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Background Reduction in detection of asymptomatic carriage of Haemophilus influenzae type b (Hib) can be used to assess vaccine impact. In Nepal, routine vaccination against Hib in children at 6, 10, and 14 weeks of age was introduced in 2009. Before vaccine introduction, Hib carriage was estimated at 5.0% among children aged Methods A total of 666 oropharyngeal swabs were collected between August and December 2018 from healthy children between 6 months and 5 years of age attending the vaccination clinic at Patan Hospital, Kathmandu, Nepal. Of these 666 swabs, 528 (79.3%) were tested for Hib by culture. Demographic and vaccination data were collected. Results Among 528 swabs tested for Hib, 100% came from fully vaccinated children. No swabs were positive for Hib (95% confidence interval, .0–.7). The absence of Hib in 2018 suggests vaccine-induced protection against Hib carriage 9 years after vaccine introduction. Conclusions Following 3 doses of pentavalent DTP-Hib-HepB vaccine, Hib carriage in children under the age of 5 years in Nepal is no longer common. Ongoing high coverage with Hib vaccine in early childhood is expected to maintain protection against Hib disease in Nepal.

BackgroundGlobally,Haemophilus influenzaetype b (Hib) vaccine has substantially reduced the burden of Hib invasive disease. However, China remains the only country not to include Hib vaccine into its national immunization program (NIP), although it accounts for 11% of global Hib deaths. We aimed to assess the cost-effectiveness of including Hib vaccine in China’s NIP at the national and provincial levels.MethodsUsing a decision-tree Markov state transition model, we estimated the cost-effectiveness of Hib vaccine in the NIP compared to thestatus quoof Hib vaccine in the private market for the 2017 birth cohort. Treatment costs and vaccine program costs were calculated from Chinese Center for Disease Control and Prevention (CDC) and national insurance databases. Epidemiological data and other model parameters were obtained from published literature. Cases and deaths averted, quality-adjusted life years (QALYs) gained, and incremental cost-effectiveness ratios (ICER) were predicted by province. Deterministic and probabilistic sensitivity analyses were performed to explore model uncertainty.ResultsIncluding Hib vaccine in the NIP was projected to prevent approximately 2700 deaths (93% reduction) and 235,700 cases of Hib disease (92% reduction) for the 2017 birth cohort at the national level. Hib vaccine was cost-effective nationally (US$ 8001 per QALY gained) compared to the GDP per capita and cost-effective in 15 of 31 provinces. One-way and scenario sensitivity analyses indicated results were robust when varying model parameters, and in probabilistic sensitivity analysis, Hib vaccine had a 64% probability of being cost-effective nationally.ConclusionIntroducing Hib vaccine in China’s NIP is cost-effective nationally and in many provinces. Less socioeconomically developed provinces with high Hib disease burden and low access to Hib vaccine in the current private market, such as those in the west region, would benefit the most from adding Hib vaccine to the NIP. In the absence of a national policy decision on Hib vaccine, this analysis provides evidence for provincial governments to include Hib vaccine into local immunization programs to substantially reduce disease burden and treatment costs.

Objective This study aimed to compare the epidemiology of bacterial meningitis (BM) before and after vaccination, and identify possible risk factors associated with mortality. Methods The medical and microbiologic records of children (1 month–18 years) with a discharge diagnosis of BM in a third level children's hospital in Mexico from 1990 to 2018 were reviewed. The epidemiology, pathogens, and outcomes were compared before and after introducing Haemophilus influenzae type b (Hib) and pneumococcal conjugate vaccines to the Mexican immunization schedule. Risk factors associated with mortality were determined. Results In the 28-year period, 226 cases with BM were included 55.8% (1990–1999), 27.4% (2000–2008), and 16.8% (2009–2018) (p = 0.0001). The most frequent pathogen was Hib, documented in 39% of cases. There was a reduction in neurological complications after introducing the Hib conjugate vaccine (59 vs. 39%; p = 0.003) and sequelae after the Streptococcus pneumoniae conjugate vaccine (43 vs. 35%; p = 0.05). Independent risk factors associated with mortality were coma (odds ratio [OR]: 15 [2.9–78]), intracerebral bleeding (OR: 3.5 [1.4–12]), and pneumococcal meningitis (OR: 9.4 [2.2–39]). Conclusion Since the introduction of Hib and pneumococcal conjugate vaccines to the national immunization schedule, there was a reduction in BM cases, mainly associated with the Hib vaccine, with the consequent reduction of neurological complications and sequelae.

Introduction Haemophilus 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. Methods A 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. Results The 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. Conclusion After 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.

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.

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.

A 40-year-old man with systemic lupus erythematosus taking consecutive oral corticosteroids developed a high-grade fever and disorder of consciousness following acute rhinitis. Haemophilus influenzae type f (Hif) was found and isolated from the blood and cerebrospinal fluid by culture, leading to a diagnosis of meningitis. The prevalence of H. influenzae type b (Hib) infections has decreased due to routine immunization. As a result, the prevalence of invasive non-Hib, including Hif infection, is increasing as a common H. influenzae infection in children and adults. Physicians should be aware of non-Hib H. influenzae infection, even though the Hib vaccine is widely used in Japan.

Background The DTaP-IPV/Hib combination vaccine can replace the acellular tetanus vaccine, polio vaccine, and the Haemophilus influenzae type B vaccine. Data on the safety of DTaP-IPV/Hib vaccines are required. We aimed to evaluate the safety of the vaccination program. Methods Using the National Adverse Events Following Immunization (AEFI) surveillance system (CNAEFIS) in Guangzhou, China, a retrospective study was performed from May 11, 2011, to December 31, 2017. There were 376 cases of adverse events after vaccination with the DTaP IPV/Hib vaccine. The primary analysis indicators were the number of vaccines used, the number of AEFI reports received, and the reporting rate (per 100,000). Results From May 1, 2011, to December 31, 2017, 516,000 doses of vaccine were inoculated, and 376 cases of adverse reactions were reported; the reporting rate was 72.8 per 100,000 vaccines. There were eight cases of serious AEFIs (1.5 per 100,000), with four cases of thrombocytopenic purpura (0.8 per 100,000); three cases of cyanosis of the lips, stiffness, and flexion of limbs, and convulsions (0.6 per 100,000); and one case of a high fever (0.2 per 100,000). The highest incidence of AEFIs occurred after the fourth dose (n = 207, 55.0%, 40.1 per 100,000), followed by the first dose (n = 81, 21.5%, 15.7 per 100,000), second dose (n = 48, 12.8%, 9.3 per 100,000) and third dose (n = 40, 10.6%, 7.7 per 100,000). The AEFI incidence was higher after injection of the vaccine into the deltoid muscle of the upper arm (n = 276, 73.4%, 53.5 per 100,000) than after injection of the vaccine into the thigh (n = 100, 26.6%, 19.4 per 100,000). There was a significant difference between AEFIs after injection into the deltoid of the upper arm deltoid and the thigh (x2 = 164.8, P Conclusions Most of the reported AEFIs after DTaP-IPV/Hib vaccination are not serious. There were four cases of TP in this study; vaccination may be a rare cause of thrombocytopenic purpura.

Individuals with immunosuppressive condition have a high risk of invasive Haemophilus influenzae type b (Hib) infection. In Japan, routine Hib vaccination program for children under 5 years old was introduced in December 2008. However, the national policy does not make provision for individuals aged ≥5 years who have medical conditions associated with a high risk of invasive Hib disease to receive Hib vaccine. We measured serum anti-polyribosylribitol phosphate specific (anti-PRP) antibodies to Hib in patients aged ≥5 years with hematological malignancies and asplenia and evaluated their levels of anti-PRP antibodies in post administration of Hib vaccine era. A total of 65 patients (48 with hematological malignancies, and 17 with asplenia) were included in this study, of which 84% had not received Hib vaccine. In addition, 95.4% had short-term protective levels of anti-PRP antibodies (defined as ≥0.15 μg/mL) and 41.5% had long-term protective levels of anti-PRP antibodies (defined as ≥1.0 μg/mL). Five patients had low anti-PRP antibody levels despite a history of Hib vaccination. Our results suggest that young patients with underlying diseases such as hematological malignancies and asplenia may be at risk of invasive Hib disease. Hence, we recommend they should receive Hib vaccines even if they are over the age limit for routine Hib vaccination program.

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.

The purpose of this study was to investigate H. influenzae epidemiology in the Republic of Ireland. We performed serotyping, multi-locus sequence typing (MLST) and susceptibility testing on H. influenzae isolates received by the Irish Meningitis and Sepsis Reference Laboratory from 2010 to 2018. Three hundred sixty-seven invasive and 41 non-invasive infection (NII) isolates were received. Invasive isolates were mostly recovered from paediatric (21%) and elderly (42%) populations. Invasive disease was more prevalent in females of childbearing age (72%) compared with males the same age (28%). Non-typeable H. influenzae (NTHi) predominated among invasive (83%) and NII (95%). Invasive Hib disease isolates were infrequent (4%, n = 15). Among invasive disease, Hif was the commonest encapsulated serotype (10%, n = 37), and the only encapsulated serotype detected in NII (5%, 2/41). The first PCR-confirmed serotypes d and a in Ireland were characterised among invasive disease in 2017 and 2018, respectively. MLST revealed a diverse NTHi population, while encapsulated serotypes were clonal. Sequence type (ST) 103 (n = 14) occurred exclusively in invasive NTHi disease. Ampicillin resistance (AmpR) was 18% among invasive isolates and 22% in NII. β-Lactamase production was the main source of ampicillin resistance in invasive and NII isolates. We detected β-lactamase negative ampicillin resistance (BLNAR) among invasive isolates. We report an NTHi fluoroquinolone-resistant clone: ST1524 among invasive (n = 2) and NII isolates (n = 2). The Hib vaccine has positively impacted on Hib disease in Ireland, given the low frequency of Hib. The dominance of NTHi, emergence of serotypes a and d and BLNAR suggest a changing H. influenzae epidemiology in Ireland.

Background Globally, pneumonia is the leading cause of death among children. Few data exist regarding the effect of Haemophilus influenzae type b (Hib) vaccine and 13-valent pneumococcal conjugate vaccine (PCV-13) on the burden of childhood pneumonia in African settings. Methods We collected data on children aged 1 to 59 months at 3 hospitals in Botswana. Hib vaccine and PCV-13 were introduced in Botswana in November 2010 and July 2012, respectively. We compared pneumonia hospitalizations and deaths prevaccine (January 2009 to October 2010) with postvaccine (January 2013 to December 2017) using seasonally adjusted, interrupted time-series analyses. Results We identified 6943 pneumonia hospitalizations and 201 pneumonia deaths. In the prevaccine period, pneumonia hospitalizations and deaths increased by 24% (rate, 1.24; 95% CI, .94–1.64) and 59% (rate, 1.59; 95% CI, .87–2.90) per year, respectively. Vaccine introduction was associated with a 48% (95% CI, 29–62%) decrease in the number of pneumonia hospitalizations and a 50% (95% CI, 1–75%) decrease in the number of pneumonia deaths between the end of the prevaccine period (October 2010) and the beginning of the postvaccine period (January 2013). During the postvaccine period, pneumonia hospitalizations and deaths declined by 6% (rate, .94; 95% CI, .89–.99) and 22% (rate, .78; 95% CI, .67–.92) per year, respectively. Conclusions Pneumonia hospitalizations and deaths among children declined sharply following introduction of Hib vaccine and PCV-13 in Botswana. This effect was sustained for more than 5 years after vaccine introduction, supporting the long-term effectiveness of these vaccines in preventing childhood pneumonia in Botswana.

The combined vaccine against diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis, and Haemophilus influenzae b (DTPa-HBV-IPV/Hib, Infanrix Hexa, GSK) has been used for childhood immunization in Australia according to a two-, four-, six-month schedule since 2009. We reviewed data available in the Australian National Notifiable Diseases Surveillance System, annual vaccination coverage reports, the Database of Adverse Event Notifications, and peer-reviewed literature to assess vaccine coverage rates, incidence of all six vaccine preventable diseases, and the safety profile of DTPa-HBV-IPV/Hib vaccine in Australian infants over a period of ten years of exclusive use. Between 2009 and 2018 vaccine coverage for infants aged 12 months increased from 91.7% to 94.0% and from 84.9% to 92.6% for all and for Indigenous infants, respectively. Over the same time period, there were no reports of poliomyelitis, diphtheria or tetanus in infants

We describe a patient with invasive Haemophilus influenzae type b (Hib) infection despite being completely immunized by a conjugate Hib vaccine. Although Hib vaccination has contributed to significant reduction in invasive Hib infection, there are some case reports of invasive Hib infections despite immunization. I mmunoglobulin (Ig) deficiency is the main cause of primary vaccine failure, and IgG2 subclass deficiency is known to be the leading cause. A previously healthy 13-month-old boy visited the outpatient clinic with a 5-day history of fever (40.0 °C), cough, and vomiting, and was diagnosed with bacterial meningitis, purulent pericarditis, and arthritis. Hib was recovered from blood, cerebrospinal fluid, and pericardial fluid. Immunological examination revealed subnormal IgG and IgA titers at 13 and 17 months of age. Serum IgG2 titer was recovered at 17 months of age despite being low at 13 months. Comprehensive gene analysis for primary immunodeficiency syndromes (primary antibody deficiency, common variable immunodeficiency, and toll-like receptor abnormalities) were negative. The antibody titer against Hib [anti-polyribosylribitol phosphate (PRP) antibody] was lower than the long-term protective titer (1.0 μg/ml) at 13 months of age, but was reactively increased to 2.38 μg/mL two months after booster immunization. Transient hypogammaglobulinemia of infancy (THI) is described as an accentuation and prolongation of the physiologic Ig nadir that is normally observed during infancy and defined as low IgG and IgA levels in the first three years of life. We speculate that he developed an invasive Hib infection as a result of primary Hib vaccine failure caused by THI.

In every year, up to one million children die due to pneumococcal disease. Children infected with Human Immunodeficiency Virus (HIV) are mostly affected, as they appear to have higher rates of pneumococcal carriage and invasive disease. Successful immunity is dependent on mounting a sufficient immune response to the vaccine. We conducted a double blinded crossover randomised controlled trial to determine the serum antibody response (≥4-fold and geometric mean concentration) to pneumococcal vaccine (PCV13) serotypes at 3 months after second vaccination. We also determined the number and proportion of children carrying new (not present at baseline) vaccine serotypes of S. pneumoniae isolated from nasopharynx at 6 months post initial vaccination in recipients of Prevenar13® compared with those given Haemophilus influenzae-type b (Hib) vaccine (control). The study was conducted at St Augustine's also known as Teule Hospital in Muheza, Tanga Tanzania. 225 HIV infected children aged 1-14 years were enrolled from Jan 2013 to Nov 2013 and randomised to Prevenar13® or Hib vaccines each given at baseline and 2-3 months later. Nasopharyngeal and serum samples were collected at baseline and 4-6 months later. Serotyping was done by Quellung Reaction using Staten antisera. Serum antibodies were ELISA quantified. The study revealed a non-significant reduction in the acquisition of new vaccine serotypes of S. pneumoniae in the recipients of PCV13 by nearly a third compared to those who received Hib vaccine. The vaccine efficacy was 30.5% (95% confidence interval [CI] –6.4-54.6%, P = 0.100)]. The antibody response was not enough to induce a 4-fold rise in GMC in 7 of the 13 vaccine serotypes. When combining the effects of preventing new acquisition and clearing existing vaccine type carriage, the overall efficacy was 31.5% (95% CI 1.5-52.4%, P = 0.045). In the PCV13 group, the proportion of participants carrying vaccine serotype was significantly lower after 2 doses of PCV13 (30%; 32/107), compared with the baseline proportion (48%; 51/107). The introduction of PCV13 targeting HIV-positive children in a setting similar to Tanzania is likely to be associated with appreciable decrease in the acquisition and carriage of pneumococci, which is an important marker of the likely effect of the vaccine on pneumococcal disease.Clinical Trial Registrationhttps://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=335579, identifier ACTRN12610000999033.

Haemophilus influenzae type b (Hib) are one of most dangerous microbes that occupies the paediatric nasopharyngeal as a commensal opportunistic bacterium, which may lead to meningitis in uncontrolled infection. Colonisation of pharyngeal tissues is the starting point for most H. influenzae infections, which may develop into invasive diseases, such meningitis. The vaccination against Hib in specific, as well as against most of vaccines preventable diseases; in general, play a major role in reducing children (< 5 years old) Hib meningitis from 57/100,000 to the lowest known Hib meningitis incidents in the history. First invented Hib vaccine was licensed in 1985 and contained Hib capsular polysaccharide (CPS); afterward, conjugate vaccines have been innovated and licensed on the road to improve Hib vaccine efficacy. Polyribosylribitol phosphate (PRP) is the main vaccine unite structure. Since anti-CPS antibodies in the serum reflect the extent of the acquired immunity against Hib infections, the concentration of ⩾ 0.15 g/ml of anti-CPS is believed to be an indicator for short-term protection from invasive Hib diseases, whereas one-month post-completion of primary Hib immunization concentration of ⩾ 1.0 g/ml is trusted to be immunological protective. As considered that serum anti-CPS antibodies are effectively linked to protection, the evaluation of antibodies concentration and reconsideration of published worldwide populations antibodies concentration are consider vital strides on the way to accurate valuation of Hib immunity that induced by vaccination; either direct or herd. As documented, some populations; worldwide, still susceptible to invasive Hib infections. Several populations worldwide remain vulnerable to Hib-related infections. We believe that up-to-date review article regarding circulated Hib immunology, represented in anti-Hib antibodies and worldwide Hib incidences will provide a precious information for microbiologists, public health officials, epidemiologists, immunologists, and strategic preventive healthcare executives.

Background: \ud India accounts for a disproportionate burden of global childhood illnesses. To inform policies and measure progress towards achieving child health targets, we estimated the annual national and state-specific childhood mortality and morbidity attributable to Streptococcus pneumoniae and Haemophilus influenzae type b (Hib) between 2000 and 2015.\ud \ud Methods: \ud In this modelling study, we used vaccine clinical trial data to estimate the proportion of pneumonia deaths attributable to pneumococcus and Hib. The proportion of meningitis deaths attributable to each pathogen was derived from pathogen-specific meningitis case fatality and bacterial meningitis case data from surveillance studies. We applied these proportions to modelled state-specific pneumonia and meningitis deaths from 2000 to 2015 prepared by the WHO Maternal and Child Epidemiology Estimation collaboration (WHO/MCEE) on the basis of verbal autopsy studies from India. The burden of clinical and severe pneumonia cases attributable to pneumococcus and Hib was ascertained with vaccine clinical trial data and state-specific all-cause pneumonia case estimates prepared by WHO/MCEE by use of risk factor prevalence data from India. Pathogen-specific meningitis cases were derived from state-level modelled pathogen-specific meningitis deaths and state-level meningitis case fatality estimates. Pneumococcal and Hib morbidity due to non-pneumonia, non-meningitis (NPNM) invasive syndromes were derived by applying the ratio of pathogen-specific NPNM cases to pathogen-specific meningitis cases to the state-level pathogen-specific meningitis cases. Mortality due to pathogen-specific NPNM was calculated with the ratio of pneumococcal and Hib meningitis case fatality to pneumococcal and Hib meningitis NPNM case fatality. Census data from India provided the population at risk.\ud \ud Findings: \ud Between 2000 and 2015, estimates of pneumococcal deaths in Indian children aged 1–59 months fell from 166 000 (uncertainty range [UR] 110 000–198 000) to 68 700 (44 600–86 000), while Hib deaths fell from 82 600 (52 300–112 000) to 15 600 (9800–21 500), representing a 58% (UR 22–78) decline in pneumococcal deaths and an 81% (59–91) decline in Hib deaths. In 2015, national mortality rates in children aged 1–59 months were 56 (UR 37–71) per 100 000 for pneumococcal infection and 13 (UR 8–18) per 100 000 for Hib. Uttar Pradesh (18 900 [UR 12 300–23 600]) and Bihar (8600 [5600–10 700]) had the highest numbers of pneumococcal deaths in 2015. Uttar Pradesh (9300 [UR 5900–12 700]) and Odisha (1100 [700–1500]) had the highest numbers of Hib deaths in 2015. Less conservative assumptions related to the proportion of pneumonia deaths attributable to pneumococcus indicate that as many as 118 000 (UR 69 000–140 000) total pneumococcal deaths could have occurred in 2015 in India.\ud \ud Interpretation: \ud Pneumococcal and Hib mortality have declined in children aged 1–59 months in India since 2000, even before nationwide implementation of conjugate vaccines. Introduction of the Hib vaccine in several states corresponded with a more rapid reduction in morbidity and mortality associated with Hib infection. Rapid scale-up and widespread use of the pneumococcal conjugate vaccine and sustained use of the Hib vaccine could help accelerate achievement of child survival targets in India.\ud \ud Funding: \ud Bill & Melinda Gates Foundation.

Haemophilus influenzae type b (Hib) affects 337,000 Indian children every year. A vaccine against Hib was introduced in 2011 as part of the pentavalent vaccine and scaled up nationwide. This study investigated the associations between Hib vaccination and child anthropometry, cognition, and schooling outcomes in India. We used longitudinal survey data and employed propensity score matching to control for observed systematic differences between children who reported receipt or nonreceipt of Hib vaccine before age 6 years (n = 1824). Z‐scores of height‐for‐age (HAZ) and BMI‐for‐age (BMIZ), percentage scores of English, mathematics, reading, and Peabody Picture Vocabulary tests, and attained schooling grade of children were examined. Hib‐vaccinated children had 0.25 higher HAZ, scored 4.09 percentage points (pp) higher on the English test and 4.78 pp higher on the mathematics test, and attained 0.16 more schooling grades than Hib‐unvaccinated children at age 11–12 years. At age 14–15 years, they had 0.18 higher HAZ, scored 3.63 pp higher on the reading test and 3.22 pp higher on the mathematics test, and attained 0.15 more schooling grades than Hib‐unvaccinated children. The findings indicate potential long‐term health, cognitive, and schooling benefits of the Hib vaccine, subject to the effect of unobserved confounding factors.

Background Use of Haemophilus influenzae type b conjugate vaccine is effective in reducing the disease burden, but its coverage in China is unclear. The aim of this meta-analysis is to assess the coverage of Hib conjugate vaccines in children in Mainland China. Methods We systematically searched Pubmed, Web of Science, Medline, CNKI and Wanfang to identify studies assessing the coverage of Hib vaccine in Chinese children. Random-effects models were used to obtain pooled estimates for Hib vaccine coverage and analyzed heterogeneity with meta-regression and subgroup analyses. Results Thirty-three studies that included 7,227,480 subjects in 12 provinces met our inclusion criteria. The pooled overall coverage of Hib conjugate vaccine was 54.9% [95% confidence interval (CI): 52.9-57.0]. The pooled coverage for the nonlocal population (54.3%; 95% CI: 52.4-56.3) was lower than that for the local residents (62.0%; 95% CI: 58.4-65.6). The region-pooled coverage was higher in the east of China (59.7%; 95% CI: 57.3-62.1) than in the central and west parts of the country (48.5%; 95% CI: 40.6-56.4). Overall, 26.7% (95% CI: 20.1-33.2) had 1 dose only, 14.8% (95% CI: 10.0-19.6%) had 2 doses, 13.5% (95% CI: 9.1-17.8) had 3 doses and 14.3% (95% CI: 9.7-18.9) had 4 doses. Conclusions We found a low coverage of Hib conjugate vaccine, particularly for the nonlocal children and those living in the central and west parts of China. Including Hib vaccine into the national immunization program is recommended to reduce disparities in vaccination coverage.

Background Haemophilus influenzae type b (Hib) vaccine is effective in reducing the burden of Hib related diseases, but little is known about factors influencing the uptake of Hib vaccine. This study aimed to assess the uptake of Hib vaccination and its associated factors in Shanghai City, China. Methods We used data from a retrospective cohort of 183,246 children born in 2012–2016 obtained from the Shanghai Immunization Program Information System, which provided information on the uptake of Hib vaccination. We conducted a cross-sectional study of 451 children to collect information on demographic and other factors that might be associated with Hib vaccination. Results In the retrospective cohort study, the proportions of Hib dose-1 coverage, vaccination completion and timeliness were 67.7, 52.2 and 29.4%, respectively. These measures were better among local children and increased with birth year, while there were regional differences. Hib vaccine uptake was significantly associated with maternal occupation (non-health vs health workers, OR = 2.33, 95% CI: 1.32–4.13, P = 0.004) and caregivers’ awareness of Hib (yes vs no, OR = 1.75, 95% CI: 1.12–2.74, P = 0.013). Conclusions We found low levels of coverage of dose-1 Hib vaccine, timeliness and completion, suggesting inadequate protection against Hib disease for children in Shanghai. Non-local children and those of health workers should be targeted for interventions. The inclusion of Hib vaccine into the national immunization program could help improve the uptake of Hib vaccines.

BACKGROUND The 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. METHODS In 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. RESULTS Six 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

Background. Haemophilus influenzae (H. influenzae) strains, which commonly reside as commensals within the human pharynx and can remain as an asymptomatic carrier, but become invasive leading to pneumonia, septic arthritis, or meningitis. The Pentavac (pentavalent vaccine, manufactured by India, SII (DTwP-HepB-Hib)) was introduced to the Iranian National Immunization Plan in November 2014. The aim of this study is to investigate H. influenzae type b (Hib) carrier rate among children under 6 years old in Tehran. Methods. This cross-sectional study was performed on 902 children including vaccinated/unvaccinated in the age of 6 months to 6 years, in Tehran. Sampling was performed from July 2019 to September 2019. Nasopharyngeal samples were taken from children by sterile swab. The PCR method was used to extract DNA. Then, all H. influenzae isolates were initially confirmed by molecular tests. BexA was used to distinguish typeable H. influenzae strains from nontypeable Haemophilus influenzae (NTHi). Results. A total of 902 children were enrolled in the study: 452 were female (51%). H. influenzae carriage rate was 267 (29%), of that 150 samples (16.6%) were typeable. The nasopharyngeal Hib carrier rate in the children was 2.6% (24/902). 262 cases did not receive Hib vaccine. Analysis in nonnursery’s children aged 4 to 6 (unvaccinated) years showed that the lower educational level of father, mother, and family number correlated with increased odds of colonization of children with Hib. Conclusion. Our findings showed a significant decrease (60%) in the overall Hib nasopharyngeal carriage in healthy children under six years after 5 years after the start of Hib vaccination.

Prior to widespread use of vaccine, Haemophilus influenzae type b (Hib) was the leading cause of bacteremia, pneumonia, and meningitis among US infants and young children. Invasive Hib disease was estimated to infect 1 in 200 children younger than 5 years of age in the USA. Hib vaccines were introduced into the national pediatric immunization schedule in the late 1980s. Almost immediately following their widespread use, there was a dramatic decline in disease incidence. While developed countries were early adopters of the conjugate Hib vaccine, developing countries were slower to do so for a variety of reasons, including but not limited to the perceived lack of disease burden to justify adding another vaccine to the schedule and the associated financial constraints of being able to do so. The African nation of Gambia, however, introduced Hib vaccine in 1997, being among the first African countries to routinely immunize their children against this infection. Prior to vaccine initiation, the incidence of Hib meningitis in The Gambia was 297 per 100,000 children younger than 1 year of age and 60 per 100,000 children younger than 5 years of age. Only 55% of infected children fully recovered (Bijlmer et al., J Infect Dis 161:1210–5, 1990). Although the incidence of Hib meningitis in The Gambia was similar to that in the USA, Gambian children were significantly more likely to have devastating outcomes (Bijlmer et al., J Infect Dis 161:1210–5, 1990). Five years after introduction of conjugate Hib vaccine in The Gambia, the incidence of Hib meningitis decreased to zero in children less than 5 years of age (Oluwalana et al., J Pediatr 163:S4–7, 2013; Adegbola et al., Lancet 366:144–50, 2005). In addition, Hib nasopharyngeal carriage among toddlers decreased from 12% to 0.25% during this time period (Adegbola et al., Lancet 366:144–50, 2005). The data from The Gambia highlight the effectiveness of conjugate Hib vaccines in the prevention of invasive disease. Observations regarding the effectiveness of Hib vaccine are not isolated to the USA and The Gambia. Similar impressive results have been achieved in every part of the world where Hib vaccination has been introduced.

Background: Concomitant administration of vaccines simplifies delivery. DTaP5-HB-IPV-Hib is a fully liquid, combination vaccine against 6 diseases. This study evaluated the compatibility of DTaP5-HB-IPV-Hib with 2 different meningococcus group C conjugate (MCC) vaccines in infants.Methods: In a phase 3, open-label study, 284 healthy infants from 11 UK centres received DTaP5-HB-IPV-Hib at age 2, 3, and 4 months; 13-valent pneumococcal conjugate vaccine (PCV13) at 2 and 4 months; a Haemophilus influenzae type b (Hib)-MCC vaccine and a measles/mumps/rubella vaccine at 12 months. Participants were randomised 1:1 to receive either an MCC-detoxified tetanus toxin vaccine (MCC-TT; n = 141) or an MCC-Corynebacterium diphtheriae CRM197 protein vaccine (MCC-CRM; n = 143) at 3 and 4 months. The primary outcome was seroprotection rate (SPR) to MCC (percent with rabbit complement serum bactericidal antibody titer ≥8).Results: Per protocol analysis, MCC SPRs were 100 and 96.4 one month after the first dose, 100 and 99.1 after the second dose, and 100 and 97.3 after the third (booster) dose of MCC in the MCC-TT and MCC-CRM groups, respectively. One month after all 3 doses of DTaP5-HB-IPV-Hib, immunoglobulin G anti-polyribosylribitol phosphate SPRs (% ≥0.15 µg/mL) were 97.8 in the MCC-TT group and 100 in the MCC-CRM group; anti-hepatitis B antigen SPRs (% ≥10 mIU/mL) were 96.8 and 96.3 in the MCC-TT and MCC-CRM groups, respectively. All participants were seroprotected against diphtheria and tetanus (≥0.01 IU/mL) and poliovirus types 1, 2, and 3 (≥8 dilution), and seroresponse rates to all pertussis antigens were ≥90.4%. Two vaccine-related serious adverse events (transient severe abdominal pain and crying) occurred concomitantly in 1 participant in the MCC-CRM group. Adverse event rates were similar to other studies of DTaP5-HB-IPV-Hib, with pyrexia ≥38 °C in 10.9% of participants following any dose.Conclusions: DTaP5-HB-IPV-Hib can be effectively used in a 2-, 3-, and 4-month infant priming schedule when given with 2 doses of MCC.

Hemin is one of the critical components of medium required for growth of Haemophilus influenzae type b (Hib) organisms. It is important to have different sources of critical components to ensure continuous supply for commercial production. Regulatory bodies also recommend having multiple sources for critical components. Hemin is produced from animal blood and the main sources are porcine and bovine origin. The approved Hib vaccine of SIIPL used for immunization is produced using hemin obtained from porcine origin. The present work focuses on the comparison of the growth of organisms on a large scale using hemin from bovine or porcine origin. Purified polysaccharide obtained using bovine source is tested with respect to the set WHO specifications as recommended by regulatory bodies and compared with commercial lots of PRP obtained from using hemin of porcine source. Identical product profile and quality attributes were obtained for PRP produced using bovine hemin and the regular commercial product suggests that there is no change in the product. Hemin from bovine source can be used as a replacement for hemin from porcine source in the fermentation medium for country specific requirement of Hib conjugate vaccine as long as it meets the guidelines on TSE/BSE risk.

Background: Globally, pneumonia is the leading cause of death among children. Few data exist regarding the effect of Haemophilus influenzae type B (Hib) vaccine and 13-valent pneumococcal conjugate vaccine (PCV-13) on the burden of childhood pneumonia in African settings. Methods: We collected data on children 1 to 59 months of age from patient registers at three hospitals in Botswana. Hib vaccine and PCV-13 were introduced in Botswana in November 2010 and July 2012, respectively. To evaluate the effect of Hib vaccine and PCV-13 introduction, we compared pneumonia hospitalizations and deaths pre-vaccine (January 2009 to October 2010) to post-vaccine (January 2013 to December 2017) using seasonally-adjusted interrupted time-series analyses. Findings: We identified 6943 pneumonia hospitalizations and 201 pneumonia deaths during the study period. In the pre-vaccine period, pneumonia hospitalizations and deaths increased by 1·8% (rate: 1·018; 95% CI: 0·994, 1·042) and 3·9% (rate: 1·039; 95% CI: 0·988, 1·093) per month, respectively. Vaccine introduction was associated with a 48·3% (95% CI: 28·9%, 62·4%) decrease in the number of pneumonia hospitalizations and a 50·1% (95% CI: 0·8%, 74·9%) decrease in the number of pneumonia deaths between the end of the pre-vaccine period (October 2010) and the beginning of the post-vaccine period (January 2013). During the post-vaccine period, pneumonia hospitalizations and deaths declined by 0·5% (rate 0.995; 95% CI: 0·990, 0·999) and 2·0% (rate: 0·980; 95% CI: 0·967, 0·993) per month, respectively. Interpretation: Pneumonia hospitalizations and deaths among children declined sharply following introduction of Hib vaccine and PCV-13 in Botswana. This effect was sustained for more than five years after vaccine introduction, supporting the long-term effectiveness of these vaccines in preventing childhood pneumonia in sub-Saharan Africa. Funding Statement: Melissa Ketunuti Endowment, Children’s Hospital of Philadelphia, American Academy of Pediatrics. Declaration of Interests: The authors have no conflicts of interest to disclose. Ethics Approval Statement: This study was approved by the Health Research and Development Committee (Ministry of Health, Botswana), ethics committees at each hospital site, and institutional review boards at the University of Botswana, the Children’s Hospital of Philadelphia, the University of Pennsylvania, and Duke University.

The etiology of bacterial meningitis in Turkey changed after the implementation of conjugated vaccines against Streptococcus pneumoniae and Haemophilus influenzae type b (Hib) in the Turkish National Immunization Program (NIP). Administration of Hib vaccine and PCV-7 (7-valent pneumococcal conjugate vaccine) was implemented in NIP in 2006 and 2009, respectively. in 2011, PCV-7 was replaced with PCV-13. Meningococcal vaccines have not yet been included in Turkish NIP. This prospective study comprised 27 hospitals located in seven regions of Turkey and represented 45% of the population. Children aged between 1 month and 18 years who were hospitalized with suspected meningitis were included. Cerebrospinal fluid (CSF) samples were collected, and bacterial identification was made according to the multiplex PCR assay results. During the study period, 994 children were hospitalized for suspected meningitis, and Hib (n = 3, 2.4%), S. pneumoniae (n = 33, 26.4%), and Neisseria meningitidis (n = 89, 71%) were detected in 125 samples. The most common meningococcal serogroup was MenB. Serogroup W comprised 13.9% (n = 5) and 7.5% (n = 4) of the meningococci in 2015 to 2016 and 2017 to 2018, respectively. Serogroup C was not detected. There were four deaths in the study; one was a pneumococcus case, and the others were serogroup B meningococcus cases. The epidemiology of meningococcal diseases has varied over time in Turkey. Differing from the previous surveillance periods, MenB was the most common serogroup in the 2015-to-2018 period. Meningococcal epidemiology is so dynamic that, for vaccination policies, close monitoring is crucial. IMPORTANCE Acute bacterial meningitis (ABM) is one of the most common life-threatening infections in children. The incidence and prevalence of ABM vary both geographically and temporally; therefore, surveillance systems are necessary to determine the accurate burden of ABM. The Turkish Meningitis Surveillance Group has been performing a hospital-based meningitis surveillance study since 2005 across several regions in Turkey. Meningococcus was the major ABM-causing agent during the 2015-to-2018 period, during which MenB was the dominant serogroup., GlaxoSmithKlineGlaxoSmithKline, Funding for this study was provided by GlaxoSmithKline.

Splenectomy is a surgery indicated in case of splenic rupture after injury, when there are tumors in the spleen, or as a treatment for certain diseases, such as idiopathic thrombocytopenic purpura and spherocytosis. The aims of the study were to assess the immunological response to the Haemophilus influenzae type b (Hib) vaccine and the post-vaccination changes in lymphocyte subsets and cell activation markers in splenectomized patients and healthy volunteers. Blood samples were collected from 25 patients that had undergone splenectomy and from 15 healthy, non-splenectomized volunteers. All participants received a single dose of Hib vaccine. The concentration of specific Hib antibodies was assessed by an enzyme-linked immunosorbent assay. Selected immune cell populations were evaluated using flow cytometry. The analysis of the antibody titers against Hib showed statistically significant differences in both groups. There was a significantly higher percentage (p = 0.0012) and absolute value (p = 0.0003) of natural killer T (NKT)-like cells (CD3+/CD16+ CD56+) in the study group, compared to the control group. The levels of natural killer (NK) and NKT cells did not change relative to the cause and age of splenectomy. The quantity and percentage of regulatory T (Treg) cells were higher in the study group compared to the control group (p

We assessed the immunogenicity and safety of a three-dose primary vaccination schedule with the combined diphtheria-tetanus-acellular pertussis-inactivated poliovirus/Haemophilus influenzae type b vaccine (DTPa-IPV/Hib) in Korean infants. In this phase III open-label, multicenter study (NCT01309646), healthy infants aged 42–69 days (randomized 1:1) received three doses of either pentavalent DTPa-IPV/Hib (DTPa-IPV/Hib group) or DTPa-IPV and Hib vaccines administered separately (DTPa-IPV+Hib group) at 2, 4, 6 months of age. The primary objective was to demonstrate non-inferiority of DTPa-IPV/Hib compared to DTPa-IPV+Hib vaccines in terms of immune responses to all vaccine antigens, 1 month post-dose 3. Solicited symptoms (local and general) were recorded during 4 days, and unsolicited adverse events (AEs) during 31 days, after each vaccination. Serious AEs (SAEs) were recorded throughout the study duration. The immunogenicity of the pentavalent DTPa-IPV/Hib vaccine was non-inferior compared to concomitant administration of DTPa-IPV+Hib vaccines. One month post-dose 3, nearly all infants had antibody levels above the seroprotective thresholds for anti-diphtheria toxoid, anti-tetanus toxoid, anti-polyribosyl-ribitol phosphate, and anti-poliovirus type 1, 2 and 3, and had antibody levels above the seropositive thresholds for anti-pertussis toxoid (PT), anti-filamentous hemagglutinin (FHA) and anti-pertactin (PRN) antibodies. A vaccine response for PT, FHA and PRN was observed in at least 96.7% of study participants. Anti-PRP geometric mean concentrations appeared lower for the DTPa-IPV/Hib group (8.456 µg/mL) than for the DTPa-IPV+Hib group (18.700 µg/mL). In both groups, the most common solicited symptoms were injection site redness and irritability. Fifty-seven SAEs were reported throughout the study; none were considered to be vaccination related.

BACKGROUND Haemophilus influenzae type b (Hib) vaccine was introduced as a voluntary vaccine in December 2008 and was included in the national routine immunization program in April 2013 in Japan. Currently, no nationwide data are available to evaluate the effectiveness of Hib vaccine in Japan. METHODS To evaluate the effectiveness of Hib vaccine in Japan, nationwide active population-based surveillance of culture-proven invasive infections caused by H. influenzae in children was performed in 2008-2017 in 10 prefectures in Japan (covering approximately 23% of the total Japanese population). Clinical data were recorded on a standardized case report form. Capsular type and antimicrobial susceptibility of the H. influenzae isolates were examined. The incidence rate ratio (IRR) and its confidence interval (CI) were calculated to compare data from 5 years before and that from after the introduction of the national routine Hib vaccine immunization program. RESULTS During the 10-year study period, 566 invasive H. influenzae disease cases including 336 meningitis cases were identified. The average number of invasive H. influenzae disease cases among children

Background The aim of this study was to analyze the microbiological characteristics of nasopharyngeal carriage Haemophilus influenzae isolates collected from children with respiratory infections in Beijing hospital and Youyang Hospital of China. Methods The serotypes of all isolates were determined using latex agglutinated antisera (a‐f). The minimum inhibitory concentrations (MICs) of 11 antibiotics were determined using E‐test strips. For the beta‐lactamase‐negative ampicillin‐resistant (BLNAR) isolates, ftsI gene was sequenced based on fragments amplified by PCR. STs of H influenzae isolates were determined by multi‐locus sequence typing. Results The overall carriage rate of H influenzae in the study population was 9.1% (362/3984). One hundred and ninety H influenzae isolates which were selected in our study were non‐typeable (NTHi) and 44 (23.2%) of them were positive for β‐lactamase. All isolates were susceptible to ceftriaxone and levofloxacin. Susceptibility rates to erythromycin and sulfamethoxazole‐trimethoprim in Beijing were significantly higher than Youyang (P

In this national comprehensive seroprevalence study, indirect ELISA test was used to evaluate Haemophilus influenzae type b (Hib) anti-polyribosyl-ribitol phosphate (PRP) total antibodies (IgM, IgG, IgA) in 1,003 sera samples from routine medical check-up of healthy individuals attending the local medical facility in Jeddah, Saudi Arabia in the period from February 2014 to January 2016. Serum anti-CPS antibodies confer immunity against invasive Hib disease. An anti-CPS concentration of ⩾ 0.15 μg/mL is believed to be a serological indication for short-term immunity protection against invasive Hib disease, while a concentration of ⩾ 1.0 μg/mL is believed to be long-term protective. Results showed higher level of anti-Hib IgG (2.41 μg/ml average geometric mean concentration (GMC) regardless of age and gender, followed by levels of IgM (0.91 μg/ml) and IgA (0.34 μg/ml), reflecting the community immunity against Hib. Low anti-Hib level (< 0.15 μg/ml of anti-PRP IgG) in elderly people (males aged 57-91 years and females aged 35-64 years) may indicate a need for a booster dose of Hib vaccine to elderly people in the community. The IgG prevalence over IgM, and IgM prevalence over IgA indicate the major role of IgG over IgM and IgA in keeping immunity in the track against Hib. Low level of IgM and IgA comparing to IgG may indicate the absence of Hib acute infections in the population.

Investigators postulated that early-life exposure to organic mercury (Hg) significantly increases the risk of childhood neurodevelopmental disorders (NDs). The Vaccine Adverse Event Reporting System database was utilized to conduct a hypothesis testing case-control study by evaluating 3486 total adverse event reports reported following Haemophilus influenza type b (Hib) vaccination. Exposed subjects received a Thimerosal-containing formulation (HIBTITER™, Wyeth-Lederle), while unexposed subjects received a Thimerosal-free formulation (PEDVAXHIB™, Merck). Subjects were included if they received either of these two Hib vaccine formulations between 1995 and 1999. Cases were defined as adverse event reports with a reported outcome of autism, developmental delay, psychomotor delay, or NDs in general. Cases with reported outcomes of febrile convulsions, pyrexia, or injection site pain, all of which have no biologically plausible relation to Hg exposure, were also examined. Controls were defined as adverse event reports without any mention of the specific case outcome examined. Cases of reported autism (odds ratio (OR) = 2.75, p

Background Japan licensed the conjugate Haemophilus influenzae type b vaccine, Vaxem™ Hib, based on clinical studies using subcutaneous injection. The present study was performed to ensure this vaccine is suitable for intramuscular injection in Japanese children. Methods Thirty-one healthy 2–6-month-old infants received three doses of Vaxem™ Hib by intramuscular injection at 4-week intervals and a booster dose 1 year later, concomitant with routine infant (DTaP-IPV and pneumococcal) and toddler (measles–rubella) vaccines. Immunogenicity was assessed before and after the primary series and booster dose by enzyme-linked immunosorbent assay for anti-polyribosyl-ribitol-phosphate (PRP) antibodies. Safety was assessed by medical examination and diary cards completed by the subjects’ parents/legal guardians. Results There were no vaccine-related serious adverse events or withdrawals; all children completed the study. Four weeks after the primary series, the geometric mean anti-PRP titer (GMT) was 19.68 μg/mL, and all children had seroprotective titers (≥0.15 μg/mL) that persisted until the booster dose. Proportions of titers indicative of long-term protection (≥1.0 μg/mL) were 100% after the primary series and 77.4% before the booster. Anamnestic responses to the booster had a GMT of 51.33 μg/mL, and 100% had titers ≥1.0 μg/mL. All but one subject reported injection site reactions as resolved within 3 days of vaccination; systemic reactions due to Hib and routine vaccines were also resolved within this period. Conclusions Vaxem™ Hib was generally well tolerated and immunogenic in Japanese children when administered by intramuscular injection in a three-dose primary series and as a booster with concomitant routine vaccines. Clinical trial registry: Registered on Clinical Trials.gov : NCT02074345.

The introduction of the Haemophilus influenzae type b (Hib) vaccine and the 7-valent pneumococcal conjugate vaccine (PCV7) has led to dramatic reductions in cases of invasive H. influenzae disease and invasive pneumococcal disease (IPD). After the introduction of the PCV7 and the 13-valent pneumococcal conjugate vaccine (PCV13), the number of children with IPD markedly decreased in our hospital. However, since 2015, three children with IPD have been admitted to our hospital. We analyzed the serotype, multilocus sequence type, and antimicrobial susceptibility of Streptococcus pneumoniae strains isolated in these newly diagnosed cases. The strains were serotypes 7F and 12F. In addition, we analyzed the incidence of invasive bacterial disease before and after the introduction of conjugate vaccines and found no change in the incidences. We found that cases of IPD and invasive H. influenzae disease clearly decreased following the introduction of the PCV7, the PCV13, and the Hib vaccine, as well as disease caused by antibiotic-resistant strains.