Cryptosporidium Priming Is More Effective than Vaccine for Protection against Cryptosporidiosis in a Murine Protein Malnutrition Model

Cryptosporidium is a major cause of severe diarrhea, especially in malnourished children. Using a murine model of C. parvum oocyst challenge that recapitulates clinical features of severe cryptosporidiosis during malnutrition, we interrogated the effect of protein malnutrition (PM) on primary and secondary responses to C. parvum challenge, and tested the differential ability of mucosal priming strategies to overcome the PM-induced susceptibility. We determined that while PM fundamentally alters systemic and mucosal primary immune responses to Cryptosporidium, priming with C. parvum (106 oocysts) provides robust protective immunity against re-challenge despite ongoing PM. C. parvum priming restores mucosal Th1-type effectors (CD3+CD8+CD103+ T-cells) and cytokines (IFNγ, and IL12p40) that otherwise decrease with ongoing PM. Vaccination strategies with Cryptosporidium antigens expressed in the S. Typhi vector 908htr, however, do not enhance Th1-type responses to C. parvum challenge during PM, even though vaccination strongly boosts immunity in challenged fully nourished hosts. Remote non-specific exposures to the attenuated S. Typhi vector alone or the TLR9 agonist CpG ODN-1668 can partially attenuate C. parvum severity during PM, but neither as effectively as viable C. parvum priming. We conclude that although PM interferes with basal and vaccine-boosted immune responses to C. parvum, sustained reductions in disease severity are possible through mucosal activators of host defenses, and specifically C. parvum priming can elicit impressively robust Th1-type protective immunity despite ongoing protein malnutrition. These findings add insight into potential correlates of Cryptosporidium immunity and future vaccine strategies in malnourished children

Excessive alcohol consumption increases risk taking behaviour in travellers to Cusco, Peru

The risks associated with alcohol intoxication are rarely discussed during pre-travel counselling. However, alcohol immoderation abroad may increase the exposure to health risks. Few studies have addressed alcohol consumption and risk taking behaviour in travellers to South America. From October to December of 2004, travellers leaving the city of Cusco in Peru were asked to fill out anonymous questionnaires regarding demographics, self-reported alcohol consumption, illness and risk behaviour for sexually-transmitted infection (STI) and travellers diarrhoea. Most travellers (87.2%) consumed alcohol and 20.4% reported inebriation in Cusco. Those admitting inebriation were more likely to be male, single, <26 years old, and travelling alone or with friends. Travellers who admitted inebriation and fell ill while in Cusco were more likely to seek medical attention, change itinerary, and report decreased satisfaction with the trip experience. In the multivariate analysis, inebriation was independently associated with reporting higher numbers of unsafe food choices, illicit drug use, and risky sexual activity. It is concluded that alcohol intoxication during travel was associated with increased risk taking behaviour for common travel related conditions. Although travel related illnesses were not associated with inebriation, some markers of illness severity were more often reported by those who admitted intoxication. Risk for heavy alcohol use abroad should be assessed during the pre-travel visit in certain groups and appropriate counselling should be provided