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2.
N Engl J Med ; 387(19): 1770-1782, 2022 11 10.
Artículo en Inglés | MEDLINE | ID: mdl-36286260

RESUMEN

BACKGROUND: Information regarding the protection conferred by vaccination and previous infection against infection with the B.1.1.529 (omicron) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is limited. METHODS: We evaluated the protection conferred by mRNA vaccines and previous infection against infection with the omicron variant in two high-risk populations: residents and staff in the California state prison system. We used a retrospective cohort design to analyze the risk of infection during the omicron wave using data collected from December 24, 2021, through April 14, 2022. Weighted Cox models were used to compare the effectiveness (measured as 1 minus the hazard ratio) of vaccination and previous infection across combinations of vaccination history (stratified according to the number of mRNA doses received) and infection history (none or infection before or during the period of B.1.617.2 [delta]-variant predominance). A secondary analysis used a rolling matched-cohort design to evaluate the effectiveness of three vaccine doses as compared with two doses. RESULTS: Among 59,794 residents and 16,572 staff, the estimated effectiveness of previous infection against omicron infection among unvaccinated persons who had been infected before or during the period of delta predominance ranged from 16.3% (95% confidence interval [CI], 8.1 to 23.7) to 48.9% (95% CI, 41.6 to 55.3). Depending on previous infection status, the estimated effectiveness of vaccination (relative to being unvaccinated and without previous documented infection) ranged from 18.6% (95% CI, 7.7 to 28.1) to 83.2% (95% CI, 77.7 to 87.4) with two vaccine doses and from 40.9% (95% CI, 31.9 to 48.7) to 87.9% (95% CI, 76.0 to 93.9) with three vaccine doses. Incremental effectiveness estimates of a third (booster) dose (relative to two doses) ranged from 25.0% (95% CI, 16.6 to 32.5) to 57.9% (95% CI, 48.4 to 65.7) among persons who either had not had previous documented infection or had been infected before the period of delta predominance. CONCLUSIONS: Our findings in two high-risk populations suggest that mRNA vaccination and previous infection were effective against omicron infection, with lower estimates among those infected before the period of delta predominance. Three vaccine doses offered significantly more protection than two doses, including among previously infected persons.


Asunto(s)
Vacunas contra la COVID-19 , COVID-19 , Prisiones , Vacunación , Humanos , COVID-19/epidemiología , COVID-19/prevención & control , Prisiones/estadística & datos numéricos , Estudios Retrospectivos , SARS-CoV-2 , Vacunas contra la COVID-19/administración & dosificación , Vacunas contra la COVID-19/uso terapéutico , California/epidemiología , Prisioneros/estadística & datos numéricos , Policia/estadística & datos numéricos , Eficacia de las Vacunas/estadística & datos numéricos , Reinfección/epidemiología , Reinfección/prevención & control , Inmunización Secundaria/estadística & datos numéricos
3.
medRxiv ; 2022 May 27.
Artículo en Inglés | MEDLINE | ID: mdl-35665013

RESUMEN

B ackground: Prisons and jails are high-risk settings for Covid-19 transmission, morbidity, and mortality. We evaluate protection conferred by prior infection and vaccination against the SARS-CoV-2 Omicron variant within the California state prison system. M ethods: We employed a test-negative design to match resident and staff cases during the Omicron wave (December 24, 2021-April 14, 2022) to controls according to a case's test-week as well as demographic, clinical, and carceral characteristics. We estimated protection against infection using conditional logistic regression, with exposure status defined by vaccination, stratified by number of mRNA doses received, and prior infection, stratified by periods before or during Delta variant predominance. R esults: We matched 15,783 resident and 8,539 staff cases to 180,169 resident and 90,409 staff controls. Among cases, 29.7% and 2.2% were infected before or during the emergence of the Delta variant, respectively; 30.6% and 36.3% were vaccinated with two or three doses, respectively. Estimated protection from Omicron infection for two and three doses were 14.9% (95% Confidence Interval [CI], 12.3-19.7%) and 43.2% (42.2-47.4%) for those without known prior infections, 47.8% (95% CI, 46.6-52.8%) and 61.3% (95% CI, 60.7-64.8%) for those infected before the emergence of Delta, and 73.1% (95% CI, 69.8-80.1%) and 86.8% (95% CI, 82.1-92.7) for those infected during the period of Delta predominance. C onclusion: A third mRNA dose provided significant, additional protection over two doses, including among individuals with prior infection. Our findings suggest that vaccination should remain a priority-even in settings with high levels of transmission and prior infection.

4.
PLoS One ; 16(6): e0251635, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34106932

RESUMEN

BACKGROUND: The Eliminate Hepatitis C San Diego County Initiative was established to provide a roadmap to reduce new HCV infections by 80% and HCV-related deaths by 65% by 2030. An estimate of the burden of HCV infections in San Diego County is necessary to inform planning and evaluation efforts. Our analysis was designed to estimate the HCV burden in San Diego County in 2018. METHODS: We synthesized data from the American Community Survey, Centers for Disease Control and Prevention, California Department of Public Health, Public Health Branch of California Correctional Health Care Services, San Diego Blood Bank, and published literature. Burden estimates were stratified by subgroup (people who inject drugs in the community [PWID], men who have sex with men in the community [MSM], general population in the community [stratified by age and sex], and incarcerated individuals). To account for parameter uncertainty, 100,000 parameter sets were sampled from each parameter's uncertainty distribution, and used to calculate the mean and 95% confidence interval estimates of the number of HCV seropositive adults in San Diego in 2018. FINDINGS: We found there were 55,354 (95% CI: 25,411-93,329) adults with a history of HCV infection in San Diego County in 2018, corresponding to an HCV seroprevalence of 2.1% (95% CI: 1.1-3.4%). Over 40% of HCV infections were among the general population aged 55-74 and one-third were among PWID. CONCLUSION: Our study found that the largest share of infections was among adults aged 55-74, indicating the importance of surveillance, prevention, testing, and linkages to care in this group to reduce mortality. Further, programs prioritizing PWID for increased HCV testing and linkage to care are important for reducing new HCV infections.


Asunto(s)
Hepatitis C/epidemiología , Adolescente , Adulto , Factores de Edad , Anciano , California/epidemiología , Femenino , Hepatitis C/etiología , Homosexualidad Masculina/estadística & datos numéricos , Humanos , Masculino , Persona de Mediana Edad , Prisioneros/estadística & datos numéricos , Factores de Riesgo , Estudios Seroepidemiológicos , Factores Sexuales , Abuso de Sustancias por Vía Intravenosa/complicaciones , Abuso de Sustancias por Vía Intravenosa/epidemiología , Abuso de Sustancias por Vía Intravenosa/virología , Adulto Joven
5.
Public Health Rep ; 135(1_suppl): 50S-56S, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32735197

RESUMEN

In 2014, California passed Assembly Bill 966, which required condom access for persons incarcerated in all 35 California state prisons (33 men's and 2 women's prisons). The California Correctional Health Care Services and the Sexually Transmitted Disease Control Branch and the Office of AIDS of the California Department of Public Health collaborated in a prison administration-led multidisciplinary implementation workgroup. Our workgroup, representing public health, correctional health, legal and legislative affairs, labor relations, and prison staff members, participated in 4 planning meetings during May-September 2015. We surveyed prison staff members and incarcerated men to identify and address potential challenges; conceptualized a tamper-resistant condom dispenser; developed educational materials, frequently asked questions for staff members, and fact sheets for the public; and conducted forums for custody and medical staff members at each prison. Key lessons learned included the need for high-level custody support, engagement of labor unions early in the decision-making process, and flexibility within defined parameters for sites to determine best practices given their unique institutional population, culture, and physical layout. Condom access was initiated at 4 prisons in July 2015 and expanded incrementally to the remaining 29 men's prisons through July 2016. A total of 243 563 condoms were accessed in the men's prisons, for an average of 354 condoms per 1000 population per month. The start-up dispenser cost was $69 825 (735 dispensers at $95 each). We estimated an annual condom cost of $0.60 per person. Although staff members and incarcerated men expressed concern that this legislation would condone sex and provide repositories for contraband, no serious adverse incidents involving condoms were reported. California demonstrated that condom access is a safe, low-cost intervention with high uptake for a large correctional system and provided a replicable implementation model for other states. Prison condom programs have the potential to decrease transmission of sexually transmitted infections (STIs) among incarcerated persons and their communities, which are often disproportionately affected by STIs, HIV, and other chronic diseases.


Asunto(s)
Condones/provisión & distribución , Prisiones/organización & administración , Salud Pública , Enfermedades de Transmisión Sexual/prevención & control , California/epidemiología , Técnicas de Apoyo para la Decisión , Femenino , Infecciones por VIH/epidemiología , Infecciones por VIH/prevención & control , Educación en Salud/organización & administración , Humanos , Capacitación en Servicio/organización & administración , Sindicatos/organización & administración , Masculino , Prisiones/economía , Prisiones/normas , Desarrollo de Programa , Enfermedades de Transmisión Sexual/epidemiología
6.
MMWR Morb Mortal Wkly Rep ; 69(33): 1139-1143, 2020 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-32817597

RESUMEN

Preventing coronavirus disease 2019 (COVID-19) in correctional and detention facilities* can be challenging because of population-dense housing, varied access to hygiene facilities and supplies, and limited space for isolation and quarantine (1). Incarcerated and detained populations have a high prevalence of chronic diseases, increasing their risk for severe COVID-19-associated illness and making early detection critical (2,3). Correctional and detention facilities are not closed systems; SARS-CoV-2, the virus that causes COVID-19, can be transmitted to and from the surrounding community through staff member and visitor movements as well as entry, transfer, and release of incarcerated and detained persons (1). To better understand SARS-CoV-2 prevalence in these settings, CDC requested data from 15 jurisdictions describing results of mass testing events among incarcerated and detained persons and cases identified through earlier symptom-based testing. Six jurisdictions reported SARS-CoV-2 prevalence of 0%-86.8% (median = 29.3%) from mass testing events in 16 adult facilities. Before mass testing, 15 of the 16 facilities had identified at least one COVID-19 case among incarcerated or detained persons using symptom-based testing, and mass testing increased the total number of known cases from 642 to 8,239. Case surveillance from symptom-based testing has likely underestimated SARS-CoV-2 prevalence in correctional and detention facilities. Broad-based testing can provide a more accurate assessment of prevalence and generate data to help control transmission (4).


Asunto(s)
Técnicas de Laboratorio Clínico/estadística & datos numéricos , Infecciones por Coronavirus/epidemiología , Brotes de Enfermedades/prevención & control , Tamizaje Masivo , Neumonía Viral/epidemiología , Prisiones , COVID-19 , Prueba de COVID-19 , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/prevención & control , Vivienda/estadística & datos numéricos , Humanos , Pandemias/prevención & control , Neumonía Viral/prevención & control , Prevalencia , Estados Unidos/epidemiología
7.
MMWR Morb Mortal Wkly Rep ; 69(19): 587-590, 2020 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-32407300

RESUMEN

An estimated 2.1 million U.S. adults are housed within approximately 5,000 correctional and detention facilities† on any given day (1). Many facilities face significant challenges in controlling the spread of highly infectious pathogens such as SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19). Such challenges include crowded dormitories, shared lavatories, limited medical and isolation resources, daily entry and exit of staff members and visitors, continual introduction of newly incarcerated or detained persons, and transport of incarcerated or detained persons in multiperson vehicles for court-related, medical, or security reasons (2,3). During April 22-28, 2020, aggregate data on COVID-19 cases were reported to CDC by 37 of 54 state and territorial health department jurisdictions. Thirty-two (86%) jurisdictions reported at least one laboratory-confirmed case from a total of 420 correctional and detention facilities. Among these facilities, COVID-19 was diagnosed in 4,893 incarcerated or detained persons and 2,778 facility staff members, resulting in 88 deaths in incarcerated or detained persons and 15 deaths among staff members. Prompt identification of COVID-19 cases and consistent application of prevention measures, such as symptom screening and quarantine, are critical to protecting incarcerated and detained persons and staff members.


Asunto(s)
Betacoronavirus/aislamiento & purificación , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/epidemiología , Neumonía Viral/diagnóstico , Neumonía Viral/epidemiología , Prisiones , COVID-19 , Infecciones por Coronavirus/mortalidad , Infecciones por Coronavirus/prevención & control , Humanos , Pandemias/prevención & control , Neumonía Viral/mortalidad , Neumonía Viral/prevención & control , Prevalencia , SARS-CoV-2 , Estados Unidos/epidemiología
8.
Med Mycol ; 57(Supplement_1): S30-S40, 2019 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-30690599

RESUMEN

The incidence of reported coccidioidomycosis in the past two decades has increased greatly; monitoring its changing epidemiology is essential for understanding its burden on patients and the healthcare system and for identifying opportunities for prevention and education. We provide an update on recent coccidioidomycosis trends and public health efforts nationally and in Arizona, California, and Washington State. In Arizona, enhanced surveillance shows that coccidioidomycosis continues to be associated with substantial morbidity. California reported its highest yearly number of cases ever in 2016 and has implemented interventions to reduce coccidioidomycosis in the prison population by excluding certain inmates from residing in prisons in high-risk areas. Coccidioidomycosis is emerging in Washington State, where phylogenetic analyses confirm the existence of a unique Coccidioides clade. Additional studies of the molecular epidemiology of Coccidioides will improve understanding its expanding endemic range. Ongoing public health collaborations and future research priorities are focused on characterizing geographic risk, particularly in the context of environmental change; identifying further risk reduction strategies for high-risk groups; and improving reporting of cases to public health agencies.


Asunto(s)
Coccidioides/aislamiento & purificación , Coccidioidomicosis/epidemiología , Coccidioidomicosis/prevención & control , Arizona/epidemiología , California/epidemiología , Coccidioides/genética , Humanos , Incidencia , Filogenia , Prisioneros , Salud Pública , Factores de Riesgo , Estados Unidos/epidemiología , Washingtón/epidemiología
9.
J Correct Health Care ; 24(4): 342-351, 2018 10.
Artículo en Inglés | MEDLINE | ID: mdl-30099936

RESUMEN

Two California state prisons (A and B) have very high rates of coccidioidomycosis (Valley Fever). The prison health care service sought to improve their prevention strategy by risk stratification with a newly available spherulin-based Coccidioides delayed-type hypersensitivity test. Of the 36,789 voluntarily screened inmates, 4.7% experienced adverse reactions. A positive test (8.6% of those tested) was independently associated with (1) incarceration at prisons A and B, (2) admission to prison from a Coccidioides-endemic county, (3) length of stay at prisons A and B, and (4) increasing age. These findings suggest that the test is safe and performing well at risk stratification; the prison system now restricts inmates with negative tests from prisons A and B. This novel use of the test might benefit other coccidioidomycosis prevention programs.


Asunto(s)
Coccidioidomicosis/diagnóstico , Coccidioidomicosis/epidemiología , Prisiones/organización & administración , Pruebas Cutáneas/efectos adversos , Pruebas Cutáneas/métodos , Adolescente , Adulto , Negro o Afroamericano , Anciano , California/epidemiología , Coccidioidomicosis/etnología , Hispánicos o Latinos , Hospitalización , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Factores de Riesgo , Adulto Joven
10.
MMWR Morb Mortal Wkly Rep ; 65(7): 178-81, 2016 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-26914322

RESUMEN

Early diagnosis of human immunodeficiency virus (HIV) infection and initiation of antiretroviral treatment (ART) improves health outcomes and prevents HIV transmission. Before 2010, HIV testing was available to inmates in the California state prison system upon request. In 2010, the California Correctional Health Care Services (CCHCS) integrated HIV opt-out screening into the health assessment for inmates entering California state prisons. Under this system, a medical care provider informs the inmate that an HIV test is routinely done, along with screening for sexually transmitted, communicable, and vaccine-preventable diseases, unless the inmate specifically declines the test. During 2012-2013, CCHCS, the California Department of Public Health, and CDC evaluated HIV screening, rates of new diagnoses, linkage to and retention in care, ART response, and post-release linkage to care among California prison inmates. All prison inmates are processed through one of eight specialized reception center facilities, where they undergo a comprehensive evaluation of their medical needs, mental health, and custody requirements for placement in one of 35 state prisons. Among 17,436 inmates who entered a reception center during April-September 2012, 77% were screened for HIV infection; 135 (1%) tested positive, including 10 (0.1%) with newly diagnosed infections. Among the 135 HIV-positive patient-inmates, 134 (99%) were linked to care within 90 days of diagnosis, including 122 (91%) who initiated ART. Among 83 who initiated ART and remained incarcerated through July 2013, 81 (98%) continued ART; 71 (88%) achieved viral suppression (<200 HIV RNA copies/mL). Thirty-nine patient-inmates were released on ART; 12 of 14 who were linked to care within 30 days of release were virally suppressed at that time. Only one of nine persons with a viral load test conducted between 91 days and 1 year post-release had viral suppression. Although high rates of viral suppression were achieved in prison, continuity of care in the community remains a challenge. An infrastructure for post-release linkage to care is needed to help ensure sustained HIV disease control.


Asunto(s)
Continuidad de la Atención al Paciente/estadística & datos numéricos , Infecciones por VIH/diagnóstico , Infecciones por VIH/tratamiento farmacológico , Tamizaje Masivo/estadística & datos numéricos , Prisioneros , Terapia Antirretroviral Altamente Activa/estadística & datos numéricos , Recuento de Linfocito CD4/estadística & datos numéricos , California , Femenino , Investigación sobre Servicios de Salud , Humanos , Masculino , Prisioneros/estadística & datos numéricos , Prisiones/estadística & datos numéricos , Carga Viral/estadística & datos numéricos
11.
Emerg Infect Dis ; 21(1): 70-5, 2015 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-25533149

RESUMEN

In California, coccidioidomycosis is a disease acquired by inhaling spores of Coccidioides immitis, a fungus found in certain arid regions, including the San Joaquin Valley, California, USA, where 8 state prisons are located. During 2011, we reviewed coccidioidomycosis rates at 2 of the prisons that consistently report >80% of California's inmate cases and determined inmate risk factors for primary, severe (defined as pulmonary coccidioidomycosis requiring >10 hospital days), and disseminated coccidioidomycosis (defined by hospital discharge International Classification of Disease, Ninth Revision code). Inmates of African American ethnicity who were >40 years of age were at significantly higher risk for primary coccidioidomycosis than their white counterparts (odds ratio = 2.0, 95% CI 1.5-2.8). Diabetes was a risk factor for severe pulmonary coccidioidomycosis, and black race a risk factor for disseminated disease. These findings contributed to a court decision mandating exclusion of black inmates and inmates with diabetes from the 2 California prisons with the highest rates of coccidioidomycosis.


Asunto(s)
Coccidioidomicosis/epidemiología , Prisioneros , Adolescente , Adulto , Negro o Afroamericano , Anciano , Anciano de 80 o más Años , California/epidemiología , Hispánicos o Latinos , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Factores de Riesgo , Adulto Joven
12.
J Correct Health Care ; 20(3): 184-194, 2014 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-24934836

RESUMEN

This study evaluated the safety and security impact, feasibility, and cost of a program to provide condoms to inmates. A 1-year pilot study of wall-mounted condom dispensing machines in one California state prison compared pre- and post-intervention rates of penal code violations related to sexual misconduct, contraband, controlled substances, and violence. The rates of penal code violations were unchanged or decreased compared to the pre-pilot year. Discreetly located condom dispensers were vandalized less frequently than those in plain view (p < .05). Distributing condoms using the pilot model would cost less than $2 per inmate annually. Results suggest that the use of discreetly located dispensing machines is an acceptable, feasible, low-cost option to prevent the transmission of sexually transmitted diseases and poses no safety or security risk in a typical medium-security prison setting.

13.
Int J Parasitol ; 34(1): 27-36, 2004 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-14711587

RESUMEN

CD4(+) T cell responses and macrophage activation are essential components of schistosome egg-induced granuloma formation. Previous studies implicated tumour necrosis factor (TNF) as a potential mediator of macrophage recruitment and activation during schistosome infection. Here we demonstrate that signalling by TNF and its receptors can influence granuloma formation, but is ultimately dispensable for granuloma formation in this system. However, we identify a previously unrecognised role for TNF in limiting hepatocellular damage in response to schistosome eggs. Further, we show that this activity of TNF is independent of TNF receptors (TNFR1 and TNFR2). Taken together, these data suggest that additional, as yet unrecognised receptors exist for TNF and that these receptors are capable of mediating important pathological effects in the liver. Finally, we provide evidence that TNF plays an unexpected role in maintaining adult schistosome viability in the portal system.


Asunto(s)
Parasitosis Hepáticas/patología , Hígado/patología , Esquistosomiasis/patología , Factor de Necrosis Tumoral alfa/fisiología , Animales , Apoptosis , Huevos , Femenino , Ligandos , Hígado/parasitología , Circulación Hepática , Parasitosis Hepáticas/inmunología , Masculino , Ratones , Ratones Noqueados , Receptores del Factor de Necrosis Tumoral/metabolismo , Schistosoma/fisiología , Esquistosomiasis/inmunología
14.
Mol Biochem Parasitol ; 131(1): 65-75, 2003 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-12967713

RESUMEN

Peptidases are essential for the establishment and survival of the medically important parasite, Schistosoma mansoni. This helminth expresses a number of gut-associated peptidases that degrade host blood proteins, including hemoglobin, as a means of nutrition. Using irreversible affinity probes, we demonstrate that S. mansoni cathepsin B-like endopeptidase 1 (SmCB1) is the most abundant papain family cysteine peptidase in both the parasite gut and somatic extracts. SmCB1 zymogen (SmCB1pm) was functionally expressed in Pichia pastoris (4-11mgl(-1)). Monospecific and immunoselected antibodies raised against SmCB1pm localized the enzyme exclusively to the gut lumen and surrounding gastrodermis of adult worms. Recombinant SmCB1pm was unable to catalyze its activation, even at low pH. However, recombinant S. mansoni asparaginyl endopeptidase (SmAE), another gut-associated cysteine peptidase, processed and activated SmCB1pm in trans. Consistent with the known specificity of AEs, processing occurred on the carboxyl side of an asparagine residue, two residues upstream of the start of the mature SmCB1 sequence. The remaining pro-region dipeptide was removed by rat cathepsin C (dipeptidyl-peptidase I)-an action conceivably performed by an endogenous cathepsin C in vivo. The activated recombinant SmCB1 is biochemically identical to the native enzyme with respect to dipeptidyl substrate kinetics and pH profiles. Also, the serum proteins, hemoglobin, serum albumin, IgG, and alpha-2 macroglobulin were efficiently degraded. Further, a novel application of an assay to measure the peptidyl carboxypeptidase activity of SmCB1 and other cathepsins B was developed using the synthetic substrate benzoyl-glycinyl-histidinyl-leucine (Bz-Gly-His-Leu). This study characterizes the major digestive cysteine peptidase in schistosomes and defines novel trans-processing events required to activate the SmCB1 zymogen in vitro which may facilitate the digestive process in vivo.


Asunto(s)
Catepsina B/metabolismo , Cisteína Endopeptidasas/metabolismo , Proteínas del Helminto/metabolismo , Proteínas de Plantas/metabolismo , Schistosoma mansoni/enzimología , Activación Transcripcional , Animales , Catepsina B/química , Catepsina B/genética , Mucosa Gástrica/metabolismo , Regulación de la Expresión Génica , Proteínas del Helminto/química , Proteínas del Helminto/genética , Datos de Secuencia Molecular , Pichia/enzimología , Pichia/genética , Schistosoma mansoni/genética , Análisis de Secuencia de ADN , Especificidad por Sustrato
15.
Mol Biochem Parasitol ; 121(1): 49-61, 2002 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-11985862

RESUMEN

Papain-like cysteine endopeptidases have been recognized as potential targets for chemotherapy and serodiagnostic reagents in infections with the human parasitic helminth Schistosoma. A novel cathepsin B endopeptidase from adult S. mansoni has been isolated and characterized. The enzyme is termed SmCB2 to distinguish it from the first recorded schistosome cathepsin B, SmCB1, also known as Sm31. A rapid and convenient protocol involving anion exchange and affinity chromatography is described for the isolation of SmCB1 and SmCB2 from the same parasite starting material. SmCB2 has been functionally expressed in and purified from Pichia pastoris. Both native and recombinant SmCB2 migrate similarly (33 kDa) by SDS-PAGE. Both display strict acidic pH activity profiles and similar K(m) and k(cat) for dipeptidyl amidomethylcoumarin substrates. We conclude that the recombinant enzyme is properly folded. The S(2) subsite specificity of recombinant SmCB2 exhibits the preferences Phe>Leu>Val>>Arg. By immunoblotting with anti-SmCB2 IgG, a 33 kDa protein was identified in soluble extracts of male schistosomes. By immunohistochemistry, SmCB2 was localized in the tegumental tubercles and parenchyma of males with less product being visualized in the parenchyma of females. The enzyme may be lysosomal and function at the host parasite-interface.


Asunto(s)
Catepsina B/aislamiento & purificación , Catepsina B/metabolismo , Proteínas del Helminto/aislamiento & purificación , Schistosoma mansoni/enzimología , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Catepsina B/química , Catepsina B/genética , Femenino , Proteínas del Helminto/química , Proteínas del Helminto/genética , Proteínas del Helminto/metabolismo , Masculino , Datos de Secuencia Molecular , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Schistosoma mansoni/crecimiento & desarrollo , Alineación de Secuencia , Análisis de Secuencia de ADN , Especificidad por Sustrato
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