Olivier Bouchaud

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 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.

Plasmodium falciparum Clonal Population Dynamics during Malaria Treatment

We have developed a new fragment-analysis method to enumerate the clones and to quantify their proportions within Plasmodium falciparum isolates. We prospectively enrolled 20 adult patients with uncomplicated malaria who were returning to France from various sub-Saharan countries, from January 2000 through July 2001. The analysis of clonal populations was performed on blood samples obtained at 10 times: 1 before treatment with oral quinine and 9 during the first 96 h of the treatment. The resistance genotypes pfcrt and dhfr were determined for chloroquine and antifolinics. Multiple P. falciparum genotypes were detected in 19 (95%) of 20 patients: 2, 3, 4, and 5 genotypes were found in 4, 9, 4 and 2 patients, respectively. Disappearance and reappearance of some clones within a few hours was observed. Individual clones represented 0.4%-99.4% of total parasitemia. Surprisingly, in 10 of 15 subjects tested, resistance genotypes varied according to the time of blood collection. These findings may have important implications with regard to the interpretations of resistance studies.

Autoimmune diseases in HIV-infected patients: 52 cases and literature review

OBJECTIVES 1) To describe autoimmune diseases (AD) in HIV-infected people; and 2) to perform a literature review concerning this issue. DESIGN 52 HIV-infected patients that presented an AD in 14 medical departments in Paris and Ile-de-France area were retrospectively included in this study. RESULTS The ADs were vasculitis (11), immune cytopenias (8), rheumatic diseases (8), lupus (7), sarcoidosis (7), thyroid diseases (6), hepatic diseases (5), and antiphospholipid syndrome (4). Four patients presented 2 ADs. In 5 patients the AD preceded HIV infection, in 14 HIV infection was diagnosed at the same time as the AD and 34 were HIV-infected when they developed an AD. 40 ADs (80%) occurred in patients with a CD4 T lymphocyte count of more than 200/mm(3). Cases of autoimmune hemolytic anemia occurred only in patients severely immunodepressed. In five patients (a vasculitis case, a sarcoidosis case, three thyroid disease cases) the AD presented as a form of immune restoration inflammatory syndrome (IRIS). Some ADs allowed HIV-infection diagnosis at a stage of moderate immune deficiency (vasculitis, antiphospholipid syndrome, immune thrombocytopenia). 37 patients received immunosuppressant treatments with good tolerance. These results confirm in a large series of patients previous data concerning autoimmune diseases occurrence in HIV-infected people. CONCLUSION In the HAART era, when HIV-infected people are treated more and more early, autoimmune diseases can occur, mainly at the phase of immunological recovery. HIV infection should not limit immunosuppressant treatment use.

The comparative efficacy and tolerability of CGP 56697 (artemether + lumefantrine) versus halofantrine in the treatment of uncomplicated falciparum malaria in travellers returning from the Tropics to The Netherlands and France.

CGP 56697 (Riamet) is a new oral anti-malarial drug composed of artemether and lumefantrine (benflumetol) which combines the fast, short-acting artemether for rapid parasite clearance with the prolonged action of lumefantrine for intended radical cure. In this double-blind, comparative trial, the efficacy and tolerability of CGP 56697, given as a course of 4 x 4 tablets over 48 h, was compared to halofantrine, given as 3 x 2 tablets over 12 h with a second course 1 week later. Patients (mostly non-immune) with acute, uncomplicated Plasmodium falciparum infection were randomly assigned to either CGP 56697 (n = 51) or halofantrine (n = 52). CGP 56697 proved superior with respect to parasite clearance time (median 32 vs. 48 h, P < 0.001) and parasite reduction at 24 h (median 99.7 vs. 89.6%, P < 0.001) with a non-significant difference in resolution of fever (median 24 vs. 32 h, P = 0.835). However, a 28-day cure rate of 82% was observed for CGP 56697 and 100% for halofantrine. Significant QTc prolongations (> 30 ms) were seen 6-12 h after halofantrine intake but not after CGP 56697 intake. CGP 56697 is an effective, well-tolerated treatment for uncomplicated falciparum malaria but for this dosing regimen the recrudescence rate is unacceptablyhigh (18%). For travellers contracting malaria abroad, we propose a six-dose regimen of CGP 56697 over 3 days.

The low and declining risk of malaria in travellers to Latin America: is there still an indication for chemoprophylaxis?

A comparison was made between local malaria transmission and malaria imported by travellers to identify the utility of national and regional annual parasite index (API) in predicting malaria risk and its value in generating recommendations on malaria prophylaxis for travellers.Regional malaria transmission data was correlated with malaria acquired in Latin America and imported into the USA and nine European countries. Between 2000 and 2004, most countries reported declining malaria transmission. Highest APIs in 2003/4 were in Surinam (287.4) Guyana (209.2) and French Guiana (147.4). The major source of travel associated malaria was Honduras, French Guiana, Guatemala, Mexico and Ecuador. During 2004 there were 6.3 million visits from the ten study countries and in 2005, 209 cases of malaria of which 22 (11%) were Plasmodium falciparum. The risk of adverse events are high and the benefit of avoided benign vivax malaria is very low under current policy, which may be causing more harm than benefit.

Severe imported Plasmodium falciparum malaria, France, 1996-2003.

Little is known about severe imported Plasmodium falciparum malaria in industrialized countries where the disease is not endemic because most studies have been case reports or have included <200 patients. To identify factors independently associated with the severity of P. falciparum, we conducted a retrospective study using surveillance data obtained from 21,888 P. falciparum patients in France during 1996-2003; 832 were classified as having severe malaria. The global case-fatality rate was 0.4% and the rate of severe malaria was ≈3.8%. Factors independently associated with severe imported P. falciparum malaria were older age, European origin, travel to eastern Africa, absence of chemoprophylaxis, initial visit to a general practitioner, time to diagnosis of 4 to 12 days, and diagnosis during the fall-winter season. Pretravel advice should take into account these factors and promote the use of antimalarial chemoprophylaxis for every traveler, with a particular focus on nonimmune travelers and elderly persons.

Acquisition of carbapenemase-producing Enterobacteriaceae by healthy travellers to India, France, February 2012 to March 2013.

Healthy travellers to countries where carbapenemases-producing Enterobacteriaceae (CPE) are endemic might be at risk for their acquisition, even without contact with the local healthcare system. Here, we report the acquisition of CPE (two OXA-181, one New Delhi metallo-beta-lactamase 1 (NDM-1)) in three healthy travellers returning from India. The duration of CPE intestinal carriage was less than one month. The results indicate that healthy travellers recently returning from India might be considered as at risk for CPE carriage.

Prolonged Plasmodium falciparum Infection in Immigrants, Paris

Few immigrant travelers have Plasmodium falciparum infections >2 months after leaving malaria-endemic areas. We conducted a case–control study to identify factors associated with prolonged P. falciparum infection in immigrant travelers. Results suggest that P. falciparum infection should be systematically suspected, even months after travel, especially in pregnant women and first-arrival immigrants.

Comparison of Methods for Assessing Nutritional Status in HIV-Infected Adults

Malnutrition is a frequent complication of human immunodeficiency virus (HIV) infection and is associated with a poor prognosis. To compare different measures of nutritional status in HIV-infected patients, we prospectively studied 88 outpatients seen at a Paris AIDS outpatient clinic for routine follow-up examinations. Nutritional status was assessed according to body weight loss (BWL, 4 classes), anthropometry, bioelectric impedance analysis (BIA), and subjective global assessment of nutritional status (SGA). Malnutrition was diagnosed in 22.4% of subjects using SGA, and 37.1% by BWL. SGA rapidly detected a worsening of nutritional status, while BWL detected malnutrition at an earlier stage. A good correlation was found between SGA class and body composition assessed by anthropometry and BIA. Deteriorating nutritional status diagnosed by SGA correlated with the CDC HIV disease class. SGA, a simple nutritional assessment, can serve as a basis for prescribing artificial nutrition, while BWL detects malnutrition at an earlier stage.

Phase II study of liposomal encapsulated daunorubicin in the treatment of AIDS-associated mucocutaneous Kaposi's sarcoma

ObjectiveTo evaluate the efficacy and safety of liposomal encapsulated daunorubicin (DaunoXome) in the treatment of AIDS-associated mucocutaneous Kaposis sarcoma. DesignA Phase II, multicentre, European, non-comparative, open study to assess the use of DaunoXome in patients with no prior anthracycline chemotherapy for Kaposis sarcoma. The response rate, time to disease progression, and the incidence and severity of adverse events were documented. SettingHospital-based HIV units. PatientsThirty HIV-seropositive patients with mucocutaneous Kaposis sarcoma were enrolled and treated. InterventionsTreatment with DaunoXome at a dose of 40 mg/m2 intravenously once every 2 weeks. Treatment with antiretroviral agents and prophylaxis of opportunistic infections where indicated. ResultsOf the 30 evaluable patients, 22 patients (73%) achieved a partial response. Median time to treatment response was 30 days (range, 15–202). For patients with a partial response, median time to treatment failure was 153 days (range, 15–558). Patients received a median of 10 cycles (range, 1–44). Adverse events were minimal. The most common side effect was granulocytopenia in 16 patients (53%). ConclusionDaunoXome is an effective and well-tolerated treatment for AIDS-associated mucocutaneous Kaposis sarcoma and can be administered for prolonged periods. The myelosuppression can be managed by dose reductions and does not preclude the concurrent use of antiretroviral therapies.