Safety of hepatitis E vaccine in pregnancy: an emulated target trial following a mass reactive vaccination campaign in Bentiu internally displaced persons camp, South Sudan.

BACKGROUND: Epidemic forms of hepatitis E cause high mortality among pregnant people, with case fatality risks over 30% and adverse fetal outcomes. In 2022, the first mass reactive vaccination campaign against hepatitis E was conducted in South Sudan with the HEV239 vaccine. We aimed to assess whether vaccination against hepatitis E in pregnancy increases the risk of fetal loss in a cohort of vaccinated and unvaccinated pregnant people. METHODS: In this emulated target trial, an exhaustive pregnancy census was conducted in Bentiu internally displaced persons camp after the second of three vaccination rounds. Women and girls aged 14-45 years with no current jaundice or acute illness were eligible for participation. Individuals who consented were revisited 28 days after their delivery date to document the pregnancy outcome. We used an emulated target trial framework to address biases inherent in observational studies. We matched vaccinated to unvaccinated participants on age, gestational age, and vaccination propensity score and estimated cumulative incidence functions for fetal loss in vaccinated compared to unvaccinated women in a competing risks framework using the Aalen-Johansen estimator. FINDINGS: Between May 16 and June 30, 2022, 3421 participants were enrolled and followed up for inclusion in analysis. Among 2741 women who had a pregnancy outcome after the start of the vaccination campaign, 67 (2·4%) were vaccinated before conception, 2036 (74·3%) were vaccinated during pregnancy, and 638 (23·2%) were not vaccinated. Among the 2407 women retained in the matched analyses, the cumulative risk of fetal loss among individuals vaccinated during pregnancy was 7·2% (95% CI 5·6-8·7) compared with 6·1% (3·7-9·2) among unvaccinated individuals, implying a risk ratio of 1·2 (95% CI 0·7-1·9). INTERPRETATION: No evidence of increased risk of fetal loss was found among individuals vaccinated during pregnancy. FUNDING: Médecins Sans Frontières.

Prevention of mother-to-child transmission of hepatitis B virus in antenatal care and maternity services, Mozambique.

OBJECTIVE: To pilot an intervention on the prevention of mother-to-child transmission (PMTCT) of hepatitis B virus (HBV) in an antenatal care and maternity unit in Maputo, Mozambique, during 2017-2019. METHODS: We included HBV in the existing screening programme (for human immunodeficiency virus (HIV) and syphilis) for pregnant women at their first consultation, and followed mother-child dyads until 9 months after delivery. We referred women who tested positive for hepatitis B surface antigen (HBsAg) for further tests, including hepatitis B e antigen (HBeAg) and HBV viral load. According to the results, we proposed tenofovir for their own health or for PMTCT. We administered birth-dose HBV vaccine and assessed infant HBV status at 9 months. FINDINGS: Of 6775 screened women, 270 (4.0%) were HBsAg positive; in those for whom data were available, 24/265 (9.1%) were HBeAg positive and 14/267 (5.2%) had a viral load of > 200 000 IU/mL. Ninety-eight (36.3%) HBsAg-positive women were HIV coinfected, 97 of whom were receiving antiretroviral treatment with tenofovir. Among HIV-negative women, four had an indication for tenofovir treatment and four for tenofovir PMTCT. Of 217 exposed liveborn babies, 181 (83.4%) received birth-dose HBV vaccine, 160 (88.4%) of these < 24 hours after birth. At the 9-month follow-up, only one out of the 134 tested infants was HBV positive. CONCLUSION: Our nurse-led intervention highlights the feasibility of integrating PMTCT of HBV into existing antenatal care departments, essential for the implementation of the triple elimination initiative. Universal birth-dose vaccination is key to achieving HBV elimination.

Evaluating smartphone strategies for reliability, reproducibility, and quality of VIA for cervical cancer screening in the Shiselweni region of Eswatini: A cohort study.

BACKGROUND: Cervical cancer is among the most common preventable cancers with the highest morbidity and mortality. The World Health Organization (WHO) recommends visual inspection of the cervix with acetic acid (VIA) as cervical cancer screening strategy in resource-poor settings. However, there are barriers to the sustainability of VIA programs including declining providers' VIA competence without mentorship and quality assurances and challenges of integration into primary healthcare. This study seeks to evaluate the impact of smartphone-based strategies in improving reliability, reproducibility, and quality of VIA in humanitarian settings. METHODS AND FINDINGS: We implemented smartphone-based VIA that included standard VIA training, adapted refresher, and 6-month mHealth mentorship, sequentially, in the rural Shiselweni region of Eswatini. A remote expert reviewer provided diagnostic and management feedback on patients' cervical images, which were reviewed weekly by nurses. Program's outcomes, VIA image agreement rates, and Kappa statistic were compared before, during, and after training. From September 1, 2016 to December 31, 2018, 4,247 patients underwent screening; 247 were reviewed weekly by a VIA diagnostic expert. Of the 247, 128 (49%) were HIV-positive; mean age was 30.80 years (standard deviation [SD]: 7.74 years). Initial VIA positivity of 16% (436/2,637) after standard training gradually increased to 25.1% (293/1,168), dropped to an average of 9.7% (143/1,469) with a lowest of 7% (20/284) after refresher in 2017 (p = 0.001), increased again to an average of 9.6% (240/2,488) with a highest of 17% (17/100) before the start of mentorship, and dropped to an average of 8.3% (134/1,610) in 2018 with an average of 6.3% (37/591) after the start of mentorship (p = 0.019). Overall, 88% were eligible for and 68% received cryotherapy the same day: 10 cases were clinically suspicious for cancer; however, only 5 of those cases were confirmed using punch biopsy. Agreement rates with the expert reviewer for positive and negative cases were 100% (95% confidence interval [CI]: 79.4% to 100%) and 95.7% (95% CI: 92.2% to 97.9%), respectively, with negative predictive value (NPV) (100%), positive predictive value (PPV) (63.5%), and area under the curve of receiver operating characteristics (AUC ROC) (0.978). Kappa statistic was 0.74 (95% CI; 0.58 to 0.89); 0.64 and 0.79 at 3 and 6 months, respectively. In logistic regression, HIV and age were associated with VIA positivity (adjusted Odds Ratio [aOR]: 3.53, 95% CI: 1.10 to 11.29; p = 0.033 and aOR: 1.06, 95% CI: 1.0004 to 1.13; p = 0.048, respectively). We were unable to incorporate a control arm due to logistical constraints in routine humanitarian settings. CONCLUSIONS: Our findings suggest that smartphone mentorship provided experiential learning to improve nurses' competencies and VIA reliability and reproducibility, reduced false positive, and introduced peer-to-peer education and quality control services. Local collaboration; extending services to remote populations; decreasing unnecessary burden to screened women, providers, and tertiary centers; and capacity building through low-tech high-yield screening are promising strategies for scale-up of VIA programs.

Reproductive health in humanitarian settings in Lebanon and Iraq: results from four cross-sectional studies, 2014-2015.

BACKGROUND: Reproductive health is an important component of humanitarian response. Displaced women need access to family planning, antenatal care, and the presence of a skilled birth attendant at delivery. Since the beginning of the Syrian conflict in 2011, Lebanon and Iraq have been hosting large numbers of refugees, thereby straining local capacities to provide these services. In order to identify salient health needs, Médecins Sans Frontières conducted a survey in several sites hosting refugees and internally displaced persons across the region. Here we describe the reproductive health profile of Syrian refugees, Iraqi displaced persons, and vulnerable Lebanese and their use of services. METHODS: We conducted four cross-sectional surveys in 2014-2015 in two sites in Lebanon and two sites in Iraq. Depending on the site, two-stage cluster sampling or systematic sampling was intended, but non-probability methods were employed at the second stage due to implementation challenges. We collected information on overall health (including reproductive health) and demographic information from heads of households on the basis of a standardized questionnaire. Pearson chi-square tests were used to compare proportions, and generalized linear models were used to calculate odds ratios with regard to risk factors. All analyses were performed using the survey suite of commands in Stata version 14.1. RESULTS: A total of 23,604 individuals were surveyed, including 5925 women of childbearing age. Overall, it was reported that 7.5% of women were currently pregnant and 12.8% had given birth within the previous 12 months. It was reported that pregnancy was unplanned for 57% of currently pregnant women and 66.7% of women who had delivered in the previous year. A slight majority of women from both groups had accessed antenatal care at least once. Amongst women who had delivered in the previous year, 84.5% had done so with a skilled birth attendant and 22.1% had had a cesarean section. Location and head of household education were predictors of unplanned pregnancy in multivariable analysis. Head of household education was also significantly associated with higher uptake of antenatal care. CONCLUSIONS: Considering the large number of pregnant women and women having recently delivered in these settings, addressing their sexual and reproductive health needs emerges as a crucial aspect of humanitarian response. This study identified unmet needs for family planning and high cesarean section rates at all sites, suggesting both lack of access to certain services (contraception, antenatal care), but also over-recourse to cesarean section. These specific challenges can impact directly on maternal and child health and need today to be kept high on the humanitarian agenda.

Challenges and successes in the implementation of option B+ to prevent mother-to-child transmission of HIV in southern Swaziland.

BACKGROUND: Universal antiretroviral therapy (ART) for all pregnant/ breastfeeding women living with Human Immunodeficiency Virus (HIV), known as Prevention of mother-to child transmission of HIV (PMTCT) Option B+ (PMTCTB+), is being scaled up in most countries in Sub-Saharan Africa. In the transition to PMTCTB+, many countries face challenges with proper implementation of the HIV care cascade. We aimed to describe the feasibility of a PMTCTB+ approach in the public health sector in Swaziland. METHODS: Lifelong ART was offered to a cohort of HIV+ pregnant women aged ≥16 years at the first antenatal care (ANC1) visit in 9 public sector facilities, between 01/2013 and 06/2014. The study enrolment period was divided into 3 phases (early: 01-06/2013, mid: 07-12/2013 and late: 01-06/2014) to account for temporal trends. Kaplan-Meier estimates and Cox proportional-hazards regression models were applied for ART initiation and attrition analyses. RESULTS: Of 665 HIV+ pregnant women, 496 (74.6%) initiated ART. ART initiation increased in later study enrolment phases (mid: aHR: 1.41; later: aHR: 2.36), and decreased at CD4 ≥ 500 (aHR: 0.69). 52.9% were retained in care at 24 months. Attrition was associated with ANC1 in the third trimester (aHR: 2.37), attending a secondary care facility (aHR: 1.98) and ART initiation during later enrolment phases (mid aHR: 1.48; late aHR: 1.67). Of 373 women eligible, 67.3% received a first VL. 223/251 (88.8%) were virologically suppressed (< 1000 copies/mL). Of 670 infants, 53.6% received an EID test, 320/359 had a test result recorded and of whom 7 (2.2%) were HIV+. CONCLUSIONS: PMTCTB+ was found to be feasible in this setting, with high rates of maternal viral suppression and low transmission to the infant. High treatment attrition, poor follow-up of mother-baby pairs and under-utilisation of VL and EID testing are important programmatic challenges.

Why Médecins Sans Frontières (MSF) provides safe abortion care and what that involves.

MSF responds to needs for the termination of pregnancy, including on request (TPR); it is part of the organization's work aimed at reducing maternal mortality and suffering; and preventing unsafe abortions in the countries where we work. Following the publication of "Why don't humanitarian organizations provide safe abortion care?" we offer an insight into MSF's experience over the past few years. The article looks at the legal concerns and proposes that the importance of addressing maternal mortality should replace them and the operational set-up and action organized in a way that mitigates risks. MSF took a policy decision on safe abortion care in 2004; the fact that care did not expand rapidly to relevant MSF projects came as a surprise, reflecting the important weight social norms around abortion have everywhere. The need to engage in an open dialogue with staff, relevant medical actors and at community level became more obvious. Finally the article looks some key lessons that have emerged for the organization as part of the effort to prevent ill health, maternal death and suffering caused by unwanted pregnancy and unsafe abortion.

Pregnancy Outcomes after a Mass Vaccination Campaign with an Oral Cholera Vaccine in Guinea: A Retrospective Cohort Study.

INTRODUCTION: Since 2010, WHO has recommended oral cholera vaccines as an additional strategy for cholera control. During a cholera episode, pregnant women are at high risk of complications, and the risk of fetal death has been reported to be 2-36%. Due to a lack of safety data, pregnant women have been excluded from most cholera vaccination campaigns. In 2012, reactive campaigns using the bivalent killed whole-cell oral cholera vaccine (BivWC), included all people living in the targeted areas aged ≥ 1 year regardless of pregnancy status, were implemented in Guinea. We aimed to determine whether there was a difference in pregnancy outcomes between vaccinated and non-vaccinated pregnant women. METHODS AND FINDINGS: From 11 November to 4 December 2013, we conducted a retrospective cohort study in Boffa prefecture among women who were pregnant in 2012 during or after the vaccination campaign. The primary outcome was pregnancy loss, as reported by the mother, and fetal malformations, after clinical examination. Primary exposure was the intake of the BivWC vaccine (Shanchol) during pregnancy, as determined by a vaccination card or oral history. We compared the risk of pregnancy loss between vaccinated and non-vaccinated women through binomial regression analysis. A total of 2,494 pregnancies were included in the analysis. The crude incidence of pregnancy loss was 3.7% (95%CI 2.7-4.8) for fetuses exposed to BivWC vaccine and 2.6% (0.7-4.5) for non-exposed fetuses. The incidence of malformation was 0.6% (0.1-1.0) and 1.2% (0.0-2.5) in BivWC-exposed and non-exposed fetuses, respectively. In both crude and adjusted analyses, fetal exposure to BivWC was not significantly associated with pregnancy loss (adjusted risk ratio (aRR = 1.09 [95%CI: 0.5-2.25], p = 0.818) or malformations (aRR = 0.50 [95%CI: 0.13-1.91], p = 0.314). CONCLUSIONS: In this large retrospective cohort study, we found no association between fetal exposure to BivWC and risk of pregnancy loss or malformation. Despite the weaknesses of a retrospective design, we can conclude that if a risk exists, it is very low. Additional prospective studies are warranted to add to the evidence base on OCV use during pregnancy. Pregnant women are particularly vulnerable during cholera episodes and should be included in vaccination campaigns when the risk of cholera is high, such as during outbreaks.

Cholera in Pregnancy: A Systematic Review and Meta-Analysis of Fetal, Neonatal, and Maternal Mortality.

BACKGROUND: Maternal infection with cholera may negatively affect pregnancy outcomes. The objective of this research is to systematically review the literature and determine the risk of fetal, neonatal and maternal death associated with cholera during pregnancy. MATERIALS AND METHODS: Medline, Global Health Library, and Cochrane Library databases were searched using the key terms cholera and pregnancy for articles published in any language and at any time before August 2013 to quantitatively summarize estimates of fetal, maternal, and neonatal mortality. 95% confidence intervals (CIs) were calculated for each selected study. Random-effect non-linear logistic regression was used to calculate pooled rates and 95% CIs by time period. Studies from the recent period (1991-2013) were compared with studies from 1969-1990. Relative risk (RR) estimates and 95% CIs were obtained by comparing mortality of selected recent studies with published national normative data from the closest year. RESULTS: The meta-analysis included seven studies that together involved 737 pregnant women with cholera from six countries. The pooled fetal death rate for 4 studies during 1991-2013 was 7.9% (95% CIs 5.3-10.4), significantly lower than that of 3 studies from 1969-1990 (31.0%, 95% CIs 25.2-36.8). There was no difference in fetal death rate by trimester. The pooled neonatal death rate for 1991-2013 studies was 0.8% (95% CIs 0.0-1.6), and 6.4% (95% CIs 0.0-20.8) for 1969-1990. The pooled maternal death rate for 1991-2013 studies was 0.2% (95% CIs 0.0-0.7), and 5.0% (95% CIs 0.0-16.0) for 1969-1990. Compared with published national mortality estimates, the RR for fetal death of 5.8 (95% CIs 2.9-11.3) was calculated for Haiti (2013), 1.8 (95% CIs 0.3-10.4) for Senegal (2007), and 2.6 (95% CIs 0.5-14.9) for Peru (1991); there were no significant differences in the RR for neonatal or maternal death. CONCLUSION: Results are limited by the inconsistencies found across included studies but suggest that maternal cholera is associated with adverse pregnancy outcomes, particularly fetal death. These findings can inform a research agenda on cholera in pregnancy and guidance for the timely management of pregnant women with cholera.

Cholera in pregnancy: outcomes from a specialized cholera treatment unit for pregnant women in Léogâne, Haiti.

BACKGROUND: The association between cholera in pregnancy and negative fetal outcome has been described since the 19(th) century. However, there is limited published literature on the subject. We describe pregnancy outcomes from a specialized multidisciplinary hospital unit at the onset of a large cholera outbreak in Haiti in 2010 and 2011. METHODS: Pregnant women with cholera were hospitalized in a specialized unit within the MSF hospital compound in Léogâne and treated using standard cholera treatment guidelines but with earlier, more intense fluid replacement. All women had intravenous access established at admission regardless of their hydration status, and all received antibiotic treatment. Data were collected on patient demographics, pregnancy and cholera status, and pregnancy outcome. In this analysis we calculated risk ratios for fetal death and performed logistic regression analysis to control for confounding factors. RESULTS: 263 pregnant women with cholera were hospitalized between December 2010 and July 2011. None died during hospitalization, 226 (86%) were discharged with a preserved pregnancy and 16 (6%) had live fullterm singleton births, of whom 2 died within the first 5 days postpartum. The remaining 21 pregnancies (8%) resulted in intrauterine fetal death. The risk of fetal death was associated with factors reflecting severity of the cholera episode: after adjusting for confounding factors, the strongest risk factor for fetal death was severe maternal dehydration (adjusted risk ratio for severe vs. mild dehydration was 9.4, 95% CI 2.5-35.3, p = 0.005), followed by severe vomiting (adjusted risk ratio 5.1, 95% 1.1-23.8, p = 0.041). CONCLUSION: This is the largest cohort of pregnant women with cholera described to date. The main risk factor identified for fetal death was severity of dehydration. Our experience suggests that establishing specialized multidisciplinary units which facilitate close follow-up of both pregnancy and dehydration status due to cholera could be beneficial for patients, especially in large epidemics.

Which anthropometric indicators identify a pregnant woman as acutely malnourished and predict adverse birth outcomes in the humanitarian context?

Currently there is no consensus on how to identify pregnant women as acutely malnourished and when to enroll them in nutritional programmes. Médecins Sans Frontières Switzerland undertook a literature review with the purpose of determining values of anthropometric indicators for acute malnutrition that are associated with adverse birth outcomes (such as low birth weight (LBW)), pre-term birth and intra-uterine growth retardation (IUGR). A literature search in PUBMED was done covering 1 January 1995 to 12 September 2012 with the key terms maternal anthropometry and pregnancy. The review focused on the humanitarian context. Mid-upper-arm circumference (MUAC) was identified as the preferential indicator of choice because of its relatively strong association with LBW, narrow range of cut-off values, simplicity of measurement (important in humanitarian settings) and it does not require prior knowledge of gestational age. The MUAC values below which most adverse effects were identified were <22 and <23 cm. A conservative cut-off of <23 cm is recommended to include most pregnant women at risk of LBW for their infants in the African and Asian contexts.