Surveillance report of Zika virus among Canadian travellers returning from the Americas.

BACKGROUND: Widespread transmission of Zika virus in the Americas has occurred since late 2015. We examined demographic and travel-related characteristics of returned Canadian travellers with Zika infection acquired in the Americas to illuminate risk factors for acquisition and the clinical spectrum. METHODS: We analyzed demographic and travel-related data for returned Canadian travellers who presented to a CanTravNet site between October 2015 and September 2016 for care of Zika virus acquired in the Americas. Data were collected with use of the GeoSentinel Surveillance Network data platform. RESULTS: During the study period, 1118 travellers presented to a CanTravNet site after returning from the Americas, 41 (3.7%) of whom had Zika infection. Zika infection from the Americas was diagnosed at CanTravNet sites as often as dengue (n = 41) over the study period. In the first half of the study period, Zika virus burden was borne by people visiting friends and relatives in South America. In the latter half, coincident with the increased spread of Zika throughout the Caribbean and Central America, Zika virus occurred more often in tourists in the Caribbean. Forty (98%) of the travellers with Zika infection acquired it through probable mosquito exposure, and 1 had confirmed sexual acquisition. Congenital transmission occurred in 2 of 3 pregnancies. Two (5%) of those with Zika had symptoms resembling those of Guillain-Barré syndrome, 1 of whom also had Zika viral meningitis. INTERPRETATION: Even in this small cohort, we observed the full clinical spectrum of acute Zika virus, including adverse fetal and neurologic outcomes. Our observations suggest that complications from Zika infection are underestimated by data arising exclusively from populations where Zika is endemic. Travellers should adhere to mosquito-avoidance measures and barrier protection during sexual activity.

A dengue vaccine whirlwind update.

Dengue virus (DENV) is a mosquito-borne single-stranded RNA virus of the Flaviviridae family with four serotypes (DENV1, DENV2, DENV3, and DENV4) circulating many tropical and subtropical regions of the world. Endemic in more than 100 countries, DENV results in over 400 million cases annually, a subset presenting with severe or life-threatening illnesses such as dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS). While no specific treatments outside of supportive management exist, vaccines are an area of major research with two vaccines, Dengvaxia® (CYD-TDV) and Denvax® (TAK003), recently licensed for clinical use. CYD-TDV is highly efficacious in children 9 years or older who have had prior DENV infection due to the high risk of severe disease in seronegative children aged 2-5 years. Meanwhile, TAK003 has shown efficacy at 97.7% and 73.7% against, DENV2 and DENV1, respectively, in phase 3 clinical trials across Latin America and Asia in healthy children aged 4-16 with virologically confirmed dengue. Other vaccines including TV003 and TV005 continue to be developed across the world, with the hopes of entering clinical trials in the near future. We discuss the current state of vaccine development against dengue, with a focus on CYD-TDV and TAK003 as promising novel vaccines to target this neglected tropical disease (NTD).

2018 in review: five hot topics in tropical medicine.

The year 2018 heralded many new developments in the field of tropical medicine, including licensure of novel drugs for novel indications, licensure of existing drugs for existing indications but in novel settings, and globalized outbreaks of both vector-borne and zoonotic diseases. We herein describe five top stories in tropical medicine that occurred during 2018, and illuminate the practice-changing development within each story.

Cutaneous and mucocutaneous leishmaniasis in travellers and migrants: a 20-year GeoSentinel Surveillance Network analysis.

BACKGROUND: Cutaneous leishmaniasis (CL) may be emerging among international travellers and migrants. Limited data exist on mucocutaneous leishmaniasis (MCL) in travellers. We describe the epidemiology of travel-associated CL and MCL among international travellers and immigrants over a 20-year period through descriptive analysis of GeoSentinel data. METHODS: Demographic and travel-related data on returned international travellers diagnosed with CL or MCL at a GeoSentinel Surveillance Network site between 1 September 1997 and 31 August 2017 were analysed. RESULTS: A total of 955 returned travellers or migrants were diagnosed with travel-acquired CL (n = 916) or MCL during the study period, of whom 10% (n = 97) were migrants. For the 858 non-migrant travellers, common source countries were Bolivia (n = 156, 18.2%) and Costa Rica (n = 97, 11.3%), while for migrants, they were Syria (n = 34, 35%) and Afghanistan (n = 22, 22.7%). A total of 99 travellers (10%) acquired their disease on trips of ≤ 2 weeks. Of 274 cases for which species identification was available, Leishmania Viannia braziliensis was the most well-represented strain (n = 117, 42.7%), followed by L. major (n = 40, 14.6%) and L. V. panamensis (n = 38, 13.9%). Forty cases of MCL occurred, most commonly in tourists (n = 29, 72.5%) and from Bolivia (n = 18, 45%). A total of 10% of MCL cases were acquired in the Old World. CONCLUSIONS: Among GeoSentinel reporting sites, CL is predominantly a disease of tourists travelling mostly to countries in Central and South America such as Bolivia where risk of acquiring L. V. braziliensis and subsequent MCL is high. The finding that some travellers acquired leishmaniasis on trips of short duration challenges the common notion that CL is a disease of prolonged travel. Migrants from areas of conflict and political instability, such as Afghanistan and Syria, were well represented, suggesting that as mass migration of refugees continues, CL will be increasingly encountered in intake countries.

Spectrum of illness in migrants to Canada: sentinel surveillance through CanTravNet.

BACKGROUND: Due to ongoing political instability and conflict in many parts of the world, migrants are increasingly seeking asylum and refuge in Canada. METHODS: We examined demographic and travel correlates of illnesses among migrants to Canada to establish a detailed epidemiologic framework of this population for Canadian practitioners. Data on ill-returned Canadian travellers presenting to a CanTravNet site between 1 January 2015 and 31 December 2015 were analyzed. RESULTS: During the study period, 2415 ill travellers and migrants presented to a CanTravNet site, and of those, 519 (21.5%) travelled for the purpose of migration. Sub-Saharan Africa (n = 160, 30.8%), southeast Asia (n = 84, 16.2%) and south central Asia (n = 75, 14.5%) were the most common source regions for migrants, while the top specific source countries, of 98 represented, were the Philippines (n = 45, 8.7%), China (n = 36, 6.9%) and Vietnam (n = 31, 6.0%). Compared with non-migrant travellers, migrants were more likely to have a pre-existing immunocompromising medical condition, such as HIV or diabetes mellitus (P < 0.0001), and to require inpatient management of their illness (P < 0.0001). Diagnoses such as tuberculosis (n = 263, 50.7%), hepatitis B and C (n = 78, 15%) and HIV (n = 11, 2.1%) were over-represented in the migrant population compared with non-migrant travellers (P < 0.0001). Most cases of tuberculosis in the migrant population (n = 263) were latent (82% [n = 216]); only 18% (n = 47) were active. CONCLUSIONS: Compared with non-migrant travellers, migrants were more likely to present with a communicable infectious disease, such as tuberculosis, potentially complicated by an underlying immunosuppressing condition such as HIV. These differences highlight the divergent healthcare needs in the migrant population, and underscore the importance of surveillance programmes to understand their burden of illness. Intake programming should be adequately resourced to accommodate the medical needs of this vulnerable population of new Canadians.

Role of prostaglandin E2 receptors in migration of murine and human breast cancer cells.

Aberrant upregulation of COX-2 enzyme resulting in accumulation of PGE2 in a cancer cell environment is a marker for progression of many cancers, including breast cancer. Four subtypes of cell surface receptors (EP1, EP2, EP3, and EP4), which are coupled with different G-proteins, mediate PGE2 actions. Since migration is an essential step in invasion and metastasis, in the present study we defined the expression of EP receptors and their roles in migratory function of breast cancer cells of murine (C3L5) and human (MDA-MB-231 and MCF-7) origin. Highly metastatic C3L5 and MDA-MB-231 cells, found to be highly migratory in a Transwell migration assay, were shown to accumulate much higher levels of PGE2 in culture media in comparison with nonmetastatic and poorly migrating MCF-7 cells; the levels of PGF2alpha and 6-keto-PGF1alpha were low in all cases. The elevated PGE2 production by metastatic cancer cells was due to COX-2 activity since dual COX-1/2 inhibitor indomethacin and selective COX-2 inhibitor NS-398 equally suppressed both basal and inducible (by IFN-gamma/LPS or Ca2+-ionophores) PGE2 accumulation. RT-PCR analysis revealed that murine C3L5 cells expressed mRNA of EP1, EP3, and EP4 but not EP2 receptors. On the other hand, human MDA-MB-231 and MCF-7 cells expressed all the above receptors. High levels of expression of functional EP4 receptors coupled with Gs-protein was confirmed in C3L5 cells by biochemical assay showing a dose-dependent increase of intracellular cAMP synthesis in response to PGE2. EP receptor antagonists SC-19220, AH-6809, and AH-23848B, having highest affinity for EP1, EP1/EP2/DP, and EP4 receptors, respectively, variably inhibited migration of metastatic breast cancer cells. An autocrine PGE2-mediated migratory activity of these cells appeared to be associated predominantly with EP4 receptor-mediated signaling pathway, which uses cAMP as a second messenger. This conclusion is based on several observations: (1) selective EP4 antagonist AH-23848B effectively inhibited migration of both C3L5 and MDA-MB-231 cells in a dose-dependent manner; (2) exogenous PGE2 and EP4 agonist PGE1 alcohol increased migration of C3L5 cells; (3) forskolin, a potent activator of adenylate cyclase, as well as membrane-permeable analogues of cAMP (8-bromo-cAMP, dibutyryl-cAMP) stimulated migration of C3L5 cells; and (4) Rp-cAMPS, a selective protein kinase A inhibitor, reduced migration of C3L5 cells. Migration of poorly migratory MCF-7 cells remained unaffected with either PGE2 or EP4 antagonist. These findings are relevant for designing therapeutic strategies against breast cancer metastasis.