for phone calls.
Conclusions: Peer mentorship in youths is acceptable to both mentors and mentees and appears to increase linkage to care and viral load completion rates.
Introduction: Yellow fever is endemic in specific regions of sub-Saharan Africa and the Americas, with recent epidemics occurring on both continents. The yellow fever vaccine is effective, affordable and safe, providing life-long immunity following a single dose vaccination. However, the vaccine production process is slow and cannot be readily scaled up during epidemics. This has led the World Health Organization (WHO) to recommend the use of fractional doses as a dose-sparing strategy during epidemics, but there are no randomized controlled trials of fractional yellow fever vaccine doses in Africa.
Methods and analysis: We will recruit healthy adult volunteers, adults living with HIV, and children to a series of randomized controlled trials aiming to determine the immunogenicity and safety of fractional vaccine doses in comparison to the standard vaccine dose. The trials will be conducted across two sites; Kilifi, Kenya and Mbarara, Uganda. Recruited participants will be randomized to receive fractional or standard doses of yellow fever vaccine. Scheduled visits will include blood collection for serum and peripheral blood mononuclear cells (PBMCs) before vaccination and on various days – up to 2 years – post-vaccination. The primary outcome is the rate of seroconversion as measured by the plaque reduction neutralization test (PRNT50) at 28 days post-vaccination. Secondary outcomes include antibody titre changes, longevity of the immune response, safety assessment using clinical data, the nature and magnitude of the cellular immune response and post-vaccination control of viremia by vaccine dose.
Ethics and dissemination: The clinical trial protocols have received approval from the relevant institutional ethics and regulatory review committees in Kenya and Uganda, and the WHO Ethics Review Committee. The research findings will be disseminated through open-access publications and presented at relevant conferences and workshops.
Contributors:Ansbro, EM, Roberts, B, Jobanputra, K, Biringanine, M, Caleo, G, Prieto-Merino, D, Sadique, Z, Perel, P
Objective We aimed to evaluate an Integrated Diabetic Clinic within a Hospital Outpatient Department (IDC-OPD) in a complex humanitarian setting in North Kivu, Democratic Republic of Congo. Specific objectives were to: (1) analyse diabetes intermediate clinical and programmatic outcomes (blood pressure (BP)/glycaemic control, visit volume and frequency); (2) explore the association of key insecurity and related programmatic events with these outcomes; and (3) describe incremental IDC-OPD programme costs. Design Retrospective cohort analysis of routine programmatic data collected from January 2014 to February 2017; analysis of programme costs for 2014/2015. Setting Outpatient diabetes programme in Mweso hospital, supported by Médecins sans Frontières, in North Kivu, Demographic Republic of Congo. Participants Diabetes patients attending IDC-OPD. Outcome measures Intermediate clinical and programmatic outcome trends (BP/ glycaemic control; visit volume/frequency); incremental programme costs. Results Of 243 diabetes patients, 44.6% were women, median age was 45 (IQR 32–56); 51.4% were classified type 2. On introduction of IDC-OPD, glucose control improved and patient volume and visit interval increased. During insecurity, control rates were initially maintained by a nurse-provided, scaled-back service, while patient volume and visit interval decreased. Following service suspension due to drug stock-outs, patients were less likely to achieve control, improving on service resumption. Total costs decreased 16% from 2014 (€36 573) to 2015 (€30 861). Annual cost per patient dropped from €475 in 2014 to €214 in 2015 due to reduced supply costs and increased patient numbers. Conclusions In a chronic conflict setting, we documented that control of diabetes intermediate outcomes was achievable during stable periods. During insecure periods, a simplified, nurse-led model maintained control rates until drug stock-outs occurred. Incremental per patient annual costs were lower than chronic HIV care costs in low-income settings. Future operational research should define a simplified diabetes care package including emergency preparedness.
Contributors:Dodd, L, Follman, D, Proschan, M, Wang, J, Malvy, D, Horby, P, Gouel-Cheron, A, Ciglenecki, I, Davey, R, Lane, C, van Griensven, J, Ansumana, R, Jiang, J
Recent Ebola virus disease outbreaks affirm the dire need for treatments with proven efficacy. Randomized controlled clinical trials remain the gold standard but, during disease outbreaks, may be difficult to conduct due to ethical concerns and challenging field conditions. In the absence of a randomized control group, statistical modeling to create a control group could be a possibility. Such a model-based reference control would only be credible if it had the same mortality risk as that of the experimental group in the absence of treatment. One way to test this counterfactual assumption is to evaluate whether reasonable similarity exists across nonrandomized control groups from different clinical studies, which might suggest that a future control group would be similarly homogeneous. We evaluated similarity across six clinical studies conducted during the 2013-2016 West Africa outbreak of Ebola virus disease. These studies evaluated favipiravir, the biologic ZMapp, the antimalarial drug amodiaquine, or administration of convalescent plasma or convalescent whole blood. We compared the nonrandomized control groups of these six studies comprising 1147 individuals infected with Ebola virus. We found considerable heterogeneity, which did not disappear after statistical modeling to adjust for prognostic variables. Mortality risk varied widely (31 to 66%) across the nonrandomized control arms of these six studies. Models adjusting for baseline covariates (age, sex, and cycle threshold, a proxy for viral load) failed to sufficiently recalibrate these studies and showed that heterogeneity remained. Our findings highlight concerns about making invalid conclusions when comparing nonrandomized control groups to cohorts receiving experimental treatments.
Contributors:Robinson, E, Crispino, V, Ouabo, A, Soung Iballa, F, Kremer, R, Serbassi, M, van Lenthe, M, Carrion Martin, A
Background: During humanitarian crises, health information systems are often lacking and surveys are a valuable tool to assess the health needs of affected populations. In 2013, a mortality and health survey undertaken by Médecins Sans Frontières (MSF) in the conflict affected Walikale territory of North Kivu, Democratic Republic of the Congo (DRC), indicated mortality rates exceeding humanitarian crisis thresholds and a high burden of mortality and morbidity due to malaria. In late 2017, after a period of relative stability, MSF reassessed the health status of the population through a second survey to guide ongoing operations. Methods: A two-stage cluster survey, selecting villages using probability proportional to size and households using random walk procedures, was conducted. Household members were interviewed on morbidity and mortality, healthcare use, vaccination status, and bednet availability. Results: The sample included 5711 persons in 794 households. The crude mortality rate (CMR) and under-five mortality rate (U5MR) were 0.98 per 10,000 persons/day (95% confidence interval (CI) 0.78–1.2) and 1.3 per 10,000 persons/day (95% CI): 0.82–2.0), respectively. The most frequently reported causes of death were fever/malaria (31%), diarrhoea (15%) and respiratory infections (8%). In 89% of households at least one person was reported as falling ill in the previous 2 weeks, and 58% sought healthcare. Cost was the main barrier amongst 58% of those who did not seek healthcare. Coverage of measles-containing-vaccine was 62% in under-fives. Sufficient bednet coverage (1 bednet/2 people) was reported from 17% of households. Conclusion: The second survey illustrates that although mortality is now just below crisis thresholds, the area still experiences excess mortality and has substantial health needs. The study results have supported the further expansion of integrated community case management to improve access to care for malaria, diarrhoea and respiratory infections. Such surveys are important to orient operations to the health needs of the population being served and also highlight the ongoing vulnerability of populations after humanitarian crises.