Bacterial Meningitis Epidemiology in Five Countries in the Meningitis Belt of Sub-Saharan Africa, 2015-2017.

BACKGROUND: The MenAfriNet Consortium supports strategic implementation of case-based meningitis surveillance in key high-risk countries of the African meningitis belt: Burkina Faso, Chad, Mali, Niger, and Togo. We describe bacterial meningitis epidemiology in these 5 countries in 2015-2017. METHODS: Case-based meningitis surveillance collects case-level demographic and clinical information and cerebrospinal fluid (CSF) laboratory results. Neisseria meningitidis, Streptococcus pneumoniae, or Haemophilus influenzae cases were confirmed and N. meningitidis/H. influenzae were serogrouped/serotyped by real-time polymerase chain reaction, culture, or latex agglutination. We calculated annual incidence in participating districts in each country in cases/100 000 population. RESULTS: From 2015-2017, 18 262 suspected meningitis cases were reported; 92% had a CSF specimen available, of which 26% were confirmed as N. meningitidis (n = 2433; 56%), S. pneumoniae (n = 1758; 40%), or H. influenzae (n = 180; 4%). Average annual incidences for N. meningitidis, S. pneumoniae, and H. influenzae, respectively, were 7.5, 2.5, and 0.3. N. meningitidis incidence was 1.5 in Burkina Faso, 2.7 in Chad, 0.4 in Mali, 14.7 in Niger, and 12.5 in Togo. Several outbreaks occurred: NmC in Niger in 2015-2017, NmC in Mali in 2016, and NmW in Togo in 2016-2017. Of N. meningitidis cases, 53% were NmC, 30% NmW, and 13% NmX. Five NmA cases were reported (Burkina Faso, 2015). NmX increased from 0.6% of N. meningitidis cases in 2015 to 27% in 2017. CONCLUSIONS: Although bacterial meningitis epidemiology varied widely by country, NmC and NmW caused several outbreaks, NmX increased although was not associated with outbreaks, and overall NmA incidence remained low. An effective low-cost multivalent meningococcal conjugate vaccine could help further control meningococcal meningitis in the region.

MenAfriNet: A Network Supporting Case-Based Meningitis Surveillance and Vaccine Evaluation in the Meningitis Belt of Africa.

Meningococcal meningitis remains a significant public health threat, especially in the African meningitis belt where Neisseria meningitidis serogroup A historically caused large-scale epidemics. With the rollout of a novel meningococcal serogroup A conjugate vaccine (MACV) in the belt, the World Health Organization recommended case-based meningitis surveillance to monitor MACV impact and meningitis epidemiology. In 2014, the MenAfriNet consortium was established to support strategic implementation of case-based meningitis surveillance in 5 key countries: Burkina Faso, Chad, Mali, Niger, and Togo. MenAfriNet aimed to develop a high-quality surveillance network using standardized laboratory and data collection protocols, develop sustainable systems for data management and analysis to monitor MACV impact, and leverage the surveillance platform to perform special studies. We describe the MenAfriNet consortium, its history, strategy, implementation, accomplishments, and challenges.

Prospective evaluation of the SD BIOLINE Dengue Duo rapid test during a dengue virus epidemic.

Dengue virus is endemic in French Guiana with occurrence of cyclical outbreaks. There is a need for rapid tests allowing dengue laboratory diagnosis in healthcare centers scattered throughout this wide Amazonian territory. Our objective was to evaluate the real-life performance of the SD BIOLINE Dengue Duo (IgG/IgM + NS1 Ag) rapid test (RDT) during the 2012-2013 dengue epidemics. The RDT was evaluated in parallel with routine laboratory tests, PlateliaTM Dengue NS1 Ag and Focus Diagnostics Dengue Fever Virus IgM Capture DxSelect. A total of 3,347 patients with suspected dengue acute infection were evaluated. The diagnostic performances of the SD BIOLINE NS1 Ag were equivalent to Platelia NS1, 471 patients (14.1%) were NS1 Ag positive with the RDT and 14.2% with Platelia. The Cohen's Kappa coefficient was 0.86 [95%CI: 0.83-0.88], indicating an almost perfect agreement. Moreover, the sensitivity of SD BIOLINE NS1 Ag relative to the RT-PCR method was 87% [95%CI: 80-93%] and the specificity was 92% [95% CI: 87-97%]. However, the SD BIOLINE IgM test was found positive in 6.3% of the samples in comparison to 10.7% with Dx Select IgM. The Cohen's Kappa coefficient was 0.53 [95%CI: 0.47-0.58] indicating a moderate agreement. This raised concern about the SD BIOLINE IgM for the diagnostic of dengue in endemic areas. When considering only NS1 Ag results and not IgM, the RDT could be a viable solution to manage dengue outbreaks in healthcare centers where no laboratory services are available, in the early phase of the disease.

Frequent intragenic rearrangements of DPYD in colorectal tumours.

Dihydropyrimidine dehydrogenase is a crucial enzyme for the degradation of 5-fluorouracil (5FU). DPYD, which encodes dihydropyrimidine dehydrogenase, is prone to acquire genomic rearrangements because of the presence of an intragenic fragile site FRA1E. We evaluated DPYD copy number variations (CNVs) in a prospective series of 242 stage I-III colorectal tumours (including 87 patients receiving 5FU-based treatment). CNVs in one or more exons of DPYD were detected in 27% of tumours (deletions or amplifications of one or more DPYD exons observed in 17% and 10% of cases, respectively). A significant relationship was observed between the DPYD intragenic rearrangement status and dihydropyrimidine dehydrogenase (DPD) mRNA levels (both at the tumour level). The presence of somatic DPYD aberrations was not associated with known prognostic or predictive biomarkers, except for LOH of chromosome 8p. No association was observed between DPYD aberrations and patient survival, suggesting that assessment of somatic DPYD intragenic rearrangement status is not a powerful biomarker to predict the outcome of 5FU-based chemotherapy in patients with colorectal cancer.

Molecular patterns in deficient mismatch repair colorectal tumours: results from a French prospective multicentric biological and genetic study.

BACKGROUND: To test the prognostic value of tumour protein and genetic markers in colorectal cancer (CRC) and examine whether deficient mismatch repair (dMMR) tumours had a distinct profile relative to proficient mismatch repair (pMMR) tumours. METHODS: This prospective multicentric study involved 251 stage I-III CRC patients. Analysed biomarkers were EGFR (binding assay), VEGFA, thymidylate synthase (TS), thymidine phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD) expressions, MMR status, mutations of KRAS (codons 12-13), BRAF (V600E), PIK3CA (exons 9 and 20), APC (exon 15) and P53 (exons 4-9), CpG island methylation phenotype status, ploidy, S-phase, LOH. RESULTS: The only significant predictor of relapse-free survival (RFS) was tumour staging. Analyses restricted to stage III showed a trend towards a shorter RFS in KRAS-mutated (P=0.005), BRAF wt (P=0.009) and pMMR tumours (P=0.036). Deficient mismatch repair tumours significantly demonstrated higher TS (median 3.1 vs 1.4) and TP (median 5.8 vs 3.5) expression relative to pMMR (P<0.001) and show higher DPD expression (median 14.9 vs 7.9, P=0.027) and EGFR content (median 69 vs 38, P=0.037) relative to pMMR. CONCLUSIONS: Present data suggesting that both TS and DPD are overexpressed in dMMR tumours as compared with pMMR tumours provide a strong rationale that may explain the resistance of dMMR tumours to 5FU-based therapy.

Comparative effectiveness of continuing a virologically effective first-line boosted protease inhibitor combination or of switching to a three-drug regimen containing either efavirenz, nevirapine or abacavir.

OBJECTIVES: To compare virological effectiveness in patients who continued on a virologically successful first-line boosted protease inhibitor (PI)-containing combination antiretroviral therapy (cART) regimen or who switched to a PI-free cART including efavirenz, nevirapine or abacavir. METHODS: From the French Hospital Database on HIV, we selected 439 patients with undetectable viral load (VL) on a first-line boosted PI-containing cART regimen who switched to a PI-free combination including efavirenz, nevirapine or abacavir. Each of these patients was matched with three patients who continued to take their first-line cART regimen, on the basis of gender, age, CD4 cell count, VL, date of cART initiation and the duration of VL undetectability. Time to virological failure (VF) was analysed with Kaplan-Meier curves and Cox models. RESULTS: The 12 month probabilities of VF were 3.7% and 5.7% in non-switch and switch patients, respectively, and 3.9%, 7.2% and 9.0% in patients switching to efavirenz-, nevirapine- and abacavir-containing cART, respectively. After adjustment, only patients switching to abacavir-containing cART had a higher risk of VF than non-switch patients (adjusted hazard ratio, 1.99; 95% confidence interval, 1.05-3.79). CONCLUSIONS: Switching from a virologically successful first-line boosted PI-containing cART regimen to a non-nucleoside reverse transcriptase inhibitor-containing cART regimen containing either efavirenz or nevirapine is virologically safe, while switching to abacavir-containing cART should be avoided.

PREMIUM: A French prospective multicenter observational study of factors impacting on efficacy and compliance to cetuximab treatment in first-line KRAS wild-type metastatic colorectal cancer.

BACKGROUND: Cetuximab improves progression-free survival (PFS) and overall survival (OS) in patients with KRAS wild type (wt) metastatic colorectal cancer (mCRC). Few data are available on factors impacting both efficacy and compliance to cetuximab treatment, which is, in combination with chemotherapy, a standard-of-care first-line treatment regimen for patients with KRAS wt mCRC. PATIENTS AND METHODS: PREMIUM is a prospective, French multicenter, observational study that recruited patients with KRAS wt mCRC scheduled to receive cetuximab, with or without first-line chemotherapy, as part of routine clinical practice, between October 28, 2009 and April 5, 2012 (ClinicalTrials.gov Identifier: NCT01756625). The main endpoints were the factors impacting on efficacy and compliance to cetuximab treatment. Predefined efficacy endpoints were PFS and safety. RESULTS: A total of 493 patients were recruited by 94 physicians. Median follow-up was 12.9 months. Median progression-free survival was 11 months [9.6-12]. In univariate analyses, ECOG performance status (PS), smoking status, primary tumor location, number of metastatic organs, metastasis resectability, surgery, folliculitis, xerosis and paronychia maximum grade, and acne preventive treatment were statistically significant. In multivariate analysis (Hazard Ratios of multivariate stepwise Cox models), ECOG PS, surgery, xerosis and folliculitis were positive prognostics factors for longer PFS. Among all patients, 69 (14%) were non-compliant. In multivariate analysis, no variables were statistically significant. The safety profile of cetuximab was consistent with previous studies. CONCLUSIONS: ECOG PS <2, surgical treatment performed, and maximum grade xerosis or folliculitis developed were predictive factors of cetuximab efficacy on KRAS wt mCRC patients. Unfortunately, we failed in identifying predictive factors for compliance in these patients.

Bone metastasis from endometrioid ovarian carcinoma: a case study and literature review.

INTRODUCTION: Bone metastases from epithelial ovarian carcinoma are rare, usually discovered postmortem. The survival of these patients is poor. Furthermore, only two cases of endometrioid ovarian carcinoma with metastasis to the skeletal structures have been described in the literature. CASE REPORT: We present the case of a 58-year-old woman with a lytic metastasis in the left iliac ramus from endometrioid ovarian carcinoma that occurred seven years after the initial diagnosis. DISCUSSION: A review of the literature since 1966 on bone metastasis of ovarian cancer is also presented. In patients suffering from a neoplasm that rarely metastasises to bone, histological proof should be obtained to diagnose uncommon sites of disease relapse.

Assessment of agro-morphological variability of dry-season sorghum cultivars in Chad as novel sources of drought tolerance.

Dry-season sorghum is a type of sorghum whose establishment ends at the end of the rainy season and its development takes place during the dry and cold harmattan period. Its root system is particularly well developed with deep penetration for water withdrawal. This study was conducted to assess the level of genetic diversity present among dry-season sorghum in Chad's Sudanese zone using phenotypic traits, and to identify new sources of drought tolerance that could be used in sorghum breeding programs. A high variability in qualitative traits was observed except for the botanical race which showed that all cultivars were of durra race. It was also observed that most cultivars had compact panicles (66.67%), mostly black glumes (66.67%), glume hairiness (58.33%) and did not have aristation (91.67%). Most qualitative traits showed a coefficient of variation of less than 30%, and the analysis of the variance showed that at 0.1% probability, there were significant differences between cultivars for all traits except botanical race. It was observed that the potential productivity of dry-season sorghum of this collection was strongly related to their staygreen characteristic; a trait of enormous importance in breeding for postflowering drought tolerance in sorghum. Plant height was highly heritable (91.9%), followed by the peduncle length (90.2%), panicle length (87.5%) and the internodes number (86.5%). Structuring of diversity separated the cultivars into four statistically distinct groups; with group 2 clustering cultivars with panicle productivity, early maturity and high staygreen, and other traits that contribute to the performance of cultivars. The findings will help to enhance the selection and production of dry-season sorghum in Chad and also provide alternative sources for staygreen introgression into the larger sorghum breeding community.

Mortality attributable to nosocomial infection: a cohort of patients with and without nosocomial infection in a French university hospital.

OBJECTIVE: To assess nosocomial infection (NI) as a risk factor for death and to estimate the population-attributable risk of death from NI. DESIGN: A prospective cohort study of patients with and without NI. SETTING: Nimes University Hospital, Nimes, France. PATIENTS: Patients were recruited from May 7, 2001, to January 10, 2003. Patients in acute care and long-term care units who had NI were enrolled, and patients without NI were randomly selected and matched with patients with NI for age, sex, type of care (acute care vs. long-term care) and length of stay in hospital at study inclusion. OUTCOME MEASURES: Vital status within 60 days after study inclusion was assessed. We used conditional logistic regression to estimate the relative death risk from NI after adjusting for comorbidities, severity of the underlying disease, and all other confounding factors. The adjusted population-attributable risk was assessed using the Mantel-Haenszel method. RESULTS: We recruited 1,914 patients with NI and 5,172 patients without NI. The median age of the patients with NI was 73 years; 1,045 (54.6%) were female. NI was associated with death within 60 days (adjusted odds ratio, 1.7 [95% confidence interval {CI}, 1.4-;2.2]; P<.001). The adjusted population-attributable risk of death for all sites of infection was 1.7% (95% CI, 1.4-2.1). If we consider the NI incidence to be 3%-6% in French hospitals, the population-attributable risk of death from NI would range from 2.1% (95% CI, 1.7%-2.5%) to 4.0% (95% CI, 3.3%-4.9%). CONCLUSION: In this study, NI appeared to have a significant impact on mortality. Multicenter studies will be needed to confirm these results.

Impact of infection control interventions and antibiotic use on hospital MRSA: a multivariate interrupted time-series analysis.

Hospitals in the northeast of Scotland have experienced methicillin-resistant Staphylococcus aureus (MRSA) outbreaks since 1997. Several infection control measures were introduced sequentially to control MRSA, and antibiotic use has been monitored. From January 1997 to December 2004, data on the monthly percentage of non-duplicate MRSA infections (%MRSA) were collated from an intervention hospital (IH) and a control hospital (CH). Both hospitals introduced the use of alcohol hand gel in November 2002. Furthermore, the IH introduced an environmental MRSA swabbing programme in March 2001, chlorine disinfection of the environment in September 2001, discharge screening in December 2001, admission screening in November 2003 and environmental audits in March 2004. Multivariate dynamic regression analysis was used to evaluate the longitudinal effects of these interventions as measured by new clinical cases of MRSA. At the IH, the %MRSA increased between January 1998 and January 2001 and then decreased. At the CH, the %MRSA increased from January 1997 to December 2004. Introduction of alcohol hand gel was associated with an absolute decrease in %MRSA of 21% and 30%, respectively, for the IH and CH. At the IH, introduction of chlorine disinfection and environmental swabbing were, respectively, associated with a decrease in %MRSA of 27% immediately and 32% 3 months later. Discharge screening and environmental audit did not significantly affect %MRSA, whereas admission screening was associated with a 22% decrease in %MRSA 4 months later. Increasing macrolide use was associated with increasing %MRSA in both hospitals, and increasing quinolone use was associated with increasing %MRSA in the CH. Implementation of stepwise infection control measures was associated with a decrease in %MRSA in the IH. Introduction of an alcohol gel for hand hygiene was associated with a decrease in %MRSA in both hospitals. Antibiotic use also affects %MRSA, in particular that of macrolides and quinolones.

Evolution of fluoroquinolone resistance among Escherichia coli urinary tract isolates from a French university hospital: application of the dynamic regression model.

Escherichia coli urinary tract isolates were collected in 1997-2003 from Nimes University Hospital in order to investigate long-term trends in antibiotic resistance and to explore the relationship between antibiotic use and the emergence of resistance. Time-series analysis (ARIMA models) and dynamic regression models were used to investigate relationships between antibiotic use and resistance to ofloxacin and ciprofloxacin. Significant increases were seen in the frequency of ofloxacin (8.9 to 16.7%) and ciprofloxacin resistance (6.2 to 10.1%) (p < 0.001). Using multivariate dynamic regression analysis, it was found that an increased use of one defined daily dose (DDD)/1000 patient-days for ofloxacin, ciprofloxacin and norfloxacin induced average increases of 0.81%, 0.65% and 0.53% in E. coli ofloxacin resistance (p < 0.01), with average delays of 4, 4 and 6 months, respectively. An increase of 1 DDD/1000 patient-days of ciprofloxacin, ofloxacin and norfloxacin use induced increases of 0.73%, 0.82% and 0.63% in E. coli ciprofloxacin resistance (p < 0.01), with average delays of 4, 4 and 5 months, respectively. The use of nalidixic acid was not associated significantly with an increase in resistance to fluoroquinolones by multivariate analysis.

[Evaluation of the relation between consumption of fluoroquinolones and emergence of resistance among Escherichia coli: contribution of observational and quasi-experimental studies]. / Evaluation de la relation consommation de fluoroquinolones et émergence de résistance chez Escherichia coli: rôles respectif et comparatif des études observationnelles et quasi expérimentales.

The emergence of Escherichia coli (E. coli) resistance to fluoroquinolones (FQs) increased and spread gradually worldwide since the early 1990s. The selective pressure of FQs is the main mechanism responsible for the emergence of FQ resistance as shown by in vitro studies. Clinical trials are required to prove the causality between exposure to FQs and emergence of resistance. But this would not be ethical in humans. Non experimental studies must answer several principles to establish causality: association, anteriority, and directional change. We described and compared the contribution of observational and quasi-experimental studies implemented to answer several of these principles. Quasi-experimental studies using interventional models (ARIMA models with transfer function), can answer several of these principles, unlike observational studies. Thus, in addition to assessment of the association, they were able to show that the exposure to FQs precedes the emergence of FQ resistance to E. coli. They were also able to estimate the time necessary for the emergence of resistance and the dose effect, and to show if this association was reversible.

Risk factors for multidrug-resistant Pseudomonas aeruginosa nosocomial infection.

A case-control study was conducted in a university hospital to determine the risk factors for nosocomial infection with multidrug-resistant Pseudomonas aeruginosa (MDR-PA) among all hospitalized patients and among those with a nosocomial infection due to P. aeruginosa. Eighty patients infected with MDR-PA, 75 infected with a non-MDR phenotype and 240 random controls were included in the 12-month study. Among all hospitalized patients, age, severity index, having a bedridden condition, transfer from other units, nasogastric feeding, urinary catheterization and exposure to beta-lactams (OR=2.5) or fluoroquinolones (OR=4.1) in the seven days before infection were linked to nosocomial infection due to MDR-PA. Among patients infected by P. aeruginosa, exposure to fluoroquinolones (OR=4.7) or surgery (OR=0.5) were linked to the isolation of MDR-PA. This study showed that, in addition to urinary catheterization, nasogastric feeding is an important risk factor in MDR-PA infection. Indeed, an imbalance in gut flora, modifications to the mucous membranes due to the use of nasogastric feeding and the selection pressures exerted by antibiotics were implicated in the occurrence of this infection.

[Short term effects of hypertonic saline during severe sepsis and septic shock]. / Effets hémodynamiques du sérum salé hypertonique au cours du choc septique et du sepsis sévère.

OBJECTIVE: Assessment of haemodynamic effects of 250 ml hypertonic saline 7.5% (HS) perfusion in critically ill patients with severe sepsis or septic shock. STUDY DESIGN: Observational study. PATIENTS: Twelve mechanically ventilated patients with severe sepsis or septic shock requiring a pulmonary artery catheter and volume loading. INTERVENTION: Two hundred and fifty millilitres HS were given over 15 min. Were measured: heart rate (HR), mean arterial pressure (MAP) and pulmonary artery pressure (MPAP), pulmonary capillary wedge pressure (PCWP), right atrial pressure (RAP), cardiac index (CI), indexed systemic vascular resistance (ISVR), indexed pulmonary vascular resistance (IPVR), plasma sodium, chloride, protein and haemoglobin concentrations and arterial blood lactate. Studied parameters were assessed at baseline (T(0)) and 5 (T(0)) and 105 min (T(120)) after the end of HS infusion. RESULTS: MAP, HR and RAP were not altered. HS increased PAPM (25 +/- 5-30 +/- 6 mmHg), PCWP (13 +/- 3-18 +/- 4 mmHg) and CI (3.5 +/- 1.2-4.6 +/- 1.1 l/min per m(2)) at T(20) (P < 0.05). ISVR and IPVR were decreased at T(20). Protein and haemoglobin were decreased at T(20). Sodium and chloride were increased at T(20) (from 136 +/- 4 to 147 +/- 4 and from 110 +/- 6 to 123 +/- 6 mmol/l, respectively, P < 0.01) and T(120). CONCLUSION: In patients with severe sepsis or septic shock, 250 ml HS transiently (<120 min) increases CI and PCWP and induces an increase in sodium and chloride concentrations.

[Acute pancreatitis: resultos of a diagnostic-therapeutic protocol in 80 consecutive cases]. / Pancreatiti acute: risultati di un protocollo diagnostico-terapeutico in 80 casi consecutivi.

The treatment of acute pancreatitis cannot be standardized in the absence of a prompt diagnosis and of an accurate severity and prognostic score. This study, based on 80 consecutively observed patients, compared the aetiological, clinical, diagnostic (laboratory and imaging) and prognostic data used to select the most appropriate therapy for each patient. The results confirm that the Ranson score shows a satisfactory prognostic relationship between the number of positive parameters and the severity of the disease. Ultrasound, which is useful for defining the aetiologic factors and in the follow-up of peripancreatic effusions, has proved to be limited as a means of imaging abnormalities of the pancreatic parenchyma. CT scans are confirmed as being the only method of accurately demonstrating the presence of necrosis and of evaluating its effective extent. ERCP was performed as soon as possible in the presence of biliary stasis or of suspect ultrasonographic signs. Surgical treatment proved necessary only in 7.5% of cases, on each occasion to drain infected necrotic foci. Promptness of the surgical indication plays an important role in the outcome of necrosectomy and drainage performed with the closed technique. Mortality was limited to 1.25% in our series. A correct diagnostic approach together with prompt treatment can reduce the mortality rate of this disease to a minimum.

Climatic drivers of seasonal influenza epidemics in French Guiana, 2006-2010.

OBJECTIVES: Influenza seasonality remains poorly studied in Equatorial regions. Here we assessed the seasonal characteristics and environmental drivers of influenza epidemics in French Guiana, where influenza surveillance was established in 2006. METHODS: Sentinel GPs monitored weekly incidence of Influenza-like illnesses (ILI) from January 2006 through December 2010 and collected nasopharyngeal specimens from patients for virological confirmation. Times series analysis was used to investigate relationship between ILI and climatic parameters (rainfall and specific humidity). RESULTS: Based on 1533 viruses identified during the study period, we observed marked seasonality in the circulation of influenza virus in the pre-pandemic period, followed by year-round activity in the post-pandemic period, with a peak in the rainy season. ILI incidence showed seasonal autoregressive variation based on ARIMA analysis. Multivariate dynamic regression revealed that a 1 mm increase of rainfall resulted in an increase of 0.33% in ILI incidence one week later, adjusting for specific humidity (SH). Conversely, an increase of 1 g/kg of SH resulted in a decrease of 11% in ILI incidence 3 weeks later, adjusting for rainfall. CONCLUSIONS: Increased rainfall and low levels of specific humidity favour influenza transmission in French Guiana.