Last data update: Apr 29, 2024. (Total: 46658 publications since 2009)
Records 1-30 (of 56 Records) |
Query Trace: Gutman JR[original query] |
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Trends in SARS-CoV-2 seroprevalence among pregnant women attending first antenatal care visits in Zambia: A repeated cross-sectional survey, 2021-2022
Heilmann E , Tembo T , Fwoloshi S , Kabamba B , Chilambe F , Kalenga K , Siwingwa M , Mulube C , Seffren V , Bolton-Moore C , Simwanza J , Yingst S , Yadav R , Rogier E , Auld AF , Agolory S , Kapina M , Gutman JR , Savory T , Kangale C , Mulenga LB , Sikazwe I , Hines JZ . PLOS Glob Public Health 2024 4 (4) e0003073 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
Tenthani L , Seffren V , Kabaghe AN , Ogollah F , Soko M , Yadav R , Kayigamba F , Payne D , Wadonda-Kabondo N , Kampira E , Volkmann T , Sugandhi NS , Seydel K , Rogier E , Thwing JI , Gutman JR . Am J Trop Med Hyg 2024 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
Popkin-Hall ZR , Seth MD , Madebe RA , Budodo R , Bakari C , Francis F , Pereus D , Giesbrecht DJ , Mandara CI , Mbwambo D , Aaron S , Lusasi A , Lazaro S , Bailey JA , Juliano JJ , Gutman JR , Ishengoma DS . Parasit Vectors 2024 17 (1) 153 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
Schneider ZD , Busbee AL , Boily MC , Shah MP , Hwang J , Lindblade KA , Gutman JR . Am J Trop Med Hyg 2024 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. |
Malaria species prevalence among asymptomatic individuals in four regions of Mainland Tanzania
Popkin Hall ZR , Seth MD , Madebe RA , Budodo R , Bakari C , Francis F , Pereus D , Giesbrecht DJ , Mandara CI , Mbwambo D , Aaron S , Lusasi A , Lazaro S , Bailey JA , Juliano JJ , Gutman JR , Ishengoma DS . medRxiv 2023 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 Plasmodium falciparum infection is typically more severe, diagnosis, treatment, and control for P. malariae, P. ovale spp., and P. vivax may be more challenging. The prevalence of these species throughout sub-Saharan Africa is poorly defined. Tanzania has geographically heterogeneous transmission levels but an overall high malaria burden. In order to estimate the prevalence of malaria species in Mainland Tanzania, 1,428 samples were randomly selected from 6,005 asymptomatic isolates collected in cross-sectional community surveys across four regions and analyzed via qPCR to detect each Plasmodium species. P. falciparum was most prevalent, with P. malariae and P. ovale spp. detected at lower prevalence (<5%) in all four regions. P. vivax was not detected. Malaria elimination efforts in Tanzania will need to account for these non-falciparum species. |
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
Barsosio HC , Madanitsa M , Ondieki ED , Dodd J , Onyango ED , Otieno K , Wang D , Hill J , Mwapasa V , Phiri KS , Maleta K , Taegtmeyer M , Kariuki S , Schmiegelow C , Gutman JR , Ter Kuile FO . Lancet 2024 403 (10424) 365-378 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. |
Mass drug administration to reduce malaria transmission: A systematic review and meta-analysis
Schneider ZD , Shah MP , Boily MC , Busbee AL , Hwang J , Lindblade KA , Gutman JR . Am J Trop Med Hyg 2023 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
Wolf K , Mostel J , Oseni L , Gomez P , Kibuka T , Emerson C , Gutman JR , Malpass A , Youll S , Mukamba JY , Tchinda E , Achu D , Tjek P , Assa JL , Silue M , Tanoh MA , Kokrasset-Yah C , Babanawo F , Asiedu A , Komey M , Boateng P , Mabiria M , Ngindu A , Njiru P , Omar AH , Sidibe FA , Diallo C , Kamate B , Kone A , Elisha S , Maiga AD , Mayaki AI , Tidjani Issa Gana F , Tetteh G . Am J Trop Med Hyg 2023 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. |
Contextual factors to improve implementation of malaria chemoprevention in children: A systematic review
Gatiba P , Laury J , Steinhardt L , Hwang J , Thwing JI , Zulliger R , Emerson C , Gutman JR . Am J Trop Med Hyg 2023 110 (1) 69-78 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. |
Systematic review and meta-analysis of seasonal malaria chemoprevention
Thwing J , Williamson J , Cavros I , Gutman JR . Am J Trop Med Hyg 2023 110 (1) 20-31 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. |
Late morning biting behaviour of Anopheles funestus is a risk factor for transmission in schools in Siaya, western Kenya
Omondi S , Kosgei J , Musula G , Muchoki M , Abong'o B , Agumba S , Ogwang C , McDermott DP , Donnelly MJ , Staedke SG , Schultz J , Gutman JR , Gimnig JE , Ochomo E . Malar J 2023 22 (1) 366 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. |
Have you heard the news? Artemether-lumefantrine is now recommended for ALL uncomplicated malaria in the United States, including in pregnancy
Castro L , Ridpath A , Mace K , Gutman JR . Clin Infect Dis 2023 Malaria is a serious and potentially fatal disease transmitted through the bite of an infective | female anopheline mosquito; pregnant people are more susceptible to malaria infection than nonpregnant people, and are at risk of significant adverse consequences for both mother and infant.1 | | These include maternal anemia, fetal growth retardation, stillbirth, premature birth, and low | birthweight.2 | Rarely, malaria can be transmitted congenitally from mother to fetus or to the | neonate at birth. Globally, it is estimated that over 13 million pregnancies were affected by | malaria in 2021, leading to an estimated 505,000 infants born with low birth weight.3 While | malaria in pregnancy is rarely seen in the United States, it nonetheless occurs, with 19 cases | among pregnant women (both travelers and refugees/immigrants) reported in the US in 2018, | 4 27 | in 2019 (Mace, unpublished data), and 8 in 2020 (Mace, unpublished data), and needs to be | recognized and treated quickly to prevent adverse effects to the mother and infant. |
Peripheral and placental prevalence of sulfadoxine-pyrimethamine resistance markers in plasmodium falciparum among pregnant women in Southern Province, Rwanda
Alruwaili M , Uwimana A , Sethi R , Murindahabi M , Piercefield E , Umulisa N , Abram A , Eckert E , Munguti K , Mbituyumuremyi A , Gutman JR , Sullivan DJ . Am J Trop Med Hyg 2023 109 (5) 1057-1062 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. |
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
Osoro CB , Dellicour S , Ochodo E , Young T , Ter Kuile FO , Gutman JR , Hill J . Malar J 2023 22 (1) 274 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. |
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
Osoro CB , Dellicour S , Ochodo E , Young T , Ter Kuile F , Gutman JR , Hill J . Malar J 2023 22 (1) 262 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. |
Assessing the utility of pregnant women as a sentinel surveillance population for malaria in Geita, Tanzania, 2019 - 2021
Munsey A , Kinyina A , Assenga M , Almeida A , Kitojo C , Reaves E , Simeo J , Aron S , Chacky F , Nhiga SL , Drake M , Lemwayi R , Walker P , Gutman JR . Int J Infect Dis 2023 136 57-63 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% confidence interval, 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 in 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
Mtove G , Chico RM , Madanitsa M , Barsosio HC , Msemo OA , Saidi Q , Gore-Langton GR , Minja DTR , Mukerebe C , Gesase S , Mwapasa V , Phiri KS , Hansson H , Dodd J , Magnussen P , Kavishe RA , Mosha F , Kariuki S , Lusingu JPA , Gutman JR , Alifrangis M , Ter Kuile FO , Schmiegelow C . Int J Infect Dis 2023 135 28-40 OBJECTIVE: 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 versus 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 enrolment 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: 1,435 pregnant women had fetal/birth weight assessed 3,950 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% CI]: 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. |
Fetal sex and risk of pregnancy-associated malaria in Plasmodium falciparum-endemic regions: a meta-analysis
Unger HW , Hadiprodjo AJ , Gutman JR , Briand V , Fievet N , Valea I , Tinto H , D'Alessandro U , Landis SH , Ter Kuile F , Ouma P , Oneko M , Mwapasa V , Slutsker L , Terlouw DJ , Kariuki S , Ayisi J , Nahlen B , Desai M , Madanitsa M , Kalilani-Phiri L , Ashorn P , Maleta K , Tshefu-Kitoto A , Mueller I , Stanisic D , Cates J , Van Eijk AM , Ome-Kaius M , Aitken EH , Rogerson SJ . Sci Rep 2023 13 (1) 10310 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. |
Plasmodium falciparum infection and disease in infancy associated with increased risk of malaria and anaemia in childhood
Andronescu LR , Buchwald AG , Sharma A , Bauleni A , Mawindo P , Liang Y , Gutman JR , Mathanga DP , Chinkhumba J , Laufer MK . Malar J 2023 22 (1) 217 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. |
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
Olapeju B , Bride M , Gutman JR , Butts JK , Malpass A , McCartney-Melstad A , Van Lith LM , Rodriguez K , Youll S , Mbeye N , Ntoya F , Lankhulani S , Mpata F , Babalola S . Am J Trop Med Hyg 2023 109 (2) 277-283 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. |
Prevalence of and risk factors for microscopic and submicroscopic malaria infections in pregnancy: a systematic review and meta-analysis
van Eijk AM , Stepniewska K , Hill J , Taylor SM , Rogerson SJ , Cottrell G , Chico RM , Gutman JR , Tinto H , Unger HW , Yanow SK , Meshnick SR , Ter Kuile FO , Mayor A . Lancet Glob Health 2023 11 (7) e1061-e1074 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. |
Using antenatal care as a platform for malaria surveillance data collection: study protocol
Gutman JR , Mwesigwa JN , Arnett K , Kangale C , Aaron S , Babarinde D , Buekens J , Candrinho B , Debe S , Digre P , Drake M , Gansané A , Gogue C , Griffith KS , Hicks J , Kinda R , Koenker H , Lemwayi R , Munsey A , Obi E , Ogouyèmi-Hounto A , Okoko OO , Onikpo F , Onoja A , Porter T , Savaio B , Tynuv K , Uhomoibhi P , Wagman J , Wolf K , Zulliger R , Walker P , Miller JM , Robertson M . Malar J 2023 22 (1) 99 BACKGROUND: While many malaria-endemic countries have health management information systems that can measure and report malaria trends in a timely manner, these routine systems have limitations. Periodic community cross-sectional household surveys are used to estimate malaria prevalence and intervention coverage but lack geographic granularity and are resource intensive. Incorporating malaria testing for all women at their first antenatal care (ANC) visit (i.e., ANC1) could provide a more timely and granular source of data for monitoring trends in malaria burden and intervention coverage. This article describes a protocol designed to assess if ANC-based surveillance could be a pragmatic tool to monitor malaria. METHODS: This is an observational, cross-sectional study conducted in Benin, Burkina Faso, Mozambique, Nigeria, Tanzania, and Zambia. Pregnant women attending ANC1 in selected health facilities will be tested for malaria infection by rapid diagnostic test and administered a brief questionnaire to capture key indicators of malaria control intervention coverage and care-seeking behaviour. In each location, contemporaneous cross-sectional household surveys will be leveraged to assess correlations between estimates obtained using each method, and the use of ANC data as a tool to track trends in malaria burden and intervention coverage will be validated. RESULTS: This study will assess malaria prevalence at ANC1 aggregated at health facility and district levels, and by gravidity relative to current pregnancy (i.e., gravida 1, gravida 2, and gravida 3 +). ANC1 malaria prevalence will be presented as monthly trends. Additionally, correlation between ANC1 and household survey-derived estimates of malaria prevalence, bed net ownership and use, and care-seeking will be assessed. CONCLUSION: ANC1-based surveillance has the potential to provide a cost-effective, localized measure of malaria prevalence that is representative of the general population and useful for tracking monthly changes in parasite prevalence, as well as providing population-representative estimates of intervention coverage and care-seeking behavior. This study will evaluate the representativeness of these measures and collect information on operational feasibility, usefulness for programmatic decision-making, and potential for scale-up of malaria ANC1 surveillance. |
Effect of monthly intermittent preventive treatment with dihydroartemisinin-piperaquine with and without azithromycin versus monthly sulfadoxine-pyrimethamine on adverse pregnancy outcomes in Africa: a double-blind randomised, partly placebo-controlled trial
Madanitsa M , Barsosio HC , Minja DTR , Mtove G , Kavishe RA , Dodd J , Saidi Q , Onyango ED , Otieno K , Wang D , Ashorn U , Hill J , Mukerebe C , Gesase S , Msemo OA , Mwapasa V , Phiri KS , Maleta K , Klein N , Magnussen P , Lusingu JPA , Kariuki S , Mosha JF , Alifrangis M , Hansson H , Schmiegelow C , Gutman JR , Chico RM , Ter Kuile FO . Lancet 2023 401 (10381) 1020-1036 BACKGROUND: Intermittent preventive treatment in pregnancy (IPTp) with dihydroartemisinin-piperaquine is more effective than IPTp with sulfadoxine-pyrimethamine at reducing malaria infection during pregnancy in areas with high-grade resistance to sulfadoxine-pyrimethamine by Plasmodium falciparum in east Africa. We aimed to assess whether IPTp with dihydroartemisinin-piperaquine, alone or combined with azithromycin, can reduce adverse pregnancy outcomes compared with IPTp with sulfadoxine-pyrimethamine. METHODS: We did an individually randomised, double-blind, three-arm, partly placebo-controlled trial in areas of high sulfadoxine-pyrimethamine resistance in Kenya, Malawi, and Tanzania. HIV-negative women with a viable singleton pregnancy were randomly assigned (1:1:1) by computer-generated block randomisation, stratified by site and gravidity, to receive monthly IPTp with sulfadoxine-pyrimethamine (500 mg of sulfadoxine and 25 mg of pyrimethamine for 1 day), monthly IPTp with dihydroartemisinin-piperaquine (dosed by weight; three to five tablets containing 40 mg of dihydroartemisinin and 320 mg of piperaquine once daily for 3 consecutive days) plus a single treatment course of placebo, or monthly IPTp with dihydroartemisinin-piperaquine plus a single treatment course of azithromycin (two tablets containing 500 mg once daily for 2 consecutive days). Outcome assessors in the delivery units were masked to treatment group. The composite primary endpoint was adverse pregnancy outcome, defined as fetal loss, adverse newborn baby outcomes (small for gestational age, low birthweight, or preterm), or neonatal death. The primary analysis was by modified intention to treat, consisting of all randomised participants with primary endpoint data. Women who received at least one dose of study drug were included in the safety analyses. This trial is registered with ClinicalTrials.gov, NCT03208179. FINDINGS: From March-29, 2018, to July 5, 2019, 4680 women (mean age 25·0 years [SD 6·0]) were enrolled and randomly assigned: 1561 (33%; mean age 24·9 years [SD 6·1]) to the sulfadoxine-pyrimethamine group, 1561 (33%; mean age 25·1 years [6·1]) to the dihydroartemisinin-piperaquine group, and 1558 (33%; mean age 24·9 years [6.0]) to the dihydroartemisinin-piperaquine plus azithromycin group. Compared with 335 (23·3%) of 1435 women in the sulfadoxine-pyrimethamine group, the primary composite endpoint of adverse pregnancy outcomes was reported more frequently in the dihydroartemisinin-piperaquine group (403 [27·9%] of 1442; risk ratio 1·20, 95% CI 1·06-1·36; p=0·0040) and in the dihydroartemisinin-piperaquine plus azithromycin group (396 [27·6%] of 1433; 1·16, 1·03-1·32; p=0·017). The incidence of serious adverse events was similar in mothers (sulfadoxine-pyrimethamine group 17·7 per 100 person-years, dihydroartemisinin-piperaquine group 14·8 per 100 person-years, and dihydroartemisinin-piperaquine plus azithromycin group 16·9 per 100 person-years) and infants (sulfadoxine-pyrimethamine group 49·2 per 100 person-years, dihydroartemisinin-piperaquine group 42·4 per 100 person-years, and dihydroartemisinin-piperaquine plus azithromycin group 47·8 per 100 person-years) across treatment groups. 12 (0·2%) of 6685 sulfadoxine-pyrimethamine, 19 (0·3%) of 7014 dihydroartemisinin-piperaquine, and 23 (0·3%) of 6849 dihydroartemisinin-piperaquine plus azithromycin treatment courses were vomited within 30 min. INTERPRETATION: Monthly IPTp with dihydroartemisinin-piperaquine did not improve pregnancy outcomes, and the addition of a single course of azithromycin did not enhance the effect of monthly IPTp with dihydroartemisinin-piperaquine. Trials that combine sulfadoxine-pyrimethamine and dihydroartemisinin-piperaquine for IPTp should be considered. FUNDING: European & Developing Countries Clinical Trials Partnership 2, supported by the EU, and the UK Joint-Global-Health-Trials-Scheme of the Foreign, Commonwealth and Development Office, Medical Research Council, Department of Health and Social Care, Wellcome, and the Bill-&-Melinda-Gates-Foundation. |
Effectiveness of intermittent screening and treatment of malaria in pregnancy on maternal and birth outcomes in selected districts in Rwanda: A cluster randomized controlled trial
Uwimana A , Sethi R , Murindahabi M , Ntirandeka C , Piercefield E , Umulisa N , Abram A , Eckert E , Munguti K , Sullivan D , Uyizeye D , Mbituyumuremyi A , Gutman JR . Clin Infect Dis 2023 77 (1) 127-134 BACKGROUND: Malaria during pregnancy can cause serious consequences including maternal anemia and low birthweight (LBW). Routine antenatal care (ANC) in Rwanda includes malaria symptom screening at each ANC visit. This cluster randomized controlled trial investigated whether adding intermittent screening with a malaria rapid diagnostic test (RDT) at each routine ANC visit and treatment of positives during pregnancy (ISTp) is more effective than routine ANC for reducing malaria prevalence at delivery. METHODS: Between September 2016- June 2018, pregnant women initiating ANC at 14 health centers in Rwanda were enrolled into ISTp or control arms. All women received an insecticide-treated bed net at enrolment. Hemoglobin concentration, placental and peripheral parasitemia, newborn outcome, birthweight, and prematurity were assessed at delivery. RESULTS: 975 were enrolled in ISTp and 811 in the control. Routine ANC plus ISTp did not significantly reduce PCR-confirmed placental malaria compared to control (adjusted relative risk [aRR] 0.94, 95% confidence interval [CI] 0.59-1.50, p=0.799). ISTp had no impact on anemia (aRR 1.08, 95% CI 0.57-2.04, p=0.821). The mean birthweight of singleton newborns was not significantly different between arms (3054gm vs 3096gm, p=0.395), however women in the ISTp arm had a higher proportion of LBW (aRR = 1.59, 95% CI 1.02-2.49, p=0.042). CONCLUSIONS: This is the only study to compare ISTp to symptomatic screening at ANC in a setting where intermittent preventive treatment is not routinely provided. ISTp did not reduce the prevalence of malaria or anemia at delivery and was associated with an increased risk of LBW. CLINICAL TRIALS REGISTRATION: NCT03508349. |
Women attending antenatal care as a sentinel surveillance population for malaria in Geita region, Tanzania: feasibility and acceptability to women and providers
Emerson C , Ulimboka S , Lemwayi R , Kinyina A , Nhiga SL , Aaron S , Simeo J , Kitojo C , Reaves EJ , Drake M , Hussein Y , Bungire L , Gutman JR , Winch PJ . Malar J 2023 22 (1) 66 BACKGROUND: Measurement of malaria prevalence is conventionally estimated through infrequent cross-sectional household surveys that do not provide continuous information regarding malaria parasitaemia. Recent studies have suggested that malaria parasitaemia prevalence among women attending antenatal care (ANC) correlates with prevalence among children under 5 years old and that pregnant women could be a sentinel population for tracking malaria prevalence. In mainland Tanzania, 97% of women are tested for malaria parasitaemia during first ANC visits. However, acceptability among pregnant women and healthcare providers of collecting malaria risk factor data during ANC visits is limited. METHODS: A tablet-based questionnaire including 15 questions on insecticide-treated net ownership and use and care-seeking for febrile children was introduced at 40 healthcare facilities in Geita Region, Tanzania. Facilities were randomly selected from among those with 15-120 first ANC visits per month. To assess perspectives regarding introduction of the questionnaire, 21 semi-structured interviews were held with providers and facility in-charges at 12 facilities. Thirty pregnant and recently delivered women participated in focus group discussions at seven facilities to assess the acceptability of spending additional time answering questions about malaria risk. RESULTS: All pregnant women reported that introduction of ANC surveillance and spending 10 more minutes with providers answering questions about their health would be neutral or beneficial. They perceived being asked about their health as standard of care. Providers and in-charges reported that introduction of ANC surveillance was within their scope of practice. Nine of 21 indicated it could potentially benefit women's health. Six providers expressed concern about staffing shortages and need for reimbursement for extra time and noted that data management occurs after hours. CONCLUSIONS: Pregnant women and providers generally perceived ANC surveillance for malaria as acceptable and positive. Pregnant and recently delivered women saw this as a reasonable and even helpful intervention. To be seen as a part of standard practice, efforts are needed to ensure providers perceive a benefit for ANC clients and that staffing concerns are addressed. In addition, staff should receive feedback related to data submissions regarding malaria prevalence and risk factors among women at their facility, with actions to take. |
The choice of reference chart affects the strength of the association between malaria in pregnancy and small for gestational age: an individual participant data meta-analysis comparing the Intergrowth-21 with a Tanzanian birthweight chart
Mtove G , Minja DTR , Abdul O , Gesase S , Maleta K , Divala TH , Patson N , Ashorn U , Laufer MK , Madanitsa M , Ashorn P , Mathanga D , Chinkhumba J , Gutman JR , TerKuile FO , Mller SL , Bygbjerg IC , Alifrangis M , Theander T , Lusingu JPA , Schmiegelow C . Malar J 2022 21 (1) 292 BACKGROUND: The prevalence of small for gestational age (SGA) may vary depending on the chosen weight-for-gestational-age reference chart. An individual participant data meta-analysis was conducted to assess the implications of using a local reference (STOPPAM) instead of a universal reference (Intergrowth-21) on the association between malaria in pregnancy and SGA. METHODS: Individual participant data of 6,236 newborns were pooled from seven conveniently identified studies conducted in Tanzania and Malawi from 2003-2018 with data on malaria in pregnancy, birthweight, and ultrasound estimated gestational age. Mixed-effects regression models were used to compare the association between malaria in pregnancy and SGA when using the STOPPAM and the Intergrowth-21 references, respectively. RESULTS: The 10th percentile for birthweights-for-gestational age was lower for STOPPAM than for Intergrowth-21, leading to a prevalence of SGA(STOPPAM) of 14.2% and SGA(IG21) of 18.0%, p<0.001. The association between malaria in pregnancy and SGA was stronger for STOPPAM (adjusted odds ratio (aOR) 1.30 [1.09-1.56], p<0.01) than for Intergrowth-21 (aOR 1.19 [1.00-1.40], p=0.04), particularly among paucigravidae (SGA(STOPPAM) aOR 1.36 [1.09-1.71], p<0.01 vs SGA(IG21) aOR 1.21 [0.97-1.50], p=0.08). CONCLUSIONS: The prevalence of SGA may be overestimated and the impact of malaria in pregnancy underestimated when using Intergrowth-21. Comparing local reference charts to global references when assessing and interpreting the impact of malaria in pregnancy may be appropriate. |
Routine healthcare facility- and antenatal care-based malaria surveillance: Challenges and opportunities
Gutman JR , Thwing J , Mwesigwa J , McElroy P , Robertson M . Am J Trop Med Hyg 2022 108 4-7 Most monitoring and evaluation tools for measuring malaria burden, intervention coverage, and impact of interventions use periodic nationally representative cross-sectional household surveys. These provide advantages in terms of selecting a large, unbiased, population-based sample; however, they are infrequently conducted, are resource-intensive, and do not provide longitudinal data with sufficient granularity. Given the heterogeneity of malaria transmission within most endemic countries, systems with the capacity to provide more granular and frequent data would be more actionable by national malaria control programs and local implementing partners. There is increasing interest in using routine health facility data, usually from outpatient department visits, for monitoring malaria burden. Data from pregnant women attending antenatal care (ANC) could minimize bias related to fever care-seeking among outpatient department visits and provide more granular parasite prevalence data. Most pregnant women attend ANC at least once and are thus highly representative of the overall pregnant population. A growing body of evidence suggests that malaria parasitemia in pregnant women is correlated with parasitemia in children aged < 5 years in moderate to high transmission areas, allowing for monitoring parasitemia in real time. Additional data are needed to assess whether pregnant women are sufficiently representative of the overall population to yield valid malaria prevalence and intervention coverage estimates. Although use of routinely collected ANC data faces many of the same challenges experienced by other routinely collected health facility data, the opportunity to improve parasite prevalence monitoring and the associated health benefits to mothers and infants of early detection of parasitemia make these efforts valuable. |
A cluster randomized trial of delivery of intermittent preventive treatment of malaria in pregnancy at the community level in Malawi
Rubenstein BL , Chinkhumba J , Chilima E , Kwizombe C , Malpass A , Cash S , Wright K , Troell P , Nsona H , Kachale F , Ali D , Kaunda E , Lankhulani S , Kayange M , Mathanga DP , Munthali J , Gutman JR . Malar J 2022 21 (1) 195 BACKGROUND: Malaria in pregnancy doubles the risk of low birthweight; up to 11% of all neonatal deaths in sub-Saharan Africa are associated with malaria in pregnancy. To prevent these and other adverse health consequences, the World Health Organization recommends administering intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine for all pregnant women at each antenatal care (ANC) visit, starting as early as possible in the second trimester. The target is for countries to administer a minimum of three doses (IPTp3+) to at least 85% of pregnant women. METHODS: A cluster randomized, controlled trial was conducted to assess the effect of delivery of IPTp by community health workers on the coverage of IPTp3+and ANC visits in Malawi. Community delivery of IPTp was implemented within two districts in Malawi over a 21-month period, from November 2018 to July 2020. In control sites, IPTp was delivered at health facilities. Representative samples of women who delivered in the prior 12 months were surveyed at baseline (n=370, December 2017) and endline (n=687, August 2020). A difference in differences analysis was conducted to assess the change in coverage of IPTp and ANC over time, accounting for clustering at the health facility level. RESULTS: Overall IPTp coverage increased over the study period. At baseline, women received a mean of 2.3 IPTp doses (range 0-5 doses) across both arms, and at endline, women received a mean of 2.8 doses (range 0-9 doses). Despite overall increases, the change in IPTp3+coverage was not significantly different between intervention and control groups (6.9%, 95% CI: -5.9%, 19.6%). ANC4+coverage increased significantly in the intervention group compared with the control group, with a difference-in-differences of 25.3% points (95% CI: 1.3%, 49.3%). CONCLUSIONS: In order to reduce the burden of malaria in pregnancy, new strategies are needed to improve uptake of effective interventions such as IPTp. While community health workers' delivery of IPTp did not increase uptake in this study, they may be effective in other settings or circumstances. Further research can help identify the health systems characteristics that are conducive to community delivery of IPTp and the operational requirements for effective implementation. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03376217. Registered December 6, 2017, https://clinicaltrials.gov/ct2/show/NCT03376217 . |
The positive effect of malaria IPTp-SP on birthweight is mediated by gestational weight gain but modifiable by maternal carriage of enteric pathogens
Waltmann A , McQuade ETR , Chinkhumba J , Operario DJ , Mzembe E , Itoh M , Kayange M , Puerto-Meredith SM , Mathanga DP , Juliano JJ , Carroll I , Bartelt LA , Gutman JR , Meshnick SR . EBioMedicine 2022 77 103871 BACKGROUND: Poor pregnancy and birth outcomes are common in sub-Saharan Africa and have complex aetiologies. Sulfadoxine-pyrimethamine (SP), given for intermittent preventive therapy of malaria in pregnancy (IPTp), is one of few existing interventions that improves outcomes of both mother and baby despite widespread SP-resistant malaria. Compelling evidence exists that malaria-independent pathways contribute to this protective effect, but the exact sources of non anti-malarial protection remained unknown. We hypothesized that the beneficial effect of SP on birthweight is mediated by SP activity on maternal factors, including increased gestational weight gain and antibiotic activity on pathogens in the maternal gut. METHODS: Expectant mothers from a larger randomized control trial comparing the efficacy of IPTp-SP to IPTp with dihydroartemisinin-piperaquine (DP) were also enrolled in this sub-study study at their first antenatal care visit before commencement of IPTp (n = 105). Participants were followed monthly until delivery. Weights and mid-to-upper-arm circumferences (MUAC) were recorded. Monthly stool samples were collected and screened for five Escherichia coli pathotypes, Shigella spp., Vibrio cholerae, Salmonella, Campylobacter coli/jejuni, and three protozoa (Giardia spp., Entameba histolytica, and Cryptosporidium spp.) using previously validated molecular assays. FINDINGS: IPTp-SP vs. IPTP-DP was associated with higher maternal gestational weight gain (GWG) and nutritional indicators (MUAC and body-mass index, BMI). GWG was found to be a mediator of the birthweight and IPTp-SP relationship, as the birthweight of SP infants, but not DP infants, varied according to maternal GWG. The burden of maternal enteric infections was high. The three most commonly observed pathogens were enteroaggregative E. coli (EAEC), atypical enteropathogenic E.coli/enterohaemorrhagic E. coli (aEPEC/EHEC), and typical enteropathogenic E.coli (tEPEC). We found that SP reduced the prevalence of EAEC in a dose-dependent manner. After 3 or more doses, SP-recipients were 90% less likely to be infected with EAEC compared to DP-recipients (OR(adj) = 0.07, CI95 = 0.12, 0.39, p = 0.002). Compared to DP, this coincided with higher maternal gestational weight gain (GWG) and nutritional indicators (MUAC and body-mass index, BMI). The beneficial effect of SP on maternal GWG, MUAC and BMI, was lower if SP mothers had detectable EAEC, aEPEC/EHEC, tEPEC, and LT-ETEC at baseline. Maternal EAEC and tEPEC at baseline associated with lower birthweight for babies of both SP mothers and DP mothers. When comparing IPTp regimens, the positive effect of SP on birthweight compared to DP was only observed for infants of women who did not test positive for EAEC at baseline (adjusted mean birthweight difference SP vs. DP = 156.0 g, CI95 = -18.0 g, 336.9 g, p = 0.087), though confidence intervals crossed the null. INTERPRETATION: Our findings indicate that in pregnant Malawian women, IPTp-SP vs. IPTp-DP is consistently associated with higher MUAC, BMI, and GWG following the WHO-recommended regimen of at least 3 doses, but carriage of maternal gut pathogens before initiation of IPTp lessens this effect. Because GWG was a mediator of the association between birthweight and SP, we show that SP's previously proven positive effect on birthweight is by promoting maternal weight gain. Overall, our results present one plausible pathway SP exerts malaria-independent protection against poor birth outcomes in the context of its waning antimalarial activity and warrants further investigation. FUNDING: A full list of funding bodies that contributed to this study can be found in the Acknowledgements section. |
Intermittent screening and treatment with artemisinin-combination therapy versus intermittent preventive treatment with sulphadoxine-pyrimethamine for malaria in pregnancy: a systematic review and individual participant data meta-analysis of randomised clinical trials
Gutman JR , Khairallah C , Stepniewska K , Tagbor H , Madanitsa M , Cairns M , L'Lanziva A J , Kalilani L , Otieno K , Mwapasa V , Meshnick S , Kariuki S , Chandramohan D , Desai M , Taylor SM , Greenwood B , Ter Kuile FO . EClinicalMedicine 2021 41 101160 BACKGROUND: In sub-Saharan Africa, the efficacy of intermittent preventive therapy in pregnancy with sulphadoxine-pyrimethamine (IPTp-SP) for malaria in pregnancy is threatened by parasite resistance. We conducted an individual-participant data (IPD) meta-analysis to assess the efficacy of intermittent screening with malaria rapid diagnostic tests (RDTs) and treatment of RDT-positive women with artemisinin-based combination therapy (ISTp-ACT) compared to IPTp-SP, and understand the importance of subpatent infections. METHODS: We searched MEDLINE and the Malaria-in-Pregnancy Library on May 6, 2021 for trials comparing ISTp-ACT and IPTp-SP. Generalised linear regression was used to compare adverse pregnancy outcomes (composite of small-for-gestational-age, low birthweight (LBW), or preterm delivery) and peripheral or placental Plasmodium falciparum at delivery. The effects of subpatent (PCR-positive, RDT/microscopy-negative) infections were assessed in both arms pooled using multi-variable fixed-effect models adjusting for the number of patent infections. PROSPERO registration: CRD42016043789. FINDINGS: Five trials conducted between 2007 and 2014 contributed (10,821 pregnancies), two from high SP-resistance areas where dhfr/dhps quintuple mutant parasites are saturated, but sextuple mutants are still rare (Kenya and Malawi), and three from low-resistance areas (West-Africa). Four trials contributed IPD data (N=10,362). At delivery, the prevalence of any malaria infection (relative risk [RR]=1.08, 95% CI 1.00-1.16, I(2)=67.0 %) and patent infection (RR=1.02, 0.61-1.16, I(2)=0.0%) were similar. Subpatent infections were more common in ISTp recipients (RR=1.31, 1.05-1.62, I(2)=0.0%). There was no difference in adverse pregnancy outcome (RR=1.00, 0.96-1.05; studies=4, N=9,191, I(2)=54.5%). Subpatent infections were associated with LBW (adjusted RR=1.13, 1.07-1.19), lower mean birthweight (adjusted mean difference=32g, 15-49), and preterm delivery (aRR=1.35, 1.15-1.57). INTERPRETATION: ISTp-ACT was not superior to IPTp-SP and may result in more subpatent infections than the existing IPTp-SP policy. Subpatent infections were associated with increased LBW and preterm delivery. More sensitive diagnostic tests are needed to detect and treat low-grade infections. FUNDING: Centers for Disease Control and Prevention and Worldwide Antimalarial Resistance Network. |
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