Effect of integrating paediatric tuberculosis services into child healthcare services on case detection in Africa: the INPUT stepped-wedge cluster-randomised trial.

Introduction: Paediatric tuberculosis (TB) underdiagnosis is a critical concern. The INPUT stepped-wedge cluster-randomised trial assessed the impact of integrating child TB services into child healthcare on TB case detection among children under age 5 years.

Methods: We compared the standard of care, providing TB care in specific TB clinics (control phase), with the Catalysing Paediatric TB Innovations (CaP-TB) intervention, integrating TB services across all child health services (intervention phase).

Cost-effectiveness of integrating paediatric tuberculosis services into child healthcare services in Africa: a modelling analysis of a cluster-randomised trial.

Background: In 2021, over one million children developed tuberculosis, resulting in 214 000 deaths, largely due to inadequate diagnosis and treatment. The diagnosis and treatment of tuberculosis is limited in most high-burden countries because services are highly centralised at secondary/tertiary levels and are managed in a vertical, non-integrated way. To improve case detection and treatment among children, the World Health Organisation (WHO) recommends decentralised and integrated tuberculosis care models.

A Cross-Sectional Study of the Use of Antigen Rapid Diagnostic Tests for Community Identification of Severe Acute Respiratory Syndrome Coronavirus-2 in Kenya.

Mass testing with antigen-detecting rapid diagnostic tests (Ag-RDT), including testing of asymptomatic individuals, is expected to improve the identification of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infections. Mass testing was offered at large gatherings to determine the SARS-CoV-2 case detection rate and the acceptance and cost of implementing this community testing strategy. In 49 high-attendance venues in Kiambu County, Kenya, from June to September 2022, individuals 2 years and older were offered coronavirus disease 2019 (COVID-19) testing, vaccination, and participation in a survey.

Effect of COVID-19 on paediatric TB service delivery and patients' comfort receiving TB services in Cameroon and Kenya during COVID: a qualitative assessment.

Background: The outbreak of COVID-19 has caused a setback to the gains achieved in tuberculosis (TB) control by impairing TB diagnosis, delaying treatment initiation and aggravating TB deaths. This study explored the effect of COVID-19 on paediatric TB services provided through the Catalysing Paediatric TB Innovations (CaP-TB) project among caregivers of children receiving TB services and healthcare workers (HCWs) providing TB services in Cameroon and Kenya.

Methods: From March to September 2021, in-depth interviews (44) were conducted with caregivers whose children under 5 years had gone through TB services and programme managers (10) overseeing the CaP-TB project.

Understanding health systems challenges in providing Advanced HIV Disease (AHD) care in a hub and spoke model: a qualitative analysis to improve AHD care program in Malawi.

Background: Despite tremendous progress in antiretroviral therapy (ART) and access to ART, many patients have advanced human immunodeficiency virus (HIV) disease (AHD). Patients on AHD, whether initiating ART or providing care after disengagement, have an increased risk of morbidity and mortality. The Elizabeth Glaser Pediatric AIDS Foundation (EGPAF) launched an enhanced care package using a hub-and-spoke model to optimize AHD care in Malawi.

Understanding gender differences of people with HIV newly diagnosed or returning to care with advanced HIV disease in Malawi: a qualitative study.

Background: Despite tremendous progress in improving antiretroviral therapy (ART) access, advanced HIV disease (AHD) still remains a challenge globally. Reasons for delayed presentation to care and ART adherence may be affected by gender. We present qualitative study findings on gender differences in decisions for HIV testing and ART initiation/adherence in adults with AHD in Malawi.

HIV matters when diagnosing TB in young children: an ancillary analysis in children enrolled in the INPUT stepped wedge cluster randomized study.

Background: Children under age five years, particularly those living with HIV (CLHIV), are at risk for rapid progression of tuberculosis (TB). We aimed to describe TB clinical presentations, diagnostic pathways and treatment outcomes in CLHIV compared to children without HIV in Cameroon and Kenya.

Methods: This sub-analysis of a cluster-randomized trial evaluating the integration of pediatric TB services from May 2019 to March 2021 enrolled children age < 5 years with TB.

Integrating pediatric TB services into child healthcare services in Africa: study protocol for the INPUT cluster-randomized stepped wedge trial.

Background: Tuberculosis is among the top-10 causes of mortality in children with more than 1 million children suffering from TB disease annually worldwide. The main challenge in young children is the difficulty in establishing an accurate diagnosis of active TB. The INPUT study is a stepped-wedge cluster-randomized intervention study aiming to assess the effectiveness of integrating TB services into child healthcare services on TB diagnosis capacities in children under 5 years of age.

Severe Acute Malnutrition Results in Lower Lumefantrine Exposure in Children Treated With Artemether-Lumefantrine for Uncomplicated Malaria.

Severe acute malnutrition (SAM) has been reported to be associated with increased malaria morbidity in Sub-Saharan African children and may affect the pharmacology of antimalarial drugs. This population pharmacokinetic (PK)-pharmacodynamic study included 131 SAM and 266 non-SAM children administered artemether-lumefantrine twice daily for 3 days. Lumefantrine capillary plasma concentrations were adequately described by two transit-absorption compartments followed by two distribution compartments.

Efficacy of artemether-lumefantrine in relation to drug exposure in children with and without severe acute malnutrition: an open comparative intervention study in Mali and Niger.

Background: Severe acute malnutrition (SAM) affects almost all organs and has been associated with reduced intestinal absorption of medicines. However, very limited information is available on the pharmacokinetic properties of antimalarial drugs in this vulnerable population. We assessed artemether-lumefantrine (AL) clinical efficacy in children with SAM compared to those without.

Insights Into Circulating Cytokine Dynamics During Pregnancy in HIV-Infected Beninese Exposed to Plasmodium falciparum Malaria.

We investigated the circulating plasma levels of Th1- (Interleukin-2 [IL-2], tumor necrosis factor-α [TNF-α], interferon-gamma [IFN-γ]) and Th2-type (IL-4, IL-5, IL-10) cytokines in human immunodeficiency virus (HIV)-infected pregnant women living in a malaria-endemic area. We analyzed samples from 200 pregnant women included in the prevention of pregnancy-associated malaria in HIV-infected women: cotrimoxazole prophylaxis versus mefloquine (PACOME) clinical trial who were followed until delivery. Cytokine concentrations were measured by flow cytometry-based multiplex bead array.

A multi-center, open-label trial to compare the efficacy and pharmacokinetics of Artemether-Lumefantrine in children with severe acute malnutrition versus children without severe acute malnutrition: study protocol for the MAL-NUT study.

Background: Malnutrition and malaria frequently coexist in sub-Saharan African countries. Studies on efficacy of antimalarial treatments usually follow the WHO standardized protocol in which severely malnourished children are systematically excluded. Few studies have assessed the efficacy of chloroquine, sulfadoxine-pyrimethamine and quinine in severe acute malnourished children.

Protective Antibodies against Placental Malaria and Poor Outcomes during Pregnancy, Benin.

Placental malaria is caused by Plasmodium falciparum-infected erythrocytes that bind to placental tissue. Binding is mediated by VAR2CSA, a parasite antigen coded by the var gene, which interacts with chondroitin sulfate A (CSA). Consequences include maternal anemia and fetal growth retardation.

Early biting and insecticide resistance in the malaria vector Anopheles might compromise the effectiveness of vector control intervention in Southwestern Uganda.

Background: Southwestern Uganda has high malaria heterogeneity despite moderate vector control and other interventions. Moreover, the early biting transmission and increased resistance to insecticides might compromise strategies relying on vector control. Consequently, monitoring of vector behaviour and insecticide efficacy is needed to assess the effectiveness of strategies aiming at malaria control.

High plasma levels of soluble endothelial protein C receptor are associated with increased mortality among children with cerebral malaria in Benin.

Loss of endothelial protein C receptor (EPCR) occurs at the sites of Plasmodium falciparum-infected erythrocyte sequestration in patients with or who died from cerebral malaria. In children presenting with different clinical syndromes of malaria, we assessed the relationships between endogenous plasma soluble EPCR (sEPCR) levels and clinical presentation or mortality. After adjustment for age, for treatment before admission, and for a known genetic factor, sEPCR level at admission was positively associated with cerebral malaria (P = .

Worrisome trends in incidence and mortality of candidemia in intensive care units (Paris area, 2002-2010).

Purpose: To analyze trends in incidence and mortality of candidemia in intensive care units (ICUs) vs. non-ICU hospitalized patients and to determine risk factors for infection by specific species and for death.

Methods: Active hospital-based surveillance program of incident episodes of candidemia due to common species in 24 tertiary care hospitals in the Paris area, France between October 2002 and September 2010.

Incidence of malaria-related fever and morbidity due to Plasmodium falciparum among HIV1-infected pregnant women: a prospective cohort study in South Benin.

Background: Malaria and HIV are two major causes of morbidity and mortality among pregnant women in sub-Saharan Africa. Foetal and neonatal outcomes of this co-infection have been extensively studied. However, little is known about maternal morbidity due to clinical malaria in pregnancy, especially malaria-related fever, in the era of generalized access to antiretroviral therapy and anti-malarial preventive strategies.

Cotrimoxazole prophylaxis versus mefloquine intermittent preventive treatment to prevent malaria in HIV-infected pregnant women: two randomized controlled trials.

Background: Malaria during pregnancy has serious consequences that are worsened by HIV infection. Malaria preventive measures for HIV-infected pregnant women include cotrimoxazole (CTX) prophylaxis given to prevent HIV-related opportunistic infections and also protective against malaria, or intermittent preventive treatment (IPTp) with an antimalarial drug. Here, we present the first study evaluating CTX efficacy versus mefloquine (MQ)-IPTp, alone and in combination, in HIV-infected pregnant women.

Predictive factors of plasma HIV suppression during pregnancy: a prospective cohort study in Benin.

Objective: To investigate the factors associated with HIV1 RNA plasma viral load (pVL) below 40 copies/mL at the third trimester of pregnancy, as part of prevention of mother-to-child transmission (PMTCT) in Benin.

Design: Sub study of the PACOME clinical trial of malaria prophylaxis in HIV-infected pregnant women, conducted before and after the implementation of the WHO 2009 revised guidelines for PMTCT.

Methods: HIV-infected women were enrolled in the second trimester of pregnancy.

Tolerability of mefloquine intermittent preventive treatment for malaria in HIV-infected pregnant women in Benin.

Objective: To investigate the tolerability of mefloquine intermittent preventive treatment (MQ IPTp) for malaria in HIV-infected pregnant women compared with HIV-negative women.

Design: Prospective cohort study comparing samples of HIV-negative and HIV-infected pregnant women from 2 clinical trials conducted in Benin.

Methods: One hundred and three HIV-infected women from the ongoing PACOME trial were compared with 421 HIV-negative women from a former trial, both trials aiming to evaluate the efficacy and tolerability of MQ IPTp, administered at the dose of 15 mg/kg.