Eleanor Turyakira

Knowledge of obstetric danger signs and birth preparedness practices among women in rural Uganda

BackgroundImproving knowledge of obstetric danger signs and promoting birth preparedness practices are strategies aimed at enhancing utilization of skilled care in low-income countries. The aim of the study was to explore the association between knowledge of obstetric danger signs and birth preparedness among recently delivered women in south-western Uganda.MethodsThe study included 764 recently delivered women from 112 villages in Mbarara district. Community survey methods were used and 764 recently delivered women from 112 villages in Mbarara district were included in study. Interviewer administered questionnaire were used to collect data. Logistic regression analyses were conducted to explore the relationship between knowledge of key danger signs and birth preparedness.ResultsFifty two percent of women knew at least one key danger sign during pregnancy, 72% during delivery and 72% during postpartum. Only 19% had knowledge of 3 or more key danger signs during the three periods. Of the four birth preparedness practices; 91% had saved money, 71% had bought birth materials, 61% identified a health professional and 61% identified means of transport. Overall 35% of the respondents were birth prepared. The relationship between knowledge of at least one key danger sign during pregnancy or during postpartum and birth preparedness showed statistical significance which persisted after adjusting for probable confounders (OR 1.8, 95% CI: 1.2-2.6) and (OR 1.9, 95% CI: 1.2-3.0) respectively. Young age and high levels of education had synergistic effect on the relationship between knowledge and birth preparedness. The associations between knowledge of at least one key danger sign during childbirth or knowledge that prolonged labour was a key danger sign and birth preparedness were not statistically significant.ConclusionsThe prevalence of recently delivered women who had knowledge of key danger signs or those who were birth prepared was very low. Since the majority of women attend antenatal care sessions, the quality and methods of delivery of antenatal care education require review so as to improve its effectiveness. Universal primary and secondary education programmes ought to be promoted so as to enhance the impact of knowledge of key danger signs on birth preparedness practices.

Efficacy and safety of artemether–lumefantrine compared with quinine in pregnant women with uncomplicated Plasmodium falciparum malaria: an open-label, randomised, non-inferiority trial

BACKGROUND Malaria in pregnancy is associated with maternal and fetal morbidity and mortality. In 2006, WHO recommended use of artemisinin-based combination treatments during the second or third trimesters, but data on efficacy and safety in Africa were scarce. We aimed to assess whether artemether-lumefantrine was at least as efficacious as oral quinine for the treatment of uncomplicated falciparum malaria during the second and third trimesters of pregnancy in Mbarara, Uganda. METHODS We did an open-label, randomised, non-inferiority trial between October, 2006, and May, 2009, at the antenatal clinics of the Mbarara University of Science and Technology Hospital in Uganda. Pregnant women were randomly assigned (1:1) by computer generated sequence to receive either quinine hydrochloride or artemether-lumefantrine, and were followed up weekly until delivery. Our primary endpoint was cure rate at day 42, confirmed by PCR. The non-inferiority margin was a difference in cure rate of 5%. Analysis of efficacy was for all randomised patients without study deviations that could have affected the efficacy outcome. This study was registered with ClinicalTrials.gov, number NCT00495508. FINDINGS 304 women were randomly assigned, 152 to each treatment group. By day 42, 16 patients were lost to follow-up and 25 were excluded from the analysis. At day 42, 137 (99.3%) of 138 patients taking artemether-lumefantrine and 122 (97.6%) of 125 taking quinine were cured-difference 1.7% (lower limit of 95% CI -0.9). There were 290 adverse events in the quinine group and 141 in the artemether-lumefantrine group. INTERPRETATION Artemisinin derivatives are not inferior to oral quinine for the treatment of uncomplicated malaria in pregnancy and might be preferable on the basis of safety and efficacy. FUNDING Médecins Sans Frontières and the European Commission.

Influence of Birth Preparedness, Decision-Making on Location of Birth and Assistance by Skilled Birth Attendants among Women in South-Western Uganda

Introduction Assistance by skilled birth attendants (SBAs) during childbirth is one of the strategies aimed at reducing maternal morbidity and mortality in low-income countries. However, the relationship between birth preparedness and decision-making on location of birth and assistance by skilled birth attendants in this context is not well studied. The aim of this study was to assess the influence of birth preparedness practices and decision-making and assistance by SBAs among women in south-western Uganda. Methods Community survey methods were used to identify 759 recently delivered women from 120 villages in rural Mbarara district. Interviewer-administered questionnaires were used to collect data. Logistic regression analyses were conducted to assess the relationship between birth preparedness, decision-making on location of birth and assistance by SBAs. Results 35% of the women had been prepared for childbirth and the prevalence of assistance by SBAs in the sample was 68%. The final decision regarding location of birth was made by the woman herself (36%), the woman with spouse (56%) and the woman with relative/friend (8%). The relationships between birth preparedness and women decision-making on location of birth in consultation with spouse/friends/relatives and choosing assistance by SBAs showed statistical significance which persisted after adjusting for possible confounders (OR 1.5, 95% CI: 1.0–2.4) and (OR 4.4, 95% CI: 3.0–6.7) respectively. Education, household assets and birth preparedness showed clear synergistic effect on the relationship between decision-maker on location of birth and assistance by SBAs. Other factors which showed statistical significant relationships with assistance by SBAs were ANC attendance, parity and residence. Conclusion Women’s decision-making on location of birth in consultation with spouse/friends/relatives and birth preparedness showed significant effect on choosing assistance by SBAs at birth. Education and household assets ownership showed a synergistic effect on the relationship between the decision-maker and assistance by SBAs.

Impact of malaria during pregnancy on pregnancy outcomes in a Ugandan prospective cohort with intensive malaria screening and prompt treatment

BackgroundMalaria in pregnancy (MiP) is a major public health problem in endemic areasof sub-Saharan Africa and has important consequences on birth outcome.Because MiP is a complex phenomenon and malaria epidemiology is rapidlychanging, additional evidence is still required to understand how best tocontrol malaria. This study followed a prospective cohort of pregnant womenwho had access to intensive malaria screening and prompt treatment toidentify factors associated with increased risk of MiP and to analyse howvarious characteristics of MiP affect delivery outcomes.MethodsBetween October 2006 and May 2009, 1,218 pregnant women were enrolled in aprospective cohort. After an initial assessment, they were screened weeklyfor malaria. At delivery, blood smears were obtained from the mother,placenta, cord and newborn. Multivariate analyses were performed to analysethe association between mothers’ characteristics and malaria risk, aswell as between MiP and birth outcome, length and weight at birth. Thisstudy is a secondary analysis of a trial registered with ClinicalTrials.gov,number NCT00495508.ResultsOverall, 288/1,069 (27%) mothers had 345 peripheral malaria infections. Therisk of peripheral malaria was higher in mothers who were younger, infectedwith HIV, had less education, lived in rural areas or reported no bed netuse, whereas the risk of placental infection was associated with morefrequent malaria infections and with infection during late pregnancy. Therisk of pre-term delivery and of miscarriage was increased in mothersinfected with HIV, living in rural areas and with MiP occurring within twoweeks of delivery.In adjusted analysis, birth weight but not length was reduced in babies ofmothers exposed to MiP (−60g, 95%CI: -120 to 0 for at least oneinfection and -150 g, 95%CI: -280 to −20 for >1 infections).ConclusionsIn this study, the timing, parasitaemia level and number ofperipherally-detected malaria infections, but not the presence of fever,were associated with adverse birth outcomes. Hence, prompt malaria detectionand treatment should be offered to pregnant women regardless of symptoms orother preventive measures used during pregnancy, and with increased focus onmothers living in remote areas.

Heterogeneous decrease in malaria prevalence in children over a six-year period in south-western Uganda

BackgroundMalaria is a major public health problem, especially for children. However, recent reports suggest a decline in the malaria burden. The aim of this study was to assess the change in the prevalence of malaria infection among children below five years of age between 2004 and 2010 in a mesoendemic area of Uganda and to analyse the risk factors of malaria infection.MethodsTwo cross-sectional surveys were conducted in 2004 and in 2010 at the end of the rainy and dry seasons to measure the prevalence of P. falciparum infection among children less than five years of age. Rapid diagnostic tests and blood smears were used to diagnose malaria infection. In 2010, sampling was stratified by urban and rural areas. In each selected household, knowledge of malaria and bed nets, and bed net ownership and use, were assessed.ResultsIn 2004 and 2010, respectively, a total of 527 and 2,320 (999 in the urban area and 1,321 in rural areas) children less than five years old were enrolled. Prevalence of malaria infection declined from 43% (95% CI: 34-52) in 2004, to 23% (95% CI: 17-30) in rural areas in 2010 and 3% (95% CI: 2-5) in the urban area in 2010. From the rainy to dry season in 2010, prevalence decreased from 23% to 10% (95% CI: 6-14) in rural areas (P = 0.001) and remained stable from 3% to 4% (95% CI: 1-7) in the urban area (P = 0.9). The proportion of households reporting ownership and use of at least one bed net increased from 22.9% in 2004 to 64.7% in the urban area and 44.5% in rural areas in 2010 (P < 0.001). In 2010, the risk of malaria infection was consistently associated with child age and household wealth. In rural areas, malaria infection was also associated with geographic factors.ConclusionsThis study reports a significant drop in the prevalence of malaria infection among children below five years of age, paralleled by an uptake in bed-net use. However, prevalence remains unacceptably high in rural areas and is strongly associated with poverty.

Population pharmacokinetics of Artemether and dihydroartemisinin in pregnant women with uncomplicated Plasmodium falciparum malaria in Uganda

BackgroundMalaria in pregnancy increases the risk of maternal anemia, abortion and low birth weight. Approximately 85.3 million pregnancies occur annually in areas with Plasmodium falciparum transmission. Pregnancy has been reported to alter the pharmacokinetic properties of many anti-malarial drugs. Reduced drug exposure increases the risk of treatment failure. The objective of this study was to evaluate the population pharmacokinetic properties of artemether and its active metabolite dihydroartemisinin in pregnant women with uncomplicated P. falciparum malaria in Uganda.MethodsTwenty-one women with uncomplicated P. falciparum malaria in the second and third trimesters of pregnancy received the fixed oral combination of 80 mg artemether and 480 mg lumefantrine twice daily for three days. Artemether and dihydroartemisinin plasma concentrations after the last dose administration were quantified using liquid chromatography coupled to tandem mass-spectroscopy. A simultaneous drug-metabolite population pharmacokinetic model for artemether and dihydroartemisinin was developed taking into account different disposition, absorption, error and covariate models. A separate modeling approach and a non-compartmental analysis (NCA) were also performed to enable a comparison with literature values and different modeling strategies.ResultsThe treatment was well tolerated and there were no cases of recurrent malaria. A flexible absorption model with sequential zero-order and transit-compartment absorption followed by a simultaneous one-compartment disposition model for both artemether and dihydroartemisinin provided the best fit to the data. Artemether and dihydroartemisinin exposure was lower than that reported in non-pregnant populations. An approximately four-fold higher apparent volume of distribution for dihydroartemisinin was obtained by non-compartmental analysis and separate modeling compared to that from simultaneous modeling of the drug and metabolite. This highlights a potential pitfall when analyzing drug/metabolite data with traditional approaches.ConclusionThe population pharmacokinetic properties of artemether and dihydroartemisinin, in pregnant women with uncomplicated P. falciparum malaria in Uganda, were described satisfactorily by a simultaneous drug-metabolite model without covariates. Concentrations of artemether and its metabolite dihydroartemisinin were relatively low in pregnancy compared to literature data. However, this should be interpreted with caution considered the limited literature available. Further studies in larger series are urgently needed for this vulnerable group.

Population Pharmacokinetics of Lumefantrine in Pregnant and Nonpregnant Women With Uncomplicated Plasmodium falciparum Malaria in Uganda

Pregnancy alters the pharmacokinetic properties of many antimalarial compounds. The objective of this study was to evaluate the pharmacokinetic properties of lumefantrine in pregnant and nonpregnant women with uncomplicated Plasmodium falciparum malaria in Uganda after a standard fixed oral artemether–lumefantrine treatment. Dense venous (n = 26) and sparse capillary (n = 90) lumefantrine samples were drawn from pregnant patients. A total of 17 nonpregnant women contributed with dense venous lumefantrine samples. Lumefantrine pharmacokinetics was best described by a flexible absorption model with multiphasic disposition. Pregnancy and body temperature had a significant impact on the pharmacokinetic properties of lumefantrine. Simulations from the final model indicated 27% lower day 7 concentrations in pregnant women compared with nonpregnant women and a decreased median time of 0.92 and 0.42 days above previously defined critical concentration cutoff values (280 and 175 ng/ml, respectively). The standard artemether–lumefantrine dose regimen in P. falciparum malaria may need reevaluation in nonimmune pregnant women.

Performance of a Histidine-Rich Protein 2 Rapid Diagnostic Test, Paracheck Pf®, for Detection of Malaria Infections in Ugandan Pregnant Women

Improved laboratory diagnosis is critical to reduce the burden of malaria in pregnancy. Peripheral blood smears appear less sensitive than Plasmodium falciparum histidine-rich protein 2-based rapid diagnostic tests (RDTs) for placental malaria infections in studies conducted at delivery. In this study, 81 women in Uganda in the second or third trimester of pregnancy were followed-up until delivery. At each visit, peripheral blood was tested by blood smear, RDT, and nested species-specific polymerase chain reaction (PCR). Sensitivity and specificity of the tests was calculated with PCR, which detected 22 infections of P. falciparum, as the gold standard. The sensitivity and specificity of blood smears were 36.4% (95% confidence interval [CI] = 18.0-59.2%) and 99.6% (95% CI = 97.7-100%), respectively. The corresponding values for RDT were 31.8% (95% CI = 14.7-54.9%) and 100% (95% CI = 98.3-100%). The RDTs could replace blood smears for diagnosis of malaria in pregnancy by virtue of their relative ease of use. Field-based sensitive tests for malaria in pregnancy are urgently needed.

Individual and health facility factors and the risk for obstructed labour and its adverse outcomes in south-western Uganda

BackgroundObstructed labour is still a major cause of maternal morbidity and mortality and of adverse outcome for newborns in low-income countries. The aim of this study was to investigate the role of individual and health facility factors and the risk for obstructed labour and its adverse outcomes in south-western Uganda.MethodsA review was performed on 12,463 obstetric records for the year 2006 from six hospitals located in south-western Uganda and 11,180 women records were analysed. Multivariate logistic regression analyses were applied to control for probable confounders.ResultsPrevalence of obstructed labour for the six hospitals was 10.5% and the main causes were cephalopelvic disproportion (63.3%), malpresentation or malposition (36.4%) and hydrocephalus (0.3%). The risk of obstructed labour was statistically significantly associated with being resident of a particular district [Isingiro] (AOR 1.39, 95% CI: 1.04-1.86), with nulliparous status (AOR 1.47, 95% CI: 1.22-1.78), having delivered once before (AOR 1.57, 95% CI: 1.30-1.91) and age group 15-19 years (AOR 1.21, 95% CI: 1.02-1.45). The risk for perinatal death as an adverse outcome was statistically significantly associated with districts other than five comprising the study area (AOR 2.85, 95% CI: 1.60-5.08) and grand multiparous status (AOR 1.89, 95% CI: 1.11-3.22). Women who lacked paid employment were at increased risk of obstructed labour. Perinatal mortality rate was 142/1000 total births in women with obstructed labour compared to 65/1000 total births in women without the condition. The odds of having maternal complications in women with obstructed labour were 8 times those without the condition. The case fatality rate for obstructed labour was 1.2%.ConclusionsIndividual socio-demographic and health system factors are strongly associated with obstructed labour and its adverse outcome in south-western Uganda. Our study provides baseline information which may be used by policy makers and implementers to improve implementation of safe motherhood programmes.

Different methodological approaches to the assessment of in vivo efficacy of three artemisinin-based combination antimalarial treatments for the treatment of uncomplicated falciparum malaria in African children

BackgroundUse of different methods for assessing the efficacy of artemisinin-based combination antimalarial treatments (ACTs) will result in different estimates being reported, with implications for changes in treatment policy.MethodsData from different in vivo studies of ACT treatment of uncomplicated falciparum malaria were combined in a single database. Efficacy at day 28 corrected by PCR genotyping was estimated using four methods. In the first two methods, failure rates were calculated as proportions with either (1a) reinfections excluded from the analysis (standard WHO per-protocol analysis) or (1b) reinfections considered as treatment successes. In the second two methods, failure rates were estimated using the Kaplan-Meier product limit formula using either (2a) WHO (2001) definitions of failure, or (2b) failure defined using parasitological criteria only.ResultsData analysed represented 2926 patients from 17 studies in nine African countries. Three ACTs were studied: artesunate-amodiaquine (AS+AQ, N = 1702), artesunate-sulphadoxine-pyrimethamine (AS+SP, N = 706) and artemether-lumefantrine (AL, N = 518).Using method (1a), the day 28 failure rates ranged from 0% to 39.3% for AS+AQ treatment, from 1.0% to 33.3% for AS+SP treatment and from 0% to 3.3% for AL treatment. The median [range] difference in point estimates between method 1a (reference) and the others were: (i) method 1b = 1.3% [0 to24.8], (ii) method 2a = 1.1% [0 to21.5], and (iii) method 2b = 0% [-38 to19.3].The standard per-protocol method (1a) tended to overestimate the risk of failure when compared to alternative methods using the same endpoint definitions (methods 1b and 2a). It either overestimated or underestimated the risk when endpoints based on parasitological rather than clinical criteria were applied. The standard method was also associated with a 34% reduction in the number of patients evaluated compared to the number of patients enrolled. Only 2% of the sample size was lost when failures were classified on the first day of parasite recurrence and survival analytical methods were used.ConclusionThe primary purpose of an in vivo study should be to provide a precise estimate of the risk of antimalarial treatment failure due to drug resistance. Use of survival analysis is the most appropriate way to estimate failure rates with parasitological recurrence classified as treatment failure on the day it occurs.