Browsing by Author "Okiror, William"

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    Characterising Childhood Blackwater Fever and Its Clinical Care at Two Tertiary Hospitals in Eastern Uganda
    (Research Square, 2021) Paasi, George; Ndila, Carolyne; Okiror, William; Namayanja, Cate; Okalebo, Benard Phelan; Abongo, Grace; Alaroker, Florence; Abeso, Julian; Kasoro, Andrew; Okello, Francis; Olupot, Peter Olupot
    In eastern Uganda, reports suggest that cases of Blackwater Fever (BWF) are on the rise. We summarise the base-line characteristics and routine care available to patients with BWF presenting at two tertiary hospitals in Eastern Uganda prior to the Phase I/II trial on use of paracetamol for acute kidney injury in children with BWF (PARIST; ISRCTN84974248). This was a retrospective descriptive study for the period January – December 2018 for children admitted with a clinical diagnosis of BWF at Mbale and Soroti Regional Referral Hospitals in Eastern Uganda. Data on sociodemographic and clinical characteristics, routine in-patient care and outcomes were abstracted using a customised study proforma and analysed using STATA. We obtained 9578 admission records during the study period, of which 1241 (13.0%) were admitted with a diagnosis of BWF. The median age was 60 months (IQR 36–90). Male: female ratio was 1.5:1. More cases of BWF 682/1241 (55.0%) were in children > 5 years compared to 559/1241 (45.0%) ≤ 5 years [95%CI (0.41–0.59); P = 0.0002]. The common symptoms included fever 1109/1241 (89.4%), vomiting 599/1241 (48.3%) and abdominal pain 494/1241 (39.8%). Conversely, the common signs recorded were clinical pallor 742/1241 (59.8%), clinical jaundice 369/1241 (29.7%), fever 332/1241 (26.7%) and prostration 231/1241 (18.6%). In addition, abdominal tenderness was documented in 120/1241 (9.7%), splenomegaly in 122/1241 (9.8%) and hepatomegaly in 86/1241 (6.9%). Case records with BWF were more in the second half of the year with a peak in the months of July and September. 510/1241 (41.1%) were treated with antimalarial drugs mainly parenteral Artesunate 501/510 (98.2%). 660/1241(53.2%) of the patients were managed with antibiotics mainly parenteral ceftriaxone 616/660 (93.3%). There were 426/1241 (34.3%) patients who received blood transfusion during admission. Clinicians used steroid treatment in 388/1241 (31.3%), mainly parenteral hydrocortisone 370/388 (95.4%).BWF accounted for 13% paediatric hospital admissions in the region. It was predominant in children > 5 years of age. It typically presents with passing dark urine, fever, abdominal pain, clinical jaundice and pallor. Locally there are no treatment guidelines for BWF. These data provide background data useful for future studies on BWF in the region.
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    Characterising Demographics, Knowledge, Practices And Clinical Care Among Patients Attending Sickle Cell Disease Clinics In Eastern Uganda
    (Wellcome Open Research, 2020) Olupot, Peter Olupot; Wabwire, Ham; Ndila, Carolyne; Adong, Ruth; Ochen, Linus; Amorut, Denis; Abongo, Grace; Okalebo, Charles B.; Akello, Sarah Rachael; Oketcho, Joy B.; Okiror, William; Asio, Sarah; Odiit, Amos; Alaroker, Florence; Nyutu, Gideon; Maitland, Kathryn; Williams, Thomas N.
    In Uganda to date, there are neither established registries nor descriptions of facility-based sickle cell disease (SCD) patient characteristics beyond the central region. Here, we summarize data on the baseline clinical characteristics and routine care available to patients at four clinics in Eastern Uganda as a prelude to a clinical trial.Between February and August 2018, we conducted a cross-sectional survey of patients attending four SCD clinics in Mbale, Soroti, Atutur and Ngora, all in Eastern Uganda, the planned sites for an upcoming clinical trial (H-PRIME: ISRCTN15724013). Data on socio-demographic characteristics, diagnostic methods, clinic schedules, the use of prophylactic and therapeutic drugs, clinical complications and patient understanding of SCD were collected using a structured questionnaire.Data were collected on 1829 patients. Their ages ranged from 0 to 64 years with a median (IQR) of 6 (3-11) years. 49.1% of participants were male. The majority (1151; 62.9%) reported a positive family history for SCD. Approximately half knew that SCD is inherited from both parents but a substantial proportion did not know how SCD is transmitted and small numbers believed that it is acquired by either transfusion or from other people. Only 118/1819 (6.5%) participants had heard about or were using hydroxyurea while 356/1794 (19.8%) reported stigmatization. Participants reported a median of three (IQR 1-4) hospital admissions during the preceding 12 months; 80.8% had been admitted at least once, while 14.2% had been admitted more than five times. Pain was the most common symptom, while 83.9% of those admitted had received at least one blood transfusion.The majority of patients attending SCD clinics in Eastern Uganda are children and few are currently being treated with hydroxyurea. The data collected through this facility-based survey will provide background data that will be useful in planning for the H-PRIME trial.
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    Modifying Intestinal Integrity and MicroBiome in Severe Malnutrition with Legume-Based Feeds (MIMBLE 2.0): Protocol For A Phase Ii Refined Feed And Intervention Trial
    (Wellcome open research, 2018) Walsh, Kevin; Calder, Nuala; Olupot, Peter Olupot; Ssenyondo, Tonny; Okiror, William; Okalebo, Charles Bernard; Muhindo, Rita; Mpoya, Ayub; Holmes, Elaine; Marchesi, Julian; Chenevarin, Gael Delamare de la Villenaise de; Frost, Gary; Maitland, Kathryn
    Changes in intestinal mucosal integrity and gut microbial balance occur in severe acute malnutrition (SAM), resulting in treatment failure and adverse clinical outcomes (gram-negative sepsis, diarrhoea and high case-fatality). Transient lactose intolerance, due to loss of intestinal brush border lactase, also complicates SAM, thus milk based feeds may not be optimal for nutritional rehabilitation. Since the gut epithelial barrier can be supported by short chain fatty acids, derived from microbiota fermentation by particular fermentable carbohydrates, we postulated that an energy-dense nutritional feed comprising of legume-based fermentable carbohydrates, incorporated with lactose-free versions of standard World Health Organization (WHO) F75/F100 nutritional feeds will enhance epithelial barrier function in malnourished children, reduce and promote resolution of diarrhoea and improve overall outcome.We will investigate in an open-label trial in 160 Ugandan children with SAM, defined by mid-upper arm circumference <11.5cm and/or presence of kwashiorkor. Children will be randomised to a lactose-free, chickpea-enriched feed containing 2 kcal/ml, provided in quantities to match usual energy provision (experimental) or WHO standard treatment F75 (0.75 kcal/ml) and F100 (1 kcal/ml) feeds on a 1:1 basis, conducted at Mbale Regional Referral Hospital nutritional rehabilitation unit. The primary outcomes are change in MUAC at day 90 and survival to day 90. Secondary outcomes include: i) moderate to good weight gain (>5 g/kg/day), ii) de novo development of diarrhoea (>3 loose stools/day), iii) time to diarrhoea resolution (if >3 loose stools/day), and iv) time to oedema resolution (if kwashiorkor) and change in intestinal biomarkers (faecal calprotectin).We hypothesize that, if introduced early in the management of malnutrition, such lactose-free, fermentable carbohydrate-based feeds, could safely and cheaply improve global outcome by reducing lactose intolerance-related diarrhoea, improving mucosal integrity and enhancing immunity, and limiting the risk of systemic infection and associated broad-spectrum antibiotic resistance.
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    Pharmacokinetics And Pharmacodynamics Of Azithromycin In Severe Malaria Bacterial Co-Infection In African Children (TABS-PKPD): A Protocol For A Phase II Randomised Controlled Trial
    (Wellcome Open Research, 2021) Olupot, Peter Olupot; Okiror, William; Mnjalla, Hellen; Muhindo, Rita; Uyoga, Sophie; Mpoya, Ayub; Williams, Thomas N.; terHeine, Rob; Burger, David M.; Urban, Britta; Connon, Roisin; George, Elizabeth C.; Gibb, Diana M.; Walker, A. Sarah; Maitland, Kathryn
    African children with severe malaria are susceptible to Gram-negative bacterial co-infection, largely non-typhoidal Salmonellae, leading to a substantially higher rates of in-hospital and post-discharge mortality than those without bacteraemia. Current evidence for treating co-infection is lacking, and there is no consensus on the dosage or length of treatment required. We therefore aimed to establish the appropriate dose of oral dispersible azithromycin as an antimicrobial treatment for children with severe malaria and to investigate whether antibiotics can be targeted to those at greatest risk of bacterial co-infection using clinical criteria alone or in combination with rapid diagnostic biomarker tests. A Phase I/II open-label trial comparing three doses of azithromycin: 10, 15 and 20 mg/kg spanning the lowest to highest mg/kg doses previously demonstrated to be equally effective as parenteral treatment for other salmonellae infection. Children with the highest risk of bacterial infection will receive five days of azithromycin and followed for 90 days. We will generate relevant pharmacokinetic data by sparse sampling during dosing intervals. We will use population pharmacokinetic modelling to determine the optimal azithromycin dose in severe malaria and investigate azithromycin exposure to change in C-reactive protein, a putative marker of sepsis at 72 hours, and microbiological cure (seven-day), alone and as a composite with seven-day survival. We will also evaluate whether a combination of clinical, point-of-care diagnostic tests, and/or biomarkers can accurately identify the sub-group of severe malaria with culture-proven bacteraemia by comparison with a control cohort of children hospitalized with severe malaria at low risk of bacterial co-infection.