BackgroundEarly recognition of antiretroviral therapy (ART) failure in resource limited settings is a challenge given the limited laboratory facilities and trained personnel. This study aimed at describing the incidence, risk factors and the resistance associated mutations (RAMs) of first line treatment failure among HIV-1-infected children attending the Joint Clinical Research Centre (JCRC), Kampala, Uganda.MethodsA retrospective cohort of 701 children who had been initiated on ART between January 2004 and September 2009 at the JCRC was studied. Data of children aged 6 months up to 18 years who had been started on ART for at least 6 months was extracted from the clinic charts. The children who failed the first-line ART were taken as cases and those who did not fail as the controls. Data was analysed using STATA version10.ResultsOf 701 children, 240(34%) failed on first line ART (cases) and 461(66%) did not fail (controls). The overall median time (IQR) to first line ART failure was 26.4 (18.9 – 39.1) months. The factors associated with treatment failure were poor adherence [(OR = 10, 95 CI: 6.4 – 16.7) p < 0.001], exposure to single dose nevirapine (sdNVP) [(OR = 4.2, 95% CI:1.8-9.4), p = 0.005] and a NVP containing regimen [(OR = 2.2,95% CI:1.4-3.6), p < 0.001]. Of 109 genotypic resistance profiles analyzed, the commonest non nucleoside reverse transcriptase inhibitor (NNRTI) resistance associated mutations (RAM) were: K103N (59; 54%)), Y181C (36; 27%)) and G190A (26; 24%)) while the commonest nucleoside reverse transcriptase inhibitor (NRTI) RAM was the M184V (89; 81%). Thymidine analogue- mutations (TAMs) were detected in 20% of patients.ConclusionsOne in three children on first-line ART are likely to develop virological treatment failure after the first 24 months of therapy. Poor adherence to ART, a NVP based first-line regimen, prior exposure to sdNVP were associated with treatment failure.

Overall immunological and virologic ART responses were similar in children in both cohorts. Poorer CD4 recovery in more immunosuppressed Kampala children and blunted growth responses likely reflect higher background malnutrition and infection rates in Uganda, suggesting the need for earlier HIV diagnosis, nutritional support, cotrimoxazole prophylaxis, and ART.

Enterocytozoon bieneusi is clinically the most significant of the microsporidia in humans, causing chronic diarrhea wasting and cholangitis in individuals with human immunodeficiency virus infection and AIDS. Little progress on this infection has been made because of the inability to propagate E. bieneusi in vitro and in vivo, which limits the source of parasite spores to the stools of infected human patients. Given the size and shape of the E. bieneusi spores (1.1 to 1.6 by 0.7 to 1.0 m) and the lack of specific immune reagents, the identification and purification of large quantities of spores from feces are technically challenging. Consequently, diagnosis relies entirely on PCR, a labor-intensive approach that requires highly skilled personnel. We describe a method for the purification of E. bieneusi spores from human stools and the production of rabbit-specific antisera. Spores were purified by a combination of isopycnic Percoll gradient centrifugation and continuous sucrose gradient centrifugation. Specific polyclonal antibodies raised in mice and rabbits reacted by indirect immunofluorescence with E. bieneusi but not with Encephalitozoon spp., Candida albicans, Staphylococcus aureus, Escherichia coli, or other forms present in human stools.Enterocytozoon bieneusi is a widespread enteric microsporidium which probably infects most mammals. The infection was first identified two decades ago in individuals with AIDS with severe symptoms of chronic diarrhea and wasting (10) and has remained a significant pathogen in this subpopulation ever since (5,6,18). E. bieneusi is recognized as the most common and clinically significant organism among the microsporidia which infect humans who have immunodeficiencies (18,21) or who are receiving immunosuppressive therapy (13,22). E. bieneusi is only rarely symptomatic in immunocompetent individuals, possibly contributing to traveler's diarrhea (11). It is an intracellular microorganism which appears to infect the epithelium of the upper small intestine and the hepatobiliary tract (26), causing chronic diarrhea and cholangitis. The number of E. bieneusi cases has diminished considerably in developed countries due to the use of antiretroviral therapy in people with human immunodeficiency virus infection and AIDS (12). The number of cases, however, in such individuals in developing countries, where antiretroviral therapy is either not available or not affordable, remains very high (4, 14, 23).Scientific progress on E. bieneusi has been slow, largely because of a lack of in vitro and in vivo models for parasite propagation and laboratory investigations. While E. bieneusi did appear to infect cells in culture, the spore yields were low and continuous culture could not be maintained (25). Natural infections of immunologically competent and immunodeficient macaques have also been reported, and the distribution of infection and lesions are similar to those seen in infected humans (8,9,16,17,20). In macaques infected with simian immunodeficiency virus, lesions associated with E. bie...

Tuberculosis (TB) remains a significant, yet under-recognized cause of death in the pediatric population, with a WHO estimate of 1 million new cases of childhood TB in 2016 resulting in 250,000 deaths. Diagnosis is notoriously difficult; manifestations are protean due to the high proportion of cases of extra-pulmonary TB in children, and logistical problems exist in obtaining suitable specimens. These issues are compounded by the paucibacillary nature of disease with the result that an estimated 96% of pediatric TB-associated mortality occurs prior to commencing anti-tuberculous treatment. Further development of sensitive, rapid diagnostic tests and their incorporation into diagnostic algorithms is vital in this population, and central to the WHO End-TB strategy. Initial gains were made with the expansion of nucleic acid amplification technology, particularly the introduction of the GeneXpert fully-automated PCR Xpert MTB/Rif assay in 2010, and more recently, the Xpert MTB/Rif Ultra (Ultra) assay in 2017. Ultra provides increased analytical sensitivity when compared with the initial Xpert assay in vitro ; a finding now also supported by six clinical studies to date, two of which included pediatric samples. Here, we review the published evidence for the performance of Ultra in TB diagnosis in children, as well as studies in adults with paucibacillary disease providing results relevant to the pediatric population. Following on from this, we speculate upon future directions for Ultra, with focus on its potential use with alternative diagnostic specimens, which may be of particular utility in children.

BackgroundAttention deficit hyperactivity disorder (ADHD) is a common neuropsychiatric disorder among the children. The burden of ADHD or its associated factors in Uganda are not known. The objective of this study was to determine the prevalence and the associated factors of ADHD among children attending the neurology and psychiatry clinics at Mulago National Referral Hospital.MethodsUsing the disruptive behavior scale (45 items), we investigated the presence of ADHD symptoms among children attending Mulago Hospital. Questionnaires were administered to the primary care-takers of the study participants to gather information on the factors associated with ADHD. All children were subject to a clinical examination. Children presumed to have ADHD, using the aforementioned rating scale were further assessed by a child psychiatrist to confirm the diagnosis and associated co-morbid conditions.ResultsThe estimated prevalence of DSM-IV ADHD symptoms was 11%. Children aged less than 10 years were four times likely to have ADHD (OR 4.1, 95% CI 1.7–9.6, p < 0.001). The demographic factors independently associated with ADHD were age less than 10 years, male gender, history of maternal abnormal vaginal discharge during pregnancy, and no formal education or the highest level of education being primary school.ConclusionThe prevalence of ADHD among children attending the pediatric neurology and psychiatry clinics is high in our settings and is associated with delayed milestones. Early identification and addressing the co-morbid conditions associated with ADHD such as epilepsy, autism spectrum of disorder, conduct disorder, opposition defiant disorder and intellectual disability in our setting is needed.

BackgroundAdolescents experience high rates of depression, initiation of sexual activity, and substance use.ObjectivesTo better understand the demographics of adolescents presenting to an adolescent clinic in Uganda, and to elucidate which factors are associated with depressive symptoms, sexual initiation, and substance use.MethodsA retrospective review was performed on intake forms obtained during interviews with adolescents presenting to the Makerere/Mulago Columbia Adolescent Health Clinic (MMCAH) in Kampala, Uganda.ResultsDepressive symptoms in adolescents were correlated with having a chronic illness (p=.026), and reported poor quality of home life (p<.001). Initiation of sexual activity was also correlated with chronic illness (p=.008) and poor quality of home life (p=.006). Substance use was correlated with maternal death (p=.041), chronic illness (p=.038), and substance use among family members (p<.001) and friends (p<.001).ConclusionsKnowing the aforementioned risk factors can help us better understand the needs of adolescents presenting to MMCAH, and allows us to develop targeted interventions aimed at decreasing health risks in Kampala's adolescent population.

Background: Diabetes mellitus is on the rise in low-income countries, including Uganda, owing to the 'westernization' of individual lifestyles. It remains unanswered whether the majority of university students who are rapidly embracing 'western' lifestyles have any knowledge of diabetes or perceive themselves to be at risk of acquiring the disease. The aim of the study was to assess the knowledge, attitudes, and perceived risks related to diabetes mellitus among university students in Uganda.Methods: This descriptive cross-sectional study was conducted in 4 universities in Uganda from August to November 2013. The data collection tool included questions on risk factors, symptoms, personal risks, and practices to prevent diabetes mellitus. We interviewed 378 university students using pretested self-administered semi-structured questionnaires. Only students who consented to participate in the study were included. Data were entered into EpiData version 3.1 and analysed using SPSS version 18.Results: Almost all (99%) of the students had knowledge about diabetes mellitus. The majority (83.1%) reported that diabetes mellitus is not completely a genetic/hereditary disease. Only a minority of respondents reported that they should worry about diabetes before 45 years of age. Common symptoms of diabetes reported by the respondents included constant hunger, blurred vision, fatigue, and frequent urination. Conclusions:Our study revealed that the majority of university students in Uganda had good knowledge about the risk factors and symptoms of diabetes mellitus. The majority also perceived themselves to be at risk of diabetes.

Background Adolescent medicine (AM) has been increasingly recognized as critically important to the health of individuals during their transition to adulthood. On a global scale, AM is often underprioritized and underfunded. In low-and middle-income countries (LMICs), education and AM training is developing, and AM physicians often are from general medicine backgrounds.Objective The objective of our scoping review was to identify existing training curricula and educational tools designed to teach AM skills to health care workers in LMICs. MethodsWe followed PRISMA guidelines for scoping reviews for article identification and inclusion. Online databases, including MEDLINE, Embase, CINAHL, and Scopus, were used to identify papers. We included studies that took place in a LMIC, were available in English, and described any of the following: published educational curricula in AM, education-based intervention for HCWs that focused on AM, or a training opportunity in AM located in a LMIC.Results Our review includes 14 publications: 5 published curricula and 9 articles describing educational interventions or training opportunities in AM in LMICs. Curricula were relatively consistent in the topics included, although they varied in implementation and teaching strategies. The scholarly articles described educational materials and identified a number of innovative strategies for training programs.Conclusions Our review found existing high-quality AM curricula designed for LMICs. However, there is limited published data on their implementation and utilization. There is a continued need for funding and implementation of education in AM in resourceconstrained settings.