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Item Comparison of the penile microbiome in infant male circumcision: Mogen clamp versus Shangring(Elsevier B.V, 2024-07) Salazar, Juan E; Park, Daniel E; Punjani, Nahid; Pham, Tony; Aziz, Maliha; Kigozi, Godfrey; Gray, Ronald H.; Kiboneka, Stephen D; Goldstein, Marc; Li, Philip S; Lee, Richard; Liu, Cindy M.This study aimed to characterise the infant penile (coronal sulcus) microbiome and the effects of early infant male circumcision (EIMC), following a standard surgical method (Mogen Clamp) and a non-surgical alternative (ShangRing). We collected coronal sulcus swabs at baseline and on days 7 and 14 post-circumcision from infants assigned to receive EIMC by Mogen Clamp (n = 15) or ShangRing (n = 15), in a randomised trial in Rakai and Kakuuto, Uganda. We used 16S rRNA gene-based sequencing and broad-coverage qPCR to characterise the infant penile microbiome and assess the effects of EIMC in both study arms. Prior to EIMC, the infant penile microbiome had a mixture of facultative and strict anaerobes. In both study arms, EIMC caused penile microbiome proportional abundance changes characterised by decreases in penile anaerobes [ShangRing Prevotella: −15.0%, (SD = 19.1); Mogen clamp Prevotella: −3.6% (11.2); ShangRing Veillonella: −11.3% (17.2); Mogen clamp Veillonella: −2.6% (11.8)] and increases in skin-associated facultative anaerobes [ShangRing Corynebacterium: 24.9%, (22.4); Mogen clamp Corynebacterium: 4.7% (21.3); ShangRing Staphylococcus: 21.1% (20.5); Mogen clamp Staphylococcus: 18.1% (20.1)]. Clostridium tetani was not detected during the study. Mogen Clamp and ShangRing EIMC both changed the composition of the infant penile microbiome by reducing the proportional abundances of anaerobes and uropathogens, which is consistent with medical male circumcision findings in adults. C. tetani was not increased by either EIMC method. Bill and Melinda Gates Foundation.Item Death after cure: Mortality among pulmonary tuberculosis survivors in rural Uganda Joseph Baruch Baluku Brenda Namanda Sharon Namiiro Aggrey Byaruhang(Elsevier Ltd, 2024-07) Baluku, Joseph Baruch; Namanda, Brenda; Namiiro, Sharon; Rwabwera, Diana Karungi; Mwesigwa, Gloria; Namaara, Catherine; Twinomugisha, Bright; Nyirazihawe, Isabella; Nuwagira, Edwin; Kansiime, Grace; Kizito, Enock; Nabukenya-Mudiope, Mary G; Sekadde, Moorine Penninah; Bongomin, Felix; Senfuka, Joshua; Olum, Ronald; Byaruhanga, Aggrey; Munabi, Ian; Kiguli, SarahObjectives: To determine the incidence of mortality and its predictors among pulmonary tuberculosis (PTB) survivors treated at a rural Ugandan tertiary hospital. Methods: We conducted a retrospective chart review of data between 2013 and 2023. We included all people that met the World Health Organisation's definition of tuberculosis cure and traced them or their next of kin to determine vital status (alive/deceased). We estimated the cumulative incidence of mortality per 1000 population, crude all-cause mortality rate per 1000 person-years, and median years of potential life lost for deceased individuals. Using Cox proportional hazard models, we investigated predictors of mortality. Results: Of 334 PTB survivors enrolled, 38 (11.4%) had died. The cumulative incidence of all-cause mortality was 113.7 per 1000 population, and the crude all-cause mortality rate was 28.5 per 1000 person-years. The median years of potential life lost for deceased individuals was 23.8 years (IQR: 9.6-32.8). Hospitalization (adjusted hazard ratio (aHR): 4.3, 95% CI: 1.1-16.6) and unemployment (aHR: 7.04, 95% CI: 1.5-31.6) at TB treatment initiation predicted mortality. Conclusion: PTB survivors experience post high mortality rates after TB cure. Survivors who were hospitalized and unemployed at treatment initiation were more likely to die after cure. Social protection measures and long-term follow-up of previously hospitalized patients could improve the long-term survival of TB survivors.Item Doxycycline for the treatment of nodding syndrome: a randomised, placebo-controlled, phase 2 trial(Elsevier Ltd, 2024-07) Idro, Richard; Ogwang, Rodney; Anguzu, Ronald; Akun, Pamela; Ningwa, Albert; Abbo, Catherine; Giannoccaro, Maria P; Kubofcik, Joseph; Mwaka, Amos D; Nakamya, Phellister; Opar, Bernard; Taylor, Mark; Nutman, Thomas B; Elliott, Alison; Vincent, Angela; Newton, Charles R; Marsh, KevinNodding syndrome is a poorly understood neurological disorder that predominantly occurs in Africa. We hypothesised that nodding syndrome is a neuroinflammatory disorder, induced by antibodies to Onchocerca volvulus or its Wolbachia symbiont, cross-reacting with host neuronal proteins (HNPs), and that doxycycline can be used as treatment.BACKGROUNDNodding syndrome is a poorly understood neurological disorder that predominantly occurs in Africa. We hypothesised that nodding syndrome is a neuroinflammatory disorder, induced by antibodies to Onchocerca volvulus or its Wolbachia symbiont, cross-reacting with host neuronal proteins (HNPs), and that doxycycline can be used as treatment.In this randomised, double-blind, placebo-controlled, phase 2 trial, we recruited participants from districts affected by nodding syndrome in northern Uganda. We included children and adolescents aged 8-18 years with nodding syndrome, as defined by WHO consensus criteria. Participants were randomly assigned (1:1) to receive either 100 mg doxycycline daily or placebo for 6 weeks via a computer-generated schedule stratified by skin microscopy results, and all parties were masked to group assignment. Diagnoses of O volvulus and antibodies to HNPs were made using luciferase immunoprecipitation system assays and immunohistochemistry. The primary outcome was change in the proportion with antibodies to HNPs, assessed at 24 months. All participants were included in safety analyses, and surviving participants (those with samples at 24 months) were included in primary analyses. Secondary outcomes were: change in concentrations of antibodies to HNPs at 24 months compared with baseline; proportion of participants testing positive for antibodies to O volvulus-specific proteins and concentrations of Ov16 or OVOC3261 antibodies at 24 months compared with baseline; change in seizure burden, proportion achieving seizure freedom, and the proportions with interictal epileptiform discharges on the diagnostic EEG; overall quality of life; disease severity at 24 months; and incidence of all-cause adverse events, serious adverse events, and seizure-related mortality by 24 months. This trial is registered with ClinicalTrials.gov, NCT02850913.METHODSIn this randomised, double-blind, placebo-controlled, phase 2 trial, we recruited participants from districts affected by nodding syndrome in northern Uganda. We included children and adolescents aged 8-18 years with nodding syndrome, as defined by WHO consensus criteria. Participants were randomly assigned (1:1) to receive either 100 mg doxycycline daily or placebo for 6 weeks via a computer-generated schedule stratified by skin microscopy results, and all parties were masked to group assignment. Diagnoses of O volvulus and antibodies to HNPs were made using luciferase immunoprecipitation system assays and immunohistochemistry. The primary outcome was change in the proportion with antibodies to HNPs, assessed at 24 months. All participants were included in safety analyses, and surviving participants (those with samples at 24 months) were included in primary analyses. Secondary outcomes were: change in concentrations of antibodies to HNPs at 24 months compared with baseline; proportion of participants testing positive for antibodies to O volvulus-specific proteins and concentrations of Ov16 or OVOC3261 antibodies at 24 months compared with baseline; change in seizure burden, proportion achieving seizure freedom, and the proportions with interictal epileptiform discharges on the diagnostic EEG; overall quality of life; disease severity at 24 months; and incidence of all-cause adverse events, serious adverse events, and seizure-related mortality by 24 months. This trial is registered with ClinicalTrials.gov, NCT02850913.Between Sept 1, 2016, and Aug 31, 2018, 329 children and adolescents were screened, of whom 240 were included in the study. 140 (58%) participants were boys and 100 (42%) were girls. 120 (50%) participants were allocated to receive doxycycline and 120 (50%) to receive placebo. At recruitment, the median duration of symptoms was 9 years (IQR 6-10); 232 (97%) participants had O volvulus-specific antibodies and 157 (65%) had autoantibodies to HNPs. The most common plasma autoantibodies were to human protein deglycase DJ-1 (85 [35%] participants) and leiomodin-1 (77 [32%] participants) and, in cerebrospinal fluid (CSF), to human DJ-1 (27 [11%] participants) and leiomodin-1 (14 [6%] participants). On immunohistochemistry, 46 (19%) participants had CSF autoantibodies to HNPs, including leiomodin-1 (26 [11%]), γ-aminobutyric acid B receptors (two [<1%]), CASPR2 (one [<1%]), or unknown targets (28 [12%]). At 24 months, 161 (72%) of 225 participants had antibodies to HNPs compared with 157 (65%) of 240 at baseline. 6 weeks of doxycycline did not affect the concentration of autoantibodies to HNPs, seizure control, disease severity, or quality of life at the 24-month follow-up but substantially decreased Ov16 antibody concentrations; the median plasma signal-to-noise Ov16 ratio was 16·4 (95% CI 6·4-38·4), compared with 27·9 (8·2-65·8; p=0·033) for placebo. 14 (6%) participants died and, other than one traffic death, all deaths were seizure-related. Acute seizure-related hospitalisations (rate ratio [RR] 0·43 [95% CI 0·20-0·94], p=0·028) and deaths (RR 0·46 [0·24-0·89], p=0·028) were significantly lower in the doxycycline group. At 24 months, 96 (84%) of 114 participants who received doxycycline tested positive for antibodies to Ov16, compared with 97 (87%) of 111 on placebo (p=0·50), and 74 (65%) participants on doxycycline tested positive for antibodies to OVOC3261, compared with 57 (51%) on placebo (p=0·039). Doxycycline was safe; there was no difference in the incidence of grade 3-5 adverse events across the two groups.FINDINGSBetween Sept 1, 2016, and Aug 31, 2018, 329 children and adolescents were screened, of whom 240 were included in the study. 140 (58%) participants were boys and 100 (42%) were girls. 120 (50%) participants were allocated to receive doxycycline and 120 (50%) to receive placebo. At recruitment, the median duration of symptoms was 9 years (IQR 6-10); 232 (97%) participants had O volvulus-specific antibodies and 157 (65%) had autoantibodies to HNPs. The most common plasma autoantibodies were to human protein deglycase DJ-1 (85 [35%] participants) and leiomodin-1 (77 [32%] participants) and, in cerebrospinal fluid (CSF), to human DJ-1 (27 [11%] participants) and leiomodin-1 (14 [6%] participants). On immunohistochemistry, 46 (19%) participants had CSF autoantibodies to HNPs, including leiomodin-1 (26 [11%]), γ-aminobutyric acid B receptors (two [<1%]), CASPR2 (one [<1%]), or unknown targets (28 [12%]). At 24 months, 161 (72%) of 225 participants had antibodies to HNPs compared with 157 (65%) of 240 at baseline. 6 weeks of doxycycline did not affect the concentration of autoantibodies to HNPs, seizure control, disease severity, or quality of life at the 24-month follow-up but substantially decreased Ov16 antibody concentrations; the median plasma signal-to-noise Ov16 ratio was 16·4 (95% CI 6·4-38·4), compared with 27·9 (8·2-65·8; p=0·033) for placebo. 14 (6%) participants died and, other than one traffic death, all deaths were seizure-related. Acute seizure-related hospitalisations (rate ratio [RR] 0·43 [95% CI 0·20-0·94], p=0·028) and deaths (RR 0·46 [0·24-0·89], p=0·028) were significantly lower in the doxycycline group. At 24 months, 96 (84%) of 114 participants who received doxycycline tested positive for antibodies to Ov16, compared with 97 (87%) of 111 on placebo (p=0·50), and 74 (65%) participants on doxycycline tested positive for antibodies to OVOC3261, compared with 57 (51%) on placebo (p=0·039). Doxycycline was safe; there was no difference in the incidence of grade 3-5 adverse events across the two groups.Nodding syndrome is strongly associated with O volvulus and the pathogenesis is probably mediated through an O volvulus induced autoantibody response to multiple proteins. Although it did not reverse disease symptoms, doxycycline or another prophylactic antibiotic could be considered as adjunct therapy to antiseizure medication, as it might reduce fatal complications from acute seizures and status epilepticus induced by febrile infections.INTERPRETATIONNodding syndrome is strongly associated with O volvulus and the pathogenesis is probably mediated through an O volvulus induced autoantibody response to multiple proteins. Although it did not reverse disease symptoms, doxycycline or another prophylactic antibiotic could be considered as adjunct therapy to antiseizure medication, as it might reduce fatal complications from acute seizures and status epilepticus induced by febrile infections.Medical Research Council (UK).FUNDINGMedical Research Council (UK).For the Luo translation of the abstract see Supplementary Materials section.TRANSLATIONFor the Luo translation of the abstract see Supplementary Materials section. MEDLINE - AcademicItem Characterization of urinary metabolites associated with malaria infection using infra‑red spectroscopy and liquid chromatography–mass spectrometry in South Western Uganda(2024-07) Birungi, Grace; Achar, Joan Beryl; Byamugisha, DenisEarly malaria diagnosis improves outcomes during malaria treatment; routine diagnostic techniques rely on blood samples obtained invasively. Therefore, this study used infra-red (IR) spectroscopy coupled with Principle Component Analysis (PCA) to study the urinary profile of malaria patients and that of controls aimed at understanding metabolite perturbation during malaria infection so as to contribute towards development of non-invasive malaria diagnosis methods. Freeze dried human urine samples form malaria infected individuals (cases) and controls were screened in the IR region of 4000 cm−1 to 600 cm−1 and overall spectral differences were observed at wave numbers 1618 cm−1, 1679 cm−1 (amino acids). Peaks at 3030 cm−1 (NH4+) and 940 cm−1 (O–H of carboxylic acids) showed high absorbance in patients compared to controls. Liquid-chromatography–mass spectrometry (LC–MS/MS) was used to quantify amino acids in the urine samples and the results indicated a significant increase of amino acid cystine (P = 0.012). Lysine and tyrosine also increased in patients compared to controls. The use of IR-PCA differentiated clusters of urine samples from patients with malaria from control and the demonstrated amino acid perturbation is consistent with malaria infection. This data provides baseline information for application in development of a non-invasive diagnostic tests for malaria.Article HighlightsInfrared (IR) spectroscopy and Principle Component Analysis (PCA) were used to differentiate urine of malaria patients from controls.LC–MS/MS was used to determine creatinine, tyrosine, cystine, lysine and histidine in urine from malaria patients and controlsThe average concentration of cystine in patients and controls urine differed significantly. Publicly Available Content DatabaseItem Current pediatric pain practice in Nigeria, South Africa, Uganda, and Zambia: A prospective survey of anesthetists(Wiley Subscription Services, Inc, 2024-06) Bhettay, Anisa; Gray, Rebecca; Desalu, Ibironke; Parker, Romy; Maswime, SalomeAbstract Children in hospital experience significant pain, either inherent with their pathology, or caused by diagnostic/therapeutic procedures. Little is known about pediatric pain practices in sub-Saharan Africa. This survey aimed to gain insight into current pain management practices among specialist physician anesthetists in four sub-Saharan African countries. A survey was sent to 365 specialist physician anesthetists in Nigeria, South Africa, Uganda and Zambia. Content analysis included descriptive information about the respondents and their work environment. Thematic analysis considered resources available for pediatric pain management, personal and institutional pain practices. One hundred and sixty-six responses were received (response rate 45.5%), with data from 141 analyzed; Nigeria (27), South Africa (52), Uganda (41) and Zambia (21). Most respondents (71.83%) worked at tertiary/national referral hospitals. The majority of respondents (130/141, 91.55%) had received teaching in pediatric pain management. Good availability was reported for simple analgesia, opioids, ketamine, and local anesthetics. Just over half always/often had access to nurses trained in pediatric care, and infusion pumps for continuous drug delivery. Catheters for regional anesthesia techniques and for patient-controlled analgesia were largely unavailable. Two thirds (94/141, 66.67%) did not have an institutional pediatric pain management guideline, but good pharmacological pain management practices were reported, in line with World Health Organization recommendations. Eighty-eight respondents (62.41%) indicated that they felt appropriate pain control in children was always/often achieved in their setting. This survey provides insight into pediatric pain practices in these four countries. Good availability of a variety of analgesics, positive pain prescription practices, and utilization of some non-pharmacological pain management strategies are encouraging, and suggest that achieving good pain control despite limited resources is attainable. Areas for improvement include the development of institutional guidelines, routine utilization of pain assessment tools, and access to regional anesthesia and other advanced pain management techniques. PubMedItem Viral load non-suppression status among women exposed to Dolutegravir-based versus Efavirenz-based regimens in Ethiopia: A before-and-after study(Public Library of Science, 2024-06) Facha, Wolde; Tadesse, Takele;; Wolka, Eskinder; Astatkie, AyalewAbstract High viral load during pregnancy and breastfeeding period is the risk factor for vertical transmission of human immunodeficiency virus (HIV). Currently, Dolutegravir (DTG)-based regimens are recommended to attain adequate viral load suppression (VLS) among women. However, its effect on VLS has not been investigated among women in PMTCT care in Ethiopia. This study aimed to investigate the rate of viral load non-suppression among women exposed to DTG-based versus Efavirenz (EFV)-based regimens in Ethiopia. An uncontrolled before-and-after study design was conducted among 924 women (462 on EFV-based and 462 on DTG-based regimens) enrolled in PMTCT care from September 2015 to February 2023. The outcome variable was the viral load (VL) non-suppression among women on PMTCT care. A modified Poisson regression model was employed, and the proportion was computed to compare the rate of VL non-suppression in both groups. The risk ratio (RR) with a 95% confidence interval (CI) was calculated to assess viral load non-suppression among women on DTG-based and EFV-based regimens by adjusting for other variables. The overall rate of non-suppressed VL was 16.2% (95% CI: 14.0-18.8%). Mothers on DTG-based regimens had approximately a 30% (adjusted risk ratio (aRR): 0.70; 95% CI: 0.52-0.94) lesser risk of developing non-suppressed VL than women on EFV-based regimens. Besides, older women were 1.38 times (aRR: 1.38; 95% CI: 1.04-1.83); mothers who did not disclose their HIV status to their partners were 2.54 times (aRR: 2.54; 95% CI: 1.91-3.38); and mothers who had poor or fair adherence to antiretroviral (ARV) drugs were 2.11 times (aRR: 2.11; 95% CI: 1.45-3.07) at higher risk of non-suppressed VL. Women on DTG-based regimens had a significantly suppressed VL compared to those on EFV-based regimens. Thus, administering DTG-based first-line ART regimens should be strengthened to achieve global and national targets on VLS.Item Understanding the outcome and management of children aged 2–59 months with chest indrawing pneumonia: a study protocol for an observational study in Ethiopia, India, Nigeria, Pakistan, Uganda and Zambia(BMJ Publishing Group LTD, 2024-06) Cipam Study Group, Chest Indrawing Pneumonia ManagementAbstract IntroductionChildhood pneumonia is a leading cause of morbidity and mortality among children aged 2–59 months, particularly in low-income and middle-income countries (LMICs), where healthcare providers face significant challenges in diagnosing and treating childhood pneumonia. Many LMICs have taken steps to address this issue by revising their national policies and aligning them with WHO’s revised guidelines for pneumonia management. These revised guidelines aim to facilitate the outpatient management of children aged 2–59 months chest indrawing pneumonia. Despite these efforts, there is limited empirical evidence regarding the management and outcomes of these children in primary-level healthcare settings. This study aims to assess the survival status of children aged 2–59 months with chest indrawing pneumonia presenting at primary healthcare facilities.Methods and analysisA prospective, observational cohort study will be conducted in Ethiopia, Nigeria, Uganda, Zambia, India and Pakistan on children aged 2–59 months presenting at selected primary-level healthcare facilities with chest indrawing pneumonia. Eligible participants will be enrolled and managed by facility healthcare providers who are trained in Integrated Management of Childhood Illness and will be followed up on day 15 to record the treatment-related information and vital status, including conducting verbal autopsies in case of child death. The sample size for each site will be 310. The analysis will involve exploring site-specific trends before conducting a pooled analysis of de-identified data from all sites. The first data collection started at the Ethiopian site in September 2022, followed by other sites. The data collection will continue until June 2025.Ethics and disseminationThe study protocol, enrolment forms and consent forms will undergo ethical review by the Institutional Review Boards of the University of Gondar, Gondar, Ethiopia; the INCLEN Trust International Independent Ethics Committee, New Delhi, India; Ethical Review Committee of the University of Ibadan, Ethical Review Committees of Lagos State and Ethical Review Committee of University College London, UK; Institutional Review Board, International Research Force, Islamabad, Pakistan; Institutional Review Board, People’s Primary Healthcare Initiative-Sindh, Karachi and National Bioethics Committee, Islamabad, Pakistan; Makerere University School of Biomedical Sciences Research Ethical Committee, Kampala, Uganda; University of Zambia Biomedical Research Ethics committee, Lusaka, Zambia and Ethical Review Committee of WHO, Geneva, Switzerland. Ethical procedures include WHO and local review board evaluations, parental consent in the local/national language, permits enrolment, follow-up, and, if required, clinical video recording for children with chest indrawing pneumonia, ensuring their eligibility. Adherence to local regulations encompasses precollection ethical approvals, risk management strategies and secure, de-identified data storage. Findings will be disseminated through seminars, publications and meetings, engaging diverse stakeholders to foster collaborations.Trial registration numberISRCTN12687253. Publicly Available Content DatabaseItem Attitudes of female market vendors of reproductive age towards use of mobile phones and access to family planning self-care interventions in Northern Uganda: a cross-sectional study(BioMed Central Ltd, 2024-06) Walter, Yagos Onen; Atim, Pamela; Amone, Derrick; Peter, Alarakol Simon; Tabo, Geoffrey OlokBackgroundMobile phones are potential digital technologies for accessing family planning self-care interventions. However, their utilization could be possible if women of reproductive age have positive attitudes towards the use of this technology for healthcare purposes. This study aimed to examine the relationship between attitudes towards the use of mobile phones and access to family planning self-care interventions among female market vendors of reproductive age in northern Uganda.MethodsA cross-sectional survey design was used. Two hundred and five randomly selected female vendors from the Gulu city main market participated. A structured researcher-administered questionnaire was used to collect the data. Descriptive statistics and standard multiple regression were performed, and the data were analysed using SPSS software version 15.ResultsOf the 205 participants, 112 (54.6%) reported using smartphones, and 147 (71.7%) were aware of family planning self-care interventions. Participants had moderate attitudes towards access to family planning self-care interventions (mean = 3.18), positive attitudes towards ease of use (mean = 3.31) and usefulness of mobile phones (mean = 3.30), strong positive attitudes towards privacy (mean = 4.04), and skills associated with using mobile phones (mean = 4.04). Furthermore, significant positive relationships existed between ease of use (p value = 0.000), skills (p value = 0.001), privacy (p value = 0.002) and access to family planning self-care interventions. There was, however, an insignificant positive relationship between mobile phone usefulness and access to family planning self-care interventions (p value = 0.189). Conclusions. Participants’ positive attitudes towards the use of mobile phones could lead to access to FP self-care interventions, although uncertainty about the usefulness of the use of mobile phones for accessing FP self-care interventions exists. It is therefore important for healthcare practitioners, health development partners and the government to encourage and integrate the use of mHealth into regular FP self-care services and promotional activities while targeting underserved communities in Uganda.Item Airway microbiome signature accurately discriminates Mycobacterium tuberculosis infection status(Elsevier Inc, 2024-06) Kayongo, Alex; Ntayi, Moses Levi; Olweny, Geoffrey; Kyalo, Edward; Ndawula, Josephine; Ssengooba, Willy; Kigozi, Edgar; Kalyesubula, Robert; Munana, Richard; Namaganda, Jesca; Caroline, Musiime; Sekibira, Rogers; Bagaya, Bernard Sentalo; Kateete, David Patrick; Joloba, Moses Lutaakome; Jjingo, Daudi; Sande, Obondo James; Mayanja-Kizza, HarrietAbstract Mycobacterium tuberculosis remains one of the deadliest infectious agents globally. Amidst efforts to control TB, long treatment duration, drug toxicity, and resistance underscore the need for novel therapeutic strategies. Despite advances in understanding the interplay between microbiome and disease in humans, the specific role of the microbiome in predicting disease susceptibility and discriminating infection status in tuberculosis still needs to be fully investigated. We investigated the impact of M.tb infection and M.tb-specific IFNγ immune responses on airway microbiome diversity by performing TB GeneXpert and QuantiFERON-GOLD assays during the follow-up phase of a longitudinal HIV-Lung Microbiome cohort of individuals recruited from two large independent cohorts in rural Uganda. M.tb rather than IFNγ immune response mainly drove a significant reduction in airway microbiome diversity. A microbiome signature comprising Streptococcus, Neisseria, Fusobacterium, Prevotella, Schaalia, Actinomyces, Cutibacterium, Brevibacillus, Microbacterium, and Beijerinckiacea accurately discriminated active TB from Latent TB and M.tb-uninfected individuals. [Display omitted] •M.tb infection drives a significant reduction in airway microbiome diversity•M.tb-specific IFNg does not directly impact airway microbiome diversity•Airway microbiome signature discriminates active TB from LTBI and uninfected states•LTBI and M.tb-uninfected states display similar airway microbiome diversity Microbiology; Bacteriology; MicrobiomeItem COVID-19 post-pandemic reflections from sub-Saharan Africa: what we know now that we wish we knew then(Elsevier Ltd, 2024-06) Oleribe, Obinna O; Taylor-Robinson, Simon D; Taylor-Robinson, Andrew W.The commonly heard aphorism about history repeating itself suggests an endless cycle of recurring events. However, George Santayana offered a similar sentiment when he said, "Those who do not learn from history are doomed to repeat it". This emphasises that the responsibility for the recurrence of events lies not with history itself, but with humanity. It underscores that if we desire change, it is our responsibility to initiate it, rather than attributing it to external forces such as fate, luck, or time. With this thought in mind, here we offer a narrative view from sub-Saharan Africa, focusing primarily on our own experiences in Nigeria and Uganda, on what harsh lessons can be learnt from the COVID-19 pandemic regarding emergency preparedness to respond effectively to the next major infectious disease outbreak. Four strategies are suggested, the implementation of which may contribute substantially to safeguarding against an experience similar to the catastrophic public health, social and economic costs borne by African nations during COVID-19 and in its immediate aftermath. PubMedItem Acute and subacute toxicity profile of ethanolic stem bark extract of Albizia coriaria Welw. ex Oliv. in Wistar albino rats Author links open overlay panel(Elsevier Ltd, 2024-06) Obakiro, Samuel Baker; Kiyimba, Kenedy; Owor, Richard Oriko; Andima, Moses; Lukwago, Tonny Wotoyitide; Kawuma, Carol; Gavamukulya, Yahaya; Nabatanzi, Alice; Kibuule, Dan; Kato, Charles Drago; Anywar, Godwin; Waako, PaulAbstract Albizia coriaria (Fabaceae) crude extracts are key ingredients of several licensed and unlicensed herbal products in East Africa. However, there is limited and often contradicting information regarding its toxicity. We therefore evaluated the acute and subacute toxicity of the ethanolic stem bark extract of A. coriaria in mature healthy Wistar albino rats following Lorke’s method and OECD guidelines 407. The LD 50 of the ethanolic stem bark extract of A. coriaria was 2000 mg/kg. The acute toxicity signs observed included piloerection, hyperventilation, lethargy, and loss of righting reflex. There was a significant increase in aspartate aminotransferase, alkaline phosphatase, red blood cells and haemoglobin in rats after 28 days at the dose of 500 mg/kg. Histological analyses revealed multifocal random parenchymal necrosis and scattered periportal mononuclear inflammatory cells infiltration in the liver, interstitial nephritis in the kidney and multifocal lymphoid accumulation in the peribronchiolar and perivascular lung tissue at 500 mg/kg. The ethanolic stem bark of A. coriaria was therefore moderately toxic to the rats when administered in a single high oral dose within 24 h. The extract caused a dose dependent toxicity with significant damage to the kidney, liver and lung tissues at a dose of 500 mg/kg after 28 days. Herbal medicines containing A. coriaria extracts should be consumed cautiously due to likelihood of toxicity particularly at higher doses greater than 500 mg/kg. ga1 • This study assesed the acute and subacute toxicity effects of the ethanolic stem bark extract of A. coriaria, a key ingredient of several licensed and unlicensed herbal products on Uganda market. • The ethanolic stem bark extract of A. coriaria was found to be moderately toxic when administered in a single high oral dose within 24 h with a median lethal dose of 2000 mg/kg. • In repeated daily doses of 500 mg/kg, the ethanolic stem bark extract of A. coriaria caused significant toxicity to the lungs, liver and kidney tissues. • Herbal medicines containing A. coriaria extracts should be consumed cautiously due to likelihood of associated toxicity particularly at higher doses greater 500 mg/kg.Item Ethnobotanical survey and phytochemistry of medicinal plants used in the management of HIV/AIDS in Eastern Uganda(Elsevier Ltd, 2024-06) Owor, Richard Oriko; Kawuma, Carol; Nantale, Gauden; Kiyimba, Kenedy; Obakiro, Samuel Baker; Ouma, Simple; Lulenzi, Jalia; Gavamukulya, Yahaya; Chebijira, Mercy; Lukwago, Tonny Wotoyitide; Egor, Moses; Musagala, Peter; Andima, Moses; Kibuule, Dan; Waako, Paul; Hokello, JosephCurrently, highly active antiretroviral therapy is unable to cure HIV/AIDS because of HIV latency. This study aimed at documenting medicinal plants used in the management of HIV/AIDS in Eastern Uganda so as to identify phytochemicals with HIV latency reversing potential. An ethnobotanical survey was conducted across eight districts in Eastern Uganda. Traditional medicine practitioners were interviewed using semi-structured questionnaires. Qualitative and quantitative phytochemical tests were respectively, performed to determine the presence and quantity of phytochemicals in frequently mentioned plant species. Data were analysed and presented using descriptive statistics and Informant Consensus Factor (ICF). Twenty-one plant species from fourteen plant families were reported to be used in the management of HIV/AIDS. Six plant species with the highest frequency of mention were: Zanthoxylum chalybeum, Gymnosporia senegalensis, Warbugia ugandensis, Leonatis nepetifolia, Croton macrostachyus and Rhoicissus tridentata. Qualitative phytochemical analysis of all the six most frequently mentioned plant species revealed the presence of flavonoids, tannins, terpenoids, alkaloids and phenolics. Quantitative analysis revealed the highest content of flavonoids in L. nepetifolia (20.4 mg/g of dry extract) while the lowest content was determined in C. macrostachyus (7.1 mg/g of dry extract). On the other hand, the highest content of tannins was observed in L. nepetifolia. (199.9 mg/g of dry extract) while the lowest content was found in R. tridentata. (42.6 mg/g of dry extract). Medicinal plants used by traditional medicine practitioners in Eastern Uganda to manage HIV/AIDS are rich in phytochemicals including flavonoids and tannins. Further studies to evaluate the HIV-1 latency reversing ability of these phytochemicals are recommended to discover novel molecules against HIV/AIDS.Item Perspectives on competency-based feedback for training non-specialists to deliver psychological interventions: multi-site qualitative study of the EQUIP competency-based approach(Cambridge University Press, 2024-05) Elnasseh, Abdelrhman; Mehta, Varun S; Manolova, Gergana; Pedersen, Gloria A; Golden, Shannon; Eloul, Liyam; Gebrekristos, Frezgi; Collins, Pamela Y; Mutavi, Teresia; Mbwayo, Anne W; Mathai, Muthoni; Concepcion, Tessa; El Masri, Rozane; Steen, Frederik; Galea, Jerome T; Contreras, Carmen; Akellot, Josephine; Kasujja, Rosco; Wasereka, Samuel; Mutamba, Byamah Brian; Tol, Wietse A.; Raji, Mansurat; Moufarrej, Sacha; Schafer, Alison; Kohrt, Brandon AAbstract Background The use of feedback to address gaps and reinforce skills is a key component of successful competency-based mental health and psychosocial support intervention training approaches. Competency-based feedback during training and supervision for personnel delivering psychological interventions is vital for safe and effective care. Aims For non-specialists trained in low-resource settings, there is a lack of standardised feedback systems. This study explores perspectives on competency-based feedback, using structured role-plays that are featured on the Ensuring Quality in Psychosocial and Mental Health Care (EQUIP) platform developed by the World Health Organization and United Nations Children’s Fund. Method Qualitative data were collected from supervisors, trainers and trainees from multiple EQUIP training sites (Ethiopia, Kenya, Lebanon, Peru and Uganda), from 18 key informant interviews and five focus group discussions (N = 41 participants). Qualitative analysis was conducted in Dedoose, using a codebook with deductively and inductively developed themes. Results Four main themes demonstrated how a competency-based structure enhanced the feedback process: (a) competency-based feedback was personalised and goal-specific, (b) competency-based feedback supported a feedback loop, (c) competency-based feedback supported a comfortable and objective feedback environment, and (d) competency-based feedback created greater opportunities for flexibility in training and supervision. Conclusions A better understanding of the role of feedback supports the implementation of competency-based training that is systematic and effective for trainers and supervisors, which ultimately benefits the learning process for trainees.Item A randomized control trial to compare mortality in recipients of leucoreduced and non-leucoreduced whole blood transfusion in patients with cancer in Uganda(BioMed Central, 2024-05) Okello, Clement D; Orem, Jackson; Nabwana, Martin; Kiwanuka, Noah; Shih, Andrew W; Heddle, Nancy; Mayanja-Kizza, HarrietAbstract BACKGROUNDMortality benefit of transfusion with leucoreduced whole blood has not been demonstrated in the sub-Saharan Africa (SSA). We compared mortality in patients with cancer transfused with leucoreduced and non-leucoreduced whole blood in a SSA setting.METHODSAn open-label randomized controlled trial was conducted at the Uganda Cancer Institute where participants were randomized in a 1:1 ratio into the leucoreduced and non-leucoreduced whole blood transfusion arms. Leucocyte filtration of whole blood was performed within 72 h of blood collection. Patients aged ≥ 15 years who were prescribed blood transfusion by the primary physicians were eligible for study enrolment. Mortality difference was analyzed using intention-to-treat survival analysis and cox proportional hazard model was used to analyze factors associated with mortality.RESULTSThere were 137 participants randomized to the leucoreduced and 140 to the non-leucoreduced arms. Baseline characteristics were similar between the two arms. The median number of blood transfusions received was 1 (IQR, 1-3) unit and 2 (IQR, 1-3) units in the leucoreduced and non-leucoreduced arms respectively, p = 0.07. The 30-day mortality rate in the leucoreduced arm was 4.6% (95% CI, 2.1-10) and was 6.2% (95% CI, 3.2-12.1) in the non-leucoreduced arm (p = 0.57), representing an absolute effect size of only 1.6%. Increasing age (HR = 0.92, 95% CI, 0.86-0.98, p = 0.02) and Eastern Co-operative Oncology Group (ECOG) performance score of 1 (HR = 0.03, 95% CI, 0.00-0.31, p < 0.01) were associated with reduced 30-day mortality.CONCLUSIONSThe study failed to demonstrate mortality difference between cancer patients transfused with leucoreduced and non-leucoreduced whole blood. Although this study does not support nor refute universal leucoreduction to reduce mortality in patients with cancer in SSA, it demonstrates the feasibility of doing transfusion RCTs in Uganda, where a multi-center trial with an appropriate sample size is needed.TRIAL REGISTRATIONPan African Clinical Trial Registry, https://pactr.samrc.ac.za/ (PACTR202302787440132). Registered on 06/02/2023. MEDLINE - AcademicItem Factors associated with early inhospital adverse outcome following surgery for acute appendicitis in Uganda: a multicenter cohort(BioMed Central, 2024-05) Farhan, Sharif Yusuf; Abraha, Demoz; Edyedu, Isaac; Molen, Selamo Fabrice; Mauricio, William; Odong, Samuel Oledo; Mugeni, Michael; Muhumuza, JoshuaINTRODUCTIONSurgery for acute appendicitis has been associated with significant morbidity. This study aimed to determine the factors associated with early inhospital adverse outcomes following surgery for acute appendicitis in Uganda.METHODSThis was a multicentre, prospective cohort in which early inhospital outcome following surgery for acute appendicitis was assessed at 4 regional referral hospitals in Uganda. The occurrence of complications during the admission period was documented as well as the length of hospital stay. Factors associated with adverse outcomes were determined using Poisson regression.RESULTSOf the 102 patients who underwent surgery for acute appendicitis, the majority were males 79(77.5%) with a mean age of 23.8(SD = 12.5) years. The perforated appendix was seen in 26 (25.5%) patients. Post-operative complications occurred in 21(20.6%) with the commonest being surgical site infection in 19(18.6%) patients. The median length of hospital stay was 3(IQR = 3-4) days with 43(42.2%) staying in hospital for more than 3 days. The presence of anemia (Hb < 8) (aRR = 1.376, CI = 1.159-1.634, P = < 0.001) and having a perforated appendix (aRR = 1.263, CI = 1.026-1.555, P = 0.027) were independently associated with occurrence of complications while being HIV positive (aRR = 1.379, CI = 1.105-1.721, P = 0.005) and having a perforated appendix (aRR = 1.258, CI = 1.019-1.554, P = 0.033) were independently associated with prolonged hospital stay.CONCLUSIONCommunity education about early presentation is still required in order to reduce the number of patients that present late which should, in turn, reduce the risk of complications and length of hospital stay. MEDLINE - AcademicItem Implementation of gender-based violence screening guidelines in public HIV treatment programs: A mixed methods evaluation in Uganda(Public Library of Science, 2024-05) Thomas, Dorothy; Nalumansi, Alisaati; Reichman, Mira; Metitiri, Mine; Nambi, Florence; Kibuuka, Joseph; Nakabugo, Lylianne; Kamusiime, Brenda; Kasiita, Vicent; Nalukwago, Grace K.; Muwonge, Timothy R; Simoni, Jane; Montgomery, Elizabeth T.; Mujugira, Andrew; Heffron, ReneeBackground HIV and gender-based violence (GBV) intersect to threaten population health. The Uganda Ministry of Health recommends routine GBV screening alongside HIV care but evidence detailing its implementation in HIV care settings is limited. We evaluated screening practices in public HIV clinics to generate evidence supporting GBV screening optimization. Methods To evaluate GBV screening implementation in antiretroviral therapy (ART) clinics, we extracted client data from GBV registers at 12 public ART clinics in Uganda (January 2019-December 2021). We concurrently evaluated perceptions of GBV screening/referral practices by conducting in-depth qualitative interviews with providers (N = 30) and referral partners (N = 10). We contextualized quantitative findings with interview data which were analyzed using a thematic analysis approach. Results During the evaluation period, >90% of providers in participating health facilities implemented GBV screening. Among 107,767 clients served in public ART clinics, providers identified 9,290 (8.6%) clients who experienced past-year physical, sexual and/or emotional GBV of whom 86% received counseling and 19% were referred to support services—most commonly to legal services. Key factors influencing GBV screening implementation included awareness of screening guidelines; client volume; and client’s level of engagement in HIV care. Providers and referral partners identified important benefits to clients (e.g., pursuit of justice and removal from violent environments) when referrals were successful. Key factors influencing referrals included financial constraints that limited referral partners’ ability to provide services at no cost to clients and socio-cultural norms that inhibited client willingness to pursue support services. Conclusions GBV screening implementation in ART clinics supports identification and referral of clients exposed to violence. The effectiveness of GBV screening may be limited by socio-cultural factors that inhibit client capacity to pursue referrals and fragmented and resource-constrained referral networks. Providers and referral partners identified allocating funds to support referrals and collaborative networking meetings as important opportunities for strengthening GBV referrals.Item Use of dental care services among adolescents living with HIV on antiretroviral treatment in Kampala, Uganda: a cross-sectional study(BioMed Central Ltd, 2024-05) Nakyonyi, Maria Gorretti; Birungi, Nancy; Mwesigwa, Catherine Lutalo; Åstrøm, Anne NordrehaugObjective The primary purpose of this study was to assess the prevalence and socio-behavioral determinants of ever-use of dental care services among adolescents aged 10–18 years, living with HIV, on Antiretroviral treatment (ART), and attending selected HIV clinics in Kampala, Uganda. Methods A cross-sectional study was carried out between March and September 2020. The study conveniently recruited 154 adolescents between 10 and 18 years old from 4 specific HIV clinics in Kampala. Andersen’s behavioral model guided the selection of variables, with the ever-use of dental care services as the outcome and predisposing, enabling, need-related factors and personal dental health practices as exposure variables. Data were analyzed using Fischer’s exact test for cross-tabulation and modified Poisson regression for multivariate analysis. Results The prevalence of ever-use of dental care services was 12.3%. The adolescents aged 14–18 had higher odds of using dental care services (Prevalence ratio (PR) of 3.35 than those aged 10–13 years. Fear of the spread of HIV was negatively associated with ever-use of dental care services (PR of 0.06). Participants who were afraid of going to the dentist had higher odds of using dental care services (PR of 2.98) than those not afraid. Failure to receive dental treatment because it was not part of the medical appointment had a positive association with the ever-use of dental care services (PR of 4.50). Those who were satisfied with their dental condition had lower odds of using dental care services. The bad oral odor was positively associated with the ever-use of dental care services (PR of 2.80). The use of soap for toothbrushing was positively associated with the ever-use of dental care services (PR of 2.51). Conclusion The study found a low frequency of dental care use among HIV-infected adolescents in Kampala, Uganda, with age being a predisposing factor. Enabling factors included fear of HIV spread, medical-dental appointment incoordination, and satisfaction with the dental condition and bad oral odor while under personal dental health practices. The use of soap for toothbrushing was an important association with dental care. Nevertheless, these study results cannot be generalized to the entire HIV adolescent population in Uganda. Keywords Use of dental care services, HIV, ART, Adolescents, Kampala, UgandaItem “The burden is upon your shoulders to feed and take care of your children, not religion or culture”: qualitative evaluation of participatory community dialogues to promote family planning’s holistic benefits and reshape community norms on family success in rural Uganda(BioMed Central, 2024-05) Sileo, Katelyn M.; Muhumuza, Christine; Tuhebwe, Doreen; Muñoz, Suyapa; Wanyenze, Rhoda K.; Kershaw, Trace S; Sekamatte, Samuel; Lule, Haruna; Kiene, Susan M.Background Family planning has significant health and social benefits, but in settings like Uganda, is underutilized due to prevalent community and religious norms promoting large family size and gender inequity. Family Health = Family Wealth (FH = FW) is a multi-level, community-based intervention that used community dialogues grounded in Campbell and Cornish’s social psychological theory of transformative communication to reshape individual endorsement of community norms that negatively affect gender equitable reproductive decision-making among couples in rural Uganda. Methods This study aimed to qualitatively evaluate the effect of FH = FW’s community dialogue approach on participants’ personal endorsement of community norms counter to family planning acceptance and gender equity. A pilot quasi-experimental controlled trial was implemented in 2021. This paper uses qualitative, post-intervention data collected from intervention arm participants (N = 70) at two time points: 3 weeks post-intervention (in-depth interviews, n = 64) and after 10-months follow-up (focus group discussions [n = 39] or semi-structured interviews [n = 27]). Data were analyzed through thematic analysis. Results The community dialogue approach helped couples to reassess community beliefs that reinforce gender inequity and disapproval of family planning. FH = FW’s inclusion of economic and relationship content served as key entry points for couples to discuss family planning. Results are presented in five central themes: (1) Community family size expectations were reconsidered through discussions on economic factors; (2) Showcasing how relationship health and gender equity are central to economic health influenced men’s acceptance of gender equity; (3) Linking relationship health and family planning helped increase positive attitudes towards family planning and the perceived importance of shared household decision-making to family wellness; (4) Program elements to strengthen relationship skills helped to translate gender equitable attitudes into changes in relationship dynamics and to facilitate equitable family planning communication; (5) FH = FW participation increased couples’ collective family planning (and overall health) decision-making and uptake of contraceptive methods. Conclusion Community dialogues may be an effective intervention approach to change individual endorsement of widespread community norms that reduce family planning acceptance. Future work should continue to explore innovative ways to use this approach to increase gender equitable reproductive decision-making among couples in settings where gender, religious, and community norms limit reproductive autonomy. Future evaluations of this work should aim to examine change in norms at the community-level.Item Expansion of artemisinin partial resistance mutations and lack of histidine rich protein-2 and -3 deletions in Plasmodium falciparum infections from Rukara, Rwanda(BioMed Central Ltd, 2024-05) Schreidah, Cecile; Giesbrecht, David; Gashema, Pierre; Young, Neeva Wernsman; Munyaneza, Tharcisse; Muvunyi, Claude Mambo; Thwai, Kyaw; Mazarati, Jean-Baptiste; Bailey, Jeffrey A; Juliano, Jonathan J; Karema, CorineBACKGROUNDEmerging artemisinin partial resistance and diagnostic resistance are a threat to malaria control in Africa. Plasmodium falciparum kelch13 (k13) propeller-domain mutations that confer artemisinin partial resistance have emerged in Africa. k13-561H was initially described at a frequency of 7.4% from Masaka in 2014-2015, but not present in nearby Rukara. By 2018, 19.6% of isolates in Masaka and 22% of isolates in Rukara contained the mutation. Longitudinal monitoring is essential to inform control efforts. In Rukara, an assessment was conducted to evaluate recent k13-561H prevalence changes, as well as other key mutations. Prevalence of hrp2/3 deletions was also assessed.METHODSSamples collected in Rukara in 2021 were genotyped for key artemisinin and partner drug resistance mutations using molecular inversion probe assays and for hrp2/3 deletions using qPCR.RESULTSClinically validated k13 artemisinin partial resistance mutations continue to increase in prevalence with the overall level of mutant infections reaching 32% in Rwanda. The increase appears to be due to the rapid emergence of k13-675V (6.4%, 6/94 infections), previously not observed, rather than continued expansion of 561H (23.5% 20/85). Mutations to partner drugs and other anti-malarials were variable, with high levels of multidrug resistance 1 (mdr1) N86 (95.5%) associated with lumefantrine decreased susceptibility and dihydrofolate reductase (dhfr) 164L (24.7%) associated with a high level of antifolate resistance, but low levels of amodiaquine resistance polymorphisms with chloroquine resistance transporter (crt) 76T: at 6.1% prevalence. No hrp2 or hrp3 gene deletions associated with diagnostic resistance were found.CONCLUSIONSIncreasing prevalence of artemisinin partial resistance due to k13-561H and the rapid expansion of k13-675V is concerning for the longevity of artemisinin effectiveness in the region. False negative RDT results do not appear to be an issue with no hrp2 or hpr3 deletions detected. Continued molecular surveillance in this region and surrounding areas is needed to follow artemisinin partial resistance and provide early detection of partner drug resistance, which would likely compromise control and increase malaria morbidity and mortality in East Africa. MEDLINE - AcademicItem Sero-antigen prevalence of lymphatic filariasis and risk factors of podoconiosis in Busiriba sub-county, Kamwenge district, Southwestern Uganda, August–September 2018(BioMed Central Ltd, 2024-05) Mwesigye, Vicent; Musinguzi, Benson; Okongo, Benson; Mucunguzi, William; Kakaire, Michael Nyende; Migisha, RichardAbstract Given the neglected nature of filariasis, especially in Uganda where data are scarce, this cross-sectional study aimed to determine the sero-antigen prevalence of lymphatic filariasis and risk factors associated with non-lymphatic filariasis (podoconiosis) in Busiriba Sub-county, Kamwenge District, Uganda, during August-September 2018, to inform targeted elimination efforts. We enrolled 101 participants, among whom 35 (34.7%) had podoconiosis. The sero-antigen prevalence of lymphatic filariasis was 1.0%. Older age and walking barefoot were associated with increased podoconiosis risk. Specifically, individuals aged 25-49 years with had 7.38 times higher odds of podoconiosis (adjusted odds ratio [aOR] = 7.38, 95% CI: 1.36-40.13) compared to those under 25 years, while those aged ≥ 50 years had even higher odds (aOR = 8.49, 95%CI: 1.44-50.15). Additionally, individuals who reported walking barefoot had 14 times higher odds of podoconiosis (aOR = 14.08; 95% CI: 2.49-79.50).