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IntroductionBabies born preterm often have challenges in feeding, temperature control and breathing difficulty and are prone to infection during the neonatal period. These usually necessitate admission to the neonatal intensive care unit (NICU). Admission to NICU disrupts the mother–baby bonding.ObjectiveThis study explored the lived experiences of mothers with preterm babies admitted to NICU in a low-resource setting.Study designThis was a qualitative study where 16 participants took part in indepth interviews and 35 in focus group discussions. We included mothers who delivered and were caring for preterm babies at the NICU of Mulago National Referral Hospital.Study settingData were collected from a public hospital, which works as a district and national referral hospital located in the capital of Uganda.ParticipantsFifty-one mothers with preterm babies in the NICU were sampled and recruited after informed consent. Data were analysed using manual thematic analysis.ResultsThere were six themes on the experiences of mothers of preterm babies in NICU: constant worry and uncertainty about the survival of their babies, baby feeding challenges, worries of discharge, communication gaps between mothers and nurses, community acceptability and disdain for preterm babies, and financial challenges.Conclusions and recommendationsMothers of preterm babies admitted to NICU in a low-resource setting still need a lot of support other than the medical care given to their babies. Support groups in the hospital and community are recommended to help in dealing with these challenges.

BackgroundCOVID-19 impacted global maternal, neonatal and child health outcomes. We hypothesised that the early, strict lockdown which restricted individuals movements in Uganda limited access to services. MethodsAn observational study, using routinely collected data from Electronic Medical Records was carried out, in Kawempe district, Kampala. An interrupted time series analysis assessed the impact on maternal, neonatal, child, sexual and reproductive health services from July 2019 to December 2020. Descriptive statistics summarised the main outcomes before (July 2019 - March 2020), during (April 2020 - June 2020) and after the national lockdown (July 2020 - December 2020). ResultsBetween 1st July 2019 and 31st December 2020 there were 14,401 antenatal clinic attendances, 33,499 deliveries, 111,658 childhood service attendances and 57,174 for sexual health. All antenatal and vaccination services ceased in lockdown for four weeks. During the three-month lockdown, the number of antenatal attendances significantly decreased, and remain below pre-COVID levels (370 fewer/month). Attendances for prevention of mother-to-child transmission of HIV dropped then stabilised. Increases during lockdown and immediately postlockdown included the number of women treated for high blood pressure, eclampsia and pre-eclampsia (218 more/month), adverse pregnancy outcomes (stillbirths, low-birth-weight and premature infant births), the rate of neonatal unit admissions, neonatal deaths and abortions. Maternal mortality remained stable. Immunisation clinic attendance declined whilst neonatal death rate rose (from 39-49/1000 livebirths). The number of children treated for pneumonia, diarrhoea and malaria decreased during lockdown. ConclusionThe Ugandan response to COVID-19 negatively impacted maternal, child and neonatal health, with an increase seen in pregnancy complications, and fetal and infant outcomes, likely due to delayed care-seeking behaviour. Decreased vaccination clinic attendance leaves a cohort of infants unprotected, affecting all vaccine-preventable diseases. Future pandemic responses must consider impacts of movement restrictions and access to preventative services to protect maternal and child health. O_TEXTBOXKEY QUESTIONS What is already known?O_LIThe response to COVID-19 has been shown to have indirectly impacted on maternal, child, neonatal, sexual, and reproductive health. C_LIO_LIThis is largely related to access to services and fear of contracting COVID-19 in outpatient departments. C_LIO_LIThere has been very little data published on the health impacts of the COVID-19 response in Uganda. C_LI What are the new findings?O_LIAntenatal attendances decreased dramatically in April, followed by increased numbers low-birthweight infants and neonatal deaths. C_LIO_LINewborn immunisations against polio, tetanus, diphtheria, hepatitis B, haemophilus influenzae, rotavirus and pneumococcus decreased significantly. C_LIO_LISexual, and reproductive health services were reduced in number. C_LI What do the new findings imply?O_LIAlthough Uganda has been less affected directly by COVID-19 infections in the first wave, the indirect impacts are far-reaching and will have future influences on population health. C_LIO_LIThere is a degree of resilience within the healthcare service, but many services were adversely affected by the lockdown leading to poorer pregnancy and neonatal outcomes. C_LIO_LIAntenatal and vaccination services are of particular importance in ensuring the safety of mother and child and must be prioritised in the responses to future pandemics. C_LI C_TEXTBOX

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).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.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.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.

The World Health Organisation (WHO) and others have identified, as a priority, the need to improve antimicrobial stewardship (AMS) interventions as part of the effort to tackle antimicrobial resistance (AMR). An international health partnership model, the Commonwealth Partnerships for Antimicrobial Stewardship (CwPAMS) programme, was established between selected countries in Africa (Ghana, Tanzania, Zambia and Uganda) and the UK to support AMS. This was funded by UK aid under the Fleming Fund and managed by the Commonwealth Pharmacists Association (CPA) and Tropical Health and Education Trust (THET). The primary aims were to develop local AMS teams and generate antimicrobial consumption surveillance data, quality improvement initiatives, infection prevention and control (IPC) and education/training to reduce AMR. Education and training were key components in achieving this, with pharmacists taking a lead role in developing and leading AMS interventions. Pharmacist-led interventions in Ghana improved access to national antimicrobial prescribing guidelines via the CwPAMS mobile app and improved compliance with policy from 18% to 70% initially for patients with pneumonia in one outpatient clinic. Capacity development on AMS and IPC were achieved in both Tanzania and Zambia, and a train-the-trainer model on the local production of alcohol hand rub in Uganda and Zambia. The model of pharmacy health partnerships has been identified as a model with great potential to be used in other low and middle income countries (LMICs) to support tackling AMR.

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.

Background: Pregnancy is associated with complications which must be differentiated from adverse events associated with the administration of vaccines during pregnancy both in clinical trials and post licensure surveillance. The frequency of pregnancy related complications varies significantly by geographical location and the prevalence of pregnancy and neonatal outcomes are poorly documented in most low-resource settings. In preparation for Group B Streptococcus maternal vaccination trials, we describe a protocol for a pregnancy register at Kawempe National Referral Hospital, Kampala, Uganda to describe pregnancy maternal and infant outcomes. Methods: The study has two components. Firstly, an active, prospective surveillance cohort consisting of pregnant women in their first or second trimester recruited and followed up through their hospital scheduled antenatal visits, delivery and their infants through their extended programme of immunisation visits until 14 weeks of age. Data on obstetric and neonatal outcomes defined by the Brighton Collaboration Global Alliance of Immunisation Safety Assessment in Pregnancy criteria will be collected. Secondly, a passive surveillance cohort collecting data through routine electronic health records on all women and infants attending care at KNRH. Data will be collected on vaccinations and medications including antiretroviral therapy received in antenatal clinic and prior to hospital discharge. Discussion: Conducting vaccine research in resource-limited settings is essential for equity and to answer priority safety questions specific to these settings. It requires improved vaccine safety monitoring, which is especially pertinent in maternal vaccine research. During a trial, understanding the epidemiology and background rates of adverse events in the study population is essential to establish thresholds which indicate a safety signal. These data need to be systematically and reliably collected. This study will describe rates of adverse pregnancy outcomes in a cohort of 4,000 women and infants and any associated medications or vaccines received at a new vaccine trial site in Uganda.

In the African context, there is a paucity of data on SARS-CoV-2 infection and associated COVID-19 in pregnancy. Given the endemicity of infections such as malaria, HIV, and tuberculosis (TB) in sub-Saharan Africa (SSA), it is important to evaluate coinfections with SARS-CoV-2 and their impact on maternal/infant outcomes. Robust research is critically needed to evaluate the effects of the added burden of COVID-19 in pregnancy, to help develop evidence-based policies toward improving maternal and infant outcomes. In this perspective, we briefly review current knowledge on the clinical features of COVID-19 in pregnancy; the risks of preterm birth and cesarean delivery secondary to comorbid severity; the effects of maternal SARS-CoV-2 infection on the fetus/neonate; and in utero mother-to-child SARS-CoV-2 transmission. We further highlight the need to conduct multicountry surveillance as well as retrospective and prospective cohort studies across SSA. This will enable assessments of SARS-CoV-2 burden among pregnant African women and improve the understanding of the spectrum of COVID-19 manifestations in this population, which may be living with or without HIV, TB, and/or other coinfections/comorbidities. In addition, multicountry studies will allow a better understanding of risk factors and outcomes to be compared across countries and subregions. Such an approach will encourage and strengthen much-needed intra-African, south-to-south multidisciplinary and interprofessional research collaborations. The African Forum for Research and Education in Health’s COVID-19 Research Working Group has embarked upon such a collaboration across Western, Central, Eastern and Southern Africa.

Background The burden of Gestational diabetes mellitus (GDM) is significantly increasing worldwide and the disorder causes substantial short term and long-term adverse effects both to the mother and the unborn baby. Public health measures to increase awareness of GDM among pregnant women may aid in prevention of the disease through life style modification, screening, early diagnosis and management but very few studies have assessed awareness of GDM among pregnant women in sub Saharan Africa and none of these are from Uganda. This study therefore sought to evaluate the level of and factors associated with awareness of GDM among pregnant women attending antenatal care at Kawempe National Referral Hospital (KNRH), the busiest obstetric unit in Uganda, so as to assess their health sensitization needs. Methods This was a cross-sectional study. We recruited 403 participants at 30 weeks of gestation and above after giving written informed consent. Systematic sampling was used to select participants and data was collected using pretested interviewer-administered questionnaires. The collected data was entered in Epidata version 4.2 and exported to Stata for analysis. Continuous variables were summarized using mean and standard deviation. Categorical variables were summarized using frequencies and proportions. Factors associated with awareness were assessed at both bivariate and multivariate levels. Results Four hundred three pregnant women were recruited, majority (35.5 %) were between 20 and 24 years and their mean age was 26.6 years. Only 125 (31 %) participants were aware of GDM. Age and educational level were significantly associated with awareness of GDM. Women aged 35 years and above were more likely to be aware of GDM (OR = 2.34 (95 % CI = 1.14–4.81) p = 0.021. Women with primary education or no education were less likely to be aware (OR = 0.48 (CI 0.24–0.96) p = 0.038. Conclusions Awareness of GDM was poor among study participants. There is need to improve the health education programs in order to increase awareness of GDM among women attending ANC at KNRH. Women below 35 years of age and those with primary education or less should be specifically targeted when giving health education sessions so as to increase their awareness of GDM.

The vaginal microbial community ("microbiota") is a key component of the reproductive health of women, providing protection against urogenital infections. In sub-Saharan Africa, there is a high prevalence of bacterial vaginosis, a condition defined by bacterial overgrowth and a shift away from a Lactobacillus-dominated profile toward increased percentages of strict anaerobic species. Bacterial vaginosis is associated with an increased risk of HIV acquisition and transmission, as well as an increased risk of acquiring other sexually transmitted infections, preterm births, and pelvic inflammatory disease. Vaginal microbiota, rich in taxa of strict anaerobic species, disrupts the mucosal epithelial barrier through secretion of metabolites and enzymes that mediate inflammation. Advancements in next-generation sequencing technologies such as whole-genome sequencing have led to deeper profiling of the vaginal microbiome and further study of its potential role in HIV pathogenesis and treatment. Until recently data on the composition of the vaginal microbiome in sub-Saharan Africa have been limited; however, a number of studies have been published that highlight the critical role of vaginal microbiota in disease and health in African women. This article reviews these recent findings and identifies gaps in knowledge about variations in female genital commensal bacteria that could provide vital information to improve the effectiveness of interventions to prevent HIV and other sexually transmitted infections. In addition, we review the effects of pregnancy, contraception, and sexual practices on vaginal microbiome and the potential of vaginal microbiota on HIV transmission and prevention. A better understanding of the role of vaginal microbiota in host susceptibility to HIV infection and its prevention among African women could inform the development of novel local and systemic interventions to minimize new HIV infections among high-risk women.

Objective: To determine whether hyperglycaemia in the gestational diabetes (GDM) range independently predicts adverse pregnancy outcomes in Uganda. Design: Prospective observational cohort study. Setting:Five major hospitals in urban/semi-urban central Uganda. Sample:237 women with gestational diabetes, 2,641 normoglycaemic controls. Methods:Women were screened with oral glucose tolerance test (OGTT) at 24-28 weeks of gestation. Cases of GDM were identified (WHO 2013 diagnostic criteria) and received standard care. Data was collected on maternal demographics, anthropometrics, prenatal management, umbilical cord c-peptide levels, and pregnancy outcomes. Participants with diabetes in pregnancy (DIP) were excluded from the analysis. Outcomes:Primary outcomes: Birthweight large for gestational age (LGA; >90th centile) and perinatal death. Secondary outcomes: Caesarean delivery, preterm birth 90th centile (>1.35 mcg/L), and neonatal admission. Results:Women with GDM had a median of only two glucose measurements recorded in third trimester, and only one fifth received therapeutic management (mostly metformin, one participant received insulin). GDM was not independently associated with LGA (adjusted odds ratio, aOR 1.12; 95% CI 0.81-1.56) or perinatal death (aOR 0.66; 95% CI 0.26-1.66), but increased the risk of Caesarean delivery. Mid-gestational BMI of >30kg/m2 was strongly associated with LGA, and mean arterial pressure >90 mmHg was the strongest predictor of perinatal death. Conclusions:Even without active management, GDM was not associated with large birthweight or perinatal death in this population. Interventions that target blood pressure and obesity are likely to be more beneficial in improving LGA and perinatal mortality, than management of GDM. Funding:Medical Research Council Keywords:Gestational diabetes, Africa

Background Urinary tract infections (UTIs) are one of the most common bacterial infections in women. During pregnancy physiological changes, like frequency, mimic UTI symptoms, and therefore bacteriological cultures are needed to confirm the diagnosis. However, in developing countries antibiotic therapy is commonly initiated without culture confirmation. Methods We investigated the prevalence of bacteriuria among pregnant women with and without UTI symptoms in Uganda. In total 2 562 urine samples were evaluated with nitrite and leukocyte esterase tests, using urine culture and/or dipslide with species identification as reference. Results The prevalence of culture-proven UTI among pregnant women with UTI symptoms was 4%. Since treatment is initiated based only on the presence of symptoms, 96% were erroneously given antibiotics. Further, there is a high prevalence of resistance to commonly used antibiotics, with 18 % ESBL and 36 % multidrug resistant Escherichia coli strains. Nitrite, leukocyte esterase tests, and urine microscopy alone were of poor diagnostic value. Using dipslide, gynecologists and nurses, not trained in microbiology, were mostly able to identify E. coli and negative cultures. Mixed Gram-negative flora, suggesting fecal contamination was, however, in the majority of cases interpreted as a single pathogenic bacterium and would have resulted in antibiotic treatment. Conclusions To prevent excessive use of antibiotics, dipslide possibly supported by a combination of nitrite and leukocyte esterase tests can be used. Trained frontline health care professionals correctly diagnosed E. coli UTI and negative urine cultures, which would help preventing antibiotic misuse. In addition, regular screening for antibiotic resistance would improve correct treatment.

The incidence of cervical cancer in low- and middle-income countries (LMICs) is five times higher than that observed in high-income countries (HICs). This discrepancy is largely attributed to the implementation of cytology-based screening programmes in HICs. However, due to reduced health system infrastructure requirements, HPV testing (self- and provider-collected) and visual inspection with acetic acid (VIA) have been proposed as alternatives that may be better suited to LMICs. Knowing the relative value of different screening options can inform policy and the development of sustainable prevention programs. We searched MEDLINE and EMBASE for English language publications detailing model-based cost-effectiveness analyses of cervical cancer screening methods in LMICs from 2000 to 2016. The main outcome of interest was the incremental cost-effectiveness ratio (ICER). Quantitative data were extracted to compare commonly evaluated screening methods and a descriptive review was conducted for each included study. Of the initial 152 articles reviewed, 19 met inclusion criteria. Generally, cytology-based screening was shown to be the least effective and most costly screening method. Whether provider-collected HPV testing or VIA was the more efficient alternative depended on the cost of the HPV test, loss to follow-up and VIA test performance. Self-collected HPV testing was cost-effective when it yielded population coverage gains over other screening methods. We conclude that HPV testing and VIA are more cost-effective screening methods than cytology in LMICs. Policy makers should consider HPV testing with self-collection of samples if it yields gains in population coverage.

Highlights • Pre-eclampsia is the major determinant of birthweight across all gestations in Uganda. • Pre-eclampsia accounts for ×10 more birthweight variability than all other factors. • In pre-eclampsia, gestation predicts birthweight better than disease severity., 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

GMZ2 is a recombinant protein malaria vaccine, comprising two blood-stage antigens of Plasmodium falciparum, glutamate-rich protein and merozoite surface protein 3. We assessed efficacy of GMZ2 in children in Burkina Faso, Gabon, Ghana and Uganda. : Children 12-60months old were randomized to receive three injections of either 100μg GMZ2 adjuvanted with aluminum hydroxide or a control vaccine (rabies) four weeks apart and were followed up for six months to measure the incidence of malaria defined as fever or history of fever and a parasite density ⩾5000/μL. : A cohort of 1849 children were randomized, 1735 received three doses of vaccine (868 GMZ2, 867 control-vaccine). There were 641 malaria episodes in the GMZ2/Alum group and 720 in the control group. In the ATP analysis, vaccine efficacy (VE), adjusted for age and site was 14% (95% confidence interval [CI]: 3.6%, 23%, p-value=0.009). In the ITT analysis, age-adjusted VE was 11.3% (95% CI 2.5%, 19%, p-value=0.013). VE was higher in older children. In GMZ2-vaccinated children, the incidence of malaria decreased with increasing vaccine-induced anti-GMZ2 IgG concentration. There were 32 cases of severe malaria (18 in the rabies vaccine group and 14 in the GMZ2 group), VE 27% (95% CI -44%, 63%). : GMZ2 is the first blood-stage malaria vaccine to be evaluated in a large multicenter trial. GMZ2 was well tolerated and immunogenic, and reduced the incidence of malaria, but efficacy would need to be substantially improved, using a more immunogenic formulation, for the vaccine to have a public health role.

Vaginal microbiota has been postulated as a key contributor to the disproportionately higher HIV acquisition risk in women. The commensal bacterial communities in the vaginal tract have been implicated in HIV pathogenesis, with strict anaerobes such as Gardnerella and Prevotella causing inflammation and increased frequency of HIV target cells. Young African women are up to six times more likely to be infected with HIV than their male counterparts. The underlying biological mechanisms for increased susceptibility to HIV infection are not fully known, particularly among pregnant women who are also at risk of transmitting the infection to their unborn babies. We characterized the vaginal microbiome of pregnant women receiving antenatal care. Using 16S rRNA sequencing, we analyzed the richness and abundances of the commensal bacterial communities within the female genital tract. Data was analyzed using qiime2 version 2018, Dada2 plugin, and Naive-Bayes classifier for Taxonomic assignment. We report that 19% (35/179) of pregnant women had a Lactobacillus-dominant vaginal microbiota profile. Our findings show that the main cervicotypes (“CTs”) were CT1 which was predominantly non-iners Lactobacillus (6%, 11/179), CT2 which was dominated by L. iners (13%, 24/179), CT3 that was Gardnerella dominant (49%, 87/179) and CT4, a mixed CT co-dominated by L. iners, Gardnerella and Atopobium. Cervical lavage of women with non-Lactobacillus CT had significantly higher levels of inflammatory cytokines IL-1beta, TNF-alpha, and chemokines IL-6 and IL-8. Highly diverse cervicotype (CT4) was associated with inflammation, a known catalyst of HIV acquisition and transmission, within pregnant women regardless of HIV sero-status.

Background Cervical cancer is the leading cause of cancer death for women in Uganda, despite the potential for prevention through organised screening. Community-based self-collected human papillomavirus (HPV) testing has been proposed to reduce barriers to screening. Objective Our objective was to evaluate the cost-effectiveness of the Advances in Screening and Prevention of Reproductive Cancers (ASPIRE) trial, conducted in Kisenyi, Uganda in April 2014 (n=500). The trial compared screening uptake and compliance with follow-up in two arms: (1) community-based (ie, home or workplace) self-collected HPV testing (facilitated by community health workers) with clinic-based visual inspection with acetic acid (VIA) triage of HPV-positive women (‘HPV-VIA’) and (2) clinic-based VIA (‘VIA’). In both arms, VIA was performed at the local health unit by midwives with VIA-positive women receiving immediate treatment with cryotherapy. Design We informed a Monte Carlo simulation model of HPV infection and cervical cancer with screening uptake, compliance and retrospective cost data from the ASPIRE trial; additional cost, test performance and treatment effectiveness data were drawn from observational studies. The model was used to assess the cost-effectiveness of each arm of ASPIRE, as well as an HPV screen-and-treat strategy (‘HPV-ST’) involving community-based self-collected HPV testing followed by treatment for all HPV-positive women at the clinic. Outcome measures The primary outcomes were reductions in cervical cancer risk and incremental cost-effectiveness ratios (ICERs), expressed in dollars per year of life saved (YLS). Results HPV-ST was the most effective and cost-effective screening strategy, reducing the lifetime absolute risk of cervical cancer from 4.2% (range: 3.8%–4.7%) to 3.5% (range: 3.2%–4%), 2.8% (range: 2.4%–3.1%) and 2.4% (range: 2.1%–2.7%) with ICERs of US$130 (US$110–US$150) per YLS, US$240 (US$210–US$280) per YLS, and US$470 (US$410–US$550) per YLS when performed one, three and five times per lifetime, respectively. Findings were robust across sensitivity analyses, unless HPV costs were more than quadrupled. Conclusions Community-based self-collected HPV testing followed by treatment for HPV-positive women has the potential to be an effective and cost-effective screening strategy.

Objectives To compare two cervical cancer screening methods: community-based self-collection of high-risk human papillomavirus (HR-HPV) testing and visual inspection with acetic acid (VIA). Methods Pilot randomised controlled trial of 500 women aged 30–65 in the community of Kisenyi, Uganda. Women randomised to self-collection-based HR-HPV testing provided a cervico-vaginal swab for HR-HPV, and results were provided by phone after laboratory testing. Women who tested HPV positive were referred for VIA at the local health unit. Women randomised to VIA underwent screening at the local health unit, where women who tested positive with VIA were provided cryotherapy at time of screening, as per local standard of care. Women were referred for colposcopy when indicated. Outcome measures were uptake of screening, HR-HPV prevalence, VIA result and treatment rates. Results In the HR-HPV arm, 248 of 250 (p

In this study, normal ranges for hematology and serum biochemistry in children aged 1 to 5 years inUgandawere determined. By a cross-sectional study, 1168 children from Iganga, a prospective site for clinical trials in Uganda, were screened. From 1168 households, 460 children were selected for enrollment, while 600 (58%) were excluded because of either a history of fever in the previous 24 hours, presence of asexual malaria parasites in the peripheral blood or presence of fever. Accordingly, 460 children (39.4%) of median age = 3 years were enrolled in the baseline study. While the lower limits of hemoglobin, hematocrit levels, mean corpuscular volume and platelet counts for the Ugandan children were found to be less than conventional reference values of Caucasisan children, the white blood cell count reference values were higher than the international intervals. On the other hand, the upper limits of the reference intervals for serum transaminases, bilirubin, creatinine, urea, total protein and albumin in sera of the Ugandan children were higher than the corresponding values for a Caucasian pediatric population. This study showed that, if hematology test results of the Ugandan children were assessed against “imported” international reference values, up to 44.6% of the study participants would have been excluded from clinical trials or would have been reported as adverse events in such trials. The present study was not only the first report of serum biochemistry reference ranges for children aged one to five years in Uganda but also one of very few such studies in Africa.

The incidence of cervical cancer in low- and middle-income countries (LMICs) is five times higher than that observed in high-income countries (HICs). This discrepancy is largely attributed to the implementation of cytology-based screening programmes in HICs. However, due to reduced health system infrastructure requirements, HPV testing (self- and provider-collected) and visual inspection with acetic acid (VIA) have been proposed as alternatives that may be better suited to LMICs. Knowing the relative value of different screening options can inform policy and the development of sustainable prevention programs. We searched MEDLINE and EMBASE for English language publications detailing model-based cost-effectiveness analyses of cervical cancer screening methods in LMICs from 2000 to 2016. The main outcome of interest was the incremental cost-effectiveness ratio (ICER). Quantitative data were extracted to compare commonly evaluated screening methods and a descriptive review was conducted for each included study. Of the initial 152 articles reviewed, 19 met inclusion criteria. Generally, cytology-based screening was shown to be the least effective and most costly screening method. Whether provider-collected HPV testing or VIA was the more efficient alternative depended on the cost of the HPV test, loss to follow-up and VIA test performance. Self-collected HPV testing was cost-effective when it yielded population coverage gains over other screening methods. We conclude that HPV testing and VIA are more cost-effective screening methods than cytology in LMICs. Policy makers should consider HPV testing with self-collection of samples if it yields gains in population coverage.

Urinary tract infection (UTI) is common during pregnancy and can be associated with negative outcomes for both the mother and fetus. Increased risk of infection among these patients has been attributed to physiological changes, and less focus has been placed on Escherichia coli , the most frequent causative agent. We investigated the virulence properties of isolates causing UTI in pregnant women in Sweden, Uganda, and Vietnam, as well as nonpregnant women in Sweden. Although phylogenetic group B2 was the most prevalent group, more Ugandan isolates belonged to group B1, associated with commensal strains, than isolates from other countries. Adherence to and invasion of urothelial cells, key events in the infection process, were low among group B1 isolates from pregnant Swedish women compared to those from nonpregnant patients. Similar levels of adherence and invasion were seen in isolates from pregnant women in Uganda and Vietnam. More biofilm was formed by group B2 isolates than by those belonging to group B1 and by Ugandan group B2 isolates than by those from pregnant Swedish and Vietnamese women. The antigen 43a-encoding gene, fluA CFT073 , was most prevalent among Ugandan isolates. Expression of the biofilm components, curli and cellulose, was low among all isolates. Multidrug resistance was more common among isolates from Uganda and Vietnam than among those from Swedish patients. We suggest that while bacterial virulence properties play an important role in UTI during pregnancy, physiological changes in the host may contribute more to the incidence of infection caused by less virulent E. coli .

Ethnopharmacological relevance Labisia pumila var. alata (LPva) is a traditional medicinal herb used by Malaysian women to treat many ailments of the genitourinary tract. Its phytoestrogenic properties suggest potential to prevent recurrent urinary tract infection (UTI) in women post menopause. The aim of this study was therefore to investigate the mechanisms of action of LPva in an in vitro model of UTI. Materials and methods Bladder epithelial cell lines T24 and 5637 and uropathogenic Escherichia coli (UPEC) strain CFT073 were used to model uroepithelial infection. The ability of LPva to induce programmed cell death was tested using the Annexin-V-FLUOS and TUNEL assays. Expression of caveolin-1, β1 integrin and antimicrobial peptides HBD-2 and LL-37 in response to LPva treatment and/or infection, was assessed using RT real-time PCR. Effects on protein expression were confirmed by Western blot analysis. Sensitivity and yeast agglutination assays were employed to determine if LPva had antimicrobial activities and/or interacted with type 1 fimbriae, respectively. Finally, bacterial adherence and invasion to cells treated with LPva was examined. Results LPva induced uroepithelial apoptosis which was coupled with upregulated expression of caveolin-1 and downregulation of β1 integrin. LPva did not exhibit direct antimicrobial properties and did not influence antimicrobial peptide levels in cells. Additionally, LPva did not interact with type 1 fimbriae and did not affect adherence in comparison to non-treated control cells. However, LPva significantly reduced the number of intracellular UPEC in bladder epithelial cells. Conclusions Our findings suggest that LPva has beneficial applications against UPEC infection due to its ability to induce programmed cell death and reduce bacterial invasion of the uroepithelium.

Background Prophylactic antibiotics are used to prevent postoperative infections after caesarean section. Studies have suggested that the timing of prophylaxis plays an important role. Over the years, the role of the anaesthesiologist in the administration of prophylactic antibiotics has become prominent. Therefore, there is an increasing need for anaesthesia providers to understand the rationale of antibiotic prophylaxis. We therefore sought to compare the effect of antibiotics prophylaxis within 1 hour before skin incision and after skin incision on the incidence of postoperative infections in patients undergoing caesarean section at Mulago Hospital. Methods We conducted a single-blind randomised clinical trial conducted at Mulago Hospital evaluating 464 patients undergoing emergency caesarean section. Patients were randomly assigned a group number that allocated them to either arm of the study. They received the same prophylactic antibiotic according to their allotment, that is, either within 1 hour before skin incision or after skin incision as per current standards of practice in Mulago Hospital. They were followed up to detect infection up to 10 days postoperatively. The primary outcome was postoperative infection. The data collected were analysed with STATA version 12 using univariate and bivariate analysis. Results The risk of overall postoperative infection was significantly lower when prophylaxis was given within an hour before incision (RR O.77, 95% CI 0.62–0.97). We also found endometritis to be significantly reduced in the pre-incision group (RR 0.62; 95% CI 0.39–0.99; P value 0.036). Conclusions Giving prophylactic antibiotics before skin incision reduces risk of postoperative infection, in particular of endometritis. Trial registration Pan African Clinical Trial Registry PACTR201311000610495. Date of trial registration: 12th August 2013.

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

Objective To define embarrassment and develop an understanding of the role of embarrassment in relation to cervical cancer screening and self-collected human papillomavirus (HPV) DNA testing in Uganda. Design Cross-sectional, qualitative study using semistructured one-to-one interviews and focus groups. Participants 6 key-informant health workers and 16 local women, purposively sampled. Key informant inclusion criteria: Ugandan members of the project team. Focus group inclusion criteria: woman age 30–69 years, Luganda or Swahili speaking, living or working in the target Ugandan community. Exclusion criteria: unwillingness to sign informed consent. Setting Primary and tertiary low-resource setting in Kampala, Uganda. Results In Luganda, embarrassment relating to cervical cancer is described in two forms. ‘Community embarrassment’ describes discomfort based on how a person may be perceived by others. ‘Personal embarrassment’ relates to shyness or discomfort with her own genitalia. Community embarrassment was described in themes relating to place of study recruitment, amount of privacy in dwellings, personal relationship with health workers, handling of the vaginal swab and misunderstanding of HPV self-collection as HIV testing. Themes of personal embarrassment related to lack of knowledge, age and novelty of the self-collection swab. Overall, embarrassment was a barrier to screening at the outset and diminished over time through education and knowledge. Fatalism regarding cervical cancer diagnosis, worry about results and stigma associated with a cervical cancer diagnosis were other psychosocial barriers described. Overcoming psychosocial barriers to screening can include peer-to-peer education, drama and media campaigns. Conclusions Embarrassment and other psychosocial barriers may play a large role at the onset of a screening programme, but over time as education and knowledge increase, and the social norms around screening evolve, its role diminishes. The role of peer-to-peer education and community authorities on healthcare cannot be overlooked and can have a major impact in overcoming psychosocial and social barriers to screening.

Objective To examine the feasibility of a community-based screening program using human papillomavirus (HPV) self-sampling in a low-income country with a high burden of cervical cancer. Methods A pilot study was conducted among 205 women aged 30–69 years in the Kisenyi district of Kampala, Uganda, from September 5 to October 30, 2011. Women were invited to provide a self-collected specimen for high-risk oncogenic HPV testing by outreach workers at their homes and places of gathering in their community. Specimens were tested for HPV, Neisseria gonorrhoeae and Chlamydia trachomatis . Women who tested positive for HPV were referred for colposcopy, biopsy, and treatment at a regional hospital. Results Of the 199 women who provided a specimen, 35 (17.6%) tested positive for HPV. The outreach workers were able to provide results to 30 women (85.7%). In all, 26 (74.3%) of the women infected with HPV attended their colposcopy appointments and 4 (11.4%) women were diagnosed with grade 3 cervical intraepithelial neoplasia. Conclusion Self-collection of samples for community-based HPV testing was an acceptable option; most women who tested positive attended for definitive treatment. Self-sampling could potentially allow for effective recruitment to screening programs in limited-resource settings.

Objective To determine the prevalence of and factors associated with urologic complications among women with advanced cervical cancer before treatment in Uganda. Methods In total, 283 women with histologically confirmed stage IIB–IVB cervical cancer who were admitted to Mulago Hospital over a 6-month period were studied. Abdominopelvic scan was carried out to check for hydronephrosis and hydroureter and to measure the tumor volume. Serum creatinine and urea levels were measured, and the presence of anuria and vesicovaginal fistula (VVF) was ascertained from self-reporting and clinical records. Results Urologic complications were present in 138 (48.8%) women. Hydronephrosis, VVF, hydroureter, and anuria were present in 112 (39.6%), 21 (7.4%), 11 (3.9%), and 9 (3.2%) women, respectively; serum creatinine and urea levels were elevated in 48 (17.0%) women. Stage of disease was significantly associated with urologic complications: stage IIIB odds ratio (OR) 3.36 (95% confidence interval [CI], 1.57–7.20); stage IVA OR 17.10 (95% CI, 6.07–48.16); P Conclusion There is a high prevalence of urologic complications among women with advanced cervical cancer; these complications are significantly associated with the stage of cervical cancer.

Objective To assess women's willingness to collect their own samples for HPV testing as the first part of a screening program for cervical cancer in Uganda. Methods In March and April 2010, trained assistants from Kisenyi interviewed 300 women aged 30 to 65 years who lived and/or worked in this community. Descriptive data and multivariate modeling were used to identify the predictors of the women's willingness to collect their own cervical samples. Results More than 80% of the 300 participants were willing to collect their own samples. In multivariate modeling, factors positively associated with this willingness were agreement to let outreach workers deliver the necessary swab at their homes (adjusted odds ratio [AOR], 4.10; 95% confidence interval [CI], 1.83–9.18) and willingness to undergo a pelvic examination if the sample was abnormal (AOR, 3.91; 95% CI,1.03–14.90). Factors negatively associated were embarrassment at collecting the sample at home where they lacked privacy (AOR, 0.09; 95% CI, 0.03–0.29) and concern of not collecting the sample properly (AOR, 0.1; 95% CI, 0.05–0.3). Conclusion Self-collection is an option in impoverished settings in Africa. To improve acceptability, women should be taught how to properly collect their own cervical sample and encouraged to find ways to make the collection less embarrassing.

Introduction With innovations in cervical cancer prevention, researchers must define best practices for cervical cancer screening in diverse populations and contexts. This pilot RCT compares the standard of care in most resource constrained settings, visual inspection with acetic acid (VIA), to self collected sampling for detection of high risk human papillomavirus (HR-HPV) DNA. We compared HPV prevalence and uptake of screening among women living with HIV (WHIV) and HIV negative (HIV-) women who participated in the trial. Methods The pilot RCT was conducted between April and June 2014 when 500 women were recruited by community outreach workers in Kisenyi and completed a survey for demographic and risk factors including self-identified HIV status. Women were randomised to self-collected HR-HPV testing or VIA screening at the local health unit. Women who were HPV positive were referred for VIA. Women who tested positive at VIA were provided treatment with cryotherapy at the same visit or referred for colposcopy. Uptake rates of screening and HPV status in WHIV vs HIV- women were compared using Chi-square or Fisher’s exact test. Results Uptake of self-collected HR-HPV testing was 95.5% (21/22) in WHIV and 99.6% (226/227) in HIV- women (p = 0.17). Among WHIV, 42.9% (9/21) were HPV positive compared to 28.3% (64/226) HIV- women (p = 0.25). A greater proportion of WHIV were infected with HPV genotype 16 or 18 (28.6%, 6/21) than HIV- women (5.3%, 12/226) (p = 0.004). All 9 WHIV who were HPV positive attended VIA follow up, compared to 24/64 HIV- women. In the VIA arm, 64.0% (16/25) WHIV attended screening compared to 46.7% (105/225) HIV- women (p = 0.23). Conclusion Self-collection based screening had high uptake in WHIV and HIV- women, suggesting that this method is highly acceptable and improves access compared to VIA. As more WHIV were HR-HPV infected, there is additional benefit to providing this type of screening given their increased risk for cervical cancer. Disclosure of interest statement None of the authors have any conflicts to declare.

Objective We sought to determine demographic and behavioral factors associated with human papillomavirus (HPV) positivity in a community-based HPV self-collection cervical cancer screening pilot project. Study design HPV self-collected samples were obtained from 199 women aged 30-69 years in the impoverished urban Ugandan community of Kisenyi, during September through November 2011. Demographic and behavioral information was collected. Descriptive statistics and a logistic regression model were used to analyze factors associated with HPV positivity. Results There was overwhelming acceptance of HPV self-collection in this community. High-risk HPV prevalence was found to be 17.6%. Lower levels of formal education (adjusted odds ratio [AOR], 0.40; 95% confidence interval [CI], 0.08–2.03) were associated with higher prevalence of HPV as was use of oral contraception (AOR, 2.01; 95% CI, 0.83–4.90) and human immunodeficiency virus status (AOR, 0.43; 95% CI, 0.14–1.37). Conclusion Screening should be targeted and prioritized for women with lower levels of education, oral contraceptive use, and human immunodeficiency virus positivity as they have the highest HPV prevalence in this low-resource population.