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Introduction: Unrecognized Ebola Virus Disease (EVD) can lead to multiple chains of transmissions if the first caretakers are not trained and prepared. This study aimed to assess healthcare workers (HCWs) preparedness in private hospitals located in Kampala, to detect, respond and prevent EVD., Methodology: A descriptive cross-sectional study was carried out among HCWs in direct clinical care provision in four private hospitals, and in one Ebola Treatment Unit (ETU) using a self-administered questionnaire from March to June 2020., Results: 222 HCWs agreed to participate aged from 19 to 64 years and with 6 months to 38 years of practice where most were nurses (44%). 3/5 hospitals did not have written protocols on EVD case management, and only one (ETU) had an exclusive emergency team. 59% were not sure whether contact tracing was taking place. Private hospitals were not included in EVD trainings organized by the Ministry of Health (MoH). In addition, HCWs in private hospitals were not empowered by the MoH to take part in EVD case management. Despite these shortcomings, only 66% of HCWs showed an interest to be immunized. Knowledge about potential Ebola vaccines was generally poor., Conclusions: In Kampala, Uganda, establishment of a more comprehensive preparedness and response strategy for EVD outbreaks is imperative for HCWs in private facilities, including a wide vaccination educational program on Ebola vaccination. The findings from this study if addressed will likely improve the preparedness and management of future Ebola outbreaks in Uganda., Competing Interests: No Conflict of Interest is declared, (Copyright (c) 2024 Collins Ankunda, Stuart Martin Kanyesigye, Susan Nakubulwa, Brendah Kyomuhangi, Jakob Cramer, Enrique Chacon-Cruz, Sue Ann Costa Clemens, Ralf Clemens.)

Background: Early resumption of sexual intercourse in the puerperium is a concern for couples because it is often not discussed during pre-natal or postpartum care., Objective: This cross-sectional survey aimed to establish the current burden and factors associated with the early resumption of sexual intercourse within the puerperium at the National Referral Hospital and Mengo Hospital., Methods: We conducted a descriptive cross-sectional study among 445 parous women attending the six-week postpartum review and the young child clinic at Kawempe National Referral and Mengo Hospitals between March and May 2021., Results: The prevalence of ERSP within the puerperium was 39%. This study's earliest time to resume sexual intercourse was one week; the majority had resumed by week four (9.2%). Factors associated with the early resumption of sexual relations were the person's tribe, going to the husband's home after birth, and parity. The prevalence of sexual morbidities was 13%. Seventy-five (75%) of mothers did not receive information from the health care workers on when they can resume sex following childbirth., Conclusion: Puerperal sexual intercourse is still prevalent in Uganda. Interventions to reduce the resumption of sexual intercourse in the puerperium should focus on these determinants to delay puerperal sexual intercourse., Competing Interests: The authors declare no competing interest or conflict of interest., (© 2023 Namulema E et al.)

Objectives: The COVID-19 pandemic affected provision and use of maternal health services. This study describes changes in obstetric complications, referrals, stillbirths and maternal deaths during the first year of the pandemic and elucidates pathways to these changes., Design: Prospective observational mixed-methods study, combining monthly routine data (March 2019-February 2021) and qualitative data from prospective semi-structured interviews. Data were analysed separately, triangulated during synthesis and presented along three country-specific pandemic periods: first wave, slow period and second wave., Setting: Six referral maternities in four sub-Saharan African countries: Guinea, Nigeria, Tanzania and Uganda., Participants: 22 skilled health personnel (SHP) working in the maternity wards of various cadres and seniority levels., Results: Percentages of obstetric complications were constant in four of the six hospitals. The percentage of obstetric referrals received was stable in Guinea and increased at various times in other hospitals. SHP reported unpredictability in the number of referrals due to changing referral networks. All six hospitals registered a slight increase in stillbirths during the study period, the highest increase (by 30%-40%) was observed in Uganda. Four hospitals registered increases in facility maternal mortality ratio; the highest increase was in Guinea (by 158%), which had a relatively mild COVID-19 epidemic. These increases were not due to mortality among women with COVID-19. The main pathways leading to these trends were delayed care utilisation and disruptions in accessing care, including sub-optimal referral linkages and health service closures., Conclusions: Maternal and perinatal survival was negatively affected in referral hospitals in sub-Saharan Africa during COVID-19. Routine data systems in referral hospitals must be fully used as they hold potential in informing adaptations of maternal care services. If combined with information on women's and care providers' needs, this can contribute to ensuring continuation of essential care provision during emergency., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Objectives: Haemolytic disease of the newborn (HDN) is an immune haemolytic anaemia from maternal alloantibodies. Rh immunoglobulin (RhIg) prophylaxis can prevent alloimmunization to the D antigen. However, RhIg is not universally available in Uganda. ABO incompatibility also causes HDN. We determined the prevalence of HDN among newborn infants with jaundice in Uganda., Materials and Methods: We conducted a prospective cross-sectional study at Kawempe National Referral Hospital, Kampala, Uganda. Infants aged 0-14 days with neonatal jaundice (or total bilirubin >50 μmol/L) were enrolled. Clinical evaluation and laboratory testing, including ABO, RhD typing and maternal antibody screen, were performed., Results: A total of 466 babies were enrolled. The mean (SD) age was 3.4 (1.5) days. Of newborn babies with jaundice, 17.2% (80/466) had HDN. Babies with HDN had lower haemoglobin (SD); 15.7 (2.7) compared with those without HDN; 16.4 (2.4) g/dL, p = 0.016; and a higher bilirubin (interquartile range); 241 (200-318) compared with those without HDN; 219 (191-263) μmol/L, p < 0.001. One baby had anti-D HDN, while 46/466 had HDN from an ABO incompatibility (anti-A 43.5% and anti-B 56.5%); 82% of babies with HDN also had suspected neonatal sepsis or birth asphyxia. About 79.2% (57/72) of mothers did not have ABO/Rh blood group performed antenatally. All infants with HDN survived except one., Conclusion: Among newborn infants with jaundice, HDN is not rare. The majority is due to ABO HDN affecting group A and group B babies equally. Ensuring routine ABO/Rh grouping for all pregnant women is an area for improvement., (© 2022 International Society of Blood Transfusion.)

Aims: The study aims to evaluate the strength of fasting versus post-load glucose levels in predicting adverse outcomes in women with hyperglycaemia in pregnancy (HIP)., Methods: Women attending antenatal clinics in urban and peri-urban Uganda had oral glucose tolerance test between 24 and 28 weeks of gestation to screen for HIP, and were followed up to collect data on maternal and neonatal outcomes. Univariable and multivariable Poisson regression models were used to estimate the relative risk adverse outcome associated with fasting hyperglycaemia alone post-load hyperglycaemia alone, or elevation of both fasting and post-load glucose levels., Results: We included 3206 participants in the final analysis. HIP was associated with increased risk of Caesarean section, large for gestaional age babies, and neonatal intensive care admission. The risk was highest (2.54-fold compared to normal glycaemic women) when both FBG and post-load glucose levels were elevated. After adjustment for potential confounders, having elevated post-load glucose alone was not associated with increased risk of any of the outcomes, but elevated FBG alone increased the risk of Caesarian section by 1.36-fold., Conclusion: Fasting hyperglycemia appears to be more strongly associated with adverse pregnancy outcomes than post-load hyperglycaemia, but the risk is even higher in women with elevation of both fasting and post-load glucose levels., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier B.V.)

Introduction: Referral hospitals in sub-Saharan Africa are located in crowded urban areas, which were often epicentres of the COVID-19 pandemic. This paper prospectively assesses how maternal healthcare was provided in six referral hospitals in Guinea, Nigeria, Tanzania and Uganda during the first year of the COVID-19 pandemic., Methods: Mixed-methods design using three data sources: (1) qualitative data from repeated rounds of semi-structured interviews conducted between July 2020 and February 2021 with 22 maternity skilled heath personnel (SHP) on perceptions of care provision; (2) quantitative monthly routine data on caesarean section and labour induction from March 2019 to February 2021; and (3) timeline data of COVID-19 epidemiology, national and hospital-level events. Qualitative and quantitative data were analysed separately, framed based on timeline analysis, and triangulated during reporting., Results: We identified three periods: first wave, slow period and second wave. The first wave was challenging for SHP given little knowledge about COVID-19, lack of infection prevention and control training, and difficulties reaching workplace. Challenges that persisted beyond the first wave were shortage of personal protective equipment and no rapid testing for women suspected with COVID-19. We noted no change in the proportion of caesarean sections during the pandemic, and a small increase in the proportion of labour inductions. All hospitals arranged isolation areas for women suspected/confirmed with COVID-19 and three hospitals provided care to women with suspected/confirmed COVID-19. Breastfeeding was not discouraged and newborns were not separated from mothers confirmed with COVID-19. Care provision was maintained through dedication of SHP, support from hospital management and remote communication between SHP., Conclusion: Routine maternal care provision was maintained in referral hospitals, despite first wave challenges. Referral hospitals and SHP contributed to guideline development for pregnant women suspected/confirmed with COVID-19. Maternity SHP, women and pregnancy must always be included in priority setting when responding to health system shocks, including outbreaks., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: In sub-Saharan Africa, referral hospitals are important sources of key maternal health services, especially during a crisis such as the COVID-19 pandemic. This study prospectively assessed the effect of the COVID-19 pandemic on maternal health service utilisation in six large referral hospitals in Guinea, Nigeria, Tanzania and Uganda during the first year of the pandemic., Methods: Mixed-methods design combining three data sources: (1) quantitative data based on routine antenatal, childbirth and postnatal care data collected March 2019-February 2021, (2) qualitative data from recurring rounds of semi-structured interviews conducted July 2020-February 2021 with 22 maternity skilled heath personnel exploring their perceptions of service utilisation and (3) timeline data of COVID-19 epidemiology, global, national and hospital-level events. Qualitative and quantitative data were analysed separately, framed based on the timeline analysis and triangulated when reporting., Results: Three periods including a first wave, slow period and second wave were identified. Maternal health service utilisation was lower during the pandemic compared with the prepandemic year in all but one selected referral hospital. During the pandemic, service utilisation was particularly lower during the waves and higher or stable during the slow period. Fear of being infected in hospitals, lack of transportation, and even when available, high cost of transportation and service closures were key reasons affecting utilisation during the waves. However, community perception that the pandemic was over or insinuation by Government of the same appeared to stabilise use of referral hospitals for childbirth., Conclusion: Utilisation of maternal health services across the continuum of care varied through the different periods and across countries. In crisis situations such as COVID-19, restrictions and service closures need to be implemented with consideration given to alternative options for women to access and use services. Information on measures put in place for safe hospital use should be communicated to women., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Hyperglycaemia in pregnancy (HIP) is associated with complications for both mother and baby. The prevalence of the condition is likely to increase across Africa as the continent undergoes a rapid demographic transition. However, little is known about the management and pregnancy outcomes associated with HIP in the region, particularly less severe forms of hyperglycaemia. It is therefore important to generate local data so that resources may be distributed effectively. The aim of this study was to describe the antenatal management and maternal/fetal outcomes associated with HIP in Ugandan women., Methods: A prospective cohort study of 2917 pregnant women in five major hospitals in urban/semi-urban central Uganda. Women were screened with oral glucose tolerance test (OGTT) at 24-28 weeks of gestation. Cases of gestational diabetes (GDM) and diabetes in pregnancy (DIP) were identified (WHO 2013 diagnostic criteria) and received standard care. Data was collected on maternal demographics, anthropometrics, antenatal management, umbilical cord c-peptide levels, and pregnancy outcomes., Results: Two hundred and seventy-six women were diagnosed with HIP (237 classified as GDM and 39 DIP). Women had between one and four fasting capillary blood glucose checks during third trimester. All received lifestyle advice, one quarter (69/276) received metformin therapy, and one woman received insulin. HIP was associated with large birthweight (unadjusted relative risk 1.30, 95% CI 1.00-1.68), Caesarean delivery (RR 1.34, 95% CI 1.14-1.57) and neonatal hypoglycaemia (RR 4.37, 95% CI 1.36-14.1), but not perinatal mortality or preterm birth. Pregnancy outcomes were generally worse for women with DIP compared with GDM., Conclusion: HIP is associated with significant adverse pregnancy outcomes in this population, particularly overt diabetes in pregnancy. However pregnancy outcomes in women with milder forms of hyperglycaemia are similar to those with normoglycaemic pregnancies. Intervention strategies are required to improve current monitoring and management practice, and more research needed to understand if this is a cost-effective way of preventing poor perinatal outcomes.

Background: The association between overt hypertension and diabetes and adverse pregnancy outcomes is well documented. Recent evidence suggests that even moderate elevations in blood pressure or blood glucose may confer a significant risk in a dose-dependent manner. However, these studies have primarily been undertaken in white populations in high-income settings. Hypertension and diabetes are emerging as major public health issues in sub-Saharan Africa as the region undergoes rapid urbanization. It is therefore important to understand how such noncommunicable conditions contribute to pregnancy outcomes in these populations., Objective: This study aimed to determine the association between stage 1 hypertension or fasting blood glucose in the gestational diabetes mellitus-range and adverse pregnancy outcomes in Uganda, and to describe the effects of other contributing factors such as maternal obesity., Study Design: This was a prospective cohort study of 2857 women at 5 major hospitals in urban and semiurban central Uganda. Women were enrolled at 24 to 28 weeks' gestation. Data about the maternal demographics, anthropometrics, fasting venous blood glucose, blood pressure, and pregnancy outcomes were collected. Moderate elevations in blood pressure and blood glucose were defined using the latest American College of Cardiology and American Heart Association definition of stage 1 hypertension and the World Health Organization's criteria for fasting blood glucose in the gestational diabetes mellitus-range. The primary outcomes of interest were perinatal death and large birthweight for gestational age, and the secondary outcomes were preterm birth, cesarean delivery, and neonatal admission. A multivariable logistic regression analysis was used., Results: Stage 1 hypertension increased the odds of perinatal death by more than 2-fold (adjusted odds ratio, 2.68; 95% confidence interval, 1.36-5.29), with a positive but insignificant association with preterm birth. Hyperglycemia in the gestational diabetes mellitus-range was associated with cesarean delivery only (adjusted odds ratio, 1.65; 95% confidence interval, 1.20-2.27). Maternal obesity increased the risk of having large birthweight babies (adjusted odds ratio, 2.30; 95% confidence interval, 1.74-3.02), a cesarean delivery (adjusted odds ratio, 2.75; 95% confidence interval, 2.17-3.48), and neonatal admission (adjusted odds ratio, 1.63; 95% confidence interval, 1.16-2.30)., Conclusion: Moderate elevations in blood pressure and maternal obesity are stronger predictors of adverse maternal and neonatal outcomes than moderate elevations in blood glucose levels and should be the focus of intervention in these resource-poor settings. Further research is needed to determine the cost-effectiveness of identifying and managing moderate elevations in blood pressure and maternal obesity., (© 2021 The Authors.)

Background: Accuracy of fetal weight estimation by ultrasound is essential in making decisions on the time and mode of delivery. There are many proposed formulas for fetal weight estimation such as Hadlock 1, Hadlock 2, Hadlock 3, Hadlock 4 and Shepard. What best applies to the Ugandan population is not known since no verification of any of the formulas has been done before. The primary aim of this study was to determine the accuracy of sonographic estimation of fetal weight using five most commonly used formulas, and analyze formula variations for different weight ranges., Methods: This was a hospital based prospective cohort study at Mulago National Referral Hospital, Kampala, Uganda. A total of 356 pregnant women who consented and were within 3 days of birth were enrolled. Prenatal ultrasound fetal weight determined by measuring the biparietal diameter, head circumference, abdominal circumference, femoral length, and then was compared with actual birth weight., Results: The overall accuracy of Hadlock 1, Hadlock 2, Hadlock 3, Hadlock 4 and Shepard formula were 66.9, 73.3, 77.3, 78.4 and 69.7% respectively. All Hadlocks showed significant mean difference between weight estimates and actual birth weight (p < 0.01) whereas Shepard formula did not [p - 0.2], when no stratification of fetal weights was done. However, all Hadlocks showed a none significant (p-values > 0.05) mean difference between weight estimates and actual birth weight when the actual birth weight was ≥4000.0 g. Shepard weight estimates showed a none significant mean difference when actual birth weight was < 4000 g. Bland-Altman graphs also showed a better agreement of weight estimated by Shepard formula and actual birth weights., Conclusion: All the five formulas were accurate at estimating actual birth weights within 10% accuracy. However, this accuracy varied with the fetal birth weight. Shepard was more accurate in estimating actual birth weights < 4000 g whereas all Hadlocks were more accurate when the actual birthweight was ≥4000 g.

COVID-19 measures that restrict movement may negatively impact access to HIV care and treatment. To contribute to the currently limited evidence, we used telephone interviews with quantitative and qualitative questions to examine how clients perceived COVID-19 and its effect on their HIV care and ART adherence. One hundred (n = 100) Ugandan adults on ART from an existing study were randomly selected and enrolled. Interviews were recorded, transcribed, and analyzed using descriptive statistics and rapid content analyses. 76% of clients indicated that COVID-19 negatively impacted travel to HIV clinics; 54% perceived that coming to the clinic increased their risk of acquiring COVID-19; and 14% said that COVID-19 had negatively impacted their ART adherence. Qualitative feedback suggests that fear of COVID-19 infection discouraged clinic attendance while stay-at-home orders helped routinize ART adherence and employ new community-based approaches for HIV care. Addressing negative unintended consequences of COVID-19 lockdowns on HIV care is urgently needed.

Objectives: Low birth-weight is a major risk factor for perinatal death in sub-Saharan Africa, but the relative contribution of determinants of birth-weight are difficult to disentangle in low resource settings. We sought to delineate the relationship between birth-weight and maternal pre-eclampsia across gestation in a low-resource obstetric setting., Study Design: Prospective cohort study in a tertiary referral centre in urban Uganda, including 971 pre-eclampsia cases and 1461 control pregnancies between 28 and 42 weeks gestation., Main Outcome Measures: Nonlinear modeling of birth-weight versus maternal pre-eclampsia status across gestation. Models were adjusted for maternal-fetal characteristics including maternal age, parity, HIV status, and socio-economic status. Propensity score matching was used to control for the severity of pre-eclampsia at different gestational ages., Results: Mean birth-weight for pre-eclampsia cases was 2.48 kg (±0.81SD) compared to 3.06 kg (±0.46SD) for controls (p < 0.001). At 28 weeks, the mean birth-weight difference between pre-eclampsia cases and controls was 0.58 kg (p < 0.05), narrowing to 0.17 kg at 39 weeks (p < 0.01). Controlling for pre-eclampsia severity only partially explained this gestational difference in mean birth-weight between pre-eclampsia cases and controls. Holding gestational age constant, pre-eclampsia status predicted 7.1-10.5% of total variation in birth-weight, compared to 0.05-0.7% for all other maternal-fetal characteristics combined., Conclusions: Pre-eclampsia is the dominant predictor of birth-weight in low-resource settings and hence likely to heavily influence perinatal survival. The impact of pre-eclampsia on birth-weight is smaller with advancing gestational age, a difference that is not fully explained by controlling for pre-eclampsia severity., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

On October 25, 2016, media reports alerted the Uganda Ministry of Health to an outbreak of >80 cases of vomiting, syncope, and acute diarrhea among workers at a flower farm in central Uganda; 27 workers were hospitalized. On November 1, an investigation was undertaken by the Uganda Public Health Fellowship Program.* A case-control study found that working inside greenhouse 7, which had been fumigated with the organosulfur compound metam sodium the night of October 13, was strongly associated with illness. Employees who worked in this greenhouse during October 14-21 reported a strong "suffocating" smell in the greenhouse. Investigation revealed that, in violation of safety protocols, workers did not properly cover the soil after fumigation, allowing vapors to become trapped inside the greenhouse. The farm management, unaware of the lapse, failed to inform workers to avoid the vicinity of the fumigation. Respiratory protective measures were not routinely available for workers, which likely contributed to the severity and extent of the outbreak. Although metam sodium is generally considered to be of low risk when used according to manufacturer's instructions (1), occupational exposure in the absence of recommended safety measures can have serious health consequences. The investigation highlighted the importance of identifying potential occupational hazards to workers, as well as establishing safety protocols in occupational settings, training workers at risk, such as pesticide sprayers and flower pickers, † and ensuring enforcement of safety protocols. After this outbreak, the farm management reviewed, revised, and trained the workers on safety protocols to prevent future outbreaks., Competing Interests: No conflicts of interest were reported.

Background: Superinfection of individuals already infected with HIV-1 suggests that pre-existing immune responses may not adequately protect against re-infection. We assessed high-risk female sex workers initially infected with HIV-1 clades A, D or A/D recombinants, to determine if HIV-1 broadly neutralizing antibodies were lacking prior to superinfection., Methods: Six superinfected female sex workers previously stratified by HIV-1 high-risk behavior, infecting virus clade and volunteer CD4 counts were evaluated at baseline (n = 5) and at 350 days post-superinfection (n = 6); one superinfected volunteer lacked pre-superinfection plasma. Retrospective plasmas were assessed for neutralization of a multi-clade panel of 12 HIV-1 viruses before superinfection, and then at quarterly intervals thereafter. Similarly stratified singly infected female sex workers were correspondingly assessed at baseline (n = 19) and 350 days after superinfection (n = 24). Neutralization of at least 50% of the 12 viruses (broad neutralization), and geometric means of the neutralization titers (IC 50 ) were compared before and after superinfection; and were correlated with the volunteer HIV-1 superinfection status, CD4 counts, and pseudovirus clade., Results: Preexisting broad neutralization occurred in 80% (4/5) of the superinfected subjects with no further broadening by 350 days after superinfection. In one of the five subjects, HIV-1 superinfection occurred when broad neutralization was lacking; with subsequent broadening of neutralizing antibodies occuring within 9 months and plateauing by 30 months after detection of superinfection. Clade B and C pseudoviruses were more sensitive to neutralization (13; [87%]); and (12; [80%]) than the locally circulating clades A (10; [67%]) and D (6; [40%]), respectively (p = 0.025). Low antibody titers correlated with clade D viruses and with >500 CD4 T cell counts, but not with the superinfection status., Conclusion: These data demonstrate that HIV-1 superinfection can occur both in the presence, and in the absence of broadly neutralizing antibodies., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Acyclovir (ACV) given to HSV-2 positive women after 36 weeks reduces adverse outcomes but its benefit at lower gestation was undocumented. We determined the effect of oral acyclovir administered from 28 to 36 weeks on premature rupture of membranes (PROM) primarily and preterm delivery risk., Methods: This was a randomized, double-blind placebo-controlled trial among 200 HSV-2 positive pregnant women at 28 weeks of gestation at Mulago Hospital, Uganda. Participants were assigned randomly (1:1) to take either acyclovir 400 mg orally twice daily (intervention) or placebo (control) from 28 to 36 weeks. Both arms received acyclovir after 36 weeks until delivery. Development of Pre-PROM by 36 weeks and preterm delivery were outcomes., Results: One hundred women were randomised to acyclovir and 100 to placebo arms between January 2014 and February 2015. There was tendency towards reduction of incidence of PROM at 36 weeks but this was not statistically significant (4.0% versus 10.0%; RR 0.35; 95% 0.11-1.10) in the acyclovir and placebo arms respectively. However, there was a significant reduction in the incidence of preterm delivery (11.1% versus 23.5%; RR 0.41; 95% 0.20-0.85) in the acyclovir and placebo arms respectively., Conclusions: Oral acyclovir given to HSV-2 positive pregnant women from 28 to 36 weeks reduced incidence of preterm delivery but did not significantly reduce incidence of pre-PROM., Trial Registration: www.pactr.org, PACTR201311000558197 .

Introduction: Herpes simplex virus type 2 (HSV-2) acquired during pregnancy is associated with adverse outcomes such as perinatal HSV-2 transmission. HSV-2 seroconversion occurs within four weeks of HSV-2 acquisition. There was neither documented incidence nor risk factors for HSV-2 seroconversion during pregnancy in Uganda. The objective of this study was to determine the incidence and risk factors for HSV-2 seroconversion among pregnant women in Mulago Hospital, Uganda., Methodology: A prospective study of 200 consenting HSV-2-negative women between 26 and 28 weeks of gestation was done between November 2013 and October 2014. HSV-2 serostatus was determined using HerpeSelect HSV-2 enzyme-linked immunosorbent assay (ELISA). Interviewer-administered questionnaires were used to collect socio-demographic characteristics and sexual history. Human immunodeficiency virus (HIV) serostatus was obtained from antenatal records. A total of 191 women completed follow-up and repeat HSV-2 serology by 38 weeks. Negative binomial regression analysis was used to estimate risk ratios for risk factors for HSV-2 seroconversion., Results: Of 191 women, 15 (7.9%) seroconverted during pregnancy. Having multiple sexual partners, being in polygamous unions, and having HIV-positive serostatus were found to be risk factors for HSV-2 seroconversion., Conclusions: The incidence of HSV-2 seroconversion during pregnancy in Uganda was high. Multiple sexual partners, polygamy, and HIV-positive serostatus were risk factors for HSV-2 seroconversion during pregnancy. Strengthening health education on the avoidance of multiple sexual partners during pregnancy is paramount in prevention of HSV-2 seroconversion.

Background: Hypertensive disorders of pregnancy are a major cause of morbidity and mortality. The objective was to estimate the disease burden attributable to hypertensive disorders of pregnancy in two referral hospitals in Uganda., Methods: Through a prospective cohort study conducted in Jinja and Mulago hospitals in Uganda from March 1, 2013 and February 28, 2014, hypertension-related cases were analyzed. Maternal near miss cases were defined according to the WHO criteria. Maternal deaths were also analyzed. The maternal near miss incidence ratio, the case-specific severe maternal outcome ratio, the case-specific maternal mortality ratio and the case-fatality ratio were computed., Results: Of 403 women with hypertensive disorders of pregnancy, 218 (54.1 %) had severe preeclampsia, 172 (42.7 %) had eclampsia, and 13 had chronic hypertension or Hemolysis, elevated liver enzymes or low platelets (HELLP) syndrome. The case-specific maternal near miss incidence ratios was 8.60 per 1,000 live births for all hypertensive disorders, 3.06 per 1,000 live births for severe preeclampsia and 5.11 per 1,000 live births for eclampsia. The case-specific severe maternal outcome ratio was 9.37 per 1,000 live births for all hypertensive disorders, and was 3.25 per 1,000 live births for severe preeclampsia and 5.61 per 1,000 live births for eclampsia. The case-specific maternal mortality ratio was 780 per 100,000 live births for all hypertensive disorders, and was 1940 per 100,000 live births for severe preeclampsia and 501 per 100,000 live births for eclampsia. The case-fatality ratio was 5.1 % overall (for all hypertensive disorders), but was 8 times higher for eclampsia compared to severe preeclampsia. Cyanosis, abnormal respiration, oliguria, circulatory collapse, coagulopathy, thrombocytopenia, and elevated serum lactate were significantly associated with severe maternal outcomes., Conclusion: There is high morbidity attributable to hypertensive disorders in pregnancy. Since some of the complications associated with morbidity can be recognized early, it is possible to prevent severe morbidity through early intervention with delivery, antihypertensive therapy and prophylactic magnesium sulphate treatment. The findings highlight the feasibility of implementing a facility-based surveillance system for severe maternal morbidity due to hypertensive disorders.

Background: The prevalence of sexually transmitted infections (STIs) among female sex workers (FSWs) in sub-Saharan Africa remains high. Providing treatment to the affected FSWs is a challenge, and more so to their stable sexual partners. There is scanty research information on acceptance of STI treatment for stable sexual partners by FSWs. We conducted a study to assess acceptance of STI treatment for stable sexual partners by FSWs, and to identify factors associated with acceptance., Methods: We enrolled 241 FSWs in a cross sectional study; they were aged ≥ 18 years, had a stable sexual partner and a diagnosis of STI. Factors associated with acceptance of STI treatment for stable sexual partners were analysed in STATA (12) using Poisson regression. Mantel-Haenszel tests for interaction were performed., Results: Acceptance of partner treatment was 50.6%. Majority (83.8%) of partners at the last sexual act were stable partners, and 32.4% of participants had asymptomatic STIs. Factors independently associated with acceptance were: earning ≤ $4 USD per sexual act (aPR 0.68; 95% CI: 0.49-0.94) and a clinical STI diagnosis (aPR 1.95; 95% CI: 1.30-2.92). The effect of low income on acceptance of partner treatment was seen in those with less education., Conclusion: Acceptance of STI treatment for stable sexual partners was lower than that seen in other studies. Interventions to improve economic empowerment among FSWs may increase acceptance of partner treatment.

Background: The most recent reports on global trends in neonatal mortality continue to show alarmingly slow progress on improvements in neonatal mortality rates, with sub-Saharan Africa still lagging behind. This emphasised the urgent need to innovatively employ alternative solutions that take into account the intricate complexities of neonatal health and the health systems in which the various strategies operate., Methods: In our first paper, we empirically explored the causes of the stagnating neonatal mortality in Uganda using a dynamic synthesis methodology (DSM) approach. In this paper, we completed the last three stages of DSM, which involved the development of a quantitative (simulation) model, using STELLA modelling software. We used statistical data to populate the model. Through brainstorming sessions with stakeholders, iterations to test and validate the model were undertaken. The different strategies and policy interventions that could possibly lower neonatal mortality rates were tested using what-if analysis. Sensitivity analysis was used to determine the strategies that could have a great impact on neonatal mortality., Results: We developed a neonatal health simulation model (NEOSIM) to explore potential interventions that could possibly improve neonatal health within a health system context. The model has four sectors, namely population, demand for services, health of the mothers and choices of clinical care. It tests the effects of various interventions validated by a number of Ugandan health practitioners, including health education campaigns, free delivery kits, motorcycle coupons, kangaroo mother care, improving neonatal resuscitation and labour management skills, and interventions to improve the mothers health, i.e. targeting malaria, anaemia and tetanus. Among the tested interventions, the package with the highest impact on reducing neonatal mortality rates was a combination of the free delivery kits in a setting where delivery services were free and motorcycle coupons to take women to hospital during emergencies., Conclusions: This study presents a System Dynamics model with a broad and integrated view of the neonatal health system facilitating a deeper understanding of its current state and constraints and how these can be mitigated. A tool with a user friendly interface presents the dynamic nature of the model using 'what-if' scenarios, thus enabling health practitioners to discuss the consequences or effects of various decisions. Key findings of the research show that proposed interventions and their impact can be tested through simulation experiments thereby generating policies and interventions with the highest impact for improved healthcare service delivery.

Objectives: Bacterial vaginosis (BV) is associated with increased risk for sexually transmitted infections (STIs) and HIV acquisition. This study describes the epidemiology of BV in a cohort of women at high risk for STI/HIV in Uganda over 2 years of follow-up between 2008-2011., Methods: 1027 sex workers or bar workers were enrolled and asked to attend 3-monthly follow-up visits. Factors associated with prevalent BV were analysed using multivariate random-effects logistic regression. The effect of treatment on subsequent episodes of BV was evaluated with survival analysis., Results: Prevalences of BV and HIV at enrolment were 56% (573/1027) and 37% (382/1027), respectively. Overall, 905 (88%) women tested positive for BV at least once in the study, over a median of four visits. Younger age, a higher number of previous sexual partners and current alcohol use were independently associated with prevalent BV. BV was associated with STIs, including HIV. Hormonal contraception and condom use were protective against BV. Among 853 treated BV cases, 72% tested positive again within 3 months. There was no difference in time to subsequent BV diagnosis between treated and untreated women., Conclusions: BV was highly prevalent and persistent in this cohort despite treatment. More effective treatment strategies are urgently needed., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Background: Maternal near misses occur more often than maternal deaths and could enable more comprehensive analysis of risk factors, short-term outcomes and prognostic factors of complications during pregnancy and childbirth. The study determined the incidence, determinants and prognostic factors of severe maternal outcomes (near miss or maternal death) in two referral hospitals in Uganda., Methods: A prospective cohort study was conducted between March 1, 2013 and February 28, 2014, where cases of severe pregnancy and childbirth complications were included. The clinical conditions included abortion-related complications, obstetric haemorrhage, hypertensive disorders, obstructed labour, infection and pregnancy-specific complications such as febrile illness, anemia and premature rupture of membranes. Near miss cases were defined according to the WHO criteria. Multivariate logistic regression analysis was conducted to identify prognostic factors for severe maternal outcomes., Results: Of 3100 women with severe obstetric complications, 130 (4.2%) were maternal deaths and 695 (22.7%) were near miss cases. Severe pre-eclampsia was the commonest morbidity (incidence ratio (IR) 7.0%, case-fatality rate (CFR) 2.3%), followed by postpartum haemorrhage (IR 6.7%, CFR 7.2%). Uterine rupture (IR 5.5%) caused the highest CFR (17.9%), followed by eclampsia (IR 0.4%, CFR 17.8%). The three groups (maternal deaths, near misses and non-life-threatening obstetric complications) differed significantly regarding gravidity and education level. The commonest diagnostic criteria for maternal near miss were admission to the high dependency unit (HDU) or to the intensive care unit (ICU). Thrombocytopenia, circulatory collapse, referral to a more specialized unit, intubation unrelated to anaesthesia, and cardiopulmonary resuscitation were predictive of maternal death (p < 0.05). Gravidity (ARR 1.4, 95% C1 1.0-1.2); elevated serum lactate levels (ARR 4.5, 95% CI 2.3-8.7); intubation for conditions unrelated to general anaesthesia (ARR 2.6 (95% CI 1.2-5.7), cardiovascular collapse (ARR 4.9, 95% CI 2.5-9.5); transfusion of 4 or more units of blood (ARR 1.9, 95% CI 1.1-3.1); being an emergency referral (ARR 2.6, 95% CI 1.2-5.6); and need for cardiopulmonary resuscitation (ARR 6.1, 95% CI 3.2-11.7), were prognostic factors., Conclusions: The analysis of near misses is a useful tool in the investigation of severe maternal morbidity. The prognostic factors for maternal death, if instituted, might save many women with obstetric complications.

The aim of this study was to describe the epidemiology of problem drinking in a cohort of women at high-risk of HIV in Kampala, Uganda. Overall, 1027 women at high risk of HIV infection were followed from 2008 to 2013. The CAGE and AUDIT questionnaires were used to identify problem drinkers in the cohort. Interviewer-administered questionnaires were used to ascertain socio-demographic and behavioural factors. Blood and genital samples were tested for HIV and other sexually transmitted infections. At enrollment, most women (71%) reported using alcohol at least weekly and about a third reported having drunk alcohol daily for at least 2 weeks during the past 3 months. Over half (56%) were problem drinkers by CAGE at enrollment, and this was independently associated with vulnerability (being divorced/separated/widowed, less education, recruiting clients at bars/clubs, and forced sex at first sexual experience). Factors associated with problem drinking during follow-up included younger age, meeting clients in bars/clubs, number of clients, using drugs and HSV-2 infection. HIV prevalence was associated with drinking at enrollment, but not during follow-up. This longitudinal study found high levels of persistent problem drinking. Further research is needed to adapt and implement alcohol-focused interventions in vulnerable key populations in sub-Saharan Africa.

Background: Elective caesarean sections (ECS) have been implicated in increased risk of adverse neonatal outcomes. The primary objective was to assess the incidence and determinants of neonatal morbidity after elective caesarean section deliveries. The secondary objective was to describe the maternal morbidity associated with elective caesarean section., Methods: This was a prospective cohort study of women admitted for ECS, as well as their newborns, conducted at Mulago hospital from March 1, 2013 to February 28, 2014. These were followed from the time of the operation until 6 weeks after hospitalization following the caesarean delivery. Data was collected using an interviewer-administered questionnaire and review of medical records for demographic characteristics, obstetric history, current pregnancy complications and pregnancy outcomes up to hospital discharge. Study outcomes were maternal and neonatal morbidity. The data was analyzed using Stata version 12., Results: There were 25,846 deliveries during the study period, of which 20,083 (77.7%) were vaginal deliveries or assisted deliveries, and 5763 (22.3%) were caesarean sections. Of the caesarean sections, 920 (15.9%) were ECS. The commonest maternal morbidity was hemorrhage (17.2%). A birth weight less than 2500 g (aRR 11.0 [95% CI 8.1-17.2]) or more than 4000 g (aRR 12.2 [95% CI 10.6-23.2]), delivery at gestation age less than or equal to 38 weeks (aRR 1.62 [95% 1.20-2.10]), multigravidity (aRR 1.70 [95% CI 1.20-2.90]) and using general anaesthesia (aRR 2.43 [95% CI 1.20-5.90]) were associated with risk of neonatal morbidity. The commonest neonatal morbidity is respiratory distress especially if delivery occurs at a gestation age of 37 weeks or lower, if the birth weight is less than 2500 g or more than 4000 g, and if general anesthesia is used., Conclusion: Our study shows that at Mulago Hospital, ECS is associated with significant neonatal and maternal morbidity. We recommend that elective caesarean sections be performed after 39 weeks of gestation, and preferably avoid using general anaesthesia.

Background: Inflammatory mediators that weaken and cause membrane rupture are released during the course of genital infections among pregnant women. We set out to determine the association of common genital infections (Trichomonas vaginalis, syphilis, Neisseria gonorrhea, Chlamydia trachomatis, Group B Streptococcus, Bacterial vaginosis, Herpes Simplex Virus Type 2 and candidiasis) and premature rupture of membranes in Mulago hospital, Uganda., Methods: We conducted an unmatched case-control study among women who were in the third trimester of pregnancy at New Mulago hospital, Uganda. The cases had PROM and the controls had intact membranes during latent phase of labour in the labour ward. We used interviewer-administered questionnaires to collect data on socio-demographic characteristics, obstetric and medical history. Laboratory tests were conducted to identify T. vaginalis, syphilis, N. gonorrhea, C. trachomatis, Group B Streptococcus, Bacterial vaginosis, Herpes Simplex Virus Type 2 (HSV-2) and candidiasis. Logistic regression models were used to estimate the odds ratios (OR) and 95% CI of the association between genital infections and PROM., Results: There was an association between PROM and abnormal vaginal discharge (OR = 2.02, 95% CI 1.10-3.70 and AOR = 2.30, 95% CI 1.18-4.47), presence of candidiasis (OR = 0.27, 95% CI 0.14-0.52 and AOR = 0.22, 95% CI 0.10-0.46) and T. vaginalis (OR = 2.98, 95% CI 1.18-7.56 and AOR = 4.22, 95% CI 1.51-11.80). However, there was no association between PROM and presence of C. trachomatis (OR = 2.05, 95% CI 0.37-11.49) and HSV-2 serostatus (OR = 1.15, 95% CI 0.63-2.09). Few or no patients with Bacterial vaginosis, Neisseria gonorrhoea, Group B streptococcus or syphilis were identified among the cases and controls. Co-infection of Trichomoniasis and candidiasis was not associated with PROM (AOR = 1.34, 95% CI 0.16-11.10). Co infection with T. vaginalis and C. trachomatis was associated with PROM (OR = 3.09, 95% CI 1.21-7.84 and AOR = 4.22, 95% CI 1.51-11.83)., Conclusion: Trichomonas vaginalis alone, T. vaginalis with C. trachomatis co-infection and abnormal per vaginal discharge were found as risk factors for PROM. There was no association of HSV-2 serostatus, syphilis, N. gonorrhea, C. trachomatis, Group B Streptococcus and Bacterial vaginosis with PROM. Candidiasis seemed to have a protective effect on PROM.

The World Health Organization recommends for tuberculosis retreatment a regimen of isoniazid (H), rifampicin (R), ethambutol (E), pyrazinamide (Z), and streptomycin (S) for 2 months, followed by H, R, E, and Z for 1 month and H, R, and E for 5 months. Using data from the National Tuberculosis and Leprosy Program registry, this study determined the long-term outcome under programmatic conditions of patients who were prescribed the retreatment regimen in Kampala, Uganda, between 1997 and 2003. Patients were traced to determine their vital status; 62% (234/377) patients were found dead. Having ≤ 2 treatment courses and not completing retreatment were associated with mortality in adjusted analyses., (© The American Society of Tropical Medicine and Hygiene.)

Background: Neonatal near miss cases occur more often than neonatal deaths and could enable a more comprehensive analysis of risk factors, short-term outcomes and prognostic factors in neonates born to mothers with severe obstetric complications. The objective was to assess the incidence, presentation and perinatal outcomes of severe obstetric morbidity in two referral hospitals in Central Uganda., Methods: A prospective cohort study was conducted between March 1, 2013 and February 28, 2014, in which all newborns from cases of severe pregnancy and childbirth complications were eligible for inclusion. The obstetric conditions included obstetric haemorrhage, hypertensive disorders, obstructed labour, chorioamnionitis and pregnancy-specific complications such as malaria, anemia and premature rupture of membranes. Still births, neonatal deaths and neonatal near miss cases (defined using criteria that employed clinical features, presence of organ-system dysfunction and management provided to the newborns were compiled). Stratified and multivariate logistic regression analysis was conducted to identify risk factors for perinatal death., Results: Of the 3100 mothers, 192 (6.2%) had abortion complications. Of the remainder, there were 2142 (73.1%) deliveries, from whom the fetal outcomes were 257 (12.0%) still births, 369 (17.2%) neonatal deaths, 786 (36.7%) neonatal near misses and 730 (34.1%) were newborns with no or minimal life threatening complications. Of the 235 babies admitted to the neonatal intensive care unit (NICU), the main reasons for admission were prematurity for 64 (26.8%), birth asphyxia for 59 (23.7%), and grunting respiration for 26 (11.1%). Of the 235 babies, 38 (16.2%) died in the neonatal period, and of these, 16 died in the first 24 hours after admission. Ruptured uterus caused the highest case-specific mortality of 76.8%, and led to 16.9% of all newborn deaths. Across the four groups, there were significant differences in mean birth weight, p = 0.003., Conclusions: Antepartum hemorrhage, ruptured uterus, severe preeclampsia, eclampsia, and the syndrome of Hemolysis, Elevated Liver Enzymes, Low Platelets (HELLP syndrome), led to statistically significant attributable risk of newborn deaths (still birth or neonatal deaths). Development of severe maternal outcomes, the mothers having been referred, and gravidity of 5 or more were significantly associated with newborn deaths.

Background: Severe obstetric complications have potential negative impact on the family and household of the survivors, with potential negative effects during (and in the aftermath of) the traumatic obstetric events. The objective was to gain deeper understanding of how severe obstetric complications are perceived by male partners, and their impact on the livelihoods of the family and community., Methods: Data was collected through 25 in-depth narrative interviews with male partners of women with severe obstetric morbidity. The interviews occurred 4-12 months after the traumatic childbirth events. To gain a deeper understanding of the meanings and spouses attach to the experiences, we employed the notions of social capital and resilience., Results: Male partners' perceptions and experiences were mostly characterized by losses, dreams and dilemmas, disempowerment and alienation, seclusion and self isolation or reliance on the social networks. During the aftermath of the events, there was disruption of the livelihoods of the partners and the whole family., Conclusion: While a maternal near miss obstetric event might appear as a positive outcome for the survivors, partners and caregivers of women who experience severe obstetric morbidity are deeply affected by the experiences of this life-threatening episode.

Introduction: Globally every year 529,000 maternal deaths occur, 99% of this in developing countries. Uganda has high maternal and neonatal morbidity and mortality ratios, typical of many countries in sub-Saharan Africa. Recent findings reveal maternal mortality ratio of 435:100,000 live births and neonatal mortality rate of 29 deaths per 1000 live births in Uganda; these still remain a challenge. Women in rural areas of Uganda are two times less likely to attend ANC than the urban women. Most women in Uganda have registered late ANC attendance, averagely at 5.5 months of pregnancy and do not complete the required four visits. The inadequate utilization of ANC is greatly contributing to persisting high rates of maternal and neonatal mortality in Uganda. This study was set to identify the factors associated with late booking and inadequate utilization of Antenatal Care services in upcountry areas of Uganda., Method: Cross-sectional study design with mixed methods of interviewer administered questionnaires, focus group discussions and key informant interviews. Data was entered using Epidata and analyzed using Stata into frequency tables using actual tallies and percentages. Ethical approval was sought from SOM-REC MakCHS under approval number "#REC REF 2012-117" before conducting the study., Results: A total of four hundred one were enrolled with the majority being in the age group 20 - 24 years (mean age, 25.87 ± 6.26). Health workers played a great role (72.04%), followed by the media (15.46%) and friends (12.50%) in creating awareness about ANC. A significant number of respondents went to TBAs with reasons such as "near and accessible", "my husband decided", and "they are the only people I know". 37.63% of the respondents considered getting an antenatal Card as an importance of ANC. 71 (19.67%) respondents gave a wrong opinion (late) on booking time with reasons like demands at work, no problems during pregnancy, advised by friends, just to get a card, long distance and others didn't know. Almost half of the respondents never knew the recommended number of visits. Religion, occupation, level of education, and parity were found to influence place of ANC attendance, number of ANC visits and booking time. Husbands were necessary to provide financial support, accompany their wives ANC clinic, and ensure that they complete the visits. But their response was poor due to: fear of routine investigations and constrained economically., Conclusion: The study findings show the actual rural setting of ANC services attendance and utilization. Much sensitization has to be done specifically in these rural areas to empower pregnant women and their husbands as to improve ANC attendance and utilization.

Objective: To determine the incidence and risk factors for early neonatal death among newborns with severe perinatal morbidity., Methods: A prospective cohort study was performed of 341 newborns with severe perinatal morbidity admitted to the neonatal intensive care unit of Mulago Hospital, Uganda. All newborns were followed up for 7 days or until time of death. Information surrounding the mother's obstetric history and pregnancy, the birth, and the neonatal history was collected using an interviewer-administered questionnaire and by review of relevant records. Multivariate logistic regression analysis was performed to assess factors independently associated with early neonatal death., Results: A total of 37 (10.9%) neonates died within 7 days, giving an incidence of early neonatal death of 109 deaths per 1000 live births (3 per 100 person-days). In multivariate analysis, respiratory distress (adjusted risk ratio [aRR] 31.29; 95% CI, 4.17-234.20; P=0.001) and inadequate fetal heart monitoring during labor (aRR 6.0; 95% CI 1.40-25.67; P=0.016) were significantly associated with an increased risk of early neonatal death., Conclusion: Approximately one in 10 neonates with severe perinatal morbidity died within 7 days of birth. Respiratory distress and poor monitoring of labor were risk factors for early neonatal death., (Copyright © 2014. Published by Elsevier Ireland Ltd.)

Objective: To determine and compare the rates of HIV superinfection and primary HIV infection in high-risk female sex workers (FSWs) in Kampala, Uganda., Design: A retrospective analysis of individuals who participated in a clinical cohort study among high-risk FSWs in Kampala, Uganda., Methods: Plasma samples from HIV-infected FSWs in Kampala, Uganda were examined with next-generation sequencing of the p24 and gp41 HIV genomic regions for the occurrence of superinfection. Primary HIV incidence was determined from initially HIV-uninfected FSWs from the same cohort, and incidence rate ratios were compared., Results: The rate of superinfection in these women (7/85; 3.4/100 person-years) was not significantly different from the rate of primary infection in the same population (3.7/100 person-years; incidence rate ratio = 0.91, P = 0.42). Seven women also entered the study dual-infected (16.5% either dual or superinfected). The women with any presence of dual infection were more likely to report sex work as their only source of income (P = 0.05), and trended to be older and more likely to be widowed (P = 0.07)., Conclusions: In this cohort of FSWs, HIV superinfection occurred at a high rate and was similar to that of primary HIV infection. These results differ from a similar study of high-risk female bar workers in Kenya that found the rate of superinfection to be significantly lower than the rate of primary HIV infection.

Background: Of the three million newborns that die each year, Uganda ranks fifth highest in neonatal mortality rates, with 43,000 neonatal deaths each year. Despite child survival and safe motherhood programmes towards reducing child mortality, insufficient attention has been given to this critical first month of life. There is urgent need to innovatively employ alternative solutions that take into account the intricate complexities of neonatal health and the health systems. In this paper, we set out to empirically contribute to understanding the causes of the stagnating neonatal mortality by applying a systems thinking approach to explore the dynamics arising from the neonatal health complexity and non-linearity and its interplay with health systems factors, using Uganda as a case study., Methods: Literature reviews and interviews were conducted in two divisions of Kampala district with high neonatal mortality rates with mothers at antenatal clinics and at home, village health workers, community leaders, healthcare decision and policy makers, and frontline health workers from both public and private health facilities. Data analysis and brainstorming sessions were used to develop causal loop diagrams (CLDs) depicting the causes of neonatal mortality, which were validated by local and international stakeholders., Results: We developed two CLDs for demand and supply side issues, depicting the range of factors associated with neonatal mortality such as maternal health, level of awareness of maternal and newborn health, and availability and quality of health services, among others. Further, the reinforcing and balancing feedback loops that resulted from this complexity were also examined. The potential high leverage points include special gender considerations to ensure that girls receive essential education, thereby increasing maternal literacy rates, improved socioeconomic status enabling mothers to keep healthy and utilise health services, improved supervision, and internal audits at the health facilities as well as addressing the gaps in resources (human, logistics, and drugs)., Conclusions: Synthesis of theoretical concepts through CLDs facilitated our understanding and interpretation of the interactions and feedback loops that contributed to the stagnant neonatal mortality rates in Uganda, which is the first step towards discussing and exploring the potential strategies and their likely impact.

Background: In most resource limited settings, new tuberculosis (TB) patients are usually treated as outpatients. We sought to investigate the reasons for hospitalisation and the predictors of poor treatment outcomes and mortality in a cohort of hospitalized new TB patients in Kampala, Uganda., Methods and Findings: Ninety-six new TB patients hospitalised between 2003 and 2006 were enrolled and followed for two years. Thirty two were HIV-uninfected and 64 were HIV-infected. Among the HIV-uninfected, the commonest reasons for hospitalization were low Karnofsky score (47%) and need for diagnostic evaluation (25%). HIV-infected patients were commonly hospitalized due to low Karnofsky score (72%), concurrent illness (16%) and diagnostic evaluation (14%). Eleven HIV uninfected patients died (mortality rate 19.7 per 100 person-years) while 41 deaths occurred among the HIV-infected patients (mortality rate 46.9 per 100 person years). In all patients an unsuccessful treatment outcome (treatment failure, death during the treatment period or an unknown outcome) was associated with duration of TB symptoms, with the odds of an unsuccessful outcome decreasing with increasing duration. Among HIV-infected patients, an unsuccessful treatment outcome was also associated with male sex (P = 0.004) and age (P = 0.034). Low Karnofsky score (aHR = 8.93, 95% CI 1.88 - 42.40, P = 0.001) was the only factor significantly associated with mortality among the HIV-uninfected. Mortality among the HIV-infected was associated with the composite variable of CD4 and ART use, with patients with baseline CD4 below 200 cells/µL who were not on ART at a greater risk of death than those who were on ART, and low Karnofsky score (aHR = 2.02, 95% CI 1.02 - 4.01, P = 0.045)., Conclusion: Poor health status is a common cause of hospitalisation for new TB patients. Mortality in this study was very high and associated with advanced HIV Disease and no use of ART.

Background: Umbilical cord prolapse is an obstetric complication associated with high perinatal morbidity and mortality. A few interventions may improve fetal outcome. In developed countries these have advanced to giving intrauterine fetal resuscitation. Conditions in low resource settings do not allow for some of these advanced techniques. Putting the mother in knee chest position and immediate delivery may be the only options possible.We set out to determine the incidence of fetal demise and associated factors following umbilical cord prolapsed (UCP) in Mulago Hospital, Uganda., Methods: In a retrospective study conducted in Mulago hospital, Uganda, file records of mothers who delivered between 1st January 2000 to 31st December 2009 and had pregnancies complicated by umbilical cord prolapse with live fetus were selected. We collected information on referral status, cord position, cervical dilatation, fetal heart state at the time of diagnosis of UCP, diagnosis to delivery interval, use of knee chest position, mode of delivery, birth weight and fetal outcome.We computed incidence of fetal demise following UCP and determined factors associated with fetal demise in pregnancies complicated by UCP., Results: Of 438 cases with prolapsed cord, 101(23%) lost their babies within 24 hours after birth or were delivered dead. This gave annual cumulative incidence of fetal death following UCP of 23/1000 live UCP cases delivered /year.The major factors associated with fetal outcome in pregnancies complicated by UCP included; diagnosis to delivery interval <30 min, RR 0.79 (CI 0.74-0.85), mode of delivery, RR 1.14 (CI 1.02-1.28), knee chest position, RR 0.81 (CI 0.70-0.95)., Conclusions: The annual cumulative incidence of fetal death in our study was 23/1000 live UCP cases delivery per year for the period of 10 years studied. Cesarean section reduced perinatal mortality by a factor of 2. Diagnosis to delivery interval <30 minutes and putting mother in knee chest position were protective against fetal death.

Objective: To evaluate the effect of nevirapine-containing antiretroviral therapy (ART) on combined oral contraceptive (COC) effectiveness., Design: Nonrandomized prospective clinical trial., Methods: We enrolled HIV-infected women aged 18-35 years in South Africa and Uganda who had regular menses, were sexually active, and had no medical contraindications to COC use. We enrolled 196 women taking nevirapine-containing ART and 206 women not yet eligible for ART as a control group. We treated all participants with low-dose COCs. Our main outcomes were ovulation and pregnancy rates. We estimated ovulation in the first two cycles using weekly serum progesterone and tested for pregnancy monthly for 24 weeks., Results: The median age of participants was 29 and their median CD4 cell count was 486. In the ART group, 43 of 168 (26%) ovulated in cycle 1, 30 of 163 (18%) in cycle 2, and 18 of 163 (11%) in both cycles. In the non-ART group, 26 of 168 (16%) ovulated in cycle 1, 31 of 165 (19%) in cycle 2, and 20 of 165 (12%) in both cycles. We found no significant difference in ovulation rates between groups: unadjusted odds ratio 1.36 (95% confidence interval 0.85-2.18). Pregnancy rates also did not differ: 10.0 per 100-women-years in the ART group and 10.1 per 100-women-years in the non-ART group. Self-reported COC adherence, condom use, vaginal bleeding, and adverse events were similar. Five serious adverse events were reported, all in the non-ART group., Conclusion: ART use did not affect risk of ovulation or pregnancy in women taking COCs, suggesting that nevirapine-containing ART does not interfere with COC contraceptive effectiveness.

Background: There have been few studies of the natural history of Mycoplasma genitalium in women. We investigated patterns of clearance and recurrence of untreated M. genitalium infection in a cohort of female sex workers in Uganda., Methods: Women diagnosed as having M. genitalium infection at enrollment were retested for the infection at 3-month intervals. Clearance of infection was defined as testing negative after having a previous positive result: persistence was defined as testing positive after a preceding positive test result, and recurrence as testing positive after a preceding negative test result. Adjusted hazard ratios for M. genitalium clearance were estimated using Cox proportional hazards regression., Results: Among 119 participants infected with M. genitalium at enrollment (prevalence, 14%), 55% had spontaneously cleared the infection within 3 months; 83%, within 6; and 93%, within 12 months. The overall clearance rate was 25.7/100 person-years (pyr; 95% confidence interval, 21.4-31.0). HIV-positive women cleared M. genitalium infection more slowly than did HIV-negative women (20.6/100 pyr vs. 31.3/100 pyr, P = 0.03). The clearance rate was slower among HIV-positive women with CD4 counts less than 350/mL than among those with higher CD4 counts (9.88/100 pyr vs. 29.5/100 pyr, P <; 0.001). After clearing the infection, M. genitalium infection recurred in 39% women., Conclusions: M. genitalium is likely to persist and recur in the female genital tract. Because of the urogenital tract morbidity caused by the infection and the observed association with HIV acquisition, further research is needed to define screening modalities, especially in populations at high risk for HIV, and to optimize effective and affordable treatment options.

Background: In 2008, the first clinic for women involved in high-risk sexual behavior was established in Kampala, offering targeted HIV prevention. This article describes rates, determinants, and trends of HIV incidence over 3 years., Methods: A total of 1027 women at high risk were enrolled into a closed cohort. At 3-monthly visits, data were collected on sociodemographic variables and risk behavior; biological samples were tested for HIV and other reproductive tract infections/sexually transmitted infections (RTI/STIs). Hazard ratios for HIV incidence were estimated using Cox proportional hazards regression among the 646 women HIV negative at enrolment., Results: HIV incidence was 3.66/100 person-years (pyr) and declined from 6.80/100 pyr in the first calendar year to 2.24/100 pyr and 2.53/100 pyr in the following years (P trend = 0.003). Sociodemographic and behavioral factors independently associated with HIV incidence were younger age, younger age at first sex, alcohol use (including frequency of use and binge drinking), number of paying clients in the past month, inconsistent condom use with clients, and not being pregnant. HIV incidence was also independently associated with Mycoplasma genitalium infection at enrolment [adjusted hazard ratio (aHR) = 2.28, 95% confidence interval (CI): 1.15 to 4.52] and with Neisseria gonorrhoeae (aHR = 5.91, 95% CI: 3.04 to 11.49) and Trichomonas vaginalis infections at the most recent visit (aHR = 2.72, 95% CI: 1.27 to 5.84). The population attributable fractions of HIV incidence for alcohol use was 63.5% (95% CI: 6.5 to 85.8) and for treatable RTI/STIs was 70.0% (95% CI: 18.8 to 87.5)., Conclusions: Alcohol use and STIs remain important risk factors for HIV acquisition, which call for more intensive control measures in women at high risk. Further longitudinal studies are needed to confirm the association between M. genitalium and HIV acquisition.

Reagents for evaluating non-clade B HIV-specific T cell responses are uncommon. Peptides based on highly conserved HIV-1 consensus group M sequences that are phylogenetically closer to most circulating strains may provide potential alternative reagents in populations with diverse infections, and may be relevant for vaccine design. Recognition of such reagents in clade A1-and D-infected populations has not been previously evaluated. Interferon (IFN)-γ ELISpot assay was used to evaluate T cell recognition of Gag and Nef peptides based on consensus group M sequences in 50 treatment-naive adults predominantly infected with HIV-1 clades A1 and D. Gag-induced T cell responses were correlated with gag sequence diversity. Infecting clades were determined from gag sequences for 45 of the 50 subjects as 40% clade A1 (18/45), 45% clade D (20/45), 2% clade C (1/45), 2% A1/C recombinant (1/45), 2% A1/D (1/45), 7% CRF10&#95;CD (3/45), and 2% U (unclassifiable) (1/45). The mean genetic divergence and diversity of clade A and D gag region compared to group M consensus sequences at synonymous and nonsynonymous nucleotide and amino acid levels were not always significant. Gag peptides were targeted at significantly higher frequency [88% (44/50)] than Nef [64% (32/50)]; p=0.014, although their mean IFN-γ magnitudes were comparable ([3703 (95% CI 2567-4839)] vs. [2120 (95% CI 478-3762)]), respectively. Measurable virus-induced IFN-γ responses were detected in 96% (48/50) individuals, primarily targeting the more conserved Gag p24 and Nef central core regions. Use of these reagents to screen for HIV-specific IFN-γ responses may mitigate the challenge of viral diversity; although this targeting is apparently biased toward a few highly conserved epitopes.

Background: The importance of Mycoplasma genitalium in human immunodeficiency virus (HIV)-burdened sub-Saharan Africa is relatively unknown. We assessed the prevalence and explored determinants of this emerging sexually transmitted infection (STI) in high-risk women in Uganda., Methods: Endocervical swabs from 1025 female sex workers in Kampala were tested for Mycoplasma genitalium using a commercial Real-TM polymerase chain reaction assay. Factors associated with prevalent Mycoplasma genitalium, including sociodemographics, reproductive history, risk behavior, and HIV and other STIs, were examined using multivariable logistic regression., Results: The prevalence of Mycoplasma genitalium was 14% and higher in HIV-positive women than in HIV-negative women (adjusted odds ratio [OR], 1.64; 95% confidence interval [CI], 1.12-2.41). Mycoplasma genitalium infection was less prevalent in older women (adjusted OR, 0.61; 95% CI, .41-.90 for women ages 25-34 years vs <25 years; adjusted OR, 0.32; 95% CI, .15-.71 for women ≥ 35 years vs those <25 years) and in those who had been pregnant but never had a live birth (adjusted OR, 2.25; 95% CI, 1.04-4.88). Mycoplasma genitalium was associated with Neisseria gonorrhoeae (adjusted OR, 1.84; 95% CI, 1.13-2.98) and with Candida infection (adjusted OR, 0.41; 95% CI, .18-.91), and there was some evidence of association with Trichomonas vaginalis (adjusted OR, 1.56; 95% CI, 1.00-2.44)., Conclusions: The relatively high prevalence of Mycoplasma genitalium and its association with prevalent HIV urgently calls for further research to explore the potential role this emerging STI plays in the acquisition and transmission of HIV infection.

Objective: To investigate the effect of antiretroviral therapy on trends of incidence, aetiology and clinical outcomes of bacteraemia among HIV-infected Ugandans in a semi-urban setting., Methods: A cohort of HIV-1-infected Ugandans aged 15 or older was followed from 2000 to 2008. Clinical, haematological and immunological measurements were taken at 6-monthly visits. Additionally, patients reported to outpatient clinics whenever they were ill. Patients with elevated axillary temperature above 37.4 °C consistently triggered clinical assessment (with mandatory blood cultures) and empirical management protocol. Daily cotrimoxazole prophylaxis and highly active antiretroviral therapy (HAART) were introduced stepwise to eligible patients in August 2000 and February 2003, respectively. We compared the rates of bacteraemia across five calendar periods using random-effects Poisson regression for the effect of HAART at the population level., Results: A total of 246 bacteraemia episodes (including multiple episodes) were documented among 188 individuals (crude incidence: 42.4 events per 1000 person-years; 95% CI: 35.0, 51.4). The most common species isolated was Streptococcus pneumoniae. After adjustment for current age, clinical characteristics at enrollment (CD4+ T-cell counts and WHO stage) and time since enrollment, the incidence of bacteraemia dropped significantly when HAART was widely available compared with the period when treatment was not available (adjusted hazard ratio: 0.17; 95% CI: 0.09, 0.35). No poor health outcomes (death or lack of clinical response to antibiotics) after bacteraemia occurred after complete access to HAART., Conclusions: HAART availability in a resource-poor setting substantially reduced the trends of bacteraemia among HIV-infected adults. This may further impact on future morbidity and healthcare costs of HIV-infected people., (© 2011 Blackwell Publishing Ltd.)

Background: Uganda has long been successful in controlling the HIV epidemic; however, there is evidence that HIV prevalence and incidence are increasing again. Data on the HIV/STI epidemic among sex workers are so far lacking from Uganda. This paper describes the baseline epidemiology of HIV/STI in a newly established cohort of women involved in high-risk sexual behavior in Kampala, Uganda., Methods: Women were recruited from red-light areas in Kampala. Between April 2008 and May 2009, 1027 eligible women were enrolled. Sociodemographic and behavioral information were collected; blood and genital samples were tested for HIV/STI. Risk factors for HIV infection were examined using multivariate logistic regression., Results: HIV seroprevalence was 37%. The prevalence of Neisseria gonorrhoeae was 13%, Chlamydia trachomatis, 9%; Trichomonas vaginalis, 17%; bacterial vaginosis, 56% and candida infection, 11%. Eighty percent had herpes simplex virus 2 antibodies (HSV-2), 21% were TPHA-positive and 10% had active syphilis (RPR+TPHA+). In 3% of the genital ulcers, Treponema pallidum (TP) was identified, Haemophilus ducreyi in 6%, and HSV-2 in 35%. Prevalent HIV was independently associated with older age, being widowed, lack of education, sex work as sole income, street-based sex work, not knowing HIV-status, using alcohol, and intravaginal cleansing with soap. HIV infection was associated with N. gonorrhoeae, T. vaginalis, bacterial vaginosis, HSV-2 seropositivity and active syphilis., Conclusions: Prevalence of HIV/STI is high among women involved in high-risk sexual behavior in Kampala. Targeted HIV prevention interventions including regular STI screening, voluntary HIV testing and counseling, condom promotion, and counseling for reducing alcohol use are urgently needed in this population.

Background: Each year, 10%-20% of patients with tuberculosis (TB) in low- and middle-income countries present with previously treated TB and are empirically started on a World Health Organization (WHO)-recommended standardized retreatment regimen. The effectiveness of this retreatment regimen has not been systematically evaluated., Methods and Findings: From July 2003 to January 2007, we enrolled smear-positive, pulmonary TB patients into a prospective cohort to study treatment outcomes and mortality during and after treatment with the standardized retreatment regimen. Median time of follow-up was 21 months (interquartile range 12-33 months). A total of 29/148 (20%) HIV-uninfected and 37/140 (26%) HIV-infected patients had an unsuccessful treatment outcome. In a multiple logistic regression analysis to adjust for confounding, factors associated with an unsuccessful treatment outcome were poor adherence (adjusted odds ratio [aOR] associated with missing half or more of scheduled doses 2.39; 95% confidence interval (CI) 1.10-5.22), HIV infection (2.16; 1.01-4.61), age (aOR for 10-year increase 1.59; 1.13-2.25), and duration of TB symptoms (aOR for 1-month increase 1.12; 1.04-1.20). All patients with multidrug-resistant TB had an unsuccessful treatment outcome. HIV-infected individuals were more likely to die than HIV-uninfected individuals (p<0.0001). Multidrug-resistant TB at enrollment was the only common risk factor for death during follow-up for both HIV-infected (adjusted hazard ratio [aHR] 17.9; 6.0-53.4) and HIV-uninfected (14.7; 4.1-52.2) individuals. Other risk factors for death during follow-up among HIV-infected patients were CD4<50 cells/ml and no antiretroviral treatment (aHR 7.4, compared to patients with CD4≥200; 3.0-18.8) and Karnofsky score <70 (2.1; 1.1-4.1); and among HIV-uninfected patients were poor adherence (missing half or more of doses) (3.5; 1.1-10.6) and duration of TB symptoms (aHR for a 1-month increase 1.9; 1.0-3.5)., Conclusions: The recommended regimen for retreatment TB in Uganda yields an unacceptable proportion of unsuccessful outcomes. There is a need to evaluate new treatment strategies in these patients., (© 2011 Jones-Lo´pez et al.)

Background: Studies show that STIs such as HSV-2 increase the probability of HIV-1 acquisition and enhance transmission by increasing susceptibility and infectiousness respectively. The objective of this study was to compare the proportion of HSV-2 in HIV-positive and HIV-negative pregnant mothers attending the antenatal clinic in Mulago Teaching Hospital in Kampala, Uganda., Methods: This case control study included 50 pregnant women who were HIV positive and 200 controls of pregnant women who were HIV negative and were aware of their serostatus. Data was collected in two parts: the first part involved a pretested interviewer-administered semi-structured questionnaire for socio-demographic characteristics, sexual and behavioral history. The second part consisted of a serological test using an ELISA assay specific for IgG against viral glycoprotein G, specific to HSV-2., Results: The proportion of HSV-2 was 86% (43/50) among the HIV-positive cases and 62% (125/200) among the HIV-negative controls. The odds of being HSV-2 seropositive was 3.7 times higher (95% CI was 1.58 - 8.61) in HIV-positive cases than in the HIV negative controls. The odds of HSV-2 was significantly increased to 5.32 (95 CI was 1.92 - 14.73) among cases when adjustment was done for age, education, marital status, religion, age at first sexual experience, lifetime partners, type of earning, and whether the mother involved the partner in seeking treatment for sexually transmitted diseases., Conclusion: The proportion of HSV-2 was higher in HIV-positive cases than in the HIV negative controls.

Objective: To evaluate the effect of highly active anti-retroviral therapy (HAART) and cotrimoxazole prophylaxis on morbidity after HAART eligibility., Methods: Between 1999 and 2006, we collected morbidity data from a community-based cohort of HAART-eligible patients, comparing patients initiating HAART and those non-HAART. Patients aged 15 years or older visited the clinic every 6 months and when ill. Baseline data on patients' characteristics, WHO stage, haemoglobin and CD4+ T-cell counts, along with follow-up data on morbidity (new, recurrent and drug-related), were collected for the first year after initiating HAART or becoming HAART-eligible. We estimated the overall effect of HAART on morbidity; adjusted for the effect of cotrimoxazole prophylaxis by Mantel-Haenszel methods. A negative binomial regression model was used to assess rate ratios (RR) after adjustment for other confounders, including cotrimoxazole., Results: A total of 219 HAART patients (median age 37 years; 73% women; 82% using cotrimoxazole prophylaxis, median haemoglobin 11.7 g/dl and median CD4+ 131 cells/microl) experienced 94 events in 127 person-years. 616 non-HAART patients (median age 33 years; 70% women; 26% using cotrimoxazole prophylaxis, median haemoglobin 11.2 g/dl and median CD4+ 130 cells/microl) experienced 862 events in 474 person-years. The overall morbidity during the first year of HAART was 80% lower than among non-HAART patients (adjusted RR = 0.20, 95% CI: 0.12-0.34). Cotrimoxazole prophylaxis also reduced morbidity (adjusted RR = 0.65, 95% CI: 0.45-0.94)., Conclusion: These results confirm the reduction in morbidity due to HAART, and the additional protection of cotrimoxazole prophylaxis.

Background: Drug-resistant Mycobacterium tuberculosis has emerged as a global threat. In resource-constrained settings, patients with a history of tuberculosis (TB) treatment may have drug-resistant disease and may experience poor outcomes. There is a need to measure the extent of and risk factors for drug resistance in such patients., Methods: From July 2003 through November 2006, we enrolled 410 previously treated patients with TB in Kampala, Uganda. We measured the prevalence of resistance to first- and second-line drugs and analyzed risk factors associated with baseline and acquired drug resistance., Results: The prevalence of multidrug-resistant TB was 12.7% (95% confidence interval [95% CI], 9.6%-16.3%). Resistance to second-line drugs was low. Factors associated with multidrug-resistant TB at enrollment included a history of treatment failure (odds ratio, 23.6; 95% CI, 7.7-72.4), multiple previous TB episodes (odds ratio, 15.6; 95% CI, 5.0-49.1), and cavities present on chest radiograph (odds ratio, 5.9; 95% CI, 1.2-29.5). Among a cohort of 250 patients, 5.2% (95% CI, 2.8%-8.7%) were infected with M. tuberculosis that developed additional drug resistance. Amplification of drug resistance was associated with existing drug resistance at baseline (P < .01) and delayed sputum culture conversion (P < .01)., Conclusions: The burden of drug resistance in previously treated patients with TB in Uganda is sizeable, and the risk of generating additional drug resistance is significant. There is an urgent need to improve the treatment for such patients in low-income countries.