Paediatric enteric fever in Brussels: a case series over 16 years.

Enteric fever (EF) is a major public health problem and a witness of the global health disparities. It is caused by Salmonella enterica serovar Typhi (Salmonella ser. Typhi) and Salmonella enterica serovar Paratyphi A, B, C (Salmonella ser. Paratyphi) and is estimated to infect 12-26 million persons yearly. Paediatric data on enteric fever in Europe are scarce. A case series of EF was analysed to describe the clinical presentation, laboratory characteristics and diagnostic challenges identified in a paediatric population in Brussels. We performed a retrospective study of all lab-confirmed cases of enteric fever in children aged 0-15 years at two Brussels teaching hospitals, between January 2005 and December 2020. We reviewed age, gender, travel history, consultations before diagnosis, hospitalisation duration, clinical symptoms and laboratory findings. There were 34 positive isolates of S. typhi and S. paratyphi: 31 patients had positive blood culture, 1 patient had positive bone aspirate and 2 patients had positive stool culture (one was excluded for missing data). There were 20 girls (60%). Median age was 3.5 years (range 5 months to 14 years). Travel to EF endemic areas was present in 55% of patients. Diagnosis was delayed in 80% of children. Eosinopenia was present in 93% of the cohort. The patients had not received any preventive travel education or vaccination.  Conlusion: Enteric fever poses diagnostic challenges to clinicians. Eosinopenia in a febrile patient coming from the tropics should raise suspicion of EF. Travellers to endemic areas should be better educated about EF risks, and typhoid fever vaccination must be promoted. What is Known: • Enteric fever is a global public health problem and includes typhoid and paratyphoid fever. • Typhoid fever is vaccine preventable disease. Paratyphoid fever is not vaccine preventable. What is New: • Enteric fever diagnosis is very challenging in non-endemic settings, and a large proportion of patients may develop serious complications if they receive delayed management. Occurrence of small family clusters is possible and mandates education and monitoring of the families of enteric fever affected children. • We report that the widest majority of our enteric fever affected patients (69%) had aneosinophilia (zero eosinophil count), and almost all patients (93%) had eosinopaenia (less than 50 eosinophil count) during their bacteriaemic phase.

Efavirenz-based simplification after successful early lopinavir-boosted-ritonavir-based therapy in HIV-infected children in Burkina Faso and Côte d'Ivoire: the MONOD ANRS 12206 non-inferiority randomised trial.

BACKGROUND: The 2016 World Health Organization guidelines recommend all children <3 years start antiretroviral therapy (ART) on protease inhibitor-based regimens. But lopinavir/ritonavir (LPV/r) syrup has many challenges in low-income countries, including limited availability, requires refrigeration, interactions with anti-tuberculous drugs, twice-daily dosing, poor palatability in young children, and higher cost than non-nucleoside reverse transcriptase inhibitor (NNRTI) drugs. Successfully initiating LPV/r-based ART in HIV-infected children aged <2 years raises operational challenges that could be simplified by switching to a protease inhibitor-sparing therapy based on efavirenz (EFV), although, to date, EFV is not recommended in children <3 years. METHODS: The MONOD ANRS 12026 study is a phase 3 non-inferiority open-label randomised clinical trial conducted in Abidjan, Côte d'Ivoire, and Ouagadougou, Burkina Faso (ClinicalTrial.gov registry: NCT01127204). HIV-1-infected children who were tuberculosis-free and treated before the age of 2 years with 12-15 months of suppressive twice-daily LPV/r-based ART (HIV-1 RNA viral load (VL) <500 copies/mL, confirmed) were randomised to two arms: once-daily combination of abacavir (ABC) + lamivudine (3TC) + EFV (referred to as EFV) versus continuation of the twice-daily combination zidovudine (ZDV) or ABC + 3TC + LPV/r (referred to as LPV). The primary endpoint was the difference in the proportion of children with virological suppression by 12 months post-randomisation between arms (14% non-inferiority bound, Chi-squared test). RESULTS: Between May 2011 and January 2013, 156 children (median age 13.7 months) were initiated on ART. After 12-15 months on ART, 106 (68%) were randomised to one of the two treatment arms (54 LPV, 52 EFV); 97 (91%) were aged <3 years. At 12 months post-randomisation, 46 children (85.2%) from LPV versus 43 (82.7%) from EFV showed virological suppression (defined as a VL <500 copies/mL; difference, 2.5%; 95% confidence interval (CI), -11.5 to 16.5), whereas seven (13%) in LPV and seven (13.5%) in EFV were classed as having virological failure (secondary outcome, defined as a VL ≥1000 copies/mL; difference, 0.5%; 95% CI, -13.4 to 12.4). No significant differences in adverse events were observed, with two adverse events in LPV (3.7%) versus four (7.7%) in EFV (p = 0.43). On genotyping, 13 out of 14 children with virological failure (six out of seven EFV, seven out of seven LPV) had a drug-resistance mutation: nine (five out of six EFV, four out of seven LPV) had one or more major NNRTI-resistance mutations whereas none had an LPV/r-resistance mutation. CONCLUSIONS: At the VL threshold of 500 copies/mL, we could not conclusively demonstrate the non-inferiority of EFV on viral suppression compared to LPV because of low statistical power. However, non-inferiority was confirmed for a VL threshold of <1000 copies/mL. Resistance analyses highlighted a high frequency of NNRTI-resistance mutations. A switch to an EFV-based regimen as a simplification strategy around the age of 3 years needs to be closely monitored. TRIAL REGISTRATION: ClinicalTrial.gov registry n° NCT01127204 , 19 May 2010.

Accuracy of Automated Flow Cytometry-Based Leukocyte Counts To Rule Out Urinary Tract Infection in Febrile Children: a Prospective Cross-Sectional Study.

Automated flow cytometry of urine remains an incompletely validated method to rule out urinary tract infection (UTI) in children. This cross-sectional analytical study was performed to compare the predictive values of flow cytometry and a dipstick test as initial diagnostic tests for UTI in febrile children and prospectively included 1,106 children (1,247 episodes). Urine culture was used as the gold standard test for diagnosing UTI. The performance of screening tests to diagnose UTI were established using receiver operating characteristic (ROC) analysis. Among these 1,247 febrile episodes, 221 UTIs were diagnosed (17.7% [95% confidence interval {CI}, 15.6 to 19.8%]). The area under the ROC curve for flow cytometry white blood cell (WBC) counts (0.99 [95% CI, 0.98 to 0.99]) was significantly superior to that for red blood cell (0.74 [95% CI, 0.70 to 0.78]) and bacterial counts (0.89 [95% CI, 0.87 to 0.92]) (P < 0.001). Urinary WBC counts also had a significantly higher area under the ROC curve than that of the leukocyte esterase (LE) dipstick (0.92 [95% CI, 0.90 to 0.94]), nitrite dipstick (0.83 [95% CI, 0.80 to 0.87]), or the combination of positive LE and/or nitrite dipstick (0.91 [95% CI, 0.89 to 0.93]) test (P < 0.001). The presence of ≥35 WBC/µl of urine was the best cutoff point, yielding both a high sensitivity (99.5% [95% CI, 99 to 100%]) and an acceptable specificity (80.6% [95% CI, 78 to 83%]). Using this cutoff point would have reduced the number of samples sent to the laboratory for culture by 67%. In conclusion, the determination of urinary WBC counts by flow cytometry provides optimal performance as an initial diagnostic test for UTI in febrile children.

FGFR1 mutations cause Hartsfield syndrome, the unique association of holoprosencephaly and ectrodactyly.

BACKGROUND: Harstfield syndrome is the rare and unique association of holoprosencephaly (HPE) and ectrodactyly, with or without cleft lip and palate, and variable additional features. All the reported cases occurred sporadically. Although several causal genes of HPE and ectrodactyly have been identified, the genetic cause of Hartsfield syndrome remains unknown. We hypothesised that a single key developmental gene may underlie the co-occurrence of HPE and ectrodactyly. METHODS: We used whole exome sequencing in four isolated cases including one case-parents trio, and direct Sanger sequencing of three additional cases, to investigate the causative variants in Hartsfield syndrome. RESULTS: We identified a novel FGFR1 mutation in six out of seven patients. Affected residues are highly conserved and are located in the extracellular binding domain of the receptor (two homozygous mutations) or the intracellular tyrosine kinase domain (four heterozygous de novo variants). Strikingly, among the six novel mutations, three are located in close proximity to the ATP's phosphates or the coordinating magnesium, with one position required for kinase activity, and three are adjacent to known mutations involved in Kallmann syndrome plus other developmental anomalies. CONCLUSIONS: Dominant or recessive FGFR1 mutations are responsible for Hartsfield syndrome, consistent with the known roles of FGFR1 in vertebrate ontogeny and conditional Fgfr1-deficient mice. Our study shows that, in humans, lack of accurate FGFR1 activation can disrupt both brain and hand/foot midline development, and that FGFR1 loss-of-function mutations are responsible for a wider spectrum of clinical anomalies than previously thought, ranging in severity from seemingly isolated hypogonadotropic hypogonadism, through Kallmann syndrome with or without additional features, to Hartsfield syndrome at its most severe end.

Public health impact and return on investment of Belgium's pediatric immunization program.

Objective: We evaluated the public health impact and return on investment of Belgium's pediatric immunization program (PIP) from both healthcare-sector and societal perspectives. Methods: We developed a decision analytic model for 6 vaccines routinely administered in Belgium for children aged 0-10 years: DTaP-IPV-HepB-Hib, DTaP-IPV, MMR, PCV, rotavirus, and meningococcal type C. We used separate decision trees to model each of the 11 vaccine-preventable pathogens: diphtheria, tetanus, pertussis, poliomyelitis, Haemophilus influenzae type b, measles, mumps, rubella, Streptococcus pneumoniae, rotavirus, and meningococcal type C; hepatitis B was excluded because of surveillance limitations. The 2018 birth cohort was followed over its lifetime. The model projected and compared health outcomes and costs with and without immunization (based on vaccine-era and pre-vaccine era disease incidence estimates, respectively), assuming that observed reductions in disease incidence were fully attributable to vaccination. For the societal perspective, the model included productivity loss costs associated with immunization and disease in addition to direct medical costs. The model estimated discounted cases averted, disease-related deaths averted, life-years gained, quality-adjusted life-years gained, costs (2020 euros), and an overall benefit-cost ratio. Scenario analyses considered alternate assumptions for key model inputs. Results: Across all 11 pathogens, we estimated that the PIP prevented 226,000 cases of infections and 200 deaths, as well as the loss of 7,000 life-years and 8,000 quality-adjusted life-years over the lifetime of a birth cohort of 118,000 children. The PIP was associated with discounted vaccination costs of €91 million from the healthcare-sector perspective and €122 million from the societal perspective. However, vaccination costs were more than fully offset by disease-related costs averted, with the latter amounting to a discounted €126 million and €390 million from the healthcare-sector and societal perspectives, respectively. As a result, pediatric immunization was associated with overall discounted savings of €35 million and €268 million from the healthcare-sector and societal perspectives, respectively; every €1 invested in childhood immunization resulted in approximately €1.4 in disease-related cost savings to the health system and €3.2 in cost savings from a societal perspective for Belgium's PIP. Estimates of the value of the PIP were most sensitive to changes in input assumptions for disease incidence, productivity losses due to disease-related mortality, and direct medical disease costs. Conclusion: Belgium's PIP, which previously had not been systematically assessed, provides large-scale prevention of disease-related morbidity and premature mortality, and is associated with net savings to health system and society. Continued investment in the PIP is warranted to sustain its positive public health and financial impact.

Enteroviral infection of a cardiac prosthetic device.

BACKGROUND: Identification of the causative pathogen may be challenging in culture negative infective endocarditis (IE). METHODS: A 4 month-old 21-trisomic boy with congenital atrioventricular septal defect presented 3 episodes of dehiscence of his prosthetic patch, attributed to IE. He presented heart failure, but neither fever, nor inflammatory syndrome. RESULTS: Surgical and histopathological findings confirmed the diagnosis of IE, but blood cultures remained sterile. Extensive work up failed to demonstrate bacterial or fungal etiology. Coxsackie B2 virus was cultured from the excised patch, nasopharyngeal secretions and stools. CONCLUSIONS: Viral IE has only been described in animal models. This case is the first reported probable human viral IE. We suggest that a viral etiology should be considered in case of culture negative IE.

Febrile urinary tract infections in 0- to 3-month-old infants: a prospective follow-up study.

OBJECTIVE: To track the clinical evolution of febrile urinary tract infection (UTI) diagnosed in 0- to 3-month-old infants and characterize uropathogen frequencies, antimicrobial resistance rates, renal abnormalities, and differences in the sexes in this age group. STUDY DESIGN: We observed prospectively 46 infants identified in a cohort of 209 children with first UTI diagnosed between July 2006 and July 2008 at the age of 0 to 3 months. Renal ultrasound scanning and voiding cystourethrography examinations were performed in all infants. RESULTS: Infants < 3 months old represented 21% of all children with first UTI. Of these children, 26% were female and 74% were male. Escherichia coli was isolated in 88% of cases and had a high rate of resistance to ampicillin (71%) and to trimethoprim/sulfamethoxazole (47%); 21% of children had vesicoureteral reflux, which was of low-grade in 67% of cases, with spontaneous resolution before 2 years in all cases. In infants with normal ultrasound scanning results, a low-grade vesicoureteral reflux was subsequently found in 10% of cases. CONCLUSION: Infants aged 0 to 3 months represent 21% of children treated for febrile UTI. Boys represent 74% of these cases. E coli is responsible for 88% of UTIs, with a high rate of resistance to antibiotics. When ultrasound scanning examination results are normal, the risk of missing a significant renal abnormality is expected to be extremely low.

Pandemic A/H1N1v influenza 2009 in hospitalized children: a multicenter Belgian survey.

BACKGROUND: During the 2009 influenza A/H1N1v pandemic, children were identified as a specific "at risk" group. We conducted a multicentric study to describe pattern of influenza A/H1N1v infection among hospitalized children in Brussels, Belgium. METHODS: From July 1, 2009, to January 31, 2010, we collected epidemiological and clinical data of all proven (positive H1N1v PCR) and probable (positive influenza A antigen or culture) pediatric cases of influenza A/H1N1v infections, hospitalized in four tertiary centers. RESULTS: During the epidemic period, an excess of 18% of pediatric outpatients and emergency department visits was registered. 215 children were hospitalized with proven/probable influenza A/H1N1v infection. Median age was 31 months. 47% had ≥ 1 comorbid conditions. Febrile respiratory illness was the most common presentation. 36% presented with initial gastrointestinal symptoms and 10% with neurological manifestations. 34% had pneumonia. Only 24% of the patients received oseltamivir but 57% received antibiotics. 10% of children were admitted to PICU, seven of whom with ARDS. Case fatality-rate was 5/215 (2%), concerning only children suffering from chronic neurological disorders. Children over 2 years of age showed a higher propensity to be admitted to PICU (16% vs 1%, p = 0.002) and a higher mortality rate (4% vs 0%, p = 0.06). Infants less than 3 months old showed a milder course of infection, with few respiratory and neurological complications. CONCLUSION: Although influenza A/H1N1v infections were generally self-limited, pediatric burden of disease was significant. Compared to other countries experiencing different health care systems, our Belgian cohort was younger and received less frequently antiviral therapy; disease course and mortality were however similar.

Management of varicella in neonates and infants.

In countries where vaccination is not implemented, varicella is a common ubiquitous disease offering a broad range of clinical presentations. Whereas mother-to-child perinatal transmission of varicella zoster virus (VZV) can lead to disseminated life-threatening diseases in unimmunised newborns, postnatal acquisition will be generally a source of milder infections. The pattern and severity of the disease are known to be partly determined by the timing of VZV acquisition during pregnancy with the highest risk period located around delivery. Management of youngest children after contact with a varicella case remains difficult for clinicians not only because of unawareness of varicella natural history and risks factors for serious complications, but also because of the lack of consensus from experts available in the literature. This state of uncertainty often leads to overconsumption of healthcare resources with systematic hospitalisation and unjustified antiviral intravenous therapies. After a concise literature review, this article proposes pragmatic recommendations considering newborns in various scenarios following a contact with VZV, taking into account the timing and mode of virus transmission, the maternal immunological status, the baby's gestational age and the presence of other underlying conditions.

Campylobacter Concisus and Acute Gastroenteritis in Children: Lack of Association.

The role of Campylobacter concisus as a cause of acute gastroenteritis remains to be demonstrated. This prospective study includes 184 cases and 176 controls. It shows no evidence that C. concisus plays a role in acute gastroenteritis. Considering the very low prevalence in cases and controls, if there is an etiologic link, it would be moderate and difficult to demonstrate.

Symptomatic Management of Febrile Illnesses in Children: A Systematic Review and Meta-Analysis of Parents' Knowledge and Behaviors and Their Evolution Over Time.

Recommendations to guide parents' symptomatic management of febrile illnesses in children have been published in many countries. The lack of systematic appraisal of parents' knowledge and behaviors and their evolution over time precludes an analysis of their impact and identification of targets for future educational messages. We systematically searched for studies published between 1980 and 2016 that reported a quantitative evaluation of knowledge and behaviors of >50 parents for managing fever in children. We used MEDLINE and tracked related articles, citations and co-authors personal files. Study selection and data extraction were independently performed by two reviewers. For each item of knowledge and behaviors, we calculated mean frequencies during the first and last quinquennials of the studied period and assessed temporal trends with inverse-variance weighted linear regression of frequencies over years. We observed substantial methodological heterogeneity among the 62 included articles (64 primary studies, 36,791 participants, 30 countries) that met inclusion criteria. Statistically significant changes over time were found in the use of rectal (98 to 4%) and axillary temperature measurement (1-19%), encouraging fluid intake (19-62%), and use of acetylsalicylic acid (60 to 1%). No statistically significant change was observed for the accurate definition of fever (38-55%), or the use of acetaminophen (91-92%) or ibuprofen (20-43%). Parents' knowledge and behaviors have changed over time but continue to show poor concordance with recommendations. Our study identified future targets for educational messages, including basic ones such as the definition of fever.

[Feasibility of HIV prophylaxis with nevirapine in a northeastern rural area of the Democratic Republic of the Congo]. / Faisabilité de la prophylaxie du VIH par la névirapine en milieu rural au nord-est de la République démocratique du Congo.

Several developing countries, including the Democratic Republic of the Congo have adopted HIV NET 012, i.e. a single dose of nevirapine to mother (200 mg at labour onset) and baby (2 mg/kg within 72 h of birth), because of the accessible cost of nevirapine and its supposedly easy use in MTCTP programs [2]. The protocol can nonetheless prove complex to apply in rural regions of Africa and must be evaluated. This article aims to present the difficulties encountered in implementation of this protocol at the Oicha General Reference Hospital, in the northeastern region of the Democratic Republic of the Congo. The study took place time from December 2002 through December 2004. During the study period, 94 women were identified as HIV positive at the prenatal clinic of Oicha Hospital. Of the 94 HIV positive women: 59 (62.8%) received antiretroviral prophylaxis and 35 (37.2%) did not receive nevirapine despite their identification at the prenatal clinic. Among these 35 women, 26 (27.7%) of the expected women arrived fully dilated and thus went directly to the delivery room. Nine (9.5%) of the expected women who delivered at the Oicha maternity were not administered the product by the midwives. For administration of nevirapine to the mother: 33 pregnant women out of 59 (55.9%) received nevirapine within the time recommended - within two hours of the onset of contractions. Twenty four of 59 women (40.7%) did not receive the nevirapine within the time recommended, but within an average delay of 11.00 hours. For 2 of 59 women (3.4%), the hour of administration of the nevirapine was not specified. For administration of nevirapine to the child: 48 of 101 children (47.5%) received nevirapine within the recommended period, i.e. in the 24-72 hours after birth. 52 of 101 children (51.5%) received the nevirapine in an average of 2.9 hours of birth. This is the proportion of the children whose mothers arrived at the maternity ward ready for delivery. Only 1 child (1%) received the nevirapine later than the recommended period, 13.9 hours later. Applying as simple a protocol as the HIV prophylaxis program with nevirapine in African rural areas encounters difficulties.

Varicella paediatric hospitalisations in Belgium: a 1-year national survey.

BACKGROUND: Varicella universal vaccination (UV) has been implemented in many countries for several years. Nevertheless, varicella UV remains debated in Europe and few data are available on the real burden of infection. We assessed the burden of varicella in Belgium through analysis of hospitalised cases during a 1-year period. METHODS: Data on children admitted to hospital with varicella were collected through a national network from November 2011 to October 2012. Inclusion criteria were either acute varicella or related complications up to 3 weeks after the rash. RESULTS: Participation of 101 hospitals was obtained, covering 97.7% of the total paediatric beds in Belgium. 552 children were included with a median age of 2.1 years. Incidence of paediatric varicella hospitalisations reached 29.5/10(5) person-years, with the highest impact among those 0-4 years old (global incidence and odds of hospitalisation: 79/10(5) person-years and 1.6/100 varicella cases, respectively). Only 14% (79/552) of the cohort had an underlying chronic condition. 65% (357/552) of children had ≥1 complication justifying their admission, 49% were bacterial superinfections and 10% neurological disorders. Only a quarter of children (141/552) received acyclovir. Incidence of complicated hospitalised cases was 19/10(5) person-years. Paediatric intensive care unit admission and surgery were required in 4% and 3% of hospitalised cases, respectively. Mortality among Belgian paediatric population was 0.5/10(6) and fatality ratio 0.2% among our cohort. CONCLUSIONS: Varicella demonstrated a substantial burden of disease in Belgian children, especially among the youngest. Our thorough nationwide study, run in a country without varicella UV, offers data to support varicella UV in Belgium.

Effect of pentavalent rotavirus vaccine introduction on hospital admissions for diarrhoea and rotavirus in children in Rwanda: a time-series analysis.

BACKGROUND: In May, 2012, Rwanda became the first low-income African country to introduce pentavalent rotavirus vaccine into its routine national immunisation programme. Although the potential health benefits of rotavirus vaccination are huge in low-income African countries that account for more than half the global deaths from rotavirus, concerns remain about the performance of oral rotavirus vaccines in these challenging settings. METHODS: We conducted a time-series analysis to examine trends in admissions to hospital for non-bloody diarrhoea in children younger than 5 years in Rwanda between Jan 1, 2009, and Dec 31, 2014, using monthly discharge data from the Health Management Information System. Additionally, we reviewed the registries in the paediatric wards at six hospitals from 2009 to 2014 and abstracted the number of total admissions and admissions for diarrhoea in children younger than 5 years by admission month and age group. We studied trends in admissions specific to rotavirus at one hospital that had undertaken active rotavirus surveillance from 2011 to 2014. We assessed changes in rotavirus epidemiology by use of data from eight active surveillance hospitals. FINDINGS: Compared with the 2009-11 prevaccine baseline, hospital admissions for non-bloody diarrhoea captured by the Health Management Information System fell by 17-29% from a pre-vaccine median of 4051 to 2881 in 2013 and 3371 in 2014, admissions for acute gastroenteritis captured in paediatric ward registries decreased by 48-49%, and admissions specific to rotavirus captured by active surveillance fell by 61-70%. The greatest effect was recorded in children age-eligible to be vaccinated, but we noted a decrease in the proportion of children with diarrhoea testing positive for rotavirus in almost every age group. INTERPRETATION: The number of admissions to hospital for diarrhoea and rotavirus in Rwanda fell substantially after rotavirus vaccine implementation, including among older children age-ineligible for vaccination, suggesting indirect protection through reduced transmission of rotavirus. These data highlight the benefits of routine vaccination against rotavirus in low-income settings. FUNDING: Gavi, the Vaccine Alliance and the Government of Rwanda.

The Economic Burden Attributable to a Child's Inpatient Admission for Diarrheal Disease in Rwanda.

BACKGROUND: Diarrhea is one of the leading causes of childhood morbidity and mortality. Hospitalization for diarrhea can pose a significant burden to health systems and households. The objective of this study was to estimate the economic burden attributable to hospitalization for diarrhea among children less than five years old in Rwanda. These data can be used by decision-makers to assess the impact of interventions that reduce diarrhea morbidity, including rotavirus vaccine introduction. METHODS: This was a prospective costing study where medical records and hospital bills for children admitted with diarrhea at three hospitals were collected to estimate resource use and costs. Hospital length of stay was calculated from medical records. Costs incurred during the hospitalization were abstracted from the hospital bills. Interviews with the child's caregivers provided data to estimate household costs which included transport costs and lost income. The portion of medical costs borne by insurance and household were reported separately. Annual economic burden before and after rotavirus vaccine introduction was estimated by multiplying the reported number of diarrhea hospitalizations in public health centers and district hospitals by the estimated economic burden per hospitalization. All costs are presented in 2014 US$. RESULTS: Costs for 203 children were analyzed. Approximately 93% of the children had health insurance coverage. Average hospital length of stay was 5.3 ± 3.9 days. Average medical costs for each child for the illness resulting in a hospitalization were $44.22 ± $23.74 and the total economic burden was $101, of which 65% was borne by the household. For households in the lowest income quintile, the household costs were 110% of their monthly income. The annual economic burden to Rwanda attributable to diarrhea hospitalizations ranged from $1.3 million to $1.7 million before rotavirus vaccine introduction. CONCLUSION: Households often bear the largest share of the economic burden attributable to diarrhea hospitalization and the burden can be substantial, especially for households in the lowest income quintile.

Missed opportunities of inclusion in a cohort of HIV-infected children to initiate antiretroviral treatment before the age of two in West Africa, 2011 to 2013.

INTRODUCTION: The World Health Organization (WHO) 2010 guidelines recommended to treat all HIV-infected children less than two years of age. We described the inclusion process and its correlates of HIV-infected children initiated on early antiretroviral therapy (EART) at less than two years of age in Abidjan, Côte d'Ivoire, and Ouagadougou, Burkina Faso. METHODS: All children with HIV-1 infection confirmed with a DNA PCR test of a blood sample, aged less than two years, living at a distance less than two hours from the centres and whose parents (or mother if she was the only legal guardian or the legal caregiver if parents were not alive) agreed to participate in the MONOD ANRS 12206 project were included in a cohort to receive EART based on lopinavir/r. We used logistic regression to identify correlates of inclusion. RESULTS: Among the 217 children screened and referred to the MONOD centres, 161 (74%) were included and initiated on EART. The main reasons of non-inclusion were fear of father's refusal (48%), mortality (24%), false-positive HIV infection test (16%) and other ineligibility reasons (12%). Having previously disclosed the child's and mother's HIV status to the father (adjusted odds ratio (aOR): 3.20; 95% confidence interval (95% CI): 1.55 to 6.69) and being older than 12 months (aOR: 2.05; 95% CI: 1.02 to 4.12) were correlates of EART initiation. At EART initiation, the median age was 13.5 months, 70% had reached WHO Stage 3/4 and 57% had a severe immune deficiency. CONCLUSIONS: Fear of stigmatization by the father and early competing mortality were the major reasons for missed opportunities of EART initiation. There is an urgent need to involve fathers in the care of their HIV-exposed children and to promote early infant diagnosis to improve their future access to EART and survival.

A cost comparison of introducing and delivering pneumococcal, rotavirus and human papillomavirus vaccines in Rwanda.

BACKGROUND: Detailed cost evaluations of delivery of new vaccines such as pneumococcal conjugate, human papillomavirus (HPV), and rotavirus vaccines in low and middle-income countries are scarce. This paper differs from others by comparing the costs of introducing multiple vaccines in a single country and then assessing the financial and economic impact at the time and implications for the future. The objective of the analysis was to understand the introduction and delivery cost per dose or per child of the three new vaccines in Rwanda to inform domestic and external financial resource mobilization. METHODS: Start-up, recurrent, and capital costs from a government perspective were collected in 2012. Since pneumococcal conjugate and HPV vaccines had already been introduced, cost data for those vaccines were collected retrospectively while prospective (projected) costing was done for rotavirus vaccine. RESULTS: The financial unit cost per fully immunized child (or girl for HPV vaccine) of delivering 3 doses of each vaccine (without costs related to vaccine procurement) was $0.37 for rotavirus (RotaTeq(®)) vaccine, $0.54 for pneumococcal (Prevnar(®)) vaccine in pre-filled syringes, and $10.23 for HPV (Gardasil (®)) vaccine. The financial delivery costs of Prevnar(®) and RotaTeq(®) were similar since both were delivered using existing health system infrastructure to deliver infant vaccines at health centers. The total financial cost of delivering Gardasil(®) was higher than those of the two infant vaccines due to greater resource requirements associated with creating a new vaccine delivery system in for a new target population of 12-year-old girls who have not previously been served by the existing routine infant immunization program. CONCLUSION: The analysis indicates that service delivery strategies have an important influence on costs of introducing new vaccines and costs per girl reached with HPV vaccine are higher than the other two vaccines because of its delivery strategy. Documented information on financial commitments for new vaccines, particularly from government sources, is a useful input into country policy dialogue on sustainable financing and co-financing of new vaccines, as well as for policy decisions by donors such as Gavi, the Vaccine Alliance.

Spondylometaphyseal dysplasia, east-African type: a new form of early, severe SMD with rounded vertebrae.

Spondylometaphyseal dysplasias (SMD) are a heterogeneous group of bone dysplasias characterized by vertebral and metaphyseal changes of various severities. We report two unrelated patients of east African origin with a skeletal disorder consisting of 1) severe metaphyseal dysplasia of early onset, sparing hand bones, with bracket-shaped metaphyses; 2) dysplastic pelvis with irregular iliac rim; and 3) oval-shaped vertebral bodies. Contrasting with most types of SMD, the spinal dysplasia is limited to mild changes in the vertebral body shape that tend to soften with time, whereas the iliac rims have a striking lacy appearance. Except for the most common types (Kozlowski type and Schmidt type), most of the literature on SMD deals with single case reports, without longitudinal data, for which molecular definition is still lacking and classification remains unclear. These two patients could belongs to the A4 group in the classification of Maroteaux and Spranger [1991: Pediatr Radiol 2l:293-297], and illustrate the difficulties of a clinical classification of SMD.

Chest pain in pediatric patients presenting to an emergency department or to a cardiac clinic.

UNLABELLED: The aim of this study was to assess the epidemiology of chest pain among unselected Belgian children referred to an emergency department or to a cardiology clinic. MATERIAL AND METHODS: We analyzed the etiology to chest pain and the diagnostic workup of 168 consecutive pediatric patients, seen in our emergency department with the primary diagnosis of chest pain over a 5-year period (group A). Simultaneously a sample of 69 consecutive pediatric patients referred to the cardiology clinic by primary care physicians with the same chief complaint was prospectively included in the study (group B). RESULTS: Chest wall pain was the most common diagnosis in the group A (64%). Other causes included pulmonary (13%), psychological (9%), cardiac (5%), traumatic (5%), and gastrointestinal problems (4%). The organic causes were easily identified or suspected by history and physical examination. Chest radiography, electrocardiography, and blood analysis were performed in most patients with suspected nonorganic chest pain but in no case were organic diseases diagnosed by those ancillary studies. In group B, chest wall pain was also the most common diagnosis (89%). Supraventricular tachyarrhythmia and exercise-induced asthma were demonstrated in 5 (7%) and 3 patients (4%), respectively. The most important tools in assessing a child with acute chest pain in an emergency department are thorough history and physical examination. Assessment of recurrent chest pain is more difficult; arrhythmia, and allergic and exercise-induced asthma may be underestimated when investigations are not performed.