Intermittent preventive treatment regimens for malaria in HIV-positive pregnant women.

BACKGROUND: Malaria and HIV infection overlap geographically in sub-Saharan Africa and share risk factors. HIV infection increases malaria's severity, especially in pregnant women. The World Health Organization (WHO) recommends intermittent preventive treatment in pregnancy (IPTp) with sulphadoxine-pyrimethamine (SP) for pregnant women living in areas of stable malaria transmission. However, HIV-positive women on daily cotrimoxazole prophylaxis (recommended for prevention of opportunistic infections in people with HIV) cannot receive SP due to adverse drug interactions, so malaria prevention in this vulnerable population currently relies on daily cotrimoxazole prophylaxis alone. This review is based on a new protocol and provides an update to the 2011 Cochrane Review that evaluated alternative drugs for IPTp to prevent malaria in HIV-positive women. OBJECTIVES: To compare the safety and efficacy of intermittent preventive treatment regimens for malaria prevention in HIV-positive pregnant women. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, three other databases, and two trial registries to 31 January 2024. To identify relevant additional studies or unpublished work, we checked references and contacted study authors and other researchers working on malaria and HIV. SELECTION CRITERIA: We included randomized controlled trials (RCTs) comparing any intermittent preventive treatment regimen for preventing malaria in HIV-positive pregnant women against daily cotrimoxazole prophylaxis alone, placebo, current or previous standard of care, or combinations of these options. By 'standard of care' we refer to the country's recommended drug regimen to prevent malaria in pregnancy among HIV-positive women, or the treatment that a trial's research team considered to be the standard of care. DATA COLLECTION AND ANALYSIS: Review authors, in pairs, independently screened all records identified by the search strategy, applied inclusion criteria, assessed risk of bias in included trials, and extracted data. We contacted trial authors when additional information was required. We presented dichotomous outcomes using risk ratios (RRs), count outcomes as incidence rate ratios (IRRs), and continuous outcomes as mean differences (MDs). We presented all measures of effect with 95% confidence intervals (CIs). We assessed the certainty of the evidence using the GRADE approach for what we considered to be the main comparisons and outcomes. MAIN RESULTS: We included 14 RCTs, with a total of 4976 HIV-positive pregnant women initially randomized. All trials assessed the efficacy and safety of one antimalarial used as IPTp (mefloquine, dihydroartemisinin/piperaquine, SP, or azithromycin) with or without daily cotrimoxazole, compared to daily cotrimoxazole alone, placebo, or a standard of care regimen. We grouped the trials into nine comparisons. Our main comparison evaluated the current standard of care (daily cotrimoxazole) with another drug regimen (mefloquine or dihydroartemisinin/piperaquine) versus daily cotrimoxazole with or without placebo. In this comparison, two trials evaluated mefloquine and three evaluated dihydroartemisinin/piperaquine. We conducted meta-analyses that included trials evaluating dihydroartemisinin/piperaquine plus cotrimoxazole, and trials that evaluated mefloquine plus cotrimoxazole, as we considered there to be no qualitative or quantitative heterogeneity among trials for most outcomes. We considered drug-related adverse events and HIV-related outcomes to be drug-specific. Daily cotrimoxazole prophylaxis plus another drug regimen (mefloquine or dihydroartemisinin/piperaquine) probably results in lower risk of maternal peripheral parasitaemia at delivery (RR 0.62, 95% CI 0.41 to 0.95; 2406 participants, 5 trials; moderate-certainty evidence). It results in little or no difference in maternal anaemia cases at delivery (RR 0.98, 95% CI 0.90 to 1.07; 2417 participants, 3 trials; high-certainty evidence). It probably results in a decrease in placental malaria measured by blood smear (RR 0.54, 95% CI 0.31 to 0.93; 1337 participants, 3 trials; moderate-certainty evidence), and probably results in little or no difference in low birth weight (RR 1.16, 95% CI 0.95 to 1.41; 2915 participants, 5 trials; moderate-certainty evidence). There is insufficient evidence to ascertain whether daily cotrimoxazole prophylaxis plus another drug regimen affects the risk of cord blood parasitaemia (RR 0.27, 95% CI 0.04 to 1.64; 2696 participants, 5 trials; very low-certainty evidence). Daily cotrimoxazole prophylaxis plus another drug regimen probably results in little or no difference in foetal loss (RR 1.03, 95% CI 0.73 to 1.46; 2957 participants, 5 trials; moderate-certainty evidence), and may result in little or no difference in neonatal mortality (RR 1.21, 95% CI 0.68 to 2.14; 2706 participants, 4 trials; low-certainty evidence). Due to the probability of an increased risk of mother-to-child HIV transmission and some adverse drug effects noted with mefloquine, we also looked at the results for dihydroartemisinin/piperaquine specifically. Dihydroartemisinin/piperaquine plus daily contrimoxazole probably results in little to no difference in maternal peripheral parasitaemia (RR 0.59, 95% CI 0.31 to 1.11; 1517 participants, 3 trials; moderate-certainty evidence) or anaemia at delivery (RR 0.95, 95% CI 0.82 to 1.10; 1454 participants, 2 trials; moderate-certainty evidence), but leads to fewer women having placental malaria when measured by histopathologic analysis (RR 0.67, 95% CI 0.50 to 0.90; 1570 participants, 3 trials; high-certainty evidence). The addition of dihydroartemisinin/piperaquine to daily cotrimoxazole probably made little to no difference to rates of low birth weight (RR 1.13, 95% CI 0.87 to 1.48; 1695 participants, 3 trials), foetal loss (RR 1.14, 95% CI 0.68 to 1.90; 1610 participants, 3 trials), or neonatal mortality (RR 1.03, 95% CI 0.39 to 2.72; 1467 participants, 2 trials) (all moderate-certainty evidence). We found low-certainty evidence of no increased risk of gastrointestinal drug-related adverse events (RR 1.42, 95% CI 0.51 to 3.98; 1447 participants, 2 trials) or mother-to-child HIV transmission (RR 1.54, 95% CI 0.26 to 9.19; 1063 participants, 2 trials). AUTHORS' CONCLUSIONS: Dihydroartemisinin/piperaquine and mefloquine added to daily cotrimoxazole seem to be efficacious in preventing malaria infection in HIV-positive pregnant women compared to daily cotrimoxazole alone. However, increased risk of HIV transmission to the foetus and poor drug tolerability may be barriers to implementation of mefloquine in practice. In contrast, the evidence suggests that dihydroartemisinin/piperaquine does not increase the risk of HIV mother-to-child transmission and is well tolerated.

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.

Coverage of intermittent preventive treatment of malaria in infants after four years of implementation in Sierra Leone.

BACKGROUND: Intermittent Preventive Treatment of malaria in infants (IPTi) is a malaria control strategy consisting of the administration of an anti-malarial drug alongside routine immunizations. So far, this is being implemented nationwide in Sierra Leone only. IPTi has been renamed as Perennial Malaria Chemoprevention -PMC-, accounting for its recently recommended expansion into the second year of life. Before starting a pilot implementation on PMC, the currently implemented strategy and malaria prevalence were assessed in young children in selected areas of Sierra Leone. METHODS: A cross-sectional, community-based, multi-stage cluster household survey was conducted from November to December 2021 in selected districts of the Northern and northwestern provinces of Sierra Leone among 10-23 months old children, whose caretakers gave written informed consent to participate in the survey. Coverage of IPTi and malaria prevalence-assessed with rapid diagnostic tests-were calculated using percentages and 95% confidence intervals weighted for the sampling design and adjusted for non-response within clusters. Factors associated with RDT + and iPTi coverage were also assessed. RESULTS: A total of 720 children were recruited. Coverage of three IPTi doses was 50.57% (368/707; 95% CI 45.38-55.75), while prevalence of malaria infection was 28.19% (95% CI 24.81-31.84). Most children had received IPTi1 (80.26%, 574/707; 95% CI 75.30-84.44), and IPTi2 (80.09%, 577/707; 95% CI 76.30-83.40) and over half of the children also received IPTi3 (57.72%, 420/707; 95% CI 53.20-62.11). The uptake of each IPTi dose was lower than that of the vaccines administered at the same timepoint at all contacts. CONCLUSION: In Sierra Leone, half of the children received the three recommended doses of IPTi indicating an increase in its uptake compared to previous data of just a third of children receiving the intervention. However, efforts need to be made in improving IPTi coverage, especially in the planned expansion of the strategy into the second year of life following recent WHO guidelines.