Evaluation of Multiplex Real-time PCR and WHO Criteria for Diagnosing Childhood Bacterial Meningitis in a Tertiary Referral Hospital in Iran

Background: Childhood bacterial meningitis (BM) requires prompt and precise diagnosis to provide proper treatment and decline mortality and morbidity. Objectives: We aimed to evaluate the World Health Organization (WHO) criteria and polymerase chain reaction (PCR) for diagnosing BM in children admitted to a tertiary referral hospital in Shiraz, southern Iran. Materials: We included all 492 children aged one month to 17 years suspected of meningitis who had cerebrospinal fluid (CSF) leukocytosis admitted to Nemazi Hospital from August 2016 to September 2017. The CSF specimens were examined for routine analysis, Gram staining, and culture. A multiplex real-time PCR was used to identify Streptococcus pneumoniae, Haemophilus influenzae type b (Hib), and Neisseria meningitidis in the CSF samples. Seven viruses were also investigated using real-time PCR. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated using the WHO criteria and the multiplex real-time PCR results. Results: Seventy-four CSF samples had leukocytosis. Nineteen (22.9%) patients had BM caused by S. pneumoniae (n = 14), Hib (n = 2), Salmonella enterica (n = 2), and N. meningitidis (n = 1). The PCR test detected all cases, except for two with Salmonella meningitis (sensitivity 89.4%, specificity 100%, PPV 100%, and NPV 96%). The WHO criteria detected all cases, except three who received antibiotics at least four days before performing lumbar puncture (sensitivity 84.2%, specificity 98.2%, PPV 94.1%, and NPV 94.7%). Enterovirus was the most common viral etiology (6.75%). Conclusions: The WHO criteria and the multiplex real-time PCR had high accuracy in our setting, and their use could decrease the antibiotic over-prescription in febrile children suspected of meningitis.

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.

Epidemiological Study and Associated Risk Factors for Developing Bacterial Meningitis in Children of Odisha, India

Background: Bacterial meningitis is a leading cause of high childhood transience. It is the foremost cause of fatality in pediatric age group of 0-5 years in India accounting 0.5 to 2.6% of hospital admissions with CFR 16-30%. Based on above scenario, the study was undertaken to address the prevalence, etiology, social determinants of health factors of bacterial meningitis among under five children Odisha, India. Methods: A cross sectional study comprising of children under five years of age admitted to tertiary care hospital and teaching institutions in Cuttack with suspected clinical diagnosis of bacterial meningitis during April, 2012 to September 2013. About 634 children enrolled into the study after getting appropriate consent from parents or their legal guardians. Lumbar puncture was done and CSF was sent for biochemical analysis, cell counts, staining, culture, latex agglutination test (LAT) and real time polymerase chain reaction (RT PCR). Results: About 61 children (10.4%) were confirmed with diagnosis of bacterial meningitis by either culture, latex or RT PCR. Male children (74.7%) were significantly more prone to bacterial meningitis than females (24.3%). The common isolated pathogens were Streptococcus pneumonia, Haemophilus influenza type b, E. coli, Pseudomonas aeruginosa, Klebseilla pneumoniae and Staphylococcus aureus. Streptococcus pneumoniae was observed to be most common pathogen (57.6%) followed by Haemophilus influenzae type b (26.2%). The risk factors analyzed showed statistically significant association (p<0.01) with low household income, mother’s education, overcrowding (more than 3 persons in a single room), smoking and poor ventilation of household. Conclusion: Strengthening early detection of bacteria meningitis by rapid diagnostic test like LATEX, RT PCR and prompt treatment of emergent case at the household level, improvement in mother’s education and awareness, transportation to local hospital and facility for treatment and care should be utmost priority in the present scenario. It is crucial to assess the burden of bacterial meningitis with its etiology is in this region as vaccines are yet to be introduced in the child vaccine program.

Haemophilus Influenzae Type B-Diseases

Haemophilus influenzae is a small Gram negative coccobacillus colonizing the respiratory tract of humans. The bacterium may cause direct local infections like otitis media, as well as severe invasive diseases like meningitis. In the prevaccine era, of the 6 capsular serotypes (a–f), type b caused the majority of invasive disease cases, whereas “nontypeable H. influenzae” (NTHi) and other capsular types predominate today. H. influenzae infections affect mainly children <5 years as well as persons >60 years with underlying diseases like COPD. Diagnosis of Hib disease is performed by classical microbiological culture techniques, antigen detection tests and polymerase chain reaction from blood samples, CSF or puncture samples. If untreated or if treatment is delayed, invasive Hib diseases may result in severe consequences such as hearing loss, chronic seizures, learning disabilities, and even death. Safe and effective polysaccharide-conjugate vaccines have been available for children for almost 30 years, reducing invasive Hib-incidences from about 60 to <1 / 105. Today, largely DTP-based Hib-combinations are used. After the primary series with 2 or 3 doses depending on the product and local recommendations, a booster dose in the second year of life is needed to ensure long-term protection.

Vaccine Responses in Adult Hematopoietic Stem Cell Transplant Recipients: A Comprehensive Review

Consensus on timing of post-hematopoietic stem cell transplantation (HSCT) vaccination is currently lacking and is therefore assessed in this review. PubMed was searched systematically for articles concerning vaccination post-HSCT and included a basis in predefined criteria. To enable comparison, data were extracted and tables were constructed per vaccine, displaying vaccine response as either seroprotection or seroconversion for allogeneic HSCT (alloHSCT) and autologous HSCT (autoHSCT) separately. A total of 33 studies were included with 1914 patients in total: 1654 alloHSCT recipients and 260 autoHSCT recipients. In alloHSCT recipients, influenza vaccine at 7–48 months post-transplant resulted in responses of 10–97%. After 12 months post-transplant, responses were >45%. Pneumococcal vaccination 3–25 months post-transplant resulted in responses of 43–99%, with the response increasing with time. Diphtheria, tetanus, pertussis, poliomyelitis and Haemophilus influenzae type b at 6–17 months post-transplant: 26–100%. Meningococcal vaccination at 12 months post-transplant: 65%. Hepatitis B vaccine at 6–23 months post-transplant: 40–94%. Measles, mumps and rubella at 41–69 months post-transplant: 19–72%. In general, autoHSCT recipients obtained slightly higher responses compared with alloHSCT recipients. Conclusively, responses to childhood immunization vaccines post-HSCT are poor in comparison with healthy individuals. Therefore, evaluation of response might be indicated. Timing of revaccination is essential for optimal response. An individualized approach might be necessary for optimizing vaccine responses.

Vaccination programs for children aged up to 18 years in Europe, 2020

Although all European countries have vaccination policies for children, there are no comprehensive studies of pediatric vaccination programs in Europe. We studied vaccination programs for children in Europe. Vaccinations against diphtheria, tetanus, pertussis, poliomyelitis, Haemophilus influenzae type b, hepatitis B, measles, mumps, rubella, and influenza existed in 42 countries, against human papilloma virus in 41 countries, and against pneumococcus in 40 countries. In addition, the following vaccinations existed: against tuberculosis (35 countries), hepatitis A (33), meningococcus A, C, W, Y (30), rotavirus and varicella (28 countries each), meningococcus B (24), tick-born encephalitis (22), and meningococcus C (16). Mandatory vaccinations are implemented in 21 countries, mainly against diphtheria, tetanus, pertussis, poliomyelitis, H. influenzae type b, hepatitis B, measles, mumps, rubella, tuberculosis, and pneumococcus. There are significant differences among pediatric vaccination programs in Europe regarding number, schedules, indications, and regulatory frame (recommended or mandatory vaccinations). A consensus-based vaccination program for all children is needed.

Vaccine Types

Vaccines are biological preparations, often made from attenuated or killed forms of microorganisms or fractions thereof. They work by stimulating the immune system to produce antibodies and cells directed against a particular organism, mimicking "natural infection". Based on their biological and chemical characteristics, vaccines can be categorized into two basic types, "Live-attenuated" (bacterial or viral) vaccines and "inactivated" or "non-live" vaccines. Examples of live-attenuated vaccines include: measles-, mumps-, and rubella-, varicella-, yellow fever-, oral polio- (OPV), rotavirus-, ("nasal-spray") live-attenuated influenza- (LAIV), and BCG-vaccine. Attenuation results in micro-organisms that may still infect and multiply in humans, but they do not cause disease. Some of these vaccines are associated with life-long immunity. Inactivated or non-live vaccines include those against hepatitis A, influenza, pertussis, rabies or the polysaccharide vaccines directed against encapsulated bacteria (Haemophilus influenzae type b, Streptococcus pneumoniae, Neisseria meningitidis). Most non-live vaccines generally require additional doses ("boosters") to maintain long-term protective immunity. There are many other subcategories of these basic groups, like subunit vaccines, whole cell vaccines, toxoid vaccines, polysaccharide vaccines, recombinant protein vaccines, mucosal vaccines, or DNA-, mRNA- and vector-vaccines.

Chemically Synthesized Alcaligenes Lipid A as an Adjuvant to Augment Immune Responses to Haemophilus Influenzae Type B Conjugate Vaccine

We previously identified Alcaligenes spp. as a commensal bacterium that resides in lymphoid tissues, including Peyer’s patches. We found that Alcaligenes-derived lipopolysaccharide acted as a weak agonist of Toll-like receptor four due to the unique structure of lipid A, which lies in the core of lipopolysaccharide. This feature allowed the use of chemically synthesized Alcaligenes lipid A as a safe synthetic vaccine adjuvant that induces Th17 polarization to enhance systemic IgG and respiratory IgA responses to T-cell–dependent antigens (e.g., ovalbumin and pneumococcal surface protein A) without excessive inflammation. Here, we examined the adjuvant activity of Alcaligenes lipid A on a Haemophilus influenzae B conjugate vaccine that contains capsular polysaccharide polyribosyl ribitol phosphate (PRP), a T-cell–independent antigen, conjugated with the T-cell–dependent tetanus toxoid (TT) antigen (i.e., PRP-TT). When mice were subcutaneously immunized with PRP alone or mixed with TT, Alcaligenes lipid A did not affect PRP-specific IgG production. In contrast, PRP-specific serum IgG responses were enhanced when mice were immunized with PRP-TT, but these responses were impaired in similarly immunized T-cell—deficient nude mice. Furthermore, TT-specific—but not PRP-specific—T-cell activation occurred in mice immunized with PRP-TT together with Alcaligenes lipid A. In addition, coculture with Alcaligenes lipid A promoted significant proliferation of and enhanced antibody production by B cells. Together, these findings suggest that Alcaligenes lipid A exerts an adjuvant activity on thymus-independent Hib polysaccharide antigen in the presence of a T-cell–dependent conjugate carrier antigen.