Perspectives from Young South African and Zimbabwean Women on Attributes of Four (Placebo) Vaginal Microbicide Delivery Forms.

INTRODUCTION: Incorporating end-user input into the design of new vaginal microbicides for women is key to optimizing their uptake, consistent use, and, ultimately, success in combatting the heterosexual HIV epidemic. METHODS: The Quatro Study assessed four placebo forms of vaginally inserted HIV-microbicides among young microbicide-naïve African women: on-demand film, insert and gel, and monthly ring. Participants randomly used each product for 1 month and provided product satisfaction ratings (1-5 scale), and opinions on product attributes and potential alternative designs. Qualitative data were collected through focus group discussions at study exit. Multivariable associations between attribute opinions and overall product rating were examined using Poisson regression models with robust standard errors to assess the attributes most influential to satisfaction. RESULTS: Overall opinions of products and their individual attributes were generally positive; all products were rated either 4 or a 5 by ≥ 50% of participants. Attributes related to ease of use and interference with normal activities were the most salient predictors of satisfaction. Preferences for duration of use tended toward relatively shorter use periods for the ring (i.e., 1-3 months vs. 12 months) and for coitally independent dosing for the on-demand products. CONCLUSIONS: How well a product fit in with participants' lifestyles was important to their overall satisfaction. For on-demand products, greater flexibility around timing of use was desired, to avoid coital dependency of the dosing.

No associations of human pulmonary tuberculosis with Sp110 variants.

BACKGROUND: After a recent report on the role of the Ipr1 gene in mediating innate immunity in a mouse model of Mycobacterium tuberculosis infection, the human Ipr1 homologue, Sp110, was considered a promising candidate for an association study in human tuberculosis. METHODS: In a sample of >1000 sputum positive, HIV negative West African patients with pulmonary tuberculosis and >1000 exposed, apparently healthy controls, we have genotyped 21 Sp110 gene variants that were either available from public databases, including HapMap data, or identified by DNA re-sequencing. RESULTS: No significant differences in the frequencies of any of the 21 variants were observed between patients and controls. This applied also for HapMap tagging variants and the corresponding haplotypes, when including sliding window analyses with three adjacent variants, and when stratifying controls for positivity and negativity according to the results of intradermal tuberculin (purified protein derivative, PPD) skin tests. DNA re-sequencing revealed 13 novel Sp110 variants in the 5'-UTR, exons, and adjacent intronic regions. CONCLUSIONS: Based on the results obtained in this case-control study, the hypothesis that Sp110 variants and haplotypes might be associated with distinct phenotypes of human M tuberculosis infection is doubtful.

The species Mycobacterium africanum in the light of new molecular markers.

The findings of recent studies addressing the molecular characteristics of Mycobacterium tuberculosis complex isolates have initiated a discussion on the classification of M. africanum, especially of those isolates originating from East Africa (cluster F, subtype II) and displaying phenotypic and biochemical characteristics more similar to those of M. tuberculosis. To further address this question, we analyzed a representative collection of 63 M. tuberculosis complex strains comprising 30 M. africanum subtype I strains, 20 M. africanum subtype II strains, 10 randomly chosen M. tuberculosis isolates, and type strains of M. tuberculosis, M. bovis, and M. africanum for the following biochemical and molecular characteristics: single-nucleotide polymorphisms (SNPs) in gyrB and narGHJI and the presence or absence of RD1, RD9, and RD12. For all molecular markers analyzed, subtype II strains were identical to the M. tuberculosis strains tested. In contrast, the subtype I strains as well as the M. africanum type strain showed unique combinations of SNPs in gyrB and genomic deletions (the absence of RD9 and the presence of RD12), which proves their independence from M. tuberculosis and M. bovis. Accordingly, all subtype I strains displayed main biochemical characteristics included in the original species description of M. africanum. We conclude that the isolates from West Africa were proved to be M. africanum with respect to the phenotypic and genetic markers analyzed, while the isolates from East Africa must be regarded as phenotypic variants of M. tuberculosis (genotype Uganda). We propose the addition of the molecular characteristics defined here to the species description of M. africanum, which will allow clearer species differentiation in the future.

Factors influencing participation in national immunization days in Kumasi, Ghana.

A study of the factors influencing participation in national immunization days (NID) in Kumasi, Ghana was carried out between the April and June of 1999. Polio-immunization coverage during NID was assessed among children aged < 5 years; > 90% of these children had received polio vaccinations on both of the two previous NID. The mothers who participated most in the NID tended to be those who were better educated and Ghanaian. Mothers who were salaried workers participated fully in NID. Radio and television played a major role in public education about NID, whereas the attitude of health workers was a strong factor that prevented many mothers/caregivers from bringing their children to be immunized. The coverage of the Expanded Programme on Immunization (EPI) was assessed in children aged 12-23 months; nearly 70% of these children were fully immunized. BCG had the highest coverage (97.0%) and measles the lowest (79%). Again, full coverage of the children of mothers who had been educated beyond primary level was higher than that of the other children (75.9% v. 65.2%), and coverage of the children of Ghanaian women was higher than that of the others (70.8%. v. 50.0%). Although the mothers/caregivers raised concerns about the costs of the routine immunizations, these charges apparently did not prevent them from taking their children to be immunized. NID complement the routine EPI-associated work in Ghana, increasing overall polio-immunization coverage. The results of this study will be used to improve the overall performance of immunization programmes, especially in the Kumasi metropolis. Hopefully, sustained, increased polio-immunization coverage will contribute positively towards polio eradication in Ghana.

Spleen size determined by ultrasound in patients with sickle cell trait, HbAC trait and glucose-6-phosphate-dehydrogenase deficiency in a malaria hyperendemic area (Ashanti Region, Ghana).

The occurrence of enlarged spleens and its age distribution has long been used as a crude measure to estimate malaria endemicity in cross-sectional surveys. Spleen size, however, is influenced by several variables that should be considered if they are observed in a population under study. We hypothesized that spleen indices are dependent on distinct red blood cell polymorphisms. Accordingly, we expected a lower prevalence of splenomegaly among patients with the sickle-cell trait (HbAS), HbAC trait and G6PD deficiency than in patients without red cell disorders, possibly due to the lower incidence of malaria attacks in these individuals. In our survey, however, spleen rates and sizes did not differ significantly between HbAA-, HbAS- and HbAC-positive individuals. Furthermore, enlargement of spleens was found at similar frequencies in persons with and without glucose-6-phosphate-dehydrogenase (G6PD)-deficiency (G6PD-A(-)).

The impact of insecticide-treated bednets on malaria and anaemia in pregnancy in Kassena-Nankana district, Ghana: a randomized controlled trial.

The impact of insecticide-treated bednet use on malaria and anaemia in pregnancy was assessed, as a supplementary study, in a major WHO/TDR-supported bednet trial in northern Ghana between July 1994 and April 1995. The study area was divided into 96 clusters of compounds, with 48 clusters being randomly allocated to intervention. All pregnant women were included in the study but the focus was on primigravidae and secundigravidae. 1961 pregnant women were recruited into the study--1033 (52.7%) in the treated bednet group and 928 (47.3%) in the no net group. 1806 (92.1%) had blood taken for malaria microscopy and haemoglobin determination in the third trimester. Pregnancy outcomes were reported for 847 women. The characteristics of women in intervention and control groups were comparable. The odds ratios, with 95% confidence interval (CI), for different study endpoints were, for Plasmodium falciparum parasitaemia--0.89 (0.73, 1.08), for anaemia--0.88 (0.70, 1.09), for low birthweight (LBW)--0.87 (0.63, 1.19), indicating no benefit for treated bednet use. Effective net use by parity varied from 42% in primigravidae to 63% in multigravidae, in spite of free nets and insecticide impregnation. The main reasons for not using a net were warm weather and perceived absence of mosquito biting. Chloroquine use in pregnancy was low and comparable in both groups. Implications of findings for malaria control in pregnancy and further research are discussed.

Malariometric update for the rainforest and savanna of Ashanti region, Ghana.

The epidemiological features of human infection with Plasmodium were studied in a community-based survey of 35 villages in the Ashanti region of Ghana. The overall prevalences of malarial parasitaemia in subjects aged > or = 2 years were 50.72% in forest areas and 49.72% in savanna. Plasmodium falciparum was the predominant species everywhere, followed by P. malariae in the savanna and P. ovale in the forest. The highest prevalence of asexual parasitaemia (of any species) occurred in the youngest age-group (2-9 years). The geometric mean intensities of parasitaemia among the parasitaemic (i.e. the parasite density indices) were 557, 640 and 452 parasites/microliter for P. falciparum, P. ovale and P. malariae, respectively. For each Plasmodium species encountered, the mean intensity of parasitaemia decreased with age. Mixed infections were observed in 24% and 30% of the parasitaemic subjects from the forest and savanna, respectively. Those infected with P. falciparum were more likely to carry P. ovale (odds ratio = 2.02) or P. malariae (odds ratio = 2.63) than those who were not infected with P. falciparum. Mean intensities of the parasitaemias in mixed infections were substantially higher than the sums of those in the corresponding single infections. When comparing villages, parasite density indices were found to be correlated with the prevalences of parasitaemia (r = 0.56).

Referrals for obstetrical complications from Ejisu district, Ghana.

A study of referrals due to obstetrical complications from the Ejisu district, Ashanti region, Ghana was done to determine the institutions that receive them, their outcome and the effectiveness of the referral system. This formed part of a multidisciplinary research on the prevention of maternal mortality in the district. It covered 15 health facilities in the district. The receiving institutions identified in the study were Komfo Anokye teaching Hospital (KATH) in Kumasi, Agogo Presbyterian Hospital in the neighbouring Ashanti Akim district and the St. Michael's Hospital at Pramso in the same district. In the period under review, there were 192 referrals from the district, 139 to KATH with 87 (63%) reporting, 19 to Pramso with 14 (74%) reporting and 34 to Agogo with 17 (50%) reporting. The 3 most important complications referred were maternal haemorrhage (29%), high-risk pregnancy (24%) and delayed second stage (21%). The referring institutions had a defaulting rate varying from 8-56% with a median of 42%. This study did not specifically investigate the factors influencing the high defaulting rates in some institutions. However, focus-group discussions (FGDs) held in selected communities revealed the following factors as inhibiting the utilization of health services: * prohibitive hospital fees; * illegal fees and bribes; * irregular transport and uncooperative drivers; * poor and unmotorable roads; * lack of drugs and essential supplies and; * negative staff attitudes. Those health facilities with low defaulting rates had their own transport or were close to major trunk roads. From the study, the referral system was very weak. It is also possible that some of the referrals reported at the receiving institutions but were not classified as such. Interventions to improve the situation are currently being implemented.

Upgrading obstetric care at the health center level, Juaben, Ghana. The Kumasi PMM Team.

PRELIMINARY STUDIES: Inventory and observations at Juaben Teaching Health Center (JTHC) revealed an inability to treat obstetric complications. Women with complications needed to be referred to other institutions, resulting in delays. INTERVENTIONS: During 1993 and 1994, an operating theater and blood bank were established and equipped, the maternity refurbished, and a revolving drug fund created. A physician was posted and trained in obstetrics, and midwives were trained in life-saving skills. A running water supply was established. Subsequent community interventions focused on improving access and reducing the delay in seeking care. RESULTS: The number of women with complications coming for care increased almost three-fold, from 26 in 1993 to 73 in 1995 and the proportion of these who were referred for treatment dropped from 42 to 14%. Surgical obstetric procedures performed at JTHC increased from 23 in 1993 to 90 in 1995. Midwives performed 32% of manual removals, 58% of vacuum extractions and 98% of episiotomy repairs. No deaths occurred among the women treated. COSTS: The cost of improvements was approximately US $30,000, mostly for equipment and supplies. Forty percent came from project funds, 36% from non-governmental organizations (NGOs), 15% from government and 9% from community members. The salary of the new physician cost an additional $4700 annually. CONCLUSIONS: Modest improvements can increase the provision and utilization of emergency obstetric care. Collaboration with NGOs, government and the community can be beneficial.

Community education to improve utilization of emergency obstetric services in Ghana. The Kumasi PMM Team.

PRELIMINARY STUDIES: Focus group studies in the Ashanti region showed that people avoided utilizing health facilities because of lack of confidence in the services and concern about the availability of drugs and supplies, among other reasons. INTERVENTIONS: After services at the health center were upgraded, community education activities began in early 1994. These activities were carried out through existing mechanisms--e.g. Ministry of Health (MOH) outreach workers and village health workers, public health nurses and midwives, and village health committees. They addressed a variety of audiences, including women's and church groups, emphasizing early recognition and treatment of obstetric complications, and the improved availability of services. RESULTS: The number of women with obstetric complications admitted to the health center rose from 26 in 1993 to 73 in 1995. It was the impression of the health center staff that women were also coming for treatment more promptly. COSTS: The cost of this intervention was US$1950. This was mostly project funds, with the government and community together contributing approximately one-fifth. CONCLUSIONS: Once services are available, community education and information activities can enhance utilization. The cost of such activities can be reduced, and sustainability promoted, by involving MOH personnel and community groups.

Utilization of maternal health services in Ejisu District, Ghana.

A study on the utilization of maternal health services in Ejisu district of Ghana was carried out in January and February 1990. 1200 women aged between 15 and 49 were interviewed in 80 communities. The findings of the study indicated that over 50% of respondents married under 20 years, 70% of them attended antenatal clinic at least 4 times in their last pregnancy, over 80% had their last delivery in a health facility and over 80% knew about at least one modern method of family planning. Only 5.5% were currently using a modern family planning method. 90% of them were willing to stay in a maternity waiting home if advised to do so. Most would be prepared to stay for a month or 2. 20% of the respondents knew about local herbal preparations used for first aid in bleeding in pregnancy, although they would seek definitive treatment at a health facility. From the study, some women were not using the services. These would have to be reached through improving the quality of care in health facilities and increasing community awareness on maternal health in order to improve accessibility and utilization further.

PIP: This operations research project on the use of maternal health care services in Ejisu district in Ghana was performed during January and February 1990. The sample was comprised of 1200 women from 80 communities (population 131,199 persons in 1984) in the district, which has 19 health facilities (a Catholic mission hospital, 8 government health centers, 5 mission clinics, and 3 private maternity homes serving a population in 160 communities). Retrospective data was collected on health service use during January 1985-December 1989. Characteristics of the sample population included 59% 20-34 years old, 11% younger than 20, and 33% with no formal education. 37.9% were farmers, 26.7% were housewives, and 25% were traders. 74% were married. 50.3% married before the age of 20. 70.9% made at least 4 visits for prenatal care before their last pregnancy. 17.3% did not receive any prenatal care. 33.3% delivered at a health center. 28% used a Government Maternity Home, 22% used a hospital, and 13% relied on traditional birth attendants at home. 29% (349 women) reported complaints during their last pregnancy. 85.5% knew at least 1 method of contraception. 5.5% were current users of modern contraception, of which the pill was the most popular (45.4% of users). Treatment for bleeding during pregnancy was reported by 16.7% of the sample to involve eating a ripe banana or a banana in combination with cassava products. External use of plantain leaves or sanitary pads was also mentioned. These treatments were considered as first aid and not definitive treatment. 90% indicated a willingness to stay in a maternity waiting home if advised to do so. 58% would be able to stay 1 month, 21% would stay 2 months, and 21% would stay 3 or more months. Effective community education and social mobilization is still needed in order to attract those not using services.

Maternal mortality and related factors in Ejisu District, Ghana.

A community-based survey on maternal mortality was carried out in the Ejisu health district of Ghana in January and February 1990 to identify all women who died in pregnancy, delivery or the puerperium from January 1985 to December 1989, determine their characteristics, the presumptive causes of death and related factors. Forty-four women who died in pregnancy, delivery or the puerperium were identified over the stated period. 59% were aged between 20 and 34 years. Eighty-two percent were married and sixty-six percent had at least primary education. Based on an average crude birth rate of 40 per 1000 population for the district over the period, the lowest maternal mortality rate occurred in 1988, 120 per 100,000 total births and the highest occurred a year later, 235 per 100,000 total births. The main presumptive causes of maternal mortality in the district were postpartum haemorrhage 45.5%, jaundice in pregnancy 22.7%, obstructed labour 6.8%, eclampsia 6.8% and fever 4.6%. 59% of them died in a hospital, 2% died at a Government Maternity Home and 7% died during referral from health facilities in the district. Thirty-four percent of the women who died did not attend any antenatal clinic. The actual number of deaths may be underestimated due to the sampling method used and the difficulties encountered in linking survey data with hospital records. Based on the survey findings and other related PMM research, plans have been developed to reduce maternal mortality in the district as outline in the conclusion.

PIP: A community-based survey was conducted among 1200 reproductive age women living in 80 out of 160 communities in Ejisu health district in Ghana during January-February 1990. Retrospective data was collected for the period January 1985-December 1989. Data was analyzed in order to determine maternal mortality, causes of death, and the characteristics of the mothers who died. The sample community was comprised of 223,632 persons in 1990. 44 women were identified as having died in pregnancy, delivery, or postpartum. 59% were 20-34 years old, and 41% were in high-risk age groups. 65.9% had at least some primary education, and 81.8% were married at the time of death. 27.3% were childless at the time of death. Maternal deaths were distributed by year as follows: 9 deaths in 1985, 10 in 1986, 7 in 1987, 6 in 1988, and 12 in 1989. The estimated maternal mortality was 211 per 100,000 live births in 1986 and 235 per 100,000 in 1989. The 4-year average was 181 per 100,000. 34% of deaths were to women who had not received any prenatal care in the last pregnancy. Almost 75% died during delivery. 59% died in a hospital, 7% during a referral to a hospital, and 2% at a Government Maternity Home. Over 66% died after reaching a health facility. 27% died at home. 2% died while under the care of a local traditional birth attendant. Causes of maternal death were postpartum hemorrhage (45.5%), jaundice in pregnancy (22.7%), obstructed labor (6.8%), eclampsia (6.8%), and fever (4.6%). 2.3% of deaths were attributed to antepartum hemorrhage, ectopic pregnancy, and septic abortion. Prenatal care alone is not sufficient to prevent some deaths. The high mortality rate during delivery is a justification to improve the quality of care during delivery at all levels of the district health system. Listed are 9 potential interventions to reduce maternal mortality, including: establishing operating facilities at local health centers and maintaining a resident doctor for obstetric emergencies.

Maternal mortality due to hemorrhage in Ghana.

OBJECTIVE: This hospital-based review of maternal mortality due to hemorrhage in Kumasi, Ghana was undertaken to determine the factors related to and influencing cases of fatal maternal hemorrhage. METHOD: The review was based on inpatient case notes, labor ward delivery notes, and operative records at the Maternity Block of the Komfo Anokye Teaching Hospital, Kumasi. The diagnoses were based on International Classification of Diseases (ICD) 9th and 10th editions. It covered the period 1981 to 1989. RESULT: It was observed that maternal hemorrhage accounted for over 40% of all obstetric complications admitted and also 27% of all maternal deaths in the period under review. However, the case fatality rate for maternal hemorrhage decreased from 1.34% in 1981 to 0.7% in 1989. The cesarean section rate increased from 6.7% in 1981 to 9.1% in 1989. The maternal mortality rate over the period was 1140 per 100,000 births. CONCLUSION: Based on this review and other related research, the following interventions have been planned for implementation in order to improve the situation: improving staff-patient relationship through training in interpersonal skills; ensuring 24-h availability of drugs, supplies and blood; establishment of a resuscitation unit at the casualty department so that first aid can be provided to patients with obstetric emergencies before transfer to the wards; establishment of a maternity care monitoring system to continually improve the quality of care; introduction of confidential enquiry into all maternal deaths in order to reduce their incidence. A monitoring and evaluation plan has been developed to assess regularly progress on implementation. Although, maternal deaths are due to multifactorial causes, it is hoped that these interventions, if successfully implemented, will contribute significantly towards the reduction of maternal deaths due to institutional factors, especially direct obstetric causes like maternal hemorrhage.

Antihyperglycemic activity of novel naphthalenyl 3H-1,2,3,5-oxathiadiazole 2-oxides.

A series of naphthalenyl 3H-1,2,3,5-oxathiadiazole 2-oxides was prepared and tested for antihyperglycemic activity in the db/db mouse, a model for type 2 (non-insulin dependent) diabetes mellitus. Substitution at the 1-, 5-, or 8-positions of the naphthalene ring with a halogen was found to be beneficial to antihyperglycemic activity. 4-[(5-Chloronaphthalen-2-yl)methyl]-3H-1,2,3,5-oxathiadiazole++ + 2-oxide (45), one of the most potent compounds in this series, was selected for further pharmacological evaluation.