RESUMO
Routinely collected testing data have been a vital resource for public health response during the COVID-19 pandemic and have revealed the extent to which Black and Hispanic persons have borne a disproportionate burden of SARS-CoV-2 infections and hospitalizations in the United States. However, missing race and ethnicity data and missed infections due to testing disparities limit the interpretation of testing data and obscure the true toll of the pandemic. We investigated potential bias arising from these 2 types of missing data through a case study carried out in Holyoke, Massachusetts, during the prevaccination phase of the pandemic. First, we estimated SARS-CoV-2 testing and case rates by race and ethnicity, imputing missing data using a joint modeling approach. We then investigated disparities in SARS-CoV-2 reported case rates and missed infections by comparing case rate estimates with estimates derived from a COVID-19 seroprevalence survey. Compared with the non-Hispanic White population, we found that the Hispanic population had similar testing rates (476 tested per 1000 vs 480 per 1000) but twice the case rate (8.1% vs 3.7%). We found evidence of inequitable testing, with a higher rate of missed infections in the Hispanic population than in the non-Hispanic White population (79 infections missed per 1000 vs 60 missed per 1000).
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Teste para COVID-19 , COVID-19 , Hispânico ou Latino , SARS-CoV-2 , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Negro ou Afro-Americano/estatística & dados numéricos , COVID-19/etnologia , COVID-19/epidemiologia , COVID-19/diagnóstico , Teste para COVID-19/estatística & dados numéricos , Etnicidade/estatística & dados numéricos , Disparidades nos Níveis de Saúde , Disparidades em Assistência à Saúde/etnologia , Disparidades em Assistência à Saúde/estatística & dados numéricos , Hispânico ou Latino/estatística & dados numéricos , Massachusetts/epidemiologia , Diagnóstico Ausente/estatística & dados numéricos , BrancosRESUMO
Importance: Patients with limited English proficiency (LEP) face multiple barriers and are at risk for worse health outcomes compared with patients with English proficiency (EP). In sepsis, a major cause of mortality in the US, the association of LEP with health outcomes is not widely explored. Objective: To assess the association between LEP and inpatient mortality among patients with sepsis and test the hypothesis that LEP would be associated with higher mortality rates. Design, Setting, and Participants: This retrospective cohort study of hospitalized patients with sepsis included those who met the Centers for Disease Control and Prevention's sepsis criteria, received antibiotics within 24 hours, and were admitted through the emergency department. Data were collected from the electronic medical records of a large New England tertiary care center from January 1, 2016, to December 31, 2019. Data were analyzed from January 8, 2021, to March 2, 2023. Exposures: Limited English proficiency, gathered via self-reported language preference in electronic medical records. Main Outcomes and Measures: The primary outcome was inpatient mortality. The analysis used multivariable generalized estimating equation models with propensity score adjustment and analysis of covariance to analyze the association between LEP and inpatient mortality due to sepsis. Results: A total of 2709 patients met the inclusion criteria, with a mean (SD) age of 65.0 (16.2) years; 1523 (56.2%) were men and 327 (12.1%) had LEP. Nine patients (0.3%) were American Indian or Alaska Native, 101 (3.7%) were Asian, 314 (11.6%) were Black, 226 (8.3%) were Hispanic, 38 (1.4%) were Native Hawaiian or Other Pacific Islander or of other race or ethnicity, 1968 (72.6%) were White, and 6 (0.2%) were multiracial. Unadjusted mortality included 466 of 2382 patients with EP (19.6%) and 69 of 327 with LEP (21.1%). No significant difference was found in mortality odds for the LEP compared with EP groups (odds ratio [OR], 1.12 [95% CI, 0.88-1.42]). When stratified by race and ethnicity, odds of inpatient mortality for patients with LEP were significantly higher among the non-Hispanic White subgroup (OR, 1.76 [95% CI, 1.41-2.21]). This significant difference was also present in adjusted analyses (adjusted OR, 1.56 [95% CI, 1.02-2.39]). No significant differences were found in inpatient mortality between LEP and EP in the racial and ethnic minority subgroup (OR, 0.99 [95% CI, 0.63-1.58]; adjusted OR, 0.91 [95% CI, 0.56-1.48]). Conclusions and Relevance: In a large diverse academic medical center, LEP had no significant association overall with sepsis mortality. In a subgroup analysis, LEP was associated with increased mortality among individuals identifying as non-Hispanic White. This finding highlights a potential language-based inequity in sepsis care. Further studies are needed to understand drivers of this inequity, how it may manifest in other diverse health systems, and to inform equitable care models for patients with LEP.
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Proficiência Limitada em Inglês , Sepse , Estados Unidos/epidemiologia , Masculino , Humanos , Idoso , Feminino , Etnicidade , Estudos Retrospectivos , Grupos MinoritáriosRESUMO
OBJECTIVES: The World Health Organization recommends the use of oral cholera vaccine (OCV) in cholera control efforts. Euvichol®, pre-qualified in 2015, is the leading component of the Global OCV stockpile, but data on its field effectiveness are limited. To evaluate Euvichol® vaccine effectiveness (VE), we conducted a case-control study between September 2018 to March 2020 following an OCV campaign in November 2017 in Haiti. METHODS: Cases were individuals with acute watery diarrhea. Stool samples were tested by culture and real-time polymerase chain reaction of the Vibrio cholerae ctxA gene. Cases were matched to four community controls without diarrhea by residence, enrollment time, age, and gender, and interviewed for sociodemographics, risk factors, and self-reported vaccination. Cholera cases were analyzed by conditional logistic regression in the VE study. Non-cholera diarrhea cases were analyzed in a bias-indicator study. RESULTS: We enrolled 15 cholera cases matched to 60 controls, and 63 non-cholera diarrhea cases matched to 249 controls. In the VE analysis, eight (53%) cases reported vaccination with any number of doses compared to 43 (72%) controls. Adjusted two-dose OCV VE was 69% (95% CI -71 to 94%). CONCLUSIONS: Between 10-27 months after vaccination, Euvichol® was effective and similar to Shanchol™, suggesting that it can serve as one component of multi-sectoral comprehensive cholera control.
Assuntos
Vacinas contra Cólera , Cólera , Humanos , Cólera/epidemiologia , Cólera/prevenção & controle , Estudos de Casos e Controles , Haiti/epidemiologia , Administração Oral , Vacinação , DiarreiaRESUMO
OBJECTIVES: Uncovering and addressing disparities in infectious disease outbreaks require a rapid, methodical understanding of local epidemiology. We conducted a seroprevalence study of SARS-CoV-2 infection in Holyoke, Massachusetts, a majority Hispanic city with high levels of socio-economic disadvantage to estimate seroprevalence and identify disparities in SARS-CoV-2 infection. METHODS: We invited 2000 randomly sampled households between 11/5/2020 and 12/31/2020 to complete questionnaires and provide dried blood spots for SARS-CoV-2 antibody testing. We calculated seroprevalence based on the presence of IgG antibodies using a weighted Bayesian procedure that incorporated uncertainty in antibody test sensitivity and specificity and accounted for household clustering. RESULTS: Two hundred eighty households including 472 individuals were enrolled. Three hundred twenty-eight individuals underwent antibody testing. Citywide seroprevalence of SARS-CoV-2 IgG was 13.1% (95% CI 6.9-22.3) compared to 9.8% of the population infected based on publicly reported cases. Seroprevalence was 16.1% (95% CI 6.2-31.8) among Hispanic individuals compared to 9.4% (95% CI 4.6-16.4) among non-Hispanic white individuals. Seroprevalence was higher among Spanish-speaking households (21.9%; 95% CI 8.3-43.9) compared to English-speaking households (10.2%; 95% CI 5.2-18.0) and among individuals in high social vulnerability index (SVI) areas based on the CDC SVI (14.4%; 95% CI 7.1-25.5) compared to low SVI areas (8.2%; 95% CI 3.1-16.9). CONCLUSIONS: The SARS-CoV-2 IgG seroprevalence in a city with high levels of social vulnerability was 13.1% during the pre-vaccination period of the COVID-19 pandemic. Hispanic individuals and individuals in communities characterized by high SVI were at the highest risk of infection. Public health interventions should be designed to ensure that individuals in high social vulnerability communities have access to the tools to combat COVID-19.
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COVID-19 , Etnicidade , Humanos , Teorema de Bayes , Pandemias , Estudos Soroepidemiológicos , Vulnerabilidade Social , SARS-CoV-2 , Idioma , Massachusetts/epidemiologia , Anticorpos Antivirais , Imunoglobulina GRESUMO
In Haiti in 2017, the prevalence of serum vibriocidal antibody titers against Vibrio cholerae serogroup O1 among adults was 12.4% in Cerca-la-Source and 9.54% in Mirebalais, suggesting a high recent prevalence of infection. Improved surveillance programs to monitor cholera and guide public health interventions in Haiti are necessary.
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Cólera , Vibrio cholerae O1 , Adulto , Humanos , Haiti/epidemiologia , Estudos Soroepidemiológicos , Cólera/epidemiologia , Saúde PúblicaRESUMO
Background: The number of global health (GH) physician training programs in the United States has increased in the past decade. Few studies have explored the demographics of individuals in these programs, the impact of global health training on career development, and specific factors associated with whether graduates achieve a career in global health. Objectives: We aimed to describe characteristics of program graduates and quantify which previously identified factors were associated with achieving a self-defined career in GH among a cohort of graduates from one GH post-graduate training program in a highly resourced academic medical center in the United States between 2003 and 2018. Methods: We conducted a cross-sectional survey and analyzed differences between participants who self-identified as having a career in GH compared to those who did not. Findings: Among 59 individuals invited to participate, 53 (89.9%) responded to the survey. Having a GH mentor was associated with having a career in GH (OR 10.3; p = 0.004). Those who had a GH career were more likely to have a clearly-defined career path (p = 0.03), have institutional support in their current job (p = 0.00006), be able to manage the split between their GH and non-GH work (p = 0.0001), find funding to achieve their objectives in GH (p = 0.01), invest in their personal and family life (p = 0.05), and split work abroad and domestically with few challenges (p = 0.01). Conclusions: We present sociodemographic and career characteristics for graduates from a GH training program in a highly resourced academic medical center in the United States. Mentorship, institutional support, funding, ability to balance GH with non-GH work, and time spent domestically or abroad are key factors associated with successful careers in GH. If institutional funding is allocated to strengthen these aspects of GH training, we anticipate more sustained GH career development.
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Internato e Residência , Humanos , Estados Unidos , Saúde Global , Estudos Transversais , Escolha da Profissão , Educação de Pós-Graduação em MedicinaRESUMO
The COVID-19 pandemic disrupted all aspects of life globally and laid bare the pervasive inequities in access to education, employment, healthcare and economic security in both high-resource and low-resource settings. The global health field's brittle attempts of addressing global health inequities, through efforts that in some cases have evoked the colonialist forces implicated in shaping these disparities, have been further challenged by the pandemic. COVID-19 has forced global health leaders to reimagine their field through innovation such as shifting the application of global health to a local focus, collaborating with community organisations and exploring virtual education technologies. We present four case studies illustrating this promising movement towards a more sustainable, ethical and equitable model of global health education practice.Case 1: trainees from the Massachusetts General Hospital Center for Global Health partnered with the Board of Health of Holyoke, a majority Latinx city with high poverty levels, to respond to the COVID-19 pandemic through research and intervention. Case 2: Prevencasa, a community health organisation in Tijuana, Mexico, providing healthcare to local underserved communities, shifted its focus from hosting international trainees to developing a multidisciplinary training programme for Mexican healthcare professionals. Case 3: the Johns Hopkins Global Health Leadership Program adapted its curriculum into a hybrid online and in-person migrant health and human rights elective, collaborating with local organisations. Case 4: a US-based and a Latin American-based organisation collaborated to create a longitudinal, virtual urogynaecology training programme with hybrid simulation practice to increase accessibility of procedural-based training.
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COVID-19 , Humanos , COVID-19/epidemiologia , Pandemias , Saúde Global , Pessoal de Saúde/educação , Promoção da SaúdeRESUMO
Point-of-care antigen-detecting rapid diagnostic tests (RDTs) to detect Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) represent a scalable tool for surveillance of active SARS-CoV-2 infections in the population. Data on the performance of these tests in real-world community settings are paramount to guide their implementation to combat the COVID-19 pandemic. We evaluated the performance characteristics of the CareStart COVID-19 Antigen test (CareStart) in a community testing site in Holyoke, Massachusetts. We compared CareStart to a SARS-CoV-2 reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) reference, both using anterior nasal swab samples. We calculated the sensitivity, specificity, and the expected positive and negative predictive values at different SARS-CoV-2 prevalence estimates. We performed 666 total tests on 591 unique individuals. 573 (86%) were asymptomatic. There were 52 positive tests by RT-qPCR. The sensitivity of CareStart was 49.0% (95% Confidence Interval (CI) 34.8-63.4) and specificity was 99.5% (95% CI 98.5-99.9). Among positive RT-qPCR tests, the median cycle threshold (Ct) was significantly lower in samples that tested positive on CareStart. Using a Ct ≤ 30 as a benchmark for positivity increased the sensitivity of the test to 64.9% (95% CI 47.5-79.8). Our study shows that CareStart has a high specificity and moderate sensitivity. The utility of RDTs, such as CareStart, in mass implementation should prioritize use cases in which a higher specificity is more important, such as triage tests to rule-in active infections in community surveillance programs.
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COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , Pandemias , COVID-19/diagnóstico , COVID-19/epidemiologia , Sensibilidade e Especificidade , Teste para COVID-19RESUMO
A large, ongoing multicountry outbreak of human monkeypox has the potential to cause considerable morbidity and mortality. Therapeutics for the treatment of smallpox, a related Orthopoxvirus, may be used and affect the natural history of monkeypox. We present 3 patients from our hospitals treated with tecovirimat, a pan-Orthopoxvirus inhibitor currently available under an expanded access investigational new drug protocol for monkeypox.
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COVID-19/diagnóstico , Pulmão/patologia , Nasofaringe/virologia , Síndrome do Desconforto Respiratório/diagnóstico , SARS-CoV-2/isolamento & purificação , Monofosfato de Adenosina/análogos & derivados , Monofosfato de Adenosina/uso terapêutico , Alanina/análogos & derivados , Alanina/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Antivirais/uso terapêutico , COVID-19/complicações , COVID-19/terapia , Terapia Combinada , Dexametasona/uso terapêutico , Diagnóstico Diferencial , Dispneia/etiologia , Feminino , Febre/etiologia , Humanos , Contagem de Leucócitos , Pulmão/diagnóstico por imagem , Pessoa de Meia-Idade , Mialgia/etiologia , Oxigênio/sangue , Radiografia Torácica , Respiração Artificial , Síndrome do Desconforto Respiratório/etiologia , Síndrome do Desconforto Respiratório/terapiaRESUMO
The bivalent killed whole-cell oral cholera vaccine (BivWC) is being increasingly used to prevent cholera. The presence of O-antigen-specific memory B cells (MBC) has been associated with protective immunity against cholera, yet MBC responses have not been evaluated after BivWC vaccination. To address this knowledge gap, we measured V. cholerae O1-antigen MBC responses following BivWC vaccination. Adults in St. Marc, Haiti, received 2 doses of the BivWC vaccine, Shanchol, two weeks apart. Participants were invited to return at days 7, 21, 44, 90, 180 and 360 after the initial vaccination. Serum antibody and MBC responses were assessed at each time-point before and following vaccination. We observed that vaccination with BivWC resulted in significant O-antigen specific MBC responses to both Ogawa and Inaba serotypes that were detected by day 21 and remained significantly elevated over baseline for up to 12 months following vaccination. The BivWC oral cholera vaccine induces durable MBC responses to the V. cholerae O1-antigen. This suggests that long-term protection observed following vaccination with BivWC could be mediated or maintained by MBC responses.
Assuntos
Linfócitos B/imunologia , Vacinas contra Cólera/administração & dosagem , Vacinas contra Cólera/imunologia , Cólera/prevenção & controle , Antígenos O/imunologia , Vacinação/métodos , Vibrio cholerae/imunologia , Adulto , Anticorpos Antibacterianos/sangue , Anticorpos Antibacterianos/imunologia , Feminino , Haiti , Humanos , Memória Imunológica , Masculino , Antígenos O/sangue , Fatores de Tempo , Vacinas de Produtos Inativados/administração & dosagem , Vacinas de Produtos Inativados/imunologiaRESUMO
BACKGROUND: No study of long-term protection following killed oral cholera vaccination has been done outside of the historically cholera-endemic areas of south Asia, or has examined protection after a single-dose vaccination regimen. To address this, we examined the duration of protection of the standard two-dose regimen and an incomplete regimen of one dose up to 4 years after vaccination in Haiti. METHODS: In the setting of two-dose vaccination campaigns with a killed, bivalent, whole-cell oral cholera vaccination, we did a case-control study from October, 2012 through November, 2016. Eligible participants were required to be resident in the vaccine catchment area (Artibonite Department or Central Department) where they were recruited at the start of the study; and be eligible for the vaccination campaign (ie, aged ≥12 months, not pregnant, and living in the region at the time of the vaccine campaign). Patients with cholera had a positive stool culture and were recruited from cholera treatment centres. Community controls were matched to people with cholera by age group, time, and neighbourhood. We did adjusted matched regression analyses to calculate vaccine effectiveness and examine heterogeneity in effectiveness over time. The primary outcome was the effectiveness of one and two oral cholera doses as compared with zero doses from 2 months to 48 months after vaccination, measured by self reporting. FINDINGS: Among 178 people assigned to the case group and 706 people assigned to the control group, we found no evidence that two-dose effectiveness decreased during follow-up. In adjusted analyses, the average cumulative 4 year effectiveness for two doses was 76% (95% CI 59-86). In contrast, single-dose effectiveness decreased over time in a log-linear fashion, with a predicted vaccine effectiveness of 79% at the end of 12 months (95% CI 43-93), which declined to zero before the end of the second year. INTERPRETATION: In a setting of epidemic and newly endemic cholera in Haiti, single-dose vaccination with killed, bivalent, whole-cell oral cholera vaccination provided short-term protection; however, vaccination with two doses was required for long-term protection, which lasted up to 4 years after vaccination. These results add to the evidence in support of the use of killed, bivalent, whole-cell oral cholera vaccination as part of comprehensive cholera control plans. FUNDING: US National Institute of Allergy and Infectious Diseases of the National Institutes of Health and the Bill & Melinda Gates Foundation.
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Vacinas contra Cólera/administração & dosagem , Cólera/prevenção & controle , Vacinação/métodos , Administração Oral , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Criança , Pré-Escolar , Cólera/epidemiologia , Feminino , Haiti/epidemiologia , Humanos , Programas de Imunização , Imunização Secundária , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Vacinas de Produtos Inativados/administração & dosagem , Adulto JovemRESUMO
BACKGROUND: Rapid diagnostic tests (RDT) for cholera are promising tools for detecting cholera in areas with limited laboratory infrastructure. However, evidence on the characteristics of the many available RDTs is scarce, and their use has been limited by suboptimal performance. We evaluated the performance characteristics of three cholera RDTs from Span Diagnostics, Artron Laboratories, and Standard Diagnostics in a regional laboratory in Haiti. METHODOLOGY/PRINCIPAL FINDINGS: We retrospectively reviewed records from May 2014 to October 2015 of a laboratory-based surveillance program for Vibrio cholerae at Hôpital Saint-Nicolas in Saint-Marc, Haiti. We compared the results of 511 Crystal VC, 129 Artron and 451 SD Bioline RDTs to bacterial culture as the gold standard. Of 905 cultures, 477 (52.7%) were positive for V. cholerae O1, of which 27.7% were serotype Inaba. No cultures grew V. cholerae O139. Sensitivity and specificity of Crystal VC were 98.6% (95%CI: 96.5%-99.6%) and 71.1% (95%CI: 64.7%-76.9%), respectively. Artron demonstrated a sensitivity of 98.6% (95%CI: 92.7%-100%) and specificity of 69.1% (95%CI: 55.2%-80.9%). SD Bioline demonstrated a sensitivity of 81.1% (95%CI: 75.6%-85.8%) and specificity of 92.8% (95%CI: 88.4%-95.9%). Crystal VC and Artron frequently showed false positive O139 bands, whereas none were seen with SD Bioline. CONCLUSIONS/SIGNIFICANCE: There is significant variation in the performance of different cholera diagnostic RDTs. Artron and Crystal VC RDTs have high sensitivity and low specificity, while SD Bioline RDT has low to moderate sensitivity and high specificity when performed by laboratory technicians in Haiti. Study limitations included its retrospective design. The suboptimal characteristics of these tests limit their use as clinical point-of-care tests; however, they may be useful in outbreak response, surveillance, and research in resource-limited settings.
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Cólera/diagnóstico , Cromatografia de Afinidade/métodos , Kit de Reagentes para Diagnóstico/normas , Cólera/epidemiologia , Haiti/epidemiologia , Humanos , Estudos RetrospectivosRESUMO
BACKGROUND: Case-control studies to quantify oral cholera vaccine effectiveness (VE) often rely on neighbors without diarrhea as community controls. Test-negative controls can be easily recruited and may minimize bias due to differential health-seeking behavior and recall. We compared VE estimates derived from community and test-negative controls and conducted bias-indicator analyses to assess potential bias with community controls. METHODS: From October 2012 through November 2016, patients with acute watery diarrhea were recruited from cholera treatment centers in rural Haiti. Cholera cases had a positive stool culture. Non-cholera diarrhea cases (test-negative controls and non-cholera diarrhea cases for bias-indicator analyses) had a negative culture and rapid test. Up to four community controls were matched to diarrhea cases by age group, time, and neighborhood. RESULTS: Primary analyses included 181 cholera cases, 157 non-cholera diarrhea cases, 716 VE community controls and 625 bias-indicator community controls. VE for self-reported vaccination with two doses was consistent across the two control groups, with statistically significant VE estimates ranging from 72 to 74%. Sensitivity analyses revealed similar, though somewhat attenuated estimates for self-reported two dose VE. Bias-indicator estimates were consistently less than one, with VE estimates ranging from 19 to 43%, some of which were statistically significant. CONCLUSIONS: OCV estimates from case-control analyses using community and test-negative controls were similar. While bias-indicator analyses suggested possible over-estimation of VE estimates using community controls, test-negative analyses suggested this bias, if present, was minimal. Test-negative controls can be a valid low-cost and time-efficient alternative to community controls for OCV effectiveness estimation and may be especially relevant in emergency situations.
Assuntos
Vacinas contra Cólera/imunologia , Cólera/imunologia , Cólera/prevenção & controle , Administração Oral , Adolescente , Adulto , Estudos de Casos e Controles , Criança , Diarreia/imunologia , Diarreia/prevenção & controle , Feminino , Haiti , Humanos , Masculino , Pessoa de Meia-Idade , População Rural , Vacinação/métodos , Adulto JovemRESUMO
Oral cholera vaccination was used as part of cholera control in Haiti, but the vaccine does not provide complete protection. We conducted secondary data analyses of a vaccine effectiveness study in Haiti to evaluate risk factors for cholera among cholera vaccine recipients. Individuals vaccinated against cholera that presented with acute watery diarrhea and had a stool sample positive for Vibrio cholerae O1 were included as cases. Up to four vaccinated individuals who did not present for treatment of diarrhea were included as controls for each case, and matched by location of residence, enrollment time, and age. We evaluated sociodemographic characteristics and risk factors for cholera. Univariable and multivariable logistic regression were performed to identify risk factors for cholera among vaccinees. Thirty-three vaccine recipients with culture-confirmed cholera were included as cases. One-hundred-and-seventeen of their matched controls reported receiving vaccine and were included as controls. In a multivariable analysis, self-reporting use of branded household water disinfection products as a means of treating water (adjusted relative risk [aRR] = 44.3, 95% confidence interval [CI] = 4.19-468.05, P = 0.002), and reporting having a latrine as the main household toilet (aRR = 4.22, 95% CI = 1.23-14.43, P = 0.02), were independent risk factors for cholera. Self-reporting always treating water (aRR = 0.09, 95% CI = 0.01-0.57, P = 0.01) was associated with protection against cholera. The field effectiveness of water, sanitation, and hygiene interventions used in combination with cholera vaccination in cholera control should be measured and monitored over time to identify and remediate shortcomings, and ensure successful impact on disease control.
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Vacinas contra Cólera/administração & dosagem , Cólera/epidemiologia , Cólera/prevenção & controle , Vacinação em Massa/estatística & dados numéricos , Avaliação de Programas e Projetos de Saúde/estatística & dados numéricos , População Rural/estatística & dados numéricos , Administração Oral , Adulto , Estudos de Casos e Controles , Feminino , Haiti , Humanos , Modelos Logísticos , Masculino , Fatores de RiscoRESUMO
Leptotrichia species are normal constituents of the oral cavity and the genitourinary tract microbiota that are known to provoke disease in immunocompromised patients and rarely in immunocompetent individuals. Following the description of Leptotrichia goodfellowii sp. nov., two cases of endocarditis by this species have been reported. Here, we report a case of Leptotrichia goodfellowii endocarditis in an immunocompetent patient with a valvular allograft. The isolation and identification of Leptotrichia can be challenging, and it is likely that infection with this pathogen is significantly underdiagnosed. A definitive identification, as in this case, most often requires 16S rRNA gene sequencing, highlighting the increasingly important role of this diagnostic modality among immunocompetent patients with undetermined anaerobic bacteremia.
RESUMO
BACKGROUND: The bivalent whole-cell (BivWC) oral cholera vaccine (Shanchol) is effective in preventing cholera. However, evaluations of immune responses following vaccination with BivWC have been limited. To determine whether BivWC induces significant mucosal immune responses, we measured V. cholerae O1 antigen-specific antibody secreting cell (ASC) responses following vaccination. METHODOLOGY/PRINCIPAL FINDINGS: We enrolled 24 Haitian adults in this study, and administered doses of oral BivWC vaccine 14 days apart (day 0 and day 14). We drew blood at baseline, and 7 days following each vaccine dose (day 7 and 21). Peripheral blood mononuclear cells (PBMCs) were isolated, and ASCs were enumerated using an ELISPOT assay. Significant increases in Ogawa (6.9 cells per million PBMCs) and Inaba (9.5 cells per million PBMCs) OSP-specific IgA ASCs were detected 7 days following the first dose (P < 0.001), but not the second dose. The magnitude of V. cholerae-specific ASC responses did not appear to be associated with recent exposure to cholera. ASC responses measured against the whole lipolysaccharide (LPS) antigen and the OSP moiety of LPS were equivalent, suggesting that all or nearly all of the LPS response targets the OSP moiety. CONCLUSIONS/SIGNIFICANCE: Immunization with the BivWC oral cholera vaccine induced ASC responses among a cohort of healthy adults in Haiti after a single dose. The second dose of vaccine resulted in minimal ASC responses over baseline, suggesting that the current dosing schedule may not be optimal for boosting mucosal immune responses to V. cholerae antigens for adults in a cholera-endemic area.
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Anticorpos Antibacterianos/sangue , Vacinas contra Cólera/imunologia , Cólera/prevenção & controle , Administração Oral , Adulto , Anticorpos Antibacterianos/biossíntese , Células Produtoras de Anticorpos/imunologia , Células Produtoras de Anticorpos/metabolismo , Vacinas contra Cólera/administração & dosagem , Feminino , Haiti/epidemiologia , Humanos , Imunoglobulina A/biossíntese , Imunoglobulina A/sangue , Imunoglobulina G/biossíntese , Imunoglobulina G/sangue , Masculino , Pessoa de Meia-Idade , Vacinação , Adulto JovemRESUMO
Male Drosophila flies secrete seminal-fluid proteins that mediate proper sperm storage and fertilization, and that induce changes in female behavior. Females also produce reproductive-tract secretions, yet their contributions to postmating physiology are poorly understood. Large secretory cells line the female's spermathecae, a pair of sperm-storage organs. We identified the regulatory regions controlling transcription of two genes exclusively expressed in these spermathecal secretory cells (SSC): Spermathecal endopeptidase 1 (Send1), which is expressed in both unmated and mated females, and Spermathecal endopeptidase 2 (Send2), which is induced by mating. We used these regulatory sequences to perform precise genetic ablations of the SSC at distinct time points relative to mating. We show that the SSC are required for recruiting sperm to the spermathecae, but not for retaining sperm there. The SSC also act at a distance in the reproductive tract, in that their ablation: (1) reduces sperm motility in the female's other sperm-storage organ, the seminal receptacle; and (2) causes ovoviviparity--the retention and internal development of fertilized eggs. These results establish the reproductive functions of the SSC, shed light on the evolution of live birth, and open new avenues for studying and manipulating female fertility in insects.