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Abstract Background Asymptomatic Cryptococcal Antigenemia (CrAg) patients develop meningitis within a month of testing positive. Pre-emptive antifungal therapy can prevent progression to Cryptococcal meningitis (CM). In April 2016, a national CrAg screening program was initiated in 206 high-volume health facilities that provide antiretroviral therapy in Uganda. We report the evaluation of the CrAg screening cascade focusing on linkage to care, fluconazole therapy for 10 weeks and 6 months follow up, and ART initiation in a subset of facilities. Methods We conducted a retrospective, cross-sectional survey of patients with CD4

Abstract Background HIV and anaemia are major health challenges in Africa. Anaemia in HIV-infected individuals is associated with more rapid disease progression and a poorer prognosis if not addressed appropriately. This study aimed at determining the severity and types of anaemia among HIV infected children and its effect on short term response to antiretroviral therapy (ART). Methods At baseline, clinical and haematological parameters of 257 HIV-infected ART-naïve children aged 3 months to 18 years were assessed to determine the prevalence, severity and types of anaemia. ART eligible patients were started on therapy according to WHO criteria, enrolled (n=88) into an observational cohort and followed up for 6 months. Results Anaemia was present in 148/257 (57.6%) of children, including (93/148) 62.2% with mild anaemia, 47/148 (32.0%) moderate anaemia, and 7/148 (4.8%) with severe anaemia. The mean haemoglobin (hb) was lower among children with more advanced HIV disease (p Conclusion Anaemia is highly prevalent among HIV-infected children in a rural Ugandan clinic and is associated with poorer virological suppression. However, the anaemia did not impact clinical and immunological response to ART among these children.

The increase in cell phone use has manifested a growing interest in using this technology for health promotion. The portability and "always on" features of the cell phone, along with increasing capability for the devices to carry and transfer data suggest that they will reach more people than computers and the Internet in coming years. Self-reported quantitative survey data from 1503 secondary school students in Mbarara, Uganda collected in 2008-2009 suggest that 27% currently have cell phones and about half (51%) of all students and 61% of those who owned a cell phone believe that they would access a text messaging-based HIV prevention program if it were available. Other forms of program delivery modality (e.g. Internet, religious organizations, schools) were preferred to text messaging however. We are in need of effective HIV prevention programs that can reach large audiences at low cost and are culturally relevant for the East African context. Researchers are encouraged to consider translation of effective HIV prevention programs for cell phone delivery in Africa.

Introduction: The incidence of colorectal cancer (CRC) is increasing in East Africa. Changes in lifestyle and dietary changes, particularly alcohol consumption, smoking, and consumption of cooked meats with a reduction in fibre in the diet may be responsible. The objective of our study was to determine the risk factors responsible for CRC in Uganda. Methods: We recruited 129 participants with histologically proven colorectal adenocarcinoma and 258 control participants from four specialized hospitals in central Uganda from 2019 to 2021. Controls were block matched for age (± 5 years) and sex of the case participants. The risk factor variables included; area of residence, tribe, body mass index (BMI), smoking, alcohol consumption and family history of gastrointestinal cancer. We used conditional or ordinal logistic regression to obtain crude and adjusted odds ratios for risk factors associated with CRC. Results: In bivariate analysis, case participants were more likely to be associated with urban residence (cOR:62.11; p< 0.001); family history of GI cancer (cOR: 14.34; p=0.001); past smokers (cOR: 2.10; p=0.080); past alcohol drinkers (cOR: 2.35; p=0.012); current alcohol drinkers (cOR: 3.55; p< 0.001); high BMI 25– 29.9 kg/m2 (cOR: 2.49; p< 0.001); and high BMI ≥ 30kg/m2 (cOR: 2.37; p=0.012). In the multivariate analysis, urban residence (aOR: 82.79; p< 0.001), family history of GI cancer (aOR: 61.09; p< 0.001) and past smoking (aOR: 4.73; p=0.036) were independently associated with a higher risk of developing CRC. Conclusion: A family history of gastrointestinal cancer was a risk factor for CRC. While population-based CRC screening may not be feasible in low income-countries, targeted CRC screening for first-degree relatives with CRC should be considered in East Africa. Molecular genetic studies need to be carried out to determine the role of hereditary factors in our population. Prevention strategies should be adopted to avoid smoking in our population which was associated with an increased risk of CRC. [ABSTRACT FROM AUTHOR]

Background The Internet is fast gaining recognition as a powerful, low-cost method to deliver health intervention and prevention programs to large numbers of young people across diverse geographic regions. The [...]

Background: In Uganda, similar to other countries in East Africa, the incidence of colorectal cancer (CRC) has been steadily increasing. This increase in incidence is accompanied by a poor prognosis. There is limited knowledge on factors responsible for the poor outcome of patients with CRC in Uganda. Cancer survival analysis is one way of determining some of these prognostic factors. The aim of this study was to determine prognostic factors associated with CRC survival in Ugandan patients. Methods: This was a retroprospective cohort study involving patients with linked data in the Kampala cancer registry and medical records from hospitals in Uganda. Participants with a diagnosis of colorectal adenocarcinoma between 1st January 2008 and 31st December 2018 were included. Variables included patients' demographic data, grade, stage and location of CRC, data on whether a patient was operated on, type of operation, treatment modalities and date of diagnosis. Our outcome variable was time to death after diagnosis. We computed and compared survival using the Log rank test and used Cox proportional hazards regression to determine factors associated with survival. Results: A total of 247 patients were included in the study with a mean (SD) age of 53.3 (15.7) years and a female: male ratio of 1.14:1. The proportions of patients surviving at 1, 2 and 3 years were 65.2% (95% CI: 58.8– 70.9), 42.0% (95% CI:35.6– 48.3) and 33.3% (95% CI:27.3– 39.4) respectively. In multivariate analysis, factors associated with increased mortality included clinical stage II (aHR = 2.44, 95% CI: 1.10– 5.41, p=0.028), stage III (aHR=2.65, 95% CI: 1.31– 5.39, p=0.007) and stage IV (aHR=5.47, 95% CI: 2.40– 12.48, p< 0.001). Curative surgery alone (aHR=0.63, 95% CI: 0.39– 1.01, p=0.057) and curative surgery with chemotherapy (aHR=0.53, 95% CI: 0.32– 0.88, p=0.015) were associated with a better survival. Conclusion: The survival rate among CRC patients in Uganda is low. Advanced stage CRC accelerates mortality, while surgery alone or in combination with chemotherapy improves survival. Implementation of national screening programmes for early diagnosis of CRC and increasing surgery and oncology infrastructure is recommended to improve the CRC survival rate in the Ugandan population. [ABSTRACT FROM AUTHOR]

Background: Cryptococcal meningitis (CCM) remains one of the leading causes of mortality among HIV infected patients. Due to factors such as the severity of CCM pathology, the quality of life (QOL) of patients post-treatment is likely to be poor. Few studies have reported on QOL of CCM patients post treatment completion. We used data collected among patients in the CryptoDex trial (ISRCTN59144167) to determine QOL and associated factors at week 10 and six months from treatment initiation. Methodology: CryptoDex was a double-blind placebo-controlled trial of adjunctive dexamethasone in HIV infected adults with CCM, conducted between 2013 and 2015 in six countries in Asia and Africa. QOL was determined using the descriptive and Visual Analog Scales (VAS) of the EuroQol Five-Dimension-Three-Level (EQ-5D-3L) tool. We derived index scores, and described these and the VAS scores at 10 weeks and 6 months; and used linear regression to determine the relationship between various characteristics and VAS scores at both time points. VAS scores were interpreted as very good (81–100), good (51–80), normal (31–50) and bad/very bad (0–30). Results: Of 451 patients enrolled in the trial, 238 had QOL evaluations at week 10. At baseline, their mean age (SD) was 35.2(8.5) years. The mean index scores (SD) were 0.785(0.2) and 0.619(0.4) among African and Asian patients respectively at week 10, and 0.879(0.2) and 0.731(0.4) among African and Asian patients respectively at month six. The overall mean VAS score (SD) at 10 weeks was 57.2 (29.7), increasing significantly to 72(27.4) at month six (p<0.001). At week 10, higher VAS score was associated with greater weight (p = 0.007) and being African (p<0.001), while lower VAS score was associated with positive yeast culture at day 14 (p = 0.026). At month six, higher VAS score remained associated with African origin (p = 0.006) while lower VAS score was associated with positive yeast culture (p = 0.006). Lower VAS scores were associated with higher number of inpatient days at 10 weeks and 6 months (p = 0.003 and 0.002 respectively). Conclusion: QOL was good among patients that had completed therapy for CCM, but below perfect. Strategies to improve QOL among CCM survivors are required. Author summary: In spite of the remarkable reduction in Cryptococcal meningitis (CCM) related morbidity and mortality with increased use of antiretroviral therapy, incidence remains unacceptably high especially in sub-Saharan Africa and Asia where more than 90% of the cases and deaths occur. Due to factors such as the severity of CCM pathology, the quality of life (QOL) of patients post-treatment is also likely to be poor. Few studies have reported on QOL of CCM patients post treatment completion. We used data collected among patients in the CryptoDex trial (ISRCTN59144167) to determine self-perceived QOL and associated factors among 238 survivors at week 10 and 203 survivors at six months from treatment initiation. We determined QOL using the descriptive and Visual Analog Scales (VAS) of the EuroQol Five-Dimension-Three-Level (EQ-5D-3L) tool. We found that while self-perceived QOL was only relatively good among this cohort of patients who had survived through treatment for CCM, it continued to improve over the 6 months following diagnosis. Low weight at diagnosis, prolonged hospital admission, positive yeast culture at day 14/treatment completion, and being Asian were associated with lower QOL. QOL is an important outcome that should be considered among HIV infected patients treated for serious infections such as CCM. [ABSTRACT FROM AUTHOR]

Globally, early initiation of antiretroviral therapy for HIV led to a reduction in the estimated mortality from cryptococcal meningitis (CCM) from 624,700 in 2009 to 181,100 in 2014. However, CCM remains one of the leading causes of mortality among HIV infected patients especially in sub-Saharan Africa where 75% of the deaths occur. Most of the studies evaluating mortality have reported short-term mortality (at or before 10 weeks of therapy). We determined mortality and associated factors among patients treated for CCM in the CryptoDex trial (ISRCTN59144167) in Uganda, and the effect of dexamethasone adjunctive therapy on mortality at two years. We conducted a retrospective cohort study between May 2017 and July 2017 to determine the long term survival (up to 2 years post-randomization) of all patients who had been enrolled into the CryptoDex trial in Uganda. The CryptoDex trial recruited between April 2013 and February 2015. We estimated mortality rates and determined factors affecting mortality at two years using Cox regression. The study followed up 211 participants, 127 (60.2%) of whom were male. Sixteen participants (7.58%) were diagnosed with HIV at the same admission when CCM was diagnosed. By two years following randomization 127 (60%) participants had died, a mortality rate of 67 deaths per 100 person-years. Mortality was associated with Glasgow coma score (GCS) below 15 (adjusted Hazard ratio (aHR) 1.77, 95% CI: 1.02–2.44), p = 0.040; weight (aHR 0.97, per 1 Kg increase; 95% CI: 0.94–0.99), p = 0.003; and presence of convulsions (aHR 2.31, 95% CI: 1.32–4.04), p = 0.004, while dexamethasone use and fungal burden had no effect. Long-term mortality in CCM patients remains high even among patients receiving recommended therapy. Strategies to improve long-term survival in CCM patients are urgently needed, especially targeting those with reduced GCS, low weight, and convulsions. Author summary: With early initiation of ART among HIV infected patients, mortality from CCM has significantly gone down. CCM however remains the second highest cause of mortality in HIV, the highest burden being in sub-Saharan Africa where 75% of all deaths occur. Most of the studies evaluating mortality have reported short-term mortality. We determined mortality and associated factors among patients treated for CCM using recommended therapy in the CryptoDex trial (ISRCTN59144167) in Uganda, and the effect of dexamethasone adjunctive therapy on mortality at two years. This was done by looking back at all 211 patients who had previously been enrolled into a trial of treatment for CCM (the CryptoDex trial, which recruited patients between April 2013 and February 2015) and determining their survival up to 2 years after they entered the study. This retrospective cohort study was done between May 2017 and July 2017. 127 (60%) of the patients had died by two years. Those with Glasgow coma score (GCS) below 15, those with lower weight, and those that had convulsions were more likely to die, while dexamethasone use and fungal burden did not affect mortality. Long-term mortality in CCM patients remains high even among patients receiving recommended therapy. Strategies to improve long-term survival in CCM patients are urgently needed, especially targeting those with reduced GCS, low weight, and convulsions. [ABSTRACT FROM AUTHOR]

Hiding in plain sight: Hydrocephalus is a serious brain disorder in children and the most common indication for pediatric neurosurgery. Worldwide, the most frequent cause of hydrocephalus is previous infection such as neonatal sepsis. Such postinfectious hydrocephalus (PIH) occurs principally in low- and middle-income countries, and the pathogens responsible remain uncharacterized. Paulson et al. used pan-microbial analysis of CSF samples from infants with PIH in Uganda to identify the bacteria, viruses, fungi, or parasites potentially contributing to PIH. They found a new strain of the bacterium Paenibacillus as well as frequent coinfection with cytomegalovirus as contributors to PIH in this infant cohort. Postinfectious hydrocephalus (PIH), which often follows neonatal sepsis, is the most common cause of pediatric hydrocephalus worldwide, yet the microbial pathogens underlying this disease remain to be elucidated. Characterization of the microbial agents causing PIH would enable a shift from surgical palliation of cerebrospinal fluid (CSF) accumulation to prevention of the disease. Here, we examined blood and CSF samples collected from 100 consecutive infant cases of PIH and control cases comprising infants with non-postinfectious hydrocephalus in Uganda. Genomic sequencing of samples was undertaken to test for bacterial, fungal, and parasitic DNA; DNA and RNA sequencing was used to identify viruses; and bacterial culture recovery was used to identify potential causative organisms. We found that infection with the bacterium Paenibacillus, together with frequent cytomegalovirus (CMV) coinfection, was associated with PIH in our infant cohort. Assembly of the genome of a facultative anaerobic bacterial isolate recovered from cultures of CSF samples from PIH cases identified a strain of Paenibacillus thiaminolyticus. This strain, designated Mbale, was lethal when injected into mice in contrast to the benign reference Paenibacillus strain. These findings show that an unbiased pan-microbial approach enabled characterization of Paenibacillus in CSF samples from PIH cases, and point toward a pathway of more optimal treatment and prevention for PIH and other proximate neonatal infections. [ABSTRACT FROM AUTHOR]

Background: Retaining patients starting antiretroviral therapy (ART) and ensuring good adherence remain cornerstone of long-term viral suppression. In this era of test and treat (T&T) policy, ensuring that patients starting ART remain connected to HIV clinics is key to achieve the UNAIDS 90-90-90 targets. Currently, limited studies have evaluated the effect of early ART initiation on loss to follow up in a routine health care delivery setting. We studied the cumulative incidence, incidence rate of loss to follow up (LTFU), and factors associated with LTFU in a primary healthcare clinic that has practiced T&T since 2012. Methods: We retrospectively analyzed extracted routine program data on patients who started ART from January 2012 to 4th July 2016. We defined LTFU as failure of a patient to return to the HIV clinic for at least 90 days from the date of their last appointment. We calculated cumulative incidence, incidence rate and fitted a multivariable Cox proportion hazards regression model to determine factors associated with LTFU. Results: Of the 7,553 patients included in our sample, 3,231 (42.8%) started ART within seven days following HIV diagnosis. There were 1,180 cases of LTFU observed over 15,807.7 person years at risk. The overall incidence rate (IR) of LTFU was 7.5 (95% CI, 7.1–7.9) per 100 person years of observation (pyo). Cumulative incidence of LTFU increased with duration of follow up from 8.9% (95% CI, 8.2–9.6%) at 6 months to 20.2% (95% CI, 19.0–21.4%) at 48 months. Predictors of elevated risk of LTFU were: starting ART within 7 days following HIV diagnosis ((aHR) = 1.69, 95% CI, 1.50–1.91), lack of a telephone set (aHR = 1.52, 95% CI, 1.35–1.71), CD4 cell count of 200–350μ/ml (aHR = 1.21, 95% CI, 1.01–1.45) and baseline WHO clinical stage 3 or 4 (aHR = 1.35, 95% CI, 1.10–1.65). Factors associated with a reduced risk of LTFU were: baseline age ≥25 years (aHR ranging from 0.62, 95% CI, 0.47–0.81 for age group 25–29 years to 0.24, 95% CI, 0.13–0.44 for age group ≥50 years), at least primary education level (aHR ranging from aHR = 0.77, 95% CI, 0.62–0.94 for primary education level to 0.50, 95% CI, 0.34–0.75 for post-secondary education level), and having a BMI ≥ 30 (aHR = 0.28, 95% CI, 0.15–0.51). Conclusion: The risk of loss to follow up increased with time and was higher among patients who started ART within seven days following HIV diagnosis, higher among patients without a telephone set, lower among patients aged ≥ 25 years, lower among patients with at least primary education and lower among patients with BMI of ≥ 30. In this era of T&T, it will be important for HIV programs to initiate and continue enhanced therapeutic education programs that target high risk groups, as well as leveraging on mHealth to improve patients' retention on ART throughout the cascade of care. [ABSTRACT FROM AUTHOR]

Background: Cryptococcal meningitis (CCM) remains a leading cause of mortality amongst HIV infected patients in sub-Saharan Africa. When patients receive recommended therapy, mortality at 10 weeks has been reported to vary between 20 to 36%. However, mortality rate and factors affecting mortality after completing recommended therapy are not well known. We investigated mortality rate, and factors affecting mortality at 2 years among CCM patients following completion of recommended CCM therapy in Uganda. Methods: A retrospective cohort study was conducted among HIV infected patients that had completed 10 weeks of recommended therapy for CCM (2 weeks of intravenous amphotericin B 1mg/kg and 10 weeks of oral Fluconazole 800mg daily) in the CryptoDex trial (ISRCTN59144167) between 2013 and 2015. Survival analysis applying Cox regression was used to determine the mortality rate and factors affecting mortality at 2 years. Results: This study followed up 112 participants for 2 years. Mean age (±SD) was 34.9 ± 8, 48 (57.1%) were female and 80 (74.8%) had been on ART for less than 1 year. At 2 years, overall mortality was 30.9% (20 deaths per 100 person-years). Majority of deaths (61.8%) occurred during the first 6 months. In multivariable analysis, mortality was associated with ever being re-admitted since discharge after hospital-based management of CCM (aHR = 13.33, 95% CI: 5.92–30.03), p<0.001; and self-perceived quality of life, with quality of life 50–75% having reduced risk compared to <50% (aHR = 0.21, 95% CI: 0.09–0.5), p<0.001, as well as >75% compared to <50% (HR = 0.29, 95% CI: 0.11–0.81), p = 0.018. Conclusion: There remains a considerable risk of mortality in the first two years after completion of standard therapy for CCM in resource-limited settings with risk highest during the first 6 months. Maintenance of patient follow up during this period may reduce mortality. [ABSTRACT FROM AUTHOR]

Background: East and South Africa contributes 59% of all pediatric HIV infections globally. In Uganda, HIV prevalence among HIV exposed infants was estimated at 5.3% in 2014. Understanding the remaining bottlenecks to elimination of mother-to-child transmission (eMTCT) is critical to accelerating efforts towards eMTCT. This study determined factors associated with HIV positive sero-status among exposed infants attending mother-baby care clinics in rural Kasese so as to inform enhancement of interventions to further reduce MTCT.Methods: This was a cross-sectional mixed methods study. Quantitative data was derived from routine service data from the mother's HIV care card and exposed infant clinical chart. Key informant interviews were conducted with health workers and in-depth interviews with HIV infected mothers. Quantitative data was analyzed using Stata version 12. Logistic regression was used to determine factors associated with HIV sero-status. Latent content analysis was used to analyse qualitative data.Results: Overall, 32 of the 493 exposed infants (6.5%) were HIV infected. Infants who did not receive ART prophylaxis at birth (AOR = 4.9, 95% CI: 1.901-13.051, p=0.001) and those delivered outside of a health facility (AOR = 5.1, 95% CI: 1.038 - 24.742, p = 0.045) were five times more likely to be HIV infected than those who received prophylaxis and those delivered in health facilities, respectively. Based on the qualitative findings, health system factors affecting eMTCT were long waiting time, understaffing, weak community follow up system, stock outs of Neverapine syrup and lack of HIV testing kits.Conclusion: Increasing facility based deliveries and addressing underlying health system challenges related to staffing and availability of the required commodities may further accelerate eMTCT. [ABSTRACT FROM AUTHOR]

Background: Pediatric hospital mortality from infectious diseases in resource constrained countries remains unacceptably high. Improved methods of risk-stratification can assist in referral decision making and resource allocation. The purpose of this study was to create prediction models for in-hospital mortality among children admitted with suspected infectious diseases. Methods: This two-site prospective observational study enrolled children between 6 months and 5 years admitted with a proven or suspected infection. Baseline clinical and laboratory variables were collected on enrolled children. The primary outcome was death during admission. Stepwise logistic regression minimizing Akaike’s information criterion was used to identify the most promising multivariate models. The final model was chosen based on parsimony. Results: 1307 children were enrolled consecutively, and 65 (5%) of whom died during their admission. Malaria, pneumonia and gastroenteritis were diagnosed in 50%, 31% and 8% of children, respectively. The primary model included an abnormal Blantyre coma scale, HIV and weight-for-age z-score. This model had an area under the curve (AUC) of 0.85 (95% CI, 0.80–0.89) with a sensitivity and specificity of 83% and 76%, respectively. The positive and negative predictive values were 15% and 99%, respectively. Two alternate models with similar performance characteristics were developed withholding HIV and weight-for-age z-score, for use when these variables are not available. Conclusions: Risk stratification of children admitted with infectious diseases can be calculated based on several easily measured variables. Risk stratification at admission can be used for allocation of scarce human and physical resources and to guide referral among children admitted to lower level health facilities. [ABSTRACT FROM AUTHOR]

Highly active antiretroviral therapy has enabled HIV-infected children to survive into adolescence and adulthood, creating need for their own HIV diagnosis disclosure. Disclosure has numerous social and medical benefits for the child and family; however, disclosure rates tend to be low, especially in developing countries, and further understanding of the barriers is needed. This study describes the patterns and correlates of disclosure among HIV-infected children in southwestern Uganda. A cross-sectional study was conducted in a referral hospital pediatric HIV clinic between February and April 2012. Interviews were administered to caregivers of HIV-infected children aged 5–17 years. Data collected included socio-demographic characteristics of the child and caregiver, reported disclosure status, and caregivers' reasons for full disclosure or non-full disclosure of HIV status to their children. Bivariate and multivariate analysis was done to establish the socio-demographic correlates of disclosure. Caregivers provided data for 307 children; the median age was eight years (interquartile range [IQR] 7–11) and 52% were males. Ninety-five (31%) children had received full disclosure (48% of whom were >12 years), 22 children (7%) had received partial disclosure, 39 (13%) misinformation, and 151 (49%) no disclosure. Full disclosure was significantly more prevalent among the 9–11 and 12- to 17-year-olds compared to 5- to 8-year-olds (p-value< 0.001). The most frequently stated reason for disclosure was the hope that disclosure would improve medication adherence; the most frequently stated reason for nondisclosure was the belief that the child was too young to understand his/her illness. There was an inverse relationship between age and full disclosure and partial disclosure was rare across all age groups, suggesting a pattern of rapid, late disclosure. Disclosure programs should emphasize the importance of gradual disclosure, starting at younger ages, to maximize the benefits to the child and caregiver. [ABSTRACT FROM PUBLISHER]

Current tools for measuring medication adherence have significant limitations, especially among pediatric populations. We conducted a prospective observational study to assess the use of antiretroviral (ARV) drug levels in hair for evaluating antiretroviral therapy (ART) adherence among HIV-infected children in rural Uganda. Three-day caregiver recall, 30-day visual analog scale (VAS), Medication Event Monitoring System (MEMS), and unannounced pill counts and liquid formulation weights (UPC) were collected monthly over a one-year period. Hair samples were collected quarterly and analyzed for nevirapine (NVP) levels, and plasma HIV RNA levels were collected every six months. Among children with at least one hair sample collected, we used univariable random intercept linear regression models to compare log transformed NVP concentrations with each adherence measure, and the child's age, sex, and CD4 count percentage (CD4%). One hundred and twenty-one children aged 2–10 years were enrolled in the study; 74 (61%) provided at least one hair sample, and the mean number of hair samples collected per child was 1.9 (standard deviation [SD] 1.0). Three-day caregiver recall, VAS, and MEMS were found to be positively associated with increasing NVP concentration in hair, although associations were not statistically significant. UPC was found to have a nonsignificant negative association with increasing hair NVP concentration. In conclusion, NVP drug concentrations in hair were found to have nonsignificant, although generally positive, associations with other adherence measures in a cohort of HIV-infected children in Uganda. Hair collection in this population proved challenging, suggesting the need for community education and buy-in with the introduction of novel methodologies. [ABSTRACT FROM PUBLISHER]

Objective: Anaemia affects the majority of children in sub-Saharan Africa (SSA). Previous studies of risk factors for anaemia have been limited by sample size, geography and the association of many risk factors with poverty. In order to measure the relative impact of individual, maternal and household risk factors for anaemia in young children, we analysed data from all SSA countries that performed haemoglobin (Hb) testing in the Demographic and Health Surveys. Design and setting This cross-sectional study pooled household-level data from the most recent Demographic and Health Surveys conducted in 27 SSA between 2008 and 2014. Participants: 96 804 children age 6–59 months. Results: The prevalence of childhood anaemia (defined as Hb <11 g/dL) across the region was 59.9%, ranging from 23.7% in Rwanda to 87.9% in Burkina Faso. In multivariable regression models, older age, female sex, greater wealth, fewer household members, greater height-for-age, older maternal age, higher maternal body mass index, current maternal pregnancy and higher maternal Hb, and absence of recent fever were associated with higher Hb in tested children. Demographic, socioeconomic factors, family structure, water/sanitation, growth, maternal health and recent illnesses were significantly associated with the presence of childhood anaemia. These risk factor groups explain a significant fraction of anaemia (ranging from 1.0% to 16.7%) at the population level. Conclusions: The findings from our analysis of risk factors for anaemia in SSA underscore the importance of family and socioeconomic context in childhood anaemia. These data highlight the need for integrated programmes that address the multifactorial nature of childhood anaemia.

Background: Disclosure of the diagnosis of HIV to HIV-infected children is challenging for caregivers. Despite current recommendations, data suggest that levels of disclosure of HIV status to HIV-infected children receiving care in resource-limited settings are very low. Few studies describe the disclosure process for children in these settings, particularly the motivators, antecedent goals, and immediate outcomes of disclosure to HIV-infected children. This study examined caregivers' perception of the disclosure concept prior to disclosure, their motivation towards or away from disclosure, and their short- and long-term intentions for disclosure to their HIV-infected children. Methods: In-depth interviews were conducted with primary caregivers of 40 HIV-infected children (ages 5–15 years) who were receiving HIV care but did not know their HIV status. Results: Caregivers of HIV-infected children mainly perceived disclosure as a single event rather than a process of gradual delivery of information about the child's illness. They viewed disclosure as potentially beneficial both to children and themselves, as well as an opportunity to explain the parents' role in the transmission of HIV to the children. Caregivers desired to personally conduct the disclosure; however, most reported being over-whelmed with fear of negative outcomes and revealed a lack of self-efficacy towards managing the disclosure process. Consequently, most cope by deception to avoid or delay disclosure until they perceive their own readiness to disclose. Conclusions: Interventions for HIV disclosure should consider that caregivers may desire to be directly responsible for disclosure to children under their care. They, however, need to be empowered with practical skills to recognize opportunities to initiate the disclosure process early, as well as supported to manage it in a phased, developmentally appropriate manner. The potential role for peer counselors in the disclosure process deserves further study. [ABSTRACT FROM AUTHOR]

Neonatal sepsis in the developing world is incompletely characterized. We seek to characterize the microbial spectrum involved in sepsis and determine the role of maternal transmission by comparing organisms that can be cultured from septic newborn infants and their mothers. From 80 consecutive mother-infant pairs meeting clinical criteria for neonatal sepsis, we collected infant blood and spinal fluid, and maternal blood and vaginal specimens. Identifiable bacteria were recovered from the blood in 32.5% of infants, and from 2.5% of cerebrospinal fluid cultures, for a total of 35% recoverable putative causative agents. Bacteria recovered from vaginal specimens were not concordant with those recovered from infants. Similarly there was no concordance of bacteria recovered from blood and cerebrospinal fluid. We conclude that relying on traditional bacterial culture techniques does not adequately delineate the role of maternal versus environmental sources of neonatal sepsis in this setting. More sensitive molecular approaches will be needed to properly characterize the maternal and environmental microbial community involved in neonatal sepsis in such developing countries. [ABSTRACT FROM AUTHOR]

Context: Cost-effective, scalable programs are urgently needed in countries deeply affected by HIV. Methods: This parallel-group RCT was conducted in four secondary schools in Mbarara, Uganda. Participants were 12 years and older, reported past-year computer or Internet use, and provided informed caregiver permission and youth assent. The intervention, CyberSenga, was a five-hour online healthy sexuality program. Half of the intervention group was further randomized to receive a booster at four-months post-intervention. The control arm received ‘treatment as usual’ (i.e., school-delivered sexuality programming). The main outcome measures were: 1) condom use and 2) abstinence in the past three months at six-months' post-intervention. Secondary outcomes were: 1) condom use and 2) abstinence at three-month's post-intervention; and 6-month outcomes by booster exposure. Analyses were intention to treat. Results: All 416 eligible youth were invited to participate, 88% (n = 366) of whom enrolled. Participants were randomized to the intervention (n = 183) or control (n = 183) arm; 91 intervention participants were further randomized to the booster. No statistically significant results were noted among the main outcomes. Among the secondary outcomes: At three-month follow-up, trends suggested that intervention participants (81%) were more likely to be abstinent than control participants (74%; p = 0.08), and this was particularly true among youth who were abstinent at baseline (88% vs. 77%; p = 0.02). At six-month follow-up, those in the booster group (80%) reported higher rates of abstinence than youth in the intervention, no booster (57%) and control (55%) groups (p = 0.15); they also reported lower rates of unprotected sex (5%) compared to youth in the intervention, no booster (24%) and control (21%) groups (p = 0.21) among youth sexually active at baseline. Conclusions: The CyberSenga program may affect HIV preventive behavior among abstinent youth in the short term and, with the booster, may also promote HIV preventive behavior among sexually active youth in the longer term. Trial Registration: NCT00906178. [ABSTRACT FROM AUTHOR]

Coercion is consistently reported as a risk factor for HIV in sub-Saharan Africa (SSA). Because of the gendered nature of previous research, however, little is known about male victims or female perpetrators. To address this gap, we report survey data from 354 sexually experienced secondary school students in Mbarara, Uganda. Findings suggest that females are more likely to report involvement in coercive sex compared to males (66% vs. 56%, respectively). Of those involved, females are most likely to report being a victim-only (40%) and males, perpetrator-victims (32%). Although involvement in violent and coercive sex is gendered, 47% of males report victim experiences and 25% of females report perpetration behavior. Furthermore, about one in ten female and male perpetrators reported using physical force or threats to compel sex. When all potentially influential factors were considered simultaneously, several characteristics seem to differentiate youth by their coercive sex (in) experience. For example, victims are more likely to have lower levels of social support from their families and feel that they have an above average or very strong chance of getting HIV compared to otherwise similar youth with no experience with coercive sex. Perpetrators are more likely to have had an HIV test but use condoms less than half the time or never compared to their otherwise similar, yet uninvolved peers. They also are significantly more likely to report dating violence perpetration. Perpetrator-victims share some similarities with other involved youth, as well as some differences. Findings underscore both the importance of asking all youth, irrespective of biological sex, perpetrator and victimization questions; and also the need for more work to be done to help youth plan for a healthy and wanted first sexual experience. [ABSTRACT FROM PUBLISHER]

Background: Adherence to HIV antiretroviral therapy (ART) among children in developing settings is poorly understood. Methodology/Principal Findings: To understand the level, distribution, and correlates of ART adherence behavior, we prospectively determined monthly ART adherence through multiple measures and six-monthly HIV RNA levels among 121 Ugandan children aged 2-10 years for one year. Median adherence levels were 100% by three-day recall, 97.4% by 30-day visual analog scale, 97.3% by unannounced pill count/liquid formulation weights, and 96.3% by medication event monitors (MEMS). Interruptions in MEMS adherence of ≥48 hours were seen in 57.0% of children; 36.3% had detectable HIV RNA at one year. Only MEMS correlated significantly with HIV RNA levels (r =-0.25, p = 0.04). Multivariable regression found the following to be associated with <90% MEMS adherence: hospitalization of child (adjusted odds ratio [AOR] 3.0, 95% confidence interval [CI] 1.6-5.5; p = 0.001), liquid formulation use (AOR 1.4, 95%CI 1.0-2.0; p = 0.04), and caregiver's alcohol use (AOR 3.1, 95%CI 1.8-5.2; p<0.0001). Child's use of co-trimoxazole (AOR 0.5, 95%CI 0.4-0.9; p = 0.009), caregiver's use of ART (AOR 0.6, 95%CI 0.4-0.9; p = 0.03), possible caregiver depression (AOR 0.6, 95%CI 0.4-0.8; p = 0.001), and caregiver feeling ashamed of child's HIV status (AOR 0.5, 95%CI 0.3-0.6; p<0.0001) were protective against <90% MEMS adherence. Change in drug manufacturer (AOR 4.1, 95%CI 1.5-11.5; p = 0.009) and caregiver's alcohol use (AOR 5.5, 95%CI 2.8-10.7; p<0.0001) were associated with ≥48-hour interruptions by MEMS, while second-line ART (AOR 0.3, 95%CI 0.1-0.99; p = 0.049) and increasing assets (AOR 0.7, 95%CI 0.6-0.9; p = 0.0007) were protective against these interruptions. Conclusions/Significance: Adherence success depends on a well-established medication taking routine, including caregiver support and adequate education on medication changes. Caregiver-reported depression and shame may reflect fear of poor outcomes, functioning as motivation for the child to adhere. Further research is needed to better understand and build on these key influential factors for adherence intervention development. [ABSTRACT FROM AUTHOR]

Background: HIV and anaemia are major health challenges in Africa. Anaemia in HIV-infected individuals is associated with more rapid disease progression and a poorer prognosis if not addressed appropriately. This study aimed at determining the severity and types of anaemia among HIV infected children and its effect on short term response to antiretroviral therapy (ART). Methods: At baseline, clinical and haematological parameters of 257 HIV-infected ART-naïve children aged 3 months to18 years were assessed to determine the prevalence, severity and types of anaemia. ART eligible patients were started on therapy according to WHO criteria, enrolled (n=88) into an observational cohort and followed up for 6 months. Results: Anaemia was present in 148/257 (57.6%) of children, including (93/148) 62.2% with mild anaemia, 47/148(32.0%) moderate anaemia, and 7/148 (4.8%) with severe anaemia. The mean haemoglobin (hb) was lower among children with more advanced HIV disease (p<0.0001). Microcytic-hypochromic anaemia (44.9%) was the commonest type of anaemia. Anaemia was independently associated with young age (p <0.0001), advanced HIV WHO disease stage(p = 0.034) and low CD4 percentage (p = 0.048). The proportion of children who had attained viral suppression (viral load <400 copies/ml) at 3 months was significantly lower among the anaemic children, 31/58 (53.4%) compared to the non-anaemic children 26/30 (86.7%) (p=0.002). However, the difference in clinical and immunological response between the anaemic and non-anaemic patients did not reach statistical significance. Conclusion: Anaemia is highly prevalent among HIV-infected children in a rural Ugandan clinic and is associated with poorer virological suppression. However, the anaemia did not impact clinical and immunological response to ART among these children. [ABSTRACT FROM AUTHOR]

Neonatal sepsis (NS) is responsible for over 1 million yearly deaths worldwide. In the developing world, NS is often treated without an identified microbial pathogen. Amplicon sequencing of the bacterial 16S rRNA gene can be used to identify organisms that are difficult to detect by routine microbiological methods. However, contaminating bacteria are ubiquitous in both hospital settings and research reagents and must be accounted for to make effective use of these data. In this study, we sequenced the bacterial 16S rRNA gene obtained from blood and cerebrospinal fluid (CSF) of 80 neonates presenting with NS to the Mbarara Regional Hospital in Uganda. Assuming that patterns of background contamination would be independent of pathogenic microorganism DNA, we applied a novel quantitative approach using principal orthogonal decomposition to separate background contamination from potential pathogens in sequencing data. We designed our quantitative approach contrasting blood, CSF, and control specimens and employed a variety of statistical random matrix bootstrap hypotheses to estimate statistical significance. These analyses demonstrate that Leptospira appears present in some infants presenting within 48 h of birth, indicative of infection in utero, and up to 28 days of age, suggesting environmental exposure. This organism cannot be cultured in routine bacteriological settings and is enzootic in the cattle that often live in close proximity to the rural peoples of western Uganda. Our findings demonstrate that statistical approaches to remove background organisms common in 16S sequence data can reveal putative pathogens in small volume biological samples from newborns. This computational analysis thus reveals an important medical finding that has the potential to alter therapy and prevention efforts in a critically ill population.

Objective: To ascertain Ugandan youth access to complete information about sexual health and identify preferences for website design and content for a comprehensive sexuality education program. Methods: Qualitative focus group discussions with 15 youth enrolled in secondary school, levels S1-S3 Results: Youth get inconsistent information about sexual health that is incomplete at best and erroneous at worst. Information sources of information include family members, teachers and peers. Ugandan youth perceive the concept of receiving Internet-based sexuality information as a way to obtain private and credible information. They appreciate content that is tailored to the Ugandan culture, particularly the use of a Senga to deliver information. The Senga is the name given to a paternal Aunt, who traditionally is charged with teaching and advising on matters related to marriage and adulthood. Conclusions: With increasing access to and use of the Internet in Sub-Saharan Africa, coupled with continued high rates of HIV prevalence, using the Internet to deliver comprehensive sexual health information is feasible and acceptable. Ugandan youth like the idea and have particular appreciation for a program that offers information that is culturally relevant for them. [ABSTRACT FROM AUTHOR]

Background: Paenibacillus thiaminolyticus may be an underdiagnosed cause of neonatal sepsis., Methods: We prospectively enrolled a cohort of 800 full-term neonates presenting with a clinical diagnosis of sepsis at 2 Ugandan hospitals. Quantitative polymerase chain reaction specific to P. thiaminolyticus and to the Paenibacillus genus were performed on the blood and cerebrospinal fluid (CSF) of 631 neonates who had both specimen types available. Neonates with Paenibacillus genus or species detected in either specimen type were considered to potentially have paenibacilliosis, (37/631, 6%). We described antenatal, perinatal, and neonatal characteristics, presenting signs, and 12-month developmental outcomes for neonates with paenibacilliosis versus clinical sepsis due to other causes., Results: Median age at presentation was 3 days (interquartile range 1, 7). Fever (92%), irritability (84%), and clinical signs of seizures (51%) were common. Eleven (30%) had an adverse outcome: 5 (14%) neonates died during the first year of life; 5 of 32 (16%) survivors developed postinfectious hydrocephalus (PIH) and 1 (3%) additional survivor had neurodevelopmental impairment without hydrocephalus., Conclusions: Paenibacillus species was identified in 6% of neonates with signs of sepsis who presented to 2 Ugandan referral hospitals; 70% were P. thiaminolyticus. Improved diagnostics for neonatal sepsis are urgently needed. Optimal antibiotic treatment for this infection is unknown but ampicillin and vancomycin will be ineffective in many cases. These results highlight the need to consider local pathogen prevalence and the possibility of unusual pathogens when determining antibiotic choice for neonatal sepsis., Competing Interests: Potential conflicts of interest. J. N. P. received salary support and stock/stock options from Genentech and N-Power Medicine. He has patents planned, issued, or pending with Genentech and N-Power Medicine. He received honoraria for lectures from the International Human Microbiome Consortia. J. E. E. received consulting fees from AbbVie for participation in a data safety and monitoring board unrelated to the current work. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Uvulitis is the inflammation and swelling of the uvula, usually associated with infection of nearby structures. Uvulitis can be treated symptomatically, using medication or in some cases with uvulectomy, the uvula surgical removal or shortening. Traditional uvulectomy by traditional practitioners has been practiced in Africa for ages, associated with adverse outcomes. Although there is no empirical evidence for the association between adverse outcomes and traditional uvulectomy in Uganda, anecdotal findings showed incidents of uvula infections following uvulectomy in central Uganda. While these findings also indicate that traditional uvulectomy is common, the community understanding of uvulitis, the beliefs and practices are not well understood. This qualitative study sought to understand beliefs and practices using interviews with community health workers, traditional uvulectomy clients, and traditional surgeons, and focus group discussions with community members. Transcribed data were analysed in Atlas.ti 9 using thematic analysis steps. The findings show that uvula infection, locally known as "Akamiro" and the associated traditional uvulectomy are common in Luwero and beyond. "Akamiro" was described as larger than the normal, the size of a chicken heart or a big pimple, visible when a child cries, with unknown causes. Symptoms included persistent cough, diarrhoea, vomiting, loss of appetite, inability to swallow and ultimately weight loss, swollen stomach, saliva overflow, fever, breathing and speech difficulty. Diagnosis was confirmed after seeking care from health workers or in consultation with significant others and finally the traditional surgeon; in a hierarchical pattern. Uvulectomy was conducted by traditional surgeons, with surgery lasting a few minutes, in the morning or after sun-set. Tools used were razor blades, reeds, strings, wires, sickle knives and spoons. Payment was flexible; cash or in-kind. Surgeons had immense community trust, including community health workers. Interventions to support persons with uvula infections need to address the health system weaknesses, and health education., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Kibira et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: HAART and chronic HIV associated inflammation has been attributed to abnormal lipids in HIV infected people. Little is known about dyslipidemia among children in Uganda in the era of increasing Highly Active Anti Retroviral Therapy (HAART) use. We determined the prevalence of lipid abnormalities, the correlation of the lipid abnormalities to CD4 count, HIV clinical stage and duration on HAART among HIV infected children., Methods: This was a cross-sectional, descriptive and analytical study of HIV infected children age 1-17 years receiving HAART for more than 6 months in Mbarara Regional Referral Hospital. Consent and assent were obtained as appropriate. Sociodemographic, clinical and immunological data were collected and recorded in a questionnaire. A blood sample was taken for lipid profiling. Dyslipidemia was defined as any low HDL (<=40mg/dl), high LDL (>130mg/dl), high TG (>130mg/dl) and a high total cholesterol (>200mg/dl) or a combination of these in the study population. The proportion of children with dyslipidemia was calculated and logistic regression analysis for associated factors., Results: The mean age was 118 months (SD 49 months) with 49.5% of the children male and 62.1% had severe HIV disease at initiation of HAART. Mean duration of HAART was 55.6 months (SD 31.2 months). The prevalence of dyslipidemia was 74%. Among the children with dyslipidemia, 56.6% exhibited low HDL, 22% had hypertriglyceridemia, 15.6% had high LDL and 11% had hypercholesterolemia. We found significant association between dyslipidemia and WHO clinical stage at initiation of HAART (AOR 2.9 1.05 - 8.45 p =0.040)., Conclusion: There was a high prevalence of dyslipidemia associated with severe HIV disease at initiation of HAART among HIV-infected children on HAART.

With more than half of new infections occurring among youth, HIV/AIDS remains a major contributor to morbidity and mortality in Uganda. Semi-structured interviews were performed with 48 adolescents and 15 adult key informants in a rural Ugandan community to identify influences on adolescent sexual decision-making. Inductive data analytic methods revealed five thematic influences: (1) social pressure, (2) decline of the Senga (a familial figure who traditionally taught female adolescents about how to run a household), (3) cultural barriers to condom use, (4) knowledge of HIV transmission and modes of prevention, and (5) a moral injunction against sex before marriage. Influences were classified as HIV/AIDS risk and protective factors and organized to form an explanatory framework of adolescent sexual risk-taking. Risk factors pull youth toward risky behavior, while protective factors push them away. Predominance of risk over protective influences explains persistent sexual risk-taking by Ugandan youth. HIV prevention programs designed for Ugandan adolescents should take competing factors and sociocultural and economic influences into account.