Operational analysis of the national sickle cell screening programme in the Republic of Uganda

Background: Sickle cell anaemia is a common global life-threatening haematological disorder. Most affected births occur in sub-Saharan Africa where children usually go undiagnosed and die early in life. Uganda's national sickle cell screening programme was developed in response to a 2014 sickle cell surveillance study that documented a high disease prevalence. Objective: This study describes the temporal and financial aspects of Uganda's 2014­2019 sickle cell screening programme. Methods: National sickle cell screening data from Uganda's Central Public Health Laboratories were used to calculate turn-around times (TATs) from sample collection to delivery, testing, and result reporting for blood samples collected from February 2014 to March 2019. The parameters affecting specific TATs were assessed. The exact programme expenditures were analysed to determine cost per test and per positive sickle cell disease case detected. Results: A total of 278 651 samples were analysed. The median TAT from sample collection to laboratory receipt was 8 days (interquartile range [IQR]: 6­12), receipt to testing was 3 days (IQR: 1­7), and testing to result reporting was 6 days (IQR: 3­12). Altogether, the sample continuum averaged 16 days (IQR: 11­24). Lower level healthcare facilities were associated with longer sample delivery TATs. Calendar months (January and December) and larger sample volumes impacted testing and result reporting TATs. The cost per test was $4.46 (United States dollars [USD]) and $483.74 USD per positive case detected. Conclusion: Uganda's sickle cell screening programme is efficient and cost-effective. Universal newborn screening is the best strategy for detecting sickle cell anaemia in Uganda.

Feasibility and acceptability of a midwife-led health education strategy to reduce exposure to biomass smoke among pregnant women in Uganda, A FRESH AIR project.

Biomass smoke exposure is a threat to child and maternal health in many resource-limited countries and is associated with poor pregnancy outcomes and serious lung diseases in the offspring. We aimed to assess the feasibility, acceptability and impact of a midwife-led education programme on biomass risks and prevention for women attending maternity clinics in Uganda. Education materials were co-developed through an iterative process by midwives and other stakeholders. The materials were serially tested and approved by the Ministry of Health and used by midwives and village health teams (VHTs). The district health team, 12 midwives and 40 VHTs were sensitised on biomass smoke. Two hundred and forty-four women were educated about biomass smoke by midwives; pre- and post-session questionnaires showed major improvements in knowledge of biomass smoke risks. Qualitative interviews with women three months after the sessions showed that they made behavioural changes such as avoiding smoke while cooking, using dry wood, solar power for lighting and improved ventilation. The major barrier to behavioural changes was poverty, but some improvements cost no money. The programme delivered by midwives was feasible and acceptable; implementing this programme has the potential to reduce exposure to smoke with major benefits to mother, foetus, and children throughout their lives.

Determinants of Health Facility Utilization at Birth in South Sudan.

South Sudan has a high maternal mortality ratio estimated at 800 deaths per 100,000 live births. Birth in health facilities with skilled attendants can lower this mortality. In this cross-sectional study, we determined the level and determinants of health facility utilization and skilled birth attendance in Jubek State, South Sudan. Mothers of children aged less than two years were interviewed in their homes. Multivariable regression analysis was performed to determine factors associated with health facility births. Only a quarter of the mothers had given birth at health facilities, 209/810 (25.8%; 95% CI 18.2-35.3) and 207/810 had a skilled birth attendant (defined as either nurse, midwife, clinical officer, or doctor). Factors positively associated with health facility births were four or more antenatal visits (adjusted odds ratio (AOR) 19; 95% CI 6.2, 61), secondary or higher education (AOR 7.9; 95% CI 3, 21), high socio-economic status (AOR 4.5; 95% CI 2.2, 9.4), and being primipara (AOR 2.9; 95% CI 1.5, 5.4). These findings highlight the need for efforts to increase health facility births in South Sudan.

Understanding the context of delays in seeking appropriate care for children with symptoms of severe malaria in Uganda.

INTRODUCTION: A large proportion of children with uncomplicated malaria receive appropriate treatment late, contributing to progression of illness to severe disease. We explored contexts of caregiver delays in seeking appropriate care for children with severe malaria. METHODS: This qualitative study was conducted at the Children's Ward of Jinja Hospital, where children with severe malaria were hospitalized. A total of 22in-depth interviews were conducted with caregivers of children hospitalized with severe malaria. Issues explored were formulated based on the Partners for Applied Social Sciences (PASS) model, focusing on facilitators and barriersto caregivers'promptseeking and accessing ofappropriate care. The data were coded deductively using ATLAS.ti (version 7.5). Codes were then grouped into families based on emerging themes. RESULTS: Caregivers' rating of initial symptoms as mild illness lead to delays in response. Use of home initiated interventions with presumably ineffective herbs or medicines was common, leading to further delay. When care was sought outside the home, drug shops were preferred over public health facilities for reasons of convenience. Drug shops often provided sub-optimal care, and thus contributed to delays in access to appropriate care. Public facilities were often a last resort when illness was perceived to be progressing to severe disease. Further delays occurred at health facilities due to inadequate referral systems. CONCLUSION: Communities living in endemic areas need to be sensitized about the significance of fever, even if mild, as an indicator of malaria. Additionally, amidst ongoing efforts at bringing antimalarial treatment services closer to communities, the value of drug shops as providers ofrationalantimalarialtreatment needs to be reviewed.

Sickle cell screening in Uganda: High burden, human immunodeficiency virus comorbidity, and genetic modifiers.

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 < .0001). Alpha-thalassemia trait and G6PD deficiency were common with sickle cell disease, but with different geospatial distribution. CONCLUSIONS: High sickle cell burden and potential HIV comorbidity are confirmed in Uganda. Genetic modifiers are common and likely influence laboratory and clinical phenotypes. These prospective data document that targeted sickle cell screening is feasible and effective in Uganda, and support development of district-level comprehensive care programs.

Key Decision Makers and Actors in Selected Newborn Care Practices: A Community-Based Survey in Northern Uganda.

Knowledge of key decision makers and actors in newborn care is necessary to ensure that health interventions are targeted at the right people. This was a cross-sectional study carried out in Lira district, Northern Uganda. Multivariable logistic regression was used to determine factors associated with mothers being the key decision maker regarding where to give birth from and when to initiate breastfeeding. Fathers were the key decision makers on the place of birth (54.3%, n = 505) and on whether to seek care for a sick newborn child (47.7%, n = 92). Grandmothers most commonly bathed the baby immediately after birth (55.5%, n = 516), whereas mothers and health workers were common decision makers regarding breastfeeding initiation. Predictors for a mother being the key decision maker on the place of birth included: Mother having a secondary education (AOR 1.9: 95% C.I (1.0-3.6)) and mother being formally employed (AOR 2.0: 95% (1.5-2.9)). Mothers, fathers, grandmothers, health-workers, and traditional birth attendants were the most influential in the selected newborn care practices. Programs that aim to promote newborn care need to involve husbands, grandmothers, and health workers in addition to mothers.

"We shall count it as a part of kyogero": acceptability and considerations for scale up of single dose chlorhexidine for umbilical cord care in Central Uganda.

BACKGROUND: Cleansing the umbilical cord with chlorhexidine reduces neonatal morbidity and mortality, particularly in communities where newborn deaths and home births are common. As a result, the World Health Organization and national authorities are advocating the scale up of this intervention. In order for such a scale up to be effective, it has to be acceptable to the targeted population. With the overall aim to clarify conditions for scale-up, this study explored the acceptability of single dose chlorhexidine solution for umbilical cord care among health workers and infant care providers in the districts of Kampala and Mukono in Central Uganda. METHODS: This was a qualitative study that involved mothers of neonates enrolled in a chlorhexidine trial, nurses implementing the trial, key community members and opinion leaders in childcare. We conducted 30 in depth interviews (IDIs) with mothers (18), health workers (8), traditional birth attendants (2), a father (1) and a grandmother (1) and 4 focus group discussions (FGDs), 3 with mothers and 1 with health workers. We used qualitative content analysis to analyze our findings and borrow upon Sekhon's model when presenting our findings. RESULTS: Cognitive and emotional responses to chlorhexidine use included ease of use, and a perception that chlorhexidine reduced smell and abdominal colic. We also found that wider social and cultural factors were important to chlorhexidine use. These included cultural value put on quick separation of the umbilical cord as well as the practice of bathing the baby in a herbal mixture called kyogero. We also found that older relatives were key decision makers in umbilical cord care for newborns, but were seldom present during health workers' counseling of mothers about hygienic care of the cord. CONCLUSIONS: The application of chlorhexidine on the umbilical cord stump at birth was acceptable as an addition rather than a total replacement of traditional substances. The scale up of chlorhexidine should consider how to accommodate local beliefs and practices in a way that does not compromise the effect of the intervention; encouraging mothers to delay the bathing of babies in kyogero could be one way of doing this.

Multiple micronutrient supplementation does not reduce diarrhoea morbidity in Ugandan HIV-infected children: a randomised controlled trial.

OBJECTIVES: To determine the effect of multiple micronutrient supplementation on the incidence and prevalence of diarrhoea in Ugandan HIV-infected children aged 1-5 years. METHODS: We enrolled 847 HIV-infected Ugandan children in a randomised trial of a supplement containing 14 micronutrients (MMS) given at twice the recommended dietary allowance (RDA) versus a six-multivitamin (MV) supplement given in one RDA as the 'standard of care'. The participants were stratified into a highly active antiretroviral therapy (HAART) group of 85/847 (10%) and a non-HAART group of 762/847 (90%) participants. The supplements were given daily for 6 months. Episodes of diarrhoea assessed at routine visits, sick visits and those reported within 2 weeks before the routine visit were counted against weeks of observation for each participant. Diarrhoea incidence per child was calculated as the number of episodes per child year. Rate ratios were used to compare person-time rates in the two groups. RESULTS: The incidence of diarrhoea was 3·8 (95% CI 3·4-4·3) in the MMS and 3·5 (95% CI 3·1-4·0) in the MV group per child year. The rate ratio was 1·1 (0·9-1·3), similar in both strata, except that HAART-treated children had a lower incidence rate of diarrhoea. The prevalence of diarrhoea at 6 months was also similar in the two groups. CONCLUSION: The 14-multiple-micronutrient supplement given in two RDA doses compared with a six-multivitamin 'standard of care' supplement given in one RDA dose did not reduce the incidence or prevalence of diarrhoea in HIV-infected children aged 1-5 years.

Zinc adjunct therapy reduces case fatality in severe childhood pneumonia: a randomized double blind placebo-controlled trial.

BACKGROUND: Pneumonia is a leading cause of children's deaths in developing countries and hinders achievement of the fourth Millennium Development Goal. This goal aims to reduce the under-five mortality rate, by two thirds, between 1990 and 2015.Few studies have examined the impact of zinc adjunct therapy on the outcome of childhood pneumonia. We determined the effect of zinc as adjunct therapy on time to normalization of respiratory rate, temperature and oxygen saturation. We also studied the effect of zinc adjunct therapy on case fatality of severe childhood pneumonia (as a secondary outcome) in Mulago Hospital, Uganda. METHODS: In this double blind, randomized, placebo-controlled clinical trial, 352 children aged 6 to 59 months, with severe pneumonia were randomized to zinc (20 mg for children ≥ 12 months, and 10 mg for those < 12 months) or a placebo once daily for seven days, in addition to standard antibiotics for severe pneumonia. Children were assessed every six hours. Oxygen saturation was normal if it was above 92% (breathing room air) for more than 15 minutes. The respiratory rate was normal if it was consistently (more than 24 hours) below 50 breaths per minute in infants and 40 breaths per minute in children above 12 months of age. Temperature was normal if consistently below 37.5°C. The difference in case fatality was expressed by the risk ratio between the two groups. RESULTS: Time to normalization of the respiratory rate, temperature and oxygen saturation was not significantly different between the two arms.Case fatality was 7/176 (4.0%) in the zinc group and 21/176 (11.9%) in the placebo group: Relative Risk 0.33 (95% CI 0.15 to 0.76). Relative Risk Reduction was 0.67 (95% CI 0.24 to 0.85), while the number needed to treat was 13. Among HIV infected children, case fatality was higher in the placebo (7/27) than in the zinc (0/28) group; RR 0.1 (95% CI 0.0, 1.0).Among 127 HIV uninfected children receiving the placebo, case fatality was 7/127 (5.5%); versus 5/129 (3.9%) among HIV uninfected group receiving zinc: RR 0.7 (95% CI 0.2, 2.2). The excess risk of death attributable to the placebo arm (Absolute Risk Reduction or ARR) was 8/100 (95% CI: 2/100, 14/100) children. This excess risk was substantially greater among HIV positive children than in HIV negative children (ARR: 26 (95% CI: 9, 42) per 100 versus 2 (95% CI: -4, 7) per 100); P-value for homogeneity of risk differences = 0.006. CONCLUSION: Zinc adjunct therapy for severe pneumonia had no significant effect on time to normalization of the respiratory rate, temperature and oxygen saturation. However, zinc supplementation in these children significantly decreased case fatality.The difference in case fatality attributable to the protective effect of zinc therapy was greater among HIV infected than HIV uninfected children. Given these results, zinc could be considered for use as adjunct therapy for severe pneumonia, especially among Highly Active Antiretroviral Therapynaïve HIV infected children in our environment. CLINICAL TRIALS REGISTRATION NUMBER: clinicaltrials.gov NCT00373100.

Male partner antenatal attendance and HIV testing in eastern Uganda: a randomized facility-based intervention trial.

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.

Multiple micronutrient supplementation improves vitamin B12 and folate concentrations of HIV infected children in Uganda: a randomized controlled trial.

BACKGROUND: The effect of multiple micronutrient supplementation on vitamin B12 and folate has hither to not been reported in African HIV infected children. This paper describes vitamin B12 and folate status of Ugandan HIV infected children aged 1-5 years and reports the effect of multiple micronutrient supplementation on serum vitamin B12 and folate concentrations. METHODS: Of 847 children who participated in a multiple micronutrient supplementation trial, 214 were assessed for vitamin B12 and folate concentrations pre and post supplementation. One hundred and four children were randomised to two times the recommended dietary allowance (RDA) of a 14 multiple micronutrient supplement (MMS) and 114 to a 'standard of care' supplement of 6 multivitamins (MV). Serum vitamin B12 was measured by an electrochemiluminescence immunoassay and folate by a competitive protein-binding assay using Modular E (Roche) automatic analyzer. Vitamin B12 concentrations were considered low if less than 221 picomoles per litre (pmol/L) and folate if < 13.4 nanomoles per litre (nmol/L). The Wilcoxon Signed Ranks test was used to measure the difference between pre and post supplementation concentrations. RESULTS: Vitamin B12 was low in 60/214 (28%) and folate in 62/214 (29.0%) children. In the MMS group, the median concentration (IQR) of vitamin B12 at 6 months was 401.5 (264.3 - 518.8) pmol/L compared to the baseline of 285.5 (216.5 - 371.8) pmol/L, p < 0.001. The median (IQR) folate concentrations increased from 17.3 (13.5-26.6) nmol/L to 27.7 (21.1-33.4) nmol/L, p < 0.001. In the 'standard of care' MV supplemented group, the median concentration (IQR) of vitamin B12 at 6 months was 288.5 (198.8-391.0) pmol/L compared to the baseline of 280.0 (211.5-386.3) pmol/L while the median (IQR) folate concentrations at 6 months were 16.5 (11.7-22.1) nmol/L compared to 15.7 (11.9-22.1) nmol/L at baseline. There was a significant difference in the MMS group in both vitamin B12 and folate concentrations but no difference in the MV group. CONCLUSIONS: Almost a third of the HIV infected Ugandan children aged 1-5 years had low serum concentrations of vitamin B12 and folate. Multiple micronutrient supplementation compared to the 'standard of care' supplement of 6 multivitamins improved the vitamin B12 and folate status of HIV infected children in Uganda. TRIAL REGISTRATION: http://ClinicalTrials.govNCT00122941).

Zinc status in HIV infected Ugandan children aged 1-5 years: a cross sectional baseline survey.

BACKGROUND: Low concentrations of serum zinc have been reported in HIV infected adults and are associated with disease progression and an increased risk of death. Few studies have been conducted in HIV infected children in Africa. We determined serum zinc levels and factors associated with zinc deficiency in HIV infected Ugandan children. METHODS: We measured the baseline zinc status of 247 children aged 1-5 years enrolled in a randomised trial for multiple micronutrient supplementation at paediatric HIV clinics in Uganda (http://ClinicalTrials.gov NCT00122941). Zinc status was determined using inductively coupled atomic emission spectrophotometry (ICP-AES). Clinical and laboratory characteristics were compared among zinc deficient (zinc < 10.0 µmol/L) and non deficient children. Logistic regression was used to determine predictors of low serum zinc. RESULTS: Of the 247 children, 134 (54.3%) had low serum zinc (< 10.0 µmol/L). Of the 44 children on highly active antiretroviral therapy (HAART), 13 (29.5%) had low zinc compared to 121/203 (59.6%) who were not on HAART. Overall, independent predictors of low zinc were fever (OR 2.2; 95%CI 1.1-4.6) and not taking HAART (OR 3.7; 95%CI 1.8-7.6). CONCLUSION: Almost two thirds of HAART naïve and a third of HAART treated HIV infected children were zinc deficient. Increased access to HAART among HIV infected children living in Uganda might reduce the prevalence of zinc deficiency.

Effect of multiple micronutrient supplementation on survival of HIV-infected children in Uganda: a randomized, controlled trial.

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.

Establishing individual peer counselling for exclusive breastfeeding in Uganda: implications for scaling-up.

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).