Dietary risk factors for colorectal cancer in Uganda: a case-control study.

INTRODUCTION: Low-income countries in East Africa have a lower incidence of colorectal cancer (CRC) than high-income countries; however, the incidence has steadily increased in the last few decades. In Uganda, the extent to which genetic and environmental factors, particularly dietary factors, contribute to the aetiology of CRC is unclear. Therefore, the objective of our study was to determine the relationship between dietary factors and CRC in Uganda. METHODS: We conducted a case-control study and recruited 128 cases and 256 controls, matched for age (± 5 years) and sex. Data regarding the frequency of consumption of the dietary factors were obtained from all the participants using an interview-based questionnaire. The potential dietary risk factors and protective factors evaluated included the type and frequency of meat consumed and the type and frequency of high-fibre foods consumed. The frequency was either 4 or more times/week, 2-3 times/week, once/week or never. Conditional logistic regression analyses were used to determine the odds ratios associated with the different risk and protective factors. RESULTS: The median age (IQR) for the case participants was 55.5 (43-67.5) years, and that of the control participants was 54 (42-65) years. The male-to-female ratio was 1:1 for all the participants. Factors significantly associated with CRC cases included:- the consumption of boiled beef 2-3 times/week (aOR:3.24; 95% CI: 1.08-9.69; p < 0.035). Consumption of high-fibre foods, including:- millet for ≥ 4 times/week (aOR: 0.23; 95% CI: 0.09-0.62; p = 0.003)), spinach for ≥ 4 times/week (aOR:0.32; 95% CI: 0.11-0.97; p = 0.043), and potatoes 2-3 times/week (aOR: 0.30; 95% CI: 0.09-0.97; p = 0.044), were protective against CRC. Boiled cassava showed a tendency to reduce the likelihood of CRC when consumed ≥ 4 times/week (aOR:0.38; 95% CI: 0.12-1.18) however this did not reach statistical significance (p = 0.093). CONCLUSIONS: The consumption of boiled beef increases the risk of CRC, while the intake of high-fibre foods may reduce the risk of CRC among Ugandans. We recommend nutritional educational programmes to increase public awareness regarding the protective role of a high-fibre diet and to limit the intake of cooked meat in our Ugandan population.

Colorectal adenocarcinoma in Uganda: are right-sided and left-sided colon cancers two distinct disease entities?

INTRODUCTION: In Western countries, right-sided colon cancers (RSCC) present at an older age and advanced stage. Researchers believe that there is a difference between left-sided colon cancer (LSCC) and RSCC. In Uganda, however, it is unknown whether differences exist in the pathological profile between RSCC and LSCC. The aim of this study was to determine the differences in clinicopathological characteristics between RSCC and LSCC in Ugandan patients. METHODOLOGY: A cross-sectional study was conducted in which colorectal adenocarcinoma formalin-fixed paraffin-embedded tissue (FFPE) blocks were obtained from 2008 to 2021. Colorectal specimens were obtained from prospectively recruited patients. In the retrospective study arm, FFPE blocks and data were obtained from the archives of pathology laboratory repositories. Parameters studied included age, sex, location of the tumour, grade, stage, lymphovascular (LVI) status, and histopathological subtype between LSCC and RSCC. RESULTS: Patients with RSCC were not older than those with LSCC (mean age, 56.3 years vs 53.5 years; p = 0.170). There was no difference in the stage between RSCC and LSCC. Poorly differentiated tumours were more commonly found in RSCC than in LSCC (18.7% vs 10.1%; p = 0.038). Moderately and poorly differentiated colonic tumours were more common with RSCC (89.3%) than with LSCC (75.1%) (p = 0.007). Younger patients had more poorly differentiated tumours than older patients (19.6% versus 8.6%; p = 0.002). LVI was more common with RSCC than with LSCC (96.8% vs 85.3%; p = 0.014). Mucinous adenocarcinoma (MAC) was more common with RSCC (15.8%) compared with LSCC (8.5%) (p = 0.056) although statistical significance was borderline. CONCLUSIONS: Clinicopathological features of RSCCs tend to be different from those of LSCCs. RSCCs tend to be associated with MAC, a higher grade and LVI status compared to LSCC. LSCC and RSCC present predominantly with an advanced stage; therefore, national screening programmes for the early detection of CRC are necessary to reduce mortality in our Ugandan population.

Uvula infections and traditional uvulectomy: Beliefs and practices in Luwero district, central Uganda.

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.

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.

Neonatal Paenibacilliosis: Paenibacillus Infection as a Novel Cause of Sepsis in Term Neonates With High Risk of Sequelae in Uganda.

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.

Risk Factors for Colorectal Adenocarcinoma in an Indigenous Population in East 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.

Prognostic Factors for Survival of Colorectal Adenocarcinoma Patients in Uganda.

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.

Cytomegalovirus infections in infants in Uganda: Newborn-mother pairs, neonates with sepsis, and infants with hydrocephalus.

OBJECTIVES: To estimate the prevalence of cytomegalovirus (CMV) infections among newborn-mother pairs, neonates with sepsis, and infants with hydrocephalus in Uganda. DESIGN AND METHODS: Three populations-newborn-mother pairs, neonates with sepsis, and infants (≤3 months) with nonpostinfectious (NPIH) or postinfectious (PIH) hydrocephalus-were evaluated for CMV infection at 3 medical centers in Uganda. Quantitative PCR (qPCR) was used to characterize the prevalence of CMV. RESULTS: The overall CMV prevalence in 2498 samples across all groups was 9%. In newborn-mother pairs, there was a 3% prevalence of cord blood CMV positivity and 33% prevalence of maternal vaginal shedding. In neonates with clinical sepsis, there was a 2% CMV prevalence. Maternal HIV seropositivity (adjusted odds ratio [aOR] 25.20; 95% confidence interval [CI] 4.43-134.26; p = 0.0001), residence in eastern Uganda (aOR 11.06; 95% CI 2.30-76.18; p = 0.003), maternal age <25 years (aOR 4.54; 95% CI 1.40-19.29; p = 0.02), and increasing neonatal age (aOR 1.08 for each day older; 95% CI 1.00-1.16; p = 0.05), were associated risk factors for CMV in neonates with clinical sepsis. We found a 2-fold higher maternal vaginal shedding in eastern (45%) vs western (22%) Uganda during parturition (n = 22/49 vs 11/50, the Fisher exact test; p = 0.02). In infants with PIH, the prevalence in blood was 24% and in infants with NPIH, it was 20%. CMV was present in the cerebrospinal fluid (CSF) of 13% of infants with PIH compared with 0.5% of infants with NPIH (n = 26/205 vs 1/194, p < 0.0001). CONCLUSIONS: Our findings highlight that congenital and postnatal CMV prevalence is substantial in this African setting, and the long-term consequences are uncharacterized.

Quality of life and associated factors among HIV positive patients after completion of treatment for Cryptococcal meningitis.

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.

Determinants of two-year mortality among HIV positive patients with Cryptococcal meningitis initiating standard antifungal treatment with or without adjunctive dexamethasone in Uganda.

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.

Paenibacillus infection with frequent viral coinfection contributes to postinfectious hydrocephalus in Ugandan infants.

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.

Prevalence, associated factors and clinical features of congenital syphilis among newborns in Mbarara hospital, Uganda.

BACKGROUND: While congenital syphilis is a significant public health problem that can cause severe disabilities, little is known about the situation in Uganda. We describe prevalence, associated factors and clinical presentation of congenital syphilis in Mbarara, Uganda. METHODS: A cross sectional study was carried out among mother- newborn dyads from the postnatal ward of Mbarara Regional Referral Hospital (MRRH). After obtaining informed consent, a structured questionnaire was used to capture data on risk factors for congenital syphilis. A finger prick was performed on the mothers for Treponema Pallidum Haemagglutination Assay (TPHA). If TPHA was positive, a venous blood sample was collected from the mother to confirm active infection using Rapid Plasma Reagin (RPR). Venous blood was drawn from a newborn if the mother tested positive by TPHA and RPR. A newborn with RPR titres 4 times higher than the mother was considered to have congenital syphilis. We fit logistic regression models to determine factors associated with congenital syphilis. RESULTS: Between June and September 2015, we enrolled 2500 mothers and 2502 newborns. Prevalence of syphilis was 3.8% (95% CI 3.1-4.6) among newborn infants and 4.1% (95% CI 3.4-5.0) among their mothers. Maternal age <25 years, past history of genital ulcer, a past history of abnormal vaginal discharge, and not receiving treatment of at least one of genital ulcer, genital itching, lower abdominal pain and abnormal vaginal discharge in the current pregnancy were the risk factors associated with congenital syphilis. The most common clinical feature was hepatosplenomegaly. CONCLUSIONS: We found higher-than-expected syphilis sero-prevalence rates in a high risk population of postnatal mothers and their newborns in Uganda. Bridge populations for syphilis may include mothers not tested during pregnancy, who are usually married and not treated. In accordance with our results, the national policy for syphilis control in Uganda should be strengthened to include universal syphilis screening amongst mother-newborn pairs in postnatal clinics with subsequent partner notification.

Determinants of loss to follow-up among HIV positive patients receiving antiretroviral therapy in a test and treat setting: A retrospective cohort study in Masaka, Uganda.

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.

Factors affecting mortality among HIV positive patients two years after completing recommended therapy for Cryptococcal meningitis in Uganda.

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.

Individual, maternal and household risk factors for anaemia among young children in sub-Saharan Africa: a cross-sectional study.

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.

Pneumonia in HIV-exposed and Infected Children and Association With Malnutrition.

We evaluated the association between HIV exposed-uninfected (HEU) status, malnutrition and risk of death in Ugandan children hospitalized with pneumonia. Both HIV exposure and infection were associated with lower anthropometric indices on univariate analysis, and mid-upper arm circumference was significantly associated with overall mortality (odds ratio (OR), 0.96) in a multivariable model. HIV infection (OR 5.0) but not HEU status was associated with overall mortality. Malnutrition may contribute to poor pneumonia outcomes among HIV-infected and HEU children requiring hospitalization.

Factors associated with HIV positive sero-status among exposed infants attending care at health facilities: a cross sectional study in rural Uganda.

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.

Outcome of Children With Presumptive Tuberculosis in Mbarara, Rural Uganda.

BACKGROUND: Mortality among children with presumptive tuberculosis (TB) empiric TB treatment can be high. We describe the predictors of death among children with presumptive TB, and the relation between treatment and mortality. METHODS: A prospective cohort of children with presumptive TB who underwent clinical assessment, chest radiograph, tuberculin skin test and sputum bacterial tests for TB was followed up for 3 months. TB diagnosis was based on mycobacterial, clinical and radiologic findings. Predictors of deaths were determined using cox regression model. RESULTS: Of 360 children included in the analysis, 31.4% were younger than 2 years; 31.6% were HIV infected and 11.3% were severely malnourished. One hundred forty (38.9%) were diagnosed with TB, 18 (13%) of whom were bacteriologically confirmed. At 3 months of follow up, 25 of 360 (6.9%) children had died: 15 of 140 (10.7%) were receiving TB treatment versus 10 of 220 (4.5%) were not receiving treatment (P = 0.025). Severely malnourished children [adjusted hazard ratio (aHR), 9.86; 95% confidence interval (CI): 3.11-31.23] and those with chest radiographs suggestive of TB (aHR, 4.20; 95% CI: 0.93-19.01) were more likely to die. Children receiving empiric TB treatment had an increased risk of death (aHR, 2.37; 95% CI: 1.01-5.55) compared with children without treatment after adjustment for age, sex, HIV status and Bacillus Calmette-Guérin (BCG) vaccination. CONCLUSIONS: The high mortality in children receiving empirically TB treatment highlights the difficulty in diagnosing childhood TB, the increased likelihood of starting treatment in critically ill children and in children with chronic disease, and the possibility of misdiagnosis. It strengthens the need to invest further in early TB detection and diagnosing nonsevere illness.

Dyslipidemia and its Correlates among HIV Infected Children on HAART Attending Mbarara Regional Referral Hospital.

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.

Selecting candidate predictor variables for the modelling of post-discharge mortality from sepsis: a protocol development project.

BACKGROUND: Post-discharge mortality is a frequent but poorly recognized contributor to child mortality in resource limited countries. The identification of children at high risk for post-discharge mortality is a critically important first step in addressing this problem. OBJECTIVES: The objective of this project was to determine the variables most likely to be associated with post-discharge mortality which are to be included in a prediction modelling study. METHODS: A two-round modified Delphi process was completed for the review of a priori selected variables and selection of new variables. Variables were evaluated on relevance according to (1) prediction (2) availability (3) cost and (4) time required for measurement. Participants included experts in a variety of relevant fields. RESULTS: During the first round of the modified Delphi process, 23 experts evaluated 17 variables. Forty further variables were suggested and were reviewed during the second round by 12 experts. During the second round 16 additional variables were evaluated. Thirty unique variables were compiled for use in the prediction modelling study. CONCLUSION: A systematic approach was utilized to generate an optimal list of candidate predictor variables for the incorporation into a study on prediction of pediatric post-discharge mortality in a resource poor setting.