Haemophilus influenzae type b (Hib) seroprevalence in France: impact of vaccination schedules.

BACKGROUND: Haemophilus influenzae serotype b (Hib) conjugate vaccine was introduced in France in 1992 as a 3 + 1 scheme at 2, 3, and 4 months (primary vaccination) with a booster at the age of 16-18 months. The vaccination was simplified in 2013 to a 2 + 1 scheme at 2 and 4 months (primary immunization) and a booster at the age of 11 months. The coverage was 95.4% in France at 24 months in 2017. During the period 2017-2019 the number of Hib invasive infections increased with several cases of vaccine failure. METHODS: The numbers and proportions of Hib invasive isolates during the period 2017-2019 were compared and vaccine failure cases were explored. A seroprevalence study was performed by measuring anti-polyribosyl-ribitol phosphate (PRP) IgG concentrations by ELISA among children < 5 years of age at the time of sampling covering the periods of the 3 + 1 or 2 + 1 schemes of Hib vaccination. A collection of residual 232 sera was tested (group 3 + 1 n = 130) and (group 2 + 1, n = 102) was used. RESULTS: Anti-PRP IgG concentrations were significantly higher in toddlers of 2 years (median 2.9 µg/ml) in the 3 + 1 group while these concentrations showed a median of 0.58 µg/ml among children in 2 + 1 group. The proportion of children of 2 years of age who achieved 1 µg/ml threshold (56%) was higher in the 3 + 1 group than that observed in the 2 + 1 group (25%). All the detected cases of vaccine failure received the 2 + 1 scheme and anti-PRP IgG levels were less than 1 µg/ml at the admission. However, these levels increased significantly 1 month after the admission suggesting a secondary immune response to the Hib infection. CONCLUSIONS: The simplification of the vaccination to a 2 + 1 scheme seems to reduce the level of anti PRP IgG. Hib antibodies wane rapidly after the 11 months booster and may not be enough to ensure long term protection. Surveillance of cases and monitoring of titres need to be continued to inform future vaccination policy.

Community-acquired bacterial meningitis.

Progress has been made in the prevention and treatment of community-acquired bacterial meningitis during the past three decades but the burden of the disease remains high globally. Conjugate vaccines against the three most common causative pathogens (Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae) have reduced the incidence of disease, but with the replacement by non-vaccine pneumococcal serotypes and the emergence of bacterial strains with reduced susceptibility to antimicrobial treatment, meningitis continues to pose a major health challenge worldwide. In patients presenting with bacterial meningitis, typical clinical characteristics (such as the classic triad of neck stiffness, fever, and an altered mental status) might be absent and cerebrospinal fluid examination for biochemistry, microscopy, culture, and PCR to identify bacterial DNA are essential for the diagnosis. Multiplex PCR point-of-care panels in cerebrospinal fluid show promise in accelerating the diagnosis, but diagnostic accuracy studies to justify routine implementation are scarce and randomised, controlled studies are absent. Early administration of antimicrobial treatment (within 1 hour of presentation) improves outcomes and needs to be adjusted according to local emergence of drug resistance. Adjunctive dexamethasone treatment has proven efficacy beyond the neonatal age but only in patients from high-income countries. Further progress can be expected from implementing preventive measures, especially the development of new vaccines, implementation of hospital protocols aimed at early treatment, and new treatments targeting checkpoints of the inflammatory cascade.

Association of Bacteremia with Vaccination Status in Children Aged 2 to 36 Months.

OBJECTIVE: To determine the association between bacteremia and vaccination status in children aged 2-36 months presenting to a pediatric emergency department. STUDY DESIGN: Retrospective cohort study of children aged 2-36 months with blood cultures obtained in the pediatric emergency department between January 2013 and December 2017. The exposure of interest was immunization status, defined as number of Haemophilus influenzae type B (Hib) and Streptococcus pneumoniae vaccinations, and the main outcome positive blood culture. Subjects with high-risk medical conditions were excluded. RESULTS: Of 5534 encounters, 4742 met inclusion criteria. The incidence of bacteremia was 1.5%. The incidence of contaminated blood culture was 5.0%. The relative risk of bacteremia was 0.79 (95% CI 0.39-1.59) for unvaccinated and 1.20 (95% CI 0.52-2.75) for undervaccinated children relative to those who had received age-appropriate vaccines. Five children were found to have S pneumoniae bacteremia and 1 child had Hib bacteremia; all of these subjects had at least 3 sets of vaccinations. No vaccine preventable pathogens were isolated from blood cultures of unvaccinated children. We found no S pneumoniae or Hib in children 2-6 months of age who were not fully vaccinated due to age (95% CI 0-0.13%) and the contamination rate in this group was high compared with children 7-36 months (6.6% vs 3.7%). CONCLUSIONS: Bacteremia in young children is an uncommon event. Contaminated blood cultures were more common than pathogens. Bacteremia from S pneumoniae or Hib is uncommon and, in this cohort, was independent of vaccine status.

Epidemiology and antibiotic resistance profile of bacterial meningitis in Morocco from 2015 to 2018.

Over a 4-year study period from 2015 to 2018, altogether 183 isolates of bacterial meningitis were collected from 12 hospitals covering the entire Moroccan territory. Neisseria meningitidis represented 58.5%, Streptococcus pneumoniae 35.5%, and Haemophilus influenzae type b 6%. H. influenzae type b mainly affected 5-year-olds and unvaccinated adults. N. meningitidis serogroup B represented 90.7% followed by serogroup W135 with 6.5%. Decreased susceptibility to penicillin G (DSPG) for all isolates accounted for 15.7%, with 11.6% being resistant to penicillin G (PG) and 4.1% decreased susceptibility. Cumulative results of all strains showed 2.7% decreased susceptibility to amoxicillin and 3.3% resistant, 2.2% of isolates were resistant to third-generation cephalosporin and 2.2% were decreased susceptible, 5.5% were resistant to chloramphenicol and 2.7% were resistant to rifampin. The frequency of DSPG observed in our study is more common in S. pneumoniae than in N. meningitidis (P < 0.05). These isolates have been found to be highly susceptible to antibiotics used for treatment and prophylaxis chemotherapy and the observed resistance remains rare. The impact of introduction of conjugate vaccines against H. influenzae type b and S. pneumoniae (PCVs) is an advantage in reducing meningitis cases due to these two species.

Invasive Haemophilus influenzae Type b Disease in the Post Hexavalent Era: Ten Years of Molecular Surveillance in Tuscany.

BACKGROUND: The epidemiologic characteristics of invasive Haemophilus influenzae type b disease (HIBD) have markedly changed since the introduction of the Haemophilus influenzae type b (Hib) conjugate vaccine worldwide. The immunization schedule against Haemophilus influenzae type b differs in Europe. METHODS: This is a retrospective observational study which evaluates all the data included in the molecular surveillance register for invasive infectious diseases at the Laboratory of Molecular Diagnosis at Meyer Children's University Hospital from December 2008 to December 2018 with a diagnosis of invasive HIBD in children <5 years of age. RESULTS: We identified 4 cases of HIBD: all the cases presented signs or symptoms of invasive infection and the H. influenzae type b was identified in cerebrospinal fluid, or blood or bronchoalveolar lavage by molecular test. The crude incidence for Hib invasive disease in Tuscany is 0.26/100,000 p-y in children younger than 5 years, significantly different from the incidence rate before the introduction of the Hib vaccination. Vaccination effectiveness can be estimated at 97.9% and the impact of hexavalent (2p+1) vaccine at 99.6%. CONCLUSIONS: This work confirms the high impact of the hexavalent vaccine 2p+1 schedule for HIBD in children <5 years, emphasizing the role of molecular test for HIBD diagnosis and surveillance.

Analysis of meningitis outbreak data, Jaman North District, Brong Ahafo Region, Ghana.

BACKGROUND: Descriptive analysis of meningitis outbreak in Jaman North districts of Brong Ahafo Region. DESIGN: Descriptive secondary data analysis. DATA SOURCE: records of meningitis cases were extracted from case-based forms and line list. MAIN OUTCOME MEASURE: The source and pattern of outbreak. RESULTS: A total of 367 suspected cases with 44 confirmed were recorded from Jaman North during the period of January to March 2016. The mean age of those affected was 58 ± 13 years. The case fatality rate was 0.82% and the proportion of males to females was 1:1.3 (160/207). The age group most affected was 15-29 years (54.7%) and the least was 45-49 years (3.0%). Streptococcus pneumoniae formed 77.3% of confirmed cases whilst Neisseria meningitides was 20.5%. Cases with Neisseria meningitides came from a border town in La Cote d'Ivoire. CONCLUSION: A protracted propagated meningitis outbreak occurred; and the predominant bacteria strain among confirmed cases was Streptococcus pneumoniae. Cases were mainly females and the most vulnerable group were people aged 15-29 years. FUNDING: This work was funded by the authors. Author BKD was sponsored under CDC (Frontline FETP)-CDC CoAg 6NU2GGH001876.

Epidemiological study of bacterial meningitis in Tunisian children, beyond neonatal age, using molecular methods: 2014-2017.

BACKGROUND: Since the 1990s, the epidemiology of bacterial meningitis worldwide has changed thanks to vaccination. In Tunisia, the main causative pathogens were Streptococcus pneumoniae, Neisseria meningitidis and Haemophilus influenzae serotype b (Hib). Only Hib vaccination was available during our study period. OBJECTIVES: We performed a laboratory case report based-study of suspected bacterial meningitis in Northern Tunisia from January 2014 to June 2017. METHODS: CSF samples obtained from children beyond neonatal age with suspicion of meningitis were tested by two real time PCRs, targeting pneumococcus, meningococcus and Hib, and conventional methods. RESULTS: Using real-time PCR, 63 were positive including ten supplementary cases compared to conventional methods. A general decrease of bacterial meningitis cases was demonstrated comparing to previous data. Pneumococcus was predominant (69.84%) followed by meningococcus (28.57%) and Hib (1.59%). The main serotypes were 14, 19F, 6B and 23F for pneumococcus and serogroup B for meningococcus. Most cases occurred during cold season and children under one year were the most affected by bacterial meningitis. CONCLUSION: Our study suggests the predominance of pneumococcal cases. It may provide valuable data on meningitis epidemiology before the introduction of pneumococcal vaccine, which may be useful for future evaluation.

Causes of severe pneumonia requiring hospital admission in children without HIV infection from Africa and Asia: the PERCH multi-country case-control study.

BACKGROUND: Pneumonia is the leading cause of death among children younger than 5 years. In this study, we estimated causes of pneumonia in young African and Asian children, using novel analytical methods applied to clinical and microbiological findings. METHODS: We did a multi-site, international case-control study in nine study sites in seven countries: Bangladesh, The Gambia, Kenya, Mali, South Africa, Thailand, and Zambia. All sites enrolled in the study for 24 months. Cases were children aged 1-59 months admitted to hospital with severe pneumonia. Controls were age-group-matched children randomly selected from communities surrounding study sites. Nasopharyngeal and oropharyngeal (NP-OP), urine, blood, induced sputum, lung aspirate, pleural fluid, and gastric aspirates were tested with cultures, multiplex PCR, or both. Primary analyses were restricted to cases without HIV infection and with abnormal chest x-rays and to controls without HIV infection. We applied a Bayesian, partial latent class analysis to estimate probabilities of aetiological agents at the individual and population level, incorporating case and control data. FINDINGS: Between Aug 15, 2011, and Jan 30, 2014, we enrolled 4232 cases and 5119 community controls. The primary analysis group was comprised of 1769 (41·8% of 4232) cases without HIV infection and with positive chest x-rays and 5102 (99·7% of 5119) community controls without HIV infection. Wheezing was present in 555 (31·7%) of 1752 cases (range by site 10·6-97·3%). 30-day case-fatality ratio was 6·4% (114 of 1769 cases). Blood cultures were positive in 56 (3·2%) of 1749 cases, and Streptococcus pneumoniae was the most common bacteria isolated (19 [33·9%] of 56). Almost all cases (98·9%) and controls (98·0%) had at least one pathogen detected by PCR in the NP-OP specimen. The detection of respiratory syncytial virus (RSV), parainfluenza virus, human metapneumovirus, influenza virus, S pneumoniae, Haemophilus influenzae type b (Hib), H influenzae non-type b, and Pneumocystis jirovecii in NP-OP specimens was associated with case status. The aetiology analysis estimated that viruses accounted for 61·4% (95% credible interval [CrI] 57·3-65·6) of causes, whereas bacteria accounted for 27·3% (23·3-31·6) and Mycobacterium tuberculosis for 5·9% (3·9-8·3). Viruses were less common (54·5%, 95% CrI 47·4-61·5 vs 68·0%, 62·7-72·7) and bacteria more common (33·7%, 27·2-40·8 vs 22·8%, 18·3-27·6) in very severe pneumonia cases than in severe cases. RSV had the greatest aetiological fraction (31·1%, 95% CrI 28·4-34·2) of all pathogens. Human rhinovirus, human metapneumovirus A or B, human parainfluenza virus, S pneumoniae, M tuberculosis, and H influenzae each accounted for 5% or more of the aetiological distribution. We observed differences in aetiological fraction by age for Bordetella pertussis, parainfluenza types 1 and 3, parechovirus-enterovirus, P jirovecii, RSV, rhinovirus, Staphylococcus aureus, and S pneumoniae, and differences by severity for RSV, S aureus, S pneumoniae, and parainfluenza type 3. The leading ten pathogens of each site accounted for 79% or more of the site's aetiological fraction. INTERPRETATION: In our study, a small set of pathogens accounted for most cases of pneumonia requiring hospital admission. Preventing and treating a subset of pathogens could substantially affect childhood pneumonia outcomes. FUNDING: Bill & Melinda Gates Foundation.

Unnecessary prescribing of antibiotics to healthy/asymptomatic school-age carriers of potentially pathogenic bacteria.

OBJECTIVES: To re-draw attention to the unnecessary prescribing of antibiotics. METHODS: We monitored nasopharyngeal colonization by 3 potentially pathogenic bacteria, Streptococcus pyogenes, Streptococcus pneumoniae, and Haemophilus influenzae type b in 81 children between the ages of 6 and 7 years who attended the same primary school. The children's health status was also monitored, without using antimicrobial treatment for healthy/asymptomatic carriers. Nasopharyngeal swabs were collected on 6 occasions during autumn months, from mid-September to mid-December 2016. The children who fell ill during the study were treated at the Ear, Nose and Throat Clinic, Sisters of Mercy University Hospital Center, Zagreb, Croatia. RESULTS: Four hundred and sixty-three  nasopharyngeal swabs were collected. Each child had at least one positive swab result. Bacterial colonization with Streptococcus pyogenes had the highest colonization rate. During the study, 83% of the children were healthy/asymptomatic carriers with no clinical signs of disease,  while 17% became ill. The statistical results showed that the increase in all examined bacteria was statistically significant. CONCLUSIONS:   Our  study results showed that positive bacterial findings in nasopharyngeal swabs from clinically healthy carriers were not an indication for antibiotic therapy.

[Acute meningitis and encephalitis syndrome surveillance disease burden in four China prefectures].

Objectives: To explore acute meningitis and encephalitis syndrome (AMES) surveillance in 4 China prefectures, to understand the epidemiological features and disease burden of neisseria meningitides (Nm) meningitis, streptococcus pneumoniae (Sp) meningitis, haemophilus influenza type b (Hib) meningitis and Japanese encephalitis and provide evidence for related disease prevention and control. Methods: AMES surveillance were conducted in Jinan, Shandong Province and Yichang, Hubei Province in September 2006, and in 13 districts of Shijiazhuang, Hebei Province and Guigang City, Guangxi Zhuang Autonomous Region in April 2007. Six hospitals in each city were selected as monitoring pilot hospitals to carry out reports of suspected cases of acute meningitis and encephalitis, case investigation, blood specimens and cerebrospinal fluid specimen collection, anti-JEV IgM antibody enzyme-linked immunosorbent assay, Nm, Sp and Hib culture and polymerase chain reaction detection, etc. According to the age group, the incidence of bacterial meningitis and Japanese encephalitis in local residents <20 years old was estimated. Results: From 2006 to 2013, a total of 19 423 surveillance cases were reported in four cities, of which 11 071 (56.99%) were reported in the pilot hospitals. Of the 11 071 cases, 5 315 were tested for bacteriology and 9 180 were tested for anti-JEV IgM antibodies. Among the bacteriological tests, 176 cases were positive, including 75 cases of Nm positive, 91 cases of Sp positive and 10 cases of Hib positive. The incidence of three bacterial meningitis is estimated for people under 20 years old, with estimated incidence of Nm, Sp and Hib meningitis in children <5 years old was 0.46/100 000-0.71/100 000, 0.34/100 000-0.83/100 000 and 0.32/100 000-0.57/100 000 respectively; the estimated incidence of Nm and Sp meningitis in children aged 5-9 years was 0.59/100 000-1.14/100 000 and 0.50/100 000-1.66/100 000 respectively. In 732 cases of positive JE cases, the positive detection rates of <5 years old, 40-49 years old and ≥50 years old were 9.51% (95/999), 28.09% (66/235) and 33.85% (130/384), respectively. The estimated annual incidence rate of JE was 0.12/100 000-0.79/100 000.ratio of cases 1.19∶1. Most of cases (27.30%) were children and adolescents aged 5-14 years and those (26.84%) aged over 45 year. Conclusion: The study found that primary and secondary school students are the key population of Nm meningitis, suggesting that it is necessary to explore the enhanced immunization study of meningococcal vaccine in this population; Sp has the possibility of occurrence in all age groups; <5 years old children are the main population of Hib meningitis.

Clinical Characterization of Invasive Disease Caused by Haemophilus influenzae Serotype b in a High Vaccination Coverage Setting.

This national study characterized invasive Haemophilus influenzae serotype b infections. Vaccinated (n = 41) and nonvaccinated (n = 10) cases were similar regarding presentation as meningitis (68.8% vs 90.0%; P = .25), predisposing factors (29.3% vs 20.0%; P = .76), admission to intensive care unit or death (22.0% vs 10.0%; P = 1.00), or sequelae (21.6% vs 10.0%; P = .81). Haemophilus influenzae serotype b occurred in vaccinated, healthy children with comparable disease course.

Association between semi-quantitative microbial load and respiratory symptoms among Thai military recruits: a prospective cohort study.

BACKGROUND: Multiplex real-time polymerase chain reaction assays have improved diagnostic sensitivity for a wide range of pathogens. However, co-detection of multiple agents and bacterial colonization make it difficult to distinguish between asymptomatic infection or illness aetiology. We assessed whether semi-quantitative microbial load data can differentiate between symptomatic and asymptomatic states for common respiratory pathogens. METHODS: We obtained throat and nasal swab samples from military trainees at two Thai Army barracks. Specimens were collected at the start and end of 10-week training periods (non-acute samples), and from individuals who developed upper respiratory tract infection during training (acute samples). We analysed the samples using a commercial multiplex respiratory panel comprising 33 bacterial, viral and fungal targets. We used random effects tobit models to compare cycle threshold (Ct) value distributions from non-acute and acute samples. RESULTS: We analysed 341 non-acute and 145 acute swab samples from 274 participants. Haemophilus influenzae type B was the most commonly detected microbe (77.4% of non-acute and 64.8% of acute samples). In acute samples, nine specific microbe pairs were detected more frequently than expected by chance. Regression models indicated significantly lower microbial load in non-acute relative to acute samples for H. influenzae non-type B, Streptococcus pneumoniae and rhinovirus, although it was not possible to identify a Ct-value threshold indicating causal etiology for any of these organisms. CONCLUSIONS: Semi-quantitative measures of microbial concentration did not reliably differentiate between illness and asymptomatic colonization, suggesting that clinical symptoms may not always be directly related to microbial load for common respiratory infections.

Epidemiology and Transmission of Respiratory Infections in Thai Army Recruits: A Prospective Cohort Study.

Military recruits are at high risk of respiratory infections. However, limited data exist on military populations in tropical settings, where the epidemiology of respiratory infections differs substantially from temperate settings. We enrolled recruits undertaking a 10-week military training at two Royal Thai Army barracks between May 2014 and July 2015. We used a multiplex respiratory panel to analyze nose and throat swabs collected at the start and end of the training period, and from participants experiencing respiratory symptoms during follow-up. Paired sera were tested for influenza seroconversion using a hemagglutinin inhibition assay. Overall rates of upper respiratory illness and influenza-like illness were 3.1 and 2.0 episodes per 100 person-weeks, respectively. A pathogen was detected in 96% of samples. The most commonly detected microbes were Haemophilus influenzae type B (62.7%) or non-type B (58.2%) and rhinovirus (22.4%). At baseline, bacterial colonization was high and included H. influenzae type B (82.3%), H. influenzae non-type B (31.5%), Klebsiella pneumoniae (14.6%), Staphylococcus aureus (8.5%), and Streptococcus pneumoniae (8.5%). At the end of follow-up, colonization with H. influenzae non-type B had increased to 74.1%, and S. pneumoniae to 33.6%. In the serology subset, the rate of influenza infection was 3.4 per 100 person-months; 58% of influenza infections resulted in clinical disease. Our study provides key data on the epidemiology and transmission of respiratory pathogens in tropical settings. Our results emphasize the need for improved infection prevention and control in military environments, given the high burden of illness and potential for intense transmission of respiratory pathogens.

Sudden death from acute epiglottitis in a toddler.

The bacterium Haemophilus influenzae type b (Hib) can cause severe and life-threatening infections such as epiglottitis and meningitis. The course of the disease can be very rapid, resulting in sudden death. The incidence of Hib-induced epiglottitis in children has declined since the introduction of vaccinations in countries where such vaccinations are routinely administered. We herein present a case involving a 2.5-year-old boy who died suddenly at home. He had developed acute-onset throat and abdominal pain and a high fever. Despite an emergency cricothyrotomy due to a complicated intubation because of a massively swollen epiglottis, the efforts to resuscitate the child were unsuccessful. He was a previously healthy toddler, but he had not yet been vaccinated. Microbiologic analysis revealed the pathogenic bacterium Hib. The main autopsy finding was acute epiglottitis with swelling and cherry-red coloring of the epiglottis. Postmortem cultures of the cerebrospinal fluid and heart blood also revealed Hib as the pathogenic agent. Acute pneumonia was also diagnosed microscopically. The present report describes a rare case of Hib-induced acute epiglottitis and presents the key findings of forensic investigations in this type of disease.

Haemophilus influenzae type b (Hib) seroprevalence and current epidemiology in England and Wales.

INTRODUCTION: The implementation of the Hib conjugate vaccine in the United Kingdom in 1992 resulted in a rapid decline in invasive Hib disease across all age groups. However, a resurgence in 2000-2002 prompted the introduction of additional control measures, including a routine 12-month booster in 2006. Here we describe results from a national serosurvey in children eligible for the 12-month booster and recent Haemophilus influenzae epidemiology in England and Wales. METHODS: A national serosurvey was performed to determine the prevalence of anti-polyribosyl-phosphate (anti-PRP) IgG antibodies in 1000 residual samples from children up to 8 years of age in 2013-2014. Data were compared to previous national serosurveys performed by the same laboratory. Current epidemiology of invasive H. influenzae disease in England and Wales is also reported. RESULTS: Median anti-PRP IgG concentrations were highest among 1 year olds at 4.4 µg/mL (IQR, 1.3-14.9; n = 99) and then declined rapidly but remained ≥1.0 µg/mL across the age-groups in the cohort eligible for the 12-month booster. Overall, 89% of children (719/817) had anti-PRP concentrations ≥0.15 µg/mL, the putative threshold for short-term protection against invasive Hib disease. During 2012-2016, annual Hib disease incidence remained below one case per million population, responsible for only 67 of 3523 laboratory-confirmed H. influenzae cases, including one case of Hib meningitis during the 5-year period. There were only two deaths within 30 days over the five-year period (case fatality rate, 3.0%). CONCLUSIONS: Hib control in England and Wales is currently the best achieved since the vaccine was introduced more than two decades ago. However, Hib antibodies wane rapidly after the 12 months booster. Although most children remain protected against disease, antibody levels may not be high enough to prevent carriage among toddlers. Ongoing monitoring is essential to inform future vaccination policy.

Changing Epidemiology of Haemophilus influenzae in Children.

Haemophilus influenzae remains a common cause of illness in children throughout the world. Before the introduction of vaccination, H influenzae type b (Hib) disease was the leading cause of bacterial meningitis in young children and a frequent cause of pneumonia, epiglottitis, and septic arthritis. Clinicians should remain diligent in counseling parents on the dangers of Hib and provide vaccination starting at 2 months of age. The epidemiology of invasive H influenzae disease is shifting. It is imperative that clinicians recognize the changing epidemiology and antibiotic resistance patterns for H influenzae to optimize care in hospital and ambulatory settings.

[Detection of influenza A, B and subtypes A (H1N1) pdm09, A (H3N2) viruses by multiple qrt-pcr in clinical samples]. / Detección de virus influenza A, B y subtipos a (H1N1) pdm09, A (H3N2) por múltiple rt-pcr en muestras clínicas.

OBJECTIVES.: To describe the clinical and epidemiological characteristics of patients diagnosed with epidermolysis bullosa (EB) at the Instituto Nacional de Salud (INSN) in Lima, Peru; a National Reference Center for this disease. MATERIAL AND METHODS: . Observational, descriptive and transversal study. We reviewed the clinical histories and laboratory tests of patients diagnosed with EB treated in INSN from 1993 to 2015. RESULTS.: 93 patients were registered. The average age was 7.9 ± 5.6 years; 53.8% (n = 50) were boys. Clinical forms corresponded to dystrophic EB with 41 (44.1%) cases, simple EB with 39 (41.9%) union EB cases with 8 (8.6%) and Kindler syndrome with 4 (4.3%) cases. The clinical form could not be identified in a case. A total of 48 cases (51.6%) came from Lima and Callao, and 45 cases (48.4%) from other provinces of the country. Extracutaneous manifestations involved gastrointestinal (44.1%), ocular (37.6%), odontogenic (87.1%), and nutritional (79.6%) involvement, as well as pseudosindactilia (16.1%). Chronic malnutrition (71.6%), acute malnutrition (17.6%) and anemia (62.4%) were found. Mortality corresponded to 6 cases (6.5%). CONCLUSIONS.: 93 cases of EB were reported in INSN, the predominant clinical presentation was the dystrophic form.

OBJETIVOS.: Estandarizar la técnica de reacción en cadena de la polimerasa en tiempo real (RT-PCR) múltiple para la detección de virus influenza A, B y tipificación de subtipos A (H1N1) pdm09, A (H3N2) en muestras clínicas. MATERIALES Y MÉTODOS.: Se analizaron 300 muestras de hisopado nasofaríngeo. Esta metodología fue estandarizada en dos pasos: la primera reacción detectó el gen de la matriz del virus de influenza A, gen de la nucleoproteína del virus influenza B y el gen GAPDH de las células huésped. La segunda reacción detectó el gen de la hemaglutinina de los subtipos A (H1N1) pandémico (pdm09) y A (H3N2). RESULTADOS.: Se identificaron 109 muestras positivas a influenza A y B, de las cuales 72 fueron positivas a influenza A (36 positivas a influenza A (H1N1) pdm09 y 36 positivos a influenza A (H3N2)) y 37 muestras positivas a influenza B. 191 fueron negativas a ambos virus mediante RT-PCR en tiempo real multiplex. Se encontró una sensibilidad y especificidad del 100% al analizar los resultados de ambas reacciones. El límite de detección viral fue del rango de 7 a 9 copias/µL por virus. Los resultados no mostraron ninguna reacción cruzada con otros virus tales como adenovirus, virus sincitial respiratorio, parainfluenza (1,2 y 3), metapneumovirus, subtipos A (H1N1) estacional, A (H5N2) y VIH. CONCLUSIONES.: La RT-PCR múltiple demostró ser una prueba muy sensible y específica para la detección de virus influenza A, B y subtipos A (H1N1, H3N2) y su uso puede ser conveniente en brotes estacionales.

Haemophilus influenzae type b carriage and burden of its related diseases in Chinese children: Systematic review and meta-analysis.

BACKGROUND: Haemophilus influenzae type b (Hib) is an important cause of invasive bacterial disease in children worldwide. The limited awareness of disease burden is a major barrier to the introduction of Hib vaccine into China's National Immunization Program. Therefore, we conducted a systematic review and meta-analysis to estimate carriage of Hib and burden of its related diseases in Chinese children. METHODS: We systematically searched Pubmed, Web of Science, Ovid, Chinese National Knowledge Infrastructure (CNKI), and Wanfang databases for studies published up to December 31, 2016, reporting Hib carriage and burden of Hib diseases among children in Mainland China. Pooled estimates were obtained using random-effects models. RESULTS: We included 27 studies with 15783 children across 14 provinces. The pooled carriage of Hib was 5.87% (95% CI 3.42-8.33) for healthy children. The pooled proportion of disease due to Hib were 4.06% (95% CI 3.29-4.83) for acute lower respiratory tract infection (ALRI) and 27.32% (95% CI 0.41-54.24) for bacterial meningitis. The proportion of ALRI caused by Hib was higher in northern China than that in the south. Significant heterogeneity was noted across and within regions (P<0.001). After the induction of Hib vaccine, meta-regression showed that carriage of Hib changed little (P=0.725), but the proportion of ALRI caused by Hib in children decreased (P<0.001). CONCLUSIONS: Hib carriage persists at low levels among children in China. The proportion of ALRI due to Hib infection decreased with year. Incorporation of Hib vaccine into the National Immunization Program could reduce the burden of Hib disease in China.

Multipathogenic necrotising supraglottitis in an immunocompetent patient.

Supraglottitis is a potentially life-threatening condition. It is now uncommon due to the Haemophilus influenzae type B vaccination and is more recently caused by Streptococcus pneumoniae, S. pyogenes, H. influenzae non-type B, H. parainfluenzae, Staphylococcus aureus and Pasteurella multocida Very rarely, it can cause necrotising supraglottitis/epiglottitis, and this has been reported in immunocompromised individuals. We present a unique case of multipathogenic supraglottitis causing laryngeal fibrinoid necrosis in an immunocompetent patient. During his admission, the patient was critically unwell and required surgical intervention and tracheostomy. However, he made a full recovery with no persisting morbidity. We believe that this was owed to the aggressive antimicrobial therapy, timely surgical management of the disease process and the patient’s immunocompetency.