Plasmodium falciparum GBP2 Is a Telomere-Associated Protein That Binds to G-Quadruplex DNA and RNA

In the early-diverging protozoan parasite Plasmodium, few telomere-binding proteins have been identified and several are unique. Plasmodium telomeres, like those of most eukaryotes, contain guanine-rich repeats that can form G-quadruplex structures. In model systems, quadruplex-binding drugs can disrupt telomere maintenance and some quadruplex-binding drugs are potent anti-plasmodial agents. Therefore, telomere-interacting and quadruplex-interacting proteins may offer new targets for anti-malarial therapy. Here, we report that P. falciparum GBP2 is such a protein. It was identified via ‘Proteomics of Isolated Chromatin fragments’, applied here for the first time in Plasmodium. In vitro, PfGBP2 binds specifically to G-rich telomere repeats in quadruplex form and it can also bind to G-rich RNA. In vivo, PfGBP2 partially colocalises with the known telomeric protein HP1 but is also found in the cytoplasm, probably due to its affinity for RNA. Consistently, its interactome includes numerous RNA-associated proteins. PfGBP2 is evidently a multifunctional DNA/RNA-binding factor in Plasmodium.</jats:p

Fear of Birth Defects Is a Major Barrier to Soil-Transmitted Helminth Treatment (STH) for Pregnant Women in the Philippines

The World Health Organization recommends anthelminthic treatment for pregnant women after the first trimester in soil-transmitted helminth (STH) endemic regions to prevent adverse maternal-fetal consequences. Although studies have shown the high prevalence of infection in the Philippines, no research has evaluated deworming practices. We hypothesized that pregnant women are not receiving deworming treatment and we aimed to identify barriers to World Health Organization guideline implementation. We conducted key informant interviews with local Department of Health (DOH) administrators, focus group discussions with nurses, midwives, and health care workers, and knowledge, attitudes, and practices surveys with women of reproductive age to elicit perspectives about deworming during pregnancy. Key informant interviews revealed that healthcare workers were not deworming pregnant women due to inadequate drug supply, infrastructure and personnel as well as fear of teratogenicity. Focus group discussions showed that healthcare workers similarly had not implemented guidelines due to infrastructure challenges and concerns for fetal malformations. The majority of local women believed that STH treatment causes side effects (74.8%) as well as maternal harm (67.3%) and fetal harm (77.9%). Women who were willing to take anthelminthics while pregnant had significantly greater knowledge as demonstrated by higher Treatment Scores (mean rank 146.92 versus 103.1, z = −4.40, p<0.001) and higher Birth Defect Scores (mean rank 128.09 versus 108.65, z = −2.43, p = 0.015). This study concludes that World Health Organization guidelines are not being implemented in the Philippines. Infrastructure, specific protocols, and education for providers and patients regarding anthelminthic treatment are necessary for the successful prevention of STH morbidity and mortality among pregnant women

Characteristics of KAP survey participants.

<p>A total of 226 women of reproductive age completed a Knowledge, Attitudes, and Practices survey regarding STH infections during pregnancy. The majority of women surveyed were between the ages of 20–37 years old, unemployed, and did not complete a high school education.</p

Soil-transmitted helminth (STH) knowledge scores, by willingness to participate in a government deworming program.

<p>The Mann-Whitney U Test was used to compare the mean knowledge scale scores to the “yes/no” responses to the question, “Would you be willing to participate in a government-sponsored deworming program?” The 149 women who were willing to participate in a government sponsored deworming program had a higher knowledge of treatment methods and modes of infection than the 77 women who were not willing to participate in a government program.</p

STH Treatment for Pregnant Women: Perspectives of Health Care Providers.

<p>The National STH Coordinator, Regional STH Coordinator, and municipal health officers (MHOs) provided their perspectives during key informant interviews (KIIs). Nurses, midwives, and barangay health workers provided data during focus group discussions (FGDs).</p

Study sites and participants.

<p>Key informant interviews were conducted with the National STH Coordinator, the Regional STH Coordinator and four local municipal health officers from Baguio City and Cavite. Focus group discussions with nurses, midwives, and barangay healthcare workers were conducted at each of the local health units along with Knowledge, Attitudes, and Practices surveys of women of reproductive age.</p

Soil-transmitted helminth (STH) knowledge score, by willingness to take deworming medication while pregnant.

<p>The Mann-Whitney U Test was used to compare the mean knowledge scale scores to the “yes/no” responses to the question, “Would you be willing to take deworming medication while pregnant?” The 54 women who were willing to take deworming medications while pregnant had a greater knowledge of treatment methods and potential birth defects than the 172 women who were not willing to take deworming medications while pregnant.</p

Willingness to take deworming medication while pregnant, by perceived medication side effects.

<p>The chi square test was used to compare the “yes/no” response to the question, “Would you take deworming while pregnant?” to their perception of side effect frequency, potential fetal harm, and potential maternal harm. A negative response includes no, unsure, and no response. Women who were not willing to take deworming medications while pregnant were more likely to believe that anthelminthics commonly cause adverse effects including maternal-fetal harm.</p