Philippe Parola

Tick-Borne Rickettsioses around the World: Emerging Diseases Challenging Old Concepts

SUMMARY During most of the 20th century, the epidemiology of tick-borne rickettsioses could be summarized as the occurrence of a single pathogenic rickettsia on each continent. An element of this paradigm suggested that the many other characterized and noncharacterized rickettsiae isolated from ticks were not pathogenic to humans. In this context, it was considered that relatively few tick-borne rickettsiae caused human disease. This concept was modified extensively from 1984 through 2005 by the identification of at least 11 additional rickettsial species or subspecies that cause tick-borne rickettsioses around the world. Of these agents, seven were initially isolated from ticks, often years or decades before a definitive association with human disease was established. We present here the tick-borne rickettsioses described through 2005 and focus on the epidemiological circumstances that have played a role in the emergence of the newly recognized diseases.

Ticks and Tickborne Bacterial Diseases in Humans: An Emerging Infectious Threat

Ticks are currently considered to be second only to mosquitoes as vectors of human infectious diseases in the world. Each tick species has preferred environmental conditions and biotopes that determine the geographic distribution of the ticks and, consequently, the risk areas for tickborne diseases. This is particularly the case when ticks are vectors and reservoirs of the pathogens. Since the identification of Borrelia burgdorferi as the agent of Lyme disease in 1982, 15 ixodid-borne bacterial pathogens have been described throughout the world, including 8 rickettsiae, 3 ehrlichiae, and 4 species of the Borrelia burgdorferi complex. This article reviews and illustrate various aspects of the biology of ticks and the tickborne bacterial diseases (rickettsioses, ehrlichioses, Lyme disease, relapsing fever borrelioses, tularemia, Q fever), particularly those regarded as emerging diseases. Methods are described for the detection and isolation of bacteria from ticks and advice is given on how tick bites may be prevented and how clinicians should deal with patients who have been bitten by ticks.

Update on Tick-Borne Rickettsioses around the World: a Geographic Approach

SUMMARY Tick-borne rickettsioses are caused by obligate intracellular bacteria belonging to the spotted fever group of the genus Rickettsia. These zoonoses are among the oldest known vector-borne diseases. However, in the past 25 years, the scope and importance of the recognized tick-associated rickettsial pathogens have increased dramatically, making this complex of diseases an ideal paradigm for the understanding of emerging and reemerging infections. Several species of tick-borne rickettsiae that were considered nonpathogenic for decades are now associated with human infections, and novel Rickettsia species of undetermined pathogenicity continue to be detected in or isolated from ticks around the world. This remarkable expansion of information has been driven largely by the use of molecular techniques that have facilitated the identification of novel and previously recognized rickettsiae in ticks. New approaches, such as swabbing of eschars to obtain material to be tested by PCR, have emerged in recent years and have played a role in describing emerging tick-borne rickettsioses. Here, we present the current knowledge on tick-borne rickettsiae and rickettsioses using a geographic approach toward the epidemiology of these diseases.

Novel Chikungunya Virus Variant in Travelers Returning from Indian Ocean Islands

Aedes albopictus may cause epidemics when infected persons travel to areas where vectors are prevalent.

Chikungunya infection: an emerging rheumatism among travelers returned from Indian Ocean islands. Report of 47 cases.

A large chikungunya virus (CHIKV) outbreak emerged in 2005-2006 in the Indian Ocean islands, including Comoros, Mayotte, Mauritius, the Seychelles, and particularly in Reunion Island where 35% of 770,000 inhabitants were infected in 6 months. More recently, circulation of the virus has been documented in Madagascar and in India where CHIKV is spreading rapidly. CHIKV-infected visitors have returned home to nonendemic regions from these islands. We conducted a 14-month prospective observational study on the clinical aspects of CHIKV infection imported to Marseilles, France, in travelers returning from the Indian Ocean islands. A total of 47 patients have been diagnosed with imported CHIKV infection confirmed by serology, reverse transcription-polymerase chain reaction, and/or viral culture. At the early stage of the disease (within 10 days of the disease onset), fever was present in 45 of 47 patients. A rash was present in the first week in 25 cases. All patients suffered with arthritis. The most frequently affected joints were fingers, wrists, toes, and ankles. Eight patients were hospitalized during the acute stage, including 2 severe life-threatening cases. A total of 38 patients remained symptomatic after the tenth day with chronic peripheral rheumatism, characterized by severe joint pain and multiple tenosynovitis, with a dramatically limited ability to ambulate and carry out activities in daily life. Three patients were hospitalized at this stage for severe persistent handicap. Follow-up demonstrated slow improvement in joint pain and stiffness despite symptomatic treatment, mainly antiinflammatory and analgesic drugs. In the current series we describe 2 stages of the disease, an initial severe febrile and eruptive polyarthritis, followed by disabling peripheral rheumatism that can persist for months. We point out the possibility of transitory peripheral vascular disorders during the second stage and the occasional benefit of short-term corticosteroids. As CHIKV could spread throughout the world, all physicians should be prepared to encounter this arboviral infection.Abbreviations: CHIKV = chikungunya virus, MRI = magnetic resonance imaging, NSAIDs = nonsteroidal antiinflammatory drugs, RT-PCR = reverse transcription-polymerase chain reaction.

Warmer Weather Linked to Tick Attack and Emergence of Severe Rickettsioses

The impact of climate on the vector behaviour of the worldwide dog tick Rhipicephalus sanguineus is a cause of concern. This tick is a vector for life-threatening organisms including Rickettsia rickettsii, the agent of Rocky Mountain spotted fever, R. conorii, the agent of Mediterranean spotted fever, and the ubiquitous emerging pathogen R. massiliae. A focus of spotted fever was investigated in France in May 2007. Blood and tissue samples from two patients were tested. An entomological survey was organised with the study of climatic conditions. An experimental model was designed to test the affinity of Rh. sanguineus for biting humans in variable temperature conditions. Serological and/or molecular tools confirmed that one patient was infected by R. conorii, whereas the other was infected by R. massiliae. Dense populations of Rh. sanguineus were found. They were infected with new genotypes of clonal populations of either R. conorii (24/133; 18%) or R. massiliae (13/133; 10%). April 2007 was the warmest since 1950, with summer-like temperatures. We show herein that the human affinity of Rh. sanguineus was increased in warmer temperatures. In addition to the originality of theses cases (ophthalmic involvements, the second reported case of R. massiliae infection), we provide evidence that this cluster of cases was related to a warming-mediated increase in the aggressiveness of Rh. sanguineus, leading to increased human attacks. From a global perspective, we predict that as a result of globalisation and warming, more pathogens transmitted by the brown dog tick may emerge in the future.

Rickettsial infections and fever, Vientiane, Laos.

Rickettsia spp. are an underrecognized cause of undifferentiated febrile illness.

Rickettsia slovaca and R. raoultii in tick-borne Rickettsioses.

Tick-borne lymphadenopathy (TIBOLA), also called Dermacentor-borne necrosis erythema and lymphadenopathy (DEBONEL), is defined as the association of a tick bite, an inoculation eschar on the scalp, and cervical adenopathies. We identified the etiologic agent for 65% of 86 patients with TIBOLA/DEBONEL as either Rickettsia slovaca (49/86, 57%) or R. raoultii (7/86, 8%).

New Delhi metallo-beta-lactamase (NDM-1): towards a new pandemia?

During the past decade the increase of antibiotic resistance in Enterobacteriaceae has become a major concern worldwide. Although beta-lactams have been widely used as the mainstay of treatment for severe infections due to these bacteria, with carbapenems often representing last-resource drugs, carbapenem resistance due to acquired carbapenemases has emerged and spread worldwide since the early 2000s, being even more worrisome for public health because these bacteria are a common source of hospital-acquired infections. Carbapenemases have been now studied in depth, and widely differ from one another, including enzymes from class B (metallo-beta-lactamases, MBLs), class A and class D (serine carbapenemases) [1]. The most prevalent carbapenemase so far in Enterobacteriaceae is the KPC-type class-A carbapenemase, which has been found in Klebsiella pneumonia, especially in the United States, Asia, the United Kingdom, Israel and southern Europe [2]. Interestingly, acquired carbapenemases have been mainly restricted to geographical areas and to specific bacterial species, and outbreaks as well as spread in other countries have been often associated with imported cases from countries where the bacteria are endemic. Population mobility is known to be a main factor in globalization and spreading of antimicrobial drug-resistant organisms [3]. For example, the emergence of KPC-producing Enterobacteriaceae in the United States in 2001 [2] could be later associated with the emergence of travel-related outbreaks in other countries [1,4]. The New Delhi metallo-beta-lactamase (NDM-1) is a novel type of MBL named after the city of origin, which has been recently criticized, following a common practice with transferable MBLs since VIM-1 was named after Verona, Italy [5]. NDM-1 was first reported in 2009 in a Swedish patient of Indian origin, who travelled to New Delhi and acquired a urinary tract infection due to a carbapenem-resistant K. pneumoniae strain resistant to all antibiotics tested except colistin [6]. Faecal samples collected from this patient during his stay at the nursing home yielded an NDM-1 positive E. coli as well [6]. The NDM-1 encoding gene is located on different large plasmids (a 180-kb plasmid for K. pneumoniae and a 140-kb plasmid for E. coli) that are easily transferable to susceptible E. coli J53 at a high frequency [6]. These plasmids also harbour genes conferring resistance to almost all antibiotics, thus making their rapid dissemination in clinically relevant bacteria a serious threat for therapy. Following this first case, sporadic cases of infection due to NDM-1 positive bacteria have been detected, including an E. coli from blood cultures of a patient of Indian origin in the United Kingdom [7], three cases of Enterobacteriaceae isolates (one E. coli, one K. pneumoniae and one E. cloacae) in the United States from patients who received care in India [8], and three cases of Acinetobacter baumannii from New Delhi [9]. In the August issue of the journal The Lancet: Infectious Diseases, a multinational team reported the emergence and spread of 180 cases of patients infected by bacteria carrying the NDM-1, including 37 cases in the United Kingdom and 143 cases in various sites in Pakistan and India, thus suggesting a widespread dissemination [10]. Among these bacteria many different Enterobacteriaceae species were identified, including K. pneumonia, E. coli, E. cloacae, Proteus spp., Citrobacter freundii, K. oxytoca, M. morganii and Providencia spp. Most isolates remained susceptible to colistin and tigecycline, except those Enterobacteriaceae endowed with a natural resistance to these compounds such as M. morganii, Proteus spp. and Providencia spp. Most plasmids detected in these bacteria were easily transferable and capable of wide rearrangement, suggesting a widespread transmission and plasticity among bacterial populations. Interestingly, among the 25 patients detected in the UK, 17 patients had travelled to India or Pakistan within 1 year and 14 had been hospitalized in these countries showing a worldwide dissemination of a new ‘superbug’ from a local source in Asia [10]. Indeed, since August 2010, spreading and dissemination has occurred, with several cases being reported by national and international media from other countries in all continents, including the United States and Canada, Europe (Sweden, the United Kingdom, Austria, Belgium, France, Netherlands and Germany), Japan, Africa,

Emerging rickettsioses of the Thai-Myanmar border.

To investigate the presence of rickettsioses in rural residents of the central Thai-Myanmar border, we tested the blood of 46 patients with fever. Four patients had murine typhus, three patients had scrub typhus, and eight patients had spotted fever group rickettsioses, including the first case of Rickettsia felis infection reported in Asia.