Improving pediatric TB diagnosis in North Kivu (DR Congo), focusing on a clinical algorithm including targeted Xpert MTB/RIF on gastric aspirates

Background The incidence of tuberculosis (TB) in the Democratic Republic of the Congo (DRC) is 323/100,000. A context of civil conflict, internally displaced people and mining activities suggests a higher regional TB incidence in North Kivu. Medecins Sans Frontieres (MSF) supports the General Reference Hospital of Masisi, North Kivu, covering a population of 520,000, with an elevated rate of pediatric malnutrition. In July 2017, an adapted MSF pediatric TB diagnostic algorithm, including Xpert MTB/RIF on gastric aspirates (GAs), was implemented. The aim of this study was to evaluate whether the introduction of this clinical pediatric TB diagnostic algorithm influenced the number of children started on TB treatment. Methods We performed a retrospective analysis of pediatric TB cases started on treatment in the inpatient therapeutic feeding centre (ITFC) and the pediatric ward. We compared data collected in the second half (July to December) of 2016 (before introduction of the new diagnostic algorithm) and the second half of 2017. For the outcome variables the difference between the two years was calculated by a Pearson Chi-square test. Results In 2017, 94 GAs were performed, compared to none in 2016. Twelve percent (11/94) of samples were Xpert MTB/RIF positive. Sixty-eight children (2.9% of total exits) aged between 3 months and 15 years started TB treatment in 2017, compared to 19 (1.4% of total exits) in 2016 (p 0.002). The largest increase in pediatric TB diagnoses in 2017 occurred in patients with a negative Xpert MTB/RIF result, but clinically highly suggestive of TB according to the newly introduced diagnostic algorithm. Fifty-two (3.1%) children under five years old started treatment in 2017, as compared to 14 (1.3%) in 2016 (p 0.004). The increase was less pronounced and not statistically significant in older patients: sixteen children (2.6%) above 5 years old started TB treatment in 2017 as compared to five (1.3%) in 2016 (p 0.17). Conclusion After the introduction of an adapted clinical pediatric TB diagnostic algorithm, including Xpert MTB/RIF on gastric aspirates, we observed a significant increase in the number of children - especially under 5 years old - started on TB treatment, mostly on clinical grounds. Increased 'clinician awareness' of pediatric TB likely played an important role

Metal mining and birth defects : a case-control study in Lubumbashi, Democratic Republic of the Congo

Background Widespread environmental contamination caused by mining of copper and cobalt has led to concerns about the possible association between birth defects and exposure to several toxic metals in southern Katanga, Democratic Republic of the Congo (DRC). We therefore aimed to assess the possible contribution of parental and antenatal exposure to trace metals to the occurrence of visible birth defects among neonates. Methods We did a case-control study between March 1, 2013, and Feb 28, 2015, in Lubumbashi, DRC. We included newborns with visible birth defects (cases) and healthy neonates born in the same maternity ward (controls). Mothers were interviewed about potentially relevant exposures, including their partners' jobs. Various trace metals were measured by inductively coupled plasma mass spectrometry in maternal urine, maternal blood, umbilical cord blood, placental tissue, and surface dust at home. Multivariable logistic regression analyses were done to calculate adjusted odds ratios and their 95% CIs (CI). Findings Our study included 138 neonates with visible birth defects (about 0.1% of the 133 662 births in Lubumbashi during the study period) and 108 control neonates. Potential confounders were similarly distributed between cases and controls. Vitamin consumption during pregnancy was associated with a lower risk of birth defects (adjusted odds ratio 0.2, 95% CI 0.1-0.5). Mothers having paid jobs outside the home (2.8, 1.2-6.9) and fathers having mining-related jobs (5.5, 1.2-25.0) were associated with a higher risk of birth defects. We found no associations for trace metal concentrations in biological samples, except for a doubling of manganese (Mn; 1.7, 1.1-2.7) and zinc (Zn; 1.6, 0.9-2.8) in cord blood. In a separate model including placentas, a doubling of Mn at the fetal side of the placenta was associated with an increased risk of birth defects (3.3, 1.2-8.0), as was a doubling of cord blood Zn (5.3, 1.6-16.6). Interpretation To our knowledge, this is the first study of the effects of mining-related pollution on newborns in sub-Saharan Africa. Paternal occupational mining exposure was the factor most strongly associated with birth defects. Because neither Mn nor Zn are mined in Lubumbashi, the mechanism of the association between their increased prenatal concentrations and birth defects is unclear

Growth and neurodevelopment in low birth weight versus normal birth weight infants from birth to 24 months, born in an obstetric emergency hospital in Haiti, a prospective cohort study

Background Low birthweight (LBW) infants are at higher risk of mortality and morbidity (growth, chronic disease and neurological problems) during their life. Due to the high incidence of (pre-) eclampsia in Haiti, LBW infants are common. We assessed the anthropometric growth (weight and length) and neurodevelopmental delay in LBW and normal birthweight (NBW) infants born at an obstetric emergency hospital in Port au Prince, Haiti, between 2014 and 2017. Methods Infants were followed at discharge and 3, 6, 12, 15, 18, 21 and 24 months of corrected gestational age. At each visit they underwent a physical checkup (weight, length, physical abnormalities, identification of morbidities). At 6, 12, 18 and 24 months they underwent a neurodevelopmental assessment using the Bayley Scale III (motor, cognitive and communication skills). We modelled the trajectories between birth and 24 months of age of NBW compared to LBW infants for weight, length, and raw scores for Bayley III assessments using mixed linear models. Results In total 500 LBW and 210 NBW infants were recruited of which 333 (46.7%) were followed up for 24 months (127 NBW; 60.5% and 206 LBW; 41.2%) and 150 died (LBW = 137 and NBW = 13). LBW and NBW babies gained a mean 15.8 g and 11.4 g per kg of weight from discharge per day respectively. The speed of weight gain decreased rapidly after 3 months in both groups. Both groups grow rapidly up to 6 months of age. LBW grew more than the NBW group during this period (22.8 cm vs. 21.1 cm). Both groups had WHZ scores <− 2 up to 15 months. At 24 months NBW babies scored significantly higher on the Bayley scales for gross motor, cognitive and receptive and expressive communication skills. There was no difference between the groups for fine motor skills. Conclusion LBW babies that survive neonatal care in urban Haiti and live up to 24 months of age, perform similar to their NBW for weight, length and fine motor skills. LBW babies are delayed in gross motor, cognitive and communication skills development. Further research on the clinical significance of these findings and long term implications of this neurodevelopmental delay is needed

COVID-19 in children and adolescents in Europe: a multinational, multicentre cohort study

Background To date, few data on paediatric COVID-19 have been published, and most reports originate from China. This study aimed to capture key data on children and adolescents with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection across Europe to inform physicians and health-care service planning during the ongoing pandemic. Methods This multicentre cohort study involved 82 participating health-care institutions across 25 European countries, using a well established research network—the Paediatric Tuberculosis Network European Trials Group (ptbnet)—that mainly comprises paediatric infectious diseases specialists and paediatric pulmonologists. We included all individuals aged 18 years or younger with confirmed SARS-CoV-2 infection, detected at any anatomical site by RT-PCR, between April 1 and April 24, 2020, during the initial peak of the European COVID-19 pandemic. We explored factors associated with need for intensive care unit (ICU) admission and initiation of drug treatment for COVID-19 using univariable analysis, and applied multivariable logistic regression with backwards stepwise analysis to further explore those factors significantly associated with ICU admission. Findings 582 individuals with PCR-confirmed SARS-CoV-2 infection were included, with a median age of 5·0 years (IQR 0·5–12·0) and a sex ratio of 1·15 males per female. 145 (25%) had pre-existing medical conditions. 363 (62%) individuals were admitted to hospital. 48 (8%) individuals required ICU admission, 25 (4%) mechanical ventilation (median duration 7 days, IQR 2–11, range 1–34), 19 (3%) inotropic support, and one (<1%) extracorporeal membrane oxygenation. Significant risk factors for requiring ICU admission in multivariable analyses were being younger than 1 month (odds ratio 5·06, 95% CI 1·72–14·87; p=0·0035), male sex (2·12, 1·06–4·21; p=0·033), pre-existing medical conditions (3·27, 1·67–6·42; p=0·0015), and presence of lower respiratory tract infection signs or symptoms at presentation (10·46, 5·16–21·23; p<0·0001). The most frequently used drug with antiviral activity was hydroxychloroquine (40 [7%] patients), followed by remdesivir (17 [3%] patients), lopinavir–ritonavir (six [1%] patients), and oseltamivir (three [1%] patients). Immunomodulatory medication used included corticosteroids (22 [4%] patients), intravenous immunoglobulin (seven [1%] patients), tocilizumab (four [1%] patients), anakinra (three [1%] patients), and siltuximab (one [<1%] patient). Four children died (case-fatality rate 0·69%, 95% CI 0·20–1·82); at study end, the remaining 578 were alive and only 25 (4%) were still symptomatic or requiring respiratory support. Interpretation COVID-19 is generally a mild disease in children, including infants. However, a small proportion develop severe disease requiring ICU admission and prolonged ventilation, although fatal outcome is overall rare. The data also reflect the current uncertainties regarding specific treatment options, highlighting that additional data on antiviral and immunomodulatory drugs are urgently needed. Funding ptbnet is supported by Deutsche Gesellschaft für Internationale Zusammenarbeit

Budd-Chiari syndrome as presenting symptom of hepatic sarcoidosis in a child, with recurrence after liver transplantation

Van Brusselen D, Janssen CEI, Scott C, Bevers N, Roskams T, Wouters C, Van Damme-Lombaerts R. Budd-Chiari syndrome as presenting symptom of hepatic sarcoidosis in a child, with recurrence after liver transplantation. Pediatr Transplantation 2011: 00: 000-000. © 2011 John Wiley & Sons A/S. Abstract:  A seven-yr-old boy presented with a severe Budd-Chiari syndrome, complicated by recurrent thrombosis of several successive TIPSs. Because of liver failure secondary to venous outflow tract obstruction and deterioration of his general condition, an emergency liver transplantation was performed. Steroids were discontinued three months after transplantation, and maintenance immunosuppressive therapy consisted of tacrolimus and azathioprine. Seven years later, this patient presented symptoms of recurrence of venous outflow obstruction in the transplant liver, comparable to the initial event. Histopathology of the liver revealed diffuse granulomatous inflammation with confluent non-caseating granulomas compressing the centrolobular veins. Extensive investigations excluded infections, immune deficiency, and systemic vasculitides. After treatment with a high dose of corticosteroids, the granulomas in the allograft disappeared completely. We report the first case of hepatic sarcoidosis, presenting with venous outflow obstruction and recurring after liver transplantation, in a child.status: publishe

Streptococcal pharyngitis in children: to treat or not to treat?

Controversy remains about the need for antibiotic therapy of group A streptococcal (GAS) pharyngitis in high-resource settings. Guidelines on the management of GAS pharyngitis differ considerably, especially in children. We performed a literature search on the diagnosis and treatment of GAS pharyngitis in children and compared different guidelines with current epidemiology and the available evidence on management. Some European guidelines only recommend antibiotic treatment in certain high-risk patients, while many other, including all American, still advise antimicrobial treatment for all children with GAS pharyngitis, given the severity and re-emerging incidence of complications. Empirical antimicrobial treatment in children with sore throat and a high clinical suspicion of GAS pharyngitis will still result in significant overtreatment of nonstreptococcal pharyngitis. This is costly and leads to emerging antibiotic resistance. Early differential diagnosis between viral and GAS pharyngitis, by means of a 'rapid antigen detection test' (RADT) and/or a throat culture, is therefore needed if 'pro treatment' guidelines are used. Conclusion: Large scale randomized controlled trials are necessary to assess the value of antibiotics for GAS pharyngitis in high-resource countries, in order to achieve uniform and evidence-based guidelines. The severity and the possibly increasing incidence of complications in school-aged children suggests that testing and treating proven GAS pharyngitis can still be beneficial