Prevalence of cervical intraepithelial lesions and associated factors among women attending a cervical cancer clinic in Western Uganda; results based on Pap smear cytology.

Introduction: There are high incidence and mortality rates of cervical cancer among females in East Africa. This is exacerbated by limited up-to-date data on premalignant lesions and associated factors in this setting. In this study, we determined the prevalence of cervical intraepithelial lesions and associated factors among women attending the Mbarara Regional Referral Hospital cervical cancer clinic in Southwestern Uganda. Methods: In this cross-sectional study, 364 participants were recruited from among women attending the Mbarara Regional Referral Hospital cervical cancer clinic from 1 April to 30 June 2023. On consent, the study nurse collected demographic data and Pap smears, which were microscopically examined and reported by a laboratory scientist and a pathologist following the Bethesda grading system (2014). Statistical analyses were done in STATA version 17, using proportions, Chi-square, bivariate, and multivariate logistic regression analysis to determine associated factors at ⩽0.05 significance level. Results: The mean age of participants was 41.9 years. A third of all study participants (37.6%, 132/351) were contraceptive users, mostly hormonal contraceptives (87.1%, 115/132). Almost 88% (307/351) had an unknown Human Papilloma Virus status. The prevalence of cervical intraepithelial lesions among our study participants was 6.6% (23/351), of which 73.9% (17/23) were low-grade squamous intraepithelial lesions. More than half (9/17, 52.9%) of low-grade squamous intraepithelial lesions were active hormonal contraceptive users. Use of hormonal contraceptives (OR: 3.032, p: 0.0253), use of intrauterine devices (OR: 6.284, p: 0.039), and any family history of cervical cancer (OR: 4.144, p: 0.049) were significantly associated with cervical intraepithelial lesions. Conclusion: The prevalence of cervical intraepithelial lesions was 6.6%, lower than global estimates. Use of hormonal and intrauterine device contraceptives, as well as family history of cervical cancer, were significantly associated with cervical intraepithelial lesions among our study population. Prospective studies are recommended to further understand associations between different types of intrauterine devices and hormonal contraceptives, and cervical lesions.

Distinct cytokine profiles in late pregnancy in Ugandan people with HIV.

During pregnancy, multiple immune regulatory mechanisms establish an immune-tolerant environment for the allogeneic fetus, including cellular signals called cytokines that modify immune responses. However, the impact of maternal HIV infection on these responses is incompletely characterized. We analyzed paired maternal and umbilical cord plasma collected during labor from 147 people with HIV taking antiretroviral therapy and 142 HIV-uninfected comparators. Though cytokine concentrations were overall similar between groups, using Partial Least Squares Discriminant Analysis we identified distinct cytokine profiles in each group, driven by higher IL-5 and lower IL-8 and MIP-1α levels in pregnant people with HIV and higher RANTES and E-selectin in HIV-unexposed umbilical cord plasma (P-value < 0.01). Furthermore, maternal RANTES, SDF-α, gro α -KC, IL-6, and IP-10 levels differed significantly by HIV serostatus (P < 0.01). Although global maternal and umbilical cord cytokine profiles differed significantly (P < 0.01), umbilical cord plasma profiles were similar by maternal HIV serostatus. We demonstrate that HIV infection is associated with a distinct maternal plasma cytokine profile which is not transferred across the placenta, indicating a placental role in coordinating local inflammatory response. Furthermore, maternal cytokine profiles in people with HIV suggest an incomplete shift from Th2 to Th1 immune phenotype at the end of pregnancy.

Association between serum P16ink4A concentration and CIN and cervical cancer among women attending a cervical cancer clinic in western Uganda: A case control study.

Introduction: Tissue expression of P16ink4A is correlated with cervical lesions. In this study we determined the association between serum P16ink4A concentrations and cervical lesions among women attending the cervical cancer clinic at Mbarara Regional Hospital (MRRH) South Western Uganda. Material and Methods: We recruited 90 cervical intraepithelial neoplasia (CIN) cases, 90 cervical cancer (CC) cases before treatment and 90 controls. Clinical and demographic data were recorded. Serum P16ink4A concentrations were measured by quantitative Elisa. Cases were confirmed with cytology and/or histology. Descriptive statistics and logistic regression were done with STATA 17 and P-values of <0.05 were considered statistically significant. Results: The mean serum P16ink4A concentration among CIN cases, CC cases and controls was 1.11(+/-0.66) ng/ml, 1.45(+/-1.11) ng/ml and 1.13(+/-0.61) ng/ml respectively (p = 0.008). 50 % of CIN cases and controls as well as 60 % of CC cases had P16ink4A concentration above 0.946 ng/ml. There were increased odds of CIN for serum P16ink4A though statistically insignificant (AOR: 1.11, p-value: 0.70). There was also a statistically significant reduction in odds of CC for serum P16ink4A (AOR: 0.55, p-value: 0.01). Conclusion: Serum P16ink4A may likely be associated with cervical lesions especially CC in our study population and this may aid detection of such lesions. Diagnostic utility studies for circulating P16ink4A in detection of cervical cancer are recommended.

Prevalence and Risk Factors for Newborn Anemia in Southwestern Uganda: A Cross-Sectional Study.

Introduction: The global prevalence of maternal anemia is about 42%, and in sub-Saharan Africa, the prevalence of newborn anemia ranges from 25% to 30%. Anemia in newborn babies may cause complications such as delayed brain maturation and arrested growth. However, there is limited data on the prevalence of newborn anemia and its risk factors in people living in resource-limited settings. Objectives: We determined the prevalence and risk factors for newborn anemia and its correlation with maternal anemia in southwestern Uganda. Methods: This was a cross sectional study of 352 pregnant women presenting to the Mbarara Regional Referral Hospital for delivery. We collected maternal blood in labor and umbilical cord blood from the placental vein. We measured hemoglobin using a point-of-care Hemocue machine. We used summary statistics to characterize the study participants and compared demographic characteristics and outcomes using chi-square, t-test, and Wilcoxon rank sum analyses. We defined newborn anemia as umbilical cord hemoglobin <13 g/dl and measured the relationship between maternal and umbilical cord hemoglobin using linear regression analysis. Results: The prevalence of newborn anemia was 17%. Maternal parity was significantly higher for anemic than nonanemic newborns (3 versus 2, P=0.01). The mean age in years (SD) was significantly lower for participants with umbilical cord hemoglobin <13 g/dl than those ≥13 g/dl (26 years [5.6] versus 28 [6.3], P=0.01). In multivariable linear regression analysis, a 1-point decrease in maternal hemoglobin was associated with a 0.14-point decrease in umbilical cord hemoglobin (P=0.02). Each one-unit increase in parity was associated with a 0.25-point decrease in umbilical cord hemoglobin (P=0.01). Cesarean delivery was associated with a 0.46-point lower umbilical cord hemoglobin level compared with vaginal delivery (P=0.03). Conclusions: We found a significant association between maternal and newborn hemoglobin, underscoring the importance of preventing and correcting maternal anemia in pregnancy. Furthermore, maternal anemia should be considered a risk factor for neonatal anemia.

Impact of the Mbarara University of Science and Technology residency training on increasing access to specialty care workforce.

Graduate tracer studies provide an avenue for assessing the impact of residency training on the distribution and access to specialty care and exploring job and professional satisfaction of alumnus. This study examined how the Mbarara University of Science and Technology (MUST) clinical residency training program influenced the spatial distribution and career paths of specialists. We conducted a mixed methods study involving an online survey and 12 in-depth interviews (IDIs) from June to September 2022. The online survey was distributed to a convenient sample of clinical residency alumnus from MUST via email and Whatsapp groups. Alumnus were mapped across the countries of current work in QGIS (version 3.16.3) using GPS coordinates. Descriptive and thematic analyses were also conducted. Ninety-five alumni (34.3%) responded to the tracer survey. The majority were males (80%), aged 31-40 years (69%), and Ugandans (72%). Most graduated after 2018 (83%) as obstetricians/gynecologists (38%) and general surgeons (19%). There was uneven distribution of specialists across Uganda and the East-African community-with significant concentration in urban cities of Uganda at specialized hospitals and academic institutions. Residency training helped prepare and equip alumnus with competencies relevant to their current work tasks (48%) and other spheres of life (45%). All respondents were currently employed, with the majority engaged in clinical practice (82%) and had obtained their first employment within six months after graduation (76%). The qualitative interviews revealed the reported ease in finding jobs after the training and the relevance of the training in enhancing the alumnus' ability to impact those they serve in teaching, research, management, and clinical care. Graduates cited low payment, limited resources, and slow career advancement concerns. Residency training improves the graduates' professional/career growth and the quality of health care services. Strategic specialty training addressing imbalances in subspecialties and rural areas coverage could optimize access to specialist services.

Maternal near miss as a predictor of adverse perinatal outcomes: findings from a prospective cohort study in southwestern Uganda.

BACKGROUND: Despite efforts, Uganda has not met the World Health Organization target of < 12 newborn deaths per 1,000 live births. Severe maternal morbidity or 'near miss' is a major contributor to adverse perinatal outcomes, particularly in low-resource settings. However, the specific impact of maternal near miss on perinatal outcomes in Uganda remains insufficiently investigated. We examined the association between maternal near miss and adverse perinatal outcomes at Mbarara Regional Referral Hospital (MRRH) in southwestern Uganda. METHODS: We conducted a prospective cohort study among women admitted for delivery at MRRH's maternity ward from April 2022 to August 2022. We included mothers at ≥ 28 weeks of gestation with singleton pregnancies, while intrauterine fetal death cases were excluded. For the near-miss group, we consecutively included mothers with any one of the following: antepartum hemorrhage with shock, uterine rupture, hypertensive disorders, coma, and cardiac arrest; those without these complications constituted the non-near-miss group. We followed the mothers until delivery, and their infants until seven days postpartum or death. Adverse perinatal outcomes considered were low birth weight (< 2,500 g), low Apgar score (< 7 at five minutes), intrapartum stillbirths, early neonatal death, or admission to neonatal intensive care unit. Multivariable log-binomial regression was used to determine predictors of adverse perinatal outcomes. RESULTS: We enrolled 220 participants (55 maternal near misses and 165 non-near misses) with a mean age of 27 ± 5.8 years. Most of the near misses were pregnancies with hypertensive disorders (49%). Maternal near misses had a four-fold (adjusted risk ratio [aRR] = 4.02, 95% CI: 2.32-6.98) increased risk of adverse perinatal outcomes compared to non-near misses. Other predictors of adverse perinatal outcomes were primigravidity (aRR = 1.53, 95%CI: 1.01-2.31), and gestational age < 34 weeks (aRR = 1.81, 95%CI: 1.19-2.77). CONCLUSION: Maternal near misses, primigravidity, and preterm pregnancies were independent predictors of adverse perinatal outcomes in this study. We recommend implementing maternal near-miss surveillance as an integral component of comprehensive perinatal care protocols, to improve perinatal outcomes in Uganda and similar low-resource settings. Targeted interventions, including specialized care for women with maternal near misses, particularly primigravidas and those with preterm pregnancies, could mitigate the burden of adverse perinatal outcomes.

Abnormal obstetric shock index and associated factors among immediate postpartum women following vaginal delivery at a tertiary hospital in southwestern Uganda.

BACKGROUND: Early recognition of haemodynamic instability after birth and prompt interventions are necessary to reduce adverse maternal outcomes due to postpartum haemorrhage. Obstetric shock Index (OSI) has been recommended as a simple, accurate, reliable, and low-cost early diagnostic measure that identifies hemodynamically unstable women. OBJECTIVES: We determined the prevalence of abnormal obstetric shock index and associated factors among women in the immediate postpartum period following vaginal delivery at Mbarara Regional Referral Hospital (MRRH) in southwestern Uganda. METHODS: We conducted a cross-sectional study at the labour suite and postnatal ward of MRRH from January 2022 to April 2022. We systematically sampled women who had delivered vaginally, and measured their blood pressures and pulse rates at 1 h postpartum. We excluded mothers with hypertensive disorders of pregnancy. Sociodemographic, medical and obstetric data were obtained through interviewer-administered questionnaires. The prevalence of abnormal OSI was the proportion of participants with an OSI ≥ 0.9 (calculated as the pulse rate divided by the systolic BP). Logistic regression analysis was used to determine associations between abnormal OSI and independent variables. RESULTS: We enrolled 427 women with a mean age of 25.66 ± 5.30 years. Of these, 83 (19.44%), 95% CI (15.79-23.52) had an abnormal obstetric shock index. Being referred [aPR 1.94, 95% CI (1.31-2.88), p = 0.001], having had antepartum haemorrhage [aPR 2.63, 95% CI (1.26-5.73), p = 0.010] and having a visually estimated blood loss > 200 mls [aPR 1.59, 95% CI (1.08-2.33), p = 0.018] were significantly associated with abnormal OSI. CONCLUSION: Approximately one in every five women who delivered vaginally at MRRH during the study period had an abnormal OSI. We recommend that clinicians have a high index of suspicion for haemodynamic instability among women in the immediate postpartum period. Mothers who are referred in from other facilities, those that get antepartum haemorrhage and those with estimated blood loss > 200mls should be prioritized for close monitoring. It should be noted that the study was not powered to study the factors associated with AOSI and therefore the analysis for factors associated should be considered exploratory.

Magnitude and trends in cervical cancer at Mbarara Regional Referral Hospital in South Western Uganda: Retrospective analysis of data from 2017-2022.

High-income countries have documented a significant decline in the incidence and mortality of cervical cancer over the past decade but such data from low and middle-income countries such as Uganda is limited to ascertain trends. There is also paucity of data on the burden of cervical cancer in comparison to other gynaecologic malignancies and there is a likelihood that the incidence might be on the rise. To describe the current trends and magnitude of cervical cancer in comparison to other gynaecological malignancies histological types, we conducted a retrospective records review of charts of patients admitted with gynaecological malignancies on the gynaecological ward of Mbarara Regional Referral Hospital (MRRH) between January 2017 and December 2022. Of 875 patients with gynaecological malignancies admitted to the MRRH in the 6-year review period, 721 (82.4%) had cervical cancer. Patients with cervical cancer were significantly older than those with other gynaecological malignancies: (50.2±11.5 versus 43.8± 15.0 respectively, p<0.001). Between 2017 and 2022, cervical cancer rates increased by 17% annually compared to other gynaecological cancers (OR:1.17; 95% CI 1.06-1.28, p = 0.0046), with the majority of patients of cervical cancer patients (92.7%, n = 668) having squamous cell carcinoma. Most patients (87.9%, n = 634) had late-stage disease (stage 2 and above) and were referred to the Uganda Cancer Institute for chemoradiation. These results imply that there is a need to scale up screening services and other preventive measures such as vaccination against human papilloma virus.

A practical tool for managing change: cross-sectional psychometric assessment of the safe surgery organizational readiness tool.

BACKGROUND: Strengthening health systems through planned safety and quality improvement initiatives is an imperative to achieve more equitable, resilient, and effective care. And yet, years of organizational behavior research demonstrate that change initiatives often fall short because managers fail to account for organizational readiness for change. This finding remains true especially among surgical safety and quality improvement initiatives in low-income countries and middle-income countries. In this study, our aim was to psychometrically assess the construct validity and internal consistency of the Safe Surgery Organizational Readiness Tool (SSORT), a short survey tool designed to provide change leaders with insight into facility infrastructure that supports learning and readiness to undertake change. MATERIALS AND METHODS: To demonstrate generalizability and achieve a large sample size ( n =1706) to conduct exploratory factor analysis (EFA) and confirmatory factor analysis (CFA), a collaboration between seven surgical and anesthesia safety and quality improvement initiatives was formed. Collected survey data from health care workers were divided into pilot, exploration, and confirmation samples. The pilot sample was used to assess feasibility. The exploration sample was used to conduct EFA, while the confirmation sample was used to conduct CFA. Factor internal consistency was assessed using Cronbach's alpha coefficient. RESULTS: Results of the EFA retained 9 of the 16 proposed factors associated with readiness to change. CFA results of the identified 9 factor model, measured by 28 survey items, demonstrated excellent fit to data. These factors (appropriateness, resistance to change, team efficacy, team learning orientation, team valence, communication about change, learning environment, vision for sustainability, and facility capacity) were also found to be internally consistent. CONCLUSION: Our findings suggest that communication, team learning, and supportive environment are components of change readiness that can be reliably measured prior to implementation of projects that promote surgical safety and quality improvement in low-income countries and middle-income countries. Future research can link performance on identified factors to outcomes that matter most to patients.

Effects of Maternal HIV Infection and Alcohol Use in Pregnancy on Birth Outcomes in Uganda.

Alcohol use and HIV infection are prevalent in sub-Saharan Africa (sSA), and both are associated with low birth weight. Yet, few studies have evaluated the combined effects of maternal HIV infection and alcohol use on birth outcomes. We analyzed data from a prospective cohort study of HIV-related placental changes in Ugandan women. We defined alcohol use as self-reported alcohol use within the last year, using the AUDIT questionnaire and used linear and logistic regression to measure associations between maternal alcohol use, HIV serostatus, and birth weight. In a subsample, we measured alcohol exposure using phosphatidylethanol (PEth) in neonatal heelstick dried blood spots to confirm maternal alcohol use. Of 352 participants, 176 (50%) were women with HIV (WHIV). Three of 176 (2%) HIVuninfected women and 17/176 (10%) of WHIV self-reported alcohol use (P = 0.002). Maternal HIV infection was associated with lower birth weight (ß = -0.12, 95% CI [-0.20, -0.02], P = 0.02), but self-reported alcohol use was not (ß = 0.06, 95% CI [-0.15, 0.26], P = 0.54), and the interaction between HIV serostatus and alcohol use was not significant (P = 0.13). Among the PEth subsample, neither HIV status nor PEthconfirmed alcohol use were associated with low birth weight. Maternal HIV infection was associated with lower birth weight, but alcohol use was not, and there was no significant interaction between maternal HIV infection and alcohol use. Alcohol use was more prevalent in WHIV and under-reporting was common. A larger study of the effects of laboratory-confirmed alcohol and HIV exposure on birth outcomes is warranted.

Validating the Edinburgh Postnatal Depression Scale Against the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition for Use in Uganda.

Background: The Edinburgh Postnatal Depression Scale (EPDS) is a widely acknowledged screening tool for postpartum depression (PPD) globally, but its validation in Uganda has been lacking. This study aimed to assess the EPDS's accuracy as a PPD screening tool in Uganda compared to the Mini-International Neuropsychiatric Interview (MINI 7.0.2) based on the DSM-5. Methods: This was a descriptive cross-sectional study conducted at a referral hospital and two peri-urban primary care postpartum clinics in rural southwestern Uganda. We enrolled 287 mothers aged 18 to 49 at their six-week postpartum visit. The EPDS was used for initial screening, and the MINI 7.0.2 was employed for clinical diagnosis. The study used the Runyankore-Rukiga language version of the EPDS and collected data from November 11, 2019, to June 10, 2020, with the MINI 7.0.2 as the reference standard. Results: The overall PPD prevalence was 29.5%, as opposed to 26.5% with EPDS and MINI 7.0.2 DSM-5 criteria (p = 0.239). The EPDS demonstrated a sensitivity of 86.8%, specificity of 92.1%, positive predictive value of 80.5%, and negative predictive value of 94.9%. A cutoff score of ≥10 was found to be the most effective acceptable point after drawing the AUC of ROC and determining the most appropriate point using Youden's index. The area under the ROC curve, indicating the scale's overall performance against MINI 7.0.2, was 0.89 for Bwizibwera HCIV, 0.97 for Kinoni HCIV, and 0.84 for MRRH. In conclusion, the EPDS can effectively screen for postpartum depression in southwestern Uganda using a cutoff score of ≥10. It exhibits strong diagnostic performance in correctly identifying PPD in postpartum mothers.

Bacterial isolates and antibiotic susceptibility among women with abnormal vaginal discharge attending the gynecology clinic at a tertiary hospital in southwestern Uganda: a cross-sectional study.

BACKGROUND: Abnormal vaginal discharge is a common complaint among women of reproductive age, affecting about one- third of all women. In resource-limited settings where access to laboratory services is limited, treatment is usually syndromic. This approach may result in ineffective treatment, with high recurrence rates and a potential of developing antibiotic resistance. This study aimed to determine the bacterial isolates and antibiotic susceptibility among women with an abnormal vaginal discharge attending the gynecology clinic at a tertiary hospital in Southwestern Uganda. METHODS: We conducted a hospital based cross-sectional study among 361 women aged 15-49 years, presenting with abnormal vaginal discharge at the gynecology clinic of Mbarara Regional Referral Hospital from December 2020 to June 2021. Demographic characteristics were collected using a structured questionnaire. We collected cervical and vaginal sterile swabs and subjected them to wet preparation and gram stain. The specimens were cultured for bacterial isolates. Susceptibility testing was performed on samples with bacterial isolates using the Kirby-Bauer disc diffusion method, on the commonly prescribed antibiotics in this setting. We summarized and described the bacterial isolates and antibiotic susceptibility patterns as frequencies and percentages. RESULTS: We enrolled 361 women with abnormal vaginal discharge. Bacteria were isolated in 29.6% (107/361) of the women, and the commonest isolates included; Staphylococcus aureus 48.6% (52/107), Klebsiella pneumoniae 29.9% (32/107) and Enterococcus faecalis 15% (16/107). Yeast cells were found in 17.7% (64/361) of the women with abnormal vaginal discharge. Cefuroxime (90.7%) and Ciprofloxacin (81.3%) had a high level of sensitivity while high levels of resistance were observed for Doxycycline (86.0%) and Azithromycin (67.0%). CONCLUSION: The common bacterial isolates were Staphylococcus aureus, Klebsiella pneumoniae and Enterococcus faecalis. The isolated bacteria were most sensitive to Cefuroxime and Ciprofloxacin but resistant to Doxycycline and Azithromycin. There is need for routine culture and susceptibility testing of women with abnormal vaginal discharge so as to guide treatment, minimize inappropriate antibiotic use and consequently reduce antibiotic resistance.

Prevalence and risk factors for newborn anemia in southwestern Uganda: a prospective cohort study.

Introduction: The global prevalence of anemia in pregnancy is about 42%, and in sub-Saharan Africa, the prevalence of newborn anemia ranges from 25-30%. Anemia in newborn babies may cause complications such as delayed brain maturation and arrested growth. However, there is limited data on prevalence of newborn anemia and its risk factors in people living in resource-limited settings. Objectives: We determined the prevalence and risk factors for newborn anemia and its correlation with maternal anemia in southwestern Uganda. Methods: This was a prospective cohort study of 352 pregnant women presenting to Mbarara Regional Referral Hospital for delivery. We collected maternal blood in labor and umbilical cord blood from the placental vein, as a proxy for newborn hemoglobin. We estimated hemoglobin using a point-of-care Hemocue machine. We used summary statistics to characterize the cohort, and compared demographic characteristics and outcomes using Chi-square, t-test, and Wilcoxon Ranksum analyses. We defined newborn anemia as umbilical cord hemoglobin < 13g/dl and estimated the relationship between maternal and umbilical cord hemoglobin using linear regression analysis, adjusting for potential confounders. Results: The prevalence of newborn anemia was 17%. The average maternal parity was significantly higher for anemic and non-anemic newborns (3.5 versus 2.8, P = 0.01). Mean age [SD] was significantly lower for participants with umbilical cord hemoglobin < 13g/dl than those > = 13 g/dl, (26 [5.6] versus 28 [6.3], P = 0.01). In multivariable linear regression analysis, a 1-point decrease in maternal hemoglobin was associated with a 0.14-point decrease in umbilical cord hemoglobin (P = 0.02). Each one-unit increase in maternal parity was associated with a 0.25-point decrease in umbilical cord hemoglobin (P = 0.01). Cesarean delivery was associated with a 0.46-point lower umbilical cord hemoglobin level compared to vaginal delivery (P = 0.03). Conclusions: We found a significant correlation between maternal and newborn hemoglobin levels, underscoring the importance of preventing and correcting maternal anemia in pregnancy. Furthermore, maternal anemia should be considered a risk factor neonatal anemia.

Paenibacillus spp infection among infants with postinfectious hydrocephalus in Uganda: an observational case-control study.

BACKGROUND: Paenibacillus thiaminolyticus is a cause of postinfectious hydrocephalus among Ugandan infants. To determine whether Paenibacillus spp is a pathogen in neonatal sepsis, meningitis, and postinfectious hydrocephalus, we aimed to complete three separate studies of Ugandan infants. The first study was on peripartum prevalence of Paenibacillus in mother-newborn pairs. The second study assessed Paenibacillus in blood and cerebrospinal fluid (CSF) from neonates with sepsis. The third study assessed Paenibacillus in CSF from infants with hydrocephalus. METHODS: In this observational study, we recruited mother-newborn pairs with and without maternal fever (mother-newborn cohort), neonates (aged ≤28 days) with sepsis (sepsis cohort), and infants (aged ≤90 days) with hydrocephalus with and without a history of neonatal sepsis and meningitis (hydrocephalus cohort) from three hospitals in Uganda between Jan 13, 2016 and Oct 2, 2019. We collected maternal blood, vaginal swabs, and placental samples and the cord from the mother-newborn pairs, and blood and CSF from neonates and infants. Bacterial content of infant CSF was characterised by 16S rDNA sequencing. We analysed all samples using quantitative PCR (qPCR) targeting either the Paenibacillus genus or Paenibacillus thiaminolyticus spp. We collected cranial ultrasound and computed tomography images in the subset of participants represented in more than one cohort. FINDINGS: No Paenibacillus spp were detected in vaginal, maternal blood, placental, or cord blood specimens from the mother-newborn cohort by qPCR. Paenibacillus spp was detected in 6% (37 of 631 neonates) in the sepsis cohort and, of these, 14% (5 of 37 neonates) developed postinfectious hydrocephalus. Paenibacillus was the most enriched bacterial genera in postinfectious hydrocephalus CSF (91 [44%] of 209 patients) from the hydrocephalus cohort, with 16S showing 94% accuracy when validated by qPCR. Imaging showed progression from Paenibacillus spp-related meningitis to postinfectious hydrocephalus over 1-3 months. Patients with postinfectious hydrocephalus with Paenibacillus spp infections were geographically clustered. INTERPRETATION: Paenibacillus spp causes neonatal sepsis and meningitis in Uganda and is the dominant cause of subsequent postinfectious hydrocephalus. There was no evidence of transplacental transmission, and geographical evidence was consistent with an environmental source of neonatal infection. Further work is needed to identify routes of infection and optimise treatment of neonatal Paenibacillus spp infection to lessen the burden of morbidity and mortality. FUNDING: National Institutes of Health and Boston Children's Hospital Office of Faculty Development.

Maternal anemia is associated with adverse maternal and neonatal outcomes in Mbarara, Uganda.

PURPOSE: Maternal anemia is a significant risk factor for maternal morbidity and mortality, increasing risk of preterm birth, intrauterine growth restriction, stillbirth, and death. Moderate and severe anemia in pregnancy is defined as hemoglobin (Hb) <10 g/dl and Hb < 7 g/dl, respectively. We aimed to characterize the association of maternal anemia with maternal, neonatal, and placental outcomes in a resource-limited setting. METHODS: Data were collected from a prospective cohort of 352 pregnant women at a tertiary academic Ugandan hospital. One hundred and seventy-six (50%) of women were living with HIV. Hemoglobin was measured in labor, and placentas were collected postpartum. Maternal outcomes included mode of delivery, hemorrhage, blood transfusion, intensive care unit admission, and maternal mortality. Neonatal outcomes included gestational age at delivery, birthweight, stillbirth, and neonatal mortality. Placental descriptors included weight and thickness. Categorical variables were analyzed using Chi-squared and Fisher's exact tests. RESULTS: Hemoglobin < 10 g/dl, was present in 17/352 (5%) of women. Significantly more women with moderate or severe anemia were HIV-infected: 14/17 (82%) versus 162/335 (48%) (p = .006). Blood transfusions (2/17, 12% versus 5/335, 2%, p = .04) and neonatal deaths (2/17, 12% versus 9/335, 3%, p = .01) were more common in the anemia group. Placental thickness was lower in the anemia group (1.4 cm versus 1.7 cm, p = .04). CONCLUSIONS: Moderate and severe anemia was associated with maternal HIV infection, maternal blood transfusion, neonatal death, and decreased placental thickness. The overall rate of moderate and severe anemia among this cohort was lower than previously reported.

Maternal HIV infection drives altered placental Mtb-specific antibody transfer.

Introduction: Placental transfer of maternal antibodies is essential for neonatal immunity over the first months of life. In the setting of maternal HIV infection, HIV-exposed uninfected (HEU) infants are at higher risk of developing severe infections, including active tuberculosis (TB). Given our emerging appreciation for the potential role of antibodies in the control of Mycobacterium tuberculosis (Mtb), the bacteria that causes TB, here we aimed to determine whether maternal HIV status altered the quality of Mtb-specific placental antibody transfer. Methods: Antigen-specific antibody systems serology was performed to comprehensively characterize the Mtb-specific humoral immune response in maternal and umbilical cord blood from HIV infected and uninfected pregnant people in Uganda. Results: Significant differences were noted in overall antibody profiles in HIV positive and negative maternal plasma, resulting in heterogeneous transfer of Mtb-specific antibodies. Altered antibody transfer in HIV infected dyads was associated with impaired binding to IgG Fc-receptors, which was directly linked to HIV viral loads and CD4 counts. Conclusions: These results highlight the importance of maternal HIV status on antibody transfer, providing clues related to alterations in transferred maternal immunity that may render HEU infants more vulnerable to TB than their HIV-unexposed peers.

Thirty-Day Outcomes of Young and Middle-Aged Adults Admitted with Severe COVID-19 in Uganda: A Retrospective Cohort Study.

Background: There is scarcity of data regarding young and middle-aged adults hospitalized with severe Corona Virus Disease 2019 (COVID-19) in Africa. In this study, we describe the clinical characteristics and 30-day survival among adults aged 18 to 49 years admitted with severe COVID-19 in Uganda. Methods: We reviewed treatment records of patients admitted with severe COVID-19 across five COVID-19 treatment units (CTU) in Uganda. We included individuals aged 18 to 49 years, who had a positive test or met the clinical criteria for COVID-19. We defined severe COVID-19 as having an oxygen saturation <94%, lung infiltrates >50% on imaging and presence of a co-morbidity that required admission in the CTU. Our main outcome was the 30-day survival from the time of admission. We used a Cox proportional hazards model to determine the factors associated with 30-day survival at a 5% level of significance. Results: Of the 246 patient files reviewed, 50.8% (n = 125) were male, the mean ± (standard deviation) age was 39 ± 8 years, majority presented with cough, 85.8% (n = 211) and median C-reactive protein (interquartile range) was 48 (47.5, 178.8) mg/L. The 30-day mortality was 23.9% (59/246). At admission, anemia (hazard ratio (HR): 3.00, 95% confidence interval (CI), 1.32-6.82; p = 0.009) and altered mental state (GCS <15) (HR: 6.89, 95% CI: 1.48-32.08, p = 0.014) were significant predictors of 30-day mortality. Conclusion: There was a high 30-day mortality among young and middle-aged adults with severe COVID-19 in Uganda. Early recognition and targeted management of anemia and altered consciousness are needed to improve clinical outcomes.

Association between obesity and cervical intraepithelial neoplasia: results from a case control study in south western Uganda.

BACKGROUND: Though obesity has been said to be associated with a number of malignancies including cervical cancer, its association with cervical intraepithelial neoplasia (CIN) is still a contentious issue. This study was designed to determining the prevalence and association between obesity and CIN. METHODS: This was an unmatched case control study, involving women with cervical intraepithelial neoplasia (cases) and those negative for intraepithelial lesions or malignancy (controls) at the cervical cancer clinic of Mbarara Regional Referral Hospital, in south-western Uganda, between April and November 2022. Cases and controls provided written informed consent and were recruited in a ratio of 1:1. Cases were identified by visual inspection with acetic acid (VIA) and subsequent confirmation with cytology and/or histology. Demographic information was collected using an enrolment form and height, weight and waist circumference were recorded. We calculated body mass index (BMI) and identified obese women as those with body mass index of ≥ 30 kg/m2 from both case and control groups. Central obesity was defined as waist: height ration of ≥ 0.5. Data was analysed using STATA version 17. Categorical variables were analysed using proportions, chi-square and logistic regression analysis to determine association between obesity and CIN. Our level of statistical significance was set at ≤ 0.05. RESULTS: The prevalence of general and central obesity among cases was 25.5% (24/94) and 0% (0/94) respectively while the prevalence of general and central obesity among controls was 33.3% (37/111) and 0% (0/111) respectively. There was an increased prevalence of general obesity among women with low grade squamous intraepithelial lesions (LSIL). However, there was no statistically significant association between general obesity and CIN. Factors associated with general obesity included residing in Mbarara city (AOR 2.156, 95%CI 1.085-4.282, P-value 0.028), age group of 31-45 years (AOR 2.421, 95%CI 1.577-9.705, P-value 0.003) and ≥ 46 years (AOR 1.971, 95%CI 1.022-11.157, P-value 0.046). CONCLUSION: We observed an increased prevalence of general obesity among women with LSIL. However, there was no association between obesity and CIN. Factors associated with general obesity included residing in Mbarara city, and being in the age groups of 31-40 and ≥ 46 years. This highlights the need to rethink management of CIN to control other non-communicable diseases that could arise due to general obesity.