African Tick Bite Fever Research Articles

Unusual Location of an Inoculation Lesion in a Traveler with African Tick‐Bite Fever Returning from South Africa

African tick-bite fever is a common tick-borne rickettsiosis in sub-Saharan Africa. It is an acute febrile illness associated with one (or more) inoculation eschar, an inconstant eruption, and local lymphadenopathies. We describe the first case of mucosal inoculation lesion on the vulva in a female traveler returning from South Africa.

Tache Noire in African Tick Bite Fever

A fever of 39°C, headache, and malaise developed in a traveler from Germany who had returned from a four week vacation to the east coast of South Africa. She had visited friends in a rural area and had been on a safari. During the tour, she had discovered a painless lesion on her abdomen. A similar, but smaller lesion had developed on her arm. On examination, two typical eschars were found ( Figure 1 ). There was no rash or regional lymphadenopathy. The patient did not recall a tick bite and no other travelers in her group were affected. C-reactive protein and lactate dehydrogenase levels were increased (5.82 mg/dL and 348 U/L, respectively). A leukocyte count and results of liver function tests were normal. Treatment with doxycycline, 100 mg twice a day, was initiated for suspected African tick bite fever (ATBF) and the patient was seen again four days later ( Figure 2 ). The result of a rickettsial immunofluorescence assay 1 using cross-reactive Rickettsia conorii antigen was positive for an acute-phase serum sample and a reconvalescent-phase sample eight weeks later (1:40 and 1:160, respectively). A panRickettsia real-time polymerase chain reaction (PCR) 2 of the necrotic center of the lesion ( Figure 3 ) yielded a positive result, confirming the rickettsial etiology of the infection. Fragments of the bacterial citrate synthase gene were amplified by PCR. 3 ( Figure 4 ). Amplicons were subsequently sequenced and identified R . africae as causative agent. African tick bite fever is endemic in large parts of sub-Saharan Africa and is the most common rickettsiosis in travelers. Aggressive cattle ticks ( Amblyomma sp.) act as vectors and reservoirs. 1 Unlike Rocky Mountain spotted fever, ATBF is not a life-threatening disease. However, travelers should receive pre-travel advice on how to avoid the infection, i.e., F igure 2. Aspect of an abdominal lesion of the patient 4 days after the start of doxycycline treatment. The inflammatory zone is less marked. Epidermis shows shedding in concentric rings. This figure appears in color at www.ajtmh.org .

African Tick Bite Fever in a Taiwanese Traveler Returning from South Africa: Molecular and Serologic Studies

We report the first imported case of African tick bite fever (ATBF) in a patient from Taiwan who returned from a 10-day trip to South Africa. Diagnosis was confirmed by polymerase chain reaction (PCR) from eschar biopsies. Portions of rickettsial ompA (491 bp) and ompB (273 bp) genes were amplified and subsequent sequencing of PCR product showed its 100% identity with R. africae. Microimmunofluorescence (MIF) assay of patient's serum on Days 14 and 46 after the onset of illness revealed IgG seroconversion when tested with spotted fever group (SFG) rickettsiae antigens, including R. africae. The patient clinically improved on the third day of 14-day treatment with a combination of ciprofloxacin and minocycline. Based on the patient's travel history and chronology of clinical symptoms, we strongly suspect that the tick-biting event occurred in Kruger National Park.

New Approaches to Detection and Identification of <I>Rickettsia africae</I> and <I>Ehrlichia ruminantium</I> in <I>Amblyomma variegatum</I> (Acari: Ixodidae) Ticks From the Caribbean

Imported from Africa in the 1700s and despite frequent modern eradication efforts, Amblyomma variegatum (F.) spread through the Caribbean by cattle transport, small ruminants, and migrating birds. A. variegatum is a vector for Rickettsia africae, the causative agent of African tick bite fever, and Ehrlichia ruminantium, the causative agent of heartwater. We examined 95 A. variegatum and six Rhipicephalus (Boophilus) microplus (Canestrini) collected from cattle at an abattoir in Antigua. Engorged tick extracts adsorbed on Nobotu filter paper strips and new nested polymerase chain reaction (PCR) assays for E. ruminantium and Dermatophilus congolensis were used to evaluate these ticks for the presence of these pathogenic bacteria. Amblyomma ticks (62.4%) contained R. africae DNA by PCR/restriction fragment length polymorphism analysis and DNA sequencing of the OmpA and 17-kDa antigen genes. Twenty Amblyomma and two Rh. microplus contained E. ruminantium DNA. No E. chaffeensis, Anaplasma phagocytophilum, Coxiella burnetii, or D. congolensis DNA was detected in these ticks. The continued presence of Am. variegatum in the Caribbean poses a significant risk of infection in cattle with E. ruminantium and in humans by R. africae. Eradication efforts are essential to prevent the further spread of Am. variegatum.

Diagnosis of Queensland Tick Typhus and African Tick Bite Fever by PCR of Lesion Swabs

We report 3 cases of Queensland tick typhus (QTT) and 1 case of African tick bite fever in which the causative rickettsiae were detected by PCR of eschar and skin lesions in all cases. An oral mucosal lesion in 1 QTT case was also positive.

Typhus and Other Rickettsioses

Rickettsioses are diseases caused by rickettsiae, obligate intracellular bacteria that are transmitted by arthropods to humans. They cause various types of spotted fever and typhus. A review of the literature is presented along with the authors' own findings. Six indigenous species of rickettsiae have been found in Germany to date, five of which have been described as human pathogens in other countries. Rickettsia slovaca causes tick-borne lymphadenitis (TIBOLA). Rickettsia helvetica is a known pathogen of nonspecific fever; its role in endocarditis is still under investigation. Rickettsia felis causes so-called flea-borne spotted fever. Rickettsia monacensis and Rickettsia massiliae were recently shown to cause the classical form of tick-borne spotted fever. The sixth indigenous species in Germany, Rickettsia sp. RpA4, has not yet been associated with any human disease. The most important rickettsioses imported to Germany by travelers are African tick bite fever and Mediterranean spotted fever. Modern molecular biological techniques have enabled the detection of a number of rickettsial species in Germany. The medical importance of these illnesses in Germany remains to be determined. In travel medicine, imported rickettsioses play a role that should not be underestimated.

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].

Pristinamycin forRickettsia africaeInfection

African tick bite fever is caused by Rickettsia africae. The number of reported cases in international travelers has significantly increased recently. The gold standard treatment is doxycycline. Here, we present a case of R africae infection associated with quick complete resolution following the initiation of pristinamycin therapy.

Relative chemokine and adhesion molecule expression in Mediterranean spotted fever and African tick bite fever

Mediterranean spotted fever (MSF) caused by Rickettsia conorii (R. conorii) is a potential lethal disease while African tick bite fever (ATBF) caused by Rickettsia africae is a self-limiting flu-like illness. We hypothesized that different inflammatory potential in endothelial cells could contribute to the different clinical features in these rickettsioses. We analyzed the effect of heat-inactivated R. africae and R. conorii on the mRNA and protein levels of monocyte chemoattractant protein (MCP)-1, interleukin (IL)-8 and adhesion molecules in endothelial cells. Serum samples from patients with MSF (n=16) and ATBF (n=15) were collected before and after therapy. R. conorii induced a marked increase in MCP-1, IL-8, and adhesion molecules in endothelial cells, involving toll-like receptor 4 activation. In contrast, R. africae induced MCP-1 expression, but only modest or no responses were seen on IL-8 and adhesion molecules. Comparable to the in vitro response, levels of IL-8 and adhesion molecules showed no or only a modest increase in ATBF patients while these inflammatory markers were markedly elevated during MSF. Our findings suggest a superior inflammatory potential of R. conorii as compared to R. africae in endothelial cells, potentially related to the more severe inflammation in MSF comparing ATBF.

African Tick Bite Fever in Elderly Patients: 8 Cases in French Tourists Returning from South Africa

African tick-bite fever, a tickborne disease caused by Rickettsia africae, is endemic in rural areas of sub-Saharan Africa and in the French West Indies. Most cases reported in the literature occurred in middle-aged, otherwise-healthy persons and corresponded to benign diseases. The course of African tick bite fever in elderly people is less well documented. The medical records of 8 elderly patients infected with R. africae during a trip to South Africa in 2005 are presented to summarize the epidemiologic, clinical, microbiological, treatment, and disease course characteristics. Eight patients, aged 63-75 years, developed African tick bite fever symptoms after a trip to South Africa. R. africae was grown from cutaneous eschar biopsy specimens obtained from 4 patients, confirming African tick bite fever. We observed unusual findings in this elderly population. Rash was frequent (present in 87.5% of patients), vesicular (in 100% of patients with rash), and often associated with an enanthema (in 50% of patients with rash). Severe clinical manifestations occurred: lymphangitis and myocarditis in 1 patient and suspected brain involvement in 2 patients. We observed severe and long-lasting general symptoms, including fever (in 75% of patients), chills (87.5%), asthenia (50%), anorexia (50%), and weight loss (12.5%). With doxycycline therapy, the outcome was favorable in all cases, but complete recovery was slow. Ecotourism to sub-Saharan Africa is expanding, and people of advanced age, often with underlying chronic diseases, account for an increasing proportion of travelers. African tick bite fever appears to be more symptomatic in this population. Recommendations advising personal prophylactic measures to prevent tick bites in travelers to regions of endemicity may be particularly important for elderly individuals.

Management of Travelers with Fever and Exanthema, Notably Dengue and Chikungunya Infections

Febrile exanthema frequently presents as an acute condition in travelers. Sixty-two travelers who presented with febrile exanthema were prospectively included over a 20-month period. Diagnostic tests were performed according to clinical presentation and risk exposures. Symptoms occurred after return in 56% of these travelers, and the median interval between return and symptom onset was 2 days. The 3 main travel destinations were the Indian Ocean (35%), Africa (21%), and Asia (18%). The 3 main etiologies were chikungunya (35%), dengue (26%), and African tick bite fever (ATBF) (10%). Travel to the Indian Ocean and South Africa was significantly associated with respectively chikungunya and ATBF. Arthralgias were significantly more frequent in chikungunya than in dengue, whereas leucopenia, neutropenia, and thrombopenia were significantly more frequent in dengue. Travelers presenting with febrile exanthema should therefore be screened for arboviral infections according to the area visited.

Lymphangitis in aPortuguese Patient Infected withRickettsia sibirica

Lymphangitis in a<b />Portuguese Patient Infected with<i>Rickettsia sibirica</i>

Tick bite fever in South Africa

Tick bite fever has been a constant feature of the South African medical landscape. While it was recognised many years ago that there was a wide spectrum of clinical severity of infection, only recently has it been established that there are two aetiological agents, with different epidemiologies and clinical presentations. Rickettsia conorii infections resemble the classical Mediterranean spotted fever (fievre boutonneuse), and patients are sometimes at risk of severe or even fatal complications. On the other hand, African tick bite fever is a separate entity caused by Rickettsia africae and tends to be a milder illness, with less prominent rash and little tendency to progress to complicated disease. Irrespective of the agent, the treatment of choice for tick bite fever in South Africa remains doxycycline or tetracycline, and the role of macrolide and quinolone antibiotics is still unclear, or at least restricted.

African Tick Bite Fever

Physicians may encounter unfamiliar diseases as a result of international travel. Fever with rash is an important sign that usually represents initial manifestation of infectious disorders. A 62-year-old Taiwanese woman presented with multiple eschars, a papulovesicular rash, and fever 5 days after returning from South Africa. A biopsy specimen of an eschar had wedge-shaped tissue necrosis, hemorrhage, necrotizing vasculitis of the small venules and arterioles, and a dense perivascular lymphocytic infiltrate in the dermis. Serologically, there was cross reaction with both Rickettsia conorii and R. rickettsii. DNA sequencing demonstrated R. africae, confirming the diagnosis of African tick bite fever. The patient responded well to minocycline. Recognition of the symptoms and signs, and diagnostic tools for different types of rickettsiosis are essential for correct diagnosis and treatment.

African tick bite fever – Papulovesicular exanthem with fever after staying in South Africa

In the wake of expanding international tourism, rickettsioses are increasingly observed also in central Europe. African tick bite fever is a recently described, acute febrile illness with characteristic skin lesions. It is caused by Rickettsia africae, which is transmitted to humans by ticks of the Amblyomma genus. A 60-year-old woman presented with a papulovesic-ular exanthem, fever, and headache after returning from South Africa. A purple nodule with central necrosis ("tache noire"or "inoculation eschar") was noticed on the lower leg. Antibodies against rickettsia of the spotted fever group were detected serologically. Oral doxycycline led to clearance of the disease after few days of treatment.

Identification of Rickettsiae, Uganda and Djibouti

To the Editor: Tickborne rickettsioses are caused by obligate intracellular gram-negative bacteria that belong to the spotted fever group of the genus Rickettsia. These zoonoses share characteristic clinical features, including fever, headache, rash, and sometimes eschar formation at the site of the bite (1). Although rickettsioses are important emerging vectorborne infections of humans worldwide, little is known about rickettsioses in sub-Saharan Africa (1,2). In 2002, 94 ticks were collected in Djibouti: 5 Amblyomma lepidum, 1 A. variegatum, 5 Hyalomma marginatum rufipes, 40 Rhipicephalus pulchellus, and 10 Rh. evertsi evertsi from cattle that had just arrived from Ethiopia; 30 H. dromedarii from dromedaries; and 3 Rh. sanguineus group ticks from cheetahs. In 2003, 57 ticks were collected from dogs in Kampala, Uganda: 1 A. variegatum, 9 Haemaphysalis punctaleachi, 28 Rh. praetextatus, and 19 Rh. sanguineus. All ticks were partially or fully engorged adults. This convenience sample of ticks was obtained as part of other ongoing studies. Ticks were identified by using taxonomic keys (3) and kept in 70% ethanol before being tested. DNA of each tick was extracted, and rickettsial DNA was detected by PCR that used primers Rp.877p and Rp.1258r, which amplify a 396-bp fragment of the citrate synthase gene (gltA) of rickettsia, as described (4). Rickettsia-positive samples were tested by a second PCR that used Rr.190.70p and Rr.190.701n primers, which amplify a 629–632 bp fragment of ompA gene (4). Controls (2 negative [DNA extracted from noninfected laboratory ticks and distilled water] and 1 positive [R. montanensis DNA]) were included in each test. The sequences of PCR products were obtained and compared with those available in GenBank (4). One specimen of Ha. punctaleachi from Uganda and 1 A. lepidum from Djibouti, as well as positive controls, were positive according to PCR using both primer pairs. No signal was obtained from negative controls. The sequence of a 474-bp fragment of ompA obtained from Ha. punctaleachi showed 99.8% (473/474) similarity with R. conorii (GenBank accession no. {type:entrez-nucleotide,attrs:{text:AY346453,term_id:76152011}}AY346453); those of a 340-bp segment of gltA showed 100% similarity with that of R. conorii ({type:entrez-nucleotide,attrs:{text:AE008677,term_id:25307999}}AE008677). The sequences of a 517-bp segment of ompA and a 341-bp segment of gltA amplified from A. lepidum showed 100% similarity to the corresponding sequences of R. africae ({type:entrez-nucleotide,attrs:{text:U83436,term_id:62861416}}U83436 and {type:entrez-nucleotide,attrs:{text:U59733,term_id:1389980}}U59733, respectively). To our knowledge, this is the first detection of R. conorii, the agent of Mediterranean spotted fever, in Uganda. Although the main vector of this rickettsia is Rh. sanguineus, the few ticks of this species we tested were negative (1). It is also the first detection of R. conorii in Ha. punctaleachi, although it has been detected in the closely related Ha. leachi in Zimbabwe (5). Ha. punctaleachi prefers warm and humid conditions but can exist wherever rodent hosts for its immature stages and canine hosts for its adult stages are present (6). Adults are found throughout the year; peak numbers occur either from winter to early summer or from spring to late summer (7). Although the detection of R. conorii in Ha. punctaleachi does not mean that this tick is an efficient vector (8), clinicians in Uganda should be aware of the presence of Mediterranean spotted fever in their country. This is also, to our knowledge, the first detection of R. africae, the agent of African tick bite fever, in Djibouti. R. africae was also detected in 1 A. lepidum collected in Sudan (4), but it is more frequently detected in A. variegatum and A. hebraeum with high infection rates throughout sub-Saharan Africa (7). A. lepidum, which coexists with A. variegatum in limited locations, is chiefly a cattle parasite. It will also attach to smaller domestic animals and a few wild herbivores, but it attacks humans less frequently than A. variegatum or A. hebraeum. A. lepidum occurs in a variety of climatic regions but most commonly inhabits semiarid regions in eastern Africa. The cattle in our study had been imported from Ethiopia, and the ticks may have infested these animals before their arrival in Djibouti. Indeed, in 1973 Burgdorfer obtained an isolate from A. variegatum in Ethiopia, which was thereafter shown to be indistinguishable from the rickettsia described as R. africae (7,9). Again, clinicians should be aware of the presence of R. africae in Djibouti and that it could affect their patients, both local and international, including French and American soldiers based in this country (10). Because we did not do systematic sampling, our results cannot address the prevalence and distribution of R. conorii and R. africae in Uganda and Djibouti, respectively. However, healthcare workers who treat persons who live in or have traveled to these countries should be alert for spotted fever group rickettsial infections in their patients (1).

Detection of Rickettsia africae in Rhipicephalus (Boophilus) decoloratus Ticks from the Republic of Botswana, South Africa

A total of 53 engorged adult ticks belonging to the species Rhipicephalus (Boophilus) decoloratus (N = 9), Rhipicephalus evertsi evertsi (N = 27), Rhipicephalus appendiculatus (N = 9), Amblyomma hebraeum (N = 5), and Hyalomma marginatum turanicum (N = 3), were removed from oryx in Botswana (South Africa). They were tested for the presence of spotted fever group (SFG) Rickettsia and Anaplasma phagocytophilum using polymerase chain reaction (PCR). Seventy-seven percent of R. decoloratus as well as twenty percent of A. hebraeum were positive for ompA, gltA and 16S rRNA SFG Rickettsia PCR assays. All nucleotide sequences were homologous to Rickettsia africae, the agent of African tick-bite fever (ATBF). None of the tested ticks was positive for 16S rRNA A. phagocytophilum PCR assays. These results suggest for the first time that R. decoloratus ticks may be reservoirs of R. africae, and support the ATBF risk in this area.

African Tickbite Fever in Travelers, Swaziland

To the Editor: African tickbite fever (ATBF), which is caused by Rickettsia africae, is well documented in travelers to southern Africa (1–3) and transmitted by ungulate ticks of the genus Amblyomma. Positive serologic results were reported in 9% of patients (1) and 11% of travelers (4) from southern Africa. We report an outbreak of ATBF with an attack rate of 100% among 12 Dutch travelers to Swaziland.

Fever After a Stay in the Tropics

Differential diagnosis of fever in travelers returning from the tropics is extremely diverse. Apart from the travel destination, other diagnostic predictors of tropical infections are poorly documented in returning travelers. From April 2000 to December 2005, we prospectively enrolled all patients presenting at our referral centers with fever within 1 year after visiting a tropical or subtropical area. For clinical relevance, the diagnostic predictors of the leading tropical conditions were particularly investigated in the febrile episodes occurring during travel or within 1 month after return (defined as early-onset fever). In total, 2071 fever episodes were included, occurring in 1962 patients. Most patients were western travelers (60%) or expatriates (15%). Regions of exposure were mainly sub-Saharan Africa (68%) and southern Asia/Pacific (14%). Early-onset fever accounted for 1619 episodes (78%). Most tropical infections were related to specific travel destinations. Malaria (mainly Plasmodium falciparum) was strongly predicted by the following features: enlarged spleen, thrombocytopenia (platelet count <150 x 10(3)/microL), fever without localizing symptoms, and hyperbilirubinemia (total bilirubin level >or=1.3 mg/dL). When malaria had been ruled out, main predictors were skin rash and skin ulcer for rickettsial infection (mainly African tick bite fever); skin rash, thrombocytopenia, and leukopenia (leukocyte count <4 x 10(3)/microL) for dengue; eosinophil count >or=0.5 x 10(3)/microL for acute schistosomiasis; and enlarged spleen and elevated alanine aminotransferase level (>or=70 IU/L) for enteric fever. The initial clinical and laboratory assessment can help in selecting appropriate investigations and empiric treatments for patients with imported fever.

African tick bite fever

A 13-year-old boy presented with a 2-day history of fever, malaise, headache, and myalgia. He had recently returned from safari in the Zambezi Valley, Zimbabwe, where he sustained bites from both ticks and mosquitoes while hunting wildebeest. On examination, the patient had a temperature of 39°C. Many cutaneous eschars were noted over his back, groin, and arms (fi gure), with tender regional lymphadenopathy. Three sets of blood cultures and thick and thin fi lms were negative. Haematological and biochemical investigations were all normal. A clinical diagnosis of African tick bite fever was made. Treatment with doxycycline was commenced and followed by a rapid recovery. Acute serology for African tick bite fever was negative but anti-rickettsial IgM was positive in convalescence. The child remains well more than 1 year after presentation. African tick bite fever is a rickettsial spotted fever, the causative organism being identifi ed as Rickettsia africae in 1992. The symptoms are non-specifi c and include fever, malaise, myalgia, and neck pain. The characteristic inoculation eschars consist of a central black crust surrounded by a red halo. The eschars are often multiple and associated with regional lymphadenopathy. Rapid response to doxycycline is anecdotally reported. Diagnosis is by serology, with PCR available as a research tool. Although the infection is usually mild, with no fatalities reported, it may be responsible for 26% of fever in travellers returning from sub-Saharan Africa. This high incidence requires that African tick bite fever be included in the diff erential diagnosis of all febrile children returning from the savannah of southern Africa. Lancet Infect Dis 2006; 6: 750