PubMed Health⌕ Search

Biomedical subjects

Martin O Ota

Publications and source records attributed to Martin O Ota.

6 recordsLinked to original sources

Sense and the science of childhood immunization: can we achieve more with less?

The threat of biological terrorism with small pox virus and a global influenza pandemic in the face of limited vaccine supply recently stimulated research into the evaluation of fractional dose vaccine regimens, with promising immunogenicity results. While this approach is not new, it has been less applied to vaccines for less sensational but nevertheless, significant killer diseases. This manuscript provides an overview of the basics of immunization as it applies to the current practice of immunization in children, comments on the untapped avenues for cost reduction of vaccine delivery, and the potential for saving more lives with currently available resources.

Antigens↗

Protective immunity provided by HLA-A2 epitopes for fusion and hemagglutinin proteins of measles virus.

Natural infection and vaccination with a live-attenuated measles virus (MV) induce CD8(+) T-cell-mediated immune responses that may play a central role in controlling MV infection. In this study, we show that newly identified human HLA-A2 epitopes from MV hemagglutinin (H) and fusion (F) proteins induced protective immunity in HLA-A2 transgenic mice challenged with recombinant vaccinia viruses expressing F or H protein. HLA-A2 epitopes were predicted and synthesized. Five and four peptides from H and F, respectively, bound to HLA-A2 molecules in a T2-binding assay, and four from H and two from F could induce peptide-specific CD8+ T cell responses in HLA-A2 transgenic mice. Further experiments proved that three peptides from H (H9-567, H10-250, and H10-516) and one from F protein (F9-57) were endogenously processed and presented on HLA-A2 molecules. All peptides tested in this study are common to 5 different strains of MV including Edmonston. In both A2K(b) and HHD-2 mice, the identified peptide epitopes induced protective immunity against recombinant vaccinia viruses expressing H or F. Because F and H proteins induce neutralizing antibodies, they are major components of new vaccine strategies, and therefore data from this study will contribute to the development of new vaccines against MV infection.

Amino Acid Sequence↗

Emerging diseases: measles.

High vaccination coverage rates and the administration of a second dose of measles vaccine have resulted in a significant decline in the incidence of measles and neurologic diseases due to measles in many countries. However, intermittent outbreaks of measles still occur even in countries with excellent vaccination coverage, suggesting the existence of high rates of measles virus introduction from endemic regions and/or waning of vaccine-induced immunity. Strategies to sustain high levels of global immunity to measles virus by increasing vaccine coverage with routine and supplementary vaccination campaigns must be supported.

Communicable Diseases, Emerging↗

Measles: immune suppression and immune responses.

Measles is a highly contagious viral disease that remains the leading vaccine-preventable cause of child mortality worldwide. Deaths from measles are due largely to an increased susceptibility to secondary bacterial and viral infections, attributed to a prolonged state of immune suppression. Several abnormalities of the immune system have been described, including changes in lymphocyte number and function, shifts in cytokine responses, immunomodulatory effects of interleukin-10, down regulation of interleukin-12, impaired antigen presentation, and altered interferon alpha/beta signaling pathways. Although the current vaccine is very effective, knowledge of the molecular basis of the immune responses to measles virus could contribute to the development of a safer, more immunogenic measles vaccine. However, the safety of new measles vaccines must be carefully investigated, as two measles vaccines have resulted in unintended immunologic consequences: atypical measles following administration of the formalin-inactivated measles vaccine and increased mortality in girls following administration of high-titer measles vaccines.

Humans↗

Survival of HIV-1 and HIV-2 perinatally infected children in The Gambia.

BACKGROUND: The risk of mother-to-child transmission (MTCT) of HIV-2 is much lower than that of HIV-1, but the long-term prognosis of perinatally infected HIV-2 children is unknown. We re-visited children who were part of a large MTCT study in The Gambia (conducted during 1993-1997), in order to compare the long-term survival of children perinatally infected with HIV-2 with that of seronegative and of HIV-1 infected children. METHODS: Five to eight years' follow-up of a cohort of children born to HIV-negative, HIV-1 positive, and HIV-2 positive mothers. RESULTS: Seven hundred and seventy-four children were followed up for a median of 6.6 years. Of 17 perinatally HIV-1 infected children, three were still alive on 1 July 2001, two had been lost to follow-up, and 12 had died. The median survival was 2.5 years. Of eight HIV-2 infected children five were still alive, none were lost to follow-up and three had died. The mortality hazards ratio of both HIV-1 [9.9; 95% confidence interval (CI), 5.2-19], and of HIV-2 infected children (3.9; CI, 1.2-12) was significantly increased compared with children of seronegative mothers. The mortality hazards ratio of HIV uninfected children of HIV-1 or HIV-2 infected mothers was not significantly increased compared to that of children of seronegative mothers (P = 0.17 and P = 0.5 respectively). CONCLUSIONS: Children with perinatally acquired HIV-2 infection have a higher mortality than children of seronegative mothers. Guidelines for treatment of HIV-1 infected children should be used for treatment of HIV-2 infected children.

Developing Countries↗

Influence of placental malaria infection on foetal outcome in the Gambia: twenty years after Ian Mcgregor.

Malaria infection in pregnancy has serious health consequences among mothers and offspring. The influence of placental malaria infection on foetal outcome was studied in a Gambian rural setting where few pregnant women take antimalarial chemoprophylaxis. During July-December 1997, three hundred thirteen mother-newborn pairs (singletons only) were consecutively recruited into a study of the effects of placental malaria infection on the outcome of pregnancy. Placental blood and tissue were collected at delivery. Babies were clinically assessed until discharge. The overall prevalence of placental malaria infection was 51.1% by placental histology and 37.1% by blood smear. The primigravid women were more susceptible to placental malaria than the multigravidae (65.3% vs 44.7%, p=0.01). Placental malaria was significantly associated with pre-term deliveryand intrauterine growth retardation (p<0.01), and there was a four-fold risk of delivering low-birth-weight babies if mothers had parasitized placentae [OR=4.42, 95% confidence interval (CI) 2.10-9.27]. A reduction of mean birth-weight of babies by 320 g was associated with placental malaria infection (p<0.001). Similarly, a two-fold risk of stillbirth delivery (OR=2.22, 95% CI 1.04-4.72) was observed among the infected mothers. The findings showed that there was still an overall poor foetal outcome associated with placental malaria infection. The findings of this study confirm the findings of an earlier study by McGregor in the Gambia that the low birth-weight rate is significantly higher if the placenta is parasitized. In addition, this study observed that the high stillbirth and prematurity rates were associated with placental malaria infection. The findings of the present study suggest undertaking of effective malaria-control strategies during pregnancy, such as use of insecticide-impregnated bednets, intermittent and early treatment for malaria, and antimalarial chemoprophylaxis, in the Gambia.

Adolescent↗