Efficacy and safety of hydroxychloroquine for treatment of mild SARS-CoV-2 infection and prevention of COVID-19 severity in pregnant and postpartum women: A randomized, double-blind, placebo-controlled trial.

INTRODUCTION: Pregnant women have an increased risk of severe COVID-19. Evaluation of drugs with a safety reproductive toxicity profile is a priority. At the beginning of the pandemic, hydroxychloroquine (HCQ) was recommended for COVID-19 treatment. MATERIAL AND METHODS: A randomized, double-blind, placebo-controlled clinical trial was conducted in eight teaching hospitals in Spain to evaluate the safety and efficacy of HCQ in reducing viral shedding and preventing COVID-19 progression. Pregnant and postpartum women with a positive SARS-CoV-2 PCR (with or without mild COVID-19 signs/symptoms) and a normal electrocardiogram were randomized to receive either HCQ orally (400 mg/day for 3 days and 200 mg/day for 11 days) or placebo. PCR and electrocardiogram were repeated at day 21 after treatment start. Enrollment was stopped before reaching the target sample due to low recruitment rate. Trial registration EudraCT #: 2020-001587-29, on April 2, 2020. CLINICAL TRIALS: gov # NCT04410562, registered on June 1, 2020. RESULTS: A total of 116 women (75 pregnant and 41 post-partum) were enrolled from May 2020 to June 2021. The proportion of women with a positive SARS-CoV-2 PCR at day 21 was lower in the HCQ group (21.8%, 12/55) than in the placebo group (31.6%, 18/57), although the difference was not statistically significant (P = 0.499). No differences were observed in COVID-19 progression, adverse events, median change in QTc, hospital admissions, preeclampsia or poor pregnancy and perinatal outcomes between groups. CONCLUSIONS: HCQ was found to be safe in pregnant and postpartum women with asymptomatic or mild SARS-CoV-2 infection. Although the prevalence of infection was decreased in the HCQ group, the statistical power was insufficient to confirm the potential beneficial effect of HCQ for COVID-19 treatment.

Immunisation coverage and factors associated with incomplete immunisation in children under two during the COVID-19 pandemic in Sierra Leone.

BACKGROUND: Routine childhood immunisation is one of the most important life-saving public health interventions. However, many children still have inadequate access to these vaccines and millions remain (partially) unvaccinated globally. As the COVID-19 pandemic disrupted health systems worldwide, its effects on immunisation have become apparent. This study aimed to estimate routine immunisation coverage among children under two in Sierra Leone and to identify factors associated with incomplete immunisation during the COVID-19 pandemic. METHODS: A cross-sectional household survey was conducted in three districts in Sierra Leone: Bombali, Tonkolili and Port Loko. A three-stage cluster sampling method was followed to enrol children aged 10-23 months. Information regarding immunisation status was based on vaccination cards or caretaker's recall. Using WHO's definition, a fully immunised child received one BCG dose, three oral polio vaccine doses, three pentavalent vaccine doses and one measles-containing vaccine dose. Following the national schedule, full immunisation status can be achieved at 9 months of age. Data were weighted to reflect the survey's sampling design. Associations between incomplete immunisation and sociodemographic characteristics were assessed through multivariable logistic regression. RESULTS: A total of 720 children were enrolled between November and December 2021. Full vaccination coverage was estimated at 65.8% (95% CI 60.3%-71.0%). Coverage estimates were highest for vaccines administered at birth and decreased with doses administered subsequently. Adjusting for age, the lowest estimated coverage was 40.7% (95% CI 34.5%-47.2%) for the second dose of the measles-containing vaccine. Factors found to be associated with incomplete immunisation status were: living in Port Loko district (aOR = 3.47, 95% CI = 2.00-6.06; p-value < 0.001), the interviewed caretaker being Muslim (aOR = 1.94, 95% CI = 1.25-3.02; p-value = 0.015) and the interviewed caretaker being male (aOR = 1.93, 95% CI = 1.03-3.59, p-value = 0.039). CONCLUSION: Though full immunisation coverage at district level improved compared with pre-pandemic district estimates from 2019, around one in three surveyed children had missed at least one basic routine vaccination and over half of eligible children had not received the recommended two doses of a measles-containing vaccine. These findings highlight the need to strengthen health systems to improve vaccination uptake in Sierra Leone, and to further explore barriers that may jeopardise equitable access to these life-saving interventions.

Sustained clinical benefit of malaria chemoprevention with sulfadoxine-pyrimethamine (SP) in pregnant women in a region with high SP resistance markers.

OBJECTIVE: The effectiveness of intermittent preventive treatment of malaria in pregnancy with sulfadoxine-pyrimethamine (IPTp-SP) is threatened by increasing SP-resistance in Africa. We assessed the level of SP-resistance markers, and the clinical and parasitological effectiveness of IPTp-SP in southern Mozambique. METHODS: P. falciparum infection, antimalarial antibodies and dhfr/dhps SP-resistance mutants were detected by quantitative polymerase chain reaction (qPCR), suspension array technology and targeted deep sequencing, respectively, among 4016 HIV-negative women in Maputo province (2016-2019). Univariate and multivariate regression models were used to assess the association between taking the recommended three or more IPTp-SP doses (IPTp3+) and parasitological and clinical outcomes. RESULTS: 84.3% (3385/4016) women received three or more IPTp-SP doses. The prevalence of quintuple mutants at first antenatal care (ANC) visit was 94.2%. IPTp3+ was associated with a higher clearance rate of qPCR-detected infections from first ANC visit to delivery (adjusted odds ratio [aOR]=5.9, 95% CI: 1.5-33.3; p = 0.012), lower seroprevalence at delivery of antibodies against the pregnancy-specific antigen VAR2CSADBL34 (aOR=0.72, 95% CI: 0.54-0.95; p = 0.022), and lower prevalence of low birth weight deliveries (aOR: 0.61, 95% CI: 0.41-0.90; p = 0.013). CONCLUSION: A sustained parasitological effect of IPTp-SP contributes to the clinical effectiveness of IPTp3+ in areas with high prevalence of SP-resistance markers.