Plasmodium falciparum is responsible for the most severe form of malaria disease in humans, causing more than 1 million deaths each year. As an obligate intracellular parasite, P. falciparum's ability to invade erythrocytes is essential for its survival within the human host. P. falciparum invades erythrocytes using multiple host receptor-parasite ligand interactions known as invasion pathways. Here we show that CR1 is the host erythrocyte receptor for PfRh4, a major P. falciparum ligand essential for sialic acid-independent invasion. PfRh4 and CR1 interact directly, with a K d of 2.9 μM. PfRh4 binding is strongly correlated with the CR1 level on the erythrocyte surface. Parasite invasion via sialic acid-independent pathways is reduced in low-CR1 erythrocytes due to limited availability of this receptor on the surface. Furthermore, soluble CR1 can competitively block binding of PfRh4 to the erythrocyte surface and specifically inhibit sialic acid-independent parasite invasion. These results demonstrate that CR1 is an erythrocyte receptor used by the parasite ligand PfRh4 for P. falciparum invasion.malaria | red blood cell | merozoite | reticulocyte-binding-like homologue
The study was carried out to estimate the prevalence of self-medication with antibiotics among tertiary level students in Accra (Ghana) and evaluate factors associated with the practice. This was a descriptive cross-sectional study and involved face-to-face interviews of 600 respondents selected by convenient sampling. Prevalence of self medication was 70% (95% CI: 66.3–73.7), and the practice was significantly lower among medically inclined students (OR: 0.2, 95% CI: 0.1–0.4, p < 0.001). Among the respondents who practiced self medication, the most common frequency of antibiotic usage was at intervals of one month (30%, 95% CI: 25.6–34.4%), and the most common antibiotic used was amoxacillin (23.9%, 95% CI: 21.0–26.8%). Treatment failure were reported by 35% (95% CI: 30.5–39.6%) of the respondents, and the main reasons cited for self medication were that, it was less expensive compared to medical care in the hospital and secondly, medical care in hospitals were associated with long delays. Forty nine percent (95% CI: 44.2–53.8%) of the respondents had poor knowledge about the health implications of irrational use of antibiotics, and 46% (95% CI: 41.2–50.8%) did not comply with the completion of the full course of antibiotics. Self medication among tertiary students in Accra is an important public health problem and this may reflect the situation among tertiary students in the whole of Ghana.
BackgroundConsuming raw vegetables offers essential nutrients that one may not get when such vegetables are usually cooked. However, eating them raw may pose a great risk for transmissions of pathogens. Such risks may be influenced by the sources of the vegetables and washing techniques used. The aim of the study was to compare the prevalence and diversity of parasitic pathogens associated with vegetables sold at the two types of markets in Ghana and compare effectiveness of various washing techniques.MethodsWe purchased two batches of samples of cabbage, sweet bell pepper, carrot, lettuce, tomato and onion within a two week interval. The vegetables were washed by three methods and the wash solution was concentrated and analyzed for parasites.ResultsThe prevalent parasites detected were Strongyloides stercoralis larvae (43%) and Cryptosporidium parvum oocyst (16%). Others present were Hookworm ova, Entamoeba histolytica cysts, Giardia lamblia cysts, Cyclospora cayetanensis oocysts, Entamoeba coli cysts, Trichuris trichiuria ova, Enterobius vermicularis ova, Isospora belli oocysts and Fasciolopsis buski ova. Contamination was highest in lettuce (61%) and cabbage and the least contaminated was tomato (18%). Contamination of vegetables sold at the open-aired markets was about ten-times that of the supermarkets.ConclusionsIn Ghana, the large open-aired markets are the most patronized and serve as a supply point for most corner shops and stalls. The results thus highlight the potential of fresh vegetables serving as a major source of food-borne disease outbreaks and the contribution of open-aired markets to their transmission. Urgent public education on handling of fresh vegetables is recommended.
The Plasmodium falciparum adhesin PfRh4 binds to complement receptor type-1 (CR1) on human erythrocytes and mediates a glycophorin-independent invasion pathway. CR1 is a complement regulator and immune-adherence receptor on erythrocytes required for shuttling of C3b/ C4b-opsonized particles to liver and spleen for phagocytosis. Using recombinant CR1 constructs, we mapped the recognition site for PfRh4 to complement control protein modules 1 to 3 (CCP1-3) at the membrane-distal amino terminus of CR1. This region of CR1 binds to C4b and C3b and accelerates decay of both classic pathway and alternative pathway C3 and C5 convertases. CCP1-3 competed for PfRh4 binding to erythroid CR1 and inhibited the PfRh4-CR1 invasion pathways across a wide range of P falciparum strains. PfRh4 did not bind significantly to other CR1 constructs, including CCP15-17, which is 85% identical to CCP1-3. PfRh4 binding to CR1 did not affect its C3b/C4b binding capability, and we show evidence for a ternary complex between CCP1-3, C4b, and PfRh4. PfRh4 binding specifically inhibited CR1's convertase decay-accelerating activity, whereas there was no effect on factor H-mediated decay-accelerating activity. These results increase our understanding of the functional implications of CR1 engagement with PfRh4 and highlight the interplay between complement regulation and infection. (Blood. 2011; 118(7): [1923][1924][1925][1926][1927][1928][1929][1930][1931][1932][1933] IntroductionThe complement system is a first line of defense against invasion by infectious agents. On pathogen entry into the host and detection of a pathogen-associated or danger-associated molecular pattern, the complement cascade is activated in seconds and results in the production of anaphylatoxins, deposition of opsonic C3 and C4 fragments, and assembly of the potentially cytolytic membrane attack complex. By ensuring that the complement system acts in a directed manner, the regulators of complement activation (RCA) protein family protect self-tissue from complement-mediated attack. 1 Interestingly, RCA family members also contribute to cell attachment or invasion strategies of disparate pathogens, including multiple viruses and bacteria. [2][3][4][5][6] Recently, complement receptor type-1 (CR1), an erythroid membrane-bound RCA protein, was shown to be a receptor used by the malaria parasite Plasmodium falciparum for invasion of human erythrocytes. 7,8 Invasion of human erythrocytes by malaria parasites depends on specific interactions between parasite adhesins and host receptors. In P falciparum, 2 gene families encode important parasite proteins that engage with erythrocyte receptors: the erythrocyte binding-like antigens (PfEBAs; these include EBA-140/BAEBL, EBA-175, EBA-181/JESEBL, and EBL-1); and reticulocyte binding-like homolog proteins (RBPs or PfRhs; these include PfRh1, PfRh2a, PfRh2b, PfRh4 and PfRh5). 9-12 During invasion these adhesins localize to the apical tip of the merozoite and interact with specific host receptors to initiate parasite entry. Invasion pat...
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