Long-term neuro-functional disability in adult patients with community-acquired bacterial meningitis.

PURPOSE: To investigate the prevalence of neuro-functional disability and its determinants 12 months after community-acquired bacterial meningitis (CABM) in adult patients. METHODS: In a prospective multicenter cohort study (COMBAT), all consecutive cases of CABM were enrolled and followed up for 12 months. Neuro-functional disability at 12 months was evaluated using a combination of the Glasgow Outcome Scale (functional disability), and the modified Rankin Disability Scale (physical disability). Factors associated with neuro-functional disability were identified by multivariate logistic regression. RESULTS: Among 281 patients, 84 (29.9%) patients exhibited neuro-functional disability at 12 months: 79 (28.1%) with functional disability and 51 (18.1%) with physical disability. Overall, 6 patients (2.1%) died during the follow-up. The most common pathogen identified was Streptococcus pneumoniae (131/272, 48.2%); 77/268 patients (28.7%) had a physical disability at hospital discharge. Factors independently associated with 12-month neuro-functional disability were a pneumococcal meningitis (adjusted OR = 2.8; 95% confidence interval (CI) = [1.3; 6.7]), the presence of a physical disability at hospital discharge (aOR = 2.3; 95%CI = [1.2; 4.4]) and the presence of behavioral disorders at hospital-discharge (aOR = 5.9; 95%CI = [1.6; 28.4]). Dexamethasone use was not significantly associated with neuro-functional disability (OR = 0.2; 95%CI = [< 0.1;1.3]). CONCLUSION: Neuro-functional disability is frequently reported 12 months after CABM. Detailed neurological examination at discharge is needed to improve the follow-up. TRIAL REGISTRATION: NCT01730690.

High Prevalence of Headaches During Covid-19 Infection: A Retrospective Cohort Study.

OBJECTIVES: To document the prevalence of new headaches in patients with Covid-19 infection and the potential association with other neuro-sensorial symptoms (anosmia and ageusia). The persistence of these symptoms 1 month after recovery was also documented. BACKGROUND: Headaches are a very common symptom of viral infections. Surprisingly, early Chinese studies reported a relatively low prevalence (12-15%) of headaches associated with Covid-19. METHODS: All the patients with laboratory-confirmed or chest-CT-confirmed Covid-19 infection, diagnosed between February 27th and April 15th , 2020 in the dedicated laboratory of Clermont-Ferrand University Hospital were followed for 1 month after recovery. RESULTS: A total of 139 consecutive patients (mean [SD] age, 48.5 [15.3] years; 87 women [62.6%]) were interviewed 1 month after disappearance of fever and dyspnea (semi-structured phone interview). Overall, 59.0% (82/139) of people with Covid-19 had mild disease, 36.7% (51/139) had severe disease, and 4.3% (6/139) had critical illness. Eighty-two (59.0%; 95% CI: 50.3 to 67.3) reported new headaches during the acute phase and 3.6% (5/139) had persistent headaches 1 month after fever and dyspnea remission. Anosmia and ageusia were also very common, occurring in 60.4% (84/139) and 58.3% (81/139) of the patients, respectively. These 2 symptoms persisted in 14.4% (20/139) and 11.5% (16/139) of Covid-19 patients 1 month after recovery. Headaches were neither clearly associated with anosmia, nor with ageusia, and were not associated with disease severity (ie, requiring hospitalization or intensive care unit). CONCLUSION: This specific study highlights the high prevalence of new headaches during Covid-19 infection in French patients. Further studies are needed to refine the characterization of patients with Covid-19-associated headaches.

Health related quality of life in patients with community-acquired pneumococcal pneumonia in France.

BACKGROUND: Community Acquired Pneumococcal Pneumonia is a lung infection that causes serious health problems and can lead to complications and death. The aim of this study was to observe and analyze health related quality of life after a hospital episode for patients with community acquired pneumococcal pneumonia in France. METHODS: A total of 524 individuals were enrolled prospectively in the study and were followed for 12 months after hospital discharge. Presence of streptococcus pneumoniae was confirmed by microbiological sampling. Quality of life was reported at four different points of time with the EQ-5D-3 L health states using the French reference tariff. Complete data on all four periods was available for 269 patients. We used descriptive and econometric analysis to assess quality of life over time during follow-up, and to identify factors that impact the utility indexes and their evolution through time. We used Tobit panel data estimators to deal with the bounded nature of utility values. RESULTS: Average age of patients was 63 and 55% of patients were men. Negative predictors of quality of life were the severity of the initial event, history of pneumonia, smokers, age and being male. On average, quality of life improved in the first 6 months after discharge and stabilized beyond. At month 1, mean utility index was 0.53 (SD: 0.34) for men and 0.45 (SD: 0.34) for women, versus mean of 0.69 (SD: 0.33) and 0.70 (SD: 0.35) at Month 12. "Usual activities" was the dimension the most impacted by the disease episode. Utilities for men were significantly higher than for women, although male patients were more severe. Individuals over 85 years old did not improve quality of life during follow-up, and quality of life did not improve or deteriorated for 34% of patients. We found that length of hospital stay was negatively correlated with quality of life immediately after discharge. CONCLUSION: This study provides with evidence that quality of life after an episode of community acquired pneumococcal pneumonia improves overall until the sixth month after hospital discharge, but older patients with previous history of pneumonia may not experience health gains after the initial episode.

Flexibility of interval between vaccinations with AS03A-adjuvanted influenza A (H1N1) 2009 vaccine in adults aged 18-60 and >60 years: a randomized trial.

BACKGROUND: Flexibility of vaccination schedule and lower antigen content can facilitate pandemic vaccine coverage. We assessed the immune response and safety of AS03-adjuvanted A/California/7/2009 H1N1 pandemic vaccine containing half of the registered adult haemagglutinin (HA) antigen content, administered as a two-dose schedule at intervals of 21 days or 6 months in both young and elderly adults. METHODS: In this open-label randomized trial, healthy adults aged 18-60 years (N = 163) and >60 years (N = 143) received AS03A-adjuvanted A/California/7/2009 H1N1 vaccine containing 1.9 µg HA on Day 0. A second dose was given on Day 21 (n = 177) or Day 182 (n = 106). Haemagglutination-inhibition (HI) antibody responses were analyzed on Days 0, 21, 42, 182, 364 and additionally on Day 203 for subjects vaccinated on Day 182. Solicited and unsolicited adverse events were recorded. RESULTS: The HI antibody response in both age strata 21 days after the first dose met and exceeded all regulatory acceptance criteria although the results suggested a lower response in the older age stratum (geometric mean titres [GMTs] for HI antibodies of 420.5 for subjects aged 18-60 years and 174.4 for those >60 years). A second dose of AS03A adjuvanted A/H1N1/2009 vaccine induced a further increase in antibody titres and the response was similar whether the second dose was administered at 21 days (GMTs of 771.8 for 18-60 years and 400.9 for >60 years) or 6 months (GMTs of 708.3 for 18-60 years and 512.1 for >60 years) following the first dose. Seroprotection rates remained high at 6 months after one dose or two doses while at 12 months rates tended to be higher for the 6 month interval schedule (93.3% for 18-60 years and 80.4% for >60 years) than the 21 day schedule (82.3% for 18-60 years and 50.0% for >60 years). Reactogenicity/safety profiles were similar for both schedules, there was no evidence of an increase in reactogenicity following the second dose. CONCLUSIONS: The results indicate that flexibility in the dosing interval for AS03A adjuvanted vaccine may be possible. Such flexibility could help to reduce the logistic stress on delivery of pandemic vaccination programmes. TRIAL REGISTRATION: ClinicalTrials.gov, NCT00975884.

Bloodstream infection after positive catheter cultures: what are the risks in the intensive care unit when catheters are routinely cultured on removal?

OBJECTIVES: The aim of the study was to assess whether an isolated positive catheter culture is predictive of a subsequent bloodstream infection in intensive care unit patients. DESIGN: Retrospective clinical study between 2000 and 2007. SETTING: Intensive care unit of a university hospital. SUBJECTS: All arterial, central venous, and dialysis catheters yielding selected pathogenic microorganisms from isolated positive catheter cultures. Positive catheter culture was defined by a catheter tip culture performed with the Brun-Buisson technique yielding ≥103 colony-forming units/mL; isolated positive catheter culture by a positive catheter culture without concomitant bloodstream infection due to the microorganism of the positive catheter culture evidenced within 48 hrs before or after catheter removal; and subsequent bloodstream infection by a bloodstream infection developing between 48 hrs and 30 days after catheter removal and due to a selected pathogenic microorganism of an isolated positive catheter culture. Active antibiotic therapy was active if at least one of the antibiotics administered was effective against the selected pathogenic microorganism of the positive catheter culture. INTERVENTION: None. MEASUREMENT AND MAIN RESULTS: The end point of the study was the ratio of the number of subsequent bloodstream infections to that of selected pathogenic microorganisms isolated from positive catheter culture 30 days after catheter removal. A total of 138 isolated positive catheter cultures for 149 selected pathogenic micro-organisms was included in the study. Only two cases (1.3%) of subsequent bloodstream infection were evidenced, one resulting from Escherichia coli and the other from Staphylococcus epidermidis. The incidence of subsequent bloodstream infection did not differ with regard to the presence or absence of active antibiotics at catheter removal: zero of 23 vs. two of 121 (p = 1), respectively. CONCLUSIONS: Our results suggest that the risk of subsequent bloodstream infection in intensive care unit patients when the Brun-Buisson technique is used to define isolated positive catheter culture is low.

Severe COVID-19 is characterized by the co-occurrence of moderate cytokine inflammation and severe monocyte dysregulation.

BACKGROUND: SARS-CoV-2 has been responsible for considerable mortality worldwide, owing in particular to pulmonary failures such as ARDS, but also to other visceral failures and secondary infections. Recent progress in the characterization of the immunological mechanisms that result in severe organ injury led to the emergence of two successive hypotheses simultaneously tested here: hyperinflammation with cytokine storm syndrome or dysregulation of protective immunity resulting in immunosuppression and unrestrained viral dissemination. METHODS: In a prospective observational monocentric study of 134 patients, we analysed a panel of plasma inflammatory and anti-inflammatory cytokines and measured monocyte dysregulation via their membrane expression of HLA-DR. We first compared the results of patients with moderate forms hospitalized in an infectious disease unit with those of patients with severe forms hospitalized in an intensive care unit. In the latter group of patients, we then analysed the differences between the surviving and non-surviving groups and between the groups with or without secondary infections. FINDINGS: Higher blood IL-6 levels, lower quantitative expression of HLA-DR on blood monocytes and higher IL-6/mHLA-DR ratios were statistically associated with the risk of severe forms of the disease and among the latter with death and the early onset of secondary infections. INTERPRETATION: The unique immunological profile in patients with severe COVID-19 corresponds to a moderate cytokine inflammation associated with severe monocyte dysregulation. Individuals with major CSS were rare in our cohort of hospitalized patients, especially since the use of corticosteroids, but formed a very severe subgroup of the disease. FUNDING: None.

Impact of Vitamin D Supplementation on Influenza Vaccine Response and Immune Functions in Deficient Elderly Persons: A Randomized Placebo-Controlled Trial.

Background: Immunosenescence contributes to reduced vaccine response in elderly persons, and is worsened by deficiencies in nutrients such as Vitamin (Vit-D). The immune system is a well-known target of Vit-D, which can both potentiate the innate immune response and inhibit the adaptive system, and so modulate vaccination response. Objective: This randomized placebo-controlled double-blind trial investigated whether Vit-D supplementation in deficient elderly persons could improve influenza seroprotection and immune response. Design: Deficient volunteers (Vit-D serum <30 ng/mL) were assigned (V1) to receive either 100,000 IU/15 days of cholecalciferol (D, n = 19), or a placebo (P, n = 19), over a 3 month period. Influenza vaccination was performed at the end of this period (V2), and the vaccine response was evaluated 28 days later (V3). At each visit, serum cathelicidin, immune response to vaccination, plasma cytokines, lymphocyte phenotyping, and phagocyte ROS production were assessed. Results: Levels of serum 25-(OH)D increased after supplementation (D group, V1 vs. V2: 20.7 ± 5.7 vs. 44.3 ± 8.6 ng/mL, p < 0.001). No difference was observed for serum cathelicidin levels, antibody titers, and ROS production in D vs. P groups at V3. Lower plasma levels of TNFα (p = 0.040) and IL-6 (p = 0.046), and higher ones for TFGß (p = 0.0028) were observed at V3. The Th1/Th2 ratio was lower in the D group at V2 (D: 0.12 ± 0.05 vs. P: 0.18 ± 0.05, p = 0.039). Conclusions: Vit-D supplementation promotes a higher TGFß plasma level in response to influenza vaccination without improving antibody production. This supplementation seems to direct the lymphocyte polarization toward a tolerogenic immune response. A deeper characterization of metabolic and molecular pathways of these observations will aid in the understanding of Vit-D's effects on cell-mediated immunity in aging. This clinical trial was registered at clinicaltrials.gov as NCT01893385.

Costs associated with community acquired pneumonia in France.

OBJECTIVES: Pneumocost is a prospective study that aimed at documenting the costs of the management of patients hospitalized with a pneumococcal pneumonia and the post-discharge costs during a 6-month period in the French context. METHODS: Billing data were used to document hospital costs. Resource use during the follow-up period was collected through phone interviews at month 1, 3 and 6. Descriptive statistics and multivariate analyses were performed. We used generalized linear models with log-link functions to estimate parameters associated with hospital and follow-up costs of patients. RESULTS: Five hundred twenty-four patients were enrolled in 40 public centers from October 2011 to April 2014. Average age was 63 (SD 17); 55.0% of them were male. Average length of stay was 15 days (SD 23). Average cost of stay for the French Sickness Fund was €7293 (SD €7363). Average cost of follow-up was €1242 (SD €3000) and decreased steadily through time. When controlling for patient's socioeconomic characteristics, severity of disease and hospital stay, results showed a concave relationship between hospital costs and age. Obesity, the severity of the disease and comorbidities were associated with constantly increasing inpatient costs. Concerning follow-up costs, we found the same concave relationship with age, while gender, a history of pneumonia and severity of the disease were the most important predictors of high costs after discharge. CONCLUSION: Pneumocost is the first French study providing a robust estimation of the cost of managing invasive pneumococcal pneumonia in the French context.

[Prophylaxis for contacts of an index case of hepatitis A: immunoglobulins or vaccination?]. / Prophylaxie autour d'un cas index d'hépatite A: immunoglobulines ou vaccination?

France has changed from a country where hepatitis A is endemic to one where residents are at risk of hepatitis A infection: in 20 years, the seroprevalence in 20-year-olds has fallen from 50% to less than 10%. Prophylaxis for close contacts of an index case has therefore become a major problem because their risk of hepatitis A is high. Polyvalent immunoglobulins are recommended in several countries, but no immunoglobulins are approved for this indication in France. Immunoglobulins are also expensive and only slightly efficacious. A vaccine against hepatitis A administered to young children or adolescents can break the epidemic chain and protect adults very effectively by limiting virus circulation. Many countries propose early vaccination to at-risk contacts, with vaccination generally advised within a week of the initial infectious contact. Although more specific and more plentiful data are still necessary before this recommendation can be generalized, it must be taken into account. This medical decision should thus be made on an individualized basis after discussion between the physician and family about the risk.

[Emergence of monomicrobial methicillin-resistant Staphylococcus aureus infections in diabetic foot osteomyelitis (retrospective study of 48 cases)]. / Emergence des infections monomicrobiennes à staphylocoque doré méticilline-résistant dans les ostéites du pied diabétique. Etude rétrospective de 48 cas.

OBJECTIVE: Describe the clinical appearance, microorganisms involved, and prognosis of diabetic foot osteomyelitis. METHOD: Retrospective study of 48 patients seen in 2004 for presumed osteomyelitis (exposed bone or suggestive radiographic or clinical picture). Specimens for culture came from swabs of wound discharge, needle aspiration and bone biopsy. RESULTS: Forty-eight patients with diabetes and contiguous osteomyelitis of the foot were followed for a year. The principal microorganisms isolated were Staphylococcus aureus (58%) and Gram-negative bacilli (29%); 58% of the infections were monomicrobial, 31% of the microorganisms multidrug-resistant, and 85% of the patients were hospitalized, for a median duration of 30 days. Healing occurred in 40 patients, although 15 required amputation first, and 18 had a new infection at a different site (11 involving osteomyelitis) in the year after antibiotic treatment ended. PERSPECTIVES: Diabetic foot osteomyelitis is a serious disease in view of its site and the microorganisms involved, which are often multidrug-resistant. There is a clear predominance of S. aureus. Medical treatment has an increasingly important role in its management and requires that samples be properly collected for bacteriological testing. The prognosis for these infections, which remains grim in view of the amputation rate and the high risk of new infection, could be improved by reinforcing prevention measures.

Lemierre's syndrome and genetic polymorphisms: a case report.

BACKGROUND: Lemierre's syndrome presents a classic clinical picture, the pathophysiology of which remains obscure. Attempts have been made to trace genetic predispositions that modify the host detection of pathogen or the resultant systemic reaction. CASE PRESENTATION: A 17-year old female, with no previous medical history, was admitted to the intensive care unit for septic shock, acute respiratory distress syndrome and Lemierre's syndrome. Her DNA was assayed for single nucleotide polymorphisms previously incriminated in the detection of the pathogen, the inflammatory response and the coagulation cascade. We observed functional variations in her Toll like 5 receptor (TLR 5) gene and two coagulation variations (Tissue Factor (TF) 603 and Plasminogen-Activator-Inhibitor-1 (PAI-1) 4G-4G homozygosity) associated with thrombotic events. CONCLUSION: The innate immune response and the prothrombogenic mutations could explain, at least in part, the symptoms of Lemierre's syndrome. Genomic study of several patients with Lemierre's syndrome may reveal its pathophysiology.

[Vancomycin-resistant Enterococcus in an epidemic situation: screening at admission for patients at risk of carriage]. / Entérocoques résistant aux glycopeptides dans un contexte endémo-épidémique. Stratégie d'isolement àl'admission des patients à risque.

OBJECTIVES: To evaluate a strategy based on screening and isolation at admission to a department of infectious diseases during an epidemic of vancomycin-resistant Enterococcus (VRE) at the University Hospital of Clermont-Ferrand. METHODS: Systematic screening for VRE by anal swabs began on November 15, 2004. Patients were isolated on admission if (a) they had been hospitalized more than 24 h in an at-risk department of our hospital or (b) they had received a course of wide-spectrum antimicrobial therapy for longer than 48 h in the three months preceding admission. Patients hospitalized in our department were screened weekly if they were treated with wide-spectrum antibiotics, had a urinary catheter left in place for one week, or were neutropenic. RESULTS: Through May 15, 2005, 12 (3.5%) of 341 swabs were found to be positive for VRE: eight were detected on admission and four during hospitalization. In all, 81 patients were isolated on admission. A case-control study confirmed that the criteria for patient isolation were indeed risk factors for VRE. Isolation was well accepted when it was clearly explained. No new case has been detected since March 2005. CONCLUSION: An isolation strategy based on known risk factors for VRE with systematic screening on admission appears to be an effective way to control an outbreak of VRE, perhaps in part because it helps to keep the medical staff alert to this problem. Isolation is well tolerated as long as it is explained clearly.

Staphylococcus aureus-Related Diabetic Osteomyelitis: Medical or Surgical Management? A French and Spanish Retrospective Cohort.

Staphylococcus aureus is the main cause of diabetic foot osteomyelitis (DFO) and can be treated medically or by surgery. We investigated the outcome of consecutive patients with a diagnosis of S aureus DFO retrospectively in 4 hospitals according to the type of management, medical (including debridement at bedside) or surgical. The outcome was classified as either favorable or failure (relapse, impaired wound healing, or amputation). Seventy-four patients with S aureus DFO, including 26 with methicillin-resistant S aureus, were included with a mean duration of follow-up of 21 ± 1 months. As part of the initial treatment, 47% underwent bone surgery followed with a short course of antibiotic. Others were treated with antibiotic therapy alone with bedside debridement. The outcome was favorable for 84% of these patients, with similar rates in the surgical and medical groups (80% vs 87%, P > .05). Patients in the medical group were less frequently hospitalized (49% vs 94%, P < .001) and had a shorter length of hospital stay (17 ± 3 vs 50 ± 12 days, P = .004). Patients in the surgery group received a shorter course of antibiotic therapy (10 ± 2 vs 11 ± 1 weeks, P = .001) with fewer side effects (9% vs 33%, P = .01). The type of management was not associated with subsequent new episode of noncontiguous DFO, which developed in 32% of cases. In conclusion, except significant differences in duration of hospitalization and antibiotic therapy, medical and surgical management of S aureus DFO had similar outcomes with a cure rate >80%.

[Adult immunization in France: an update]. / Actualités des vaccinations de l'adulte.

French immunisation schedule recommends tetanus and poliomyelitis vaccine every 10 years and influenza every year after the age of 65. Several other vaccinations related to occupational health are implemented. Travellers or immunocompromised people who could be exposed to infections need some other vaccinations, too. Pneumoccocal vaccine coverage is insufficient. Reinforcing diphteria immunization is considered, using a recently licensed combined vaccine. Maintenance of immunity against "childhood infectious diseases" preventable with vaccinations is a new challenge; measles, rubella and pertussis occur now quite often in adults: the risk of complications is higher in these ages (measles), or expose to specific risk (rubella in pregnant women); adults may even become the source of the contamination of younger people (many infants affected with whooping cough have contracted the disease from their own parents). The immunisation against these diseases should be prosecuted in adults. Related with the development of more efficacious new vaccines, the indications of pneumococcus, meningococcus or varicella vaccines should be defined in some populations of adults. Immunization policy of adults should be revised in order to continue the vaccination program of childhood. Some infections that may affect adults should be prevented by improving vaccine application. A real adult immunisation schedule and recommendations should be set up towards populations at risk of preventable infections. The implementation of these recommendations should be reinforced.

Suppressive therapy using azithromycin in 2 rare cases of recurrent staphylococcal infections.

Recurrent staphylococcal skin and soft tissue infections may recur despite decontamination and multiple courses of antibiotic therapy and may dramatically impair the patient's quality of life. We report successful use of long-term azithromycin prophylaxis in a recurrent laryngitis and a scalp folliculitis due to methicillin-susceptible Staphylococcus aureus.

Improvement of the management of infants, children and adults with a molecular diagnosis of Enterovirus meningitis during two observational study periods.

Enteroviruses (EVs) are a major cause of aseptic meningitis, and RNA detection using molecular assay is the gold standard diagnostic test. The aim of this study was to assess the impact of an EV positive diagnosis on the clinical management of patients admitted for meningitis over the course of two observational study periods (2005 and 2008-09) in the same clinical departments. We further investigated in multivariate analysis various factors possibly associated with hospital length of stay (LOS) in all age groups (infants, children, and adults). The results showed an overall improvement in the management of patients (n = 142) between the study periods, resulting in a significantly shorter hospital LOS for adults and children, and a shorter duration of antibiotic use for adults and infants. In multivariate analysis, we observed that the time from molecular test results to discharge of patients and the median duration of antibiotic treatment were associated with an increase in LOS in all age groups. In addition, among adults, the turnaround time of the molecular assay was significantly correlated with LOS. The use of CT scan in children and hospital admission outside the peak of EV prevalence in infants tended to increase LOS. In conclusion, the shorter length of stay of patients with meningitis in this study was due to various factors including the rapidity of the EV molecular test (particularly in adults), greater physician responsiveness after a positive result (in adults and children), and greater experience on the part of physicians in handling EV meningitis, as evidenced by the shorter duration of antibiotic use in adults and infants.

Health care support issues for internationally adopted children: a qualitative approach to the needs and expectations of families.

BACKGROUND: Families of internationally adopted children may face specific problems with which general practitioners (GPs) may not be familiar. The aim of the study was to explore problems faced by families before, during and after the arrival of their internationally adopted child and to assess the usefulness of a specific medical structure for internationally adopted children, which could be a resource for the GP. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a qualitative study using individual semistructured guided conversations and interviewed 21 families that had adopted a total of 26 children internationally in the Puy de Dome department, France, in 2003. Quantitative data were used to describe the pathologies diagnosed and the investigations performed.Our study showed that the history of these families, from the start of the adoption project to its achievement, is complex and warrants careful analysis. Health-care providers should not only consider the medical aspects of adoption, but should also be interested in the histories of these families, which may play a role in the forming of attachments between the adoptee and their adoptive parents and prevent further trouble during the development of the child. We also showed that adoptive parents have similar fears or transient difficulties that may be resolved quickly by listening and reassurance. Most such families would support the existence of a specific medical structure for internationally adopted children, which could be a resource for the general practitioner. However, the health-care providers interviewed were divided on the subject and expressed their fear that a special consultation could be stigmatizing to children and families. CONCLUSIONS/SIGNIFICANCE: A specific consultation with well-trained and experienced practitioners acting in close collaboration with GPs and paediatricians may be of help in better understanding and supporting adopted children and their families.

Immunogenicity and safety results from a randomized multicenter trial comparing a Tdap-IPV vaccine (REPEVAX®) and a tetanus monovalent vaccine in healthy adults: new considerations for the management of patients with tetanus-prone injuries.

UNLABELLED: In adults with a tetanus-prone injury, combined vaccines such as Tdap-IPV (REPEVAX®) can boost immunity against several diseases simultaneously. This Phase IIIb, parallel-group, open-label trial compared antibody responses to Tdap-IPV and tetanus monovalent vaccine (TMV; Vaccin Tétanique Pasteur® or Tetavax®) against tetanus toxoid 10 and 28 d post-vaccination. Between July and December 2009, four centers in France and five in Germany recruited healthy adults who had received a tetanus-containing vaccine 5-10 y previously. Participants were randomized 1:1 to receive at the first visit a single dose (0.5 mL) of Tdap-IPV or TMV, with follow-up visits at Day 10 and Day 28. OUTCOMES: per protocol (PP) population immunogenicity at Day 10 (primary) and at Day 28 (secondary); safety throughout the study. Of 456 adults randomized, 223 received Tdap-IPV and 233 received TMV (PP population: 183 and 199 participants, respectively). All participants receiving Tdap-IPV and 99.0% receiving TMV had an anti-tetanus antibody concentration ≥ 0.1 IU/mL, confirming non-inferiority of Tdap-IPV to TMV (95% confidence interval of the difference: -1.2, 3.6). Number of adverse events reported was comparable in each group. Injection-site reactions were reported by 76.6% participants receiving Tdap-IPV and 74.6% receiving TMV. Systemic events (e.g., malaise, myalgia and headache) were reported in 47.7% and 39.7% of the Tdap-IPV and the TMV groups, respectively. Tdap-IPV is effective and well-tolerated for use in the management of tetanus-prone injuries in emergency settings in persons for whom a booster against diphtheria, pertussis and poliomyelitis is also needed.