Fasciola hepatica calcium-binding protein FhCaBP2: structure of the dynein light chain-like domain

The common liver fluke Fasciola hepatica causes an increasing burden on human and animal health, partly because of the spread of drug-resistant isolates. As a consequence, there is considerable interest in developing new drugs to combat liver fluke infections. A group of potential targets is a family of calcium-binding proteins which combine an N-terminal domain with two EF-hand motifs and a C-terminal domain with predicted similarity to dynein light chains (DLC-like domain)

Epidemiology and Molecular Relationships of Cryptosporidium spp. in People, Primates, and Livestock from Western Uganda

Cryptosporidium is a common gastrointestinal parasite known for its zoonotic potential. We found Cryptosporidium in 32.4% of people, 11.1% of non-human primates, and 2.2% of livestock in the region of Kibale National Park, Uganda. In people, infection rates were higher in one community than elsewhere, and fetching water from an open water source increased the probability of infection. Phylogenetic analyses identified clusters of Cryptosporidium with mixed host origins in people, primates, and livestock outside the park; however, parasites from primates inside the park were genetically divergent, suggesting a separate sylvatic transmission cycle. Infection was not associated with clinical disease in people, even in the case of co-infection with the gastrointestinal parasite Giardia duodenalis. Parasites such as Cryptosporidium may be maintained through frequent cross-species transmission in tropical settings where people, livestock, and wildlife interact frequently, but the parasite may undergo more host-specific transmission where such interactions do not occur. Persistent low-level shedding and immunity may limit the clinical effects of infection in such settings

Travel risk behaviours and uptake of pre-travel health preventions by university students in Australia

<p>Abstract</p> <p>Background</p> <p>Forward planning and preventative measures before travelling can significantly reduce the risk of many vaccine preventable travel-related infectious diseases. Higher education students may be at an increased risk of importing infectious disease as many undertake multiple visits to regions with higher infectious disease endemicity. Little is known about the health behaviours of domestic or international university students, particularly students from low resource countries who travel to high-resource countries for education. This study aimed to assess travel-associated health risks and preventative behaviours in a sample of both domestic and international university students in Australia.</p> <p>Methods</p> <p>In 2010, a 28 item self-administered online survey was distributed to students enrolled at the University of New South Wales, Sydney, Australia. Multiple methods of distributing links to the online survey were utilised. The survey examined the international travel history, travel intentions, infection control behaviours and self-reported vaccination history.</p> <p>Results</p> <p>A total of 1663 respondents completed the online survey, 22.1% were international students and 83.9% were enrolled at an undergraduate level. Half had travelled internationally in the previous 12 months, with 69% of those travelling only once during that time with no difference in travel from Australia between domestic and international students (<it>p </it>= 0.8). Uptake of pre-travel health advice was low overall with 68% of respondents reporting they had not sought any advice from a health professional prior to their last international trip. Domestic students were more likely to report uptake of a range of preventative travel health measures compared to international students, including diarrhoeal medication, insect repellent, food avoidance and condoms (<it>P </it>< 0.0001). Overall, students reported low risk perception of travel threats and a low corresponding concern for these threats.</p> <p>Conclusions</p> <p>Our study highlights the need to educate students about the risk associated with travel and improve preventative health-seeking and uptake of precautionary health measures in this highly mobile young adult population. Although immunisation is not an entry requirement to study at Universities in Australia, large tertiary institutions provide an opportunity to engage with young adults on the importance of travel health and provision of vaccines required for travel, including missed childhood vaccines.</p

The Cryptosporidium parvum Kinome

<p>Abstract</p> <p>Background</p> <p>Hundreds of millions of people are infected with cryptosporidiosis annually, with immunocompromised individuals suffering debilitating symptoms and children in socioeconomically challenged regions at risk of repeated infections. There is currently no effective drug available. In order to facilitate the pursuit of anti-cryptosporidiosis targets and compounds, our study spans the classification of the <it>Cryptosporidium parvum </it>kinome and the structural and biochemical characterization of representatives from the CDPK family and a MAP kinase.</p> <p>Results</p> <p>The <it>C</it>. <it>parvum </it>kinome comprises over 70 members, some of which may be promising drug targets. These <it>C. parvum </it>protein kinases include members in the AGC, Atypical, CaMK, CK1, CMGC, and TKL groups; however, almost 35% could only be classified as OPK (other protein kinases). In addition, about 25% of the kinases identified did not have any known orthologues outside of <it>Cryptosporidium spp</it>. Comparison of specific kinases with their <it>Plasmodium falciparum </it>and <it>Toxoplasma gondii </it>orthologues revealed some distinct characteristics within the <it>C. parvum </it>kinome, including potential targets and opportunities for drug design. Structural and biochemical analysis of 4 representatives of the CaMK group and a MAP kinase confirms features that may be exploited in inhibitor design. Indeed, screening <it>Cp</it>CDPK1 against a library of kinase inhibitors yielded a set of the pyrazolopyrimidine derivatives (PP1-derivatives) with IC₅₀values of < 10 nM. The binding of a PP1-derivative is further described by an inhibitor-bound crystal structure of <it>Cp</it>CDPK1. In addition, structural analysis of <it>Cp</it>CDPK4 identified an unprecedented Zn-finger within the CDPK kinase domain that may have implications for its regulation.</p> <p>Conclusions</p> <p>Identification and comparison of the <it>C. parvum </it>protein kinases against other parasitic kinases shows how orthologue- and family-based research can be used to facilitate characterization of promising drug targets and the search for new drugs.</p

Travelers' health problems and behavior : prospective study with post-travel follow-up

Background: The annual number of international tourist arrivals has recently exceeded one billion, yet surprisingly few studies have characterized travelers' behavior, illness, and risk factors in a prospective setting. Particularly scarce are surveys of data spanning travel, return, and follow-up of the same cohort. This study examines behavior and illness among travelers while abroad, after return home, and at follow-up. Patterns of behavior connected to type of travel and illness are characterized so as to identify risk factors and provide background data for pre-travel advice. Methods: Volunteers to this prospective cohort study were recruited at visits to a travel clinic prior to departure. Data on the subjects' health and behavior were collected by questionnaires before and after journeys and over a three-week follow-up. In addition, the subjects were asked to fill in health diaries while traveling. Results: The final study population consisted of 460 subjects, 79 % of whom reported illness during travel or on arrival: 69 % had travelers' diarrhea (TD), 17 % skin problems, 17 % fever, 12 % vomiting, 8 % respiratory tract infection, 4 % urinary tract infection, 2 % ear infection, 4 % gastrointestinal complaints other than TD or vomiting, and 4 % other symptoms. Of all subjects, 10 % consulted a doctor and 0.7 % were hospitalized; 18 % took antimicrobials, with TD as the most common indication (64 %). Ongoing symptoms were reported by 25 % of all travelers upon return home. During the three-week follow-up (return rate 51 %), 32 % of respondents developed new-onset symptoms, 20 % visited a doctor and 1.7 % were hospitalized. Factors predisposing to health problems were identified by multivariable analysis: certain regions (Southern Asia, South-Eastern Asia, and Eastern Africa), female gender, young age, and long travel duration. Conclusions: Despite proper preventive measures like vaccinations, malaria prophylaxis, and travel advice, the majority of our subjects fell ill during or after travel. As the symptoms mostly remained mild, health care services were seldom needed. Typical traveler profiles were identified, thereby providing a tool for pre-travel advice. The finding that one third reported new-onset illness during follow-up attests to the importance of advising clients on potential post-travel health problems already during pre-travel visits.Peer reviewe