Counter-intuitive plasma vitamin D and zinc status in HIV-1-infected adults with persistent low-level viraemia after treatment initiation: a pilot case-control study.

Determinants of persistent low-level viraemia [PLLV, a viral load (VL) of between 50 and 500 copies/mL] have not been elucidated. In a case-control study, we evaluated the influence of micronutrients on PLLV in a population of 454 HIV-1 adults having initiated antiretroviral therapy (ART) between January 2007 and December 2011. Plasma levels of retinol (vitamin A), 25-OH vitamin D2 + D3, vitamin E and zinc were measured at ART initiation in cases (PLLV after 6 months of ART) and in controls (VL <50 copies/mL after 6 months). Cases and controls were matched for the CD4 cell count (±50/mm3) and ethnic origin. Intergroup differences in demographic, biological and treatment parameters and sunshine intensity at ART initiation were adjusted using a propensity score. A receiver operating characteristic (ROC) curve was used to assess intergroup differences in plasma micronutrient levels. Thirty-three of the 454 patients (7.3%) displayed PLLV (median VL: 92 copies/mL). Patients were predominantly male (89%), Caucasian (64%) and CDC stage C (25%). The median age was 38 years, the median initial VL was 5.2 log10 copies/mL and the median CD4 count was 74/mm3. The 22 cases and matched controls were balanced in these respects, and had similar vitamin A/E levels. Two cases (9%) and 9 controls (41%) had a vitamin D level <10.3 ng/mL (p = 0.0015), and 2 cases (9%) and 10 controls (48%) had a zinc level <74.6 µg/dL (p = 0.04). Our results support in vitro studies suggesting that vitamin D favours HIV-1 replication and that HIV-1 is zinc-dependent. Wide-scale, prospective studies are required.

Time to initiation of antiretroviral therapy in HIV-infected patients diagnosed with an opportunistic disease: a cohort study.

OBJECTIVES: The aim of the study was to identify factors associated with the time between opportunistic disease (OD) diagnosis and antiretroviral therapy (ART) initiation in HIV-infected patients presenting for care with an OD, and to evaluate the outcomes associated with any delay. METHODS: A multicentre cohort study was undertaken in London, Paris and Lille/Tourcoing. The medical records of patients diagnosed from 2002 to 2012 were reviewed. RESULTS: A total of 437 patients were enrolled in the study: 70% were male, the median age was 40 years, 42% were from sub-Saharan Africa, 68% were heterosexual, the median CD4 count was 40 cells/µL, and the most common ODs were Pneumocystis pneumonia (37%), tuberculosis (24%), toxoplasmosis (12%) and Kaposi's sarcoma (11%). Of these patients, 400 (92%) started ART within 24 weeks after HIV diagnosis, with a median time from OD diagnosis to ART initiation of 30 [interquartile range (IQR) 16-58] days. Patients diagnosed between 2009 and 2012 had a shorter time to ART initiation than those diagnosed in earlier years [hazard ratio (HR) 2.07; 95% confidence interval (CI) 1.58-2.72]. Factors associated with a longer time to ART initiation were a CD4 count ≥ 200 cells/µL (HR 0.30; 95% CI 0.20-0.44), tuberculosis (HR 0.40; 95% CI 0.30-0.55) and diagnosis in London (HR 0.62; 95% CI 0.48-0.80). Patients initiating 'deferred' ART (by ≥ 30 days) exhibited no difference in disease progression or immunovirological response compared with patients who had shorter times to ART initiation. Patients in the 'deferred' group were less likely to have ART modifications (HR 0.69; 95% CI 0.48-1.00) and had shorter in-patient stays (mean 14.2 days shorter; 95% CI 8.9-19.5 days) than patients in the group whose ART was not deferred. CONCLUSIONS: The time between OD diagnosis and ART initiation remains heterogeneous and relatively long, particularly in individuals with a high CD4 count or tuberculosis or those diagnosed in London. Deferring ART was associated with fewer ART modifications and shorter in-patient stays.

[A case of neurological syphilis mimicking Horton's disease and polymyalgia rheumatica]. / Syphilis neurologique révélée par un tableau évocateur d'artérite temporale et de pseudopolyarthrite rhizomélique.

BACKGROUND: Syphilis has been making a comeback over the last 10 years. Neurosyphilis can occur at any stage of the infection but is difficult to diagnose because of the existence of misleading forms, of which we describe an example below. PATIENTS AND METHODS: A 56-year-old woman presented symptoms evoking polymyalgia rheumatica and giant-cell arteritis in a context of ibuprofen treatment for a few weeks. She also had myodesospsia, syphilids and syphilitic roseola, together with laboratory indicators of inflammation. A lumbar puncture revealed lymphocytic meningitis and a positive Treponema Pallidum Haemagglutination Assay (TPHA) for cerebrospinal fluid, thus confirming the diagnosis of neurosyphilis. Moreover, the ophthalmologic examination showed optic neuritis with papilla lesions of syphilitic origin. This was successfully treated with a 3-week course of penicillin G infusions. CONCLUSION: Symptoms evocative of Horton's disease and polymyalgia rheumatica can reveal syphilis, a disease dubbed "the great simulator" on account of the variety of clinical forms it can take.

Staphylococcus simulans as an authentic pathogenic agent of osteoarticular infections.

OBJECTIVES: To evaluate the role of Staphylococcus simulans in bone and joint infections (BJI) and determine their main characteristics. METHODS: A search of the database of the microbiology laboratories of Lille hospital and Tourcoing hospital was performed. Only results from blood, bone, and orthopedic device cultures were taken into account for hospitalized patients between January 2004 and January 2009. We considered cases in which S. simulans was the only bacteria isolated in all of the patients' biological samples with clinical and laboratory signs of infection. For patients with complete medical records, we recorded the clinical and epidemiological data. RESULTS: Six cases of BJI due to S. simulans were recorded, with five cases related to orthopedic devices infections. Three patients lived in rural areas. In four out of six patients, S. simulans was isolated in intraoperative biopsy material. In one patient, S. simulans grew in synovial fluid and in another in blood cultures only. The latter patient had a spondylodiscitis, and chronic foot ulcers due to gout disease were suspected to be the origin of the infection. All patients were healed after a mean follow up of 9 ± 3 months. Orthopedic devices were removed in four of the five patients concerned. The combination of rifampicin plus levofloxacin was used in four patients. CONCLUSION: The present data suggest that, even though S. simulans remains rarely observed in clinical pathology, its role in osteoarticular infections, especially in the case of infected orthopedic devices, is not exceptional. As for the antibiotic treatment, the combination of rifampicin and levofloxacin seems to be an effective strategy according to our clinical results.

ABCB1 allele polymorphism is associated with virological efficacy in naïve HIV-infected patients on HAART containing nonboosted PIs but not boosted PIs.

OBJECTIVE: To assess the effect of the multidrug resistance-1 single nucleotide polymorphism (ABCB1 SNP) C3435T in exon 26 on the virological responses to first-line protease inhibitor (PI)-containing HAART regimens. METHOD: A cohort of 182 HIV-infected patients with a PI-containing HAART regimen initiated from 1997 to 2004 was enrolled. Time to the first indetectable viral load (VL) was determined in patients with the CC, CT, or TT genotype. RESULTS: There were 37%, 44%, and 19% of patients who had the CC, CT and TT genotypes, respectively. The median estimated times to VL indetectability in the CC, CT, and TT groups were respectively 5.9, 3.9, and 4.8 months (p= .06). In patients on a non-boosted PI regimen, ABCB1 genotype was associated with time to VL indetectability that was shorter in patients with the CT than CC genotype (CT vs. CC, hazard ratio [HR]=0.62, p= .02; TT vs. CC, HR= 0.72, p= .21). This association was not found in patients with first-generation boosted PI-containing regimens and especially not with second-generation boosted PI-containing regimens. CONCLUSION: Our results show that the ABCB1 SNP in exon 26 is associated with virological efficacy in HIV-infected patients treated with non-boosted PI-containing regimens but not with those containing boosted PIs, particularly of the second generation.

[Non-cutaneous manifestations of secondary syphilis]. / Manifestations extra-cutanéomuqueuses de la syphilis secondaire.

BACKGROUND: The usual presentation of secondary syphilis is with cutaneous and mucosal symptoms. However, systematic symptoms can also occur. The purpose of this study was to describe non-mucocutaneous manifestations of secondary syphilis. PATIENTS AND METHODS: Patients from the Infectious Diseases Department of Tourcoing Hospital in whom secondary syphilis was diagnosed between January 2000 and December 2006 were enrolled in this study. Patients with secondary syphilis had the typical cutaneous and mucosal symptoms and a VDRLgreater than or equal to one quarter (or a fourfold increase in the VDRL if previously positive). RESULTS: Seventy-seven patients presenting a total of 80 cases of secondary syphilis were enrolled, 50 of whom were HIV-positive. Of these patients, 21 (26.3 p. 100) had neurological symptoms with three cases (3.8 p. 100) of uveitis, four (5 p. 100) of papillitis, two (2.5 p. 100) of retinitis and one (1.25 p. 100) of otosyphilis. In 14 of these 21 patients (67 p. 100), lumbar puncture was performed, confirming the diagnosis of neurosyphilis in six cases. Three patients (3.8 p. 100) had diarrhoea, four (5 p. 100) had abdominal pain and six (7.5 p. 100) had hepatomegaly. Seven (11.5 p. 100) patients had alanine aminotransferase levels above twice the normal upper limit and two above 10 times the normal upper limit. Three patients had bone pain and in one patient, osteitis was confirmed by technetium and gallium scintigraphy (osteolysis). CONCLUSION: In patients with secondary syphilis, clinicians should search for non-mucocutaneous symptoms. In the presence of these symptoms, appropriate syphilis treatment should be initiated.

[Pneumonia with septicemia caused by Pasteurella multocida in an immunocompetent patient]. / Pneumonie à Pasteurella multocida compliquée de choc septique chez un patient non immunodéprimé

Pneumonia with septicemia caused by Pasteurella multocida was diagnosed in an immunocompetent patient exposed to a dog. This case is remarkable by two aspects: first the absence of visible cutaneous lesion, and second the localization and severity of the infection caused by P. multocida even though the patient was immunocompetent. P. multocida can cause respiratory and systemic infection, and it is a possible diagnosis in case of exposure to animals, even without history of bite or scratch. Furthermore, severe infections caused by this pathogen can occur in immunocompetent patients, so that the implication of specific host factors in the severity of the disease can be suspected. Genetic features could be one of these.

[Mitochondrial cytopathies associated with HIV infection]. / Cytopathies mitochondriales au cours de l'infection par le VIH.

The tremendous progress achieved during the last few years with the use of highly active antiretroviral therapy in suppressing HIV replication together with improvements in immunity have been tempered by a growing number of new adverse effects. Mitochondrial toxicity is one aspect of these long-term toxicities of antiretroviral drugs, with the role of nucleoside analogs particularly underlined. Some cases of impaired mitochondrial function have been clearly identified, such as pancreatitis due to didanosine, neuropathy due to zalcitabine, myopathy due to zidovudine, and lactic acidosis due to stavudine. These mitochondrial toxicities can affect several organs, presenting different patterns of symptoms: from asymptomatic to states with few symptoms despite huge metabolic abnormalities whose prognosis is immediately life-threatening. Beyond the inhibition of DNA polymerase gamma using nucleoside analogs, responsible for decreasing mitochondrial DNA in certain targeted organs, it appears that several physiopathologic mechanisms interact to explain this observed toxicity, HIV itself plays a role, and the underlying genetic pool needs to be better identified. Such cases mean that, it is imperative to avoid cumulated toxicities caused by associated treatments. With serious cases, or persistent symptoms despite discontinuing the nucleoside analogs responsible for such toxicity, one must propose vitamins, mitochondrial co-factors, or anti-oxidants. However, the future lies in the use of potent, less toxic nucleoside analogs, and in developing compounds belonging to other classes of antiretrovirals.

[Morbidity and cost of rotavirus infections in France]. / Morbidité et coût des infections à rotavirus en France.

BACKGROUND: Rotavirus is the most common cause of severe diarrhea in children. Morbidity and mortality related to rotavirus infection is not well known in temperate countries in general, and in France in particular. OBJECTIVES: The aim of this study was estimate the morbidity, mortality, and cost related to the rotavirus infection in France, in order to assess the potential impact of a vaccination program. METHODS: A birth cohort was followed until 5 years of age using a decision tree model. Rotavirus infection incidence rates were modeled according to age, seasons, and breast-feeding status. RESULTS: Based on estimates from a decision model, we found that in France, rotavirus infection was responsible for 300,000 annual episodes of acute diarrhea, 138,000 visits to general practitioners, 18,000 hospitalizations, and 9 deaths. The annual direct cost related to rotavirus infection care was estimated at 28 million euros. CONCLUSION: This study demonstrates the high morbidity and cost of care associated with rotavirus infection in France. The decision tree model developed in this study could be used in the future to estimate the potential effectiveness, cost and cost-effectiveness of childhood vaccination strategies using new rotavirus vaccines.

Tropical infection after a case of total hip arthroplasty.

In non-endemic areas, malaria is mainly an imported disease. This article reports a case of transfusion-related Plasmodium falciparum malaria in a non-endemic area. Despite initial clinical signs consistent with malaria, the diagnosis was not elicited because of the absence of any identified epidemiological risk factors. The case indicates that transfusion-transmitted malaria still occurs in non-endemic countries. The role of laboratory testing to prevent and diagnose transfusion-transmitted malaria in non-endemic malaria countries is crucial.

Management and control of a carbapenem-resistant Acinetobacter baumannii outbreak in an intensive care unit.

OBJECTIVE: We had for aim to describe the identification and management of a 14-clonal carbapenem-resistant Acinetobacter baumannii (CRAB) outbreak, following admission of a known CRAB-infected patient in an ICU. METHODS: We reviewed the carriers' files and outbreak management procedures. RESULTS: The index patient was admitted with strict isolation precautions. The outbreak started 2 months after his discharge. It persisted despite reinforcement of strict isolation precautions, staff and patient cohorting, and extensive environmental decontamination including 2 rounds of routine terminal cleaning and disinfection or 1 round of cleaning and disinfection followed by hydrogen peroxide treatment. A second epidemic peak, after 4 weeks without any case, led to another wide environmental sampling and decontamination rounds. The source of the CRAB outbreak was suspected to be the blood pressure cuffs Velcro. Switching to cuffs submersible in a disinfectant stopped the outbreak. CONCLUSIONS: CRAB outbreaks are difficult to manage and sources of persistent colonization can be unexpected.

Cost-effectiveness of QuantiFERON-TB test vs. tuberculin skin test in the diagnosis of latent tuberculosis infection.

OBJECTIVE: To evaluate the cost-effectiveness of the tuberculin skin test (TST), the QuantiFERON-TB Gold test (QFT) and a combination of TST and QFT (TST+QFT) for diagnosing latent tuberculosis infection (LTBI) in France in a bacille Calmette-Guérin (BCG) vaccinated population. METHODS: A decision analysis model evaluated three strategies among simulated adults in close contact with tuberculosis (TB). We calculated direct lifetime medical costs, life expectancies and incremental cost-effectiveness ratios (ICERs). RESULTS: The discounted direct medical costs of care per patient of no testing, TST, QFT and TST+QFT were respectively euro417, euro476, euro443 and euro435, while discounted life expectancies were respectively 25.030, 25.071, 25.073 and 25.062 years. TST had higher costs and lower efficacy than QFT; TST+QFT was associated with an ICER of euro560 per year of life gained (YLG) compared to no testing, and QFT was associated with an ICER of euro730/YLG compared to TST+QFT. The only scenario where QFT was associated with an ICER of >euro75 000/YLG was when the prevalence of LTBI around TB was low (<5%) and TST specificity high (>90%). CONCLUSIONS: In France, for the diagnosis of LTBI after close contact with TB, the TST is more expensive and less effective than QFT. Although it is more expensive, QFT is more effective and cost-effective than TST+QFT under a wide range of realistic test performance scenarios.

Cost and cost-effectiveness of childhood vaccination against rotavirus in France.

OBJECTIVES: To assess the effectiveness and cost-effectiveness of routine childhood vaccination by new vaccines against rotavirus in France. METHODS: We constructed a Markov decision tree to compare two alternatives: "no vaccination" and "vaccination". A hypothetical birth cohort of 750,000 children was followed until 3 years of age. First, the disease burden without vaccine was estimated using data from French databases and medical literature. Incidence rates in unvaccinated children were modelled as a function of age and seasons. Next, using data from the medical literature, the vaccine's protective effect on rotavirus diarrhoea was considered. RESULTS: A routine universal rotavirus immunization programme was estimated capable of annually avoiding 89,000 cases of diarrhoea, 10,500 hospitalizations, and 8 deaths. At a vaccination cost of euro 150/course, assuming 75% vaccine coverage, the programme would cost euro 95 million and involve a net loss of euro 68 million to the health care system. The vaccination programme would cost euro 298,000/year of life saved, and euro 138,000/QALY saved. Key variables affecting the results were disease incidence, mortality rates and vaccine price. CONCLUSION: In France, childhood rotavirus vaccination with new anti-rotavirus vaccines would reduce the morbidity burden of rotavirus infection, but would not be cost-effective unless the price of vaccine decreased considerably.

Effectiveness of childhood vaccination against rotavirus in sub-Saharan Africa: the case of Nigeria.

Rotavirus diarrhoea is associated with high childhood mortality in developing countries. A new vaccine was recently licensed in Mexico. The objective of this study was to assess the effectiveness of routine childhood vaccination by this new vaccine in a developing country. We constructed a decision tree to compare two alternatives: "no vaccination programme" and "vaccination programme". The estimates used for disease incidence, vaccine efficacy and coverage rates were derived from published data. We followed a hypothetical Nigerian cohort from birth to age five. The vaccine programme would prevent 284,000 cases of rotavirus diarrhoea annually and 6129 deaths due to the disease. In this study in a sub-Saharan country, we showed that rotavirus vaccination with a new vaccine substantially reduces the number of deaths from rotavirus diarrhoea and may be of great use in developing countries.