RESUMO
Survival rates among children with leukaemia in low-income countries are lower than those in high-income countries. This has been attributed in part to higher treatment-related mortality (TRM). We examined the demographics, treatment, and outcomes of paediatric patients in El Salvador with acute lymphoblastic leukaemia (ALL) or acute myeloid leukaemia (AML) to determine the incidence, causes, and risk factors for TRM. Two trained data managers collected data prospectively; no patients were excluded. Biological, socioeconomic and nutritional predictors were examined. A total of 469 patients with ALL and 78 patients with AML were included. The 2-year cumulative incidence of TRM was significantly higher among children with AML (35.4+/-6.4%) than those with ALL (12.5+/-1.7%; P<0.0001). However, the proportion of deaths attributable to the toxicity of treatment did not differ significantly between AML (25/47, 53.2%) and ALL (55/107, 51.4%; P=0.98). Among children with ALL, low monthly income (P=0.04) and low parental education (P=0.02) significantly increased the risk of TRM. Among children with AML, biological, socioeconomic, and nutritional variables were not associated with TRM. In this low-income country, toxic death significantly contributes to mortality in both ALL and AML. A better understanding of the effect of socioeconomic status on TRM may suggest specific strategies for patients with ALL.
Assuntos
Leucemia Mieloide Aguda/mortalidade , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Adolescente , Criança , Pré-Escolar , Escolaridade , El Salvador/epidemiologia , Feminino , Humanos , Incidência , Renda , Lactente , Recém-Nascido , Leucemia Mieloide Aguda/epidemiologia , Leucemia Mieloide Aguda/terapia , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Fatores SocioeconômicosRESUMO
OBJECTIVE: Varicella vaccination was introduced at the end of 1999 into the Uruguayan immunisation schedule for children aged 12 months. Varilrix (Oka strain; GlaxoSmithKline Biologicals) has been the only vaccine used since then and coverage has been estimated to exceed 90% since the start of the universal varicella vaccination programme. We assessed the impact of the Uruguayan varicella vaccination programme during 2005, 6 years after its introduction. METHODS: Information on hospitalisations was collected from the main paediatric referral hospital and information on medical consultations for varicella was collected from two private health insurance systems in Montevideo. The proportion of hospitalisations due to varicella and the proportion of ambulatory visits for varicella since the introduction of the vaccine were compared between 1999 and 2005 and 1997 and 1999 in the following age groups: <1 year, 1-4 years, 5-9 years and 10-14 years. RESULTS: By 2005, the proportion of hospitalisations due to varicella among children, was reduced by 81% overall and by 63%, 94%, 73% and 62% in the <1, 1-4, 5-9 and 10-14 years age groups, respectively. The incidence of ambulatory visits for varicella among children was reduced by 87% overall and by 80%, 97%, 81% and 65% in the <1, 1-4, 5-9 and 10-14 years age groups, respectively. CONCLUSIONS: The burden of varicella has decreased substantially in Uruguayan children since the introduction of the varicella vaccination, including those groups outside the recommended vaccination age. It is expected to decrease further as more cohorts of children are vaccinated and herd immunity increases.
Assuntos
Vacina contra Varicela/administração & dosagem , Varicela/prevenção & controle , Vacinação em Massa , Adolescente , Distribuição por Idade , Assistência Ambulatorial/estatística & dados numéricos , Varicela/epidemiologia , Criança , Pré-Escolar , Métodos Epidemiológicos , Hospitalização/estatística & dados numéricos , Humanos , Lactente , Vigilância da População , Uruguai/epidemiologiaRESUMO
We examined factors associated with high-grade squamous intraepithelial lesions (HSIL) and cervical cancer among human papillomavirus (HPV)-infected women in a prevalent case-control study conducted within a population-based cohort of 10 077 women in Costa Rica. We compared 146 women with HPV-positive HSIL or cancer (HSIL/CA) against 843 HPV-positive women without evidence of HSIL/CA. Subjects completed a risk factor questionnaire. We evaluated the associations between exposures and HSIL/CA among women positive for any HPV and restricted to those positive for high-risk HPV types. Risk of HSIL/CA increased with increasing number of live births (P(trend)= 0.04). Women who smoked 6+ cigarettes/day had a RR for HSIL/CA of 2.7 (95% CI = 1.1-6.7) compared to non-smokers. Current use of barrier contraceptives was associated with a reduction in risk of HSIL/CA (RR = 0.39; 95% CI = 0.16-0.96). Sexual behaviour and a self-reported history of sexually transmitted diseases (STDs) other than HPV were not associated with HSIL/CA. Oral contraceptive use was associated with HSIL/CA among women with <3 pregnancies. Effects were similar in analysis restricted to women positive for high-risk HPV types. Among women positive for high-risk HPV types, 44% of HSIL/CA could be attributed to multiparity (>/=3 pregnancies) and/or smoking. Among HPV-positive women, multiparity and smoking are risk factors for HSIL/CA. Oral contraceptive use may be associated with HSIL/CA in subgroups of women.
Assuntos
Carcinoma in Situ/virologia , Carcinoma de Células Escamosas/virologia , Papillomaviridae , Infecções por Papillomavirus/complicações , Infecções Tumorais por Vírus/complicações , Neoplasias do Colo do Útero/virologia , Adolescente , Adulto , Carcinoma in Situ/epidemiologia , Carcinoma in Situ/etiologia , Carcinoma de Células Escamosas/epidemiologia , Carcinoma de Células Escamosas/etiologia , Estudos de Casos e Controles , Costa Rica/epidemiologia , Feminino , Humanos , Incidência , Papillomaviridae/patogenicidade , Paridade , Fatores de Risco , Comportamento Sexual , Infecções Sexualmente Transmissíveis/complicações , Fumar/efeitos adversos , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/etiologiaRESUMO
HIV-1 transmission worldwide is predominantly associated with heterosexual activity, and non-clade B viruses account for the most spread. The HIV-1 epidemic in Trinidad/Tobago and the Caribbean shares many features with such heterosexual epidemics, including a prominent role for coincident sexually transmitted diseases. This study evaluates the molecular epidemiology of HIV-1 in Trinidad/Tobago during a period when abrupt transition from homosexual to heterosexual transmission occurred in the absence of injecting drug use, concomitant with a rapid rise in HIV-1 prevalence in the heterosexual population. Of 31 viral isolates studied during 1987-1995, all cluster with subtype B reference strains. In the analysis of full env genes from 22 early seroconverters, the Trinidad isolates constitute a significant subcluster within the B subtype. The Trinidad V3 consensus sequence differs by a single amino acid from the prototype B V3 consensus and demonstrates stability over the decade of this study. In the majority of isolates, the V3 loop of env contains a signature threonine deletion that marks the lineage of the Trinidad HIV-1 clade B epidemic from pre-1984. No phenotypic features, including syncitium induction, neutralization profiles, and chemokine receptor usage, distinguish this virus population from other subtype B viruses. Thus, although the subtype B HIV-1 viruses being transmitted in Trinidad are genetically distinguishable from other subtype B viruses, this is probably the result of a strong founder effect in a geographically circumscribed population rather than genetic selection for heterosexual transmission. These results demonstrate that canonical clade B HIV-1 can generate a typical heterosexual epidemic.
Assuntos
Infecções por HIV/transmissão , HIV-1/classificação , Comportamento Sexual , Sequência de Aminoácidos , Sequência de Bases , Primers do DNA , Feminino , Proteína gp120 do Envelope de HIV/química , Proteína gp120 do Envelope de HIV/genética , Infecções por HIV/epidemiologia , Humanos , Masculino , Dados de Sequência Molecular , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/genética , Homologia de Sequência de Aminoácidos , Especificidade da Espécie , Trinidad e Tobago/epidemiologiaRESUMO
BACKGROUND: Human papillomavirus (HPV) is the main cause of cervical neoplasia. Because few population-based studies have investigated the prevalence of type-specific infection in relation to cervical disease, we studied a high-risk population, estimating the prevalence of HPV infection and the risk associated with various HPV types. METHODS: We screened 9175 women in Guanacaste, Costa Rica, to obtain a referent standard final diagnosis, and tested 3024 women for more than 40 types of HPV with a polymerase chain reaction-based system. RESULTS: Among women with normal cytology, HPV infections peaked first in women younger than 25 years, and they peaked again at age 55 years or older with predominantly non-cancer-associated types of HPV and uncharacterized HPV types. Low-grade squamous intraepithelial lesions (LSILs) (n = 189) decreased consistently with age. The prevalence of high-grade squamous intraepithelial lesions (HSILs) (n = 128) peaked first around age 30 years and again at age 65 years or older. Seventy-three percent of LSILs were HPV positive, with HPV16 being the predominant type (16% of positive subjects). HPV was found in 89% of HSILs and 88% of cancers, with HPV16 being strongly predominant (51% and 53% of positive subjects). Virtually all HSILs and cancers had cancer-associated HPV types, with high odds ratios (ORs) and attributable fractions around 80%. Risk for HPV16 was particularly high (OR for HSILs = 320, 95% confidence interval [CI] = 97-1000; OR for cancer = 710, 95% CI = 110-4500). CONCLUSIONS: We confirm the early decline of HPV infection with age but note increased prevalence after menopause, which could be related to a second peak of HSILs, an observation that warrants further investigation. At least 80% of HPVs involved in cervical carcinogenesis in this population have been characterized. Polyvalent vaccines including the main cancer-associated HPV types may be able to prevent most cases of cervical disease in this region.
Assuntos
Papillomaviridae , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/virologia , Vigilância da População , Saúde da População Rural/estatística & dados numéricos , Infecções Tumorais por Vírus/epidemiologia , Infecções Tumorais por Vírus/virologia , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/virologia , Adulto , Distribuição por Idade , Idoso , Carcinoma de Células Escamosas/epidemiologia , Carcinoma de Células Escamosas/virologia , Costa Rica/epidemiologia , Estudos Transversais , Feminino , Humanos , Pessoa de Meia-Idade , Razão de Chances , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/diagnóstico , Reação em Cadeia da Polimerase , Prevalência , Infecções Tumorais por Vírus/diagnóstico , Neoplasias do Colo do Útero/diagnósticoRESUMO
CONTEXT: Human papillomaviruses (HPVs) are known to cause most cervical cancer worldwide, but the utility of HPV DNA testing in cervical cancer prevention has not been determined. OBJECTIVE: To provide comprehensive data on the screening performance of HPV testing for the most common carcinogenic types, at different levels of analytic sensitivity. DESIGN: Laboratory analysis conducted during 1993-1995, using 3 cytologic techniques and cervicography, followed by colposcopic examination of women with any abnormal cervical finding, to detect all high-grade intraepithelial lesions and cancer (reference standard of clinically significant disease). The HPV testing was performed subsequently with masking regarding clinical findings. SETTING: Guanacaste Province, Costa Rica, a region with a high age-adjusted incidence of cervical cancer. PARTICIPANTS: Of 11742 randomly selected women, 8554 nonpregnant, sexually active women without hysterectomies underwent initial HPV DNA testing using the original Hybrid Capture Tube test; a stratified subsample of 1119 specimens was retested using the more analytically sensitive second generation assay, the Hybrid Capture II test. MAIN OUTCOME MEASURES: Receiver operating characteristic analysis of detection of cervical high-grade intraepithelial lesions and cancer by HPV DNA testing based on different cut points of positivity. RESULTS: An analytic sensitivity of 1.0 pg/mL using the second generation assay would have permitted detection of 88.4% of 138 high-grade lesions and cancers (all 12 cancers were HPV-positive), with colposcopic referral of 12.3% of women. Papanicolaou testing using atypical squamous cells of undetermined significance as a cut point for referral resulted in 77.7% sensitivity and 94.2% specificity, with 6.9% referred. Specificity of the second generation assay for positivity for high-grade lesions and cancer was 89.0%, with 33.8% of remaining HPV DNA-positive subjects having low-grade or equivocal microscopically evident lesions. The higher detection threshold of 10 pg/mL used with the original assay had a sensitivity of 74.8% and a specificity of 93.4%. Lower levels of detection with the second generation assay (<1 pg/mL) proved clinically nonspecific without gains in diagnostic sensitivity. CONCLUSIONS: In this study population, a cut point of 1.0 pg/mL using the second generation assay permitted sensitive detection of cervical high-grade lesions and cancer, yielding an apparently optimal trade-off between high sensitivity and reasonable specificity for this test. The test will perform best in settings in which sensitive detection of high-grade lesions and cancer is paramount. Because HPV prevalence varies by population, HPV testing positive predictive value for detection of high-grade lesions and cancer will vary accordingly, with implications for utility relative to other cervical cancer screening methods.
Assuntos
DNA Viral/análise , Programas de Rastreamento , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/diagnóstico , Infecções Tumorais por Vírus/diagnóstico , Displasia do Colo do Útero/prevenção & controle , Neoplasias do Colo do Útero/prevenção & controle , Adulto , Idoso , Colposcopia , Costa Rica , Feminino , Humanos , Programas de Rastreamento/métodos , Pessoa de Meia-Idade , Teste de Papanicolaou , Papillomaviridae/genética , Sensibilidade e Especificidade , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/virologia , Esfregaço Vaginal , Displasia do Colo do Útero/diagnóstico , Displasia do Colo do Útero/virologiaRESUMO
BACKGROUND: In a study using a split-sample design, liquid-based cytology (ThinPrep Processor, Cytyc Corporation, Boxborough, MA) was compared with the conventional Papanicolaou (Pap) smear in Guanacaste, Costa Rica. The study provides the first population-based comparison of the ThinPrep screening technology and includes "gold standard" measures of diagnostic accuracy. METHODS: The population-based study was performed among over 8000 women residing in a Costa Rican province with a high incidence of cervical carcinoma. Conventional smears were prepared and diagnosed in Costa Rica, while the residual material on the sampling device was collected into a liquid preservative and shipped to the U.S., where ThinPrep cytologic slides were prepared and diagnosed. Cytologic diagnoses based on the two techniques, categorized according to the Bethesda System, were compared with a "gold standard" final case diagnosis for each patient, also based on Bethesda terminology, that reflected an integrated interpretation of all available data, including cytology, histology, and cervicography. Results were also compared with the results of HPV DNA detection (Hybrid Capture, Digene Corporation, Silver Spring, MD). RESULTS: ASCUS was the threshold for colposcopy referral. There were significantly more women referred according to this threshold with the ThinPrep slide (12.7%) than with the conventional smear (6.7%, P<0.001). Compared with the final case diagnosis, referral by ThinPrep slides detected 92.9% of cases with high grade squamous intraepithelial lesions (HSIL) and 100% of carcinoma cases. Smears detected 77.8% of HSIL and 90.9% of carcinomas. Thus, ThinPrep cytology was significantly more sensitive in the detection of HSIL and cancer (McNemar test, P<0.001). Adjudication of cases in which the ThinPrep and smear diagnoses disagreed, using the final case diagnoses and the HPV DNA test results as reference standards, suggested that the ThinPrep method was detecting additional true SIL as opposed to false-positives. CONCLUSIONS: In a population-based study of high risk women, ThinPrep cytology demonstrated significantly increased sensitivity for detecting HSIL and carcinoma, with a concurrent significant increase in colposcopy referrals.
Assuntos
Citodiagnóstico/métodos , Neoplasias do Colo do Útero/patologia , Colo do Útero/patologia , Estudos de Coortes , Costa Rica/epidemiologia , Citodiagnóstico/instrumentação , DNA Viral/análise , Feminino , Humanos , Incidência , Programas de Rastreamento , Teste de Papanicolaou , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/diagnóstico , Infecções Tumorais por Vírus/diagnóstico , Displasia do Colo do Útero/patologia , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/virologia , Esfregaço VaginalRESUMO
BACKGROUND: Automated cytology devices have utility in quality assurance applications, but the effectiveness of these devices in primary screening is unknown. METHODS: Enrollment smears obtained from 7323 women participating in a population-based study sponsored by the National Cancer Institute were screened manually in Costa Rica and then evaluated independently in the U.S. with the PAPNET system (Neuromedical Systems, Inc., Suffern, NY), a semiautomated, neural network-based device. Smears with abnormal PAPNET images were microscopically rescreened and then diagnosed by a U.S. cytopathologist. ThinPrep slides (Cytyc Corporation, Boxborough, MA), prepared from rinses of the cytologic sampler, and cervigrams (National Testing Laboratories, Fenton, MO) were also evaluated. Women with any abnormal cytologic diagnosis or a positive cervigram were referred for colposcopy with biopsy and definitive therapy if indicated. RESULTS: Based on the U.S. cytotechnologist's review of the PAPNET images, 1017 (13.9%) of 7323 smears were selected for manual screening, resulting in the selection of 492 (6.7%) possibly abnormal slides for referral to the U.S. pathologist. Ultimately, 312 smears (4.3% of the total) were diagnosed as containing squamous cells of undetermined significance or a more severe abnormality (> or =ASCUS), resulting, hypothetically, in the referral of 66.5% of women with a final diagnosis of a squamous intraepithelial lesion or a more severe abnormality (> or =SIL) and 86.0% of patients with > or =high grade SIL. Conventional microscopic screening performed in Costa Rica resulted in the hypothetical referral of 6.5% of patients with > or =ASCUS for colposcopy, including 69.5% of patients with > or =SIL and 79.8% of those with > or =high grade SIL. CONCLUSIONS: In this study, PAPNET-assisted cytologic screening accurately identified smears obtained from women with high grade SIL or carcinoma. Determination of the clinical cost-effectiveness of PAPNET-assisted screening in routine practice awaits future study.
Assuntos
Programas de Rastreamento/métodos , Teste de Papanicolaou , Lesões Pré-Cancerosas/patologia , Neoplasias do Colo do Útero/patologia , Esfregaço Vaginal/métodos , Estudos de Coortes , Costa Rica , DNA Viral/isolamento & purificação , Feminino , Humanos , Redes Neurais de Computação , Papillomaviridae/isolamento & purificação , Lesões Pré-Cancerosas/virologia , Estudos Prospectivos , Encaminhamento e Consulta , Estados Unidos , Neoplasias do Colo do Útero/virologia , Esfregaço Vaginal/instrumentaçãoRESUMO
While the worldwide AIDS epidemic continues to expand, directly measured incidence data are difficult to obtain. Methods to reliably estimate human immunodeficiency virus type 1 (HIV-1) incidence from more easily available data are particularly relevant in those parts of the world where prevalence is rising in heterosexually exposed populations. The authors set out to estimate HIV-1 incidence in a population of heterosexual sexually transmitted disease clinic attendees in Trinidad who had a known high prevalence of HIV-1 subtype B. Over the period 1987-1995, HIV-1 incidence estimates from serial cross-sectional studies of HIV-1 prevalence, passive follow-up of clinic recidivists, modeling of early markers of HIV-1 infection (p24 antigen screening), and a cohort study of seronegative genital ulcer disease cases were compared. Measuring incidence density in the genital ulcer disease cases directly gave the highest estimate, 6.9% per annum. Screening for the detection of early HIV-1 markers yielded an incidence of 5.0% per annum, while estimating incidence from serial cross-sectional prevalence data and clinic recidivists gave estimates of 3.5% and 4.5% per annum, respectively. These results were found to be internally consistent. Indirect estimates of incidence based on prevalence data can give accurate surrogates of true incidence. Within limitations, even crude measures of incidence are robust enough for health planning and evaluation purposes. For planning vaccine efficacy trials, consistent conservative estimates may be used to evaluate populations before targeting them for cohort studies.
PIP: HIV incidence data, necessary for the planning and evaluation of national AIDS control programs, are difficult to obtain directly. In this study, HIV-1 incidence in Trinidad was estimated in a population known to be at high risk: heterosexuals attending a sexually transmitted disease clinic in Port of Spain in 1987-95. HIV incidence estimates were obtained from serial cross-sectional studies of HIV-1 prevalence (n = 3625), passive follow-up of clinic recidivists (n = 98), modeling of early markers of HIV-1 infection (p24 antigen screening) (n = 12,154), and a cohort study of seronegative genital ulcer disease cases (n = 196). Measuring incidence density in genital ulcer disease cases directly gave the highest estimate: 6.9% per year. Screening for the detection of early HIV-1 markers yielded an incidence of 5.0% per year, while estimating incidence from serial cross-sectional prevalence data and clinic recidivists provided estimates of 3.5% and 4.5%, respectively. Although these estimates come from groups within the clinic population with differential HIV-1 risk, they were internally consistent. These findings suggest that indirect estimates of incidence based on prevalence data can provide accurate surrogates of true HIV incidence and may be used to target suitable populations for cohort studies.
Assuntos
Infecções por HIV/epidemiologia , HIV-1 , Western Blotting , Estudos Transversais , Ensaio de Imunoadsorção Enzimática , Feminino , Seguimentos , Anticorpos Anti-HIV/análise , Proteína do Núcleo p24 do HIV/imunologia , Infecções por HIV/imunologia , HIV-1/imunologia , Humanos , Incidência , Masculino , Prevalência , Reprodutibilidade dos Testes , Estudos Retrospectivos , Trinidad e Tobago/epidemiologiaRESUMO
While the worldwide AIDS epidemic continues to expand, directly measured incidence data are difficult to obtain. Methods to reliably estimate human immunodeficiency virus type 1 (HIV-1) incidence from more easily available data are particularly relevant in those parts of the world where prevalence is rising in heterosexually exposed populations. The authors set out to estimate HIV-1 incidence in a population of heterosexual sexually transmitted disease clinic attended in Trinidad who had a known high prevalence of HIV-1 subtype B. Over the period 1987-1995, HIV-1 incidence estimates from serial cross-sectional studies of HIV-1 prevalence, passive follow-up of clinic recidivists, modeling of early markers of HIV-1 infection (p24 antigen screening), and a cohort study of seronegative genital ulcer disease cases were compared. Measuring incidence density in the genital ulcer disease cases directly gave the highest estimate, 6.9 percent per annum. Screening for the detection of early HIV-1 markers yielded an incidence of 5.0 percent per annum, while estimating incidence from serial cross-sectional prevalence data and clinic recidivists gave estimates of 3.5 percent and 4.5 percent per annum, respectively. These results were found to be internally consistent. Indirect estimates of incidence based on prevalence data can give accurate surrogates of true incidence. Within limitations, even crude measures of incidence are robust enough for health planning and evaluation purposes. For planning vaccine efficacy trails, consistent conservative estimates may be used to evaluate population before targeting them to cohort studies(AU)