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Introduction: Although the use of illicit drugs is common among young people, limited data exists on the use of illicit drugs among adolescent boys and young men (ABYM). We assessed the use of tobacco, marijuana and khat among ABYM to inform the design of harm-reduction interventions. Methods: This secondary analysis uses data from a formative study conducted among 2,500 ABYM across the five divisions of Kampala between July and August 2020. Survey questions were adopted from the Global Youth Tobacco Survey and Global School-based Student Health Survey. We computed proportions of ABYM that had ever used any form of tobacco or marijuana or khat in the past year and the proportion that had used any of these products in the past 30 days (i.e. 'current users'). In a sub-group analysis, we assessed if any patterns existed between ABYM's use of illicit drugs and selected parental attention attributes. Results: Of 2,500 ABYM, 47.3% (n = 1,182) were aged 15–19 years. Overall, 16.4% (n = 410) reported past-year use of tobacco products while 11.6% (n = 289) and 10.5% (n = 263) reported past-year use of marijuana and khat, respectively. Current use of any illicit drugs was higher among past-year khat (46%, n = 133) and marijuana users (36.9%, n = 97) than past-year tobacco users (4%, n = 17). Current use of any illicit drugs was higher among out-of-school than in-school ABYM and increased with increasing age and education levels. However, parental attention was lower among out-of-school than in-school ABYM and decreased with increasing age and education levels. Conclusion: Use of illicit drugs is common among ABYM and increased with age and education levels but parental attention among current illicit drug users decreased with increasing age and education levels. These findings suggest that interventions intended to improve parental attention among illicit drug users may help to reduce the prevalence of illicit drug use among ABYM. [ABSTRACT FROM AUTHOR]

Background: Research and clinical use of clinical pharmacology laboratories are limited in low- and middle-income countries. We describe our experience in building and sustaining laboratory capacity for clinical pharmacology at the Infectious Diseases Institute, Kampala, Uganda. Intervention: Existing laboratory infrastructure was repurposed, and new equipment was acquired. Laboratory personnel were hired and trained to optimise, validate, and develop in-house methods for testing antiretroviral, anti-tuberculosis and other drugs, including 10 high-performance liquid chromatography methods and four mass spectrometry methods. We reviewed all research collaborations and projects for which samples were assayed in the laboratory from January 2006 to November 2020. We assessed laboratory staff mentorship from collaborative relationships and the contribution of research projects towards human resource development, assay development, and equipment and maintenance costs. We further assessed the quality of testing and use of the laboratory for research and clinical care. Lessons learnt: Fourteen years post inception, the clinical pharmacology laboratory had contributed significantly to the overall research output at the institute by supporting 26 pharmacokinetic studies. The laboratory has actively participated in an international external quality assurance programme for the last four years. For clinical care, a therapeutic drug monitoring service is accessible to patients living with HIV at the Adult Infectious Diseases clinic in Kampala, Uganda. Recommendations: Driven primarily by research projects, clinical pharmacology laboratory capacity was successfully established in Uganda, resulting in sustained research output and clinical support. Strategies implemented in building capacity for this laboratory may guide similar processes in other low- and middle-income countries. [ABSTRACT FROM AUTHOR]

Background: Viral load (VL) testing is key in monitoring adherence to antiretroviral therapy (ART) and documenting HIV treatment response. As per HIV treatment guidelines in Uganda, the first VL test is recommended 6 months after initiation of ART. Undetectable VL (uVL) at ART initiation may be helpful in detecting elite controllers in the absence of previous ART use. We investigated viral suppression at ART initiation among a cohort of HIV-positive pregnant women enrolled in the Friends for Life Circles (FLC) for Option B+ randomized controlled trial (RCT).Methods: Pregnant women ≥ 18 years of age testing positive for HIV at their first antenatal care visit and starting on ART Option B+ as per the National PMTCT Program guidelines were enrolled into the FLC for Option B+ RCT in urban Kampala and rural Mityana districts of Uganda. Each participant had whole blood samples collected at enrolment to assess baseline VL. Plasma HIV-1 RNA was quantified using COBAS Ampliprep /COBAS Taqman. Baseline VL below 400 RNA copies/ml was considered as viral suppression while baseline VL below 20 RNA copies/ml was considered uVL.Results: The mean duration from the date of ART initiation to time of sample collection for baseline VL assessment was 4.4 days (SD 3.6). Of the 532 HIV-positive pregnant women enrolled in the FLC for Option B+ study and newly starting Option B+ without a self-reported history of prior ART use, 29 (5.5%) had uVL and 113 (21.4%) had suppressed VL at baseline. There was no association between participants' age, gravidity, marital status, mean monthly income, educational level, disclosure of HIV status to partner, and uVL or viral suppression at baseline. However, non-disclosure of HIV status to any other person was associated with decreased odds of viral suppression at baseline (OR 0.640; 0.416-0.982).Conclusion: Twenty-one percent of HIV-positive Ugandan pregnant women initiating ART (Option B+) showed virological suppression at baseline and were presumed to be "elite controllers" or to have misreported being ART-naive. Further studies are needed to better understand the biologic mechanisms of elite controllers among pregnant women as well as to differentiate elite controllers from concealed ART use. Trial Registration The trial was registered as NCT02515370 (04/08/2015) on Clinicaltrials.gov. [ABSTRACT FROM AUTHOR]

Aims: Patients on antituberculosis (anti‐TB) therapy are at risk of drug‐induced liver injury (DILI). MicroRNA‐122 (miR‐122) and cytokeratin‐18 (K18) are DILI biomarkers. To explore their utility in this global context, circulating miR‐122 and K18 were measured in UK and Ugandan populations on anti‐TB therapy for mycobacterial infection. Methods: Healthy subjects and patients receiving anti‐TB therapy were recruited at the Royal Infirmary of Edinburgh, UK (ALISTER—ClinicalTrials.gov Identifier: NCT03211208). African patients with human immunodeficiency virus–TB coinfection were recruited at the Infectious Diseases Institute, Kampala, Uganda (SAEFRIF—NCT03982277). Serial blood samples, demographic and clinical data were collected. In ALISTER samples, MiR‐122 was quantified using polymerase chain reaction. In ALISTER and SAEFRIF samples, K18 was quantified by enzyme‐linked immunosorbent assay. Results: The study had 235 participants (healthy volunteers [n = 28]; ALISTER: active TB [n = 30], latent TB [n = 88], nontuberculous mycobacterial infection [n = 25]; SAEFRIF: human immunodeficiency virus‐TB coinfection [n = 64]). In the absence of DILI, there was no difference in miR‐122 and K18 across the groups. Both miR‐122 and K18 correlated with alanine transaminase (ALT) activity (miR‐122: R =.52, 95%CI = 0.42–0.61, P <.0001. K18: R =0.42, 95%CI = 0.34–0.49, P <.0001). miR‐122 distinguished those patients with ALT>50 U/L with higher sensitivity/specificity than K18. There were 2 DILI cases: baseline ALT, 18 and 28 IU/L, peak ALT 431 and 194 IU/L; baseline K18, 58 and 219 U/L, peak K18 1247 and 3490 U/L; baseline miR‐122 4 and 17 fM, peak miR‐122 60 and 336 fM, respectively. Conclusion: In patients treated with anti‐TB therapy, miR‐122 and K18 correlated with ALT and increased with DILI. Further work should determine their diagnostic and prognostic utility in this global context‐of‐use. [ABSTRACT FROM AUTHOR]

Background: Alcohol use leads to about 3 million deaths globally. The alcohol industry employs marketing strategies to establish their brands in the lives of young people at a time when addictive behaviors are initiated and reinforced. We conducted a survey among adolescent boys and young men (ABYM) to estimate the prevalence of alcohol use and associated factors using the Health Belief Model as the guiding framework.Methods: The study was conducted among ABYM in- or out-of-school aged 10-24 years in Kampala, Uganda. We used questions adopted from the Global School-based Student Health Survey and the WHO STEPwise approach to Surveillance questionnaire to collect data. The outcome of interest was alcohol use within 30 days before the interview. We also asked about characteristics such as alcohol use by siblings, parents/ guardians, school status among others. We used odds ratios obtained via a logistic regression model as the measure of association.Results: A total of 2500 ABYM participated, of which 262 (10.5 %, 95 %CI 9.3-11.7) had consumed alcohol within 30 days before the interview. Out-of-school ABYM had higher odds of consuming alcohol compared with their in-school counterparts AOR 1.55 (95 %CI 1.09-2.20). Compared with ABYM whose parents/ guardians did not drink alcohol, ABYM whose both parents consumed alcohol had higher odds of consuming alcohol AOR 2.24 (95 %CI 1.38-3.64) as were those with only a mother or female guardian who consumed alcohol AOR 1.95 (95 %CI 1.11-3.41). ABYM with siblings that drink alcohol had higher odds of consuming alcohol AOR 2.25 (95 %CI 1.80-3.52). ABYM who possessed items with an alcohol brand logo had higher odds of consuming alcohol AOR 2.00 (95 %CI 1.33-3.01).Conclusions: There are significant levels of alcohol consumption among ABYM which calls for evidence-based measures targeting this age group to reduce consumption and recognizing the role of the family, school and community in prevention and promotion of use. There is need to regulate alcohol marketing and ensuring availability of alcohol dependence treatment services that build confidence among youth. [ABSTRACT FROM AUTHOR]

A rapid point-of-care test for gonorrhea: Rapid diagnosis of sexually transmitted infections in the clinic ensures treatment with the appropriate antibiotic. Trick et al. developed a cartridge-based magnetofluidic polymerase chain reaction platform that detects Neisseria gonorrhoeae, the pathogen causing gonorrhea, in urethral swabs from patients within 15 min. This test simultaneously reported whether the strains detected are resistant to the antimicrobial drug ciprofloxacin. Testing of urethral swab samples was performed at sexual health clinics in Baltimore and in Kampala, Uganda. This study demonstrates that this rapid assay can detect gonorrhea at the point of care and determine ciprofloxacin resistance of the pathogen. Effective treatment of sexually transmitted infections (STIs) is limited by diagnostics that cannot deliver results rapidly while the patient is still in the clinic. The gold standard methods for identification of STIs are nucleic acid amplification tests (NAATs), which are too expensive for widespread use and have lengthy turnaround times. To address the need for fast and affordable diagnostics, we have developed a portable, rapid, on-cartridge magnetofluidic purification and testing (PROMPT) polymerase chain reaction (PCR) test. We show that it can detect Neisseria gonorrhoeae, the pathogen causing gonorrhea, with simultaneous genotyping of the pathogen for resistance to the antimicrobial drug ciprofloxacin in <15 min. The duplex test was integrated into a low-cost thermoplastic cartridge with automated processing of penile swab samples from patients using magnetic beads. A compact instrument conducted DNA extraction, PCR, and analysis of results while relaying data to the user via a smartphone app. This platform was tested on penile swab samples from sexual health clinics in Baltimore, MD, USA (n = 66) and Kampala, Uganda (n = 151) with an overall sensitivity and specificity of 97.7% (95% CI, 94.7 to 100%) and 97.6% (95% CI, 94.1 to 100%), respectively, for N. gonorrhoeae detection and 100% concordance with culture results for ciprofloxacin resistance. This study paves the way for delivering accessible PCR diagnostics for rapidly detecting STIs at the point of care, helping to guide treatment decisions and combat the rise of antimicrobial resistant pathogens. [ABSTRACT FROM AUTHOR]

• Large-scale rollout of viral load monitoring since 2013. • Implementation challenges persist. • Only 1.9% of the women had First Viral load Test (FVLT) done in a timely fashion. • The median time to FVLT post ART initiation was 12 months. • Constant review of EMTCT viral load data to achieve UNAIDS 3rd 95 by 2030 is needed. Timely viral load (VL) testing is critical in the care of pregnant women living with HIV and receiving anti-retroviral therapy (ART). There is paucity of data regarding the Time to First Viral Load (TFVL) testing in resource-limited settings. We extracted clinical and VL test data from records of a cohort of ART-naïve pregnant women living with HIV who initiated Option B + and were retained in care between 01 Jan 2015 and 31 Dec 2015. The data were verified against laboratory VL registers. TFVL (in months) was calculated based on the time difference between the date of ART initiation and FVL test. Descriptive and Cox regression analyses of data up to 30 Sep 2017 (33 months later) were done. Of the 622 records retrieved, 424 women were retained in care. Of 424 women retained in care, 182/424 (43%) had at least one VL result post ART initiation while 242/424 (57%) had no VL performed. Only 30/182 (16.5%) had a second VL. At six, nine, and twelve months, only 8/424 (1.9%), 47/424 (11.1%), and 94/424 (22.2%) had VL testing performed respectively post ART initiation. The median TFVL testing was 12.7 months (95 CI 11.6-13.7) post ART initiation. Across the five clinics, patient factors (age, gravidity, gestational age, marital status, and adherence at 12 months) were not significant predictors. A dismal 1.9% rate of achieving WHO-recommended TFVL testing and a median TFVL testing of twelve months post ART initiation were observed. The non-association of patient factors to these observations may suggest a serious need to review health system factors likely associated with these observations and their effective interventions. [ABSTRACT FROM AUTHOR]

Most studies evaluating BMD in human immunodeficiency virus (HIV)‐infected populations have focused on antiretroviral therapy (ART)‐experienced patients. In this study, the association between HIV‐1 and/or depot medroxyprogesterone acetate (DMPA) and BMD among untreated HIV‐1–infected women in a resource‐limited setting was assessed before long‐term exposure to ART. The data were then compared with that of the 2005–2008 United States National Health and Nutrition Examination Survey data for non‐Hispanic White and Black women. Women aged 18–35 years, recruited from health facilities in Kampala, Uganda, were classified based on their combination of HIV‐1 status and DMPA use: (i) HIV‐1–infected current DMPA users, (ii) HIV‐1–infected previous DMPA users, (iii) HIV‐1–infected nonhormonal‐contraceptive users, and (iv) HIV‐uninfected nonhormonal‐contraceptive users. All HIV‐1–infected women reported being ART‐naïve at baseline. BMD was measured at the lumbar spine, total hip, and femoral neck using DXA. Multivariate linear regression was used to assess the association between HIV‐1 and/or DMPA and BMD Z‐scores. Baseline data were analyzed for 452 HIV‐1–infected (220 nonhormonal users, and 177 current and 55 previous DMPA users) and 69 HIV‐1–uninfected nonhormonal‐contraceptive users. The mean age was 26.1 years (SD, 4.2) with a median duration of DMPA use among current users of 24.0 months [medians (interquartile range), 12‐48]. A higher proportion of HIV‐1–infected previous (12.7%) or current DMPA users (20.3%) and nonhormonal users (15.0%) had low BMD (Z‐score ≤−2 at any of the three sites) compared with age‐matched HIV‐1–uninfected women (2.9%). HIV‐1 infection and DMPA use were independently associated with significantly lower mean BMD Z‐scores at all sites, with the greatest difference being among HIV‐1–infected current DMPA users (5.6%–8.0%) versus uninfected nonhormonal users. Compared with non‐Hispanic White and Black women, the Ugandan local reference population had generally lower mean BMD at all sites. Newer treatment interventions are needed to mitigate BMD loss in HIV‐1–infected women in resource‐limited settings. © 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

Background: While the proportion of HIV-positive children (under 15 years) enrolled on antiretroviral therapy (ART) has increased in recent years, up to 60% of children started on ART do not achieve virological suppression. We set out to determine the factors associated with virological non-suppression among children living with HIV receiving ART at a peri-urban HIV care clinic in Kampala, Uganda. Method: This was a retrospective cohort study conducted at the pediatric HIV/AIDS clinic at the Joint Clinical Research Centre (JCRC) in Kampala, Uganda. Three hundred (300) HIV-positive children (0–14 years) were randomly selected from existing medical records and data on children's socio-demographic and clinical characteristics (age at ART initiation, WHO clinical staging, and ART-induced side effects) were abstracted using a data abstraction form. Virological non-suppression was defined as a viral load ≥1000 copies/Ml of blood after six months of ART initiation. Incident rate ratios (IRRs) were determined as a measure of association between virological non-suppression and child/patient characteristics. The IRRs were obtained via a modified Poisson regression with corresponding 95% confidence intervals (95%CI). All analyses were done using statistical package, Stata version 15. Results: The overall non-suppression rate among HIV-positive children on ART was 23%. Being at WHO clinical stage 4 at ART initiation [adj. IRR 2.74; 95%CI: 1.63, 4.61] and ART-induced side effects [adj. IRR 1.77; 95%CI: 1.06, 2.97] were significantly associated with non-suppression. Older age at ART initiation (age 5–9 years: [adj. IRR 0.42; 95%CI: 0.28, 0.65]; age 10–14 years: [adj. IRR 0.34; 95%CI: 0.18, 0.64] was less likely to be associated with virological non-suppression. Conclusion: Nearly a quarter of HIV-positive children on ART had a non-suppressed viral load after six months of treatment. Being at WHO clinical stage 4 at ART initiation and ART-induced side effects were significantly associated with virological non-suppression while older age at ART initiation was protective. Our findings suggest a need for age-specific interventions, particularly those targeting children below five years of age, to improve virological suppression among HIV-positive children receiving ART in this setting. [ABSTRACT FROM AUTHOR]

Background: On 6 February 2015, Kampala city authorities alerted the Ugandan Ministry of Health of a "strange disease" that killed one person and sickened dozens. We conducted an epidemiologic investigation to identify the nature of the disease, mode of transmission, and risk factors to inform timely and effective control measures.Methods: We defined a suspected case as onset of fever (≥37.5 °C) for more than 3 days with abdominal pain, headache, negative malaria test or failed anti-malaria treatment, and at least 2 of the following: diarrhea, nausea or vomiting, constipation, fatigue. A probable case was defined as a suspected case with a positive TUBEX® TF test. A confirmed case had blood culture yielding Salmonella Typhi. We conducted a case-control study to compare exposures of 33 suspected case-patients and 78 controls, and tested water and juice samples.Results: From 17 February-12 June, we identified 10,230 suspected, 1038 probable, and 51 confirmed cases. Approximately 22.58% (7/31) of case-patients and 2.56% (2/78) of controls drank water sold in small plastic bags (ORM-H = 8.90; 95%CI = 1.60-49.00); 54.54% (18/33) of case-patients and 19.23% (15/78) of controls consumed locally-made drinks (ORM-H = 4.60; 95%CI: 1.90-11.00). All isolates were susceptible to ciprofloxacin and ceftriaxone. Water and juice samples exhibited evidence of fecal contamination.Conclusion: Contaminated water and street-vended beverages were likely vehicles of this outbreak. At our recommendation authorities closed unsafe water sources and supplied safe water to affected areas. [ABSTRACT FROM AUTHOR]

Polybrominated diphenyl ethers (PBDEs) are ubiquitous environmental pollutants with adverse effects on the foetus and infants. This study aimed at assessing in utero exposure levels and transplacental transfer (TPT) characteristics of BDE congeners in primiparous mothers from Kampala, the capital city of Uganda. Paired human samples (30 placenta and 30 cord blood samples) were collected between April and June 2018; and analysed for a suite of 24 tri-to deca-BDE congeners. Extraction was carried out using liquid-liquid extraction and sonication for cord blood and placenta samples, respectively. Clean-up was done on a solid phase (SPE) column and analysis was performed using gas chromatography/mass spectrometry (GC/MS). Total (∑) PBDEs were 0.25–30.9 ng/g lipid weight (lw) (median; 7.11 ng/g lw) in placental tissues and 1.65–34.5 ng/g lw (median; 11.9 ng/g lw) in cord blood serum, with a mean difference of 1.26 ng/g lw between the compartments. Statistical analysis showed no significant difference between the levels of PBDEs in cord blood and placenta samples (Wilcoxon signed rank test, p = 0.665), possibly because foetus and neonates have poorly developed systems to metabolise the pollutants from the mothers. BDE-209 was the dominant congener in both matrices (contributed 40.5% and 51.2% to ∑PBDEs in placenta and cord blood, respectively), suggesting recent and on-going maternal exposure to deca-BDE formulation. Non-significant associations were observed between ∑PBDEs in maternal placenta and maternal age, household income, pre-pregnancy body mass index (BMI), and beef/fish consumption. This suggested on-going exposure to PBDEs through multiple sources such as dust from indoor/outdoor environments and, ingestion of other foods. Based on absolute concentrations, the extent of transplacental transport was greater for higher congeners (BDE-209, -206 and −207) than for lower ones (such as BDE-47), suggesting alternative TPT mechanisms besides passive diffusion. More studies with bigger sample sizes are required to confirm these findings. Image 1047 • PBDEs were ubiquitous in placenta and cord blood samples of mothers from Uganda. • No significant difference between PBDE levels in cord blood and placenta samples. • BDE-209 was the dominant congener in both matrices. • Fish and beef consumption did not significantly affect placental PBDE levels. • Transplacental transfer was higher for deca- and nonaBDEs than for tri-pentaBDEs. Transplacental transport is higher for highly brominated diphenyl ether congeners (BDE-209, 206 and 207) than for lower ones (such as BDE-47) in Uganda. [ABSTRACT FROM AUTHOR]

The article presents a study regarding the impact of antiretroviral (ARV) drugs in HIV infection rates among early infants. The study describes the prevention of mother-to-child transmission (PMTCT) program of Mulago Hospital in Kampala, Uganda from January 2007 to May 2009 wherein HIV-infected pregnant women received one of the regimens of highly active ARV therapy or short-course combination AVR with nevirapine. Results show low infant infection rates for mothers who received combination ARVs.