The mode of action of antimalarial endoperoxides

The mechanism of action of artemisinin appears to involve two steps. In the first step, activation, intra-parasitic iron catalyses the cleavage of the endoperoxide bridge and the generation of free radicals. In the second step, alkylation, the artemisinin-derived free radical forms covalent bonds with parasite proteins.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/31511/1/0000433.pd

The interaction of artemisinin with malarial hemozoin

[14C]Artemisinin was taken up by Plasmodium falciparum in culture and concentrated in hemozoin. In vitro, hemin and artemisinin were found to undergo a chemical reaction forming two major products which were isolated by high-performance liquid chromatography (HPLC). The m/z values of the two products were 856 and 871. Thin-layer chromatography (TLC) and HPLC of hemozoin isolated from [14C]artemisinin-treated parasites showed that the majority of the hemozoin-associated radioactivity comigrated with the synthetic adducts. When [14C]artemisinin was incubated with isolated hemozoin, [14C]artemisinin disappeared from the solution in a time-dependent manner. Some of the radioactivity present in the treated hemozoin also comigrated with the adducts on TLC. Thus, artemisinin appears to react covalently with heme in malaria hemozoin both in vitro and in situ.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/31892/1/0000844.pd

An overview of malaria in pregnancy

One hundred twenty-five million pregnant women are at risk for contracting malaria, a preventable cause of maternal and infant morbidity and death. Malaria parasites contribute to adverse pregnancy and birth outcomes due to their preferential accumulation in placental intervillous spaces. Pregnant women are particularly vulnerable to malaria infections, and malaria infections during pregnancy put their fetuses at risk. Malaria in pregnancy is associated with anemia, stillbirth, low birth weight and maternal and fetal death. We review the challenges to diagnosing malaria in pregnancy, as well as strategies to prevent and treat malaria in pregnancy. Finally, we discuss the current gaps in knowledge and potential areas for continued research

The effectiveness of community bed net use on malaria parasitemia among children less than 5 years old in Liberia

In 2013, the under-5 mortality rate in Liberia was 71 deaths per 1,000 live births, with malaria responsible for 22% of those deaths. One of the primary existing control tools, long-lasting insecticide-treated bed nets (LLINs), is thought to be dually effective, acting as a physical barrier but also decreasing the mosquito population in communities. However, there has been little investigation into the protective effects of community-wide bed net use above and beyond the individual level. Using data from the population-representative 2011 Liberia Malaria Indicator Survey, we estimated the association between proportion of a community using LLINs and malaria in children using multi-level logistic regression. To investigate the potential effect measure modification of the relationship by urbanicity, we included an interaction term and calculated stratum-specific prevalence odds ratios (PORs) for rural and urban communities. We calculated a POR of malaria for an absolute 10% increase in community bed net use of 1.13 (95% confidence interval [CI]: 0.91, 1.41) and 0.35 (95% CI: 0.13, 0.92) for rural and urban communities, respectively, indicating a strong, though imprecise, protective effect within urban communities only. Our results indicate that bed net use has an indirect protective effect in urban areas, above and beyond individual use. Little or no such effect of community-wide use is seen in rural areas, likely because of population density factors. Therefore, although all control efforts should be multifaceted, promotion of bed net use in urban areas in particular will likely be a highly effective tool for control

Duration of Effectiveness of Permethrin-Treated Clothing to Prevent Mosquito Bites Under Simulated Conditions

Presented for World Environmental Health Day, September 26, 2016 in Greenville, North Carolina.Biological hazards such as exposure to ticks and mosquitoes can affect worker health. Permethrin is a repellant/insecticide approved for human use by the Environmental Protection Agency. Permethrin-treated clothing is commercially available to the public. Permethrin-treated clothing (50% cotton/50% nylon) has been shown to retain repellency through 70 washings. Work attire differs between state and consulting foresters, park rangers, etc.; hence, variation in protection from vector borne disease may existThis study was funded by the Southeast Center for Agricultural Health and Injury Prevention (# 3049025288-14-060)

Evaluation of Sulfa Drugs against Recombinant Pneumocystis carinii Dihydropteroate Synthetase and In vivo

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74851/1/j.1550-7408.1996.tb04976.x.pd

Sulfa Resistance in Mouse-Derived Pneumocystis carinii

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74674/1/j.1550-7408.1996.tb04975.x.pd

Development and Validation of an Improved PCR Method Using the 23S-5S Intergenic Spacer for Detection of Rickettsiae in Dermacentor variabilis Ticks and Tissue Samples from Humans and Laboratory Animals

A novel nested PCR assay was developed to detect Rickettsia spp. in ticks and tissue samples from humans and laboratory animals. Primers were designed for the nested run to amplify a variable region of the 23S-5S intergenic spacer (IGS) of Rickettsia spp. The newly designed primers were evaluated using genomic DNA from 11 Rickettsia species belonging to the spotted fever, typhus, and ancestral groups and, in parallel, compared to other Rickettsia -specific PCR targets ( ompA , gltA , and the 17-kDa protein gene). The new 23S-5S IGS nested PCR assay amplified all 11 Rickettsia spp., but the assays employing other PCR targets did not. The novel nested assay was sensitive enough to detect one copy of a cloned 23S-5S IGS fragment from “ Candidatus Rickettsia amblyommii.” Subsequently, the detection efficiency of the 23S-5S IGS nested assay was compared to those of the other three assays using genomic DNA extracted from 40 adult Dermacentor variabilis ticks. The nested 23S-5S IGS assay detected Rickettsia DNA in 45% of the ticks, while the amplification rates of the other three assays ranged between 5 and 20%. The novel PCR assay was validated using clinical samples from humans and laboratory animals that were known to be infected with pathogenic species of Rickettsia . The nested 23S-5S IGS PCR assay was coupled with reverse line blot hybridization with species-specific probes for high-throughput detection and simultaneous identification of the species of Rickettsia in the ticks. “ Candidatus Rickettsia amblyommii,” R. montanensis , R. felis , and R. bellii were frequently identified species, along with some potentially novel Rickettsia strains that were closely related to R. bellii and R. conorii

Cost-Effectiveness of Adding Bed Net Distribution for Malaria Prevention to Antenatal Services in Kinshasa, Democratic Republic of the Congo

We evaluated the cost-effectiveness of distributing insecticide-treated bed nets (ITNs) for malaria prevention at antenatal clinics in Kinshasa, Democratic Republic of the Congo. A decision tree model was used to estimate costs, outcomes, and incremental cost-effectiveness for 17,893 pregnant women attending 28 antenatal clinics who received long-lasting ITNs free of charge. Costs including purchase, transportation, storage, and distribution of ITNs were derived from program records. The ITN efficacy and other parameters were derived from peer-reviewed literature. Outcomes modeled included low birth weight (LBW) deliveries, infant deaths averted, life-years saved (LYs), and disability-adjusted life-years (DALYs) averted. Deterministic and probabilistic sensitivity analyses were conducted. For the 17,893 women in our program, ITN distribution would be expected to avert 587 LBW deliveries and 414 infant deaths. The incremental cost-effectiveness was US $17.22 per DALY averted (95$8.54-$30.90), US$15.70 per LY saved (95% CI = US $7.65-$27.68), and US $411.13 per infant death averted (95$353.95-$1,085.89). If resources were constrained, the greatest benefit would be among women in their first through fourth pregnancies. Thus, ITN distribution is a cost-effective addition to antenatal services