Impact of a twelve-year rotavirus vaccine program on acute diarrhea mortality and hospitalization in Brazil

Background Monitoring the impact of vaccine programs is necessary to identify changes in vaccine efficacy. We report the impact of the 12-year rotavirus vaccine program on diarrhea mortality and hospitalizations and their correlation to socioeconomic indicators. Methods this ecological study describes diarrhea hospitalizations and deaths from 2006 to 2018 in Brazil and correlates rotavirus vaccine coverage, hospitalizations and deaths to socioeconomic indicators and social vulnerability index (SVI) by state and region. Hospitalizations, deaths, and vaccine coverage trends were analyzed using Joinpoint regression models. Associations between hospitalizations, mortality and rotavirus vaccination coverage and socioeconomic and SVI indicators were established using Ordinary Least Square regressions. Results Rotavirus vaccine coverage remained stable between 2006 and 2018 (annual percentage changes (APC) [95%CI]: 4.4% [−0.3%, 9.2%]). Diarrhea hospitalization rates decreased 52.5% (−5.7% [−7.5%, −3.8%]), from 68.4 to 32.5 hospitalizations per 10,000 children <5 years-old between 2006 and 2018, with significant decreases in diarrhea mortality (−9.8% [−11.2%, −8.5%]). The Northeast region experienced the largest reductions (−13.9% [−15.7%, −12.2%]). Vaccination coverage and diarrhea-mortality were inversely correlated with the SVI. Conclusion The burden of childhood diarrhea has decreased over an extended period. States with high SVI, but high vaccination coverage had the largest reductions in hospitalizations and deaths

Avaliação da resposta de anticorpos contra antígenos de Plasmodium vivax relacionada a fatores genéticos do parasito e do hospedeiro humano

O presente estudo avaliou a resposta de anticorpos contra diferentes antígenos de merozoíto e esporozoíto de Plasmodium vivax, relacionando com as variantes da porção repetitiva do domínio central do gene da Proteína Circunsporozoítica (CSP) do parasito (VK210, VK247 e P. vivax-like) e com os polimorfismos do HLA-DRB1 no hospedeiro humano. A resposta de anticorpos foi avaliada para peptídeos das regiões conservadas e centrais variáveis da CSP, da porção N-terminal da Proteína de Superfície do Merozoíto 1-MSP1 (Pv200L), e recombinante do Antígeno 1 de Membrana Apical (AMA-1) e a Proteína de ligação ao Duffy (DBP) por ELISA, em amostras de plasma de pacientes naturalmente infectados com P. vivax. Inicialmente nós avaliamos a distribuição destas variantes da CSP em cinco diferentes áreas da Amazônia a fim de entender sua atual dinâmica de transmissão. A variante VK210 continua sendo a mais prevalente em todas as áreas estudadas. No entanto, pela primeira vez documentamos a presença das variantes VK247 e P. vivax-like como infecções simples na Amazônia brasileira evidenciando um novo perfil distribuição destas, o que possa sugerir um processo de adaptação das mesmas. Quando comparamos a resposta de anticorpos e a infecção pelas variantes de P. vivax, não foram observadas associações significativas entre a presença de determinada variante da CSP e a freqüência de resposta de anticorpos contra os três peptídeos do merozoíto analisados, MSP1 (Pv200L), AMA-1 e DBP e nem contra as frações conservadas da CSP no esporozíto, N-terminal [N] e C-terminal [C]. A falta de associações significativas entre resposta sorológica contra esses peptídeos fornece informações promissoras quanto à utilização destes antígenos para o desenvolvimento de uma vacina contra malária. Todavia, a variação na porção central da CSP deve ser considerada...The present study evaluated the antibody response against merozoite and sporozoite antigens of Plasmodium vivax and its relationship with the variants of the repetitive central region of the gene for Circunsporozoite protein (CSP) in parasite (VK210, VK247 and P. vivax-like) and, with the HLA-DRB1 polymorphisms in human host. The antibody response to synthetic peptides of the CSP conserved and variable regions and of the N-terminal portion of Merozoite surface protein - MSP1 (Pv200L), and, to recombinants peptides of the Apical Membrane Antige 1 (AMA-1) and of the Duffy Binding Protein (DBP) was evaluable by ELISA in plasma samples of malaria patients naturally infected with P. vivax. Firstly, we evaluated the CSP variants distribution among five different areas from Brazilian Amazon, in order to understand their current dynamic of transmissions. VK210 variant remains the most prevalent in all study areas. However, it is the first detection of VK247 e P. vivax-like variants as simple infection in the Brazilian Amazon, showing a new distribution profile, which may suggest an adaptation process of them. When comparing the antibody response and infection by variants of P. vivax, there were no significant associations between the presence of particular CSP variant and the frequency of antibody response against all three merozoite peptides analyzed, MSP1 (Pv200L), AMA-1, DBP and against the CSP conserved fractions in the sporozoite, N-terminal and C-terminal. The lack of significant associations among immune response against these peptides provides promising information regarding the use of these antigens for malaria vaccine development. On the other hand, the central variability of CSP should be considered to employment of this region as an immunogen, since the antibody response appears to be variant-specific. In order to evaluate the polymorphisms... (Complete abstract click electronic access below

The genetic diversity of Plasmodium vivax: a review

The genetic diversity of Plasmodium vivax has been investigated in several malaria-endemic areas, including the Brazilian Amazon region, where this is currently the most prevalent species causing malaria in humans. This review summarizes current views on the use of molecular markers to examine P. vivax populations, with a focus on studies performed in Brazilian research laboratories. We emphasize the importance of phylogenetic studies on this parasite and discuss the perspectives created by our increasing understanding of genetic diversity and population structure of this parasite for the development of new control strategies, including vaccines, and more effective drugs for the treatment of P. vivax malaria

Circumsporozoite Protein from <em>Plasmodium vivax</em> and its Relationship to Human Malaria

The circumsporozoite surface protein (CSP) is the most abundant polypeptide in the sporozoite covering. This protein is involved in the motility and invasion of the sporozoite during its entrance in the hepatocyte. Plasmodium vivax CSP sequences analyses revealed that parasites have repeats belonging to three types of peptide repeat units, named VK210, VK247 or P. vivax-like, this last differ from the two previously described variants. All P. vivax CS genotypes have a worldwide distribution by genetic and serological evaluation. Studies have also reported differences in the infectivity of anophelines to the variant genotypes, indicating that different malaria vectors were more susceptible to the infection by VK210. These findings could be a consequence of differences in the emergence of this genotype in specific regions around the world. These polymorphisms are associated to the increase of nonregulated inflammatory immune responses, which in turn may be associated with the outcome of infection. Geographic coexistence of these variants increase drug resistance and also recurrent parasite behavior. Knowledge of the P. vivax genome contributed to several discoveries, however, new studies are still needed to evaluate its potential as a promising vaccine target

Os polimorfismos do gene da citocina não estão associados aos níveis de anticorpos IgG anti-PvDBP, anti-PvAMA-1 ou anti-PvMSP-119 em uma área endêmica da malária da Amazônia brasileira

This study was financed by the Brazilian National Council for Scientific and Technological Development (Conselho Nacional de Desenvolvimento Cientí‑ fico e Tecnológico) process number 472135/2012, the Pará State Research Support Foundation (Fundação de Amparo à Pesquisa do Estado do Pará) and CAPPES. We thank Dr. Irene Soares and Luzia Carvalho for their help in serological analysis. This project was funded by CNPq and Capes.São José do Rio Preto Medical School. Department of Dermatology, Infectious and Parasitic Diseases. São José do Rio Preto, SP, Brazil.São Paulo State University. Department of Biology. São José do Rio Preto, SP, Brazil.Federal University of Sergipe. Department of Biology. Laboratory of Molecular Genetics and Biotechnology. São Cristóvão, SE, Brazil.Federal University of Pará. Institute of Biological Sciences. Laboratory of Microbiology and Immunology. Belém, PA, Brazil.Universidade de Campinas. Department of Genetics, Evolution and Bioagents. Laboratory of Tropical Diseases. Campinas, SP, Brazil.São José do Rio Preto Medical School. Department of Dermatology, Infectious and Parasitic Diseases. São José do Rio Preto, SP, Brazil / São Paulo State University. Department of Biology. São José do Rio Preto, SP, Brazil / Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Laboratório de Pesquisa Básica em Malária. Ananindeua, PA, Brasil.The immune response against Plasmodium vivax immunogenic epitopes is regulated by pro- and anti-inflammatory cytokines that determine antibody levels and class switching. Cytokine gene polymorphisms may be responsible for changes in the humoral immune response against malaria. The aim of this study was to evaluate whether polymorphisms in the TNFA, IFNG and IL10 genes would alter the levels of anti-PvAMA1, PvDBP and -PvMSP119 IgG antibodies in patients with vivax malaria. Methods: Samples from 90 vivax malaria-infected and 51 uninfected subjects from an endemic area of the Brazilian Amazon were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) to identify polymorphisms of the genes TNFA (-1031T > C, -308G > A, -238G > A), IFNG (+874T > A) and IL10 (-819C > T, -592C > A). The levels of total IgG against PvAMA1, PvDBP and PvMSP-119 were determined using an enzyme-linked immunosorbent assay (ELISA). Associations between the polymorphisms and the antibody response were assessed by means of logistic regression models. Results: No significant differences were found in the levels of IgG antibodies against the PvAMA-1, PvDBP or PvMSP119 proteins in relation to the studied polymorphisms. Conclusions: Although no associations were found among the evaluated genotypes and alleles and anti-merozoite IgG class P. vivax antibody levels, this study helps elucidate the immunogenic profile involved in the humoral immune response in malaria

The frequency of HLA-DRB1 polymorphisms in Brazilian Plasmodium vivax malaria patients and in blood donors from the Amazon Region

We evaluated the frequency of different HLA-DRB1 alleles in Plasmodium vivax-infected individuals and in healthy blood donors from malaria endemic areas of Brazil. Low-resolution human leukocyte antigen-DRB1 genotyping was performed for 73 malaria patients and 29 healthy blood donors. The most frequent alleles in individuals from northern Brazil were human leukocyte antigen-DRB1*04, *08, *07 and *13. The frequency of human leukocyte antigen-DRB1*07 was higher in malaria-infected individuals than in the control group, which reinforces the theory that this allele plays an important role in susceptibility to malaria. This study offers new information about a potential susceptibility factor for P. vivax malaria in a Brazilian population that is naturally exposed to malaria.Este estudo avaliou a frequência de diferentes alelos HLA-DRB1 em indivíduos infectados por Plasmodium vivax e em doadores de sangue saudáveis provenientes de áreas endêmicas de malária do Brasil. Foi realizada uma genotipagem de baixa resolução dos alelos HLA-DRB1 em 73 pacientes com malária e em 29 doadores de sangue saudáveis. Os alelos mais frequentes em indivíduos do norte do Brasil foram HLA-DRB1 *04, *08, *07 e *13. A frequência de HLA-DRB1 *07 foi maior nos indivíduos infectados com malária do que no grupo controle, o que reforça a hipótese de que esse alelo desempenha um papel importante na suscetibilidade à malária. Esta pesquisa fornece novas informações sobre um fator potencial de suscetibilidade à malária por P. vivax em uma população brasileira naturalmente exposta à doença.Este estudio evaluó la frecuencia de diferentes alelos HLA-DRB1 en individuos infectados por Plasmodium vivax y en donantes de sangre saludables provenientes de áreas endémicas de malaria de Brasil. Se realizó un genotipado de baja resolución de los alelos HLA-DRB1 en 73 pacientes con malaria y en 29 donantes de sangre saludables. Los alelos más frecuentes en individuos del norte de Brasil fueron HLA-DRB1*04, *08, *07 y *13. La frecuencia de HLA-DRB1*07 fue más grande en individuos infectados con malaria que en el grupo control, lo que refuerza la hipótesis de que ese alelo desempeña un papel importante en la susceptibilidad a la malaria. Esta investigación suministra nuevas informaciones sobre un factor potencial de susceptibilidad a la malaria por P. vivax en una población brasileña naturalmente expuesta a la enfermedad