Antiretroviral preexposure prophylaxis for heterosexual HIV transmission in Botswana.

BACKGROUND: Preexposure prophylaxis with antiretroviral agents has been shown to reduce the transmission of human immunodeficiency virus (HIV) among men who have sex with men; however, the efficacy among heterosexuals is uncertain. METHODS: We randomly assigned HIV-seronegative men and women to receive either tenofovir disoproxil fumarate and emtricitabine (TDF-FTC) or matching placebo once daily. Monthly study visits were scheduled, and participants received a comprehensive package of prevention services, including HIV testing, counseling on adherence to medication, management of sexually transmitted infections, monitoring for adverse events, and individualized counseling on risk reduction; bone mineral density testing was performed semiannually in a subgroup of participants. RESULTS: A total of 1219 men and women underwent randomization (45.7% women) and were followed for 1563 person-years (median, 1.1 years; maximum, 3.7 years). Because of low retention and logistic limitations, we concluded the study early and followed enrolled participants through an orderly study closure rather than expanding enrollment. The TDF-FTC group had higher rates of nausea (18.5% vs. 7.1%, P<0.001), vomiting (11.3% vs. 7.1%, P=0.008), and dizziness (15.1% vs. 11.0%, P=0.03) than the placebo group, but the rates of serious adverse events were similar (P=0.90). Participants who received TDF-FTC, as compared with those who received placebo, had a significant decline in bone mineral density. K65R, M184V, and A62V resistance mutations developed in 1 participant in the TDF-FTC group who had had an unrecognized acute HIV infection at enrollment. In a modified intention-to-treat analysis that included the 33 participants who became infected during the study (9 in the TDF-FTC group and 24 in the placebo group; 1.2 and 3.1 infections per 100 person-years, respectively), the efficacy of TDF-FTC was 62.2% (95% confidence interval, 21.5 to 83.4; P=0.03). CONCLUSIONS: Daily TDF-FTC prophylaxis prevented HIV infection in sexually active heterosexual adults. The long-term safety of daily TDF-FTC prophylaxis, including the effect on bone mineral density, remains unknown. (Funded by the Centers for Disease Control and Prevention and the National Institutes of Health; TDF2 ClinicalTrials.gov number, NCT00448669.).

A qualitative analysis of vaccine safety perceptions and concerns among caretakers in Uganda.

Parents and caretakers of young children often have concerns about vaccine safety and adverse events following immunization (AEFI). Little is known about vaccine safety perceptions in Uganda and their influence on parental decision-making about infant immunization. The study objectives were: to identify community sources of information on immunization, vaccine safety and AEFI; determine caretakers' knowledge of immunization; identify community concerns/fears about immunization and AEFI and their influence on caretakers' decisions to vaccinate; and obtain an understanding of knowledge, perceptions, and experience of health care workers (HCWs) and policy administrators on vaccine safety and AEFI. Twelve focus group discussions with 136 caretakers who were very or somewhat concerned about vaccine safety and 25 key informant interviews were conducted in two districts (1 urban and 1 rural) with district authorities and health facility staff as well as national level decision-makers between December and April 2006. Content analysis was used to analyze the results. The main themes identified related to general lack of information among caretakers about immunization, perceived immunization benefits, immunization concerns, and misconceptions. Specific caretaker concerns related to vaccine administration, immunization services and vaccine safety. Experiences with AEFI and concerns about vaccine safety negatively affected caretakers' decisions to vaccinate their children, notably in rural areas. HCWs demonstrated knowledge about AEFI and their management although incidences reported to facilities were rare. Inadequate communication between HCWs and caretakers was noted. Concerns and misconceptions about vaccination still exist among caretakers in Uganda and influence decisions to vaccinate. Effective inter personal communication initiated by HCWs towards caretakers is needed.

Risk factors for mumps at a university with a large mumps outbreak.

OBJECTIVES: Routine measles-mumps-rubella (MMR) vaccine use has greatly decreased the incidence of mumps in the U.S. However, a resurgence of mumps occurred in 2006. We investigated the large outbreak at a university and assessed risk factors for disease. METHODS: We described the outbreak and conducted a case-control study. We interviewed case students (identified from student health service and health department records) and control students (selected from a randomly ordered administrative list) and assessed their vaccination status. We compared case students with > or = 2 MMR doses and control students with > or = 2 MMR doses in univariate and multivariate analyses. RESULTS: The mean age of the 174 case students was 20.9 years; 65% were women. Ninety-seven case students and 147 control students were enrolled in the study. Two-dose MMR coverage was 99% among case and control students with complete records. Only 33% of case students reported exposure to someone with mumps. Case students were more likely than control students to be aged 18 to 19 years (vs. aged 22 years, adjusted odds ratio [AOR] = 5.55; 95% confidence interval [CI] 2.09, 14.74), to report exposure to mumps (AOR=2.31, 95% CI 1.13, 4.73), and to have worked/volunteered on campus (AOR=2.91, 95% CI 1.33, 6.33). Also, women in dormitories had increased odds of mumps compared with men in dormitories. CONCLUSION: High two-dose MMR coverage was not sufficient to prevent the outbreak. Further study is needed to better understand the effects of dormitory residency and gender on mumps transmission. Clinicians should be vigilant for mumps in young adults presenting with parotitis regardless of immunization history.

Community Perspectives of a 3-Delays Model Intervention: A Qualitative Evaluation of Saving Mothers, Giving Life in Zambia.

BACKGROUND: Saving Mothers, Giving Life (SMGL), a health systems strengthening approach based on the 3-delays model, aimed to reduce maternal and perinatal mortality in 6 districts in Zambia between 2012 and 2017. By 2016, the maternal mortality ratio in SMGL-supported districts declined by 41% compared to its level at the beginning of SMGL-from 480 to 284 deaths per 100,000 live births. The 10.5% annual reduction between the baseline and 2016 was about 4.5 times higher than the annual reduction rate for sub-Saharan Africa and about 2.6 times higher than the annual reduction estimated for Zambia as a whole. OBJECTIVES: While outcome measures demonstrate reductions in maternal and perinatal mortality, this qualitative endline evaluation assessed community perceptions of the SMGL intervention package, including (1) messaging about use of maternal health services, (2) access to maternal health services, and (3) quality improvement of maternal health services. METHODS: We used purposive sampling to conduct semistructured in-depth interviews with women who delivered at home (n=20), women who delivered in health facilities (n=20), community leaders (n=8), clinicians (n=15), and public health stakeholders (n=15). We also conducted 12 focus group discussions with a total of 93 men and women from the community and Safe Motherhood Action Group members. Data were coded and analyzed using NVivo version 10. RESULTS: Delay 1: Participants were receptive to SMGL's messages related to early antenatal care, health facility-based deliveries, and involving male partners in pregnancy and childbirth. However, top-down pressure to increase health facility deliveries led to unintended consequences, such as community-imposed penalty fees for home deliveries. Delay 2: Community members perceived some improvements, such as refurbished maternity waiting homes and dedicated maternity ambulances, but many still had difficulty reaching the health facilities in time to deliver. Delay 3: SMGL's clinician trainings were considered a strength, but the increased demand for health facility deliveries led to human resource challenges, which affected perceived quality of care. CONCLUSION AND LESSONS LEARNED: While SMGL's health systems strengthening approach aimed to reduce challenges related to the 3 delays, participants still reported significant barriers accessing maternal and newborn health care. More research is needed to understand the necessary intervention package to affect system-wide change.

Clinical presentation of pregnant women in isolation units for Ebola virus disease in Sierra Leone, 2014.

OBJECTIVES: To examine Ebola virus disease (EVD) symptom prevalence and EVD status among pregnant women in Ebola isolation units in Sierra Leone. METHODS: In an observational study, data were obtained for pregnant women admitted to Ebola isolation units across four districts in Sierra Leone from June 29, 2014, to December 20, 2014. Women were admitted to isolation units if they had suspected EVD exposures or fever (temperature >38°C) and three or more self-reported symptoms suggestive of EVD. Associations were examined between EVD status and each symptom using χ2 tests and logistic regression adjusting for age/labor status. RESULTS: Of 176 pregnant women isolated, 55 (32.5%) tested positive for EVD. Using logistic regression models adjusted for age, EVD-positive women were significantly more likely to have fever, self-reported fatigue/weakness, nausea/vomiting, headache, muscle/joint pain, chest pain, vaginal bleeding, unexplained bleeding, or sore throat upon admission. In models adjusted for age/labor, only women with fever or vaginal bleeding upon admission were significantly more likely to be EVD-positive. CONCLUSIONS: Several EVD symptoms and complications increased the odds of testing EVD-positive; some of these were also signs and symptoms of labor/pregnancy complications. The study results highlight the need to refine screening for pregnant women with EVD.

Saving Mothers, Giving Life: It Takes a System to Save a Mother.

BACKGROUND: Ending preventable maternal and newborn deaths remains a global health imperative under United Nations Sustainable Development Goal targets 3.1 and 3.2. Saving Mothers, Giving Life (SMGL) was designed in 2011 within the Global Health Initiative as a public-private partnership between the U.S. government, Merck for Mothers, Every Mother Counts, the American College of Obstetricians and Gynecologists, the government of Norway, and Project C.U.R.E. SMGL's initial aim was to dramatically reduce maternal mortality in low-resource, high-burden sub-Saharan African countries. SMGL used a district health systems strengthening approach combining both supply- and demand-side interventions to address the 3 key delays to accessing effective maternity care in a timely manner: delays in seeking, reaching, and receiving quality obstetric services. IMPLEMENTATION: The SMGL approach was piloted from June 2012 to December 2013 in 8 rural districts (4 each) in Uganda and Zambia with high levels of maternal deaths. Over the next 4 years, SMGL expanded to a total of 13 districts in Uganda and 18 in Zambia. SMGL built on existing host government and private maternal and child health platforms, and was aligned with and guided by Ugandan and Zambian maternal and newborn health policies and programs. A 35% reduction in the maternal mortality ratio (MMR) was achieved in SMGL-designated facilities in both countries during the first 12 months of implementation. RESULTS: Maternal health outcomes achieved after 5 years of implementation in the SMGL-designated pilot districts were substantial: a 44% reduction in both facility and districtwide MMR in Uganda, and a 38% decrease in facility and a 41% decline in districtwide MMR in Zambia. Facility deliveries increased by 47% (from 46% to 67%) in Uganda and by 44% (from 62% to 90%) in Zambia. Cesarean delivery rates also increased: by 71% in Uganda (from 5.3% to 9.0%) and by 79% in Zambia (from 2.7% to 4.8%). The average annual rate of reduction for maternal deaths in the SMGL-supported districts exceeded that found countrywide: 11.5% versus 3.5% in Uganda and 10.5% versus 2.8% in Zambia. The changes in stillbirth rates were significant (-13% in Uganda and -36% in Zambia) but those for pre-discharge neonatal mortality rates were not significant in either Uganda or Zambia. CONCLUSION: A district health systems strengthening approach to addressing the 3 delays to accessing timely, appropriate, high-quality care for pregnant women can save women's lives from preventable causes and reduce stillbirths. The approach appears not to significantly impact pre-discharge neonatal mortality.

Saving Mothers, Giving Life: It Takes a System to Save a Mother (Republication).

BACKGROUND: Ending preventable maternal and newborn deaths remains a global health imperative under United Nations Sustainable Development Goal targets 3.1 and 3.2. Saving Mothers, Giving Life (SMGL) was designed in 2011 within the Global Health Initiative as a public-private partnership between the U.S. government, Merck for Mothers, Every Mother Counts, the American College of Obstetricians and Gynecologists, the government of Norway, and Project C.U.R.E. SMGL's initial aim was to dramatically reduce maternal mortality in low-resource, high-burden sub-Saharan African countries. SMGL used a district health systems strengthening approach combining both supply- and demand-side interventions to address the 3 key delays to accessing effective maternity care in a timely manner: delays in seeking, reaching, and receiving quality obstetric services. IMPLEMENTATION: The SMGL approach was piloted from June 2012 to December 2013 in 8 rural districts (4 each) in Uganda and Zambia with high levels of maternal deaths. Over the next 4 years, SMGL expanded to a total of 13 districts in Uganda and 18 in Zambia. SMGL built on existing host government and private maternal and child health platforms, and was aligned with and guided by Ugandan and Zambian maternal and newborn health policies and programs. A 35% reduction in the maternal mortality ratio (MMR) was achieved in SMGL-designated facilities in both countries during the first 12 months of implementation. RESULTS: Maternal health outcomes achieved after 5 years of implementation in the SMGL-designated pilot districts were substantial: a 44% reduction in both facility and districtwide MMR in Uganda, and a 38% decrease in facility and a 41% decline in districtwide MMR in Zambia. Facility deliveries increased by 47% (from 46% to 67%) in Uganda and by 44% (from 62% to 90%) in Zambia. Cesarean delivery rates also increased: by 71% in Uganda (from 5.3% to 9.0%) and by 79% in Zambia (from 2.7% to 4.8%). The average annual rate of reduction for maternal deaths in the SMGL-supported districts exceeded that found countrywide: 11.5% versus 3.5% in Uganda and 10.5% versus 2.8% in Zambia. The changes in stillbirth rates were significant (-13% in Uganda and -36% in Zambia) but those for pre-discharge neonatal mortality rates were not significant in either Uganda or Zambia. CONCLUSION: A district health systems strengthening approach to addressing the 3 delays to accessing timely, appropriate, high-quality care for pregnant women can save women's lives from preventable causes and reduce stillbirths. The approach appears not to significantly impact pre-discharge neonatal mortality.

Maternal and perinatal outcomes in pregnant women with suspected Ebola virus disease in Sierra Leone, 2014.

OBJECTIVE: To describe maternal and perinatal outcomes among pregnant women with suspected Ebola virus disease (EVD) in Sierra Leone. METHODS: Observational investigation of maternal and perinatal outcomes among pregnant women with suspected EVD from five districts in Sierra Leone from June to December 2014. Suspected cases were ill pregnant women with symptoms suggestive of EVD or relevant exposures who were tested for EVD. Case frequencies and odds ratios were calculated to compare patient characteristics and outcomes by EVD status. RESULTS: There were 192 suspected cases: 67 (34.9%) EVD-positive, 118 (61.5%) EVD-negative, and 7 (3.6%) EVD status unknown. Women with EVD had increased odds of death (OR 10.22; 95% CI, 4.87-21.46) and spontaneous abortion (OR 4.93; 95% CI, 1.79-13.55) compared with those without EVD. Women without EVD had a high frequency of death (30.2%) and stillbirths (65.9%). One of 14 neonates born following EVD-negative and five of six neonates born following EVD-positive pregnancies died. CONCLUSION: EVD-positive and EVD-negative women with suspected EVD had poor outcomes, highlighting the need for increased attention and resources focused on maternal and perinatal health during an urgent public health response. Capturing pregnancy status in nationwide surveillance of EVD can help improve understanding of disease burden and design effective interventions.

Evaluation of Sexual Risk Behavior Among Study Participants in the TDF2 PrEP Study Among Heterosexual Adults in Botswana.

OBJECTIVE: Among participants of a clinical trial to test the efficacy of tenofovir/emtricitabine in protecting heterosexual men and women living in Botswana from HIV infection, the aim was to determine (1) if sexual risk behavior, specifically condomless sex acts and number of sex partners, changed over time, (2) factors associated with condomless sex acts and number of sex partners, and (3) the effect of participant treatment arm perception on risk behavior to address the possibility of risk compensation. METHODS: A longitudinal modeling of rates of risk behaviors was used to determine if the rate of condomless sex acts (#acts/person) and rate of sex partners (#partners/person) changed over time and which factors were associated with behavior change. RESULTS: One thousand two hundred participants were analyzed over 1 year. There was a 25% decrease in the rate of sex partners among participants sexually active in the last 30 days. The rate of reported condomless sex acts was greater for males [rate ratio (RR) = 1.34; confidence interval (CI): 1.07 to 1.67] and participants whose sexual debut in years was ≤15 years of age (RR = 1.65; CI: 1.14 to 2.38) and 16-17 (RR = 1.68; CI: 1.22 to 2.31) compared with those ≥20 years. Rate of reported sex partners was greater for males (RR = 3.67; CI: 2.86 to 4.71) and participants whose age at sexual debut in years was ≤15 (RR = 2.92; CI: 2.01 to 4.22) and 16-17 (RR = 2.34; CI: 1.69 to 3.24) compared with those ≥20. There was no effect of participant treatment arm perception on risk behavior. CONCLUSIONS: Our study of preexposure prophylaxis to prevent HIV infection found no evidence of risk compensation which may have been due to participants' motivations to reduce their risk behaviors and risk-reduction counseling.

Physicians who do and do not recommend children get all vaccinations.

The objectives of this study were to determine (1) the proportion of physicians who do and do not recommend that children receive all available vaccines and (2) physician characteristics, attitudes, and behaviors associated with not recommending children receive all vaccines. A self-administered, cross-sectional electronic survey of physicians was conducted in 2005. Analyses were restricted to pediatricians (n = 250) and family practitioners (n = 484) who indicated they see at least five pediatric patients per week. A total of 1,935 surveys were distributed, and 1,251 (65%) physicians responded. Eleven percent of the physicians included in the analysis did not recommend to parents that children receive all available vaccines. Compared with physicians who recommended all vaccines for children, physicians who did not were more likely to be family practitioners versus pediatricians (OR = 2.9, CI = 1.4-5.8), agree or be neutral versus disagree that they have some concerns about childhood immunization safety (OR = 3.1, CI = 1.8-5.2), and have or= 8 physicians in their practice (OR = 2.0, CI = 1.1-3.7). We conclude that physician characteristics and concerns about childhood immunizations are associated with not recommending all childhood vaccines. Further investigation of physicians' concerns about vaccine safety is needed to improve health communications directed toward health care providers.