Cost-effectiveness of COVID rapid diagnostic tests for patients with severe/critical illness in low- and middle-income countries: A modeling study.

Background: Rapid diagnostic tests (RDTs) for coronavirus disease (COVID) are used in low- and middle-income countries (LMICs) to inform treatment decisions. However, to date, it is unclear when this use is cost-effective. Existing analyses are limited to a narrow set of countries and uses.

Concomitant assessment of PD-1 and CD56 expression identifies subsets of resting cord blood Vδ2 T cells with disparate cytotoxic potential.

Vγ9Vδ2 T lymphocytes are programmed for broad antimicrobial responses with rapid production of Th1 cytokines even before birth, and thus thought to play key roles against pathogens in infants. The process regulating Vδ2 cell acquisition of cytotoxic potential shortly after birth remains understudied. We observed that perforin production in cord blood Vδ2 cells correlates with phenotypes defined by the concomitant assessment of PD-1 and CD56.

Paediatric acute hepatitis of unknown aetiology: a national investigation and adenoviraemia case-control study in the UK.

Background: An increase in acute severe hepatitis of unknown aetiology in previously healthy children in the UK in March, 2022, triggered global case-finding. We aimed to describe UK epidemiological investigations of cases and their possible causes.

Methods: We actively surveilled unexplained paediatric acute hepatitis (transaminase >500 international units per litre) in children younger than 16 years presenting since Jan 1, 2022, through notifications from paediatricians, microbiologists, and paediatric liver units; we collected demographic, clinical, and exposure information.

Adoption of mHealth Technologies by Community Health Workers to Improve the Use of Maternal Health Services in Sub-Saharan Africa: Protocol for a Mixed Method Systematic Review.

Background: Studies have shown that mobile health technologies (mHealth) enhance the use of maternal health services. However, there is limited evidence of the impact of mHealth use by community health workers (CHWs) on the use of maternal health services in sub-Saharan Africa.

Objective: This mixed method systematic review will explore the impact of mHealth use by CHWs on the use of the maternal health continuum of care (antenatal care, intrapartum care, and postnatal care [PNC]), as well as barriers and facilitators of mHealth use by CHWs when supporting maternal health services.

Trial-of-antibiotics to assist tuberculosis diagnosis in symptomatic adults in Malawi (ACT-TB study): a randomised controlled trial.

Background: Clinical practice and diagnostic algorithms often assume that tuberculosis can be ruled out in mycobacteriology-negative individuals whose symptoms improve with a trial-of-antibiotics. We aimed to investigate diagnostic performance, clinical benefit, and antimicrobial resistance using a randomised controlled trial.

Methods: In this three-arm, individually randomised, open-label, controlled trial, we enrolled Malawian adults (aged ≥18 years) attending primary care who reported being unwell for at least 14 days (including cough) with no immediate indication for hospitalisation at Limbe and Ndirande Health Centres in Blantyre.

Artemether-lumefantrine efficacy among adults on antiretroviral therapy in Malawi.

Background: When people with human immunodeficiency virus (HIV) infection (PWH) develop malaria, they are at risk of poor anti-malarial treatment efficacy resulting from impairment in the immune response and/or drug-drug interactions that alter anti-malarial metabolism. The therapeutic efficacy of artemether-lumefantrine was evaluated in a cohort of PWH on antiretroviral therapy (ART) and included measurement of day 7 lumefantrine levels in a subset to evaluate for associations between lumefantrine exposure and treatment response.

Methods: Adults living with HIV (≥ 18 years), on ART for ≥ 6 months with undetectable HIV RNA viral load and CD4 count ≥ 250/mm were randomized to daily trimethoprim-sulfamethoxazole (TS), weekly chloroquine (CQ) or no prophylaxis.

SARS-CoV-2 Prevalence in Malawi Based on Data from Survey of Communities and Health Workers in 5 High-Burden Districts, October 2020.

To determine early COVID-19 burden in Malawi, we conducted a multistage cluster survey in 5 districts. During October-December 2020, we recruited 5,010 community members (median age 32 years, interquartile range 21-43 years) and 1,021 health facility staff (HFS) (median age 35 years, interquartile range 28-43 years). Real-time PCR-confirmed SARS-CoV-2 infection prevalence was 0.

The choice of reference chart affects the strength of the association between malaria in pregnancy and small for gestational age: an individual participant data meta-analysis comparing the Intergrowth-21 with a Tanzanian birthweight chart.

Background: The prevalence of small for gestational age (SGA) may vary depending on the chosen weight-for-gestational-age reference chart. An individual participant data meta-analysis was conducted to assess the implications of using a local reference (STOPPAM) instead of a universal reference (Intergrowth-21) on the association between malaria in pregnancy and SGA.

Methods: Individual participant data of 6,236 newborns were pooled from seven conveniently identified studies conducted in Tanzania and Malawi from 2003-2018 with data on malaria in pregnancy, birthweight, and ultrasound estimated gestational age.

Computer-aided X-ray screening for tuberculosis and HIV testing among adults with cough in Malawi (the PROSPECT study): A randomised trial and cost-effectiveness analysis.

Background: Suboptimal tuberculosis (TB) diagnostics and HIV contribute to the high global burden of TB. We investigated costs and yield from systematic HIV-TB screening, including computer-aided digital chest X-ray (DCXR-CAD).

Methods And Findings: In this open, three-arm randomised trial, adults (≥18 years) with cough attending acute primary services in Malawi were randomised (1:1:1) to standard of care (SOC); oral HIV testing (HIV screening) and linkage to care; or HIV testing and linkage to care plus DCXR-CAD with sputum Xpert for high CAD4TBv5 scores (HIV-TB screening).

Effects of Coronavirus Disease Pandemic on Tuberculosis Notifications, Malawi.

The coronavirus disease (COVID-19) pandemic might affect tuberculosis (TB) diagnosis and patient care. We analyzed a citywide electronic TB register in Blantyre, Malawi and interviewed TB officers. Malawi did not have an official COVID-19 lockdown but closed schools and borders on March 23, 2020.

Revisiting Co-trimoxazole Prophylaxis for African Adults in the Era of Antiretroviral Therapy: A Randomized Controlled Clinical Trial.

Background: Daily co-trimoxazole is recommended for African adults living with human immunodeficiency virus (HIV) irrespective of antiretroviral treatment, immune status, or disease stage. Benefits of continued prophylaxis and whether co-trimoxazole can be stopped following immune reconstitution are unknown.

Methods: We conducted a randomized controlled trial at 2 sites in Malawi that enrolled adults with HIV with undetectable viral load and CD4 count of >250/mm3 and randomized them to continue daily co-trimoxazole, discontinue daily co-trimoxazole and begin weekly chloroquine, or discontinue daily co-trimoxazole.

Tuberculosis case notifications in Malawi have strong seasonal and weather-related trends.

Seasonal trends in tuberculosis (TB) notifications have been observed in several countries but are poorly understood. Explanatory factors may include weather, indoor crowding, seasonal respiratory infections and migration. Using enhanced citywide TB surveillance data collected over nine years in Blantyre, Malawi, we set out to investigate how weather and seasonality affect temporal trends in TB case notification rates (CNRs) across different demographic groups.

Tuberculosis diagnosis cascade in Blantyre, Malawi: a prospective cohort study.

Background: Tuberculosis (TB) control relies on early diagnosis and treatment. International guidelines recommend systematic TB screening at health facilities, but implementation is challenging. We investigated completion of recommended TB screening steps in Blantyre, Malawi.

Age-related changes in PD-1 expression coincide with increased cytotoxic potential in Vδ2 T cells during infancy.

Human Vγ9Vδ2 T cells respond to several diverse pathogens by sensing microbial cholesterol intermediates. Unlike CD4 T cells, they are poised for rapid Th1-like responses even before birth, which allows them to play a key role in the first line of defense against pathogens in early life. However, their regulation and functional maturation during infancy (in particular the acquisition of cytotoxic potential) remain understudied.

Utility of broad-spectrum antibiotics for diagnosing pulmonary tuberculosis in adults: a systematic review and meta-analysis.

Background: Suboptimal diagnostics for pulmonary tuberculosis drive the use of the so-called trial of antibiotics, a course of broad-spectrum antibiotics without activity against Mycobacterium tuberculosis that is given to patients who are mycobacteriology negative but symptomatic, with the aim of distinguishing pulmonary tuberculosis from bacterial lower respiratory tract infection. The underlying assumption-that patients with lower respiratory tract infection will improve, whereas those with pulmonary tuberculosis will not-has an unclear evidence base for such a widely used intervention (at least 26·5 million courses are prescribed per year). We aimed to collate available evidence on the diagnostic performance of the trial of antibiotics.

Effect of the duration of antimicrobial exposure on the development of antimicrobial resistance (AMR) for macrolide antibiotics: protocol for a systematic review with a network meta-analysis.

Background: Antimicrobial resistance generates a huge health and economic burden and has the potential to become the leading cause of death globally, but its underlying drivers are yet to be fully described. The association between a microbe's exposure to antimicrobials and subsequent development of, or selection for, resistance is well documented, as are the exacerbating microbial and human factors. However, the nature and extent of this risk, and how it varies by antimicrobial class and duration of treatment, is poorly defined.

Sensitivity and specificity of using trial-of-antibiotics versus sputum mycobacteriology for diagnosis of tuberculosis: protocol for a systematic literature review.

Background: Suboptimal diagnostics for pulmonary tuberculosis (PTB) drives use of 'trial-of-antibiotics (non-tuberculosis)' in an attempt to distinguish PTB patients from those with bacterial lower respiratory tract infection (LRTI). The underlying assumption-that patients with LRTI will report 'response' to broad-spectrum antibiotics, while those with PTB will not-has minimal evidence base for such a widely used intervention. Numerous potential causes of misclassification include bacterial super-infection of active PTB, placebo effect, and antimicrobial resistance (AMR).

Chloroquine as weekly chemoprophylaxis or intermittent treatment to prevent malaria in pregnancy in Malawi: a randomised controlled trial.

Background: Sulfadoxine-pyrimethamine resistance threatens efficacy of intermittent preventive treatment of malaria during pregnancy, and alternative regimens need to be identified. With the return of chloroquine efficacy in southern Africa, we postulated that chloroquine either as an intermittent therapy or as weekly chemoprophylaxis would be more efficacious than intermittent sulfadoxine-pyrimethamine for prevention of malaria in pregnancy and associated maternal and newborn adverse outcomes.

Methods: We did an open-label, single-centre, randomised controlled trial at Ndirande Health Centre, Blantyre, in southern Malawi.

A targeted approach for routine viral load monitoring in Malawian adults on antiretroviral therapy.

Objectives: WHO recommends HIV viral load (VL) testing 6 months after antiretroviral therapy (ART) initiation and every 12 months thereafter, but cost prohibits routine, universal VL testing in many developing countries. We sought to devise a targeted approach to routine VL monitoring that could reduce cost and identify those at low risk for virologic failure (VF).

Methods: We analysed screening data from a clinical trial enrolling adults on ART in Malawi.

Frequent malaria illness episodes in two Malawian patients on antiretroviral therapy soon after stopping cotrimoxazole preventive therapy.

We describe two Malawian adults on successful antiretroviral therapy who experienced frequent malaria episodes after stopping cotrimoxazole prophylaxis. We argue that, in addition to stopping cotrimoxazole, diminished malaria immunity and drug interactions between efavirenz and artemether-lumefantrine may have played a causative role in the recurrent malaria our patients experienced.