[Emergent and reemergent infectious diseases]. / Maladies infectieuses émergentes et réémergentes.

Emergent and reemergent infectious diseases. The notion of emerging and re-emerging infection has been developed recently, even if it rests on an already former concept. The emergence is doubtless delicate to define but can globally be an infectious disease by which the real incidence increases for a population and a geographical zone given to a period of time. Numerous factors condition an emergence, very unknown or not mastered. They report the difficulty or the impossibility to plan in a reliable way a future phenomenon, which would be nevertheless desirable. Yet to assure a legitimate effective coverage, serious preliminary data is essential. The modern companies wish to get organized and to form themselves to fight at best. Diverse ways can be set up.

Maladies infectieuses émergentes et réémergentes. La notion d'infection émergente et réémergente s'est développé récemment, même si elle repose sur un concept déjà ancien. L'émergence est sans doute délicate à définir mais peut globalement être une maladie infectieuse dont l'incidence réelle augmente pour une population et une zone géographique données sur une période de temps. De nombreux facteurs conditionnent une émergence, beaucoup inconnus ou non maîtrisés. Ils rendent compte de la difficulté ou de l'impossibilité de prévoir de façon fiable un futur phénomène, ce qui serait pourtant souhaitable. Or, pour assurer une légitime prise en charge efficace, des données prévisionnelles sérieuses sont essentielles. Les sociétés modernes désirent s'organiser et se structurer pour lutter au mieux. Divers moyens peuvent être mis en place. Des plans correctement définis permettent de les mettre en oeuvre.

Postartesunate delayed hemolysis is a predictable event related to the lifesaving effect of artemisinins.

Patients with severe malaria treated with artesunate sometimes experience a delayed hemolytic episode. Artesunate (AS) induces pitting, a splenic process whereby dead parasites are expelled from their host erythrocytes. These once-infected erythrocytes then return to the circulation. We analyzed hematologic parameters in 123 travelers treated with AS for severe malaria. Among 60 nontransfused patients observed for more than 8 days, 13 (22%) had delayed hemolysis. The peak concentration of circulating once-infected erythrocytes was measured during the first week in 21 patients and was significantly higher in 9 patients with delayed hemolysis than in 12 with other patterns of anemia (0.30 vs 0.07; P = .0001). The threshold of 180 million once-infected erythrocytes per liter discriminated patients with delayed hemolysis with 89% sensitivity and 83% specificity. Once-infected erythrocyte morphology analyzed by using ImageStream in 4 patients showed an 8.9% reduction in their projected area, an alteration likely contributing to their shorter lifespan. Delayed clearance of infected erythrocytes spared by pitting during AS treatment is an original mechanism of hemolytic anemia. Our findings consolidate a disease framework for posttreatment anemia in malaria in which delayed hemolysis is a new entity. The early concentration of once-infected erythrocytes is a solid candidate marker to predict post-AS delayed hemolysis.

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Under diverse pretexts the vaccination sees itself controversial in particular in France, and it in a increasing way. This establishes a real problem of public health. The doubt which settles down in the population becomes source of grave potential risk in the fight against the infectious diseases. Yet more we try to fight this phenomenon more the anti-vaccinal react helped in it by the modern ways of communication. So in a country where the pleasure to dispute the public action is big, why not to react in a provocating way on the same register and to ask the question of a stop to inoculate to show the consequences and so try to make sensitive the citizens to put them in front of their responsibilities towards the whole population as for the vaccinations.

Delayed-onset hemolytic anemia in patients with travel-associated severe malaria treated with artesunate, France, 2011-2013.

Artesunate is the most effective treatment for severe malaria. However, delayed-onset hemolytic anemia has been observed in ≈20% of travelers who receive artesunate, ≈60% of whom require transfusion. This finding could discourage physicians from using artesunate. We prospectively evaluated a cohort of 123 patients in France who had severe imported malaria that was treated with artesunate; our evaluation focused on outcome, adverse events, and postartesunate delayed-onset hemolysis (PADH). Of the 123 patients, 6 (5%) died. Overall, 97 adverse events occurred. Among the 78 patients who received follow-up for >8 days after treatment initiation, 76 (97%) had anemia, and 21 (27%) of the 78 cases were recorded as PADH. The median drop in hemoglobin levels was 1.3 g/dL; 15% of patients with PADH had hemoglobin levels of <7 g/dL, and 1 required transfusion. Despite the high incidence of PADH, the resulting anemia remained mild in 85% of cases. This reassuring result confirms the safety and therapeutic benefit of artesunate.

Longitudinal and integrative biomodeling of effector and memory immune compartments after inactivated influenza vaccination.

Most vaccines, including those against influenza, were developed by focusing solely on humoral response for protection. However, vaccination activates different adaptive compartments that might play a role in protection. We took advantage of the pandemic 2009 A(H1N1) influenza vaccination to conduct a longitudinal integrative multiparametric analysis of seven immune parameters in vaccinated subjects. A global analysis underlined the predominance of induction of humoral and CD4 T cell responses, whereas pandemic 2009 A(H1N1)-specific CD8 responses did not improve after vaccination. A principal component analysis and hierarchical clustering of individuals showed a differential upregulation of influenza vaccine-specific immunity including hemagglutination inhibition titers, IgA(+) and IgG(+) Ab-secreting cells, effector CD4 or CD8 T cell frequencies at day 21 among individuals, suggesting a fine-tuning of the immune parameters after vaccination. This is related to individual factors including the magnitude and quality of influenza-specific immune responses before vaccination. We propose a graphical delineation of immune determinants that would be essential for a better understanding of vaccine-induced immunity in vaccination strategies.

Vaccine knowledge in students in Paris, France, and surrounding regions.

INTRODUCTION: In France, young adults are legally freed from parental authority at the age of 18 years and are, thus, responsible for their own vaccine record. This young adult population is more frequently exposed to vaccine-preventable infectious diseases. OBJECTIVE: To determine the factors associated with students' knowledge of the interval between two antitetanus boosters and their report of having up-to-date vaccinations. METHODS: In April 2009, a survey was conducted involving a random sample of students between 18 and 25 years of age eating lunch at university dining facilities in Paris and its suburbs (Ile de France). RESULTS: Among the 677 students approached, 583 agreed to participate. Only 207 (36%) of respondents knew the recommended dosing interval between two doses of tetanus vaccine booster (10 years). The majority of students (69%) reported having up-to-date vaccinations. Declaring having up-to-date vaccinations was significantly associated with having a general practitioner (OR 3.03 [95% CI 1.69 to 5.55]). Health care students were significantly more likely to know the decennial interval between two antitetanus boosters (OR 2 [95% CI 1.28 to 3.25]). Most of responding students (n=519 [89%]) believed that vaccines were very useful. CONCLUSIONS: An overall lack of knowledge of vaccines was observed among this student population. Health care providers, such as GPs and university medical practice staff, who interact with these young individuals have an essential role to promote better vaccination coverage in this population.

INTRODUCTION: En France, les jeunes adultes sont légalement libérés de l'autorité parentale à 18 ans et deviennent donc responsables de leur dossier de vaccination. La population de jeunes adultes est davantage exposée aux maladies infectieuses évitables par la vaccination. OBJECTIF: Déterminer les facteurs associés aux connaissances des étudiants sur l'intervalle entre les deux doses de rappel du vaccin contre le tétanos et sur leur déclaration d'avoir une couverture vaccinale. MÉTHODOLOGIE: En avril 2009, un sondage a été mené auprès d'un échantillon aléatoire d'étudiants de 18 à 25 ans qui, le midi, mangent aux cafétérias universitaires de Paris et des banlieues (Île de France). RÉSULTATS: Sur les 677 étudiants abordés, 583 ont accepté de participer. Seulement 207 des répondants (36 %) connaissaient l'intervalle recommandé entre deux doses de rappel du vaccin contre le tétanos (dix ans). La majorité des étudiants (69 %) déclarai avoir une couverture vaccinale à jour. Cette déclaration s'associait de manière significative au fait d'avoir un praticien général (RC 3,03 95 % IC 1,69 à 5,55]). Les étudiants du milieu de la santé étaient considérablement plus enclins à connaître l'intervalle de dix ans entre deux doses de rappel du vaccin antitétanique (RC 2 [95 % IC 1,28 à 3,25]). La plupart des étudiants répondants (n=519 [89 %]) croyaient en l'utilité des vaccins. CONCLUSIONS: Les chercheurs ont constaté une ignorance globale des vaccins au sein de cette population de patients. Les dispensateurs de soins, tels que les praticiens généraux et le personnel médical en milieu universitaire, qui dialoguent avec ces jeunes, ont un rôle essentiel à jouer pour promouvoir une meilleure couverture vaccinale au sein de cette population.

[Imported severe falciparum malaria in France in 2000-2011: epidemiological trends and the need for new treatments]. / Le paludisme grave a P. falciparum en France, 2000- 2011: evolution epidémiologique et nécessité d'une nouvelle prise en charge thérapeutique.

In France malaria is monitored by the Centre National de Référence (CNR) du Paludisme (French National Malaria Reference Centre). The annual incidence of imported malaria currently ranges from 4 800 to 3 500 cases and has fallen gradually since 2000. However, the proportion of patients with severe P. falciparum malaria is increasing (2.5% in 2000, 7% in 2011), particularly among French residents from sub-Saharan Africa who neglect preventive measures. Overall mortality remains stable at 0.4%, but survival is improving in severe cases. The survival rate is higher among patients of African origin than among Europeans. Nonetheless, between 10 and 20 patients die of malaria every year in France. Two large controlled trials published in 2005 and 2010 showed that IV artesunate, a new treatment for severe falciparum malaria, is associated with a 22-38% absolute reduction in mortality relative to quinine. Artesunate is not licensed in Europe but has been available in France since May 2011 through a named-patient program controlled by the French Agency for Drug Safety [ANSM]. The first 99 patients treated with artesunate up to September 2012 experienced satisfactory efficacy and tolerability. Delayed, sometimes persistent anemia was observed in 13 patients, a rate similar to that noted in recent reports on imported malaria in Europe. This unexpected adverse effect requires further investigation. IV artesunate is now recommended as the first-line treatment for severe falciparum malaria in France.

Lateral rectus muscle paralysis induced by ribavirin and pegylated interferon-α2a in a patient with HIV/HCV co-infection.

We report a lateral rectus muscle paralysis occurring 2 weeks after initiation of an interferon-α and ribavirin treatment in a patient with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) virus co-infection. This patient presented with horizontal diplopia that appeared rapidly and without any other neurological symptoms. Symptoms fully resolved with treatment interruption without any ophthalmological sequelae. This side effect is rare and has never been reported in a HIV-HCV co-infected patient.

[Antibiotherapy of infectious endocarditis]. / Antibiothérapie des endocardites infectieuses.

Antibiotherapy is the pillar of the infectious endocarditis treatment. Bactericidal drugs must be used and their choice has to be adapted to bacterial sensitivity. The duration of treatment, traditionaly lengthy, especially in prosthetic valve endocarditis, depends on bacteria and has been shortened in some guidelines because of the combination of aminoglycoside.

Successful treatment of nodular lymphangitis due to Mycobacterium chelonae in two immunosuppressed patients.

M. chelonae is a classical but uncommon etiology of nodular lymphangitis. We report 2 cases of nodular lymphangitis caused by M. chelonae occurring in immunocompromised hosts; both were cleared with antibiotic therapy.

[Inflammation and HIV]. / Inflammation et VIH.

Although antiretroviral therapy for HIV infection prevents AIDS-related complications and prolongs life, it does not fully restore health. Long-term treated patients remain at a higher-than-expected risk of complications, including cardiovascular disease, cancer, osteoporosis and other end-organ diseases. The potential effect of HIV on health is perhaps most clearly demonstrated by the immune activation and inflammation that persist despite effective suppression of HIV replication.

Distinct time effects of vaccination on long-term proliferative and IFN-gamma-producing T cell memory to smallpox in humans.

Residual immunity to the smallpox virus raises key questions about the persistence of long-term immune memory in the absence of antigen, since vaccination ended in 1980. IFN-gamma-producing effector-memory and proliferative memory T cells were compared in 79 vaccinees 13-25 yr after their last immunization and in unvaccinated individuals. Only 20% of the vaccinees displayed both immediate IFN-gamma-producing effector-memory responses and proliferative memory responses at 6 d; 52.5% showed only proliferative responses; and 27.5% had no detectable vaccinia-specific responses at all. Both responses were mediated by CD4 and CD8 T cells. The vaccinia-specific IFN-gamma-producing cells were composed mainly of CD4Pos CD45RANeg CD11aHi CD27Pos and CCR7Neg T cells. Their frequency was low but could be expanded in vitro within 7 d. Time since first immunization affected their persistence: they vanished 45 yr after priming, but proliferative responses remained detectable. The number of recalls did not affect the persistence of residual effector-memory T cells. Programmed revaccination boosted both IFN-gamma and proliferative responses within 2 mo of recall, even in vaccinees with previously undetectable residual effector-memory cells. Such long-term maintenance of vaccinia-specific immune memory in the absence of smallpox virus modifies our understanding of the mechanism of persistence of long-term memory to poxviruses and challenges vaccination strategies.

Impact of hepatitis C and liver fibrosis on antiretroviral plasma drug concentrations in HIV-HCV co-infected patients: the HEPADOSE study.

OBJECTIVES: To compare plasma antiretroviral concentrations in HIV-HCV co-infected and in matched HIV mono-infected patients. METHODS: This was a cross-sectional, observational study. Antiretroviral trough concentrations (C(min)) in plasma were measured in HIV-HCV co-infected patients with liver disease documented by liver biopsy, matched with HIV mono-infected patients according to gender and antiretroviral treatment. C(min) values in serum were measured using an HPLC method. Statistical analysis was performed using the Wilcoxon test. RESULTS: Seventy-three HIV-HCV co-infected patients and 66 HIV-infected patients were enrolled; 70% of patients were receiving a protease inhibitor (PI)- and 30% a non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimen. Among the 73 co-infected patients, 27 had a fibrosis score (Fibrotest(®)) of F4. Abacavir was the only nucleoside reverse transcriptase inhibitor whose trough concentrations differed between the co-infected and mono-infected groups. PI median plasma C(min) values were not different in the two groups, except for lopinavir, with a lower C(min) in the co-infected group than in the HIV-infected group (median 3673 versus 5990 ng/mL, P=0.04), and nelfinavir, with significantly higher concentrations in the co-infected group. Seventy-five percent of co-infected patients scoring F4, 33% of those scoring F0-F3 and 12% of HIV-infected patients were underdosed (P=0.02). Co-infected patients receiving an NNRTI had a higher plasma C(min) than HIV-infected patients; median C(min) was 3583 versus 1494 ng/mL (P=0.025) and 5331 versus 3954 ng/mL (P=0.10) for efavirenz and nevirapine, respectively. Overall, there was a greater proportion of co-infected patients with high concentrations of both NNRTIs (15/23) compared with HIV mono-infected patients (5/21) (P=0.008), especially in co-infected patients with an advanced liver fibrosis stage. CONCLUSIONS: Median plasma C(min) values differed significantly between HIV and HIV-HCV co-infected patients for abacavir, lopinavir and efavirenz. NNRTIs were strongly overdosed in HIV-HCV co-infected patients.

Clinical management of rapidly growing mycobacterial cutaneous infections in patients after mesotherapy.

BACKGROUND: Increasing numbers of patients are expressing an interest in mesotherapy as a method of reducing body fat. Cutaneous infections due to rapidly growing mycobacteria are a common complication of such procedures. METHODS: We followed up patients who had developed cutaneous infections after undergoing mesotherapy during the period October 2006-January 2007. RESULTS: Sixteen patients were infected after mesotherapy injections performed by the same physician. All patients presented with painful, erythematous, draining subcutaneous nodules at the injection sites. All patients were treated with surgical drainage. Microbiological examination was performed on specimens that were obtained before and during the surgical procedure. Direct examination of skin smears demonstrated acid-fast bacilli in 25% of the specimens that were obtained before the procedure and 37% of the specimens obtained during the procedure; culture results were positive in 75% of the patients. Mycobacterium chelonae was identified in 11 patients, and Mycobacterium frederiksbergense was identified in 2 patients. Fourteen patients were treated with antibiotics, 6 received triple therapy as first-line treatment (tigecycline, tobramycin, and clarithromycin), and 8 received dual therapy (clarithromycin and ciprofloxacin). The mean duration of treatment was 14 weeks (range, 1-24 weeks). All of the patients except 1 were fully recovered 2 years after the onset of infection, with the mean time to healing estimated at 6.2 months (range, 1-15 months). CONCLUSIONS: This series of rapidly growing mycobacterial cutaneous infections highlights the difficulties in treating such infections and suggests that in vitro susceptibility to antibiotics does not accurately predict their clinical efficacy.

Treatment of acute uncomplicated falciparum malaria with artemether-lumefantrine in nonimmune populations: a safety, efficacy, and pharmacokinetic study.

The efficacy and safety of artemether-lumefantrine for the treatment of malaria in nonimmune populations are not well defined. In this study, 165 nonimmune patients from Europe and non-malarious areas of Colombia with acute, uncomplicated falciparum malaria or mixed infection including P. falciparum were treated with the six-dose regimen of artemether-lumefantrine. The parasitologic cure rate at 28 days was 96.0% for the per protocol population (119/124 patients). Median times to parasite clearance and fever clearance were 41.5 and 36.8 hours, respectively. No patient had gametocytes after Day 7. Treatment was well tolerated; most adverse events were mild to moderate and seemed to be related to malaria. There were few serious adverse events, none of which were considered to be drug-related. No significant effects on ECG or laboratory parameters were observed. In conclusion, the six-dose regimen of artemether-lumefantrine was effective and well tolerated in the treatment of acute uncomplicated falciparum malaria in nonimmune patients.

[Herpes simplex virus meningitis in 11 patients]. / Méningite herpétique chez 11 patients.

METHOD: We reviewed retrospectively the demographic, clinical, biological characteristics and outcomes of 11 patients with HSV meningitis. RESULTS: Among the 11 patients, six were infected with HIV, four had a documented history of genital herpes, and one recurrent meningitis. In all cases, the onset of symptoms was abrupt, with severe headache and fever. On admission, 9/11 patients had severe meningismus; two patients had HSV anogenital ulcerations. CSF analysis showed in every case a significant increased of leukocytes with a lymphocytic pleocytosis, a mild elevated protein level and a normal glucose level. HSV was detected in the CSF in every case by PCR: the typing performed on six patients was positive in every case for HSV-2. Intravenous acyclovir (IV ACV) was started in 10/11 cases (range: 3-10 days), switched to valaciclovir (VACV) (range: 5-7 days); one patient was treated with ACV per os for 10 days. The total resolution of symptoms occurred within 48hours in every case. Two patients presented with recurrent HSV-2 meningitis in the next two months, with favorable outcome under IV ACV: a switch to long term VACV 500mg/day was prescribed without any recurrence. No patient presented with recurrence after a median follow-up of 30 months. CONCLUSION: Early recognition and treatment might improve the outcome of such infections. Adjunctive oral VACV after IV ACV treatment seems to be associated with a good clinical response in patients presenting with HSV meningitis. The duration of such treatments, including prophylactic treatments to prevent recurrent episodes must be better documented.