Uganda has one of the highest rates of cervical cancer in the world. Many women are diagnosed and treated with advanced stages of the disease. With only one facility offering comprehensive cervical cancer care in Uganda, many women are required to travel significant distances and spend time away from their homes to receive cervical cancer care. It is important to understand the burden of time away from home while attending treatment because it can inform the expansion of cervical cancer treatment programmes. The aim of this mixed-methods paper is to describe how the distance to cervical cancer treatment locations impacts women in Uganda. Women were recruited from 19 September, 2022, to 17 January, 2023, at the Uganda Cancer Institute (UCI) and the cancer clinic at Jinja Regional Referral Hospital (JRRF). Women were eligible for the study if they were (i) aged ≥18 years with a histopathologic diagnosis of cervical cancer; (ii) being treated at the UCI or JRRF for cervical cancer; and (iii) able to provide consent to participate in the study in English, Luganda, Lusoga, Luo, or Runyankole. All participants completed a quantitative survey and a selected group was sampled for semi-structured interviews. Data were analysed using the convergent parallel mixed-methods approach. Descriptive statistics were reported for the quantitative data and qualitative data using an inductive-deductive thematic analysis approach. In all, 351 women participated in the quantitative section of the study and 24 in the qualitative. The quantitative and qualitative findings largely aligned and supported one another. Women reported travelling up to 14 h to receive treatment and 20% noted that they would spend three or more nights away from home during their current visit. Major themes of the qualitative include means of transportation, spending the night away from home, and financial factors. Our findings show that travelling to obtain cervical cancer care can be a significant burden for women in Uganda. Approaches should be considered to reduce this burden such as additional satellite cervical cancer clinics or subsidised transportation options.

BackgroundDespite reduction of HIV-associated mortality in children with the implementation of antiretroviral treatment (ART), HIV-associated neurocognitive deficits are still of great concern. These are thought to result mainly from intra-cranial HIV-associated pathology. The contribution of extra-cranial infections like pneumonia is not well described. We compared neurocognitive function between infants living with HIV (ILHIV), with and without severe pneumonia. MethodsThis EDCTP-funded case-control study (TMA2020CDF-3198) was conducted among ILHIV with severe pneumonia enrolled in the EMPIRICAL trial (#NCT03915366) (cases), and age-matched ILHIV without severe pneumonia (controls). We assessed neurocognitive function using the Bayley’s Scales of Infant and Toddler Development-III within 3weeks of hospital discharge or recruitment among cases and controls respectively. We compared demographic and clinical characteristics as well as neurocognitive mean scaled scores between the two groups.ResultsAmong 66 infants (44 cases and 22 controls) included in the study, 36 (54.5%) were male and the median age was 6 months (IQR = 4.47 - 8.98). There was no difference in age (p = 0.83), sex distribution (p = 0.43), prematurity proportions (p = 0.16), breastfeeding (p = 0.56) proportion on ART and its duration, (p = 0.05, and p = 0.07 respectively), viral load (p = 0.28), or hemoglobin (p = 0.06). The cases had lower weight-for-height z-scores than the controls (-1.73 [IQR = -2.68 – 0.44] vs -0.08 [IQR = -1.85 - 0.85] respectively, p = 0.04). There was no difference in family care indicators between groups. Among infants with complete data, the cases (n=40) scored poorer than the controls (n=18) in all neurocognitive domains; cognitive (p = <0.01), language (p = 0.04), and motor (p = <0.01).ConclusionSevere pneumonia increases the likelihood of neurocognitive deficits among ILHIV. Interventions reducing the risk and severity of pneumonia may be beneficial in reducing neurocognitive decline in this population.

BackgroundChildren with advanced HIV disease (AHD) are at an increased risk of morbidity and mortality. We describe mortality rates among infants with AHD hospitalized with severe pneumonia.MethodsEMPIRICAL is an ongoing Phase II-III, open-label randomized factorial (2×2) trial supported by EDCTP (GA RIA2017MC_2013/#NCT03915366) to assess the impact of empirical treatment against cytomegalovirus and tuberculosis in infants living with HIV hospitalized with severe pneumonia. The primary endpoint is all-cause mortality at 15-days and 12-months post enrolment. Recruitment is on-going and includes 22 hospitals from 6 African countries (Côte d’Ivoire, Malawi, Mozambique, Uganda, Zambia, Zimbabwe). ResultsIn March 2023, 431 infants had been recruited and 429 were included in analysis. Their median age was 4.36 months (IQR, 3.18–7.08) and 49% were female; 164 (38%) had a history of maternal and/or infant prophylaxis for prevention-mother-to-child-transmission (PMTCT); 306 (71%) were newly diagnosed of HIV during hospitalization; Median HIV viral load and CD4% were 6.3 logs copies/mL (IQR, 5.8–7.0) and 14.4% (IQR, 9.9–21.6) respectively. 196 (46%) of the infants died within a 6 months follow up period (2.16 months (IQR, 0.26–6.16), 110 (56%) in the first admission and 86 (44%) after it. The main register causes of death are pneumonia 91 (46%), sepsis 32 (16%) and gastroenteritis 10 (5%). An in-depth analysis of deaths is ongoing, including minimally invasive tissue sampling, microbiological and histopathological evaluation.ConclusionChildren living with HIV and severe pneumonia have a very high mortality, both during the initial hospitalization and after hospital discharge. Measures focused on earlier identification and treatment as well as focused on decreasing post-discharge mortality are urgently needed. EMPIRICAL will report on the survival benefit of cytomegalovirus and tuberculosis treatment at trial conclusion. Emphasis should be put into reducing missed opportunities for PMTCT; strengthening early infant diagnosis and antiretrovirals initiation for those who fail PMTCT.

BackgroundInfants living with HIV are at high risk of tuberculosis and death. Optimal antituberculosis therapy is essential for favourable clinical outcomes particularly in severely ill children. Using WHO-recommended weight-band dosing, younger children weighing <8kg are at risk of suboptimal exposures. We aimed to evaluate plasma concentration of first line antituberculosis drugs in infants with HIV. MethodsEMPIRICAL trial (#NCT03915366; EDCTP2-funded (RIA2017MC-2013)) is a randomized controlled trial evaluating empirical antituberculosis and cytomegalovirus treatment in infants with HIV hospitalized for severe pneumonia in 5 African countries. Eligible infants aged <1 year, weighing ≥3kg, on antituberculosis treatment had a blood sample taken 2-hours post-dose at days 30, 90 and 180 in a pharmacokinetic sub-study. Antituberculosis drugs were dosed according to WHO weight-bands using fixed-dose-combination dispersible tablets of rifampicin(15mg/kg)/isoniazid(10mg/kg)/pyrazinamide(35mg/kg) 75/50/150mg with ethambutol(20mg/kg) 100mg. Antiretroviral-naïve infants initiated treatment in accordance with national guidelines. We compared C2hr plasma concentrations for rifampicin, isoniazid, pyrazinamide, and ethambutol with published Cmax references. ResultsForty-nine infants of whom 21 were female, median (range) age 6.1(2.5–13.5) months and weighing 5.3(3.4–8.7) kg were included in the analysis of study day 30. The geometric mean (CV%) C2hr for rifampicin, isoniazid, pyrazinamide and ethambutol were 3.66(161) mg/L, 2.80(102) mg/L, 22.27(97) mg/L, and 0.56(101) mg/L, respectively. The C2hr values were substantially below adult reference Cmax for rifampicin [ref in adults (10 mg/kg dose): 8–24 mg/L] and ethambutol [ref: 2–6 mg/L], slightly lower for isoniazid [ref: 3–6 mg/L], and within range for pyrazinamide [ref: 20–60 mg/L].ConclusionPlasma levels of first-line TB drugs in infants with HIV and severe pneumonia were low compared to adults. This is consistent with other studies showing that infants and younger children do not achieve adult references for first-line TB drugs at current recommended doses. Our data support considerations for optimising dosing of first-line TB drugs for infants.

BackgroundRegional Referral Hospitals (RRHs) are mandated by MoH to conduct research to provide evidence-based care to patients, however most lack the knowledge and skills. These provide mostly tertiary care to patients and serve as referrals for several districts under their catchment. Eastern Africa Consortium for Clinical Research (EACCR) through its HIV work package builds capacity for conducting ICH-GCP complaint research in the region. MethodsTwo RRHs from two regions in Uganda with high volumes of patients were considered: Masaka RRH and Jinja RRH located in Central and Eastern Uganda respectively. ResultsThe needs assessment done to identify the research capacity gaps, showed that the hospitals lacked Institutional review board (IRBs) to guide and evaluate research protocols. Memorandum of understanding were signed between Masaka and Jinja RRHs and the EACCR HIV work package. The parties agreed to train and build capacity of the members of the IRBs to review protocols and establish IRB offices in Masaka and Jinja RRHs.Over 10 staff from each of the two hospitals were trained in good clinical practice, Research management, protocol reviews and research bioethics during pandemics. Masaka RRH had their IRB office refurbished with lockable cabins, a computer, and a printer scanner. The administrators received a one-weeks mentorship attachment to the IRB office at UVRI to learn IRB office operations. The IRB in Masaka and Jinja were guided to develop Standard Operational procedures (SOPs) as reference documents for operations. The IRB Office in Jinja had their office renovated and lockable -movable cabins were installed. All these RRHs are in the process getting accreditation from Uganda National Council of Science and Technology (UNCST). UVRI IRB continues to provide peer mentorship to these two IRBs. ConclusionWhen accredited, the two hospitals will use the patients and cohorts’ data for health research to answer research questions affecting communities in Uganda.

BackgroundCOVID-19, first reported in Wuhan, China in December 2019, was declared a pandemic in March 2020, causing restrictions of movement of people and goods worldwide. This affected every aspect of life, including the conduct of clinical trials. We highlight the challenges faced by the PediCAP consortium and how we navigated them.MethodsThe PediCAP consortium is composed of 14 partners (https://projectpedicap.org/the-consortium/) in Africa and Europe. The EDCTP-funded clinical trial (ISRCTN63115131) is enrolling children aged 2months to 6years with pneumonia in Mozambique, Uganda, South Africa, Zambia and Zimbabwe. Participant recruitment started in December 2020, during the COVID-19 pandemic; and by end of April 2023, 987 of the targeted 1100 participants (89.7%) had been enrolled. The challenges faced by the clinical sites, and measures taken to mitigate them, were obtained from minutes of monthly teleconferences and interviews with site staff, and summarized in themes. ResultsThe following were reported as challenges and their mitigating measures: Delays in obtaining ethical and regulatory approvals: Ethical and regulatory bodies adopted paperless submissions, virtual review meetings, and used online tools to interact with applicants.Slow recruitment of participants resulting from reduction in numbers of patients attending hospitals, due to fear of contracting COVID-19, and lockdowns restricting movement. This was solved by adding a partner and satellite sites. Additionally, a no-cost extension of the project was made to allow for extension of the recruitment period. Site initiation, protocol training, procurement of trial drugs, and clinical trial monitoring were delayed/problematic. The sponsor adopted virtual platforms and local monitors to mitigate this.A need to protect site staff and participants from contracting COVID-19. Country specific COVID-19 risk management plans were developed and implemented.ConclusionCOVID-19 impeded smooth progress of PediCAP trial activities. However, a joint and collaborative effort was key in navigating the challenges.

In low-income country settings, the first six weeks after birth remain a critical period of vulnerability for both mother and newborn. Despite recommendations for routine follow-up after delivery and facility discharge, few mothers and newborns receive guideline recommended care during this period. Prediction modelling of post-delivery outcomes has the potential to improve outcomes for both mother and newborn by identifying high-risk dyads, improving risk communication, and informing a patient-centered approach to postnatal care interventions. This study aims to derive post-discharge risk prediction algorithms that identify mother-newborn dyads who are at risk of re-admission or death in the first six weeks after delivery at a health facility. This prospective observational study will enroll 7,000 mother-newborn dyads from two regional referral hospitals in southwestern and eastern Uganda. Women and adolescent girls aged 12 and above delivering singletons and twins at the study hospitals will be eligible to participate. Candidate predictor variables will be collected prospectively by research nurses. Outcomes will be captured six weeks following delivery through a follow-up phone call, or an in-person visit if not reachable by phone. Two separate sets of prediction models will be built, one set of models for newborn outcomes and one set for maternal outcomes. Derivation of models will be based on optimization of the area under the receiver operator curve (AUROC) and specificity using an elastic net regression modelling approach. Internal validation will be conducted using 10-fold cross-validation. Our focus will be on the development of parsimonious models (5-10 predictor variables) with high sensitivity (>80%). AUROC, sensitivity, and specificity will be reported for each model, along with positive and negative predictive values. The current recommendations for routine postnatal care are largely absent of benefit to most mothers and newborns due to poor adherence. Data-driven improvements to postnatal care can facilitate a more patient-centered approach to such care. Increasing digitization of facility care across low-income settings can further facilitate the integration of prediction algorithms as decision support tools for routine care, leading to improved quality and efficiency. Such strategies are urgently required to improve newborn and maternal postnatal outcomes. https://clinicaltrials.gov/, identifier (NCT05730387).

Birth asphyxia is a leading cause of global neonatal mortality. Most cases occur in low- and middle- income countries and contribute to half of neonatal deaths in Uganda. Improved understanding of the risk factors associated with mortality among these patients is needed. We performed a retrospective cohort study of a clinical database and report maternal demographics, clinical characteristics and outcomes from neonates with birth asphyxia at a Ugandan level two unit from 2014 through 2021. “Inborn” patients were born at the hospital studied and “outborn” were born at another facility or home and then admitted to the hospital studied. Doctors assigned the patient’s primary diagnosis at death or discharge. We performed a Poisson model regression of factors associated with mortality among patients with asphyxia. The study included 1,565 patients with birth asphyxia and the proportion who were outborn rose from 26% to 71% over eight years. Mortality in asphyxiated patients increased over the same period from 9% to 27%. Factors independently associated with increased death included outborn birth location (ARR 2.1, p&lt;0.001), admission in the year 2020 (ARR 2.4, p&lt;0.05) and admission respiratory rate below 30bpm (RR 3.9, p&lt;0.001), oxygen saturation &lt;90% (ARR 2.0, p&lt;0.001) and blood sugar &gt;8.3 mmol/L (RR 1.7, p&lt;0.05). Conversely, a respiratory rate &gt;60bpm was protective against death (ARR 0.6, p&lt;0.05). Increased birth asphyxia mortality at this referral unit was associated with increasing admission of outborn patients. Patients born at another facility and transferred face unique challenges. Increased capacity building at lower-level birth facilities could include improved staffing, training and equipment for labor monitoring and newborn resuscitation as well as training on the timely identification of newborns with birth asphyxia and resources for transfer. These changes may reduce incidence of birth asphyxia, improve outcomes among birth asphyxia patients and help meet global targets for newborn mortality.

Enhancing cervical cancer knowledge among women who have screened for cervical cancer is key to empowering these women to engage in cervical cancer prevention advocacy and acting as change agents for encouraging other women to screen.