BACKGROUND

Hepatitis E virus (HEV) is a leading cause of acute viral hepatitis, particularly in Asia and Africa, where HEV genotypes 1 and 2 are prevalent. Although a recombinant vaccine, Hecolin, is available, it has not been used to control outbreaks. The licensed three-dose regimen might pose challenges for it to be an impactful outbreak control tool. Our study aimed to estimate the effectiveness of two doses of Hecolin in the context of the first-ever reactive use of the vaccine.

METHODS

We conducted a case-control study during an HEV outbreak in the Bentiu internally displaced persons camp, South Sudan. Patients with acute jaundice syndrome (suspected cases) seeking care at the Médecins Sans Frontières hospital were screened for study eligibility. Eligible participants were those that had been eligible for vaccination (ie, living in the camp and aged 16-40 years). Confirmed cases were defined as individuals who tested positive for hepatitis E by RT-PCR or anti-HEV IgM ELISA. Each case was matched to six controls by age, sex, pregnancy status, and residence. Self-reported vaccination status was verified through vaccination cards. The primary analysis was two-dose vaccine effectiveness, which we estimated with a matched case-control design using conditional logistic regression models. In secondary analyses we estimated vaccine effectiveness using a test-negative design and the screening method. We used test-negative cases and their matched controls as a bias indicator analysis to help quantify potential health seeking behaviour biases.

FINDINGS

Between May 10 and Dec 30, 2022, we identified 859 patients with suspected hepatitis E. Of these, 201 met the eligibility criteria and 21 cases had laboratory confirmed hepatitis E. Among the confirmed cases, 10 (48%) were unvaccinated compared with 33 (27%) of 121 matched controls. In the primary analysis we estimated an unadjusted two-dose vaccine effectiveness of 67·8% (95% CI -28·6 to 91·9), and a two-dose vaccine effectiveness of 84·0% (-208·5 to 99·2) after adjustment for potential confounders. The bias indicator analysis suggested that test-negative cases might have been more likely to have been vaccinated than their matched community controls due to different health-care seeking behaviours, potentially meaning underestimation of effectiveness estimates. The test-negative design, which uses facility-matched controls, led to an adjusted two-dose effectiveness of 89·4% (56·4 to 98·0).

INTERPRETATION

Despite the small sample size, our estimates provide evidence of effectiveness of a two-dose regimen against HEV genotype 1 during a protracted outbreak, supporting its use in similar contexts.

BACKGROUND

In settings with low pneumococcal conjugate vaccine (PCV) coverage, multi-age cohort mass campaigns could increase population immunity, and fractional dosing could increase affordability. We aimed to evaluate the effect of mass campaigns on nasopharyngeal pneumococcal carriage of Pneumosil (PCV10) in children aged 1-9 years in Niger.

METHODS

In this three-arm, open-label, cluster-randomised trial, 63 clusters of one to four villages in Niger were randomly assigned (3:3:1) using block randomisation to receive campaigns consisting of a single full dose of a 10-valent PCV (Pneumosil), a single one-fifth dose of Pneumosil, or no campaign. Independently sampled carriage surveys were done among 2268 households 6 months before and after vaccination, collecting nasopharyngeal swabs from healthy children for culture and serotyping; those with contraindication to nasopharyngeal swabbing were excluded. The primary outcome was nasopharyngeal carriage of vaccine-serotype pneumococcus. We tested whether vaccine-type carriage was reduced in full-dose versus control clusters; and whether fractional doses were non-inferior to full-doses (lower bound 95% CI more than -7·5%), using generalised estimating equations to analyse cluster summaries at baseline and follow-up, controlling for covariates to estimate risk differences and their 95% CIs. The study is registered with ClinicalTrials.gov (NCT05175014) and the Pan-African Clinical Trials Registry (PACTR20211257448484).

FINDINGS

Surveys were done between Dec 22, 2021, and March 18, 2022, and between Dec 12, 2022, and March 9, 2023. The vaccination campaign ran from June 15 to Aug 2, 2022. Participants' characteristics were consistent across surveys and groups. Pre-vaccination, vaccine-type carriage was 15·6% (149 of 955 participants) in the full-dose group, 17·9% (170 of 948) in the fractional-dose group, and 18·8% (60 of 320) in the control group. Post-vaccination, vaccine-type carriage was 4·6% (44 of 967) in the full-dose group, 8·0% (77 of 962) in the fractional-dose group, and 16·5% (53 of 321) in the control group. The primary analysis showed a risk difference of -16·2% (95% CI -28·6 to -3·0) between the full-dose group and control group (p=0·002 for superiority), and -3·8% (-6·1 to -1·6) between the full-dose group and fractional-dose group, meeting the non-inferiority criteria. No adverse events were judged to be related to vaccination.

INTERPRETATION

Multi-age cohort campaigns had a marked effect on vaccine-type carriage and fractional-dose campaigns met non-inferiority criteria. Such campaigns should be considered in low-coverage settings, including humanitarian emergencies, to accelerate population protection.

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

Nipah virus (NiV), a highly lethal virus in humans, circulates in Pteropus bats throughout South and Southeast Asia. Difficulty in obtaining viral genomes from bats means we have a poor understanding of NiV diversity.

METHODS

We develop phylogenetic approaches applied to the most comprehensive collection of genomes to date (N = 257, 175 from bats, 73 from humans) from 6 countries over 22 years (1999–2020). We divide the 4 major NiV sublineages into 15 genetic clusters. Using Approximate Bayesian Computation fit to a spatial signature of viral diversity, we estimate the presence and the average size of genetic clusters per area.

RESULTS

We find that, within any bat roost, there are an average of 2.4 co-circulating genetic clusters, rising to 5.5 clusters at areas of 1500–2000 km2. We estimate that each genetic cluster occupies an average area of 1.3 million km2 (95% confidence interval [CI], .6–2.3 million km2), with 14 clusters in an area of 100 000 km2 (95% CI, 6–24 km2). In the few sites in Bangladesh and Cambodia where genomic surveillance has been concentrated, we estimate that most clusters have been identified, but only approximately 15% of overall NiV diversity has been uncovered.

CONCLUSIONS

Our findings are consistent with entrenched co-circulation of distinct lineages, even within roosts, coupled with slow migration over larger spatial scales.

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.

BACKGROUND

The 2022 WHO guidelines on multi-drug/rifampicin resistant tuberculosis (MDR/RR-TB) recommend six months of bedaquiline (Bdq) in the all-oral 9-month shorter regimen and six months or longer for Bdq and delamanid (Dlm) in the 18-20-month longer regimen. However, lack of evidence on extended treatment using Bdq or Dlm has limited their use to six months. We examine the frequency and incidence of QT prolongation based on duration of Bdq and/or Dlm use in longer regimens.

METHODS

We analyzed a prospective cohort of MDR/RR-TB patients from 16 countries who initiated treatment with Bdq and/or Dlm containing regimens from 1 April 2015-30 September 2018. Data were systematically collected using a shared protocol. The outcome of interest was the first clinically relevant prolonged QT interval (grade 3 or above) or a Serious Adverse Event (SAE) involving prolonged QT of any grade.

RESULTS

Among 2,553 patients, 59% received >6 months of Bdq and/or Dlm. Of these, 579 (20.9%) patients experienced a prolonged QT event, the majority (95.5%) being grade 1 or 2. Sixty-four(2.5%) patients experienced the outcome of interest with only 12 (0.5%) having ≥ 1 QT prolonging drugs permanently suspended. The incidence rate of the first prolonged QT event was highest in the first six months of treatment and lower in subsequent six-month periods.

CONCLUSION

We demonstrate that Bdq and/or Dlm use beyond six months is safe in longer MDR/RR-TB regimens with most clinically relevant QT prolongation events occurring in the first six months. ECG monitoring for early identification of QT prolongating events is possible in programmatic conditions.

In refugee and internally displaced person settlements, hygienic water handling and free residual chlorine (FRC) are crucial for protecting water against recontamination after distribution up to the household point-of-consumption. We conducted a secondary analysis of water quality and water handling data collected in refugee camps in South Sudan, Jordan, and Rwanda using statistical and process-based modeling to explore how water handling practices affect FRC decay and household FRC outcomes. The two practices that consistently produced a significant effect on FRC decay and household FRC were storing water in direct sunlight and transferring water between containers during household storage. Samples stored in direct sunlight had 0.22–0.31 mg/L lower household FRC and had FRC decay rates between 2 and 3.7 times higher than samples stored in the shade, and samples that were transferred between containers had 0.031–0.51 mg/L lower household FRC and decay rates 1.65–3 times higher than non-transferred samples in sites in which the effect was significant, suggesting that humanitarian responders should aim to provide additional water storage containers to prevent water transferring in households and encourage water-users not to store water in direct sunlight. By contrast, the effect of the three recommended hygienic water handling behaviors (clean, covered containers and drawing by tap or pouring) was mixed or inconclusive. These inconclusive results were likely due to imbalanced or unreliable approaches to gathering the data, and we recommend that hygienic water handling practices that mechanistically provide a physical barrier against recontamination should always be promoted in humanitarian settings.

INTRODUCTION

The retention in care of patients undergoing antiretroviral therapy (ART) is a cornerstone for preventing AIDS‐associated morbidity and mortality, as well as further transmission of HIV. Adherence to ART poses particular challenges in conflict‐affected settings like the Central African Republic (CAR). The study objective was to estimate the rate of lost‐to‐follow‐up (LTFU) and determine factors associated with LTFU among patients living with HIV under ART in CAR.

METHODS

A retrospective cohort analysis was conducted using data from patients being managed at 42 representative ART dispensing sites (i.e. management of ≥200 patients) in the seven health regions of CAR which started ART between January 2019 to September 2021 and followed up to December 2021. The outcome of LTFU was defined as a failure of a patient to attend a scheduled ART refill appointment for at least 90 days from the last appointment. Patients were censored at the first LTFU event.

RESULTS

A total of 6844 patients enrolled in ART care were included in the analysis, of whom 67.5% were females. The mean age (standard deviation) was 35.3 years (10.5). Forty‐two per cent (n = 2874/6844) had an LTFU event during the follow‐up period. However, 23.2% (n = 666/2874) returned to care after LTFU. Overall retention in antiretroviral care at 12 months was 64.2% (CI 63.0−65.5), which ranged from 76.1% in the capital to 48.2% in the inner country region. Risk factors related to LTFU were being male (adjusted hazard ratio [aHR] 1.33; CI 1.1−1.5), age < 25 (aHR 1.46; CI 1.1−1.9), living in regions outside the capital (aHR 1.83; CI 1.6−2.3) and undernutrition (aHR 1.13; CI 1.0−1.3).

CONCLUSIONS

Retention to care in CAR is suboptimal, especially in the inner country. Our results underline the difficulties involved in retaining patients in ART in complex settings, the interplay between poor retention, social unrest, stigma, food insecurity and HIV epidemic control, and the need for tailored programming and interventions like differentiated treatment strategies and complementary food provision.