Dataset Information

Host immune response in returning travellers infected with malaria.

ABSTRACT:

Background

Clinical observations suggest that Canadian-born (CB) travellers are prone to more severe malaria, characterized by higher parasite density in the blood, and severe symptoms, such as cerebral malaria and renal failure, than foreign-born travellers (FB) from areas of malaria endemicity. It was hypothesized that host cytokine and chemokine responses differ significantly in CB versus FB patients returning with malaria, contributing to the courses of severity. A more detailed understanding of the profiles of cytokines, chemokines, and endothelial activation may be useful in developing biomarkers and novel therapeutic approaches for malaria.

Materials and methods

The patient population for the study (n = 186) was comprised of travellers returning to Toronto, Canada between 2007 and 2011. The patient blood samples' cytokine, chemokine and angiopoietin concentrations were determined using cytokine multiplex assays, and ELISA assays.

Results

Significantly higher plasma cytokine levels of IL-12 (p40) were observed in CB compared to FB travellers, while epidermal growth factor (EGF) was observed to be higher in FB than CB travellers. Older travellers (55 years old or greater) with Plasmodium vivax infections had significantly higher mean cytokine levels for IL-6 and macrophage colony-stimulating factor (M-CSF) than other adults with P. vivax (ages 18-55). Patients with P. vivax infections had significantly higher mean cytokine levels for monocyte chemotactic protein-1 (MCP-1), and M-CSF than patients with Plasmodium falciparum. Angiopoietin 2 (Ang-2) was higher for patients infected with P. falciparum than P. vivax, especially when comparing just the FB groups. IL-12 (p40) was higher in FB patients with P. vivax compared to P. falciparum. Il-12 (p40) was also higher in patients infected with P. vivax than those infected with Plasmodium ovale. For patients travelling to West Africa, IFN-γ and IL-6 was lower than for patients who were in other regions of Africa.

Conclusion

Significantly higher levels of IL-12 (p40) and lower levels of EGF in CB travellers may serve as useful prognostic markers of disease severity and help guide clinical management upon return. IL-6 and M-CSF in older adults and MCP-1, IL-12 (p40) and M-CSF for P. vivax infected patients may also prove useful in understanding age-associated and species-specific host immune responses, as could the species-specific differences in Ang-2. Regional differences in host immune response to malaria infection within the same species may speak to unique strains circulating in parts of West Africa.

SUBMITTER: MacMullin G

PROVIDER: S-EPMC3586951 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Malaria remains the most common specific cause of fever in returned travellers and can be life-threatening. We examined demographic and travel correlates of malaria among Canadian travellers and immigrants to identify groups for targeted pretravel intervention.Descriptive data on ill returned Canadian travellers and immigrants presenting to a CanTravNet site between 2004 and 2014 with a diagnosis of malaria were analyzed. Data were collected using the GeoSentinel data platform. This network comprises 63 specialized travel and tropical medicine clinics, including 7 Canadian sites (Vancouver, Calgary, Toronto, Ottawa, Winnipeg and Montréal), that contribute anonymous, delinked, clinician- and questionnaire-based travel surveillance data on all ill travellers examined to a centralized Structure Query Language database.During the study period, 20?345 travellers and immigrants were evaluated, and 93% had a travel-related diagnosis. Of these, 437 (2.1%) patients received 456 malaria diagnoses, the most common species being Plasmodium falciparum (n = 282, 61.8%). People travelling to visit friends and relatives were most well-represented (n = 169, 38.7%), followed by business travellers (n = 71, 16.2%). Sub-Saharan Africa was the most common source region, accounting for 341 (74.8%) malaria diagnoses, followed by South Central Asia (n = 55, 12%). Nigeria was the most well-represented source country, accounting for 41 cases (9.0%). India, a high-volume destination for Canadians, accounted for 40 cases (8.8%), 36 of which were caused by Plasmodium vivax. Of 456 malaria diagnoses, 26 (5.7%) were severe. Of 377 nonimmigrant travellers with malaria, 19.9% (n = 75) travelled for less than 2 weeks, and 7.2% (n = 27) travelled for less than 1 week.This analysis provides an epidemiologic framework for Canadian practitioners encountering prospective and returned travellers. It confirms the importance of preventive measures and surveillance associated with travel to sub-Saharan Africa and India, particularly by travellers visiting friends or relatives. Short-duration travel confers important malaria risk.

Project description:Objectives(1) To understand the experiences and perceptions of those who underwent supported isolation, particularly in relation to factors that were associated with improved compliance and well-being; (2) to inform recommendations for the management of similar supported isolation procedures.DesignWe carried out a qualitative study using semistructured interviews to capture participants' experiences and perceptions of supported isolation. Data were analysed using the framework approach, a type of thematic analysis that is commonly used in research that has implications for policy.SettingTelephone interviews carried out within approximately 1 month of an individual leaving supported isolation.Participants26 people who underwent supported isolation at either Arrowe Park Hospital (n=18) or Kents Hill Park Conference Centre (n=8) after being repatriated from Wuhan in January to February 2020.ResultsSix key themes were identified: factors affecting compliance with supported isolation; risk perceptions around catching COVID-19; management of supported isolation; communication with those outside supported isolation; relationship with others in supported isolation; and feelings on leaving supported isolation. Participants were willing to undergo supported isolation because they understood that it would protect themselves and others. Positive treatment by staff was fundamental to participants' willingness to comply with isolation procedures. Despite the high level of compliance, participants expressed some uncertainty about what the process would involve.ConclusionsAs hotel quarantine is introduced across the UK for international arrivals, our findings suggest that those in charge should: communicate effectively before, during and after quarantine, emphasising why quarantine is important and how it will protect others; avoid coercion if possible and focus on supporting and promoting voluntary compliance; facilitate shared social experiences for those in quarantine; and ensure all necessary supplies are provided. Doing so is likely to increase adherence and reduce any negative effects on well-being.

Project description:BackgroundLeishmaniasis is increasingly reported among travellers. Leishmania species vary in sensitivity to available therapies. Fast and reliable molecular techniques have made species-directed treatment feasible. Many treatment trials have been designed poorly, thus developing evidence-based guidelines for species-directed treatment is difficult. Published guidelines on leishmaniasis in travellers do not aim to be comprehensive or do not quantify overall treatment success for available therapies. We aimed at providing comprehensive species-directed treatment guidelines.Methodology/principal findingsEnglish literature was searched using PubMed. Trials and observational studies were included if all cases were parasitologically confirmed, the Leishmania species was known, clear clinical end-points and time points for evaluation of treatment success were defined, duration of follow-up was adequate and loss to follow-up was acceptable. The proportion of successful treatment responses was pooled using mixed effects methods to estimate the efficacy of specific therapies. Final ranking of treatment options was done by an expert panel based on pooled efficacy estimates and practical considerations. 168 studies were included, with 287 treatment arms. Based on Leishmania species, symptoms and geography, 25 clinical categories were defined and therapy options ranked. In 12/25 categories, proposed treatment agreed with highest efficacy data from literature. For 5/25 categories no literature was found, and in 8/25 categories treatment advise differed from literature evidence. For uncomplicated cutaneous leishmaniasis, combination of intralesional antimony with cryotherapy is advised, except for L. guyanensis and L. braziliensis infections, for which systemic treatment is preferred. Treatment of complicated (muco)cutaneous leishmaniasis differs per species. For visceral leishmaniasis, liposomal amphotericin B is treatment of choice.Conclusions/significanceOur study highlights current knowledge about species-directed therapy of leishmaniasis in returning travellers and also demonstrates lack of evidence for treatment of several clinical categories. New data can easily be incorporated in the presented overview. Updates will be of use for clinical decision making and for defining further research.

Project description:The two main agents of human malaria, Plasmodium vivax and Plasmodium falciparum, can induce severe anemia and provoke strong, complex immune reactions. Which dynamical behaviors of host immune and erythropoietic responses would foster control of infection, and which would lead to runaway parasitemia and/or severe anemia? To answer these questions, we developed differential equation models of interacting parasite and red blood cell (RBC) populations modulated by host immune and erythropoietic responses. The model immune responses incorporate both a rapidly responding innate component and a slower-responding, long-term antibody component, with several parasite developmental stages considered as targets for each type of immune response. We found that simulated infections with the highest parasitemia tended to be those with ineffective innate immunity even if antibodies were present. We also compared infections with dyserythropoiesis (reduced RBC production during infection) to those with compensatory erythropoiesis (boosted RBC production) or a fixed basal RBC production rate. Dyserythropoiesis tended to reduce parasitemia slightly but at a cost to the host of aggravating anemia. On the other hand, compensatory erythropoiesis tended to reduce the severity of anemia but with enhanced parasitemia if the innate response was ineffective. For both parasite species, sharp transitions between the schizont and the merozoite stages of development (i.e., with standard deviation in intra-RBC development time <or=2.4 h) were associated with lower parasitemia and less severe anemia. Thus tight synchronization in asexual parasite development might help control parasitemia. Finally, our simulations suggest that P. vivax can induce severe anemia as readily as P. falciparum for the same type of immune response, though P. vivax attacks a much smaller subset of RBCs. Since most P. vivax infections are nonlethal (if debilitating) clinically, this suggests that P. falciparum adaptations for countering or evading immune responses are more effective than those of P. vivax.