Intestinal protozoa in returning travellers: a GeoSentinel analysis from 2007 to 2019.

BACKGROUND: Prolonged diarrhoea is common amongst returning travellers and is often caused by intestinal protozoa. However, the epidemiology of travel-associated illness caused by protozoal pathogens is not well described. METHODS: We analysed records of returning international travellers with illness caused by Giardia duodenalis, Cryptosporidium spp., Cyclospora cayetanensis or Cystoisospora belli, reported to the GeoSentinel Network during January 2007-December 2019. We excluded records of travellers migrating, with an unascertainable exposure country, or from GeoSentinel sites that were not located in high-income countries. RESULTS: There were 2517 cases, 82.3% giardiasis (n = 2072), 11.4% cryptosporidiosis (n = 287), 6.0% cyclosporiasis (n = 150) and 0.3% cystoisosporiasis (n = 8). Overall, most travellers were tourists (64.4%) on long trips (median durations: 18-30 days). Cryptosporidiosis more frequently affected people < 18 years (13.9%) and cyclosporiasis affected people ≥ 40 years (59.4%). Giardiasis was most frequently acquired in South Central Asia (45.8%) and sub-Saharan Africa (22.6%), cryptosporidiosis in sub-Saharan Africa (24.7%) and South-Central Asia (19.5%), cyclosporiasis in South East Asia (31.3%) and Central America (27.3%), and cystoisosporiasis in sub-Saharan Africa (62.5%). Cyclosporiasis cases were reported from countries of uncertain endemicity (e.g. Cambodia) or in countries with no previous evidence of this parasite (e.g. French Guiana). The time from symptom onset to presentation at a GeoSentinel site was the longest amongst travellers with giardiasis (median: 30 days). Over 14% of travellers with cryptosporidiosis were hospitalized. CONCLUSIONS: This analysis provides new insights into the epidemiology and clinical significance of four intestinal protozoa that can cause morbidity in international travellers. These data might help optimize pretravel advice and post-travel management of patients with travel-associated prolonged gastrointestinal illnesses. This analysis reinforces the importance of international travel-related surveillance to identify sentinel cases and areas where protozoal infections might be undetected or underreported.

Chikungunya infection in returned travellers: results from the geosentinel network, 2005-2020.

BACKGROUND: Chikungunya is an important travel-related disease because of its rapid geographical expansion and potential for prolonged morbidity. Improved understanding of the epidemiology of travel-related chikungunya infections may influence prevention strategies including education and vaccination. METHODS: We analysed data from travellers with confirmed or probable chikungunya reported to GeoSentinel sites from 2005 to 2020. Confirmed chikungunya was defined as a compatible clinical history plus either virus isolation, positive nucleic acid test or seroconversion/rising titre in paired sera. Probable chikungunya was defined as a compatible clinical history with a single positive serology result. RESULTS: 1202 travellers (896 confirmed and 306 probable) with chikungunya were included. The median age was 43 years (range 0-91; interquartile range [IQR]: 31-55); 707 (58.8%) travellers were female. Most infections were acquired in the Caribbean (28.8%), Southeast Asia (22.8%), South Central Asia (14.2%) and South America (14.2%). The highest numbers of chikungunya cases reported to GeoSentinel were in 2014 (28.3%), 2015 (14.3%) and 2019 (11.9%). The most frequent reasons for travel were tourism (n = 592; 49.3%) and visiting friends or relatives (n = 334; 27.7%). The median time to presentation to a GeoSentinel site was 23 days (IQR: 7-52) after symptom onset. In travellers with confirmed chikungunya and no other reported illnesses, the most frequently reported symptoms included musculoskeletal symptoms (98.8%), fever/chills/sweats (68.7%) and dermatologic symptoms (35.5%). Among 917 travellers with information available, 296 (32.3%) had a pretravel consultation. CONCLUSIONS: Chikungunya was acquired by international travellers in almost 100 destinations globally. Vector precautions and vaccination where recommended should be integrated into pretravel visits for travellers going to areas with chikungunya or areas with the potential for transmission. Continued surveillance of travel-related chikungunya may help public health officials and clinicians limit the transmission of this potentially debilitating disease by defining regions where protective measures (e.g. pretravel vaccination) should be strongly considered.

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.

Mucosal Leishmaniasis in Travelers with Leishmania braziliensis Complex Returning to Israel.

Mucosal leishmaniasis (ML) is a complication of New World cutaneous leishmaniasis (CL) caused mainly by Leishmania (Viannia) braziliensis. This retrospective study investigated all cases of ML caused by L. (V.) braziliensis in a tertiary medical center in Israel, evaluating the risk factors, clinical presentations, diagnosis, treatment, and outcome of mucosal involvement in ML caused by L. (V.) braziliensis in travelers returning to Israel. During 1993-2015, a total of 145 New World CL cases were seen in travelers returning from Bolivia; among them, 17 (11.7%) developed ML. Nasopharyngeal symptoms developed 0-3 years (median 8 months) after exposure. The only significant risk factor for developing ML was the absence of previous systemic treatment. Among untreated patients, 41% developed ML, compared with only 3% of treated patients (p = 0.005). Systemic treatment for CL seems to be a protective factor against developing ML.

Leptospirosis among Returned Travelers: A GeoSentinel Site Survey and Multicenter Analysis-1997-2016.

Leptospirosis is a potentially fatal emerging zoonosis with worldwide distribution and a broad range of clinical presentations and exposure risks. It typically affects vulnerable populations in (sub)tropical countries but is increasingly reported in travelers as well. Diagnostic methods are cumbersome and require further improvement. Here, we describe leptospirosis among travelers presenting to the GeoSentinel Global Surveillance Network. We performed a descriptive analysis of leptospirosis cases reported in GeoSentinel from January 1997 through December 2016. We included 180 travelers with leptospirosis (mostly male; 74%; mostly tourists; 81%). The most frequent region of infection was Southeast Asia (52%); the most common source countries were Thailand (N = 52), Costa Rica (N = 13), Indonesia, and Laos (N = 11 each). Fifty-nine percent were hospitalized; one fatality was reported. We also distributed a supplemental survey to GeoSentinel sites to assess clinical and diagnostic practices. Of 56 GeoSentinel sites, three-quarters responded to the survey. Leptospirosis was reported to have been most frequently considered in febrile travelers with hepatic and renal abnormalities and a history of freshwater exposure. Serology was the most commonly used diagnostic method, although convalescent samples were reported to have been collected infrequently. Within GeoSentinel, leptospirosis was diagnosed mostly among international tourists and caused serious illness. Clinical suspicion and diagnostic workup among surveyed GeoSentinel clinicians were mainly triggered by a classical presentation and exposure history, possibly resulting in underdiagnosis. Suboptimal usage of available diagnostic methods may have resulted in additional missed, or misdiagnosed, cases.

Sensitivity and Kinetics of an NS1-Based Zika Virus Enzyme-Linked Immunosorbent Assay in Zika Virus-Infected Travelers from Israel, the Czech Republic, Italy, Belgium, Germany, and Chile.

Serological diagnosis of Zika virus is challenging due to high cross-reactivity of Zika virus with other flavivirus antibodies. Recently, a Zika NS1-based enzyme-linked immunosorbent assay (ELISA) was developed and shown to be highly specific for Zika antibody detection; however, sensitivity was evaluated for only a small number of confirmed Zika-infected patients. In this study, we measured the sensitivity and kinetics of Zika IgM and IgG antibodies using the Zika NS1-based ELISA in 105 samples from 63 returning travelers infected with Zika virus (proven by PCR or neutralization assay) from Israel, Czech Republic, Italy, Belgium, Germany, and Chile. Zika virus IgM was detected from 2 to 42 days post-symptom onset (PSO) with an overall sensitivity of 79% in the first month and 68% until 2 months PSO, while IgG antibodies were detected from 5 days to 3 years PSO with 79% sensitivity. Interestingly, significant differences in IgM sensitivity and IgM detection period were observed between Israeli and European/Chilean Zika-infected travelers, adding to the complexity of Zika infection diagnosis and suggesting that other diagnostic methods should be complemented to reduce false-negative results.

Travel-Associated Zika Virus Disease Acquired in the Americas Through February 2016: A GeoSentinel Analysis.

Background: Zika virus has spread rapidly in the Americas and has been imported into many nonendemic countries by travelers. Objective: To describe clinical manifestations and epidemiology of Zika virus disease in travelers exposed in the Americas. Design: Descriptive, using GeoSentinel records. Setting: 63 travel and tropical medicine clinics in 30 countries. Patients: Ill returned travelers with a confirmed, probable, or clinically suspected diagnosis of Zika virus disease seen between January 2013 and 29 February 2016. Measurements: Frequencies of demographic, trip, and clinical characteristics and complications. Results: Starting in May 2015, 93 cases of Zika virus disease were reported. Common symptoms included exanthema (88%), fever (76%), and arthralgia (72%). Fifty-nine percent of patients were exposed in South America; 71% were diagnosed in Europe. Case status was established most commonly by polymerase chain reaction (PCR) testing of blood and less often by PCR testing of other body fluids or serology and plaque-reduction neutralization testing. Two patients developed Guillain-Barré syndrome, and 3 of 4 pregnancies had adverse outcomes (microcephaly, major fetal neurologic abnormalities, and intrauterine fetal death). Limitation: Surveillance data collected by specialized clinics may not be representative of all ill returned travelers, and denominator data are unavailable. Conclusion: These surveillance data help characterize the clinical manifestations and adverse outcomes of Zika virus disease among travelers infected in the Americas and show a need for global standardization of diagnostic testing. The serious fetal complications observed in this study highlight the importance of travel advisories and prevention measures for pregnant women and their partners. Travelers are sentinels for global Zika virus circulation and may facilitate further transmission. Primary Funding Source: Centers for Disease Control and Prevention, International Society of Travel Medicine, and Public Health Agency of Canada.

Vector-borne diseases in Haiti: a review.

Haiti lies on the western third of the island of Hispaniola in the Caribbean, and is one of the poorest nations in the Western hemisphere. Haiti attracts a lot of medical attention and support due to severe natural disasters followed by disastrous health consequences. Vector-borne infections are still prevalent there with some unique aspects comparing it to Latin American countries and other Caribbean islands. Although vector-borne viral diseases such as dengue and recently chikungunya can be found in many of the Caribbean islands, including Haiti, there is an apparent distinction of the vector-borne parasitic diseases. Contrary to neighboring Carribbean islands, Haiti is highly endemic for malaria, lymphatic filariasis and mansonellosis. Affected by repeat natural disasters, poverty and lack of adequate infrastructure, control of transmission within Haiti and prevention of dissemination of vector-borne pathogens to other regions is challenging. In this review we summarize some aspects concerning diseases caused by vector-borne pathogens in Haiti.

Epidemiologic profile of patients seen in primary care clinics in an urban and a rural setting in Haiti, 2010-11.

BACKGROUND: This study examined the demographic and epidemiological differences between patient populations presenting to a rural and an urban clinic in Haiti. METHODS: A primary health clinic was established in urban Leogane, and a once-weekly clinic was established in Magandou, a rural village. Patient data were recorded for all individuals presenting to each clinic. RESULTS: Over 7 months, 6632 patients (median age 25) were seen in the urban clinic, and 567 (median age 47) in the rural clinic. There was a female majority at both sites. Hypertension was diagnosed in 41.9% (238/567) of the rural population over 40 years of age, while 29.5% (1956/6632) of patients in the urban setting had the same diagnosis (p<0.001). Among women of reproductive age, 20.4% (1353/6632) were diagnosed with STDs in the urban setting versus 8.6% (49/567) at the rural clinic (p=0.004). Eighty-eight patients at the urban clinic had a vector-borne disease, while none were diagnosed among the rural population. CONCLUSIONS: Screening and treatment of hypertension in Haiti must address the wide rural prevalence. STDs are a major urban health issue requiring treatment for both patients and their partners. Vector-borne disease was unseen in the rural clinic, despite an altitude insufficient to prevent mosquito-borne illness.

Illness in travelers returned from Brazil: the GeoSentinel experience and implications for the 2014 FIFA World Cup and the 2016 Summer Olympics.

BACKGROUND: Brazil will host the 2014 FIFA World Cup and the 2016 Olympic and Paralympic Games, events that are expected to attract hundreds of thousands of international travelers. Travelers to Brazil will encounter locally endemic infections as well as mass event-specific risks. METHODS: We describe 1586 ill returned travelers who had visited Brazil and were seen at a GeoSentinel Clinic from July 1997 through May 2013. RESULTS: The most common travel-related illnesses were dermatologic conditions (40%), diarrheal syndromes (25%), and febrile systemic illness (19%). The most common specific dermatologic diagnoses were cutaneous larva migrans, myiasis, and tungiasis. Dengue and malaria, predominantly Plasmodium vivax, were the most frequently identified specific causes of fever and the most common reasons for hospitalization after travel. Dengue fever diagnoses displayed marked seasonality, although cases were seen throughout the year. Among the 28 ill returned travelers with human immunodeficiency virus (HIV) infection, 11 had newly diagnosed asymptomatic infection and 9 had acute symptomatic HIV. CONCLUSIONS: Our analysis primarily identified infectious diseases among travelers to Brazil. Knowledge of illness in travelers returning from Brazil can assist clinicians to advise prospective travelers and guide pretravel preparation, including itinerary-tailored advice, vaccines, and chemoprophylaxis; it can also help to focus posttravel evaluation of ill returned travelers. Travelers planning to attend mass events will encounter other risks that are not captured in our surveillance network.

Liposomal amphotericin B in comparison to sodium stibogluconate for Leishmania braziliensis cutaneous leishmaniasis in travelers.

BACKGROUND: New World cutaneous leishmaniasis is mostly acquired in the Amazon Basin of Bolivia where L viannia (V) braziliensis is endemic. Treatment with systemic pentavalent antimonial compounds has been shown to be effective in achieving clinical cure in only 75% of cases. OBJECTIVE: We sought to assess the efficacy and safety of liposomal amphotericin B (L-AmB) treatment for primary infection of cutaneous L (V) braziliensis. METHODS: A prospective observational evaluation was performed for cutaneous leishmaniasis due to L (V) braziliensis which was treated with L-AmB, 3 mg/kg, for 5 consecutive days, and a sixth dose on day 10. This therapy regimen was compared with the treatment regimen of sodium stibogluconate (SSG) 20 mg/kg for 3 weeks. RESULTS: Our study was divided into two groups; 34 patients received L-AmB and 34 received SSG treatment. Almost all patients were infected in Bolivia. In the L-AmB group, 29 patients (85%) had complete cure compared with 70% in the SSG group (P = not significant), 4 other patients were slow healers, and only one patient needed additional treatment with SSG. No relapses were seen during a mean 29-month follow-up period. Failure rate was 3% in the L-AmB versus 29% in the SSG group (P = .006). Treatment was interrupted in 65% of patients taking SSG because of adverse events, whereas all patients receiving L-AmB completed treatment. LIMITATIONS: This was a non-blinded comparative study. CONCLUSIONS: Comparison of L-Amb to SSG treatment for L (V) braziliensis shows that the former is effective, better tolerated, and more cost effective. L-AmB should therefore be considered as the first-line treatment option for cutaneous L (V) braziliensis infection.

Lack of evidence for chloroquine-resistant Plasmodium falciparum malaria, Leogane, Haiti.

Plasmodium falciparum malaria in Haiti is considered chloroquine susceptible, although resistance transporter alleles associated with chloroquine resistance were recently detected. Among 49 patients with falciparum malaria, we found neither parasites carrying haplotypes associated with chloroquine resistance nor instances of chloroquine treatment failure. Continued vigilance to detect emergence of chloroquine resistance is needed.

Infectious diseases seen in a primary care clinic in Leogane, Haiti.

All diseases diagnosed in a primary healthcare clinic situated in Leogane, Haiti, were recorded prospectively during a 7-month period. Among the patients in this cohort, 2,821 of 6,631 (42.6%) presented with an infectious disease. The three most common syndromes among the patients presenting with infections were respiratory tract infections (33.5%), suspected sexually transmitted diseases--mostly among females with recurrent disease (18.1%)--and skin and soft tissue infections, including multiple cases of tinea capitis (12.8%). Of the 255 patients presenting with undifferentiated fever, 76 (29.8%) were diagnosed with falciparum malaria. Other vector-borne diseases included 13 cases of filariasis and 6 cases of dengue fever. Human immunodeficiency virus infection was diagnosed in 19 patients. Four cases of mumps were detected among unimmunized children. A large proportion of these infections are preventable. Concerted efforts should be made to create large-scale preventive medicine programs for various infectious diseases.

Characteristics and spectrum of disease among ill returned travelers from pre- and post-earthquake Haiti: The GeoSentinel experience.

To describe patient characteristics and disease spectrum among foreign visitors to Haiti before and after the 2010 earthquake, we used GeoSentinel Global Surveillance Network data and compared 1 year post-earthquake versus 3 years pre-earthquake. Post-earthquake travelers were younger, predominantly from the United States, more frequently international assistance workers, and more often medically counseled before their trip than pre-earthquake travelers. Work-related stress and upper respiratory tract infections were more frequent post-earthquake; acute diarrhea, dengue, and Plasmodium falciparum malaria were important contributors of morbidity both pre- and post-earthquake. These data highlight the importance of providing destination- and disaster-specific pre-travel counseling and post-travel evaluation and medical management to persons traveling to or returning from a disaster location, and evaluations should include attention to the psychological wellbeing of these travelers. For travel to Haiti, focus should be on mosquito-borne illnesses (dengue and P. falciparum malaria) and travelers' diarrhea.

Clostridium difficile infection after malaria chemoprophylaxis with doxycycline: is there an association?

Malaria chemoprophylaxis with doxycycline is commonly used in the United Kingdom and in many other countries. It is considered to be associated with an increased risk of Clostridium difficile associated diarrhea (CDAD). We describe a case of diarrhea and a positive stool assay for C. difficile in a returning traveler, and review available literature. The commonly held concept of an association between doxycycline chemoprophylaxis and CDAD is not supported by available data.

Seasonality, annual trends, and characteristics of dengue among ill returned travelers, 1997-2006.

We examined seasonality and annual trends for dengue cases among 522 returned travelers reported to the international GeoSentinel Surveillance Network. Dengue cases showed region-specific peaks for Southeast Asia (June, September), South Central Asia (October), South America (March), and the Caribbean (August, October). Travel-related dengue exhibited annual oscillations with several epidemics occurring during the study period. In Southeast Asia, annual proportionate morbidity increased from 50 dengue cases per 1,000 ill returned travelers in nonepidemic years to an average of 159 cases per 1,000 travelers during epidemic years. Dengue can thus be added to the list of diseases for which pretravel advice should include information on relative risk according to season. Also, dengue cases detected at atypical times in sentinel travelers may inform the international community of the onset of epidemic activity in specific areas.

Liposomal amphotericin B in comparison to sodium stibogluconate for cutaneous infection due to Leishmania braziliensis.

BACKGROUND: New World cutaneous leishmaniasis among Israeli travelers is mostly acquired in the Amazon Basin of Bolivia where Leishmania viannia (V.) braziliensis is endemic. Treatment with systemic pentavalent antimonial compounds is effective in achieving clinical cure in only 75% of cases. In this study, we assessed liposomal amphotericin B (AmBisome) as an alternative treatment for cutaneous L (V.) braziliensis infection. METHODS: A prospective evaluation was performed for cutaneous leishmaniasis due to L (V.) braziliensis, proven by polymerase chain reaction. A 3-mg/kg AmBisome dose was given for 5 consecutive days, and a sixth dose on day 10, all in an outpatient setting. This therapy was compared with a series of historical patients who were treated with sodium stibogluconate (SSG). RESULTS: Seven consecutive patients, 5 males and 2 females, received AmBisome treatment. All were returned travelers infected in Bolivia; their mean age was 23.1 years; 5 had failed to respond to a full course of SSG; two had a primary lesion; none had mucosal lesions. All achieved complete clinical cure within less than 1 month. Mean follow-up of 12 months revealed no relapses. Side effects were mild, and none had to terminate treatment prematurely. Comparison of AmBisome to SSG treatment shows that the former is safer, with fewer recurrence rates. Additionally, the expense of the total care with AmBisome is less than with SSG: 45% less if SSG was given in an inpatient setting; 15% less when SSG was given in an outpatient setting. LIMITATIONS: This was a nonrandomized study, with relatively few patients. CONCLUSION: AmBisome treatment for L (V.) braziliensis appears to be effective, better tolerated, and to have more cost benefit in countries where hospital-care costs are significant.

Malaria in travelers: a review of the GeoSentinel surveillance network.

BACKGROUND: Malaria is a common and important infection in travelers. METHODS: We have examined data reported to the GeoSentinel surveillance network to highlight characteristics of malaria in travelers. RESULTS: A total of 1140 malaria cases were reported (60% of cases were due to Plasmodium falciparum, 24% were due to Plasmodium vivax). Male subjects constituted 69% of the study population. The median duration of travel was 34 days; however, 37% of subjects had a travel duration of < or =4 weeks. The majority of travellers did not have a pretravel encounter with a health care provider. Most cases occurred in travelers (39%) or immigrants/refugees (38%). The most common reasons for travel were to visit friends/relatives (35%) or for tourism (26%). Three-quarters of infections were acquired in sub-Saharan Africa. Severe and/or complicated malaria occurred in 33 cases, with 3 deaths. Compared with others in the GeoSentinel database, patients with malaria had traveled to sub-Saharan Africa more often, were more commonly visiting friends/relatives, had traveled for longer periods, presented sooner after return, were more likely to have a fever at presentation, and were less likely to have had a pretravel encounter. In contrast to immigrants and visitors of friends or relatives, a higher proportion (73%) of the missionary/volunteer group who developed malaria had a pretravel encounter with a health care provider. Travel to sub-Saharan Africa and Oceania was associated with the greatest relative risk of acquiring malaria. CONCLUSIONS: We have used a global database to identify patient and travel characteristics associated with malaria acquisition and characterized differences in patient type, destinations visited, travel duration, and malaria species acquired.