Post-vaccination Era Research Articles

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.

Molecular epidemiological characterization in mucoid-type Streptococcus pneumoniae isolates obtained from invasive pneumococcal disease patients in Japan

IntroductionStreptococcus pneumoniae with a mucoid-type capsule is associated with invasive pneumococcal diseases (IPDs). Despite the introduction of pneumococcal vaccines, IPDs caused by mucoid-type isolates are still prevalent. The present study aimed to characterize mucoid-type S. pneumoniae isolated from IPD patients throughout Japan in 2017 (post-vaccination era). MethodsA total of 225 mucoid-type isolates were collected. The serotype, antimicrobial susceptibility, and multilocus sequence type of these isolates were determined. ResultsThe prevalence of IPDs caused by mucoid-type isolates was high in adults, especially in the elderly (≥65 years of age), and prognosis in these patients was significantly poor. Of the mucoid-type isolates, the predominant serotype was serotype 3 (84.4%), and the remaining were serotypes 37 (15.1%) and 8 (0.4%). Antimicrobial susceptibility showed that most mucoid isolates exhibited the penicillin-intermediate resistant S. pneumoniae genotype (gPISP). However, the serotype 3 isolate exhibited the penicillin-resistant S. pneumoniae genotype (gPRSP). This gPRSP isolate was classified into ST166, which is related to serotypes 9 V and 11 strains. Sequence analysis of the capsule-coding regions and its flanking regions indicated that recombination occurred upstream and downstream of the capsule-coding region, suggesting that gPRSP (serotype 9 V/ST166) obtaining the type-3 capsule gene cluster resulted in the emergence of gPRSP (serotype 3/ST166). ConclusionsOur findings indicated that IPDs caused by mucoid-type S. pneumoniae are still a serious concern and mucoid-type S. pneumoniae with novel phenotype could emerge via capsular switching in response to environmental changes such as introduction of vaccines and improper use of antimicrobial agents.

Human papillomavirus genotype-specific risks for cervical intraepithelial lesions

ABSTRACT Prevalence of different HPV genotypes is changing after HPV vaccination. The associated risks are needed for optimizing cervical cancer screening. To estimate HPV type-specific prevalence, odds ratio (OR), and positive predictive value (PPV) for cervical cytological abnormalities, we determined 41 different HPV genotypes in cervical samples from a population-based sample of 8351 women aged 18–51 years before HPV vaccination era (V501-033; NCT01077856). Prevalence of HPV16 was 4.9% (95% CI: 4.4–5.5) with the PPV for high-grade cytology 11.2%, and OR 11.9 (95% CI: 8.5–16.5). Carcinogenic HPVs included in the nonavalent vaccine (HPV16,18,31,33,45,52,58) had a population prevalence of 14.4% (95% CI: 13.5–15.4), with PPV of 8.0% (95% CI: 6.8–9.3) and OR 23.7 (95% CI: 16.0–63.5) for high-grade cytology. HPV types currently included in most screening tests, but not vaccinated against (HPV35,39,51,56,59,66,68) had a joint prevalence of 8.5% (95% CI: 7.8–9.2) with PPV of 4.4% (95% CI: 3.3–5.7) and OR of 2.9 (95% CI: 2.0–4.0) for high-grade cytology. The other 27 non-carcinogenic genotypes had a prevalence of 11.8%, PPV of 2.9% (95% CI:2.1–3.9), and OR 1.5 (95% CI: 1.1–2.2.) for high-grade cytology. These results suggest that HPV screening tests in the post-vaccination era might perform better if restricted to the HPV types in the nonavalent vaccine and screening for all 14 HPV types might result in suboptimal balance of harms and benefits.

Outbreak of hepatitis A in a post-vaccination era: High rate of co-infection with sexually transmitted diseases

Introduction and objectivesAfter hepatitis A (HAV) mandatory immunization in 2005 in Argentina, the incidence of HAV declined drastically. However, several new autochthonous cases of HAV have been reported since 2017. We aimed to evaluate the clinical and epidemiological characteristics and possible transmission routes of affected patients. Patients or Materials and methodsWe performed a cross-sectional study of patients residing in Argentina with acute hepatitis A between 30.06.2017 and 31.12.2018. Results66 cases of HAV were registered. Fifty-six patients (86%) were males, with a mean age of 34 ± 12 years old. The most likely routes of transmission were sexual intercourse of men with men, reported by 31 patients. Additionally, 23% and 26% of patients tested positive for HIV and syphilis, respectively. In total, 35% of patients required hospitalization. When assessing outcomes, 79% had a mild presentation and 21% had a severe/fulminant presentation: one patient underwent liver transplantation, and one patient died. ConclusionsOur study describes that during the study period, HAV infection affected predominantly young adults, particularly men who have sex with men. An elevated proportion of them was diagnosed with a concomitant sexually transmitted disease, and several patients had a severe presentation of the disease.

Analysis of Haemophilus species in patients with respiratory tract infections in Yaoundé, Cameroon

ObjectivesTo identifyHaemophilus species and characterize antimicrobial susceptibility of isolates from patients with respiratory tract infections (RTIs) in Cameroon. MethodsIsolates (n = 95) were from patients with RTIs obtained from two Hospitals in Yaoundé, Cameroon. Isolates were identified by biochemical assay, PCR-based method, MALDI-TOF and whole genome sequencing. Antibiotic minimum inhibitory concentrations were determined by E-test. ResultsH. influenzae was the most prevalent species varying from 76.8% to 84.2% according to different methods. The isolates were mainly nontypable (n = 70, 96%). Three isolates of H. influenzae were capsulated (b, e and f). The isolates were genetically diverse and 40 unique sequence types were identified including 11 new ones. Resistance to ampicillin was observed among 55.3% (52/94) and 9% (14/52) produced TEM-1 β-lactamase. PBP3 mutations occurred in 57.7% of ampicillin resistant isolates (30/52). Eleven isolates were chloramphenicol resistant with 80% producing chloramphenicol acetyltransferase (8/10). Four Haemophilus isolates were rifampicin resistant with two mutations in rpoB gene. Five isolates were ciprofloxacin resistant and harbored mutations in the quinolone resistance determining regions of gyrA and parC genes. ConclusionH. influenzae isolates are highly diverse and show high levels of antibiotic resistance. H. influenzae serotype b is still circulating in the post-vaccination era.

Genetic Characterizations and Molecular Evolution of VP7 Gene in Human Group A Rotavirus G1.

Rotavirus group A (RVA) G1 is one leading genotype circulating in humans worldwide, and related molecular information from a global perspective is still limited. Here, we present a comprehensive description of the genetic characterizations and molecular evolution of the RVA G1 VP7 gene. Our results show that RVA G1 can be divided into two lineages and multiple sub-lineages with a relatively high genetic diversity. Vaccine strains are phylogenetic, closer to lineage I. The evolutionary rate of the RVA G1 VP7 gene is 8.869 × 10−4 substitutions/site/year, and its most recent common ancestor was in 1933. The RVA G1 VP7 gene shows a linear evolution at the nucleotide level and a linear accumulation of difference at the amino acid level. Sub-lineage replacement of G1 VP7 gene is also observed and the effective population size of the G1 VP7 gene has had great change in the past decades and has remained stable in recent years. Altogether, the RVA G1 VP7 gene constantly evolves and there is no clear evidence that the evolution of the RVA G1 VP7 gene was influenced by vaccines. Continuous surveillance is still indispensable to evaluate the molecular epidemiology of RVA, especially in the post-vaccination era.

Distribution of rotavirus genotypes in Japan from 2015 to 2018: Diversity in genotypes before and after introduction of rotavirus vaccines

BackgroundDiversity in group A rotavirus (RVA) strains after introduction of RV-vaccines remains an emerging concern worldwide. In this study, we investigated the prevalence and distribution of RVA genotypes in Japanese children with acute gastroenteritis (AGE) from 2015 to 2018. In addition, a comparison of the genotypes in pre-vaccination (2006–2012) and post-vaccination (2012–2018) periods was conducted to understand the impact of these vaccines on genotype distribution. MethodsFecal samples were collected regularly from outpatient clinics in six localities: Hokkaido, Tokyo, Shizuoka, Osaka, Kyoto, and Saga. RVA were screened and genotyped by RT-PCR and sequence-based genotyping. ResultsDuring the period 2015–2018, RVA was detected in 307 (19.7%) samples out of 1557 specimens: 29.9% (95% CI: 25.8% to 34.3%), 17.9% (95% CI: 14.7% to 21.5%), and 13% (95% CI: 10.3% to 16.0%) were detected RVA-positive in 2015–2016, 2016–2017 and 2017–2018, respectively. The average detection of RVA in pre-vaccination (2006–2012) and post-vaccination (2012–2018) era remained almost similar (18%-20%). The G2P[4]I2 (52.1%, 95% CI: 43.5%-60.6%) remained the most common genotype in 2015–2016, whereas G8P[8]I2 (55.9%, 95% CI: 45.2%-66.2%) dominated in 2016–2017. In 2017–2018, G9P[8]I2 (42.0%, 95% CI: 30.5%-53.9%) prevailed, followed by G9P[8]I1 (23.0%, 95% CI: 14.0%-34.2%). The detection rate of some common genotypes of pre-vaccination era like G1P[8] and G3P[8] has been reduced after introduction of RV-vaccine, whereas genotypes that were sporadic before the introduction of vaccines like G2P[4], G2P[8], G9P[8] and G8P[8] were emerged/reemerged in post-vaccination period. ConclusionsOur study presented the diversity in circulating RVA genotypes in Japan before and after introduction of RV-vaccines. Sudden emergence of DS-1-like (I2) unusual strains in post-vaccination era remains alarming. Continuous monitoring of RVA genotypes is therefore indispensable to refine future vaccine strategy.

Pre-vaccine rotavirus surveillance in Buenos Aires, Argentina. Characterization of an emergent G1P[8] strain associated to fatal cases in 2014

Group A rotaviruses (RVA) are the most frequent etiological agents causing severe diarrhea in infants and surveillance of genotype, and genetic characteristics of circulating strains are necessary in order to evaluate vaccine programs. The objectives of this work were to describe G and P genotype from 2012 through 2014 in Buenos Aires, Argentina completing an overview of 19 years of genotype surveillance in our region and to characterize an emerging G1P[8] strain associated with severe cases and five fatalities in 2014.We performed genotyping by RT-PCR. The sequencing of several genes, phylogenetic analyses, and comparative epidemiological data were used to know the origin and phylogenetic relationships of the emerging G1P[8] strain.Along with this report, 19 years of continuous RVA genotype surveillance in Argentina in the pre-vaccine era was covered. During the last year of this surveillance, 2014, a significantly increased incidence of RVA associated gastroenteritis was related to the reemergence of G1P[8] strains, being these ones detected in low frequency in the last nine years. Interestingly, the patients affected were significantly older when compared with those from the last six seasons. Additionally, phylogenetic analysis of several genes infer that these G1P[8] strains were closely related to Asian strains circulating during 2012 and 2013. In addition to this, the suggested extra continental origin for the 2014 G1P[8] strains and the very low circulation of G1 type during nine years probably explain the increased incidence and severity in the gastroenteritis cases and the particular epidemiologic characteristics.In conclusion, this work gives us a whole panorama of the pre-vaccine era of the RVA molecular epidemiology in the most populated region of Argentina. In this way, this work inspires us to continue with this type of studies in the post-vaccination era.

Resurgence of diphtheria and its outcome among children in western Uttar Pradesh: a battle to conquer

Background: Considered as a rare clinical entity in immediate post-vaccination era, diphtheria has now started gaining surface in India for last few years, with an epidemiological shift involving older children owing to poor immunization coverage and waning immunity. Thus, it is imperative to quantify disease burden, analyses the clinical profile and factors affecting the outcome of diphtheria in children.Methods: A prospective observational study conducted in the Pediatric department of a teaching hospital where all children admitted with clinical diagnosis of diphtheria during the study period were included. Demographic data and clinically relevant information along with complications and outcome were recorded. Cases were managed as per standard treatment protocol providing intensive care support wherever required. Complications and factors affecting the outcome in all diphtheria cases were analysed.Results: Total 53 children were enrolled into study, and the mean age of study population was 7.55±2 years. Fever, pseudo membrane and throat pain were observed in all the cases. Palatal palsy was the earliest and the commonest complication (60.4%) followed by myocarditis (55%). Case fatality rate was 33.9% and myocarditis (77%) was the commonest complication attributing to it. Poor immunization status, late presentation and delayed ADS administration were associated with increased complication rate and unfavorable outcome.Conclusions: Robust immunization activity coupled with improved case-based surveillance would go a long way in preventing further diphtheria outbreaks in community. Sensitization about this re-emerging disease and high index of suspicion in diagnosing it, amongst primary care physicians and peripheral health workers would promote early referral and prompt management thereby reducing morbidity and high mortality associated with diphtheria.

Bezold Abscess in a patient with Juvenile Rheumatoid Arthritis

A Bezold abscess is a rare complication of acute otitis media and mastoiditis which is characterized by the collection of pus in the sub-muscular spaces from the mastoid cavity. A 27-year-old female with history of Juvenile Rheumatoid Arthritis presented with right ear discharge and post auricular swelling extending along the sternocleidomastoid muscle. A Bezold abscess was diagnosed upon review of the patient’s CT scan. She subsequently underwent incision and drainage of the abscess in addition to a cortical mastoidectomy. Although the development of intra and extra axial complications of acute otitis media are very rare in the post antibiotic and vaccination era, it should be noted that a compromised immune system is a significant risk factor for this complication.

Age-Related Changes in the Fraction of Cervical Intraepithelial Neoplasia Grade 3 Related to HPV Genotypes Included in the Nonavalent Vaccine.

Objective The prevalence of some human papillomavirus (HPV) genotypes has been shown to change with age. So, also the distribution of HPV genotypes included in the nonavalent vaccine may not be the same at all ages, and this could mean that vaccine protection against cervical cancer may be affected by age. The present study aimed to evaluate whether there are age-related changes in the fraction of high-grade cervical intraepithelial neoplasia (CIN) attributable to HPV genotypes included in the nonavalent vaccine. Methods Two hundred four consecutive women undergoing conization with a histological diagnosis of CIN3 were retrospectively analyzed. All included women had a preconization HPV genotyping (HPV Sign® Genotyping Test). The women were divided into three groups according to age: <35, 35–44, and ≥45 years of age. Based on HPV genotypes detected in cervical lesions, the age-related changes in the expected vaccine protection were evaluated by the Cochran–Armitage test for trend. Results The fraction of CIN3 attributable to HPV genotypes included in the nonavalent vaccine showed a significant negative trend with increasing age, with potential vaccine protection of 82% after the age of 45 (p=0.006). The rate of HPV-16 and HPV-33, included in the vaccine, showed a negative trend with age (p=0.047 and p=0.044, respectively). Among HPV genotypes not covered by the vaccine, the rate of non-high-risk HPVs (genotypes: 53-54-70-73-82-85-87) showed a significant positive trend with increasing age (p=0.018). Conclusions Although the fraction of CIN3 attributable to genotypes included in the nonavalent HPV vaccine was high even after age 45, older women appeared to be more at risk of high-grade CIN related to HPV genotypes not included in the vaccine. Interestingly, older women showed a higher rate of precancerous cervical lesions associated with non-high-risk HPV. The present findings seem to raise the question about the management of cervical pathology at a later age in a future postvaccination era.

Rotavirus A Infections in Community Childhood Diarrhea in the Brazilian Semiarid Region During Postvaccination Era.

Rotavirus A (RVA) is one of the leading causes of acute gastroenteritis worldwide; however, few studies assessed RVA genetics with community surveillance. This study aimed to investigate clinical data, genetic diversity, and coinfection patterns of RVA infections in children from 2 to 36 months old with or without community childhood diarrhea in the Brazilian semiarid region during postvaccination era. We enrolled and collected socioeconomic/clinical information using a standardized questionnaire and fecal samples from 291 children. Viral RNA samples were extracted and analyzed using quantitative reverse transcription polymerase chain reaction to establish the diagnosis of RVA. Sequencing of VP7 and VP4 (VP8*) regions and phylogenetic analysis were performed. RVA-negative diagnosis was associated with children 24 to 36 months old with complete vaccination schedule. Genotype G1P[8] was the most prevalent (57%), whereas unusual genotypes including G1P[4], G2P[8], and G3P[9] were also detected. G1- and P[8]-positive samples showed high degrees of similarity with the vaccine strain. RVA coinfections were frequently observed, and enteroaggregative Escherichia coli was the most prevalent copathogen. These results demonstrate that genotype G1P[8] is the most prevalent strain. VP7 and/or VP8* gene segments arising from RV1 vaccine strain were documented in these children, suggesting shedding or herd vaccination. Moreover, our study indicates full vaccination is important for protection against RVA infections.

Genetic characterization of group-A rotaviruses among children in eastern India during 2014–2016: Phylodynamics of co-circulating genotypes

BackgroundGroup-A human rotaviruses (GARV) are among the major cause of childhood diarrhea worldwide. In lieu of monitoring the circulatory GARV strains and underscoring the burden of GARV related hospitalization, a systematic surveillance was conducted in three hospitals of eastern India. In this hospital-based diarrheal disease surveillance (2014–2016), GARV was the most common cause of acute infantile gastroenteritis. The strains were genotyped and characterized to understand their prevalence and phylodynamics prior to the introduction of vaccine in eastern India. Materials and methodsA total of 3652 stool samples were screened from children (≤5 years) hospitalized with acute diarrhea during 2014–2016. Initial screening for VP6 antigen was done by ELISA. GARV positive samples were genotyped by multiplex semi-nested PCR and DNA sequencing and phylogenetic analyses were based on the capsid proteins VP4 and VP7. ResultsOf 3652 samples, 1817 (49.8%) were GARV positive. G1, G2, G3 and G9 in conjunction with P[4], P[6]and P[8]genotypes were seen to co-circulate in the population. A sharp deflection from G1 to G3 occurred since 2016; upsurge of G9 strains was seen in alternate years, whereas G2 strains had a low frequency. All the circulating genotypes depicted a low phylogenetic relatedness to the vaccine strains. Differences in antigenic epitopes of VP4 and VP7 proteins in local strains were seen when compared to the vaccine strains. A significant difference in the degree of dehydration, duration of mean hospital stay and frequency of vomiting/24 h between GARV positive and negative children was evident. ConclusionThe study provides a relevant set of base-line data on high burden of rotaviral gastroenteritis and the varied genotypic diversity among children prior to the introduction of GARV vaccine in this endemic region. Continuous monitoring during post-vaccination era will be required to assess the impact of vaccination in this region.

Genetic analysis of Ghanaian G1P[8] and G9P[8] rotavirus A strains reveals the impact of P[8] VP4 gene polymorphism on P-genotyping.

The World Health Organisation rotavirus surveillance networks have documented and shown eclectic geographic and temporal diversity in circulating G- and P- genotypes identified in children <5 years of age. To effectively monitor vaccine performance and effectiveness, robust molecular and phylogenetic techniques are essential to detect novel strain variants that might emerge due to vaccine pressure. This study inferred the phylogenetic history of the VP7 and VP4 genes of previously non-typeable strains and provided insight into the diversity of P[8] VP4 sequences which impacted the outcome of our routine VP4 genotyping method. Near-full-length VP7 gene and the VP8* fragment of the VP4 gene were obtained by Sanger sequencing and genotypes were determined using RotaC v2.0 web-based genotyping tool. The genotypes of the 57 rotavirus-positive samples with sufficient stool was determined. Forty-eight of the 57 (84.2%) had the P[8] specificity, of which 43 (89.6%) were characterized as P[8]a subtype and 5 (10.4%) as the rare OP354-like subtype. The VP7 gene of 27 samples were successfully sequenced and their G-genotypes confirmed as G1 (18/27) and G9 (9/27). Phylogenetic analysis of the P[8]a sequences placed them in subcluster IIIc within lineage III together with contemporary G1P[8], G3P[8], G8P[8], and G9P[8] strains detected globally from 2006–2016. The G1 VP7 sequences of the study strains formed a monophyletic cluster with African G1P[8] strains, previously detected in Ghana and Mali during the RotaTeq vaccine trial as well as Togo. The G9 VP7 sequences of the study strains formed a monophyletic cluster with contemporary African G9 sequences from neighbouring Burkina Faso within the major sub-cluster of lineage III. Mutations identified in the primer binding region of the VP8* sequence of the Ghanaian P[8]a strains may have resulted in the genotyping failure since the newly designed primer successfully genotyped the previously non-typeable P[8] strains. In summary, the G1, G9, and P[8]a sequences were highly similar to contemporary African strains at the lineage level. The study also resolved the methodological challenges of the standard genotyping techniques and highlighted the need for regular evaluation of the multiplex PCR-typing method especially in the post-vaccination era. The study further highlights the need for regions to start using sequencing data from local rotavirus strains to design and update genotyping primers.

Complex Febrile Seizures: An Update

AbstractFebrile seizures are the most common seizures in childhood. Febrile seizures are divided into two groups: simple and complex. Simple febrile seizures (SFS) are generalized, short, and occur only once in 24 hours. Complex febrile seizures are prolonged, focal, or repeat more than once in 24 hours. Around 35% of children experience complex features as part of their initial seizure event. These children have more chances of complex recurrences than children with SFS. While the guidelines for SFS remain clear, there are no clear guidelines for the evaluation of children with complex febrile seizures. The conflicting results about electroencephalography (EEG) utilization preclude drawing meaningful conclusions. An EEG can be obtained in children with persistent alteration of consciousness after the seizure, and emergent neuroimaging is not required in most cases. Due to low incidence of bacterial meningitis in the post-vaccination era, it is reasonable to perform lumbar puncture (LP) only if there is clinical concern for central nervous system infection. LP should also be considered in children between 6 and 12 months of age with incomplete or unknown vaccination status or who have been previously treated with antibiotics. Further, antipyretics are used to make children more comfortable during the febrile process, but are ineffective in reducing the rate of seizure reoccurrence. Continuous antiepileptic therapy and intermittent oral diazepam are effective in the prevention of subsequent febrile seizures, but they do not reduce the risk of epilepsy and have potential unwanted side effects. In specific circumstances, the benefits of antiseizure medications may outweigh the risks. Treatment may be a consideration in cases of febrile status: patients with electroclinical features suggesting a specific epilepsy syndrome or children with limited access to health care services.

Effect of ten-valent pneumococcal conjugate vaccine on invasive pneumococcal disease and nasopharyngeal carriage in Kenya: a longitudinal surveillance study

SummaryBackgroundTen-valent pneumococcal conjugate vaccine (PCV10), delivered at 6, 10, and 14 weeks of age was introduced in Kenya in January, 2011, accompanied by a catch-up campaign in Kilifi County for children aged younger than 5 years. Coverage with at least two PCV10 doses in children aged 2–11 months was 80% in 2011 and 84% in 2016; coverage with at least one dose in children aged 12–59 months was 66% in 2011 and 87% in 2016. We aimed to assess PCV10 effect against nasopharyngeal carriage and invasive pneumococcal disease (IPD) in children and adults in Kilifi County.MethodsThis study was done at the KEMRI-Wellcome Trust Research Programme among residents of the Kilifi Health and Demographic Surveillance System, a rural community on the Kenyan coast covering an area of 891 km2. We linked clinical and microbiological surveillance for IPD among admissions of all ages at Kilifi County Hospital, Kenya, which serves the community, to the Kilifi Health and Demographic Surveillance System from 1999 to 2016. We calculated the incidence rate ratio (IRR) comparing the prevaccine (Jan 1, 1999–Dec 31, 2010) and postvaccine (Jan 1, 2012–Dec 31, 2016) eras, adjusted for confounding, and reported percentage reduction in IPD as 1 minus IRR. Annual cross-sectional surveys of nasopharyngeal carriage were done from 2009 to 2016.FindingsSurveillance identified 667 cases of IPD in 3 211 403 person-years of observation. Yearly IPD incidence in children younger than 5 years reduced sharply in 2011 following vaccine introduction and remained low (PCV10-type IPD: 60·8 cases per 100 000 in the prevaccine era vs 3·2 per 100 000 in the postvaccine era [adjusted IRR 0·08, 95% CI 0·03–0·22]; IPD caused by any serotype: 81·6 per 100 000 vs 15·3 per 100 000 [0·32, 0·17–0·60]). PCV10-type IPD also declined in the post-vaccination era in unvaccinated age groups (<2 months [no cases in the postvaccine era], 5–14 years [adjusted IRR 0·26, 95% CI 0·11–0·59], and ≥15 years [0·19, 0·07–0·51]). Incidence of non-PCV10-type IPD did not differ between eras. In children younger than 5 years, PCV10-type carriage declined between eras (age-standardised adjusted prevalence ratio 0·26, 95% CI 0·19–0·35) and non-PCV10-type carriage increased (1·71, 1·47–1·99).InterpretationIntroduction of PCV10 in Kenya, accompanied by a catch-up campaign, resulted in a substantial reduction in PCV10-type IPD in children and adults without significant replacement disease. Although the catch-up campaign is likely to have brought forward the benefits by several years, the study suggests that routine infant PCV10 immunisation programmes will provide substantial direct and indirect protection in low-income settings in tropical Africa.FundingGavi, The Vaccine Alliance and The Wellcome Trust of Great Britain.

Population-Based Human Papillomavirus Serosurvey Reveals HPV16/18 Herd Effect But No Clear Type-Replacement in Unvaccinated Females 6 Years Post Gender-Neutral Vaccination in a Cluster Randomised Trial

Background: Human papillomavirus (HPV) basic reproductive numbers are low, except for HPV type 16. Thus, vaccination can induce herd effects to reduce the prevalence of many HPV types, especially if gender-neutral vaccination strategy and a vaccine with broad protection against HPV types are used. Methods: We used a cluster-randomized trial implemented in 2007-2009 among early, 1992-1995 born adolescents to create differential herd effects in 11 communities with gender-neutral (Arm A), and 11 communities with girls-only (Arm B) HPV16/18 vaccination achieving 20% coverage in Arm A boys and 45% coverage in Arm A and Arm B girls. In 11 control communities, devoid of any opportunistic HPV vaccination, hepatitis B-virus vaccination covered 30% of boys and 50% of girls. Seroprevalence was assessed for 17 HPV types in consecutive calendar-time (2005-07, 2008-10, 2011-13, 2014-16) strata comprising unvaccinated adolescent and young adult females, who were respectively 19 years or younger, and 20 to 22 years of age at the time of serum sampling. Sexual risk-taking behaviour core-group was defined by herpes simplex virus type-2 antibody positivity. From observed data probabilistic networks and simulated equal size seroprevalence datasets (N=100,000) were also derived. Findings: Following gender-neutral vaccination significant HPV16/18 herd effects were rapidly detected in the adolescent core-group of the gender-neutral vaccination Arm A. HPV51 prevalence tended to increase later in the post-vaccination era (2014-16) among adolescent core-group girls-only vaccination Arm B, as also supported by the simulations. Interpretation: Low to moderate coverage HPV vaccination induces a strong herd effect against HPV16/18 infection reducing circulation of vaccine-targeted HPV types following gender-neutral vaccination. The ecological niche vacated is not immediately filled. Funding Statement: This study was partially funded by Academy of Finland, Finnish Cancer Organizations and EU FP7 networks PREHDICT and CoheaHR. GlaxoSmithKline Biologicals SA funded the community randomized HPV-040 trial (NCT00534638), (data to be published in a separate manuscript) however was not in any way involved in the conduct of this study. This study received some support via a personal grant from the Ministry of Health, Government of Catalonia (PERIS SLT002/16/00496).The study was supported by grants from the Swedish Cancer Society (CAN 2015/399 and CAN 2017/459), from the Swedish Foundation for Strategic Research (grant number RB13-0011) and from Karolinska Institutet (Dnr. 2018-01523). ML received funding from KI to his Professorship (Dnr. 2-3698/2017). Declaration of Interests: JD and ML have received grants from Merck & Co. Inc and the GSK group of companies through their employers the Karolinska Institute (both JD and ML), or the University of Tampere (ML) for conducting HPV vaccination studies. Ethics Approval Statement: The community randomized study obtained permissions from the Ethical Review Board of Pirkanmaa Hospital District (R07113M 14.6.2007) and the Ethical Review Board of North Bothnia Hospital District (EETTMK:111/2009). Informed consent to use the FMC serum samples for research purposes is granted by the pregnant women when they donate their 1st trimester sample for screening of congenital infections.

Emergence of serotype 19A Streptococcus pneumoniae after PCV10 associated with a ST320 in adult population, in Porto Alegre, Brazil.

Use of pneumococcal conjugate vaccines has caused emergence of non-vaccine serotypes. No Brazilian data specifically about serotype 19A are available. We aimed to evaluate the frequency of occurrence, susceptibility profile and molecular epidemiology of serotype 19A before and after vaccine introduction in Brazil. Pneumococcal identification was performed by the conventional method. Strain serotype was determined by multiplex polymerase chain reaction (PCR) and/or Quellung reaction. Resistance was determined by Etest® and PCR was performed to determine the presence of macrolide resistance genes, ermB and/or mefA. Pneumococci were typed by Multilocus Sequence Typing. Thirty-eight serotype 19A Streptococcus pneumoniae were recovered, mostly from invasive diseases. Prevalence of serotype 19A increased following vaccination (from 3.5% before vaccination to 8.1% after, p = 0.04196). Non-susceptibility increased to most antimicrobials after vaccine introduction and was associated with clonal complex (CC)320. MLST showed nine different STs, which were grouped in one main CC: CC320 (63.9%). During the post-vaccination era, the frequency of this serotype increased significantly from 1.2% in 2011 to 18.5% in 2014 (p = 0.00001), with a concomitant decrease in the genetic variability: ST320 consistently predominated after vaccine-introduction (61.1%). Overall, our results showed a post-PCV10 increase in the frequency of serotype 19A. This was accompanied by a selection of CC320 and antimicrobial resistance.

Conjugate Haemophilus influenzae type b vaccines for sickle cell disease.

People affected with sickle cell disease (SCD) are at high risk of infection from Haemophilus influenzae type b (Hib). Before the implementation of Haemophilus influenzae type b conjugate vaccination in high-income countries, this was responsible for a high mortality rate in children under five years of age. In African countries, where coverage of this vaccination is still extremely low, Hib remains one of the most common causes of bacteraemias in children with SCD. The increased uptake of this conjugate vaccination may substantially improve the survival of children with SCD. This is an update of a previously published Cochrane Review. The primary objective was to determine whether Hib conjugate vaccines reduce mortality and morbidity in children and adults with SCD.The secondary objectives were to assess the following in children and adults with SCD: the immunogenicity of Hib conjugate vaccines; the safety of these vaccines; and any variation in effect according to type of vaccine, mode of administration (separately or in combination with other vaccines), number of doses, and age at first dose. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched trial registries (04 July 2018) and contacted relevant pharmaceutical companies to identify unpublished trials.Date of last search of the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinoapthies Trials Register: 18 December 2017. All randomised controlled trials (RCTs) and quasi-RCTs comparing Hib conjugate vaccines with placebo or no treatment, or comparing different types of Hib conjugate vaccines in people with SCD. No trials of Hib conjugate vaccines in people with SCD were found. There is an absence of evidence from RCTs relating to the subject of this review. There has been a dramatic decrease in the incidence of invasive Hib infections observed in the post-vaccination era in people with SCD living in high-income countries. Therefore, despite the absence of evidence from RCTs, it is expected that Hib conjugate vaccines may be useful in children affected with SCD, especially in African countries where there is a high prevalence of the disease. The implementation of childhood immunisation schedules, including universal Hib conjugate vaccination, may substantially improve the survival of children with SCD living in low-income countries. We currently lack data to evaluate the potential effect of Hib vaccination among unvaccinated adults with SCD. Further research should assess the optimal Hib immunisation schedule in children and adults with SCD.

Register-Based Ecologic Evaluation of Safety Signals Related to Pneumococcal Conjugate Vaccine in Children.

Background:In clinical trials of Pneumococcal Conjugate Vaccines (PCV), some adverse events have been reported more frequently in the PCV vaccinated. Ten-valent PCV (PCV10) was introduced into the Finnish National Vaccination Programme (NVP) in September 2010.Objective:We conducted an ecologic register-based study to investigate further the reported adverse events after PCV.Methods:This study included data obtained from the Finnish nationwide, population-based registers. First diagnoses of febrile seizures, breath-holding, urticarial rash, asthma and Kawasaki’s disease were included as outcomes obtained from the hospital discharge register. Data from Finnish Population Register during 2000-2014 for children age from 3 months to 10 years were used to estimate annual incidence rates. Incidence rate ratios of the outcomes were calculated between the target cohort of children eligible for PCV10 during 2010-2014 and a reference cohort before the NVP introduction (2004-2008).Results:No increases in the incidence of the adverse events after PCV10 introduction were found except for urticarial rash (incidence rate 2.48 vs. 1.60/1000 pyrs; incidence rate ratio, 1.54;95% CI 1.42-1.67). This increase was seen also in the unvaccinated older age groups in the post-vaccination era. The higher incidence of urticarial rash after the PCV10 introduction was due to the inclusion of diagnoses made in general medicine specialty in the discharge register because of a concomitant administrative change.Conclusion:The results do not support public health concerns related to the previously reported adverse events. Concomitant changes in health care administration and coding introduced bias, which was controlled after further evaluation of the data. We consider this register-based approach with real-world data feasible in the signal validation process after any signal detection.