Antiretroviral treatment Long-Term (ALT) cohort: a prospective cohort of 10 years of ART-experienced patients in Uganda.

PURPOSE: Little information is available on patients on antiretroviral treatment (ART) after a long-term period from sub-Saharan Africa, with the longest follow-up and related outcomes being after 10 years on ART. At the Infectious Diseases Institute (IDI) (Kampala, Uganda), we set up a cohort of patients already on ART for 10 years at the time of enrolment, who will be followed up for additional 10 years. PARTICIPANTS: A prospective observational cohort of 1000 adult patients previously on ART for 10 years was enrolled between May 2014 and September 2015. Patients were eligible for enrolment if they were in their consecutive 10th year of ART regardless of the combination of drugs for both first- and second-line ART. Data were collected at enrolment and all annual study visits. Follow-up visits are scheduled once a year for 10 years. Biological samples (packed cells, plasma and serum) are stored at enrolment and follow-up visits. FINDINGS TO DATE: Out of 1000 patients enrolled, 345 (34.5%) originate from a pre-existing research cohort at IDI, while 655 (65.5%) were enrolled from the routine clinic. Overall, 81% of the patients were on first line at the time of the enrolment in the ART long-term cohort, with the more frequent regimen being zidovudine plus lamivudine plus nevirapine (44% of the cohort), followed by zidovudine plus lamivudine plus efavirenz (22%) and tenofovir plus lamivudine or emtricitabine plus efavirenz (10%). At cohort enrolment, viral suppression was defined as HIV-RNA <400 copies/mL was 95.8%. FUTURE PLANS: Through collaboration with other institutions, we are planning several substudies, including the evaluation of the risk for cardiovascular diseases, the assessment of bone mineral density, screening for liver cirrhosis using fibroscan technology and investigation of drug-drug interactions between ART and common drugs used for non-communicable diseases

Treatment decisions and mortality in HIV-positive presumptive smear-negative TB in the Xpert™ MTB/RIF era: a cohort study.

BACKGROUND: The Xpert™ MTB/RIF (XP) has a higher sensitivity than sputum smear microscopy (70% versus 35%) for TB diagnosis and has been endorsed by the WHO for TB high burden countries to increase case finding among HIV co-infected presumptive TB patients. Its impact on the diagnosis of smear-negative TB in a routine care setting is unclear. We determined the change in diagnosis, treatment and mortality of smear-negative presumptive TB with routine use of Xpert MTB/RIF (XP). METHODS: Prospective cohort study of HIV-positive smear-negative presumptive TB patients during a 12-month period after XP implementation in a well-staffed and trained integrated TB/HIV clinic in Kampala, Uganda. Prior to testing clinicians were asked to decide whether they would treat empirically prior to Xpert result; actual treatment was decided upon receipt of the XP result. We compared empirical and XP-informed treatment decisions and all-cause mortality in the first year. RESULTS: Of 411 smear-negative presumptive TB patients, 175 (43%) received an XP; their baseline characteristics did not differ. XP positivity was similar in patients with a pre-XP empirical diagnosis and those without (9/29 [17%] versus 14/142 [10%], P = 0.23). Despite XP testing high levels of empirical treatment prevailed (18%), although XP results did change who ultimately was treated for TB. When adjusted for CD4 count, empirical treatment was not associated with higher mortality compared to no or microbiologically confirmed treatment. CONCLUSIONS: XP usage was lower than expected. The lower sensitivity of XP in smear-negative HIV-positive patients led experienced clinicians to use XP as a "rule-in" rather than "rule-out" test, with the majority of patients still treated empirically

Building clinical pharmacology laboratory capacity in low- and middle-income countries: Experience from Uganda

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

Rapid gene fusion testing using the NanoString nCounter platform to improve pediatric leukemia diagnoses in Sub-Saharan Africa

Risk stratification and molecular targeting have been key to increasing cure rates for pediatric cancers in high-income countries. In contrast, precise diagnosis in low-resource settings is hindered by insufficient pathology infrastructure. The Global HOPE program aims to improve outcomes for pediatric cancer in Sub-Saharan Africa (SSA) by building local clinical care and diagnostic capacity. This study aimed to assess the feasibility of implementing molecular assays to improve leukemia diagnoses in SSA. Custom NanoString nCounter gene fusion assays, previously validated in the US, were used to test samples from suspected leukemia patients. The NanoString platform was chosen due to relatively low cost, minimal technical and bioinformatics expertise required, ability to test sub-optimal RNA, and rapid turnaround time. Fusion results were analyzed blindly, then compared to morphology and flow cytometry results. Of 117 leukemia samples, 74 were fusion-positive, 30 were negative, 7 were not interpretable, and 6 failed RNA quality. Nine additional samples were negative for leukemia by flow cytometry and negative for gene fusions. All 74 gene fusions aligned with the immunophenotype determined by flow cytometry. Fourteen samples had additional information available to further confirm the accuracy of the gene fusion results. The testing provided a more precise diagnosis in &gt;60% of cases, and 9 cases were identified that could be treated with an available tyrosine kinase inhibitor, if detected at diagnosis. As risk-stratified and targeted therapies become more available in SSA, implementing this testing in real-time will enable the treatment of pediatric cancer to move toward incorporating risk stratification for optimized therapy

Implications of COVID-19 Lockdown on Child Preparedness among Rwandan Families

The world is currently facing the fatal viral pandemic called coronavirus disease 2019 (COVID-19), earlier named 2019-novel coronavirus (2019- nCoV). Every country of the world keeps responding to the challenges posed by covid-19 in all aspects of human endeavour with high demand and burden on health care. The report of the first case in Rwanda on 14th March 2020 was accompanied by actions to drive control measures by the government of Rwanda importantly to prevent the spread of COVID-19. Those measures included education on personal preventive behaviours, social distancing and restricting the movement of people locally, nationally and internationally resulting to lockdown that allowed only essential services. Lockdown has particularly affected Rwandan families with pregnant mothers in the context of childbirth preparation in different aspects.&nbsp; This review paper articulates the possible various dimensions of influence of the COVID-19 lockdown on birth preparedness by families and the possible maternal and neonatal health adverse outcomes that may be associated. This is with the intention of helping health care providers and other stakeholders anticipate, track and prepare for appropriate mitigation to reduce maternal-neonatal morbidity and mortality. &nbsp; French title: Implications du verrouillage de COVID-19 sur la préparation des enfants dans les familles RwandaisesLe monde est actuellement confronté à la pandémie virale mortelle appelée maladie à coronavirus 2019 (COVID-19), précédemment appelée 2019-nouveau coronavirus (2019-nCoV). Chaque pays du monde continue de répondre aux défis posés par le Covid-19 dans tous les aspects de l'activité humaine avec une forte demande et un fardeau sur les soins de santé. Le rapport du premier cas au Rwanda le 14e mars 2020 a été accompagné d'actions à conduire des mesures de contrôle par le gouvernement du Rwanda important pour prévenir la propagation de Covid-19. Ces mesures comprenaient une éducation sur les comportements personnels de prévention, la distanciation sociale et la restriction de la circulation des personnes aux niveaux local, national et international, entraînant un verrouillage qui n'autorisait que les services essentiels. Le verrouillage a particulièrement affecté les familles Rwandaises de mères enceintes dans le cadre de la préparation à l'accouchement sous différents aspects. Cet article de synthèse articule les différentes dimensions possibles de l'influence du verrouillage du COVID-19 sur la préparation à la naissance des familles et les éventuels effets indésirables sur la santé maternelle et néonatale qui peuvent être associés. Ceci dans le but d'aider les prestataires de soins de santé et les autres parties prenantes à anticiper, suivre et préparer des mesures d'atténuation appropriées pour réduire la morbidité et la mortalité materné-néonatales

Complete ciprofloxacin resistance in gonococcal isolates in an urban Ugandan clinic: findings from a cross-sectional study.

Antimicrobial resistance (AMR) to gonorrhoea is a threat to global health security. There have been concerns expressed that countries with high rates of disease have poor surveillance. The objectives of the study were to determine the AMR patterns of Neisseria gonorrhoeae clinical isolates to antimicrobial agents in patients with HIV or high risk of HIV acquisition, to compare the concordance of disk diffusion and agar dilution as methods for determining AMR to N. gonorrhoeae, and to describe methodological challenges to carrying out AMR testing. The study was conducted at an HIV outpatient service for at-risk populations and an outreach clinic for commercial sex workers in Kampala. Patients were offered a sexually transmitted infection screen using a polymerase chain reaction (PCR)-based assay. Samples positive for gonorrhoea were cultured. Antimicrobial susceptibility testing was performed using disk diffusion and isolates were sent to a reference laboratory for agar dilution direct susceptibility testing. Five hundred and seventy-five patients were screened. There were 33 (5.7%) patients with gonorrhoea detected by PCR. Of the 16 viable N. gonorrhoeae isolates, 100% were resistant to ciprofloxacin and tetracycline by disk diffusion and 31% exhibited reduced susceptibility to ceftriaxone and cefixime. By agar dilution, 100% of isolates were resistant to ciprofloxacin and all isolates were susceptible to ceftriaxone and cefixime. There was concordance between disk diffusion and agar dilution for ciprofloxacin and tetracycline resistance and a significant discordance for third-generation cephalosporins. More than half the women with gonorrhoea were asymptomatic and represent a potential reservoir for ongoing transmission. AMR testing of N. gonorrhoeae isolates is needed to ensure optimal treatment and prevention of antibiotic resistance progression.The work was supported by grants from the National Institute of Health (grant number 5U54EB007958 to Professor Charlotte Gaydos and Dr Yukari Manabe), the Sacharuna Foundation and Johns Hopkins Center for Innovation Medicin

Diagram of study flow.

<p>NTM =  non-tuberculous mycobacteria, Mtb  =  <i>Mycobacterium tuberculosis</i>.</p

Sensitivities compared to positive culture (LJ or MGIT) at different CD4 T cell strata.

<p>Empty cells under reader 5 show that there were 13 patients and all tested negative for all 3 tests (i.e. iLed, Lumin, and Fraen). Overall-4 represents the overall sensitivities of readers 5 & 6 excluding reader 4 who had the highest false positivity rate. Table includes only those patients with a CD4 count record.</p