Pregnancy outcomes after first-trimester treatment with artemisinin derivatives versus non-artemisinin antimalarials: a systematic review and individual patient data meta-analysis.

BACKGROUND: Malaria in the first trimester of pregnancy is associated with adverse pregnancy outcomes. Artemisinin-based combination therapies (ACTs) are a highly effective, first-line treatment for uncomplicated Plasmodium falciparum malaria, except in the first trimester of pregnancy, when quinine with clindamycin is recommended due to concerns about the potential embryotoxicity of artemisinins. We compared adverse pregnancy outcomes after artemisinin-based treatment (ABT) versus non-ABTs in the first trimester of pregnancy. METHODS: For this systematic review and individual patient data (IPD) meta-analysis, we searched MEDLINE, Embase, and the Malaria in Pregnancy Library for prospective cohort studies published between Nov 1, 2015, and Dec 21, 2021, containing data on outcomes of pregnancies exposed to ABT and non-ABT in the first trimester. The results of this search were added to those of a previous systematic review that included publications published up until November, 2015. We included pregnancies enrolled before the pregnancy outcome was known. We excluded pregnancies with missing estimated gestational age or exposure information, multiple gestation pregnancies, and if the fetus was confirmed to be unviable before antimalarial treatment. The primary endpoint was adverse pregnancy outcome, defined as a composite of either miscarriage, stillbirth, or major congenital anomalies. A one-stage IPD meta-analysis was done by use of shared-frailty Cox models. This study is registered with PROSPERO, number CRD42015032371. FINDINGS: We identified seven eligible studies that included 12 cohorts. All 12 cohorts contributed IPD, including 34 178 pregnancies, 737 with confirmed first-trimester exposure to ABTs and 1076 with confirmed first-trimester exposure to non-ABTs. Adverse pregnancy outcomes occurred in 42 (5·7%) of 736 ABT-exposed pregnancies compared with 96 (8·9%) of 1074 non-ABT-exposed pregnancies in the first trimester (adjusted hazard ratio [aHR] 0·71, 95% CI 0·49-1·03). Similar results were seen for the individual components of miscarriage (aHR=0·74, 0·47-1·17), stillbirth (aHR=0·71, 0·32-1·57), and major congenital anomalies (aHR=0·60, 0·13-2·87). The risk of adverse pregnancy outcomes was lower with artemether-lumefantrine than with oral quinine in the first trimester of pregnancy (25 [4·8%] of 524 vs 84 [9·2%] of 915; aHR 0·58, 0·36-0·92). INTERPRETATION: We found no evidence of embryotoxicity or teratogenicity based on the risk of miscarriage, stillbirth, or major congenital anomalies associated with ABT during the first trimester of pregnancy. Given that treatment with artemether-lumefantrine was associated with fewer adverse pregnancy outcomes than quinine, and because of the known superior tolerability and antimalarial effectiveness of ACTs, artemether-lumefantrine should be considered the preferred treatment for uncomplicated P falciparum malaria in the first trimester. If artemether-lumefantrine is unavailable, other ACTs (except artesunate-sulfadoxine-pyrimethamine) should be preferred to quinine. Continued active pharmacovigilance is warranted. FUNDING: Medicines for Malaria Venture, WHO, and the Worldwide Antimalarial Resistance Network funded by the Bill & Melinda Gates Foundation.

Multi-country collaborative citizen science projects to co-design cardiovascular disease prevention strategies and advocacy: findings from Ethiopia, Malawi, Rwanda, and South Africa.

BACKGROUND: Cardiovascular diseases (CVD) were responsible for 20.5 million annual deaths globally in 2021, with a disproportionally high burden in sub-Saharan Africa (SSA). There is growing evidence of the use of citizen science and co-design approaches in developing interventions in different fields, but less so in the context of CVD prevention interventions in SSA. This paper reports on the collaborative multi-country project that employed citizen science and a co-design approach to (i) explore CVD risk perceptions, (ii) develop tailored prevention strategies, and (iii) support advocacy in different low-income settings in SSA. METHODS: This is a participatory citizen science study with a co-design component. Data was collected from 205 participants aged 18 to 75 years in rural and urban communities in Malawi, Ethiopia and Rwanda, and urban South Africa. Fifty-one trained citizen scientists used a mobile app-based (EpiCollect) semi-structured survey questionnaire to collect data on CVD risk perceptions from participants purposively selected from two communities per country. Data collected per community included 100-150 photographs and 150-240 voice recordings on CVD risk perceptions, communication and health-seeking intentions. Thematic and comparative analysis were undertaken with the citizen scientists and the results were used to support citizen scientists-led stakeholder advocacy workshops. Findings are presented using bubble graphs based on weighted proportions of key risk factors indicated. RESULTS: Nearly three in every five of the participants interviewed reported having a relative with CVD. The main perceived causes of CVD in all communities were substance use, food-related factors, and litter, followed by physical inactivity, emotional factors, poverty, crime, and violence. The perceived positive factors for cardiovascular health were nutrition, physical activity, green space, and clean/peaceful communities. Multi-level stakeholders (45-84 persons/country) including key decision makers participated in advocacy workshops and supported the identification and prioritization of community-specific CVD prevention strategies and implementation actions. Citizen science-informed CVD risk screening and referral to care interventions were piloted in six communities in three countries with about 4795 adults screened and those at risk referred for care. Health sector stakeholders indicated their support for utilising a citizen-engaged approach in national NCDs prevention programmes. The citizen scientists were excited by the opportunity to lead research and advocacy. CONCLUSION: The collaborative engagement, participatory learning, and co-designing activities enhanced active engagement between citizen scientists, researchers, and stakeholders. This, in turn, provided context-specific insights on CVD prevention in the different SSA settings.

Perceived cardiovascular disease risk and tailored communication strategies among rural and urban community dwellers in Rwanda: a qualitative study.

BACKGROUND: In Rwanda, cardiovascular diseases (CVDs) are the third leading cause of death, and hence constitute an important public health issue. Worldwide, most CVDs are due to lifestyle and preventable risk factors. Prevention interventions are based on risk factors for CVD risk, yet the outcome of such interventions might be limited by the lack of awareness or misconception of CVD risk. This study aimed to explore how rural and urban population groups in Rwanda perceive CVD risk and tailor communication strategies for estimated total cardiovascular risk. METHODS: An exploratory qualitative study design was applied using focus group discussions to collect data from rural and urban community dwellers. In total, 65 community members took part in this study. Thematic analysis with Atlas ti 7.5.18 was used and the main findings for each theme were reported as a narrative summary. RESULTS: Participants thought that CVD risk is due to either financial stress, psychosocial stress, substance abuse, noise pollution, unhealthy diets, diabetes or overworking. Participants did not understand CVD risk presented in a quantitative format, but preferred qualitative formats or colours to represent low, moderate and high CVD risk through in-person communication. Participants preferred to be screened for CVD risk by community health workers using mobile health technology. CONCLUSION: Rural and urban community members in Rwanda are aware of what could potentially put them at CVD risk in their respective local communities. Community health workers are preferred by local communities for CVD risk screening. Quantitative formats to present the total CVD risk appear inappropriate to the Rwandan population and qualitative formats are therefore advisable. Thus, operational research on the use of qualitative formats to communicate CVD risk is recommended to improve decision-making on CVD risk communication in the context of Rwanda.

Assessing the association between periodontitis and premature birth: a case-control study.

BACKGROUND: Premature delivery is among the leading causes of perinatal mortality and morbidity in developed societies, which is an important obstetrics problem. Maternal periodontitis is a prevalent condition that has been suspected to be associated with adverse pregnancy outcomes such as premature birth. However, there are still conflicting results about this possible relationship, therefore this study was designed to test the association between maternal periodontitis and premature birth. This study also provides information about a new screening tool recommended for use by nurses and midwives to screen for periodontal diseases during antenatal consultations in order to improve the health of mothers and children. METHODS: A retrospective case-control study was conducted at 12 health facilities in the Southern Province of Rwanda from February to August, 2018. A total of 555 women in the postpartum period were enrolled in the study. Cases and controls were enrolled in a ratio of 1:2; each enrolled case of preterm birth was followed by 2 unmatched control subjects that were next on the register and who delivered at term gestation. A total of 185 cases of preterm deliveries and 370 controls of term delivery were enrolled in the study. Multivariate regression analysis was used and the independent variables were hierarchically entered in three groups: The first group involved demographic variables that were put in the regression model as Step 1. The second group was made up of other potential risk factors that were placed in the regression model as the second step. Periodontitis was entered in the final regression step, as it was hypothesized as the main predictor variable. RESULTS: A statistically significant association was found between periodontitis and premature birth. Women who had periodontitis had 6 times the odds of giving birth to premature birth infants compared to women who had no periodontitis (OR: 6.360, 95% CI 3.9, 10.4). CONCLUSION: The study results indicate that periodontitis is strongly associated with premature birth. Preventive solutions including the use of a periodontitis screening tool for nurses and midwives during antenatal care consultations, are highly recommended.

Maternal genitourinary infections and poor nutritional status increase risk of preterm birth in Gasabo District, Rwanda: a prospective, longitudinal, cohort study.

BACKGROUND: Preterm birth (PTB) is a leading cause of early childhood mortality and morbidity, including long-term physical and mental impairment. The risk factors for PTB are complex and include maternal nutritional status and infections. This study aimed to identify potentially modifiable risk factors for targeted interventions to reduce the occurrence of PTB in Rwanda. METHODS: We conducted a prospective, longitudinal cohort study of healthy pregnant women aged 18 to 49 years. Women at 9-15 gestational weeks were recruited from 10 health centers in Gasabo District, Kigali Province between September and October 2017. Pregnancy age was estimated using ultrasonography and date of last menstruation. Anthropometric and laboratory measurements were performed using standard procedures for both mothers and newborns. Surveys were administered to assess demographic and health histories. Categorical and continuous variables were depicted as proportions and means, respectively. Variables with p <  0.25 in bivariate analyses were included in multivariable logistic regression models to determine independent predictors of PTB. The results were reported as odds ratios (ORs) and 95% confidence intervals (CI), with statistical significance set at p <  0.05. RESULTS: Among 367 participants who delivered at a mean of 38.0 ± 2.2 gestational weeks, the overall PTB rate was 10.1%. After adjusting for potential confounders, we identified the following independent risk factors for PTB: anemia (hemoglobin < 11 g/dl) (OR: 4.27; 95%CI: 1.85-9.85), urinary tract infection (UTI) (OR:9.82; 95%CI: 3.88-24.83), chlamydia infection (OR: 2.79; 95%CI: 1.17-6.63), inadequate minimum dietary diversity for women (MDD-W) score (OR:3.94; CI: 1.57-9.91) and low mid-upper arm circumference (MUAC) < 23 cm (OR: 3.12, 95%CI; 1.31-7.43). indicators of nutritional inadequacy (low MDD-W and MUAC) predicted risk for low birth weight (LBW) but only UTI was associated with LBW in contrast with PTB. CONCLUSION: Targeted interventions are needed to improve the nutritional status of pregnant women, such as maternal education on dietary diversity and prevention of anemia pre-pregnancy. Additionally, prevention and treatment of maternal infections, especially sexually transmitted infections and UTIs should be reinforced during standard antenatal care screening which currently only includes HIV and syphilis testing.

Association between micronutrients and maternal leukocyte telomere length in early pregnancy in Rwanda.

BACKGROUND: Exposure to environmental stressors can lead to shorter leukocyte telomere length and increase the risk of chronic diseases. Preservation of leukocyte telomere length by reducing oxidative stress exposure and reinforcing immunity may be a mechanism by which nutritional factors delay or prevent chronic disease development. METHODS: Healthy pregnant women (aged 18-45 years) at 9-15 weeks of gestation living in Gasabo District, Kigali, Rwanda, were recruited from 10 health centers for a prospective, longitudinal study from September to October 2017 to determine possible associations between nutrition health, infectious disease and leukocyte telomere length. Anthropometric and laboratory measurements were performed using standard procedures; sociodemographic parameters and health histories were assessed via surveys, and leukocyte telomere length was assessed using quantitative PCR expressed as the ratio of a telomeric product to a single-copy gene product (T/S). RESULTS: Mean gestational age of participants (n = 297) at enrollment was 13.04 ± 3.50 weeks, age was 28.16 ± 6.10 years and leukocyte telomere length was 1.16 ± 0.22 (T/S). Younger age; no schooling vs. primary schooling; and lower levels of ferritin, soluble transferrin receptors and retinol-binding protein were independent predictors of longer telomere length in multivariable models. CONCLUSIONS: Leukocyte telomere length is an indicator of biological aging in pregnant Rwandan women. Maternal micronutrient status, specifically lower ferritin, soluble transferrin receptor levels, and retinol-binding protein levels were associated with longer maternal telomere length in contrast with some studies from North America and Europe. There were no associations between inflammation and infectious disease status and maternal leukocyte telomere length. Further studies are needed to enhance our understanding of the interplay between maternal nutritional status and infectious disease in relation to leukocyte telomere length in developing countries.

"I cannot say no when a pregnant woman needs my support to get to the health centre": involvement of community health workers in Rwanda's maternal health.

BACKGROUND: In Rwanda, maternal community health workers (M-CHWs) are involved in the country's overall health system. In maternal health, their role includes the provision of preventive and promotional health services at the community level. They provide services such as health education on maternal health wellbeing, advice and information on access and timely utilization of health facilities for prenatal, delivery and postpartum care. The contribution of M-CHWs in the health sector combined with other government initiatives led the country to achieving the fifth Millennium Development Goal (MDG) - target 5A- that aimed to improve maternal health through the reduction of maternal mortality ratio by 75% between 1990 and 2015). The objective of this study was to explore M-CHWs' perceptions and experiences on access and provision of maternal health services. METHODS: We used a case study methodology, a qualitative research approach to explore M-CHWs' experiences and perceptions on access and provision of maternal health services at the community level in Rwanda. For the period of June-August 2014, in-depth interviews were conducted with sixteen M-CHWs who had been providing maternal health services in the Eastern Province of Rwanda. Participants shared their experiences and perceptions on access and provision of maternal health service in their communities. RESULTS: The results of this research highlight the role of M-CHWs in promoting the use of health facilities for prenatal care and delivery and the ways they use to reach out to women. Several challenges prohibit M-CHWs to deliver adequate maternal health services and these are related to the poor resources settings in which they operate. CONCLUSION: The results of this study highlight the experiences and perceptions of M-CHWs on the provision and access to maternal health services in their communities. The fact that M-CHWs are volunteers operating in limited resources settings with no formal training in maternal health and with considerable workloads translates into challenges regarding the quality and quantity of services they provide in their communities. Such challenges create an impact on M-CHWs service provision, satisfaction and retention. The voices of M-CHWs and the communities they serve are needed to explore areas that are specific to each community context that would contribute to making the M-CHW program sustainable to achieve equitable access to maternal health services.

Obstetrics and Gynecology Residents Can Accurately Classify Benign Ovarian Tumors Using the International Ovarian Tumor Analysis Rules.

OBJECTIVES: Recognition of benign versus malignant tumors is essential in gynecologic ultrasound (US). The International Ovarian Tumor Analysis (IOTA) rules have been proposed as part of resident US training. The objective of this study was to examine whether they could be accurately used by obstetrics and gynecology residents in Rwanda. METHODS: Patients undergoing explorative laparotomy for adnexal masses at the University Teaching Hospital of Kigali were included. Before the study, a didactic lecture on the IOTA rules for classifying adnexal masses was performed. Preoperative transabdominal US examinations were performed by residents at different levels of training, who were blinded to the results of prior US examinations. The IOTA classification was compared to the final pathologic diagnosis. RESULTS: There were 72 patients who underwent 116 US examinations. Only 15.5% of US examinations were considered inconclusive. First-year residents (12) correctly diagnosed 18 of 20 masses (90%) as benign and 4 of 4 as malignant. Second-year residents (9) classified 29 of 29 masses correctly. Third-year residents (10) accurately identified 21 of 22 (95.5%) as benign and 5 of 5 as malignant. Fourth-year residents (13) accurately identified 11 of 12 (91.7%) as benign and 6 of 6 as malignant. Therefore, 74 of 78 tumors (94.9%) considered benign by IOTA rules were confirmed by histologic results. Similarly, all 20 tumors classified as malignant were confirmed. Overall, the sensitivities to diagnose benign and malignant tumors by the IOTA rules were 83.3% and 100%, respectively. The positive and negative predictive values were 100% and 94.9%. There were no significant differences noted between residency years. CONCLUSIONS: All levels of Rwandan obstetrics and gynecology residents were able to use the IOTA rules to accurately distinguish benign from malignant tumors.

Point of care ultrasound: does the presence of ascites in severe pre-eclampsia correlate with poor maternal and neonatal outcome?

OBJECTIVE: Ascites in severe pre-eclampsia may impact foetal and maternal outcomes. The objective was to determine the prevalence of ascites in women with severe pre-eclampsia by point of care (POC) ultrasound and to determine whether it correlates with higher perinatal risks. METHODS: Prospective cohort study of patients admitted with severe pre-eclampsia at 2 teaching hospitals in Kigali, Rwanda. Serial POC ultrasound was performed to document ascites. Patients were stratified by the presence of ascites in perinatal period. Maternal demographics and complications were recorded and compared between groups. RESULTS: There were 112 patients with severe pre-eclampsia, and ascites was found in 53.5% (76.7% antepartum, and 23.3% postpartum). Antepartum ascites correlated with an earlier delivery (32.2 ± 0.51 vs. 33.8 ± 0.47 weeks, P = 0.022) as well as lower birthweight (1587.3 ± 77.03 vs. 2011.6 ± 103.5 g, P = 0.002). Antepartum ascites was associated with higher stillbirth rates (P = 0.034) and NICU admission (87.2% vs. 68%, P = 0.034). Maternal hospital stay was increased in the ascites group (P < 0.0001). CONCLUSIONS: Ascites is common in severe pre-eclampsia in Rwanda and maybe a prognosticator for poor outcomes. A larger sample is necessary to determine whether ascites is independently associated with maternal morbidity and mortality and whether documenting its presence aids in the management of the foetus and mother.

OBJECTIF: L'ascite dans la pré-éclampsie sévère peut avoir un impact sur les résultats pour le fœtus et la mère. L'objectif était de déterminer la prévalence de l'ascite chez les femmes présentant une échographie de pré-éclampsie sévère au point des soins et de déterminer si elle corrélait avec des risques périnataux plus élevés. MÉTHODES: Etude de cohorte prospective de patientes admises avec une pré-éclampsie sévère dans deux hôpitaux universitaires de Kigali, au Rwanda. Une échographie au point des soins a été réalisée en série pour documenter l'ascite. Les patientes ont été stratifiées en fonction de la présence d'ascite en période périnatale. Les données démographiques maternelles et les complications ont été enregistrées et comparées entre les groupes. RÉSULTATS: Il y avait 112 patientes atteintes de pré-éclampsie sévère et l'ascite a été trouvé chez 53,5% (76,7% antépartum et 23,3% postpartum). L'ascite antépartum corrélait avec un accouchement antérieur (32,2 ± 0,51 vs 33,8 ± 0,47 semaines, p = 0,022) ainsi qu'avec un poids à la naissance plus faible (1587,3 ± 77,03 vs 2011,6 ± 103,5 g, p = 0,002). L'ascite antépartum était associée à des taux de mortinatalité plus élevés (p = 0,034) et à une admission en USIN-US (87,2% contre 68%, p = 0,034). Le séjour à l'hôpital de la mère était augmenté dans le groupe ascite (p <0,0001). CONCLUSIONS: L'ascite est fréquente dans la pré-éclampsie sévère au Rwanda et peut être un pronostic pour des résultats médiocres. Un échantillon plus important est nécessaire pour déterminer si l'ascite est associée de manière indépendante à la morbidité et à la mortalité maternelles et si la documentation de sa présence facilite la prise en charge du fœtus et de la mère.

The assessment of gestational age: a comparison of different methods from a malaria pregnancy cohort in sub-Saharan Africa.

BACKGROUND: Determining gestational age in resource-poor settings is challenging because of limited availability of ultrasound technology and late first presentation to antenatal clinic. Last menstrual period (LMP), symphysio-pubis fundal height (SFH) and Ballard Score (BS) at delivery are therefore often used. We assessed the accuracy of LMP, SFH, and BS to estimate gestational age at delivery and preterm birth compared to ultrasound (US) using a large dataset derived from a randomized controlled trial in pregnant malaria patients in four African countries. METHODS: Mean and median gestational age for US, LMP, SFH and BS were calculated for the entire study population and stratified by country. Correlation coefficients were calculated using Pearson's rho, and Bland Altman plots were used to calculate mean differences in findings with 95% limit of agreements. Sensitivity, specificity, positive predictive value and negative predictive value were calculated considering US as reference method to identify term and preterm babies. RESULTS: A total of 1630 women with P. falciparum infection and a gestational age > 24 weeks determined by ultrasound at enrolment were included in the analysis. The mean gestational age at delivery using US was 38.7 weeks (95%CI: 38.6-38.8), by LMP, 38.4 weeks (95%CI: 38.0-38.9), by SFH, 38.3 weeks (95%CI: 38.2-38.5), and by BS 38.0 weeks (95%CI: 37.9-38.1) (p < 0.001). Correlation between US and any of the other three methods was poor to moderate. Sensitivity and specificity to determine prematurity were 0.63 (95%CI 0.50-0.75) and 0.72 (95%CI, 0.66-0.76) for LMP, 0.80 (95%CI 0.74-0.85) and 0.74 (95%CI 0.72-0.76) for SFH and 0.42 (95%CI 0.35-0.49) and 0.77 (95%CI 0.74-0.79) for BS. CONCLUSIONS: In settings with limited access to ultrasound, and in women who had been treated with P. falciparum malaria, SFH may be the most useful antenatal tool to date a pregnancy when women present first in second and third trimester. The Ballard postnatal maturation assessment has a limited role and lacks precision. Improving ultrasound facilities and skills, and early attendance, together with the development of new technologies such as automated image analysis and new postnatal methods to assess gestational age, are essential for the study and management of preterm birth in low-income settings.

Mothers' perceptions and experiences of using maternal health-care services in Rwanda.

Reducing barriers to use maternal health care is one of the critical components to improving maternal health. Rwanda is among the countries that have made tremendous efforts to reduce maternal mortality. However, the current maternal mortality ratio is still high which calls for further efforts to be considered. This study used a qualitative approach to understand mothers' perceptions and experiences of using maternal health care in Rwanda. Using in-depth interviews and focus group discussions, data were collected in the Western and Eastern provinces of the country where forty-five women participated in the study from June to August 2014. This paper highlights perceptions of these participants regarding issues that contribute to suboptimal use of maternal health-care services. The geographical, financial, and social-cultural barriers that emerged in this study highlight the need to understand mothers' experiences and perceptions when using maternal health care as Rwanda and other countries strive to reduce negative maternal health outcomes.

Is Prolonged Labor Managed Adequately in Rural Rwandan Hospitals?

Unnecessary interventions to manage prolonged labor may cause considerable maternal and perinatal ill-health. We explored how prolonged labor was managed in three rural Rwandan hospitals using a partograph. A retrospective chart review was done to assess whether (A) the action line on the partograph was reached or crossed, (B) artificial rupture of membranes (ARM) performed, (C) oxytocin augmentation instituted, and (D) vacuum extraction (VE) considered when in second stage of labor. Adequate management of prolonged labor was considered if three clinical criteria were fulfilled in the first and four in the second stage. Out of 7605 partographs, 299/7605 women (3.9%) were managed adequately and 1252/7605 women (16.5%) inadequately for prolonged labor. While 6054 women (79.6%) remained at the left of the alert line, still 1651/6054 (27.3%) received oxytocin augmentation unjustifiably. Amongst women whom were managed adequately for prolonged labor until their cervical dilatation plot reached or crossed the action line. In 115/299 women (38.5%), however, second stage of labor was reached but CS performed without a trial of VE. In 1252/7605 women (16.5%) management was inadequate, when their cervical dilatation plot reached between the alert and action lines, 495/1252 women (39.5%) did not reach the second stage of labor and remained left of the action line had their membranes ruptured and labor augmented, and gave birth by CS. CS was, however, also performed in 151/1252 women (12.1%) whose membranes were still intact. We recommend training for more appropriate decision-making during labor to prevent unnecessary CS and proper use of ARM, oxytocin augmentation and VE can be provided safely.

Population Pharmacokinetics of Artemether, Dihydroartemisinin, and Lumefantrine in Rwandese Pregnant Women Treated for Uncomplicated Plasmodium falciparum Malaria.

The artemisinin-based combination therapy artemether-lumefantrine is commonly used in pregnant malaria patients. However, the effect of pregnancy-related changes on exposure is unclear, and pregnancy has been associated with decreased efficacy in previous studies. This study aimed to characterize the population pharmacokinetics of artemether, its active metabolite dihydroartemisinin, and lumefantrine in 22 Rwandese pregnant women in their second (n = 11) or third (n = 11) trimester with uncomplicated Plasmodium falciparum malaria. These patients were enrolled from Rwamagana district hospital and received the standard fixed oral dose combination of 80 mg of artemether and 480 mg of lumefantrine twice daily for 3 days. Venous plasma concentrations were quantified for all three analytes using liquid chromatography coupled with tandem mass spectroscopy, and data were analyzed using nonlinear mixed-effects modeling. Lumefantrine pharmacokinetics was described by a flexible but highly variable absorption, with a mean absorption time of 4.04 h, followed by a biphasic disposition model. The median area under the concentration-time curve from 0 h to infinity (AUC0-∞) for lumefantrine was 641 h · mg/liter. Model-based simulations indicated that 11.7% of the study population did not attain the target day 7 plasma concentration (280 ng/ml), a threshold associated with increased risk of recrudescence. The pharmacokinetics of artemether was time dependent, and the autoinduction of its clearance was described using an enzyme turnover model. The turnover half-life was predicted to be 30.4 h. The typical oral clearance, which started at 467 liters/h, increased 1.43-fold at the end of treatment. Simulations suggested that lumefantrine pharmacokinetic target attainment appeared to be reassuring in Rwandese pregnant women, particularly compared to target attainment in Southeast Asia. Larger cohorts will be required to confirm this finding.

Continuing Professional Development in Maternal Health Care: Barriers to Applying New Knowledge and Skills in the Hospitals of Rwanda.

Objectives Training healthcare professionals in emergency maternal healthcare is a critical component of improving overall maternal health in developing countries like Rwanda. This paper explored the challenges that healthcare professionals who participated in a Continuing Professional Development (CPD) program on Advanced Life Support in Obstetrics® (ALSO) face in putting the learned knowledge and skills into practice in hospitals of Rwanda. Methods This study used a mixed methods approach to understand the challenges/barriers to applying new knowledge and skills in the hospitals of Rwanda. We conducted thirteen purposive in-depth interviews with ALSO® trainees (nurses, midwives and physicians) complemented with a cross-sectional survey on staff turnover in eight of the nine hospitals in the Eastern province of Rwanda. Results Our study found that trainees do not get enough opportunity to apply the new knowledge and skills in their hospitals and expand to health centers. In part because they are frequently rotating to different departments of the hospital and are not getting the opportunity to train their colleagues to share the learned knowledge and skills. The lack of refresher trainings/mentorship and the high personnel turnover were also reported as a barrier to applying new knowledge and skills. Reasons for staff turnover included pursuing further studies, a better opportunity (job/remuneration), low morale, and family related motives including joining a spouse or better schools for children. Conclusions for Practice Expanding and formalizing CPD training to all the healthcare professionals involved in providing maternal care services would improve the provision of emergency maternal healthcare in Rwanda.

First-trimester artemisinin derivatives and quinine treatments and the risk of adverse pregnancy outcomes in Africa and Asia: A meta-analysis of observational studies.

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.

False-negative malaria rapid diagnostic tests in Rwanda: impact of Plasmodium falciparum isolates lacking hrp2 and declining malaria transmission.

BACKGROUND: Rapid diagnostic tests (RDTs) for histidine rich protein 2 (HRP2) are often used to determine whether persons with fever should be treated with anti-malarials. However, Plasmodium falciparum parasites with a deletion of the hrp2 gene yield false-negative RDTs and there are concerns the sensitivity of HRP2-based RDTs may fall when the intensity of transmission decreases. METHODS: This observational study enrolled 9226 patients at three health centres in Rwanda from April 2014 to April 2015. It then compared the sensitivity of RDTs based on HRP2 and the Plasmodium lactate dehydrogenase (pLDH) to microscopy (thick smears) for the diagnosis of malaria. PCR was used to determine whether deletions of the histidine-rich central repeat region of the hrp2 gene (exon 2) were associated with false-negative HRP2-based RDTs. RESULTS: In comparison to microscopy, the sensitivity and specificity of HRP2- and pLDH-based RDTs were 89.5 and 86.2% and 80.2 and 94.3%, respectively. When the results for both RDTs were combined, sensitivity rose to 91.8% and specificity was 85.7%. Additionally, when smear positivity fell from 46 to 3%, the sensitivity of the HRP2-based RDT fell from 88 to 67%. Of 370 samples with false-negative HRP2 RDT results for which PCR was performed, 140 (38%) were identified as P. falciparum by PCR. Of the isolates identified as P. falciparum by PCR, 32 (23%) were negative for the hrp2 gene based on PCR. Of the 32 P. falciparum isolates negative for hrp2 by PCR, 17 (53%) were positive based on the pLDH RDT. CONCLUSION: This prospective study of RDT performance coincided with a decline in the intensity of malaria transmission in Kibirizi (fall in slide positivity from 46 to 3%). This decline was associated with a decrease in HRP2 RDT sensitivity (from 88 to 67%). While P. falciparum isolates without the hrp2 gene were an important cause of false-negative HRP2-based RDTs, most were identified by the pLDH-based RDT. Although WHO does not recommend the use of combined HRP2/pLDH testing in sub-Saharan Africa, these results suggest that combination HRP2/pLDH-based RDTs could reduce the impact of false-negative HRP2-based RDTs for detection of symptomatic P. falciparum malaria.

Maternal and perinatal outcome after previous caesarean section in rural Rwanda.

BACKGROUND: Offering a trial of labor (ToL) after previous caesarean section (CS) is an important strategy to reduce short- and long-term morbidity associated with repeated CS. We compared maternal and perinatal outcomes between ToL and elective repeat caesarean section (ERCS) at a district hospital in rural Rwanda. METHODS: Audit of women's records with one prior CS who delivered at Ruhengeri district hospital in Rwanda between June 2013 and December 2014. RESULTS: Out of 4131 women who came for delivery, 435 (11%) had scarred uteri. ToL, which often started at home or at health centers without appropriate counseling, occurred in 297/435 women (68.3%), while 138 women (31.7%) delivered by ERCS. ToL was successful in 134/297 (45.1%) women. There were no maternal deaths. Twenty-eight out of all 435 women with a scarred uterus (6.4%) sustained severe acute maternal morbidity (puerperal sepsis, postpartum hemorrhage, uterine rupture), which was higher in women with ToL (n = 23, 7.7%) compared with women who had an ERCS (n = 5, 3.6%): adjusted odds ration (aOR) 1.4 (95% CI 1.2-5.4). There was no difference in neonatal admissions between women who underwent ToL (n = 64/297; 21.5%) and those who delivered by ERCS (n = 35/138; 25.4%: aOR 0.8; CI 0.5-1.6). The majority of admissions were due to perinatal asphyxia that occurred more often in infants whose mothers underwent ToL (n = 40, 13.4%) compared to those who delivered by ERCS (n = 15, 10.9%: aOR 1.9; CI 1.6-3.6). Perinatal mortality was similar among infants whose mothers had ToL (n = 8; 27/1000 ToLs) and infants whose mothers underwent ERCS (n = 4; 29/1000 ERCSs). CONCLUSIONS: A considerable proportion of women delivering at a rural Rwandan hospital had scarred uteri. Severe acute maternal morbidity was higher in the ToL group, perinatal mortality did not differ. ToL took place under suboptimal conditions: access for women with scarred uteri into a facility with 24-h surgery should be guaranteed to increase the safety of ToL.

Longer travel time to district hospital worsens neonatal outcomes: a retrospective cross-sectional study of the effect of delays in receiving emergency cesarean section in Rwanda.

BACKGROUND: In low-resource settings, access to emergency cesarean section is associated with various delays leading to poor neonatal outcomes. In this study, we described the delays a mother faces when needing emergency cesarean delivery and assessed the effect of these delays on neonatal outcomes in Rwanda. METHODS: This retrospective study included 441 neonates and their mothers who underwent emergency cesarean section in 2015 at three district hospitals in Rwanda. Four delays were measured: duration of labor prior to hospital admission, travel time from health center to district hospital, time from admission to surgical incision, and time from decision for emergency cesarean section to surgical incision. Neonatal outcomes were categorized as unfavorable (APGAR <7 at 5 min or death) and favorable (alive and APGAR ≥7 at 5 min). We assessed the relationship between each type of delay and neonatal outcomes using multivariate logistic regression. RESULTS: In our study, 9.1% (40 out of 401) of neonates had an unfavorable outcome, 38.7% (108 out of 279) of neonates' mothers labored for 12-24 h before hospital admission, and 44.7% (159 of 356) of mothers were transferred from health centers that required 30-60 min of travel time to reach the district hospital. Furthermore, 48.1% (178 of 370) of cesarean sections started within 5 h after hospital admission and 85.2% (288 of 338) started more than 30 min after the decision for cesarean section was made. Neonatal outcomes were significantly worse among mothers with more than 90 min of travel time from the health center to the district hospital compared to mothers referred from health centers located on the same compound as the hospital (aOR = 5.12, p = 0.02). Neonates with cesarean deliveries starting more than 30 min after decision for cesarean section had better outcomes than those starting immediately (aOR = 0.32, p = 0.04). CONCLUSIONS: Longer travel time between health center and district hospital was associated with poor neonatal outcomes, highlighting a need to decrease barriers to accessing emergency maternal services. However, longer decision to incision interval posed less risk for adverse neonatal outcome. While this could indicate thorough pre-operative interventions including triage and resuscitation, this relationship should be studied prospectively in the future.

Point-of-Care Ultrasound Use, Accuracy, and Impact on Clinical Decision Making in Rwanda Hospitals.

OBJECTIVES: Few studies of point-of-care ultrasound training and use in low resource settings have reported the impact of examinations on clinical management or the longer-term quality of trainee-performed studies. We characterized the long-term effect of a point-of-care ultrasound program on clinical decision making, and evaluated the quality of clinician-performed ultrasound studies. METHODS: We conducted point-of-care ultrasound training for physicians from Rwandan hospitals. Physicians then used point-of-care ultrasound and recorded their findings, interpretation, and effects on patient management. Data were collected for 6 months. Trainee studies were reviewed for image quality and accuracy. RESULTS: Fifteen participants documented 1158 ultrasounds; 590 studies (50.9%) had matched images and interpretations for review. Abdominal ultrasound for free fluid was the most frequently performed application. The mean image quality score was 2.36 (95% confidence interval, 2.28-2.44). Overall sensitivity and specificity for trainee-performed examinations was 94 and 98%. Point-of-care ultrasound use most commonly changed medications administered (42.4%) and disposition (30%). CONCLUSIONS: A point-of-care ultrasound training intervention in a low-resource setting resulted in high numbers of diagnostic-quality studies over long-term follow-up. Ultrasound use routinely changed clinical decision making.