Benoit Faucher

Understanding the Cholera Epidemic, Haiti

After onset of a cholera epidemic in Haiti in mid-October 2010, a team of researchers from France and Haiti implemented field investigations and built a database of daily cases to facilitate identification of communes most affected. Several models were used to identify spatiotemporal clusters, assess relative risk associated with the epidemic’s spread, and investigate causes of its rapid expansion in Artibonite Department. Spatiotemporal analyses highlighted 5 significant clusters (p<0.001): 1 near Mirebalais (October 16–19) next to a United Nations camp with deficient sanitation, 1 along the Artibonite River (October 20–28), and 3 caused by the centrifugal epidemic spread during November. The regression model indicated that cholera more severely affected communes in the coastal plain (risk ratio 4.91) along the Artibonite River downstream of Mirebalais (risk ratio 4.60). Our findings strongly suggest that contamination of the Artibonite and 1 of its tributaries downstream from a military camp triggered the epidemic.

Spatio-temporal dynamics of cholera during the first year of the epidemic in Haiti.

Background In October 2010, cholera importation in Haiti triggered an epidemic that rapidly proved to be the worlds largest epidemic of the seventh cholera pandemic. To establish effective control and elimination policies, strategies rely on the analysis of cholera dynamics. In this report, we describe the spatio-temporal dynamics of cholera and the associated environmental factors. Methodology/Principal findings Cholera-associated morbidity and mortality data were prospectively collected at the commune level according to the World Health Organization standard definition. Attack and mortality rates were estimated and mapped to assess epidemic clusters and trends. The relationships between environmental factors were assessed at the commune level using multivariate analysis. The global attack and mortality rates were 488.9 cases/10,000 inhabitants and 6.24 deaths/10,000 inhabitants, respectively. Attack rates displayed a significantly high level of spatial heterogeneity (varying from 64.7 to 3070.9 per 10,000 inhabitants), thereby suggesting disparate outbreak processes. The epidemic course exhibited two principal outbreaks. The first outbreak (October 16, 2010–January 30, 2011) displayed a centrifugal spread of a damping wave that suddenly emerged from Mirebalais. The second outbreak began at the end of May 2011, concomitant with the onset of the rainy season, and displayed a highly fragmented epidemic pattern. Environmental factors (river and rice fields: p<0.003) played a role in disease dynamics exclusively during the early phases of the epidemic. Conclusion Our findings demonstrate that the epidemic is still evolving, with a changing transmission pattern as time passes. Such an evolution could have hardly been anticipated, especially in a country struck by cholera for the first time. These results argue for the need for control measures involving intense efforts in rapid and exhaustive case tracking.

Environmental Determinants of Cholera Outbreaks in Inland Africa: A Systematic Review of Main Transmission Foci and Propagation Routes

Cholera is generally regarded as the prototypical waterborne and environmental disease. In Africa, available studies are scarce, and the relevance of this disease paradigm is questionable. Cholera outbreaks have been repeatedly reported far from the coasts: from 2009 through 2011, three-quarters of all cholera cases in Africa occurred in inland regions. Such outbreaks are either influenced by rainfall and subsequent floods or by drought- and water-induced stress. Their concurrence with global climatic events has also been observed. In lakes and rivers, aquatic reservoirs of Vibrio cholerae have been evocated. However, the role of these reservoirs in cholera epidemiology has not been established. Starting from inland cholera-endemic areas, epidemics burst and spread to various environments, including crowded slums and refugee camps. Human displacements constitute a major determinant of this spread. Further studies are urgently needed to better understand these complex dynamics, improve water and sanitation efforts, and eliminate cholera from Africa.

Human leptospirosis: An emerging risk in Europe?

Leptospirosis has been reemerging in both developed and developing countries including Europe, where, this phenomenon has notably been associated with urban transmission. However, the comprehensive data that are needed to fully understand the ongoing epidemiological trends are lacking. In this article, we report surveillance data from throughout Europe, especially in France, to have an overview of this neglected disease in temperate countries. Our results underline the important role of wild rodents as reservoir of leptospirosis, and highlight the potential danger of a reemergence of this under-reported infectious disease in European cities, associated with the important expansion of the rat population in urban areas.

Mucosal Leishmania infantum leishmaniasis: Specific pattern in a multicentre survey and historical cases

OBJECTIVE Leishmania infantum mucosally restricted leishmaniasis was rarely reported, so that diagnostic and treatment strategies remain debated. A long-term multicentric survey appeared thereby necessary. METHODS Cases were prospectively collected over 12 years in 3 academic hospitals of Southern France. Predisposing factors, clinical findings, diagnostic procedures, treatment and outcome were compared to medical literature. RESULTS Ten new cases and 40 historical reports were collected. Respectively 10/10 and 35/40 patients were adult males. Immunodeficiency was frequent (5/10 and 18/40). No previous cutaneous lesion was reported. Leishmaniasis affected mostly larynx (5/10 and 19/40), but also mouth (2/10 and 19/40) and nose (3/10 and 5/40). Lesions were highly polymorph. Mucosa histological examination provided respectively 1/10 and 2/40 false negative results, contrary to serum immunoblotting and PCR on mucosal biopsy. Although local response was always satisfactory even using topical treatment, subsequent visceral spreading was observed in 2/10 and 1/40 cases. CONCLUSION L. infantum mucosally restricted leishmaniasis exhibits a specific pattern, marked by tropism for adult males, high clinical and histological polymorphism. Immunoblot screening and PCR confirmation of suspected lesions are necessary because of direct examination occasional false negative results. The risk of visceral spreading sustains systemic therapy. SUMMARY Leishmania infantum mucosal leishmaniasis mostly affects adult males, half of them immunodeficient. Clinical and histological polymorphism makes the diagnosis difficult, stressing the need for immunoblot screening and mucosa PCR analysis of suspected cases. Possible visceralization sustains systemic therapy.

Comparison of mother and child antibodies that target high-molecular-mass Toxoplasma gondii antigens by immunoblotting improves neonatal diagnosis of congenital toxoplasmosis.

ABSTRACT This retrospective study proposes a new reading of immunoblotting (IB) in the diagnosis of congenital toxoplasmosis. Our findings demonstrate that a three-IgM-band association at 75, 90, and 100 kDa called the IgM triplet increases the sensitivity to 95.8% when combined with prenatal and serological neonatal tests.

Heterogeneity of environments associated with transmission of visceral leishmaniasis in South-Eastern France and implication for control strategies.

Background Visceral leishmaniasis due to Leishmania infantum is currently spreading into new foci across Europe. Leishmania infantum transmission in the Old World was reported to be strongly associated with a few specific environments. Environmental changes due to global warming or human activity were therefore incriminated in the spread of the disease. However, comprehensive studies were lacking to reliably identify all the environments at risk and thereby optimize monitoring and control strategy. Methodology/Findings We exhaustively collected 328 cases of autochthonous visceral leishmaniasis from 1993 to 2009 in South-Eastern France. Leishmaniasis incidence decreased from 31 yearly cases between 1993 and 1997 to 12 yearly cases between 2005 and 2009 mostly because Leishmania/HIV coinfection were less frequent. No spread of human visceral leishmaniasis was observed in the studied region. Two major foci were identified, associated with opposite environments: whereas one involved semi-rural hillside environments partly made of mixed forests, the other involved urban and peri-urban areas in and around the region main town, Marseille. The two neighboring foci were related to differing environments despite similar vectors (P. perniciosus), canine reservoir, parasite (L. infantum zymodeme MON-1), and human host. Conclusions/Significance This unprecedented collection of cases highlighted the occurrence of protracted urban transmission of L. infantum in France, a worrisome finding as the disease is currently spreading in other areas around the Mediterranean. These results complete previous studies about more widespread canine leishmaniasis or human asymptomatic carriage. This first application of systematic geostatistical methods to European human visceral leishmaniasis demonstrated an unsuspected heterogeneity of environments associated with the transmission of the disease. These findings modify the current view of leishmaniasis epidemiology. They notably stress the need for locally defined control strategies and extensive monitoring including in urban environments.

Babesia microti:an unusual travel-related disease

BackgroundHuman babesiosis is a rare tick-borne infectious disease. The clinical presentation ranges from an asymptomatic form to a life threatening infection with severe hemolysis. Human babesiosis due to Babesia microti is the most common and is endemic in North America.Case presentationWe report a European patient with severe pancytopenia and reactive hemophagocytosis related to a Babesia microti infection. Babesia infection was acquired during a travel in the USA.ConclusionBabesiosis should be considered in patients who traveled in endemic areas, especially North America for the most common agent Babesia microti.

Low prevalence of anti-RNA polymerase III antibodies in a French scleroderma population: Anti-RNA polymerase III scleroderma

BACKGROUND Anti-RNA polymerase III antibodies (anti-RNAP III) have been reported as potential immune markers of Systemic Sclerosis (SSc). Until now, their clinical use was disregarded because of technical difficulties to perform immunoprecipitation. Recently, ELISA kits became commercially available allowing an easy detection of anti-RNAP III. We intended to clarify the relevance of these antibodies in the diagnosis of SSc by ELISA detection. METHODS The prevalence of anti-RNAP III was analyzed using two ELISA kits in 50 consecutive SSc patients from Marseilles in South of France. Controls included 66 patients with other systemic autoimmune diseases, 34 viral diseases and 50 healthy subjects. Positive results with at least one ELISA kit were controlled by immunoprecipitation which is the reference assay. RESULTS In this study, positivity for anti-centromere and/or anti-topoisomerase I antibodies was observed in 84% of SSc patients. The prevalence of anti-RNAP III in SSc patients was 0% to 6% (3/50) depending on the ELISA kit and only 2% by immunoprecipitation. Concerning controls, two rheumatoid arthritis patients were positive using ELISA (6%), including one with immunoprecipitation confirmation. No anti-RNAP III was detected in systemic lupus erythematosus patients. Three blood donors and one viral disease control were positive using ELISA, but all were negative by immunoprecipitation. CONCLUSIONS Anti-RNAP III was rarely detected in a French population of SSc patients. Their prevalence was even lower than the one observed in rheumatoid arthritis controls. Therefore local immunologic profiles should be established before deciding a change in clinical practice for SSc immune screening.

Failure of conventional treatment with pyrimethamine and sulfadiazine for secondary prophylaxis of cerebral toxoplasmosis in a patient with AIDS

patient did not receive any medication known to alter the pharmacokinetics of levofloxacin. During levofloxacin treatment, renal function improved (creatinine clearance ¼102.3 mL/min) and glucose levels were unchanged. No electrocardiographic abnormalities or any adverse effect related to levofloxacin administration were found. The patient received this dose of intravenous levofloxacin for a total of 6 days, followed by oral levofloxacin at 500 mg/12 h for an additional 4 days. Clinical cure of the respiratory infection was rapidly achieved and the patient was discharged. Written informed consent was obtained from the patient to use this treatment regimen and to obtain blood samples. Very few studies have examined fluoroquinolone pharmacoki-netics in obese patients, 2,3 and, to our knowledge, this is the first pharmacokinetic evaluation of levofloxacin in a patient with severe morbid obesity. Levofloxacin was administered at an actual body weight-adjusted dose of 4 mg/kg/12 h based on a ciprofloxacin dosage recommendation for obese patients. 2 With this regimen, the values of C max and CL were similar to those obtained in non-obese healthy volunteers receiving a dose of 750 mg/24 h, 5 the dose recommended for the treatment of community-acquired pneumonia in adults, 4 but the AUC 0 – 24 was double (143.27 mg h/L, twice the value of the AUC 0 – t because levofloxacin was administered twice daily). It has also been previously recommended that the dose of quinolones should be based on a weight correction factor of 45% of excess body weight. 3 This dose was administered to a morbidly obese patient who reached a therapeutic peak plasma concentration , but no other pharmacokinetic parameters were reported. 6 It has been suggested that this lower adjusted dosing could result in low interstitial levofloxacin levels due to impaired levofloxacin penetration in the tissues of obese patients. 2 In our patient, levofloxacin had larger absolute V ss and t 1/2 compared with those described in non-obese patients, which may be explained by a significant distribution of levoflox-acin into excess weight. 1 Regarding pharmacodynamic parameters, an AUC 0 – 24 /MIC ratio of 143.27 was achieved, a value that exceeds the optimal ratio for favourable outcomes in patients with S. pneumoniae infections. 7 In conclusion, an intravenous levofloxacin dose of 750 mg/ 12 h (4 mg/kg/12 h) in our patient with morbid obesity achieved double the adult exposure following a standard dose of 750 mg per day to non-obese healthy volunteers. Consequently, …