Facilitators and barriers to initiating and completing tuberculosis preventive treatment among children and adolescents living with HIV in Uganda: a qualitative study of adolescents, caretakers and health workers.

INTRODUCTION: People living with HIV (PLHIV) have a 20-fold risk of tuberculosis (TB) disease compared to HIV-negative people. In 2021, the uptake of TB preventive treatment among the children and adolescents living with HIV at the Baylor-Uganda HIV clinic was 45%, which was below the national target of 90%. Minimal evidence documents the enablers and barriers to TB preventive treatment (TPT) initiation and completion among children and adolescents living with HIV(CALHIV). We explored the facilitators and barriers to TPT initiation and completion among CALHIV among adolescents aged 10-19years and caretakers of children below 18years. METHODS: We conducted a qualitative study from February 2022 to March 2023, at three paediatric and adolescent HIV treatment centers in Uganda. In-depth interviews were conducted at TPT initiation and after completion for purposively selected health workers, adolescents aged 10-19 years living with HIV, and caretakers of children aged below 18years. RESULTS: The desire to avoid TB disease, previous TB treatment, encouragement from family members, and ministry of health policies emerged as key facilitators for the children and adolescents to initiate TPT. Barriers to TPT initiation included; TB and HIV-related stigma, busy carer and adolescent work schedules, reduced social support from parents and family, history of drug side effects, high pill burden and fatigue, and perception of not being ill. TPT completion was enabled by combined TPT and ART refill visits, delivery of ART and TPT within the community, and continuous education and counseling from health workers. Reported barriers to TPT completion included TB and HIV-related stigma, long waiting time. Non-disclosure of HIV status by caretakers to CALHIV and fear of side effects was cited by health workers as a barrier to starting TPT. Facilitators of TPT initiation and completion reported by healthcare workers included patient and caretaker health education, counselling about benefits of TPT and risk of TB disease, having same appointment for TPT and ART refill to reduce patient waiting time, adolescent-friendly services, and appointment reminder phone calls. CONCLUSION: The facilitators and barriers of TPT initiation and completion among CALHIV span from individual, to health system and structural factors. Health education about benefits of TPT and risk of TB, social support, adolescent-friendly services, and joint appointments for TPT and ART refill are major facilitators of TPT initiation and completion among CALHIV in Uganda.

Patient characteristics and predictors of mortality among children hospitalised with tuberculosis: A six-year case series study in Uganda.

BACKGROUND: The high case-fatality rates among children with tuberculosis (TB) are reportedly driven by in-hospital mortality and severe forms of TB. Therefore, there is need to better understand the predictors of mortality among children hospitalised with TB. We examined the patient clinical profiles, length of hospital stay from date of admission to date of final admission outcome, and predictors of mortality among children hospitalised with TB at two tertiary hospitals in Uganda. METHODS: We conducted a case-series study of children below 15 years of age hospitalised with TB, from January 1st, 2016, to December 31st, 2021. Convenience sampling was done to select TB cases from paper-based medical records at Mulago National Referral Hospital (MNRH) in urban Kampala, and Fort Portal Regional Referral Hospital (FRRH) in rural Fort Portal. We fitted linear and logistic regression models with length of stay and in-hospital mortality as key outcomes. RESULTS: Out of the 201 children hospitalised with TB, 50 were at FRRH, and 151 at MNRH. The male to female ratio was 1.5 with median age of 2.6 years (Interquartile range-IQR 1-6). There was a high prevalence of HIV (67/171, 39%), severe malnutrition reported as weight-for-age Z-score <-3SD (51/168, 30%). Among children with pulmonary TB who initiated anti-tuberculosis therapy (ATT) either during hospitalisation or within seven days prior to hospitalisation; cough (134/143, 94%), fever (111/143, 78%), and dyspnoea (78/143, 55%) were common symptoms. Children with TB meningitis commonly presented with fever (17/24, 71%), convulsions (14/24 58%), and cough (13/24, 54%). The median length of hospital stay was 8 days (IQR 5-15). Of the 199 children with known in-hospital outcomes, 34 (17.1%) died during hospitalisation. TB meningitis was associated with in-hospital mortality (aOR = 3.50, 95% CI = 1.10-11.17, p = 0.035), while male sex was associated with reduced mortality (aOR = 0.33, 95% CI = 0.12-0.95, p = 0.035). Hospitalisation in the urban hospital predicted a 0.48-day increase in natural log-transformed length of hospital stay (ln-length of stay) (95% CI 0.15-0.82, p = 0.005), but not age, sex, HIV, malnutrition, or TB meningitis. CONCLUSIONS: In-hospital mortality was high, and significantly driven almost four times higher by TB meningitis, with longer hospital stay among children in urban hospitals. The high in-hospital mortality and long hospital stay may be reduced by timely TB diagnosis and treatment initiation among 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.

Lived experiences of frontline healthcare providers offering maternal and newborn services amidst the novel corona virus disease 19 pandemic in Uganda: A qualitative study.

BACKGROUND: The COVID-19 pandemic has brought many health systems in low resource settings to their knees. The pandemic has had crippling effects on the already strained health systems in provision of maternal and newborn healthcare. With the travel restrictions, social distancing associated with the containment of theCOVID-19 pandemic, healthcare providers could be faced with challenges of accessing their work stations, and risked burnout as they offered maternal and newborn services. This study sought to understand the experiences and perceptions of healthcare providers at the frontline during the first phase of the lockdown as they offered maternal and newborn health care services in both public and private health facilities in Uganda with the aim of streamlining patient care in face of the current COVID-19 pandemic and in future disasters. METHODS: Between June 2020 and December 2020, 25 in-depth interviews were conducted among healthcare providers of different cadres in eight Public, Private-Not-for Profit and Private Health facilities in Kampala, Uganda. The interview guide primarily explored the lived experiences of healthcare providers as they offered maternal and newborn healthcare services during the COVID-19 pandemic. All of the in depth interviews were audio recorded and transcribed verbatim. Themes and subthemes were identified using both inductive thematic and phenomenological approaches. RESULTS: The content analysis of the in depth interviews revealed that the facilitators of maternal and newborn care service delivery among the healthcare providers during the COVID-19 pandemic included; salary bonuses, the passion to serve their patients, availability of accommodation during the pandemic, transportation to and from the health facilities by the health facilities, teamwork, fear of losing their jobs and fear of litigation if something went wrong with the mothers or their babies. The barriers to their service delivery included; lack of transport means to access their work stations, fear of contracting COVID-19 and transmitting it to their family members, salary cuts, loss of jobs especially in the private health facilities, closure of the non-essential services to combat high patient numbers, inadequate supply of Personal Protective equipment (PPE), being put in isolation or quarantine for two weeks which meant no earning, brutality from the security personnel during curfew hours and burnout from long hours of work and high patient turnovers. CONCLUSION: The COVID-19 Pandemic has led to a decline in quality of maternal and newborn service delivery by the healthcare providers as evidenced by shorter consultation time and failure to keep appointments to attend to patients. Challenges with transport, fears of losing jobs and fear of contracting COVID-19 with the limited access to personal protective equipment affected majority of the participants. The healthcare providers in Uganda despite the limitations imposed by the COVID-19 pandemic are driven by the inherent passion to serve their patients. Availability of accommodation and transport at the health facilities, provision of PPE, bonuses and inter professional teamwork are critical motivators that needed to be tapped to drive teams during the current and future pandemics.

Incidence, associated risk factors, and the ideal mode of delivery following preterm labour between 24 to 28 weeks of gestation in a low resource setting.

BACKGROUND: Preterm labour, between 24 to 28 weeks of gestation, remains prevalent in low resource settings. There is evidence of improved survival after 24 weeks though the ideal mode of delivery remains unclear. There are no clear management protocols to guide patient management. We sought to determine the incidence of preterm labour occurring between 24 to 28 weeks, its associated risk factors and the preferred mode of delivery in a low resource setting with the aim of streamlining patient care. METHODS: Between February 2020 and September 2020, we prospectively followed 392 women with preterm labour between 24 to 28 weeks of gestation and their newborns from admission to discharge at Kawempe National Referral hospital in Kampala, Uganda. The primary outcome was perinatal mortality associated with the different modes of delivery. Secondary outcomes included neonatal and maternal infections, admission to the Neonatal Special Care Unit (SCU), need for neonatal resuscitation, preterm birth and maternal death. Chi-square test was used to assess the association between perinatal mortality and categorical variables such as parity, mode of delivery, employment status, age, antepartum hemorrhage, digital vaginal examination, and admission to Special Care unit. Multivariate logistic regression was used to assess the association between comparative outcomes of the different modes of delivery and maternal and neonatal risk factors. RESULTS: The incidence of preterm labour among women who delivered preterm babies between 24 to 28 weeks was 68.9% 95% CI 64.2-73.4). Preterm deliveries between 24 to 28 weeks contributed 20% of the all preterm deliveries and 2.5% of the total hospital deliveries. Preterm labour was independently associated with gravidity (p-value = 0.038), whether labour was medically induced (p-value <0.001), number of digital examinations (p-value <0.001), history of vaginal bleeding prior to onset of labour (p-value < 0.001), whether tocolytics were given (p-value < 0.001), whether an obstetric ultrasound scan was done (p-value <0.001 and number of babies carried (p-value < 0.001). At multivariate analysis; multiple pregnancy OR 15.45 (2.00-119.53), p-value < 0.001, presence of fever prior to admission OR 4.03 (95% CI .23-13.23), p-value = 0.002 and duration of drainage of liquor OR 0.16 (0.03-0.87), p-value = 0.034 were independently associated with preterm labour. The perinatal mortality rate in our study was 778 per 1000 live births. Of the 392 participants, 359 (91.5%), had vaginal delivery, 29 (7.3%) underwent Caesarean delivery and 4 (1%) had assisted vaginal delivery. Caesarean delivery was protective against perinatal mortality compared to vaginal delivery OR = 0.36, 95% CI 0.14-0.82, p-value = 0.017). The other protective factors included receiving antenatal corticosteroids OR = 0.57, 95% CI 0.33-0.98, p-value = 0.040, Doing 3-4 digital exams per day, OR = 0.41, 95% 0.18-0.91, p-value = 0.028) and hospital stay of > 7 days, p value = 0.001. Vaginal delivery was associated with maternal infections, postpartum hemorrhage, and admission to the Special Care Unit. CONCLUSION: Caesarean delivery is the preferred mode of delivery for preterm deliveries between 24 to 28 weeks of gestation especially when labour is not established in low resource settings. It is associated with lesser adverse pregnancy outcomes when compared to vaginal delivery for remote gestation ages.

Impact of mode of delivery on pregnancy outcomes in women with premature rupture of membranes after 28 weeks of gestation in a low-resource setting: A prospective cohort study.

BACKGROUND: Despite the high prevalence of premature rupture of membranes (PROM) in low-resource settings, the preferred mode of delivery remains unclear. We compared the perinatal mortality in a prospective cohort of women with PROM after 28 weeks following vaginal or caesarean delivery at Mulago Hospital with the aim of adopting evidence based practice and improving patient care. METHODS: Between November 2015 and May 2016, 1455 women with PROM after 28 weeks of gestation and their newborns were prospectively followed from admission to discharge at Mulago Hospital. The primary outcome was perinatal mortality. Secondary neonatal outcomes included sepsis and admission to the Special Care Unit. Maternal outcomes included maternal deaths and complications. Outcomes were compared between women who had vaginal vs. caesarean delivery using multivariable logistic regression. All statistical tests were 2-sided with the level of statistical significance set at p < 0.05. RESULTS: The incidence of PROM was 12.1%. The perinatal mortality following PROM was 65 per 1000 live births. Of the 1425 women with PROM, 991 (69.5%) had vaginal delivery and 434 (30.5%) underwent Caesarean section. There was no statistical difference in perinatal mortality by the mode of delivery (vaginal vs. caesarean) in PROM (p = 0.12). The risk factors for perinatal mortality included chorioamnionitis, failure to administer corticosteroids in preterm PROM, gestational age (28-33 weeks), duration of drainage of liquor (24-48 hours), and presence of maternal complications. Caesarean delivery was associated with increased maternal postpartum infections, admission to the Special Care Unit and maternal death. CONCLUSION: In low resource settings, vaginal delivery is the preferred mode of delivery for PROM after 28 weeks gestation. It is associated with lesser maternal and perinatal morbidity when compared to caesarean delivery.