Modulation of cytokine and cytokine receptor/antagonist by treatment with doxycycline and tetracycline in patients with dengue fever.

Dengue virus infection can lead to dengue fever (DF) or dengue hemorrhagic fever (DHF). Disease severity has been linked to an increase in various cytokine levels. In this study, we evaluated the effectiveness of doxycycline and tetracycline to modulate serum levels of IL-6, IL-1B, and TNF and cytokine receptor/receptor antagonist TNF-R1 and IL-1RA in patients with DF or DHF. Hospitalized patients were randomized to receive standard supportive care or supportive care combined with doxycycline or tetracycline therapy. Serum cytokine and cytokine receptor/antagonist levels were determined at the onset of therapy and after 3 and 7 days. Cytokine and cytokine receptor/antagonist levels were substantially elevated at day 0. IL-6, IL-1ß, and TNF remained at or above day 0 levels throughout the study period in untreated patients. Treatment with tetracycline or doxycycline resulted in a significant decline in cytokine levels. Similarly, IL-1RA and TNF-R1 serum concentrations were elevated at baseline and showed a moderate increase among untreated patients. Both drugs resulted in a significant rise in IL-1Ra levels by day 3 in patients. In contrast, treatment did not affect a similar result for TNF-R1. When compared to the control group, however, a significant rise post-treatment was seen upon intragroup analysis. Further analysis demonstrated that doxycycline was significantly more effective at modulating cytokine and cytokine receptor/antagonist levels than tetracycline.

Serological survey of Ehrlichia canis in stray dogs from Yucatan, Mexico, using two different diagnostic tests.

Canine ehrlichiosis is a disease produced by the rickettsial organism Ehrlichia canis. Reported prevalence may vary greatly depending on the test and sampling method used. For the serological detection of antibodies against E. canis, the indirect immunofluorescence antibody test (IFA) is considered the gold standard. However, other available serological techniques such as the indirect immunoperoxidase technique (IPT) have not yet been tested and may be efficient in detecting specific antibodies. Prevalence found (8.7% and 8.1% for IFA and IPT, respectively) was lower than previously reported in the studied area despite the well-established technique used for the determination of antigens. A kappa value of 0.958 (95% CI 0.9-1.0) was found with a sensitivity and specificity for IPT of 92.59% (95% CI 80.8-99.9) and 99.9% (95% CI 99.8 -100), respectively. The positive predictive value was 99.9% and the negative predictive value was 99.29%. The IPT technique can be used safely for serological determination of E. canis antibodies.

Identification of Ctenocephalides felis fleas as a host of Rickettsia felis, the agent of a spotted fever rickettsiosis in Yucatan, Mexico.

In search for the vector of the recently recognized spotted fever rickettsiosis of the Yucatán, ticks, fleas, and lice were collected from vegetation and dogs in localities where seropositive persons had been found. The arthropods were examined by polymerase chain reaction (PCR) using primers for the genus-specific 17-kDa protein gene followed by restriction fragment length polymorphism (RFLP) and DNA sequencing. Eleven (20%) of 54 pools of Ctenocephalides felis fleas contained DNA of Rickettsia felis. None of 219 Amblyomma cajennense, 474 Rhiphicephalus sanguineus, 258 Boophilus sp. ticks, and 33 Poliplax species lice contained DNA of Rickettsia. The identity of the rickettsial DNA was confirmed as R. felis by PCR/RFLP for the citrate synthase and outer membrane protein A genes and by DNA sequencing. The results indicate that the host of R. felis in Yucatán is C. felis and suggest that the spotted fever rickettsiosis that has infected >5% of the population of the Yucatán and can present as a dengue-like illness is likely to be caused by R. felis.

Serologic study of the prevalence of rickettsiosis in Yucatán: evidence for a prevalent spotted fever group rickettsiosis.

Because of the discovery of a spotted fever group rickettsiosis with signs and symptoms similar to dengue fever in Yucatan, Mexico, immunofluorescence assay (IFA) serology was performed on sera from 390 persons selected from a representative geographic distribution of rural Yucatan to detect antibodies reactive with Rickettsia rickettsii, R. akari, a Thai strain (TT-118) that is most closely related to a rickettsia identified in Amblyomma cajennense ticks in southern Texas, and R. typhi. The IFA antibodies at titers > or = 1:64 against R. akari were detected in 22 (5.6%) of the samples with the expected cross-reactivity against the other antigens of the spotted fever group. Immunoblotting with antigens of R. akari identified antibodies against antigens of spotted fever group lipopolysaccharides and not against rickettsial outer membrane proteins A and B, which contain the species-specific epitopes. A rickettsiosis most likely caused by a relative of R. akari appears to be both prevalent and widely distributed geographically in Yucatan.