BACKGROUND

Yellow fever vaccine is highly effective with a single dose, but vaccine supply is limited. The minimum dose requirements for seroconversion remain unknown.

METHODS

In this double-blind, randomized, noninferiority trial in Uganda and Kenya, we assigned adults with no history of yellow fever vaccination or infection to receive vaccination with the Institut Pasteur de Dakar 17D-204 yellow fever vaccine at a standard dose (13,803 IU) or at a fractional dose of 1000 IU, 500 IU, or 250 IU. The primary outcome was seroconversion at 28 days after vaccination with each fractional dose as compared with the standard dose, evaluated in a noninferiority analysis. Seroconversion was defined as an antibody titer at day 28 that was at least four times as high as the antibody titer before vaccination, as measured by a plaque reduction neutralization test. We conducted noninferiority analyses in the per-protocol and intention-to-treat populations. Noninferiority was shown if the lower boundary of the 95% confidence interval for the difference in the incidence of seroconversion between the fractional dose and the standard dose was higher than -10 percentage points.

RESULTS

A total of 480 participants underwent randomization (120 participants in each group). The incidence of seroconversion was 98% (95% confidence interval [CI], 94 to 100) with the standard dose. The difference in the incidence of seroconversion between the 1000-IU dose and the standard dose was 0.01 percentage points (95% CI, -5.0 to 5.1) in the intention-to-treat population and -1.9 percentage points (95% CI, -7.0 to 3.2) in the per-protocol population; the corresponding differences between the 500-IU dose and the standard dose were 0.01 percentage points (95% CI, -5.0 to 5.1) and -1.8 percentage points (95% CI, -6.7 to 3.2), and those between the 250-IU dose and the standard dose were -4.4 percentage points (95% CI, -9.4 to 0.7) and -6.7 percentage points (95% CI, -11.7 to 1.6). A total of 111 vaccine-related adverse events were reported: 103 were mild in severity, 7 were moderate, and 1 was severe. The incidence of adverse events was similar in the four groups.

CONCLUSIONS

A yellow fever vaccination dose as low as 500 IU was noninferior to the standard dose of 13,803 IU for producing seroconversion within 28 days.

INTRODUCTION

Refugee settings may increase the risk of SARS-CoV-2 infection and death, yet data on the response to the pandemic in these populations is scarce.

METHODS

We describe interventions to mitigate SARS-CoV-2 transmission in Dadaab Refugee Camp Complex, Kenya and performed descriptive analyses using March 2020 to December 2022 data from Kenya's national SARS-CoV-2 repository and line list of positive cases maintained by United Nations High Commissioner for Refugees (UNHCR). We calculated case fatality rates (CFR) and attack rates per 100,000 (AR) using the 2019 national census and population statistics from UNHCR and compared them to national figures.

RESULTS

SARS-CoV-2 infection was first reported in April and May 2020, among host community members and refugees respectively. Of 964 laboratory-confirmed cases, 700 (72.6 %) were refugees. The AR was 82.7 (95 % CI 72.6–92.8) for host community members, 228.3 (95 % CI 211.3–245.4) for refugees and 721.1 (95 % CI 718.7–723.5) nationally. The CFR was 1.5 % (95 % CI 0.15–3.18) for host community members, 1.76 % (95 % CI 1.71–1.80) nationally and 7.4 % (95 % CI 5.4–9.4) for refugees.

Mitigation measures implemented by the Government of Kenya, UNHCR and partners during the pandemic included multisectoral coordination, movement restrictions, mass gathering bans, and health promotion. Social distancing, symptom screening and mandatory mask usage were enforced during mass gatherings. Testing capacity was bolstered, quarantine and isolation facilities established, and vaccination initiated.

CONCLUSIONS

Despite a low AR and UNHCR's swift and comprehensive response, refugees' CFR was high, underscoring their vulnerability and need for targeted interventions during epidemic responses.

BACKGROUND

Expanding contraceptive options could better meet users’ diverse needs and preferences. Annovera^® is a contraceptive vaginal ring that provides a year of pregnancy prevention while remaining under user control and allowing for regular menstrual cycles. This method may also help to reduce burdens on some health care and supply chain systems. However, knowledge gaps exist regarding initial and ongoing acceptability of contraceptive vaginal rings in African settings.

METHODS

We will undertake an open-label, non-randomized, two-arm, parallel clinical acceptability study with an embedded qualitative component, based in clinics providing contraceptive services in Kenya and Zimbabwe. Women aged 18-45 interested in newly initiating or switching contraception will choose from among all available contraceptive options, including Annovera. We aim to enroll 200 participants selecting Annovera and 200 participants selecting either contraceptive injectables or pills. We will compare method uptake, continuation, and satisfaction over one year. Participants will complete questionnaires administered by study staff during two in-person visits (a screening/enrollment visit, and an end of study visit after 52 weeks of method use or at discontinuation) and four phone appointments (at 4, 12, 24, and 36 weeks of use). We will evaluate used rings for discoloration and residual drug levels. The qualitative component involve in-depth interviews with women in the clinical study, their sexual partners, and their service providers, to further examine drivers of and barriers to interest in and use of contraceptive vaginal rings.

DISCUSSION

This study will explore acceptability of contraceptive vaginal rings in ‘real-world’ contraceptive service settings in two African countries. Findings will be based on actual ring use and contextualized via comparison to two other commonly available methods. As vaginal rings are being considered for multiple reproductive health indications, this work can fill key knowledge gaps and empower decision-makers with information needed to inform future investments in reproductive health.

Treatment regimens for post-kala-azar dermal leishmaniasis (PKDL) are usually extrapolated from those for visceral leishmaniasis (VL), but drug pharmacokinetics (PK) can differ due to disease-specific variations in absorption, distribution, and elimination. This study characterized PK differences in paromomycin and miltefosine between 109 PKDL and 264 VL patients from eastern Africa. VL patients showed 0.55-fold (95%CI: 0.41-0.74) lower capacity for paromomycin saturable reabsorption in renal tubules, and required a 1.44-fold (1.23-1.71) adjustment when relating renal clearance to creatinine-based eGFR. Miltefosine bioavailability in VL patients was lowered by 69% (62-76) at treatment start. Comparing PKDL to VL patients on the same regimen, paromomycin plasma exposures were 0.74-0.87-fold, while miltefosine exposure until the end of treatment day was 1.4-fold. These pronounced PK differences between PKDL and VL patients in eastern Africa highlight the challenges of directly extrapolating dosing regimens from one leishmaniasis presentation to another.

INTRODUCTION

The Médecins Sans Frontières (MSF) Kiambu People Who Use Drugs (PWUD) project, which started in September 2019, had enrolled 590 PWUD in its Medically Assisted Therapy (MAT) program by April 2022. This project provides a one-stop-shop model, offering a comprehensive range of medical and psychosocial services. This study aimed to explore how PWUD navigate from heroin use to MAT enrolment.

METHODS

The study involved individual, paired and group interviews conducted between August and October 2022. Purposive sampling was applied. Interviews were recorded, transcribed, coded with NVivo and analysed using reflexive thematic analysis. Methodological triangulation enhanced interpretation.

RESULTS

PWUD faced various challenges to engage in the MAT program. Replacing heroin with MAT, the ‘medicine,’ was insufficient to ensure meaningful recovery. Engaging in MAT required personal motivation to exit the hotspots that their lives revolve around. Main barriers were coping with changed lifestyles and behavioural patterns, and the need to develop new perspectives on dealing with ‘idleness.’

CONCLUSION

The study revealed the complex realities PWUD are confronted with when trying to engage in MAT. MAT programs need to address medical, psychosocial, employment and other structural factors while supporting people to restore their broken social conditions.