Newly Identified Genes May be Key in Preventing Pregnancy Malaria
Identification of a new group of genes believed to be responsible for the phenomenon now known as ‘pregnancy malaria’ has researchers steps closer to developing preventative treatment for a condition that is a significant cause of infant mortality in Africa. They report their findings in the October 2007 issue of the journal Infection and Immunity.
Most individuals living in areas of the world where malaria transmission is constant acquire clinical immunity by adulthood, however women becoming pregnant for the first time have shown increased susceptibility to Plasmodium falciparum parasites that specifically target the placenta. What is now known as ‘pregnancy malaria’ can cause severe problems for both mother and child such as maternal anemia, low birth weight and increased neonatal and infant mortality rates, which are now averaging between 100,000 and 200,000 African newborns each year. Previous studies show that women build up antibodies to placental malaria through successive pregnancies, therefore raising hopes of developing a vaccine.
Through whole-genome-expression analysis of parasites collected from Tanzanian women with pregnancy malaria researchers identified six genes significantly higher in both placental and peripheral parasites. A member of a variant group of genes previously linked to pregnancy malaria, as well as five genes of unknown functions, were identified.
“These findings suggest that a suite of genes may be important for the genesis of the placental binding phenotype of P. falciparum and may provide novel targets for therapeutic intervention,” say the researchers.
(S.E. Francis, V.A. Malkov, A.V. Oleinikov, E. Rossnagle, J.P. Wendler, T.K. Mutabingwa, M. Fried, P.E. Duffy. 2007. Six genes are preferentially transcribed by the circulating and sequestered forms of Plasmodium falciparum parasites that infect pregnant women. Infection and Immunity, 75. 10: 4838-4850.)
Protein-Based Vaccine May Protect Against Malaria
By studying antibodies in the blood of Amazonian natives living in malaria endemic areas, researchers have discovered promising new targets for a malarial vaccine. They report their findings in the October 2007 issue of the journal Clinical and Vaccine Immunology.
In Brazil, Plasmodium vivax was responsible for 80% of the 600,000 cases of malaria reported in 2005 and malaria-related morbidity across the Amazon Basin. Emerging resistance to the frontline antimalarial drug, chloroquine, is of major concern as the mutation of target antigens complicates the development of new preventative therapies.
PvMSP-1, a protein of P. vivax is a target of naturally acquired and vaccine-induced immunity to malaria, however it can occur in up to six different forms. In the study researchers studied noninfected subjects exposed to malaria in rural Amazonia for antibody responses to proteins corresponding to PvMSP-1 commonly found in local parasites. Initially, less than one third had detectable antibodies, however antibody response increased dramatically following acute P. vivax infection.
“We suggest that antibody responses to the repertoire of variable domains of PvMsP-1 to which subjects are continuously exposed are elicited only after several repeated infections and may require frequent boosting, with clear implications for the development of PvMSP-1-based subunit vaccines,” say the researchers.
(M.S. Bastos, M. da Silva-Nunes, R.S. Malafronte, E. Hellena, E. Hoffmann, G. Wunderlich, S.L. Moraes, M.U. Ferreira. 2007. Antigenic polymorphism and naturally acquired antibodies to Plasmodium vivax merozoite surface protein 1 in rural Amazonians. Clinical and Vaccine Immunology, 14. 10:1249-1259.)
New Screening Method May Identify Tumor Viruses
For the first time, a new screening method shows promise for identifying new human tumor viruses, as well as determining which cancers are caused by infection and which are not. The researchers report their findings in the October 2007 issue of the Journal of Virology.
Statistics now show that infection contributes to over 20% of human cancers worldwide. Presently, the list of confirmed carcinogenic infectious agents is short, however studies suggest that new infectious agents yet to be identified contribute to a wide range of diseases, including cancers. A major obstacle in new pathogen discovery is whether an infectious agent isn’t identified due to lack of presence or technical failure, emphasizing the need for reliable screening methods.
Conjunctival carcinomas are tumors long suspected of having a direct infectious origin, meaning direct carcinogens are present in the tumor mass with at least one genome copy per cell. In the study researchers developed a process called digital transcript subtraction (DTS), a system for subtracting known human sequences from library data sets while leaving nonhuman sequences behind for further analysis. DTS analysis of 241,122 conjunctival carcinoma cells disclosed only 21 that didn’t concur with previous sequences from human databases, indicating its ability to screen human sequence data and identify those most likely to be of viral origin.
“DTS is a simple screening method to discover novel nucleic acids,” say the researchers. “It provides, for the first time, quantitative evidence against some classes of viral etiology when no viral transcripts are found, thereby reducing the uncertainty involved in new pathogen discovery.”
(H. Feng, J.L. Taylor, P.V. Benos, R. Newton, K. Waddell, S.B. Lucas, Y. Chang, P.S. Moore. 2007. Human transcriptome subtraction by using short sequence tags to search for tumor viruses in conjunctival carcinoma. Journal of Virology, 81. 20: 11332-11340.)