Schistosome infection among pregnant women in the rural highlands of Madagascar: A cross-sectional study calling for public health interventions in vulnerable populations.

INTRODUCTION: Schistosomiasis is a parasitic infection highly prevalent in sub-Saharan Africa (SSA) with Madagascar being among the countries with highest burden of the disease worldwide. Despite WHO recommendations, suggesting treatment of pregnant women after the first trimester, this group is still excluded from Mass Drug Administration programs. Our study, had the objective to measure the prevalence of schistosome infection among pregnant women in Madagascar in order to inform public health policies for treatment in this vulnerable population. METHODS: Women were recruited for this cross-sectional study between April 2019 and February 2020 when attending Antenatal Care Services (ANCs) at one of 42 included Primary Health Care Centers. The urine-based upconverting reporter particle, lateral flow (UCP-LF) test detecting circulating anodic antigen was used for the detection of schistosome infections. To identify factors associated with the prevalence of schistosome infection crude and adjusted prevalence ratios and 95% CIs were estimated using mixed-effect Poisson regression. RESULTS: Among 4,448 participating women aged between 16 and 47 years, the majority (70.4%, 38 n = 3,133) resided in rural settings. Overall, the prevalence of schistosome infection was 55.9% (n = 2486, CI 95%: 53.3-58.5). A statistically significant association was found with age group (increased prevalence in 31-47 years old, compared to 16-20 years old (aPR = 1.15, CI 95%: 1.02-1.29) and with uptake of antimalaria preventive treatment (decreased prevalence, aPR = 0.85, CI 95%: 0.77-0.95). No other associations of any personal characteristics or contextual factors with schistosome infection were found in our multivariate regression analysis. DISCUSSION AND CONCLUSION: The high prevalence of schistosome infection in pregnant women supports the consideration of preventive schistosomiasis treatment in ANCs of the Malagasy highlands. We strongly advocate for adapting schistosomiasis programs in highly endemic contexts. This, would contribute to both the WHO and SDGs agendas overall to improving the well-being of women and consequently breaking the vicious cycle of poverty perpetuated by schistosomiasis.

Sustained clinical benefit of malaria chemoprevention with sulfadoxine-pyrimethamine (SP) in pregnant women in a region with high SP resistance markers.

OBJECTIVE: The effectiveness of intermittent preventive treatment of malaria in pregnancy with sulfadoxine-pyrimethamine (IPTp-SP) is threatened by increasing SP-resistance in Africa. We assessed the level of SP-resistance markers, and the clinical and parasitological effectiveness of IPTp-SP in southern Mozambique. METHODS: P. falciparum infection, antimalarial antibodies and dhfr/dhps SP-resistance mutants were detected by quantitative polymerase chain reaction (qPCR), suspension array technology and targeted deep sequencing, respectively, among 4016 HIV-negative women in Maputo province (2016-2019). Univariate and multivariate regression models were used to assess the association between taking the recommended three or more IPTp-SP doses (IPTp3+) and parasitological and clinical outcomes. RESULTS: 84.3% (3385/4016) women received three or more IPTp-SP doses. The prevalence of quintuple mutants at first antenatal care (ANC) visit was 94.2%. IPTp3+ was associated with a higher clearance rate of qPCR-detected infections from first ANC visit to delivery (adjusted odds ratio [aOR]=5.9, 95% CI: 1.5-33.3; p = 0.012), lower seroprevalence at delivery of antibodies against the pregnancy-specific antigen VAR2CSADBL34 (aOR=0.72, 95% CI: 0.54-0.95; p = 0.022), and lower prevalence of low birth weight deliveries (aOR: 0.61, 95% CI: 0.41-0.90; p = 0.013). CONCLUSION: A sustained parasitological effect of IPTp-SP contributes to the clinical effectiveness of IPTp3+ in areas with high prevalence of SP-resistance markers.

Safety and efficacy of dihydroartemisinin-piperaquine for intermittent preventive treatment of malaria in pregnant women with HIV from Gabon and Mozambique: a randomised, double-blind, placebo-controlled trial.

BACKGROUND: The cornerstone of malaria prevention in pregnancy, intermittent preventive treatment (IPTp) with sulfadoxine-pyrimethamine, is contraindicated in women with HIV who are receiving co-trimoxazole prophylaxis. We assessed whether IPTp with dihydroartemisinin-piperaquine is safe and effective in reducing the risk of malaria infection in women with HIV receiving co-trimoxazole prophylaxis and antiretroviral drugs. METHODS: For this randomised, double-blind, placebo-controlled clinical trial, women with HIV attending the first antenatal care clinic visit, resident in the study area, and with a gestational age up to 28 weeks were enrolled at five sites in Gabon and Mozambique. Participants were randomly assigned (1:1) to receive either IPTp with dihydroartemisinin-piperaquine at each scheduled antenatal care visit plus daily co-trimoxazole (intervention group) or placebo at each scheduled antenatal care visit plus daily co-trimoxazole (control group). Randomisation was done centrally via block randomisation (block sizes of eight), stratified by country. IPTp was given over 3 days under direct observation by masked study personnel. The number of daily IPTp tablets was based on bodyweight and according to the treatment guidelines set by WHO (target dose of 4 mg/kg per day [range 2-10 mg/kg per day] of dihydroartemisinin and 18 mg/kg per day [range 16-27 mg/kg per day] of piperaquine given once a day for 3 days). At enrolment, all participants received co-trimoxazole (fixed combination drug containing 800 mg trimethoprim and 160 mg sulfamethoxazole) for daily intake. The primary study outcome was prevalence of peripheral parasitaemia detected by microscopy at delivery. The modified intention-to-treat population included all randomly assigned women who had data for the primary outcome. Secondary outcomes included frequency of adverse events, incidence of clinical malaria during pregnancy, and frequency of poor pregnancy outcomes. All study personnel, investigators, outcome assessors, data analysts, and participants were masked to treatment assignment. This study is registered with ClinicalTrials.gov, NCT03671109. FINDINGS: From Sept 18, 2019, to Nov 26, 2021, 666 women (mean age 28·5 years [SD 6·4]) were enrolled and randomly assigned to the intervention (n=332) and control (n=334) groups. 294 women in the intervention group and 308 women in the control group had peripheral blood samples taken at delivery and were included in the primary analysis. Peripheral parasitaemia at delivery was detected in one (<1%) of 294 women in the intervention group and none of 308 women in the control group. The incidence of clinical malaria during pregnancy was lower in the intervention group than in the control group (one episode in the intervention group vs six in the control group; relative risk [RR] 0·12, 95% CI 0·03-0·52, p=0·045). In a post-hoc analysis, the composite outcome of overall malaria infection (detected by any diagnostic test during pregnancy or delivery) was lower in the intervention group than in the control group (14 [5%] of 311 women vs 31 [10%] of 320 women; RR 0·48, 95% CI 0·27-0·84, p=0·010). The frequency of serious adverse events and poor pregnancy outcomes (such as miscarriages, stillbirths, premature births, and congenital malformations) did not differ between groups. The most frequently reported drug-related adverse events were gastrointestinal disorder (reported in less than 4% of participants) and headache (reported in less than 2% of participants), with no differences between study groups. INTERPRETATION: In the context of low malaria transmission, the addition of IPTp with dihydroartemisinin-piperaquine to co-trimoxazole prophylaxis in pregnant women with HIV did not reduce peripheral parasitaemia at delivery. However, the intervention was safe and associated with a decreased risk of clinical malaria and overall Plasmodium falciparum infection, so it should be considered as a strategy to protect pregnant women with HIV from malaria. FUNDING: European and Developing Countries Clinical Trials Partnership 2 (EDCTP2) and Medicines for Malaria Venture. TRANSLATIONS: For the Portuguese and French translations of the abstract see Supplementary Materials section.

Considerations in the management of ocular toxoplasmosis in pregnancy: a review of literature.

Ocular toxoplasmosis is the most common cause of infectious posterior uveitis. Available literature is still conflicting regarding the incidence of recurrence during pregnancy as various calculations were employed in the different published studies. Although earlier reports have suggested a difference in presentation and an increase in severity during pregnancy, newer studies appear to show otherwise. Further diagnostic testing, including serologic and intraocular fluid sampling, may be indicated to increase the diagnostic accuracy in this special population of patients. The management of ocular toxoplasmosis during pregnancy is challenging as the foetus is additionally considered in the choice of treatment. Traditionally preferred anti-toxoplasmosis regimens containing antifolate drugs, such as pyrimethamine and trimethoprim-sulfamethoxazole, cannot be used routinely in pregnant patients, especially during the first trimester. This review includes literature on alternative treatments for ocular toxoplasmosis during pregnancy, including spiramycin and intravitreal treatment options.

Uptake of intermittent preventive treatment of malaria in pregnancy and risk factors for maternal anaemia and low birthweight among HIV-negative mothers in Dschang, West region of Cameroon: a cross sectional study.

BACKGROUND: Approximately 32 million pregnant women are at risk of malaria with up to 10,000 maternal deaths and 200,000 neonates at risk annually. Intermittent Preventive Treatment (IPT) with sulfadoxine-pyrimethamine (SP) is recommended by the World Health Organization (WHO) to reduce disease in pregnancy and adverse maternal and newborn outcomes. At least three doses of SP should be taken by pregnant women during antenatal consultation (ANC) beginning from the thirteenth week of pregnancy till parturition. The aim of this study was to assess uptake of IPT during pregnancy and risk factors for maternal anaemia and infant birth weight in Dschang, West region of Cameroon. METHODS: A total of 380 consenting pregnant women at delivery were recruited in a cross- sectional prospective survey between January to December 2021. Data on ANC attendance, total dose of IPT and history of malaria were abstracted from hospital ANC records while socio-demographic characteristics, bed net use and obstetrics history of each participant were also recorded through an interview. Further, blood samples were collected from the intervillous space for assessment of maternal anaemia and microscopic parasitology. Nested PCR based on amplification of the Plasmodium 18S sRNA was carried out to detect submicroscopic infection. IPTp coverage was calculated per WHO recommendation and the prevalence of anaemia and low birth weight were estimated as proportions in the total sample of pregnant women and live births, respectively. Crude and adjusted odds ratios and their 95% confidence intervals were used to estimate associations between pregnancy outcomes considered and risk factors in specific and general models. A p < 0.05 was considered significant. The R software (V4.1.4) was used for all analyses. RESULTS: A majority of pregnant women was aged between 24 and 34 years old (59.2%) and had secondary education (58.8%). Uptake of ≥ 3 IPTp was 64.99% with 77.20% of all who received at least one IPTp doses taking a mix of SP and DP or DP alone in successive ANC contacts. Those with four or more ANC contacts (73.42%) were more likely to have received at least one IPTp. Furthermore, 13.9% of live births had low birthweights (BW < 2500 g) and one in four parturient women with moderate anaemia by WHO criteria. Microscopy (blood smear examination) and PCR-based diagnosis revealed between 0% and 1.57% of parasite-infected placental samples, respectively. Reported malaria in pregnancy predicted maternal anaemia at birth but not birth weight. Only gestational age (< 37 weeks) and bed net use (< 5 months) significantly predicted infant birth weight at delivery. CONCLUSION: The uptake of WHO recommended IPT doses during pregnancy was moderately high. Reported malaria in pregnancy, poor bed net coverage, gestational age less than 37 weeks adversely affect maternal haemoglobin levels at birth and infant birth weight. Asymptomatic and submicroscopic placental parasite infections was found at low prevalence. Together these results highlight the importance of maintaining aggressive measures to prevent malaria in pregnancy and protect the health of mother and baby.

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

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

Gestational toxoplasmosis treatment changes the child's prognosis: A cohort study in southern Brazil.

BACKGROUND: We evaluate the drug treatment for pregnant women with acute toxoplasmosis to reduce the risk of congenital infection, side effects (prenatal and postnatal treatment in children) and the hazard of discontinuing the infant's medication. METHODS: We conducted a prospective cohort study to assess the risks of congenital toxoplasmosis among children born to acutely infected women with and without treatment. We examined the relationship between "exposed" and "infected children", "number of infant neutrophils", "prenatal" and "postnatal treatment". Factor analysis of mixed data (FAMD) was used to analyze the data. All children started treatment at the hospital. FINDINGS: Between 2017 and 2021, 233 pregnant women were evaluated at the University Hospital of Maringá; ninety-four met criteria for acute gestational toxoplasmosis. We followed up 61 children; eleven (18%) had the infection confirmed and 50 (82%) were free of toxoplasmosis (exposed). Children born to untreated mothers have 6.5-times higher risk of being infected; the transmission rate among untreated mothers was 50% versus 8.3% among treated ones. Three decreasing values of immunoglobulin G were a security parameter for stopping the child's medication in the exposed group (50/61). Neutropenia was the leading side effect among children and the infected had a 2.7 times higher risk. There was no correlation between maternal use of pyrimethamine and children's neutropenia. INTERPRETATION: The follow-up of women with acute T. gondii infection and their children, through a multidisciplinary team, availability of anti-T. gondii serology and pre- and post-natal treatments reduced the risk of toxoplasmosis transmission.

Malaria and Pregnancy.

Recent identification of local mosquito-borne transmission of malaria in Florida, Texas, and Maryland and increasing travel to malaria-endemic countries raise the likelihood that U.S. obstetricians might encounter a pregnant patient with malaria. Pregnancy increases the risk of becoming infected with malaria and of developing severe disease. Malaria during pregnancy also increases the risk of adverse pregnancy outcomes, including low birth weight, pregnancy loss, and preterm birth; thus, prevention and prompt diagnosis and treatment are essential. Diagnosis can be challenging during pregnancy among persons with partial immunity because placental sequestration of parasite-infected red blood cells can result in lower parasite levels in peripheral blood. Treatment for uncomplicated malaria depends on the expected resistance pattern, which is determined by the specific Plasmodium species identified and where infection was acquired. For severe disease, parenteral artesunate treatment needs to be initiated immediately. Given the dire consequences of malaria in pregnancy, prevention is crucial. For persons born and raised in endemic areas, interventions include use of insecticide-treated bed nets, intermittent preventive treatment, and prompt diagnosis and treatment of illness. U.S. pregnant persons should avoid travel to endemic countries; for unavoidable travel, pregnant travelers should receive chemoprophylaxis and avoid mosquito bites. Although the risk is low to U.S. pregnant persons who are not traveling internationally, avoiding mosquito bites is important, especially for pregnant persons residing in or visiting areas with recent local mosquito-borne transmission.

Uptake of four or more doses of sulfadoxine pyrimethamine for intermittent preventive treatment of malaria during pregnancy in Zambia: findings from the 2018 malaria in pregnancy survey.

OBJECTIVE: To determine the prevalence and predictors of the uptake of four or more doses of sulfadoxine pyrimethamine (IPTp-SP 4+) in Zambia. DESIGN: A cross-sectional study using secondary data from the malaria in pregnancy survey (Malaria Indicator Survey) data set conducted from April to May 2018. SETTING: The primary survey was conducted at community level and covered all the 10 provinces of Zambia. PARTICIPANTS: A total of 3686 women of reproductive age (15-45 years) who gave birth within the 5 years before the survey. PRIMARY OUTCOME: Proportion of participants with four or more doses of IPTp-SP. STATISTICAL ANALYSIS: All analyses were conducted using RStudio statistical software V.4.2.1. Descriptive statistics were computed to summarise participant characteristics and IPTp-SP uptake. Univariate logistic regression was carried out to determine association between the explanatory and outcome variables. Explanatory variables with a p value less than 0.20 on univariate analysis were included in the multivariable logistic regression model and crude and adjusted ORs (aORs) along with their 95% CIs were computed (p<0.05). RESULTS: Of the total sample of 1163, only 7.5% of participants received IPTp-SP 4+. Province of residence and wealth tertile were associated with uptake of IPTp-SP doses; participants from Luapula (aOR=8.72, 95% CI (1.72 to 44.26, p=0.009)) and Muchinga (aOR=6.67, 95% CI (1.19 to 37.47, p=0.031)) provinces were more likely to receive IPTp-SP 4+ compared with to those from Copperbelt province. Conversely, women in the highest wealth tertile were less likely to receive IPTp-SP 4+ doses compared with those in the lowest quintile (aOR=0.32; 95% CI (0.13 to 0.79, p=0.014)). CONCLUSION: These findings confirm a low uptake of four or more doses of IPTp-SP in the country. Strategies should focus on increased coverage of IPTp-SP in provinces with much higher malaria burden where the risk is greatest and the ability to afford healthcare lowest.

Antenatal care and adherence to intermittent preventive treatment for malaria during pregnancy with sulfadoxine-pyrimethamine in Gambia: an examination of Demographic and Health Survey data 2019-2020.

BACKGROUND: Malaria during pregnancy is a major contributor to maternal and infant morbidity and mortality in Gambia. The World Health Organization recommends that women adhere to intermittent preventive treatment with sulfadoxine-pyrimethamine (SP-IPTp) provided through antenatal care (ANC) to prevent adverse outcomes. The aim of this study was to examine predictors of SP-IPTp adherence among women in Gambia. METHODS: Data analysis was conducted using the 2019-2020 Women's Health Survey from the Gambia Demographic and Health Survey dataset. χ2 tests and multivariate logistic regression were employed to assess the influence of ANC and sociodemographic characteristics on SP-IPTp adherence. RESULTS: Among 5381 women, less than half (47.3%) achieved adherence (three or more doses) to SP-IPTp. More than three-quarters (79.7%) attended four or more ANC visits. Women who attended four ANC visits were twice as likely to adhere to SP-IPTp than women who attended none to three ANC visits (adjusted odds ratio 2.042 [95% confidence interval 1.611 to 2.590]). CONCLUSIONS: Attending four or more and earlier initiation of ANC visits may be related to improved SP-IPTp adherence. Additional research is needed to assess structural and healthcare system components that influence SP-IPTp adherence.

Podcast POEMs (BVS APS): Desvermifugação em massa com anti-helmínticos na gestação e tipos de coorte

No nono episódio do Podcast POEMs da BVS APS vou apresentar os resultados de uma revisão sistemática da Cochrane, publicada em maio de 2021, atualizando uma outra feita em 2015, demonstrando os resultados do uso de anti-helmínticos em massa para gestantes, a fim de proteger contra infecções oriundas deste verme pelo solo. Também vou aproveitar e comentar um pouco sobre como uma coorte pode ser criada e pensada, em termos de temporalidade. Será que toda coorte é prospectiva?

The impact of community delivery of intermittent preventive treatment of malaria in pregnancy on its coverage in four sub-Saharan African countries (Democratic Republic of the Congo, Madagascar, Mozambique, and Nigeria): a quasi-experimental multicentre evaluation.

BACKGROUND: Intermittent preventive treatment of malaria in pregnancy (IPTp) with sulfadoxine-pyrimethamine is recommended at each antenatal care clinic visit in high-moderate transmission areas. However, its coverage remains unacceptably low in many countries. Community health workers can effectively deliver malaria preventive interventions. The aim of this study was to assess the effect of community delivery of IPTp (C-IPTp) on antenatal care and IPTp coverage. METHODS: A community-based IPTp administration approach was implemented in four sub-Saharan countries: the Democratic Republic of the Congo (DR Congo), Madagascar, Mozambique, and Nigeria. A quasi-experimental before and after evaluation by cluster sampling was designed where C-IPTp was implemented in selected country areas in different phases. Baseline (before C-IPTp implementation), midline, and endline household surveys were carried out to assess IPTp intake in pregnant women in 2018, 2019, and 2021. Eligible participants of the household survey were women of reproductive age (13-50 years old, depending on the country) that had a pregnancy that ended (any pregnancy regardless of pregnancy outcome) in the 6 months before the interview. For the first baseline surveys, the target population was women who had a pregnancy that ended in the 12 months before the interview. The primary outcome from the household surveys was the proportion of women who reported having received at least three doses of IPTp during pregnancy. The trial is registered at ClinicalTrials.gov, NCT03600844. FINDINGS: A total of 32 household surveys were conducted between March 15, and Oct 30, 2018, and data from 18 215 interviewed women were analysed. The coverage of at least three doses of IPTp (IPTp3+) increased after the first year of C-IPTp implementation in all project areas in DR Congo (from 22·5% [170/755] to 31·8% [507/1596]), Madagascar (from 17·7% [101/572] to 40·8% [573/1404]), and Nigeria (from 12·7% [130/1027] to 35·2% [423/1203]), with increases between 145·6% (Madagascar) and 506·6% (Nigeria). IPTp3+ coverage increased between baseline and endline in all districts, except for Murrupula (Mozambique) and ranged between 9·6% and 533·6%. This pattern was similar in DR Congo, Madagascar, and Nigeria, and in Mozambique, the increase was lower than the other countries. Antenatal care attendance did not change or increased lightly in all study countries. INTERPRETATION: C-IPTp was associated with an increase in IPTp uptake without reducing antenatal care attendance. The strategy might be considered for malaria control in pregnancy. FUNDING: UNITAID [2017-13-TIPTOP].

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.

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.

Status of malaria in pregnancy services in Madagascar 2010-2021: a scoping review.

BACKGROUND: Malaria in pregnancy (MIP) increases the risk of poor maternal and infant outcomes. To reduce these risks, WHO recommends insecticide-treated net (ITN) use, intermittent preventive treatment during pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP), and prompt case management. However, uptake of these interventions remains sub-optimal in Madagascar. A scoping review was conducted to determine the breadth and depth of information available during 2010-2021 about Madagascar's MIP activities and to identify barriers and facilitators to MIP interventions uptake. METHODS: PubMed, Google Scholar, and USAID's files (Development Experience Catalog) were searched using the terms "Madagascar AND pregnancy AND malaria," and reports and materials from stakeholders were collected. Documents in English and French from 2010 to 2021 with data regarding MIP were included. Documents were systematically reviewed and summarized; results were captured in an Excel database. RESULTS: Of 91 project reports, surveys and published articles, 23 (25%) fell within the stated time period and contained relevant data on MIP activities in Madagascar and were categorized accordingly: eight (35%) quality of care, including health facility readiness, provider knowledge and commodity availability; nine (39%) care-seeking behaviour; and, six (26%) prevention of MIP. Key barriers were identified: nine articles mentioned SP stockouts; seven found limitations of provider knowledge, attitudes, and behaviours (KAB) regarding MIP treatment and prevention; and, one reported limited supervision. MIP care seeking and prevention barriers and facilitators included women's KAB regarding MIP treatment and prevention, distance, wait times, poor service quality, cost, and/or unwelcoming providers. A 2015 survey of 52 health facilities revealed limited client access to antenatal care due to financial and geographic barriers; two 2018 surveys revealed similar findings. Self-treatment and care-seeking delays were reported even when distance was not a barrier. CONCLUSION: Among the studies and reports on MIP in Madagascar, the scoping review frequently noted barriers that could be mitigated by reducing stockouts, improving provider knowledge and attitudes, refining MIP communication, and improving service access. There is a need for coordinated efforts to address the identified barriers is the key implication of the findings.

Impact of Intermittent Presumptive Treatment for Malaria in Pregnancy on Hospital Birth Outcomes on the Kenyan Coast.

BACKGROUND: Intermittent preventive treatment (IPTp) for pregnant women with sulfadoxine-pyrimethamine (SP) is widely implemented for the prevention of malaria in pregnancy and adverse birth outcomes. The efficacy of SP is declining, and there are concerns that IPTp may have reduced impact in areas of high resistance. We sought to determine the protection afforded by SP as part of IPTp against adverse birth outcomes in an area with high levels of SP resistance on the Kenyan coast. METHODS: A secondary analysis of surveillance data on deliveries at the Kilifi County Hospital between 2015 and 2021 was undertaken in an area of low malaria transmission and high parasite mutations associated with SP resistance. A multivariable logistic regression model was developed to estimate the effect of SP doses on the risk of low birthweight (LBW) deliveries and stillbirths. RESULTS: Among 27 786 deliveries, 3 or more doses of IPTp-SP were associated with a 27% reduction in the risk of LBW (adjusted odds ratio [aOR], 0.73; 95% confidence interval [CI], .64-.83; P < .001) compared with no dose. A dose-response association was observed with increasing doses of SP from the second trimester linked to increasing protection against LBW deliveries. Three or more doses of IPTp-SP were also associated with a 21% reduction in stillbirth deliveries (aOR, 0.79; 95% CI, .65-.97; P = .044) compared with women who did not take any dose of IPTp-SP. CONCLUSIONS: The continued significant association of SP on LBW deliveries suggests that the intervention may have a non-malaria impact on pregnancy outcomes.

Strengthening the capacity of healthcare providers to administer intermittent preventive therapy for malaria in pregnancy in Nigeria using a quality improvement strategy.

BACKGROUND: Intermittent Preventive Therapy using Sulfadoxine Pyrimethamine (IPTp-SP) is a malaria control strategy to reduce cases of malaria in pregnancy in endemic countries. However, the administration of the recommended three doses of Intermittent Preventive Therapy (IPTp) throughout the stages of pregnancy still remains low in Nigeria. Limited knowledge by health workers on the administration of the recommended doses of IPTp to pregnant women receiving antenatal care (ANC) services is partly responsible for this gap. This study applied Quality Improvement (QI) approach to improve knowledge and practice among healthcare providers with respect to the administration of IPTp-SP. METHODS: A quasi-experimental study design was carried out to evaluate the effect of QI approach consisting of training and coaching of healthcare providers to improve the administration of IPTp during ANC services. Primary Healthcare Centre Samaru was purposively selected and 11 healthcare providers participated in the study. The total duration of the intervention was for a period of 4 weeks which comprises of four training sessions conducted over a period of 2 weeks and four coaching sessions conducted for a period of another 2 weeks. The training package involved the use of the Information, Education and Communication approach of healthcare providers on IPTp administration while the coaching package involved supervision and follow-up meetings guiding healthcare providers on the protocol of IPTp administration. Antenatal care daily register was reviewed pre-intervention, intervention and post-intervention period of the study. Data were analysed using line graphs and run charts. RESULTS: A total of 36 ANC visit weeks were observed between 21 November 2016 and 27 July 2017. There was overestimation of first dose of IPTp (IPTp1) as 8 of the 16 Weeks in the pre-intervention period had more than 100% of eligible women administered IPTp1. There was evidence indicating the process of IPTp1 was relatively stable post-intervention as the data crosses the median line only six times that is, 7 runs. This indicates that the process of IPTp1 was within normal variation over the post-intervention period. The patterns of IPTp2+ administrations shows the levels of IPTp2+ administration were erratic. There was an upward shift showing immediate improvement of the administration of IPTp2+ post-intervention. CONCLUSIONS: The integrated training and coaching intervention approach improved the administration of the recommended three doses of IPTp within the context of a Primary Healthcare Centre. The data quality of the ANC daily register improved post-intervention.

Intermittent preventive treatment with Sulfadoxine pyrimethamine for malaria: a global overview and challenges affecting optimal drug uptake in pregnant women.

Malaria in Pregnancy (MiP) leading to morbidity and mortality is a major public health problem that poses significant risk to pregnant women and their fetus. To cope with this alarming situation, administration of Sulfadoxine-pyrimethamine (SP) drugs to pregnant women as an intermittent preventive treatment (IPT) from 16 weeks of gestation is recommended by the World Health Organization (WHO) guidelines. We conducted a comprehensive search of published articles related to MiP in last 10 years with predefined keywords or their synonyms. The mapping of malaria in pregnant women showed a prevalence rate up to 35% in many countries. Although IPTp-SP has been implemented in endemic regions since several years but the IPTp-SP coverage percentage vary from country to country and continue to remain below the target of 80%. Major reasons for low IPTp-SP involve gestational age at first prenatal visit, level of education, place of residence, knowledge of IPTp-SP benefits, and use of antenatal services. Several challenges including the emergence of septuple and octuple SP-resistant parasites is reported from many countries which make the prophylactic use of IPTp-SP currently debatable. This narrative review addresses the barriers for optimal use of IPTp-SP and discusses alternative approaches to increase the use and effectiveness of SP intervention for preventing MiP. The COVID pandemic has drastically affected the public health disrupting the management of diseases worldwide. In view of this, a brief summary of COVID impact on MiP situation is also included.

Determinants of utilization of malaria preventive measures during pregnancy among women aged 15 to 49 years in Kenya: an analysis of the Malaria Indicator Survey 2020.

BACKGROUND: Malaria is a significant cause of morbidity and mortality. Malaria infection in pregnancy can have severe consequences for the fetus and the mother. To fight against malaria infection in pregnancy, Kenya integrated the issuance of an insecticide-treated net (ITN) and intermittent preventive treatment with sulfadoxine-pyrimethamine (IPTpSP) with antenatal care (ANC) for pregnant women. However, the uptake of the ITN and IPTpSP is still low. Individual, social, or structural factors may influence the low uptake. It is, therefore, important to identify the determinants associated with the uptake of ITN and IPTpSP during pregnancy in Kenya. METHODS: Data were from the 2020 Kenya Malaria Indicator Survey (MIS). A total of 1779 women between the ages of 15 to 49 years who had a history of either being pregnant or having given birth within 5 years before the MIS survey were included. Survey-adjusted multinomial logistic regression was used in the analysis. RESULTS: During pregnancy, ITN use was more than half (54.9%). The use of at least one dose of IPTpSP was 43.5%, three or more doses of IPTpSP was 27.2%, and only 28.2% of the participants used both ITN and IPTpSP during pregnancy. The significant determinants of combined use of ITN and IPTpSP during pregnancy were maternal age (RR 3.57, CI 1.80-7.08; p=<0.001), maternal education (RRR 2.84, CI 1.33-6.06; p=0.007), wealth index (RR 2.14, CI 1.19-3.84; p=0.011) and living in the different malaria epidemiological zones: lake endemic (RRR 10.57 CI 5.65-19.76; p=<0.001), coastal endemic area (RRR 4.86 CI 1.86-12.67; p=0.001), seasonal (RRR 0.21 CI 0.10-0.39; p=<0.001) and low risk (RRR 0.07, CI 0.03-0.17; p=<0.001). CONCLUSION: The uptake of malaria preventive measures is still below 80% for both ITN and IPTpSP during pregnancy in Kenya. The significant results on determinants of the use of ITN and IPTpSP could be considered in implementing malaria prevention programmes during pregnancy. For example, sensitizing the community on the importance of antenatal care visits will provide a platform to teach the importance of malaria prevention in pregnancy. Moreover, the pregnant mothers receive an ITN and IPTpSP during the ANC visit.

Factors influencing intermittent preventive treatment for malaria prevention among pregnant women accessing antenatal care in selected primary health care facilities of Bwari Area Council, Abuja Nigeria.

BACKGROUND: Although studies in Nigeria showed the efficacy of intermittent preventive treatment using sulfadoxine-pyrimethamine (IPT-SP) in preventing malaria in pregnancy among Nigerian women there is still poor implementation of the intervention in Nigeria. METHODS: A mixed method study was conducted in Bwari Area Council, Nigeria in 2018. The quantitative part of the study is presented and discussed in this paper. Pregnant women were interviewed using a validated interviewer-administered questionnaire and observations of current practice were performed. RESULTS: A total of 422 pregnant women were recruited into the study (mean age, 26 years) with the majority being married women (90.3%). Most respondents (68.5%) did not know who could take IPT-SP and 58.5% of respondents did not know when and how many times IPT-SP should be taken during pregnancy. Nearly all participants (99.5%) did not take SP at the facility under direct observation of the health worker. None of the facilities had free SP and all respondents paid for SP through the Drug Revolving Fund. The knowledge of the use of SP was significantly influenced by respondents' parity, ward of residence, antenatal clinic (ANC) attendance history and education. Respondents who had tertiary and secondary education were 8.3 (95% CI: 1.01-68.27) times more likely to use IPT-SP than those without formal education. CONCLUSION: Most women who attend ANC in Bwari Area council did not receive IPT-SP as per the national guidelines. The unavailability of logistics (SP, Water and Cup) on a regular basis, the cost of the SP, poor knowledge of the importance of IPT in malaria prevention, and the non-implementation of the administration of SP under direct observation were factors influencing the use of IPT-SP. Outcomes could be enhanced through the provision of measures to address identified gaps by this study.