"I abandoned my job to look after my baby." Understanding the unpriced cost of care of a preterm infant: Caregivers' lived experiences.

BACKGROUND: Preterm birth is associated with life-long cost implications on the infant, family, health system, and society at large. The costs related to lost productivity at contributions at work during care of preterm infants are difficult to measure. We aimed to explore and document the unpriced costs parents incur following birth of a preterm infant in the first year of life in a low resource setting. METHODS: Thirty-nine mothers and five fathers of preterm infants who had ever attended the preterm follow-up clinic after discharge from Mulago National Referral Hospital, were included in a qualitative study between November 2019 and February 2020. Participants were purposively selected, and data were collected using four focused group discussions with mothers and in-depth interviews with the fathers lasting 30-70 minutes each. These were audio-recorded, transcribed and translated. The data were manually analysed using the thematic approach. FINDINGS: Three themes were generated: i) complex nature of the infant, ii) time to care for the infant, iii) mother as the predominant caregiver. The parents perceived preterm infants as delicate, complicated and their care more costly compared to those born at term. Expressions of need for time to care for their infants, frequent hospital visits and readmission were raised. Availability of the mother as the predominant caregiver some of whose roles cannot be delegated and their experiences following return to work after birth of a preterm were cited by the participants. CONCLUSION: The results highlight the unpriced costs incurred by the parents through disruption of the work pattern due to the actual and perceived needs of a preterm infant and time to care in a low resource setting. We recommend guidance on financial planning, development of policies and programs on social and financial support for parents and future studies on indirect costs of preterm care.

A randomized clinical trial of on-demand oral pre-exposure prophylaxis does not modulate lymphoid/myeloid HIV target cell density in the foreskin.

OBJECTIVES: As topical pre-exposure prophylaxis (PrEP) has been shown to cause immune modulation in rectal or cervical tissue, our aim was to examine the impact of oral PrEP on lymphoid and myeloid changes in the foreskin in response to dosing and timing of drug administration. DESIGN: HIV-negative male individuals ( n  = 144) were recruited in South Africa and Uganda into an open-label randomized controlled trial in a 1 : 1 : 1 : 1 : 1 : 1 : 1 : 1 : 1 ratio to control arm (with no PrEP) or one of eight arms receiving emtricitabine-tenofovir disoproxil fumarate (F/TDF) or emtricitabine-tenofovir alafenamide (F/TAF) at one of two different doses, 5 or 21 h before undergoing voluntary medical male circumcision (VMMC). METHODS: After dorsal-slit circumcision, foreskin tissue sections were embedded into Optimal Cutting Temperature media and analysed, blinded to trial allocation, to determine numbers of CD4 + CCR5 + , CD1a + cells and claudin-1 expression. Cell densities were correlated with tissue-bound drug metabolites and p24 production after ex-vivo foreskin challenge with HIV-1 bal . RESULTS: There was no significant difference in CD4 + CCR5 + or CD1a + cell numbers in foreskins between treatment arms compared with the control arm. Claudin-1 expression was 34% higher ( P  = 0.003) in foreskin tissue from participants receiving PrEP relative to controls, but was no longer statistically significant after controlling for multiple comparisons. There was neither correlation of CD4 + CCR5 + , CD1a + cell numbers, or claudin-1 expression with tissue-bound drug metabolites, nor with p24 production after ex-vivo viral challenge. CONCLUSION: Oral doses and timing of on-demand PrEP and in-situ drug metabolite levels in tissue have no effect on numbers or anatomical location of lymphoid or myeloid HIV target cells in foreskin tissue.

Dose finding study for on-demand HIV pre-exposure prophylaxis for insertive sex in sub-Saharan Africa: results from the CHAPS open label randomised controlled trial.

BACKGROUND: The efficacy of on-demand HIV pre-exposure prophylaxis (PrEP) for men in sub-Saharan Africa has not been evaluated, and the on-demand PrEP dosing requirement for insertive sex remains unknown. METHODS: HIV-negative males 13-24 years, requesting voluntary medical male circumcision (VMMC), were enrolled into an open-label randomised controlled trial (NCT03986970), and randomised 1:1:1:1:1:1:1:1:1 to control arm or one of eight arms receiving emtricitabine-tenofovir disoproxil fumarate (F/TDF) or emtricitabine-tenofovir alafenamide (F/TAF) over one or two days, and circumcised 5 or 21 h thereafter. The primary outcome was foreskin p24 concentrations following ex vivo HIV-1BaL challenge. Secondary outcomes included peripheral blood mononuclear cell (PBMC) p24 concentration, and drug concentrations in foreskin tissue, PBMCs, plasma and foreskin CD4+/CD4-cells. In the control arm, post-exposure prophylaxis (PEP) activity of non-formulated tenofovir-emtricitabine (TFV-FTC) or TAF-FTC was assessed with ex vivo dosing 1, 24, 48 or 72 h post-HIV-1 challenge. FINDINGS: 144 participants were analysed. PrEP with F/TDF or F/TAF prevented ex vivo infection of foreskins and PBMCs both 5 and 21 h after PrEP dosing. There was no difference between F/TDF and F/TAF (p24day15 geometric mean ratio 1.06, 95% confidence interval: 0.65-1.74). Additional ex vivo dosing did not further increase inhibition. In the control arm, PEP ex vivo dosing was effective up to 48 post-exposure diminishing thereafter, with TAF-FTC showing prolonged protection compared to TFV-FTC. Participants receiving F/TAF had higher TFV-DP concentrations in foreskin tissue and PBMCs compared with F/TDF, irrespective of dose and sampling interval; but F/TAF did not confer preferential TFV-DP distribution into foreskin HIV target cells. FTC-TP concentrations with both drug regimens were equivalent and ∼1 log higher than TFV-DP in foreskin. INTERPRETATION: A double dose of either F/TDF or F/TAF given once either 5 or 21 h before ex vivo HIV-challenge provided protection across foreskin tissue. Further clinical evaluation of pre-coital PrEP for insertive sex is warranted. FUNDING: EDCTP2, Gilead Sciences, Vetenskapsrådet.

Short-term oral pre-exposure prophylaxis against HIV-1 modulates the transcriptome of foreskin tissue in young men in Africa.

Whilst short-term oral pre-exposure prophylaxis (PrEP) with antiretroviral drugs in men who have sex with men has shown protection against HIV-1 infection, the impact of this regimen on the in vivo foreskin transcriptome is unknown. We collected foreskin tissue after voluntary medical male circumcision from 144 young men (72 from Uganda and 72 from South Africa) randomized to one to two doses of either oral tenofovir (TFV) disoproxil fumarate (FTC-TDF) or tenofovir alafenamide (FTC-TAF) or no drug (untreated controls). This novel approach allowed us to examine the impact of short-term oral PrEP on transcriptome of the male genital tract. A single dose of FTC-TDF did not affect the foreskin transcriptome in relation to control arm, however one dose of FTC-TAF induced upregulation of four genes AKAP8, KIAA0141, HSCB and METTL17. Following two doses of either FTC-TDF or FTC-TAF, there was an increase in 34 differentially expressed genes for FTC-TDF and 15 for FTC-TAF, with nine DEGs in common: KIAA0141, SAFB2, CACTIN, FXR2, AKAP8, HSCB, CLNS1A, DDX27 and DCAF15. Functional analysis of differentially expressed genes revealed modulation of biological processes related to mitochondrial stress (KIAA0141, HSCB and METTL17), anti-viral and anti-inflammatory pathways (CACTIN and AKAP8). Our results show that short-course on-demand oral PrEP in men modulates genes in foreskin tissue which are likely unfavorable to HIV acquisition and replication. We also describe an upregulated expression of genes involved in diverse mitochondria biology which may potentially result in worsened mitochondria-related. These results warrant further studies to assess the role of short-course and prolonged oral PrEP on biological processes of the foreskin mucosa.

Mobilization of systemic CCL4 following HIV pre-exposure prophylaxis in young men in Africa.

HIV-1 pre-exposure prophylaxis (PrEP) relies on inhibition of HIV-1 replication steps. To understand how PrEP modulates the immunological environment, we derived the plasma proteomic profile of men receiving emtricitabine-tenofovir (FTC-TDF) or emtricitabine-tenofovir alafenamide (FTC-TAF) during the CHAPS trial in South Africa and Uganda (NCT03986970). The CHAPS trial randomized 144 participants to one control and 8 PrEP arms, differing by drug type, number of PrEP doses and timing from final PrEP dose to sampling. Blood was collected pre- and post-PrEP. The inflammatory profile of plasma samples was analyzed using Olink (N=92 proteins) and Luminex (N=33) and associated with plasma drug concentrations using mass spectrometry. The proteins whose levels changed most significantly from pre- to post-PrEP were CCL4, CCL3 and TNF-α; CCL4 was the key discriminator between pre- and post-PrEP samples. CCL4 and CCL3 levels were significantly increased in post-PrEP samples compared to control specimens. CCL4 was significantly correlated with FTC drug levels in plasma. Production of inflammatory chemokines CCL4 and CCL3 in response to short-term PrEP indicates the mobilization of ligands which potentially block virus attachment to CCR5 HIV-1 co-receptor. The significant correlation between CCL4 and FTC levels suggests that CCL4 increase is modulated as an inflammatory response to PrEP.

Antiretroviral therapy initiation and outcomes of hospitalized HIV-infected patients in Uganda-An evaluation of the HIV test and treat strategy.

BACKGROUND: Uganda adopted the HIV Test and Treat in 2016. There is paucity of data about its implementation among hospitalized patients. We aimed to determine the proportion of patients initiating anti-retroviral therapy (ART) during hospitalization, barriers and mortality outcome. METHODS: In this mixed methods cohort study, we enrolled hospitalized patients with a recent HIV diagnosis from three public hospitals in Uganda. We collected data on clinical characteristics, ART initiation and reasons for failure to initiate ART, as well as 30 day outcomes. Healthcare workers in-depth interviews were also conducted and data analyzed by sub-themes. RESULTS: We enrolled 234 patients; females 140/234 (59.8%), median age 34.5 years (IQR 29-42), 195/234 (83.7%) had WHO HIV stage 3 or 4, and 74/116 (63.8%) had CD4 ≤ 200 cell/µL. The proportion who initiated ART during hospitalization was 123/234 (52.6%) (95% CI 46.0-59.1), of these 35/123 (28.5%) initiated ART on the same day of hospitalization, while 99/123 (80.5%) within a week of hospitalization. By 30 days 34/234 (14.5%) (95% CI 10.3-19.7) died. Patients residing ≥ 35 kilometers from the hospital were more likely not to initiate ART during hospitalization, [aRR = 1.39, (95% CI 1.22-1.59). Inadequate patient preparation for ART initiation and advanced HIV disease were highlighted as barriers of ART initiation during hospitalization. CONCLUSION: In this high HIV prevalence setting, only half of newly diagnosed HIV patients are initiated on ART during hospitalization. Inadequate pre-ART patient preparation and advanced HIV are barriers to rapid ART initiation among hospitalized patients in public hospitals.

The association of cognitive impairment with quality of life and functional impairment in Ugandan first-episode psychosis patients: a cross sectional study.

INTRODUCTION: Cognitive impairment is common in first-episode psychosis patients and often associated with poor quality of life and functional impairment. However, most literature on this association is from high income countries and not low resource countries like Uganda. We aimed to determine the association between cognitive impairment with quality of life and functional impairment in Ugandan first-episode psychosis patients. METHODS: At Butabika national psychiatric hospital of Uganda, we enrolled 94 first-episode psychosis patients aged 18-60 years with a confirmed first-episode of psychosis and no previous treatment with antipsychotic medication. Neuropsychological assessment was performed using the MATRICS consensus cognitive battery (MCCB). Quality of life and functional impairment were assessed using the brief version of the World Health Organisation Quality of Life scale (WHOQOL-BREF) and the MINI International Neuropsychiatric Inventory (MINI) respectively. Linear regression analyses determined the association between impairment in different cognitive domains with various quality of life and functional impairment domains while controlling for age, gender and level of education. RESULTS: High scores in the reasoning and problem solving cognitive domain were associated with better quality of life in the psychological domain of WHOQOL-BREF (p = 0.029). For functional impairment, high cognitive scores in the domains of speed of processing (p = 0.018), reasoning and problem solving (p = 0.015), working memory (p = 0.017) and visual learning and memory (p = 0.002) were associated with psychosis "having a greater impact on other members of the family" on the MINI. Higher scores in the social cognition domain were associated with "less aggressive and disruptive behaviour" (p = 0.003). CONCLUSION: Cognitive impairment in Ugandan first-episode psychotic patients is associated with both poorer quality of life and functional impairment. Remediation of cognitive function may be a plausible intervention to improve outcomes in Ugandan first-episode psychosis patients.

Symptoms of post-traumatic stress and associations with sexual behaviour and PrEP preferences among young people in South Africa, Uganda and Zimbabwe.

BACKGROUND: It is not known whether post-traumatic stress disorder (PTSD) increases HIV-risk behaviours among young people in sub-Saharan Africa. We assessed associations of PTSD symptoms with sexual behaviour, HIV risk perception, and attitudes towards PrEP among young people taking part in the CHAPS community survey. We hypothesised that PTSD symptoms would increase sexual behaviours associated with HIV risk, hinder PrEP uptake and influence preference for daily versus on-demand PrEP. METHODS: Young people without HIV, aged 13-24 years, were purposively recruited in Johannesburg and Cape Town in South Africa, Wakiso in Uganda, and Chitungwiza in Zimbabwe, and surveyed on socio-demographic characteristics, PrEP knowledge and attitudes, sexual behaviour, HIV perception and salience, and mental health. PTSD symptoms were measured using the Primary Care PTSD Screen for the Diagnostic and Statistical Manual of Mental Disorders 5 (PC-PTSD-5). Logistic and ordinal logistic regression was used to assess associations between PC-PTSD-5 score and socio-demographic characteristics, sexual behaviour, HIV risk perception, PrEP attitudes, and substance use, adjusting for age, sex, setting, depression and anxiety. RESULTS: Of 1330 young people (51% male, median age 19 years), 522 (39%) reported at least one PTSD symptom. There was strong evidence that having a higher PC-PTSD-5 score was associated with reported forced sex (OR 3.18, 95%CI: 2.05-4.93), self-perception as a person who takes risks (OR 1.12, 95%CI: 1.04-1.20), and increased frequency of thinking about risk of HIV acquisition (OR 1.16, 95%CI: 1.08-1.25). PTSD symptoms were not associated with willingness to take PrEP, preference for on-demand versus daily PrEP, or actual HIV risk behaviour such as condomless sex. CONCLUSIONS: Symptoms consistent with probable PTSD were common among young people in South Africa, Uganda and Zimbabwe but did not impact PrEP attitudes or PrEP preferences. Evaluation for PTSD might form part of a general assessment in sexual and reproductive health services in these countries. More work is needed to understand the impact of PTSD on HIV-risk behaviour, forced sex and response to preventive strategies including PrEP.

A qualitative study to identify critical attributes and attribute-levels for a discrete choice experiment on oral pre-exposure prophylaxis (PrEP) delivery among young people in Cape Town and Johannesburg, South Africa.

BACKGROUND: The uptake and adherence of daily oral PrEP has been poor in high-risk populations in South Africa including young people. We used qualitative research methods to explore user preferences for daily and on-demand oral PrEP use among young South Africans, and to inform the identification of critical attributes and attribute-levels for quantitative analysis of user preferences, i.e. a discrete choice experiment (DCE). METHODS: Data were collected between September and November 2018 from eight group discussions and 20 in-depth interviews with young people 13 to 24 years in Cape Town and Johannesburg. Using a convenience sampling strategy, participants were stratified by sex and age. Interviewers used a semi-structured interview guide to discuss several attributes (dosing regimen, location, costs, side effects, and protection period) for PrEP access and use. Group discussions and in-depth interviews were audio-recorded, transcribed verbatim and translated to English. We used framework analysis to explore context-specific attributes and attribute-levels for delivering oral PrEP in South Africa. The adolescent community advisory board, expert and study team opinions were consulted for the final DCE attributes and levels. RESULTS: We enrolled 74 participants who were 51% (n = 38/74) male, had a median age of 18.5 [Interquartile range = 16-21.25] years, 91% (n = 67/74) identified as heterosexual and 49% (n = 36/74) had not completed 12th grade education. Using the qualitative data, we identified five candidate attributes including (1) dosing regimen, (2) location to get PrEP, (3) cost, (4) route of administration and (5) frequency. After discussions with experts and the study team, we revised the DCE to include the following five attributes and levels: dosing regime: daily, and on-demand PrEP; location: private pharmacy, public clinic, mobile clinic, ATM); cost: free-of-charge, R50 (~2GBP), R265 (~12GBP); side effects: nausea, headache, rash; and duration of protection: fulltime protection versus when PrEP is used). CONCLUSIONS: There is limited literature on qualitative research methods describing the step-by-step process of developing a DCE for PrEP in adolescents, especially in resource-constrained countries. We provide the process followed for the DCE technique to understand user preferences for daily and on-demand oral PrEP among young people in South Africa.

Neurodevelopmental performance among pre-schoolers treated for severe anaemia at Lira Regional Referral Hospital, Uganda.

BACKGROUND: Severe anaemia is a common clinical problem among young children in sub-Saharan Africa. However, the effect of severe anaemia on neurodevelopment of these children is not well described. Therefore, we assessed the neurodevelopmental performance of preschool children diagnosed with severe anaemia in Northern Uganda. METHODS: We conducted a prospective cohort study among children < 5 years of age 14 days post discharge after an episode of severe anaemia (Hb < 5.0 g/dl; n = 171; mean Hb = 3.9g/dl) at Lira Regional Referral Hospital, Uganda. Neurodevelopmental outcomes (cognitive, language and motor) were assessed using Bayley Scales of Infant and Toddler Development, 3rd edition (Bayley-III). Age-adjusted z-scores for each domain were calculated using scores from healthy community control children (n = 88) recruited from the same environment for each age category. Multiple linear regression was used to compare z-scores in the cognitive, language and motor scales between the two groups after adjusting for weight-for-age z-score, socioeconomic status, mother's education, and father's employment on all the scales. RESULTS: The prevalence of neurodevelopmental impairment was 2.3% (95% CI: 0.8-6.1) for cognition, 1.7% (95%: 0.6-5.3) for language and 3.5% (95% CI: 1.6-7.6) for motor scales and 4.6% (95% CI: 2.3-9.1) for deficits in ≥1 area of neurodevelopment. Significant differences were observed between the two groups with the SA group performing worse on cognition [adjusted mean score, (Standard error, SE), P-value] [-0.20, (0.01) vs. 0.00, (0.01), P = 0.02]; language [-0.25, (0.01) vs. 0.00, (0.01), P< 0.001]; and motor [-0.17, (0.01) vs. 0.00, (0.01), P = 0.05] scales. CONCLUSION: In children < 5 years of age, severe anaemia was associated with neurocognitive (cognition, language and motor) deficits in the immediate period post treatment. Further research is needed to identify risk factors and determine the long-term effects of poor neurodevelopment in young children with severe anaemia.

Delayed iron does not alter cognition or behavior among children with severe malaria and iron deficiency.

BACKGROUND: Malaria and iron deficiency (ID) in childhood are both associated with cognitive and behavioral dysfunction. The current standard of care for children with malaria and ID is concurrent antimalarial and iron therapy. Delaying iron therapy until inflammation subsides could increase iron absorption but also impair cognition. METHODS: In this study, Ugandan children 18 months to 5 years old with cerebral malaria (CM, n = 79), severe malarial anemia (SMA, n = 77), or community children (CC, n = 83) were enrolled and tested for ID. Children with ID were randomized to immediate vs. 28-day delayed iron therapy. Cognitive and neurobehavioral outcomes were assessed at baseline and 6 and 12 months (primary endpoint) after enrollment. RESULTS: All children with CM or SMA and 35 CC had ID (zinc protoporphyrin concentration ≥80 µmol/mol heme). No significant differences were seen at 12-month follow-up in overall cognitive ability, attention, associative memory, or behavioral outcomes between immediate and delayed iron treatment (mean difference (standard error of mean) ranged from -0.2 (0.39) to 0.98 (0.5), all P ≥ 0.06). CONCLUSIONS: Children with CM or SMA and ID who received immediate vs. delayed iron therapy had similar cognitive and neurobehavioral outcomes at 12-month follow-up. IMPACT: The optimal time to provide iron therapy in children with severe malaria is not known. The present study shows that delay of iron treatment to 28 days after the malaria episode, does not lead to worse cognitive or behavioral outcomes at 12-month follow-up. The study contributes new data to the ongoing discussion of how best to treat ID in children with severe malaria.

Delayed iron improves iron status without altering malaria risk in severe malarial anemia.

BACKGROUND: WHO guidelines recommend concurrent iron and antimalarial treatment in children with malaria and iron deficiency, but iron may not be well absorbed or utilized during a malaria episode. OBJECTIVES: We aimed to determine whether starting iron 28 d after antimalarial treatment in children with severe malaria and iron deficiency would improve iron status and lower malaria risk. METHODS: We conducted a randomized clinical trial on the effect of immediate compared with delayed iron treatment in Ugandan children 18 mo-5 y of age with 2 forms of severe malaria: cerebral malaria (CM; n = 79) or severe malarial anemia (SMA; n = 77). Asymptomatic community children (CC; n = 83) were enrolled as a comparison group. Children with iron deficiency, defined as zinc protoporphyrin (ZPP) ≥ 80 µmol/mol heme, were randomly assigned to receive a 3-mo course of daily oral ferrous sulfate (2 mg · kg-1 · d-1) either concurrently with antimalarial treatment (immediate arm) or 28 d after receiving antimalarial treatment (delayed arm). Children were followed for 12 mo. RESULTS: All children with CM or SMA, and 35 (42.2%) CC, were iron-deficient and were randomly assigned to immediate or delayed iron treatment. Immediate compared with delayed iron had no effect in any of the 3 study groups on the primary study outcomes (hemoglobin concentration and prevalence of ZPP ≥ 80 µmol/mol heme at 6 mo, malaria incidence over 12 mo). However, after 12 mo, children with SMA in the delayed compared with the immediate arm had a lower prevalence of iron deficiency defined by ZPP (29.4% compared with 65.6%, P = 0.006), a lower mean concentration of soluble transferrin receptor (6.1 compared with 7.8 mg/L, P = 0.03), and showed a trend toward fewer episodes of severe malaria (incidence rate ratio: 0.39; 95% CI: 0.14, 1.12). CONCLUSIONS: In children with SMA, delayed iron treatment did not increase hemoglobin concentration, but did improve long-term iron status over 12 mo without affecting malaria incidence.This trial was registered at clinicaltrials.gov as NCT01093989.

Perceived benefits and risks of participation in a clinical trial for Ugandan children with sickle cell anemia.

INTRODUCTION: Understanding factors that affect the decisions of caregivers of African children to enroll their children in clinical trials would lead to more fully informed consent. METHODS: During the NOHARM study (NCT01976416), a placebo-controlled clinical trial of hydroxyurea for Ugandan children with sickle cell anemia (SCA), 206 caregivers were given a semistructured questionnaire about factors that influenced participation in the study and their perceptions of study benefits and risks. Factors were further assessed with focus group discussions. RESULTS: Caregivers identified education provided during the recruitment process (44%), the child's current poor state of health (35%), and the possibility of improvement in the child's health (16%) as their primary initial reasons for deciding to participate in the NOHARM trial. Concerns regarding the drug or participation in a research study, including the stated concern of death by several caregivers, were outweighed by the possibility of improvement in the child's health. During the study, 72% of caregivers cited improved health as an advantage of study participation, while disadvantages cited included the potential side effects of hydroxyurea, most of which did not occur during the trial. DISCUSSION: Our study findings highlight the generally poor state of health of Ugandan children with SCA, the desperation by caregivers for anything that could improve the child's health, and the inevitable improvements in care that result from strict adherence to a study protocol, even a protocol based on local guidelines. Studies in this vulnerable population must be careful not to portray improved care as a primary incentive for participation.

Level of Partograph completion and healthcare workers' perspectives on its use in Mulago National Referral and teaching hospital, Kampala, Uganda.

BACKGROUND: The appropriate use of the Partograph allows early identification of labour related complications and prevents deaths. We, therefore, sought to determine the level of Partograph completion and healthcare worker perspectives towards its utilization. METHODS: This study had two components; a hospital-based cross-sectional descriptive chart review at the Mulago National Referral Hospital, Kampala, Uganda and a qualitative study involving four Focus Group Discussions (FGDs) with ward nurses, midwives and postgraduate residents. Data from the FGDs were analyzed using thematic -content analysis in Open Code software. The quantitative data were summarized using descriptive statistical analysis, means and proportions. RESULTS: Among the 355 Partographs reviewed, 79.1% had incomplete documentation of age, 52.7% gravidity, and 3.2% parity. In about 61%, the specific parameters for fetal monitoring, maternal monitoring and labour progress were incomplete. From the FGDs, the healthcare workers reported being unable to complete the Partographs due to the overwhelming numbers of expectant mothers and other staff responsibilities. Congestion in the maternity ward reduced the Partograph completion rates. The availability of other monitoring tools, limitation in skills, inadequate equipment and supplies, and the state of the mother at the presentation to the hospital all made Partograph use and completion challenging. CONCLUSIONS: The majority of Partographs started by health workers were incomplete. The time required to document, health system challenges, status of mother at presentation, and the high workload undermined completion of the Partograph at this high volume facility.

Adherence to clinical guidelines is associated with reduced inpatient mortality among children with severe anemia in Ugandan hospitals.

BACKGROUND: In resource limited settings, there is variability in the level of adherence to clinical guidelines in the inpatient management of children with common conditions like severe anemia. However, there is limited data on the effect of adherence to clinical guidelines on inpatient mortality in children managed for severe anemia. METHODS: We analyzed data from an uncontrolled before and after in-service training intervention to improve quality of care in Lira and Jinja regional referral hospitals in Uganda. Inpatient records of children aged 0 to 5 years managed as cases of 'severe anemia (SA)' were reviewed to ascertain adherence to clinical guidelines and compare inpatient deaths in SA children managed versus those not managed according to clinical guidelines. Logistic regression analysis was conducted to evaluate the relationship between clinical care factors and inpatient deaths amongst patients managed for SA. RESULTS: A total of 1,131 children were assigned a clinical diagnosis of 'severe anemia' in the two hospitals. There was improvement in the level of care after the in-service training intervention with more children being managed according to clinical guidelines compared to the period before, 218/510 (42.7%) vs 158/621 (25.4%) (p < 0.001). Overall, children managed according to clinical guidelines had reduced risk of inpatient mortality compared to those not managed according to clinical guidelines, [OR 0.28, (95%, CI 0.14, 0.55), p = 0.001]. Clinical care factors associated with decreased risk of inpatient death included, having pre-transfusion hemoglobin done to confirm diagnosis [OR 0.5; 95% CI 0.29, 0.87], a co-morbid diagnosis of severe malaria [OR 0.4; 95% CI 0.25, 0.76], and being reviewed after admission by a clinician [OR 0.3; 95% CI 0.18, 0.59], while a co-morbid diagnosis of severe acute malnutrition was associated with increased risk of inpatient death [OR 4.2; 95% CI 2.15, 8.22]. CONCLUSION: Children with suspected SA who are managed according to clinical guidelines have lower in-hospital mortality than those not managed according to the guidelines. Efforts to reduce inpatient mortality in SA children in resource-limited settings should focus on training and supporting health workers to adhere to clinical guidelines.

"I feel so bad but have nothing to do." Exploring Ugandan caregivers' experiences of parenting a child with severe malaria and subsequent repeated uncomplicated malaria.

BACKGROUND: Severe malaria in children is often associated with long-term behavioural and cognitive problems. A sizeable minority of children go on to experience repeated malaria due to the high transmission and infection rates in the region. The purpose of this study was to explore caregivers' experiences of parenting a child with a history of severe malaria followed by repeated episodes of uncomplicated malaria in comparison to healthy community children. METHODS: Thirty-one caregivers were enrolled in the study. These included caregivers of children previously exposed to severe malaria and who had experienced repeated uncomplicated malaria attacks (SM with RMA, n = 15), caregivers of children exposed to severe malaria who did not experience repeated episodes (SM, n = 10), and caregivers of healthy community children (CC, n = 6) were purposively selected. RESULTS: Thematic-content analysis generated eight areas of concern, six of which were noted only by caregivers of children with SM or SM with RMA: (1) a sense of helplessness; (2) challenges with changes in behaviour; (3) responses to a child's behaviour; (4) family life disruptions, including breakdown of relationships and inadequate male-spouse involvement in child care; (5) disagreements in seeking healthcare; (6) societal burden; and two by caregivers of children with SM, SM with RMA and also CC; (7) concern about academic achievement; and, (8) balancing work and family life. CONCLUSIONS: The study findings suggest that severe malaria, especially when followed by repeated malaria episodes, affects not only children who have the illness but also their caregivers. The effects on caregivers can decrease their social functioning and isolate them from other parents and may disrupt families. Interventions to support caregivers by counselling the ongoing problems that might be expected in children who have had severe malaria and repeated episodes of malaria, and how to manage these problems, may provide a way to improve behavioural and mental health outcomes for those children and their caregivers.

High rate of inappropriate blood transfusions in the management of children with severe anemia in Ugandan hospitals.

BACKGROUND: Severe anaemia (SA) is a common reason for hospitalisation of children in sub-Saharan Africa but the extent to which blood transfusion is used appropriately in the management of severe anemia has hitherto remained unknown. We report on the use of blood transfusion in the management of anemic children in two hospitals in Uganda. METHODS: Inpatient records of children 0-5 years of age admitted to Lira and Jinja regional referral hospitals in Uganda were reviewed for children admitted on selected days between June 2016 and May 2017. Data was extracted on the results, if any, of pre-transfusion hemoglobin (Hb) level, whether or not a blood transfusion was given and inpatient outcome for all children with a diagnosis of 'severe anemia'. Qualitative data was also collected from health workers to explain the reasons for the clinical practices at the two hospitals. RESULTS: Overall, 574/2275 (25.2%) of the children admitted in the two hospitals were assigned a diagnosis of SA. However 551 (95.9%) of children assigned a diagnosis of SA received a blood transfusion, accounting for 551/560 (98.4%) of the blood transfusions in the pediatric wards. Of the blood transfusions in SA children, only 245 (44.5%) was given appropriately per criteria (Pre-transfusion Hb ≤ 6 g/dL), while 306 (55.5%) was given inappropriately; (pre-transfusion Hb not done, n = 216, or when a transfusion is not indicated [Hb > 6.0 g/dl], n = 90). SA children transfused appropriately per Hb criteria had lower inpatient mortality compared to those transfused inappropriately, (7 (2.9%) vs. 22 (7.2%), [OR 0.4, 95% CI 0.16, 0.90]). Major issues identified by health workers as affecting use of blood transfusion included late presentation of SA children to hospital and unreliable availability of equipment for measurement of Hb. CONCLUSION: More than half the blood transfusions given in the management of anemic children admitted to Lira and Jinja hospitals was given inappropriately either without pre-transfusion Hb testing or when not indicated. Verification of Hb level by laboratory testing and training of health workers to adhere to transfusion guidelines could result in a substantial decrease in inappropriate blood transfusion in Ugandan hospitals.

Assessment of blood levels of heavy metals including lead and manganese in healthy children living in the Katanga settlement of Kampala, Uganda.

BACKGROUND: Exposure to environmental heavy metals is common among African children. Although many of these metals are known neurotoxicants, to date, monitoring of this exposure is limited, even in countries such as Uganda that are undergoing rapid industrialization. An assessment of the burden and potential causes of metal exposure is a critical first step in gauging the public health burden of metal exposure and in guiding its elimination. METHODS: In May 2016, we enrolled 100 children between the ages of 6 and 59 months living in the Katanga urban settlement of Kampala, Uganda. We measured whole blood concentrations of antimony, arsenic, barium, cadmium, cesium, chromium, cobalt, copper, lead, manganese, nickel, selenium, and zinc. Applying reference cutoffs, we identified metals whose prevalence of elevated blood concentrations was > 10%. We also administered an environmental questionnaire to each child's caregiver to assess potential exposures, including source of drinking water, cooking location and fuel, materials used for roof, walls, and floor, and proximity to potential pollution sources such as main roads, garbage landfills, and fuel stations. We compared log-transformed blood metal concentrations by exposure category, using t-test for dichotomous comparisons and ANOVA for comparisons of three categories, using Tukeys test to adjust for multiple comparisons. RESULTS: The prevalence of high blood levels was elevated for six of the metals: antimony (99%), copper (12%), cadmium (17%), cobalt (19.2%), lead (97%), and manganese (36.4%). Higher blood manganese was significantly associated with having cement walls (p = 0.04) or floors (p = 0.04). Cadmium was greater among children who attended school (< 0.01), and cobalt was higher among children who lived near a garbage landfill (p = 0.01). CONCLUSIONS: Heavy metal exposure is prevalent in the Katanga settlement and may limit neurodevelopment of children living there. Future studies are needed to definitively identify the sources of exposure and to correct potential nutritional deficiencies that may worsen metal absorption.

Developing mentorship in a resource-limited context: a qualitative research study of the experiences and perceptions of the makerere university student and faculty mentorship programme.

BACKGROUND: The aim of mentorship is to build the mentees capacity, enhance their skills and improve their ability to produce desired outcomes. However, the mentoring relationship is vulnerable to a number of challenges that may undermine its effectiveness and sustainability. We aimed to explore the experiences and perceptions of student and junior faculty mentees and senior faculty mentors at the Makerere University College of Health Sciences and identify the key factors defined by mentees and mentors as necessary for a successful mentorship program. METHODS: A qualitative design involving focus group discussions (FGDs) and key informant interviews (KII) was used. A total of eight KII and four FGDs were conducted, audio recorded and transcribed verbatim. Open coding of the transcripts was performed, and major themes were identified through multiple readings based on thematic analysis. RESULTS: Six key themes were shared by the mentees and mentors including: 1) defining the role of the mentor; 2) desired characteristics of a mentor and a mentoring relationship, with an emphasis on mutual trust and respect; 3) overlapping roles of mentors and supervisors; 4) issues with the process for identifying mentors, including the benefits and drawbacks of the mentee selecting mentor vs. being assigned a mentor; 5) current barriers to mentoring, including lack of knowledge about current program, lack of formal structure, uncertainly about who should initiate relationship, and unclear roles and expectations and 6) recommendations for the future development of mentoring programme, including the need for a formalized programme, and training adapted to the local context. CONCLUSIONS: The mentees and mentors described the role of the mentor and desired characteristics of mentors and a mentoring relationship similarly. Most concerns about mentoring occurred when current mentoring programmes and practices were not well aligned with these desired characteristics. Recommendations for future development of mentoring included greater formalization of mentoring with mentoring programmes based on shared expectations and adapted to the local context.

Comparison of iron status 28 d after provision of antimalarial treatment with iron therapy compared with antimalarial treatment alone in Ugandan children with severe malaria.

BACKGROUND: The provision of iron with antimalarial treatment is the standard of care for concurrent iron deficiency and malaria. However, iron that is given during a malaria episode may not be well absorbed or used, particularly in children with severe malaria and profound inflammation. OBJECTIVES: We aimed to 1) determine baseline values of iron and inflammatory markers in children with severe malarial anemia (SMA), children with cerebral malaria (CM), and community children (CC) and 2) compare markers in iron-deficient children in each group who received 28 d of iron supplementation during antimalarial treatment with those in children who did not receive iron during treatment.. DESIGN: Seventy-nine children with CM, 77 children with SMA, and 83 CC who presented to Mulago Hospital, Kampala, Uganda, were enrolled in a 28-d iron-therapy study. Children with malaria received antimalarial treatment. All children with CM or SMA, as well as 35 CC, had zinc protoporphyrin (ZPP) concentrations ≥80 µmol/mol heme and were randomly assigned to receive a 28-d course of iron or no iron. We compared iron markers at day 0 among study groups (CM, SMA, and CC groups) and at day 28 between children in each group who were randomly assigned to receive iron or to not receive iron. RESULTS: At day 0, children with CM and SMA had greater values of C-reactive protein, ferritin, and hepcidin than those of CC. At day 28, interactions between study and treatment group were NS. Children in the no-iron compared with iron groups had similar mean values for hemoglobin (115 compared with 113 g/L, respectively; P = 0.73) and ZPP (124 compared with 124 µmol/mol heme, respectively; P = 0.96) but had lower median ferritin [101.0 µg/L (95% CI: 84.2, 121.0 µg/L) compared with 152.9 µg/L (128.8, 181.6 µg/L), respectively; P ≤ 0.001] and hepcidin [45.8 ng/mL (36.8, 56.9 ng/mL) compared with 83.1 ng/mL (67.6, 102.2 ng/mL), respectively; P < 0.011]. CONCLUSIONS: Severe inflammation is a characterization of children with CM and SMA. The withholding of iron from children with severe malaria is associated with lower ferritin and hepcidin at day 28 but not a lower hemoglobin concentration. This trial was registered at clinicaltrials.gov as NCT01093989.