RESUMO
SETTING: Timely diagnosis of tuberculous meningitis (TBM) in patients with human immunodeficiency virus (HIV) infection remains a challenge. Despite the current scale-up of the Xpert® MTB/RIF assay, other molecular diagnostic tools are necessary, particularly in referral centres in low- and middle-income countries without Xpert testing. OBJECTIVE: To determine the diagnostic performance of nested real-time polymerase chain reaction (nRT-PCR) in HIV-infected TBM patients categorised according to standardised clinical case definitions. DESIGN: Based on clinical, laboratory and imaging data, HIV-infected patients with suspected TBM were prospectively categorised as 'definite TBM', 'probable TBM', 'possible TBM' or 'not TBM'. We evaluated nRT-PCR sensitivity and specificity in diagnosing TBM among definite TBM cases, and among definite + probable TBM cases. RESULTS: Ninety-two participants were enrolled in the study. nRT-PCR sensitivity for definite TBM (n = 8) was 100% (95%CI 67-100) and 86% (95%CI 60-96) for both definite and probable TBM (n = 6). Assuming that 'not TBM' patients (n = 74) were true-negatives, nRT-PCR specificity was 100% (95%CI 95-100). The possible TBM group (n = 4) had no nRT-PCR positives. CONCLUSIONS: The nRT-PCR is a useful rule-in test for HIV-infected patients with TBM according to international consensus case definitions. As nRT-PCR cannot exclude TBM, studies comparing and combining nRT-PCR with other assays are necessary for a rule-out test
Assuntos
Humanos , Tuberculose Meníngea/diagnóstico , Infecções por HIV , Reação em Cadeia da PolimeraseRESUMO
SETTING: Timely diagnosis of tuberculous meningitis (TBM) in patients with human immunodeficiency virus (HIV) infection remains a challenge. Despite the current scale-up of the Xpert® MTB/RIF assay, other molecular diagnostic tools are necessary, particularly in referral centres in low- and middle-income countries without Xpert testing. OBJECTIVE: To determine the diagnostic performance of nested real-time polymerase chain reaction (nRT-PCR) in HIV-infected TBM patients categorised according to standardised clinical case definitions. DESIGN: Based on clinical, laboratory and imaging data, HIV-infected patients with suspected TBM were prospectively categorised as 'definite TBM', 'probable TBM', 'possible TBM' or 'not TBM'. We evaluated nRT-PCR sensitivity and specificity in diagnosing TBM among definite TBM cases, and among definite + probable TBM cases. RESULTS: Ninety-two participants were enrolled in the study. nRT-PCR sensitivity for definite TBM (n = 8) was 100% (95%CI 67-100) and 86% (95%CI 60-96) for both definite and probable TBM (n = 6). Assuming that 'not TBM' patients (n = 74) were true-negatives, nRT-PCR specificity was 100% (95%CI 95-100). The possible TBM group (n = 4) had no nRT-PCR positives. CONCLUSIONS: The nRT-PCR is a useful rule-in test for HIV-infected patients with TBM according to international consensus case definitions. As nRT-PCR cannot exclude TBM, studies comparing and combining nRT-PCR with other assays are necessary for a rule-out test.
Assuntos
Infecções por HIV/epidemiologia , Reação em Cadeia da Polimerase em Tempo Real/métodos , Tuberculose Meníngea/diagnóstico , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: Depending on the presence of mutations that determine isoniazid (INH) susceptibility (katG and inhA), Mycobacterium tuberculosis may be susceptible to high doses of INH or ethionamide (ETH). OBJECTIVE: To describe the INH resistance profile and association of katG mutation with previous INH treatment and level of drug resistance based on rapid molecular drug susceptibility testing (DST) in southern Brazil and central Mozambique. DESIGN: Descriptive study of 311 isolates from Ribeirão Preto, São Paulo, Brazil (2011-2014) and 155 isolates from Beira, Mozambique (2014-2015). Drug resistance patterns and specific gene mutations were determined using GenoType(®) MTBDRplus. RESULTS: katG gene mutations were detected in 12/22 (54.5%) Brazilian and 32/38 (84.2%) Mozambican isolates. inhA mutations were observed in 9/22 (40.9%) isolates in Brazil and in 4/38 (10.5%) in Mozambique. Both katG and inhA mutations were detected in respectively 1/22 (5%) and 2/38 (5.2%). The difference in the frequency of katG mutations in Brazil and Mozambique was statistically significant (P = 0.04). katG mutations were present in 68.8% (33/48) of patients previously treated with INH and 31.2% (15/48) of patients without previous INH. This difference was not statistically significant (P = 0.223). CONCLUSION: INH mutations varied geographically; molecular DST can be used to guide and accelerate decision making in the use of ETH or high doses of INH.
Assuntos
Antituberculosos/uso terapêutico , Proteínas de Bactérias/genética , Catalase/genética , Análise Mutacional de DNA , Farmacorresistência Bacteriana Múltipla/genética , Etionamida/uso terapêutico , Isoniazida/uso terapêutico , Mutação , Mycobacterium tuberculosis/efeitos dos fármacos , Oxirredutases/genética , Tuberculose Resistente a Múltiplos Medicamentos/diagnóstico , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Brasil/epidemiologia , Tomada de Decisão Clínica , Humanos , Testes de Sensibilidade Microbiana , Moçambique/epidemiologia , Mycobacterium tuberculosis/genética , Seleção de Pacientes , Valor Preditivo dos Testes , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Tuberculose Resistente a Múltiplos Medicamentos/microbiologiaRESUMO
OBJECTIVE: To study the impact of chemoprophylaxis for tuberculosis on the survival of HIV-infected patients with a positive tuberculin skin test. DESIGN: Prospective observational cohort study. SETTING: Outpatient clinic of a university hospital, in Rio de Janeiro, Brazil. PATIENTS: Two-hundred and ninety-seven patients with a positive tuberculin skin test (reaction > or = 5mm) who were admitted to the cohort between January 1991 and December 1994. Follow-up ended on September 30, 1998. INTERVENTION: The use of chemoprophylaxis for tuberculosis. MAIN OUTCOME MEASURES: Death was the primary outcome variable. The occurrence of tuberculosis was studied as a secondary outcome. Cox regression models were used in these analyses. RESULTS: The median follow-up time was 43.6 months. Chemoprophylaxis was used by 128 (43%) of the patients. The use of chemoprophylaxis was associated with a reduction in risk for tuberculosis (hazard ratio, 0.38; 95% confidence interval, 0.14-1.04; P = 0.05). In a regression model adjusted for baseline CD4 cell count, chemoprophylaxis was associated with longer survival (hazard ratio, 0.24; 95% confidence interval, 0.09-0.65; P = 0.002). CONCLUSIONS: Anti-tuberculosis chemoprophylaxis was associated with a substantially prolonged survival among purified protein derivative-positive HIV-infected patients in Brazil. These data have important implications for the clinical care of patients with HIV infection in areas of the world with a high prevalence of Mycobacterium tuberculosis infection.
Assuntos
Infecções Oportunistas Relacionadas com a AIDS/mortalidade , Infecções Oportunistas Relacionadas com a AIDS/prevenção & controle , Antituberculosos/uso terapêutico , Infecções por HIV/complicações , Tuberculose Pulmonar/mortalidade , Tuberculose Pulmonar/prevenção & controle , Adulto , Brasil/epidemiologia , Quimioprevenção , Estudos de Coortes , Feminino , Infecções por HIV/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Análise de Regressão , Análise de Sobrevida , Teste TuberculínicoRESUMO
BACKGROUND: Symptoms associated with HIV infection are common among HIV seroconverters, but the acute retroviral syndrome (ARS) is a diagnostic challenge because of the absence of a sensitive and specific case definition. We conducted an analysis of HIV seroconverters in Projeto Praça Onze, a HIVNET HIV seroincidence study among homosexual men in Rio de Janeiro. METHODS: Information from study subjects enrolled in Projeto Praça Onze who were documented HIV seroconverters were compared with nonseroconverters. At each semiannual study visit, participants were asked about HIV seroconversion symptoms and sexually transmitted diseases (STDs) during the preceding 6 months. All information was collected before the laboratory evaluation. A classification tree analysis was used to identify an ARS case definition, first using clinical information and then after including risk factor data for seroconversion in our cohort. RESULTS: As of July 1998, 674 volunteers were enrolled and 34 of these seroconverted; information was available for 33 of these. Among the seroconverters, 11 (34%) denied any symptoms, and 22 (66%) reported one or more symptoms, the most common of which were fever (25% of seroconverters versus 7% of nonseroconverters; p <.01), night sweats (9% versus 2%, respectively; p =.05), incapacitating disease (ID) for >/=3 days (27% versus 7%, respectively; p <.001), and weight loss of >/=2 kg (21% versus 9%, respectively; p =.05). STDs were more common in seroconverters (gonorrhea: 9% versus 1%, respectively; p <.01 and condyloma: 9% versus 3%, respectively; p =. 08). The first case definition was ID for >3 days, fever, pharyngitis, and myalgia (seroconverters, 3 of 32, versus nonseroconverters, 2 of 640). The second case definition was was ID for >3 days, anti-core hepatitis b-positive, and age <21 years (seroconverters: 6 of 32 versus nonseroconverters 4 of 640). The sensitivity and specificity for the first and second case definitions were: 9.4%, 99.4%, and 18.8%, 99.8%, respectively. CONCLUSIONS: Among HIV seroconverters, symptoms consistent with ARS were common. We were unable to identify a sensitive case definition that could be used as a screening tool. Although the clinical case definition was not validated, the specificity of our case definitions was high, suggesting that subjects within this HIV risk group who fulfill the case definition should be tested for HIV.
Assuntos
Infecções por HIV/diagnóstico , Soropositividade para HIV/diagnóstico , Homossexualidade , Adolescente , Adulto , Análise de Variância , Brasil/epidemiologia , Infecções por HIV/complicações , Soropositividade para HIV/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Infecções Sexualmente Transmissíveis/diagnóstico , SíndromeRESUMO
The study of interventions to prevent HIV transmission requires access to populations with a high rate of HIV transmission. We estimated HIV incidence among heterosexual males and females who were seen at an HIV testing site in Rio de Janeiro, Brazil. Stored sera from individuals who visited the site between March and December 1998 were analyzed using the sensitive/less sensitive (S/LS) assay and a chart abstraction was performed. During the study period, 6353 serum samples were tested. Of those tested, 1203 were found to be HIV-seropositive or indeterminate, of which 1050 (87%) remained available for further testing. In addition, 84 serum samples, representing 63 adults, were found to produce results suggesting early HIV infection. Of these, 14 were heterosexual and female (median age, 38 years), and 19 were heterosexual and male (median age, 25 years). The estimated HIV seroincidence was 1.9 (95% confidence limits (CL), 0.9%-3.9%) and 2.8 (95% CL, 1.4%-5.3%) per 100 person-years among heterosexual women and men, respectively. A survey on willingness to participate in future placebo-controlled HIV vaccine trials in this population indicated that 54.5% and 53.9% of heterosexual women and men, respectively, indicated that they would definitely be willing to participate. We have identified a heterosexual population in Rio de Janeiro with a high rate of HIV transmission willing to participate in placebo-controlled vaccine trials. This study demonstrates the usefulness of the newly described S/LS assay, which allows one to estimate HIV incidence from single serum specimens.
Assuntos
Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle , Heterossexualidade , Assunção de Riscos , Saúde da População Urbana , Adulto , Brasil/epidemiologia , Ensaio de Imunoadsorção Enzimática , Feminino , Anticorpos Anti-HIV/sangue , Infecções por HIV/transmissão , Soronegatividade para HIV , Soropositividade para HIV/epidemiologia , Humanos , Masculino , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: The effect of antiretroviral therapy on seminal HIV shedding in the community remains unknown. OBJECTIVE: To evaluate the effect of antiretroviral therapy on HIV shedding in semen. DESIGN: Prospective cohort study. SETTING: University hospital in Rio de Janeiro, Brazil. PATIENTS: 93 HIV-infected men. INTERVENTION: Antiretroviral therapy as prescribed by each patient's physician. MEASUREMENT: HIV RNA in semen and blood plasma before and after introduction of therapy. RESULTS: At baseline, HIV RNA was detected in 69 semen samples (74%) and 89 blood samples (96%). Six months after introduction of therapy, HIV RNA was detected in 29 semen samples (33%) and 33 blood samples (38%). The mean reduction in levels of HIV RNA in semen at 6 months was 1.65 log10 units. CONCLUSIONS: Antiretroviral therapy reduces shedding of HIV in semen, which probably in tum reduces HIV transmissibility. However, a substantial proportion of patients may still be infectious and may have drug-resistant strains of the virus.
Assuntos
Fármacos Anti-HIV/farmacologia , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Sêmen/virologia , Eliminação de Partículas Virais/efeitos dos fármacos , Adulto , Quimioterapia Combinada , HIV/genética , HIV/isolamento & purificação , Humanos , Estudos Longitudinais , Masculino , Estudos Prospectivos , RNA Viral/análise , RNA Viral/sangue , Estatísticas não Paramétricas , Carga ViralRESUMO
HIV-1 serotype B-Br (GWGR) is rare in the United States but predominates in Brazil. Differences in prognosis for patients infected with serotype B-Br or serotype B (GPGR) have not been addressed previously. In this prospective cohort study, we compared the rate of disease progression between patients infected with the HIV-1 V3 serotype B or B-Br in Brazil. Progression to AIDS or death was studied by the Kaplan-Meier and Cox proportional hazard methods. Among 445 HIV-infected patients who were tested with a specific enzyme immune assay, 204 (46%) had serotype B-Br infection and 127 (28%) had serotype B infection. Both groups were similar with regard to baseline CD4+ cell count, serum HIV RNA viral load, initial clinical stage, and the proportions who were treated with antiretroviral drugs. Patients with serotype B infection were significantly younger (p = 0.005) and tended to report homosexual behavior more frequently (p = 0.08). Mean follow-up was 30 +/- 13.5 months. During the study period, 41 (32%) patients infected with serotype B and 44 (22%) infected with serotype B-Br developed AIDS (p = 0.03). In a regression model adjusted for age and risk factor for HIV infection, progression to AIDS was faster in patients infected with serotype B (hazard ratio [HR] 1.59; 95% CI, 1.03-2.43; p = 0.03). A similar trend was observed in a model that considered AIDS or death as the outcome (HR, 1.43; 95% CI, 0.95-2.0; p = 0.09). These results suggest that patients infected with closely related HIV-1 serotypes may differ in the rate of progression to AIDS and indicate that serotype should be taken into account in HIV vaccine studies in Brazil.
Assuntos
Síndrome da Imunodeficiência Adquirida/virologia , Proteína gp120 do Envelope de HIV/imunologia , Infecções por HIV/fisiopatologia , Infecções por HIV/virologia , HIV-1/classificação , HIV-1/fisiologia , Fragmentos de Peptídeos/imunologia , Síndrome da Imunodeficiência Adquirida/fisiopatologia , Brasil , Estudos de Coortes , Progressão da Doença , Feminino , Infecções por HIV/mortalidade , HIV-1/genética , HIV-1/imunologia , Humanos , Masculino , Modelos de Riscos Proporcionais , Estudos Prospectivos , SorotipagemRESUMO
Evaluation of HIV vaccines requires high-risk individuals willing to participate in a vaccine trial. We investigated the willingness to participate in HIV vaccine trials of initially HIV-seronegative homosexual men enrolled in an HIV seroincidence cohort study. Of 815 initially HIV-seronegative participants, 569 (69.8%) reported willingness to participate in an HIV vaccine trial. Altruism was the primary reason given for wanting to participate. Fear of HIV infection from the study's immunizations and a vaccine-induced positive HIV test result were the main reasons for not wanting to participate. Of the 34 study subjects who eventually had HIV seroconversion, 29 (85%) had indicated a willingness to participate. In a univariate analysis, factors associated with willingness to participate included HIV seroconversion during follow-up (odds ratio [OR]. 2.6; p =.04), low educational level (OR, 1.6; p =.005), low family income (p =.02), and exchanging sex for housing, food, or clothing (OR 6.1; p =.005). Students were less likely to be willing to participate in a trial (OR, 0.7; p = .03), as well as those who reported sex at the first encounter (OR, 0.7; p = .05). In a multivariate analysis, low education level, infection with Condyloma, and exchanging sex for housing, food, or clothing were positively associated with willingness to participate, whereas being a student and reporting sex at first encounter were negatively associated. In general, factors indicative of high-risk of HIV infection were associated with a higher willingness. These data demonstrate that this high-risk homosexual male cohort has a high willingness to participate in HIV vaccine trials.
Assuntos
Vacinas contra a AIDS , Ensaios Clínicos como Assunto , Conhecimentos, Atitudes e Prática em Saúde , Homossexualidade Masculina , Motivação , Adulto , Brasil , Infecções por HIV/prevenção & controle , Soronegatividade para HIV , Homossexualidade Masculina/psicologia , Humanos , Masculino , Comportamento Sexual , Inquéritos e QuestionáriosRESUMO
An HIV seroincidence study was conducted to identify a high-risk population for HIV prevention trials. Inclusion criteria were male gender, homosexual behavior, age between 18 and 50 years, and negative HIV serostatus; 862 study subjects were screened and 753 were enrolled and observed during follow-up for a mean of 1.5 years. In this population, 34 people had HIV seroconversions for an overall annual seroincidence of 3.1% (95% confidence interval [CI], 2.1%-4.1%). Among study subjects <20 years old, annual incidence was 8.4% (95% CI, 1.7%-15%). Independent risk factors for seroconversion were age <25 years (p = .01), hepatitis B core antibody seropositivity (p > .01), sex at first encounter in the preceding 6 months (p = .11), and a history of gonorrhea or condyloma in the 6 months before seroconversion (p = .04 and p = .08, respectively). At enrollment, 85% of the eventual seroconverters said they would participate in a vaccine trial; all agreed to participate when told there would be a placebo arm. Follow-up rates were 97%, 91%, and 88% at 6, 12, and 18 months, respectively. The HIV-1 subtype was B for each of the first 17 seroconverters. These data demonstrate the suitability of this cohort for HIV prevention trials, based on high HIV incidence and retention rates, and a willingness to participate in such trials.
Assuntos
Infecções por HIV/epidemiologia , Homossexualidade Masculina , Vacinas contra a AIDS , Adolescente , Adulto , Fatores Etários , Idoso , Brasil/epidemiologia , Estudos de Coortes , Condiloma Acuminado/epidemiologia , Intervalos de Confiança , Ensaio de Imunoadsorção Enzimática , Gonorreia/epidemiologia , Infecções por HIV/transmissão , Soronegatividade para HIV , Soropositividade para HIV/epidemiologia , Humanos , Incidência , Masculino , Fatores de Risco , Assunção de Riscos , População Urbana/estatística & dados numéricosRESUMO
Argentine hemorrhagic fever (AHF) is a potentially lethal infection in Argentina. The case-fatality ratio is >15%, but treatment reduces the mortality rate to <1%. Diagnosis is based on clinical and laboratory criteria, but no case definition has been validated. A chart review was conducted for patients hospitalized with suspected AHF. Individuals with a fourfold rise in antibody titer were classified as cases. The combination of a platelet count of <100,000/mm3 and a white blood cell (WBC) count of <2,500/mm3 had a sensitivity and specificity of 87% and 88%, respectively, thus suggesting that the use of these criteria in a case definition would be helpful for epidemiological studies of AHF. The combination of a platelet count of <100,000/mm3 and a WBC count of <4,000/mm3 had a sensitivity of 100% and a specificity of 71%; the use of these criteria in a case definition should be helpful for screening patients for therapy with immune plasma in the region where AHF is endemic.
Assuntos
Infecções por Arenaviridae/diagnóstico , Febre Hemorrágica Americana/diagnóstico , Vírus Junin/isolamento & purificação , Adulto , Anticorpos Antivirais/sangue , Infecções por Arenaviridae/sangue , Argentina , Feminino , Febre Hemorrágica Americana/sangue , Humanos , Vírus Junin/imunologia , Contagem de Leucócitos , Masculino , Contagem de Plaquetas , Fatores de Risco , Sensibilidade e EspecificidadeRESUMO
OBJECTIVE: To compare three possible therapeutic strategies for the treatment of patients with an intermediate risk of HIV disease progression. DESIGN: Mathematical modeling based on assumptions derived from published data. METHODS: A parametric survival model was fitted to empirical data to describe the survival trajectory of untreated individuals. It was assumed that successful treatment decreases the risk of disease progression curing the first year after its introduction by a constant that is dependent on the magnitude of the initial drop in HIV viral load. Thereafter, individual members of the treatment cohort follow different pathways, depending on the duration of the initial response or, in case of virologic failure, the response to a new drug regimen. RESULTS: Sub-groups of patients starting therapy with two nucleoside reverse transcriptase inhibitors (NRTI) or two NRTI and a protease inhibitor had the highest instantaneous risk of disease progression at the end of the 5-year follow-up period. Patients who started therapy with two NRTI and a non-NRTI had the lowest likelihood of progression to AIDS or death at 5 years of follow-up. This is because, in the case of the subgroup whose initial treatment included a protease inhibitor, failure rates due to non-adherence to therapy are high and response to salvage therapy is limited by past protease inhibitor experience. CONCLUSIONS: Despite the superior virologic potency of the protease inhibitor-containing regimens, in this analysis other strategies performed equally well or even better. In the absence of solid empirical data and until the advent of antiretroviral regimens that are shown to be safe, simple to take, and maximally suppress viral load, caution may be required in selecting the long-term therapy for patients with less advanced HIV disease.
Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Inibidores da Protease de HIV/uso terapêutico , Modelos Biológicos , Modelos Estatísticos , Inibidores da Transcriptase Reversa/uso terapêutico , Progressão da Doença , Infecções por HIV/imunologia , Infecções por HIV/fisiopatologia , Infecções por HIV/virologia , Humanos , Fatores de RiscoRESUMO
The relation between gender and survival after a diagnosis of AIDS was studied in a cohort of patients with HIV infection in Rio de Janeiro, Brazil. During the study period, 124 of 617 patients (20%) developed AIDS. Of this group, 91 patients were men and 33 were women. There were no gender related differences regarding the access to antiretroviral therapy or to prophylaxis for Pneumocystis carinii pneumonia. Survival was shorter among women (hazard ratio [HR] = 4.43; p < .001) after adjustment for age and AIDS-defining condition. Adjusting for CD4+ and CD8+ counts reduced the difference between genders (HR = 3.33; p = .017). These results suggest that survival after an AIDS diagnosis may be shorter among women than men in Brazil. Further studies are needed to determine the factors that may be negatively influencing the prognosis of women with AIDS in Brazil.
PIP: The association between gender and survival after AIDS diagnosis was investigated through use of data from an ongoing HIV cohort study in Rio de Janeiro, Brazil. Among the 617 patients (425 men and 192 women) enrolled in this study, 124 AIDS cases were diagnosed during 1991-95. There was no significant difference between the proportion of men (21%) and women (17%) who progressed to AIDS. The median age at AIDS diagnosis was 35 years for men and 38 years for women. CD4 and CD8 counts were available at the time of AIDS diagnosis for 57 men and 20 women. Median CD4 counts were similar for men and women (86/cu. mm and 95/cu. mm, respectively), but women had significantly lower mean CD8 counts (494/cu. mm) than men (870/cu. mm). There were 33 deaths (36%) among men and 17 (52%) among women. The median survival time after AIDS diagnosis was 20.4 months for men and 11 months for women. Survival remained shorter among women after adjustment for age and AIDS-defining condition (hazard ratio, 4.43). Adjustment for CD4 and CD8 counts reduced the difference between genders (hazard ratio, 3.33). The observed difference in survival between men and women could be due, in part, to reduced T-cell homeostasis at the time of AIDS diagnosis in women.
Assuntos
Síndrome da Imunodeficiência Adquirida/mortalidade , Infecções por HIV/mortalidade , População Urbana/estatística & dados numéricos , Infecções Oportunistas Relacionadas com a AIDS/epidemiologia , Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , Adulto , Fármacos Anti-HIV/uso terapêutico , Brasil/epidemiologia , Estudos de Coortes , Feminino , Infecções por HIV/tratamento farmacológico , Humanos , Masculino , Pneumonia por Pneumocystis/epidemiologia , Prognóstico , Modelos de Riscos Proporcionais , Distribuição por Sexo , Taxa de SobrevidaRESUMO
Argentine hemorrhagic fever (AHF), caused by the arenavirus Junin, is a major public health problem among agricultural workers in Argentina. A prospective, randomized, double-blind, placebo-controlled, efficacy trial of Candid 1, a live attenuated Junin virus vaccine, was conducted over two consecutive epidemic seasons among 6500 male agricultural workers in the AHF-endemic region. Twenty-three men developed laboratory-confirmed AHF during the study; 22 received placebo and 1 received vaccine (vaccine efficacy 95%; 95% confidence interval [CI], 82%-99%). Three additional subjects in each group developed laboratory-confirmed Junin virus infection associated with mild illnesses that did not fulfill the clinical case definition for AHF, yielding a protective efficacy for prevention of any illness associated with Junin virus infection of 84% (95% CI, 60%-94%). No serious adverse events were attributed to vaccination. Candid 1, the first vaccine for the prevention of illness caused by an arenavirus, is safe and highly efficacious.
Assuntos
Arenavirus do Novo Mundo/imunologia , Febre Hemorrágica Americana/prevenção & controle , Febre Hemorrágica Americana/terapia , Vacinas Atenuadas/uso terapêutico , Vacinas Virais/uso terapêutico , Adolescente , Adulto , Doenças dos Trabalhadores Agrícolas/prevenção & controle , Doenças dos Trabalhadores Agrícolas/terapia , Doenças dos Trabalhadores Agrícolas/virologia , Animais , Anticorpos Antivirais/análise , Anticorpos Antivirais/imunologia , Arenavirus do Novo Mundo/crescimento & desenvolvimento , Argentina , Células Cultivadas , Chlorocebus aethiops , Método Duplo-Cego , Febre Hemorrágica Americana/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Estações do Ano , Vacinas Atenuadas/efeitos adversos , Células Vero , Vacinas Virais/efeitos adversosRESUMO
Human T-lymphotropic virus type I (HTLV-I) and HTLV-II have been postulated to accelerate disease progression in patients coinfected with HIV. However, recent evidence suggests that HTLV-II has no effect on HIV disease progression. In addition, it has recently been reported that HIV viral load was not increased in subjects coinfected with HTLV-I, suggesting that the biologic basis for the hypothesis does not exist. Several recent studies in Brazil, however, suggest that coinfection with HTLV-I and HIV has substantial medical consequences. For example, coinfection was associated with a higher CD4 lymphocytes count following adjustment for HIV viral load or HIV clinical stage. In addition, coinfected subjects have a high prevalence of clinical significant myelopathy. The effect of other putative viruses as cofactors in HIV disease progression is also discussed.
Assuntos
Infecções por HIV/complicações , HIV-1 , Infecções por HTLV-I/complicações , Vírus Linfotrópico T Tipo 1 Humano , Brasil/epidemiologia , Contagem de Linfócito CD4 , Progressão da Doença , Infecções por HIV/epidemiologia , Infecções por HTLV-I/epidemiologia , Humanos , Carga ViralRESUMO
Reports indicate that there is a dissociation between markers of HIV disease progression and clinical stage among subjects coinfected with human T-cell lymphotropic virus type I (HTLV-I) and HIV. HTLV-I coinfection does not appear to affect HIV viral load, currently considered to be the best marker of HIV disease progression. We measured HIV RNA levels in stored serum samples from 23 subjects with coinfection and 92 subjects with HIV single infection and examined the correlation with the CD4+ lymphocyte count. Subjects were recruited from an ongoing HIV cohort study in Rio de Janeiro, Brazil. In both groups, CD4+ lymphocyte counts declined with increasing levels of HIV RNA. In a linear regression analysis adjusting for HIV RNA serum level, coinfected individuals had an estimated 78% higher CD4+ lymphocyte count than those with single infection. Simultaneous adjustment for beta2-microglobulin level increased the difference, with coinfected individuals having 146% (p = 0.005, 95% CI: 32% to 359%) higher CD4+ counts. These data suggest that the higher CD4+ lymphocyte counts associated with coinfection do not provide immunologic benefit and may reflect HTLV-I-associated nonspecific lymphocyte proliferation. The results of this and other studies suggest that the CD4+ count cutoff values used in making clinical decisions in HIV infection may not be appropriate in coinfection. As with HIV single infection, HIV virus load may be the optimal surrogate marker for subjects with coinfection.
Assuntos
Síndrome da Imunodeficiência Adquirida/virologia , HIV-1 , HIV/isolamento & purificação , Infecções por HTLV-I/virologia , Síndrome da Imunodeficiência Adquirida/imunologia , Contagem de Linfócito CD4 , HIV/genética , Infecções por HTLV-I/imunologia , Humanos , RNA Viral/análiseRESUMO
OBJECTIVE: To determine whether subjects coinfected with HTLV-I and HIV have a higher frequency of myelopathy than subjects singly infected with HIV. DESIGN: A prospective, nested case-control study of HTLV-I and HIV coinfected (cases) and HIV singly infected adults (controls) participating in a prospective HIV cohort study at a university hospital outpatient HIV clinic in Rio de Janeiro, Brazil. MEASUREMENTS: Subjects were evaluated for evidence of myelopathy by a neurologist unaware of their HTLV serologic status. Patients with at least two pyramidal signs, such as paresis, hypertonicity or spasticity, hyperreflexia, clonus, diminished or absent superficial reflexes, or the presence of pathologic reflexes (e.g., Babinski or Hoffmann), were defined as having myelopathy. Myelopathy severity was quantified using the Kurtzke Functional Disability Scale (FDS); patients with FDS scores > or = 4 were considered to have significant myelopathy. Selected patients with myelopathy underwent lumbar puncture for the evaluation of intrathecal synthesis of HTLV-I antibodies. RESULTS: Of 15 coinfected subjects, 11 (73%) had evidence of myelopathy versus 10 of 62 subjects (16%) with HIV single infection (adjusted odds ratio [OR] = 13.0, p = 0.00002). When only myelopathy patients with FDS scores of > or = 2 or > or = 4 were included, the association between coinfection and the presence of myelopathy remained (OR = 7.3, p = 0.0003 for scores > or = 2; and OR = 8.9 for scores > or = 4, p = 0.04). In addition, a higher proportion of coinfected subjects had peripheral neuropathy (40%) than controls (16%) (OR = 3.5, p = 0.07). CONCLUSION: Coinfection with HTLV-I was strongly associated with myelopathy among subjects infected with HIV. The relative contribution of HTLV-I versus HIV in the pathogenesis of coinfection-associated myelopathy is not known. Coinfection may also be associated with peripheral neuropathy. Further studies are needed to elucidate the mechanisms of coinfection-associated neurologic conditions.
Assuntos
Infecções por HIV/complicações , Infecções por HTLV-I/complicações , Paraparesia Espástica Tropical/complicações , Paraparesia Espástica Tropical/epidemiologia , Adulto , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Razão de Chances , Estudos ProspectivosRESUMO
The incidence of invasive Haemophilus influenzae type b (Hib) infection was decreased significantly among Navajo children since the licensure of Hib conjugate vaccines, even though two lots of Hib (polyribosylribitol phosphate)-meningococcal B outer-membrane protein conjugate vaccine (PRP-OMP) widely used among the Navajo were later found to be of low immunogenicity. We measured the effectiveness of all Hib conjugate vaccines combined, PRP-OMP alone, and the PRP-OMP lots with lower-than-expected immunogenicity among Navajo infants and children. This was a matched case-control study using active, laboratory-based surveillance for the ascertainment of Navajo children 2 1/2 to 59 months of age with invasive Hib infection; 45 patients with infection and 180 control subjects were enrolled. The effectiveness of one, two, and three doses, respectively, of all Hib conjugate vaccines combined was 96% (95% confidence interval (CI) 65%, 99%), 99% (95% CI, 69%, 100%), and 99% (95% CI - 57%, 100%). The effectiveness of one or more doses of PRP-OMP was 95% (95% CI, 66%, 99%). The effectiveness of a single dose of the lots of lower-than-expected immunogenicity was 89% (95% CI, -8%, 99%). The Hib conjugate vaccine coverage increased from 49% during 1991 to 94% during 1992; no control subjects younger than 18 months of age were enrolled during 1993. The occurrence of invasive Hib infections in this population after licensure of Hib conjugate vaccines was the result of gradual vaccine uptake, not poor vaccine effectiveness. The use of PRP-OMP has been highly effective despite concerns about the immunogenicity of several lots.
Assuntos
Proteínas da Membrana Bacteriana Externa/uso terapêutico , Infecções por Haemophilus/prevenção & controle , Vacinas Anti-Haemophilus/uso terapêutico , Haemophilus influenzae , Indígenas Norte-Americanos , Polissacarídeos Bacterianos/uso terapêutico , Vacinas Conjugadas/uso terapêutico , Proteínas da Membrana Bacteriana Externa/imunologia , Estudos de Casos e Controles , Pré-Escolar , Feminino , Infecções por Haemophilus/epidemiologia , Vacinas Anti-Haemophilus/imunologia , Humanos , Incidência , Lactente , Licenciamento , Masculino , Polissacarídeos Bacterianos/imunologia , Sudoeste dos Estados Unidos/epidemiologia , Resultado do Tratamento , Vacinas Conjugadas/imunologiaRESUMO
OBJECTIVES: To study the effect of human T-cell lymph-tropic virus type I (HTLV-I) on markers of human immunodeficiency virus (HIV) disease progression. DESIGN: A retrospective, nested case-control study. SETTING: A university hospital outpatient HIV clinic in Rio de Janeiro, Brazil. PARTICIPANTS: Human immunodeficiency virus-seropositive adults participating in a prospective HIV cohort study. MAIN OUTCOME MEASURES: The HIV clinical stage, CD4+ lymphocyte counts, and other laboratory parameters in 27 individuals infected with HIV and HTLV-I (coinfection) and 99 age-matched, HIV-seropositive, HTLV-seronegative controls (single infection). RESULTS: Variables independently associated with coinfection included higher CD4+ lymphocyte count (odds ratio [OR], 2.3; 95% confidence limits [CL], 1.3, 4.1), higher CD4+ percentage (OR, 2.0; 95% CL, 1.3, 3.2), beta 2-microglobulin level of 254 nmol/L or more (OR, 6.8; 95% CL, 1.3, 35.4), World Health Organization stages 3 and 4 (OR, 4.4; 95% CL, 1.1, 18.0), and reporting a parenteral risk factor (OR, 7.4; 95% CL, 1.4, 38.9). When stratified by p24 antigenemia, coinfection was associated with an estimated 82% higher CD4+ lymphocyte count (P < .05). CONCLUSION: Coinfection was associated with higher CD4+ lymphocyte counts, more advanced clinical disease, and higher beta 2-microglobulin levels than HIV infection alone. The higher mean CD4+ lymphocyte count does not appear to offer immunologic benefit. Caution should be exercised when using CD4+ lymphocytes as a surrogate marker in studies of HIV infection in populations where HTLV-I is prevalent. Further studies are needed to address whether current CD4+ lymphocyte values for the initiation of antiretroviral therapy and chemoprophylaxis against opportunistic infections in HIV infection are appropriate in coinfection.
Assuntos
Linfócitos T CD4-Positivos/imunologia , Infecções por HIV/complicações , Infecções por HIV/imunologia , Infecções por HTLV-I/complicações , Subpopulações de Linfócitos T/imunologia , Adulto , Biomarcadores/sangue , Brasil , Relação CD4-CD8 , Estudos de Casos e Controles , Feminino , Proteína do Núcleo p24 do HIV/sangue , Infecções por HIV/fisiopatologia , Infecções por HTLV-I/imunologia , Humanos , Contagem de Leucócitos , Masculino , Estudos Retrospectivos , Microglobulina beta-2/análiseRESUMO
A competency-based training and evaluation method was developed to improve and assess the management of acute respiratory infections (ARI) in young children by community health workers (CHWs) in Bolivia. This method was used to evaluate three groups of Bolivian CHWs, provide them with a one-day refresher course in ARI management, and assess the effects of the course. The results showed the CHWs capable of acquiring the skills needed to effectively manage ARI cases in accordance with the World Health Organization's ARI case management strategy. It was found important, however, that their training emphasize how to count the respirations of children with tachypnea and how to identify chest indrawing. In general, the competency-based methods appeared to be effective in training and evaluating CHWs in the area of ARI case management; it is expected that these methods will prove useful in other community-based health interventions.
PIP: Acute respiratory infections (ARI) are a leading cause of child mortality in developing countries. With under-5 mortality due to ARI in Bolivia estimated at 172/1000 live births, these infections are the second largest cause of child mortality in the country. The World Health Organization (WHO) has developed a strategy for managing cases of child ARI with respect to treatment and community health worker (CHW) tasks. Bolivia adheres to these guidelines with some exceptions regarding the tasks of CHWs. This paper reports on the development and implementation and assess the management of ARI in young children by CHWs in Bolivia. 3 groups of Bolivian CHWs were evaluated, given a 1-day refresher course in ARI management, then reevaluated to assess the effects of the course. The short duration of the program and its focus on essential tasks had a significant impact on its participants. The CHWs were found to be capable of acquiring the skills needed to effectively manage ARI cases in accordance with the WHO ARI case management strategy. It was also found important that training emphasize how to count the respirations of children with tachypnea and how to identify chest indrawing. These competency-based methods should prove useful in other community-based health interventions.