Selection of family 1 PspA molecules capable of inducing broad-ranging cross-reactivity by complement deposition and opsonophagocytosis by murine peritoneal cells

PspA is one of the most well studied pneumococcal proteins and a promising candidate for a future protein-based anti-pneumococcal vaccine. Nevertheless, its structural and serological variability suggests the inclusion of more than one PspA molecule in order to broaden protection. Since different PspAs exhibit variable levels of cross-reactivity, the selection of the protein combination with the highest coverage potential is an essential step for PspA-based vaccine development. This work investigated the level of cross-reactivity within family 1 PspAs, and established a complement based antibody mediated opsonophagocytic assay for measuring the level of cross-protection. Among a panel of ten family 1 PspA molecules, two of them, one belonging to clade 1 and another from clade 2, induced antibodies capable of enhancing complement deposition and mediating the phagocytic killing by mouse peritoneal macrophages of all pneumococci bearing PspA family 1 strains tested, regardless of their serotype. Therefore, we suggest the inclusion of either one in a PspA-based vaccine, as a representative of family 1. Furthermore, our results suggest that opsonophagocytosis by mouse peritoneal cells can be an efficient means of evaluating the induction of protective immune responses in mice across a large number of strains.

Estimating the cost-effectiveness of pneumococcal conjugate vaccination in Brazil / Cálculo de la relación costo-efectividad de la vacuna conjugada antineumocócica en Brasil

OBJECTIVE: To compare the costs and benefits of pneumococcal conjugate vaccination compared with no vaccination from the perspectives of the health care system and society. METHODS: Using data from established sources, we estimated the incidence and mortality due to invasive pneumococcal disease, pneumonia, and acute otitis media (AOM) for a hypothetical birth cohort of children from birth to 5 years. RESULTS: A universal pneumococcal conjugate vaccination program was estimated capable of annually avoiding 1 047 cases of invasive disease, 58 226 cases of pneumonia, and 209 862 cases of AOM. When herd immunity effects were considered, the program prevented 1.3 million cases of pneumococcal disease and over 7 000 pneumococcal deaths. At a vaccination cost of R$ 51.12 (US$ 26.35) per dose, vaccination would cost annually R$ 4 289 (US$ 2,211) per disability-adjusted life years averted. This does not take into account herd immunity effects. CONCLUSIONS: At the current vaccine price, conjugate vaccination could be a cost-effective investment compared to other options to control childhood diseases. Further analysis is required to determine whether vaccination at the current price is affordable to Brazil.

OBJETIVO: Comparar los costos y los beneficios de la aplicación de la vacuna conjugada antineumocócica en comparación con la no vacunación, desde las perspectivas del sistema de salud y la sociedad. MÉTODOS: A partir de fuentes reconocidas, se estimaron la incidencia y la mortalidad por enfermedad neumocócica invasora, neumonía y otitis media aguda (OMA) para una cohorte hipotética de niños desde su nacimiento hasta los 5 años. RESULTADOS: Se estimó que un programa de vacunación universal con una vacuna conjugada antineumocócica sería capaz de evitar anualmente 1 047 casos de la enfermedad invasora, 58 226 casos de neumonía y 209 862 casos de OMA. Si se considera el efecto de la inmunidad de grupo, el programa evitaría 1,3 millones de casos de enfermedad y más de 7 000 muertes por infección neumocócica. A R$ 51,12 (US$ 26,35) por dosis, la vacunación costaría anualmente R$ 4 286 (US$ 2,211) por cada año de vida ajustado por discapacidad evitado, sin tomar en cuenta el efecto de la inmunidad de grupo. CONCLUSIONES: En comparación con otras opciones de control de estas enfermedades infantiles y con los precios actuales de la vacuna conjugada, la vacunación antineumocócica podría ser una inversión efectiva en función del costo. Se requieren más estudios para determinar si la vacunación es costeable para Brasil a los precios actuales.

Progress towards meningitis prevention in the conjugate vaccines era

Acute bacterial meningitis is an important cause of morbidity and mortality among children less than five years old. Haemophilus influenzae, Streptococcus pneumoniae and Neisseria meningitidis are the most important agents of bacterial meningitis in developing countries. The development of the conjugate vaccines in the beginning of the 90's, especially type b H. influenzae (Hib), and more recently the heptavalent pneumococcal and the serogroup C meningococcal vaccines, have contributed directly to changes in the epidemiological profile of these invasive diseases (direct effect) and of their carriage status (indirect effect). We review the impact of the Hib conjugate vaccine in Latin American countries, where this vaccine has been implemented, and the potential of pneumococcal and meningococcal conjugate vaccines for the reduction of meningitis worldwide. We also address constraints for the development and delivery of these vaccines and review new candidate state-of-the-art vaccines. The greatest challenge, undoubtedly, is to implement these vaccines worldwide, especially in the developing regions.

Assessment of anti-PGL-I as a prognostic marker of leprosy reaction

The anti-phenolic glycolipid-I (PGL-I) assay as currently applied for leprosy is conceived as an early marker of asymptomatic infection, early disease diagnosis and cure monitoring. Its use as a prognostic marker of reaction is still a matter of controversy. We conducted a case-control study to investigate whether IgM and IgG anti-PGL-I antibodies could discriminate patients at increased risk of developing reactions. Eligible cases were untreated leprosy patients at the onset of type 1 and type 2 reactions recruited from among 600 concurrent, newly detected, untreated leprosy patients attending an outpatient clinic in central Brazil. For the patients with reaction, approximately the same number of leprosy cases without reaction matched as to bacterial index (BI), age and gender were randomly selected. Individuals without clinical leprosy were evaluated as healthy controls. Sera from type 1 reaction (N = 43) and type 2 reaction (N = 26) patients were tested by an ELISA using PGL-I synthetic disaccharide-BSA antigen and 1:300 sera dilution (cut-off point > or = 0.2 OD). Antibody profiles were evaluated by exploratory data analysis and reverse cumulative distribution curves. The IgG anti-PGL-I response did not have a defined pattern, being detected only at low levels. Our results indicate that leprosy patients, independently of their reactional status, produce high levels of IgM anti-PGL-I, demonstrating a strong correlation between the magnitude of antibody response and the BI. Patients with a higher BI were at least 3.4 times more prone to produce an antibody response compared to healthy controls.

An epidemiological approach to study congenital Chagas'Disease

A transmissäo transplancentária do Trypanosoma cruzi vem despontando como tema de interesse em anos recentes, especialmente em áreas endêmicas da América do Sul. A frequência da infecçäo e os possíveis fatores associados à transmissäo congênita ainda näo estäo bem esclarecidos. Diferenças regionais em relaçäo às taxas de transmissäo têm sido explicadas por variaçoes nas cepas de parasitas. Os aspectos metodológicos inerentes à formulaçäo das hipóteses e os respectivos delineamentos dos diferentes estudos näo permitem uma combinaçäo de resultados para auxiliar a interpretaçäo das diferenças observadas. Explora as evidências epidemiológicas relativas às variaçoes nas taxas de infecçäo congênita do Brasil, Bolívia e Argentina e propoe um modelo para investigaçäo de fatores de risco para transmissäo.

Rastreamento sorològico para doenças infecciosas em banco de sangue como indicador de morbidade populacional / Serological screening for infectious diseases in blood donors as morbidity indicator

É discutido o valor do rastreamento sorològico para doença de Chagas, sífilis, hepatite B e AIDS realizado por bancos de sangue como indicador de morbidade populacional. Foram analisados os dados referentes a 62.814 doaçöes de sangue obtidas em dois bancos de sangue públicos e três privados correspondendo ao total das doaçöes no período de outubro de 1985 a outubro de 1987 em Goiânia, Goiás (Brasil). A soroprevalência foi comparada com dados obtidos pela notificaçäo compulsòria das doenças e com inquéritos epidemiològicos disponíveis. Foi encontrada soroprevalência para AIDS de 0,0@% para um único exame de ELISA, estimando-se em 1.900 o número de indivíduos supostamente infectados em Goiás, número compatível com o esperado quando se trabalha com dados de notificaçäo. Para a doença de Chagas, hepatite B e sífilis foram observadas soroprevalências de até 3,3%, 1,3% e 4,1%, respectivamente. Foram discutidas as dificuldades encontradas para validaçäo desses resultados pela ausência de notificaçäo compulsòria e características particulares dos inquéritos sorològicos .