Introducing misoprostol for the management of postpartum hemorrhage in Zimbabwe: final report on operational research.

Postpartum Haemorrhage (PPH) is the most common cause of maternal mortality globally, leading to a woman's death every seven minutes. In Zimbabwe, there has been a 300% increase in the Maternal Mortality Ratio (MMR) between 1994 and 2010 and the MMR was estimated at 960 maternal deaths per 100,000 live births in 2012.2-3 Overall, 14% of all maternal deaths in Zimbabwe are due to PPH. Ensuring prompt access to high-quality prevention and treatment of PPH for all women who deliver is an essential strategy to combat PPH-related morbidity and mortality and to make progress toward reaching Millennium Development Goal 5, the reduction of maternal mortality by three-quarters by 2015.

Interest in multipurpose prevention of HIV and pregnancy: perspectives of women, men, health professionals and community stakeholders in two vaginal gel studies in southern Africa.

OBJECTIVE: The pipeline of vaginal microbicides for HIV prevention has expanded to include products for multipurpose prevention, but the interests of potential users and those advising on use have not been sufficiently investigated. Rather, assumptions about interest in multipurpose prevention technologies (MPTs) are inferred from what is known about acceptability and use of microbicides or contraceptives. DESIGN AND SETTING: This paper presents data on concerns and preferences for multipurpose prevention of HIV and pregnancy. Data were collected in two microbicide gel studies in Malawi and Zimbabwe. Participants were women using candidate vaginal products, their male partners, health professionals and community stakeholders. METHODS: An individual interview was conducted with participants. Interviews were audio-recorded, transcribed, coded for content and analysed for key themes. RESULTS: Participants indicated strong interest in a vaginal HIV prevention product that could also prevent pregnancy. Reasons for this interest were convenience, problems with adverse effects with current contraceptive methods, concerns about long-term effects of contraceptives, and concerns about the health burdens of HIV infection during pregnancy. The main disadvantage of an MPT was recognition that while interest in preventing HIV is constant, contraceptive needs change over time. CONCLUSION: The study population indicated support for an MPT to prevent HIV and pregnancy. This support may be further strengthened if the product is also available for prevention of only HIV. Women and men will be more willing to use an MPT if they can be reassured that its use will have no long-term effect on fertility.

Optimization of the oligonucleotide ligation assay for the detection of nevirapine resistance mutations in Zimbabwean Human Immunodeficiency Virus type-1 subtype C.

An oligonucleotide ligation assay (OLA) designed to detect Human Immunodeficiency Virus type-1 (HIV)-drug-resistance to the nevirapine (NVP) selected mutations K103N, Y181C, V106M and G190A was used to evaluate 200 archived dried blood spots (DBS) from infected infants participating in the Zimbabwean Early Infant Diagnosis (EID) Program. Consensus sequencing of specimens with indeterminate OLA results was performed to identify genetic sequence polymorphisms that appeared to compromise performance of the OLA. When consistent patterns of polymorphisms were observed the probes were redesigned, and DBS specimens with indeterminate OLA results were retested with the new Zimbabwe-specific (ZW) probes. OLA results obtained in Zimbabwe were compared to repeat testing in a US reference laboratory. 188/200 (94%) DBS yielded polymerase chain reaction (PCR) amplification of HIV pol. ZW probes reduced indeterminate OLA results from 5.2% to 2.8% of codons evaluated (p=0.02), with 98.2% concordance between results obtained in the Zimbabwean and US laboratories. Optimization of OLA probes to accommodate polymorphisms in regional HIV variants improved OLA performance, and comparison to the USA results showed successful implementation of the OLA in Zimbabwe for detection of NVP resistance mutations in DBS specimens.

Provision of long-acting reversible contraception in HIV-prevalent countries: results from nationally representative surveys in southern Africa.

OBJECTIVE: To analyse the current provision of long-acting reversible contraception (LARC) and clinician training needs in HIV-prevalent settings. DESIGN: Nationally representative survey of clinicians. SETTING: HIV-prevalent settings in South Africa and Zimbabwe. POPULATION: Clinicians in South Africa and Zimbabwe. METHODS: Nationally representative surveys of clinicians were conducted in South Africa and Zimbabwe (n = 1444) to assess current clinical practice in the provision of LARC in HIV-prevalent settings. Multivariable logistic regression was used to analyse contraceptive provision and clinician training needs. MAIN OUTCOME MEASURE: Multivariable logistic regression of contraceptive provision and clinician training needs. RESULTS: Provision of the most effective reversible contraceptives is limited: only 14% of clinicians provide copper intrauterine devices (IUDs), 4% levonorgestrel-releasing IUDs and 16% contraceptive implants. Clinicians' perceptions of patient eligibility for IUD use were overly restrictive, especially related to HIV risks. Less than 5% reported that IUDs were appropriate for women at high risk of HIV or for HIV-positive women, contrary to evidence-based guidelines. Only 15% viewed implants as appropriate for women at risk of HIV. Most clinicians (82%), however, felt that IUDs were underused by patients, and over half desired additional training on LARC methods. Logistic regression analysis showed that LARC provision was largely restricted to physicians, hospital settings and urban areas. Results also showed that clinicians in rural areas and clinics, including nurses, were especially interested in training. CONCLUSIONS: Clinician competency in LARC provision is important in southern Africa, given the low use of methods and high rates of unintended pregnancy among HIV-positive and at-risk women. Despite low provision, clinician interest is high, suggesting the need for increased evidence-based training in LARC to reduce unintended pregnancy and associated morbidities.

Discrepancies in diagnosis of incident HIV infection between antibody- and DNA-based tests in a phase III prevention trial in southern Africa.

Dried blood spots (DBS) are widely used to test for HIV in a variety of research and service delivery settings; however, uniform guidelines regarding collection, storage and DNA extraction processes have neither been developed nor evaluated. Previously published reports suggested DBS may be stored at room temperature for up to 60 days, and intensive stability tests have shown that DBS can withstand high temperatures, humidity and freeze-thawing. During the implementation of a large randomized controlled trial (RCT) in southern Africa, with HIV acquisition as the primary endpoint, we observed 65 instances when DBS samples collected from the same day as a positive HIV antibody test yielded negative DNA polymerase chain reaction (PCR) results. The source of this discrepancy may have been due to inadequate specimen volume, filter paper or DNA extraction procedures, but were most likely due to storage conditions that have been reported as acceptable in other settings.

Incidence of major clinical outcomes in a cohort of Ugandan and Zimbabwean women with HIV-1 infection followed from seroconversion.

We conducted a prospective cohort study of 306 HIV-1-infected women, followed from seroconversion for median 6.4 years in Uganda (UG) and Zimbabwe (ZM) to describe the incidence of major clinical outcomes (MCOs), defined as World Health Organization stage 4 conditions and any tuberculosis (TB). In Uganda, 19 MCOs occurred in 13 participants at median 4.6 years and a median CD4 count of 213 cells/mm(3). In Zimbabwe, 29 MCOs occurred in 27 participants at median 4.0 years (P < 0.001 versus UG) and median CD4 count of 219 cells/mm(3) (P = 0.83 versus UG). MCO incidence was not statistically different (UG: 2.82 cases/100 person-years versus ZM: 2.45; P = 0.64) except for TB (UG: 0.59 versus ZM: 2.02 cases/100 person-years; P = 0.02). This significant difference in TB incidence is primarily due to a TB screening and isoniazid prevention therapy programme that was implemented in Uganda, but not in Zimbabwe, highlighting the importance of integrated TB screening and treatment within HIV programmes.

The relative contribution of viral and bacterial sexually transmitted infections on HIV acquisition in southern African women in the Methods for Improving Reproductive Health in Africa study.

We assess the relative contribution of viral and bacterial sexually transmitted infections (STIs) on HIV acquisition among southern African women in a nested case-control study within the Methods for Improving Reproductive Health in Africa (MIRA) trial. Cases were women with incident HIV infection; controls were HIV-uninfected at the time of case seroconversion selected in a 1 to 3 case to control ratio (risk-set sampling), matched on study site and time of follow-up. Conditional logistic regression models were used to calculate adjusted odds ratios (AORs) and population-attributable fractions (PAF). Among 4948 enrolled women, we analysed 309 cases and 927 controls. The overall HIV incidence rate was 4.0 per 100 women-years. The incidence of HIV infection was markedly higher in women who had prevalent Herpes simplex virus type 2 (HSV-2) (AOR: 2.14; 95% confidence interval [CI]: 1.55-2.96), incident HSV-2 (AOR: 4.43; 95% CI: 1.77-11.05) and incident Neisseria gonorrhoeae (AOR: 6.92; 95% CI: 3.01-15.90). The adjusted PAF of HIV incidence for prevalent HSV-2 was 29.0% (95% CI: 16.8-39.3), for incident HSV-2 2.1% (95% CI: 0.6-3.6) and for incident N. gonorrhoeae 4.1% (95% CI: 2.5-5.8). Women's greatest risk factors for HIV acquisition were incident bacterial and viral STIs. Women-centred interventions aimed at decreasing HIV incidence in young African women need to address these common co-morbid conditions.

Variations in CD4 cell counts among HIV-uninfected and infected women in Uganda and Zimbabwe.

We conducted a cross-sectional study with 208 HIV-uninfected and 188 HIV-infected women in Uganda and Zimbabwe to investigate differences in median CD4 counts. Absolute CD4 counts were determined by flow cytometry. Multivariate analyses were used to examine the association of country and HIV-infection status on CD4 counts. Median CD4 counts were significantly lower in Zimbabwe than in Uganda overall (649 and 783 cells/mm(3), P = 0.009) and among HIV-infected women (470 and 614 cells/mm(3), P = 0.003). In separate multivariable models, CD4 counts were significantly lower in Zimbabwe in HIV-uninfected (P = 0.014) and infected (P < 0.001) women, controlling for age, contraceptive method, education and living with partner status. In a model combining HIV-uninfected and infected women, there was no significant interaction between country and HIV infection status (P = 0.344), suggesting that the relationship between country and CD4 count was not significantly modified by HIV infection status. This study reinforces the importance of establishing country-specific reference CD4 levels as CD4 count continues to be used as a key biomarker in clinical decision-making for HIV-infected individuals in sub-Saharan Africa.

The international infections in pregnancy study: group B streptococcal colonization in pregnant women.

BACKGROUND: Heavy colonization with group B streptococcus (GBS) has been associated with increased risk of preterm birth and neonatal sepsis; the burden of neonatal GBS disease varies geographically. To determine whether variation in heavy colonization and GBS serotypes could contribute to geographic differences in disease burden, we assessed the prevalence of heavy colonization and the distribution of serotypes in asymptomatic pregnant women in multiple countries. METHODS: Cervical, lower vaginal and urine samples were collected from women attending seven prenatal clinics in six countries. Light colonization was defined as GBS isolation from Lim broth only; heavy colonization was isolation from urine or sheep blood agar plates. Isolates were serotyped using capillary precipitation. RESULTS: GBS was present in 11.3% of 1308 participants (range 7.1-21.7%); 5.0% were heavily colonized (0.4-18.8%) and 6.4% were lightly colonized (2.9-8.0%). Serotypes III and V were most common (both 17.2%). Serotypes VII and VIII were found in one study center. CONCLUSIONS: The prevalence of heavy colonization and GBS serotypes varied significantly among our study centers. Whether this variation could in part explain geographic differences in neonatal morbidity and mortality is a hypothesis that needs further study.

A randomized control trial of an Ultra-Short zidovudine regimen in the prevention of perinatal HIV transmission in rural Zimbabwe.

OBJECTIVE: To assess the practicality and effectiveness of an Ultra-Short zidovudine regimen for prevention of perinatal HIV transmission in rural Zimbabwe. DESIGN: Double-blinded placebo-controlled randomized clinical trial. SETTING: The Salvation Army Howard Hospital, a district hospital in rural Zimbabwe. SUBJECTS: 222 HIV positive pregnant women presenting for antenatal care prior to 36 weeks were randomized. Twenty nine women were lost to follow up. INTERVENTION: In the Thai regimen, mothers received zidovudine (300 mg po bid) from 36 weeks gestation until labour, and zidovudine (300 mg po q3h) during labour, and the neonates received a placebo. In the Ultra-Short regimen, the mothers received a placebo from 36 weeks to labour, then zidovudine (300 mg po q3h) in labour. The neonates received zidovudine (2 mg/kg po qid) for the first three days of life. MAIN OUTCOME MEASURE: Infant HIV RNA status at six weeks of life. RESULTS: Results were available for 90 infants from the Thai group and 89 infants from the Ultra-Short group. Infant HIV seroconversion rates at six weeks of life were 18.9% (95%CI 10.8 to 27.0) with the Thai regimen, and 15.7% [95% Confidence Interval (CI) 8.1 to 23.4] with the Ultra-Short regimen. The upper bound of seroconversion in the Ultra-Short group was lower than the 25% seroconversion boundary that was specified to show equivalence. CONCLUSIONS: Although the Ultra-Short regimen has equivalent efficacy to the Thai regimen, it also has many practical advantages. Ultra-Short is thus a preferable protocol.

Trends in maternal mortality for the Greater Harare Maternity Unit: 1976 to 1997.

OBJECTIVE: To determine the magnitude, trends and the main causes of maternal death for Harare Maternity Hospital (HMH) and thereby identify potential areas for interventions. DESIGN: A descriptive retrospective analysis of maternal mortality data from the institution included in publications and recent annual reports. SETTING: Department of Obstetrics and Gynaecology Greater Harare Maternity Unit, Zimbabwe. MAIN OUTCOME MEASURES: The trends in maternal mortality ratios (MMR) and the relative importance of different causes of death between 1976 and 1997. RESULTS: There was a decline in MMR between 1976 and the early 1980s but there has been a steady increase in MMR for Harare residents from 50/100,000 in 1988 to 224/100,000 in 1997. Sepsis has remained the leading cause of maternal death. There has been a significant increase in indirect deaths due to meningitis, tuberculosis and pneumonia where HIV infection is an underlying factor. Avoidable factors were identified at patient/community, local health facility and at the tertiary hospital. There has been a decline in the quality of care in recent years. CONCLUSION: Maternal mortality for HMH is unacceptably high and could still be rising. HIV infection has contributed to the worsening picture. Interventions to improve access and quality of care at all levels could lead to significant reduction in maternal deaths.

HPV-based cervical cancer screening in a population at high risk for HIV infection.

We determined the utility of an assay for 13 cancer-associated HPV types in primary cervical cancer screening of Zimbabwe women at high risk of HIV infection. HIV antibody status was determined by ELISA of oral mucosal specimens, and HPV DNA in the genital tract was identified by hybridization of cervical scrapes with probe B of Hybrid Capture II. Among the 466 women investigated, the prevalence of HPV, low-grade squamous intraepithelial lesions (LGSIL) and high-grade SIL (HGSIL) were 47.2%, 13.9% and 12%. Fifty-three and one-half percent of the women were HIV-seropositive. As compared with HIV-seronegative women, HIV-infected women had a greater than 2-fold HPV prevalence (64.3% vs. 27.6%), a greater than 7-fold amount of HPV DNA (RLU of 82.6 vs. 10.7) in HPV(+) women assessed as normal on the reference standard, and a nearly 3-fold greater HGSIL prevalence (17.3% vs. 5.9%). The strong link between HGSIL and HPV DNA positivity was seen in both HIV-infected and HIV-seronegative women. The amount of HPV DNA increased with disease severity in both HIV-seronegative and HIV-infected women. The sensitivity and specificity of the HPV test for HGSIL were, respectively, 90.7% (95% confidence limit 77.9-97.4%) and 41.3% (34.5-48.3%) in HIV-infected women and 61.5% (31.6-86.1%) and 74.5% (68.0-80.3%), respectively, in HIV(-) women. The usefulness of the HPV test as a screening test for cervical cancer in areas of high HPV prevalence will depend upon local health resource availability, disease priorities and policies regarding clinical case management.

Evaluation of a human papillomavirus assay in cervical screening in Zimbabwe.

OBJECTIVE: To determine the utility of an assay for high risk genital human papillomavirus (HPV) in cervical screening in Zimbabwe, Africa. DESIGN: Cross-sectional study. SETTING: Harare, Zimbabwe. POPULATION: Zimbabwe women (n = 2,140), 25 to 55 years old, recruited in clinics in Chitungwiza and Greater Harare. METHODS: Genital specimens were assessed for HPV, using the HPV DNA test Hybrid Capture II (probe B). Further assessment of the women was conducted using colposcopy and biopsy as indicated. High grade squamous intraepithelial lesions were diagnosed in 215 women. Colposcopy and/or biopsy showed low grade lesions in 346 women. RESULTS: The overall prevalences were: 42 x 7% for HPV, 10% for high grade squamous intraepithelial lesions and 16% for low grade lesions. Prevalence for HPV decreased significantly with increase in age (P for trend < 0 x 0001) and increased significantly with increasing disease severity, from 35% in normal women, to 53% in women with low grade lesions and 81% in women with high grade lesions (P for trend < 0 x 001). In specimens positive for HPV, the amount was 14-fold higher in women with high grade lesions compared with normal women. In screening for high grade lesions the assay for HPV had a sensitivity of 81% (CI 75%-86%); sensitivity for low grade lesions was 64% (CI 60%-68%). Specificity was 62% (CI 59%-64%) for high grade lesions and 65% (CI 62%-67%) for low grade lesions. The positive predictive value was 19% (CI 17%-22%) for high grade lesions and 39% (CI 36%-42%) for low grade lesions. CONCLUSION: For high grade squamous intraepithelial lesions the sensitivity of the Hybrid Capture II HPV DNA test was high, but the specificity was relatively low. The test may therefore be most useful in conjunction with other screening tests.

Visual inspection of the cervix as a primary means of cervical cancer screening: results of a pilot study.

OBJECTIVE: To measure the effectiveness of unaided visual inspection (UVI) of the cervix as a primary means of cervical cancer screening. DESIGN: A cross sectional study. SETTING: Five primary health care clinics in Mashonaland Province, Zimbabwe. SUBJECTS: 1,000 women aged between 25 and 55 years. MAIN OUTCOME MEASURES: Sensitivity and specificity of UVI. METHODS: 1,000 women attending primary health care clinics were screened for cervical cancer by six qualified nurses. An unlubricated bivalve speculum was inserted into the vagina under good light to visualize the cervix and a cervical cytology specimen was obtained followed by visual inspection of the cervix stained by 4% acetic acid. All women found to have abnormal cervices by visual inspection and/or by cervical cytology report were scheduled for colposcopy examination at Harare Central Hospital. RESULTS: 236 (23.6%) women had an abnormal cervical appearance after application with 4% acetic acid, out of which 157 (15.7%) were reported abnormal by cytology. True disease as defined by positive colposcopy and positive cytology was confirmed in 38 (3.8%) women. The sensitivity of UVI using colposcopy and cytology as a reference standard was 68.4%, specificity was 3.4%. CONCLUSION: The results of this study suggest that naked eye inspection of the cervix after application of acetic acid is a practical alternative to cervical cytology in screening for cervical cancer in countries with few resources like Zimbabwe.

Prophylactic augmentin in prelabor preterm rupture of the membranes.

OBJECTIVE: To determine whether the use of prophylactic Augmentin in PPROM prolongs gestation and reduces neonatal and maternal morbidity due to sepsis. METHOD: Study setting was Harare Maternity Hospital, Zimbabwe. Women with PPROM between 26 and 36 weeks' gestation were randomly allocated either to a group given a course of prophylactic oral Augmentin or another receiving no prophylactic antibiotic treatment. The calculated sample size was 72 women per group. Data were analyzed using the EPI INFO program. RESULTS: A total of 171 women were recruited into the study, 84 in the Augmentin group and 87 in the No Treatment group. The group receiving prophylactic Augmentin had a significantly longer latency period between rupture of membranes and delivery. There was a trend towards increased neonatal and maternal morbidity due to sepsis in the No Treatment group although no statistical significance was reached. CONCLUSION: The use of prophylactic Augmentin in PPROM significantly prolongs gestation. It appears to decrease neonatal and maternal morbidity due to sepsis.

Extra-amniotic saline infusion versus extra-amniotic prostaglandin F2alpha for cervical ripening and induction of labor.

OBJECTIVE: To compare the effectiveness of extra-amniotic saline infusion versus extra-amniotic prostaglandin F2alpha for cervical ripening, induction of labor and achievement of vaginal delivery in patients with unfavorable cervices. METHOD: A randomized trial of extra-amniotic saline infusion versus extra-amniotic prostaglandin F2alpha performed at Harare Central Hospital Maternity Unit, Zimbabwe. One hundred and sixty-four patients were recruited from those referred to Harare Central Hospital Maternity Unit who required induction of labor for either maternal or fetal indications. RESULTS: 162 patients (extra-amniotic PgF2alpha group, N = 81; extra-amniotic saline infusion group, N = 81) had complete information. Two patients (one from each group) were lost to follow up. The demographic characteristics of the patients and the indications for induction were not statistically different. There was a marginally statistically significant difference in the change of Bishop Score in favor of the extra-amniotic saline infusion (4.0, S.D. = 1.4) as compared to (4.5, S.D. = 1.5) for extra-amniotic PgF2alpha (P value = 0.047). All other parameters showed no statistically significant differences. Maternal and fetal complications were minimal and not significantly different. Extra-amniotic saline infusion was however almost six times cheaper than PgF2alpha. CONCLUSION: Extra-amniotic saline infusion is as effective as PgF2alpha, safe, but much cheaper than PgF2alpha and should be seriously considered as a method of first choice in resource-poor settings.

A randomized controlled trial of low-dose aspirin in women at risk from pre-eclampsia.

OBJECTIVES: To determine whether low-dose aspirin reduces the incidence of pre-eclampsia, reduces perinatal mortality and improves birth weights in pregnant women considered at high risk of developing pre-eclampsia. METHOD: Two-hundred fifty subjects were recruited from the antenatal clinics at Harare Central Hospital with either a previous history of pregnancy-induced hypertension or pre-existing chronic hypertension and were randomized to receive either 75 mg of aspirin (ASA) or placebo (PLA). RESULTS: Two-hundred thirty subjects (ASA, n = 113; PLA, n = 117) completed the trial. The odds of developing pre-eclampsia for those on aspirin was 0.72 times those on placebo (95% CI, 0.34-1.52). The mean birth weight was 2774 g for those on aspirin and 2694 g for those on placebo (P = 0.80). No difference was noted in the perinatal deaths (OR = 0.38; 95% CI, 0.10-1.20). CONCLUSION: Prophylactic use of aspirin was not associated with a significant effect on the major pregnancy outcomes assessed in this study.

Situation analysis for cervical cancer diagnosis and treatment in Zimbabwe.

OBJECTIVE: To establish factors influencing early diagnosis and treatment of cervical cancer in Zimbabwean women. DESIGN: A cross sectional study. SETTING: A random selection of 29 primary health care facilities, 11 district/provincial and four tertiary hospitals in Zimbabwe. RESULTS: All the institutions at primary health care, district, provincial and tertiary levels had the basic infrastructure to perform exfoliative cytology screening (Pap. smear). An average of only nine pap. smears per month were performed at primary health clinics and at district/provincial and tertiary levels seven and 23 Pap. smears per week were done respectively. Infrequent supplies of consumable materials and lack of policy guidelines were the most common reasons for not screening women. Surgical treatment for cervical cancer was offered in all tertiary hospitals but only 22% of provincial hospital had facilities to perform hysterectomy. CONCLUSION AND RECOMMENDATIONS: There is an urgent need to improve screening for cervical pre-cancer in Zimbabwean women with emphasis to provide adequate treatment facilities especially at district and provincial Hospitals. A national policy guideline should be drawn to address specific ages and frequency of screening for cervical cancer.