Evaluation of the indirect impact of the 10-valent pneumococcal Haemophilus influenzae protein D conjugate vaccine in a cluster-randomised trial

Background In the nation-wide double-blind cluster-randomised Finnish Invasive Pneumococcal disease trial (FinIP, ClinicalTrials.gov NCT00861380, NCT00839254), we assessed the indirect impact of the 10-valent pneumococcal Haemophilus influenzae protein D conjugate vaccine (PHiD-CV10) against five pneumococcal disease syndromes. Methods Children 6 weeks to 18 months received PHiD-CV10 in 48 clusters or hepatitis B/A-vaccine as control in 24 clusters according to infant 3+1/2+1 or catch-up schedules in years 2009―2011. Outcome data were collected from national health registers and included laboratory-confirmed and clinically suspected invasive pneumococcal disease (IPD), hospital-diagnosed pneumonia, tympanostomy tube placements (TTP) and outpatient antimicrobial prescriptions. Incidence rates in the unvaccinated population in years 2010―2015 were compared between PHiD-CV10 and control clusters in age groups <5 and ≥5 years (5―7 years for TTP and outpatient antimicrobial prescriptions), and in infants <3 months. PHiD-CV10 was introduced into the Finnish National Vaccination Programme (PCV-NVP) for 3-month-old infants without catch-up in 9/2010. Results From 2/2009 to 10/2010, 45398 children were enrolled. Vaccination coverage varied from 29 to 61% in PHiD-CV10 clusters. We detected no clear differences in the incidence rates between the unvaccinated cohorts of the treatment arms, except in single years. For example, the rates of vaccine-type IPD, non-laboratory-confirmed IPD and empyema were lower in PHiD-CV10 clusters compared to control clusters in 2012, 2015 and 2011, respectively, in the age-group ≥5 years. Conclusions This is the first report from a clinical trial evaluating the indirect impact of a PCV against clinical outcomes in an unvaccinated population. We did not observe consistent indirect effects in the PHiD-CV10 clusters compared to the control clusters. We consider that the sub-optimal trial vaccination coverage did not allow the development of detectable indirect effects and that the supervening PCV-NVP significantly diminished the differences in PHiD-CV10 vaccination coverage between the treatment arms.

Faktor-Faktor yang Berhubungan Dengan Status Imunisasi (DPT-HB-Hib) Pada Bayi

Imunisasi merupakan salah satu upaya kesehatan masyarakat esensial yang efektif untuk memberikan kekebalan spesifik terhadap Penyakit yang Dapat Dicegah dengan Imunisasi (PD3I). Adanya COVID-19 yang terjadi secara global dan ditetapkan sebagai pandemi oleh WHO, memberikan dampak pada pelaksanaan program kesehatan khususnya pelayanan imunisasi dan surveilans PD3I. Vaksin Pentavalen merupakan pengembangan vaksin Tetravalen (DPT-HB) dengan penambahan antigen Haemophilus influenzae type b (Hib). Kini kelima antigen tersebut diberikan dalam satu suntikan sehingga lebih efisien, tidak menambah jumlah suntikan walaupun dengan penambahan antigen, sehingga memberikan kenyamanan bagi bayi dan ibunya Data cakupan penta 1 (DPTHBHiB 1) menunjukkan bahwa sampai dengan bulan April 2020, lebih dari 500,000 bayi belum mendapatkan imunisasi penta 1, dengan penurunan terbesar terjadi di bulan April 2020 yaitu 50,1% dibandingkan tahun 2019. Hal yang sama juga terjadi pada cakupan penta 3 (DPT-HB-HiB 3). Sampel penelitian diambil dari total populasi secara Non Random dengan menggunakan teknik Accidental Sampling yaitu dengan mengambil kasus atau responden yang kebetulan ada atau tersedia, yaitu pada saat ibu-ibu membawa bayi usia ≥ 1 tahun yang mau mendapatkan pelayanan imunisasi dasar di Klinik/BP Anisa Kecamatan Sembawa Kabupaten Banyuasin yang berjumlah 46 responden. Hasil penelitian didapatkan ada hubungan antara pekerjaan ibu, pendidikan ibu, keterjangkauan tempat pelayanan kesehatan secara simultan dengan Status Imunisasi (DPT-HB-Hib) Pada Bayi dan Balita di Klinik/BP Anisa Kec. Sembawa Kab. Banyuasin Tahun 2021. Sebagai bahan masukan bagi Klinik/BP Anisa, khususnya bagi bidan dalam menjalankan perannya untuk mengembangkan program edukasi dan konseling kepada Ibu yang mempunyai bayi dalam pemberian imunisasi.

Community-Acquired Pneumonia Requiring Hospitalization among French Guianese Children

Community-acquired pneumonia remains a leading cause of hospitalizations among children worldwide. The diagnosis is based on the history, the physical examination results in children with fever plus respiratory signs and symptoms, and chest radiography. The microbiological etiology is confirmed by viral testing and hemocultures. The most likely etiology depends on the age of the child. The features of childhood pneumonia vary between countries and territories. The purpose of this study was to describe the epidemiological characteristics and current microbial ecology of community-acquired pneumonia in children in French Guiana. We performed a retrospective, descriptive, and monocentric study between January 1, 2015, and December 31, 2017, in the pediatric ward of the Cayenne Hospital in French Guiana. The studied population was aged from 0 to 15 years and 3 months and hospitalized for acute community-acquired pneumonia. A total of 415 patients (mean age 3.62 years) were included. A pathogen was identifiable in 22.4% of cases, including bacteria in 61.3%, viruses in 43%, and coinfections in 14%. The main pathogens were respiratory syncytial virus (31.2%), Streptococcus pneumoniae (20.4%), Haemophilus influenzae (11.8%), and Mycoplasma pneumoniae (10.8%). The burden of hospitalization for children with community-acquired pneumonia was highest among less than 2 years, in whom respiratory viruses were the most commonly detected causes of pneumonia. The share of vaccine-preventable diseases (S. pneumoniae, H. influenzae, and influenza) remains high. With the vaccination requirement imposed since 1 January 2018 against pneumococcus, Haemophilus influenzae, and whooping cough and the possibility of practicing multiplex PCR in our hospital, it will be interesting to study the impact of this law enforcement on new child generations and compare these new data to our study.

Quinolone resistance is transferred horizontally via uptake signal sequence recognition in Haemophilus influenzae

The presence of Haemophilus influenzae strains with low susceptibility to quinolones has been reported worldwide. However, the emergence and dissemination mechanisms remain unclear. In this study, a total of 14 quinolone-low-susceptible H. influenzae isolates were investigated phylogenetically and in vitro resistance transfer assay in order to elucidate the emergence and dissemination mechanisms. The phylogenetic analysis based on gyrA sequences showed that strains with the same sequence type determined by multilocus sequence typing were classified into different clusters, suggesting that H. influenzae quinolone resistance emerges not only by point mutation, but also by the horizontal transfer of mutated gyrA . Moreover, the in vitro resistance transfer assay confirmed the horizontal transfer of quinolone resistance and indicated an active role of extracellular DNA in the resistance transfer. Interestingly, the horizontal transfer of parC only occurred in those cells that harbored a GyrA with amino acid substitutions, suggesting a possible mechanism of quinolone resistance in clinical settings. Moreover, the uptake signal and uptake-signal-like sequences located downstream of the quinolone resistant-determining regions of gyrA and parC , respectively, contributed to the horizontal transfer of resistance in H. influenzae . Our study demonstrates that the quinolone resistance of H. influenzae could emerge due to the horizontal transfer of gyrA and parC via recognition of an uptake signal sequence or uptake-signal-like sequence. Since the presence of quinolone-low-susceptible H. influenzae with amino acid substitutions in GyrA have been increasing in recent years, it is necessary to focus our attention to the acquisition of further drug resistance in these isolates.

Epidemiology and population structure of Haemophilus influenzae causing invasive disease

This study provides an update on invasive Haemophilus influenzae disease in Bellvitge University Hospital (2014–2019), reporting its evolution from a previous period (2008–2013) and analysing the non-typeable H. influenzae (NTHi) population structure using a clade-related classification. Clinical data, antimicrobial susceptibility and serotyping were studied and compared with those of the previous period. Population structure was assessed by multilocus sequence typing (MLST), SNP-based phylogenetic analysis and clade-related classification. The incidence of invasive H. influenzae disease remained constant between the two periods (average 2.07 cases per 100 000 population), while the 30 day mortality rate decreased (20.7–14.7 %, respectively). Immunosuppressive therapy (40 %) and malignancy (36 %) were the most frequent comorbidities. Ampicillin and fluoroquinolone resistance rates had increased between the two periods (10–17.6 % and 0–4.4 %, respectively). NTHi was the main cause of invasive disease in both periods (84.3 and 85.3 %), followed by serotype f (12.9 and 8.8 %). NTHi displayed high genetic diversity. However, two clusters of 13 (n=20) and 5 sequence types (STs) (n=10) associated with clade V included NTHi strains of the most prevalent STs (ST3 and ST103), many of which showed increased frequency over time. Moreover, ST103 and ST160 from clade V were associated with β-lactam resistance. Invasive H. influenzae disease is uncommon, but can be severe, especially in the elderly with comorbidities. NTHi remains the main cause of invasive disease, with ST103 and ST160 (clade V) responsible for increasing β-lactam resistance over time.

Evaluation of Real-Time Polymerase Chain Reaction in Culture-Negative Cerebrospinal Fluid Samples of Bacterial meningitis Patients

Background: Meningitis is a rigorous childhood disease with high morbidity and mortality. It is the main cause of under five mortality in India. Mainly three bacteria Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae are responsible. In low economic set up country like India, documented bacterial meningitis mainly depend on gram staining, cerebrospinal fluid (CSF) culture results or latex agglutination test resulting in less number of positive due to the prior antimicrobial intake which affects culture and latex agglutination test results. This study was taken up rapid and accurate molecular method like RT PCR to diagnose bacterial meningitis in culture-negative CSF samples. Materials and Methods: Fifty culture-negative CSF samples from suspected cases of bacterial meningitis were examined by real-time polymerase chain reaction (real-time PCR) for the presence of lytA, bexA, and ctrA genes specific for Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis respectively. Results: Positive real-time PCR results for Streptococcus pneumoniae were detected in 36 (72%) of culture-negative CSF samples while 10% positive results for Haemophilus influenzae type b. Nine (18%) samples were negative by real-time PCR for all tested organisms. Conclusion: The use of molecular techniques as real-time PCR can provide a valuable addition to the proportion of diagnosed cases of bacterial meningitis especially in settings with high rates of culture-negative results.

Structural Characterization of Haemophilus influenzae Enolase and Its Interaction with Human Plasminogen by In Silico and In Vitro Assays

Haemophilus influenzae is the causal agent of invasive pediatric diseases, such as meningitis, epiglottitis, pneumonia, septic arthritis, pericarditis, cellulitis, and bacteremia (serotype b). Non-typeable H. influenzae (NTHi) strains are associated with localized infections, such as otitis media, conjunctivitis, sinusitis, bronchitis, and pneumonia, and can cause invasive diseases, such as as meningitis and sepsis in immunocompromised hosts. Enolase is a multifunctional protein and can act as a receptor for plasminogen, promoting its activation to plasmin, which leads to the degradation of components of the extracellular matrix, favoring host tissue invasion. In this study, using molecular docking, three important residues involved in plasminogen interaction through the plasminogen-binding motif (251EFYNKENGMYE262) were identified in non-typeable H. influenzae enolase (NTHiENO). Interaction with the human plasminogen kringle domains is conformationally stable due to the formation of four hydrogen bonds corresponding to enoTYR253-plgGLU1 (K2), enoTYR253-plgGLY310 (K3), and enoLYS255-plgARG471/enoGLU251-plgLYS468 (K5). On the other hand, in vitro assays, such as ELISA and far-western blot, showed that NTHiENO is a plasminogen-binding protein. The inhibition of this interaction using polyclonal anti-NTHiENO antibodies was significant. With these results, we can propose that NTHiENO–plasminogen interaction could be one of the mechanisms used by H. influenzae to adhere to and invade host cells.