Role of human herpesvirus 6 infection in young Brazilian children with rash illnesses.

BACKGROUND: Human herpesvirus type 6 (HHV-6) has been shown to infect almost all children by 4 years of age. Primary infection causes an undifferentiated febrile illness, with approximately 30% of children exhibiting the classic clinical manifestations of exanthem subitum. Even with typical clinical presentation, exanthem subitum is frequently misdiagnosed as measles or rubella. Our aim was to describe the frequency and clinical manifestations of HHV-6 infection in children less than 4 years of age enrolled in a study designed to define the etiology of rash diseases. PATIENTS AND METHODS: The study was conducted between January 1998 and December 2006 at a general hospital and a large primary health care unit from Niterói, Rio de Janeiro, Brazil. Sera from 223 children, in whom measles, rubella, dengue fever, and parvovirus B19 infections were excluded, were studied for anti-HHV-6 antibodies using an indirect immunofluorescence test. Demographic and clinical data of those patients were described. RESULTS: Ninety-seven (43.5%) of the children had evidence of primary HHV-6 infection. The age of onset peaked at 6-11 months and 75% of the HHV-6 infection occurred in children between 6 and 17 months. Only 21% of the HHV-6 cases had a typical roseola-like illness and 73% and 46%, respectively, fulfilled the clinical criteria of measles and rubella suspected case. CONCLUSIONS: Our study confirms the importance of HHV-6 infection in young children and highlights the difficulties of diagnosing a rash illness on clinical grounds alone.

Performance of rubella suspect case definition: implications for surveillance

OBJETIVO: Avaliar a acurácia da definição de caso suspeito de rubéola entre pacientes com doenças exantemáticas atendidos em unidades de saúde pública.MÉTODOS: A população de estudo foi constituída de pacientes com doença exantemática, com ou sem febre, atendidos em serviços de saúde pública, de janeiro de 1994 a dezembro de 2002 no município de Niterói, RJ. Dados clínicos e sorológicos foram utilizados para estimar os valores preditivos positivos da definição de caso suspeito de rubéola do Ministério da Saúde do Brasil e outras combinações de sinais e sintomas, considerando o resultado da sorologia como referência. A detecção de IgM específica para rubéola em amostras sangüíneas foi realizada por ensaio imunoenzimático. Foram calculados os valores preditivos positivos e respectivos intervalos de confiança de 95 por cento. RESULTADOS: Foram estudados 1.186 pacientes com uma doença caracterizada por uma variada combinação de rash com ou sem febre, artropatia e linfoadenopatia. Pacientes com exantema, independentemente da presença de outros sinais e sintomas, apresentaram uma probabilidade de 8,8 por cento de serem IgM positivos para rubéola. A definição de caso suspeito de rubéola utilizada no Brasil apresentou baixo valor preditivo positivo (13,5 por cento). Esta definição de caso identificou corretamente 42,3 por cento dos casos IgM positivos, e classificou de forma incorreta 26,1 por cento dos IgM negativos. CONCLUSÕES: Os resultados indicam que as doenças exantemáticas devem ser investigadas em conjunto para fins de vigilância epidemiológica e coleta de espécimens clínicos para o diagnóstico laboratorial. Esta estratégia aumenta os custos, mas gera benefícios na interrupção da circulação do vírus e na prevenção da síndrome da rubéola congênita.

Assessment of the performance of a definition of a suspected measles case: implications for measles surveillance.

OBJECTIVE: To assess the performance, in Brazil, of the definition of a suspected measles case among patients with rash diseases that has been adopted in Brazil and many other countries. METHODS: From January 1994 to December 2003, patients with acute rash were seen at two large primary health care units and a public general hospital in Niterói, a city in the metropolitan area of the city of Rio de Janeiro, Brazil. Data from clinical and serologic assessment were used to estimate sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the definition of a suspected measles case that has been adopted in Brazil, as well as other combinations of signs and symptoms; serologic status was taken as the reference. Using enzyme immunoassay, serum samples were tested for immunoglobulin M (IgM) antibodies against measles virus. RESULTS: A total of 1,221 patients with an illness characterized by different combinations of rash with other signs and symptoms were studied. The suspected case definition that has been adopted in Brazil (rash, fever, and at least one of the following: cough, coryza, or conjunctivitis) had an overall sensitivity of 100%, and a specificity of 58.7%. Confirmed measles cases were 2.4 times as likely as were other rash diseases to have that combination of signs/symptoms. The suspected case definition adopted in Brazil had a 6% PPV and 100% NPV. The combination of all five signs and symptoms had the highest specificity, PPV, and likelihood ratio, for both children (< 15 years old) and adults (> or = 15 years). That was achieved at the expense of sensitivity, which dropped to 89%, but the NPV was still very high. CONCLUSIONS: Our results show that the suspected measles case definition adopted in Brazil is extremely sensitive for measles surveillance among patients with rash diseases. However, the high false-positive rates that were found may result in a substantial number of other rash diseases being misclassified as measles, leading to the misdirection of control measures and increases in their cost.

Assessment of the performance of a definition of a suspected measles case: implications for measles surveillance

OBJETIVO: Evaluar la utilidad, en el Brasil, de la definición de "caso sospechado de sarampión", aplicada en pacientes con enfermedades exantemáticas, que se ha adoptado en el Brasil y en muchos otros países. MÉTODOS: De enero de 1994 a diciembre de 2003, se examinó a pacientes con erupción cutánea aguda en dos grandes unidades de atención primaria y en un hospital general estatal en Niterói, en la zona metropolitana de la ciudad de Río de Janeiro, Brasil. Se usaron datos de la evaluación clínica y serológica para estimar la sensibilidad, especificidad, valor pronóstico de un resultado positivo (VPRP), y valor pronóstico de un resultado negativo (VPRN) aplicables a la definición de "caso sospechado de sarampión" adoptada en el Brasil, así como otras combinaciones de signos y síntomas; el resultado de pruebas serológicas se usó como parámetro de referencia. Usando la técnica de inmunoensayo enzimático, las muestras de suero se examinaron para detectar la presencia de anticuerpos de immunoglobulina M (IgM) contra el virus del sarampión. RESULTADOS: Se estudió a un total de 1 221 pacientes con una enfermedad caracterizada por exantema cutáneo más otros signos y síntomas en diversas combinaciones. La definición de "caso sospechado" adoptada en el Brasil (erupción, fiebre y por lo menos un síntoma más, que puede ser tos, congestión nasal o conjuntivitis), tuvo una sensibilidad general de 100% y una especificidad de 58.7%. La probabilidad de encontrar esa combinación de síntomas o signos fue 2,4 mayor entre los casos confirmados de sarampión que entre los casos de otras enfermedades exantemáticas. La definición de "caso sospechado" que se ha adoptado en el Brasil tuvo un VPRP de 6% y un VPRN de 100%. La presencia combinada de todos los cinco signos y síntomas tuvo la mayor especificidad, el mayor VPRP y la mayor razón de verosimilitud, tanto en niños (< 15 años de edad) como en adultos (> 15 años). Eso se logró a expensas de la sensibilidad, que se redujo a 89%, pero el VPRN siguió siendo muy alto...

Clinical and epidemiological aspects of human parvovirus B19 infection in an urban area in Brazil (Niterói city area, State of Rio de Janeiro, Brazil).

This study was designed to analyse the clinical and epidemiological data from human parvovirus B19 cases in a six-year study of rash diseases conduct in an urban area in Brazil (Niterói city area, State of Rio de Janeiro). A total of 673 patients with acute rash diseases were seen at two primary health care units and at a general hospital. A clotted blood sample was collected from all subjects at the time of consultation. Forty-nine per cent (330 cases) of the patients were negative for dengue, rubella and measles IgM or for low avidity IgG to HHV-6. Of these 330, 105 (31.8%) were identified as IgM positive to parvovirus B19 by using an antibody capture EIA. During the study period, three distinct peaks of parvovirus infection were detected, suggesting that the disease appears to cycle in approximately 4-5 years. B19 infection was characterized by variable combinations of fever, flu-like symptoms, arthropathy, and gastrointestinal symptoms. Frequency of fever and arthropathy was substantially higher in adults, 75% [chi2 (1 D.F.) = 11.39, p = 0.0007] and 62.5% [chi2 (1 D.F.) = 29.89, p = 0.0000], respectively. "Slapped-cheek" appearance and reticular or lace-like rash were seen in only 30.1% of the children. No adult presented this typical rash. The lack of the typical rash pattern in a large proportion of parvovirus B19 and the similarity of clinical manifestations to other rash diseases, specially to rubella, highlight the difficulty of diagnosing B19 infection on clinical grounds alone.

Clinical and epidemiological aspects of human parvovirus B19 infection in an urban area in Brazil (Niterói city area, State of Rio de Janeiro, Brazil)

This study was designed to analyse the clinical and epidemiological data from human parvovirus B19 cases in a six-year study of rash diseases conduct in an urban area in Brazil (Niterói city area, State of Rio de Janeiro). A total of 673 patients with acute rash diseases were seen at two primary health care units and at a general hospital. A clotted blood sample was collected from all subjects at the time of consultation. Forty-nine per cent (330 cases) of the patients were negative for dengue, rubella and measles IgM or for low avidity IgG to HHV-6. Of these 330, 105 (31.8 percent) were identified as IgM positive to parvovirus B19 by using an antibody capture EIA. During the study period, three distinct peaks of parvovirus infection were detected, suggesting that the disease appears to cycle in approximately 4-5 years. B19 infection was characterized by variable combinations of fever, flu-like symptoms, arthropathy, and gastrointestinal symptoms. Frequency of fever and arthropathy was substantially higher in adults, 75 percent [chi2 (1 D.F.) = 11.39, p = 0.0007] and 62.5 percent [chi2 (1 D.F.) = 29.89, p = 0.0000], respectively. "Slapped-cheek" appearance and reticular or lace-like rash were seen in only 30.1 percent of the children. No adult presented this typical rash. The lack of the typical rash pattern in a large proportion of parvovirus B19 and the similarity of clinical manifestations to other rash diseases, specially to rubella, highlight the difficulty of diagnosing B19 infection on clinical grounds alone