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The effects of tick-borne fever on some functions of polymorphonuclear cells of sheep.

Peripheral leucocytes obtained from sheep experimentally infected with tick-borne fever had a significantly reduced capacity to phagocytose and kill Staphylococcus aureus in vitro. Infected neutrophils were also less able to attach to glass surfaces than normal neutrophils. The period of reduced phagocytic activity coincided with the period of parasitaemia and severe neutropenia.

Animals↗

South African tick-bite fever (1931-1981).

An historical survey is given of the personalities and events connected with the discovery and investigation of tick-bite fever in South Africa over the past half-century.

Animals↗

[Three Swedish cases of African tick-bite fever. Can our native Rickettsia species cause disease in humans?].

The article consists in a report of three cases of African tick-bite fever in Swedish tourists returning from brief visits to South Africa. The clinical course included eschar, regional lymphadenopathy, fever and, in two cases, maculopapular rash. Two cases were characterised by significant increases in anti-Rickettsia conorii IgG and IgM antibody titres. However, the aetiological agent was assumed to be Rickettsia africae, based on reports by others and the widespread serological cross-reactivity among spotted fever Rickettsia spp. The third case was diagnosed on clinical grounds. During the past ten years, 50 per cent (41/80) of cases diagnosed serologically as rickettsial (R. conorii antigen) spotted fever at the Swedish Institute for Infectious Disease Control were associated with travel to South Africa. Parallels are drawn to the recent finding of R. helvetica in Swedish ticks (Ixodes ricinus), and the possibility of its pathogenicity to humans is discussed, though no such clinical cases have been reported to date.

Adult↗

African tick-bite fever imported into Norway: presentation of 8 cases.

We report on 8 Norwegian travellers to Southern Africa with African tick-bite fever (ATBF), a recently described spotted fever group rickettsiosis. All patients had acute flu-like symptoms and developed I or multiple inoculation eschars. The patients were treated with either doxycycline or ciprofloxacin, and all recovered. The diagnosis of ATBF was confirmed by the detection of specific IgM antibodies to Rickettsia africae by microimmunofluoroscence in convalescent-phase serum samples.

Antibodies, Bacterial↗

Cardiac involvement in a patient with clinical and serological evidence of African tick-bite fever.

BACKGROUND: Myocarditis and pericarditis are rare complications of rickettsiosis, usually associated with Rickettsia rickettsii and R. conorii. African tick-bite fever (ATBF) is generally considered as a benign disease and no cases of myocardial involvement due to Rickettsia africae, the agent of ATBF, have yet been described. CASE PRESENTATION: The patient, that travelled in an endemic area, presented typical inoculation eschars, and a seroconversion against R. africae, was admitted for chest pains and increased cardiac enzymes in the context of an acute myocarditis. CONCLUSION: Our findings suggest that ATBF, that usually presents a benign course, may be complicated by an acute myocarditis.

Adult↗

Effect of tick-borne fever (Ehrlichia phagocytophila) and trypanosomiasis (Trypanosoma brucei 1066) on the pharmacokinetics of sulfadimidine and its metabolites in goats.

The effect of tick-borne fever (TBF) and trypanosomiasis (TBR) on the plasma disposition of sulfadimidine (SDD) in goats was studied after iv administration of 20 and 200 mg/kg of body weight. In each group of six goats, the plasma disappearance curves showed four animals with rapid and two with slow SDD elimination. It is likely that this difference is determined by oxidative rather than acetylation phenotype. In all goats administered 20 mg/kg, half-life increased with TBF but not with TBR. Vd(beta) decreased with both infections. With 200 mg/kg, Vd did not change, whereas AUC and MRT increased with both infections. Metabolites were examined in TBF experiments: N4-acetyl-SDD (N4Ac), 6-hydroxymethyl-SDD (CH2OH) and its glucuronide, 5-hydroxy-SDD (SOH) and its glucuronide, and 6-carboxy-SDD (COOH) and its glucuronide (COOH-glu). At low dose (20 mg/kg), TBF caused the proportion of dose recovered from urine as unchanged SDD to be halved, whereas N4Ac increased correspondingly (2x). After the high dose (200 mg/kg), elimination was saturated and changes in proportional recovery of SDD in urine were less. However, the N4Ac proportion was still doubled, in contrast to the other metabolites, suggesting that saturation was caused by oxidations rather than by acetylation. Formation of CH2OH was the same in health and disease after the low dose, but glucuronidation dropped from 20% to 4% (rapid) or 7% (slow) of total CH2OH.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Sequential changes in hematologic and biochemical parameters in African tick bite fever.

OBJECTIVE: To evaluate the sequential changes and to estimate the frequencies of abnormalities in some commonly measured biological variables in patients with African tick bite fever (ATBF), an emerging spotted fever group (SFG) rickettsiosis in international travelers to rural sub-Saharan Africa. METHODS: A study was done of hemoglobin, total leukocyte count, absolute lymphocyte count, blood platelet count and serum levels of C-reactive protein (S-CRP), alanine aminotransferase (S-ALAT), aspartate aminotransferase, lactic dehydrogenase, gamma-glutamyl transferase, alkaline phosphatase, bilirubin, sodium and creatinine during the first two weeks of illness and prior to the institution of antirickettsial therapy in 108 patients with travel-associated ATBF. RESULTS: There were significant falls in mean total leukocyte count, mean absolute lymphocyte count, and mean platelet count, and significant increases in mean S-CRP and S-ALAT. During the first ten days of illness, elevated S-CRP, lymphopenia and elevated S-ALAT were detected in 91.7%, 73.3% and 40.7% of patients, respectively. Most abnormalities were mild. For 55 patients who underwent both S-CRP and absolute lymphocyte count determination, at least one parameter was abnormal in 52 (94.5%) patients. CONCLUSIONS: The sequential changes in many biological parameters during the acute phase of ATBF mimic those reported in other SFG rickettsioses. Mild abnormalities are frequent, with increased S-CRP and lymphopenia being the two most consistent findings.

Adolescent↗

Postexposure treatment with doxycycline for the prevention of tick-borne relapsing fever.

BACKGROUND: Tick-borne relapsing fever (TBRF) is an acute febrile illness. In Israel, TBRF is caused by Borrelia persica and is transmitted by Ornithodoros tholozani ticks. We examined the safety and efficacy of postexposure treatment to prevent TBRF. METHODS: In a double-blind, placebo-controlled trial, 93 healthy subjects with suspected tick exposure (52 with signs of tick bites and 41 close contacts--those without signs but with a similar risk of contact with ticks) were randomly assigned to receive either doxycycline (Dexxon, in a dose of 200 mg the first day and then 100 mg per day for four days) or placebo after presumed exposure to TBRF. Cases of TBRF were defined by fever and a positive blood smear. Serologic analysis for cross-reactivity to Borrelia burgdorferi and polymerase chain reaction (PCR) for the borrelia glpQ gene were also performed. RESULTS: After randomization, 47 subjects (26 with signs of tick bites and 21 close contacts) received doxycycline. Forty-six other subjects (26 with signs of tick bites and 20 close contacts) received placebo. All 10 cases of TBRF identified by a positive blood smear were in the placebo group of subjects with signs of a tick bite (P<0.001). These findings suggested a 100 percent efficacy of preemptive treatment (95 percent confidence interval, 46 to 100 percent). PCR for the borrelia glpQ gene was negative at baseline for all subjects and subsequently positive in all subjects with fever and a positive blood smear. Seroconversion was detected in eight of nine cases of TBRF. PCR and serum samples were negative for all of the other subjects tested. No major treatment-associated adverse effects were identified. CONCLUSIONS: Treatment with doxycycline is safe and efficacious in preventing TBRF after suspected exposure to ticks in a high-risk environment. (ClinicalTrials.gov number, NCT00237016 [ClinicalTrials.gov].).

Adult↗

Human granulocytic ehrlichiosis as a common cause of tick-associated fever in Southeast Sweden: report from a prospective clinical study.

Between May and December 1998, tick-associated febrile illness was prospectively studied in Southeast Sweden in order to assess the occurrence of human granulocytic ehrlichiosis (HGE). Inclusion criteria were fever (> or = 38.0 degrees C), with or without headache, myalgia or arthralgia in patients with an observed tick bite or tick exposure within 1 month prior to onset of symptoms. Patients with clinical signs of Lyme borreliosis were included. Of the 27 patients included, we identified 4 cases of HGE. Three of the patients had coinfection with Lyme borreliosis, which presented as erythema migrans. All 27 patients presented with a 2-5 d history of fever. None of the clinical signs or laboratory parameters monitored was helpful in predicting ehrlichiosis in this group with tick-associated fever conditions. Within the HGE-negative group (n = 23), 12 patients had clinical or laboratory signs of Lyme borreliosis. For 11 patients, the aetiology of the fever remained unclear. Our results suggest that HGE is common in tick-infested areas of Southeast Sweden, and may occur as a coinfection of Lyme borreliosis. Granulocytic ehrlichiosis should be suspected in patients who present with tick-associated fever, with or without erythema migrans. Ehrlichia serology and PCR should be employed to confirm the diagnosis.

Adolescent↗

Serological, hematologic, and PCR studies of cattle in an area of Switzerland in which tick-borne fever (caused by Ehrlichia phagocytophila) is endemic.

The purpose of this study was to examine the seasonal variations in seroprevalence to Ehrlichia phagocytophila in cattle pastured during the summer months in an area where tick-borne fever is endemic. The study was performed during a 1-year period from April 1996 to March 1997 and involved 34 cows, 22 pregnant heifers, and 14 calves. Blood samples, collected from all 70 cattle once a month, were used to determine serum immunoglobulin G titers by indirect immunofluorescence. In addition, blood smears were examined for Ehrlichia organisms, and PCR amplification was performed for the molecular detection of E. phagocytophila. Prior to the pasture period, the seroprevalence was 16%. Two weeks after the start of pasturing, it was 43%, after which it progressively increased and reached a maximum of 63% in September. The seroprevalence progressively decreased after the end of pasturing to a low of 23%. The variation in antibody titers was similar to that of seroprevalence. E. phagocytophila organisms were detected in blood smears of 7 animals and by nested PCR in 12. Only four cows, which were on the pastures of endemicity for the first time, had clinical signs of ehrlichiosis. This study demonstrated marked seasonal variations in seroprevalence and in serum titers of antibody to E. phagocytophila in cattle. The incidence of clinical signs of ehrlichiosis was increased in cattle grazing on the pastures of endemicity for the first time.

Animals↗

Some pharmacokinetic data of aditoprim and trimethoprim in healthy and tick-borne fever infected dwarf goats.

Aditoprim (AP) is a new dihydrofolate reductase inhibitor, which is structurally related to trimethoprim (TMP). The pharmacokinetics of AP (10 mg/kg) and TMP (20 mg/kg) were assessed in healthy dwarf goats. Therapeutic efficacy against rickettsial infections was tested in tick-borne fever (TBF) infected goats. The animals were given TMP (n = 5) or AP (n = 5) by i.v. injection, and subsequently the drugs were administered orally (same groups, similar doses). Finally, both groups were infected with TBF and the i.v. experiment was repeated. Plasma concentration-time curves for both drugs followed first-order two-compartment decay. For TMP, mean t1/2 beta +/- SEM (h) was 0.84 +/- 0.06 (i.v. control) and 0.90 +/- 0.06 (i.v. infected), respectively, whereas for AP values of 8.00 +/- 0.31 (i.v. control) and 10.28 +/- 0.67 (i.v. infected) were obtained (P less than 0.05). Mean Vd beta +/- SEM values (l/kg) were 3.84 +/- 0.27 (i.v. control) and 4.07 +/- 0.85 (i.v. infected) for TMP (NS) and 7.02 +/- 0.63 vs 9.29 +/- 0.21 (P less than 0.05) for AP. After i.v. injection, rumen fluid concentrations of AP were significantly (P less than 0.05) higher and more persistent than those of TMP. For AP, the plasma and rumen fluid concentrations at 3 h were 1.20 +/- 0.06 micrograms/ml and 0.85 +/- 0.17 microgram/ml, respectively. After oral administration of TMP, Cmax in plasma was 0.12 +/- 0.01 microgram/ml and the maximum was reached after 1.2 +/- 0.16 h; systemic bioavailability (F) was 10.3% (relative to AUC i.v.). Oral treatment with AP resulted in a Cmax value of 0.21 +/- 0.02 microgram/ml with Tmax of 22.5 +/- 1.65 h and a F value of 71%. Based on WBC, serum ALP and rectal temperature responses, it was concluded that both TMP and AP were inactive against Ehrlichia phagocytophila.

Administration, Oral↗

Increased levels of soluble CD40L in African tick bite fever: possible involvement of TLRs in the pathogenic interaction between Rickettsia africae, endothelial cells, and platelets.

The pathophysiological hallmark of spotted fever group rickettsioses comprises infection of endothelial cells with subsequent infiltration of inflammatory cells. Based on its ability to promote inflammation and endothelial cell activation, we investigated the role of CD40L in African tick bite fever (ATBF), caused by Rickettsia africae, using different experimental approaches. Several significant findings were revealed. 1) Patients with ATBF (n = 15) had increased serum levels of soluble CD40 ligand (sCD40L), which decreased during follow-up. 2) These enhanced sCD40L levels seem to reflect both direct and indirect (through endothelial cell activation involving CX3CL1-related mechanisms) effects of R. africae on platelets. 3) In combination with sCD40L, R. africae promoted a procoagulant state in endothelial cells by up-regulating tissue factor and down-regulating thrombomodulin expression. 4) Although the R. africae-mediated activation of platelets involved TLR2, the combined procoagulant effects of R. africae and sCD40L on endothelial cells involved TLR4. 5) Doxycycline counteracted the combined procoagulant effects of R. africae and sCD40L on endothelial cells. Our findings suggest an inflammatory interaction between platelets and endothelial cells in ATBF, involving TLR-related mechanisms. This interaction, which includes additive effects between sCD40L and R. africae, may contribute to endothelial inflammation and hypercoagulation in this disorder.

Adult↗