Epicentre Uganda

BackgroundIn low-resource settings, limited laboratory capacity adds to the burden of central nervous system (CNS) infections in children and spurs overuse of antibiotics. The commercially available BioFire® FilmArray® Meningitis/Encephalitis Panel (FA-ME) with its capability to simultaneously detect 14 pathogens in cerebrospinal fluid (CSF), could potentially narrow such a diagnostic gap.MethodsIn Mbarara, Uganda, we compared clinical utility (clinical turnaround time [cTAT], microbial yield, and influence on patient outcome and antibiotic exposure) of FA-ME with bacterial culture, in children 0–12 years with suspected CNS infection.ResultsOf 212 enrolled children, CSF was sampled from 194. All samples underwent bacterial culture, of which 193 also underwent FA-ME analyses. FA-ME analyses prospectively influenced care for 169 of the 193 patients, and they constituted an ‘Index group’. The remaining 43/212 patients constituted a ‘Reference group’. Of all 194 CSF-sampled patients, 87% (168) had received antibiotics before lumbar puncture. Median cTAT for FA-ME was 4.2 h, vs. two days for culture. Bacterial yield was 12% (24/193) and 1.5% (3/194) for FA-ME and culture, respectively. FA-ME viral yield was 12% (23/193). Fatality rate was 14% in the Index group vs. 19% in the Reference group (P = 0.20). From clinician receival of FA-ME results, median antibiotic exposure was 6 days for bacteria-negative vs. 13 days for bacteria-positive patients (P = 0.03). Median hospitalization duration was 7 vs. 12 days for FA-ME negative and positive patients, respectively (P < 0.01).ConclusionsIn this setting, clinical FA-ME utility was found in a higher and faster microbial yield and shortened hospitalization and antibiotic exposure of patients without CSF pathology. More epidemiologically customized pathogen panels may increase FA-ME utility locally, although its use in similar settings would require major cost reductions.Trial registrationThe trial was registered with clinicaltrials.gov (NCT03900091) in March 2019, and its protocol was published in November 2020.

BackgroundDeaths occurring during the neonatal period contribute close to half of under-five mortality rate (U5MR); over 80% of these deaths occur in low- and middle-income countries (LMICs). Poor maternal antepartum and perinatal health predisposes newborns to low birth weight (LBW), birth asphyxia, and infections which increase the newborn’s risk of death.MethodsThe objective of the study was to assess the association between abnormal postpartum maternal temperature and early infant outcomes, specifically illness requiring hospitalisation or leading to death between birth and six weeks’ age. We prospectively studied a cohort of neonates born at Mbarara Regional Referral Hospital in Uganda to mothers with abnormal postpartum temperature and followed them longitudinally through early infancy. We performed a logistic regression of the relationship between maternal abnormal temperature and six-week infant hospitalization, adjusting for gestational age and 10-minute APGAR score at birth.ResultsOf the 648 postpartum participants from the parent study who agreed to enrol their neonates in the sub-study, 100 (15%) mothers had abnormal temperature. The mean maternal age was 24.6 (SD 5.3) years, and the mean parity was 2.3 (SD 1.5). There were more preterm babies born to mothers with abnormal maternal temperature (10%) compared to 1.1% to mothers with normal temperature (p=˂0.001). While the majority of newborns (92%) had a 10-minute APGAR score > 7, 14% of newborns whose mothers had abnormal temperatures had APGAR score ˂7 compared to 7% of those born to mothers with normal postpartum temperatures (P = 0.02). Six-week outcome data was available for 545 women and their infants. In the logistic regression model adjusted for gestational age at birth and 10-minute APGAR score, maternal abnormal temperature was not significantly associated with the composite adverse infant health outcome (being unwell or dead) between birth and six weeks’ age (aOR = 0.35, 95% CI 0.07–1.79, P = 0.21). The 10-minute APGAR score was significantly associated with adverse six-week outcome (P < 0.01).ConclusionsWhile our results do not demonstrate an association between abnormal maternal temperature and newborn and early infant outcomes, good routine neonate care should be emphasized, and the infants should be observed for any abnormal findings that may warrant further assessment.Target journalBMC Pregnancy and Childbirth (https://bmcpregnancychildbirth.biomedcentral.com/).

BackgroundThere are well-recognised ethical guidelines for biomedical research, though a lack of specific guidance for studies targeting healthy volunteers. Noting this, the Ethics Committee of the French National Institute for Health and Medical Research (Inserm) convened an initiative to propose elaboration of good practices to protect health volunteers in research, VolREthics. Online discussions and workshops were held at international and regional levels since February 2022 to debate experiences and best practices. This abstract presents the summary of findings from the African regional perspective.MethodsAn online Sub-Saharan Africa workshop was convened in May 2022. A pre-workshop questionnaire to capture the regional context better was distributed, and notes during the event taken. Feedback from all regional meetings and plans for developing international guidance were discussed at a workshop in Brussels, April 2023, with representatives from regulatory agencies, manufacturers, research institutions and funders, ethicists and healthy volunteers.Results78 people from 21 (14 African) countries and 3 healthy volunteers attended the African workshop, 39 completing questionnaires. Concerns raised included inadequate community engagement, informed consent, feedback of results and guidance on/compensation for secondary use of data, plus economic and/or educational vulnerability of participants. The risk of exploitation or harm, and potential for compromised scientific validity of studies was also mentioned. Proposed solutions were better oversight through legislation and competent ethics committees, national guidelines for compensation, appropriate conditions for confinement, improved dialogue between stakeholders, and innovative learning and engagement to build trust in collaboration with relevant partners such as The Global Health Network’s African communities of practices. ConclusionThis important initiative has established momentum for closing gaps in how studies enrolling healthy volunteers are conducted ethically and equitably. Further discussions with colleagues from other regions involved in VolREthics should enrich the approach toward sound good practices.Sponsorship: European Commission, EDCTP, Inserm, Anrs-Inserm, EEIdF

INTRODUCTION.Several studies indicate that infection with helminths might modulate the immune response towards intracellular pathogens including Plasmodium.We recently reported that in rural villages of Burkina Faso the seroprevalence of Strongyloides stercoralis, Wuchereria bancrofti and Schistosoma haematobium was 5%, 16% and 63% respectively, in line with estimates of infection prevalence in the region for the three parasites.The aim of the present investigation was to assess the impact of serological markers of S. hematobium infection on the prospective risk of Plasmodium falciparum parasitaemia among study populations, using a repeated cross-sectional surveys design.MATERIALS AND METHODS.IgM and IgG against S. haematobium Soluble Worm Antigen Protein (SWAP) and Soluble Egg Antigen (SEA) were measured by an in-house ELISA protocol in plasma samples collected from N=452 subjects.Statistical analysis was performed using STATAv13.Association analysis between the presence of S. haematobium-specific antibodies at baseline and the number of P. falciparum infections over 5 surveys was conducted using Poisson regression adjusting for age, sex, ethnicity and haemoglobin genotype.RESULTS AND CONCLUSIONS.Association analysis showed a significant increase in the incidence of P. falciparum infections among anti-S.haematobiumseropositive subjects (IRR=1.30,95%CI= 1.09-1.57,p-value= 0.004).These observations are in line with those of a systematic review and meta-analysis indicating an association between S. haematobium infection and increased prevalence of P. falciparum asymptomatic/uncomplicated malaria.

Barriers continue to limit access to viral load (VL) monitoring across sub-Saharan Africa adversely impacting control of the HIV epidemic. The objective of this study was to determine whether the systems and processes required to realize the potential of rapid molecular technology are available at a prototypical lower-level (i.e., level III) health center in rural Uganda. In this open-label pilot study, participants underwent parallel VL testing at both the central laboratory (i.e., standard of care) and on-site using the GeneXpert HIV-1 assay. The primary outcome was the number of VL tests completed each clinic day. Secondary outcomes included the number of days from sample collection to receipt of result at clinic and the number of days from sample collection to patient receipt of the result. From August 2020 to July 2021, we enrolled a total of 242 participants. The median number of daily tests performed on the Xpert platform was 4, (IQR = 2-7). Time from sample collection to result was 51 days (IQR = 45-62) for samples sent to the central laboratory and 0 days (IQR = 0-0.25) for the Xpert assay conducted at the health center. However, few participants elected to receive results by one of the expedited options, which contributed to similar time-to-patient between testing approaches (89 versus 84 days, p = 0.07). Implementation of a rapid, near point-of-care VL assay at a lower-level health center in rural Uganda appears feasible, but interventions to promote rapid clinical response and influence patient preferences about result receipt require further study. Trial registration: ClinicalTrials.gov Identifier: NCT04517825, Registered 18 August 2020. Available at: https://clinicaltrials.gov/ct2/show/NCT04517825.

BackgroundRapid diagnostic tests (RDT) for malaria are the primary tool for malaria diagnosis in sub-Saharan Africa but the utility of the most commonly used histidine-rich protein 2 (HRP2) antigen-based tests is limited in high transmission settings due to the long duration of positivity after successful malaria treatment. HRP2 tests are also threatened by the emergence of Plasmodium that do not carry pfhrp2 or pfhrp 3 genes. Plasmodium lactate dehydrogenase (pLDH)-based tests are promising alternatives, but less available. This study assessed the performances of HRP2 and pLDH(pan) tests under field conditions.MethodsThe study performed a prospective facility-based diagnostic evaluation of two malaria RDTs in Aweil, South Sudan, during the high transmission season. Capillary blood by fingerprick was collected from 800 children under 15 years of age with fever and no signs of severity. SD Bioline HRP2 and CareStart pLDH(pan) RDTs were performed in parallel, thick and thin smears for microscopy were examined, and dried blood was used for PCR testing.ResultsUsing microscopy as the gold standard, the sensitivity of both tests was estimated at > 99%, but the specificity of each was lower: 55.0% for the pLDH test and 61.7% for the HRP2 test. When using PCR as the gold standard, the sensitivity of both tests was lower than the values assessed using microscopy (97.0% for pLDH and 96.5% for HRP2), but the specificity increased (65.1% for pLDH and 72.9% for HRP2). Performance was similar across different production lots, sex, and age. Specificity of both the pLDH and HRP2 tests was significantly lower in children who reported taking a therapeutic course of anti-malarials in the 2 months prior to enrollment. The prevalence of pfhrp2/3 deletions in the study population was 0.6%.ConclusionsThe low specificity of the pLDH RDT in this setting confirms previous results and suggests a problem with this specific test. The prevalence of pfhrp2/3 deletions in the study area warrants continued monitoring and underscores the relevance of assessing deletion prevalence nationally. Improved malaria RDTs for high-transmission environments are needed.

Non-sputum based diagnostic approaches are crucial in children at high risk of disseminated tuberculosis [TB] who cannot expectorate sputum. We evaluated the diagnostic accuracy of Xpert MTB/RIF from stool and urine AlereLipoarabinomannan [LAM] test in this group of children. Hospitalised children with presumptive TB and either age <2 years, HIV-positive or severe malnutrition were enrolled in a diagnostic cohort. At enrolment, we attempted to collect two urine, two stool and two respiratory samples. Urine and stool were tested with AlereLAM and Xpert MTB/RIF, respectively. Respiratory samples were tested with Xpert MTB/RIF and mycobacterial culture. Both a microbiological and a composite clinical reference standard were used. The study enrolled 219 children; median age 16.4 months, 72 (32.9%) HIV-positive and 184 (84.4%) severely malnourished. Twelve (5.5%) and 58 (28.5%) children had confirmed and unconfirmed TB respectively. Stool and urine were collected in 219 (100%) and 216 (98.6%) children. Against the microbiological reference standard the sensitivity and specificity (n/N, 95% confidence intervals) of stool Xpert MTB/RIF was 50.0% (6/12, 21.1-78.9) and 99.1% (198/200 96.4-99.9), while that of urine AlereLAM was 50.0% (6/12, 21.1-78.9) and 74.6% (147/197, 67.9-80.5) respectively. Against the composite reference standard sensitivity was reduced to 11.4% (8/70) for stool and 26.2% (17/68) for urine, with no major difference by age group (<2 and >2 years) or HIV status. The Xpert MTB/RIF assay has excellent specificity on stool, but sensitivity is suboptimal. Urine AlereLAM is compromised by poor sensitivity and specificity in children.

BackgroundAlthough ≈70% of the world's population of people living with HIV reside in sub‐Saharan Africa, there are minimal prospective data on the contributions of HIV infection to atherosclerosis in the region.Methods and ResultsWe conducted a prospective observational cohort study of people living with HIV on antiretroviral therapy >40 years of age in rural Uganda, along with population‐based comparators not infected with HIV. We collected data on cardiovascular disease risk factors and carotid ultrasound measurements annually. We fitted linear mixed effects models, adjusted for cardiovascular disease risk factors, to estimate the association between HIV serostatus and progression of carotid intima media thickness (cIMT). We enrolled 155 people living with HIV and 154 individuals not infected with HIV and collected cIMT images at 1045 visits during a median of 4 annual visits per participant (interquartile range 3–4, range 1–5). Age (median 50.9 years) and sex (49% female) were similar by HIV serostatus. At enrollment, there was no difference in mean cIMT by HIV serostatus (0.665 versus 0.680 mm, P=0.15). In multivariable models, increasing age, blood pressure, and non–high‐density lipoprotein cholesterol were associated with greater cIMT (P<0.05), however change in cIMT per year was also no different by HIV serostatus (0.004 mm/year for HIV negative [95% CI, 0.001–0.007 mm], 0.006 mm/year for people living with HIV [95% CI, 0.003–0.008 mm], HIV×time interaction P=0.25).ConclusionsIn rural Uganda, treated HIV infection was not associated with faster cIMT progression. These results do not support classification of treated HIV infection as a risk factor for subclinical atherosclerosis progression in rural sub‐Saharan Africa.RegistrationURL: https://www.ClinicalTrials.gov; Unique identifier: NCT02445079.