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1.
mBio ; 12(1)2021 01 08.
Artículo en Inglés | MEDLINE | ID: mdl-33419872

RESUMEN

In December 2019 a new coronavirus (CoV) emerged as a human pathogen, SARS-CoV-2. There are few data on human coronavirus infections among individuals living with HIV. In this study we probed the role of pneumococcal coinfections with seasonal CoVs among children living with and without HIV hospitalized for pneumonia. We also described the prevalence and clinical manifestations of these infections. A total of 39,836 children who participated in a randomized, double-blind, placebo-controlled clinical trial on the efficacy of a 9-valent pneumococcal conjugate vaccine (PCV9) were followed for lower respiratory tract infection hospitalizations until 2 years of age. Nasopharyngeal aspirates were collected at the time of hospitalization and were screened by PCR for four seasonal CoVs. The frequency of CoV-associated pneumonia was higher in children living with HIV (19.9%) than in those without HIV (7.6%, P < 0.001). Serial CoV infections were detected in children living with HIV. The case fatality risk among children with CoV-associated pneumonia was higher in those living with HIV (30.4%) than without HIV (2.9%, P = 0.001). C-reactive protein and procalcitonin levels were elevated in 36.8% (≥40 mg/liter) and 64.7% (≥0.5 ng/ml), respectively, of the fatal cases living with HIV. Among children without HIV, there was a 64.0% (95% CI: 22.9% to 83.2%) lower incidence of CoV-associated pneumonia hospitalizations among PCV9 recipients compared to placebo recipients. These data suggest that Streptococcus pneumoniae infections might have a role in the development of pneumonia associated with endemic CoVs, that PCV may prevent pediatric CoV-associated hospitalization, and that children living with HIV with CoV infections develop more severe outcomes.IMPORTANCE SARS-CoV-2 may cause severe hospitalization, but little is known about the role of secondary bacterial infection in these severe cases, beyond the observation of high levels of reported inflammatory markers, associated with bacterial infection, such as procalcitonin. We did a secondary analysis of a double-blind randomized trial of PCV to examine its impact on human CoV infections before the pandemic. We found that both children living with and without HIV randomized to receive PCV had evidence of less hospitalization due to seasonal CoV, suggesting that pneumococcal coinfection may play a role in severe hospitalized CoV infections.


Asunto(s)
Infecciones Oportunistas Relacionadas con el SIDA/prevención & control , Infecciones por Coronavirus/prevención & control , Vacunas Neumococicas/administración & dosificación , Neumonía Viral/prevención & control , Streptococcus pneumoniae/inmunología , Infecciones Oportunistas Relacionadas con el SIDA/epidemiología , Infecciones Oportunistas Relacionadas con el SIDA/patología , Coinfección/epidemiología , Coinfección/microbiología , Coinfección/prevención & control , Coinfección/virología , Coronavirus/clasificación , Coronavirus/aislamiento & purificación , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/patología , Estudios de Seguimiento , Hospitalización/estadística & datos numéricos , Humanos , Incidencia , Lactante , Neumonía Neumocócica/epidemiología , Neumonía Neumocócica/prevención & control , Neumonía Viral/epidemiología , Prevalencia , Ensayos Clínicos Controlados Aleatorios como Asunto
2.
BMC Infect Dis ; 21(1): 45, 2021 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-33423657

RESUMEN

BACKGROUND: The Taiwanese national 23-valent pneumococcal polysaccharide vaccine (PPV23) program in adults ≥75 years of age and the 13-valent pneumococcal conjugate vaccine (PCV13) program for children were implemented in 2008 and 2013, respectively. In this study we evaluated PPV23 vaccine effectiveness (PPV23VE) in the elderly, with regard to both direct protection from the vaccine itself and the indirect protection conferred by PCV13 immunization in children. METHODS: The incidence of invasive pneumococcal disease (IPD) in Taiwan from July 2008 to June 2016 was collected from IPD surveillance data. A comparison of IPD incidence with a nationwide vaccination registry allowed an estimation of PPV23VE by the screening and indirect cohort methods. RESULTS: The incidence of IPD in adults ≥75 years of age ranged from 13.9 per 100,000 inhabitants during the period July 2008-June 2013 to 10.4 per 100,000 inhabitants between July 2013 and June 2016 (relative risk [RR]: 0.75; 95% confidence interval [95% CI]: 0.67-0.85). According to the screening method, PPV23VE against death within 30 days of IPD onset, all IPD, and PPV23-serotype IPD was 32.5% (95% CI: 17.5-44.7%), 33.9% (95% CI: 25.2-41.5%) and 43.4% (95% CI: 34.4-51.2%), respectively. PPV23VE with the indirect cohort method was 39.0% (95% CI: 15.5-55.9%) for all PPV23 serotypes and 71.5% (95% CI: 44.2-85.4%) for 11 serotypes included in PPV23 but not in PCV13. During the period July 2008-June 2012, PPV23VE against PPV23-serotype IPD was 55.1% (95% CI: 27.2-72.3%). CONCLUSIONS: PPV23 is able to prevent IPD and 30-day fatality in adults 75 years of age and older due to a combination of direct effects from PPV23 and indirect effects from PCV13. It might confer higher protection against PPV23-serotype IPD before the introduction of PCV13 program in children.


Asunto(s)
Infecciones Neumocócicas/prevención & control , Vacunas Neumococicas/administración & dosificación , Streptococcus pneumoniae/inmunología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Estudios de Cohortes , Femenino , Humanos , Programas de Inmunización , Masculino , Persona de Mediana Edad , Infecciones Neumocócicas/epidemiología , Infecciones Neumocócicas/microbiología , Evaluación de Programas y Proyectos de Salud , Sistema de Registros , Streptococcus pneumoniae/clasificación , Streptococcus pneumoniae/genética , Taiwán/epidemiología , Adulto Joven
3.
Methods Mol Biol ; 2183: 461-475, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-32959260

RESUMEN

A hybrid biological-biomaterial vector composed of a biocompatible polymeric biomaterial coating and an Escherichia coli core was designed and developed for antigen delivery. It provides a unique and efficient mechanism to transport antigens (protein or genetic) via different mechanisms of vector design that include antigen cellular localization (cytoplasm, periplasm, cellular surface) and nonnative functionalities that assist in antigen delivery. Based on a variety of E. coli strain development and polymer chemistry tools, the hybrid vector can be constructed into a number of formats for the purpose of optimized uptake and processing by antigen presenting cells, serving as the basis for a potent subsequent immune response. This chapter serves to outline a protocol for assembling a hybrid biological-biomaterial vector for use as a vaccine delivery system.


Asunto(s)
Antígenos/administración & dosificación , Antígenos/inmunología , Vectores Genéticos/inmunología , Vacunas de ADN/administración & dosificación , Vacunas de ADN/inmunología , Animales , Antígenos Bacterianos/administración & dosificación , Antígenos Bacterianos/inmunología , Biopelículas , Sistemas de Liberación de Medicamentos , Expresión Génica , Técnicas de Transferencia de Gen , Vectores Genéticos/administración & dosificación , Vectores Genéticos/genética , Inmunización , Plásmidos/genética , Polímeros/química , Streptococcus pneumoniae/inmunología
4.
Methods Mol Biol ; 2183: 559-574, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-32959268

RESUMEN

Antibodies against Streptococcus pneumoniae (pneumococcus) following vaccination are crucial for host protection against invasive pneumococcal infections. The antibodies induced by pneumococcal vaccines act as opsonins to mediate bacterial uptake and killing by host phagocytic cells, especially polymorphonuclear leukocytes (PMNs) also called neutrophils. Therefore, it is important to measure not only the levels of antibodies induced by a pneumococcal vaccine candidate but their actual functional capacity in mediating bacterial opsonization and killing by PMNs. Here, we describe a protocol to demonstrate effective deposition of vaccine-induced antibodies on the surface of S. pneumoniae by flow cytometry and subsequent opsonophagocytic killing (OPH) by murine bone-marrow derived PMNs.


Asunto(s)
Anticuerpos Antibacterianos/inmunología , Neutrófilos/inmunología , Infecciones Neumocócicas/inmunología , Vacunas Neumococicas/inmunología , Streptococcus pneumoniae/inmunología , Animales , Biomarcadores , Células de la Médula Ósea/inmunología , Células de la Médula Ósea/metabolismo , Citometría de Flujo , Sueros Inmunes/inmunología , Ratones , Neutrófilos/metabolismo , Fagocitos/inmunología , Fagocitos/metabolismo , Infecciones Neumocócicas/metabolismo , Infecciones Neumocócicas/microbiología
5.
Methods Mol Biol ; 2183: 9-18, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-32959237

RESUMEN

The immunoglobulin capture assay (ICA) enables the enrichment for pathogen-specific plasmablasts from individuals with a confirmed adaptive immune response to vaccination or disseminated infection. Only single recombinant antigens have been used previously as probes in this ICA and it was unclear whether the method was applicable to complex probes such as whole bacterial cells. Here, we describe the enrichment of plasmablasts specific for polysaccharide and protein antigens of both Streptococcus pneumoniae and Neisseria meningitidis using whole formalin-fixed bacterial cells as probes. The modified ICA protocol described here allowed for a pathogen-specific hmAb cloning efficiency of >80%.


Asunto(s)
Anticuerpos Monoclonales/inmunología , Anticuerpos Monoclonales/aislamiento & purificación , Especificidad de Anticuerpos/inmunología , Bacterias/inmunología , Inmunoensayo/métodos , Sondas Moleculares , Anticuerpos Antibacterianos/inmunología , Afinidad de Anticuerpos , Formación de Anticuerpos/inmunología , Antígenos Bacterianos/inmunología , Interacciones Huésped-Patógeno , Humanos , Inmunoglobulina G/inmunología , Células Plasmáticas/inmunología , Células Plasmáticas/metabolismo , Streptococcus pneumoniae/inmunología
6.
Proc Natl Acad Sci U S A ; 117(52): 33561-33569, 2020 12 29.
Artículo en Inglés | MEDLINE | ID: mdl-33376222

RESUMEN

Streptococcus pneumoniae is a leading cause of pneumonia and invasive disease, particularly, in the elderly. S. pneumoniae lung infection of aged mice is associated with high bacterial burdens and detrimental inflammatory responses. Macrophages can clear microorganisms and modulate inflammation through two distinct lysosomal trafficking pathways that involve 1A/1B-light chain 3 (LC3)-marked organelles, canonical autophagy, and LC3-associated phagocytosis (LAP). The S. pneumoniae pore-forming toxin pneumolysin (PLY) triggers an autophagic response in nonphagocytic cells, but the role of LAP in macrophage defense against S. pneumoniae or in age-related susceptibility to infection is unexplored. We found that infection of murine bone-marrow-derived macrophages (BMDMs) by PLY-producing S. pneumoniae triggered Atg5- and Atg7-dependent recruitment of LC3 to S. pneumoniae-containing vesicles. The association of LC3 with S. pneumoniae-containing phagosomes required components specific for LAP, such as Rubicon and the NADPH oxidase, but not factors, such as Ulk1, FIP200, or Atg14, required specifically for canonical autophagy. In addition, S. pneumoniae was sequestered within single-membrane compartments indicative of LAP. Importantly, compared to BMDMs from young (2-mo-old) mice, BMDMs from aged (20- to 22-mo-old) mice infected with S. pneumoniae were not only deficient in LAP and bacterial killing, but also produced higher levels of proinflammatory cytokines. Inhibition of LAP enhanced S. pneumoniae survival and cytokine responses in BMDMs from young but not aged mice. Thus, LAP is an important innate immune defense employed by BMDMs to control S. pneumoniae infection and concomitant inflammation, one that diminishes with age and may contribute to age-related susceptibility to this important pathogen.


Asunto(s)
Envejecimiento/inmunología , Interacciones Huésped-Patógeno/inmunología , Macrófagos/metabolismo , Macrófagos/microbiología , Proteínas Asociadas a Microtúbulos/metabolismo , Fagocitosis , Streptococcus pneumoniae/inmunología , Animales , Autofagia , Proteínas Bacterianas/metabolismo , Lípidos/química , Macrófagos/ultraestructura , Masculino , Ratones , Ratones Endogámicos C57BL , Viabilidad Microbiana , Células RAW 264.7 , Especies Reactivas de Oxígeno/metabolismo , Streptococcus pneumoniae/ultraestructura , Estreptolisinas/metabolismo
7.
J Nippon Med Sch ; 87(5): 299-303, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33311009

RESUMEN

In Japan, pneumococcal vaccine has been routinely administered since 2010 to prevent invasive pneumococcal diseases such as Streptococcus pneumoniae meningitis. We describe a case of pneumococcal meningitis in a 7-month-old girl who had received three doses of 13-valent pneumococcal conjugate vaccine. Brain magnetic resonance imaging showed infarcts in the right frontal region, and she was treated with antibiotics, intravenous immunoglobulin, dexamethasone, and edaravone. On day 27, an enhanced brain CT scan showed improvement of abnormal findings in the frontal region, except for slight atrophy. The S. pneumoniae serotype was 12F, which is not included in the 13-valent pneumococcal conjugate vaccine. A future vaccine is expected to use cross-reactivity to target common antigens.


Asunto(s)
Meningitis Bacterianas/etiología , Meningitis Bacterianas/microbiología , Infecciones Neumocócicas , Vacunas Neumococicas/efectos adversos , Streptococcus pneumoniae , Vacunas Conjugadas/efectos adversos , Antígenos Bacterianos/inmunología , Encéfalo/diagnóstico por imagen , Reacciones Cruzadas , Dexametasona/uso terapéutico , Edaravona/uso terapéutico , Femenino , Humanos , Inmunoglobulinas Intravenosas , Lactante , Imagen por Resonancia Magnética , Meningitis Bacterianas/diagnóstico por imagen , Meningitis Bacterianas/tratamiento farmacológico , Infecciones Neumocócicas/prevención & control , Serogrupo , Streptococcus pneumoniae/genética , Streptococcus pneumoniae/inmunología , Tomografía Computarizada por Rayos X
8.
Medicina (Kaunas) ; 56(11)2020 Oct 29.
Artículo en Inglés | MEDLINE | ID: mdl-33138045

RESUMEN

BACKGROUND AND OBJECTIVES: Streptococcus pneumoniae urinary antigen (u-Ag) testing has recently gained attention in the early diagnosis of severe and critical acute respiratory syndrome coronavirus-2/pneumococcal co-infection. The aim of this study is to assess the effectiveness of Streptococcus pneumoniae u-Ag testing in coronavirus disease 2019 (COVID-19) patients, in order to assess whether pneumococcal co-infection is associated with different mortality rate and hospital stay in these patients. MATERIALS AND METHODS: Charts, protocols, mortality, and hospitalization data of a consecutive series of COVID-19 patients admitted to a tertiary hospital in northern Italy during COVID-19 outbreak were retrospectively reviewed. All patients underwent Streptococcus pneumoniae u-Ag testing to detect an underlying pneumococcal co-infection. Covid19+/u-Ag+ and Covid19+/u-Ag- patients were compared in terms of overall survival and length of hospital stay using chi-square test and survival analysis. RESULTS: Out of 575 patients with documented pneumonia, 13% screened positive for the u-Ag test. All u-Ag+ patients underwent treatment with Ceftriaxone and Azithromycin or Levofloxacin. Lopinavir/Ritonavir or Darunavir/Cobicistat were added in 44 patients, and hydroxychloroquine and low-molecular-weight heparin (LMWH) in 47 and 33 patients, respectively. All u-Ag+ patients were hospitalized. Mortality was 15.4% and 25.9% in u-Ag+ and u-Ag- patients, respectively (p = 0.09). Survival analysis showed a better prognosis, albeit not significant, in u-Ag+ patients. Median hospital stay did not differ among groups (10 vs. 9 days, p = 0.71). CONCLUSIONS: The routine use of Streptococcus pneumoniae u-Ag testing helped to better target antibiotic therapy with a final trend of reduction in mortality of u-Ag+ COVID-19 patients having a concomitant pneumococcal infection. Randomized trials on larger cohorts are necessary in order to draw definitive conclusion.


Asunto(s)
Antibacterianos/uso terapéutico , Antivirales/uso terapéutico , Coinfección/diagnóstico , Infecciones por Coronavirus/tratamiento farmacológico , Mortalidad Hospitalaria , Neumonía Neumocócica/tratamiento farmacológico , Neumonía Viral/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Anticoagulantes/uso terapéutico , Antígenos Bacterianos/orina , Azitromicina/uso terapéutico , Betacoronavirus , Ceftriaxona/uso terapéutico , Cobicistat/uso terapéutico , Coinfección/orina , Infecciones por Coronavirus/complicaciones , Estudios Transversales , Darunavir/uso terapéutico , Combinación de Medicamentos , Femenino , Heparina de Bajo-Peso-Molecular/uso terapéutico , Humanos , Hidroxicloroquina/uso terapéutico , Tiempo de Internación/estadística & datos numéricos , Levofloxacino/uso terapéutico , Lopinavir/uso terapéutico , Masculino , Tamizaje Masivo , Persona de Mediana Edad , Pandemias , Neumonía Neumocócica/complicaciones , Neumonía Neumocócica/diagnóstico , Neumonía Neumocócica/orina , Neumonía Viral/complicaciones , Estudios Retrospectivos , Ritonavir/uso terapéutico , Streptococcus pneumoniae/inmunología
9.
BMC Infect Dis ; 20(1): 479, 2020 Jul 06.
Artículo en Inglés | MEDLINE | ID: mdl-32631331

RESUMEN

BACKGROUND: The study aimed to assess whether gastrointestinal (GI) symptoms at admission are associated with increased short-term mortality in patients with invasive pneumococcal disease (IPD). METHODS: We included all patients with IPD at Aker University Hospital in Oslo, Norway, from 1993 to 2008. Clinical data were registered. Survival data were retrieved from official registries. We used Cox regression and Kaplan-Meier curve to compare mortality within 28 days of admission in patients with and without GI symptoms. RESULTS: Four hundred sixteen patients were included. Of these, 108 patients (26%) presented with GI symptoms, and 47 patients (11%) with GI symptoms only. Patients with GI symptoms were younger (p < 0.001) and had less cardiovascular disease (p < 0.001), pulmonary disease (p = 0.048), and cancer (p = 0.035) and received appropriate antibiotic treatment later. After adjusting for risk factors, we found an increased hazard ratio of 2.28 (95% CI 1.31-3.97) in patients presenting with GI symptoms. In patients with GI symptoms only there was an increased hazard ratio of 2.24 (95% CI 1.20-4.19) in univariate analysis, which increased to 4.20 (95% CI 2.11-8.39) after multivariate adjustment. Fewer patients with GI symptoms only received antibiotics upon admission. CONCLUSIONS: A large proportion of IPD patients present with GI symptoms only or in combination with other symptoms. GI symptoms in IPD are associated with increased short-term mortality.


Asunto(s)
Enfermedades Gastrointestinales/epidemiología , Enfermedades Gastrointestinales/microbiología , Infecciones Neumocócicas/epidemiología , Infecciones Neumocócicas/mortalidad , Streptococcus pneumoniae/inmunología , Adulto , Anciano , Anciano de 80 o más Años , Antibacterianos/uso terapéutico , Comorbilidad , Femenino , Enfermedades Gastrointestinales/tratamiento farmacológico , Hospitalización , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Noruega/epidemiología , Infecciones Neumocócicas/tratamiento farmacológico , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Estudios Retrospectivos , Factores de Riesgo , Streptococcus pneumoniae/aislamiento & purificación , Resultado del Tratamiento , Adulto Joven
10.
Am J Trop Med Hyg ; 103(2): 679-683, 2020 08.
Artículo en Inglés | MEDLINE | ID: mdl-32524945

RESUMEN

Mass drug administration (MDA) with azithromycin (AZ) has been used successfully to control trachoma. However, several studies have shown that MDA with AZ has led to the emergence of resistance to AZ in Streptococcus pneumoniae. The emergence of resistance to AZ has also been observed when this antibiotic was combined with the antimalarials used for seasonal malaria chemoprevention (SMC). The development of antibiotic resistance, including resistance to AZ, is sometimes associated with the emergence of a bacterial clone that belongs to a specific serotype. We hypothesize that the increase in resistance of S. pneumoniae observed after 3 years of SMC with AZ might be associated with a change in the distribution of pneumococcal serotypes. Therefore, 698 randomly selected isolates from among the 1,468 isolates of S. pneumoniae obtained during carriage studies undertaken during an SMC plus AZ trial were serotyped. A polymerase chain reaction (PCR) multiplex assay using an algorithm adapted to the detection of the pneumococcal serotypes most prevalent in African countries was used for initial serotyping, and the Quellung technique was used to complement the PCR technique when necessary. Fifty-six serotypes were detected among the 698 isolates of S. pneumoniae. A swift appearance and disappearance of many serotypes was observed, but some serotypes including 6A, 19F, 19A, 23F, and 35B were persistent. The distribution of serotypes between isolates obtained from children who had received AZ or placebo was similar. An increase in AZ resistance was seen in several serotypes following exposure to AZ. Mass drug administration with AZ led to the emergence of resistance in pneumococci of several different serotypes and did not appear to be linked to the emergence of a single serotype.


Asunto(s)
Antibacterianos/uso terapéutico , Antimaláricos/uso terapéutico , Azitromicina/uso terapéutico , Portador Sano/microbiología , Farmacorresistencia Bacteriana , Malaria/prevención & control , Administración Masiva de Medicamentos , Nasofaringe/microbiología , Infecciones Neumocócicas/microbiología , Streptococcus pneumoniae/aislamiento & purificación , Amodiaquina/uso terapéutico , Burkina Faso , Quimioprevención/métodos , Preescolar , Combinación de Medicamentos , Quimioterapia Combinada , Femenino , Humanos , Lactante , Masculino , Infecciones Neumocócicas/prevención & control , Vacunas Neumococicas/uso terapéutico , Pirimetamina/uso terapéutico , Estaciones del Año , Serogrupo , Streptococcus pneumoniae/inmunología , Streptococcus pneumoniae/fisiología , Sulfadoxina/uso terapéutico
11.
Int J Infect Dis ; 98: 113-120, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-32562849

RESUMEN

BACKGROUND: Streptococcus pneumoniae remains a major contributor to childhood infections and deaths globally. In Cameroon, the 13-valent pneumococcal conjugate vaccine (PCV13) was introduced in July 2011, using a 3-dose Expanded programme on immunization (EPI) schedule administered to infants at 6, 10 and 14 weeks of age. To evaluate PCV13 effects, we assessed pneumococcal nasopharyngeal colonization and serotype distribution among Cameroonian children after PCV13 introduction. METHODS: Nasopharyngeal (NP) swabs were collected from eligible children aged 24-36 months in two cross-sectional surveys conducted from March to July: in 2013 (PCV13-unvaccinated), and in 2015 (PCV13-vaccinated). Using a systematic World Health Organization (WHO) cluster coverage sampling technique in 40 communities, NP swabs collected were processed following WHO recommendations. Standard bacterial culture techniques were used for the isolation of S. pneumoniae from gentamicin-blood agar plates and identification using optochin susceptibility testing. Serotyping was performed using sequential multiplex polymerase chain reaction, supplemented with Quellung test. RESULTS: Among the PCV13-vaccinated children, overall pneumococcal carriage prevalence was 61.8% (426/689) and PCV13 vaccine-type carriage prevalence was 18.0% (123/689). Eleven out of the 13 vaccine serotypes were detected in the vaccinated children. The most common serotypes were 19F (4.5%, 31/689) and 15B/C (7.3%, 50/689). CONCLUSION: In Cameroon, four years after infant vaccination nearly all of the PCV13-serotypes continued to circulate in the population. This suggests that the direct and indirect effects of the vaccination programme have not resulted in expected low levels of vaccine-type transmission. Continuous monitoring is needed to assess the long term effects of the PCV13 on nasopharyngeal carriage and disease.


Asunto(s)
Nasofaringe/microbiología , Infecciones Neumocócicas/prevención & control , Vacunas Neumococicas/administración & dosificación , Streptococcus pneumoniae/inmunología , Camerún/epidemiología , Portador Sano/epidemiología , Portador Sano/inmunología , Portador Sano/microbiología , Preescolar , Estudios Transversales , Femenino , Humanos , Programas de Inmunización , Esquemas de Inmunización , Masculino , Infecciones Neumocócicas/epidemiología , Infecciones Neumocócicas/inmunología , Infecciones Neumocócicas/microbiología , Vacunas Neumococicas/inmunología , Prevalencia , Serogrupo , Serotipificación , Streptococcus pneumoniae/genética , Streptococcus pneumoniae/crecimiento & desarrollo , Streptococcus pneumoniae/aislamiento & purificación , Vacunación
13.
BMC Infect Dis ; 20(1): 423, 2020 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-32552726

RESUMEN

BACKGROUND: Streptococcus pneumoniae infections can lead to severe morbidity and mortality, especially in patients with invasive pneumococcal disease (IPD). This study evaluated factors associated with pneumococcal disease, pneumococcal vaccine effectiveness, and risk factors for all-cause mortality in hospitalised adults with pneumococcal disease in Singapore. METHODS: Retrospective case-control study of patients tested for pneumococcal disease with streptococcal urinary antigen testing and at least one sterile site culture, during their admission to a tertiary hospital in Singapore from 2015 to 2017. Patients were defined as cases of IPD or non-IPD, or as controls, based on laboratory results and clinical diagnoses. Multivariable models were constructed to determine factors associated with IPD/non-IPD, and risk factors for mortality from pneumococcal disease. Vaccine effectiveness against IPD/non-IPD was estimated using a variation of the test-negative design. RESULTS: We identified 496 pneumococcal disease cases, of whom 92 (18.5%) had IPD. The mean age of cases was 69.1 ± 15.4 years, and 65.5% were male. Compared with controls (N = 9181), IPD patients were younger (mean age 61.5 ± 16.3 years, vs 72.2 ± 16.1 years in controls; p < 0.001) and with less co-morbidities [median Charlson's score 1 (IQR 0-4), vs 3 (1-5) in controls; p < 0.001]. IPD patients also had the highest proportions with intensive care unit (ICU) admission (20.7%), inpatient mortality (26.1%) and longest median length of stay [9 (IQR 8-17) days]. On multivariable analysis, IPD was negatively associated with prior pneumococcal vaccination (adjusted relative risk ratio = 0.20, 95%CI 0.06-0.69; p = 0.011). Risk factors for mortality among pneumococcal disease patients were ICU admission, diagnosis of IPD, age ≥ 85 years and Charlson's score > 3. CONCLUSION: Patients with pneumococcal disease (especially IPD) were younger and had less co-morbidities than controls, but had higher risk of severe clinical outcomes and mortality. Pneumococcal vaccination effectiveness against IPD was estimated to be about 80%, and should be encouraged among high-risk patients.


Asunto(s)
Hospitalización , Infecciones Neumocócicas/epidemiología , Infecciones Neumocócicas/prevención & control , Vacunas Neumococicas/inmunología , Streptococcus pneumoniae/inmunología , Vacunación , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad , Morbilidad , Infecciones Neumocócicas/mortalidad , Infecciones Neumocócicas/orina , Estudios Retrospectivos , Factores de Riesgo , Singapur/epidemiología , Centros de Atención Terciaria , Resultado del Tratamiento
14.
Int J Infect Dis ; 97: 182-189, 2020 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-32474199

RESUMEN

OBJECTIVES: To evaluate the cost-effectiveness of introducing a domestic pneumococcal conjugate vaccine (PCV7-TT) into the Cuban National Immunization Program (NIP). METHODS: We compared PCV7-TT given at two, four and six months of age to a scenario without PCV7-TT, over a ten-year period (2020-2029). We calculated the cost (Cuban pesos - CUP) per Disability Adjusted Life Year (DALY) averted from a Government perspective. We compared results from a static cohort model and a parsimonious prediction model informed by the serotype distribution among pneumococcal carriers and cases. We ran probabilistic and deterministic uncertainty analyses. RESULTS: PCV7-TT could prevent 6897 (95% uncertainty interval, 4344-8750) hospitalizations and 189 (115-253) deaths in children <5 years of age, over the period 2020-2029. This could cost around 25 million (20-31) discounted CUP but would be offset by treatment cost savings of around 23 million (14-31). A parsimonious model predicted less favourable impact and cost-effectiveness but the cost per DALY averted was still less than 0.4 times the current GDP per capita. CONCLUSIONS: PCV7-TT is likely to be cost-effective in Cuba. The impact of the vaccine would need to be carefully monitored following its introduction into the NIP.


Asunto(s)
Programas de Inmunización/economía , Infecciones Neumocócicas/economía , Infecciones Neumocócicas/prevención & control , Vacunas Neumococicas/administración & dosificación , Vacunas Neumococicas/economía , Algoritmos , Preescolar , Estudios de Cohortes , Análisis Costo-Beneficio , Cuba , Femenino , Costos de la Atención en Salud , Hospitalización/economía , Humanos , Lactante , Masculino , Infecciones Neumocócicas/inmunología , Infecciones Neumocócicas/microbiología , Vacunas Neumococicas/inmunología , Años de Vida Ajustados por Calidad de Vida , Streptococcus pneumoniae/inmunología , Vacunas Conjugadas/administración & dosificación , Vacunas Conjugadas/economía , Vacunas Conjugadas/inmunología
15.
Nat Commun ; 11(1): 2222, 2020 05 06.
Artículo en Inglés | MEDLINE | ID: mdl-32376860

RESUMEN

There are concerns that pneumococcal conjugate vaccines (PCVs) in sub-Saharan Africa sub-optimally interrupt Streptococcus pneumoniae vaccine-serotype (VT) carriage and transmission. Here we assess PCV carriage using rolling, prospective nasopharyngeal carriage surveys between 2015 and 2018, 3.6-7.1 years after Malawi's 2011 PCV13 introduction. Carriage decay rate is analysed using non-linear regression. Despite evidence of reduction in VT carriage over the study period, there is high persistent residual carriage. This includes among PCV-vaccinated children 3-5-year-old (16.1% relative reduction from 19.9% to 16.7%); PCV-unvaccinated children 6-8-year-old (40.5% reduction from 26.4% to 15.7%); HIV-infected adults 18-40-years-old on antiretroviral therapy (41.4% reduction from 15.2% to 8.9%). VT carriage prevalence half-life is similar among PCV-vaccinated and PCV-unvaccinated children (3.26 and 3.34 years, respectively). Compared with high-income settings, there is high residual VT carriage 3.6-7.1 years after PCV introduction. Rigorous evaluation of strategies to augment vaccine-induced control of carriage, including alternative schedules and catch-up campaigns, is required.


Asunto(s)
Vacunas Neumococicas , Streptococcus pneumoniae/inmunología , Adolescente , Adulto , Niño , Preescolar , Estudios Transversales , Demografía , Femenino , Infecciones por VIH , Humanos , Lactante , Malaui , Masculino , Nasofaringe/inmunología , Vacunas Neumococicas/administración & dosificación , Prevalencia , Estudios Prospectivos , Serogrupo , Streptococcus pneumoniae/aislamiento & purificación , Factores de Tiempo , Vacunación , Vacunas Conjugadas/administración & dosificación , Vacunas Conjugadas/efectos adversos
16.
Artículo en Inglés | MEDLINE | ID: mdl-32418510

RESUMEN

The number of notified cases of invasive pneumococcal disease (IPD) in the second quarter of 2019 was higher than the previous quarter as well as the second quarter of 2018. Following the July 2011 replacement of the 7-valent pneumococcal conjugate vaccine (7vPCV) in the childhood immunisation program with the 13-valent pneumococcal conjugate vaccine (13vPCV), there was an initial relatively rapid decline in disease due to the additional six serotypes covered by the 13vPCV across all age groups, however more recently this decline is no longer evident. Over this period the number of cases due to the eleven serotypes additionally covered by the 23-valent pneumococcal polysaccharide vaccine (23vPPV), and also those serotypes not covered by any available vaccine, has been increasing steadily across all age groups.


Asunto(s)
Infecciones Neumocócicas/epidemiología , Infecciones Neumocócicas/prevención & control , Vacunas Neumococicas/inmunología , Vigilancia de la Población , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Australia , Niño , Preescolar , Notificación de Enfermedades , Humanos , Lactante , Recién Nacido , Persona de Mediana Edad , Vacunas Neumococicas/administración & dosificación , Streptococcus pneumoniae/inmunología , Factores de Tiempo , Adulto Joven
17.
Artículo en Inglés | MEDLINE | ID: mdl-32418512

RESUMEN

The number of notified cases of invasive pneumococcal disease (IPD) in the third quarter of 2019 was higher than in the previous quarter, but lower than in the third quarter of 2018. Following the July 2011 replacement of the 7-valent pneumococcal conjugate vaccine (7vPCV) in the childhood immunisation program with the 13-valent pneumococcal conjugate vaccine (13vPCV), there was an initial relatively rapid decline in disease due to the additional six serotypes covered by the 13vPCV across all age groups, however more recently this decline is no longer evident. Over this period the number of cases due to the eleven serotypes additionally covered by the 23-valent pneumococcal polysaccharide vaccine (23vPPV), and also those serotypes not covered by any available vaccine, has been increasing steadily across all age groups.


Asunto(s)
Infecciones Neumocócicas/epidemiología , Infecciones Neumocócicas/prevención & control , Vacunas Neumococicas/inmunología , Vigilancia de la Población , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Australia , Niño , Preescolar , Notificación de Enfermedades , Humanos , Lactante , Recién Nacido , Persona de Mediana Edad , Vacunas Neumococicas/administración & dosificación , Serogrupo , Streptococcus pneumoniae/clasificación , Streptococcus pneumoniae/inmunología , Factores de Tiempo , Adulto Joven
19.
BMC Infect Dis ; 20(1): 291, 2020 Apr 20.
Artículo en Inglés | MEDLINE | ID: mdl-32312246

RESUMEN

BACKGROUND: Bacterial meningitis remains a major threat for the population of the meningitis belt. Between 2004 and 2009, in the countries of this belt, more than 200,000 people were infected with a 10% mortality rate. However, for almost 20 years, important meningitis epidemics are also reported outside this belt. Research is still very poorly developed in this part of the word like in the Democratic Republic of Congo (DRC), which experiences recurrent epidemics. This article describes for the first time the spatio-temporal patterns of meningitis cases and epidemics in DRC, in order to provide new insights for surveillance and control measures. METHODS: Based on weekly suspected cases of meningitis (2000-2012), we used time-series analyses to explore the spatio-temporal dynamics of the disease. We also used both geographic information systems and geostatistics to identify spatial clusters of cases. Both using conventional statistics and the Cleveland's algorithm for decomposition into general trend, seasonal and residuals, we searched for the existence of seasonality. RESULTS: We observed a low rate of biological confirmation of cases (11%) using soluble antigens search, culture and PCR. The main strains found are Streptococcus pneumoniae, Haemophilus influenzae and Neisseria meningitidis (A and C) serogroups. We identified 8 distinct spatial clusters, located in the northeastern and southeastern part of DRC, and in the capital city province, Kinshasa. A low seasonal trend was observed with higher incidence and attack rate of meningitis during the dry season, with a high heterogeneity in seasonal patterns occurring across the different districts and regions of DRC. CONCLUSION: Despite challenges related to completeness of data reporting, meningitis dynamics shows weak seasonality in DRC. This tends to suggest that climatic, environmental factors might be less preponderant in shaping seasonal patterns in central Africa. The characterization of 8 distinct clusters of meningitis could be used for a better sentinel meningitis surveillance and optimization of vaccine strategy in DRC. Improving biological monitoring of suspected cases should be a priority for future eco-epidemiological studies to better understand the emergence and spread of meningitis pathogens, and the potential ecological, environmental drivers of this disease.


Asunto(s)
Epidemias , Meningitis Bacterianas/epidemiología , República Democrática del Congo/epidemiología , Monitoreo Epidemiológico , Sistemas de Información Geográfica , Haemophilus influenzae/genética , Haemophilus influenzae/inmunología , Haemophilus influenzae/aislamiento & purificación , Humanos , Incidencia , Meningitis Bacterianas/microbiología , Neisseria meningitidis/genética , Neisseria meningitidis/inmunología , Neisseria meningitidis/aislamiento & purificación , Estaciones del Año , Streptococcus pneumoniae/genética , Streptococcus pneumoniae/inmunología , Streptococcus pneumoniae/aislamiento & purificación
20.
BMC Infect Dis ; 20(1): 279, 2020 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-32293324

RESUMEN

BACKGROUND: The 13-valent Pneumococcal Conjugate Vaccine (PCV-13) was introduced in the National Immunization Programme (NIP) schedule in Russia in March 2014. Previously, the 7-valent Pneumococcal Conjugate Vaccine (PCV-7) was marketed in Russia in 2009 but has never been offered for mass vaccination. A carriage study was performed among children in Arkhangelsk in 2006. The objective was to determine the prevalence of carriage, serotype distribution, antimicrobial susceptibility and the molecular structure of Streptococcus pneumoniae strains before marketing and introduction of PCV-13. METHODS: A cross-sectional study was conducted on a cluster-randomized sample of children and a self-administrated questionnaire for parents/guardians.  Nasopharyngeal samples were collected from 438 children younger than 7 years attending nurseries and kindergartens in the Arkhangelsk region, Russia. Detailed demographic data, as well as information about the child's health, traveling, exposure to antimicrobials within the last 3 months and anthropometric measurements were collected for all study subjects. Variables extracted from the questionnaire were analysed using statistic regression models to estimate the risk of carriage. All pneumococcal  isolates were examined with susceptibility testing, serotyping and multilocus sequence typing. RESULTS: The overall prevalence of asymptomatic carriage was high and peaking at 36 months with a rate of 57%. PCV-13 covered 67.3% of the detected strains. High rates of non-susceptibility to penicillin, macrolides and multidrug resistance were associated with specific vaccine serotypes, pandemic clones, and local sequence types. Nine percent of isolates represented three globally disseminated disease-associated pandemic clones; penicillin- and macrolide-resistant clones NorwayNT-42 and Poland6B-20, as well as penicillin- and macrolide-susceptible clone Netherlands3-31. A high level of antimicrobial consumption was noted by the study. According to the parent's reports, 89.5% of the children used at least one antimicrobial regime since birth. None of the hypothesised predictors of S. pneumoniae carriage were statistically significant in univariable and multivariable logistic models. CONCLUSIONS: The study identified a high coverage of the PCV-13-vaccine, but serotype replacement and expansion of globally disseminated disease-associated clones with non-vaccine serotypes may be expected. Further surveillance of antimicrobial resistance and serotype distribution is therefore required.


Asunto(s)
Portador Sano/epidemiología , Infecciones Neumocócicas/epidemiología , Infecciones Neumocócicas/prevención & control , Vacunas Neumococicas/inmunología , Streptococcus pneumoniae/genética , Streptococcus pneumoniae/inmunología , Vacunas Conjugadas/inmunología , Antibacterianos/uso terapéutico , Portador Sano/microbiología , Niño , Preescolar , Estudios Transversales , Farmacorresistencia Bacteriana Múltiple , Femenino , Humanos , Lactante , Macrólidos/uso terapéutico , Masculino , Pruebas de Sensibilidad Microbiana , Tipificación de Secuencias Multilocus , Nasofaringe/microbiología , Penicilinas/uso terapéutico , Infecciones Neumocócicas/tratamiento farmacológico , Prevalencia , Federación de Rusia/epidemiología , Serogrupo , Serotipificación , Streptococcus pneumoniae/efectos de los fármacos , Streptococcus pneumoniae/aislamiento & purificación
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