Atovaquone-Proguanil combination for malaria treatment: a systematic review with meta-analysis

A Research Report Submitted to the School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, in partial fulfilment of the requirements for the Degree of Master of Science in Medicine in Tropical Diseases (Epidemiology and Biostatistics Option). Johannesburg, January 2001Background: increasing spread of drug resistance among Plasmodium falciparum poses a serious threat to malaria treatment. The situation is complicated not only because new drugs are expensive and slow in development but also because they must be effective, preferably have a novel method of action, with an acceptable level of adverse effects, and be deployed in such a way as to prolong their use.IT201

Monitoring malaria using health facility based surveys: challenges and limitations.

BACKGROUND: Health facility data are more readily accessible for operational planning and evaluation of disease control programmes. The importance, potential challenges and limitations of using facility based survey as an alternative tool for monitoring changes in local malaria epidemiology were examined. METHODS: The study involved six areas within the administrative divisions of The Gambia. The areas were selected to reflect socioeconomic and malaria transmission intensities across the country. The study design involved an age stratified cross sectional surveys that were conducted during the wet season in 2008 and in the 2009 during the dry season. Participants were patients attending clinics in six health centres and the representative populations from the catchment communities of the health centres. RESULTS: Overall participants' characteristics were mostly not comparable in the two methodological approaches in the different seasons and settings. More females than males were enrolled (55.8 vs. 44.2 %) in all the surveys. Malaria infection was higher in the surveys in health centres than in the communities (p < 0.0001) and also in males than in females (OR = 1.3; p < 0.001). Males were less likely than females to sleep under an insecticide treated net in the communities (OR = 1.6; 95 % CI 1.3, 1.9) and in the health centres (OR = 1.3; 95 % CI 1.1, 1.5). Representativeness of the ethnic groups was better in the health centre surveys than in the community surveys when compared to the 2003 national population census in The Gambia. CONCLUSION: Health facility based survey though a potential tool for monitoring changes in the local epidemiology of malaria will require continuous validation of the facility and participants sociodemograhic characteristics as these may change over time. The effects of health seeking practices on service utilization and health facility surveys as an approach will also need continuous review

Glucose-6-Phosphate Dehydrogenase Deficiency and Haemoglobin Drop after Sulphadoxine-Pyrimethamine Use for Intermittent Preventive Treatment of Malaria during Pregnancy in Ghana - A Cohort Study.

BACKGROUND: Sulphadoxine-Pyrimethamine (SP) is still the only recommended antimalarial for use in intermittent preventive treatment of malaria during pregnancy (IPTp) in some malaria endemic countries including Ghana. SP has the potential to cause acute haemolysis in G6PD deficient people resulting in significant haemoglobin (Hb) drop but there is limited data on post SP-IPTp Hb drop. This study determined the difference, if any in proportions of women with significant acute haemoglobin drop between G6PD normal, partial deficient and full deficient women after SP-IPTp. METHODS AND FINDINGS: Prospectively, 1518 pregnant women who received SP for IPTp as part of their normal antenatal care were enrolled. Their G6PD status were determined at enrollment followed by assessments on days 3, 7,14 and 28 to document any adverse effects and changes in post-IPTp haemoglobin (Hb) levels. The three groups were comparable at baseline except for their mean Hb (10.3 g/dL for G6PD normal, 10.8 g/dL for G6PD partial deficient and 10.8 g/dL for G6PD full defect women).The prevalence of G6PD full defect was 2.3% and 17.0% for G6PD partial defect. There was no difference in the proportions with fractional Hb drop ≥ 20% as compared to their baseline value post SP-IPTp among the 3 groups on days 3, 7, 14. The G6PD full defect group had the highest median fractional drop at day 7. There was a weak negative correlation between G6PD activity and fractional Hb drop. There was no statistical difference between the three groups in the proportions of those who started the study with Hb ≥ 8g/dl whose Hb level subsequently fell below 8g/dl post-SP IPTp. No study participant required transfusion or hospitalization for severe anaemia. CONCLUSIONS: There was no significant difference between G6PD normal and deficient women in proportions with significant acute haemoglobin drop post SP-IPTp and lower G6PD enzyme activity was not strongly associated with significant acute drug-induced haemoglobin drop post SP-IPTp but a larger study is required to confirm consistency of findings

Effective Linkages of Continuum of Care for Improving Neonatal, Perinatal, and Maternal Mortality: A Systematic Review and Meta-Analysis.

BACKGROUND: Continuum of care has the potential to improve maternal, newborn, and child health (MNCH) by ensuring care for mothers and children. Continuum of care in MNCH is widely accepted as comprising sequential time (from pre-pregnancy to motherhood and childhood) and space dimensions (from community-family care to clinical care). However, it is unclear which linkages of care could have a greater effect on MNCH outcomes. The objective of the present study is to assess the effectiveness of different continuum of care linkages for reducing neonatal, perinatal, and maternal mortality in low- and middle-income countries. METHODS: We searched for randomized and quasi-randomized controlled trials that addressed two or more linkages of continuum of care and attempted to increase mothers' uptake of antenatal care, skilled birth attendance, and postnatal care. The outcome variables were neonatal, perinatal, and maternal mortality. RESULTS: Out of the 7,142 retrieved articles, we selected 19 as eligible for the final analysis. Of these studies, 13 used packages of intervention that linked antenatal care, skilled birth attendance, and postnatal care. One study each used packages that linked antenatal care and skilled birth attendance or skilled birth attendance and postnatal care. Four studies used an intervention package that linked antenatal care and postnatal care. Among the packages that linked antenatal care, skilled birth attendance, and postnatal care, a significant reduction was observed in combined neonatal, perinatal, and maternal mortality risks (RR 0.83; 95% CI 0.77 to 0.89, I2 79%). Furthermore, this linkage reduced combined neonatal, perinatal, and maternal mortality when integrating the continuum of care space dimension (RR 0.85; 95% CI 0.77 to 0.93, I2 81%). CONCLUSIONS: Our review suggests that continuous uptake of antenatal care, skilled birth attendance, and postnatal care is necessary to improve MNCH outcomes in low- and middle-income countries. The review was conclusive for the reduction of neonatal and perinatal deaths. Although maternal deaths were not significantly reduced, composite measures of all mortality were. Thus, the evidence is sufficient to scale up this intervention package for the improvement of MNCH outcomes

Effect of continuum-of-care intervention package on improving contacts and quality of maternal and newborn healthcare in Ghana: a cluster randomised controlled trial.

OBJECTIVE: To evaluate the effect of a continuum-of-care intervention package on adequate contacts of women and newborn with healthcare providers and their reception of high-quality care. DESIGN: Cluster randomised controlled trial. SETTING: 32 subdistricts in 3 rural sites in Ghana. PARTICIPANTS: The baseline survey involved 1480 women who delivered before the trial, and the follow-up survey involved 1490 women who received maternal and newborn care during the trial. INTERVENTIONS: The intervention package included training healthcare providers, using an educational and recording tool named 'continuum-of-care card', providing the first postnatal care (PNC) by retaining women and newborns at healthcare facility or home visit by healthcare providers. OUTCOME MEASURES: Adequate contacts were defined as at least four contacts during pregnancy, delivery with assistance of skilled healthcare providers at a healthcare facility and three timely contacts within 6 weeks postpartum. High-quality care was defined as receiving 6 care items for antenatal care (ANC), 3 for peripartum care (PPC) and 14 for PNC. RESULTS: The difference-in-difference method was used to assess the effects of the intervention on the study outcome. The percentage of adequate contacts with high-quality care in the intervention group in the follow-up survey and the adjusted difference-in-difference estimators were 12.6% and 2.2 (p=0.61) at ANC, 31.5% and 1.9 (p=0.73) at PPC and 33.7% and 12.3 (p=0.13) at PNC in the intention-to-treat design, whereas 13.0% and 2.8 (p=0.54) at ANC, 34.2% and 2.7 (p=0.66) at PPC and 38.1% and 18.1 (p=0.02) at PNC in the per-protocol design that assigned the study sample by possession of the continuum-of-care card. CONCLUSIONS: The interventions improved contacts with healthcare providers and quality of care during PNC. However, having adequate contact did not guarantee high-quality care. Maternal and newborn care in Ghana needs to improve its continuity and quality. TRIAL REGISTRATION NUMBER: ISRCTN90618993. 

Women’s overall satisfaction with health facility delivery services in Ghana: a mixed-methods study

Background: Skilled birth delivery has increased up to nearly 74% in Ghana, but its quality has been questioned over the years. As understanding women's satisfaction could be important to improving service quality, this study aimed to determine what factors were associated with women's overall satisfaction with delivery services quantitatively and qualitatively in rural Ghanaian health facilities. Results: This cross-sectional, mixed methods study used an explanatory sequential design across three Ghana Health Service research areas in 2013. Participants were women who had delivered in the preceding 2 years. Two-stage random sampling was used to recruit women for the quantitative survey. Relationships between women's socio-demographic characteristics and their overall satisfaction with health facility delivery services were examined using univariate and multiple logistic regression analyses. For qualitative analyses, women who completed the quantitative survey were purposively selected to participate in focus group discussions. Data from the focus group discussions were analyzed based on predefined and emerging themes. Overall, 1130 women were included in the quantitative analyses and 136 women participated in 15 focus group discussions. Women's mean age was 29 years. Nearly all women (94%) were satisfied with the overall services received during delivery. Women with middle level/junior high school education [adjusted odds ratio (AOR) = 0.50, 95% confidence interval (CI) = (0.26-0.98)] were less likely to be satisfied with overall delivery services compared to women with no education. Qualitatively, women were not satisfied with the unconventional demands, negative attitude, and unavailability of healthcare workers, as well as the long wait time. Conclusions: Although most women were satisfied with the overall service they received during delivery, they were not satisfied with specific aspects of the health services; therefore, higher quality service delivery is necessary to improve women's satisfaction. Additional sensitivity training and a reduction in work hours may also improve the experience of clients

Determinants of attending antenatal care at least four times in rural Ghana: analysis of a cross-sectional survey.

BACKGROUND: Improving maternal health is a global challenge. In Ghana, maternal morbidity and mortality rates remain high, particularly in rural areas. Antenatal care (ANC) attendance is known to improve maternal health. However, few studies have updated current knowledge regarding determinants of ANC attendance. OBJECTIVE: This study examined factors associated with ANC attendance in predominantly rural Ghana. METHODS: We conducted a cross-sectional study at three sites (i.e. Navrongo, Kintampo, and Dodowa) in Ghana between August and September 2013. We selected 1500 women who had delivered within the two years preceding the survey (500 from each site) using two-stage random sampling. Data concerning 1497 women's sociodemographic characteristics and antenatal care attendance were collected and analyzed, and factors associated with attending ANC at least four times were identified using logistic regression analysis. RESULTS: Of the 1497 participants, 86% reported attending ANC at least four times, which was positively associated with possession of national health insurance (AOR 1.64, 95% CI: 1.14-2.38) and having a partner with a high educational level (AOR 1.64, 95% CI: 1.02-2.64) and negatively associated with being single (AOR 0.39, 95% CI: 0.22-0.69) and cohabiting (AOR 0.57, 95% CI: 0.34-0.97). In site-specific analyses, factors associated with ANC attendance included marital status in Navrongo; marital status, possession of national health insurance, partners' educational level, and wealth in Kintampo; and preferred pregnancy timing in Dodowa. In the youngest, least educated, and poorest women and women whose partners were uneducated, those with health insurance were more likely to report at least four ANC attendances relative to those who did not have insurance. CONCLUSIONS: Ghanaian women with low socioeconomic status were less likely to report at least four ANC attendances during pregnancy if they did not possess health insurance. The national health insurance scheme should include a higher number of deprived women in predominantly rural communities

Should consent forms used in clinical trials be translated into the local dialects? A survey among past participants in rural Ghana

Obtaining informed consent is part of the expression of the principle of participant autonomy during clinical trials. It is critical that participants understand the content of informed consent forms and remain in a position to seek independent advice on its content. We conducted a survey among past participants of a clinical trial in the Kassena-Nankana Districts of rural northern Ghana about the usefulness of informed consent forms that are written in the local dialects. The written forms of local dialects are largely undeveloped.status: publishe

Should consent forms used in clinical trials be translated into the local dialects? A survey among past participants in rural Ghana.

BACKGROUND: Obtaining informed consent is part of the expression of the principle of participant autonomy during clinical trials. It is critical that participants understand the content of informed consent forms and remain in a position to seek independent advice on its content. We conducted a survey among past participants of a clinical trial in the Kassena-Nankana Districts of rural northern Ghana about the usefulness of informed consent forms that are written in the local dialects. The written forms of local dialects are largely undeveloped. METHOD: We contacted a randomly selected sample of caregivers whose children were enrolled in a completed clinical trial and interviewed them using a structured questionnaire. Analysis sought to determine participants' preference and whether or not they were likely to find confidants who will be able to read, understand and give advice on the content of the informed consent form to them when they take the informed consent forms home. RESULTS: We interviewed 394 caregivers, 88.6% of whom were women. About half (54%) of the respondents wanted the informed consent forms to be in the English language. Caregivers with higher than primary level education were more likely to prefer the informed consent form to be in English than those with no formal education (74% versus 26%, p = 0.04). The majority (85%) indicated that they would be able to find close confidants who would be able to read and explain it to them if it is in English. In contrast, only 8% thought they would be able to do the same if the informed consent form was written in the local language. Respondents were more likely to find close confidants to read and explain the informed consent form if it were written in English than if it were written in the local language (94% versus 19%, p value < 0.01). CONCLUSION: The practice of translating informed consent forms into undeveloped local dialects and giving such copies to trial participants to send home needs to be re-evaluated. In populations where the written forms of local dialects are undeveloped and literacy is low, the use of local dialect versions of informed consent forms could ironically enhance the vulnerability of trial participants