Trends in SARS-CoV-2 seroprevalence among pregnant women attending first antenatal care visits in Zambia: A repeated cross-sectional survey, 2021-2022.

SARS-CoV-2 serosurveys help estimate the extent of transmission and guide the allocation of COVID-19 vaccines. We measured SARS-CoV-2 seroprevalence among women attending ANC clinics to assess exposure trends over time in Zambia. We conducted repeated cross-sectional SARS-CoV-2 seroprevalence surveys among pregnant women aged 15-49 years attending their first ANC visits in four districts of Zambia (two urban and two rural) during September 2021-September 2022. Serologic testing was done using a multiplex bead assay which detects IgG antibodies to the nucleocapsid protein and the spike protein receptor-binding domain (RBD). We calculated monthly SARS-CoV-2 seroprevalence by district. We also categorized seropositive results as infection alone, infection and vaccination, or vaccination alone based on anti-RBD and anti-nucleocapsid test results and self-reported COVID-19 vaccination status (vaccinated was having received ≥1 dose). Among 8,304 participants, 5,296 (63.8%) were cumulatively seropositive for SARS-CoV-2 antibodies from September 2021 through September 2022. SARS-CoV-2 seroprevalence primarily increased from September 2021 to September 2022 in three districts (Lusaka: 61.8-100.0%, Chongwe: 39.6-94.7%, Chipata: 56.5-95.0%), but in Chadiza, seroprevalence increased from 27.8% in September 2021 to 77.2% in April 2022 before gradually dropping to 56.6% in July 2022. Among 5,906 participants with a valid COVID-19 vaccination status, infection alone accounted for antibody responses in 77.7% (4,590) of participants. Most women attending ANC had evidence of prior SARS-CoV-2 infection and most SARS-CoV-2 seropositivity was infection-induced. Capturing COVID-19 vaccination status and using a multiplex bead assay with anti-nucleocapsid and anti-RBD targets facilitated distinguishing infection-induced versus vaccine-induced antibody responses during a period of increasing COVID-19 vaccine coverage in Zambia. Declining seroprevalence in Chadiza may indicate waning antibodies and a need for booster vaccines. ANC clinics have a potential role in ongoing SARS-CoV-2 serosurveillance and can continue to provide insights into SARS-CoV-2 antibody dynamics to inform near real-time public health responses.

SARS-CoV-2 Seroprevalence and Vaccine Uptake among Pregnant Women at First Antenatal Care Visits in Malawi.

Many SARS-CoV-2 infections are asymptomatic, thus reported cases underestimate actual cases. To improve estimates, we conducted surveillance for SARS-CoV-2 seroprevalence among pregnant women attending their first antenatal care visit (ANC1) from June 2021 through May 2022. We administered a questionnaire to collect demographic, risk factors, and COVID-19 vaccine status information and tested dried blood spots for SARS-CoV-2 antibodies. Although <1% of ANC1 participants reported having had COVID-19, monthly SARS-CoV-2 seroprevalence increased from 15.4% (95% CI: 10.5-21.5) in June 2021 to 65.5% (95% CI: 55.5-73.7) in May 2022. Although COVID-19 vaccination was available in March 2021, uptake remained low, reaching a maximum of 9.5% (95% CI: 5.7-14.8) in May 2022. Results of ANC1 serosurveillance provided prevalence estimates helpful in understanding this population case burden that was available through self-report and national case reports. To improve vaccine uptake, efforts to address fears and misconceptions regarding COVID-19 vaccines are needed.

Prevalence of non-falciparum malaria infections among asymptomatic individuals in four regions of Mainland Tanzania.

BACKGROUND: Recent studies point to the need to incorporate the detection of non-falciparum species into malaria surveillance activities in sub-Saharan Africa, where 95% of the world's malaria cases occur. Although malaria caused by infection with Plasmodium falciparum is typically more severe than malaria caused by the non-falciparum Plasmodium species P. malariae, P. ovale spp. and P. vivax, the latter may be more challenging to diagnose, treat, control and ultimately eliminate. The prevalence of non-falciparum species throughout sub-Saharan Africa is poorly defined. Tanzania has geographical heterogeneity in transmission levels but an overall high malaria burden. METHODS: To estimate the prevalence of malaria species in Mainland Tanzania, we randomly selected 1428 samples from 6005 asymptomatic isolates collected in previous cross-sectional community surveys across four regions and analyzed these by quantitative PCR to detect and identify the Plasmodium species. RESULTS: Plasmodium falciparum was the most prevalent species in all samples, with P. malariae and P. ovale spp. detected at a lower prevalence (< 5%) in all four regions; P. vivax was not detected in any sample. CONCLUSIONS: The results of this study indicate that malaria elimination efforts in Tanzania will need to account for and enhance surveillance of these non-falciparum species.

Mass Drug Administration: Contextual Factor Considerations.

In designing mass drug administration (MDA) campaigns, it is imperative to consider contextual factors that affect uptake of the intervention, including acceptability, cost, feasibility, and health system considerations, to ensure optimal coverage. We reviewed the literature on contextual factors influencing MDA delivery to provide programs with information to design a successful campaign. From 1,044 articles screened, 37 included contextual factors relevant to participants' values and preferences, drivers of MDA acceptability, health equity concerns, financial and economic aspects, and feasibility barriers; 13 included relevant modeling data. Key findings were abstracted by two reviewers and summarized. No studies directly assessed values or direct health equity concerns with respect to MDA, which represents an evidence gap as unequal distributions of effects and factors that impact participant acceptability and program feasibility must be considered to ensure equitable access. Participant acceptability was the most widely surveyed factor, appearing in 28 of 37 studies; perceived adverse events were a frequently noted cause of nonparticipation, mentioned in 15 studies. Feasibility considerations included when, where, and how drugs will be delivered and how to address pregnant women, as these can all have substantial implications for participation. Mass drug administration costs (∼$1.04 to $19.40 per person per round) are driven primarily by drug prices, but the delivery mechanism can have varying costs as well, and integration with other interventions may provide cost savings. Both programmatic goals and sociopolitical and economic contexts must be carefully considered before embarking on an MDA program to ensure programmatic success.

Chemoprevention for malaria with monthly intermittent preventive treatment with dihydroartemisinin-piperaquine in pregnant women living with HIV on daily co-trimoxazole in Kenya and Malawi: a randomised, double-blind, placebo-controlled trial.

BACKGROUND: The efficacy of daily co-trimoxazole, an antifolate used for malaria chemoprevention in pregnant women living with HIV, is threatened by cross-resistance of Plasmodium falciparum to the antifolate sulfadoxine-pyrimethamine. We assessed whether addition of monthly dihydroartemisinin-piperaquine to daily co-trimoxazole is more effective at preventing malaria infection than monthly placebo plus daily co-trimoxazole in pregnant women living with HIV. METHODS: We did an individually randomised, two-arm, placebo-controlled trial in areas with high-grade sulfadoxine-pyrimethamine resistance in Kenya and Malawi. Pregnant women living with HIV on dolutegravir-based combination antiretroviral therapy (cART) who had singleton pregnancies between 16 weeks' and 28 weeks' gestation were randomly assigned (1:1) by computer-generated block randomisation, stratified by site and HIV status (known positive vs newly diagnosed), to daily co-trimoxazole plus monthly dihydroartemisinin-piperaquine (three tablets of 40 mg dihydroartemisinin and 320 mg piperaquine given daily for 3 days) or daily co-trimoxazole plus monthly placebo. Daily co-trimoxazole consisted of one tablet of 160 mg sulfamethoxazole and 800 mg trimethoprim. The primary endpoint was the incidence of Plasmodium infection detected in the peripheral (maternal) or placental (maternal) blood or tissue by PCR, microscopy, rapid diagnostic test, or placental histology (active infection) from 2 weeks after the first dose of dihydroartemisinin-piperaquine or placebo to delivery. Log-binomial regression was used for binary outcomes, and Poisson regression for count outcomes. The primary analysis was by modified intention to treat, consisting of all randomised eligible participants with primary endpoint data. The safety analysis included all women who received at least one dose of study drug. All investigators, laboratory staff, data analysts, and participants were masked to treatment assignment. This trial is registered with ClinicalTrials.gov, NCT04158713. FINDINGS: From Nov 11, 2019, to Aug 3, 2021, 904 women were enrolled and randomly assigned to co-trimoxazole plus dihydroartemisinin-piperaquine (n=448) or co-trimoxazole plus placebo (n=456), of whom 895 (99%) contributed to the primary analysis (co-trimoxazole plus dihydroartemisinin-piperaquine, n=443; co-trimoxazole plus placebo, n=452). The cumulative risk of any malaria infection during pregnancy or delivery was lower in the co-trimoxazole plus dihydroartemisinin-piperaquine group than in the co-trimoxazole plus placebo group (31 [7%] of 443 women vs 70 [15%] of 452 women, risk ratio 0·45, 95% CI 0·30-0·67; p=0·0001). The incidence of any malaria infection during pregnancy or delivery was 25·4 per 100 person-years in the co-trimoxazole plus dihydroartemisinin-piperaquine group versus 77·3 per 100 person-years in the co-trimoxazole plus placebo group (incidence rate ratio 0·32, 95% CI 0·22-0·47, p<0·0001). The number needed to treat to avert one malaria infection per pregnancy was 7 (95% CI 5-10). The incidence of serious adverse events was similar between groups in mothers (17·7 per 100 person-years in the co-trimoxazole plus dihydroartemisinin-piperaquine group [23 events] vs 17·8 per 100 person-years in the co-trimoxazole group [25 events]) and infants (45·4 per 100 person-years [23 events] vs 40·2 per 100 person-years [21 events]). Nausea within the first 4 days after the start of treatment was reported by 29 (7%) of 446 women in the co-trimoxazole plus dihydroartemisinin-piperaquine group versus 12 (3%) of 445 women in the co-trimoxazole plus placebo group. The risk of adverse pregnancy outcomes did not differ between groups. INTERPRETATION: Addition of monthly intermittent preventive treatment with dihydroartemisinin-piperaquine to the standard of care with daily unsupervised co-trimoxazole in areas of high antifolate resistance substantially improves malaria chemoprevention in pregnant women living with HIV on dolutegravir-based cART and should be considered for policy. FUNDING: European and Developing Countries Clinical Trials Partnership 2; UK Joint Global Health Trials Scheme (UK Foreign, Commonwealth and Development Office; Medical Research Council; National Institute for Health Research; Wellcome); and Swedish International Development Cooperation Agency.

Systematic Review and Meta-Analysis of Seasonal Malaria Chemoprevention.

Seasonal malaria chemoprevention (SMC) for children under 5 years of age for up to four monthly cycles during malaria transmission season was recommended by the WHO in 2012 and has been implemented in 13 countries in the Sahel, reaching more than 30 million children annually. Malaria control programs implementing SMC have asked the WHO to consider expanding the age range or number of monthly cycles. We conducted a systematic review and meta-analysis of SMC among children up to 15 years of age and up to six monthly cycles. Twelve randomized studies were included, with outcomes stratified by age (< 5/≥ 5 years), by three or four versus five or six cycles, and by drug where possible. Drug regimens included sulfadoxine-pyrimethamine + amodiaquine, amodiaquine-artesunate, and sulfadoxine-pyrimethamine + artesunate. Included studies were all conducted in Sahelian countries in which high-grade resistance to sulfadoxine-pyrimethamine was rare and in zones with parasite prevalence ranging from 1% to 79%. Seasonal malaria chemoprevention resulted in substantial reductions in uncomplicated malaria incidence measured during that transmission season (rate ratio: 0.27, 95% CI: 0.25-0.29 among children < 5 years; rate ratio: 0.27, 95% CI: 0.25-0.30 among children ≥ 5 years) and in the prevalence of malaria parasitemia measured within 4-6 weeks from the final SMC cycle (risk ratio: 0.38, 95% CI: 0.34-0.43 among children < 5 years; risk ratio: 0.23, 95% CI: 0.11-0.48 among children ≥ 5 years). In high-transmission zones, SMC resulted in a moderately reduced risk of any anemia (risk ratio: 0.77, 95% CI: 0.72-0.83 among children < 5 years; risk ratio: 0.70, 95% CI: 0.52-0.95 among children ≥ 5 years [one study]). Children < 10 years of age had a moderate reduction in severe malaria (risk ratio: 0.53, 95% CI: 0.37-0.76) but no evidence of a mortality reduction. The evidence suggests that in areas in which sulfadoxine-pyrimethamine and amodiaquine remained efficacious, SMC effectively reduced malaria disease burden among children both < 5 and ≥ 5 years old and that the number of cycles should be commensurate with the length of the transmission season, up to six cycles.

Contextual Factors to Improve Implementation of Malaria Chemoprevention in Children: A Systematic Review.

Malaria remains a leading cause of childhood morbidity and mortality in sub-Saharan Africa, particularly among children under 5 years of age. To help address this challenge, the WHO recommends chemoprevention for certain populations. For children and infants, the WHO recommends seasonal malaria chemoprevention (SMC), perennial malaria chemoprevention (PMC; formerly intermittent preventive treatment in infants [IPTi]), and, more recently, intermittent preventive treatment in school children (IPTsc). This review describes the contextual factors, including feasibility, acceptability, health equity, financial considerations, and values and preferences, that impact implementation of these strategies. A systematic search was conducted on July 5, 2022, and repeated April 13, 2023, to identify relevant literature. Two reviewers independently screened titles for eligibility, extracted data from eligible articles, and identified and summarized themes. Of 6,295 unique titles identified, 65 were included. The most frequently evaluated strategy was SMC (n = 40), followed by IPTi (n = 18) and then IPTsc (n = 6). Overall, these strategies were highly acceptable, although with IPTsc, there were community concerns with providing drugs to girls of reproductive age and the use of nonmedical staff for drug distribution. For SMC, door-to-door delivery resulted in higher coverage, improved caregiver acceptance, and reduced cost. Lower adherence was noted when caregivers were charged with giving doses 2 and 3 unsupervised. For SMC and IPTi, travel distances and inclement weather limited accessibility. Sensitization and caregiver education efforts, retention of high-quality drug distributors, and improved transportation were key to improving coverage. Additional research is needed to understand the role of community values and preferences in chemoprevention implementation.

Mass Drug Administration to Reduce Malaria Transmission: A Systematic Review and Meta-Analysis.

Malaria remains a significant cause of morbidity and mortality, even in low-transmission settings. With the advent of longer acting, more effective, and well-tolerated antimalarials, there is renewed interest in the efficacy of mass drug administration (MDA) to accelerate to elimination. We conducted a systematic review and meta-analysis to assess the efficacy of MDA to reduce the incidence and prevalence of Plasmodium falciparum (Pf) and Plasmodium vivax (Pv) infection. From 1,044 articles screened, 14 articles, including 10 randomized controlled trials (RCTs), were identified. Five included data on Pf only; five included Pf and Pv. Two of the Pf studies were conducted in areas of high-moderate transmission, the remainder were in areas of low-very low transmission. In higher transmission areas, MDA reduced incidence of Pf parasitemia (rate ratio = 0.61, 95% CI: 0.40-0.92; moderate certainty) 1 to 3 months after drug administration; no significant effect of MDA on Pf parasitemia prevalence was detected 1 to 3 months post-MDA (risk ratio [RR] = 1.76, 95% CI: 0.58-5.36; low certainty). In lower transmission settings, both incidence and prevalence of Pf parasitemia were reduced 1 to 3 months post-MDA (rate ratio = 0.37, 95% CI: 0.21-0.66; RR = 0.25, 95% CI: 0.15-0.41, respectively). Pv prevalence was reduced 1 to 3 months post-MDA (RR = 0.15, 95% CI: 0.10-0.24); there were no RCTs providing data on incidence of Pv. There was no significant effect of MDA at later time points. MDA may have short-term benefits; however, there was no evidence for longer term impact, although none of the trials assessed prolonged interventions.

Use of Supervision Data to Improve Quality of Care for Malaria in Pregnancy: Experience in Six African Countries.

Malaria in pregnancy (MiP) intervention coverage, especially intermittent preventive treatment in pregnancy (IPTp), lags behind other global malaria indicators. In 2020, across Africa, only 32% of eligible pregnant women received at least three IPTp doses, despite high antenatal care attendance. We conducted a secondary analysis of data collected during Outreach Training and Supportive Supervision visits from 2019 to 2020 to assess quality of care and explore factors contributing to providers' competence in providing IPTp, insecticide-treated nets, malaria case management, and respectful maternity care. Data were collected during observations of provider-patient interactions in six countries (Cameroon, Cote d'Ivoire, Ghana, Kenya, Mali, and Niger). Competency scores (i.e., composite scores of supervisory checklist observations) were calculated across three domains: MiP prevention, MiP treatment, and respectful maternity care. Scores are used to understand drivers of competency, rather than to assess individual health worker performance. Country-specific multilinear regressions were used to assess how competency score was influenced by commodity availability, training, provider gender and cadre, job aid availability, and facility type. Average competency scores varied across countries: prevention (44-90%), treatment (78-90%), and respectful maternity care (53-93%). The relative association of each factor with competency score varied. Commodity availability, training, and access to job aids correlated positively with competency in multiple countries. To improve MiP service quality, equitable access to training opportunities for different cadres, targeted training, and access to job aids and guidelines should be available for providers. Collection and analysis of routine supervision data can support tailored actions to improve quality MiP services.

Late morning biting behaviour of Anopheles funestus is a risk factor for transmission in schools in Siaya, western Kenya.

BACKGROUND: Children in Kenya spend a substantial amount of time at school, including at dawn and dusk when mosquitoes are active. With changing vector behaviour towards early morning biting, it is important to determine whether there is an additional risk of transmission in schools. This study sought to understand whether late morning biting by Anopheles funestus, previously documented in households in western Kenya, was replicated in schools. METHODS: From the 4th to the 6th of August 2023, human landing collections were conducted hourly in four schools in Alego Usonga sub-County, Siaya County. The collections were conducted in and outside five classrooms in each school and ran for 17 h, starting at 18:00 until 11:00 h the next morning. RESULTS: Anopheles funestus was the predominant species collected, forming 93.2% (N = 727) of the entire collection, with peak landing between 06:00 and 07:00 h and continuing until 11:00 h. More than half of the collected An. funestus were either fed or gravid, potentially indicative of multiple bloodmeals within each gonotrophic cycle, and had a sporozoite rate of 2.05%. CONCLUSION: School children spend up to 10 h of their daytime in schools, reporting between 06:00 and 07:00 h and staying in school until as late as 17:00 h, meaning that they receive potentially infectious mosquito bites during the morning hours in these settings. There is a need to consider vector control approaches targeting schools and other peridomestic spaces in the morning hours when An. funestus is active.

Peripheral and Placental Prevalence of Sulfadoxine-Pyrimethamine Resistance Markers in Plasmodium falciparum among Pregnant Women in Southern Province, Rwanda.

Intermittent preventive therapy during pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) is recommended in areas of moderate to high malaria transmission intensity. As a result of the increasing prevalence of SP resistance markers, IPTp-SP was withdrawn from Rwanda in 2008. Nonetheless, more recent findings suggest that SP may improve birthweight even in the face of parasite resistance, through alternative mechanisms that are independent of antimalarial effects. The prevalence of single nucleotide polymorphisms in Plasmodium falciparum dihydropteroate synthase (pfdhps) and dihydrofolate reductase (pfdhfr) genes associated with SP resistance among 148 pregnant women from 2016 to 2018 within Rwanda's Southern Province (Huye and Kamonyi districts) was measured using a ligase detection reaction-fluorescent microsphere assay. The frequency of pfdhps K540E, A581G, and the quintuple (pfdhfr N51I + C59R + S108N/pfdhps A437G + K540E) and sextuple (pfdhfr N51I + C59R + S108N/pfdhps A437G + K540E + A581G) mutant genotypes was 90%, 38%, 75%, and 28%, respectively. No significant genotype difference was seen between the two districts, which are approximately 50 km apart. Observed agreements for matched peripheral to placental blood were reported and found to be 207 of 208 (99%) for pfdhfr and 239 of 260 (92%) for pfdhps. The peripheral blood sample did not miss any pfdhfr drug-resistant mutants or pfdhps except at the S436 loci. At this level of the sextuple mutant, the antimalarial efficacy of SP for preventing low birthweight is reduced, although overall SP still exerts a nonmalarial benefit during pregnancy. This study further reveals the need to intensify preventive measures to sustain malaria control in Rwanda to keep the overall incidence of malaria during pregnancy low.

Healthcare provider and drug dispenser knowledge and adherence to guidelines for the case management of malaria in pregnancy in the context of multiple first-line artemisinin-based combination therapy in western Kenya.

BACKGROUND: Concerns about emerging resistance to artemether-lumefantrine (AL) in Africa prompted the pilot introduction of multiple first-line therapies (MFT) in Western Kenya, potentially exposing women-of-childbearing-age (WOCBA) to anti-malarials with unknown safety profiles in the first trimester. The study assessed healthcare provider knowledge and adherence to national guidelines for managing malaria in pregnancy in the context of the MFT pilot. METHODS: From March to April 2022, a cross-sectional study was conducted in 50 health facilities (HF) and 40 drug outlets (DO) using structured questionnaires to assess pregnancy detection, malaria diagnosis, and treatment choices by trimester. Differences between HF and DO providers and between MFT and non-MFT HFs were assessed using Chi-square tests. RESULTS: Of 174 providers (77% HF, 23% DO), 56% were from MFT pilot facilities. Most providers had tertiary education; 5% HF and 20% DO had only primary or secondary education. More HF than DO providers had knowledge of malaria treatment guidelines (62% vs. 40%, p = 0.023), received training in malaria in pregnancy (49% vs. 20%, p = 0.002), and reported assessing for pregnancy in WOCBA (98% vs. 78%, p < 0.001). Most providers insisted on parasitological diagnosis, with 59% HF using microscopy and 85% DO using rapid diagnostic tests. More HF than DO providers could correctly name the drugs for treating uncomplicated malaria in the first trimester (oral quinine, or AL if quinine is unavailable) (90% vs. 58%, p < 0.001), second and third trimesters (artemisinin-based combination therapy) (84% vs. 70%, p = 0.07), and for severe malaria (parenteral artesunate/artemether) (94% vs. 60%, p < 0.001). Among HF providers, those in the MFT pilot had more knowledge of malaria treatment guidelines (67% vs. 49%, p = 0.08) and had received training on treatment of malaria in pregnancy (56% vs. 32%, p = 0.03). Few providers (10% HF and 12% DO) had adequate knowledge of malaria treatment in pregnancy, defined as the correct drug and dose for uncomplicated and severe malaria in all trimesters. CONCLUSIONS: Knowledge of national malaria in pregnancy treatment guidelines among providers in Western Kenya is suboptimal. Robust training on appropriate anti-malarial and dosage is needed, particularly given the recent change in recommendation for artemether-lumefantrine use in the first trimester. Supervision of DO and HF practices is essential for correct treatment of malaria in pregnancy in the context of MFT programmes.

Perceptions and drivers of healthcare provider and drug dispenser practices for the treatment of malaria in pregnancy in the context of multiple first-line therapies in western Kenya: a qualitative study.

BACKGROUND: Emergence of Plasmodium falciparum resistance to artemether-lumefantrine in Africa prompted the pilot introduction of multiple first-line therapies (MFT) against malaria in Kenya, potentially exposing women-of-childbearing-age (WOCBAs) to anti-malarials with unknown safety profiles in the first trimester. This qualitative study explored knowledge and perceptions among healthcare providers providing malaria treatment to WOCBAs and pregnant women. METHODS: In-depth interviews were conducted with purposively selected public and private health facility (HF) and drug outlet (DO) providers within and outside the pilot-MFT area. County health managers were interviewed about their knowledge of the national treatment guidelines. Transcripts were coded by content analysis using the World Health Organization health system building blocks (leadership/governance, financing, health workforce, health information systems, access to medicines, and service delivery). RESULTS: Thirty providers (HF:21, DO:9) and three health managers were interviewed. Eighteen providers were from HFs in the pilot-MFT area; the remaining three and all nine DOs were outside the pilot-MFT area. The analysis revealed that providers had not been trained in malaria case management in the previous twelve months. DO providers were unfamiliar with national treatment guidelines in pregnancy and reported having no pregnancy tests. Health managers were unable to supervise DOs due to resource limitations. Providers from HFs and DOs noted poor sensitivity of malaria rapid diagnostic tests (RDTs) and hesitancy among patients who associated malaria-RDTs with HIV testing. Almost all providers reported anti-malarial stock-outs, with quinine most affected. Patient preference was a major factor in prescribing anti-malarials. Providers in HFs and DOs reported preferentially using artemether-lumefantrine in the first trimester due to the side effects and unavailability of quinine. CONCLUSION: Knowledge of malaria case management in drug outlets and health facilities remains poor. Improved regulation of DO providers is warranted. Optimizing treatment of malaria in pregnancy requires training, availability of malaria commodities, and pregnancy tests.

Assessing the utility of pregnant women as a sentinel surveillance population for malaria in Geita, Tanzania, 2019 - 2021.

OBJECTIVES: Estimates of malaria burden and intervention uptake in Africa are primarily based on household surveys. However, their expense and infrequency limit their utility. We investigated whether data collected during antenatal care (ANC) can provide relevant information for decision-makers. METHODS: Malaria test positivity rates and questionnaire data from ANC attendees at 39 health facilities were compared to questionnaire data and positivity rates among children from two cross-sectional surveys in the facilities' corresponding catchment areas. RESULTS: Trends in parasitemia among ANC attendees were predictive of trends in parasitemia among children at the council level (mean absolute error 6.0%). Primigravid ANC attendees had the lowest rates of net ownership (modeled odds ratio [OR] 0.28, 95% CI 0.19-0.40) and use (OR 0.58, 95% CI 0.42-0.79). ANC attendees reported higher levels of care-seeking (OR 1.78, 95% CI 1.48-2.14), malaria testing (OR 4.16, 95% CI 3.44-5.04), and treatment for children with fever (OR 7.66, 95% CI 4.89-11.98) compared to women surveyed in households, raising concerns about social desirability bias disproportionately impacting ANC surveys. CONCLUSION: ANC surveillance is an effective strategy for tracking trends in malaria burden. More work is required to elucidate the value of administering questionnaires to ANC attendees.

Fetal growth and birth weight are independently reduced by malaria infection and curable sexually transmitted and reproductive tract infections in Kenya, Tanzania, and Malawi: A pregnancy cohort study.

OBJECTIVES: Malaria and sexually transmitted and reproductive tract infections (STIs/RTIs) are highly prevalent in sub-Saharan Africa and associated with poor pregnancy outcomes. We investigated the individual and combined effects of malaria and curable STIs/RTIs on fetal growth in Kenya, Tanzania, and Malawi. METHODS: This study was nested within a randomized trial comparing monthly intermittent preventive treatment for malaria in pregnancy with sulfadoxine-pyrimethamine vs dihydroartemisinin-piperaquine, alone or combined with azithromycin. Fetal weight gain was assessed by serial prenatal ultrasound. Malaria was assessed monthly, and Treponema pallidum, Neisseria gonorrhoeae, Trichomonas vaginalis, Chlamydia trachomatis, and bacterial vaginosis at enrollment and in the third trimester. The effect of malaria and STIs/RTIs on fetal weight/birthweight Z-scores was evaluated using mixed-effects linear regression. RESULTS: In total, 1435 pregnant women had fetal/birth weight assessed 3950 times. Compared to women without malaria or STIs/RTIs (n = 399), malaria-only (n = 267), STIs/RTIs only (n = 410) or both (n = 353) were associated with reduced fetal growth (adjusted mean difference in fetal/birth weight Z-score [95% confidence interval]: malaria = -0.18 [-0.31,-0.04], P = 0.01; STIs/RTIs = -0.14 [-0.26,-0.03], P = 0.01; both = -0.20 [-0.33,-0.07], P = 0.003). Paucigravidae experienced the greatest impact. CONCLUSION: Malaria and STIs/RTIs are associated with poor fetal growth especially among paucigravidae women with dual infections. Integrated antenatal interventions are needed to reduce the burden of both malaria and STIs/RTIs.

Plasmodium falciparum infection and disease in infancy associated with increased risk of malaria and anaemia in childhood.

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.

Prevalence of and risk factors for microscopic and submicroscopic malaria infections in pregnancy: a systematic review and meta-analysis.

BACKGROUND: Malaria infections during pregnancy can cause adverse birth outcomes, yet many infections are undetected by microscopy. We aimed to describe the epidemiology of submicroscopic malaria infections in pregnant women in Asia, the Americas, and Africa using aggregated and individual participant data (IPD). METHODS: For this systematic review and meta-analysis, studies (published Jan 1, 1997 to Nov 10, 2021) with information on both microscopic and submicroscopic infections during pregnancy from Asia, the Americas, or Africa, identified in the Malaria-in-Pregnancy Library, were eligible. Studies (or subgroups or study groups) that selected participants on the basis of the presence of fever or a positive blood smear were excluded to avoid selection bias. We obtained IPD (when available) and aggregated data. Estimates of malaria transmission intensity and sulfadoxine-pyrimethamine resistance, matched by study location and year, were obtained using publicly available data. One-stage multivariable logit and multinomial models with random intercepts for study site were used in meta-analysis to assess prevalence of and risk factors for submicroscopic infections during pregnancy and at delivery. This study is registered with PROSPERO, number CRD42015027342. FINDINGS: The search identified 87 eligible studies, 68 (78%) of which contributed to the analyses. Of these 68 studies, 45 (66%) studies contributed IPD (48 869 participants) and 23 (34%) studies contributed aggregated data (11 863 participants). During pregnancy, median prevalence estimates were 13·5% (range 0·0-55·9, 66 substudies) for submicroscopic and 8·0% (0·0-50·6, 66 substudies) for microscopic malaria. Among women with positive Plasmodium nucleic acid amplification tests (NAATs), the median proportion of submicroscopic infections was 58·7% (range 0·0-100); this proportion was highest in the Americas (73·3%, 0·0-100), followed by Asia (67·2%, 36·4-100) and Africa (56·5%, 20·5-97·7). In individual patient data analysis, compared with women with no malaria infections, those with submicroscopic infections were more likely to present with fever in Africa (adjusted odds ratio 1·32, 95% CI 1·02-1·72; p=0·038) but not in other regions. Among women with NAAT-positive infections in Asia and the Americas, Plasmodium vivax infections were more likely to be submicroscopic than Plasmodium falciparum infections (3·69, 2·45-5·54; p<0·0001). Risk factors for submicroscopic infections among women with NAAT-positive infections in Africa included older age (age ≥30 years), multigravidity, and no HIV infection. INTERPRETATION: During pregnancy, submicroscopic infections are more common than microscopic infections and are associated with fever in Africa. Malaria control in pregnancy should target both microscopic and submicroscopic infections. FUNDING: Bill & Melinda Gates Foundation through the Worldwide Antimalarial Resistance Network.

Malaria-Related Psychosocial Factors, Past Antenatal Care-Seeking Behaviors, and Future Antenatal Care-Seeking Intentions by Maternal Age in Malawi and Democratic Republic of the Congo.

Young women in sub-Saharan Africa are a group at increased risk for malaria in pregnancy. Early antenatal care (ANC) seeking makes it more likely that women will receive the recommended doses of intermittent preventive treatment of malaria in pregnancy. This study used data from national Malaria Behavior Surveys conducted in Malawi and the Democratic Republic of the Congo (DRC) in 2021 to explore the association between intention to attend ANC in the first trimester for a future pregnancy (early ANC intention) and psychosocial factors among women aged 15-49 years. Eight psychosocial factors related to ANC and based on the ideation model were included, including knowledge, attitudes, and self-efficacy. The study used multivariable logistic regression models controlling for demographic characteristics to evaluate associations between early ANC intention and the individual ideational factors and the composite measure. Analysis included 2,148 women aged 15-49 years (Malawi: 827, DRC: 1,321). Antenatal care ideation was lower among young (aged 15-20 years) than among older (aged 21-49 years) women in Malawi. Young mothers with higher ANC ideation were more likely to intend to attend ANC early in their next pregnancy in both countries. Specific ideational factors associated with intention to attend ANC early varied by country and included positive attitudes, knowledge of ANC, and positive self-efficacy. In Malawi and the DRC, youth-friendly social and behavior change interventions to increase ANC-related ideation could increase future early ANC attendance among young women to improve malaria and birth outcomes.

Fetal sex and risk of pregnancy-associated malaria in Plasmodium falciparum-endemic regions: a meta-analysis.

In areas of moderate to intense Plasmodium falciparum transmission, malaria in pregnancy remains a significant cause of low birth weight, stillbirth, and severe anaemia. Previously, fetal sex has been identified to modify the risks of maternal asthma, pre-eclampsia, and gestational diabetes. One study demonstrated increased risk of placental malaria in women carrying a female fetus. We investigated the association between fetal sex and malaria in pregnancy in 11 pregnancy studies conducted in sub-Saharan African countries and Papua New Guinea through meta-analysis using log binomial regression fitted to a random-effects model. Malaria infection during pregnancy and delivery was assessed using light microscopy, polymerase chain reaction, and histology. Five studies were observational studies and six were randomised controlled trials. Studies varied in terms of gravidity, gestational age at antenatal enrolment and bed net use. Presence of a female fetus was associated with malaria infection at enrolment by light microscopy (risk ratio 1.14 [95% confidence interval 1.04, 1.24]; P = 0.003; n = 11,729). Fetal sex did not associate with malaria infection when other time points or diagnostic methods were used. There is limited evidence that fetal sex influences the risk of malaria infection in pregnancy.