Clinical trials in settings with intermittent or non-existent internet and power connectivity, for example during humanitarian emergencies, present challenges in the synchronisation of data across different sites, in addition to accessing a centralised database in real-time. To overcome these, we designed a novel hybrid analogue/digital data management system which was deployed during the rapid implementation of a Phase III evaluation of a two-dose preventative vaccine for Ebola virus disease in Goma, Democratic Republic of the Congo, from 2019 to 2022. We provided study participants with an Enhanced Participant Record Card (EPRC) that served as eligibility for, and confirmation of, vaccination and was used in combination with Open Data Kit (ODK) electronic case report forms to create an off-grid study participant management system. To understand the utility of the EPRC, we analysed data from 15,327 study participants who received both vaccines and various types of prompts or reminders to return for dose 2, including home visits, telephone calls, or short messaging service (SMS). A total of 53% participants referred to the date on the EPRC as a prompt to return for dose 2 and 36.1% mentioned this as the only prompt. A multivariable generalised linear mixed-effects model showed that those who were not working, those aged 45–64 years or who had a chronic medical condition identified prior to receiving dose 2 were more likely to use the date on the EPRC as a prompt. Our findings demonstrate the utility of this system in the facilitation of decentralised data collection in off-grid locations that may be useful for future trials in complex humanitarian settings.

People living with HIV (PLHIV) have an increased risk of tuberculosis (TB) and severe COVID-19. TB and COVID-19 present with overlapping symptoms and co-infection can lead to poor outcomes. We assessed the frequency of SARS-CoV-2 positive serology and SARS-CoV-2 infection and the risk of mortality at 6 months in PLHIV with TB disease and SARS-CoV-2 infection. This multi-country, prospective, observational study, conducted between 7^th September 2020 and 7^th April 2022, included ambulatory adult PLHIV investigated for TB (with symptoms of TB or advanced HIV disease) in Kenya, Uganda, and South Africa. Testing included CD4 cell count, Xpert MTB/RIF Ultra assay (sputum), Determine TB LAM Ag assay (urine), chest X-ray, blood SARS-CoV-2 serology test and SARS-CoV-2 PCR (only if TB or COVID-19 symptoms). Individuals were followed for 6 months. Among 1254 participants, 1204 participants had SARS-CoV-2 serology (54% women, median CD4 344 cells/µL [IQR 132–673]), and 487 had SARS-CoV-2 PCR. SARS-CoV-2 serology positivity was 27.0% (325/1204), lower in PLHIV with CD4 counts <200 cells/µL (19.9%, 99/497) than in those with CD4 counts ≥200 cells/µL (31.6%, 222/703), p<0.001. SARS-CoV-2 PCR positivity was 8.6% (42/487) and 27.7% (135/487) had probable or confirmed SARS-CoV-2 infection. Among PLHIV with symptoms of TB or of COVID-19, 6.6% (32/487) had SARS-CoV-2 infection and TB disease. In multivariable analyses, the risk of death was higher in PLHIV with both SARS-CoV-2 infection and TB compared to those with only SARS-CoV-2 infection (adjusted hazard ratio [aHR] 8.90, 95%CI 1.47-53.96, p=0.017), with only TB (aHR 3.70, 95%CI 1.00-13.72, p=0.050) or with none of them (aHR 6.83, 95%CI 1.75-26.72, p=0.006). These findings support SARS-CoV-2 testing in PLHIV with symptoms of TB, and SARS-CoV-2 vaccination, especially for those with severe immunosuppression. PLHIV with COVID-19 and TB have an increased risk of mortality and would benefit from comprehensive management and close monitoring.

Clinical trials are considered to be the largest contributor to pharmaceutical development costs. However, public disclosure of the costs of individual clinical trials is rare. Médecins Sans Frontières (MSF) sponsored a phase 2b-3 randomised controlled trial (TB-PRACTECAL), which identified a new treatment regimen for drug-resistant TB. We aimed to analyse the costs of undertaking a pivotal clinical trial conducted in relatively low-resource health settings and to demonstrate the feasibility of reporting clinical trial costs. TB-PRACTECAL trial costs were analysed using MSF accounting documents. Costs were broken down by cost category, year, and trial site. Total costs for TB-PRACTECAL were €33.9 million and the average cost per patient was €61,460. Twenty-six percent of total costs represented central activities (e.g. trial planning, trial management) and 72% represented trial site activities, with 2% uncategorizable. Within trial site costs, personnel costs were the largest cost (43%) followed by external diagnostic services (11%), medicines (9%), and other medical consumables (7%). Cost variation across trial sites was driven by different varying levels of pre-existing trial infrastructure. A review of previous studies yielded a wide range of cost estimates for clinical trials (ranging US$7–221 million/trial for pharmaceutical phase 2 and 3 trials). Nearly all previous estimates derive from industry reporting that is neither standardized nor auditable; to our knowledge, this is the first published comprehensive analysis of direct expenditures of a specific clinical trial including detailed cost breakdowns. The €34 million cost of TB-PRACTECAL included investments in developing clinical trial infrastructure, the complexity of managing six sites across three health systems, and medical expenditures that are not typical of standard clinical trials. Greater transparency in drug development costs can inform medicine pricing negotiations and is a key element in the design and implementation of more equitable systems of biomedical research and development.

Scabies is a dermatological parasitic infestation prevalent in many regions worldwide. Classified as a neglected disease by World Health Organization (WHO) since 2017, it is often associated with poor living conditions and overcrowding. Towards the end of 2021, unusual high numbers of scabies cases in outpatient consultations were observed in two Médecins Sans Frontières’ (MSF) Primary Healthcare Centers (PHCs) in Rohingya refugee camps in Cox’s Bazar, Bangladesh. Here, we aimed to describe the epidemiological and clinical characteristics of patients with scabies consulting the clinics from July 2022–November 2023. A cross-sectional study using routinely collected data from scabies’ consultations at two MSF clinics located in camp 14 and 15 (total population 91,241 in 2023) was conducted. We retrospectively analyzed programmatic data of patients of all ages attending outpatient consultations and clinically diagnosed as scabies. Data were extracted from MSF clinical routine monitoring databases and descriptive statistics were reported. During the 16-month period, a total of 178,922 scabies consultations were recorded, amongst whom 57.7% were women and 42.3% men. Children <5 years constituted 20.5% of the cases, age-groups 6-14, 36.6%, and ≥15 years, 42.9%. Camp 15 had the highest number of cases (39.4%), followed by other camps (29.7%), and then camp 14 (24.4%). Most cases were simple scabies (79.5%); one in five were scabies with secondary infection cases. Patients were mainly treated with oral ivermectin (71.2%) and topical permethrin (24.3%); 19.5% of patients also received antibiotics. Our findings indicate that scabies is a significant health concern in the Cox’s Bazar refugee camp. This study recorded over 178000 cases in the above period. The scale of this outbreak warrants further actions, including a prevalence survey, quality implementation of mass drug administration, and multidisciplinary interventions related to camps’ living conditions such as water and sanitation.

Severely malnourished patients can present with bilateral pitting oedema, which is a common sign of Kwashiorkor. However, bilateral pitting oedema can also be an expression of other pathologies. In Mali and DRC, the number of children presenting with bilateral pitting oedema at MSF (Médecins Sans Frontiers/Doctors Without Borders) hospitals are up to 30% (Mali) and 49% (DRC) higher than in other countries, however, the reasons underlying this trend are unknown. Through this qualitative study, we aimed to explore the perspectives and lived experiences of health professionals on the diagnosis and management of children with bilateral pitting oedema. Using a participatory approach, we conducted 21 in-depth interviews, and 2 focus groups with health professionals at MSF health facilities who had worked in the settings of Koutiala (Mali) and Rutshuru (DRC) for at least 6 months. The understanding of the bilateral pitting oedema phenomenon is complex. Health workers described clinical obstacles to reducing mortality, including: i) difficulties making the diagnosis due to a lack of specialized staff and insufficient resources, ii) challenges treating complications that may arise due to the complexity of the diseases associated with bilateral pitting oedema, and iii) lack of scientific evidence in the literature explaining the physiopathology of bilateral pitting oedema. Study participants shared several key recommendations for reducing mortality among children presenting with bilateral pitting oedema, including prevention of bilateral pitting oedema at the community level, standardization of the diagnostic process, strengthening of medical training, and better collaboration both within the medical teams and between teams and the children’s families.

In 2021 in response to an outbreak of hepatitis E in Bentiu internally displaced persons camp the South Sudanese Ministry of Health with support from Médecins Sans Frontières implemented the first-ever mass reactive vaccination campaign with HEV239 (Hecolin; Innovax, Xiamen, China). We conducted qualitative research to assess knowledge, attitudes, and practices related to hepatitis E and the hepatitis E vaccine. We conducted 8 focus group discussions (FGDs) with community leaders, the general population of vaccine-eligible adults, vaccine-eligible pregnant women (vaccinated and non-vaccinated), and healthcare workers. FGDs were separate by gender and were audio recorded, transcribed, and translated to English. Two coders used inductive thematic analysis to organize emergent themes. Data were collected in November 2022. Most participants had experiences with hepatitis E (e.g., infected themselves or knowing someone that had been infected) and viewed hepatitis E as a dangerous disease. Participants believed children, pregnant women, and older persons were the highest risk groups and frequently made requests for additional hepatitis E vaccination campaigns and expanded eligibility criteria for vaccination. Knowledge of the negative impacts of hepatitis E and trusted relationships with the organizations offering the vaccine were key facilitators of vaccine acceptance. The primary barriers to vaccination were practical issues related to being away from the camp during the campaign or not knowing about the campaign, but participants shared that some in the community were unvaccinated due to fears about injections, social pressure, misinformation, and concerns about why some groups were eligible for vaccination and not others (e.g., young children). Personal experiences with hepatitis E illness, perceived severity of illness, and confidence in organizations recommending the vaccine were drivers of high demand for hepatitis E vaccines in the first-ever use of the vaccine in an outbreak setting. Addressing practical issues related to population mobility can improve coverage in future campaigns.

Ultraportable (UP) X-ray devices are ideal to use in community-based settings, particularly for chest X-ray (CXR) screening of tuberculosis (TB). Unfortunately, there is insufficient guidance on the radiation safety of these devices. This study aims to determine the radiation dose by UP X-ray devices to both the public and radiographers compared to international dose limits. Radiation dose measurements were performed with four UP X-ray devices that met international criteria, utilizing a clinically representative CXR set-up made with a thorax phantom. Scatter and leakage radiation dose were measured at various positions surrounding the phantom and X-ray tube, respectively. These measurements were used to calculate yearly radiation doses for different scenarios based on the median of all UP X-ray devices. From the yearly scatter doses, the minimum distances from the phantom needed to stay below the international public dose limit (1 mSv/year) were calculated. This distance was longest in the direction back towards the X-ray tube and shortest to the left/right sides of the phantom, e.g., 4.5 m and 2.5 m resp. when performing 50 exams/day, at 90 kV, 2.5 mAs and source skin distance (SSD) 1 m. Additional calculations including leakage radiation were conducted at a typical radiographer position (i.e., behind the X-ray tube), with a correction factor for wearing a lead apron. At 2 m behind the X-ray tube, a radiographer wearing a lead apron could perform 106 exams/day at 2.5 mAs and 29 exams/day at 10 mAs (90 kV, SSD 1 m), while keeping his/her radiation dose below the public dose limit (1 mSv/year) and well below the radiographer dose limit (20 mSv/year). In most CXR screening scenarios, the radiation dose of UP X-ray devices can be kept below 1 mSv/year by employing basic radiation safety rules on time, distance and shielding and using appropriate CXR exposure parameters.

In sub-Saharan Africa, reported COVID-19 numbers have been lower than anticipated, even when considering populations’ younger age. The extent to which risk factors, established in industrialised countries, impact the risk of infection and of disease in populations in sub-Saharan Africa, remains unclear. We estimated the incidence of mild and moderate COVID-19 in urban Mozambique and analysed factors associated with infection and disease in a population-based surveillance study. During December 2020-March 2022, 1,561 households (6,049 participants, median 21 years, 54.8% female, 7.3% disclosed HIV positive) of Polana Caniço, Maputo, Mozambique, were visited biweekly to report respiratory symptoms, anosmia, or ageusia, and self-administer a nasal swab for SARS-CoV-2 testing. Every three months, dried blood spots of a subset of participants (1,412) were collected for detection of antibodies against SARS-CoV-2 spike glycoprotein and nucleocapsid protein. Per 1000 person-years, 364.5 (95%CI 352.8–376.1) respiratory illness episodes were reported, of which 72.2 (95%CI 60.6–83.9) were COVID-19. SARS-CoV-2 seroprevalence rose from 4.8% (95%CI 1.1–8.6%) in December 2020 to 34.7% (95%CI 20.2–49.3%) in June 2021, when 3.0% were vaccinated. Increasing age, chronic lung disease, hypertension, and overweight increased risk of COVID-19. Older age increased the risk of SARS-CoV-2 seroconversion. We observed no association between socio-economic status, behaviour and COVID-19 or SARS-CoV-2 seroconversion. Active surveillance in an urban population confirmed frequent COVID-19 underreporting, yet indicated that the large majority of cases were mild and non-febrile. In contrast to reports from industrialised countries, social deprivation did not increase the risk of infection nor disease.