The impact of vitamin D on the innate immune response to uropathogenic Escherichia coli during pregnancy.

Urinary tract infections are highly common during pregnancy, and can cause serious complications for the mother and baby. Vitamin D, predominantly obtained from the sunlight, is known to have an effect on the urothelium, with immunomodulatory capacity against Escherichia coli infection. However, its influence at this site remains to be further explored. This study therefore investigated its impact during pregnancy in a population of women who have the possibility of adequate year-round sun exposure. Serum from pregnant Ugandan women (n = 32) in each trimester of pregnancy, from women after delivery (n = 29) and from never-pregnant controls (n = 25) was collected. 25-Hydroxyvitamin D (25-OHD), cathelicidin LL-37, human ß-defensin 2, interleukin (IL)-8 and soluble CD14 serum concentrations were measured by chemiluminescence immunoassay or ELISA. The ability of serum to inhibit E. coli growth was tested. The immunomodulatory capacities of these serum samples and 1,25-dihydroxyvitamin D3 were investigated in urothelial cells. Increases in 25-OHD and LL-37 levels were observed as pregnancy progressed, peaking in the third trimester. Serum 25-OHD levels were higher in multigravidae than in primigravidae, and correlated positively with maternal age. IL-8 levels were lower in the third trimester than in the first trimester, increased after delivery, but remained below those of never-pregnant women. Similarly, soluble CD14 concentrations increased after delivery. As gestation advanced, serum had an increased capacity to inhibit E. coli growth. In vitro, it modulated the IL-8 response to infection in a vitamin D concentration-dependent manner. Our findings demonstrate that increasing vitamin D levels as pregnancy advances modulate the innate immune system towards a protective response to infection.

Difference in Risk Factors for Breast Cancer by ER Status in an Indigenous African Population.

Introduction. Breast cancer is the commonest cancer among women globally. In Uganda, it is on the rise, projected at a 4.5% annual ASR increase (age standardized incidence rate). The reasons for this steep increase are not fully established. In the recent past, gene profiling in tumor tissues suggests that breast cancers are divided into subtypes dependent on the presence or absence of oestrogen receptor, progesterone, and human epidermal growth factor receptor 2 (HER 2). These subtypes do have distinctive clinical outcomes and perhaps risk factors from past studies. There is paucity of data on hormonal receptor status and the traditionally known risk factors in sub-Saharan Africa. The purpose of this study therefore was to establish the differences between ER status and the traditionally known risk factors for breast cancer in Uganda. Methods. An observational analytical hospital, based study, carried out at Makerere University, College of Health Sciences. Formalin fixed and paraffin imbedded sections were prepared for haemotoxylin and eosin (H&E) stains and immunohistochemistry (IHC). Ethical approval was obtained. Results. A total of 113 women were recruited. Mean age was 45 years (SD14). There were no significant differences in selected risk factors (setting, age, contraceptive use, parity, breast feeding, or menarche) by ER status although ER negative tumors had significantly higher grade tumors (by a factor of two) compared to ER positive tumors. Conclusion. There were no significant differences among risk factors by ER status contrary to what several other studies suggest. The manifestation of breast cancer in Africa warrants further extensive inquiry.

Self-reported sexual behaviour among adolescent girls in Uganda: reliability of data debated.

OBJECTIVE: To compare self-reported information about sexual behaviour in a research interview to information retrieved during a clinical consultation. METHOD: 595 sexually experienced women below 20 years, were interviewed by a social worker about genital symptoms and sexual behaviour. A midwife interviewed, examined, and took vaginal samples for gonorrhoea and chlamydia. Four questions were embedded in both the social workers interviews and among midwife's questions. The women were asked if they perceived their latest /current partner to be faithful, if he had complained about any genital symptoms, if a condom was used at latest sexual intercourse and if the woman knew her HIV status. RESULTS: The prevalence of gonorrhoea and/or chlamydia was 7.1% but for women who reported that their partner had complained about genital symptoms it was significantly higher. Agreement between answers given in the research interview and to the midwife was good for HIV status but only fair or moderate for perceived faithfulness, partner's symptoms and recent condom use. CONCLUSION: Information about risk factors revealed in individual interviews and by the midwives taking a history was incongruent. Any approach for management of STIs, which is built on self-reported risk factors, needs careful assessment of reliability.

The Dilemma of Safe Sex and Having Children: Challenges Facing HIV Sero-Discordant Couples in Uganda

Background: Sixty percent of new HIV infections in Uganda occur in stable relationships between HIV discordant couples. Given the importance of fertility in Uganda; we hypothesized that unsafe sexual practices may be used to found a family/replace a dead child. Thus; we explored sexual practices to understand to what extent these are influenced by the desire to have children and the implications for HIV transmission among discordant couples. Methods: A cross-sectional survey of 114 HIV discordant couples in Kampala; and in-depth interviews with 15 purposively selected couples. Quantitative data were analysed using STATA. Multivariate logistic regression analysis done to identify factors associated with consistent condom use. Thematic content analysis of qualitative data was done using NVIVO 2. Results: Participants wanting children and those with multiple sexual partners were less likely to use condoms (Adj OR 0.51; and 0.36 respectively). Three of the five types of sexual practices used by couples do not allow pregnancy to occur. Main reasons for wanting a child included: ensuring lineage continuity and posterity; securing relationships and pressure from relatives to reproduce. Challenges included: risk of HIV transmission to partner and child; lack of negotiating power for safer sex; failure of health systems to offer safe methods of reproduction. Conclusions: HIV sero-discordant couples with strong desire for childbearing have a dilemma of risking HIV infection or infecting their spouse. Some risk transmission of HIV infection to reproduce. We need to address gender issues; risky behaviour and reproductive health services for HIV sero-discordant couples

Vulnerability and risk factors for sexually transmitted infections and HIV among adolescents in Kampala, Uganda.

Three hundred and six sexually experienced adolescents participated in a study on sexually transmitted infection (STI) prevalence and associated risk factors. The prevalence of Neisseria gonorrhoea (NG), Chlamydia trachomatis (CT), Trichomonas vaginalis (TV) and syphilis was 4.5%, 9%, 8% and 4% for females and 4.7%, 5.7%, 0% and 2.8% for males. HIV-seropositivity was found in 15.2% of females and 5.8% of males. Structured face-to-face interviews were used to obtain information about social background, sexual experience and genital symptoms. Four focus-group discussions were used in order to validate the interview data. Females were more likely to be infected by the four treatable STIs and HIV, despite risky behavior being more common among males. Unemployment, little formal education, the presence of bacterial STIs and post-coital bleeding or a bad smell from the vagina was highly associated with the risk for HIV in females. The higher prevalence of STIs, including HIV, among adolescent girls cannot be explained by sexual behavior only, as boys reported more risk behavior and were still less affected by STIs. Biological and social factors are definitely of importance.

A criteria-based audit of the management of severe pre-eclampsia in Kampala, Uganda.

OBJECTIVE: To improve the quality of clinical care for women with severe pre-eclampsia. METHODS: A criteria-based audit was conducted in a large government hospital in Uganda. Management practices were evaluated against standards developed by an expert panel by retrospectively evaluating 43 case files. Results of the audit were presented, and recommendations developed and implemented. A re-audit was conducted 6 months later. RESULTS: The initial audit showed that most standards were rarely achieved. Reasons were discussed. Guidelines were produced, additional supplies were purchased following a fundraising effort, labor ward procedures were streamlined, and staffing was increased. In the re-audit there were significant improvements in diagnosis, monitoring, and treatment. CONCLUSION: Criteria-based audit can improve the quality of maternity care in countries with limited resources.

Morbidity and mortality patterns in HIV-1 seropositive/ seronegative women in Kampala and Harare during pregnancy and in the subsequent two years.

OBJECTIVE: To compare birth outcomes, hospital admissions and mortality amongst HIV-1 seropositive and HIV-1 seronegative pregnant women in Kampala, Uganda and Harare, Zimbabwe. DESIGN: In Kampala and Harare about 400 HIV-1 seropositive and 400 HIV-1 seronegative pregnant women were recruited at initial visit for antenatal care into a prospective study and followed for two years after delivery. The women were classified as HIV-1 seropositive at recruitment if initial and second ELISA tests were positive and confirmed by Western Blot assay. Data on demographic, reproductive, contraceptive and medical histories were obtained using a comprehensive questionnaire at entry, 32 and 36 weeks gestation, at delivery and at six, 12, and 24 months post delivery. In addition, a physical examination and various blood tests were performed at each antenatal and post natal visit. RESULTS: During the two years after delivery, HIV-1 seropositive women had higher hospital admission and death rates than HIV-1 seronegative women. HIV-1 seropositive mothers had a two-fold increase in risk of being admitted to hospital (Kampala: RR = 2.09; 95% CI = 0.95 to 4.59; Harare: RR = 1.98; 95% CI = 1.13 to 3.45). In the six weeks after delivery eight deaths occurred, six of which were among HIV-1 seropositive women and in the period from six weeks to two years after delivery, 53 deaths occurred, 51 of which were among HIV-1 seropositive women (Kampala: RR = 17.7; 95% CI = 4.3 to 73.2; Harare: RR = 10.0; 95% CI = 2.3 to 43.1). However, there was no difference in hospital admission rates between HIV-1 seropositive and seronegative women during pregnancy itself and there was only one death during that period (in a HIV-1 seronegative woman). There was no difference in the frequency of complications of delivery between HIV-1 seropositive and HIV-1 seronegative women and the outcome of births were also similar. CONCLUSIONS: A significant number of HIV-1 positive pregnant women presented at both Harare and Kampala although there was no difference in the number of hospital admissions or mortality between HIV-1 seropositive and HIV-1 seronegative women during pregnancy. Although there were no differences in complications during pregnancy or outcome at delivery, in the two years after delivery, HIV-1 seropositive women in both centres were at increased risk of being admitted to hospital and of dying.

Reasons, methods used and decision-making for pregnancy termination among adolescents and older women in Mulago Hospital, Uganda.

OBJECTIVE: To explore the methods, reasons and decision-making process for termination of pregnancy among adolescents and older women, in Mulago hospital, Kampala, Uganda. DESIGN: Comparative study. SUBJECTS: Nine hundred and forty two women seeking postabortion care, of which 333 had induced abortion (of whom 115 were adolescents). SETTING: The emergency gynaecological ward of Mulago Hospital, Kampala, Uganda from September 2003 through June 2004. RESULTS: Women with induced abortion were single, in polygamous marital relationships and of lower parity (p<0.001); had lower education and number of living children (p<0.05), reported more (p<0.001) mistimed, unplanned or unwanted pregnancies, and were 13 times more likely to have recent history of domestic violence. Relationship issues were the most common reason for pregnancy termination for both categories. Decision-making for induced abortion was influenced by socio-economic, educational and personal considerations. Instrumentation and use of local herbs in the genitalia were the most common methods for pregnancy termination. Neither methods used for pregnancy termination nor reasons differed when adolescents were compared with older women. CONCLUSION: Relationship issues influence the decision-making process for pregnancy termination. Neither methods used for pregnancy termination nor reasons for pregnancy termination differ when adolescents are compared with older women.

Introducing criteria based audit into Ugandan maternity units.

PROBLEM: Maternal mortality in Uganda has remained unchanged at 500/100 000 over the past 10 years despite concerted efforts to improve the standard of maternity care. It is especially difficult to improve standards in rural areas, where there is little money for improvements. Furthermore, staff may be isolated, poorly paid, disempowered, lacking in morale, and have few skills to bring about change. DESIGN: Training programme to introduce criteria based audit into rural Uganda. SETTING: Makerere University Medical School, Mulago Hospital (large government teaching hospital in Kampala), and Mpigi District (rural area with 10 small health centres around a district hospital). STRATEGIES FOR CHANGE: Didactic teaching about criteria based audit followed by practical work in own units, with ongoing support and follow up workshops. EFFECTS OF CHANGE: Improvements were seen in many standards of care. Staff showed universal enthusiasm for the training; many staff produced simple, cost-free improvements in their standard of care. LESSONS LEARNT: Teaching of criteria based audit to those providing health care in developing countries can produce low cost improvements in the standards of care. Because the method is simple and can be used to provide improvements even without new funding, it has the potential to produce sustainable and cost effective changes in the standard of health care. Follow up is needed to prevent a waning of enthusiasm with time.

Maternal mortality and associated near-misses among emergency intrapartum obstetric referrals in Mulago Hospital, Kampala, Uganda.

BACKGROUND: Many maternal deaths (as well as related severe morbidity) are of women who do not attend antenatal care in a given health unit but are referred there when they develop life-threatening obstetric complications. OBJECTIVE: To determine the reproductive characteristics of emergency obstetric referrals, and determine the contribution of emergency obstetric referrals to severe acute maternal morbidity (near-misses) and maternal mortality. STUDY DESIGN: Descriptive cross-sectional study. SETTING: Mulago hospital, the National Referral hospital, Kampala, Uganda, from 1st March to August 30th 2000. SUBJECTS: Nine hundred and eighty three consecutive women admitted as emergency obstetric referrals in labour or puerperium. INTERVENTIONS: Subjects were followed from time of admission to discharge (or death). They were interviewed (or examined) to obtain data on socio-demographic characteristics, reproductive history, obstetric outcome of the index pregnancy, obstetric complications and cause of death. Their records were reviewed to determine evidence of severe acute morbidity from acute organ/system dysfunction, using the definition by Mantel et al. These data were analysed using the Epilnfo computer programme in terms of means, frequencies and percentages. MAIN OUTCOME MEASURES: Socio-demographic characteristics, obstetric complications, cause of deaths, cause and type of near miss mortality and case fatality rates. RESULTS: Of the 983 referrals, over 100 were near-misses and 17 died. Using the definition of Mantel et al of near-misses enabled identification of six times as many near-misses as maternal deaths. The commonest causes of death were postpartum haemorrhage and eclampsia. Low status was highly associated with both maternal deaths and near misses. CONCLUSION: In developing countries, with poor obstetric services, emergency transfers in labour are very common. These women, who are of low status, contribute significantly to maternal mortality and morbidity.

Risk factors, nature and severity of domestic violence among women attending antenatal clinic in Mulago Hospital, Kampala, Uganda.

OBJECTIVES: To determine the prevalence, types, severity and risk factors for domestic violence among women attending antenatal clinic. DESIGN: Cross sectional study. SETTING: The antenatal clinic, Mulago Hospital, the national referral hospital, Kampala, Uganda. SUBJECTS: Pregnant women (n = 379) attending the antenatal clinic, on their index visit. METHODS: Interviewer-administered pre-coded questionnaires about history of domestic violence during the index pregnancy (prevalence, nature, severity, and associated factors from socio-demographic history, reproductive history, childhood history and domicile); during the previous one year prior to the interview, or beyond the previous year. MAIN OUTCOME MEASURES: History of domestic violence and its severity, type, risk factors and associated factors in the index pregnancy or prior to it. RESULTS: Over 57% of the subjects reported moderate-to-severe abuse due to domestic violence. Abuse in childhood and witnessing abuse in childhood were significantly associated with domestic violence in index pregnancy (p = 0.000). Staying with co-wife, adolescent pregnancy and the first pregnancy were significantly associated with domestic violence. CONCLUSIONS: Domestic violence is common in pregnancy at Mulago; is moderate to severe and physical abuse is often associated with both sexual and psychological abuse.

Uganda: improving maternal health care efficiency and financing.

PIP: This article presents the findings of the Partnerships for Health Reform on the efficiency and financing issues of maternal health services of the Ugandan Ministry of Health. A comparison was made between provider and consumer maternal health service expenditures provided by a public and a mission hospital and center, and by 17 private midwives and 20 traditional birth attendants (TBAs). The six areas covered by the study include antenatal care, normal deliveries, cesarean deliveries, postabortion care and postpartum hemorrhage and eclampsia complications. Greater health service cost was noted among mission hospitals compared with public hospitals and health centers, while prices for cesarean deliveries and treatment of obstetrical complications are higher compared with other maternal health services. Records show relative efficiency indications of the various providers, while quality of services were noted among midwives working in hospitals and centers compared with TBAs. Most consumer costs were observed to be lower compared with other care-related expenses except for mission health care cost. Thus, mission facilities recover more financially compared with public health centers and hospitals. Key actions suggested include: increasing health service utilization, streamlining staffing, improving the drug supply, employing midwives, assessing prescription practices, establishing specific times for check-ups, regulating consumer fees and provision of contracting arrangements, intensifying performance incentives, and evaluating user incomes and the ability of the public to pay for health care services.^ieng

A situation analysis of induced abortions in Uganda.

PIP: Although abortion in Uganda is illegal and permitted only to save the life of the mother, both spontaneous and induced abortion remains a major health problem in the country. Over the years, abortion has contributed largely to a high maternal mortality and morbidity rate (550/100,000 live births). A study conducted in 3 hospitals in Kampala recorded 3132 cases of induced abortion in 13 months; 420 were certainly induced abortions, 28 of which resulted in maternal death. In spite of the high fertility rate, contraceptive prevalence remains low in the country, resulting in high rates of teenage pregnancy. Generally single, young, and low-parity women, most often secondary school and university students, account for the bulk of all induced abortions. Most common reasons for termination of pregnancy include a desire to continue education and parental fear. The leading complications resulting from induced abortions were sepsis, hemorrhage, and genital tract trauma.^ieng

HIV-1 seroprevalence rates in women attending prenatal clinics in Kampala; Uganda

The objective was to determine the HIV-1 seroprevalence in expectant women in Kampala. HIV-1 antibody status (by ELISA -Cambridge Biotech; with comformatory ELISA-Wellcozyme on positives); obstetric and socio-demographic characteristics were determined on a random proportionate to-size sample of 1002 expectant consenting women seeking care at 11 prenatal units in Kampala between august and December of 1993. HIV-1 age-specific rates were determined. Chi-square analysis; tests for linear trend in rates and 95CI were used to determine significance of seroprevalence rates. Results showed overall seroprevalence of HIV-1 for the study population (mean age = 22.4 years; range = 14 - 42 years) was 20.5(95CI:18.0; 23.1); with the highest age-specific rate of 28.55 occurring at 20 - 22 years. An increasing trend of rates was observed between 14 - 24 years (p0.0001); followed; thereafter; by a decreasing trend (p

Intraluminally injected oil induces changes in vascular permeability in the 'sensitized' and 'non-sensitized' uterus of the mouse.

After suitable sensitization of ovariectomized mice with progesterone and oestradiol, the intrauterine instillation of oil produces a massive decidual cell reaction. Vascular permeability, as reflected by the extra-vascular accumulation of 125I-labelled human serum albumin, increased after oil instillation and was maintained at 2-3 times control values for at least the next 3 days. Although oil instillation did not produce a decidual response in females treated with progesterone alone, an increase in vascular permeability (about 2 times control levels) still occurred. This response peaked 8 h after oil instillation and was not maintained. These results indicate that the progesterone-dominated uterus which has not been sensitized with oestradiol cannot be viewed as completely unresponsive to the stimulus of oil and demonstrate that a marked increase in vascular permeability is not itself sufficient to induce decidualization of progesterone-dominated uterine stromal cells. The uterine extravascular accumulation of 125I-labelled albumin was increased both in association with tribromoethanol anaesthesia and after oestradiol treatment of progesterone-primed animals. In pregnant mice, the appearance of Pontamine Sky Blue spots provided an earlier indication of implantation than did determination of total uterine extravascular 125I-labelled albumin accumulation.

Time course of the changes in uterine vascular permeability associated with the development of the decidual cell reaction in ovariectomized steroid-treated rats.

Uterine vascular permeability and tissue blood volume during the development of the oil-induced decidual cell reaction (DCR) in ovariectomized steroid-treated rats were assessed by measuring the extravascular accumulation of 125I-labelled human serum albumin and the tissue content of 51Cr-labelled red cells 30 min after intravenous administration. Within 15 min of oil instillation into one uterine horn, the vascular permeability of the horn was significantly elevated. Permeability rose to a sharp peak (10 times control levels) 9 h after oil instillation, but dropped to 5 times control values by 12 h and continued a steady decline over the next 7 days. Although a marked increase in uterine weight was associated with the development of the DCR, there was no significant change in blood volume/g tissue until 4 days after oil instillation.

HIV-1 seroprevalence rates in women attending prenatal clinics in Kampala; Uganda. (p.96)

The objective was to determine the HIV-1 seroprevalence in expectant women in Kampala. HIV-1 antibody status (by ELISA -Cambridge Biotech; with comformatory ELISA-Wellcozyme on positives); obstetric and socio-demographic characteristics were determined on a random proportionate to-size sample of 1002 expectant consenting women seeking care at 11 prenatal units in Kampala between august and December of 1993. HIV-1 age-specific rates were determined. Chi-square analysis; tests for linear trend in rates and 95CI were used to determine significance of seroprevalence rates. Results showed overall seroprevalence of HIV-1 for the study population (mean age