Factors of loss to follow-up during tuberculosis treatment in a low-incidence region.

OBJECTIVE: The proportion of successfully treated tuberculosis (TB) patients remains below the WHO target in France, because of a high proportion of loss to follow-up. We aimed to identify factors associated with loss to follow-up in northern France, a low-incidence area. METHODS: Between 1997 and 2017, all consecutive patients diagnosed with TB at the Tourcoing Hospital, except those infected with multidrug-resistant or extensively drug-resistant strains, were included in a retrospective cohort study. A logistic regression analysis was performed to determine factors associated with loss to follow-up. RESULTS: One hundred and ninety patients were included. Previous TB treatment was reported in 32 patients (17%), extrapulmonary TB in 107 (56%), and HIV infection in 44 (23%). The proportion of loss to follow-up was 15%. In multivariate analysis, the risk of loss to follow-up decreased in case of first TB treatment (OR 0.36; 95% CI: 0.14-0.92, P=0.03) and increased in non-HIV-infected patients (OR 7.67; 95% CI: 1.00-59.0, p=0.05). Support for compliance was more frequent in HIV-infected patients (23% vs. 7%, p=0.005). CONCLUSION: The proportion of loss to follow-up was high. HIV infection was associated with a lower risk of loss to follow-up, likely to be due to more frequent support for compliance.

RNA and DNA Sanger sequencing versus next-generation sequencing for HIV-1 drug resistance testing in treatment-naive patients.

Background: Sanger sequencing of plasma RNA is the standard method for HIV-1 drug resistance testing in treatment-naive patients, but is limited by the non-detection of resistance-associated mutations (RAMs) with prevalence below approximately 20%. Objectives: We compared RNA and DNA Sanger sequencing (RSS and DSS) with RNA next-generation sequencing (NGS) for RAM detection in HIV-1 reverse transcriptase (RT), protease (PR) and integrase (IN) genes. Methods: Sanger sequencing was performed on RNA and DNA, following the recommendations of the French Agency for AIDS Research (ANRS). NGS was performed on RNA using the HIV-1 Drug Resistance Assay, v. 3.0 (Roche) on the 454 GS Junior sequencer. The IAS-USA list was used to identify RAMs. ANRS, Rega and Stanford algorithms were used for drug resistance interpretation. Results: The study included 48 ART-naive patients. The number of patients with at least one major RAM was 3, 3, 4 and 8 when using RSS, DSS, NGS 20% and NGS 5%, respectively. Numerous minor mutations were detected in patients, especially in the protease gene. None of the methods detected any major mutation in the integrase gene. Overall, the mutation detection rate was similar between RSS and DSS, and higher with NGS 20%. Differences in drug resistance interpretation were found between algorithms. No impact of the minority RAMs detected by NGS was found on the short-term treatment outcome. Conclusions: DSS does not clearly improve the detection of RAMs in ART-naive patients, as compared with RSS. NGS allows detection of additional minority RAMs; however, their clinical relevance requires further investigation.

Factors associated with virological response to a switch regimen containing maraviroc for antiretroviral-experienced HIV-1-infected patients.

OBJECTIVES: There are few data on clinical and virological factors associated with maraviroc virological response (VR) in clinical practice. This study aimed to identify factors associated with VR in 94 treatment-experienced, but CCR5 inhibitor-naive, HIV-1 patients switched to maraviroc-containing regimens. METHODS: Patients with HIV-1 RNA viral load (VL) <50 copies/mL switching to an antiretroviral treatment containing maraviroc were followed. VR was defined at month 3 as VL <50 copies/mL. The impact of age, baseline tropism, zenith VL, nadir CD4 cell count and CD4 cell count, HIV subtype (B versus non-B), genotypic susceptibility score of treatment, once- or twice-daily treatment and presence of raltegravir in optimized background therapy on VR was investigated. RESULTS: Baseline characteristics were: median age 49 years (range 25-73 years), median CD4 cell count 481 cells/mm(3) (range 57-1830 cells/mm(3)) and median nadir CD4 cell count 99 cells/mm(3) (range 3-585). Maraviroc was administered twice daily in 88 of 94 patients and once daily in 6 of 94 patients (300 mg/day for 4 of 6 and 150 mg/day for 2 of 6). At month 3, 89.4% of patients were responders. A better VR to a switch regimen containing maraviroc was associated with the B subtype (P = 0.0216) and a lower zenith VL (median of 5.24 and 5.70 log10 copies/mL for patients in success or in failure, respectively) in univariate analysis. Only B subtype was associated with a better VR in multivariate analysis. CONCLUSIONS: This study evidenced the efficacy of a switch regimen containing maraviroc in clinical practice. VR was better for patients with a lower zenith VL and B subtype.

Vaccinal issues between Belgian and French travelers.

INTRODUCTION: The yellow-fever vaccination center of the Tourcoing Hospital (France) has been accessible to Belgian travelers since its opening in 1994. METHOD: The authors reported the specificities of these consultations during the year 2010, by retrospectively analyzing electronic medical records. RESULTS: Some medical issues encountered during the consultation were due to differences in vaccination schedules: for the polio vaccine, since the last dose is administered between 5 and 7 years of age in Belgium; and for the measles vaccine since a late two-dose schedule (second dose between 12 and 13 years of age) is recommended in this country. Moreover, some specific vaccines are available only in Belgium: a diphtheria-tetanus bivalent vaccine, and a live attenuated oral typhoid vaccine. DISCUSSION: The specificities of the Belgian border traveler consultation in our French yellow-fever center are due to a difference in European vaccination schedules; the physician must be aware of these. CONCLUSION: The physician has to propose updates on vaccination schedules, and be aware of yellow-fever vaccine compatibility with vaccines recently administered in Belgium.

Identification of an indigo precursor from leaves of Isatis tinctoria (Woad).

Indole is presumably a product of indole-3-glycerol phosphate catabolism in Isatis tinctoria. It is oxidized into indoxyl and stored in young leaves as indigo precursor. Further oxidation and dimerization of indoxyl produces indigoid pigments. In this work, we describe an HPLC method dedicated to the identification and quantification of indigoid pigments (indigo, indirubin, isoindigo and isoindirubin) and indigo precursors produced in I. tinctoria (Woad). This work, carried out with two cultivars of I. tinctoria, has confirmed that the quantity of indigo precursors is dependent on the species and the harvest period. In addition we have shown for the first time that young leaves of I. tinctoria, harvested in June contained a new indigo precursor in addition to isatan B (indoxyl-5-ketogluconate) and indican (indoxyl-beta-D-glucoside). We suggest the name "isatan C" for this new indigo precursor in I. tinctoria. Its chemical characteristics point to an dioxindole ester with PM of 395. We have shown that isatan C reacts with isatan B increasing the red pigment production.

Effect of hospital-acquired ventilator-associated pneumonia on mortality of severe community-acquired pneumonia.

PURPOSE: The purpose of this article is to evaluate, using two pairwise case-control studies, attributable mortality linked to hospital-acquired ventilator-associated pneumonia (HA-VAP) complicating the intensive care unit (ICU) stay of patients exhibiting severe community-acquired pneumonia (CAP). MATERIALS AND METHODS: Over an 11-year period, 498 patients with severe CAP were collected. Among them, 43 exhibited HA-VAP. In a first case-control study, these patients were matched with control on the basis of six confounding variables known to be general ICU prognosis factors. In a second case-control study, six variables specifically linked to CAP prognosis were used for matching. RESULTS: In the two case-control studies, each case patient was matched with one control patient. In the first analysis, success of matching was achieved in 198 of 258 (77%) variables used for matching. In the second analysis, matching was successful for 242 of 258 (94%) confounding variables used. Eighteen patients died, compared with, respectively, 6 (P = .003) and 7 (P = .01) controls. Attributable mortality of HA-VAP was similar in the two pairwise analyses, respectively, 28% (risk ratio = 3.0; 95% confidence interval, 1.32 to 6.82) and 26% (risk ratio = 2.57; 95% confidence interval, 1.2 to 5.52). CONCLUSION: When confounding factors were controlled, HA-VAP appeared to increase mortality of severe CAP requiring ICU admission.