[Should patients infected with HIV be screened for occult hepatitis B?]. / Faut-il rechercher une hépatite B occulte chez les patients infectés par le virus de l'immunodéficience humaine (VIH) ?

UNLABELLED: Occult hepatitis B is defined as the presence of hepatitis B virus (HBV) DNA in the absence of detectable HBs antigen. The prevalence of occult hepatitis B among patients HIV-infected is uncertain, varying between 0% and 89%, and the clinical consequences of the coinfection are poorly known. The aim of this study was to evaluate the frequency of occult hepatitis B among HIV-infected patients and determine risk factors. METHODS: This retrospective study was conducted with plasma samples from 31HIV-infected patients untreated for HBV infection and for whom at least one sample was available. All patients were found to be carriers of isolated anti-HBc antibodies between 2000 and 2008, and HBV DNA was quantified in 51 samples (one to three per patient) by real-time PCR using the Qiagen HBV PCR kit. RESULTS: HBV DNA was found in samples from seven patients (22%). Occult hepatitis B seemed to be more frequent among patients coinfected with HCV (p=0.047). The number of CD4 cells was significantly less in samples containing detectable HBV DNA than in those with no detectable HBV DNA. CONCLUSION: The prevalence of occult hepatitis B seemed high, and HBV DNA titers were weak (< 20UI/mL), among patients infected with HIV and carrying isolated anti-HBc antibodies. These results would support screening HIV-infected patients for the presence of HBV DNA if confirmed with a larger patient population.

[Evaluation of cytomegalovirus quantification in blood by the R-gene real-time PCR test]. / Evaluation de la quantification du cytomégalovirus dans le sang par le test de PCR en temps réel CMV R-gene.

AIM OF THE STUDY: Diagnosing the presence of cytomegalovirus (CMV) in the blood of immunodepressed patients is often done by quantitative polymerase chain reaction (Q-PCR) even though the reference method remains the antigenemia pp65 (Ag-pp65) test. OBJECTIVES: To define the predictive value of the Q-PCR in the diagnosis of CMV disease and assess treatment efficacy using the CMV R-gene test. To compare the Q-PCR results and feasibility with those of the Ag-pp65 test. PATIENTS AND METHODS: The Q-PCR was performed in 34 whole blood samples (frozen at -80 degrees C until use) from five patients diagnosed with CMV disease, defined as the presence of clinical signs and Ag-pp65 in the nuclei of more than two cells. After extraction, viral DNA was quantified in each sample using the Q-PCR CMV R-gene kit according to the manufacturer's instructions. Immediately after blood was drawn, the Ag-pp65 test had been performed in 32 samples using CINAkit (Argene). RESULTS: The 16 samples positive by the Ag-pp65 test were also positive by PCR; six samples negative by the Ag-pp65 test were positive by PCR; and the remaining 10 samples were negative by both techniques. During treatment, the two markers' kinetics were similar. CONCLUSION: The CMV R-gene test has a predictive value as good as that of the Ag-pp65 test but is fast and easier to use. A prospective study with a greater number of patients is needed to define the prediction threshold for CMV disease.

[Seasonal outbreak of enteroviral meningitis during summer 2005: experience of a French pediatric unit]. / Epidémie estivale de méningites à entérovirus en 2005: expérience d'un service de pédiatrie générale.

OBJECTIVE: To describe the clinical and biological characteristics of children presenting with enteroviral (EV) meningitis in a French paediatric unit during summer 2005. METHODS: Retrospective study of children with EV meningitis from May to September 2005, diagnosed by PCR and/or viral culture in cerebrospinal fluid (CSF), serum or throat. RESULTS: We reported 99 cases of EV meningitis (96 confirmed and 3 probable). The sex ratio was 2/1, and the median age was 5 years. Peak incidence was reached during the second week of July. The predominant symptom was meningism. ENT (16%), digestive (10%), cutaneous (15%) or respiratory (4%) symptoms were rare. Blood leucocyte count found a predominance of neutrophils (73%), and lymphopenia in half of the children. The mean value of CRP was 25,5 mg/l. The median leukocyte count in CSF was 65 cells/mm(3), with a prevalence of neutrophils in 60% of cases. Pleiocytosis was absent in 20 children. CSF protein level was increased in 20% of cases. The rate of hospitalization was 57,5%. Intravenous antibiotic treatment, initiated among 18 patients, was stopped in 66,6% of the cases on reception of PCR result. The latter result was obtained in 2,3 days on average. CONCLUSION: The epidemic of 2005 EV meningitis was as widespread as that of summer 2000. Characteristics of these meningitis are strong proportion of CSF without pleiocytose and high prevalence of neutrophils in blood and CSF.

[Cowpox virus infection in a child]. / Infection à cowpox virus chez l'enfant.

UNLABELLED: Although human cowpox virus infection is rare nowadays, an animal reservoir of this virus still exists. The general course of cowpox virus infections is usually benign but the diagnosis is difficult and often late. CASE REPORT: An 11-year-old boy, owner of two cats, presented with an infected sacral wound lesion associated with fever and lymph nodes. The wound became necrotic and other cutaneous and mucous membrane lesions developed secondarily. Blood tests did not show hyperleukocytosis or a systemic inflammatory response. Concurrently one of the cats was examined by a veterinary because of multifocal cutaneous lesions. Evocative skin biopsy specimens from the animal and, secondarily from the patient, allowed the identification of orthopoxvirus. Evolution was slowly favourable under symptomatic treatment. CONCLUSION: Poxviruses are responsible for many animal and human diseases, the most famous of them being smallpox which today is considered eradicated. Vaccination against smallpox is no longer performed since 1977. Whether the arrest of vaccinations against smallpox may induce the apparition of other poxviruses infections or alter their clinical expression is an open question.

[Detection of circulating Candida albicans mannan and antimannan antibodies: useful for diagnosis of deep seated candidiasis]. / Intérêt de l'antigénémie mannane, du dosage des anticorps totaux par Elisa Platelia dans le diagnostic des infections profondes à Candida.

In deep seated candidiasis, only 40% of blood cultures are positive. The aim of the study was to investigate circulating Candida albicans mannan and anti-mannan antibodies as a possible help for the diagnosis of deep seated candidiasis. We have compared the results to the detection of IgM by Elisa and antibodies by immunoflourescence. The best tests, in accord to their sensitivity and specificity, are the mannan antigenemia (43% and 100%) and IgM (86% and 100%) and have to be used together.

Prevalence of resistance mutations in antiretroviral-naive chronically HIV-infected patients in 1998: a French nationwide study.

OBJECTIVE: To estimate the prevalence of resistance-conferring mutations to antiretroviral drugs in previously untreated patients with chronic HIV-1 infection as a basis for French recommendations on viral genotyping before antiretroviral treatment initiation. DESIGN: Resistance mutations were sought in samples from 404 patients seen in 23 specialized centres throughout metropolitan France in 1998. METHODS: The protease and reverse transcriptase (RT) genes of plasma virions were sequenced. Primary and secondary protease and RT gene mutations were identified from the International AIDS Society resistance testing - USA panel. RESULTS: The prevalence of patients with primary and secondary mutations were 3.7% (95% CI 1.7-5.7) and 50.3% (95% CI 45.0-55.6), respectively. The prevalence of patients with mutations associated with resistance to nucleoside RT inhibitors (NRTI) and non-nucleoside RT inhibitors was 3.3% (95% CI 1.5-5.1) and 0.8% (95% CI 0.0-1.7), respectively. The prevalence of patients with NRTI primary mutations differed according to whether seropositivity had been diagnosed more or less than one year previously (0.2 versus 2.2% P = 0.023). Primary mutations associated with protease inhibitor resistance occurred at a prevalence of 1.9% (95% CI 0.5-3.4) with no difference according to the duration of known seropositivity. CONCLUSION: In France, in 1998, the prevalence of patients with primary mutations associated with resistance to antiretroviral drugs was low. Genotyping before the initiation of therapy was not recommended in chronically HIV-1-infected naive patients. A national sentinel survey of resistance in this clinical setting is performed regularly to update the recommendations for resistance testing.

Proviral HIV-1 DNA in subjects followed since primary HIV-1 infection who suppress plasma viral load after one year of highly active antiretroviral therapy.

OBJECTIVE: An assessment of the impact of one year potent antiretroviral treatment initiated during primary HIV infection on the cell-associated viral burden. DESIGN AND METHODS: Proviral HIV-1 DNA was quantified in serial peripheral blood mononuclear cell (PBMC) samples from 19 patients enrolled in the French prospective PRIMO Cohort for whom plasma HIV RNA was suppressed to undetectable levels after one year of triple therapy; that is, plasma HIV-1 RNA was maintained below 200 copies/ml. Results were compared with those observed in 19 patients with chronic HIV-1 infection presenting the same degree of virus suppression after 12 months of treatment. RESULTS: At study entry, PRIMO subjects presented heterogeneous levels of proviral HIV-1 DNA: 2-3.92 log10 copies/10(6) PBMC and plasma HIV RNA: 2.3-6.5 log10 copies/ml. One year of effective highly active antiretroviral therapy (HAART) resulted in a median diminution of proviral DNA of -0.78 log10/10(6) PBMC in PRIMO subjects. The median decline in chronic-phase patients was -0.32 for those who were pre-treated and -0.52 for those previously naive of treatment. CONCLUSION: The decline in cell-associated HIV DNA observed throughout one year treatment indicated that HAART reduces the proviral HIV-DNA load more effectively when initiated during the primary rather than the chronic phase of HIV infection. These findings therefore tend to lend support to the early initiation of treatment. Nevertheless, heterogeneous baseline values observed for CD4 cell count, plasma HIV RNA and proviral HIV DNA in PRIMO subjects, raise the question of whether treatment should be delayed in some to spare early adverse effects of HAART.

[Hepatitis C virus contamination of endoscopes and biopsy forceps]. / Contamination des endoscopes et des pinces à biopsies par le virus de l'hépatite C.

BACKGROUND: Procedures such as digestive endoscopy may explain some unclear contaminations by HCV. AIMS: The aims of this study were to detect HCV genome on endoscopes and biopsy-forceps used in patients with known chronic HCV infection and to determine its presence in their gastric juice and saliva. METHODS: A gastroscopy with antral biopsies was performed in 48 patients with non-treated replicative chronic hepatitis C. Samples were obtained after pushing 10 mL of sterile water through the biopsy-suction channel and after immersing the brush used to clean this channel. The biopsy-forceps were also immersed and their tips brushed in 10 mL of sterile water. This sampling technique was repeated three times: immediately after the endoscopic procedure (T0), after washing with a detergent (T1) and after immersion for 20 minutes in a 2% glutaraldehyde solution (T2). The HCV genome was detected by polymerase chain reaction (PCR, Amplicor - Roche Diagnostics Systems). For the last 15 patients, samples of gastric juice and saliva were obtained before antral biopsies and used to detect HCV genome. RESULTS: HCV genome was detected in the biopsy-suction channel in 13 cases (27%) at T0 and in one case (2%) at T1. It was undetectable after completion of the disinfection procedure (T2). Three biopsy-forceps (6%) were PCR positive immediately after the endoscopy but none at T1 and T2. HCV genome was found in the gastric juice in three cases. In all of them, it was also found at T0 in the biopsy-suction channel but not on the biopsy-forceps. When saliva contained HCV genome (4 cases), it was present in the biopsy-suction channel in only one case. In this case, the gastric juice was also PCR positive. CONCLUSIONS: HCV genome is detected in 27% of cases in the biopsy-suction channel after an endoscopic procedure performed on patients with chronic HCV infection. The biopsy-forceps are PCR positive in 6% of cases. The infected gastric juice may play a role in the contamination of the endoscopes. The complete disinfection procedure seems effective to eliminate HCV.

Cell-associated HIV-1-DNA quantitation after highly active antiretroviral therapy-treated primary infection in patients with persistently undetectable plasma HIV-1 RNA.

OBJECTIVE: To determine the usefulness of cell-associated HIV-1-DNA quantification during the follow-up of highly active antiretroviral therapy (HAART)-treated primary-infected patients with persistently undetectable plasma RNA loads. PATIENTS AND METHODS: In 27 patients given HAART within a median of 24 days after symptomatic primary HIV infection, plasma and peripheral blood mononuclear cell (PBMC) HIV-1 RNA were less than 50 copies/ml and less than 50 copies/10(6) cells after 18 months of treatment. HIV-1 RNA and DNA were quantified every 6 months in PBMC in these 27 patients, 14 of whom accepted excision lymph node biopsy after month 18 for HIV-1-RNA and -DNA quantification in lymph node mononuclear cells (LNMC). RESULTS: The median decreases in plasma HIV-1 RNA, PBMC HIV-1 RNA and DNA over the 18 months of follow-up were 3.6 log (P< 0.005), 1.1 log (P< 0.05), and 1.0 log (P<0.001), respectively. HIV-1 DNA was detected in 92.3% of PBMC samples at baseline and at month 18. In LNMC, 100% of samples were detectable for HIV-1 DNA. CONCLUSION: In this highly selected population of patients with excellent plasma virological response under HAART, HIV-1 DNA showed a progressive decrease but was still detectable in 92.3% of samples at month 18, whereas all LNMC samples tested scored positive for HIV-1 DNA. The utility of proviral HIV-1-DNA monitoring was not clearly demonstrated in this 18-month follow-up of HAART-treated primary-infected patients. However, this finding could be reconsidered when using other therapeutic strategies such as structured treatment interruptions, reinforced treatment or additive immunotherapy.

Highly active antiretroviral treatment initiated early in the course of symptomatic primary HIV-1 infection: results of the ANRS 053 trial.

Highly active antiretroviral treatment (HAART) was given early to 64 patients with symptomatic primary human immunodeficiency virus (HIV)-1 infection. At the time of analysis, patients had been followed up for 9-21 months. No patient had died or developed an AIDS-defining event. Survival analysis showed that by month 21 the proportion of patients with plasma HIV-1 RNA <50 copies/mL was 72% (95% confidence interval, 58%-95%) in intention-to-treat analysis. After 18 months of treatment, 50% of the patients with undetectable plasma HIV-1 RNA also had undetectable HIV-1 RNA in peripheral blood mononuclear cells (PBMC). Only 1 of 3 patients had undetectable HIV-1 RNA in lymphoid tissue, while all patients had quantifiable HIV-1 DNA both in PBMC and lymphoid tissue. The median CD4 lymphocyte increase from baseline was 230 cells/microL. These preliminary results support the use of HAART in patients with primary HIV-1 infection.

[Mycoplasma pneumoniae pneumopathy. 10 cases]. / Pneumopathie à Mycoplasma pneumoniae. 10 observations.

OBJECTIVES: Describe the different features of a common disease: Mycoplasma pneumoniae pneumonia. PATIENTS AND METHODS: The hospital files of 10 consecutive patients with microbiologically proven Mycoplasma pneumoniae pneumonia were reviewed retrospectively. These 10 patients were hospitalized over a 15-month period among 150 patients admitted to the Versailles general hospital for community-acquired pneumonia. We compared our series with data in the literature. RESULTS: Most of the patients with Mycoplasma pneumoniae pneumonia were young apparently healthy adults. A bronchial risk factor (smoking, allergy) was however found in 60% of the patients. The principle symptom was persistent cough (100%), with fever and joint pain, or sometimes headache and signs of ENT involvement. Dyspnea was frequent, related more to associated bronchospasticity than to the severity of the pneumonia. Radiographic findings were quite variable. In one case hemolytic anemia and cold agglutinins suggested the diagnosis. Certain diagnosis was based on positive serology after hospitalization due to the long delay between symptom onset and hospitalization. The prehospital period was characterized by a succession of ineffective empirical antibiotic regimens. In routine practice, macrolides or fluoroquinolones administered for 2 to 3 weeks are the empirical antibiotics of choice. Outcome is generally favorable with rapid clinical and radiological improvement. Antibiotic therapy is not however sufficient alone to achieve improvement in the respiratory impairment: bronchodilators and corticosteroids are necessary to treat the bronchospasticity. CONCLUSION: Despite the benign nature of community-acquired pneumonia due to Mycoplasma pneumoniae, clinical manifestations, particularly bronchial inflammation may have important consequences.

Evolution of cytotoxic T lymphocyte responses to human immunodeficiency virus type 1 in patients with symptomatic primary infection receiving antiretroviral triple therapy.

The impact of highly active antiretroviral treatment (HAART) on anti-human immunodeficiency virus (HIV) cytotoxic T lymphocytes (CTL) was studied in 17 patients with recent symptomatic HIV-1 primary infection receiving triple combination therapy. Anti-HIV CTL were initially detected in 15 patients. In 6, CTL disappeared rapidly and persistently after initiation of therapy. Most of them had a rapid and sustained decrease in plasma HIV RNA to undetectable levels. Conversely, in 6 other patients, CTL remained detectable, which was associated with a less efficient control of viral replication. In 3 others, CTL disappeared only transiently, without clear correlation with the virologic profile. Altogether, despite individual variations, there was a positive correlation between viral replication and anti-HIV-1 cytotoxicity in most subjects, suggesting that the persistence of viral antigens is the main determinant for the maintenance of CTL activity. This raises the question of the potential benefit of anti-HIV CTL induction by immunotherapy in acute seroconverters treated by HAART.

CMV-IGG avidity and CMV-IGM concentration in both immunocompromised and immunocompetent patients.

Both CMV-specific IgG avidity index (AI) and CMV-specific IgM concentration were studied in different stages of CMV infection in both immunocompromised and immunocompetent patients. In these two groups (61 patients), a past CMV infection was associated with a mean AI constantly higher than 80%, just as the secondary infections observed in 18 immunocompromised patients (mean AI = 92%). In the 5 immunocompromised patients with primary CMV infection, the maturation of CMV IgG activity was delayed for at least one year; in contrast, the CMV-specific IgM concentration was persistently high up to 12 months. In additions, the 10 pediatric liver recipients who developed a primary CMV infection despite the administration of CMV specific immunoglobulins during the first two months post-transplantation had initially a high AI for anti-CMV reflecting the AI of passively acquired immunoglobulins. In four immunocompetent patients whose sera were taken less than 100 days after seroconversion, the mean AI was low (less than 35%) and was associated for 3 out of these 4 patients with a high concentration of CMV-specific IgM (IgM ratio > 3). Likewise, the AI of CMV-specific IgG in sera from 25 immunocompetent patients with suspected CMV infection was usually inversely correlated with CMV-specific IgM concentration. Thus, the use of these two parameters may help to date a CMV infection in immunocompetent patients especially in pregnant women.

[Predictive value of a rapid negativity of serum virus C viremia during treatment with interferon alpha in patients with chronic hepatitis C]. / Valeur prédictive de la négativation rapide de la virémie plasmatique du virus C au cours du traitement par l'interféron alpha de patients avec une hépatite chronique C.

Interferon alpha (INF) used for chronic hepatitis C treatment induces a response in less than 25% of patients. The aim of this study was to appreciate the predictive value of the delay of clearance of hepatitis C virus (HCV) viremia after onset therapy and to compare it with other virological markers such as viral load before treatment and viral type. Thirty one patients with chronic hepatitis C, treated with 3 MU Interferon, 3 times a week for 6 months, were followed until 6 months post-treatment. Response was defined according to the normalisation of transaminases levels and loss of HCV viremia. Five patients were long term responder, eleven patients were complete to relapse responder and fifteen patients were non responder. Serum HCV RNA level, HCV type and serial detection of serum HCV RNA were determined and correlated with the long term response to INF. Patients with long term response had lower pre-INF viral load compared to the complete to relapse responder or to the non responder (p < 0.001). A rapid clearance of serum HCV RNA (1 month) is observed for all the long term responder (p < 0.001). The lowest viral load is also observed in these patients (p < 0 05). By contrast, although the number of patient is low, we were not able to observe a relation between the viral type and the response to treatment. In conclusion this data indicate that the delay of clearance of HCV RNA is also a good predictor of response to INF therapy. Furthermore a rapid clearance of HCV RNA in patients with a very weak pre-INF viral load is strongly associated with long term response (positive predictive value: 100%).

[Severe parvovirus B19 infection in an immunocompetent child with hemophilia A]. / Infection sévère à parvovirus B19 chez un enfant hémophile A immunocompétent.

BACKGROUND: B19 parvovirus is a widespread virus whose typical manifestations in immunocompetent children are erythema infectiosum, acute erythroblastopenia and fetal anemia. CASE REPORT: An 11 year-old immunocompetent patient with hemophilia A was referred for an hemorrhagic syndrome. Forty days after a pasteurized coagulation factor concentrates treatment, and after 12 days of treatment with solvent/detergent factor VIII concentrates, he developed fever, consciousness disorders, pancytopenia, liver cytolysis and probably minor haemophagocytic syndrome, associated with human parvovirus B19 infection. His clinical state returned to normal within 15 days. A retrospective study revealed that the patient had received every day for 12 days, one parvovirus B19 polymerase chain reaction positive batch before the occurrence of symptoms. CONCLUSION: This case highlights the possibility of severe parvovirus B19 infection transmitted by clotting factors prepared from large pools of plasma. The use of recombinant factors would allow to reduce human virus contamination, even if immune risk has to be more accurately assessed.

Cytomegalovirus colitis in HIV-1-infected patients: a prospective research in 55 patients.

OBJECTIVE: To determine criteria for the diagnosis of cytomegalovirus (CMV) colitis and to analyse stages of the course and prognosis of CMV colonic involvement in HIV-1-infected patients. DESIGN: Prospective search for CMV colonic involvement with systematic biopsies to search for CMV intranuclear inclusion bodies and for CMV culture. The evolution of CMV colonic involvement was estimated using further coloscopies and autopsy. SETTING: Infectious diseases department in a tertiary referral teaching hospital in Paris, France. PARTICIPANTS: Fifty-five consecutive patients with HIV-1 infection, who had not previously received anti-CMV drugs, and who had at least one coloscopy performed. RESULTS: According to initial coloscopy, colitis, either ulcerative or inflammatory, was found in nine (16%) out of the 55 patients, CMV intranuclear inclusions were present in the colon of four (7%) patients, and colonic cultures were positive for CMV in 15 (27%) patients. The results of the initial coloscopy showed a positive correlation between endoscopic colitis (either ulcerative or inflammatory), CMV inclusions and positive CMV culture from colonic biopsies. The absence of endoscopic ulcerative lesions had a 98% (49 out of 50) negative predictive value for recording CMV inclusions in the colon (95% confidence interval, 89-100). CMV inclusions were recorded in three out of five ulcerative colitis. Male homosexuality, HIV-1 infection stages IVB, C1, D or E, according to the Centers for Disease Control and Prevention classification, CD4 lymphocyte count < 200 x 10(6)/l and CMV viraemia also correlated positively with CMV colonic involvement. During the observation period (mean, 7.3 months), the estimated incidence of CMV colitis according to coloscopic studies was 13%. Deterioration in condition was the most frequent spontaneous evolution of CMV colonic infection, whereas anti-CMV treatment resulted in an improvement. Ulcerative lesions occurred earlier in patients with colonic CMV inclusions or positive colonic CMV culture than in patients without CMV colonic involvement at the initial coloscopy. CMV colitis occurred late in the course of HIV-1 infection, on average 4 months before death. The presence of CMV inclusions was an indicator of poor prognosis with earlier occurrence of CMV viraemia and retinitis and no survival after 9 months. CONCLUSIONS: These results confirm that the colon is a target organ for CMV in HIV-1-infected patients. Coloscopy should be used to diagnose CMV colitis, because of the close correlation between endoscopic and histological data (i.e., intranuclear inclusions). This combination allows us to propose an evolutive staging of CMV colonic involvement and provide stratification criteria to assess the efficacy of anti-CMV drugs.