Non-b Serotypes Research Articles

Hemophilus meningitis – Current Aspects of Epidemiology and Prevention: a Descriptive Review

Relevance. H. influenzae is a common cause of bacterial meningitis in children worldwide. Significant data have been accumulated worldwide on the use of H. influenzae type b conjugate vaccines over the past three decades. In the Russian Federation, constant monitoring of hemophilic meningitis is carried out, but data on the incidence of hemophilic infection are limited.Target. To consider global changes in the epidemiology of invasive forms of H. influenzae in the world and in the Russian Federation.Conclusions. The use of conjugate vaccines has resulted in a steady decline in invasive Hib infections. However, there has been a significant increase in invasive infections with non-typeable H. influenzae and non-b serotypes. In the Russian Federation, the incidence of meningitis caused by H. influenzae does not tend to increase or decrease; the majority of cases occur in children under 5 years of age.

C5 (Clinical Case) Coccobacillary Meningitis and Septic Embolic Infarcts in an Ex-Preterm Infant: An Unexpected Pathogen

Abstract Introduction/Background Pasteurella multocida causes life-threatening zoonotic invasive infections in immunocompromised individuals and those at extremes of age (neonates and elderly). Bacteremia, meningitis, and endocarditis are serious complications that are associated with up to 25-30% mortality. Case Description A 7-week-old ex-34-week preterm female infant presented with a one-day history of fever, irritability, and poor feeding without exposure to sick contacts. Household contacts included a constantly drooling Shi Tzu dog. Examination revealed an irritable, febrile infant with a bulging fontanelle and scant purulent eye discharge. No focal neurological deficits, skin rashes or murmurs were appreciated. Empiric antibiotics were initiated following a full work-up for sepsis. Cerebrospinal fluid (CSF) analysis showed neutrophilic pleocytosis with 7608 x106L nucleated cells (95% neutrophils), protein 7360 mg/L, glucose <0.2 mmol/L and gram-negative coccobacilli. Blood and CSF cultures grew Pasteurella multocida, prompting a switch to crystalline penicillin. An echogenic mitral valvular mass was identified in the absence of underlying cardiac defects. Head imaging confirmed ventriculitis with multiple small infarcts. No sequelae of abscess, hydrocephalus or hearing loss were demonstrated after the completion of 6 weeks of penicillin therapy. Discussion Haemophilus influenzae, serotype b, is the typical cause of coccobacillary meningitis in a 7-week-old infant. In addition to non-b serotypes, non-typeable species which cause conjunctivitis may also cause invasive disease in young infants. The resultant growth of P. multocida from cultures was, therefore, unexpected, particularly given there were no preceding animal bites or scratches. In vulnerable hosts, this pathogen can be transmitted across skin or mucous membranes after close animal contact, such as licking and sniffing. The constant drooling and spraying of saliva from the pet dog, a flat-faced breed known to have stenotic nares and chronic nasal secretions, likely provided an opportunity for mucosal contamination. This infant’s young age, prematurity, and exposure to a flat-faced dog placed her at high risk for Pasteurellosis, which manifested as complicated meningitis and endocarditis. Conclusion Pasteurella infections most often arise as local infections following an animal bite or scratch, are rare but important causes of life-threatening severe coccobacillary invasive infection, even without preceding trauma, in young infants. Families of at-risk individuals who own pets should have adequate education about zoonotic infections that address risk factors, including animal breed and behaviour, presenting features and preventive strategies to reduce the potential for serious morbidity and even mortality.

Carriage of Haemophilus influenzae among children attending childcare centres in Kuala Lumpur, Malaysia in the post vaccination era: A cross-sectional study

BackgroundHaemophilus influenzae (H. influenzae) is a human upper respiratory tract colonizer which causes wide range of disease especially in children<5 years old and in the elderly. Although worldwide incidence in industrialised countries where Hib vaccination is commonly used has dropped sharply since implementation of H. influenzae type b (Hib) vaccination, there is limited data on the disease burden caused by H. influenzae in Malaysia post vaccination era. A change in predominant serotype from type b to non-b serotypes of H. influenzae in invasive diseases was reported worldwide. We investigated the carriage of H. influenzae post vaccination era among 2–4 years old. MethodologyRandomly, we collected 436 oropharyngeal swabs from healthy children aged 2–4 years in 30 registered childcare centres in Kuala Lumpur (August 2018-May 2019). Informed consent and written questionnaires were obtained from parents. H. influenzae was identified by standard microbiological methods. Univariable analysis was carried out to describe variables associated with colonization. All variables with p < 0.25 were included in multivariable logistic regression model. A p value < 0.05 was considered significant. ResultsA higher carriage rate was noted among the unvaccinated children (4/28; 14.3%) compared to vaccinated children (16/326; 4.9%) but were not statistically significant. The serotypes were type a (9; 37.5%), type b (5; 20.8%), type c (3; 12.5%), type d (2; 8%), type e (1; 4.2%) and type f (4; 16.7%). Variables like age, basic sanitation, immunization status, body mass index were included in multivariable logistic regression test since p values in univariate analysis were<0.25. Planned sewage system was found to be significant (Adjusted OR, 0.06; 95% CI, 0.01–0.46; p = 0.006). ConclusionFewer carriage rates were observed among children post Hib vaccination era. Hib carriage is still possible after vaccination. The presence non-b serotypes may imply emerging replacement serotypes.

PMU18 - UK EPIDEMIOLOGY AND CLINICAL BURDEN OF VACCINE-PREVENTABLE CHILDHOOD INFECTIOUS DISEASES: A SYSTEMATIC LITERATURE REVIEW

Vaccines against diphtheria, tetanus, pertussis, hepatitis B (Hep B), poliomyelitis, and Haemophilus influenzae type b (Hib) are included in the current UK childhood vaccination schedule. Our aim was to provide an overview of recent data around the epidemiology and clinical burden of these diseases in the UK. Systematic searches for publications reporting incidence, prevalence, and risk factors were conducted in September 2017 using Embase, MEDLINE, Cochrane Library, four key conferences (2015-2017), additional sources/websites, and by hand-searching references of included publications. There was no restriction on intervention or comparator. Only English-language publications from 2012 onwards were included. Of the 11,451 publications identified, 38 (reporting on 37 studies) were included; 21 studies reported data on Hep B, eight on pertussis, five on H. influenzae, and one each on diphtheria, tetanus, and poliomyelitis. Incidence and prevalence of Hep B are low overall; those born overseas or of Asian ethnicity were at higher risk than the general population. People who inject drugs (psychoactive or image- and performance-enhancing) represent another risk group for Hep B. In 2012, there was a resurgence of pertussis primarily in very young infants; this was successfully addressed by a programme of maternal vaccination during pregnancy. Due to the effective control of Hib after two decades of routine vaccination, non-b serotypes now cause a large percentage of the remaining low H. influenzae morbidity and mortality in the UK; risk groups included expectant mothers, young infants, and adults with comorbidities or immunosuppression. The low number of studies and reported cases of diphtheria, tetanus and polio suggest that these diseases are well controlled. While the childhood vaccination schedule continues to be highly effective, certain population subgroups are at risk of vaccine-preventable hepatitis B and pertussis infections. This highlights the on-going importance of vaccination in conjunction with high population vaccine coverage rates.

Paediatric invasive Haemophilus influenzae in Queensland, Australia, 2002-2011: Young Indigenous children remain at highest risk.

Haemophilus influenzae continues to cause invasive disease in children despite widespread Hib immunisation. The significance of non-B serotypes continues to be investigated, with evidence of increased invasive non-typeable H. influenzae (NTHi) world-wide. The aim of this study was to examine the current epidemiological and clinical features of invasive H. influenzae disease in children in Queensland, Australia. A retrospective review was performed of all cases of invasive H. influenzae disease in children <18 years of age in Queensland between January 2002 and December 2011. Cases were identified from pathology records and data requested from treating hospitals. Laboratory data were obtained for 144 cases and clinical/demographic data for 123 cases. The majority (72%) of cases were children <5 years of age. Annual incidence rate for all children <5 years was 7.4/100 000, and for Aboriginal and Torres Strait Islander children <5 years was 10.2/100 000. Serotype was reported for 132 isolates, 69 NTHi and 63 encapsulated strains. The most common clinical diagnoses were pneumonia, meningitis and bacteraemia without clinical focus. Of the patients, 5 patients died, and 12 had significant morbidity at hospital discharge. While rates of invasive H. influenzae disease have decreased dramatically following the introduction of Hib vaccination, H. influenzae remains a cause of significant morbidity and mortality, and Aboriginal and Torres Strait Islander children remain particularly vulnerable.

Cervicofacial necrotizing fasciitis caused by Haemophilus influenzae serotype e in a patient with Sjogren's syndrome, systemic lupus erythematosus and hypocomplementaemia

Introduction: Haemophilus influenzae has the potential to lead to invasive disease including necrotizing fasciitis, especially in immunocompromised individuals. There are only eight previous reports of monomicrobial necrotizing fasciitis due to this organism, and, to the best of our knowledge, none of the head and neck. There is also limited epidemiological and clinical data on infections caused by non-b serotypes of H. influenzae, including serotype e. Case presentation: A 60-year-old female, with systemic lupus erythematosus, Sjogren's syndrome and hypocomplementaemia, presented with rapidly progressive right-sided facial and neck pain, swelling and erythema. She was treated initially with broad-spectrum antibiotics and underwent emergent debridement of the infected tissues. Intraoperative cultures and blood cultures grew H. influenzae. She required two additional debridements and was treated with ceftriaxone for 3 weeks with resolution of her symptoms. Conclusion: Here, we present the first reported case, to the best of our knowledge, of cervical necrotizing fasciitis due to H. influenzae serotype e. This case highlights the continued clinical importance of H. influenzae as a cause of invasive disease, including necrotizing fasciitis, particularly in immunocompromised individuals. Moreover, the case provides an example of invasive H. influenzae infection caused by a non-b serotype, an emerging concern in the era of widespread H. influenzae serotype b vaccination.

Meningite por Haemophilus influenzae tipo f

ABSTRACTWith the decline in the rate of infections caused by Haemophilus influenzae serotype b since the widespread vaccination, non-b serotypes should be considered as potential pathogenic agents in children with invasive disease younger than 5 years old. We report the case of an immunocompetent 1-year-old boy with Haemophilus influenzae type f meningitis. The agent was identified in cerebrospinal fluid and blood cultures. Serotyping was performed by tests using polyclonal sera and confirmed by polymerase chain reaction. All Haemophilus influenzae isolates associated with invasive disease should be serotyped and notified as a way to evaluate the changes and trends in serotype distribution of this disease.

Real-time polymerase chain reaction for detection of encapsulated Haemophilus influenzae using degenerate primers to target the capsule transport gene bexA

A real-time polymerase chain reaction assay that uses degenerate primers and a dual-labelled probe was developed to detect the bexA gene of Haemophilus influenzae, including those belonging to non-b serotypes as well as clonal division II strains. This assay is sensitive and specific, detecting 20 copies of the gene, but negative with a variety of bacteria associated with meningitis and bacteremia or septicemia.

Current Epidemiology and Trends in Invasive Haemophilus influenzae Disease--United States, 1989-2008

With the introduction of Haemophilus influenzae serotype b (Hib) conjugate vaccines, there has been a dramatic reduction of Hib disease in young children and the epidemiological trends of invasive H. influenzae have shifted. Data were collected from active surveillance for invasive H. influenzae disease conducted through Active Bacterial Core surveillance sites during 1989-2008. During 1999-2008, the estimated mean annual incidence of H. influenzae infection was 1.62 cases per 100 000 population; 15.3% of cases were fatal. Incidence was higher among adults aged ≥65 years, compared with other age groups. The largest burden of disease among children aged <5 years was in infants aged <1 year; many of these cases occurred during the first month of life in preterm or low-birth weight infants. An estimated 10% of the total burden of disease among children aged <5 years occurred in American Indian and Alaska Native children. During 1989-2008, 7559 cases of H. influenzae disease were reported from Active Bacterial Core surveillance sites. Small increases in the incidence of serotypes a, e, and f were observed during 1989-2008. The largest of these increases was in serotype f and was primarily among adults aged ≥18 years. Since the introduction of Hib conjugate vaccines, the incidence of invasive disease caused by H. influenzae in the United States has decreased dramatically; however, a considerable burden of non-Hib disease is still present in the oldest and youngest age groups. There is no evidence of substantial replacement disease with non-b serotypes in young children in the United States.

Changes in serotype distribution of Haemophilus influenzae meningitis isolates identified through laboratory-based surveillance following routine childhood vaccination against H. influenzae type b in Brazil

Following routine childhood vaccination against Haemophilus influenzae type b (Hib) disease in Brazil in 1999, passive laboratory surveillance reported increasing numbers of non-b serotypes and nontypeable H. influenzae (NTHi) from meningitis cases. To characterize this increase, we analyzed data on 3910 H. influenzae isolated from cerebrospinal fluid or blood from meningitis cases that were sent to the national reference laboratory for serotyping from 1990 to 2008. Hib accounted for 98% of H. influenzae meningitis isolates received during 1990-1999 versus 59% during 2000-2008, while non-b serotypes increased from 1% to 19% and NTHi increased from 2% to 22% of H. influenzae isolates received during the two periods. Higher proportions of non-b serotypes and NTHi than Hib were isolated from blood rather than cerebrospinal fluid. Estimated incidence rates for H. influenzae meningitis for Sao Paulo state remained below 1 case per million population during 2000-2008, although annual incidence of NTHi meningitis (mean, 0.03 cases per 100,000 population) increased in several age groups. Changes in surveillance for H. influenzae following introduction of Hib conjugate vaccine likely contributed to increased numbers of non-b and nontypeable H. influenzae meningitis isolates received at the national reference laboratory.

Invasive Infections Caused by Haemophilus influenzae Serotypes in Twelve Canadian IMPACT Centers, 1996–2001

Haemophilus influenzae type b (Hib) immunization has changed the epidemiology of pediatric bacterial invasive disease. We describe the epidemiology of H. influenzae invasive infections in 12 Canadian pediatric tertiary care [Immunization Monitoring Program, ACTive (IMPACT)] centers during the era of universal immunization against this pathogen. Children with positive cultures for H. influenzae serotypes a to f (Hia to Hif) and nontypable H. influenzae from sterile sites were identified from the laboratory records at 12 IMPACT centers from January 1, 1996 to December 31, 2001. Hospital records were retrospectively reviewed for demographic and clinical information. Of 166 H. influenzae cases, 58 (35%) were caused by Hib, 89 (54%) by non-b serotypes, and 19 (11%) were not serotyped. The non-b serotypes included: 25 Hia (28%), 4 Hid (4%), 2 Hie (2%), 11 Hif (12%), and 47 were nontypable isolates (53%). For patients with Hib and Hia infection, meningitis was the most common presentation, accounting for 40% and 52% respectively, whereas the most common presentation for nontypable serotypes was pneumonia, seen in 43% of cases. Epiglottitis was associated mainly with Hib. Aboriginal ethnicity was an important risk factor for Hia cases, accounting for 76% of patients with infections caused by this serotype. Mean duration of hospitalization, need for admission to a pediatric intensive care unit, and case fatality rates were similar for the cases because of Hib, Hia, Hif, and nontypable serotypes. In 1996-2001, two-thirds of H. influenzae invasive disease in the 12 IMPACT centers was caused by non-b serotypes, which were associated with significant morbidity and mortality.

Underestimation of HIV-1 plasma viral burden in patients who acquire infection abroad: the experience in a community hospital clinic.

In a suburban teaching hospital clinic, we diagnosed human immunodeficiency virus type 1 (HIV-1) infection in 10 patients who acquired the infection in Africa or Asia. All the patients had low viral plasma HIV RNA levels. This finding likely represents underestimation of true plasma viral burden in patients infected with non-B serotypes of HIV-1. Clinicians caring for immigrants with HIV infection need to be aware of the limitations of current commercial assays for the quantification of HIV-1 plasma viral burden, and better assays are needed for non-B HIV-1 serotypes.

The genetics of encapsulation in Haemophilus influenzae.

In Haemophilus influenzae type b (Hib) strains the cap locus with very few exceptions contains an unstable direct repeat of approximately 17 kb of DNA flanking an approximately 1-kb bridge region containing the gene bexA. Each repeat contains genes necessary for polysaccharide synthesis, export, and surface expression, with BexA a critical component of the polysaccharide exporter. Only rare Hib strains have been identified in which cap lacks a direct repeat, though this is the norm for non-b serotypes. Examination of the ends of this single-copy locus shows that cap has the structure of a compound transposon: Copies of the insertion element IS1016 flank the gene cluster. This gives strains the capacity to amplify genes at cap by unequal homologous recombination. The cap duplication in Hib strains--subserving augmented production of polysaccharide--has apparently arisen in this way and become fixed in the population through deletion of one copy of bexA.