Illness in Canadian travellers and migrants from Brazil: CanTravNet surveillance data, 2013-2016.

BACKGROUND: In light of the 2016 summer Olympic games it is anticipated that Canadian practitioners will require information about common illnesses that may affect travellers returning from Brazil. OBJECTIVE: To identify the demographic and travel correlates of illness among recent Canadian travellers and migrants from Brazil attending a network of travel health clinics across Canada. METHODS: Data was analyzed on returned Canadian travellers and migrants presenting to a CanTravNet site for care of an illness between June 2013 and June 2016. RESULTS: During the study period, 7,707 ill travellers and migrants presented to a CanTravNet site and 89 (0.01%) acquired their illness in Brazil. Tourists were most well represented (n=45, 50.6%), followed by those travelling to "visit friends and relatives" (n=14, 15.7%). The median age was 37 years (range <1-78 years), 49 travellers were men (55.1%) and 40 were women (44.9%). Of the 40 women, 26 (65%) were of childbearing age. Nine percent (n=8) of travellers were diagnosed with arboviruses including dengue (n=6), chikungunya (n=1) and Zika virus (n=1), while another 14.6% (n=13) presented for care of non-specific viral syndrome (n=7), non-specific febrile illness (n=1), peripheral neuropathy (n=1) and non-specific rash (n=4), which are four syndromes that may be indicative of Zika virus infection. Ill returned travellers to Brazil were more likely to present for care of arboviral or Zika-like illness than other ill returned travellers to South America (23.6 per 100 travellers versus 10.5 per 100 travellers, respectively [p=0.0024]). INTERPRETATION: An epidemiologic approach to illness among returned Canadian travellers to Brazil can inform Canadian practitioners encountering both prospective and returned travellers to the Olympic games. Analysis showed that vector-borne illnesses such as dengue are common and even in this small group of travellers, both chikungunya and Zika virus were represented. It is extremely important to educate travellers about mosquito-avoidance measures in advance of travel to Brazil.

Travel-acquired infections in Canada: CanTravNet 2011-2012.

BACKGROUND: Important gaps remain in our knowledge of the infectious diseases people acquire while travelling and the impact of pathogens imported by Canadian travellers. OBJECTIVE: To provide a surveillance update of illness in a cohort of returned Canadian travellers and new immigrants. METHODS: Data on returning Canadian travellers and new immigrants presenting to a CanTravNet site between September 2011 and September 2012 were extracted and analyzed by destination, presenting symptoms, common and emerging infectious diseases and disease severity. RESULTS: During the study period, 2283 travellers and immigrants presented to a CanTravNet site, 88% (N=2004) of whom were assigned a travel-related diagnosis. Top three destinations for non-immigrant travellers were India (N=132), Mexico (N=103) and Cuba (N=89). Fifty-one cases of malaria were imported by ill returned travellers during the study period, 60% (N=30) of which were Plasmodium falciparum infections. Individuals travelling to visit friends and relatives accounted for 83% of enteric fever cases (15/18) and 41% of malaria cases (21/51). The requirement for inpatient management was over-represented among those with malaria compared to those without malaria (25% versus 2.8%; p<0.0001) and those travelling to visit friends and relatives versus those travelling for other reasons (12.1% versus 2.4%; p<0.0001). Nine new cases of HIV were diagnosed among the cohort, as well as one case of acute hepatitis B. Emerging infections among travellers included hepatitis E virus (N=6), chikungunya fever (N=4) and cutaneous leishmaniasis (N=16). Common chief complaints included gastrointestinal (N=804), dermatologic (N=440) and fever (N=287). Common specific causes of chief complaint of fever in the cohort were malaria (N=47/51 total cases), dengue fever (14/18 total cases), enteric fever (14/17 total cases) and influenza and influenza-like illness (15/21 total cases). Animal bites were the tenth most common diagnosis among tourist travellers. INTERPRETATION: Our analysis of surveillance data on ill returned Canadian travellers provides a recent update to the spectrum of imported illness among travelling Canadians. Preventable travel-acquired illnesses and injuries in the cohort include malaria, enteric fever, HIV, hepatitis B, hepatitis A, influenza and animal bites. Strategies to improve uptake of preventive interventions such as malaria chemoprophylaxis, immunizations and arthropod/animal avoidance may be warranted.

Ongoing outbreak of an acute muscular Sarcocystis-like illness among travellers returning from Tioman Island, Malaysia, 2011-2012.

As of 4 November, 2012, 100 patients with an acute muscular Sarcocystis-like illness associated with travel to Tioman Island, Malaysia, have been identified. Thirty-five travelled there mostly during July and August 2011 and 65 mostly during July and August 2012, suggesting an ongoing outbreak. Epidemiological investigations are ongoing. Public health agencies and practicing clinicians should be aware of this rarely-reported disease in humans and consider it as differential diagnosis in travellers returning from Tioman Island.

Evaluation of the effectiveness of an international diploma course in tropical medicine.

BACKGROUND: Numerous impediments to conducting continuing education (CE) courses in remote sites, particularly those courses that take place in developing countries, can include challenges associated with planning, infrastructure, and financial risk. This study reports the effectiveness of a course planned in the United States and executed in Peru, the Gorgas Course in clinical tropical medicine. METHODS: A survey was conducted of participants who had completed the Gorgas Course as recently as 6 months and as long as 3 years earlier. The questionnaire sought to determine each participant's reason for participation, whether the course was instrumental in the participant's reaching the personal goal associated with participation, and whether the participant considered the course to be worth the time and money spent to enable participation. RESULTS: Forty-nine participants responded to the questionnaire, all of whom indicated that the Gorgas Course enabled achievement of the personal goal associated with participation. Fully 100% of course participants stated that participation was worth the time and monetary expenditure, most often citing their having access to patients with tropical diseases and the personal enrichment of living overseas as reasons the course was worth its high cost. FINDINGS: It is logistically and financially feasible to conduct CE courses in developing countries, provided that the organization in the planning country has strong, pre-established relationships with the host institution(s). Continued collaboration between planning partners and frequent, rigorous course evaluations are necessary to enable an international CE course to become a stable, continuous academic offering.

Genotyping TAP2 variants in North American Caucasians, Brazilians, and Africans.

The protein forms of transporter associated with antigen processing, subunit 2 (TAP2), differ either by amino acid substitutions (Thr374Ala, Ile379Val, Ile467Val, Thr565Ala, Val577Met, Cys651Arg, and Ala665Thr) or by a truncation (Gln687Stop) of 17 amino acid residues at the C-terminus. Nonsynonymous single nucleotide polymorphisms (N-SNPs) causing these amino acid variations except 577Val were detected in genomic DNA samples from North American Caucasians (n = 76), Brazilians (n = 148), Rwandans (n = 285), and Zambians (n = 117). Exclusive (100%) and nearly exclusive (>95%) linkage disequilibrium was seen with a number of N-SNPs. The average heterozygosity at any given dimorphic site ranged from 7.3% to 44.6%, and at least four N-SNPs showed clear population specificity. N-SNP combinations alone led to the identification of 16 relatively common alleles, which appeared to form at least three lineages. Further analyses of 101 cDNA samples from Brazilians detected nine expressed TAP2 alleles, four of which matched the official assignments. Genetic complexity at the TAP2 locus was further enhanced by two out of five synonymous SNPs (S-SNPs), especially the GGT386GGG (Gly) that had similar heterozygosity rates in Caucasians (28.9%), Rwandans (33.3%), and Zambians (33.3%). Overall, distribution of both synonymous and nonsynonymous SNPs in the various ethnic groups examined here conformed well to the Hardy-Weinberg equilibrium, and between 57.9% and 77.0% of subjects in each ethnic group were heterozygous with two TAP2 alleles predicted to differ by at least one amino acid residue. Such complexity of TAP2 polymorphisms, in the form of SNPs as well as alleles, is likely to complicate the analyses of disease associations and haplotype structures in the HLA class II region.

Effect of aggressive prolonged diethylcarbamazine therapy on circulating antigen levels in bancroftian filariasis.

BACKGROUND: Single dose diethylcarbamazine (DEC) as used in control programmes is effectively microfilaricidal for periods of up to a year or more but has incomplete ability to kill Wuchereria bancrofti adult parasites. These regimens can be effective in breaking transmission by suppression of circulating microfilariae available to mosquito vectors. Whether prolonged or aggressive therapy with DEC has a significant effect on adult worms, which may live up to 12 years or more, and is important in the context of the treatment of individual patients, is still incompletely understood. METHODS: In order to investigate the adulticidal effect of aggressive therapy, DEC was given at 6 mg/kg/day for 12-day courses at 0, 6, 12, and 18 months and Og4C3 antigenaemia followed over two years in 38 CAg + Brazilians in a W. bancrofti endemic area. RESULTS: At two year follow-up, the median level of antigenaemia was 21% of the pre-treatment value. 92% of individuals had antigen levels < 50% of pretreatment values, but only 26% had completely cleared antigenaemia. The clearance rate at 24 months was only 12% (3/26) in the asymptomatic CAg + patients but 58% (7/12) in those with clinical manifestations of filariasis. The latter individuals cleared significantly more antigen (median of 0% pretreatment antigenaemia vs. 26%; P=0.02) than asymptomatic but infected individuals. CONCLUSION: Aggressive repeated therapy with DEC alone is ineffective in consistently eradicating adult W. bancrofti, especially in infected but asymptomatic individuals. Prolonged courses of combination therapy with other antifilarial drugs should be investigated for treatment of individual patients with the means to pursue aggressive personal medical care.

Internet and computer-based resources for travel medicine practitioners.

The field of travel medicine is concerned primarily with ways to maintain the health of international travelers. Remaining current in this area requires up-to-date knowledge of global infectious diseases, patterns of drug resistance, advances in preventive measures, and public health regulations pertaining to the crossing of international borders. This review of off-line commercial databases and Internet sources will assist infectious disease consultants in accessing current reliable travel health information. Of the North American pretravel off-line databases, TRAVAX (United States) and The Medical Letter are the most comprehensive, whereas the Global Infectious Disease and Epidemiology Network is extraordinary in its provision of global infectious disease epidemiology for posttravel assessment. A total of 65 Web sites are listed within 9 categories, covering such areas as authoritative government travel health recommendations, commercially-oriented sites, and travel medicine listserv discussion groups. Even among reputable Web sites, contradictory information may be found that demands careful consideration by the clinician and by the traveling public.

TAPI polymorphisms in several human ethnic groups: characteristics, evolution, and genotyping strategies.

Genetic variations in the locus encoding the transporter associated with antigen processing, subunit 1 (TAP1), were systematically studied using samples from Caucasians, Africans, Brazilians, and compared with data from chimpanzees. PCR-amplified genomic sequences corresponding to the 11 exons were analyzed by single-strand conformation polymorphism (SSCP) and sequencing. Six nonsynonymous and 2 synonymous single nucleotide polymorphisms (SNPs) were found to be common in one ethnic group or another, and they involved codons 254 (Gly-GGC/Gly-GGT) in exon 3, 333 (Ile-ATC/Val-GTC) in exon 4, 370 (Ala-GCT/Val-GTT) in exon 5, 458 (Val-GTG/Leu-TTG) in exon 6, 518 (Val-GTC/Ile-ATC) in exon 7, 637 (Asp-GAC/Gly-GGC), 648 (Arg-CGA/Gln-CAA) and 661 (Pro-CCG/Pro-CCA) in exon 10. At each SNP site the sequence listed first was predominant in all ethnic groups. Several SNPs segregated on the same chromosome regardless of populations and species. Together, the SNPs produced 5 major human TAP1 alleles, 4 of which matched the officially recognized alleles *0101, *02011, *0301, and *0401; the 5th allele differed from each of those by at least 4 SNPs. Overall, TAP1*0101 was the predominant allele in all ethnic groups, with frequencies ranging from 0.667 in Zambians to 0.808 in US Caucasians. The TAP1*0401 frequency showed the greatest difference between Africans (0.221-0.254) and Caucasians (0.033), with Brazilians (0.058) fitting in the middle. Consistent with earlier work based on Caucasians and gorillas, *0101 appeared to be the newest human TAP1 allele, suggesting a dramatic spread of *0101 into all human populations examined. Characterization of TAP1 polymorphisms allowed the design of a PCR-based genotyping scheme that targeted 7 SNP sites and required 2 separate genotyping techniques.

Emerging infectious diseases and risk to the traveler.

This article examines the relationship between travel and emerging infections. The authors begin with an overview of disease emergence and follow with a brief infection-by-infection examination of selected emerging pathogens of particular relevance to travelers and the medical care providers who counsel them. Emphasis is given to those agents that clearly have emerged as significant new or increased risk to travelers; or are of sufficiently new interest, even in the face of inadequate data in travelers, to be of potential immediate concern. The authors also discuss several novel pathogens, such as Ebola virus, that are clearly of insignificant or minimal risk to travelers, but are the subject of frequent questions from patients requesting pre-travel advice from medical providers.

GeoSentinel: the global emerging infections sentinel network of the International Society of Travel Medicine.

GeoSentinel is a network of 22 member travel/tropical medicine clinics (14 in the United States and 8 in other countries) initiated in 1995 by the International Society of Travel Medicine (ISTM). GeoSentinel is based on the concept that these clinics are ideally situated to effectively detect geographic and temporal trends in morbidity among travelers. The core surveillance tool is a single-page faxable form submitted to a central data site for each post-travel patient, including immigrants, refugees, and foreign visitors. Diagnoses are entered either as specific etiologies or as syndromes and are then linked to geographic locations, reference dates, and clinical presentations. In addition, electronic communication with the larger body of worldwide ISTM member clinics is periodically done to obtain broader data collection in response to specific inquiries. The scope of GeoSentinel has broadened from the initial vision of a provider-based sentinel network tracking emerging infections at their point of entry into developed countries. Its present goals are (1) to monitor global trends in disease occurrence among travelers; (2) to ascertain risk factors and morbidity in groups of travelers categorized by travel purpose and type of traveler; (3) to respond to urgent public health queries; (4) to develop educational priorities for travelers' health; and (5) to effect a rapid response by electronically disseminating alerts to surveillance sites, to all ISTM members in 55 countries, and to public health authorities. In addition, a major byproduct of the network, and now one of its strongest assets, has been the growth of partnerships between ISTM, Centers for Disease Control and Prevention and health-care providers around the world, as well as other medical societies, government, and private organizations. The demographic data, travel patterns, and clinical presentations for the first 2813 patient records analyzed from the GeoSentinel sites are summarized in this paper.

Strongyloides stercoralis hyperinfection associated with human T cell lymphotropic virus type-1 infection in Peru.

A study was conducted in Lima, Peru to determine if patients with Strongyloides hyperinfection had human T cell lymphotropic virus type-1 (HTLV-I) infection. The study included patients with Strongyloides hyperinfection and a control group consisted of sex- and age-matched asymptomatic healthy individuals whose stools were negative for Strongyloides. A third group included patients with intestinal strongyloidiasis. Sera from each study subject were tested for HTLV-1/2I by an ELISA and Western blot. The HLTV-1 infection rates (85.7%, 18 of 21) were significantly (P < 0.001) associated with Strongyloides hyperinfection compared with the control group (4.7%, 1 of 21). The HTLV-1 rate (10%, 6 of 62) for patients with intestinal strongyloidiasis was significantly (P < 0.001) lower than patients with Strongyloides hyperinfection, but did not differ significantly (P > 0.05) from the control group. The association of HTLV-1 infection was observed among 17 of 19 patients more than 20 years of age and one of two younger patients. None had HTLV-2 infection. In conclusion, Strongyloides hyperinfection among Peruvian patients was highly associated with HTLV-1 infection.

Biased TCR repertoire in infiltrating lesional T cells in human Bancroftian filariasis.

To investigate the hypothesis that T cells recognizing specific Ags localize to the site of disease activity in human bancroftian filariasis, we have compared the repertoire of TCR Vbeta gene segments in lesions vs blood in individual patients by RT-PCR ELISA. Vbeta14 and Vbeta24 were overrepresented (5% greater in tissue compared with PBMCs and/or tissue/PBMC ratios in the highest 5% of all tissue/PBMC ratios for all Vbetas for all subjects) in 50% and 40% of study subjects, respectively. Overrepresentation of these two Vbetas did not occur in any control subject. In comparing three patient groups, the proportion of individuals meeting at least one criterion for Vbeta14 overrepresentation was shown to increase in tandem with our current concepts of disease progression (asymptomatic filariasis = 25%; clinical filariasis with active infection = 60%; clinical filariasis without active infection = 71%). In 6 of the 10 individuals with Vbeta14 overrepresentation, Vbeta14 represented >20% of the entire lesional Vbeta repertoire. All but one of the 20 study subjects had at least one Vbeta gene segment that was overrepresented in tissue compared with PBMCs. Only a small number of Vbetas, usually three or less, were overrepresented in any single filariasis patient. However, in the same tissue, no differences between patient groups were found when IFN-gamma, TNF-alpha, IL-4, IL-5, and IL-12 mRNA expression were examined. Taken together, these findings suggest that, in principle, in essentially all patients, whether with subclinical or with clinical filariasis, distinct and limited T cell populations are concentrated in affected tissue.

Epidemiology and immunopathology of bancroftian filariasis.

Human lymphatic filariasis affects 120 million people worldwide. Although the disease is considered to be potentially erradicable by the World Health Organization, comprehensive studies on epidemiological aspects as well as mechanisms of pathology development are still premature. The following review summarizes currently available data on these topics and ends by discussing the latest control strategies.

Keeping current. Travel medicine resources available on the Internet.

As travel medicine practices expand and multiply, practitioners increasingly need to be familiar with constantly changing disease epidemiology and drug resistance patterns in over 220 different countries. Nowadays, keeping current means utilizing the wide array of resources available on the internet. This article contains background information on the most relevant travel medicine-oriented Internet sites and provides their universal resource locators in a convenient table.

Differences in the frequency of cytokine-producing cells in antigenemic and nonantigenemic individuals with bancroftian filariasis.

Individuals with clinical manifestations of lymphatic filariasis may be currently infected or not. Twenty-five individuals from a Wuchereria bancrofti-endemic area of Brazil were classified as being asymptomatic microfilaremic individuals, antigenemic individuals with clinical filariasis, or nonantigenemic individuals with clinical filariasis. Intracellular cytokine staining of mitogen-stimulated peripheral blood mononuclear cells (PBMC) showed that the frequency of either gamma interferon (IFN-gamma)- or interleukin-4 (IL-4)-producing cells was higher in the nonantigenemic individuals with clinical filariasis than in the asymptomatic microfilaremic individuals (geometric means, 22.1 versus 10.7% [P = 0.02] and 2.9 versus 1.4% [P = 0.01], respectively). When the asymptomatic microfilaremic individuals and antigenemic individuals with clinical filariasis were grouped together to constitute all actively infected individuals, the frequency of IFN-gamma-producing cells was also lower than in the nonantigenemic individuals with clinical filariasis (P = 0.04). Likewise, the frequency of IL-4-producing cells in the actively infected individuals was also lower than in the nonantigenemic individuals with clinical filariasis (P = 0.02). No differences in the frequency of IFN-gamma-, IL-4-, or IL-5-producing cells in purified CD4 T lymphocytes were found among the groups. These findings suggest that the presence of antigenemia, which is an indicator of current active infection, is closely associated with the frequency of IFN-gamma- and IL-4-producing cells in lymphatic filariasis. The differences found in the frequency of cytokine-producing cells among the three groups appear to be due to a subset of cells other than CD4 T cells.

Immune dynamics in the pathogenesis of human lymphatic filariasis.

Despite the longstanding recognition of the spectral nature of human disease due to lymphatic filariasis, immunologists interested in pathogenesis have mostly examined patients classified as being at either one extreme pole or the other. While the clinically asymptomatic individuals with microfilaremia who sit at one pole always have active infection, it has been difficult to define who else on the clinical spectrum is actively infected with living adult worms. In this review, David Freedman discusses how the ability to measure circulating filarial antigen in patient serum has advanced our ability to understand the immunopathogenesis of lymphatic filariasis by improving the precision of patient classification. Recent work suggests that the presence (or absence) of antigenemia, rather than overt clinical manifestations of disease, is closely associated with specific cytokine responses. A framework for patient classification based on these findings is proposed.