HIV rapid screening tests and self-tests: Be aware of differences in performance and cautious of vendors.

BACKGROUND: Rapid tests for HIV testing are essential tools to achieve the 90-90-90 target of the World Health Organization. Many tests are available, some directly from websites. Evaluation of the performance of rapid tests, under close to real-life usage, is therefore needed to ensure accurate diagnosis in the context of the recommendation for their more widespread use. METHOD: Nine third- (3G) or fourth-generation (4G) rapid screening tests or self-tests (two bought on websites), were evaluated on an extensive panel of 200 HIV-negative and 312 HIV-positive samples, representative of a wide variety of clinical situations and HIV genetic diversity. A whole blood reconstitution protocol was designed to simulate real-life usage of these tests in community-based and private settings. FINDINGS: The specificity was high (98.5-100%) and sensitivity excellent (100%) for samples from patients chronically infected with the pandemic strains. The performance for infrequent situations with a major epidemiological and clinical impact, such as infection with divergent viruses or primary infection, was highly variable, depending on the test. One of the two 4G tests allowed detection of additional positive samples from early stages of infection, whereas the second (sold as a 4G test on a website) corresponded in reality to a 3G test. INTERPRETATION: Our study showed that not all tests are equal for the detection of major HIV variants or early stages of HIV infection; adding the detection of specific p24Ag improved the latter point. This study also showed, for the first time, that buying through web-based vendors can be risky, due to the varying performance of the tests and questionable sales practices. Our results are of particular importance in the context of the increasing use of rapid tests in an "outside laboratory" settings. FUND: Santé Publique France, COREVIH - Normandie, and Rouen University Hospital.

Durability of immunogenicity and strain coverage of MenBvac, a meningococcal vaccine based on outer membrane vesicles: Lessons of the Normandy campaign.

OBJECTIVES: MenBvac® is an outer membrane vesicle (OMV)-based meningococcal vaccine. From 2006 to 2012, it was used to control a clonal B outbreak in Normandy (France). We aimed to analyse the durability of the response against the epidemic strain and coverage beyond the vaccine strain. These data should help to optimize the use of OMV-containing vaccines, such as the new 4CMenB/Bexsero® recombinant vaccine. METHODS: Serum bactericidal activity (SBA) was measured in two cohorts of children who received their first dose of MenBvac® at 1-5years of age and accepted to provide a blood sample either one or four years after a 2+1+1 schedule. All sera were tested against the outbreak strain. Sera from responder subjects were also tested against 12 additional B or C strains which were chosen to entirely, partially, or not at all match the two variable regions (VR1 and VR2) of the PorA vaccine strain. RESULTS: Only 47.9% and 31.3% of subjects showed an SBA titre consistent with protection one and four years, respectively, after the last boost. Protective SBA titres were observed in all sera against B or C strains that entirely matched P1.7,16, and was high (75-100%) for all but one strain that partially matched VR1 or VR2. Extrapolating our data to the OMV component of 4CMenB/Bexsero® suggests that 14.5% of the current B strains would be covered based on PorA matching to the OMV component of 4CMenB/Bexsero® (regardless of the coverage of the three other vaccine components). CONCLUSIONS: Our data confirm that OMV-based vaccines elicit short-lasting SBA titres and may require repeated booster injections. However, strain coverage may be greater than expected.

Antiretroviral Therapy as Prevention of Pneumococcal Infections?

BACKGROUND: Despite antiretroviral therapy, it is generally believed that the risk for pneumococcal infections (PnIs) is high among patients infected with human immunodeficiency virus (HIV). However, most studies in this field have been conducted before 2010, and the proportion of virologically suppressed patients has drastically increased in these latter years thanks to larger indications and more effective antiretroviral regimens. This study aimed to re-evaluate the current risk of PnI among adult patients infected with HIV. METHODS: The incidence of PnI was evaluated between 1996 and 2014 in 2 French regional hospitals. The 80 most recent cases of PnI (2000-2014) were retrospectively compared with 160 controls (HIV patients without PnI) to analyze the residual risk factors of PnI. RESULTS: Among a mean annual follow-up cohort of 1616 patients, 116 PnIs were observed over 18 years. The risk factors of PnI among patients infected with HIV were an uncontrolled HIV infection or "classic" risk factors of PnI shared by the general population such as addiction, renal or respiratory insufficiency, or hepatitis B or C coinfection. Pneumococcal vaccination coverage was low and poorly targeted, because only 5% of the cases had been previously vaccinated. The incidence of invasive PnIs among HIV patients with a nonvirologically suppressed infection or comorbidities was 12 times higher than that reported in the general population at the country level (107 vs 9/100000 patients), whereas the incidence among virologically suppressed HIV patients without comorbidities was lower (7.6/100000 patients). CONCLUSIONS: Human immunodeficiency virus infection no longer per se seems to be a significant risk factor for PnI, suggesting a step-down from a systematic to an "at-risk patient" targeted pneumococcal vaccination strategy.

Genetic diversity and levels of expression of factor H binding protein among carriage isolates of Neisseria meningitidis.

The prevention of meningococcal disease may be improved by recombinant vaccines such as 4CMenB and rLP2086 that target the factor H binding protein (fHbp), an immunogenic surface component of Neisseria meningitidis present as one of three variants. Whether such vaccines decrease carriage of invasive isolates and thus induce herd immunity is unknown. We analyzed the genetic diversity and levels of expression of fHbp among 268 carriage strains and compare them to those of 467 invasive strains. fhbp gene sequencing showed higher proportions of variants 2 and 3 among carriage isolates (p<0.0001). Carriage isolates expressed lower levels of fHbp (p<0.01) but that remain high enough to predict targeting by antibodies against fHbp particularly in group B isolates belonging to the frequent hypervirulent clonal complexes in Europe and North America (cc32, cc41/44, cc269). This suggests that fHbp targeting meningococcal vaccines might reduce, at least in part, the acquisition of some hyperinvasive isolates.

Myopericarditis complicated by pulmonary embolism in an immunocompetent patient with acute cytomegalovirus infection: a case report.

BACKGROUND: Primary acute cytomegalovirus infection in immunocompetent patients is common worldwide. Infection is most often asymptomatic or occurs sub-clinically with a self-limited mononucleosis-like syndrome. More rarely, the infection may lead to severe organ complications with pneumonia, myocarditis, pericarditis, colitis and hemolytic anemia. Recent cases of cytomegalovirus-associated thrombosis have also been reported sporadically in the medical literature. CASE PRESENTATION: We report here a case of simultaneous myopericarditis and pulmonary embolism in a 30-year-old man with no medical history. The patient was not immunocompromised. We discuss the possible role of acute cytomegalovirus infection in the induction of vascular damage and review relevant cases in the literature. CONCLUSION: Thrombosis in patients with acute cytomegalovirus infection may be more frequent than is generally thought. Physicians need to be aware of the possible association between acute cytomegalovirus and thrombosis in immunocompetent patients, especially in the presence of severe systemic infection, as our case illustrates.

Impact of MenBvac, an outer membrane vesicle (OMV) vaccine, on the meningococcal carriage.

The aim of the study was to analyze the impact of MenBvac, an outer membrane vesicle (OMV) vaccine against P1.7,16 strains, on meningococcal carriage. During a B:14:P1.7,16/ST-32 outbreak in Normandy (France), children aged 1-7 years were randomly selected to participate in the study. Among the 1082 volunteers, there were 17 Neisseria meningitidis carriers (carriage rate of 1.57%). MenBvac vaccination appeared associated with lower carriage rate, i.e., 0.31% among the vaccinated children versus 2.10% among the non-vaccinated (p=0.03). The beneficial effect on carriage was observed regardless of the strain serogroup. OMV-vaccinated mice also showed reduction of bacterial acquisition of OMV-homolog and hererolog strains in respiratory pathways after intranasal challenge. These results suggest that meningococcal OMV-based vaccines reduce meningococcal carriage and may hence confer herd immunity.

Evolution of immune response against Neisseria meningitidis B:14:P1.7,16 before and after the outer membrane vesicle vaccine MenBvac.

A meningococcal B:14:P1.7,16 outbreak in Normandy (France) was recently controlled using MenBvac, an outer membrane vesicle vaccine previously designed against the B:15:P1.7,16 strain. The further emergence of a new B:14:P1.7,16 outbreak in another district in Normandy led us to explore immunity against B:14:P1.7,16 before and after the MenBvac campaign using a 2+1 (day 0, week 6, month 8) schedule. Children (1-5 years) were sampled before, during and up to one year after vaccination. Serum bactericidal activity against B:14:P1.7,16 was titrated using human complement (hSBA) and immune response was defined by hSBA titer ≥4 as a surrogate for protection. The percentage of hSBA titer ≥4 was 10.8% before vaccination, raised to 84.1% 6 weeks after the completion of the schedule, but declined to 39.7% one year later. This level is lower than the targeted 60% level and suggests only short-term persistence of response against B:14:P1.7,16 using this schedule.

From tailor-made to ready-to-wear meningococcal B vaccines: longitudinal study of a clonal meningococcal B outbreak.

BACKGROUND: Outer-membrane-vesicle vaccines for meningococcal B outbreaks are complex and time consuming to develop. We studied the use of already available vaccine to control an outbreak caused by a genetically close strain. METHODS: From 2006 to 2009, all individuals younger than 20 years living in the region of Normandy, France, in which an outbreak caused by a B:14:P1.7,16 strain occurred, were eligible to receive MenBvac, a Norwegian vaccine designed 20 years earlier against a strain sharing the same serosubtype (B:15:P1.7,16). The immunogenicity (in a randomly selected cohort of 400 children aged 1-5 years), safety, and epidemiological effect of the vaccination were assessed. FINDINGS: 26,014 individuals were eligible to receive the vaccine. Shortage of vaccine production prompted start of the campaign in the highest incidence groups (1-5 years). 16,709 (64%) received a complete vaccination schedule of whom 13,589 (81%) received a 2+1 dose schedule (week 0, week 6, and month 8). At 6 weeks after the third dose, of 235 vaccinees for whom samples were available, 206 (88%) had a seroresponse, and 108 (56 %) of 193 had a seroresponse at 15 months. These results were similar to those described for tailor-made vaccines and their homologous strain. Only previously described adverse effects occurred. The incidence of B:14:P1.7,16 cases decreased significantly in the vaccine targeted population after the primary vaccination period (from 31·6 per 100,000 to 5·9 per 100,000; p=0·001). INTERPRETATION: The ready-to-wear approach is reliable if epidemic and vaccine strains are genetically close. Other meningococcal B clonal outbreaks might benefit from this strategy; and previously described outer-membrane-vesicle vaccines can be effective against various strains. FUNDING: French Ministry of Health.

Clinical aspects and prognostic factors of leptospirosis in adults. Retrospective study in France.

BACKGROUND: Because early recognition and initiation of antibiotic therapy are important, clinicians should familiarize themselves with the clinical presentation of leptospirosis, and determine prognostic factors. PATIENTS AND METHODS: This study included all patients treated at Angers University Hospital between January 1995 and December 2005 for leptospirosis - both probable (cases combining epidemiologically suggestive features with compatible clinical, laboratory, and radiographic findings, with no other diagnosis envisioned) and confirmed (by finding microorganism on direct examination or culture of blood, urine or CSF, or by seroconversion or by a significant increase in the antibody titer between two samples). Severe leptospirosis was defined by hospitalization in the critical care department or need for renal dialysis. The statistical analysis used SPSS software version 12. RESULTS: Of 97 records reviewed, we retained 62 cases that met the criteria above, including 35 confirmed cases, 27 probable and 15 severe. The sex ratio was nine men for every woman. The patients' mean age was 45+/-18 years [12-77]. The principal clinical signs observed were: fever (n=59) with shivering (n=42), diffuse myalgia (n=41), headaches (n=38), jaundice (n=24), conjunctival suffusion (n=10), rash (n=11), herpes eruption (n=7), renal damage (n=33) that was sometimes severe (>500 micromol/L) (n=7), meningitis (n=12), meningoencephalitis (n=2), myocarditis or pericarditis (n=6), and atypical radiographic lung disease (n=16), sometimes with ARDS (n=6). Blood tests showed thrombocytopenia (platelets<140 G/L) in 65.5% of patients (n=40). Logistic regression modeling showed that two criteria remained independently predictive of development toward severe leptospirosis: clinical jaundice (p=0.005) and cardiac damage seen either clinically or on ECG (p<0.02). These factors can be identified easily at the first clinical examination and during evolution, and should help to reduce mortality by allowing earlier management of patients with suspected leptospirosis.

[Botulism, a clinical diagnosis]. / Botulisme, un diagnostic clinique.

Foodborne botulism results from the effect of a neurotoxin produced by a sporulated anaerobic bacillus called Clostridium botulinum. The mode of contamination occurs through the consumption of foodstuff, already contaminated by the neurotoxin. Following an incubation period that varies from 2 hours to 8 days, the symptoms start with intestinal problems. Then paralysis of the cranial nerve pairs sets in, classically manifested by diplopia, dysphagia, dysphonia, areactive mydriasis and ptosis. The onset of motor disorders occurs in descending order with possible involvement of the respiratory muscles, hence requiring reanimation measures and sometimes mechanical ventilation. The diagnosis of botulism is clinical. Identification of the botulinum toxin in the blood or faeces of the patients or in the contaminating food stuff confirms the diagnosis.

[Foodborne botulism, epidemiologic aspects]. / Botulisme alimentaire, aspects epidémiologiques.

With a mean of 30 cases reported per year, following Italy, France ranks second in the European countries in terms of incidence of botulism. Food stuff of commercial origin, of artisanal or industrial manufacture fabrication, is increasingly implicated in the genesis of outbreaks of botulism. Moreover, the modern methods of conserving food (vacuum packed food, frozen food...) allow the development of Clostridium bacteria. The diversification of the risks related to the type of products incriminated and to the new conservation methods, associated with the extension of commercial exchanges, result in the risk of widespread internationally outbreaks of botulism.

[Foodborne botulism, prevent and treatment]. / Botulisme alimentaire, prévention et traitement.

The United States and Europe agree that the treatment of botulism is based on symptomatical measures and, notably, on mechanical ventilation when the respiratory function is impaired. Opinions diverge regarding the specific treatment represented by anti-botulinum serum: used systematically in the United States and frequently in many European countries, France never uses it other than in a few cases. Identification of the contaminating foodstuff is a fundamental element in limiting extension of the disease. Reducing the delay in declaration and the identification and correction of bad cooking practices would help to reduce the number of cases of botulism.

[Key points.] / Botulisme, un diagnostic clinique.

BOTULISM, A CLINICAL DIAGNOSIS:

[Key points.] / Botulisme alimentaire, prévention et traitement.

FOODBORNE BOTULISM, PREVENT AND TREATMENT:

Vascular thrombosis and acute cytomegalovirus infection in immunocompetent patients: report of 2 cases and literature review.

Acute cytomegalovirus (CMV) infection in immunocompetent patients is common worldwide, with seroprevalence rates of 40%-100%, depending on the country, socioeconomic conditions, and the patient's age. Infection is most often asymptomatic, but acute cytomegalovirus infection is occasionally revealed by prolonged fever, cervical lymphadenitis, and arthralgia, and it is more rarely revealed by pneumonia, myocarditis, pericarditis, colitis, and hemolytic anemia. Here, we report 2 cases of acute CMV infection in nonimmunocompromised adults that were complicated by venous thrombosis with pulmonary embolism. We also review previously reported cases of vascular thrombosis and discuss the propensity of CMV to induce vascular damage with associated thrombosis.

[Hepatosplenic localization of cat scratch disease in immunocompetent adults. Two cases]. / Localisations hépatospléniques de la maladie des griffes du chat chez l'adulte immunocompétent. Deux cas.

The infective agent responsible for cat scratch disease, Bartonella henselae, is a rare cause of hepatic granulomatosis in immunocompetent adults. Clinical features include a prolonged fever or more typical symptoms such as lymphadenopathy associated with painful hepatomegaly and a fever following a cat scratch or bite. Images of micronodular hepatosplenic lesions on abdominal ultrasonography or computed tomography scan along with epithelioid granulomas in a liver biopsy can suggest this diagnosis. It is established with a serology by indirect immunofluorescence or by ELISA and/or the presence of Bartonella henselae DNA evidenced by PCR in the liver biopsy. We report two cases of hepatosplenic localizations of cat scratch disease in a 41-year-old woman and a 44-year-old man presenting asthenia and fever associated with a biological inflammatory syndrome and elevated liver enzymes.