Evaluation of the direct and indirect impact on pneumonia hospitalization after almost a decade of the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine in Brazil

Introduction: Pneumococcal pneumonia is a leading cause of severe disease, leading to approximately 2.2 million hospital admissions in 2019 in Brazil. Since 2010, the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine was introduced in Brazil, as part of the National Immunization Program (NIP) with universal access, approximated coverage of 91.4% in 2019. Although studies from many countries are available, there is still a need to understand the effect of the vaccine introduction on the incidence of pneumonia hospitalizations in Brazil.Methods: Data on hospitalization associated with the diagnosis of pneumonia in the population assisted by the Brazilian Public Health System were accessed to fit a time series analysis, which tested the main hypothesis of the influence of vaccination on the trends for the incidence of pneumonia hospitalizations.Results: The post-vaccination period showed a negative trend, reducing 1.75, 0.16, and 0.11 cases per 100,000 inhabitants per month for the groups < 1, 1­4, and 5­9 years old, respectively. In individuals older than 20 years, the post-vaccination period has a positive trend, but not as great as compared trends before the vaccination period. These results indicate a protective herd effect in the older population, nine years after introducing the pneumococcal vaccine in the NIP.Conclusion: Vaccination with pneumococcal conjugated vaccine reduces hospitalizations associated with pneumonia diagnosis in vaccinated and non-vaccinated populations in a sustained and progressive manner.

Expert consensus on immunoprophylaxis of pneumococcal disease (2020 version) / 中华流行病学杂志

Pneumococcal disease is a serious global public health problem and a leading cause of morbidity and mortality of children and adults in China. Antibiotics are commonly used to treat pneumococcal disease. However, antibiotic resistance to Streptococcus pneumoniae has become a severe problem around the world due to widespread antibiotic use. Immunoprophylaxis of pneumococcal disease with pneumococcal vaccines is therefore of great importance. In this article, we review the etiology, clinical presentation, epidemiology, and disease burden of pneumococcal disease and the vaccinology of pneumococcal vaccines. Our review is based on the Expert Consensus on Immunoprophylaxis of Pneumococcal Disease (2017 version), the Pneumococcal Vaccines WHO Position Paper (2019), and recent national and international scientific advances. This consensus article aims to provide public health and vaccination staff with appropriate evidence for pneumococcal vaccine use and to improve professional capacity for pneumococcal disease prevention and control.

Pneumococcal conjugate vaccines and hospitalization of children for pneumonia: a time-series analysis, South Africa, 2006­2014

Objective To assess the impact of immunization with pneumococcal conjugate vaccines on all-cause pneumonia hospitalizations among children in Soweto, South Africa. Methods We used data collected at the Chris Hani Baragwanath Hospital in Soweto between 2006 and 2014 ­ i.e. before and after April 2009, when a pneumococcal conjugate vaccine was first included in South Africa's routine immunization programme. Using a Bayesian generalized seasonal autoregressive moving-average model and the data collected in 2006­2008, we estimated the numbers of children that would have been hospitalized for pneumonia between 2010 and 2014 if no pneumococcal conjugate vaccines had been used. These estimates were then compared with the corresponding numbers of hospitalizations observed. Findings Between 2006 and 2014, 26 778 children younger than five years ­ including 3388 known to be infected with human immunodeficiency virus (HIV) ­ were admitted to the study hospital for pneumonia. We estimated that, for the children known to be infected with HIV and for the other children, pneumococcal conjugate vaccines reduced the numbers of hospitalizations for pneumonia in 2014 by 33% (50% credible interval, CrI: 6 to 52) and 39% (50% CrI: 24 to 50), respectively. In the study hospital in 2012­2014, as a result of immunizations with these vaccines, there were an estimated 3100 fewer pneumonia hospitalizations of children younger than five years. Conclusion. In our study hospital, following the introduction of pneumococcal conjugate vaccines into the national immunization programme, there were significant reductions in pneumonia hospitalizations among children

Enfermedad meningocóccica invasora por serogrupo B en dos niños chilenos vacunados contra serogrupos ACWY / Meningococcal invasive disease caused by serogroup B in two Chilean children vaccinated against ACWY serogroups

Invasive meningococcal disease (IMD) by serogroup W has become predominant in Chile since 2012, prompting vaccination with conjugate ACWY. We reported two pediatric cases in patients already vaccinated, which evolved with IMD by serogroup B. This should remind us to keep the alertness with this pathology, despite the current vaccination system in Chile, emphasizing in improve our epidemiological case definition and its diagnosis.

La Enfermedad Meningocóccica Invasora (EMI) por serogrupo W ha llegado a ser predominante en Chile desde el 2012, motivando estrategias de inmunización con vacunas conjugadas contra los serogrupos ACWY. Presentamos dos casos pediátricos de pacientes vacunados contra meningococo ACWY que evolucionaron con EMI por serogrupo B, lo que debe recordarnos la alerta y sospecha de esta patología, inclusive con el esquema de vacunación actual chileno, poniendo énfasis en mejorar nuestra definición epidemiológica de caso sospechoso para optimizar su diagnóstico.

Enfermedad neumoccócica invasora en recién nacidos, antes y después de la vacunación universal con vacuna conjugada 7 y 13 valente en Uruguay / Pneumococcal invasive disease in newborns before and after 7-valent and 13-valent universal pneumococcal vaccination in Uruguay

Introduction: Streptococcus pneumoniae infections are not frequent in neonates, but presents high morbidity and mortality. In 2008, the 7-valent pneumococcal conjugate vaccine (PCV) was introduced in the childhood vaccination schedule and then replaced by 13-valent PCV in 2010. First dose is given at 2 months of age. Protection of neonates is expected with universal vaccination. Objective: To describe the clinical presentation, microbiology and outcome of neonates with pneumococcal invasive infections (PII) detected in two hospitals in Uruguay in 2001-2007 (pre-vaccination), 2008 (intervention) and 2009-2013 (post-vaccination). Methods: A descriptive, retrospective study was done at Pereira Rossell Hospital and Paysandú Hospital. All isolates of S. pneumoniae obtained from normally sterile fluids were included. Data were obtained from the clinical records and the microbiology laboratory. A statistical analysis with absolute frequencies, relative, rates and relative risk was performed. Results: 25 neonates were enrolled with diagnosis of: sepsis (n = 13), meningitis (n = 9), bacteremia (n = 1), pneumonia with empyema (n = 1) and pneumonia (n = 1). The incidence of PII in the prevaccination period was 19/25, with a rate of 0.30/1,000 births, compared to post-vaccination rate of 0.04/1,000. The relative risk was 5.9. 6/20 (30%) cases of death were reported (meningitis n = 3; sepsis n = 2; empyema n = 1). Most common serotypes were 5 and 1 (14/25) and 24/25 strains were susceptible to penicillin. Discussion: The symptoms were indistinguishable to infections caused by other pathogens. PII cases decreased and no deaths occurred in the post-vaccination period. No increase in non-vaccine serotypes was observed.

Introducción: Streptococcus pneumoniae infrecuentemente produce infecciones en recién nacidos (RN), presentando elevada morbi-mortalidad. En Uruguay, en 2008 se incorporó al calendario de inmunizaciones infantil la vacuna conjugada neumocóccica (VCN) 7 valente, (sustituída por VCN13 en 2010). La vacunación comienza a los dos meses de vida. Se espera que la vacunación universal tenga impacto en la protección de RN. Objetivo: Describir la presentación clínica, microbiología y evolución de RN con enfermedad neumocóccica invasora (ENI), identificados en dos hospitales de Uruguay, años 2001-2007 (pre-vacunación), 2008 (intervención) y 2009-2013 (post-vacunación). Material y Métodos: Estudio descriptivo, retrospectivo. Lugar: Hospital Pereira Rossell y Hospital Paysandú. Se incluyeron todos los aislados de S. pneumoniae a partir de líquidos normalmente estériles. Fuente de datos: laboratorios de bacteriología e historias clínicas. Análisis estadístico: frecuencias absolutas, relativas, tasas y riesgo relativo. Resultados: RN con ENI: 25, sepsis (n: 13), meningitis (n: 9), bacteriemia (n: 1), neumonía con empiema (n: 1), neumonía (n: 1). Incidencia de ENI en el período pre-vacunación 19/25, tasa 0,30/1.000 nacimientos; tasa post-vacunación: 0,04/1.000. Riesgo relativo 5,9. Fallecimientos: 6/20 (30%): meningitis (n: 3), sepsis (n: 2), empiema (n: 1). Los serotipos más frecuentes fueron: 5 y 1 (14/25). Susceptibles a penicilina: 24/25. Discusión: Los síntomas fueron indistinguibles de infecciones causadas por otros patógenos. Disminuyeron los casos de ENI y no ocurrieron fallecimientos en el período post-vacunación. No aumentaron los serotipos no vacunales.

Vacunas anti-neumocóccicas en población pediátrica: actualización / Pneumococcal vaccines in children: an update

Conjugated pneumococal vaccines had a notable impact on prevention of invasive pneumococcal disease (IPD) in vacccinated and non vaccinated (herd immunity) populations. In Chile a 10 valent conjugated vaccine (PCV10) was introduced in the Nacional Immunization Program (NIP) in 2011, initially in a 3+1 schedule at 2, 4, 6 and 12 months of age, and since 2012 in a 2+1 schedule (2, 4 and 12 months). In prematures schedule 3+1 was mantained. No catch up or high risk groups vaccination strategies were used. The inclusion of PCV10 has reduced the rates of IPD; 66% in infants less than 12 months old and a 60% in 12-24 months old. After 3 years of the introduction of PCV10, no herd immunity has been seen. Serotype replacement shows an increase of ST 3 but not ST19A. Surveillance shows that another vaccine with 13 serotypes (PCV13) would cover an additional 5 to 10% of cases. The nule herd immunity and more extense coverage of PCV13, suggests that NIP should switch from PCV10 to PCV13.

Las vacunas antineumocóccicas conjugadas han tenido un impacto notable en la prevención de enfermedad neumocóccica invasora (ENI) en grupos vacunados y en contactos no vacunados (efecto rebaño). En Chile se incorpora en el PNI la vacuna conjugada de 10 serotipos (PCV10), el año 2011 a los 2, 4 y 6 meses , con un refuerzo a los 12 meses (esquema 3+1) y el año 2012 se elimina la dosis de los 6 meses (esquema 2+1), manteniendo esquema 3+1 en el prematuro. No se incluyen otros grupos etarios o pacientes con condiciones de riesgo. La vacunación ha reducido las tasas de ENI en 66% en menores de 12 meses, y en 60% en niños de 12 a 24 meses. A tres años de introducida la vacuna no hay evidencia de efecto rebaño. En relación a ST no contenidos en PCV10, se observa un incremento de ST 3, aunque no de ST 19A. La vigilancia realizada muestra que otra vacuna disponible (PCV13), tendría una cobertura de ST entre 5 y 15% superior a PCV10. Este hecho y el nulo efecto rebaño de PCV 10, hacen necesario considerar el reemplazo de PCV10 por PCV13 en el PNI.

Immunogenicity and safety of a pentavalent diphtheria, tetanus, acellular pertussis, inactivated poliovirus, haemophilus influenzae type b conjugate combination vaccine (pentaxim™) with hepatitis B vaccine.

Objective: To obtain immunogenicity and safety data for a pentavalent combination vaccine (diphtheria, tetanus, acellular pertussis, inactivated poliovirus, Hib polysaccharide-conjugate). Design: Multicenter, open, Phase III clinical study. A DTaP-IPV//PRP~T vaccine (PentaximTM) was given at 6,10,14 weeks of age; and Hepatitis B vaccine at 0,6,14 or at 6,10,14 weeks of age. Immunogenicity assessed 1 month post-3rd dose; safety assessed for 30 minutes by the investigator, then by parents and investigators to 8 days and 30 days post-vaccination. Setting: Tertiary-care hospitals. Participants/patients: 226 healthy Indian infants (6 weeks of age). Main outcome measures: Immunogenicity and safety. Results: Immunogenicity was high for each vaccine antigen, and similar to a historical control study (France) following a 2,3,4 month of age administration schedule. Post-3rd dose, 98.6% of subjects had anti-PRP ³0.15 mg/mL and 90.0% had titers ³1.0 mg/mL; the anti-PRP GMT was 4.1 µg/mL. Seroprotection rates for diphtheria and tetanus (³0.01 IU/mL) were 99.1% and 100%; and 100%,99.1% and 100%, for polio types 1,2 and 3 (³8 [1/dil]) respectively. Anti-polio GMTs were 440.5,458.9, and 1510.7 (1/dil) for types 1,2 and 3 respectively. The vaccine response rates to pertussis antigens (4-fold increase in antibody concentration) were 93.7% for PT and 85.7% for FHA; the 2-fold increase was 97.1% and 92.4%. Vaccine reactogenicity was low with adverse reaction incidence not increasing with subsequent doses. Conclusion: The DTaP-IPV//PRP~T vaccine, given concomitantly with monovalent hepatitis B vaccine, was highly immunogenic at 6, 10 and 14 weeks of age in infants in India. The vaccine was well tolerated.

Occurrence of Haemophilus influenzae strains in three Brazilian states since the introduction of a conjugate Haemophilus influenzae type b vaccine

Few vaccines in history have induced such a dramatic decline in incidence over such a short period of time as the Haemophilus influenzae type b (Hib) conjugate. This vaccine was introduced in 1988 in the United States, but only in 1999 was Hib immunization introduced by the Brazilian Ministry of Health as part of the routine infant National Immunization Program. The authors analyzed 229 H. influenzae (Hi) isolates from Public Health Laboratories in three Brazilian states: Pernambuco (Northeast, N = 54), Santa Catarina (South, N = 19), and Rio de Janeiro (Southeast, N = 156). The isolates were collected from Brazilian children 0-10 years of age with meningitis and other infections from 1990 to 2003 and were part of the research collection of the National Institute of Quality Control in Health, FIOCRUZ. Bacterial strains were characterized by serotyping and biotyping. During the pre-vaccination period the prevalence infection due to Hib was of 165 isolates and only 2 non-b Hi among all the notified meningitis infections caused by Hi. Our results showed a significant decrease in the prevalence of Hib meningitis from 165 to 33 isolates after 1999. However, during the post-vaccination period of 2001-2003 we observed an increase in the number of non-b Hi isolates: only 2 non-b strains isolated from 1990 to 1999 and 29 from 1999 to 2003. Based on the present data, the authors emphasize the need for more sensitive epidemiological and bacteriological studies aiming the improvement of the available Hib vaccine, in order to protect the susceptible population to infections due to other serological types of Hi and the reevaluation of immunization schedules used by the National Immunization Program.

Immunoprotective potential of polysaccharide-tetanus toxoid conjugate in Klebsiella pneumoniae induced lobar pneumonia in rats.

The polysaccharide (PS) derived from K. pneumoniae NCTC 5055 lipopolysaccharide (LPS) was covalently linked to tetanus toxoid by using carbodimide with adipic acid dihydrazide as a spacer molecule. The conjugate was found to be non-toxic and non-pyrogenic at 100 microg dose level. At a similar dose, the conjugate did not elicit any local skin reaction on intradermal preparatory injection in rabbits. The conjugate was immunoprotective as was evident from the decrease in relative colonization of bacteria in lungs of immunized rats as compared to the control animals. Immunization with the conjugate resulted in alveolar macrophage activation in terms of their ability to phagocytose bacteria in vitro.

Current status of fertility control methods in India.

Approximately 48.2% of couples of 15 to 49 years of age practice family planning methods in India. Female sterilization accounts for 34.2%, with male sterilization declining from 3.4% in 1992-93 to 1.9% in 1998-99. Use of the condom increased to 3.1% from 2.4%. There is an urgent need for research to develop new contraceptive modalities especially for men and also for women and to make existing methods more safe, affordable and acceptable. Current efforts in India to develop a male contraceptive are mainly directed towards (i) development of antispermatogenic agents to suppress sperm production, (ii) prevention of sperm maturation, (iii) prevention of sperm transport through vas deferens or rendering these sperm infertile and (iv) prevention of sperm deposition. Research work in the field of prevention of sperm transport through vas deferens has made significant advances. Styrene maleic anhydride (SMA) disturbed the electrical charge of spermatozoa leading to acrosome rupture and consequent loss in fertilizing ability of sperm. A multicentre phase-III clinical trial using SMA is continuing and it is hoped that the SMA approach would be available in the near future as an indigenously developed injectable intra-vasal male contraceptive. The safety and efficacy of available oral contraceptives were evaluated. An indigenously developed oral contraceptive 'Centchorman', which is a nonsteroidal, weakly estrogenic but potently antiestrogenic, was found to be safe and effective and is now being marketed in India since 1991 as a 'once a week' pill. Cyclofem and Mesigyna have been recommended as injectable contraceptives with proper counselling and service delivery by Indian studies. It has been recommended that these injectable contraceptives be added to the existing range of contraceptive methods available in the National Family Planning Programme. Based on the Indian studies CuT 200 was also recommended. Studies have indicated the advantage of intrauterine devices (IUD); they are long acting, relatively easily removed and fertility returns rapidly after their removal. Recent studies have recommended CuT 200 for use up to 5 years. The combination of some plant products i.e. Embelia ribes, Borax and Piper longum has been found to be safe and effective as a female contraceptive and the results of phase-I clinical trials are encouraging. Research work is going on in the country in various areas with special reference to hormonal contraceptive - a three monthly injectable contraceptive, immuno-contraceptives, antiprogestins, etc.

Analise critica sobre o uso das vacinas conjugadas contra o Haemophilus influenzae do tipo b em diferentes paises / Critical analysis about the use of Haemophylus influenzae type b conjugate vaccines in different countries

O Haemophylus influenzae do tipo b (Hib) e um dos principais agentes causadores de doencas invasivas em criancas, tais como meningite, epiglotite, pneumonia e bacteremia. Desde 1987, as vacinas conjugadas contra o Hib vem sendo amplamente utilizadas em diversos paises desenvolvidos, e o sucesso da imunizacao pode ser comprovado pelo rapido desaparecimento das infeccoes graves causadas pelo Hib, apos a introducao da vacinacao de rotina contra o Hib para todas as criancas com idade entre 2 meses e 5 anos. Neste artigo, a autora apresenta uma revisao sobre o impacto epidemiologico da vacinacao contra o Hib, em 4 paises desenvolvidos - Finlandia, Estados Unidos, Inglaterra e Suecia - e analisa as dificuldades relacionadas a introducao desta vacina nos paises em desenvolvimento

Immunogenicity and tolerance of H. influenzae type b, tetanus toxoid conjugate vaccine given concurrently or in combination.

The present prospective, open, controlled, randomised comparative trial was undertaken to evaluate the sero response and side effects of PRP-T Conjugate Vaccine (ACT-HIB) in infants and children aged 2 months and 16-24 months. Fifty four babies aged 2 months formed group A, 56 children aged 16-24 months formed group B. Groups A and B were further subdivided into two sub groups each destined to receive either PRP-T vaccine in association with DPT vaccine at different sites (I) or PRP-T and DPT both vaccines at the same site mixed in the same syringe (II). Group A received 3 doses at 2, 3 and 4 months of age and group B received one dose between 16-24 months. The Geometric mean titres of Anti PRP antibodies observed in primary immunisation schedule (A) and single dose vaccination schedule (B) were comparable and significantly higher to prevaccination titres. A serum anti PRP level of > 1.0 mcg/ml after immunisation is believed to correlate with long term protection. Ninety-six percent of infants in Group A and 98% in Group B achieved titres > 1.0 mcg/ml. The side effects were minimal, local and were comparable between the study and control groups, suggesting that PRP-T vaccine is highly immunogenic and well tolerated in Indian infants and children.