Hospital mortality data can inform planning for health interventions and may help optimize resource allocation if they are reliable and appropriately interpreted. However such data are often not ...available in low income countries including Kenya.
Data from the Clinical Information Network covering 12 county hospitals' paediatric admissions aged 2-59 months for the periods September 2013 to March 2015 were used to describe mortality across differing contexts and to explore whether simple clinical characteristics used to classify severity of illness in common treatment guidelines are consistently associated with inpatient mortality. Regression models accounting for hospital identity and malaria prevalence (low or high) were used. Multiple imputation for missing data was based on a missing at random assumption with sensitivity analyses based on pattern mixture missing not at random assumptions.
The overall cluster adjusted crude mortality rate across hospitals was 6 · 2% with an almost 5 fold variation across sites (95% CI 4 · 9 to 7 · 8; range 2 · 1% - 11 · 0%). Hospital identity was significantly associated with mortality. Clinical features included in guidelines for common diseases to assess severity of illness were consistently associated with mortality in multivariable analyses (AROC =0 · 86).
All-cause mortality is highly variable across hospitals and associated with clinical risk factors identified in disease specific guidelines. A panel of these clinical features may provide a basic common data framework as part of improved health information systems to support evaluations of quality and outcomes of care at scale and inform health system strengthening efforts.
Malaria rapid diagnostic tests (RDTs) are nowadays widely used in malaria endemic countries as an alternative to microscopy for the diagnosis of malaria. However, quality control of test performance ...and execution in the field are important in order to ensure proper use and adequate diagnosis of malaria. The current study compared the performance of a histidine-rich protein 2-based RDT used at peripheral health facilities level in real life conditions with that performed at central reference laboratory level with strict adherence to manufacturer instructions.
Febrile children attending rural health clinics were tested for malaria with a RDT provided by the Ministry of Health of Burkina Faso as recommended by the National Malaria Control Programme. In addition, a blood sample was collected in an EDTA tube from all study cases for retesting with the same brand of RDT following the manufacturer's instructions with expert malaria microscopy as gold standard at the central reference laboratory. Fisher exact test was used to compare the proportions by estimating the p-value (p ≤ 0.05) as statistically significant.
In total, 407 febrile children were included in the study and malaria was diagnosed in 59.9% (244/407) of the cases with expert malaria microscopy. The sensitivity of malaria RDT testing performed at health facilities was 97.5% and comparable to that achieved at the laboratory (98.8%). The number of malaria false negatives was not statistically significant between the two groups (p = 0.5209). However, the malaria RDT testing performed at health facilities had a specificity issue (52.8%) and was much lower compared to RDT testing performed at laboratory (74.2%). The number of malaria false positives was statistically significantly different between the two groups (p = 0.0005).
Malaria RDT testing performed at the participating rural health facilities resulted in more malaria false positives compared to those performed at central laboratory. Several factors, including storage and transportation conditions but also training of health workers, are most likely to influence test performance. Therefore, it is very important to have appropriate quality control and training programmes in place to ensure correct performance of RDT testing.
Abstract
A Ugandan child with an unexplained encephalitis was investigated using viral metagenomics. Several sequences from all segments of a novel orthobunyavirus were found. The S-segment, used for ...typing, showed 41% amino acid diversity to its closest relative. The virus was named Ntwetwe virus, after the hometown of the patient.
Severe anaemia is associated with high in-hospital mortality among young children. In malaria-endemic areas, surviving children also have an increased risk of mortality or readmission after hospital ...discharge. We conducted a systematic review and individual patient data meta-analysis to determine the efficacy of monthly post-discharge malaria chemoprevention in children recovering from severe anaemia.
This analysis was conducted according to PRISMA-IPD guidelines. We searched multiple databases on Aug 28, 2023, without date or language restrictions, for randomised controlled trials comparing monthly post-discharge malaria chemoprevention with placebo or standard of care among children (aged <15 years) admitted with severe anaemia in malaria-endemic Africa. Trials using daily or weekly malaria prophylaxis were not eligible. The investigators from all eligible trials shared pseudonymised datasets, which were standardised and merged for analysis. The primary outcome was all-cause mortality during the intervention period. Analyses were performed in the modified intention-to-treat population, including all randomly assigned participants who contributed to the endpoint. Fixed-effects two-stage meta-analysis of risk ratios (RRs) was used to generate pooled effect estimates for mortality. Recurrent time-to-event data (readmissions or clinic visits) were analysed using one-stage mixed-effects Prentice-Williams-Peterson total-time models to obtain hazard ratios (HRs). This study is registered with PROSPERO, CRD42022308791.
Our search identified 91 articles, of which 78 were excluded by title and abstract, and a further ten did not meet eligibility criteria. Three double-blind, placebo-controlled trials, including 3663 children with severe anaemia, were included in the systematic review and meta-analysis; 3507 (95·7%) contributed to the modified intention-to-treat analysis. Participants received monthly sulfadoxine-pyrimethamine until the end of the malaria transmission season (mean 3·1 courses per child range 1-6; n=1085; The Gambia), monthly artemether-lumefantrine given at the end of weeks 4 and 8 post discharge (n=1373; Malawi), or monthly dihydroartemisinin-piperaquine given at the end of weeks 2, 6, and 10 post discharge (n=1049; Uganda and Kenya). During the intervention period, post-discharge malaria chemoprevention was associated with a 77% reduction in mortality (RR 0·23 95% CI 0·08-0·70, p=0·0094, I
=0%) and a 55% reduction in all-cause readmissions (HR 0·45 95% CI 0·36-0·56, p<0·0001) compared with placebo. The protective effect was restricted to the intervention period and was not sustained after the direct pharmacodynamic effect of the drugs had waned. The small number of trials limited our ability to assess heterogeneity, its sources, and publication bias.
In malaria-endemic Africa, post-discharge malaria chemoprevention reduces mortality and readmissions in recently discharged children recovering from severe anaemia. Post-discharge malaria chemoprevention could be a valuable strategy for the management of this group at high risk. Future research should focus on methods of delivery, options to prolong the protection duration, other hospitalised groups at high risk, and interventions targeting non-malarial causes of post-discharge morbidity.
The Research-Council of Norway and the Bill-&-Melinda-Gates-Foundation through the Worldwide-Antimalarial-Research-Network.
To assess whether viral, bacterial, metabolic, and autoimmune diseases are missed by conventional diagnostics among children with severe acute encephalopathy in sub-Saharan Africa.
One hundred ...thirty-four children (6 months to 18 years) presenting with nontraumatic coma or convulsive status epilepticus to 1 of 4 medical referral centers in Uganda, Malawi, and Rwanda were enrolled between 2015 and 2016. Locally available diagnostic tests could be supplemented in 117 patients by viral, bacterial, and 16s quantitative polymerase chain reaction testing, metagenomics, untargeted metabolomics, and autoimmune immunohistochemistry screening.
Fourteen (12%) cases of viral encephalopathies, 8 (7%) cases of bacterial central nervous system (CNS) infections, and 4 (4%) cases of inherited metabolic disorders (IMDs) were newly identified by additional diagnostic testing as the most likely cause of encephalopathy. No confirmed cases of autoimmune encephalitis were found. Patients for whom additional diagnostic testing aided causal evaluation (aOR 3.59, 90% CI 1.57-8.36), patients with a viral CNS infection (aOR 7.91, 90% CI 2.49-30.07), and patients with an IMD (aOR 9.10, 90% CI 1.37-110.45) were at increased risk for poor outcome of disease.
Viral and bacterial CNS infections and IMDs are prevalent causes of severe acute encephalopathy in children in Uganda, Malawi, and Rwanda that are missed by conventional diagnostics and are associated with poor outcome of disease. Improved diagnostic capacity may increase diagnostic yield and might improve outcome of disease.
Severe anaemia is a major cause of morbidity and mortality in African children. The aetiology is multi-factorial, but interventions have often targeted only one or a few causal factors, with limited ...success.
We assessed the contribution of different pathophysiological mechanisms (red cell production failure RCPF, haemolysis and blood loss) to severe anaemia in Malawian children in whom etiological factors have been described previously. More complex associations between etiological factors and the mechanisms were explored using structural equation modelling. In 235 children with severe anaemia (haemoglobin<3.2 mMol/L 5.0 g/dl) studied, RCPF, haemolysis and blood loss were found in 48.1%, 21.7% and 6.9%, respectively. The RCPF figure increased to 86% when a less stringent definition of RCPF was applied. RCPF was the most common mechanism in each of the major etiological subgroups (39.7-59.7%). Multiple aetiologies were common in children with severe anaemia. In the final model, nutritional and infectious factors, including malaria, were directly or indirectly associated with RCPF, but not with haemolysis.
RCPF was the most common pathway leading to severe anaemia, from a variety of etiological factors, often found in combination. Unlike haemolysis or blood loss, RCPF is a defect that is likely to persist to a significant degree unless all of its contributing aetiologies are corrected. This provides a further explanation for the limited success of the single factor interventions that have commonly been applied to the prevention or treatment of severe anaemia. Our findings underline the need for a package of measures directed against all of the local aetiologies of this often fatal paediatric syndrome.
Summary Anaemia, iron deficiency and infections are three major causes of childhood morbidity and mortality throughout the world, although they predominantly occur in resource limited settings. As ...the three conditions may have the same underlying aetiologies, they often occur simultaneously and may interact. Being an essential component in erythropoiesis, iron is also essential for proper functioning of the host immune system as well as an essential nutrient for growth of various pathogens, including non-typhoid salmonella. This has resulted in a treatment dilemma in which iron is needed to treat the iron deficient anaemia and improve the immune system of the host (child), but the same treatment may also put the child at an increased, potentially fatal, infection risk.
This study aims to identify risk factors and the neurodevelopmental impact of neonatal hyperbilirubinemia in a limited-resource setting among a refugee and migrant population residing along the ...Thai-Myanmar border, an area with a high prevalence of glucose-6-phosphate dehydrogenase-deficiency.
This is an analytic, observational, prospective birth cohort study including all infants of estimated gestational age equal to or greater than 28 weeks from mothers who followed antenatal care in the Shoklo Malaria Research Unit clinics. At birth, a series of clinical exams and laboratory investigations on cord blood will be carried out. Serum bilirubin will be measured in all infants during their first week of life. All the infants of the cohort will be clinically followed until the age of one year, including monitoring of their neurodevelopment.
The strength of this study is the prospective cohort design. It will allow us to collect information about the pregnancy and detect all infants with neonatal hyperbilirubinemia, to observe their clinical response under treatment and to compare their neurodevelopment with infants who did not develop neonatal hyperbilirubinemia. Our study design has some limitations in particular the generalizability of our findings will be limited to infants born after the gestational age of 28 weeks onwards and neurodevelopment to the end of the first year of life.
ClinicalTrials.gov ID NCT02361788 , registration date September 1st, 2014.
Globally, anaemia, iron deficiency and infections are responsible for a majority of the morbidity and mortality that occurs among children. As iron is essential for erythropoiesis and the human ...immune system, as well as a crucial element for many pathogens, these three conditions often interact. This article considers the question – have the studies conducted so far unravelled the potential complex interaction between these factors sufficiently enough to be able to develop universally applicable guidelines about iron treatment in children? It is possible, however, that the area is too complex and diverse, with many sub‐populations, and that not universal, but tailor‐made guidelines are needed based on some agreed principles.
Malaria rapid diagnostic tests (RDT) are widely used in endemic areas in order to comply with the recommendation that malaria treatment should only be given after the clinical diagnosis has been ...confirmed by RDT or microscopy. However, the overestimation of malaria infection with the use of PfHRP2 based RDT, makes the management of febrile illnesses more challenging. This study aimed to assess the effect of the use of malaria RDT on antimicrobial prescription practices.
A prospective study was conducted among febrile children under-5 years of age attending four health facilities and the referral hospital in the Nanoro Health District (Burkina Faso). To assess the effect of malaria RDT testing on the prescriptions of antimicrobials in febrile children, the initial diagnosis and antimicrobial prescriptions following a malaria RDT testing were recorded. The necessity of these prescriptions was subsequently checked by assessing the actual cause of fever by expert malaria microscopy and a microbiology analysis of blood, urine, stool and nasopharynx swabs that were collected from febrile cases to determine the actual cause of the fever episode.
Malaria was diagnosed by nurses, who are the primary health care providers, with a malaria RDT in 72.7% (798/1098) of febrile children, but only 53.7% (589/1097) cases could be confirmed by expert microscopy. Health care workers were likely to prescribe antimalarials to malaria positive RDT compared to malaria negative RDT (RR = 7.74, p = 0.00001). Malaria negative RDT result had a significant influence on the antibiotic prescriptions (RR = 3.57, p = 0.0001). The risk of prescribing antimicrobials was higher in health facility level compared to referral hospital. By cross-checking of laboratory findings to antimicrobial prescriptions, an important part of children with positive bacterial infection have received antibiotic prescriptions although the majority without any infection have also received antibiotics.
Despite the good attitude of health care workers to adhere to diagnostic test results, antimalarials and antibiotics remain inappropriate prescribed to febrile children. The low specificity of malaria RDT used could be an important cause of these practices.
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