Unique Properties of Apicomplexan Mitochondria.

Apicomplexan parasites constitute more than 6,000 species infecting a wide range of hosts. These include important pathogens such as those causing malaria and toxoplasmosis. Their evolutionary emergence coincided with the dawn of animals. Mitochondrial genomes of apicomplexan parasites have undergone dramatic reduction in their coding capacity, with genes for only three proteins and ribosomal RNA genes present in scrambled fragments originating from both strands. Different branches of the apicomplexans have undergone rearrangements of these genes, with Toxoplasma having massive variations in gene arrangements spread over multiple copies. The vast evolutionary distance between the parasite and the host mitochondria has been exploited for the development of antiparasitic drugs, especially those used to treat malaria, wherein inhibition of the parasite mitochondrial respiratory chain is selectively targeted with little toxicity to the host mitochondria. We describe additional unique characteristics of the parasite mitochondria that are being investigated and provide greater insights into these deep-branching eukaryotic pathogens.

X-ray Structure Determination, Antioxidant Voltammetry Studies of Butein and 2',4'-Dihydroxy-3,4-dimethoxychalcone. Computational Studies of 4 Structurally Related 2',4'-diOH Chalcones to Examine Their Antimalarial Activity by Binding to Falcipain-2.

Malaria is a huge global health burden with resistance to currently available medicines resulting in the search for newer antimalarial compounds from traditional medicinal plants in malaria-endemic regions. Previous studies on two chalcones, homobutein and 5-prenylbutein, present in E. abyssinica, have shown moderate antiplasmodial activity. Here, we describe results from experimental and computational investigations of four structurally related chalcones, butein, 2',4'-dihydroxy-3,4-dimethoxychalcone (DHDM), homobutein and 5-prenylbutein to elucidate possible molecular mechanisms by which these compounds clear malaria parasites. The crystal structures of butein and DHDM show that butein engages in more hydrogen bonding and consequently, more intermolecular interactions than DHDM. Rotating ring-disk electrode (RRDE) voltammetry results show that butein has a higher antioxidant activity towards the superoxide radical anion compared to DHDM. Computational docking experiments were conducted to examine the inhibitory potential of all four compounds on falcipain-2, a cysteine protease that is involved in the degradation of hemoglobin in plasmodium-infected red blood cells of the host. Overall, this work suggests butein as a better antimalarial compound due to its structural features which allow it to have greater intermolecular interactions, higher antioxidant activity and to create a covalent complex at the active site of falcipain-2.

Compliance with intermittent presumptive treatment and insecticide treated nets use during pregnancy in Enugu State, Nigeria.

To identify key socio-demographic and knowledge factors associated with compliance with recommended use of commodities for preventing malaria in pregnancy (MIP) in Enugu State, Nigeria. Cross-sectional study of 720 women who delivered within 6 months preceding the survey in three local government areas in Enugu State was conducted using a structured questionnaire. About half (51.6%) of the women used IPTp1 while 25.9% took IPTp2 as recommended during their most recent pregnancy. Forty-one percent of the women slept under insecticide treat nets (ITN) during the most recent pregnancy but only 15.4% did so as recommended every night. Socio-demographic and knowledge factors associated with compliance were identified. Compliance with intermittent presumptive treatment in pregnancy (IPTp) recommendation was more common among those in the rural setting (26.9%) compared to the peri-urban (20.3%) and urban (17.3%) (P = 0.032). Those with good knowledge of the causes, effects and prevention of malaria during pregnancy complied more (23.7%) than those with poor knowledge (17.0%) (P = 0.020). With respect to sleeping under ITN, more of those with post secondary education, good knowledge of MIP and currently living with a partner used ITN every night during the last pregnancy. Knowledge about the MIP issues and having a partner influence compliance with relevant preventives. Efforts to increase compliance with recommended practices to prevent MIP should focus on providing health education to pregnant women and their partners, who reinforce what the women are told during antenatal care. More qualitative studies need to be conducted on this subject.

Prospects of using Community Directed Intervention strategy in delivering health services among Fulani Nomads in Enugu State, Nigeria.

BACKGROUND: The Community Directed Interventions (CDI) strategy has proven effective in increasing access to health services in sedentary populations. It remains to be seen if CDI strategy is feasible among nomads given the dearth of demographic and medical data on the nomads. This study thus characterized the nomadic populations in Enugu State, Nigeria and outlined the potentials of implementing CDI among nomads. STUDY DESIGN AND METHODS: This exploratory study adopted qualitative methods. Forty focus group discussions (FGD) were held with members of 10 nomadic camps in 2 LGAs in Enugu State, as well as their host communities. Thirty in-depth interviews (IDIs) were held with leaders of nomadic camps and sedentary populations. Ten IDIs with traditional healers in the nomadic camps and 14 key informant interviews with health workers and programme officers were also conducted. Documents and maps were reviewed to ascertain the grazing routes of the nomads as well as existing health interventions in the area. RESULTS: Like sedentary populations, nomads have definable community structures with leaders and followers, which is amenable to implementation of CDI. Nomads move their cattle, in a definite pattern, in search of grass and water. In this movement, the old and vulnerable are left in the camps. The nomads suffer from immunization preventable health problems as their host communities. The priority health problems in relation to CDI include malaria, measles, anemia, and other vaccine preventable infections. However, unlike the sedentary populations, the nomads lack access to health interventions, due to the mutual avoidance between the nomads and the sedentary populations in terms of health services. The later consider the services as mainly theirs. The nomads, however, are desirous of the modern health services and often task themselves to access these modern health services in private for profit health facilities when the need arises. CONCLUSION: Given the definable organizational structure of the nomads in Enugu State and their desire for modern health intervention, it is feasible to test the CDI strategy for equitable healthcare delivery among nomads. They are willing and capable to participate actively in their own health programmes with minimal support from professional health workers.