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1.
N Engl J Med ; 2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34614326

RESUMO

BACKGROUND: Despite high vaccine coverage and effectiveness, the incidence of symptomatic infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been increasing in Israel. Whether the increasing incidence of infection is due to waning immunity after the receipt of two doses of the BNT162b2 vaccine is unclear. METHODS: We conducted a 6-month longitudinal prospective study involving vaccinated health care workers who were tested monthly for the presence of anti-spike IgG and neutralizing antibodies. Linear mixed models were used to assess the dynamics of antibody levels and to determine predictors of antibody levels at 6 months. RESULTS: The study included 4868 participants, with 3808 being included in the linear mixed-model analyses. The level of IgG antibodies decreased at a consistent rate, whereas the neutralizing antibody level decreased rapidly for the first 3 months with a relatively slow decrease thereafter. Although IgG antibody levels were highly correlated with neutralizing antibody titers (Spearman's rank correlation between 0.68 and 0.75), the regression relationship between the IgG and neutralizing antibody levels depended on the time since receipt of the second vaccine dose. Six months after receipt of the second dose, neutralizing antibody titers were substantially lower among men than among women (ratio of means, 0.64; 95% confidence interval [CI], 0.55 to 0.75), lower among persons 65 years of age or older than among those 18 to less than 45 years of age (ratio of means, 0.58; 95% CI, 0.48 to 0.70), and lower among participants with immunosuppression than among those without immunosuppression (ratio of means, 0.30; 95% CI, 0.20 to 0.46). CONCLUSIONS: Six months after receipt of the second dose of the BNT162b2 vaccine, humoral response was substantially decreased, especially among men, among persons 65 years of age or older, and among persons with immunosuppression.

2.
Am J Obstet Gynecol MFM ; 4(1): 100492, 2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34547533

RESUMO

BACKGROUND: The exclusion of pregnant women from initial COVID-19 messenger RNA vaccine trials raised hesitancy regarding the benefits of vaccination for pregnant women, hence little is known about vaccines' efficacy in this population. OBJECTIVE: To determine the maternal-neonatal transplacental transfer of SARS-CoV-2 antibodies among vaccinated parturient women. A control group of COVID-19-recovered patients was included to compare the immunoglobulin G levels between vaccinated and recovered patients. STUDY DESIGN: This is a prospective cohort study conducted in a single tertiary medical center in Israel between February and March 2021; parturient women vaccinated with the BNT162b2 messenger RNA vaccine during pregnancy were included and compared with COVID-19-recovered parturient women. SARS-CoV-2 immunoglobulin G antibodies were measured in maternal and cord sera, dried blood spot samples taken from newborns, and breast milk samples. The primary aim was to determine whether neonatal cord and dried blood spot samples were positive for SARS-CoV-2 antibodies and to evaluate the transfer ratio, defined as cord blood immunoglobulin G divided by maternal immunoglobulin G levels. RESULTS: The study included 64 vaccinated parturient women and 11 parturient women who had COVID-19 during pregnancy. All maternal blood sera samples and 98.3% of the cord blood sera samples were positive for SARS-Cov-2 immunoglobulin G with median concentrations of 26.1 (interquartile range, 22.0-39.7) and 20.2 (interquartile range, 12.7-29.0), respectively. Similarly, 96.4% of neonatal blood spot samples and all breast milk samples were positive for SARS-CoV-2 immunoglobulin G with median concentrations of 11.0 (interquartile range, 7.2-12.8) and 4.9 (interquartile range, 3.8-6.0), respectively. There was a significant positive correlation between maternal serum levels of SARS-CoV-2 immunoglobulin G and cord blood (r=0.483; P=.0001), neonatal blood spot (r=0.515; P=.004), and breast milk levels (r=0.396; P=.005) of SARS-CoV-2 immunoglobulin G. The median placental transfer ratio of SARS-COV-2 immunoglobulin G was 0.77. Comparison of vaccinated and recovered COVID-19 patients revealed significantly higher SARS-CoV-2 immunoglobulin G levels in maternal serum and cord blood among vaccinated women (P<.0001). CONCLUSION: Our study demonstrated the efficient transfer of SARS-CoV-2 immunoglobulin G across the placenta in women, vaccinated with the BNT162b2 messenger RNA vaccine during pregnancy, to their neonates, with a positive correlation between maternal serum and cord blood antibody concentrations. In addition to maternal protection against COVID-19, the vaccine may also provide neonatal humoral immunity.

3.
Artigo em Inglês | MEDLINE | ID: mdl-34438069

RESUMO

OBJECTIVES: The immunogenicity and safety of the Pfizer-BioNTech BNT162b2 mRNA vaccine in people living with human immunodeficiency virus type 1 (PLWH) are unknown. We aimed to assess the immunogenicity and safety of this vaccine in PLWH. METHODS: In this prospective open study, we enrolled 143 PLWH, aged ≥18 years, who attended our clinic and 261 immunocompetent health-care workers (HCWs). Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor binding domain (RBD) IgG and neutralizing antibodies were measured. Adverse events, viral load and CD4 cell counts were monitored. RESULTS: At a median of 18 days (interquartile range 14-21 days) after the second dose, anti-RBD-IgG was positive in 139/141 (98%) PLWH. Among HCWs, 258/261 (98.9%) developed anti-RBD-IgG at a median of 26 days (interquartile range 24-27 days) after the second dose. Following the second dose, immune sera neutralized SARS-CoV-2 pseudo-virus in 97% and 98% of PLWH and HCWs, respectively. Adverse events were reported in 60% of PLWH, mainly pain at the injection site, fatigue and headache. AIDS-related adverse events were not reported. Human immunodeficiency virus load increased in 3/143 (2%) patients from <40 copies/mL to ≤100 copies/mL. CD4+ T-cell count decreased from a geometric mean of 700 cells/µL (95% CI 648-757 cells/µL) to 633.8 cells/µL (95% CI 588-683 cells/µL) (p < 0.01). CONCLUSIONS: BNT162b2 mRNA vaccine appears immunogenic and safe in PLWH who are on antiretroviral therapy with unsuppressed CD4 count and suppressed viral load.

4.
Epidemiol Infect ; 149: e153, 2021 06 24.
Artigo em Inglês | MEDLINE | ID: mdl-34372950

RESUMO

Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) pandemic is still ongoing along with the global vaccination efforts against it. Here, we aimed to understand the longevity and strength of anti-SARS-CoV-2 IgG responses in a small community (n = 283) six months following local SARS-COV-2 outbreak in March 2020. Three serological assays were compared and neutralisation capability was also determined. Overall 16.6% (47/283) of the participants were seropositive and 89.4% (42/47) of the IgG positives had neutralising antibodies. Most of the symptomatic individuals confirmed as polymerase chain reaction (PCR) positive during the outbreak were seropositive (30/32, 93.8%) and 33.3% of the individuals who quarantined with a PCR confirmed patient had antibodies. Serological assays comparison revealed that Architect (Abbott) targeting the N protein LIASON® (DiaSorin) targeting the S protein and enzyme-linked immunosorbent assay (ELISA) targeting receptor binding domain detected 9.5% (27/283), 17.3% (49/283) and 17% (48/283), respectively, as IgG positives. The latter two assays highly agreed (kappa = 0.89) between each other. In addition, 95%, (19/20, by ELISA) and 90.9% (20/22, with LIASON) and only 71.4% (15/21, by Architect) of individuals that were seropositive in May 2020 were found positive also in September. The unexpected low rate of overall immunity indicates the absence of un-noticed, asymptomatic infections. Lack of overall high correlation between the assays is attributed mainly to target-mediated antibody responses and suggests that using a single serological assay may be misleading.


Assuntos
Anticorpos Antivirais/imunologia , COVID-19/epidemiologia , Surtos de Doenças , Imunoglobulina G/imunologia , SARS-CoV-2/imunologia , Adolescente , Adulto , Fatores Etários , Anticorpos Neutralizantes/imunologia , COVID-19/imunologia , Criança , Pré-Escolar , Surtos de Doenças/estatística & dados numéricos , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imunidade Coletiva/imunologia , Lactente , Recém-Nascido , Israel/epidemiologia , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Características de Residência/estatística & dados numéricos , Estudos Soroepidemiológicos , Fatores de Tempo , Adulto Jovem
6.
Lancet Respir Med ; 9(9): 999-1009, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34224675

RESUMO

BACKGROUND: Concurrent with the Pfizer-BioNTech BNT162b2 COVID-19 vaccine roll-out in Israel initiated on Dec 19, 2020, we assessed the early antibody responses and antibody kinetics after each vaccine dose in health-care workers of different ages and sexes, and with different comorbidities. METHODS: We did a prospective, single-centre, longitudinal cohort study at the Sheba Medical Centre (Tel-Hashomer, Israel). Eligible participants were health-care workers at the centre who had a negative anti-SARS-CoV-2 IgG assay before receiving the first dose of the intramuscular vaccine, and at least one serological antibody test after the first dose of the vaccine. Health-care workers with a positive SARS-CoV-2 PCR test before vaccination, a positive anti-SARS-CoV-2 IgG serology test before vaccination, or infection with COVID-19 after vaccination were excluded from the study. Participants were followed up weekly for 5 weeks after the first vaccine dose; a second dose was given at week 3. Serum samples were obtained at baseline and at each weekly follow-up, and antibodies were tested at 1-2 weeks after the first vaccine dose, at week 3 with the administration of the second vaccine dose, and at weeks 4-5 (ie, 1-2 weeks after the second vaccine dose). Participants with comorbidities were approached to participate in an enriched comorbidities subgroup, and at least two neutralising assays were done during the 5 weeks of follow-up in those individuals. IgG assays were done for the entire study population, whereas IgM, IgA, and neutralising antibody assays were done only in the enriched comorbidities subgroup. Concentrations of IgG greater than 0·62 sample-to-cutoff (s/co) ratio and of IgA greater than 1·1 s/co, and titres of neutralising antibodies greater than 10 were considered positive. Scatter plot and correlation analyses, logistic and linear regression analyses, and linear mixed models were used to investigate the longitudinal antibody responses. FINDINGS: Between Dec 19, 2020, and Jan 30, 2021, we obtained 4026 serum samples from 2607 eligible, vaccinated participants. 342 individuals were included in the enriched comorbidities subgroup. The first vaccine dose elicited positive IgG and neutralising antibody responses at week 3 in 707 (88·0%) of 803 individuals, and 264 (71·0%) of 372 individuals, respectively, which were rapidly increased at week 4 (ie, 1 week after the second vaccine dose) in 1011 (98·4%) of 1027 and 357 (96·5%) of 370 individuals, respectively. Over 4 weeks of follow-up after vaccination, a high correlation (r=0·92) was detected between IgG against the receptor-binding domain and neutralising antibody titres. First-dose induced IgG response was significantly lower in individuals aged 66 years and older (ratio of means 0·25, 95% CI 0·19-0·31) and immunosuppressed individuals (0·21, 0·14-0·31) compared with individuals aged 18·00-45·99 years and individuals with no immunosuppression, respectively. This disparity was partly abrogated following the second dose. Overall, endpoint regression analysis showed that lower antibody concentrations were consistently associated with male sex (ratio of means 0·84, 95% CI 0·80-0·89), older age (ie, ≥66 years; 0·64, 0·58-0·71), immunosuppression (0·44, 0·33-0·58), and other specific comorbidities: diabetes (0·88, 0·79-0·98), hypertension (0·90, 0·82-0·98), heart disease (0·86, 0·75-1·00), and autoimmune diseases (0·82, 0·73-0·92). INTERPRETATION: BNT162b2 vaccine induces a robust and rapid antibody response. The significant correlation between receptor-binding domain IgG antibodies and neutralisation titres suggests that IgG antibodies might serve as a correlate of neutralisation. The second vaccine dose is particularly important for older and immunosuppressed individuals, highlighting the need for timely second vaccinations and potentially a revaluation of the long gap between doses in some countries. Antibody responses were reduced in susceptible populations and therefore they might be more prone to breakthrough infections. FUNDING: Sheba Medical Center, Israel Ministry of Health.


Assuntos
Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Vacinas contra COVID-19/imunologia , COVID-19/prevenção & controle , Pessoal de Saúde/estatística & dados numéricos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Anticorpos Antivirais/isolamento & purificação , COVID-19/epidemiologia , COVID-19/imunologia , COVID-19/virologia , Vacinas contra COVID-19/administração & dosagem , Feminino , Seguimentos , Humanos , Imunidade Humoral , Imunogenicidade da Vacina , Israel/epidemiologia , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Pandemias/prevenção & controle , Estudos Prospectivos , SARS-CoV-2/imunologia , Vacinação/métodos , Vacinação/estatística & dados numéricos , Adulto Jovem
7.
N Engl J Med ; 385(16): 1474-1484, 2021 10 14.
Artigo em Inglês | MEDLINE | ID: mdl-34320281

RESUMO

BACKGROUND: Despite the high efficacy of the BNT162b2 messenger RNA vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), rare breakthrough infections have been reported, including infections among health care workers. Data are needed to characterize these infections and define correlates of breakthrough and infectivity. METHODS: At the largest medical center in Israel, we identified breakthrough infections by performing extensive evaluations of health care workers who were symptomatic (including mild symptoms) or had known infection exposure. These evaluations included epidemiologic investigations, repeat reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assays, antigen-detecting rapid diagnostic testing (Ag-RDT), serologic assays, and genomic sequencing. Correlates of breakthrough infection were assessed in a case-control analysis. We matched patients with breakthrough infection who had antibody titers obtained within a week before SARS-CoV-2 detection (peri-infection period) with four to five uninfected controls and used generalized estimating equations to predict the geometric mean titers among cases and controls and the ratio between the titers in the two groups. We also assessed the correlation between neutralizing antibody titers and N gene cycle threshold (Ct) values with respect to infectivity. RESULTS: Among 1497 fully vaccinated health care workers for whom RT-PCR data were available, 39 SARS-CoV-2 breakthrough infections were documented. Neutralizing antibody titers in case patients during the peri-infection period were lower than those in matched uninfected controls (case-to-control ratio, 0.361; 95% confidence interval, 0.165 to 0.787). Higher peri-infection neutralizing antibody titers were associated with lower infectivity (higher Ct values). Most breakthrough cases were mild or asymptomatic, although 19% had persistent symptoms (>6 weeks). The B.1.1.7 (alpha) variant was found in 85% of samples tested. A total of 74% of case patients had a high viral load (Ct value, <30) at some point during their infection; however, of these patients, only 17 (59%) had a positive result on concurrent Ag-RDT. No secondary infections were documented. CONCLUSIONS: Among fully vaccinated health care workers, the occurrence of breakthrough infections with SARS-CoV-2 was correlated with neutralizing antibody titers during the peri-infection period. Most breakthrough infections were mild or asymptomatic, although persistent symptoms did occur.

8.
Proc Biol Sci ; 288(1952): 20210773, 2021 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-34102894

RESUMO

Disentangling the mechanisms that mediate the relationships between species diversity and disease risk has both theoretical and applied implications. We employed a model system of rodents and their Mycoplasma pathogens, in which an extreme negative diversity-disease relationship was demonstrated, to test the assumptions underlying three mechanisms that may explain this field pattern. Through quantifying the long-term dynamics and effects of the pathogen in its three host species, we estimated the between-host differences in pathogen spreading and transmission potentials, and host recovery potential and vulnerability to infection. The results suggest that one of the hosts is a pathogen amplifier and the other two hosts function as diluters. Considering the similarity in infection success and intensity among hosts, and the failure to detect any pathogen-induced damage, we could not validate the assumption underlying the hypotheses that diluters reduce the overall transmission or increase the mortality of infected hosts in the system. Instead, the results demonstrate that diluters clear the infection faster than amplifiers, supporting the possibility that the addition of diluters to the community may reduce the overall number of infected hosts through this mechanism. This study highlights the contribution of experimental studies that simultaneously explore different aspects of host-pathogen interactions in multiple hosts, in diversity-disease research.


Assuntos
Especificidade de Hospedeiro , Interações Hospedeiro-Patógeno , Animais , Modelos Biológicos , Roedores
9.
Clin Microbiol Infect ; 27(3): 474.e1-474.e3, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33309698

RESUMO

OBJECTIVE: The role of school closure in mitigating coronavirus disease 2019 (COVID-19) transmission has been questioned. In our medical centre, during a 9-week national lockdown, an alternative school was opened for health-care workers' (HCW) children with a small number of children per class and strict symptom surveillance. After lockdown was lifted we screened children and their parents for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serology. METHODS: We conducted a cross-sectional study of HCW parents and their children after one teacher contracted COVID-19 following exposure at home and 53 children were exposed, isolated and tested by RT-PCR. We compared families with children attending the alternative school with families whose children who remained at home during the 9-week lockdown. Epidemiological and medical data were collected using a short questionnaire; nasopharyngeal and oropharyngeal swabs were obtained and tested for SARS-CoV-2 by RT-PCR, and blood was collected for SARS-CoV-2 IgA and IgG titres. RESULTS: A total of 435 children attended the Sheba alternative school. Among the 53 children exposed to the infected teacher, none tested positive by RT-PCR. Of these, 18 children-parent pairs were tested for serology and all were negative. A total of 106/435 (24%) children and their 78 parents were recruited for the cross-sectional study; 70 attended the Sheba school and 36 did not. Approximately 16% of children in either group reported symptoms (11/70 in the school group and 6/36 in the 'stay home' group), but SARS-CoV-2 was not detected by PCR in any, and previous exposure, as determined by serological tests, was low and not significantly different between the groups. CONCLUSION: In an alternative school for children of HCWs, active during COVID-19 national outbreak, we found no evidence of increased infection compared with children that stayed home.


Assuntos
COVID-19/epidemiologia , COVID-19/prevenção & controle , Pessoal de Saúde/estatística & dados numéricos , Instituições Acadêmicas/estatística & dados numéricos , Adulto , COVID-19/diagnóstico , Criança , Controle de Doenças Transmissíveis/métodos , Controle de Doenças Transmissíveis/estatística & dados numéricos , Estudos Transversais , Feminino , Humanos , Israel/epidemiologia , Masculino , Pais , Prevalência , SARS-CoV-2/genética , SARS-CoV-2/imunologia , SARS-CoV-2/isolamento & purificação , Centros de Atenção Terciária
10.
PLoS One ; 15(11): e0241164, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33227020

RESUMO

The COVID-19 pandemic and the fast global spread of the disease resulted in unprecedented decline in world trade and travel. A critical priority is, therefore, to quickly develop serological diagnostic capacity and identify individuals with past exposure to SARS-CoV-2. In this study serum samples obtained from 309 persons infected by SARS-CoV-2 and 324 of healthy, uninfected individuals as well as serum from 7 COVID-19 patients with 4-7 samples each ranging between 1-92 days post first positive PCR were tested by an "in house" ELISA which detects IgM, IgA and IgG antibodies against the receptor binding domain (RBD) of SARS-CoV-2. Sensitivity of 47%, 80% and 88% and specificity of 100%, 98% and 98% in detection of IgM, IgA and IgG antibodies, respectively, were observed. IgG antibody levels against the RBD were demonstrated to be up regulated between 1-7 days after COVID-19 detection, earlier than both IgM and IgA antibodies. Study of the antibody kinetics of seven COVID 19 patients revealed that while IgG levels are high and maintained for at least 3 months, IgM and IgA levels decline after a 35-50 days following infection. Altogether, these results highlight the usefulness of the RBD based ELISA, which is both easy and cheap to prepare, to identify COVID-19 patients even at the acute phase. Most importantly our results demonstrate that measuring IgG levels alone is both sufficient and necessary to diagnose past exposure to SARS-CoV-2.


Assuntos
Anticorpos Antivirais/imunologia , Teste Sorológico para COVID-19/métodos , COVID-19/diagnóstico , COVID-19/epidemiologia , Imunoglobulina G/imunologia , Pandemias , Domínios Proteicos/imunologia , SARS-CoV-2/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19/sangue , COVID-19/virologia , Estudos de Coortes , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imunoglobulina A/sangue , Imunoglobulina A/imunologia , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Imunoglobulina M/imunologia , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase Via Transcriptase Reversa , SARS-CoV-2/genética , Sensibilidade e Especificidade , Adulto Jovem
11.
J Exp Biol ; 222(Pt 15)2019 07 31.
Artigo em Inglês | MEDLINE | ID: mdl-31285244

RESUMO

Interactions between coinfecting parasites may take various forms, either direct or indirect, facilitative or competitive, and may be mediated by either bottom-up or top-down mechanisms. Although each form of interaction leads to different evolutionary and ecological outcomes, it is challenging to tease them apart throughout the infection period. To establish the first step towards a mechanistic understanding of the interactions between coinfecting limited-term bacterial parasites and lifelong bacterial parasites, we studied the coinfection of Bartonella sp. (limited-term) and Mycoplasma sp. (lifelong), which commonly co-occur in wild rodents. We infected Bartonella- and Mycoplasma-free rodents with each species, and simultaneously with both, and quantified the infection dynamics and host responses. Bartonella benefited from the interaction; its infection load decreased more slowly in coinfected rodents than in rodents infected with Bartonella alone. There were no indications for bottom-up effects, but coinfected rodents experienced various changes, depending on the infection stage, in their body mass, stress levels and activity pattern, which may further affect bacterial replication and transmission. Interestingly, the infection dynamics and changes in the average coinfected rodent traits were more similar to the chronic effects of Mycoplasma infection, whereas coinfection uniquely impaired the host's physiological and behavioral stability. These results suggest that parasites with distinct life history strategies may interact, and their interaction may be asymmetric, non-additive, multifaceted and dynamic through time. Because multiple, sometimes contrasting, forms of interactions are simultaneously at play and their relative importance alternates throughout the course of infection, the overall outcome may change under different ecological conditions.


Assuntos
Coinfecção/microbiologia , Coinfecção/fisiopatologia , Gerbillinae/microbiologia , Animais , Bartonella/fisiologia , Infecções por Bartonella/imunologia , Infecções por Bartonella/fisiopatologia , Comportamento Animal , Peso Corporal , Coinfecção/imunologia , Feminino , Masculino , Mycoplasma/fisiologia , Infecções por Mycoplasma/fisiopatologia , Estresse Fisiológico
12.
Mol Ecol ; 27(23): 4787-4807, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30357977

RESUMO

Based on molecular data, previous studies have suggested a high overall diversity and co-infection rates of Bartonella bacteria in wild rodents and their fleas. However, partial genetic characterization of uncultured co-infecting bacteria limited sound conclusions concerning intra- and inter-specific diversity of the circulating Bartonella. To overcome this limitation, Bartonella infections of wild populations of two sympatric gerbil species and their fleas were explored by multiple isolations of Bartonella organisms. Accordingly, 448 pure Bartonella isolates, obtained from 20 rodent blood and 39 flea samples, were genetically characterized to the genotype and species levels. Results revealed a remarkable diversity and co-infection rates of Bartonella among these sympatric rodents and their associated fleas. Specifically, 38 genotypes, classified into four main Bartonella species, were identified. Co-infection was confirmed in 56% of the samples, which contained two to four Bartonella genotypes per sample, belonging to up to three different species. Recombination within and between these species was demonstrated, serving as a direct evidence of the frequent bacteria-bacteria interactions. Moreover, despite the noticeable interchange of common Bartonella genotypes between rodents and fleas, the co-occurrence of genotypes was not random and differences in the overall diversity, and the ecological and phylogenetic similarities of the infection compositions were significantly associated with the carrier type (rodent vs. flea) and the rodent species. Thus, comprehensive identification of the co-infecting organisms enabled the elucidation of ecological factors affecting the Bartonella distribution among reservoirs and vectors. This study may serve as a model for the investigation of other vector-borne organisms and their relationships with Bartonella.


Assuntos
Bartonella/classificação , Coinfecção/microbiologia , Gerbillinae/microbiologia , Sifonápteros/microbiologia , Animais , Técnicas de Tipagem Bacteriana , Infecções por Bartonella/veterinária , DNA Bacteriano/genética , Genótipo , Insetos Vetores/microbiologia , Israel , Filogenia , Doenças dos Roedores/microbiologia
13.
Mol Ecol ; 27(18): 3714-3726, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30074652

RESUMO

The way that some parasites and pathogens persist in the hostile environment of their host for long periods remains to be resolved. Here, longitudinal field surveys were combined with laboratory experiments to investigate the routes of transmission and infection dynamics of such a pathogen-a wild rodent haemotropic bacterium, specifically a Mycoplasma haemomuris-like bacterium. Fleaborne transmission, direct rodent-to-rodent transmission and vertical transmission from fleas or rodents to their offspring were experimentally quantified, and indications were found that the main route of bacterial transmission is direct, although its rate of successful transmission is low (~20%). The bacterium's temporal dynamics was then compared in the field to that observed under a controlled infection experiment in field-infected and laboratory-infected rodents, and indications were found, under all conditions, that the bacterium reached its peak infection level after 25-45 days and then decreased to low bacterial loads, which persist for the rodent's lifetime. These findings suggest that the bacterium relies on persistency with low bacterial loads for long-term coexistence with its rodent host, having both conceptual and applied implications.


Assuntos
Gerbillinae/microbiologia , Infecções por Mycoplasma/transmissão , Infecções por Mycoplasma/veterinária , Sifonápteros/microbiologia , Animais , Transmissão Vertical de Doenças Infecciosas/veterinária , Mycoplasma
14.
Genet Med ; 19(6): 628-634, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-27906198

RESUMO

PURPOSE: Population screening for BRCA1/BRCA2. mutations is being considered for Ashkenazi Jews (AJ) because 2.5% carry recurrent deleterious mutations and effective cancer prevention exists. This study aimed to provide a qualitative focus on perspectives of individuals, particularly carriers, who were tested through a screening trial. In this trial, the pretest process included only written information. METHODS: Interviews were performed with 26 carriers and 10 noncarriers who participated in a BRCA population screening trial for AJ. RESULTS: Attitudes toward screening were generally positive. The main motivator for testing was knowledge of BRCA status to enable cancer risk reduction. Knowledge of carrier status, although challenging, was thus viewed as health-empowering. The screening paradigm was sensed as increasing awareness and as overcoming access, referral, and familial barriers. Streamlining the pretest process was positively perceived as offering gradual, stepwise knowledge commensurate with test results. Participants were concerned that health systems provide the necessary conceptual and infrastructural framework and that individual autonomy be maintained. CONCLUSIONS: BRCA screening in AJ is viewed favorably, even by carriers. Stepwise acquisition of knowledge based on test results was viewed as most relevant to the screening context. Screening program development should account for safeguarding autonomy and providing requisite post-test services.Genet Med advance online publication 01 December 2016.


Assuntos
Proteína BRCA1/genética , Proteína BRCA2/genética , Triagem de Portadores Genéticos , Judeus/genética , Programas de Rastreamento , Mutação , Atitude Frente a Saúde , Feminino , Humanos , Judeus/psicologia , Masculino , Pessoa de Meia-Idade , Pesquisa Qualitativa
15.
Parasit Vectors ; 8: 429, 2015 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-26286391

RESUMO

BACKGROUND: The parasite composition of wild host individuals often impacts their behavior and physiology, and the transmission dynamics of pathogenic species thereby determines disease risk in natural communities. Yet, the determinants of parasite composition in natural communities are still obscure. In particular, three fundamental questions remain open: (1) what are the relative roles of host and environmental characteristics compared with direct interactions between parasites in determining the community composition of parasites? (2) do these determinants affect parasites belonging to the same guild and those belonging to different guilds in similar manners? and (3) can cross-sectional and longitudinal analyses work interchangeably in detecting community determinants? Our study was designed to answer these three questions in a natural community of rodents and their fleas, ticks, and two vector-borne bacteria. METHODS: We sampled a natural population of Gerbillus andersoni rodents and their blood-associated parasites on two occasions. By combining path analysis and model selection approaches, we then explored multiple direct and indirect paths that connect (i) the environmental and host-related characteristics to the infection probability of a host by each of the four parasite species, and (ii) the infection probabilities of the four species by each other. RESULTS: Our results suggest that the majority of paths shaping the blood-associated communities are indirect, mostly determined by host characteristics and not by interspecific interactions or environmental conditions. The exact effects of host characteristics on infection probability by a given parasite depend on its life history and on the method of sampling, in which the cross-sectional and longitudinal methods are complementary. CONCLUSIONS: Despite the awareness of the need of ecological investigations into natural host-vector-parasite communities in light of the emergence and re-emergence of vector-borne diseases, we lack sampling methods that are both practical and reliable. Here we illustrated how comprehensive patterns can be revealed from observational data by applying path analysis and model selection approaches and combining cross-sectional and longitudinal analyses. By employing this combined approach on blood-associated parasites, we were able to distinguish between direct and indirect effects and to predict the causal relationships between host-related characteristics and the parasite composition over time and space. We concluded that direct interactions within the community play only a minor role in determining community composition relative to host characteristics and the life history of the community members.


Assuntos
Bactérias/isolamento & purificação , Ecossistema , Gerbillinae/microbiologia , Gerbillinae/parasitologia , Interações Hospedeiro-Parasita , Sifonápteros/crescimento & desenvolvimento , Carrapatos/crescimento & desenvolvimento , Animais , Bactérias/classificação , Sangue/microbiologia , Sangue/parasitologia , Estudos Transversais , Estudos Longitudinais , Sifonápteros/classificação , Carrapatos/classificação
16.
ISME J ; 9(7): 1662-76, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25575310

RESUMO

Vector-borne microbes are subject to the ecological constraints of two distinct microenvironments: that in the arthropod vector and that in the blood of its vertebrate host. Because the structure of bacterial communities in these two microenvironments may substantially affect the abundance of vector-borne microbes, it is important to understand the relationship between bacterial communities in both microenvironments and the determinants that shape them. We used pyrosequencing analyses to compare the structure of bacterial communities in Synosternus cleopatrae fleas and in the blood of their Gerbillus andersoni hosts. We also monitored the interindividual and seasonal variability in these bacterial communities by sampling the same individual wild rodents during the spring and again during the summer. We show that the bacterial communities in each sample type (blood, female flea or male flea) had a similar phylotype composition among host individuals, but exhibited seasonal variability that was not directly associated with host characteristics. The structure of bacterial communities in male fleas and in the blood of their rodent hosts was remarkably similar and was dominated by flea-borne Bartonella and Mycoplasma phylotypes. A lower abundance of flea-borne bacteria and the presence of Wolbachia phylotypes distinguished bacterial communities in female fleas from those in male fleas and in rodent blood. These results suggest that the overall abundance of a certain vector-borne microbe is more likely to be determined by the abundance of endosymbiotic bacteria in the vector, abundance of other vector-borne microbes co-occurring in the vector and in the host blood and by seasonal changes, than by host characteristics.


Assuntos
Infecções Bacterianas/veterinária , Infestações por Pulgas/veterinária , Gerbillinae/sangue , Estações do Ano , Sifonápteros/microbiologia , Animais , Infecções Bacterianas/microbiologia , Bartonella/isolamento & purificação , Feminino , Gerbillinae/microbiologia , Insetos Vetores , Masculino , Wolbachia/isolamento & purificação
17.
PLoS One ; 9(10): e109677, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25343259

RESUMO

Relationships between host and microbial diversity have important ecological and applied implications. Theory predicts that these relationships will depend on the spatio-temporal scale of the analysis and the niche breadth of the organisms in question, but representative data on host-microbial community assemblage in nature is lacking. We employed a natural gradient of rodent species richness and quantified bacterial communities in rodent blood at several hierarchical spatial scales to test the hypothesis that associations between host and microbial species diversity will be positive in communities dominated by organisms with broad niches sampled at large scales. Following pyrosequencing of rodent blood samples, bacterial communities were found to be comprised primarily of broad niche lineages. These communities exhibited positive correlations between host diversity, microbial diversity and the likelihood for rare pathogens at the regional scale but not at finer scales. These findings demonstrate how microbial diversity is affected by host diversity at different spatial scales and suggest that the relationships between host diversity and overall disease risk are not always negative, as the dilution hypothesis predicts.


Assuntos
Meio Ambiente , Genética Populacional , Interações Hospedeiro-Patógeno/genética , Roedores/microbiologia , Animais , Bactérias/classificação , Bactérias/genética , Biodiversidade , Ecologia , Roedores/genética
18.
Ecology ; 95(5): 1173-83, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-25000749

RESUMO

While host-species diversity often influences microbial prevalence, there may be multiple mechanisms causing such effects that may also depend on the foraging strategy of the microbes. We employed a natural gradient of rodent-species richness to examine competing hypotheses describing possible mechanisms mediating the relationship between host-species richness and the prevalence of the most dominant microbes, along with microbe specificity to the different rodent host species. We sampled blood from three gerbil species in plots differing in terms of the proportion of the different species and screened for the most dominant bacteria. Two dominant bacterial lineages were detected: host-specific bacteria and host-opportunistic bacteria. Using a model selection approach, we detected evidence for both direct and indirect effects of host-species richness on the prevalence of these bacteria. Infection probability of the host-specific lineage was lower in richer host communities, most likely due to increased frequency and density of the least suitable host species. In contrast, field observations suggest that the effect of host-species richness on infection probability of the opportunistic lineage was both direct and indirect, mostly mediated by changes in flea densities on the host and by the presence of the host-specific lineage. Our results thus suggest that host-species richness has multiple effects on microbial prevalence, depending on the degree of host-specificity of the microbe in question.


Assuntos
Bartonella/classificação , Especificidade de Hospedeiro , Mycoplasma/classificação , Doenças dos Roedores/microbiologia , Sifonápteros/microbiologia , Animais , Bartonella/genética , Biodiversidade , Interações Hospedeiro-Patógeno , Israel/epidemiologia , Mycoplasma/genética , Filogenia , Doenças dos Roedores/epidemiologia , Roedores
19.
ISME J ; 8(8): 1598-608, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24577352

RESUMO

The composition of Bartonella infection was explored in wild Gerbillus andersoni rodents and their Synosternus cleopatrae fleas. Rodent blood samples and fleas were collected in two periods (two different seasons; 4 months apart) from juveniles and adult hosts, and their bartonellae lineages were identified by a 454-pyrosequencing analysis targeting a specific Bartonella citrate synthase gene (gltA) fragment. The rate of Bartonella spp. co-infection was estimated and the assemblage and distribution of bartonellae lineages across the samples with respect to ecological and phylogenetic distance similarities were analyzed. Moreover, environmental factors that could explain potential differences between samples were investigated. Out of the 91 bartonellae-positive samples, 89% were found to be co-infected with more than two phylogenetically distant Bartonella genotypes and additional closely related (but distinguishable) variants. These bartonellae lineages were distributed in a non-random manner, and a negative interaction between lineages was discovered. Interestingly, the overall composition of those infections greatly varied among samples. This variability was partially explained by factors, such as type of sample (blood versus fleas), flea sex and period of collection. This investigation sheds light on the patterns of Bartonella infection and the organization of Bartonella lineages in fleas and rodents in nature.


Assuntos
Infecções por Bartonella/veterinária , Bartonella/classificação , Doenças dos Roedores/microbiologia , Sifonápteros/microbiologia , Animais , Bartonella/genética , Bartonella/isolamento & purificação , Infecções por Bartonella/microbiologia , Fenômenos Ecológicos e Ambientais , Genótipo , Gerbillinae , Filogenia
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