Cristina Socolovschi

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.

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.

Coxiella burnetii in Humans and Ticks in Rural Senegal

Background Q fever is a worldwide zoonotic disease caused by Coxiella burnetii. Epidemiologically, animals are considered reservoirs and humans incidental hosts. Methodology/Principal Findings We investigated Q fever in rural Senegal. Human samples (e.g., sera, saliva, breast milk, feces) were screened in the generally healthy population of two villages of the Sine-Saloum region. Ticks were collected in four regions. Seroprevalence was studied by immunofluorescence, and all other samples were tested by two qPCR systems for detection of C. burnetii. Positive samples were genotyped (multispacer typing) by amplification and sequencing of three spacers. Strains were isolated by cell culture. We found that the seroprevalence may be as high as 24.5% (59 of 238 studied) in Dielmo village. We identified spontaneous excretion of C. burnetii by humans through faeces and milk. Hard and soft ticks (8 species) were infected in 0–37.6%. We identified three genotypes of C. burnetii. The previously identified genotype 6 was the most common in ticks in all studied regions and the only one found in human samples. Three strains of genotype 6 of C. burnetii were also recovered from soft tick Ornithodoros sonrai. Two other genotypes found in ticks, 35 and 36, were identified for the first time. Conclusions/Significance Q fever should be considered a significant public health threat in Senegal. Humans, similar to other mammals, may continuously excrete C. burnetii.

Rickettsia felis-associated uneruptive fever, Senegal.

During November 2008–July 2009, we investigated the origin of unknown fever in Senegalese patients with a negative malaria test result, focusing on potential rickettsial infection. Using molecular tools, we found evidence for Rickettsia felis–associated illness in the initial days of infection in febrile Senegalese patients without malaria.

Analysis of the Rickettsia africae genome reveals that virulence acquisition in Rickettsia species may be explained by genome reduction

BackgroundThe Rickettsia genus includes 25 validated species, 17 of which are proven human pathogens. Among these, the pathogenicity varies greatly, from the highly virulent R. prowazekii, which causes epidemic typhus and kills its arthropod host, to the mild pathogen R. africae, the agent of African tick-bite fever, which does not affect the fitness of its tick vector.ResultsWe evaluated the clonality of R. africae in 70 patients and 155 ticks, and determined its genome sequence, which comprises a circular chromosome of 1,278,540 bp including a tra operon and an unstable 12,377-bp plasmid. To study the genetic characteristics associated with virulence, we compared this species to R. prowazekii, R. rickettsii and R. conorii. R. africae and R. prowazekii have, respectively, the less and most decayed genomes. Eighteen genes are present only in R. africae including one with a putative protease domain upregulated at 37°C.ConclusionBased on these data, we speculate that a loss of regulatory genes causes an increase of virulence of rickettsial species in ticks and mammals. We also speculate that in Rickettsia species virulence is mostly associated with gene loss.The genome sequence was deposited in GenBank under accession number [GenBank: NZ_AAUY01000001].

The relationship between spotted fever group Rickettsiae and Ixodid ticks

Spotted fever group Rickettsiae are predominantly transmitted by ticks. Rickettsiae have developed many strategies to adapt to different environmental conditions, including those within their arthropod vectors and vertebrate hosts. The tick-Rickettsiae relationship has been a point of interest for many researchers, with most studies concentrating on the role of ticks as vectors. Unfortunately, less attention has been directed towards the relationship of Rickettsiae with tick cells, tissues, and organs. This review summarizes our current understanding of the mechanisms involved in the relationship between ticks and Rickettsiae and provides an update on the recent methodological improvements that have allowed for comprehensive studies at the molecular level.

Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry for Rapid Identification of Tick Vectors

ABSTRACT A method for rapid species identification of ticks may help clinicians predict the disease outcomes of patients with tick bites and may inform the decision as to whether to administer postexposure prophylactic antibiotic treatment. We aimed to establish a matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) spectrum database based on the analysis of the legs of six tick vectors: Amblyomma variegatum, Rhipicephalus sanguineus, Hyalomma marginatum rufipes, Ixodes ricinus, Dermacentor marginatus, and Dermacentor reticulatus. A blind test was performed on a trial set of ticks to identify specimens of each species. Subsequently, we used MALDI-TOF MS to identify ticks obtained from the wild or removed from patients. The latter tick samples were also identified by 12S ribosomal DNA (rDNA) sequencing and were tested for bacterial infections. Ticks obtained from the wild or removed from patients (R. sanguineus, I. ricinus, and D. marginatus) were accurately identified using MALDI-TOF MS, with the exception of those ticks for which no spectra were available in the database. Furthermore, one damaged specimen was correctly identified as I. ricinus, a vector of Lyme disease, using MALDI-TOF MS only. Six of the 14 ticks removed from patients were found to be infected by pathogens that included Rickettsia, Anaplasma, and Borrelia spp. MALDI-TOF MS appears to be an effective tool for the rapid identification of tick vectors that requires no previous expertise in tick identification. The benefits for clinicians include the more targeted surveillance of patients for symptoms of potentially transmitted diseases and the ability to make more informed decisions as to whether to administer postexposure prophylactic treatment.

Tick-Borne Relapsing Fever Borreliosis, Rural Senegal

Detecting spirochetes remains challenging in cases of African tick-borne relapsing fever. Using real-time PCR specific for the 16S rRNA Borrelia gene, we found 27 (13%) of 206 samples from febrile patients in rural Senegal to be positive, whereas thick blood smear examinations conducted at dispensaries identified only 4 (2%) as positive.

Tropheryma whipplei Bacteremia during Fever in Rural West Africa

BACKGROUND Tropheryma whipplei not only causes Whipple disease but also is an emerging pathogen associated with gastroenteritis and pneumonia that is commonly detected in stool samples in rural West Africa. We investigated the role of T. whipplei in febrile patients from rural Senegal who had a negative test result for malaria. METHODS From November 2008 through July 2009, we conducted a prospective study in 2 Senegalese villages; 204 blood specimens from febrile patients were collected. DNA extraction of whole-blood samples collected by finger pricks with a lancet stick was performed in Senegal; elution and quantitative polymerase chain reaction assays for T. whipplei were performed in France. In April 2009, we conducted a screening to look for the presence of T. whipplei in the saliva and stools of the overall population. Blood from French patients with chronic T. whipplei in stool samples was also analyzed. RESULTS The presence of T. whipplei DNA was detected in blood from 13 (6.4%) of 204 tested patients, mostly in children and in December and January. None of the French carriers tested positive. The patients with T. whipplei bacteremia presented with fever (13 patients), cough (10), thirst (8), fatigue (7), rhinorrhea (6), and sleep disorders (5). Cough and sleep disorders were significantly more frequent in febrile carriers than in the 191 febrile episodes without T. whipplei bacteremia (P = .002 and .005, respectively). No correlation was observed between the presence of T. whipplei in the stools and saliva and bacteremia. CONCLUSIONS Our findings suggest that T. whipplei is an agent of unexplained cold season fever with cough in rural West Africa.

Spotted Fever Group Rickettsiae in Ticks, Morocco

Identified rickettsiae were 4 pathogens, 2 suspected pathogens, and 1 incompletely described species.