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BACKGROUND The Uganda Sickle Surveillance Study provided evidence for a large sickle burden among HIV-exposed infants in Uganda. To date, however, no large scale screening program has been developed for Central or East Africa. METHODS A 3-year targeted sickle cell screening project in Uganda was designed by the Ministry of Health to (1) determine sickle cell trait and disease prevalence within high-burden districts, (2) document the prevalence among HIV-exposed and nonexposed children, (3) confirm previously suggested HIV comorbidity, and (4) estimate the co-inheritance of known genetic modifiers of sickle cell disease. RESULTS A total of 163 334 dried blood spot samples collected between April 2015 and March 2018 were analyzed, including 112 352 samples within the HIV Early Infant Diagnosis program. A high burden with >1% sickle cell disease was found within targeted East Central and Mid-Northern districts, in both HIV-exposed and nonexposed children. Based on crude birth-rate data, 236 905 sickle cell trait births and 16 695 sickle cell disease births will occur annually in Uganda. Compared to sickle cell disease without HIV, the odds ratio of having sickle cell disease plus HIV was 0.50 (95% confidence interval = 0.40-0.64, P

Exclusive breastfeeding remains critical for child survival, potentially reducing childhood morbidity and mortality. In Uganda, 98% of children are ever breastfed, but exclusive breastfeeding levels remain low. Supporting mothers in breastfeeding exclusively can improve breastfeeding practices. This paper describes experiences of establishing individual peer counselling for exclusive breastfeeding in the Uganda site of the Promoting Infant Health and Nutrition in Sub‐Saharan Africa: Safety and Efficacy of Exclusive Breastfeeding Promotion in the Era of HIV trial, and highlights some implications for scaling‐up. Twelve women were identified by their communities, one from each of 12 clusters. They were trained for 6 days and followed up for 1 year while they counselled mothers. Their knowledge and attitudes towards exclusive breastfeeding were assessed before and immediately after training, and also 10 months into peer counselling. Observations, field notes and records of interactions with peer counsellors were used to record experiences from this intervention. The communities were receptive to peer counselling and women participated willingly. After training and 10 months' follow‐up, their knowledge and attitude to exclusive breastfeeding improved. All were retained in the study, and mothers accepted them in their homes. They checked for mothers several times if they missed them on the first attempt. Husbands and grandmothers played key roles in infant feeding decisions. Involving the communities in selection helped to identify reliable breastfeeding peer counsellors who were acceptable to mothers and were retained in the study. Other key issues to consider for scaling‐up such interventions include training and follow up of peer counsellors, which led to improved knowledge and attitudes towards exclusive breastfeeding (ClinicalTrials.gov no: NCT00397150).

Background: The aim of this survey was to determine the prevalence of and factors associated with Helicobacter pylori (H. pylori) colonization in HIV-infected, highly active antiretroviral therapy-naïve Ugandan children aged 0-12 years. Methods: In a hospital-based survey, 236 HIV-infected children were tested for H. pylori colonization using a faecal antigen test. A standardized interview with socio-demographic information and medical history was used to assess risk factors. A cluster of differentiation 4 (CD4) cell percentage was prevalent in most children. Results: The overall prevalence of H. pylori in the HIV-infected children was 22.5%. Age-specific prevalence was as follows: up to one year, 14.7%; 1-3 years, 30.9%; and 3-12 years, 20.7%. HIV-infected children who were more seriously affected by their disease (low CD4 cell percentage or WHO clinical stage II-IV) were less likely to be colonized with H. pylori. There was a trend for a lower prevalence of H. pylori in children who had taken antibiotics for the preceding two weeks (21.6%) than in those who had not taken antibiotics (35.7%). There was no statistically significant difference in prevalence by gender, housing, congested living, education of the female caretaker, drinking water or toilet facilities. Conclusions: HIV-infected, HAART-naïve Ugandan children had a lower prevalence of H. pylori colonization compared with apparently healthy Ugandan children (44.3%). Children with a low CD4 cell percentage and an advanced clinical stage of HIV had an even lower risk of H. pylori colonization. Treatment with antibiotics due to co-morbidity with infectious diseases is a possible explanation for the relatively low prevalence. publishedVersion

Background The objective of the study was to evaluate the effect of a written invitation letter to the spouses of new antenatal clinic attendees on attendance by couples and on male partner acceptance of HIV testing at subsequent antenatal clinic visits. Methods The trial was conducted with 1060 new attendees from October 2009 to February 2010 in an antenatal clinic at Mbale Regional Referral Hospital, Mbale District, eastern Uganda. The intervention comprised an invitation letter delivered to the spouses of new antenatal attendees, while the control group received an information letter, a leaflet, concerning antenatal care. The primary outcome measure was the proportion of pregnant women who attended antenatal care with their male partners during a follow-up period of four weeks. Eligible pregnant women were randomly assigned to the intervention or non-intervention groups using a randomization sequence, which was computer generated utilizing a random sequence generator (RANDOM ORG) that employed a simple randomization procedure. Respondents, health workers and research assistants were masked to group assignments. Results The trial was completed with 530 women enrolled in each group. Participants were analyzed as originally assigned (intention to treat). For the primary outcome, the percentage of trial participants who attended the antenatal clinic with their partners were 16.2% (86/530) and 14.2% (75/530) in the intervention and non-intervention groups, respectively (OR = 1.2; 95% CI: 0.8, 1.6). For the secondary outcome, most of the 161 male partners attended the antenatal clinic; 82 of 86 (95%) in the intervention group and 68 of 75 (91%) in the non-intervention group were tested for HIV (OR = 2.1; 95% CI: 0.6 to 7.5). Conclusions The effect of the intervention and the control on couple antenatal attendance was similar. In addition, the trial demonstrated that a simple intervention, such as a letter to the spouse, could increase couple antenatal clinic attendance by 10%. Significantly, the majority of male partners who attended the antenatal clinic accepted HIV testing. Therefore, to further evaluate this simple and cost-effective intervention method, adequately powered studies are required to assess its effectiveness in increasing partner participation in antenatal clinics and the programme for prevention of mother to child transmission of HIV. Trial Registration ClinicalTrials.gov Identifier: NCT01144234.

Background Micronutrient deficiencies compromise the survival of HIV-infected children in low-income countries. We assessed the effect of multiple micronutrient supplementation on the mortality of HIV-infected children in Uganda. Methods In a randomized, controlled trial, 847 children aged one to five years and attending HIV clinics in Uganda were stratified by antiretroviral therapy (ART, n = 85 versus no ART, n = 762). The children were randomized to six months of either: twice the recommended dietary allowance of 14 micronutrients as the intervention arm (vitamins A, B1, B2, niacin, B6, B12, C, D and E, folate, zinc, copper, iodine and selenium); or the standard recommended dietary allowance of six multivitamins (vitamins A, D2, B1, B2, C and niacin) as a comparative "standard-of-care" arm. Mortality was analyzed at 12 months of follow up using Kaplan Meier curves and the log rank test. Results Mortality at 12 months was 25 out of 426 (5.9%) children in the intervention arm and 28 out of 421 (6.7%) in the comparative arms: risk ratio 0.9 (95% CI 0.5 - 1.5). Two out of 85 (2.4%) children in the ART stratum died compared with 51 out of 762 (6.7%) in the non-ART stratum. Of those who died in the non-ART stratum, 25 of 383 (6.5%) were in the intervention arm and 26 of 379 (6.9%) in the comparative arm; risk ratio 1.0 (95% CI 0.6 - 1.6). There was no significant difference in survival at 12 months (p = 0.64, log rank test). In addition, there was no significant difference in mean weight-for-height at 12 months; 0.70 ± 1.43 (95% CI 0.52 - 0.88) for the intervention versus 0.59 ± 1.15 (95% CI 0.45 - 0.75) in the comparative arm. The mean CD4 cell count; 1024 ± 592 (95% CI 942 - 1107) versus 1060 ± 553 (95% CI 985 - 1136) was also similar between the two groups. Conclusions Twice the recommended dietary allowance of 14 micronutrients compared with a standard recommended dietary allowance of six multivitamins for six months was well tolerated, but it did not significantly alter mortality, growth or CD4 counts. Future intervention studies should carefully consider: (1) the composition and dosing of the supplements; and (2) the power needed to detect a difference between arms. Trial Registration ClinicalTrials.gov Identifier: NCT00122941

Background The delivery of HIV counselling and testing services for children remains an uphill task for many health workers in HIV-endemic countries, including Uganda. We conducted a descriptive study to explore the challenges of providing HIV counselling and testing services to children in Uganda. Methods A descriptive study was conducted in the districts of Kampala and Kabarole in Uganda. The data were collected using semi-structured individual interviews and focus group discussions with health workers who are involved in the care of HIV-positive children. Key informant interviews were conducted with the administrators of the 10 study healthcare institutions. Quantitative data were summarized using frequency tables, while qualitative data were analyzed using the content thematic approach. Results Counselling children was reported to be a difficult exercise due to some children being unable to express themselves, being dependent on adults for their care, being fearful, and requiring more time to open up during counselling. This was compounded by some caretakers' unwillingness and difficulty to disclose the HIV status of their children. Other issues about the caretakers were: lack of consistency in caretakers; old age; sickness; and poverty. Health workers mentioned the following as some of the challenges they face in the delivery of HIV counselling and testing services for children: lack of counselling skills; failure to cope with the knowledge demand; difficulty to facilitate disclosure; heavy work load; and lack of other support services. Institutions were found to be constrained by limited space and lack of antiretrovirals for children. Conclusions The major challenges in the delivery of paediatric HIV services were related to the knowledge gap in paediatric HIV and the lack of counselling skills, as well as health system-related constraints. There is a need to train health workers in child-counselling skills, especially in the issues of disclosure, sexuality and sexual abuse, as well as in addressing fears related to death and an uncertain future, in order to improve paediatric HIV care. Provision of child-friendly services, guidelines and antiretroviral formulations for children may provide a window of hope to improve HIV counselling and testing services for children.

Background HIV testing rates have exceeded 90% among the pregnant women at Mbale Regional Referral Hospital in Mbale District, eastern Uganda, since the introduction of routine antenatal counselling and testing for HIV in June 2006. However, no documented information was available about opinions of pregnant women in eastern Uganda about this HIV testing approach. We therefore conducted a study to assess attitudes of antenatal attendees towards routine HIV counselling and testing at Mbale Hospital. We also assessed their knowledge about mother to child transmission of HIV and infant feeding options for HIV-infected mothers. Methods The study was a cross-sectional survey of 388 women, who were attending the antenatal clinic for the first time with their current pregnancy at Mbale Regional Referral Hospital from August to October 2009. Data were collected using a pre-tested questionnaire and analysed using descriptive statistics and logistic regression. Permission to conduct the study was obtained from the Makerere University College of Health Sciences, the Uganda National Council of Science and Technology, and Mbale Hospital. Results The majority of the antenatal attendees (98.5%, 382/388) had positive attitudes towards routine HIV counselling and testing, and many of them (more than 60%) had correct knowledge of how mother to child transmission of HIV could occur during pregnancy, labour and through breastfeeding, and ways of preventing it. After adjusting for independent variables, having completed secondary school (odds ratio: 2.5, 95% confidence interval: 1.3-4.9), having three or more pregnancies (OR: 2.5, 95% CI: 1.4-4.5) and belonging to a non-Bagisu ethnic group (OR: 1.7, 95% CI: 1.0-2.7) were associated with more knowledge of exclusive breastfeeding as one of the measures for prevention of mother to child transmission of HIV. Out of 388 antenatal attendees, 386 (99.5%) tested for HIV and 382 (98.5%) received same-day HIV test results. Conclusions Routine offer of antenatal HIV counselling and testing is largely acceptable to the pregnant women in eastern Uganda and has enabled most of them to know their HIV status as part of the prevention of mother to child transmission of HIV package of services. Our findings call for further strengthening and scaling up of this HIV testing approach in many more antenatal clinics countrywide in order to maximize its potential benefits to the population. publishedVersion