ABSTRACT. The basis for an evidence-based recommendation is a well-conducted systematic review that synthesizes the primary literature relevant to the policy or program question of interest. In 2020, the WHO commissioned 10 systematic reviews of potential interventions in elimination or post-elimination settings to summarize their impact on malaria transmission. This paper describes the general methods used to conduct this series of systematic reviews and notes where individual reviews diverged from the common methodology. The paper also presents lessons learned from conducting the systematic reviews to make similar future efforts more efficient, standardized, and streamlined.
Abstract Background Infants under 6 months of age are often excluded from malaria surveillance and observational studies. The impact of malaria during early infancy on health later in childhood remains unknown. Methods Infants from two birth cohorts in Malawi were monitored at quarterly intervals and whenever they were ill from birth through 24 months for Plasmodium falciparum infections and clinical malaria. Poisson regression and linear mixed effects models measured the effect of exposure to malaria in infancy on subsequent malaria incidence, weight-for-age z-scores (WAZ), and haemoglobin concentrations after 6 months. Results Infants with at least one P. falciparum infection during their first 6 months had increased incidence ratio (IRR) of P. falciparum infection (IRR = 1.27, 95% CI, 1.06–1.52) and clinical malaria (IRR = 2.37, 95% CI, 2.02–2.80) compared to infants without infection. Infants with clinical malaria had increased risk of P. falciparum infection incidence between 6 and 24 months (IRR = 1.64, 95% CI, 1.38–1.94) and clinical malaria (IRR = 1.85, 95% CI, 1.48–2.32). Exposure to malaria was associated with lower WAZ over time (p = 0.02) and lower haemoglobin levels than unexposed infants at every time interval (p = 0.02). Conclusions Infants experiencing malaria infection or clinical malaria are at increased risk of subsequent infection and disease, have poorer growth, and lower haemoglobin concentrations.
Recent studies point to the need to incorporate non-falciparum species detection into malaria surveillance activities in sub-Saharan Africa, where 95% of malaria cases occur. Although
Pregnant women are considered a high-risk group for COVID-19, and a priority for vaccination. Routine antenatal care (ANC) provides an opportunity to track trends and factors associated with vaccine uptake. We sought to evaluate COVID-19 vaccine uptake among pregnant women attending ANC and assess the factors associated with vaccine in Zambia. We conducted a repeated cross-sectional study in 39 public health facilities in four districts in Zambia from September 2021 to September 2022. Pregnant women who were aged 15-49 years were enrolled during their first ANC visit. Every month, ~20 women per facility were interviewed during individual HIV counseling and testing. We estimated vaccine uptake as the proportion of eligible participants who self-reported having received the COVID-19 vaccine. A total of 9,203 pregnant women were screened, of which 9,111 (99%) were eligible and had vaccination status. Of the 9,111 included in the analysis, 1,818 (20%) had received the COVID-19 vaccine during the study period, with a trend of increasing coverage with time (0.5% in September 2020, 27% in September 2022). Conversely, 3,789 (42%) reported not being offered a COVID-19 vaccine. We found that women aged 40-49 years, had no education or attained some primary school education, were not employed, and had prior COVID-19 infection were significantly associated with vaccine uptake. COVID-19 vaccine uptake among pregnant women was lower than estimates from the general population (27% across the four districts in September 2022), pointing to missed opportunities to protect this high-risk group. ANC visits were a viable point for conducting COVID-19 surveillance. Incorporating the vaccine as part of the routine ANC package might increase coverage in this group.
Severe malaria has a case fatality rate of 10-20 %; however, few studies have addressed the quality of severe malaria case management. This study evaluated the diagnostic and treatment practices of malaria patients admitted to inpatient health facilities (HF) in Malawi. In July–August 2012, a nationwide, cross-sectional survey of severe malaria management was conducted in 36 HFs selected with equal probability from all eligible public sector HFs in Malawi. Patient records from all admissions during October 2011 and April 2012 (low and high season, respectively) were screened for an admission diagnosis of malaria or prescription of any anti-malarial. Eligible records were stratified by age (< 5 or ≥ 5 years). A maximum of eight records was randomly selected within each age and month stratum. Severe malaria was defined by admission diagnosis or documentation of at least one sign or symptom of severe malaria. Treatment with intravenous (IV) quinine or artesunate was considered correct. Patients without documentation of severe malaria were analysed as uncomplicated malaria patients; treatment with an artemisinin-based combination therapy (ACT) or oral quinine based on malaria test results was considered correct. All analyses accounted for HF level clustering and sampling weights. The analysis included 906 records from 35 HFs. Among these, 42 % (95 % confidence interval [CI] 35–49) had a severe malaria admission diagnosis and 50 % (95 % CI 44–57) had at least one severe malaria sign or symptom documented. Severe malaria patients defined by admission diagnosis (93, 95 % CI 86–99) were more likely to be treated correctly compared to patients defined by a severe sign (82, 95 % CI 75–89) (p < 0.0001). Among uncomplicated malaria patients, 26 % (95 % CI 18–35) were correctly treated and 53 % (95 % CI 42–64) were adequately treated with IV quinine alone or in combination with an ACT or oral quinine. A majority of patients diagnosed with severe malaria received the recommended IV therapy in accordance with national treatment guidelines. However, the inconsistencies between diagnosis of severe malaria and documentation of severe signs and symptoms highlight the need to improve healthcare worker recognition and documentation of severe signs and symptoms.
Dihydroartemisinin-piperaquine (DP) is a long-acting artemisinin combination treatment that provides effective chemoprevention and has been proposed as an alternative antimalarial drug for intermittent preventive therapy in pregnancy (IPTp). Several pharmacokinetic studies have shown that dose adjustment may not be needed for the treatment of malaria in pregnancy with DP. However, there are limited data on the optimal dosing for IPTp. This study aimed to evaluate the population pharmacokinetics of piperaquine given as IPTp in pregnant women. Pregnant women were enrolled in clinical trials conducted in Kenya and Indonesia and treated with standard 3-day courses of DP, administered in 4- to 8-week intervals from the second trimester until delivery. Pharmacokinetic blood samples were collected for piperaquine drug measurements before each treatment round, at the time of breakthrough symptomatic malaria, and at delivery. Piperaquine population pharmacokinetic properties were investigated using nonlinear mixed-effects modeling with a prior approach. In total, data from 366 Kenyan and 101 Indonesian women were analyzed. The pharmacokinetic properties of piperaquine were adequately described using a flexible transit absorption (n = 5) followed by a three-compartment disposition model. Gestational age did not affect the pharmacokinetic parameters of piperaquine. After three rounds of monthly IPTp, 9.45% (95% confidence interval [CI], 1.8 to 26.5%) of pregnant women had trough piperaquine concentrations below the suggested target concentration (10.3 ng/ml). Translational simulations suggest that providing the full treatment course of DP at monthly intervals provides sufficient protection to prevent malaria infection. Monthly administration of DP has the potential to offer optimal prevention of malaria during pregnancy. (This study has been registered at ClinicalTrials.gov under identifier NCT01669941 and in the ISRCTN under number ISRCTN34010937.).
The antifolate sulphadoxine-pyrimethamine (SP) has been used in the intermittent prevention of malaria in pregnancy (IPTp). SP is an ideal choice for IPTp, however, as resistance of Plasmodium falciparum to SP increases, data are accumulating that SP may no longer provide benefit in areas of high-level resistance. Probenecid was initially used as an adjunctive therapy to increase the blood concentration of penicillin; it has since been used to augment concentrations of other drugs, including antifolates. The addition of probenecid has been shown to increase the treatment efficacy of SP against malaria, suggesting that the combination of probenecid plus SP may prolong the useful lifespan of SP as an effective agent for IPTp. Here, the literature on the pharmacokinetics, adverse reactions, interactions and available data on the use of these drugs in pregnancy is reviewed, and the possible utility of an SP-probenecid combination is discussed. This article concludes by calling for further research into this potentially useful combination.
(Abstracted from Lancet Infect Dis 2018;18:e119–e132) Although the World Health Organization (WHO) has established recommendations for prevention of malaria, it remains one of the most preventable causes of adverse birth outcomes. The WHO recommends intermittent preventive treatment in pregnancy (IPTp) with for women who are HIV-negative, or co-trimoxazole prophylaxis for women who are HIV-positive.
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