Starting at the community: Treatment-seeking pathways of children with suspected severe malaria in Uganda.

Community health workers (CHW) usually refer children with suspected severe malaria to the nearest public health facility or a designated public referral health facility (RHF). Caregivers do not always follow this recommendation. This study aimed at identifying post-referral treatment-seeking pathways that lead to appropriate antimalarial treatment for children less than five years with suspected severe malaria.

Correction: Health worker compliance with severe malaria treatment guidelines in the context of implementing pre-referral rectal artesunate in the Democratic Republic of the Congo, Nigeria, and Uganda: An operational study.

[This corrects the article DOI: 10.1371/journal.pmed.

Health worker compliance with severe malaria treatment guidelines in the context of implementing pre-referral rectal artesunate in the Democratic Republic of the Congo, Nigeria, and Uganda: An operational study.

Background: For a full treatment course of severe malaria, community-administered pre-referral rectal artesunate (RAS) should be completed by post-referral treatment consisting of an injectable antimalarial and oral artemisinin-based combination therapy (ACT). This study aimed to assess compliance with this treatment recommendation in children under 5 years.

Methods And Findings: This observational study accompanied the implementation of RAS in the Democratic Republic of the Congo (DRC), Nigeria, and Uganda between 2018 and 2020.

Health system readiness and the implementation of rectal artesunate for severe malaria in sub-Saharan Africa: an analysis of real-world costs and constraints.

Background: Rectal artesunate, an efficacious pre-referral treatment for severe malaria in children, was deployed at scale in Uganda, Nigeria, and DR Congo. In addition to distributing rectal artesunate, implementation required additional investments in crucial but neglected components in the care for severe malaria. We examined the real-world costs and constraints to rectal artesunate implementation.

Acceptability of pre-referral rectal artesunate for severe malaria in children under 5 years by health workers and caregivers in the Democratic Republic of the Congo, Nigeria and Uganda.

Background: For children below 6 years with suspected severe malaria attending a health care provider unable to provide parenteral malaria treatment, pre-referral rectal artesunate (RAS) is recommended by the World Health Organization to prevent death and disability. A number of African countries are in the process of rolling out quality-assured RAS for pre-referral treatment of severe malaria at community-level. The success of RAS depends, among other factors, on the acceptability of RAS in the communities where it is being rolled-out.

Effectiveness of rectal artesunate as pre-referral treatment for severe malaria in children under 5 years of age: a multi-country observational study.

Background: To prevent child deaths from severe malaria, early parenteral treatment is essential. Yet, in remote rural areas, accessing facilities offering parenteral antimalarials may be difficult. A randomised controlled trial found pre-referral treatment with rectal artesunate (RAS) to reduce deaths and disability in children who arrived at a referral facility with delay.

Key factors predicting suspected severe malaria case management and health outcomes: an operational study in the Democratic Republic of the Congo.

Background: Evidence suggests that pre-referral Rectal Artesunate (RAS) can be a life-saving intervention for severe malaria in remote settings in Africa. Recognition of danger signs indicative of severe malaria is critical for prompt and appropriate case management.

Methods: This was an observational study conducted in three Health Zones of the Democratic Republic of the Congo to determine the distribution of dangers signs for severe malaria and assess their impact on RAS use, referral completion, injectable treatment and ACT provision, and health outcomes including death.

Care Seeking and Treatment of Febrile Children with and without Danger Signs of Severe Disease in Northern Uganda: Results from Three Household Surveys (2018-2020).

Identification, stabilization, and prompt referral of children with signs of severe febrile disease (danger signs) in rural communities are crucial for preventing complications and death from severe malaria, pneumonia, and diarrhea. We set out to determine the treatment-seeking practices and treatment patterns for children < 5 years of age with an acute febrile illness, with or without danger signs of severe disease, in a highly malaria-endemic area of northern Uganda. Three household surveys were conducted from November through December each year in 2018, 2019, and 2020.

Prereferral rectal artesunate and referral completion among children with suspected severe malaria in the Democratic Republic of the Congo, Nigeria and Uganda.

Introduction: Children who receive prereferral rectal artesunate (RAS) require urgent referral to a health facility where appropriate treatment for severe malaria can be provided. However, the rapid improvement of a child's condition after RAS administration may influence a caregiver's decision to follow this recommendation. Currently, the evidence on the effect of RAS on referral completion is limited.

Definitions of Severity in Treatment Seeking Studies of Febrile Illness in Children in Low and Middle Income Countries: A Scoping Review.

Understanding treatment seeking for severe febrile illness (SFI) is methodologically challenging. In this scoping review, we investigate definitions of severe febrile illness in treatment seeking studies on children under 5 years of age in low and middle income countries. We analyze the association of SFI definitions with different concepts of treatment seeking and identify related research gaps.

The potential of pregnant women as a sentinel population for malaria surveillance.

Background: With increasing spatial heterogeneity of malaria transmission and a shift of the disease burden towards older children and adults, pregnant women attending antenatal care (ANC) have been proposed as a pragmatic sentinel population for malaria surveillance. However, the representativeness of routine ANC malaria test-positivity and its relationship with prevalence in other population subgroups are yet to be investigated.

Methods: Monthly ANC malaria test-positivity data from all Tanzanian health facilities for January 2014 to May 2016 was compared to prevalence data from the School Malaria Parasitaemia Survey 2015, the Malaria Indicator Survey (MIS) 2015/16, the Malaria Atlas Project 2015, and a Bayesian model fitted to MIS data.

Development and validation of an LC-MS/MS assay for the quantification of the trans-methylation pathway intermediates S-adenosylmethionine and S-adenosylhomocysteine in human plasma.

Background: Although increased levels of S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) have been implicated as markers for renal and vascular dysfunction, until now there have been no studies investigating their association with clinical post-transplant events such as organ rejection and immunosuppressant nephrotoxicity.

Methods: A newly developed and validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay for the quantification of SAM and SAH in human EDTA plasma was used for a clinical proof-of-concept pilot study. Retrospective analysis was performed using samples from a longitudinal clinical study following de novo kidney transplant patients for the first year (n=16).

Occurrence of wireworms in Austrian agricultural land.

wireworms (Coleoptera: Elateridae) are abundant soil-dwelling herbivores which can inflict considerable damage to field crops. In Europe up to 40 species occur, differing in their ecology and pest status. Their distribution in the larval stage, however, has rarely been assessed because of the considerable effort in collecting wireworms and the difficulties in identifying them to species-level.

Everolimus and sirolimus in combination with cyclosporine have different effects on renal metabolism in the rat.

Enhancement of calcineurin inhibitor nephrotoxicity by sirolimus (SRL) is limiting the clinical use of this drug combination. We compared the dose-dependent effects of the structurally related everolimus (EVL) and sirolimus (SRL) alone, and in combination with cyclosporine (CsA), on the rat kidney. Lewis rats were treated by oral gavage for 28 days using a checkerboard dosing format (0, 3.

Low-salt diet and cyclosporine nephrotoxicity: changes in kidney cell metabolism.

Cyclosporine (CsA) is a highly effective immunosuppressant used in patients after transplantation; however, its use is limited by nephrotoxicity. Salt depletion is known to enhance CsA-induced nephrotoxicity in the rat, but the underlying molecular mechanisms are not completely understood. The goal of our study was to identify the molecular effects of salt depletion alone and in combination with CsA on the kidney using a proteo-metabolomic strategy.

Biomarkers of immunosuppressant organ toxicity after transplantation: status, concepts and misconceptions.

Introduction: A major challenge in transplantation is improving long-term organ transplant and patient survival. Immunosuppressants protect the transplant organ from alloimmune reactions, but sometimes also exhibit limiting side effects. The key to improving long-term outcome following transplantation is the selection of the correct immunosuppressive regimen for an individual patient for minimizing toxicity while maintaining immunosuppressive efficacy.

Discovering antibiotic efficacy biomarkers: toward mechanism-specific high content compound screening.

As current antibiotic therapy is increasingly challenged by emerging drug-resistant bacteria, new technologies are required to identify and develop novel classes of antibiotics. A major bottleneck in today's discovery efforts, however, is a lack of an efficient and standardized method for assaying the efficacy of a drug candidate. We propose a new high content screening approach for identifying efficacious molecules suitable for development of antibiotics.

Prediction of mechanisms of action of antibacterial compounds by gene expression profiling.

We have generated a database of expression profiles carrying the transcriptional responses of the model organism Bacillus subtilis following treatment with 37 well-characterized antibacterial compounds of different classes. The database was used to build a predictor for the assignment of the mechanisms of action (MoAs) of antibacterial compounds by the use of support vector machines. This predictor was able to correctly classify the MoA class for most compounds tested.

Identification and characterization of the first class of potent bacterial acetyl-CoA carboxylase inhibitors with antibacterial activity.

The multisubunit acetyl-CoA carboxylase, which catalyzes the first committed step in fatty acid biosynthesis, is broadly conserved among bacteria. Its rate-limiting role in formation of fatty acids makes this enzyme an attractive target for the design of novel broad-spectrum antibacterials. However, no potent inhibitors have been discovered so far.

The crystal structure of the allosteric non-phosphorylating glyceraldehyde-3-phosphate dehydrogenase from the hyperthermophilic archaeum Thermoproteus tenax.

The NAD(+)-dependent non-phosphorylating glyceraldehyde-3-phosphate dehydrogenase (GAPN) from the hyperthermophilic archaeum Thermoproteus tenax represents an archaeal member of the diverse superfamily of aldehyde dehydrogenases (ALDHs). GAPN catalyzes the irreversible oxidation of d-glyceraldehyde 3-phosphate to 3-phosphoglycerate. In this study, we present the crystal structure of GAPN in complex with its natural inhibitor NADP(+) determined by multiple anomalous diffraction methods.