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Resource-limited countries face challenges in setting up effective pharmacovigilance systems. This study aimed to monitor the occurrence of adverse events (AEs) after the use of artemisinin-based combination therapies (ACTs), identify potential drivers of reporting suspected adverse drug reactions (ADRs) and monitor AEs among women who were inadvertently exposed to ACTs in the first trimester of pregnancy., info:eu-repo/semantics/published

Invasive aspergillosis (IA) affects more than 300,000 people annually worldwide with a case fatality rate reaching 80%. However, in Africa despite the presence of risk factors for the development of IA, the burden of these fungal infections remained unknown. This systematic review aimed to update the available information on the epidemiology and the therapeutic management of IA in Africa. The published papers were systematically searched on major medical databases from September 20 to October 10, 2021. The list of references of eligible articles and the Google scholar database were also checked in order to search for possible eligible articles. Results were reported following the Preferred Reporting Items for Systematic and Meta-analyses (PRISMA) guidelines. The search yielded 1864 articles of which 29 met the inclusion criteria. This systematic review showed the existence of IA in Africa. The prevalence of IA can reach 27% with a fatality rate of more than 60%. The most common clinical form of IA found was invasive pulmonary aspergillosis. The main predisposing conditions identified were neutropenia, HIV/AIDS, renal transplant recipients, and renal failure. Aspergillus section Flavi and Nigri were the main Aspergillus species identified and Aspergillus section Fumigati was uncommon. The main management strategy for IA cases was to start antifungal therapy only after a failure of broad-spectrum antibiotic therapy. This review provided evidence of the existence of invasive aspergillosis in Africa and especially a high rate of undiagnosed invasive aspergillosis cases.

Azole-resistant Aspergillus fumigatus (ARAF) strains have been reported on all continents, however, limited data exist on these strains in Africa, while several factors, mainly environmental ones, suggest their presence on this continent. This study aimed to assess the environmental prevalence of ARAF strains in Burkina Faso, a country situated in the West African region where data on ARAF is non-existent. In total, 120 environmental samples (soil) were collected and analyzed. Samples were screened for resistance using three azole-containing agar plates; one without azole antifungal (growth control) and two supplemented with either itraconazole (4 mg/L) or voriconazole (2 mg/L). The EUCAST susceptibility testing method was used to confirm the azole-resistant phenotype of A. fumigatus sensu-stricto isolates. Mutations in the cyp51A gene were determined by sequencing. Of the 120 samples, 51 positive samples showed growth of A. fumigatus isolates on control medium. One ARAF (2%; 1/51) isolate was found amongst A. fumigatus positive samples and harbored the F46Y/M172V/E427K cyp51A mutations. No TR34/L98H or TR46/Y121F/T289A mutations were observed. Our study described the first A. fumigatus isolate resistant to an azole antifungal in Burkina Faso.

Additional file 1: Table S1. Determinants of the frequency of the K1 allelic family.

Additional file 2: Table S2. Determinants of the frequency of the MAD20 allelic family.

OBJECTIVES: Areas with declining malaria transmission in sub-Saharan Africa have recently witnessed important changes in the aetiology of childhood acute febrile illness (AFI). We describe the aetiology of AFI in a high malaria transmission area in rural Burkina Faso. METHODS: In a prospective hospital-based diagnostic study, children aged 3 months to 15 years with AFI were recruited and assessed using a systematic diagnostic protocol, including blood cultures, whole blood PCR on a selection of bacterial pathogens, malaria diagnostics and a multiplex PCR on nasopharyngeal swabs targeting 21 viral and 4 bacterial respiratory pathogens. RESULTS: A total of 589 children with AFI were enrolled from whom an infectious disease was considered in 575 cases. Acute respiratory tract infections, malaria and invasive bacterial infections (IBI) accounted for 179 (31.1%), 175 (30.4%) and 75 (13%) of AFI cases respectively; 16 (21.3%) of IBI cases also had malarial parasitaemia. A viral pathogen was demonstrated from the nasopharynx in 157 children (90.7%) with respiratory tract symptoms. Of all children with viral respiratory tract infections, 154 (92.4% received antibiotics, whereas no antibiotic was provided in 13 (17%) of IBI cases. CONCLUSIONS: Viral respiratory infections are a common cause of childhood AFI in high malaria transmission areas, next to malaria and IBI. These findings highlight the importance of interventions to improve targeted treatment with antimicrobials. Most patients with viral infections received antibiotics unnecessarily, while a considerable number with IBI did not receive antibiotics. ispartof: CLINICAL MICROBIOLOGY AND INFECTION vol:27 issue:4 pages:590-596 ispartof: location:England status: published

Introduction sur le plan génétique, Plasmodium falciparum(P. falciparum) est une espèce extrêmement polymorphe. Il existe une diversité de souches parasitaires qui infestent les individus vivant en zone d´endémie palustre. La présente étude vise à étudier la relation entre le polymorphisme de P. falciparum et les mutations au niveau des gènes Pfcrt et Pfmdr1 dans la zone de Nanoro au Burkina Faso. Méthodes les échantillons sanguins de porteurs de plasmodiums résidant dans le district sanitaire de Nanoro ont fait l´objet d´un génotypage par PCR nichée. Les mutations au niveau des gènes de résistance du parasite aux antipaludiques ont été détectées par la technique PCR-RFLP. Résultats les échantillons de 672 patients ont été génotypés avec succès. Aucune famille allélique des gènes msp1et msp2n´avaient une susceptibilité accrue à développer des mutations au niveau des gènes de résistance. Par contre, les souches mutantes de ces gènes étaient significativement plus importantes dans les infections monoclonales que dans les infections multi clonales. Conclusion cette étude fournit un aperçu global de la relation entre le polymorphisme de P. falciparum et les mutations au niveau des gènes de résistance. Ces données contribueront sans doute à améliorer les connaissances sur la biologie du parasite et de ses mécanismes de résistance aux antipaludiques.

Investigating malaria transmission dynamics is essential to inform policy decision making. Whether multiplicity of infection (MOI) dynamic from individual infections could be a reliable malaria metric in high transmission settings with marked variation in seasons of malaria transmission has been poorly assessed. This study aimed at investigating factors driving Plasmodium falciparum MOI and genetic diversity in a hyperendemic area of Burkina Faso., info:eu-repo/semantics/published

Background While there is increasing evidence on the safety of artemisinin-based combination therapy (ACT) for the case management of malaria in early pregnancy, little is known about the association between exposure to ACT during the first trimester and the effect on fetal growth. Methods Data were analysed from prospective studies of pregnant women enrolled in Mozambique, Burkina Faso and Kenya designed to determine the association between anti-malarial drug exposure in the first trimester and pregnancy outcomes, including low birth weight (LBW) and small for gestational age (SGA). Exposure to anti-malarial drugs was ascertained retrospectively by record linkage using a combination of data collected from antenatal and adult outpatient clinic registries, prescription records and self-reported medication usage by the women. Site-level data synthesis (fixed effects and random effects) was conducted as well as individual-level analysis (fixed effects by site). Results Overall, 1915 newborns were included with 92 and 26 exposed to ACT (artemether–lumefantrine) and quinine, respectively. In Burkina Faso, Mozambique and Kenya at recruitment, the mean age (standard deviation) was 27.1 (6.6), 24.2 (6.2) and 25.7 (6.5) years, and the mean gestational age was 24.0 (6.2), 21.2 (5.7) and 17.9 (10.2) weeks, respectively. The LBW prevalence among newborns born to women exposed to ACT and quinine (QNN) during the first trimester was 10/92 (10.9%) and 7/26 (26.9%), respectively, compared to 9.5% (171/1797) among women unexposed to any anti-malarials during pregnancy. Compared to those unexposed to anti-malarials, ACT and QNN exposed women had the pooled LBW prevalence ratio (PR) of 1.13 (95% confidence interval (CI) 0.62–2.05, p-value 0.700) and 2.03 (95% CI 1.09–3.78, p-value 0.027), respectively. Compared to those unexposed to anti-malarials ACT and QNN-exposed women had the pooled SGA PR of 0.85 (95% CI 0.50–1.44, p-value 0.543) and 1.41 (95% CI 0.71–2.77, p-value 0.322), respectively. Whereas compared to ACT-exposed, the QNN-exposed had a PR of 2.14 (95% CI 0.78–5.89, p-value 0.142) for LBW and 8.60 (95% CI 1.29–57.6, p-value 0.027) for SGA. The level of between sites heterogeneity was moderate to high. Conclusion ACT exposure during the first trimester was not associated with an increased occurrence of LBW or SGA. However, the data suggest a higher prevalence of LBW and SGA for children born to QNN-exposed pregnancies. The findings support the use of ACT (artemether–lumefantrine) for the treatment of uncomplicated malaria during the first trimester of pregnancy.

Additional file 1. Additional Figures S1–S3, Tables S1–S16.

Additional file 2: Table S2. Determinants of the frequency of the K1 allelic family. Effect of season, patient age, sex, parasite density, and interactions on the proportion of K1 variants in infected patient. Significant effects are emphasized in bold.

Additional file 5: Table S5. Determinants of the frequency of the 3D7 allelic family. Effect of season, patient age, sex, parasite density, and interactions on the proportion of 3D7 variants in infected patient. Significant effects are emphasized in bold.

Additional file 6: Table S6. Determinants of the frequency of the FC27 allelic family. Effect of season, patient age, sex, parasite density, and interactions on the proportion of FC27 variants in infected patient. Significant effects are emphasized in bold.

Additional file 4: Table S4. Determinants of the frequency of the RO33 allelic family. Effect of season, patient age, sex, parasite density, and interactions on the proportion of RO33 variants in infected patient. Significant effects are emphasized in bold.

Additional file 1: Table S1. Determinants of the multiplicity of infection (MOI). Effect of season, patient age, sex, parasite density, and interactions on the MOI. Significant effects are emphasized in bold.

Background Salmonella Typhimurium and Enteritidis are major causes of bloodstream infection in children in sub-Saharan Africa. This study assessed evidence for their zoonotic versus human reservoir. Methods Index patients were children with blood culture confirmed Salmonella infection recruited during a microbiological surveillance study in Nanoro, rural Burkina between May 2013 and August 2014. After consent, their households were visited. Stool from household members and livestock (pooled samples per species) as well as drinking water were cultured for Salmonella. Isolates with identical serotype obtained from index patient and any household sample were defined as “paired isolates” and assessed for genetic relatedness by multilocus variable number tandem-repeat analysis (MLVA) and whole-genome sequencing (WGS). Results Twenty-nine households were visited for 32/42 (76.2%) eligible index patients: two households comprised two index patients each, and in a third household the index patient had a recurrent infection. Among the 32 index patients, serotypes were Salmonella Typhimurium (n = 26), Salmonella Enteritidis (n = 5) and Salmonella Freetown (n = 1). All Typhimurium isolates were sequence type (ST)313. Median delay between blood culture sampling and household visits was 13 days (range 6–26). Salmonella was obtained from 16/186 (8.6%) livestock samples (13 serotypes) and 18/290 (6.2%) household members (9 serotypes). None of the water samples yielded Salmonella. Paired Salmonella Typhimurium isolates were obtained from three households representing four index patients. MLVA types were identical in two pairs and similar in the third (consisting of two index patients and one household member). WGS showed a strong genetic relatedness with 0 to 2 core genome SNPs difference between pairs on a household level. Livestock samples did not yield any Salmonella Typhimurium or Salmonella Enteritidis, and the latter was exclusively obtained from blood culture. Other serotypes shared by human and/or livestock carriers in the same household were Salmonella Derby, Drac, Tennessee and Muenster. Conclusions/Significance The current study provides further evidence of a human reservoir for invasive non-Typhoidal Salmonella (iNTS) in sub-Saharan Africa., Author summary Non-Typhoidal Salmonella—particularly Salmonella Typhimurium sequence type (ST) 313—are among the most common causes of bloodstream infection in children in sub-Saharan Africa. To assess transmission and reservoir of this invasive serotype we performed a blood culture surveillance study among children < 15 years (index patients) in Nanoro, rural Burkina Faso. In case of blood culture confirmed invasive Non-Typhoidal Salmonella (iNTS) infection among index patients a household survey was performed, during which stool samples from household members, stool samples from livestock and water samples were obtained and cultured for Salmonella. Salmonella isolates obtained from blood culture of index patients were compared for genetic relatedness with Salmonella isolates obtained from samples taken from their corresponding household. In three households we found Salmonella Typhimurium ST 313 among both index patient and the stool sample of a household member, we found a strong genetic relatedness within each pair. There were no matching serotypes between index patients and livestock samples or water samples within households. Clusters from other serotypes were restricted to stool samples from household members and different species of livestock. Our results support the theory that iNTS has a human reservoir.

Background Studies on the determinants of carotid intima‐media thickness ( CIMT ), a marker of sub‐clinical atherosclerosis, mostly come from white, Asian, and diasporan black populations. We present CIMT data from sub‐Saharan Africa, which is experiencing a rising burden of cardiovascular diseases and infectious diseases. Methods and Results The H3 (Human Hereditary and Health) in Africa’s AWI‐Gen (African‐Wits‐INDEPTH partnership for Genomic) study is a cross‐sectional study conducted in adults aged 40 to 60 years from Burkina Faso, Kenya, Ghana, and South Africa. Cardiovascular disease risk and ultrasonography of the CIMT of right and left common carotids were measured. Multivariable linear and mixed‐effect multilevel regression modeling was applied to determine factors related to CIMT. Data included 8872 adults (50.8% men), mean age of 50±6 years with age‐ and sex‐adjusted mean (±SE) CIMT of 640±123μm. Participants from Ghana and Burkina Faso had higher CIMT compared with other sites. Age (β = 6.77, 95%CI [6.34–7.19]), body mass index (17.6[12.5–22.8]), systolic blood pressure (7.52[6.21–8.83]), low‐density lipoprotein cholesterol (5.08[2.10–8.06]) and men (10.3[4.75– 15.9]) were associated with higher CIMT. Smoking was associated with higher CIMT in men. High‐density lipoprotein cholesterol (−12.2 [−17.9– −6.41]), alcohol consumption (–13.5 [−19.1–−7.91]) and HIV (−8.86 [−15.7–−2.03]) were inversely associated with CIMT. Conclusions Given the rising prevalence of cardiovascular diseases risk factors in sub‐Saharan Africa, atherosclerotic diseases may become a major pan‐African epidemic unless preventive measures are taken particularly for prevention of hypertension, obesity, and smoking. HIV ‐specific studies are needed to fully understand the association between HIV and CIMT in sub‐Saharan Africa.

Azole-resistant Aspergillus fumigatus (ARAF) strains have been reported on all continents, however, limited data exist on these strains in Africa, while several factors, mainly environmental ones, suggest their presence on this continent. This study aimed to assess the environmental prevalence of ARAF strains in Burkina Faso, a country situated in the West African region where data on ARAF is non-existent. In total, 120 environmental samples (soil) were collected and analyzed. Samples were screened for resistance using three azole-containing agar plates; one without azole antifungal (growth control) and two supplemented with either itraconazole (4 mg/L) or voricona-zole (2 mg/L). The EUCAST susceptibility testing method was used to confirm the azole-resistant phenotype of A. fumigatus sensu-stricto isolates. Mutations in the cyp51A gene were determined by sequencing. Of the 120 samples, 51 positive samples showed growth of A. fumigatus isolates on control medium. One ARAF (2%; 1/51) isolate was found amongst A. fumigatus positive samples and harbored the F46Y/M172V/E427K cyp51A mutations. No TR34/L98H or TR46/Y121F/T289A mutations were observed. Our study described the first A. fumigatus isolate resistant to an azole antifun-gal in Burkina Faso., SCOPUS: ar.j, info:eu-repo/semantics/published

Spatial hotspots according to the transmission periods (as described in Table 1) year from 2010 to 01-04 to 2014-12-31. Source: Burkina Faso, Base Nationale de Découpage du territoire (BNDT, 2006); shapefile downloaded from www.maplibrary.org . The map background (raster) is captured from https://www.openstreetmap.org/#map=12/12.6228/-2.1622 . Maps created by Toussaint Rouamba, 2018. (PDF 931 kb)

With limited resources and spatio-temporal heterogeneity of malaria in developing countries, it is still difficult to assess the real impact of socioeconomic and environmental factors in order to set up targeted campaigns against malaria at an accurate scale. Our goal was to detect malaria hotspots in rural area and assess the extent to which household socioeconomic status and meteorological recordings may explain the occurrence and evolution of these hotspots., SCOPUS: ar.j, info:eu-repo/semantics/published

There is an alarming tide of cardiovascular and metabolic disease (CMD) sweeping across Africa. This may be a result of an increasingly urbanized lifestyle characterized by the growing consumption of processed and calorie-dense food, combined with physical inactivity and more sedentary behaviour. While the link between lifestyle and public health has been extensively studied in Caucasian and African American populations, few studies have been conducted in Africa. This paper describes the detailed methods for Phase 1 of the AWI-Gen study that were used to capture phenotype data and assess the associated risk factors and end points for CMD in persons over the age of 40 years in sub-Saharan Africa (SSA). We developed a population-based cross-sectional study of disease burden and phenotype in Africans, across six centres in SSA. These centres are in West Africa (Nanoro, Burkina Faso, and Navrongo, Ghana), in East Africa (Nairobi, Kenya) and in South Africa (Agincourt, Dikgale and Soweto). A total of 10,702 individuals between the ages of 40 and 60 years were recruited into the study across the six centres, plus an additional 1021 participants over the age of 60 years from the Agincourt centre. We collected socio-demographic, anthropometric, medical history, diet, physical activity, fat distribution and alcohol/tobacco consumption data from participants. Blood samples were collected for disease-related biomarker assays, and genomic DNA extraction for genome-wide association studies. Urine samples were collected to assess kidney function. The study provides base-line data for the development of a series of cohorts with a second wave of data collection in Phase 2 of the study. These data will provide valuable insights into the genetic and environmental influences on CMD on the African continent.

The global health transition is linked with an increased burden of non-communicable diseases with cardiovascular diseases leading the epidemic. In sub-Saharan Africa (SSA), the prevalence of obesity has increased during the past decades and there is a need to investigate the associated driving factors. In Burkina Faso obesity remains low, especially in rural areas. In this study we recruited middle-aged adults, as part of a larger study on genetic and environmental contributions to cardiometabolic disease among Africans., info:eu-repo/semantics/published

BACKGROUND: A major unresolved safety concern for malaria case management is the use of artemisinin combination therapies (ACTs) in the first trimester of pregnancy. There is a need for human data to inform policy makers and treatment guidelines on the safety of artemisinin combination therapies (ACT) when used during early pregnancy. METHODS: The overall goal of this paper is to describe the methods and implementation of a study aimed at developing surveillance systems for identifying exposures to antimalarials during early pregnancy and for monitoring pregnancy outcomes using health and demographic surveillance platforms. This was a multi-center prospective observational cohort study involving women at health and demographic surveillance sites in three countries in Africa: Burkina Faso, Kenya and Mozambique [(ClinicalTrials.gov Identifier: NCT01232530)]. The study was designed to identify pregnant women with artemisinin exposure in the first trimester and compare them to: 1) pregnant women without malaria, 2) pregnant women treated for malaria, but exposed to other antimalarials, and 3) pregnant women with malaria and treated with artemisinins in the 2nd or 3rd trimesters from the same settings. Pregnant women were recruited through community-based surveys and attendance at health facilities, including antenatal care clinics and followed until delivery. Data from the three sites will be pooled for analysis at the end of the study. Results are forthcoming. DISCUSSION: Despite few limitations, the methods described here are relevant to the development of sustainable pharmacovigilance systems for drugs used by pregnant women in the tropics using health and demographic surveillance sites to prospectively ascertain drug safety in early pregnancy. TRIAL REGISTRATION: NCT01232530.

Ultrasound Reference Manual for Pregnancy Dating. (PDF 3017 kb)

Newborn Examination. (PDF 1203 kb)

Background Bloodstream infections (BSI) caused by Salmonella Typhi and invasive non-Typhoidal Salmonella (iNTS) frequently affect children living in rural sub-Saharan Africa but data about incidence and serotype distribution are rare. Objective The present study assessed the population-based incidence of Salmonella BSI and severe malaria in a Health and Demographic Surveillance System in a rural area with seasonal malaria transmission in Nanoro, Burkina Faso. Methods Children between 2 months—15 years old with severe febrile illness were enrolled during a one-year surveillance period (May 2013—May 2014). Thick blood films and blood cultures were sampled and processed upon admission. Population-based incidences were corrected for non-referral, health seeking behavior, non-inclusion and blood culture sensitivity. Adjusted incidence rates were expressed per 100,000 person-years of observations (PYO). Results Among children < 5 years old, incidence rates for iNTS, Salmonella Typhi and severe malaria per 100,000 PYO were 4,138 (95% Confidence Interval (CI): 3,740–4,572), 224 (95% CI: 138–340) and 2,866 (95% CI: 2,538–3,233) respectively. Among those aged 5–15 years, corresponding incidence rates were 25 (95% CI: 8–60), 273 (95% CI: 203–355) and 135 (95% CI: 87–195) respectively. Most iNTS occurred during the peak of the rainy season and in parallel with the increase of Plasmodium falciparum malaria; for Salmonella Typhi no clear seasonal pattern was observed. Salmonella Typhi and iNTS accounted for 13.3% and 55.8% of all 118 BSI episodes; 71.6% of iNTS (48/67) isolates were Salmonella enterica serovar Typhimurium and 25.4% (17/67) Salmonella enterica serovar Enteritidis; there was no apparent geographical clustering. Conclusion The present findings from rural West-Africa confirm high incidences of Salmonella Typhi and iNTS, the latter with a seasonal and Plasmodium falciparum-related pattern. It urges prioritization of the development and implementation of Salmonella Typhi as well as iNTS vaccines in this setting.

Background Animal embryotoxicity data, and the scarcity of safety data in human pregnancies, have prevented artemisinin derivatives from being recommended for malaria treatment in the first trimester except in lifesaving circumstances. We conducted a meta-analysis of prospective observational studies comparing the risk of miscarriage, stillbirth, and major congenital anomaly (primary outcomes) among first-trimester pregnancies treated with artemisinin derivatives versus quinine or no antimalarial treatment. Methods and findings Electronic databases including Medline, Embase, and Malaria in Pregnancy Library were searched, and investigators contacted. Five studies involving 30,618 pregnancies were included; four from sub-Saharan Africa (n = 6,666 pregnancies, six sites) and one from Thailand (n = 23,952). Antimalarial exposures were ascertained by self-report or active detection and confirmed by prescriptions, clinic cards, and outpatient registers. Cox proportional hazards models, accounting for time under observation and gestational age at enrollment, were used to calculate hazard ratios. Individual participant data (IPD) meta-analysis was used to combine the African studies, and the results were then combined with those from Thailand using aggregated data meta-analysis with a random effects model. There was no difference in the risk of miscarriage associated with the use of artemisinins anytime during the first trimester (n = 37/671) compared with quinine (n = 96/945; adjusted hazard ratio [aHR] = 0.73 [95% CI 0.44, 1.21], I2 = 0%, p = 0.228), in the risk of stillbirth (artemisinins, n = 10/654; quinine, n = 11/615; aHR = 0.29 [95% CI 0.08–1.02], p = 0.053), or in the risk of miscarriage and stillbirth combined (pregnancy loss) (aHR = 0.58 [95% CI 0.36–1.02], p = 0.099). The corresponding risks of miscarriage, stillbirth, and pregnancy loss in a sensitivity analysis restricted to artemisinin exposures during the embryo sensitive period (6–12 wk gestation) were as follows: aHR = 1.04 (95% CI 0.54–2.01), I2 = 0%, p = 0.910; aHR = 0.73 (95% CI 0.26–2.06), p = 0.551; and aHR = 0.98 (95% CI 0.52–2.04), p = 0.603. The prevalence of major congenital anomalies was similar for first-trimester artemisinin (1.5% [95% CI 0.6%–3.5%]) and quinine exposures (1.2% [95% CI 0.6%–2.4%]). Key limitations of the study include the inability to control for confounding by indication in the African studies, the paucity of data on potential confounders, the limited statistical power to detect differences in congenital anomalies, and the lack of assessment of cardiovascular defects in newborns. Conclusions Compared to quinine, artemisinin treatment in the first trimester was not associated with an increased risk of miscarriage or stillbirth. While the data are limited, they indicate no difference in the prevalence of major congenital anomalies between treatment groups. The benefits of 3-d artemisinin combination therapy regimens to treat malaria in early pregnancy are likely to outweigh the adverse outcomes of partially treated malaria, which can occur with oral quinine because of the known poor adherence to 7-d regimens. Review registration PROSPERO CRD42015032371, In a meta-analysis using individual patient data from prospective observational studies, Andy Stergachis and colleagues investigate the risk of of miscarriage, stillbirth, and major congenital anomaly among pregnancies that were treated during the first trimester with artemisinin derivatives versus quinine or no antimalarial treatment., Author summary Why was this study done? Malaria infection is more frequent and severe in pregnant women compared to non-pregnant women, and the adverse consequences of malaria in pregnancy require prompt, safe, and effective treatment. Artemisinin combination therapies (ACTs), the most efficacious antimalarials available, are the recommended first-line treatment for Plasmodium falciparum malaria. Animal embryotoxicity data and the paucity of safety data in human pregnancies have prevented artemisinin derivatives from being recommended for malaria treatment in the first trimester except in life-saving circumstances, yet in malaria endemic countries, many early pregnancies are advertently or inadvertently exposed to ACTs. In this meta-analysis of prospective observational studies, we summarize all available safety data on the effect of artemisinin exposure in the first trimester and compare the risk of miscarriage, stillbirth, and major congenital anomaly for pregnancies treated with artemisinin, quinine, or no antimalarials in the first trimester. What did the researchers do and find? Our team determined the risk of miscarriages, stillbirths, and major congenital anomalies associated with first-trimester artemisinin treatment versus quinine in four independent prospective observational studies across six sites in sub-Saharan Africa using individual participant data meta-analysis. The results were then combined with summary effect estimates from the Shoklo Malaria Research Unit on the Thailand–Myanmar border using aggregated data meta-analysis. We found no difference in the risk of miscarriage, stillbirth, or major congenital anomalies associated with the use of artemisinins anytime during the first trimester compared with the use of quinine during the same gestational period. What do these findings mean? The ACT class of antimalarials should be considered for treatment of malaria in the first trimester of pregnancy. The limited data on the risk of congenital anomalies require further observational studies.