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Case fatality among African children with severe acute malnutrition remains high. We report a 3-arm pilot trial in 58 Ugandan children, comparing feeds targeting disordered gastrointestinal function containing cowpea (CpF, n = 20) or inulin (InF, n = 20) with conventional feeds (ConF, n = 18). Baseline measurements of gut permeability (lactulose:mannitol ratio 1.19 ± SD 2.00), inflammation (fecal calprotectin 539.0 μg/g, interquartile range [IQR] 904.8), and satiety (plasma polypeptide YY 62.6 pmol/l, IQR 110.3) confirm gastrointestinal dysfunction. By day 28, no differences are observable in proportion achieving weight gain >5 g/kg/day (87%, 92%, 86%; p > 0.05), mortality (16%, 30%, 17%; p > 0.05), or edema resolution (83%, 54%, 91%; p > 0.05) among CpF, InF, and ConF. Decreased fecal bacterial richness from day 1 (abundance-based coverage estimator [ACE] 53.2) to day 7 (ACE 40.8) is observed only in ConF (p = 0.025). Bifidobacterium relative abundance increases from day 7 (5.8% ± 8.6%) to day 28 (10.9% ± 8.7%) in CpF (corrected p = 1.000). Legume-enriched feeds support aspects of gut function and the microbiome. Trial registration PACTR201805003381361., Competing Interests: The authors declare no competing interests., (© 2021 The Author(s).)

Background: Globally, female sex workers (FSW) are disproportionately affected by HIV and other sexually transmitted infections (STIs). However, uptake of STI and HIV testing services among FSW in sub-Saharan Africa remains low. We aimed to assess the effect of FSW-led peer education and text message reminders on 3-monthly syphilis and HIV testing among FSW in Uganda., Methods: Between September 2019 and February 2020, we implemented weekly peer education sessions and bi-monthly SMS reminders for FSW in Mbarara (intervention city). Peer education sessions were implemented by 20 FSW, who received five days of basic training as peer educators. We held monthly meetings with peer educators throughout the six-month implementation period. FSW in Mbale (control city) continued to receive standard of care consisting of HIV testing outreach campaigns, and facility-based testing. Using a quasi-experimental design in one intervention city, and one control city, we conducted pre- and post- questionnaire-based surveys on recent syphilis and HIV testing behavior among FSW in July-October 2018, and March 2020. We compared proportions and prevalence ratios at baseline and follow-up using chi-square tests and negative binomial regression., Results: We conducted 436 interviews (200 before/236 after) with FSW. At baseline similar proportions reported taking an HIV test (57 % vs. 54 %; p = 0.72), and a syphilis serology test (35 % vs. 39 %; p = 0.67) in the intervention and control cities, respectively, in the prior three months. After the intervention, this proportion increased to 82 % (95 % confidence interval [CI] 74.0-88.2) for HIV, and 81 % (95 % CI: 73.0-87.0) for syphilis in the intervention city. Relative to baseline in the control city, the proportion testing for HIV was unchanged (52 %) but decreased for syphilis (26 %)., Conclusions: Bi-monthly text message reminders with weekly peer education sessions increased uptake of 3-monthly syphilis and HIV testing in a Ugandan female sex work population and could help increase sex worker engagement in HIV/STI services in line with World Health Organization recommendations.

Objective: To explore the experiences and lessons learnt by the study team and participants of the Workplace-based HIV self-testing among Men trial during the COVID-19 pandemic in Uganda., Design: An explorative qualitative study comprising two virtual focus group discussions (FGDs) with 12 trial team members and 32 in-depth participant interviews (N=44). Data were collected via telephone calls for in-depth interviews or Zoom for FGDs and manually analysed by inductive content analysis., Setting: Fourteen private security companies in two Uganda districts., Participants: Members of the clinical trial study team, and men working in private security companies who undertook workplace-based HIV testing., Results: The key themes for participants experiences were: 'challenges in accessing HIV treatment and care, and prevention services', 'misinformation' and 'difficulty participating in research activities'. The effects on HIV treatment and prevention resulted from; repercussions of the COVID-19 restrictions, participants fear of coinfection and negative experiences at health facilities. The difficulty in participating in research activities arose from: fear of infection with COVID-19 for the participants who tested HIV negative, transport difficulties, limited post-test psychosocial support and lack of support to initiate pre-exposure prophylaxis. The key study team reflections focused on the management of the clinical trial, effects of the local regulations and government policies and the need to adhere to ethical principles of research., Conclusions: Findings highlight the need to organise different forms of HIV support for persons living with HIV during a pandemic. Additionally, the national research regulators and ethics committees or review boards are strongly urged to develop policies and guidelines for the continuity of research and clinical trials in the event of future shocks. Furthermore, this study calls on the appropriate government agencies to ensure public and researchers' preparedness through continuing education and support., Trial Registration Number: Clinicaltrials.gov NCT04164433; Pre-results., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Good adherence to antiretroviral therapy (ART) and retention in care are essential for the effectiveness of an HIV care program. With the current increase in numbers of people living with HIV taking second-line ART in sub-Saharan Africa, there is a need to establish their treatment outcomes and the rate of loss to follow up. In this study, we determined the incidence and predictors of loss to follow up among patients taking second-line ART at an experienced HIV treatment center in southwestern Uganda., Methods: This was a retrospective review of an electronic database at Mbarara Regional Referral Hospital HIV clinic in southwestern Uganda. Second-line ART included at least two of the nucleoside reverse transcriptase inhibitors and a boosted protease inhibitor. Loss to follow-up was defined as failure to return to the health facility for care or treatment refill for 180 days or more from the previous visit. After excluding children less than 15 years, we pooled data that included socio-demographic, clinical, and laboratory data for patients who started second-line ART between 2002 and 2017. Multiple imputation was done for variables with missing data. Variables that had a p < 0.05 in unadjusted bivariate analyses were included in a multivariate binomial regression model using a stepwise backward selection procedure to describe the factors that independently predicted loss to follow-up., Results: Between 2002 and 2017, 1121 patients had been initiated on second-line ART. We included data from 924 participants and of these, 518 (56.1%) were female, the mean age (SD) was 38.4 (± 10.5) years, and 433 (52.4%) had a CD4 count less than 100 cells/µl at the start of second-line ART. The incidence of loss to follow-up was 26.7 per 100 person-years. Male gender (Adjusted risk ratio (ARR) = 1.8, 95% CI 1.5-2.0) p < 0.001 and anemia ARR 1.4, 95% CI 1.1-1.6) p < 0.001 were strongly associated with loss to follow up., Conclusions: There is a high incidence of loss to follow up among patients taking protease-inhibitor based second-line ART at a tertiary HIV center in southwestern Uganda. There is a need to routinely measure hemoglobin during clinic reviews, and establish mechanisms to retain males initiated on second-line ART in care. The association of anemia and loss to follow up needs to be investigated.

Objective: Epilepsy is the most common chronic neurological disorder in the world and imposes a large economic burden on global healthcare systems, especially in low-income settings and rural areas as is found in sub-Saharan Africa (SSA). Despite the high epilepsy prevalence, there are no systematic descriptions of healthcare provider (HCP) perceptions and needs in managing people with epilepsy (PWE) in Uganda. Identifying these perceptions and needs is crucial for understanding community priorities, thereby enhancing the development of culturally sensitive communications, interventions, and research approaches., Methods: In this qualitative study, we used semistructured interview guides to conduct focus group discussions that explored the perspectives of 32 providers of epilepsy care from health facilities around Mbarara, Uganda. Our sample included nonspecialized general physicians (n = 3), medical residents (n = 8), medical clinical officers (n = 3), psychiatric clinical nurses (n = 6), medical nurses and nursing assistants (n = 9), and other providers (n = 3), who were loosely grouped into discussion groups based on level or type of training. Self-assessed proficiency ratings were also administered to gain a better understanding of participants' confidence in their training, preparedness, and capabilities regarding epilepsy care. Thematic analysis of the focus group transcripts was conducted to ascertain commonly occurring themes about perceptions and challenges in epilepsy care., Results: Our analyses identified nine major themes that dominated the perspectives of the study participants: care management, medications, diagnostics, HCP training, human resources, location, patient education, social support, and community knowledge and beliefs. Proficiency ratings prioritized areas of confidence as knowledge related to referrals, psychosocial impacts, and seizure neurophysiology. Areas of need were revealed as knowledge of diagnostic tools and antiepileptic drug (AED) regimens., Conclusions: Our findings delineate the perspectives of providers caring for PWE, with consistent recognition of challenges centering around resource augmentation, infrastructure strengthening, and education. Participants emphasized the urgent need to augment these resources to address limitations in medication types and access, trained human resources, and diagnostic tools. They overwhelmingly recognized the need for infrastructure strengthening to address human, diagnostic, medicinal, and capital resource limitations that place undue burden on patients with epilepsy and physicians. Providers indicated a clear desire to learn more about different diagnostic tools and medical management practices, potentially through continuing education, specialized training, or more intentional in-school diagnostic preparation. They also advocated for the powerful influence of patient and family education and clearly articulated the need for community sensitization and support. This article is part of the Special Issue "The Intersection of Culture, Resources, and Disease: Epilepsy Care in Uganda"., Competing Interests: Declaration of competing interest None., (Copyright © 2020. Published by Elsevier Inc.)

Background: The spatial distribution and burden of dengue in sub-Saharan Africa remains highly uncertain, despite high levels of ecological suitability. The goal of this study was to describe the epidemiology of dengue among a cohort of febrile children presenting to outpatient facilities located in areas of western Uganda with differing levels of urbanicity and malaria transmission intensity., Methods: Eligible children were first screened for malaria using rapid diagnostic tests. Children with a negative malaria result were tested for dengue using a combination NS1/IgM/IgG rapid test (SD Bioline Dengue Duo). Confirmatory testing by RT-PCR was performed in a subset of participants. Antigen-capture ELISA was performed to estimate seroprevalence., Results: Only 6 of 1416 (0.42%) children had a positive dengue rapid test, while none of the RT-PCR results were positive. ELISA testing demonstrated reactive IgG antibodies in 28 (2.2%) participants with the highest prevalence seen at the urban site in Mbarara (19 of 392, 4.9%, p < 0.001)., Conclusions: Overall, these findings suggest that dengue, while present, is an uncommon cause of non-malarial, pediatric febrile illness in western Uganda. Further investigation into the eocological factors that sustain low-level transmission in urban settings are urgently needed to reduce the risk of epidemics.

Introduction: Hypertensive disorders of pregnancy (HDP) are a leading cause of global perinatal (fetal and neonatal) and maternal morbidity and mortality. We sought to describe HDP and determine the magnitude and risk factors for adverse perinatal and maternal outcomes among women with HDP in southwestern Uganda., Methods: We prospectively enrolled pregnant women admitted for delivery and diagnosed with HDP at a tertiary referral hospital in southwestern Uganda from January 2019 to November 2019, excluding women with pre-existing hypertension. The participants were observed and adverse perinatal and maternal outcomes were documented. We used multivariable logistic regression models to determine independent risk factors associated with adverse perinatal and maternal outcomes., Results: A total of 103 pregnant women with a new-onset HDP were enrolled. Almost all women, 93.2% (n = 96) had either pre-eclampsia with severe features or eclampsia. The majority, 58% (n = 60) of the participants had an adverse perinatal outcome (36.9% admitted to the neonatal intensive care unit (ICU), 20.3% stillbirths, and 1.1% neonatal deaths). Fewer participants, 19.4% (n = 20) had an adverse maternal outcome HELLP syndrome (7.8%), ICU admission (3%), and postpartum hemorrhage (3%). In adjusted analyses, gestational age of < 34 weeks at delivery and birth weight <2.5kg were independent risk factors for adverse perinatal outcomes while referral from another health facility and eclampsia were independent risk factors for adverse maternal outcomes., Conclusion: Among women with HDP at our institution, majority had preeclampsia with severe symptoms or eclampsia and an unacceptably high rate of adverse perinatal and maternal outcomes; over a fifth of the mothers experiencing stillbirth. This calls for improved antenatal surveillance of women with HDP and in particular improved neonatal and maternal critical care expertise at delivering facilities. Earlier detection and referral, as well as improvement in initial management at lower level health units and on arrival at the referral site is imperative., Competing Interests: The authors have declared that no competing interests exist.

Background: Few recent descriptions of severe childhood malaria have been published from high-transmission regions. In the current study, the clinical epidemiology of severe malaria in Mbale, Eastern Uganda, is described, where the entomological inoculation rate exceeds 100 infective bites per year., Methods: A prospective descriptive study was conducted to determine the prevalence, clinical spectrum and outcome of severe Plasmodium falciparum malaria at Mbale Regional Referral Hospital in Eastern Uganda. All children aged 2 months-12 years who presented on Mondays to Fridays between 8.00 am and 5.00 pm from 5th May 2011 until 30th April 2012 were screened for parasitaemia. Clinical and laboratory data were then collected from all P. falciparum positive children with features of WHO-defined severe malaria by use of a standardized proforma., Results: A total of 10 208 children were screened of which 6582 (64%) had a positive blood film. Of these children, 662 (10%) had clinical features of severe malaria and were consented for the current study. Respiratory distress was the most common severity feature (554; 83.7%), while 365/585 (62.4%) had hyperparasitaemia, 177/662 (26.7%) had clinical jaundice, 169 (25.5%) had severe anaemia, 134/660 (20.2%) had hyperlactataemia (lactate ≥ 5 mmol/L), 93 (14.0%) had passed dark red or black urine, 52 (7.9%) had impaired consciousness and 49/662 (7.4%) had hypoxaemia (oxygen saturations < 90%). In-hospital mortality was 63/662 (9.5%) overall but was higher in children with either cerebral malaria (33.3%) or severe anaemia (19.5%). Factors that were independently associated with mortality on multivariate analysis included severe anaemia [odds ratio (OR) 5.36; 2.16-1.32; P = 0.0002], hyperlactataemia (OR 3.66; 1.72-7.80; P = 0.001), hypoxaemia (OR) 3.64 (95% CI 1.39-9.52; P = 0.008), and hepatomegaly (OR 2.29; 1.29-4.06; P = 0.004). No independent association was found between mortality and either coma or hyperparasitaemia., Conclusions: Severe childhood malaria remains common in Eastern Uganda where it continues to be associated with high mortality. An unusually high proportion of children with severe malaria had jaundice or gave a history of having recently passed dark red or black urine, an issue worthy of further investigation.

Background: In Sub-Saharan Africa where HIV disproportionately affects women, heterosexual male sex workers (HMSW) and their female clients are at risk of acquiring or transmitting HIV and other STIs. However, few studies have described HIV and STI risk among HMSW. We aimed to assess and compare recent HIV and syphilis screening practices among HMSW and female sex workers (FSW) in Uganda., Methods: Between August and December 2019, we conducted a cross-sectional study among 100 HMSW and 240 female sex workers (FSW). Participants were enrolled through snowball sampling, and an interviewer-administered questionnaire used to collect data on HIV and syphilis testing in the prior 12 and 6 months respectively. Integrated change model constructs were used to assess intentions, attitudes, social influences, norms and self-efficacy of 3-monthly Syphilis and 6-monthly HIV testing. Predictors of HIV and syphilis recent testing behaviors were estimated using negative binomial regression., Results: We enrolled 340 sex workers of whom 100 (29%) were HMSW. The median age was 27 years [interquartile range (IQR) 25-30] for HMSW and 26 years [IQR], (23-29) for FSW. The median duration of sex work was 36 and 30 months for HMSW and FSW, respectively. HMSW were significantly less likely than FSW to have tested for HIV in the prior 12 months (50% vs. 86%; p = 0.001). For MSW, non-testing for HIV was associated with higher education [adjusted prevalence ratio (aPR) 1.66; 95% confidence interval (CI) 1.09-2.50], poor intention to seek HIV testing (aPR 1.64; 95% CI 1.35-2.04), perception that 6-monthly HIV testing was not normative (aPR 1.33; 95% CI 1.09-1.67) and low self-efficacy (aPR 1.41; 95% CI 1.12-1.79). Not testing for syphilis was associated with low intention to seek testing (aPR 3.13; 95% CI 2.13-4.55), low self-efficacy (aPR 2.56; 95% CI 1.35-4.76), negative testing attitudes (aPR 2.33; 95% CI 1.64-3.33), and perception that regular testing was not normative (aPR 1.59; 95% CI 1.14-2.22)., Conclusions: Non-testing for HIV and syphilis was common among HMSW relative to FSW. Future studies should evaluate strategies to increase testing uptake for this neglected sub-population of sex workers.

Background: Hypertension is a significant cardiovascular disease (CVD) and driver to CVD disorders in sub-Saharan Africa. It is a major independent risk factor for heart failure, stroke, and kidney failure. Persons living with hypertension attend to many aspects of self-care to manage their condition, including high blood pressure medication adherence to control of blood pressure. Rates of medication non-adherence, and thus uncontrolled hypertension, remain high and contribute to poor health outcomes. Understanding barriers and facilitators to adherence to hypertension therapies can help improve health outcomes., Objective: The aim of the study was to describe the common reasons for adherence and non-adherence to antihypertensive medication from patients' perspectives., Methods: A qualitative study engaged clients of an out-patient clinic of a regional referral hospital in southwestern Uganda who were living with hypertension as participants. One-on-one in-depth interviews provided the narrative data. The interview transcripts were analyzed using thematic analysis., Findings: Sixteen participants provided the data for the findings. The themes identified as facilitators for adherence to antihypertensive medication were patients' understanding of prescribed medication, availability of medication for hypertension, family support for patients living with hypertension, and regular review appointments at the hypertensive clinics. Conversely, lack of supply in government dispensaries, use of self-prescribed analgesic medication, and stigma were identified as barriers and challenges of adherence to antihypertensive medication., Conclusions: There is an urgent need for the health ministry to improve availability of high blood pressure medication and for health care providers to deliver individualized patient centered care, and sensitization on danger of self-prescription and measures that reduce stigma. These strategies may improve adherence to high blood pressure medication., Competing Interests: The authors have no competing interests to declare., (Copyright: © 2020 The Author(s).)

Background: Limited data are available regarding correlates of regular sexually transmitted infections (STIs) and HIV screening among female sex workers (FSW) in Sub-Saharan Africa. In this study, we aimed to assess the frequency of regular syphilis and HIV screening and the psychosocial correlates associated with screening among FSW in Uganda., Methods: This cross-sectional correlational study was conducted among 441 FSW, aged 17-49 years. We enrolled FSW through peer referrals and ascertained self-reported data on number of serological tests for HIV, syphilis and other STIs in the prior 12 months using an interviewer-administered questionnaire. In addition, we assessed attitudes, norms, social influences and self-efficacy towards 3-monthly Syphilis and 6-monthly HIV testing. We estimated the correlates of regular STI and HIV testing using negative binomial regression., Results: Of the respondents 420 (95.2%) reported to have ever taken an HIV test with 297 (67.4%) testing two or more times in the prior 12 months. Over half of the respondents (59%) reported ever taking a syphilis test with only 62 (14.1%) reporting testing three or more times in the prior 12 months. After adjusting for socio-demographics, attitude and norms, high perceived self-efficacy was associated with a 33% increase in the likelihood of repeated HIV testing [prevalence ratio (PR), 1.33, 95% confidence interval (CI) 1.15-1.53] while low perceived confidence was associated with a 25% decrease in the likelihood of repeated HIV testing (PR, 0.75, 95% CI 0.63-0.89). Similarly low attitudes and norms were associated with a decrease of 52.6% (PR, 0.47, 95% CI 0.37-0.61) and 47% (PR, 0.53, 95% CI 0.41-0.69) in the likelihood of repeated syphilis testing respectively., Conclusion: Compared to HIV, uptake of repeated syphilis testing was very low. Correlates of HIV testing include; perceived self-efficacy amidst barriers and perceived confidence for HIV and low attitudes and accepting norms for syphilis. Health campaigns should emphasize overcoming barriers to HIV testing while promoting attitudes and norms including integration of serological syphilis testing and other STIs into HIV services.

Background: World Health Organization rehydration management guidelines (plan C) for severe dehydration are widely practiced in resource-poor settings, but never formally evaluated in a trial. The Fluid Expansion as a Supportive Therapy trial raised concerns regarding the safety of bolus therapy for septic shock, warranting a formal evaluation of rehydration therapy for gastroenteritis., Methods: A multi-centre open-label phase II randomised controlled trial evaluated two rehydration strategies in 122 Ugandan/Kenyan children aged 60 days to 12 years with severe dehydration secondary to gastroenteritis. We compared the safety and efficacy of standard rapid rehydration using Ringer's lactate (100 ml/kg over 3 h (6 h if < 1 year), incorporating 0.9% saline boluses for children with shock (plan C) versus slower rehydration: 100 ml/kg Ringer's lactate over 8 h (all ages) without boluses (slow: experimental). The primary outcome was the frequency of serious adverse events (SAE) within 48 h including cardiovascular, respiratory and neurological complications. Secondary outcomes included clinical, biochemical and physiological measures of response to treatment by intravenous rehydration., Results: One hundred twenty-two eligible children (median (IQR) age 8 (6-12) months) were randomised to plan C (n = 61) or slow (n = 61), with two (2%) lost to follow-up at day 7). Following randomisation mean (SD) time to start intravenous rehydration started was 15 min (18) in both arms. Mean (SD) fluid received by 1 hour was greater in plan C (mean 20.2 ml/kg (12.2) and 33.1 ml/kg (17) for children < 1 year and >- 1 year respectively) versus 10.4 ml/kg (6.6) in slow arm. By 8 hours volume received were similar mean (SD) plan C: 96.3 ml/kg (15.6) and 97.8 ml/kg (10.0) for children < 1 and ≥ 1 year respectively vs 93.2 ml/kg (12.2) in slow arm. By 48-h, three (5%) plan C vs two (3%) slow had an SAE (risk ratio 0.67, 95% CI 0.12-3.85, p = 0.65). There was no difference in time to the correction of dehydration (p = 0.9) or time to discharge (p = 0.8) between groups. Atrial natriuretic peptide levels rose substantially by 8 hours in both arms, which persisted to day 7. Day 7 weights suggested only 33 (29%) could be retrospectively classified as severely dehydration (≥ 10% weight loss)., Conclusion: Slower rehydration over 8 hours appears to be safe, easier to implement than plan C. Future large trials with mortality as the primary endpoint are warranted., Trial Registration: ISRCTN67518332 . Date applied 31 August 2016.

Background: Evidence shows that negative childbirth experiences may lead to undesirable effects including failure to breastfeed, reduced love for the baby, emotional upsets, post-traumatic disorders and depression among mothers. Understanding childbirth experiences and their meaning could be important in planning individualized care for mothers. The purpose of this study was to explore childbirth experiences and their meaning among postnatal mothers., Methods: A phenomenological qualitative study was conducted at Mbale Regional Referral Hospital among 25 postnatal mothers within two months after birth using semi-structured interviews and focus group discussions and data was thematically analyzed., Results: The severity, duration and patterns of labour pains were a major concern by almost all women. Women had divergent feelings of yes and no need of biomedical pain relief administration during childbirth. Mothers were socially orientated to regard labour pains as a normal phenomenon regardless of their nature. The health providers' attitudes, care and support gave positive and negative birth experiences. The Physical and psychosocial support provided comfort, consolation and encouragement to the mothers while inappropriate care, poor communication and compromised privacy contributed to the mothers' negative childbirth experiences. The type of birth affected the interpretations of the birth experiences. Women who gave birth vaginally, thought they were strong and brave, determined and self-confident; and were respected by members of their communities. On the contrary, the women who gave birth by operation were culturally considered bewitched, weak and failures., Conclusion: Childbirth experiences were unique; elicited unique feelings, responses and challenges to individual mothers. The findings may be useful in designing interventions that focus on individualized care to meet individual needs and expectations of mothers during childbirth.

Background: Malaria is a leading cause of paediatric morbidity and mortality in Uganda. More than half of febrile children in rural areas initially seek care at private clinics and drug shops. These shops are generally unregulated and the quality of clinical care is variable, with the potential for misdiagnosis and the development of drug resistance. There is thus an urgent need to identify rural drug shops and coordinate their malaria treatment efforts with those of the public sector. The objective of the study was to identify all drug shops in the Bugoye sub-county of Western Uganda and assess their anti-malarial dispensing practices., Methods: This study is a cross-sectional survey of drug shops in a rural sub-county of Western Uganda. In the first phase, shop locations, licensing and shopkeeper's qualifications, and supply and pricing of anti-malarials were characterized. In the second phase, the proportion of anti-malarials dispensed by private drug shops was compared to public health facilities., Results: A total of 48 drug shops were identified. Only one drug shop (1 of 48, 2%) was licensed with the sub-county's records office. The drug shops stocked a variety of anti-malarials, including first-line therapies and less effective agents (e.g., sulfadoxine/pyrimethamine). Almost all drug shops (45 of 48, 94%) provided parenteral anti-malarials. Of the 3900 individuals who received anti-malarials during the study, 2080 (53.3%) purchased anti-malarials through the private sector compared to 1820 (46.7%) who obtained anti-malarials through the public sector. Drug shops were the primary source of parenteral anti-malarials. Inadequate dosing of anti-malarials was more common in drug shops., Conclusions: Drug shops are major sources of parenteral anti-malarials, which should be reserved for cases of severe malaria. Strengthening malaria case management and incorporating drug shops in future interventions is necessary to optimize malaria control efforts in the sub-county, and in similarly endemic regions.

Background: 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. Methods: 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). Discussion: 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. Registration: ISRCTN 10309022., Competing Interests: No competing interests were disclosed.

Objectives: Perturbed hemodynamic function complicates severe malaria. The Fluid Expansion as Supportive Therapy trial demonstrated that fluid resuscitation, involving children with severe malaria, was associated with increased mortality, primarily due to cardiovascular collapse, suggesting that myocardial dysfunction may have a role. The aim of this study was to characterize cardiac function in children with severe malaria., Design: A prospective observational study with clinical, laboratory, and echocardiographic data collected at presentation (T0) and 24 hours (T1) in children with severe malaria. Cardiac index and ejection fraction were calculated at T0 and T1. Cardiac troponin I and brain natriuretic peptide were measured at T0. We compared clinical and echocardiographic variables in children with and without severe malarial anemia (hemoglobin < 5 mg/dL) at T0 and T1., Setting: Mbale Regional Referral Hospital., Patients: Children 3 months to 12 years old with severe falciparum malaria., Interventions: Usual care., Measurements and Main Results: We enrolled 104 children, median age 23.3 months, including 61 children with severe malarial anemia. Cardiac troponin I levels were elevated (> 0.1 ng/mL) in n equals to 50, (48%), and median brain natriuretic peptide was within normal range (69.1 pg/mL; interquartile range, 48.4-90.8). At T0, median Cardiac index was significantly higher in the severe malarial anemia versus nonsevere malarial anemia group (6.89 vs 5.28 L/min/m) (p = 0.001), which normalized in both groups at T1 (5.60 vs 5.13 L/min/m) (p = 0.452). Cardiac index negatively correlated with hemoglobin, r equals to -0.380 (p < 0.001). Four patients (3.8%) had evidence of depressed cardiac systolic function (ejection fraction < 45%). Overall, six children died, none developed pulmonary edema, biventricular failure, or required diuretic treatment., Conclusions: Elevation of cardiac index, due to increased stroke volume, in severe malaria is a physiologic response to circulatory compromise and correlates with anemia. Following whole blood transfusion and antimalarial therapy, cardiac index in severe malarial anemia returns to normal. The majority (> 96%) of children with severe malaria have preserved myocardial systolic function. Although there is evidence for myocardial injury (elevated cardiac troponin I), this does not correlate with cardiac dysfunction.

Background: Post-operative wound sepsis remains a surgical challenge of public health concern constituting approximately 20% of the health care-associated nosocomial infections. This study aimed at determining the prevalence and antimicrobial resistance patterns of bacterial pathogens isolated from post-operative wound infections at Mbale Regional Referral Hospital., Materials and Methods: This was a descriptive cross-sectional study conducted from June to October 2015. Study participant samples were sub-cultured upon reception in the Microbiology laboratory and the isolated bacterial pathogens were analysed. Phenotypic antimicrobial susceptibility profiles were determined using the Kirby-Bauer method. Interpretation of the zone diameters was done following the Clinical and Laboratory Standards Institute guidelines. Phenotypic screening for Methicillin-resistant Staphylococcus aureus (MRSA) was performed using oxacillin (1 μg). D-test was also performed for phenotypic screening of inducible clindamycin resistant Staphylococcus aureus , Data were entered into Microsoft Excel and analysed using IBM SPSS statistics (version 16)., Results: Overall post-operative sepsis was 69/80 (86.2%) with Staphylococcus aureus as the most predominant organism 41/104 (39.4%) followed by Escherichia coli 22/104 (21.2%) and Klebsiella species 15/104 (14.4%). Of the 41/104 isolated Staphylococcus aureus , 27/41(65.9%) were MRSA strains and 5/41 (12.2%) were inducible clindamycin resistant Staphylococcus aureus strains. The isolated Staphylococcus aureus was resistant to multiple drugs though susceptible to vancomycin and clindamycin. In addition, none of the isolated Enterococci species was vancomycin resistant. Although most of the isolated Gram-negative organisms were sensitive to imipenem, resistance was observed for tetracycline, trimethoprim/sulphamethoxazole, and ceftriaxone., Conclusion: Staphylococcus aureus was the most common causative agent associated with postoperative sepsis with most of the strains being MRSA. Multi-drug resistance was observed in 63/104 (60.6%) of the isolated organisms in our study. Hence the need to better develop and strengthen antimicrobial stewardship programs as well as to understand the carriage of antimicrobial resistance genes among these organisms., Competing Interests: COMPETING INTERESTS Authors have declared that no competing interests exist.

Purpose: We determined outcomes in hospitalized patients in Uganda with World Health Organization's Integrated Management of Adolescent and Adult Illness (IMAI) defined septic shock (IMAI-shock) or severe respiratory distress without shock (IMAI-SRD) based on whether they received recommended fluid resuscitation according to IMAI guidelines., Materials and Methods: We performed a secondary analysis of a prospective cohort of adult septic patients in Uganda that included the volume of fluids patients received during the first 6h of resuscitation. We used logistic regression to determine predictors of outcomes., Results: We evaluated 122 patients with IMAI-shock and 32 patients with IMAI-SRD. For patients with IMAI-shock or IMAI-SRD, there was no difference in mortality between those that received IMAI recommended fluid volume and those that did not (30% vs 36%, p=0.788; 22% vs 57%, p=0.08). For patients with IMAI-shock, in-hospital mortality was associated with mid-upper arm circumference (adjusted odds ratio [aOR] 0.841, 95% confidence interval [CI] 0.722-0.979, p=0.026) and ambulation (aOR 0.247, 95%CI 0.084-0.727, p=0.011). We found no associations with in-hospital mortality for patients with IMAI-SRD., Conclusion: IMAI recommended fluid resuscitation was not associated with better outcomes for patients with IMAI-shock or IMAI-SRD. Further studies are needed to optimize resuscitation for patients with severe infection in resource-limited settings such as Uganda., (Copyright © 2017. Published by Elsevier Inc.)

Background: In the Fluid Expansion as a Supportive Treatment (FEAST) trial, an unexpectedly high proportion of participants from eastern Uganda presented with blackwater fever (BWF)., Methods: We describe the prevalence and outcome of BWF among trial participants and compare the prevalence of 3 malaria-protective red blood cell polymorphisms in BWF cases vs both trial (non-BWF) and population controls., Results: Of 3170 trial participants, 394 (12.4%) had BWF. The majority (318 [81.0%]) presented in eastern Uganda and were the subjects of further analysis. BWF cases typically presented with both clinical jaundice (254/318 [80%]) and severe anemia (hemoglobin level <5 g/dL) (238/310 [77%]). Plasmodium falciparum parasitemia was less frequent than in non-BWF controls, but a higher proportion were positive for P. falciparum histidine rich protein 2 (192/246 [78.0%]) vs 811/1154 [70.3%]; P = .014), suggesting recent antimalarial treatment. Overall, 282 of 318 (88.7%) received transfusions, with 94 of 282 (33.3%) and 9 of 282 (3.4%) receiving 2 or 3 transfusions, respectively. By day 28, 39 of 318 (12.3%) BWF cases and 154 of 1554 (9.9%) non-BWF controls had died (P = .21), and 7 of 255 (3.0%) vs 13/1212 (1%), respectively, had severe anemia (P = .036). We found no association with G6PD deficiency. The prevalence of both the sickle cell trait (10/218 [4.6%]) and homozygous α+thalassemia (8/216 [3.7%]) were significantly lower among cases than among population controls (334/2123 [15.7%] and 141/2114 [6.6%], respectively), providing further support for the role of malaria., Conclusions: We report the emergence of BWF in eastern Uganda, a condition that, according to local investigators, was rare until the last 7 years. We speculate that this might relate to the introduction of artemisinin-based combination therapies. Further studies investigating this possibility are urgently required., (© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.)

Introduction: The optimal resuscitation strategy for patients with severe sepsis in resource-limited settings is unknown. Therefore, we determined the association between intravenous fluids, changes in vital signs and lactate after the first 6 hours of resuscitation from severe sepsis, and in-hospital mortality at a hospital in Uganda., Materials and Methods: We enrolled patients admitted with severe sepsis to Mbarara Regional Referral Hospital and obtained vital signs and point-of-care blood lactate concentration at admission and after 6 hours of resuscitation. We used logistic regression to determine predictors of in-hospital mortality., Results: We enrolled 218 patients and had 6 hour postresuscitation data for 202 patients. The median (interquartile range) age was 35 (26-50) years, 49% of patients were female, and 57% were HIV infected. The in-hospital mortality was 32% and was associated with admission Glasgow Coma Score (adjusted odds ratio [aOR], 0.749; 95% confidence interval [CI], 0.642-0.875; P < .001), mid-upper arm circumference (aOR, 0.876; 95% CI, 0.797-0.964; P = .007), and 6-hour systolic blood pressure (aOR, 0.979; 95% CI, 0.963-0.995; P = .009) but not lactate clearance of 10% or greater (aOR, 1.2; 95% CI, 0.46-3.10; P = .73)., Conclusions: In patients with severe sepsis in Uganda, obtundation and wasting were more closely associated with in-hospital mortality than lactate clearance of 10% or greater., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Studies have shown that couple HIV counseling and testing (CHCT) increased rates of sero-status disclosure and adoption of safer sexual behaviors with better linkage to treatment and care. However, current evidence suggests that new HIV infections are occurring among heterosexual couples in stable relationships where the majority of the individuals are not aware of their partner's serostatus. This study examined the predictors of CHCT uptake among married or cohabiting couples of Bukomero sub-county Kiboga district in Uganda., Methods: This cross-sectional correlational study was conducted among 323 individuals who were either married or cohabiting, aged 18-49 years. Participants were enrolled from randomly selected households in Bukomero sub-county. Data were collected using an interviewer-administered questionnaire on socio-demographics, self-rating on awareness of CHCT benefits, couple discussion about HIV testing and CHCT practices. Couples were compared between those who had reported to have tested as a couple and those who had not. Binary logistic regression was performed to determine the adjusted odds ratio [aOR] and 95 % confidence intervals [CI] for CHCT uptake and the other independent variables., Results: Of the participants 288 (89.2 %) reported to have ever taken an HIV test only 99 (34.4 %) did so as a couple. The predictors of testing for HIV as a couple were discussing CHCT with the partner (adjusted odds ratio 4.95[aOR], 95 % confidence interval [CI]:1.99-12.98; p < 0.001), awareness of CHCT benefits (aOR 3.23; 95 % CI 1.78-5.87; p < 0.001) and having time to test as a couple (aOR 2.61; 95 % CI 1.22-5.61; p < 0.05)., Conclusion: Uptake of HIV counseling and testing among couples was low. Discussing CHCT with partner, awareness of CHCT benefits, and availability of time to test as a couple were predictive of CHCT uptake. Thus CHCT campaigns should emphasize communication and discussion of HIV counseling and testing among partners.

Background: Many HIV-infected patients in sub-Saharan Africa are not routinely screened for hepatitis B virus (HBV) infection and are on antiretroviral therapy (ART) regimens containing only lamivudine as anti-HBV active drug., Methods: In 2009-2011, we screened for hepatitis B surface antigen (HBsAg) in 2820 HIV-infected adults patients at the Mbarara Hospital Uganda and investigated risk factors for HBV infection. Using samples of dried plasma or blood spots, we tested for HBV viral load and HBV drug resistance mutations in all HBsAg-positive patients on ART for ≥ 12 months., Results: In this study, 109 patients tested HBsAg positive (3.9%; 109/2820). HBsAg-positive patients were more likely to have had >4 lifetime sexual partners (p<0.01). Of the 55 HBsAg-positive patients on ART for ≥ 12 months, 53 were only on lamivudine as anti-HBV active drug and two were on tenofovir and lamivudine. HBV-DNA was detected in 30 patients (54.5%; 30/55), all on lamivudine-monotherapy. Of the 23 patients in whom HBV-DNA sequencing was successful, 17 had lamivudine-resistant HBV strains harbouring rtM204V/I mutations accompanied by secondary/compensatory mutations., Conclusions: Our study suggests that sexual transmission may represent a major mode of spread of HBV in southwest Uganda and confirms the importance of screening for HBV and of using ART regimens containing tenofovir in HIV/HBV co-infected patients., (© The Author 2015. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Malaria is often considered a cause of adult sepsis in malaria endemic areas. However, diagnostic limitations can make distinction between malaria and other infections challenging. Therefore, the objective of this study was to determine the relative contribution of malaria to adult sepsis in south-western Uganda., Methods: Adult patients with sepsis were enrolled at the Mbarara Regional Referral Hospital between February and May 2012. Sepsis was defined as infection plus ≥2 of the following: axillary temperature >37.5°C or <35.5°C, heart rate >90 or respiratory rate >20. Severe sepsis was defined as sepsis plus organ dysfunction (blood lactate >4 mmol/L, confusion, or a systolic blood pressure <90 mmHg). Sociodemographic, clinical and laboratory data, including malaria PCR and rapid diagnostic tests, as well as acid fast bacteria sputum smears and blood cultures were collected. Patients were followed until in-patient death or discharge. The primary outcome of interest was the cause of sepsis. Multivariable logistic regression was performed to assess predictors of mortality., Results: Enrollment included 216 participants who were 51% female with a median age of 32 years (IQR 27-43 years). Of these, 122 (56%) subjects were HIV-seropositive of whom 75 (66%) had a CD4+ T cell count <100 cells/μL. The prevalence of malaria was 4% (six with Plasmodium falciparum, two with Plasmodium vivax). Bacteraemia was identified in 41 (19%) patients. In-hospital mortality was 19% (n = 42). In multivariable regression analysis, Glasgow Coma Score <9 (IRR 4.81, 95% CI 1.80-12.8) and severe sepsis (IRR, 2.07, 95% CI 1.03-4.14), but no specific diagnoses were statistically associated with in-hospital mortality., Conclusion: Malaria was an uncommon cause of adult sepsis in a regional referral hospital in south-western Uganda. In this setting, a thorough evaluation for alternate causes of disease in patients presenting with sepsis is recommended.

We evaluated the association between severity of sepsis and in-hospital mortality in 150 patients with non-surgical sepsis at a regional referral hospital in Uganda. In-hospital mortality occurred in 5 of 52 (9.6%) patients with sepsis, 24 of 71 (33.8%) patients with severe sepsis, and 16 of 27 (59.3%) patients with septic shock. In the multivariate analysis, the identification of severe sepsis (adjusted hazard ratio [AHR] = 2.9, 95% confidence interval [CI] = 1.0-8.2, P = 0.04), septic shock (AHR = 5.7, 95% CI = 1.6-20.3, P = 0.007), and dysfunction of three or more organs (AHR = 2.9, 95% CI = 1.1-7.3, P = 0.03) increased the risk of in-hospital mortality. Adding aggregate organ dysfunction to the multivariate equation that included the sepsis category statistically significantly improved the model, but the opposite did not. Predictors of mortality were easily measurable and could be used to risk stratify critically ill patients in resource-constrained settings.