High Rate of Acquisition but Short Duration of Carriage of Multidrug-Resistant Enterobacteriaceae After Travel to the Tropics.

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 ß-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.

Atovaquone-proguanil in the treatment of imported uncomplicated Plasmodium falciparum malaria: a prospective observational study of 553 cases.

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.

Plasmodium falciparum malaria and atovaquone-proguanil treatment failure.

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.

Hospitalization criteria in imported falciparum malaria.

BACKGROUND: Controversy exists about the management of patients with imported Plasmodium falciparum malaria. We postulated that rapid parasite clearance supports ambulatory care, or, conversely, that factors associated with longer parasite clearance time (PCT) could be used as hospitalization criteria. METHODS: Hospitalized patients with imported falciparum malaria recruited through one single travel clinic between 1993 and 2000. We used a linear regression to identify factors independently associated with PCT defined as the time in hours from antimalarial drug administration until the first negative malaria smear. RESULTS: Among 400 patients hospitalized with falciparum malaria, mean (range) PCT was 58 (1-189) hours. In multivariate analysis, severe malaria, gastrointestinal signs, initial temperature greater than or equal to 40 degrees C, parasitemia greater than or equal to 1%, and platelet counts less than 50,000/microL were associated with longer PCT. Offering ambulatory care to patients aged 15 to 64 years with none of the factors associated with longer PCT in the study would have resulted in 147 (37%) patients receiving outpatient care. CONCLUSION: Factors identified in this model may help physicians determine which P falciparum malaria patients can be treated on an ambulatory basis, and contribute to revisions of national guidelines for imported malaria management.

Absence of efficacy of nonviable Lactobacillus acidophilus for the prevention of traveler's diarrhea: a randomized, double-blind, controlled study.

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.

Lamivudine and indinavir/ritonavir maintenance therapy in highly pretreated HIV-infected patients (Vista ANRS 109).

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 > or = 100 cells/ml, plasma HIV RNA (viral load [VL]) > or = 4 log10 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 > or = 25% or increase in VL > or = 0.7 log copies/ml relative to baseline. RESULTS: Twenty-six patients were included. Baseline median VL was 4.5 log10 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 log10 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.

Do African immigrants living in France have long-term malarial immunity?

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.

Efficacy of antimalarial chemoprophylaxis among French residents travelling to Africa.

Controversy exists about which antimalarial chemoprophylaxis regimen should be used among travellers to Africa: the WHO and other experts recommend the use of mefloquine throughout sub-Saharan Africa, whereas French experts still support the combination of chloroquine and proguanil in most of West Africa (the so-called zone 2 countries). In this case-control study based at a travel clinic, we examined the compliance with antimalarial chemoprophylaxis and its efficacy among travellers to tropical areas. Cases were patients with Plasmodium falciparum malaria (n = 131). Controls were patients who had a negative malaria film (n = 158). Of all controls, only 36 (22.8%) were adequately protected (i.e. compliant with an adapted regimen of chemoprophylaxis). In zone 2 countries, the efficacy of the combined chloroquine and proguanil was 58% (95% CI 22-78%) for all users, but increased to 100% (95% CI 89-100%) for compliant users. In zone 3 countries, the efficacy of mefloquine was 90% (95% CI 51-98%) and 100% (95% CI 58-100%) for all users and compliant users, respectively.