Characterization and comparison of differentially expressed genes involved in Chlamydia psittaci persistent infection in vitro and in vivo.

Chlamydia psittaci is an obligate intracellular zoonotic pathogen that can enter a persistence state in host cells. While the exact pathogenesis is not well understood, this persistence state may play an important role in chronic Chlamydia disease. Here, we assess the effects of chlamydial persistence state in vitro and in vivo by transmission electron microscopy (TEM) and cDNA microarray assays. First, IFN-γ-induced C. psittaci persistence in HeLa cells resulted in the upregulation of 68 genes. These genes are involved in protein translation, carbohydrate metabolism, nucleotide metabolism, lipid metabolism and general stress. However, 109 genes were downregulated following persistent C. psittaci infection, many of which are involved in the TCA cycle, expression regulation and transcription, protein secretion, proteolysis and transport, membrane protein, presumed virulence factor, cell division and late expression. To further study differential gene expression of C. psittaci persistence in vivo, we established an experimentally tractable mouse model of C. psittaci persistence. The C. psittaci-infected mice were gavaged with either water or amoxicillin (amox), and the results indicated that the 20 mg/kg amox-exposed C. psittaci were viable but not infectious. Differentially expressed genes (DEGs) screened by cDNA microarray were detected, and interestingly, the results showed upregulation of three genes (euo, ahpC, prmC) and downregulation of five genes (pbp3, sucB_1, oppA_4, pmpH, ligA) in 20 mg/kg amox-exposed C. psittaci, which suggests that antibiotic treatment in vivo can induce chlamydial persistence state and lead to differential gene expression. However, the discrepancy on inducers between the two models requires more research to supplement. The results may help researchers better understand survival advantages during persistent infection and mechanisms influencing C. psittaci pathogenesis or evasion of the adaptive immune response.

The role of infectious agents, antibiotics, and antiviral therapy in the treatment of extranodal marginal zone lymphoma and other low-grade lymphomas.

OPINION STATEMENT: There is strong evidence to corroborate the association with Helicobacter pylori (Hp) to gastric extranodal marginal zone lymphoma (ENMZL) and hepatitis C virus (HCV) to splenic/nodal marginal zone lymphoma. Koch's postulates generally hold for these two associations and eradication of the infectious agent is well supported. Hp eradication (HPE) is recommended as front-line therapy for early stage gastric ENMZL regardless of Hp status. Complete response (CR) rate for Hp-negative patients is not as high as for Hp-positive patients; however, the benign nature of HPE and high rates of salvage allow this strategy to be safe while sparing some Hp-negative patients from systemic therapy or radiation. Similarly for HCV-seropositive patients, treatment with antivirals should be strongly considered as first-line for those who do not require immediate cytoreductive therapy or at some point even after completing chemoimmunotherapy. The controversy regarding the role for antibiotics is greatest for primary ocular adnexal lymphoma (POAL). Considering the low incidence of Chlamydia psittaci (Cp) infection with OAL and the challenges to reliably identifying Cp, we typically do not consider doxycycline in POAL treatment. Involved-field radiotherapy (IFRT) remains the treatment of choice for most with unilateral POAL. However, if reliable detection of Cp is available and Cp is identified, patients with unilateral low tumor stage POAL who do not require immediate radiotherapy could be considered for doxycycline as front-line treatment. Other infectious associations to indolent lymphomas have been made, including Borrelia borgdorferi (Bb) in cutaneous lymphoma and Campylobacter in immunoproliferative small intestinal disease (IPSID), but these associations are not as strong and primary treatment targeting the infectious agents is not recommended.

Enrofloxacin and macrolides alone or in combination with rifampicin as antimicrobial treatment in a bovine model of acute Chlamydia psittaci infection.

Chlamydia psittaci is a zoonotic bacterium with a wide host range that can cause respiratory disease in humans and cattle. In the present study, effects of treatment with macrolides and quinolones applied alone or in combination with rifampicin were tested in a previously established bovine model of respiratory C. psittaci infection. Fifty animals were inoculated intrabronchially at the age of 6-8 weeks. Seven served as untreated controls, the others were assigned to seven treatment groups: (i) rifampicin, (ii) enrofloxacin, (iii) enrofloxacin + rifampicin, (iv) azithromycin, (v) azithromycin + rifampicin, (vi) erythromycin, and (vii) erythromycin + rifampicin. Treatment started 30 hours after inoculation and continued until 14 days after inoculation (dpi), when all animals were necropsied. The infection was successful in all animals and sufficient antibiotic levels were detected in blood plasma and tissue of the treated animals. Reisolation of the pathogen was achieved more often from untreated animals than from other groups. Nevertheless, pathogen detection by PCR was possible to the same extent in all animals and there were no significant differences between treated and untreated animals in terms of local (i.e., cell count and differentiation of BALF-cells) and systemic inflammation (i.e. white blood cells and concentration of acute phase protein LBP), clinical signs, and pathological findings at necropsy. Regardless of the reduced reisolation rate in treated animals, the treatment of experimentally induced respiratory C. psittaci infection with enrofloxacin, azithromycin or erythromycin alone or in combination with rifampicin was without obvious benefit for the host, since no significant differences in clinical and pathological findings or inflammatory parameters were detected and all animals recovered clinically within two weeks.

Treatment of mucosa-associated lymphoid tissue-type ocular adnexal lymphoma.

New data have recently been reported in ocular adnexal lymphomas (OALs), particularly of mucosa-associated lymphoid tissue (MALT)-type, regarding their biological characteristics and therapeutic management. A possible association between OAL and Chlamydia psittaci infection has suggested new mechanisms of lymphomagenesis and opened the way for specific targeted treatment. Similarly, the place of rituximab monoclonal antibody therapy and more conventional chemotherapy, as well as a 'wait-and-see' policy in few clearly defined situations, must be defined in relation to the standard treatment option consisting of radiotherapy for low-grade lymphomas. The aims of this review are therefore to present the various treatment modalities and to discuss the place of each modality in the management of ophthalmologic lymphomas.

In vitro and in vivo antichlamydial activities of HSR-903, a new fluoroquinolone antibiotic.

The in vitro and in vivo antichlamydial activities of HSR-903 were investigated. The MICs of HSR-903 for different species of chlamydia were 0.016 to 0.063 microg/ml, which were superior to those of conventional fluoroquinolones. The therapeutic effect of HSR-903 in experimental mouse Chlamydia psittaci pneumonia was also excellent and almost equal to that of minocycline and superior to that of ofloxacin. These results indicate that HSR-903 may be useful in the treatment of respiratory infections caused by chlamydiae.

[Enrofloxacin (Baytril)--an alternative for psittacosis prevention and therapy in imported psittacines]. / Enrofloxacin (Baytril)--eine Alternative in der Psittakoseprophylaxe und -therapie bei importierten Psittaciden.

It was the aim of the presented work to test Enrofloxacin under field conditions of compulsory prophylaxis and treatment of psittacosis, as JUNG (1993) had already demonstrated the effectiveness of this antibiotic against Chlamydia psittaci. During official quarantine 22 groups comprising 2536 birds were treated with Baytril. With suitable feed like steamed maize and a dose of 500 mg/kg Enrofloxacin the mean blood values ranged from 0.9 to 4.1 micrograms/ml within the different species. Application via drinking water can only be advised as an alternative in sick birds with reduced food intake. Duration of excretion (limit was the minimal inhibitory dose of Enrofloxacin with Chlamydia psittaci, 0.125 micrograms/ml was depending on the uptake of Enrofloxacin and correlated with serum levels. With mean serum levels of 1.0 micrograms/ml the minimal inhibitory dose for Chlamydia psittaci was attained in all birds after 14 days. The tissue concentrations measured in Patagonian conures surpassed serum levels several-fold, with the exception of brain tissue. Out of 22 quarantine groups only two were naturally infected with Chlamydia. One group of 196 Senegal parrots could only be cured from chlamydial infection after substituting their normal mixed feed with medicated maize containing 1000 mg/kg Enrofloxacin. In 50 per cent of the Salmonella infected groups Salmonella could again be grown from faecal samples after the end of treatment. For the treatment of psittacosis mean blood levels of 0.5 micrograms/ml are imperative and duration of treatment should not be below 14 days. Satisfactory hygienic conditions provided Baytril is a valuable therapeutic drug against psittacosis.