The risk of acquisition of multidrug-resistant Enterobacteriaceae (MRE) and of occurrence of diarrhea is high when traveling to tropical regions. The relationships between these phenomena and the composition of human gut microbiota have not yet been assessed. Here, we investigated the dynamics of changes of metabolically active microbiota by sequencing total RNA from fecal samples taken before and after travel to tropical regions. We included 43 subjects who could provide fecal samples before and after a travel to tropical regions. When found positive by culturing for any MRE after travel, the subjects sent an additional sample 1 month later. In all, 104 fecal samples were considered (43 before travel, 43 at return, 18 one month after travel). We extracted the whole RNA, performed retrotranscription and sequenced the cDNA (MiSeq 2x300bp). The reads were mapped to the reference operational taxonomic units (OTUs) and species/strains using the 16S Greengenes and 23S SILVA databases. We found that the occurrence of diarrhea during the travel was associated with a higher relative abundance of Prevotella copri before departure and after return. The composition of microbiota, before travel as well as at return, was not correlated with the acquisition of MRE. However, the clearance of MRE one month after return was linked to a specific pattern of bacterial species that was also found before and after return. In conclusion, we found specific OTUs associated to a higher risk of diarrhea during a stay in tropical regions and to a faster clearance of MRE after their acquisition.

IMPORTANCE: Despite annually adapted recommendations to prevent malaria in travelers to endemic areas, France is still the industrialized country reporting the highest number of imported cases of malaria. Better understanding of the epidemiologic context and evolution during the past 2 decades may help to define a better preventive strategy. OBJECTIVE: To study epidemiologic trends of imported cases of malaria in travelers in geographic territories of France on the European continent (metropolitan France) from 1996 through 2016 to potentially explain the persistence of high imported malaria incidence despite national preventive measures. DESIGN, SETTING, AND PARTICIPANTS: In a cross-sectional study, between January 1 and May 31, 2018, data were extracted from the French National Reference Center of Malaria Surveillance. Trends in patients with imported malaria in association with age, sex, ethnicity, purpose of travel, malaria species, severity of illness, case mortality rate, and endemic countries visited were analyzed in 43 333 malaria cases among civilian travelers living in metropolitan France. MAIN OUTCOMES AND MEASURES: Evolution of the main epidemiologic characteristics of patients with imported malaria. RESULTS: Among the 43 333 patients with imported malaria in civilian travelers included in the study, 24949 were male (62.4%), and 8549 were younger than 18 years (19.9%). A total of 28 658 malaria cases (71.5%) were among African individuals, and 10618 cases (26.5%) among European individuals. From 1996 through 2016, the number of confirmed malaria cases peaked at 3400 cases in 2000, then declined to 1824 cases in 2005 and stabilized thereafter to approximately 1720 malaria cases per year. A total of 37065 cases (85.5%) were due to Plasmodium falciparum. The proportion of malaria cases among African individuals rose from 53.5% in 1996 to 83.4% in 2016, and the most frequent motivation for traveling was visiting friends and relatives (25 329 [77.1%]; P<.001). Despite an increase in the proportion of severe cases, which rose from 131 cases (8.9%) in 1996 to 279 cases (16.7%) in 2016 (P<.001), mortality remained stable, being approximately 0.4% during the study period. CONCLUSIONS AND RELEVANCE: Beyond the apparent stability of the number of imported malaria cases in France, significant changes appear to have occurred among the population who developed malaria infection following travel in endemic areas. These changes may imply that adaptation of the preventive strategy is needed to reduce the burden of the disease among travelers.

BACKGROUND:Multidrug-resistant Enterobacteriaceae (MRE) are widespread in the community, especially in tropical regions. Travelers are at risk of acquiring MRE in these regions, but the precise extent of the problem is not known.METHODS:From February 2012 to April 2013, travelers attending 6 international vaccination centers in the Paris area prior to traveling to tropical regions were asked to provide a fecal sample before and after their trip. Those found to have acquired MRE were asked to send fecal samples 1, 2, 3, 6, and 12 months after their return, or until MRE was no longer detected. The fecal relative abundance of MRE among all Enterobacteriaceae was determined in each carrier.RESULTS:Among 824 participating travelers, 574 provided fecal samples before and after travel and were not MRE carriers before departure. Of these, 292 (50.9%) acquired an average of 1.8 MRE. Three travelers (0.5%) acquired carbapenemase-producing Enterobacteriaceae. The acquisition rate was higher in Asia (142/196 [72.4%]) than in sub-Saharan Africa (93/195 [47.7%]) or Latin America (57/183 [31.1%]). MRE acquisition was associated with the type of travel, diarrhea, and exposure to β-lactams during the travel. Three months after return, 4.7% of the travelers carried MRE. Carriage lasted longer in travelers returning from Asia and in travelers with a high relative abundance of MRE at return.CONCLUSIONS:MRE acquisition is very frequent among travelers to tropical regions. Travel to these regions should be considered a risk factor of MRE carriage during the first 3 months after return, but not beyond.CLINICAL TRIALS REGISTRATION:NCT01526187.

Background: Each year, thousands of cases of uncomplicated malaria are imported into Europe by travellers. Atovaquone-proguanil (AP) has been one of the first-line regimens used in France for uncomplicated malaria for almost ten years. While AP's efficacy and tolerance were evaluated in several trials, its use in "real life" conditions has never been described. This study aimed to describe outcome and tolerance after AP treatment in a large cohort of travellers returning from endemic areas.Methods: Between September 2002 and January 2007, uncomplicated malaria treated in nine French travel clinics with AP were followed for 30 days after AP initiation. Clinical and biological data were collected at admission and during the follow-up.Results: A total of 553 patients were included. Eighty-eight percent of them were born in Africa, and 61.8% were infected in West Africa, whereas 0.5% were infected in Asia. Migrants visiting friends and relatives (VFR) constituted 77.9% of the patients, the remainder (32.1%) were backpackers. Three-hundred and sixty-four patients (66%) fulfilled follow-up at day 7 and 265 (48%) completed the study at day 30. Three patients had treatment failure. One-hundred and seventy-seven adverse drug reactions (ADR) were reported during the follow-up; 115 (77%) of them were digestive ADR. Backpackers were more likely to experiment digestive ADR compared to VFR (OR = 3.8; CI 95% [1.8-8.2]). Twenty patients had to be switched to another regimen due to ADR.Conclusion: This study seems to be the largest in terms of number of imported uncomplicated malaria cases treated by AP. The high rate of reported digestive ADR is striking and should be taken into account in the follow-up of patients since it could affect their adherence to the treatment. Beside AP, artemisinin combination therapy (ACT) is now recommended as first-line regimen. A comparison of AP and ACT, in terms of efficacy and tolerance, would be useful.

We noticed overrepresentation of atovaquone-proguanil therapeutic failures among Plasmodium falciparum-infected travelers weighing >100 kg. We report here 1 of these cases, which was not due to resistant parasites or impaired drug bioavailability. The follow-up of such patients should be strengthened.

Objective In patients with extensive HIV resistance, one option is to delay salvage therapy until new drugs become available. We hypothesized that this delay period could be based on a simplified treatment, which would reduce drug toxicity, stabilize resistance, and prevent resurgence of wild-type virus. Methods A prospective 24-week treatment simplification study in HIV-1-infected patients having failed several lines of antiretroviral therapy, with CD4 + T-cell counts ≥100 cells/ml, plasma HIV RNA (viral load [VL]) ≥4 log 10 copies/ml and a resistance genotype predicting less than two active drugs. Treatment associated ritonavir-boosted low-dose indinavir (200 mg twice daily) and lamivudine (150 mg twice daily). The primary endpoint was a decrease in CD4 + T-cell counts ≥25% or increase in VL ≥0.7 log copies/ml relative to baseline. Results; Twenty-six patients were included. Baseline median VL was 4.5 log 10 copies/ml and median CD4 + T-cell count was 290 cells/ml. During the study, 10/26 patients (38%, 95% confidence interval=20.2–59.4) reached the primary endpoint. No patient had an AIDS-defining event. At week 24, the median change in plasma VL was +0.2 log 10 copies/ml (interquartile range (IQR): 0–0.5; P=0.003). The median change in CD4 + T-cell counts was -49 cells/ml (IQR: -14 to -93, P<0.001), with a median decline slope of 10 cells/ml/month, which was not different from that measured under full highly active antiretroviral therapy during the 6 months preceding inclusion. There were no significant changes in HIV-1 protease and reverse transcriptase genotypes during the study. Conclusions In patients with advanced resistance, treatment simplification prevented resurgence of wild-type HIV, reduced drug burden, but failed to stabilize progression of the immune deficiency.

BACKGROUND:Diarrhea is the most common illness associated with international tourism. We evaluated the efficacy of a probiotic preparation of nonviable Lactobacillus acidophilus (hereafter referred to as LA) for the prevention of traveler's diarrhea.METHODS:We conducted a randomized, double-blind, controlled trial. Travelers were randomized to receive either LA or placebo twice daily from 1 day before their departure to 3 days after their return. On each day of the trip and the week following the return, travelers had to record the number and consistency of stools and their adherence to the treatment. Diarrhea was defined as > or =3 unformed stools in a 24-h period.RESULTS:From January 2001 to September 2004, a total of 174 subjects were randomized to each treatment group. Half of the travelers went to West Africa, and organized tours or backpacking were the most common modes of traveling. The incidence of diarrhea did not differ between the 2 groups; it was 61.4 cases per 100 person-months in the LA group (95% confidence interval [CI], 44.1-85.5) and 43.4 cases per 100 person-months in the placebo group (95% CI, 30.0-62.9) (P=.14). Adjustment for travel duration and other variables did not reveal any difference between the 2 groups (adjusted hazard ratios comparing the LA and placebo groups were 1.43 [95% CI, 0.87-2.36] in an intent-to-treat analysis and 1.38 [95% CI, 0.79-2.39] in an efficacy analysis).CONCLUSIONS:There was no beneficial effect of treatment with LA for the prevention of travelers' diarrhea. More studies are required to assess the efficacy of other specific probiotics (e.g., a Lactobacillus rhamnosus GG preparation) for preventing traveler's diarrhea.

Among populations living in areas endemic for malaria, repeated parasite exposure leads to a gradual increase in protective immunity to the disease. In contrast, this immunity is assumed to disappear after several years of non-exposure. This study was designed to investigate long-term immunity in subjects removed from the risk of exposure. Plasmodium falciparum malaria attacks occurring after short trips to sub-Saharan Africa were compared between 99 European patients and 252 African immigrants who had been resident in Europe for at least four years. Relative to the European patients, those originating from Africa had lower mean +/- SD parasite densities (0.8 +/- 1.5/100 red blood cells versus 1.4 +/- 2.8/100 red blood cells; P = 0.007), less frequent severe disease (4.4% versus 15.2%; P = 0.0005), accelerated parasite clearance and defervescence, and higher levels of antibodies to P. falciparum. These results suggest the persistence of acquired immunity to P. falciparum malaria after several years of non-exposure in African immigrants.

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