Hib Vaccine Research Articles

Primary vaccination in adult patients after allogeneic hematopoietic stem cell transplantation – A single center retrospective efficacy analysis

Allogeneic hematopoietic stem cell transplantation (alloHSCT) results in a loss of humoral immunity and subsequent risk for severe infections. Thus, re-vaccination is required but may fail due to incomplete immune reconstitution. We retrospectively analyzed predictors of immune response to primary vaccination applied according to the EBMT (European Blood and Marrow Transplantation Group) recommendations. Serologic response to vaccination against diphtheria (D), tetanus (T), Bordetella pertussis (aP) and Haemophilus influenzae (Hib) (administrated as combined DTaP-Hib-IPV vaccination) was studied in 84 alloHSCT patients transplanted between 2008 and 2015 (age at alloHSCT: 18.6–70.6 years). All patients with a relapse-free survival of ≥9 months, at least 3 consecutive vaccinations and absence of intravenous immunoglobulin administration within 3 months before and after vaccination met the primary inclusion criteria. Additionally, immunological response to a pneumococcal conjugate vaccine was analyzed in a subgroup of 67 patients. Patients’ characteristics at the time of first vaccination were recorded. Responses were measured as vaccine-specific antibody titers. Regarding DTaP-Hib-IPV vaccination, 89.3% (n = 75) of all patients achieved protective titers to at least 3 of the 4 vaccine components and were thus considered responders. 10.7% (n = 9) of the patients were classified as non-responders with positive immune response to less than 3 components. Highest response was observed for Hib (97.4%), tetanus (95.2%) and pneumococcal vaccination (83.6%) while only 68.3% responded to vaccination against Bordetella pertussis. Significant risk factors for failure of vaccination response included low B cell counts (p < 0.001; cut-off: 0.05 B cells/nl) and low IgG levels (p = 0.026; mean IgG of responders 816 mg/dl vs. 475 mg/dl of non-responders). Further, a trend was observed that prior cGvHD impairs vaccination response as 88.9% of the non-responders but only 54.7% of the responders had prior cGvHD (p = 0.073). The results demonstrate, that the currently proposed vaccination strategy leads to seroprotection in the majority of alloHSCT patients.

Immunogenicity and safety of 7-valent pneumococcal conjugate vaccine (PCV7) in children aged 2–5 years in China

BackgroundThe widespread use of pneumococcal conjugate vaccines (PCVs) has significantly decreased pneumococcal disease worldwide. However, China has not adopted PCVs in their national immunization schedules and had only approved these vaccines for children aged 2–15 months by 2020. MethodsIn an open-label trial, enrolled healthy children aged 2–5 years old were randomized 1:1 and divided into a 7-valent pneumococcal conjugate vaccine (PCV7) group and a Haemophilus influenzae type b conjugate vaccine (Hib) group. Children in the PCV7 group received a single dose of PCV7, and the Hib group received a single dose of Hib vaccine. Blood samples were collected before and 6 months after vaccination. Immunogenicity and safety of PCV7 were assessed at prespecified time points. ResultsSix months after a single dose of PCV7, children in the PCV7 group for all 7 serotypes, IgG mean concentrations (GMCs) and opsonophagocytic geometric mean titres (GMTs) were significantly higher (P < .001) than at baseline, and the proportion of IgG ≥ 0.35 µg/mL ranged from 90.0% to 100%. Although the antibody level increased with age, preexisting antibodies did not induce hyporesponsiveness to PCV7. In the Hib group, the antibody levels were not significantly different or had changed slightly at 6 months. PCV7 was well tolerated in all age groups, and no serious adverse events (AEs) emerged during this study. ConclusionsA single dose of PCV7 was immunogenic and safe for Chinese children aged 2–5 years, and the preexisting antibodies against the PCV7 serotypes did not change the response to vaccination. The findingssupported the effectiveness of PCV7 in this age group. PCVs with broader serotype coverage are expected to expand pneumococcal disease protection.

Correlation of Vaccine Responses.

IntroductionThe humoral response to vaccinations varies widely between individuals. There is no data available on the correlation between responses to different vaccines. In this study, we investigated the correlation of antibody responses between routine vaccine antigens in infants.MethodsOne and seven months after the 6-month vaccinations and one month after the 12-month vaccinations, antibody concentrations to diphtheria, tetanus, pertussis, polio (serotypes 1-3), Haemophilus influenzae type b (Hib), pneumococcus (13 serotypes), meningococcus C, measles, mumps and rubella were measured using fluorescent bead-based multiplex immune-assays. For the correlation of antibody responses, Spearman’s rank correlation coefficients (ρ) with 95% confidence intervals (CI) were calculated between responses to each vaccine antigen.ResultsThe correlation between concentrations of antibodies to the vaccinations ending at 6 months of age was higher one month compared to seven months after vaccination. The strongest correlations at both time points were observed between antibody responses to different polio serotypes, certain pneumococcal serotypes and between responses to diphtheria and pneumococcal (conjugated to a diphtheria toxoid) vaccine antigens. Correlation between responses to tetanus, Hib, pertussis, polio and other vaccine antigens were weak. The correlation between antibody responses to the 12-month vaccine antigens was weaker than to the 6-month vaccine antigens and there was a negative correlation between responses to measles, mumps, rubella vaccine and non-live vaccine antigens (meningococcus C, tetanus and Hib). There was only weak correlation between antibody responses to vaccines of the same type (e.g. conjugated polysaccharide or toxoid vaccines).ConclusionCorrelation between antibody responses to similar antigens in the same vaccine (such as different serotypes of a bacteria or virus), as well as responses to antigens conjugated to similar carrier proteins, are strong. In contrast, correlation between responses to other vaccines are weak. Measuring antibody responses to one or a few vaccine antigens therefore does not offer a reliable surrogate marker of responses to unrelated vaccines.

#22: Trends in Bacterial Meningitis in a Tertiary-Level Children′s Hospital in Mexico, Following Haemophilus influenzae and Streptococcus pneumoniae Vaccination (1990–2018)

Abstract Background Bacterial meningitis (BM) remains a significant global health problem in pediatric care, with substantial morbidity and mortality. The epidemiology of BM has changed over the last 20 years. The ongoing introduction of conjugate vaccines for the most common meningeal pathogens has reduced the global incidence. However, there is limited epidemiologic and microbiologic data of BM in children before and after the widespread use of these vaccines in Mexico. Methods We conducted a retrospective, observational, analytical study. Pediatric patients (from 1 month to 18 years of age) presenting with BM and hospitalized at the Instituto Nacional de Pediatria in Mexico City, from 1990 to 2018, were included. Meningitis from invasive procedures or complicated head trauma were excluded. BM was classified according to the World Health Organization (WHO) criteria. The cases were analyzed in three periods: period A (1990–1999), period B (2000–2008), and period C (2009–2018). Period A corresponds to the time before the conjugate Haemophilus influenzae type b (Hib vaccine) was introduced in Mexico, while periods B and C correspond to the time after the Hib vaccine was routinely applied. Periods A and B correspond to the period before the pneumococcal conjugate vaccine (PCV7) was administrated in Mexico, while period C is after PCV7 and PCV13 were routinely administrated. The proportion of cases between periods was compared with Chi-square or Fisher exact test; P &amp;lt; 0.05 was considered significant. Binomial logistic regression analysis was used to determine the association between potential risk factors and death due to BM. Results A total of 226 cases with BM were included, 180 (79.6%) confirmed cases, and 46 (20.4%) probable cases. The median age at diagnosis was 10 months. There were 126 (55.8%) cases in Period A, 62 (27.4%) cases in Period B, and 38 (16.8%) cases in Period C, with a statistically significant reduction between periods (P = 0.0001). Hib was the most commonly isolated pathogen, found in 38 (50%) cases. However, its proportion declined significantly after the introduction of the Hib conjugate vaccine (P &amp;lt; 0.0001). S. pneumoniae followed as the second most commonly isolated bacterial pathogen. There was a significant reduction in neurological complications after the Hib conjugate vaccine (P = 0.003) and the S. pneumoniae conjugate vaccine (P = 0. 05) were introduced. Independent risk factors associated with mortality were coma (OR 15, P = 0. 0001), intracerebral bleeding (OR 3.5, P = 0.046), and pneumococcal meningitis (OR 9.4, P = 0. 002). Conclusions BM remains a cause of morbidity and mortality in pediatric patients in this hospital, with a dramatic change in the epidemiology since the introduction of the Hib conjugate vaccine to the national immunization schedule. Routine use of childhood conjugate vaccines against the most frequent etiological agents reduced the number of cases globally, mainly those caused by Hib. Additionally, conjugate vaccines reduced neurological complications and sequelae caused by this disease.

Features of haemophilus influenzae type b vaccine in patients waitlisted for lung transplantation

Objective: to evaluate the immunological efficacy of haemophilus influenzae type b ( Hib ) vaccine in patients with severe bronchopulmonary condition waitlisted for lung transplantation. Materials and methods. 16 patients (age 22–61 years) with severe bronchopulmonary diseases were vaccinated once against Hib infection. IgG antibody concentrations to Hib capsular polysaccharide before vaccination and 1 month after was measured by ELISA using a test system developed at Mechnikov Research Institute of Vaccines and Sera. Statistical data processing was carried out using stats (v.3.6.2), lme4 (v.1.1 – 21), and lmerTest (v.3.1 – 1) packages. Results. Hib vaccine in patients with severe bronchopulmonary condition did not elicit any local or systemic reactions. The proportion of patients whose antibody (Ab) concentrations to Hib capsular polysaccharide exceeded the long-term protection threshold was 69% and 100% before and after vaccination, respectively (p = 0.02). There were differences in the formation of post-vaccination immunity depending on the nosological forms of patients’ diseases. In the group of patients with obstructive pulmonary diseases, the geometric mean level of antibodies to the Hib capsular polysaccharide after vaccination increased as compared to the baseline value – from 1.3 [0.6–2.8] to 5.5 [1.9–15.4] AU/mL, (p = 0.05). In the group of patients with restrictive lung diseases, the level did not change – 2.8 [0.6–14.1] AU/mL before vaccination and 3.4 [1.3–8.5] AU/mL 1 month after vaccination. In the group of patients taking glucocorticosteroids, there was no increase in the level of antibodies to Hib capsular polysaccharide (2.7 [0.8–9.3] AU/mL before and 2.8 [1.2–6.5] AU/mL after vaccination). In the group of patients who did not take hormones, antibody concentrations to Hib capsular polysaccharide increased from 1.2 [0.7–2.1] AU/mL to 4.8 [2.2–10.1] AU/mL (p = 0.006). Conclusion. Hib vaccination of waitlisted patients with severe bronchopulmonary disease is safe and immunologically effective.

Acute epiglottitis: Analysis of U.S. mortality trends from 1979 to 2017

PurposeEvaluate trends in mortality due to acute epiglottitis before and after adoption of Haemophilus influenza Type b vaccination (Hib) in pediatric and adult populations. Materials and methodsPatients who died from acute epiglottis from 1979 to 2017 identified using National Vital Statistics System. Mortality rates calculated using age-adjusted US census data expressed in rate per 100,000 individuals. Trends analyzed using the National Cancer Institute Joinpoint Regression Program (version 4.7.0; Bethesda, Maryland). Results1187 epiglottitis-related deaths were identified over thirty-nine years. Total deaths decreased from 65 in 1979 to 15 in 2017. Adult deaths accounted for 63.5% and decreased from 0.015 per 100,000 individuals (24 deaths) in 1979 to 0.006 per 100,000 individuals (14 deaths) in 2017. Best fitting log-liner regression model showed APC of −3.5% (95% CI, −4.2 to −2.7%) from 1979 to 2017. Pediatric and adolescent deaths accounted for 443 (37.3%) deaths, decreasing from 0.064 per 100,000 individuals (41 deaths) in 1979 to 0.001 per 100,000 individuals (1 death) in 2017. APC was −11.1% (95% CI, −13.8% to −8.3%) in 1979 to 1990; 46.5% (95% CI, −16.6% to 157.3%) in 1990 to 1993; −61.6% (95% CI, −88% to 23%) in 1993 to 1996; and 1.1% (95% CI, −2.4% to 4.7%) in 1996 to 2017. ConclusionsMortality from acute epiglottitis decreased after widespread adoption of Hib vaccination in the US. Adults are now more likely than children to die of acute epiglottitis. Further research including multi-institutional cohort studies must be done to elucidate causative factors contributing to remaining cases of mortality.

Invasive &amp;lt;i&amp;gt;Haemophilus influenzae&amp;lt;/i&amp;gt; Type b (Hib) Infections in Children in the Pediatric Department of the University Hospital Gabriel Tour&amp;#233; (UH-GT)

Introduction: According to Mali’s National Immunization Center, the Haemophilus influenzae b (Hib) vaccine coverage rate was 90% in 2015. Our work aimed to study invasive bacterial infections due to Haemophilus influenzae type b in children aged 0 - 15 years hospitalized in the pediatrics department of the UH-GT. Method: We carried out a retrospective descriptive study from January 2017 to December 2018 (i.e. 2 years) among children aged 0 - 15 years and hospitalized for Haemophilus influenzae type b infection confirmed by culture (blood culture, Cerebro-spinal Fluid, and pleural and skin fluid). Results: Thirty-three cases of Hib infections were collected giving a frequency of 0.2% and the age group 3 months to 3 years was the most affected (72.73%). Children who received no vaccine accounted for 21.21%. The Cerebro-spinal Fluid culture and other samples (pleural and skin) identified the bacterium in 100% of cases, against 72.72% in the blood culture Meningitis was the most frequent pathology (78.79%) and the lethality was high (21.21%). Conclusion: Despite the introduction of the Hib vaccine in the routine immunization program in Mali, Hib infections remain with a high lethality linked to meningitis.

Bioproduction of Pharmaceuticalsbioprocess and the Developing World

Industrial animal cell culture is used to make many life-saving biopharmaceutical proteins, vaccines and cell therapies. Contamination of an industrial animal cell culture with a microorganism, such as a bacteria or virus, may occur through many means, for example, human error, inadequate aseptic protocols within biosafety level 2 (BSL-2) cabinets, failure of a processing step such as steam sterilization, loss of equipment integrity such as a crack in a disposable bioreactor, and/or introduction of a new adventitious agent not susceptible to current removal or inactivation procedures.The term microorganism is synonymous with the common term microbe (adjective microbial). In response to such contamination crises, many firms simultaneously implemented a large number of changes, in emergency mode, without first identifying the source of the problem or thus understanding the likely effectiveness of any given change. Over time, one key change or two typically solved the problem. Sometimes the source of the problem, as well as the key change(s) that actually solved the problem, were identified. Other times, no such clear identifications were made. In nearly all cases, the whole slew of changes were carried forward, even though some were likely ineffective, as well as a waste of time, money and focus. Yet many people in developing countries who could benefit from pharmaceuticals do not receive them. The failure of antiretroviral therapy to reach more than a tiny fraction of people with AIDS in developing countries has attracted widespread publicity, but even medicines that are far cheaper and easier to deliver are not reaching many of the people who need them. More than a quarter of children worldwide and over half of children in some countries do not receive the vaccines that are part of WHO’s Expanded Program on Immunization, although these cost only pennies per dose and require no diagnosis. Three million lives are lost annually as a result (World Bank, 2001a). Only a small fraction of children in poor countries receive the newer hepatitis B and Haemophilus influenzae b (Hib) vaccines, which cost a dollar or two per dose. One in four people worldwide suffer from intestinal worms, although treatments only need to be taken once or twice per year, have virtually no side effects, and cost less than a dollar per year. When asked which viral barriers proved impractical, company representatives had mixed responses. Filtration was characterized by some as expensive, having poor flux properties, or not suitable for use with bulk medium as some important media components were filtered out. Conversely, many interviewees stated that filtration was quite practical for small volumes, including heat-sensitive supplements, as well as hydrophobic additions. While certain respondents described HTST as quite practical and cost effective, others described it as ineffective due to cost, the large space it takes in the plant, and incompatibility with serum and hydrolysed. Since the first public disclosure of a large-scale adventitious agent contamination by Genentech, the topic of viral barriers for upstream processes has become more mainstream. However, while many mid-size or large companies have investigated the implementation of barriers and their associated challenges, some companies remain uncertain about the difficulties they may face if they would like to implement a barrier in upstream cell culture processes.

Epidemiologic study of Haemophilus influenzae causing invasive and non-invasive disease in Paraguay (1999–2017)

IntroductionHaemophilus influenzae is a cause of mild and severe invasive infections, especially among children under 5 years old. Serotype b (Hib) was very frequent before the introduction of the vaccine, which was introduced in Paraguay in 2004. MethodsA total of 523 isolates of H. influenzae obtained from 1999 to 2017 and referred to the National Reference Laboratory in Paraguay were studied by conventional microbiological methods and molecular techniques. ResultsThe most frequent serotype was non-typeable (HiNT) (51.8%; 271/523), followed by Hib (43%; 225/523), Hia and Hif (1.5%; 8/523, respectively), Hic (1%; 5/523), Hie (0.8%; 4/523), and Hid (0.4%; 2/523). A total of 48.4% invasive infections were caused by HiNT, and 46.1% by Hib; 88.6% of isolates corresponded to meningitis, 70.8% to sepsis and 50.9% to pneumonia in children under 5 years. A total of 84% (181/217) of isolates corresponded to invasive infections caused by Hib in children under 5 years, with the highest proportion observed between 2001 and 2003. The most prevalent biotypes were biotype I (29%), biotype II (12%), biotype III (24%), and biotype IV (13%). Among the total of isolates, 13% (68/523) of isolates were resistant to ampicillin. ConclusionAfter the introduction of the Hib vaccine in Paraguay, the number of invasive Hib cases decreased in children under 5 years old, although we observed an increase of HiNT in children over 5 years. Continuous surveillance is necessary in order to monitor the effectiveness of the vaccine and for the development of preventive interventions.

A model for the incremental burden of invasive Haemophilus influenzae type b due to a decline of childhood vaccination during the COVID-19 outbreak: A dynamic transmission model in Japan

BackgroundThe current coronavirus disease 2019 (COVID-19) outbreak has caused a persistent decline in childhood vaccination coverage, including Haemophilus influenzae type b (Hib) vaccine, in some countries. Our objective was to evaluate the impact of decreased Hib vaccination due to COVID-19 on invasive Hib disease burden in Japan. MethodsUsing a deterministic dynamic transmission model (susceptible-carriage-infection-recovery model), the incidence rates of invasive Hib disease in under 5 year olds in rapid vaccination recovery and persistent vaccination declined scenarios were compared for the next 10 years after 2020. The national Hib vaccination rate after the impact of COVID-19 reduced to 87% and 73% in 2020 from approximately 97% each in 2013–2019 for primary and booster doses. ResultsWhile the persistent decline scenarios revealed an increase in invasive Hib disease incidence to 0.50/100,000 children under 5 years old, the incidence of the rapid recovery scenario slightly increased with a consistent decline of incidence after 2021. The shorter the duration of the decline in vaccination rate was, the smaller the incremental disease burden observed in the model. Compared to the rapid recovery scenario, the permanent decline scenario showed a 296.87 cumulative incremental quality-adjusted life years (QALY) loss for the next 10 years. ConclusionsThe persistent decline of Hib vaccination rate due to COVID-19 causes an incremental disease burden irrespective of the possible decline of Hib transmission rate by COVID-19 mitigation measures. A rapid recovery of vaccination coverage rate can prevent this possible incremental disease burden.

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.

Infant Vaccinations among Mothers with Substance-Use Disorders: A Comparative Study.

Introduction: Infants of mothers with substance use disorder (SUD) are exposed to complex social environments and increased childhood health risks that can lead to adverse consequences throughout the lifespan. GunderKids, a voluntary, specialized, comprehensive pediatric care management program, was developed to mitigate many of these adverse consequences. Our organization is evaluating several clinical outcomes related to health and development in children born to women with SUD. The current study addressed the timeliness of vaccination coverage among these infants.Methods: This descriptive comparative preliminary study evaluated data of infants and their mothers with SUD who were previously identified during prenatal care visits either by self-report or by positive urine screens. Sociodemographic and vaccination data were extracted from a longitudinal master dataset of variables developed and maintained through retrospective review of electronic health records (EHRs) of these mothers and their infants. Timeliness of vaccination coverage of SUD-exposed infants participating in GunderKids was compared with that of SUD-exposed infants receiving standard pediatric care and was determined using a cumulative vaccinations method.Results: Overall, infants in the GunderKids group (n=50) had more timely vaccination coverage than those receiving standard pediatric care (n=20). Examples of timelier coverage included Haemophilus influenzae type b (Hib) at 4 months (P = .01; OR 4.3, 95% CI 1.4-13.4), for pneumococcal (P = .004; OR 6.6, 95% CI 1.8-23.8) and Hib (P = .004; OR 5.8, 95% CI 1.6-21.9) vaccinations at 15 months. More than 77% of GunderKids received all 6-month vaccinations in a timely manner compared with less than 45% of the standard care group; odds ratios suggest that GunderKids had 4.0-5.6 higher odds of receiving 6-month vaccinations.Conclusion: Vaccination coverage of infants participating in GunderKids was timelier than that of infants receiving standard pediatric care. Results suggest that specialized programs like GunderKids may assist in mitigating adverse health consequences and timeliness of vaccination coverage might be used as a proxy for measuring program effectiveness. Further investigation is recommended to determine clinical, individual, and organizational factors that influence parental behaviors and pediatric outcomes within SUD-exposed families.

NONTYPEABLE HAEMOPHILUS INFLUENZAE VENTRICULITIS COMPLICATED BY HYDROCEPHALUS IN A PATIENT WITH SICKLE CELL DISEASE

SESSION TITLE: Fellows Critical Care Posters SESSION TYPE: Fellow Case Report Posters PRESENTED ON: October 18-21, 2020 INTRODUCTION: Community-acquired purulent ventriculitis is very rare. We present a case of community-acquired purulent nontypeable Haemophilus influenzae meningitis with ventriculitis requiring cerebrospinal fluid diversion. CASE PRESENTATION: 46-year-old female with sickle cell disease presented in late fall with two days of headache, fever, and confusion. On arrival, she was febrile to 103F. On exam, she was agitated and unable to follow commands. Laboratory studies showed a white blood cell count of 23,000 (94% neutrophils), and procalcitonin 36 mg/dL. Blood and urine cultures were collected. The patient was given dexamethasone, vancomycin, meropenem (anaphylactic to penicillin), acyclovir, and doxycycline for community-acquired meningoencephalitis. CT Brain was consistent with cerebral edema. The patient required intubation for airway protection. Lumbar puncture showed purulent cerebrospinal fluid with opening pressure 21. CSF protein was 900, glucose 1, and 24,000 neutrophils. Gram stain showed numerous gram negative coccobacilli. MRI Brain showed layering debris within the ventricles and hydrocephalus. Due to intracranial hypertension, mannitol was given and an external ventricular drain placed. Blood and CSF cultures grew non-type B Haemophilus influenzae. The patient completed 14 days of ceftriaxone and was eventually extubated and ventriculostomy removed. DISCUSSION: Anatomical and functional asplenia poses high risk for invasive infections with encapsulated organisms such as S. pneumoniae, N. meningitidis, and H. influenzae. However, we present a case of community-acquired nontypeable H influenza meningitis with associated ventriculitis requiring CSF diversion. Nontypeable Haemophilus species lack a polysaccharide capsule for which splenic function provides less immunity. Serotype B was a common invasive pathogen prior to the institution of Hib vaccination in 1987. Nontypeable H influenzae is a common pathogen in otitis media in children and exacerbations of COPD in adults. Invasive diseases such as bacteremia and pneumonia are mostly seen at the extremes of age. Our patient is also unique in that she developed purulent ventriculitis complicated by hydrocephalus. Hydrocephalus complicates community-acquired bacterial meningitis in about 5% of cases and is associated with high mortality. H influenza ventriculitis is a rare condition and is mostly described in children and patient’s after neurosurgical CNS manipulation. CONCLUSIONS: We present a case of community-acquired nontypeable Haemophilus influenzae meningitis with ventriculitis. This case is unique in that the patient had purulent ventriculitis required CSF diversion. Community-acquired purulent ventriculitis is very rare without neurosurgical manipulation or indwelling CSF drainage catheters. Also, nontypeable H flu is an uncommon pathogen in the central nervous system and usually affects the respiratory tract. Reference #1: Eldere, J.V., Slack, M, Ladhani,Shamez, Cripps, A. Non-typeable Haemophilus infl uenzae, an under-recognised pathogen.Lancet Infect Dis 2014; 14: 1281–92. Reference #2: Bakaletz, L, Novotny, L. NontypeableHaemophilusinfluenzae(NTHi). Trends in Microbiology, August 2018,Vol. 26,No.8. Reference #3: Langereis, J, Jonge, M. Invasive Disease Caused by Nontypeable Haemophilus influenzae. Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 21, No. 10, October 2015. DISCLOSURES: No relevant relationships by Andrew Holt, source=Web Response No relevant relationships by Scott Sinclair, source=Web Response

Invasive Haemophilus influenzae Infections in Germany After the Introduction of Routine Childhood Immunization, 2001-2016.

Background Haemophilus influenzae (Hi) serotype b (Hib) vaccination was introduced in Germany in 1990. This study presents a comprehensive overview on the burden of invasive Hi infections for 2001–2016, including serotype distribution and ampicillin resistance.MethodsNationwide data from statutory disease surveillance (2001–2016) were linked with laboratory surveillance data (2009–2016). Besides descriptive epidemiology, statistical analyses included multiple imputation to estimate secular trends.ResultsIn 2001–2016, 4044 invasive Hi infections were reported. The mean incidence was 3.0 per million inhabitants, higher in males (3.2 vs 2.9 in females) and in the age groups <1 year (15.2) and ≥80 years (15.5). Nontypeable Hi (NTHi) caused 81% (n = 1545) of cases in 2009–2016. Of capsulated cases, 69% were serotype f and 17% serotype b. Of Hib cases eligible for vaccination, 10% (3/29) were fully vaccinated. For 2009–2016, significant increasing trends were observed for NTHi and Hif infections in the age groups <5 years and ≥60 years and for ampicillin resistance in NTHi.ConclusionsThis is one of the most comprehensive Hi data analyses since the introduction of Hib vaccines. NTHi and Hif cause an increasing disease burden among elderly patients and infants. Ampicillin resistance in NTHi must be considered in the treatment of invasive Hi infections.

Microbiological Characterization and Antibiotic Susceptibility Pattern of Haemophilus Influenzae Isolates from a Tertiary Care Centre in South India

Haemophilus are fastidious Gram negative bacilli, which require factor X (hemin), factor V (NAD), or both for their growth. Haemophilus influenzae is the type species, and is considered to be the most pathogenic. They are associated with many invasive infections including meningitis, epiglottitis, pneumonia, and otitis media. Serotype b is most commonly associated with infections. Haemophilus species isolated from patients in a tertiary care centre in South India were studied. Identification, serotyping and biotyping were done and antibiotic susceptibility test was performed. The incidence of H. influenzae infections in our study was 65.3 cases/100,000 persons. Serotype b was the most common (66.67%), followed by non typeable H.influenzae (NTHi) (25%). Most isolates from adults were type b, while all isolates from pediatric population were non typeable. The most common biotype was type II, followed by type I and type III. Three of 24 isolates were β lactamase producers (12.5%). One isolate was β lactamase negative Ampicillin resistant (BLNAR). Resistance to ampicillin was 16.67%. Resistance to cephalosporins and fluoroquinolones was low (4-10%). Co-trimoxazole resistance was found to be very high (75%). All isolates were susceptible to azithromycin, tetracycline, chloramphenicol and meropenem. No isolates of H.influenzae type b were obtained from the paediatric population which may be due to the introduction of Hib vaccine. The increase in resistance to commonly used antibiotics is worrisome, especially penicillins and co-trimoxazole. Use of co-trimoxazole in empirical therapy of upper and lower respiratory tract infections has a high chance of failure in the current scenario.

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

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. We performed a laboratory case report based-study of suspected bacterial meningitis in Northern Tunisia from January 2014 to June 2017. 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. 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. 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.

Update on adherence to a vaccination protocol for invasive bacterial diseases in HIV patients

Abstract HIV+ patients present an increased risk of vaccine-preventable invasive bacterial diseases (IBDs), infections characterized by high lethality and frequency of serious complications. Considering that these patients frequently have to face a complex clinical-care pathway, it has been necessary to design a clear vaccination protocol in order to prevent IBDs and to guarantee adequate patient adherence. In 2013 the Local Health Unit Company of Modena's Public Health Department and the University Hospital of Modena developed a shared vaccination protocol to prevent the most common causes of IBDs: Neisseria meningitidis, Streptococcus pneumoniae and Haemophilus influenzae type B. The protocol applies to HIV+ patients receiving antiretroviral therapy who have a CD4 + cell count &amp;gt; 200 cells / µL. It provides the following vaccination schedule: administration of PCV13 + MenACWY vaccines; after 15 days administration of MenB + Hib vaccines; after 45 days administration of the MenB vaccine; after at least 60 days, administration of PPSV23 + MenACWY vaccines. The first vaccination counselling is proactively carried out by the Public Health Department healthcare workers and takes place at the Infectious Diseases Division in order to improve patient acceptance and adherence to the protocol. From October 2013 to January 2020, 503 HIV+ patients (378 males and 125 females) were vaccinated. Among these patients, 338 (67.2%) completed the vaccination schedule; 110 (21.9%) interrupted the schedule, 34 (6.7%) have a vaccination schedule currently underway and 21 (4.2%) never started the planned vaccination protocol. Overall, the percentage of patients who have completed the vaccination schedule or have scheduled appointments is 73.9%. The data analysis shows a high adherence to the protocol thanks to the collaboration between public health and infectious disease specialists, which improves the compliance of patients with a complex clinical-care pathway. Key messages HIV patients present an increased risk of IBDs and require a tailor-made vaccination protocol. Collaboration between specialists improves the compliance of patients with a complex clinical-care pathway.

COVID-19 infection presenting with acute epiglottitis.

In this case report, we present a novel presentation of acute epiglottitis in a patient with severe acute respiratory syndrome—coronavirus 2 (SARS-CoV-2) who presented to the emergency room in extremis and respiratory failure requiring emergent cricothyrotomy. Epiglottitis has become less common since the introduction and widespread use of the Haemophilus influenzae type B (Hib) vaccine. This reduction in cases has shifted demographics of the disease from the pediatric population towards adults with comorbid conditions. Interestingly there is a high degree of overlap between many of the comorbidities between epiglottitis and COVID-19. The novel severe acute respiratory syndrome—coronavirus 2 (SARS-CoV-2), also referred to as coronavirus disease 19 (COVID-19), has been reported to affect the gastrointestinal tract and neural tissue and has been implicated in necrotizing encephalitis. We report the first known case of the novel SARS-CoV-2 virus presenting with acute epiglottitis.

Respiratory Carriage of Haemophilus influenzae Associated with Hib Vaccine in Jordanian Children

Abstract Objective Haemophilus influenzae type b (Hib) is the most virulent serotype that colonizes the upper respiratory tract of children. After introducing Hib conjugate vaccine, Hib has become almost entirely replaced by nontypeable H. influenzae (NTHi) strains. This study investigated the incidence of NTHi, which may cause serious sporadic body infections. Methods A total of 300 nasal and throat swab samples were obtained from children aged 6 to 60 months, who visited outpatient pediatric clinics of Jordan University Hospital and Al-Bashir Hospital, Amman, Jordan. Colonies resembling H. influenzae were tested by conventional laboratory tests including Gram staining and antibiotic susceptibility. The 16S rRNA and bexA (capsulation gene) were amplified from the extracted DNA. Swabs (n = 100) were delivered to the laboratory in transport media. After initial culture, DNA was extracted directly and tested by conventional polymerase chain reaction (PCR) employing actin beta primers for assessing the housekeeping gene, followed by quantitative PCR (qPCR) against Hib-specific primers. Results A total of 31/300 (10.33%) of H. influenzae isolates were recovered by culture and confirmed by PCR for 16S rRNA; 96.77% (30/31) were NTHi, and only one isolate was Hib. This isolate was confirmed by detection region II of the cap locus of Hib gene by qualitative TaqMan real-time qPCR. Antibiotic resistance among NTHi to ampicillin and erythromycin was 50.0 and 20.0%, respectively. Conclusion The conjugated Hib vaccine almost eliminated the occurrence of Hib in the upper respiratory tract of the Jordanian children, while NTHi colonization was found in 10% of them.

Invasive Haemophilus influenzae type b (Hib) disease in children in Italy, after 20 years of routine use of conjugate Hib vaccines

Haemophilus influenzae serotype b (Hib) was the leading cause of bacterial meningitis in children before the implementation of infant immunization with conjugate Hib vaccines. Despite the effectiveness of the vaccine, invasive Hib disease cases (i.e. isolation of Hib from a normally sterile site) are still reported in children.All invasive Hib disease cases in children ≤ 15 years reported through the National Surveillance System of Invasive Bacterial Disease, during 2012–2018 in Italy, were analyzed. Hib PCR-confirmed isolates were subjected to MLST and PFGE analysis. The number of copies of the capb locus, a virulence factor potentially contributing to true vaccine failures (TVFs), was determined by Southern blot analysis. Vaccine effectiveness (VE) was determined using a multiple Poisson regression model.31 cases of invasive Hib disease in children were reported. Fourteen children were vaccinated (TVFs), 14 were unvaccinated and 2 partially vaccinated (vaccination status was unknown for 1 case). The median age of children was 12 months (range 3 months-15 years). A decrease in vaccination coverage was observed in 2014–2016 (source Ministry of Health), and a rise in incidence was documented from 2016 until 2018, especially in children < 5 years. Vaccine effectiveness was estimated to be 83% (95% CI:45–95).24 isolates were available. The predominant ST was ST6 (70.8%). Cluster analysis of ST6 isolates by PFGE identified five variants. Six isolates (25%) contained multiple copies of the capb locus distributed among TVFs (30%) and unvaccinated children (16.7%).Our data show that both failures to vaccinate and TVFs are associated with invasive Hib disease in children in Italy, during the vaccination era. Most cases in children ≤ 2 years were vaccine-preventable, since they occurred in unvaccinated subjects (13/21 cases, 62%). No host predisposing factors for TVF were recognized. TVFs were not significantly associated with either specific genotypes or amplification status of the capb locus.