Successful Global Health Research Partnerships: What Makes Them Work?

There are many successful global health research partnerships, but little information is available about what makes them successful. We asked 14 research colleagues from Uganda, Kenya, and the United States who have extensive global health research experience about what they considered the top three factors that led to or impeded successful international research collaborations. Four key factors were identified: 1) mutual respect and benefit, 2) trust, 3) good communication, and 4) clear partner roles and expectations. Initial and ongoing assessment of these factors in global health research partnerships may prevent misunderstandings and foster a collaborative environment that leads to successful research

It is not always Tuberculosis! A case of pulmonary cryptococcosis in an immunocompetent child in Uganda

Pulmonary cryptococcosis is rare in immunocompetent individuals. Limited data exist regarding its occurrence in children, especially in developing countries. This case report describes an 8-year-old HIV-negative child with pulmonary cryptococcosis, previously diagnosed and treated for tuberculosis twice without improvement. Fine needle aspiration biopsy confirmed the diagnosis of pulmonary cryptococcosis and serum cryptococcal antigen test was positive. The child improved on amphotericin and fluconazole treatment. Despite the limited diagnostic capacity in many resource-constrained settings like Uganda, this case report highlights the need to investigate other causes of pneumonia in immunocompetent children that are not improving on conventional antimicrobial treatments

Burden of tuberculosis disease among adolescents in a rural cohort in Eastern Uganda

BACKGROUND: The world health organization (WHO) declared tuberculosis (TB) a global emergency, mainly affecting people in sub-Saharan Africa. However there is little data about the burden of TB among adolescents. We estimated the prevalence and incidence of TB and assessed factors associated with TB among adolescents aged 12–18 years in a rural population in Uganda in order to prepare the site for phase III clinical trials with novel TB vaccines among adolescents. METHODS: In a prospective cohort study, we recruited 5000 adolescents and followed them actively, every 6 months, for 1–2 years. Participants suspected of having TB were those who had any of; TB signs and symptoms, history of TB contact or a positive tuberculin skin test (TST) of ≥10 mm. Laboratory investigations included sputum smear microscopy and culture. RESULTS: Of the 5000 participants, eight culture confirmed cases of TB were found at baseline: a prevalence of 160/100,000 (95% confidence interval (CI), 69–315). There were 13 incident TB cases detected in an average of 1.1 person years: an incidence of 235/100,000 person years (95% CI, 125–402). None of the confirmed TB cases were HIV infected. Predictors for prevalent TB disease were: a history of TB contact and a cough ≥ 2 weeks at baseline and being out of school, while the only predictor for incident TB was a positive TST during follow-up. CONCLUSION: The TB incidence among adolescents in this rural part of Uganda seemed too low for a phase III TB vaccine trial. However, the study site demonstrated capability to handle a large number of participants with minimal loss to follow-up and its suitability for future clinical trials. Improved contact tracing in TB program activities is likely to increase TB case detection among adolescents. Future studies should explore possible pockets of higher TB incidence in urban areas and among out of school youth

Growth, immune and viral responses in HIV infected African children receiving highly active antiretroviral therapy: a prospective cohort study.

BACKGROUND: Scale up of paediatric antiretroviral therapy in resource limited settings continues despite limited access to routine laboratory monitoring. We documented the weight and height responses in HIV infected Ugandan children on highly active antiretroviral therapy and determined clinical factors associated with successful treatment outcomes. METHODS: A prospective cohort of HIV infected children were initiated on HAART and followed for 48 weeks. Body mass index for age z scores(BAZ), weight and height-for-age z scores (WAZ & HAZ) were calculated: CD4 cell % and HIV-1 RNA were measured at baseline and every 12 weeks. Treatment outcomes were classified according to; both virological and immunological success (VS/IS), virological failure and immunological success (VF/IS). virological success and immunological failure (VS/IF) and both virological and immunological failure (VF/IF). RESULTS: From March 2004 until May 2006, 124 HIV infected children were initiated on HAART. The median age (IQR) was 5.0 years (2.1 - 7.0) and 49% (61/124) were female. The median [95% confidence interval (CI)] BAZ, WAZ and HAZ at baseline were 0.29 (-2.9, -1.2), -1.2 (-2.1, -0.5) and -2.06 (-2.9, -1.2) respectively. Baseline median CD4 cell % and log10 HIV-1 RNA were; 11.8% (7.5-18.0) and 5.6 (5.2-5.8) copies/ml. By 48 weeks, mean WAZ and HAZ in the VF/IS group, which was younger, increased from - 0.98 (SD 1.7) to + 1.22 (SD 1.2) and from -1.99 (1.7) to + 0.76 (2.4) respectively. Mean increase in WAZ and HAZ in the VS/IF group, an older group was modest, from -1.84 (1.3) to - 0.41 (1.2) and -2.25 (1.2) to -1.16 (1.3) respectively. Baseline CD4 cell % [OR 6.97 95% CI (2.6 -18.6)], age [OR 4.6 95% CI (1.14 -19.1)] and WHO clinical stage [OR 3.5 95%CI (1.05 -12.7)] were associated with successful treatment outcome. CONCLUSIONS: HIV infected Ugandan children demonstrated a robust increase in height and weight z scores during the first 48 weeks of HAART, including those who failed to completely suppress virus. Older children initiating HAART with severe immune suppression were less likely to achieve a successful treatment outcome. These data emphasize the importance of initiating HAART early to ensure adequate immune and growth responses

Toxic Stress and Quality of Life in Early School‐Aged Ugandan Children With and Without Perinatal Human Immunodeficiency Virus Infection

Caregiver’s and child’s self‐reported quality of life (QOL) was defined using standardized questionnaires in a sample (N = 277) of 6–10 years old HIV‐infected, HIV‐exposed uninfected, and HIV‐unexposed uninfected children from Uganda. Psychosocial stress (acute stress and cumulative lifetime adversity) and physiologic stress (dysregulations across 13 biomarkers), perinatal HIV status, and their interaction were related to child QOL via general linear models. Lower child‐ and caregiver‐reported psychosocial stress were dose‐dependently associated with higher QOL (acute stress: mean difference coefficient b = 8.1–14.8, effect size [ES] = 0.46–0.83). Lower allostasis was dose‐dependently associated with higher QOL (b = 6.1–9.7, ES = 0.34–0.54). Given low caregiver acute stress, QOL for HIV‐infected was similar to HIV‐uninfected children; however, given high caregiver acute stress, a QOL disadvantage (b = −7.8, 95% CI: −12.8, −2.8; ES = −0.73) was evident for HIV‐infected versus uninfected children. Testing of caregiver stress reduction interventions is warranted to increase wellbeing in dependent children.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/156459/2/cad20355.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/156459/1/cad20355_am.pd

Caregiver socioemotional health as a determinant of child wellâ being in schoolâ aged and adolescent Ugandan children with and without perinatal HIV exposure

ObjectiveCaregiver socioâ emotional attributes are major determinants of child wellâ being. This investigation in vulnerable schoolâ aged Ugandan children estimates relationships between children’s wellâ being and their caregiver’s anxiety, depression and social support.MethodsPerinatally HIVâ infected, HIVâ exposed uninfected and HIVâ unexposed Ugandan children and their caregivers were enrolled. Perinatal HIV status was determined by 18 months of age using DNAâ polymerase chainâ reaction test; status was confirmed via HIV rapid diagnostic test when children were 6â 18 years old. Five indicators of child wellâ being (distress, hopelessness, positive future orientation, esteem and quality of life (QOL)) and caregiversâ socioemotional status (depressive symptoms, anxiety and social support) were measured using validated, culturally adapted and translated instruments. Categories based on tertiles of each caregiver psychosocial indicator were defined. Linear regression analyses estimated percent differences (β) and corresponding 95% confidence intervals (CI) for child wellâ being in relation to caregiver’s psychosocial status.ResultsAs per tertile increment, caregiver anxiety was associated with 2.7% higher distress (95%CI:0.2%, 5.3%) and lower selfâ esteem/QOL (β = â 1.3%/â 2.6%; 95%CI: â 5.0%,â 0.2%) in their children. Child distress/hopelessness increased (β = 3.3%/7.6%; 95%CI:0.4%, 14.7%) and selfâ esteem/QOL decreased 2.3% (β = â 2.3%/â 4.4%; 95%CI: â 7.2%, â 1.3%) as per tertile increment in caregiver depression. Higher caregiver social support was associated with lower distress and higher positive outlook (β = 3%; 95%CI:1.4%, 4.5%) in their children. HIVâ infected/exposed children had most caregiver depressionâ related QOL deficit (β = â 5.2%/â 6.8%; 95%CI: â 12.4%, â 0.2%) and HIVâ unexposed children had most caregiver social supportâ related enhancements in positive outlook (β=4.5%; 95%CI:1.9%, 7.1%).ConclusionsCaregiver anxiety, depressive symptoms and low social support were associated with worse wellâ being in schoolâ aged and adolescent children. Improvement of caregiver mental health and strengthening caregiver social support systems may be a viable strategy for improving wellâ being of vulnerable children and adolescents in this setting.ObjectifLes attributs socioâ affectifs des responsables d’enfants sont des déterminants majeurs du bienâ être des enfants. Cette investigation menée auprès d’enfants ougandais vulnérables dâ âge scolaire a estimé les relations entre le bienâ être des enfants et l’anxiété, la dépression et le soutien social de leur responsable.MéthodesDes enfants ougandais infectés par le VIH de manière périnatale, exposés au VIH mais non infectés, et non exposés au VIH ainsi que leurs responsables ont été inscrits. Le statut VIH périnatal a été déterminé à lâ âge de 18 mois à l’aide du test de PCR de lâ ADN; le statut a été confirmé par un test de diagnostic rapide du VIH chez les enfants âgés de 6 à 18 ans. Cinq indicateurs du bienâ être de l’enfant (détresse, désespoir, orientation future positive, estime et qualité de vie (QV)), et le statut psychosocial des responsables (symptômes dépressifs, anxiété et soutien social) ont été mesurés à l’aide de méthodes validées, adaptées à la culture et respectées et d’outils traduits. Des catégories basées sur les tertiles de chaque indicateur psychosocial du responsable ont été définies. Des analyses de régression linéaire ont estimé les différences en pourcentage (β) et les intervalles de confiance (IC) à 95% correspondants pour le bienâ être de l’enfant par rapport au statut psychosocial de leurs responsables.RésultatsPar incrément de tertile, l’anxiété des responsables était associé à 2,7% de détresse plus élevé (IC95%: 0,2%, 5,3%) et de faible estime de soi/QV (β = â 1,3%/â 2,6%; IC95%: â 5,0%, â 0,2%) chez leurs enfants. La détresse et le désespoir des enfants augmentaient (β = 3,3%/7,6%; IC95%: 0,4%, 14,7%) et l’estime de soi/QV diminuait de 2,3% (β = â 2,3%/â 4,4%; IC95%: â 7,2%, â 1,3%) par incrément de tertile de la dépression chez le responsable. Un soutien social plus élevé des responsables était associé à une détresse moindre et à une perspective positive plus élevée (β = 3%; IC95%: 1,4%, 4,5%) chez leurs enfants. Les enfants infectés/exposés au VIH présentaient pour la plupart un déficit de QV lié à la dépression de leurs responsables (β = â 5,2%/â 6,8%; IC95%: â 12,4%, â 0,2%), et ceux non exposés au VIH présentaient pour la plupart des améliorations en perspective positive liées au soutien social de leurs responsables (β = 4,5%; IC95%: 1,9%, 7,1%).ConclusionsL’anxiété, les symptômes dépressifs et un faible soutien social du responsable étaient associés à un bienâ être précaire chez les enfants dâ âge scolaire et les adolescents. L’amélioration de la santé mentale des responsables et le renforcement des systèmes de soutien social pour les responsables peuvent constituer une stratégie viable pour améliorer le bienâ être des enfants et des adolescents vulnérables dans cette région.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149358/1/tmi13221.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149358/2/tmi13221_am.pd

HIV genotypic resistance among pregnant women initiating ART in Uganda: a baseline evaluation of participants in the Option B+ clinical trial

Background: Pre-treatment HIV drug resistance is a threat to elimination of mother to child HIV transmission and could lead to virological failure among HIV-positive pregnant women. We analysed genotypic HIV drug resistance (HIVDR) of baseline samples of participants enrolled in the Option B+ clinical trial in Uganda.Methods: HIV-infected pregnant women attending antenatal care were enrolled from Uganda’s National Referral Hospital (Mulago) and Mityana District general hospital and surrounding health centers (HCs). Genotypic HIV testing was performed on blood samples from the first 135 enrolled women out of a subset of 136 participants (25%) who had a baseline VL>1000 copies/mL as one sample failed to amplify.Results: 159/540 (29.4%) had a VL < 1000 copies/ml and 381/540 (70.6%) had a VL >1,000 copies/ml. Of the women with VL>1000 copies/ml, 32 (23.7%) had resistance mutations including 29/135 (21.5%) NNRTI mutations, 6/135 (4.4%) NRTI mutations and 3/135 (2.2%) had both NNRTI and NRTI mutations. The most common NNRTI resistance mutations were: K103KN (5), K103N (5), V179T (4) and E138A (4).Conclusions: One quarter of the HIV-infected pregnant women in this trial at baseline had NNRTI genotypic resistance mutations. Our findings support new WHO guidelines for first-line ART that were changed to dolutegravir-based regimens

PMTCT Option B+ 2012 to 2018 - Taking stock: barriers and strategies to improve adherence to Option B+ in urban and rural Uganda.

Since 2012, PMTCT Option B+ has been recommended by the World Health Organization to reduce vertical transmission but numerous adherence challenges remain. We conducted a qualitative study at baseline using six focus group discussions and 14 in-depth interviews to explore knowledge, beliefs, attitudes and challenges towards the Option B+ strategy for PMTCT among HIV-infected pregnant and post-partum women and health workers engaged in Uganda's national Option B+ PMTCT programme. Data were analysed using a thematic approach to capture latent and manifest content with the social ecological model as a theoretic foundation in order to make contextual sense of key stakeholders' needs for an effective Option B+ intervention. Overall, among all study participants, we found multi-level barriers to adhering to Option B+ cutting across all levels of the social ecological model. In line with the model, our study revealed barriers at personal, relational, organizational and societal levels. Some personal beliefs such as that the baby's health is more important that the mother's, organizational (negative attitudes and behaviour of health workers), structural such as poverty, work conflicts, fear and lack of disclosure related to community stigma were all critical obstacles to women adhering to the Option B+ programme. We found that both health workers and participants in the programme have a relatively clear understanding of the benefits of adhering to their treatment; though a more nuanced understanding and thus emphasis in counselling on side effects, is critical to helping patients adhere

'When I receive ARVs through my group, my heart settles': Participants' perceptions and experiences of Friends for Life Circles for Option B+ in Kampala and Mityana Districts, Uganda.

The Friends for Life Circles (FLC) was a parallel randomized controlled trial testing the efficacy of a group peer support intervention to support long-term adherence to Option B+ in Kampala and Mityana districts in Uganda. We explored FLC participants' experiences and perceptions of the intervention on adherence to Option B+ for PMTCT and potential implications for strengthening the PMTCT program. We collected data from six focus group discussions with lactating women enrolled in the FLC intervention, and from 14 key informant interviews with health workers, district and national level stakeholders, as well as male partners of FLC participants. Data were analysed using a content thematic approach in a continuous and iterative process. Women described the FLC intervention as acceptable and beneficial in enhancing their understanding of HIV and the need for ART. The FLC helped women, especially those newly diagnosed with HIV infection to come to terms with their diagnosis and overcome the fear of death linked to testing HIV positive, and provided opportunities to enhance ART initiation, resumption and adherence. The FLC provided safe spaces for women, to learn about ART, and to receive support from peers including adherence reminders through home visits and 'coded' reminder messages. Receiving ART from support groups protected members from stigma and long lines at health facilities. Fear of stigma, health system challenges, the high cost of caring for animals and lack of money to save in groups were key challenges noted. The FLC support groups were crucial in providing needed support for women to initiate, resume and adhere to lifelong ART for Option B+. It is important that women who test HIV positive and start ART for life receive psychosocial support from peers and health workers to improve chances of preventing HIV transmission from mothers to children

Effect of dolutegravir on folate, vitamin B12 and mean corpuscular volume levels among children and adolescents with HIV: a sub‐study of the ODYSSEY randomized controlled trial

INTRODUCTION: Dolutegravir-based antiretroviral therapy (ART) is the preferred antiretroviral treatment for children and adolescents living with HIV. A large surveillance study in Botswana previously raised concerns about an association between pre-conception dolutegravir and neural tube defects. Before these concerns were subsequently resolved, we set up a sub-study to look at the effect of dolutegravir on levels of folate and vitamin B12 in children and adolescents within the randomized ODYSSEY trial, as folate and vitamin B12 are known to play a crucial role in neural tube development. METHODS: We conducted the sub-study among Ugandan ODYSSEY participants and compared folate and vitamin B12 between children randomized to dolutegravir-based ART (DTG) and non-dolutegravir-based standard-of-care treatment (SOC). Plasma folate was measured at enrolment and week 4 on stored samples; in addition, plasma and red blood cell (RBC) folate and vitamin B12 were assayed at week ≥96 in prospectively collected samples. RBC mean corpuscular volume (MCV) was measured 24-weekly in all ODYSSEY participants. Samples analysed in the sub-study were collected between September 2016 and October 2020. RESULTS: A total of 229 children aged ≥6 years were included in the sub-study with median age at trial enrolment of 12.3 (interquartile range [IQR] 9.0, 14.7) years, and CD4 count of 501 (IQR 228, 695); 112 (49%) children were male. Most participants (225/229, 98%) had plasma folate results at enrolment and 214 (93%) children had results available for RBC folate, vitamin B12 and plasma folate at week ≥96. MCV results were analysed on 679 children aged ≥6 years enrolled in ODYSSEY. At week 4, mean plasma folate was significantly higher in the dolutegravir arm than in SOC (difference [DTG-SOC] 1.6 ng/ml, 95% CI 0.8, 2.3; p<0.001), and this difference persisted to week ≥96 (2.7 ng/ml, 95% CI 1.7, 3.7; p<0.001). Mean RBC folate at ≥96 weeks was also higher in the DTG arm (difference 73 ng/ml, 95% CI 3, 143; p = 0.041). There was no difference in the treatment arms for vitamin B12 levels at ≥96 weeks or change in MCV through trial follow-up. CONCLUSIONS: Plasma and RBC folate levels were higher in children and adolescents receiving dolutegravir-based ART than on other ART regimens. Further studies are needed to clarify the mechanisms of these interactions and the clinical implications of increased blood folate levels