Beyond the fever: shotgun metagenomic sequencing of stool unveils pathogenic players in HIV-infected children with non-malarial febrile illness.

Background: Non-malarial febrile illnesses (NMFI) pose significant challenges in HIV-infected children, often leading to severe complications and increased morbidity. While traditional diagnostic approaches focus on specific pathogens, shotgun metagenomic sequencing offers a comprehensive tool to explore the microbial landscape underlying NMFI in this vulnerable population ensuring effective management.

Methods: In this study, we employed shotgun metagenomics to analyse stool samples from HIV-infected children at the Baylor Children's Clinic Uganda presenting with non-malarial febrile illness.

Investigator-Initiated Clinical Pharmacokinetic Studies in Resource-Limited Settings: Minimal Requirements and Practical Guidance.

Clinical pharmacology studies are critical for determining the efficacy and safety of drugs. Due to the resource-intensive nature of these studies, most have been conducted in high-income countries, leading to a significant gap in clinical pharmacology data for patients in low- and middle-income countries. This paper provides an overview of the minimal requirements for performing a clinical pharmacology investigator-initiated trial (IIT), including pharmacokinetic sampling.

Subsequent pregnancies in the IMPAACT 2010/VESTED Trial: high rate of adverse outcomes in women living with HIV.

Introduction: Women with HIV (WHIV) have higher risks of adverse pregnancy outcomes, particularly in the absence of antiretroviral treatment(ART), and timing of ART may impact risk.

Methods: In IMPAACT 2010 (VESTED), 643 pregnant WHIV in 9 countries were randomized 1:1:1 to initiate ART: dolutegravir (DTG)+emtricitabine(FTC)/tenofovir alafenamide(TAF); DTG+FTC/tenofovir disoproxil fumarate (TDF) or efavirenz (EFV)/FTC/TDF. We describe adverse pregnancy outcomes in women with a subsequent pregnancy during 50 weeks of postpartum follow-up: spontaneous abortion (<20 weeks), stillbirth (≥20 weeks), preterm delivery (<37 weeks) and small-for-gestational-age (SGA).

Viral load suppression and retention in care among children and adolescents receiving multi-month anti-retroviral therapy refills: a program data review in Uganda.

Background: In July 2022, Uganda's Ministry of Health extended the 2021 WHO guidelines that recommended 3-6 monthly dispensing of antiretroviral therapy (ART) to include all children and adolescents living with HIV (CALHIV). Treatment outcomes following this recommendation have not yet been documented. We compared viral load (VL) suppression and retention in HIV care rates among CALHIV receiving 1, 2-5, and >  = 6 monthly ART dispensation in Uganda.

Building Capacity for Pediatric Hematological Diseases in Sub-Saharan Africa.

The spectrum of hematological diseases in African children includes anemias, bleeding disorders, thromboses, and oncological diseases such as leukemias. While data are limited, outcomes for these diseases are poorer in Africa. The dearth of specialists, and lack of infrastructure that supports diagnosis and management, have been identified as key barriers to improving outcomes for childhood hematological disorders in sub-Saharan Africa (SSA).

Tumor-Associated Edema in Children with Kaposi Sarcoma: 14 Years' Experience at Kamuzu Central Hospital, Lilongwe, Malawi.

Background/objectives: Kaposi sarcoma (KS) is a common lymphatic endothelial cancer among children with and without HIV in central and eastern Africa. Despite its clinical heterogeneity, its various clinical phenotypes are often grouped together in staging and treatment algorithms. Patients with KS tumor-associated edema, referring to hard, non-pitting lesions which often lead to chronic disability, represent a unique, understudied subgroup of children with KS.

Cost-effectiveness of viral load testing for transitioning antiretroviral therapy-experienced children to dolutegravir in South Africa: a modelling analysis.

Background: For children with HIV on antiretroviral therapy (ART), transitioning to dolutegravir-containing regimens is recommended. The aim of this study was to assess whether introducing viral load testing to inform new nucleoside or nucleotide reverse transcriptase inhibitors (NRTIs) for children with HIV and viraemia alongside dolutegravir-based ART is beneficial and of good economic value.

Methods: We used the Cost-Effectiveness of Preventing AIDS Complications-Pediatric model to project clinical and cost implications of three strategies among a simulated cohort of South African children aged 8 years with HIV receiving abacavir-lamivudine-efavirenz: (1) continue current ART (no dolutegravir; abacavir-lamivudine-efavirenz); (2) transition all children with HIV to dolutegravir, keeping current NRTIs (dolutegravir; abacavir-lamivudine-dolutegravir); or (3) transition to dolutegravir based on viral load testing (viral load plus dolutegravir), keeping current NRTIs if virologically suppressed (abacavir-lamivudine-dolutegravir, 70% of cohort) or switching abacavir to zidovudine (zidovudine) if viraemic (zidovudine-lamivudine-dolutegravir, 30%).

Factors Influencing Guardians' Health-Seeking Decisions for Children With Burkitt Lymphoma in Northern and Central Malawi.

Background: The survival of children with Burkitt lymphoma (BL) in sub-Saharan Africa is disproportionately low compared to high-income countries. In Malawi, many of these children are diagnosed in advanced stages. Early and accurate diagnosis is critical to survival of children with BL.

Performance of stool-based molecular tests and processing methods for paediatric tuberculosis diagnosis: a systematic review and meta-analysis.

Background: There has been a global pursuit to improve the diagnosis of tuberculosis in young children by applying diagnostic methods on accessible biospecimens such as stool. We aimed to conduct a systematic review on the accuracy of stool-based molecular tests for tuberculosis diagnosis in children and to assess the impact of the available pre-processing methods and other design characteristics.

Methods: In this systematic review and meta-analysis, we evaluated studies in children younger than 16 years with presumptive tuberculosis that were published in English, Spanish, French, and Portuguese from Jan 1, 2000, to May 3, 2024, in MEDLINE, Embase, and Embase Classic, comparing the molecular detection of Mycobacterium tuberculosis DNA in stool with microbiological tests on other samples or a clinical diagnosis.

Causes of death in people living with HIV: Lessons from five health facilities in Eswatini.

Background: Eswatini has a high HIV prevalence in adults and, despite being one of the first countries to achieve the UNAIDS 95-95-95 targets, AIDS-related deaths are still high.

Objectives: This study describes the causes of death among people living with HIV (PLHIV) receiving care at five clinics in Eswatini.

Method: A cross-sectional review of sociodemographic, clinical and mortality data of deceased clients who received care from 01 January 2021 to 30 June 2022, was conducted.

Optimising Paediatric HIV Treatment: Recent Developments and Future Directions.

Treatment options for children living with HIV have historically been less effective, less practical and more difficult to implement compared with those for adults, as the research and development of new drugs for children has lagged behind. Significant progress has been achieved in response to the paediatric HIV epidemic over the last decade. Several optimised paediatric antiretroviral formulations are currently available or in development, including fixed-dose combination tablets containing a complete World Health Organization-recommended regimen.

Cross border population movements across three East African states: Implications for disease surveillance and response.

The frequent population movement across the five East African Countries poses risk of disease spread in the region. A clear understanding of population movement patterns is critical for informing cross-border disease control interventions. We assessed population mobility patterns across the borders of the East African states of Kenya, Uganda, and Rwanda.

Incidence and predictors of virological failure among HIV infected children and adolescents receiving second-line antiretroviral therapy in Uganda, a retrospective study.

Background: In Uganda, 20% (19,073/94,579) of children and adolescents (0-19 years) living with HIV (CALHIV) were receiving second-line antiretroviral therapy (ART) by the end of March 2020. Data on incidence and predictors of virological failure among these CALHIV on second-line ART is limited. Lack of this information and limited access to HIV drug resistance testing prevents early identification of CALHIV at risk of virological failure on second-line ART.

Pharmacologic evaluation of delayed long-acting cabotegravir administration among cisgender women in HPTN 084.

Unlabelled: HPTN 084 demonstrated the superiority of long-acting injectable cabotegravir (CAB-LA) compared with daily oral tenofovir disoproxil fumarate-emtricitabine (F/TDF) for HIV prevention in women. CAB-LA (600 mg) or placebo injections were administered 4 weeks after an initial dose (loading dose) and every 2 months (Q2M) thereafter; this is the approved regimen. Participants experienced both loading dose and Q2M delays during the trial.

Factors associated with completion of intensive adherence counseling among people living with HIV at a large referral hospital in Uganda: a retrospective analysis.

Background: Among people living with HIV(PHIV) with unsuppressed viral load after six or more months of anti-retroviral therapy (ART), three intensive adherence counseling sessions (IAC) sessions are recommended. However, there is limited information about IAC completion rates. We investigated the factors associated with IAC completion among PLHIV with an unsuppressed viral load on first and second-line ART in mid-western Uganda.

Identification of a Clade-Specific HLA-C*03:02 CTL Epitope GY9 Derived from the HIV-1 p17 Matrix Protein.

Efforts towards an effective HIV-1 vaccine have remained mainly unsuccessful. There is increasing evidence for a potential role of HLA-C-restricted CD8 T cell responses in HIV-1 control, including our recent report of HLA-C*03:02 among African children. However, there are no documented optimal HIV-1 CD8 T cell epitopes restricted by HLA-C*03:02; additionally, the structural influence of HLA-C*03:02 on epitope binding is undetermined.

Setting up a new radiation therapy centre in Malawi: Opportunities and challenges.

Radiotherapy (RT) is one of the three pillars of cancer treatment (with surgery and systemic therapies) and has proven to be a cost-effective modality for curative and palliative treatment. In low and middle-income countries, access to RT treatment is limited posing many challenges to patients and caregivers. Many patients living in low and middle-income countries (LMICs) such as Malawi spend enormous sums of money to be treated abroad, through Government schemes, or, more commonly, go without treatment.

Ebola disease outbreak caused by the Sudan virus in Uganda, 2022: a descriptive epidemiological study.

Background: Uganda has had seven Ebola disease outbreaks, between 2000 and 2022. On Sept 20, 2022, the Ministry of Health declared a Sudan virus disease outbreak in Mubende District, Central Uganda. We describe the epidemiological characteristics and transmission dynamics.

Lipid and glucose profiles in pregnant women with HIV on tenofovir-based antiretroviral therapy.

Objective: Tenofovir alafenamide (TAF)-based antiretroviral therapy (ART) regimens have been associated with adverse changes in lipid and glucose profiles compared with tenofovir disoproxil fumarate (TDF)-based ART, but data in pregnancy is limited. We evaluated metabolic markers in pregnant women with HIV after starting TAF- vs TDF-based ART.

Methods: We analyzed data within the IMPAACT 2010/VESTED trial, which demonstrated better pregnancy outcomes in pregnant women randomized to initiate TAF/Emtricitabine/Dolutegravir (TAF/FTC+DTG; n=217) or TDF/FTC+DTG (n=215).