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1.
BJOG ; 127(6): 680-691, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-31913562

RESUMEN

BACKGROUND: Early-onset group B streptococcal (EOGBS) disease (including sepsis, meningitis, and pneumonia) causes significant morbidity and mortality in newborn infants worldwide. Antibiotic prophylaxis can prevent vertical streptococcal transmission, yet no uniform criteria exist to identify eligible women for prophylaxis. Some guidelines recommend universal GBS screening to pregnant women in their third trimester (screening-based protocol), whereas others employ risk-based protocols. OBJECTIVES: To compare the effectiveness of screening-based versus risk-based protocols in preventing EOGBS disease. SEARCH STRATEGY: Key words for the database searches included GBS, Streptococcus agalactiae, pregnancy, screening, culture-based, risk-based. SELECTION CRITERIA: Studies were included if they investigated EOGBS disease incidence in newborn infants and compared screening or risk-based protocols with each other or with controls. DATA COLLECTION AND ANALYSIS: Risk ratios (RR) and 95% confidence intervals (CI) were determined using Mantel-Haenszel analyses with random effects. MAIN RESULTS: Seventeen eligible studies were included. In this meta-analysis, screening was associated with a reduced risk for EOGBS disease compared either with risk-based protocols (ten studies, RR 0.43, 95% CI 0.32-0.56) or with no policy (four studies, RR 0.31, 95% CI 0.11-0.84). Meta-analysis could not demonstrate a significant effect of risk-based protocols versus no policy (seven studies, RR 0.86, 95% CI 0.61-1.20). In studies reporting on the use of antibiotics, screening was not associated with higher antibiotic administration rates (31 versus 29%). CONCLUSIONS: Screening-based protocols were associated with lower incidences of EOGBS disease compared with risk-based protocols, while not clearly overexposing women to antibiotics. This information is of relevance for future policymaking. TWEETABLE ABSTRACT: Meta-analysis: general screening is associated with lower rates of early-onset group B strep. neonatal sepsis compared with risk-based protocols.


Asunto(s)
Profilaxis Antibiótica , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Complicaciones Infecciosas del Embarazo/diagnóstico , Sepsis/prevención & control , Infecciones Estreptocócicas/prevención & control , Streptococcus agalactiae/aislamiento & purificación , Femenino , Humanos , Recién Nacido , Servicio de Ginecología y Obstetricia en Hospital , Embarazo , Complicaciones Infecciosas del Embarazo/tratamiento farmacológico , Complicaciones Infecciosas del Embarazo/microbiología , Medición de Riesgo , Factores de Riesgo , Sepsis/tratamiento farmacológico , Infecciones Estreptocócicas/tratamiento farmacológico
5.
Fish Shellfish Immunol ; 93: 924-933, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31374315

RESUMEN

Our previous studies demonstrated that the deletion of D2 fragment in tilapia Streptococcus agalactiae(GBS) attenuated strain YM001 is the main reason for the loss of virulence to tilapia. In this study, a Δ2 mutant that deletion of D2 fragment in parental virulent strain HN016 was constructed, and the safety, stability, immunogenicity, and growth characteristics, as well as the virulence mechanism of Δ2 mutant were evaluated. The results showed that Δ2 mutant was not pathogenic to tilapia, and the virulent revertants were not observed after 50 generations of passage. The RPS reached 96.11% at 15 days and 93.05% at 30 days, respectively, after intraperitoneal injection, while RPS reached 74.80% at 15 days and 53.16% at 30 days, respectively, after oral immunization. The growth of Δ2 mutant was significantly faster than YM001, and genes that were enriched in the nitrogen metabolism and arginine biosynthesis signaling pathway (arc, glnA, and gdhA) were identified as important candidate genes responsible for growth rate of S. agalactiae. The absence of D2 fragment affected the expression of Sip, therefore influencing the bacterial virulence. Altogether, this study demonstrated that deletion of D2 fragment in HN016 causes the loss of virulence to tilapia, and Δ2 mutant is a promising, better attenuated oral vaccine strain of S. agalactiae compared to YM001.


Asunto(s)
Vacunas Bacterianas/inmunología , Secuencia de Bases , Cíclidos/inmunología , Enfermedades de los Peces/prevención & control , Eliminación de Secuencia , Infecciones Estreptocócicas/veterinaria , Streptococcus agalactiae/inmunología , Animales , Enfermedades de los Peces/inmunología , Técnicas de Inactivación de Genes/veterinaria , Serogrupo , Infecciones Estreptocócicas/inmunología , Infecciones Estreptocócicas/prevención & control , Streptococcus agalactiae/patogenicidad , Vacunas Atenuadas/inmunología , Virulencia
6.
Rev. esp. quimioter ; 32(4): 333-364, ago. 2019. tab, graf
Artículo en Inglés | IBECS | ID: ibc-ET5-81

RESUMEN

The childhood immunization schedule is well known and generally well implemented in developed countries. For various reasons, the same is not true of vaccines aimed at preventing infections in adults, in which vaccination coverage is incomplete and generally very deficient. In order to assess the situation of adult vaccination in Spain, the Fundación de Ciencias de la Salud has brought together a series of experts in different fields, including doctors, nurses, representatives of patient associations, health managers and economists, health authorities and journalists to deal with this issue. The format was that of a round table in which a series of questions previously formulated by the coordinators were to be answered and debated. The document presented is not an exhaustive review of the topic, nor is it intended to make recommendations, but only to give a multidisciplinary opinion on topics that could be particularly debatable or controversial. The paper reviews the main vaccine-preventable adult diseases, their clinical and economic impact, the possibilities of reducing them with vaccination programmes and the difficulties in carrying them out. The role of nursing, pharmacy services, patient associations and the health administration itself in changing the current situation was discussed. Prospects for new vaccines were discussed and we speculated on the future in this field. Finally, particularly relevant ethical aspects in decision-making regarding vaccination were discussed, which must be faced by both individuals and states. We have tried to summarize, at the end of the presentation of each question, the environment of opinion that was agreed with all the members of the table


El calendario de vacunación infantil es bien conocido y generalmente bien implementado en los países desarrollados. Por varias razones, no ocurre lo mismo en el caso de las vacunas destinadas a prevenir las infecciones en adultos, en los que la cobertura vacunal es incompleta y generalmente muy deficiente. Con el fin de evaluar la situación de la vacunación de adultos en España, la Fundación de Ciencias de la Salud ha reunido a una serie de expertos en diferentes campos, incluyendo médicos, enfermeras, representantes de asociaciones de pacientes, gestores sanitarios, economistas, autoridades sanitarias y periodistas para discutir este asunto. El formato fue el de una mesa redonda en la que una serie de preguntas, formuladas previamente por los coordinadores, debían ser contestadas y debatidas. El documento presentado no es una revisión exhaustiva del tema, ni tiene por objeto hacer recomendaciones, simplemente pretende dar una opinión multidisciplinar sobre aspectos que pueden ser debatibles o controvertidos. El documento revisa las principales enfermedades de los adultos que pueden prevenirse con vacunas, su impacto clínico y económico, las posibilidades de reducirlos con los programas de vacunación y las dificultades para llevarlos a cabo. Se discutió el papel de la enfermería, la farmacia, los servicios de salud, las asociaciones de pacientes y la propia administración sanitaria para cambiar la situación actual. Se evaluaron las perspectivas para nuevas vacunas y se especuló sobre el futuro en este campo. Por último, se discutieron los aspectos éticos especialmente relevantes en la toma de decisiones con respecto a la vacunación, que deben ser afrontados tanto por los individuos como por los estados. Hemos intentado resumir, al final de la presentación de cada pregunta, la opinión que representaba el consenso de todos los miembros de la mesa


Asunto(s)
Humanos , Adulto , Vacunas Bacterianas/administración & dosificación , Control de Enfermedades Transmisibles , Control de Infecciones , Cobertura de Vacunación/estadística & datos numéricos , Vacunas Virales/administración & dosificación , Predicción , Infecciones por Haemophilus/epidemiología , Infecciones por Haemophilus/prevención & control , Haemophilus influenzae tipo b , Hepatitis B/epidemiología , Hepatitis B/prevención & control , Incidencia , Gripe Humana/prevención & control , Infecciones Meningocócicas/epidemiología , Infecciones Meningocócicas/prevención & control , Neisseria meningitidis , Infecciones por Papillomavirus/epidemiología , Infecciones por Papillomavirus/prevención & control , España/epidemiología , Infecciones Estreptocócicas/epidemiología , Infecciones Estreptocócicas/prevención & control , Streptococcus pneumoniae , Infección por el Virus de la Varicela-Zóster/epidemiología , Infección por el Virus de la Varicela-Zóster/prevención & control
7.
PLoS Negl Trop Dis ; 13(7): e0007511, 2019 07.
Artículo en Inglés | MEDLINE | ID: mdl-31269021

RESUMEN

The prevalence of rheumatic heart disease (RHD) in the Aboriginal population of the Australian Northern Territory is high, and Streptococcus pyogenes skin infections likely contribute to this. A promising candidate S. pyogenes "30mer" vaccine is composed of 30 pharyngitis associated type-specific antigens from the S. pyogenes M protein. Cross opsonisation experiments suggest that 30mer vaccine protection may extend to non-cognate emm types. A new "emm cluster" scheme for classifying M protein is based on the full-length coding sequence, and correlates with functional and immunological properties, and anatomical tropism. Twenty-seven years of research in the Northern Territory has yielded 1810 S. pyogenes isolates with clinical and emm type data. The primary aim was to analyse these data with reference to the emm cluster scheme and cross opsonisation information, to inform estimation of 30mer vaccine efficacy in the Northern Territory. The isolates encompass 101 emm types. Variants of cluster A-C were enriched in throat isolates, and variants of emm cluster D enriched in skin isolates. Throat isolates were enriched for 30mer vaccine cognate emm types in comparison with skin isolates of which only 25% were vaccine emm types. While cross opsonisation data indicates potential for enhancing 30mer vaccine coverage, more than one third of skin isolates were within 38 emm types untested for cross opsonisation. Emm cluster D variants, in particular emm cluster D4, were not only all non-cognate with the vaccine, but were abundant and diverse, and less likely to be cross-opsonisation positive than other emm clusters. Long term persistence of many emm types in the study area was revealed. It was concluded that the 30mer vaccine efficacy in the Northern Territory will likely require both cross protection, and additional measures to elicit immunity against variants of emm cluster D.


Asunto(s)
Antígenos Bacterianos/inmunología , Proteínas de la Membrana Bacteriana Externa/inmunología , Proteínas Portadoras/inmunología , Cardiopatía Reumática/microbiología , Infecciones Estreptocócicas/prevención & control , Vacunas Estreptocócicas/uso terapéutico , Streptococcus pyogenes , Humanos , Northern Territory/epidemiología , Faringitis/epidemiología , Faringitis/microbiología , Prevalencia , Cardiopatía Reumática/epidemiología , Cardiopatía Reumática/prevención & control , Piel/microbiología , Infecciones Estreptocócicas/complicaciones , Infecciones Estreptocócicas/epidemiología , Vacunas Estreptocócicas/inmunología
8.
Pediatrics ; 144(2)2019 08.
Artículo en Inglés | MEDLINE | ID: mdl-31285392

RESUMEN

Group B streptococcal (GBS) infection remains the most common cause of neonatal early-onset sepsis and a significant cause of late-onset sepsis among young infants. Administration of intrapartum antibiotic prophylaxis is the only currently available effective strategy for the prevention of perinatal GBS early-onset disease, and there is no effective approach for the prevention of late-onset disease. The American Academy of Pediatrics joins with the American College of Obstetricians and Gynecologists to reaffirm the use of universal antenatal microbiologic-based testing for the detection of maternal GBS colonization to facilitate appropriate administration of intrapartum antibiotic prophylaxis. The purpose of this clinical report is to provide neonatal clinicians with updated information regarding the epidemiology of GBS disease as well current recommendations for the evaluation of newborn infants at risk for GBS disease and for treatment of those with confirmed GBS infection. This clinical report is endorsed by the American College of Obstetricians and Gynecologists (ACOG), July 2019, and should be construed as ACOG clinical guidance.


Asunto(s)
Profilaxis Antibiótica/normas , Manejo de la Enfermedad , Guías de Práctica Clínica como Asunto/normas , Complicaciones Infecciosas del Embarazo/tratamiento farmacológico , Infecciones Estreptocócicas/prevención & control , Profilaxis Antibiótica/métodos , Femenino , Humanos , Recién Nacido , Embarazo , Complicaciones Infecciosas del Embarazo/diagnóstico , Factores de Riesgo , Infecciones Estreptocócicas/diagnóstico
9.
Rev Esp Quimioter ; 32(4): 333-364, 2019 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-31345005

RESUMEN

The childhood immunization schedule is well known and generally well implemented in developed countries. For various reasons, the same is not true of vaccines aimed at preventing infections in adults, in which vaccination coverage is incomplete and generally very deficient. In order to assess the situation of adult vaccination in Spain, the Fundación de Ciencias de la Salud has brought together a series of experts in different fields, including doctors, nurses, representatives of patient associations, health managers and economists, health authorities and journalists to deal with this issue. The format was that of a round table in which a series of questions previously formulated by the coordinators were to be answered and debated. The document presented is not an exhaustive review of the topic, nor is it intended to make recommendations, but only to give a multidisciplinary opinion on topics that could be particularly debatable or controversial. The paper reviews the main vaccine-preventable adult diseases, their clinical and economic impact, the possibilities of reducing them with vaccination programmes and the difficulties in carrying them out. The role of nursing, pharmacy services, patient associations and the health administration itself in changing the current situation was discussed. Prospects for new vaccines were discussed and we speculated on the future in this field. Finally, particularly relevant ethical aspects in decision-making regarding vaccination were discussed, which must be faced by both individuals and states. We have tried to summarize, at the end of the presentation of each question, the environment of opinion that was agreed with all the members of the table.


Asunto(s)
Vacunas Bacterianas/administración & dosificación , Control de Enfermedades Transmisibles , Control de Infecciones , Cobertura de Vacunación/estadística & datos numéricos , Vacunas Virales/administración & dosificación , Adulto , Predicción , Infecciones por Haemophilus/epidemiología , Infecciones por Haemophilus/prevención & control , Haemophilus influenzae tipo b , Hepatitis B/epidemiología , Hepatitis B/prevención & control , Humanos , Incidencia , Gripe Humana/prevención & control , Infecciones Meningocócicas/epidemiología , Infecciones Meningocócicas/prevención & control , Neisseria meningitidis , Infecciones por Papillomavirus/epidemiología , Infecciones por Papillomavirus/prevención & control , España/epidemiología , Infecciones Estreptocócicas/epidemiología , Infecciones Estreptocócicas/prevención & control , Streptococcus pneumoniae , Infección por el Virus de la Varicela-Zóster/epidemiología , Infección por el Virus de la Varicela-Zóster/prevención & control
10.
Res Vet Sci ; 125: 82-88, 2019 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-31174167

RESUMEN

Strangles is a highly prevalent, extremely contagious, and occasionally lethal infectious disease affecting horses worldwide. Prophylactic antibiotics are ineffective in prevention of disease but are recommended for exposed horses at the first sign of fever and any horse obviously ill from strangles or with complications and there is an urgent need of a cost-effective, safe, efficacious vaccine. In the present study, we sought to develop effective vaccines by fusing the Streptococcus equi subspecies equi (S. equi) antigen SeM with the flagellin of Salmonella abortus equi FljB. We also explored the immunogenicity and efficacy of this candidate vaccine in mice and horses by intramuscular injection. Mice and horses immunized with FljB-SeM DNA vaccine showed high levels of specific antibody and increased production of IFN-γ and IL-4. This confirmed that both Th1 and Th2 type responses were induced. The mice survival rate was significantly higher after immunization with FljB-SeM than with SeM alone. The FljB-SeM DNA could strengthen both the Th1 and Th2 immune responses compared to SeM and could provide better protection against S. equi. This technique could help develop a candidate vaccine for S. equi infection.


Asunto(s)
Anticuerpos Antibacterianos/inmunología , Vacunas Bacterianas/inmunología , Enfermedades de los Caballos/prevención & control , Infecciones Estreptocócicas/veterinaria , Streptococcus equi/inmunología , Vacunas de ADN/inmunología , Animales , Anticuerpos Antibacterianos/sangre , Antígenos Bacterianos/inmunología , Proteínas Bacterianas/inmunología , Femenino , Flagelina/inmunología , Técnica del Anticuerpo Fluorescente/veterinaria , Enfermedades de los Caballos/inmunología , Caballos , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Inyecciones Intramusculares/veterinaria , Interferón gamma/sangre , Interleucina-4/sangre , Cinética , Ratones , Ratones Endogámicos C57BL , Plásmidos , Organismos Libres de Patógenos Específicos , Infecciones Estreptocócicas/mortalidad , Infecciones Estreptocócicas/prevención & control , Streptococcus equi/genética , Tasa de Supervivencia , Vacunación/veterinaria
11.
J Med Microbiol ; 68(7): 1059-1071, 2019 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-31192782

RESUMEN

PURPOSE: Unlike western countries the knowledge of group A streptococcus (GAS) epidemiology in India remains patchy and incomplete. Typing is crucial for surveillance as well as in predicting the efficacy of multivalent M protein vaccine. The present study aimed to explore the emm types of 206 invasive and non-invasive GAS isolates from South India as well as reviewing all the published literature on GAS molecular epidemiology from India thereby generating a pan-Indian data to predict the conjectural coverage of the 30-valent M-protein vaccine in this population. METHODOLOGY: emm typing and superantigen (SAg) profiling of GAS along with reviewing literatures on GAS molecular epidemiology from India. RESULTS: This study revealed a high diversity of emm types with emm 63, 82, 183, 85, 92, 169, 42, 44, 106, 74, 12 being frequently encountered, belonging to twenty emm clusters. The pan-Indian data on prevalent emm types further supports our study findings with 135 emm different types. Six clusters dominated accounting for 80 % of the GAS isolates: E3(26 %), E6(20 %), E2(11 %), E4(10 %), D4(7 %), E1(6 %). No significant association was noted between emm types and the nature of infection (P≥0.05) while a few SAg profiles were significantly associated with certain emm types. Pan Indian data revealed that only 16 % of the emm types encountered were included in proposed 30-valent M protein based vaccine. CONCLUSION: The coverage among the South Indian GAS isolates was 28.2 % which increased to only 46.6 % with the cross-opsonic effect, thus highlighting the importance of developing a specific multivalent vaccine including the prevalent emm types in India or considering the use of conserved C-repeat vaccines and non-M protein based vaccines.


Asunto(s)
Epidemiología Molecular , Infecciones Estreptocócicas/epidemiología , Infecciones Estreptocócicas/microbiología , Streptococcus pyogenes/genética , Adolescente , Adulto , Proteínas Bacterianas/genética , Niño , Femenino , Regulación Bacteriana de la Expresión Génica , Humanos , India/epidemiología , Masculino , Persona de Mediana Edad , Infecciones Estreptocócicas/prevención & control , Vacunas Estreptocócicas/inmunología , Adulto Joven
12.
J Obstet Gynaecol ; 39(8): 1093-1097, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31195907

RESUMEN

A cross-sectional study was conducted at a Thai university hospital between November 2016 and March 2017 to evaluate the prevalence and risk factors of group B Streptococcus (GBS) colonisation in pregnant women who were admitted to the labour room for delivery. Rectovaginal specimens were collected and processed for the identification of GBS. Univariate and multiple logistic regression analyses were conducted to evaluate factors associated with GBS colonisation. Statistical significance was set at p < .05. Fifty-seven of 505 pregnant women (11.3%, 95% confidence interval [CI] 9.0-15.0%) were found to have GBS colonisation. Teenage pregnancy (odds ratio [OR] 3.83, 95% CI 1.13-13.02, p < .05), multi-parity (OR 3.59, 95% CI 1.69-7.60, p < .01) and non-Buddhist religions (OR 1.87, 95% CI 1.01-3.48, p < .05) were significantly associated with GBS colonisation. Intrapartum risk factors were not associated with GBS colonisation. Impact statement What is already known on this subject? The prevalence of GBS colonisation in pregnant women varies by geographic areas and ethnicities, ranging from 2.3 to 32.9%. Risk factors for GBS colonisation have been studied but the results were inconsistent. What do the results of this study add? This study reports the prevalence of GBS colonisation in intrapartum women in Southern Thailand to be 11.3%. We also identified some independent risk factors for GBS colonisation which were teenage pregnancy, multi-parity and non-Buddhist religions. To our knowledge, the relationship between religious belief and identification of GBS has never been reported before. We also found that intrapartum risk factors that have been used as the indication for intrapartum antibiotics administration have no correlation with GBS colonisation. What are the implications of these findings for clinical practice and/or further research? This study adds to the literature the prevalence and risk factors of GBS colonisation in the setting of a developing country. It also shows that intrapartum risk identification alone is not an optimal strategy to reduce infection associated with GBS. Instead, prenatal GBS screening should be encouraged to identify women with GBS colonisation to reduce the risk of infection and unnecessary antibiotics exposure.


Asunto(s)
Parto , Recto/microbiología , Streptococcus agalactiae/crecimiento & desarrollo , Vagina/microbiología , Adolescente , Adulto , Estudios Transversales , Femenino , Hospitales Universitarios , Humanos , Recién Nacido , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Trabajo de Parto , Paridad , Embarazo , Factores de Riesgo , Infecciones Estreptocócicas/prevención & control , Streptococcus agalactiae/aislamiento & purificación , Tailandia
13.
Aust Vet J ; 97(7): 220-224, 2019 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-31236928

RESUMEN

OBJECTIVE: To determine the nature of serological responses in Australian horses using a commercial duplex indirect ELISA (iELISA) following vaccination against strangles. DESIGN: A group (n = 19) of client-owned horses from five properties were recruited to receive a primary course of a Streptococcus equi subsp. equi (S. equi) extract vaccine. Serological responses were determined by duplex iELISA incorporating S. equi-specific fragments of two cell wall proteins, SEQ2190 and SeM (antigens (Ag) A and C, respectively). METHODS: The horses were administered a primary strangles vaccination course. Blood was collected immediately prior to each of the three vaccinations at 2-week intervals and additionally at 28 and 56 days following the 3rd vaccination (V3). RESULTS: Significant increases in mean antibody levels of horses following vaccination were limited only to AgC, which was significantly increased at T2/V3, 14 days following V2 (ratio of geometric means = 3.7; 95% confidence interval (CI): 1.6, 8.4; P = 0.003). There was no increase in mean antibody to Ag A (ratio of geometric means = 1.4; 95% CI: 0.6, 3.2; P = 0.39). Four horses (22%) exceeded the test cut-off for AgC following vaccination. CONCLUSION: Vaccination of Australian horses is unlikely to interfere greatly with detection of strangles using the duplex iELISA. No responses would be anticipated to AgA following vaccination with Equivac© S/Equivac© 2in1 and only a minority are likely to respond to AgC. We conclude that the results of this study validate the usefulness of the duplex iELISA to assist control measures for strangles outbreaks in Australian horse populations.


Asunto(s)
Ensayo de Inmunoadsorción Enzimática/veterinaria , Enfermedades de los Caballos/prevención & control , Infecciones Estreptocócicas/veterinaria , Streptococcus equi , Animales , Anticuerpos Antibacterianos/sangre , Australia , Ensayo de Inmunoadsorción Enzimática/métodos , Femenino , Enfermedades de los Caballos/sangre , Caballos , Masculino , Infecciones Estreptocócicas/sangre , Infecciones Estreptocócicas/prevención & control , Vacunación/veterinaria
16.
mBio ; 10(2)2019 04 30.
Artículo en Inglés | MEDLINE | ID: mdl-31040243

RESUMEN

Group A Streptococcus (GAS) infections account for an estimated 500,000 deaths every year. This bacterial pathogen is responsible for a variety of mild and life-threatening infections and the triggering of chronic autoimmune sequelae. Pharyngitis caused by group A Streptococcus (GAS), but not asymptomatic GAS carriage, is a prerequisite for acute rheumatic fever (ARF). Repeated bouts of ARF may trigger rheumatic heart disease (RHD), a major cause of heart failure and stroke accounting for 275,000 deaths annually. A vaccine that prevents pharyngitis would markedly reduce morbidity and mortality from ARF and RHD. Nonhuman primates (NHPs) have been utilized to model GAS diseases, and experimentally infected rhesus macaques develop pharyngitis. Here we use an NHP model of GAS pharyngitis to evaluate the efficacy of an experimental vaccine, Combo5 (arginine deiminase [ADI], C5a peptidase [SCPA], streptolysin O [SLO], interleukin-8 [IL-8] protease [SpyCEP], and trigger factor [TF]), specifically designed to exclude GAS components potentially linked to autoimmune complications. Antibody responses against all Combo5 antigens were detected in NHP serum, and immunized NHPs showed a reduction in pharyngitis and tonsillitis compared to controls. Our work establishes the NHP model as a gold standard for the assessment of GAS vaccines.IMPORTANCE GAS-related diseases disproportionally affect disadvantaged populations (e.g., indigenous populations), and development of a vaccine has been neglected. A recent strong advocacy campaign driven by the World Health Organization and the International Vaccine Institute has highlighted the urgent need for a GAS vaccine. One significant obstacle in GAS vaccine development is the lack of a widely used animal model to assess vaccine efficacy. Researchers in the field use a wide range of murine models of infection and in vitro assays, sometimes yielding conflicting results. Here we present the nonhuman primate pharyngeal infection model as a tool to assess vaccine-induced protection against colonization and clinical symptoms of pharyngitis and tonsillitis. We have tested the efficacy of an experimental vaccine candidate with promising results. We believe that the utilization of this valuable tool by the GAS vaccine research community could significantly accelerate the realization of a safe and effective GAS vaccine for humans.


Asunto(s)
Faringitis/prevención & control , Infecciones Estreptocócicas/prevención & control , Vacunas Estreptocócicas/inmunología , Streptococcus pyogenes/inmunología , Tonsilitis/prevención & control , Animales , Anticuerpos Antibacterianos/sangre , Modelos Animales de Enfermedad , Femenino , Macaca mulatta , Masculino , Vacunas Estreptocócicas/administración & dosificación , Resultado del Tratamiento
17.
Microbiol Spectr ; 7(3)2019 05.
Artículo en Inglés | MEDLINE | ID: mdl-31111819

RESUMEN

Streptococcal pharyngitis (or strep throat) is a common childhood disease affecting millions of children each year, but it is one of the only childhood diseases for which a vaccine does not exist. While for decades the development of a vaccine has been the center of attention in many laboratories worldwide, with some successes, no corporate development has yet to be initiated. The reason for this probably lies in our inability to conclusively identify the streptococcal molecule or molecules responsible for the heart cross-reactive antibodies observed in the serum of rheumatic fever patients. Without this specific knowledge, any streptococcal vaccine antigen is suspect and thus not the target for a billion-dollar investment, despite the fact that the exact role of cross-reactive antibodies in rheumatic fever is still questionable. This article will describe the development of several approaches to protect against Streptococcus pyogenes infections over the past several decades.


Asunto(s)
Faringitis/inmunología , Faringitis/prevención & control , Infecciones Estreptocócicas/inmunología , Infecciones Estreptocócicas/prevención & control , Vacunas Estreptocócicas/inmunología , Streptococcus pyogenes/inmunología , Animales , Anticuerpos Antibacterianos/sangre , Antígenos Bacterianos/inmunología , Proteínas de la Membrana Bacteriana Externa/inmunología , Proteínas Portadoras/inmunología , Niño , Reacciones Cruzadas/inmunología , Bacterias Grampositivas/inmunología , Humanos , Inmunidad Mucosa , Fiebre Reumática/inmunología , Vacunación , Virus Vaccinia
18.
Nat Genet ; 51(6): 1035-1043, 2019 06.
Artículo en Inglés | MEDLINE | ID: mdl-31133745

RESUMEN

Group A Streptococcus (GAS; Streptococcus pyogenes) is a bacterial pathogen for which a commercial vaccine for humans is not available. Employing the advantages of high-throughput DNA sequencing technology to vaccine design, we have analyzed 2,083 globally sampled GAS genomes. The global GAS population structure reveals extensive genomic heterogeneity driven by homologous recombination and overlaid with high levels of accessory gene plasticity. We identified the existence of more than 290 clinically associated genomic phylogroups across 22 countries, highlighting challenges in designing vaccines of global utility. To determine vaccine candidate coverage, we investigated all of the previously described GAS candidate antigens for gene carriage and gene sequence heterogeneity. Only 15 of 28 vaccine antigen candidates were found to have both low naturally occurring sequence variation and high (>99%) coverage across this diverse GAS population. This technological platform for vaccine coverage determination is equally applicable to prospective GAS vaccine antigens identified in future studies.


Asunto(s)
Genómica , Vacunas Estreptocócicas/genética , Vacunas Estreptocócicas/inmunología , Streptococcus pyogenes/genética , Streptococcus pyogenes/inmunología , Antígenos Bacterianos/genética , Antígenos Bacterianos/inmunología , Genoma Bacteriano , Estudio de Asociación del Genoma Completo , Genómica/métodos , Humanos , Filogenia , Recombinación Genética , Infecciones Estreptocócicas/prevención & control , Streptococcus pyogenes/clasificación
19.
Int J Gynaecol Obstet ; 146(2): 238-243, 2019 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-31127871

RESUMEN

OBJECTIVE: To evaluate group B streptococcus (GBS) colonization prevalence and feasibility of intrapartum GBS screening/antibiotic prophylaxis (IAP) in Cameroon, Africa. METHODS: Prospective cohort in the Cameroon Baptist Convention Health Services network. Maternity providers collected anogenital swabs from consenting term women in labor for testing by a rapid GBS-polymerase chain reaction (PCR) system. Positive tests (GBS+) resulted in initiation of intravenous ampicillin until delivery. Primary outcomes were GBS prevalence and proportion of GBS+ women receiving ampicillin before delivery and more than 4 hours before delivery. RESULTS: A total of 219 women were enrolled from January 10 to April 27, 2017. GBS prevalence was 12.3% (95% confidence interval [CI] 7.9-16.7) with GBS+ women more likely to reside in urban areas (19.6% vs 9.7%, P=0.004). Of 27 GBS+ women, 19 (70.4%) received ampicillin before delivery and 14 (51.9%) 4 hours or longer before delivery. A median two doses of ampicillin (interquartile range [IQR] 1-5) were given and started at a median of 105 minutes (IQR 90-155) after swab collection and 20 minutes (IQR 10-45) after GBS result. Of the 8 women who did not receive ampicillin, 7 (87.5%) delivered before test results. CONCLUSION: A GBS IAP protocol is feasible in Cameroon and should be evaluated for widespread implementation in Cameroon and other low-income countries to decrease GBS-related morbidity.


Asunto(s)
Ampicilina/administración & dosificación , Antibacterianos/administración & dosificación , Profilaxis Antibiótica/métodos , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Infecciones Estreptocócicas/prevención & control , Infecciones Estreptocócicas/transmisión , Adulto , Camerún/epidemiología , Estudios de Factibilidad , Femenino , Humanos , Recién Nacido , Trabajo de Parto , Tamizaje Masivo/métodos , Reacción en Cadena de la Polimerasa , Embarazo , Prevalencia , Estudios Prospectivos , Streptococcus agalactiae/aislamiento & purificación , Adulto Joven
20.
Glob Heart ; 14(3): 259-264, 2019 09.
Artículo en Inglés | MEDLINE | ID: mdl-31103400

RESUMEN

BACKGROUND: Globally, rheumatic heart disease (RHD) is a major contributor to the burden of cardiovascular disease. Major gaps in RHD prevention and treatment have been documented at all levels of health systems in low- and middle-income countries. Task sharing is an approach that could prove effective in remediating bottlenecks in RHD-related care. OBJECTIVES: This study conducted a systematic review to assess the state of the evidence for the use of task sharing in the diagnosis, prevention, and management of RHD. METHODS: Guided by a previously published protocol, we searched various databases using a systematic search strategy including MeSH and free-text terms for (1) group A streptococcus, acute rheumatic fever, and RHD and (2) strategies of task sharing in limited-resource settings. Two investigators independently screened the search outputs, selected the studies, extracted the data, and assessed the risk of bias, resolving discrepancies by discussion and consensus. RESULTS: The publications search yielded 212 records, of which 18 articles were deemed as potentially eligible for inclusion. None of the studies, however, met with the inclusion criteria. CONCLUSIONS: There is a lack of evidence for the use of task-sharing approaches in scaling up RHD prevention and treatment services in limited-resource settings. Considering the persistent burden of group A streptococcus, acute rheumatic fever, and RHD in low- and middle-income countries, this work highlights the urgent need to develop and test models of RHD-related care utilizing an evidence-based approach to task sharing. [Task Sharing in the Diagnosis, Prevention, and Management of Rheumatic Heart Disease: A Systematic Review; CRD42017072989].


Asunto(s)
Cardiopatía Reumática/terapia , Infecciones Estreptocócicas/terapia , Prestación de Atención de Salud/organización & administración , Humanos , Área sin Atención Médica , Grupo de Atención al Paciente/organización & administración , Cardiopatía Reumática/diagnóstico , Cardiopatía Reumática/prevención & control , Infecciones Estreptocócicas/diagnóstico , Infecciones Estreptocócicas/prevención & control
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