Host-Based Prognostic Biomarkers to Improve Risk Stratification and Outcome of Febrile Children in Low- and Middle-Income Countries.

"Fever is one of the leading causes for pediatric medical consultation and the most common symptom at clinical presentation in low- and middle-income countries (LMICs). Most febrile episodes are due to self-limited infections, but a small proportion of children will develop life-threatening infections. The early recognition of children who have or are progressing to a critical illness among all febrile cases is challenging, and there are currently no objective and quantitative tools to do so. This results in increased morbidity and mortality among children with impending life-threatening infections, whilst contributing to the unnecessary prescription of antibiotics, overwhelming health care facilities, and harm to patients receiving avoidable antimicrobial treatment. Specific fever origin is difficult to ascertain and co-infections in LMICs are common. However, many severe infections share common pathways of host injury irrespective of etiology, including immune and endothelial activation that contribute to the pathobiology of sepsis (i.e., pathogen \"agnostic\" mechanisms of disease). Importantly, mediators of these pathways are independent markers of disease severity and outcome. We propose that measuring circulating levels of these factors can provide quantitative and objective evidence to: enable early recognition of severe infection; guide patient triage and management; enhance post-discharge risk stratification and follow up; and mitigate potential gender bias in clinical decisions. Here, we review the clinical and biological evidence supporting the clinical utility of host immune and endothelial activation biomarkers as components of novel rapid triage tests, and discuss the challenges and needs for developing and implementing such tools.

Heparin-binding protein stratifies mortality risk among Ugandan children hospitalized with respiratory distress

Background Current prognostic tools do not reliably and objectively identify children with pneumonia at risk of a severe or life-threatening episode. Heparin-binding protein (HBP) is a host immune protein that is released in response to infection. We hypothesized that measuring HBP concentrations at hospital admission could help risk-stratify children with pneumonia and identify those at higher risk of an adverse prognosis. Methods We evaluated the prognostic accuracy of HBP for predicting in-hospital mortality among children with respiratory distress, and whether HBP could improve the accuracy of validated composite clinical severity scores. Results Of 778 Ugandan children under 5 years of age and presenting with clinically defined pneumonia, 60 (7.7%) died during hospital admission. HBP concentrations at presentation were significantly higher in children with fatal outcomes (median, 76 ng/mL [interquartile range {IQR}, 41–150]) compared to children who survived (median, 31 ng/mL [IQR, 18–57]) (P \u3c .001). Children with HBP \u3e41 ng/mL on admission had an elevated risk of death (hazard ratio, 5.3 [95% confidence interval {CI}, 2.9–9.5]; P \u3c .0001). In receiver operating characteristic (ROC) curve analysis, HBP concentrations distinguished between fatal and nonfatal outcomes (area under the ROC curve, 0.75 [95% CI, .66–.84]) and significantly improved the prediction provided by the Respiratory Index of Severity in Children, a composite clinical severity score (P = .0026). Conclusions Measuring HBP at presentation could help identify children at risk of severe and fatal pneumonia. Adding HBP to clinical scores could improve the recognition and triage of children with pneumonia at risk of death

Antibody responses to α-Gal in African children vary with age and site and are associated with malaria protection

Naturally-acquired antibody responses to malaria parasites are not only directed to protein antigens but also to carbohydrates on the surface of Plasmodium protozoa. Immunoglobulin M responses to α-galactose (α-Gal) (Galα1-3Galβ1-4GlcNAc-R)-containing glycoconjugates have been associated with protection from P. falciparum infection and, as a result, these molecules are under consideration as vaccine targets; however there are limited field studies in endemic populations. We assessed a wide breadth of isotype and subclass antibody response to α-Gal in children from Mozambique (South East Africa) and Ghana (West Africa) by quantitative suspension array technology. We showed that anti-α-Gal IgM, IgG and IgG1–4 levels vary mainly depending on the age of the child, and also differ in magnitude in the two sites. At an individual level, the intensity of malaria exposure to P. falciparum and maternally-transferred antibodies affected the magnitude of α-Gal responses. There was evidence for a possible protective role of anti-α-Gal IgG3 and IgG4 antibodies. However, the most consistent findings were that the magnitude of IgM responses to α-Gal was associated with protection against clinical malaria over a one-year follow up period, especially in the first months of life, while IgG levels correlated with malaria risk

Coverage, determinants of use and repurposing of long‑lasting insecticidal nets two years after a mass distribution in Lihir Islands, Papua New Guinea: a cross‑sectional study

Background: Universal coverage with long-lasting insecticidal nets (LLINs) is an essential component of malaria control programmes. Three-yearly mass distribution of LLINs in Papua New Guinea (PNG) has been successful in reducing infection transmission since 2009, but malaria prevalence ramped up from 2015 onwards. Although LLIN universal coverage is mostly achieved during these campaigns, it may not be related with net use over time. Uses given to LLINs and non-compliance of this strategy were evaluated. Methods: A knowledge, attitude and practice (KAP) cross-sectional study was conducted in Lihir Islands, PNG, 2–2.5 years after the last LLIN mass distribution campaign. Data on bed net ownership, use and maintenance behaviour was collected using a household questionnaire administered by trained community volunteers. Logistic regression models were used to identify factors associated with owning at least one LLIN and sleeping under a LLIN the previous night. Results: Among 2694 households surveyed, 27.4 % (95 % CI: 25.8–29.2) owned at least one LLIN and 8.7 % (95 % CI: 7.6–9.8) had an adequate LLIN coverage (at least one LLIN for every two people). Out of 13,595 individuals in the surveyed households, 13.6 % (95 % CI: 13.0-–4.2) reported having slept under a LLIN the preceding night. Determinants for sleeping under LLIN included living in a household with adequate LLIN coverage [adjusted OR (aOR) = 5.82 (95 % CI: 3.23–10.49)], household heads knowledge about LLINs [aOR = 16.44 (95 % CI: 8.29–32.58)], and female gender [aOR = 1.92 (95 % CI: 1.53–2.40)] (all p-values < 0.001). LLIN use decreased with older age [aOR = 0.29 (95 % CI: 0.21–0.40) for ≥ 15 year-olds, aOR = 0.38 (95 % CI: 0.27–0.55) for 5–14 year-olds] compared to < 5 year-olds (p-value < 0.001). Knowledge on the use of LLIN was good in 37.0 % of the household heads. Repurposed nets were reported serving as fishing nets (30.4 %), fruits and seedlings protection (26.6 %), covering up food (19.0 %) and bed linen (11.5 %). Conclusions: Two years after mass distribution, LLIN coverage and use in Lihir Islands is extremely low. Three yearly distribution campaigns may not suffice to maintain an acceptable LLIN coverage unless knowledge on maintenance and use is promoted trough educational campaigns

Research funding for newborn health and stillbirths, 2011–20: a systematic analysis of levels and trends

Background: Worldwide, an estimated 4·4 million newborn deaths and stillbirths occurred in 2020, and 98% of these deaths occurred in low-income and middle-income countries (LMICs). We aimed to analyse new research grants for newborns and stillbirth awarded by major funders in 2019–20, and all research funding allocated to LMIC-based institutions in 2011–20. Methods: For this systematic analysis, we searched Dimensions, the world's largest research funding database, for grants relevant to neonatal and stillbirth research. Included grants were categorised by in-depth content analysis, with descriptive quantitative analyses by funder and recipient countries, research pipeline, topic, and year. Findings: Globally, in 2019–20, major funders awarded a mean annual total of US$577·1 million per year for newborn and stillbirth research (mean total of 550 grants per year).$166·3 million (28·8%) of $577·1 million was directed to small and vulnerable newborn research, but only$8·4 million (1·5%) was directed to stillbirth research. The majority of funding, $537·0 million (93·0$486·7 million, of which $73·1 million (15·0$12·0 million (2·5%) was allocated to stillbirth research. Most LMIC funding supported preclinical or observational studies ($236·8 million [48·7$486·7 million), with implementation research receiving only $13·9 million (2·9%). Interpretation: Although investment in research related to neonatal health and stillbirths has increased between 2011 and 2020, there are marked disparities in distribution geographically, between major causes of mortality, and among research pipeline types. Stillbirth research received minimal funding in both high-income countries and LMICs, despite a similar number of deaths compared with neonates. Direct investment in LMIC-led research, especially for implementation research, could accelerate the slow global progress on stillbirth prevention and newborn survival. Funding: None. Translations: For the French, German and Spanish translations of the abstract see Supplementary Materials section

Field performance of ultrasensitive and conventional malaria rapid diagnostic tests in southern Mozambique.

BACKGROUND: An ultrasensitive malaria rapid diagnostic test (RDT) was recently developed for the improved detection of low-density Plasmodium falciparum infections. This study aimed to compare the diagnostic performance of the PfHRP2-based Abbott Malaria Ag P. falciparum ultrasensitive RDT (uRDT) to that of the conventional SD-Bioline Malaria Ag P. falciparum RDT (cRDT) when performed under field conditions. METHODS: Finger-prick blood samples were collected from adults and children in two cross-sectional surveys in May of 2017 in southern Mozambique. Using real-time quantitative PCR (RT-qPCR) as the reference method, the age-specific diagnostic performance indicators of the cRDT and uRDT were compared. The presence of histidine-rich protein 2 (HRP2) and Plasmodium lactate dehydrogenase (pLDH) antigens was evaluated in a subset from dried blood spots by a quantitative antigen assay. pfhrp2 and pfhrp3 gene deletions were assessed in samples positive by RT-qPCR and negative by both RDTs. RESULTS: Among the 4,396 participants with complete test results, the sensitivity of uRDTs (68.2; 95% CI 60.8 to 74.9) was marginally better than that of cRDTs (61.5; 95% CI 53.9 to 68.6) (p-value = 0.004), while the specificities were similar (uRDT: 99.0 [95% CI 98.6 to 99.2], cRDT: 99.2 [95% CI 98.9 to 99.4], p-value = 0.02). While the performance of both RDTs was lowest in ≥ 15-year-olds, driven by the higher prevalence of low parasite density infections in this group, the sensitivity of uRDTs was significantly higher in this age group (54.9, 95% CI 40.3 to 68.9) compared to the sensitivity of cRDTs (39.2, 95% CI 25.8 to 53.9) (p-value = 0.008). Both RDTs detected P. falciparum infections at similar geometric mean parasite densities (112.9  parasites/μL for uRDTs and 145.5 parasites/μL for cRDTs). The presence of HRP2 antigen was similar among false positive (FP) samples of both tests (80.5% among uRDT-FPs and 84.4% among cRDT-FPs). Only one false negative sample was detected with a partial pfhrp2 deletion. CONCLUSION: This study showed that the uRDTs developed by Abbott do not substantially outperform SD-Bioline Pf malaria RDTs in the community and are still not comparable to molecular methods to detect P. falciparum infections in this study setting

How Did the COVID-19 Lockdown Affect Children and Adolescent's Well-Being: Spanish Parents, Children, and Adolescents Respond.

Background: During the COVID-19 pandemic, lockdown strategies have been widely used to contain SARS-CoV-2 virus spread. Children and adolescents are especially vulnerable to suffering psychological effects as result of such measures. In Spain, children were enforced to a strict home lockdown for 42 days during the first wave. Here, we studied the effects of lockdown in children and adolescents through an online questionnaire. Methods: A cross-sectional study was conducted in Spain using an open online survey from July (after the lockdown resulting from the first pandemic wave) to November 2020 (second wave). We included families with children under 16 years-old living in Spain. Parents answered a survey regarding the lockdown effects on their children and were instructed to invite their children from 7 to 16 years-old (mandatory scholar age in Spain) to respond a specific set of questions. Answers were collected through an application programming interface system, and data analysis was performed using R. Results: We included 1,957 families who completed the questionnaires, covering a total of 3,347 children. The specific children's questionnaire was completed by 167 kids (7-11 years-old), and 100 adolescents (12-16 years-old). Children, in general, showed high resilience and capability to adapt to new situations. Sleeping problems were reported in more than half of the children (54%) and adolescents (59%), and these were strongly associated with less time doing sports and spending more than 5 h per day using electronic devices. Parents perceived their children to gain weight (41%), be more irritable and anxious (63%) and sadder (46%). Parents and children differed significantly when evaluating children's sleeping disturbances. Conclusions: Enforced lockdown measures and isolation can have a negative impact on children and adolescent's mental health and well-being. In future waves of the current pandemic, or in the light of potential epidemics of new emerging infections, lockdown measures targeting children, and adolescents should be reconsidered taking into account their infectiousness potential and their age-specific needs, especially to facilitate physical activity and to limit time spent on electronic devices. Keywords: COVID-19; adolescent; children; lockdown; mental health; well-being

Guia per a la incorporació de la perspectiva de gènere en els plans docents i les assignatures de la Universitat de Barcelona

La Universitat de Barcelona, en el seu III Pla d’igualtat, s’ha compromès a incloure i desplegar la perspectiva de gènere en tots els seus àmbits d’actuació. Un dels eixos que estructuren aquest pla (concretament, l’eix 4) està dedicat a la perspectiva de gènere en la docència. La Comissió d’Igualtat, el Vicerectorat de Política Docent, el Vicerectorat de Política Acadèmica i Qualitat, el Vicerectorat d’Igualtat i Gènere i la Unitat d’Igualtat volem facilitar-vos la tasca d’incorporar la perspectiva de gènere a totes les assignatures. Us proposem d’avançar cap a una UB més inclusiva començant pels plans docents, tal com preveu la legislació vigent. Aquesta proposta s’anirà acompanyant, al llarg del curs, d’accions de formació i d’altres materials que esperem que us siguin útils

Low transmission of SARS-CoV-2 derived from children in family clusters: An observational study of family households in the Barcelona Metropolitan Area, Spain

Background: Family clusters offer a good opportunity to study viral transmission in a stable setting. We aimed to analyze the specific role of children in transmission of SARS-CoV-2 within households. Methods: A prospective, longitudinal, observational study, including children with documented acute SARS-CoV-2 infection attending 22 summer-schools in Barcelona, Spain, was performed. Moreover, other patients and families coming from other school-like environments that voluntarily accessed the study were also studied. A longitudinal follow-up (5 weeks) of the family clusters was conducted to determine whether the children considered to be primary cases were able to transmit the virus to other family members. The household reproduction number (Re*) and the secondary attack rate (SAR) were calculated. Results: 1905 children from the summer schools were screened for SARS-CoV-2 infection and 22 (1.15%) tested positive. Moreover, 32 additional children accessed the study voluntarily. Of these, 37 children and their 26 households were studied completely. In half of the cases (13/26), the primary case was considered to be a child and secondary transmission to other members of the household was observed in 3/13, with a SAR of 14.2% and a Re* of 0.46. Conversely, the SAR of adult primary cases was 72.2% including the kids that gave rise to the contact tracing study, and 61.5% without them, and the estimated Re* was 2.6. In 4/13 of the paediatric primary cases (30.0%), nasopharyngeal PCR was persistently positive > 1 week after diagnosis, and 3/4 of these children infected another family member (p<0.01). Conclusions: Children may not be the main drivers of the infection in household transmission clusters in the study population. A prolonged positive PCR could be associated with higher transmissibility

Neurofilament Light Chain as a Biomarker of Neuronal Damage in Children With Malaria.

Malaria can cause brain injury. Neurofilament light chain (NfL) is a biomarker of neuronal damage. Here we examined longitudinal plasma NfL levels in children aged 1-12 years with uncomplicated and severe malaria from Mozambique. NfL levels were similar in all malaria cases at hospital admission. However, levels increased over time and the increment was significantly higher in severe malaria cases with neurological manifestations (ie, coma, impaired consciousness, or repeated seizures). NfL may be useful to identify and quantify brain injury in malaria