Jérôme Salomon

Rabies, still neglected after 125 years of vaccination.

Rabies is a viral zoonotic infection ofthe central nervous system caused by alyssavirus. The disease is fatal withoutproper post exposure prophylaxis (PEP).In July 1885, Louis Pasteur obtained hisfirst success against rabies by vaccinatingJoseph Meister, a 9-year-old boy present-ing with multiple deep bite wounds [1].After more than 700 successful inocula-tions, Pasteur launched an internationalsubscription and opened the world’s firstresearch institute dedicated to the preven-tion of rabies and other infectious diseases.The Institut Pasteur was born. Due tosubstantial advances during the 20thcentury, safe and effective human andanimal vaccines based on tissue culturemethodologies are available today. Today,125 years later, Institut Pasteur is at thecore of an international network of 30institutes. Through its numerous institu-tions established in enzootic areas, theworldwide contribution of the InstitutPasteur International Network to rabiessurveillance and control is still of para-mount importance. Each year, the Inter-national Network is responsible for PEPadministration to more than 180,000exposed patients, mainly in Southeast Asiaand Africa. Scientists and health staff arealso involved in various national commit-tees that work on the development andsuccessful implementation of rabies con-trol programs.Sadly, whereas extensive efforts indeveloped countries have largely con-trolled dog (the United States and Europe)and fox (western and central Europe)rabies [2,3], dog rabies remains enzooticin much of the world, and 15 millionpeople require PEP every year. Rabies isconsidered one of the most neglecteddiseases in the world’s developing coun-tries with the greatest burden in poor ruralcommunities, and disproportionately inchildren. According to the World HealthOrganization (WHO), 30% to 50% of the55,000 victims estimated each year areindividuals under 15 years of age [4]. Over95% of these human rabies cases areconcentrated in Asia (especially in India)and Africa, and 99% of them are trans-mitted by dogs. There are several reasonsfor the lack of accurate data, includingweak or non-existent rabies surveillancesystems; under-reporting of cases by localcommunities and central authorities; un-reliable diagnosis of cases, which isgenerally based on clinical criteria ratherthan laboratory confirmation; and inade-quate legislation for compulsory notifica-tion of cases. The absence of accurate dataon disease burden, upon which regionaland national priorities for research andcontrol are based, leads to a vicious cycleof indifference and neglect [5].The question now is why, despite theavailability of safe and effective humanvaccines, human rabies deaths continue toescalate in many parts of the world. Thereare several general and specific explana-tions for the continued burden of dograbies [6–8].In general, there is a lack of awarenessamongst policy-makers of the rabies bur-den and impacts and the need forprioritizing resources towards its control.Further, despite the widely advocatedneed for intersectoral collaboration be-tween government ministries, the recogni-tion of roles and responsibilities amongstagencies as well as integration of budgetsacross ministries still poses considerablechallenges.Mass vaccination of dogs is the mostcost-effective way to achieve a significantand lasting reduction in the number ofhuman deaths from rabies [9]. However,such prevention efforts are often notprioritized by national governments ineven the most endemic countries. Amongthe reasons for the low priority affordedrabies are, as for many neglected tropicaldiseases, its predominance in remote ruralareas and its disproportionate impact onpeople living in extreme poverty. There-fore, lack of resources, gaps in epidemio-logical knowledge (e.g., level of vaccina-tion coverage needed in any given setting),lack of in-country expertise on implemen-tation of canine rabies control strategies,and sustainability issues impair the successof such programs.Additionally, in most developing coun-tries (with some notable exceptions), thereis a lack of awareness among the popula-tion, including medical practitioners andhealth authorities, about the widespreadextent of the disease and the risk oftransmission from dogs to human popula-tions [6–8]. Additionally, the infrastruc-ture for the management of rabies expo-sure is scarce. Many people who areexposed to rabies do not seek PEP,because they are not aware of the risk ofcontracting this disease or because theylive in rural areas too far away from rabiesprevention centers, which are generallylocated in big cities. In some cases, theworld’s poorest people simply cannotafford the cost of PEP.A range of key scientific questions alsoremains unsolved, and there is an urgencyto promote research and development onthe fundamental aspects of rabies molec-ular pathobiology, improved control tools,and operational research. There is also aneed for multidisciplinary integrative ap-proaches that rely on the followingelements.1. It is essential to find ways to improveepidemiological surveillance using di-agnostic approaches to rabies based onvalidated protocols and specimens andevaluated under field conditions [10–12]. Epidemiological models are alsoneeded to better estimate the inci-dence of rabies [4,13,14]. Recentresearch on this topic published in thisjournal yielded rabies incidence for

Fosfomycin: Efficacy against infections caused by multidrug-resistant bacteria

Abstract Objective: To analyze the indications for and the efficacy of parenteral fosfomycin, especially against multidrug-resistant (MDR) and pan-resistant bacterial infections.Patients and methods: During a unique crisis in fosfomycin production, the supply of this antibiotic had to be carefully monitored in France over a 10-week period. One hundred and sixteen assessable patients were included in a prospective cohort study.Results: The main indications for use were osteoarthritis, lung infection, urinary tract infection, and bacteraemia. The 2 bacteria most frequently involved were Pseudomonas aeruginosa and methicillin-resistant Staphylococcus. MDR bacteria were seen in 71.5% (83/116) of cases, especially MDR P. aeruginosa (n = 28). Critical situations were common, with 44.0% (51/116) of hospitalizations occurring in an intensive care unit and 22.4% (26/116) of patients with septic shock. The overall outcome was favourable in 76.8% of cases (76/99 assessable patients).Conclusion: This study provided a unique opportunity to describe the use of fosfomycin and assess its efficacy, especially against MDR bacterial infections, even in critical situations.

Body Composition and Nutritional Parameters in HIV and AIDS Patients

Abstract Undernutrition is a frequent complication of evolutive and chronic HIV (human immunodeficiency virus) infection characterized by bodyweight loss and changes in body composition. The Centers for Disease Control and Prevention define AIDS wasting as involuntary loss of more than 10% of body weight, plus more than 30 days of either diarrhea, or weakness and fever. Wasting syndrome has been considered as a case definition of the AIDS disease since 1987. Wasting syndrome is clearly linked to disease progression and death. Despite the progress under the era of highly active antiretroviral therapy (HAART), wasting is still a problem for people with AIDS. A small part of the weight lost is fat. More important is the loss of “lean body mass”, which is mostly muscle. Body composition changes during HIV infection are different from those observed in food deprivation. Under the era of HAART, a HIV-associated adipose redistribution syndrome (HARS) was described that associates subcutaneous lipoatrophy and abdominal obesity linked to various metabolic disorders. Several factors contribute to wasting syndrome. Not only low food intake and poor nutrient absorption, but mainly altered metabolism (increased resting energy expenditure) and specific disturbances in protein turnover, which is also increased. Nutritional evaluation of HIV-infected patients should include the measurement of body composition and analysis of nutritional parameters, including albumin, transthyretin and C-reactive protein. Transthyretin seems to be particularly useful to follow the recovery period of malnutrition.

Prevention of urinary tract infection in six spinal cord-injured pregnant women who gave birth to seven children under a weekly oral cyclic antibiotic program

BACKGROUND Pregnancies in spinal cord-injured (SCI) patients present unique clinical challenges. Because of the neurogenic bladder and the use of intermittent catheterization, chronic bacteriuria and recurrent urinary tract infection (UTI) is common. During pregnancy the prevalence of UTI increases dramatically. Recurrent UTI requires multiple courses of antibiotics and increases the risks of abortion, prematurity, and low birth weight. A weekly oral cyclic antibiotic (WOCA) program was recently described for the prevention of UTI in SCI patients. OBJECTIVE To test the impact of WOCA in six SCI pregnant women (four paraplegic, two tetraplegic). DESIGN This was a prospective observational study. WOCA consists of the alternate administration of one of two antibiotics once per week. RESULTS We observed a significant reduction of UTI (6 UTI/patient/year before pregnancy to 0.4 during pregnancy and under WOCA; p<0.001) and no obstetric complications. Infant outcomes were good. CONCLUSION The WOCA regimen could be useful for UTI prophylaxis in SCI pregnant women.

Is faecal microbiota transplantation an option to eradicate highly drug-resistant enteric bacteria carriage?

Carbapenem-resistant Enterobacteriaceae (CRE) or vancomycin-resistant enterococci (VRE) carriage present a major public health challenge. Decolonization strategies are lacking. We aimed to evaluate the impact of faecal microbiota transplantation (FMT) on a cohort of patients with digestive tract colonization by CRE or VRE. Eight patients were included: six carrying CRE and two colonized by VRE. One month after FMT, two patients were free from CRE carriage, and another patient was free from VRE after three months. In our experience, this strategy is safe.

Two Cases of Foodborne Botulism Type E and Review of Epidemiology in France

Abstract In 1999, two new cases of type E botulism were observed in French hospitals. Since this type of botulism is uncommon in France, the cases prompted a national epidemiological study. Sixteen cases of type E botulism, including the two cases reported here, occurred between 1952 and 1999. The clinical and treatment characteristics of all cases were evaluated, and the results suggest that, despite its rarity, type E botulism should be considered by clinicians in France. Changes in the eating habits of people in France, as in the rest of Europe, with the increased consumption of vacuum-packed fish from endemic areas and decreased consumption of local foodstuffs, could explain the occurrence of the most recent cases.

Managing toxic shock syndrome with antibiotics

Toxic shock syndrome (TSS) is a serious disorder with a worldwide prevalence of ∼ 3/100,000 persons. TSS is mainly caused by Streptococcus pyogenes or Staphylococcus aureus. Thus, β-lactam and lincosamides, such as clindamycin, are the first-line drugs. Yet, the mortality rate remains unacceptably high; highlighting the role of bacterial toxin-mediated activation of the inflammatory cascade in TSS pathogenesis. Further strategies should be targeted towards interfering with the interaction between bacterial toxins and host T cells. This paper aims to provide an overview of the epidemiology, pathomechanisms, and clinical presentation of TSS, and criteria for selecting drugs among available antibiotics.

Diagnostic Criteria of Urinary Tract Infection in Male Patients With Spinal Cord Injury

Background. The current diagnostic criteria of urinary tract infection (UTI) in male patients with spinal cord injury (SCI) are not clear. Methods. The authors studied 381 episodes of “symptomatic” UTI (209 participants) and 277 episodes of “asymptomatic” UTI (205 participants) in male SCI patients using intermittent catheterization. UTI was defined as a bacterial count ≥102 colony-forming units (cfu)/mL (American Paraplegia Society criterion). Univariate analysis and receiver operating characteristic (ROC) curve analysis were used to determine optimal cfu and white blood cell (WBC) thresholds. Results. The most prevalent clinical signs, alone or in combination, were cloudy and/or malodorous urine (51.4%), onset of urinary incontinence (51.2%), fatigue (41.7%), fever (30.7%), and increased spasticity (30.2%). Urine cfu and WBC levels in patients with only one sign, including fever, were not significantly higher than those in asymptomatic controls. WBC, but not cfu, levels increased significantly with the number of signs (P = .026). Univariate analysis and ROC curve analysis failed to identify cfu, WBC, or a combination of cfu and WBC count thresholds, allowing discrimination between the symptomatic and asymptomatic UTI groups. Conclusions. Clinical signs of UTI correlate poorly with the urine cfu and WBC levels in SCI patients, except for a positive relationship between WBC counts and the number of signs. Fever alone has no higher diagnostic value. There are no satisfactory cfu and WBC thresholds: thresholds more restrictive than the current American Paraplegia Society criteria provide higher specificity values but with equivalent loss of sensitivity.

Intrinsic Epidemicity of Streptococcus pneumoniae Depends on Strain Serotype and Antibiotic Susceptibility Pattern

ABSTRACT Streptococcus pneumoniae is a major cause of invasive diseases worldwide. It spreads through an interindividual transmission, followed by usually harmless colonization of the host. Possible transmission differences reflecting intrinsic strain features (e.g., serotype and antibiotic susceptibility) have been little studied so far. In this study, we used epidemiological data from an interventional trial of S. pneumoniae carriage among kindergartners and developed a mathematical model to estimate the transmission parameters of the different strains isolated during that study. We found small but significant transmissibility differences between the observed serotypes: serotypes 3, 6A, and 19A were found to be the most epidemic, while serotypes 23F, 9V, and 14 were the least epidemic. Further analysis indicated that, within a serotype, susceptible and resistant strains had different abilities to be transmitted. Susceptible-to-resistant transmission rate ratios were computed for five serotypes; susceptible strains were significantly more epidemic than resistant strains for serotypes 6A (mean, 1.02) and 19F (1.05). Serotype 19A resistant strains were not outcompeted by susceptible strains (0.97). Nonsignificant trends were observed for serotypes 6B (1.01) and 15A (0.98). Our results support the existence of heterogeneous abilities of the different serotypes for host-to-host transmission. They also suggest that antibiotic susceptibility within a serotype affects this transmissibility. We conclude that pneumococcal strains should not be considered equally at-risk in terms of transmission. Further quantification of strain-specific epidemic potential is needed, especially in a context of extensive use of conjugate vaccines with the aim of preventing pneumococcal infections.

Expected and unexpected adverse effects H1N1 vaccination for health care workers in a university hospital.

HAL is a multi-disciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers. L’archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d’enseignement et de recherche français ou étrangers, des laboratoires publics ou privés. Expected and unexpected adverse effects H1N1 vaccination for health care workers in a university hospital. Aurelien Dinh, Christine Lawrence, Jérome Salomon, Alexis Descatha