Participation of Ghanaian pregnant women in an antimalarial drug trial: willingness, experiences and perceptions.

BACKGROUND: With increasing orientation towards including pregnant women in clinical trials, investigators must conduct culturally acceptable research to aid recruitment and retention. There is limited information on experiences and meanings that pregnant women make of trial participation in Africa. This study reports experiences and perceptions of Ghanaian pregnant women regarding their participation in a clinical trial. METHODS: From October to December 2012, 45 in-depth interviews were conducted among pregnant women and their male partners regarding their experiences and perceptions of clinical trial processes as part of an antimalarial drug safety and efficacy trial in pregnant women in the Ashanti region of Ghana. Analysis was by predetermined themes and inductive analysis. RESULTS: Familiarity with the disease studied in the trial and trust in health workers favoured participation with the latter underlying acceptance of study drugs in the absence of symptoms. Adverse drug events were perceived as intrinsic sickness exhibited on the path to wellness. There were no cultural barriers to blood sampling during home visits but hospital-based sampling was preferred. Home visits were linked to participants having HIV infection. CONCLUSION: This study contributes knowledge on sociocultural matters underpinning pregnant women's decisions regarding trial participation in an era of increasing drug trials involving pregnant women.

Pregnancy outcomes and risk of placental malaria after artemisinin-based and quinine-based treatment for uncomplicated falciparum malaria in pregnancy: a WorldWide Antimalarial Resistance Network systematic review and individual patient data meta-analysis.

BACKGROUND: Malaria in pregnancy, including asymptomatic infection, has a detrimental impact on foetal development. Individual patient data (IPD) meta-analysis was conducted to compare the association between antimalarial treatments and adverse pregnancy outcomes, including placental malaria, accompanied with the gestational age at diagnosis of uncomplicated falciparum malaria infection. METHODS: A systematic review and one-stage IPD meta-analysis of studies assessing the efficacy of artemisinin-based and quinine-based treatments for patent microscopic uncomplicated falciparum malaria infection (hereinafter uncomplicated falciparum malaria) in pregnancy was conducted. The risks of stillbirth (pregnancy loss at ≥ 28.0 weeks of gestation), moderate to late preterm birth (PTB, live birth between 32.0 and < 37.0 weeks), small for gestational age (SGA, birthweight of < 10th percentile), and placental malaria (defined as deposition of malaria pigment in the placenta with or without parasites) after different treatments of uncomplicated falciparum malaria were assessed by mixed-effects logistic regression, using artemether-lumefantrine, the most used antimalarial, as the reference standard. Registration PROSPERO: CRD42018104013. RESULTS: Of the 22 eligible studies (n = 5015), IPD from16 studies were shared, representing 95.0% (n = 4765) of the women enrolled in literature. Malaria treatment in this pooled analysis mostly occurred in the second (68.4%, 3064/4501) or third trimester (31.6%, 1421/4501), with gestational age confirmed by ultrasound in 91.5% (4120/4503). Quinine (n = 184) and five commonly used artemisinin-based combination therapies (ACTs) were included: artemether-lumefantrine (n = 1087), artesunate-amodiaquine (n = 775), artesunate-mefloquine (n = 965), and dihydroartemisinin-piperaquine (n = 837). The overall pooled proportion of stillbirth was 1.1% (84/4361), PTB 10.0% (619/4131), SGA 32.3% (1007/3707), and placental malaria 80.1% (2543/3035), and there were no significant differences of considered outcomes by ACT. Higher parasitaemia before treatment was associated with a higher risk of SGA (adjusted odds ratio [aOR] 1.14 per 10-fold increase, 95% confidence interval [CI] 1.03 to 1.26, p = 0.009) and deposition of malaria pigment in the placenta (aOR 1.67 per 10-fold increase, 95% CI 1.42 to 1.96, p < 0.001). CONCLUSIONS: The risks of stillbirth, PTB, SGA, and placental malaria were not different between the commonly used ACTs. The risk of SGA was high among pregnant women infected with falciparum malaria despite treatment with highly effective drugs. Reduction of malaria-associated adverse birth outcomes requires effective prevention in pregnant women.

Efficacy and tolerability of artemisinin-based and quinine-based treatments for uncomplicated falciparum malaria in pregnancy: a systematic review and individual patient data meta-analysis.

BACKGROUND: Malaria in pregnancy affects both the mother and the fetus. However, evidence supporting treatment guidelines for uncomplicated (including asymptomatic) falciparum malaria in pregnant women is scarce and assessed in varied ways. We did a systematic literature review and individual patient data (IPD) meta-analysis to compare the efficacy and tolerability of different artemisinin-based or quinine-based treatments for malaria in pregnant women. METHODS: We did a systematic review of interventional or observational cohort studies assessing the efficacy of artemisinin-based or quinine-based treatments in pregnancy. Seven databases (MEDLINE, Embase, Global Health, Cochrane Library, Scopus, Web of Science, and Literatura Latino Americana em Ciencias da Saude) and two clinical trial registries (International Clinical Trials Registry Platform and ClinicalTrials.gov) were searched. The final search was done on April 26, 2019. Studies that assessed PCR-corrected treatment efficacy in pregnancy with follow-up of 28 days or more were included. Investigators of identified studies were invited to share data from individual patients. The outcomes assessed included PCR-corrected efficacy, PCR-uncorrected efficacy, parasite clearance, fever clearance, gametocyte development, and acute adverse events. One-stage IPD meta-analysis using Cox and logistic regression with random-effects was done to estimate the risk factors associated with PCR-corrected treatment failure, using artemether-lumefantrine as the reference. This study is registered with PROSPERO, CRD42018104013. FINDINGS: Of the 30 studies assessed, 19 were included, representing 92% of patients in the literature (4968 of 5360 episodes). Risk of PCR-corrected treatment failure was higher for the quinine monotherapy (n=244, adjusted hazard ratio [aHR] 6·11, 95% CI 2·57-14·54, p<0·0001) but lower for artesunate-amodiaquine (n=840, 0·27, 95% 0·14-0·52, p<0·0001), artesunate-mefloquine (n=1028, 0·56, 95% 0·34-0·94, p=0·03), and dihydroartemisinin-piperaquine (n=872, 0·35, 95% CI 0·18-0·68, p=0·002) than artemether-lumefantrine (n=1278) after adjustment for baseline asexual parasitaemia and parity. The risk of gametocyte carriage on day 7 was higher after quinine-based therapy than artemisinin-based treatment (adjusted odds ratio [OR] 7·38, 95% CI 2·29-23·82). INTERPRETATION: Efficacy and tolerability of artemisinin-based combination therapies (ACTs) in pregnant women are better than quinine. The lower efficacy of artemether-lumefantrine compared with other ACTs might require dose optimisation. FUNDING: The Bill & Melinda Gates Foundation, ExxonMobil Foundation, and the University of Oxford Clarendon Fund.

Severe morbidities associated with induced abortions among misoprostol users and non-users in a tertiary public hospital in Ghana.

BACKGROUND: Misoprostol has become a popular over the counter self-administered abortifacient in Ghana. This study aimed to compare the socio-demographic characteristics and clinical complications associated with misoprostol and non-misoprostol induced abortions among patients admitted to a tertiary public health facility in Ghana. METHODS: This was a cross sectional study conducted at the gynaecological ward of Komfo Anokye Teaching Hospital (KATH), over a four-month period using a structured pre-tested questionnaire. Data were analysed using Chi-square, Fisher's exact and student t-tests. Factors associated with severe morbidity were examined using Poisson regression with robust error variance to estimate crude and adjusted relative risks (RRs) with 95% confidence intervals (CIs). P < 0.05 was considered statistically significant. RESULTS: Overall, 126 misoprostol users and 126 misoprostol non-users were recruited into the study. About 71% of the clients had self-induced abortions. Misoprostol users were more likely to be younger (p < 0.001), single (p < 0.001), nulliparous (p = 0.001), of higher educational background (p = 0.001), and unemployed (p < 0.001), than misoprostol non-users. Misoprostol users were more likely than non-users to undergo termination of pregnancy because they wanted to continue schooling (p < 0.001) or were not earning regular income to support a family (p = 0.001). Overall, 182 (72.2%) of the women (79.4% misoprostol users vs. 65.1% misoprostol non-users; p = 0.01) suffered severe morbidity. Nulliparous women (adjusted RR, 1.28; 95% CI, 1.08-1.52) and those who had induced abortion after 12 weeks' gestation (adjusted RR, 1.36; 95% CI, 1.18-1.57) were at increased risks of experiencing severe morbidity. The association between mode of abortion induction and severe morbidity was not statistically significant (p = 0.06). CONCLUSION: Self-induced abortions using misoprostol is a common practice among women in this study; nearly three quarters of them suffered severe morbidity. Nonetheless, severe morbidity among misoprostol users and non-users did not differ significantly but was directly related to the gestational age at which the induced abortions occurred. Health education on the dangers of self-induced abortions and appropriate use of medication abortion could help reduce complications associated with induced abortions in Ghana.

Reproductive experiences of teenagers in the Ejisu-Juabeng district of Ghana.

OBJECTIVE: To determine the proportions of male and female teenagers aged 15-19 years who have ever been involved in pregnancy, and to examine factors associated with involvement in teenage pregnancy in the Ejisu-Juabeng district of Ghana. METHODS: In a household-based cross-sectional survey, 481 randomly selected male and female teenagers were enrolled between August 3 and September 17, 2009. Study variables included demographics; sexual exposure; contraceptive use; and involvement in pregnancy, childbirth, and induced abortion. Multivariable multinomial logistic regression analyses were used to examine the association between involvement in pregnancy, and the background and reproductive profiles of the respondents via SPSS version 16.0. RESULTS: Both the mean and median ages of the respondents were 17.2 years. One-third of respondents lived with both parents, and one-third lived with single mothers. The median age of sexual debut was 16.0 years. Approximately 58% of sexually experienced females had been pregnant, and 37% had had an induced abortion. Age at sexual debut, gender, and being out of school were significantly associated with involvement in teenage pregnancy, whereas residential status, relationship with first partner, and contraceptive use were not. CONCLUSION: Keeping adolescents enrolled in school might reduce their risk of involvement in pregnancy in the Ejisu-Juabeng district of Ghana.

The safety of amodiaquine use in pregnant women.

Few antimalarial drugs have been evaluated extensively in pregnancy because of fears over toxicity. However, increasing Plasmodium falciparum resistance to chloroquine and sulfadoxine-pyrimethamine makes finding alternative antimalarials that are safe and effective in pregnancy a priority. There is a renewed interest in amodiaquine as a potential candidate, particularly as a partner drug in artemisinin-based combination therapy. The available data suggest that, at standard dosages, amodiaquine is not teratogenic and that the adverse events associated with taking amodiaquine in pregnancy are not greater than those associated with falciparum malaria in pregnancy. Thus, amodiaquine in combination with other antimalarial drugs may be useful for malaria treatment in pregnancy, but inadequate data on its safety and pharmacokinetics in pregnancy limits its deployment for intermittent preventive treatment in pregnancy.