MSF Paediatric Days: a step forward in operationalising 'Humanitarian Paediatrics'.

Around the world, one in four children live in a country affected by conflict, political insecurity and disaster. Healthcare in humanitarian and fragile settings is challenging and complex to provide, particularly for children. Furthermore, there is a distinct lack of medical literature from humanitarian settings to guide best practice in such specific and resource-limited contexts. In light of these challenges, Médecins Sans Frontières (MSF), an international medical humanitarian organisation, created the MSF Paediatric Days with the aim of uniting field staff, policymakers and academia to exchange ideas, align efforts, inspire and share frontline research and experiences to advance humanitarian paediatric and neonatal care. This 2-day event takes place regularly since 2016. The fourth edition of the MSF Paediatric Days in April 2021 covered five main topics: essential newborn care, community-based models of care, paediatric tuberculosis, antimicrobial resistance in neonatal and paediatric care and the collateral damage of COVID-19 on child health. In addition, eight virtual stands from internal MSF initiatives and external MSF collaborating partners were available, and 49 poster communications and five inspiring short talks referred to as 'PAEDTalks' were presented. In conclusion, the MSF Paediatric Days serves as a unique forum to advance knowledge on humanitarian paediatrics and creates opportunities for individual and collective learning, as well as networking spaces for interaction and exchange of ideas.

[Vulnerable populations and COVID-19 : need for innovation and cooperation to address health and social needs]. / Populations précaires et Covid-19 : innover et collaborer pour faire face aux besoins sociaux et de santé.

The COVID-19 crisis has rapidly increased the vulnerability of groups of population already facing precarious living conditions. The emergence of food and housing insecurity have forced health and social actors along with the local authorities to implement innovative responses in order to respond to these unmet needs. This article presents some of these responses, such as an interdisciplinary mobile COVID-19 screening team, an emergency housing program and a large-scale food assistance program. These examples highlight the need for an intersectoral, coordinated and collaborative response simultaneously targeting different domains of insecurity in parallel to actions on the underpinning social and political determinants of these vulnerabilities.

La crise liée au Covid-19 a fragilisé les populations en situation préalable de précarité. L'émergence de l'insécurité alimentaire et de logement a poussé les acteurs de la santé, du travail social et les autorités à mettre en place des mesures innovantes et intersectorielles permettant de répondre rapidement et efficacement aux besoins essentiels de ces populations. Cet article présente trois de ces mesures, à savoir une équipe mobile interprofessionnelle de dépistage, un dispositif d'hébergement et d'encadrement sanitaire pour les personnes sans-abri et un programme de distribution alimentaire à large échelle. Ces trois exemples illustrent la nécessité d'une approche transversale et collaborative et le besoin d'agir sur les déterminants sociaux et politiques sous-tendant ces vulnérabilités.

Ebola-negative neonates born to Ebola-infected mothers after monoclonal antibody therapy: a case series.

BACKGROUND: Few fetuses survive childbirth when the mother is positive for Ebola virus, with almost all being miscarried or stillborn, or dying shortly after birth. Before 2019, only two infants had been reported surviving past 28 days, of whom one tested positive for Ebola virus and subsequently received experimental therapies. Little is understood regarding the care of surviving neonates born to Ebola virus-positive mothers in the postnatal period and how novel anti-Ebola virus therapies might affect neonatal outcomes. METHODS: In this case series, we report on two neonates liveborn during the 2018-20 North Kivu Ebola epidemic in the Democratic Republic of the Congo who, along with their Ebola virus-positive mothers, received investigational monoclonal antibody treatment (mAB114 or REGN-EB3) as part of a randomised controlled trial (NCT03719586). FINDINGS: Both infants were born Ebola-negative and progressed well while in the Ebola Treatment Centre. Neither neonate developed evidence of Ebola virus disease during the course of the admission, and both were Ebola-negative at 21 days and remained healthy at discharge. INTERPRETATION: To our knowledge these neonates are the first documented as Ebola virus-negative at birth after being born to Ebola virus-positive mothers, and only the third and fourth neonates ever documented to have survived into infancy. Although no conclusions can be drawn from this small case series, and further research is required to investigate the neonatal effects of antibody therapies, these cases warrant review regarding whether post-delivery antibody therapy should be considered for all liveborn neonates of Ebola virus-positive mothers. In the context of a low resource setting, where survival of low-birthweight infants is poor, these cases also highlight the importance of adequate neonatal care. FUNDING: None.

2017 Outbreak of Ebola Virus Disease in Northern Democratic Republic of Congo.

BACKGROUND: In 2017, the Democratic Republic of the Congo (DRC) recorded its eighth Ebola virus disease (EVD) outbreak, approximately 3 years after the previous outbreak. METHODS: Suspect cases of EVD were identified on the basis of clinical and epidemiological information. Reverse transcription-polymerase chain reaction (RT-PCR) analysis or serological testing was used to confirm Ebola virus infection in suspected cases. The causative virus was later sequenced from a RT-PCR-positive individual and assessed using phylogenetic analysis. RESULTS: Three probable and 5 laboratory-confirmed cases of EVD were recorded between 27 March and 1 July 2017 in the DRC. Fifty percent of cases died from the infection. EVD cases were detected in 4 separate areas, resulting in > 270 contacts monitored. The complete genome of the causative agent, a variant from the Zaireebolavirus species, denoted Ebola virus Muyembe, was obtained using next-generation sequencing. This variant is genetically closest, with 98.73% homology, to the Ebola virus Mayinga variant isolated from the first DRC outbreaks in 1976-1977. CONCLUSION: A single spillover event into the human population is responsible for this DRC outbreak. Human-to-human transmission resulted in limited dissemination of the causative agent, a novel Ebola virus variant closely related to the initial Mayinga variant isolated in 1976-1977 in the DRC.

Quantitative Analysis of Gamma Interferon Release Assay Response in Children with Latent and Active Tuberculosis.

The use of interferon gamma (IFN-γ) release assays (IGRAs) for the diagnosis of tuberculosis (TB) infection in children is still under debate because of concerns about the immature immune response in children. The aim of this study was to investigate quantitative values of the QuantiFERON-TB Gold In-Tube (QFT-IT) test, a commercially available IGRA, in a large cohort of children screened for TB infection. A retrospective analysis was conducted on samples from 517 children aged 0 to 14 years old at the Pediatric Unit of S. Orsola-Malpighi University Hospital of Bologna (Italy); quantitative responses to QFT-IT stimuli were analyzed according to diagnosis and age. Elevated IFN-γ values in the QFT-IT nil (background) tube were statistically associated with diagnosis of active TB. Quantitative IFN-γ response to Mycobacterium tuberculosis-specific antigens (TB Ag) was not significantly different in children with active TB compared to those with latent TB infection (LTBI), even though the median values were higher in the first group. When children were grouped by age, those less than 5 years old produced significantly higher levels of IFN-γ in response to TB Ag if they had active TB (median 10 IU/ml) than those with LTBI (median 1.96 IU/ml). IFN-γ response to mitogen increased with age. The overall rate of indeterminate results was low (3.9%), and no indeterminate QFT-IT values were observed in active or latent TB patients. In conclusion, quantitative QFT-IT values could provide further information to clinicians to manage TB in children, and these observations could be transferred to the new version of the test, QuantiFERON-TB Gold Plus, which to date lacks data from the pediatric population.

Quantiferon-TB Gold In-Tube Improves Tuberculosis Diagnosis in Children.

BACKGROUND: The diagnostic accuracy of Quantiferon-TB Gold In-Tube (QFT-IT) is uncertain in the pediatric population, while tuberculin skin test (TST) is still conventionally used despite its limitations. The aim of this study was to compare the performance of QFT-IT with TST in a large cohort of children screened for tuberculosis (TB) infection because of contact tracing, suspected TB, arrival from endemic country or immunosuppressive therapy. METHODS: A retrospective analysis was conducted on 517 children 0-14 years of age evaluated at the pediatric unit of the S. Orsola-Malpighi University Hospital of Bologna, Italy; 366 of them were also tested with TST. Results were analyzed for Calmette-Guérin bacillus vaccination, country of origin, reason for testing, diagnosis and age. RESULTS: The overall agreement between the 2 tests was 89.9%, but it was highly affected by Calmette-Guérin bacillus vaccination (P < .0001). According to diagnosis and age, QFT-IT detected latent tuberculous infection cases better than TST in all age groups. Sensitivity for diagnosing active TB in symptomatic children was higher for QFT-IT than TST (93.3% vs. 86.5%), especially in children younger than 2 years, while specificity was high for both tests (99.3% and 98.8%, respectively). Low rate of indeterminate QFT-IT results (3.9%) was not differently distributed among age groups, but was associated with diagnosis of TB exclusion (P < 0.0001), mainly pneumonia (35%), and to Italian children (P = 0.0024). CONCLUSIONS: Despite the concern about the use of QFT-IT in children because of their immature immune system, our results suggest the preferential use of QFT-IT as a support tool for diagnosis and management of TB, even in infants.

Effect of Artesunate-Amodiaquine on Mortality Related to Ebola Virus Disease.

BACKGROUND: Malaria treatment is recommended for patients with suspected Ebola virus disease (EVD) in West Africa, whether systeomatically or based on confirmed malaria diagnosis. At the Ebola treatment center in Foya, Lofa County, Liberia, the supply of artemether-lumefantrine, a first-line antimalarial combination drug, ran out for a 12-day period in August 2014. During this time, patients received the combination drug artesunate-amodiaquine; amodiaquine is a compound with anti-Ebola virus activity in vitro. No other obvious change in the care of patients occurred during this period. METHODS: We fit unadjusted and adjusted regression models to standardized patient-level data to estimate the risk ratio for death among patients with confirmed EVD who were prescribed artesunate-amodiaquine (artesunate-amodiaquine group), as compared with those who were prescribed artemether-lumefantrine (artemether-lumefantrine group) and those who were not prescribed any antimalarial drug (no-antimalarial group). RESULTS: Between June 5 and October 24, 2014, a total of 382 patients with confirmed EVD were admitted to the Ebola treatment center in Foya. At admission, 194 patients were prescribed artemether-lumefantrine and 71 were prescribed artesunate-amodiaquine. The characteristics of the patients in the artesunate-amodiaquine group were similar to those in the artemether-lumefantrine group and those in the no-antimalarial group. A total of 125 of the 194 patients in the artemether-lumefantrine group (64.4%) died, as compared with 36 of the 71 patients in the artesunate-amodiaquine group (50.7%). In adjusted analyses, the artesunate-amodiaquine group had a 31% lower risk of death than the artemether-lumefantrine group (risk ratio, 0.69; 95% confidence interval, 0.54 to 0.89), with a stronger effect observed among patients without malaria. CONCLUSIONS: Patients who were prescribed artesunate-amodiaquine had a lower risk of death from EVD than did patients who were prescribed artemether-lumefantrine. However, our analyses cannot exclude the possibility that artemether-lumefantrine is associated with an increased risk of death or that the use of artesunate-amodiaquine was associated with unmeasured patient characteristics that directly altered the risk of death.

Use of transrenal DNA for the diagnosis of extrapulmonary tuberculosis in children: a case of tubercular otitis media.

The diagnosis of tuberculosis (TB) is difficult in children, especially for smear-negative pulmonary and extrapulmonary TB, which are common at this age. We report an 11-year-old girl with TB otitis media with negative smear microscopy and Xpert MTB/RIF but positive Mycobacterium tuberculosis-specific transrenal DNA (Tr-MTB-DNA) test results and culture for M. tuberculosis.

Infant overweight as early marker of childhood overweight in Brazil.

OBJECTIVE: To investigate infant overweight and rapid weight gain as predictors of overweight and adiposity in childhood. METHODS: Prospective, longitudinal birth cohort following 153 low-income Brazilian children. Weight, length, middle upper arm circumference (MUAC) and triceps skinfold thickness (TSF) were measured on enrolment and 6-monthly for 18 months. Anthropometric z-scores were calculated. RESULTS: Infants with overweight were >5 times likely to have MUAC z-score >2, >6 times likely to have weight-for-height/length z-score >2 and >3 times likely to have TSF z-score >2 during childhood. Children with more than two overweight episodes were 27.7 [95% confidence interval (CI) 8.1-87.9] times more likely to have MUAC z-score >2 and 13.8 (95% CI 4.4-43.9) times more likely to have TSF z-score >2 in childhood. Rapid weight gain increased 10.7 (95% CI 2.3-50.0) times the risk of childhood overweight. CONCLUSIONS: Infant overweight and rapid weight gain predict overweight and adiposity in childhood among low-income children.

Chronic eosinophilic pneumonia: a paediatric case.

Chronic eosinophilic pneumonia (CEP) is a rare disorder in children, characterised by respiratory and systemic symptoms, with a generally good prognosis. A 11-year-old asthmatic girl was admitted to our clinic with a 3-month history of progressive cough, dyspnoea, weight loss and asthenia. Peripheral blood eosinophilia, multiple bilateral pulmonary infiltrates to the x-ray, multiple nodules with a surrounding ground-glass halo and peripheral predominance to the chest CT suggested the diagnosis of eosinophilic lung disease (ELD). Further investigations ruled out other ELD and supported diagnosis of CEP. The response to oral corticosteroids was dramatic, no relapses were reported in 2-year follow-up while the patient was under inhaled corticosteroids for pre-existing asthma.

Use of tuberculin skin test, IFN-γ release assays and IFN-γ-induced protein-10 to identify children with TB infection.

Current tests of tuberculosis (TB) infection (tuberculin skin test (TST), interferon (IFN)-γ-release assays (IGRAs) and IFN-γ-induced protein (IP)-10) have limitations and their value when used consecutively to identify infected children has not been explored. This study describes TST, IGRA and IP-10 responses in children in contact with adults with TB, the agreement of the tests and whether using multiple tests indentifies more infected children. 330 children (aged 1-15 yrs) in contact with adults with pulmonary TB and 156 controls were studied in Ethiopia. Children exposed to adults with high bacilli grades in sputum were more likely to have positive TST, IFN-γ and IP-10 than controls. The agreement of positive tests was directly associated with the sputum bacilli grades (p<0.001 for all). The agreement of negative tests was higher in control children. The consecutive use of the tests increased the number of children classified as having at least one positive test. Using three tests increases the number of children classified as infected. This increase is associated with the bacilli load of the adults. Using only one test may underestimate the proportion of infected children, but the interpretation of the data is difficult due to the lack of reference standards.

Dilated cardiomyopathy due to hypocalcaemic rickets: is it always a reversible condition?

Nutritional rickets is still occasionally found in high-income countries, especially in populations at risk, and induced hypocalcaemia is a rare but possible cause of dilated cardiomyopathy. Although rare, physicians need to consider nutritional rickets in the differential diagnosis of hypocalcaemia cardiac failure, especially in high-risk populations such as immigrants. Despite being a reversible condition, the prognosis depends on the severity and time of diagnosis. We report two cases of exclusively breastfed infants with congestive cardiac failure due to hypokinetic dilated cardiomyopathy who had completely different outcomes. This report supports the need for prevention of this deficiency and underlies the role of vitamin D supplementation.

Tuberculosis diagnostics for children in high-burden countries: what is available and what is needed.

BACKGROUND: The diagnosis of childhood tuberculosis (TB) is complex and most of the new diagnostics for TB are for adults. AIMS: To review the performance of TB diagnostics and their suitability to its characteristics in young children. METHODS: Expert opinion and review of the literature. MAIN FINDINGS: The lack of a sufficient number of research studies on TB diagnostics for children hinders the preparation of systematic literature reviews. Information on test performance in children is often extrapolated from studies in adults and there is a dearth of evidence of test performance in children. Approaches to shorten the time required for diagnosis (by using a variety of specimens) are needed and there is preliminary evidence that such schemes are feasible. Diagnostics based on smear microscopy such as LED-FM, serological tests and IGRAS are unlikely to improve the diagnosis of active TB in children. Liquid and the MODS culture methods are more sensitive than solid culture, and new methods to detect mycobacterium nucleic acid or its components such as TrDNA fragments, LAMP assays and Xpert MTB/RIF have good potential to increase the number of cases confirmed. These tests should be evaluated in specimens which are easily accessible in children such as fine-needle aspiration biopsy, urine, blood and stools. INTERPRETATION: The evaluation of new diagnostic tests for TB in children is overdue. The lack of suitable diagnostic tests hinders the proper management of children, the assessment of the real burden of childhood TB, evaluation of the efficacy of new treatments and vaccines and, ultimately, the development of effective control interventions.

Can interferon-gamma or interferon-gamma-induced-protein-10 differentiate tuberculosis infection and disease in children of high endemic areas?

BACKGROUND: Diagnosis of childhood tuberculosis (TB) is difficult in high TB burden settings. Interferon-gamma-induced protein 10 (IP10) has been suggested as a marker of TB infection and disease, but its ability to differentiate the two conditions remains uncertain. OBJECTIVES: To describe Interferon-gamma (INFγ) and IP10 expression in children with TB infection and disease and controls to assess their potential to differentiate latent and active TB. METHODS: This was a cross sectional study of 322 1-15 years old children with symptoms of TB (28 confirmed, 136 probable and 131 unlikely TB), 335 children in contact with adults with pulmonary TB and 156 community controls in Southern Ethiopia. The Tuberculin Skin Test (TST) and Quantiferon-In-Tube (QFT-IT) were performed. INFγ and IP10 were measured in plasma supernatants. RESULTS AND INTERPRETATION: Children with confirmed and probable TB and contacts were more likely to have TST+ (78.6%, 59.3% and 54.1%, respectively) than children with unlikely TB (28.7%) and controls (12.8%) (p<0.001). Children with confirmed TB (59.3%) and contacts (44.7%) were more likely to have INFγ+ than children with probable (37.6%) or unlikely TB (28.1%) and controls (13.1%) (p<0.001). IP10 concentrations were higher in INFγ+ children independently of TST (p<0.001). There was no difference between IP10 concentrations of children with confirmed TB and contacts (p = 0.8) and children with and without HIV (p>0.1). INFγ and IP10 can identify children with TB infection and disease, but cannot differentiate between the two conditions. HIV status did not affect the expression of IP10.

Interferon gamma, interferon-gamma-induced-protein 10, and tuberculin responses of children at high risk of tuberculosis infection.

BACKGROUND: Children in contact with adults with pulmonary tuberculosis (TB) are at risk for infection and disease progression, and chemoprophylaxis may reduce this risk. The identification of infection is based on the tuberculin skin test (TST) and interferon-gamma (INF-gamma) release assays. Other biomarkers such as interferon-gamma-induced-protein 10 (IP-10) may have potential for the diagnosis of latent TB infections. OBJECTIVES: To describe IP-10 concentrations and their association to TST and INF-gamma responses in children recently exposed to adults with smear-positive TB in Brazil and Nepal. METHODS: : Two surveys using the same design were undertaken to describe TST, INF-gamma, and IP-10 responses in 146 children in Nepal and 113 children in Brazil. RESULTS: The concordance of TST and QuantiFERON-TB gold in-tube (QFT-IT) was high (kappa 0.73 in Brazil and 0.80 in Nepal). IP-10 responses were higher in children with both positive TST and positive QFT-IT (medians 1434 pg/mL in Brazil and 1402 pg/mL in Nepal) and lowest in children with both negative TST and negative QFT-IT (medians 206 pg/mL in Brazil and 81 pg/mL in Nepal). Children with negative TST and positive QFT-IT had higher IP-10 concentrations than children with positive TST but negative QFT-IT. CONCLUSIONS: IP-10 is a potential marker to identify latent TB infections that is expressed in large quantities and with good agreement with QFT-IT. The reasons for the discrepant results observed are discussed.