Comparative Study of Virus and Lymphocyte Distribution with clinical Data suggests early high dose Immunosuppression as potential Key Factor for the Therapy of Patients with BoDV-1 Infection.

Borna disease virus 1 (BoDV-1) was just recently shown to cause predominantly fatal encephalitis in humans. Despite its rarity, bornavirus encephalitis (BVE) can be considered a model disease for encephalitic infections caused by neurotropic viruses and understanding its pathomechanism is of utmost relevance.Aim of this study was to compare the extent and distribution pattern of cerebral inflammation with the clinical course of disease, and individual therapeutic procedures.For this, autoptic brain material from seven patients with fatal BVE was included in this study. Tissue was stained immunohistochemically for pan-lymphocytic marker CD45, the nucleoprotein of BoDV-1, as well as glial marker GFAP and microglial marker Iba1. Sections were digitalized and counted for CD45-positive and BoDV-1-positive cells. For GFAP and Iba1, a semiquantitative score was determined. Furthermore, detailed information about the individual clinical course and therapy were retrieved and summarized in a standardized way.Analysis of the distribution of lymphocytes shows interindividual patterns. In contrast, when looking at the BoDV-1-positive glial cells and neurons, a massive viral involvement in the brain stem was noticeable. Three of the seven patients received early high-dose steroids, which led to a significantly lower lymphocytic infiltration of the central nervous tissue and a longer survival compared to the patients who were treated with steroids later in the course of disease.This study highlights the potential importance of early high-dose immunosuppressive therapy in BVE. Our findings hint at a promising treatment option which should be corroborated in future observational or prospective therapy studies.

Effect of textile colour on vector mosquito host selection: a simulated field study in Mali, West Africa.

BACKGROUND: The effect of clothing colour on the biting rates of different vector mosquito species is not well understood. Studies under tropical field conditions are lacking. This study aimed to determine the influence of clothing colours on mosquito biting rates in rural and suburban settings in West Africa. METHODS: We performed a simulated field study in a suburban and a rural site in Mali using Mosquito-Magnet traps utilizing CO2 and other attractants, which were covered with black, white, and black/white striped textile sheets covers. These targets operated continuously for 10 consecutive days with bright nights (around full moon) and 10 consecutive days with dark nights (around new moon). Trapped mosquitoes were collected and catch rates counted hourly. Mosquitoes were morphologically identified to the species complex level (Anopheles gambiae s.l. and Culex pipiens s.l.) or species level (Aedes aegypti). A subset of Anopheles specimens were further identified by molecular methods. RESULTS: Under bright-night conditions, An. gambiae s.l. was significantly more attracted to black targets than to white and striped targets; during dark nights, no target preference was noted. During bright nights, Cx. pipiens s.l. was significantly more attracted to black and striped targets than to white targets; a similar trend was noted during dark nights (not significant). For day-active Ae. aegypti, striped targets were more attractive than the other targets and black were more attractive than white targets. CONCLUSIONS: The study firstly demonstrated that under field conditions in Mali, West Africa, mosquito catch rates were influenced by different clothing colours, depending on mosquito species and light conditions. Overall, light colours were least attractive to host-seeking mosquitoes. Using white or other light-coloured clothing can potentially reduce bite exposure and risk of disease transmission in endemic tropical regions.

[Pretravel medical consultation]. / Reisemedizinische Beratung.

Many patients seek pretravel advice during routine consultations in a general practice so that basic knowledge of travel medicine is warranted. Using the example of trips to Bali, Peru and Tanzania, the most relevant topics of a pretravel consultation for these popular destinations are depicted. These include vaccinations, malaria prevention and recommendations on exposure prophylaxis for insect bites. Furthermore, special risk situations, such as travel to high altitudes or freshwater contact are discussed. In special cases, the advice of an expert in travel medicine is needed.

Zika virus infection in European travellers returning from Thailand in 2022: A GeoSentinel case series.

Zika virus is a mosquito-borne flavivirus which caused major epidemics in the Pacific and the Americas between 2013 and 2015. International travellers have previously acted as a sentinel population for Zika virus transmission in endemic areas, where local transmission may be incompletely captured by local surveillance systems. We report five recent European travellers returning from Thailand with Zika virus infection, highlighting the risk of ongoing endemic transmission in this popular tourist destination.

Clinical Characteristics and Outcomes Among Travelers With Severe Dengue : A GeoSentinel Analysis.

BACKGROUND: Dengue virus is a flavivirus transmitted by Aedes mosquitoes and is an important cause of illness worldwide. Data on the severity of travel-associated dengue illness are limited. OBJECTIVE: To describe the epidemiology, clinical characteristics, and outcomes among international travelers with severe dengue or dengue with warning signs as defined by the 2009 World Health Organization classification (that is, complicated dengue). DESIGN: Retrospective chart review and analysis of travelers with complicated dengue reported to GeoSentinel from January 2007 through July 2022. SETTING: 20 of 71 international GeoSentinel sites. PATIENTS: Returning travelers with complicated dengue. MEASUREMENTS: Routinely collected surveillance data plus chart review with abstraction of clinical information using predefined grading criteria to characterize the manifestations of complicated dengue. RESULTS: Of 5958 patients with dengue, 95 (2%) had complicated dengue. Eighty-six (91%) patients had a supplemental questionnaire completed. Eighty-five of 86 (99%) patients had warning signs, and 27 (31%) were classified as severe. Median age was 34 years (range, 8 to 91 years); 48 (56%) were female. Patients acquired dengue most frequently in the Caribbean (n = 27 [31%]) and Southeast Asia (n = 21 [24%]). Frequent reasons for travel were tourism (46%) and visiting friends and relatives (32%). Twenty-one of 84 (25%) patients had comorbidities. Seventy-eight (91%) patients were hospitalized. One patient died of nondengue-related illnesses. Common laboratory findings and signs were thrombocytopenia (78%), elevated aminotransferase (62%), bleeding (52%), and plasma leakage (20%). Among severe cases, ophthalmologic pathology (n = 3), severe liver disease (n = 3), myocarditis (n = 2), and neurologic symptoms (n = 2) were reported. Of 44 patients with serologic data, 32 confirmed cases were classified as primary dengue (IgM+/IgG-) and 12 as secondary (IgM-/IgG+) dengue. LIMITATIONS: Data for some variables could not be retrieved by chart review for some patients. The generalizability of our observations may be limited. CONCLUSION: Complicated dengue is relatively rare in travelers. Clinicians should monitor patients with dengue closely for warning signs that may indicate progression to severe disease. Risk factors for developing complications of dengue in travelers need further prospective study. PRIMARY FUNDING SOURCE: Centers for Disease Control and Prevention, International Society of Travel Medicine, Public Health Agency of Canada, and GeoSentinel Foundation.

Can haematological changes constitute a surrogate diagnostic parameter to detect schistosomiasis in migrants and travellers? - A retrospective analysis.

Background: Earlier studies found characteristic haematological changes in African patients with active schistosomiasis. If consistently present, full blood counts (FBC) may be helpful to diagnose schistosomiasis also in migrants and returning travellers. Methods: A retrospective patient record review was conducted on data from seven European travel clinics, comparing FBC of Schistosoma egg-positive travellers and migrants to reference values. Sub-analyses were performed for children, returned travellers, migrants and different Schistosoma species. Results: Data analysis included 382 subjects (median age 21.0 years [range 2-73]). In returned travellers, decreases in means of haemoglobin particularly in females (ß = -0.82 g/dL, p = 0.005), MCV (ß = -1.6 fL, p = 0.009), basophils, neutrophils, lymphocytes and monocytes (ß = -0.07, p < 0.001; -0.57, p = 0.012; -0.57, p < 0.001 and -0.13 103/µL, p < 0.001, respectively) were observed. As expected, eosinophils were increased (ß = +0.45 103/µL, p < 0.001). In migrants, a similar FBC profile was observed, yet thrombocytes and leukocytes were significantly lower in migrants (ß = -48 103/µL p < 0.001 and ß = -2.35 103/µL, p < 0.001, respectively). Conclusions: Active egg-producing Schistosoma infections are associated with haematological alterations in returned travellers and migrants. However, these differences are discrete and seem to vary among disease stage and Schistosoma species. Therefore, the FBC is unsuitable as a surrogate diagnostic parameter to detect schistosomiasis.

Rabies post-exposure prophylaxis of international travellers - Results from two major German travel clinics.

BACKGROUND: Travel to regions with rabies risk has increased. However, data on adequate rabies post exposure prophylaxis (PEP) abroad is scarce. The aim of this study was to assess the appropriateness of medical management following suspected rabies exposure (SRE) in international travellers. METHOD: A cross-sectional questionnaire-based study in returning travellers with reported SRE who sought post-exposure medical care was conducted in two large German travel clinics. RESULTS: The 75 included SRE cases had a median age of 34 years (range 26-43) and showed a female predominance (59%, 44/75). Most participants returned from Asia (47%, 34/72). About 28% had received pre-exposure prophylaxis (PrEP, ≥2 vaccine doses) (20/71). In 51% the animal was actively approached (34/67). All patients had category II/III exposure according to the World Health Organization (65% category III, 49/75). With 78% (52/67), most patients cleaned the wound after SRE; 36% (24/67) used water and soap. Only 57% (41/72) of participants sought medical care during their trip. Overall, 45% (33/74) received rabies vaccination abroad which corresponds to 80% out of those who sought healthcare (33/41). CONCLUSIONS: Awareness for appropriate first aid and the urgency of seeking timely professional treatment including PEP after an SRE seems to be insufficient in German travellers. Travel practitioners need to educate travellers about rabies risk, prevention measures and the correct behaviour after SRE including adequate wound treatment and seeking immediate medical help for PEP. PrEP should be offered generously especially to travellers with high rabies-exposure risk and those visiting areas with limited healthcare access.

Symptoms of illness during travel and risk factors for non-adherence to malaria prophylaxis-a cross-sectional study in travellers from Germany.

BACKGROUND: Perceived adverse effects of antimalarial chemoprophylaxis can be difficult to distinguish from travel-related illness and are often cited as important reasons for non-adherence or refusal of antimalarial chemoprophylaxis. We aimed to investigate the occurrence of symptoms of illness in travellers with and without chemoprophylaxis in a cross-sectional study after travel and to identify risk factors for non-adherence to prophylaxis. METHODS: We enrolled 458 travellers to Africa and South America during their pre-travel medical consultation at the travel clinic of the University Medical Centre Hamburg-Eppendorf and conducted post-travel interviews on symptoms of illness and intake of malaria prophylaxis. RESULTS: Eleven percent (49/437) of the participants reported symptoms of illness during travel. In total, 36% (160/448) of the participants reported prescription of chemoprophylaxis, the vast majority of these travelled to Africa (98%) and received atovaquone/proguanil (93%). Frequency of symptoms did not differ significantly between participants without prophylaxis and those taking atovaquone/proguanil. Non-adherence to prophylaxis was frequent (20%), but only 3% (4/149) of the participants stopped the medication early because of perceived side effects. Risk factors associated with non-adherence to prophylaxis included age under 30 years, travel to West or Central Africa and travel duration greater than 14 days. CONCLUSIONS: Symptoms of illness during travel occurred at similar frequencies irrespective of intake of chemoprophylaxis. Travellers should be informed about chemoprophylaxis in a balanced way, without raising fear of side effects, especially among groups at higher risk for incorrect use of prophylaxis.

Spectrum of Helminth Infections in Migrants from Sub-Saharan Africa to Europe: A Literature Review.

Sub-Saharan Africa (SSA) is endemic to numerous neglected tropical diseases, including many helminth diseases. With the migration of people from this part of the world to Europe, as has been happening on a large scale since 2015, these diseases are becoming more relevant to European physicians. This work aims to summarize the recent literature on this topic and to raise awareness of helminth diseases afflicting SSA migrants. The databases PubMed, Embase, and MEDLINE were screened for literature published in English and German between January 1, 2015 and December 31, 2020. In total, 74 articles were included in this review. The spectrum of helminth infections in migrants from SSA found in the literature review is broad; current research, however, is particularly focused on infections with Schistosoma spp. and Strongyloides stercoralis. Both diseases are often characterized by a long course, with few or no symptoms, with the risk of long-term organ damage. Successful and reliable screening for schistosomiasis and strongyloidiasis is strongly recommended. However, the current diagnostic methods lack sensitivity and specificity, rendering the diagnosis challenging and reliable assessment of disease prevalence difficult. Novel diagnostic methods and a greater awareness of these diseases are urgently needed.

Dengue outbreak amongst travellers returning from Cuba-GeoSentinel surveillance network, January-September 2022.

Increasing numbers of travellers returning from Cuba with dengue virus infection were reported to the GeoSentinel Network from June to September 2022, reflecting an ongoing local outbreak. This report demonstrates the importance of travellers as sentinels of arboviral outbreaks and highlights the need for early identification of travel-related dengue.

Depression management and antiretroviral treatment outcome among people living with HIV in Northwest and East regions of Cameroon.

BACKGROUND: Several interventions have shown benefits in improving mental health problems such as depression which is common in people living with HIV. However, there is a paucity of evidence on the effect of these interventions in improving HIV treatment outcomes. This study aimed at bridging this evidence gap and guiding the integration of depression and HIV management, particularly in rural health settings of Cameroon. MATERIALS AND METHODS: We carried out a cluster-randomized intervention study targeting persons aged 13 years and above who had been on antiretroviral treatment for 6-9 months. Participants were followed up for 12 months during which those in the intervention group underwent routine screening and management of depression. Comparisons were done using the two-way ANOVA and Chi-squared test with significance set at 5%. RESULTS: Overall, 370 participants with a median age of 39 years (IQR: 30-49) were enrolled in this study. Of these, 42 (11.3%) were screened with moderate to severe depressive symptoms and 41 (11.1%) had poor treatment adherence. There was a significant drop in depression scores in the intervention group from 3.88 (± 3.76) to 2.29 (± 2.39) versus 4.35 (± 4.64) to 3.39 (± 3.0) in controls (p < 0.001) which was accompanied by a drop in the prevalence of moderate to severe depressive symptoms in the intervention group from 9% to 0.8% (p = 0.046). Decreased depression scores were correlated with better adherence scores with correlation coefficients of - 0.191, - 0.555, and - 0.513 at baseline, 6 months, and 12 months of follow-up respectively (p < 0.001) but there was no significant difference in adherence levels (p = 0.255) and viral suppression rates (p = 0.811) between groups. CONCLUSION: The results of this study suggest that considering routine screening and management of depression as an integral component of HIV care could positively impact HIV treatment outcomes. However, there is a need for more research to identify the best combinations of context-specific and cost-effective strategies that can impactfully be integrated with HIV management. Trial registration Trial registration Number: DRKS00027440. Name of Registry: German Clinical Trials Register. Date registration: December 10, 2021 ('retrospectively registered'). Date of enrolment of the first participant: 05/08/2019.

[Important arboviral diseases in returning travelers: dengue, chikungunya and zika]. / Wichtige Arbovirosen bei Tropenrückkehrern: Dengue, Chikungunya, Zika.

Arboviral infections are an important differential diagnosis in returning travelers with fever, muscle or joint pain and rash. Arboviruses have spread widely around the globe in the last decades. The most common arboviral infections in returning travelers from tropical and subtropical areas are dengue, chikungunya and zika. Their most important vectors, Aedes (Stegomyia) mosquito species, have adapted to the urban environment, which enabled arboviruses to establish urban transmission cycles. Population growth, urbanization, globalization, modern means of transportation and global warming are speeding up their spread.Laboratory confirmation of an arboviral infection can generally be obtained by direct virus detection (PCR, antigen test) in the first week of illness; from the second week of illness serology can be used. Treatment is mostly symptomatic.Dengue fever is the most common cause of fever in returning travelers from South-East Asia. Patients have to be educated about and observed for warning signs of severe dengue that can rarely develop around day 5 of the disease and is marked by a rise in hematocrit.Chikungunya mostly occurs in epidemics and is characterized by severe and often long-lasting arthritis.Preconceptional screening for zika virus infection is not recommended. Instead, travelers should delay conception for up to three months after returning from a zika endemic area.Dengue, chikungunya and zika vaccine development has been hampered by difficulties, for example antibody-dependent-enhancement or the unpredictability of outbreaks, and up to now no vaccines for travelers have been licensed. Yet several promising vaccine candidates are currently under development.

COVID-19 Testing Unit Munich: Impact of Public Health and Safety Measures on Patient Characteristics and Test Results, January to September 2020.

To assess the course of the COVID-19 pandemic and the impact of non-pharmaceutical interventions, the number of reported positive test results is frequently used as an estimate of the true number of population-wide infections. We conducted a retrospective observational analysis of patient data of the Corona Testing Unit (CTU) in Munich, Bavaria, Germany between January 27th, and September 30th, 2020. We analyzed the course of daily patient numbers over time by fitting a negative binomial model with multiple breakpoints. Additionally, we investigated possible influencing factors on patient numbers and characteristics by literature review of policy papers and key informant interviews with individuals involved in the set-up of the CTU. The 3,963 patients included were mostly young (median age: 34, interquartile range: 27-48), female (66.2%), and working in the healthcare sector (77%). For these, 5,314 real-time RT-PCR tests were conducted with 157 (2.94%) positive results. The overall curve of daily tests and positive results fits the re-ported state-wide incidence in large parts but shows multiple breakpoints with considerable trend changes. These can be most fittingly attributed to testing capacities and -strategies and individual risk behavior, rather than public health measures. With the large impact on patient numbers and pre-test probabilities of various strategic and operational factors, we consider the derived re-ported incidence as a poor measurement to base policy decisions on. Testing units should be prepared to encounter these fluctuations with a quickly adaptable structure.

Causes of fever in returning travelers: a European multicenter prospective cohort study.

BACKGROUND: Etiological diagnosis of febrile illnesses in returning travelers is a great challenge, particularly when presenting with no focal symptoms [acute undifferentiated febrile illnesses (AUFI)], but is crucial to guide clinical decisions and public health policies. In this study, we describe the frequencies and predictors of the main causes of fever in travelers. METHODS: Prospective European multicenter cohort study of febrile international travelers (November 2017-November 2019). A predefined diagnostic algorithm was used ensuring a systematic evaluation of all participants. After ruling out malaria, PCRs and serologies for dengue, chikungunya and Zika viruses were performed in all patients presenting with AUFI ≤ 14 days after return. Clinical suspicion guided further microbiological investigations. RESULTS: Among 765 enrolled participants, 310/765 (40.5%) had a clear source of infection (mainly traveler's diarrhea or respiratory infections), and 455/765 (59.5%) were categorized as AUFI. AUFI presented longer duration of fever (p < 0.001), higher hospitalization (p < 0.001) and ICU admission rates (p < 0.001). Among travelers with AUFI, 132/455 (29.0%) had viral infections, including 108 arboviruses, 96/455 (21.1%) malaria and 82/455 (18.0%) bacterial infections. The majority of arboviral cases (80/108, 74.1%) was diagnosed between May and November. Dengue was the most frequent arbovirosis (92/108, 85.2%). After 1 month of follow-up, 136/455 (29.9%) patients with AUFI remained undiagnosed using standard diagnostic methods. No relevant differences in laboratory presentation were observed between undiagnosed and bacterial AUFI. CONCLUSIONS: Over 40% of returning travelers with AUFI were diagnosed with malaria or dengue, infections that can be easily diagnosed by rapid diagnostic tests. Arboviruses were the most common cause of AUFI (above malaria) and most cases were diagnosed during Aedes spp. high season. This is particularly relevant for those areas at risk of introduction of these pathogens. Empirical antibiotic regimens including doxycycline or azithromycin should be considered in patients with AUFI, after ruling out malaria and arboviruses.

From first to second wave: follow-up of the prospective COVID-19 cohort (KoCo19) in Munich (Germany).

BACKGROUND: In the 2nd year of the COVID-19 pandemic, knowledge about the dynamics of the infection in the general population is still limited. Such information is essential for health planners, as many of those infected show no or only mild symptoms and thus, escape the surveillance system. We therefore aimed to describe the course of the pandemic in the Munich general population living in private households from April 2020 to January 2021. METHODS: The KoCo19 baseline study took place from April to June 2020 including 5313 participants (age 14 years and above). From November 2020 to January 2021, we could again measure SARS-CoV-2 antibody status in 4433 of the baseline participants (response 83%). Participants were offered a self-sampling kit to take a capillary blood sample (dry blood spot; DBS). Blood was analysed using the Elecsys® Anti-SARS-CoV-2 assay (Roche). Questionnaire information on socio-demographics and potential risk factors assessed at baseline was available for all participants. In addition, follow-up information on health-risk taking behaviour and number of personal contacts outside the household (N = 2768) as well as leisure time activities (N = 1263) were collected in summer 2020. RESULTS: Weighted and adjusted (for specificity and sensitivity) SARS-CoV-2 sero-prevalence at follow-up was 3.6% (95% CI 2.9-4.3%) as compared to 1.8% (95% CI 1.3-3.4%) at baseline. 91% of those tested positive at baseline were also antibody-positive at follow-up. While sero-prevalence increased from early November 2020 to January 2021, no indication of geospatial clustering across the city of Munich was found, although cases clustered within households. Taking baseline result and time to follow-up into account, men and participants in the age group 20-34 years were at the highest risk of sero-positivity. In the sensitivity analyses, differences in health-risk taking behaviour, number of personal contacts and leisure time activities partly explained these differences. CONCLUSION: The number of citizens in Munich with SARS-CoV-2 antibodies was still below 5% during the 2nd wave of the pandemic. Antibodies remained present in the majority of SARS-CoV-2 sero-positive baseline participants. Besides age and sex, potentially confounded by differences in behaviour, no major risk factors could be identified. Non-pharmaceutical public health measures are thus still important.

Risk factors for and management of metronidazole-refractory giardiasis in international travellers: A retrospective analysis.

BACKGROUND: Giardia lamblia is a common cause of diarrhoea in returning travellers. Failure of the recommended first-line treatment, metronidazole, has frequently been observed. Recommendations for treatment of metronidazole-refractory giardiasis lack clarity and evidence. METHODS: We conducted a retrospective data analysis of returned travellers with confirmed giardiasis at the Bernhard-Nocht-Clinic in Hamburg, Germany, between 2007 and 2016. RESULTS: We identified 339 cases of giardiasis, mostly acquired in South Asia (n = 157). 308 patients received metronidazole as first-line treatment, leading to treatment failure in 93 cases. Statistical analysis suggested by far the highest risk of metronidazole treatment failure for travellers returning from South Asia (Odds Ratio 8.73). Second-line therapy consisted of various different therapy regimens. Combination therapy as second-line treatment seemed to be more effective than monotherapy. A repeat course of metronidazole proved to be futile. CONCLUSION: This study reveals a strikingly low effectiveness of metronidazole, especially in patients returning from South Asia. Second-line treatment showed inconsistency of regimens and yielded unsatisfactory results. These findings require reconsideration of treatment strategies for giardiasis. Large prospective trials are urgently needed to assess new first-line treatment options and to help implement advice for effective, agreed second-line treatment strategies. Translational projects should be created to link the understanding of resistance mechanisms with epidemiological data and clinical outcome.

Efficacy and Tolerability of Quinacrine Monotherapy and Albendazole Plus Chloroquine Combination Therapy in Nitroimidazole-Refractory Giardiasis: A TropNet Study.

BACKGROUND: Giardiasis failing nitroimidazole first-line treatment is an emerging problem in returning European travelers. We present data on the efficacy and tolerability of 2 second-line treatment regimens. METHODS: This prospective, open-label, multicenter study assessed the efficacy and tolerability of quinacrine monotherapy (100 mg 3 times per day for 5 days) and albendazole plus chloroquine combination therapy (400 mg twice daily plus 155 mg twice daily for 5 days) in nitroimidazole-refractory giardiasis. The defined end points were the clinical outcome, assessed at week 5 after treatment and the parasitological outcome, assessed using microscopy of 2 stool samples, ≥2 to ≤5 weeks after treatment. RESULTS: A total of 106 patients were included in the study. Quinacrine achieved clinical and parasitological cure in 81% (59/73) and 100% (56/56), respectively. Albendazole plus chloroquine achieved clinical and parasitological cure in 36% (12/33) and 48% (12/25), respectively. All patients (9/9) who clinically and parasitologically failed albendazole plus chloroquine treatment and opted for retreatment with quinacrine achieved clinical cure. Mild to moderate treatment-related adverse events were reported by 45% and 30% of patients treated with quinacrine and albendazole plus chloroquine, respectively. One patient treated with quinacrine developed severe neuropsychiatric side effects. The majority of nitroimidazole-refractory Giardia infections (57%) were acquired in India. CONCLUSIONS: Quinacrine was a highly effective treatment in nitroimidazole-refractory giardiasis, but patients should be cautioned on the low risk of severe neuropsychiatric adverse event. Albendazole plus chloroquine had a low cure rate in nitroimidazole-refractory giardiasis. Nitroimidazole-refractory giardiasis was primarily seen in travelers returning from India.