Immune Compromise in HIV-1/HTLV-1 Coinfection With Paradoxical Resolution of CD4 Lymphocytosis During Antiretroviral Therapy: A Case Report.

Human immunodeficiency virus type-1 (HIV-1) and human T lymphotropic virus type-1 (HTLV-1) infections have complex effects on adaptive immunity, with specific tropism for, but contrasting effects on, CD4 T lymphocytes: depletion with HIV-1, proliferation with HTLV-1. Impaired T lymphocyte function occurs early in HIV-1 infection but opportunistic infections (OIs) rarely occur in the absence of CD4 lymphopenia. In the unusual case where a HIV-1 infected individual with a high CD4 count presents with recurrent OIs, a clinician is faced with the possibility of a second underlying comorbidity. We present a case of pseudo-adult T cell leukemia/lymphoma (ATLL) in HIV-1/HTLV-1 coinfection where the individual fulfilled Shimoyama criteria for chronic ATLL and had pulmonary Mycobacterium kansasii, despite a high CD4 lymphocyte count. However, there was no evidence of clonal T-cell proliferation by T-cell receptor gene rearrangement studies nor of monoclonal HTLV-1 integration by high-throughput sequencing. Mutually beneficial interplay between HIV-1 and HTLV-1, maintaining high level HIV-1 and HTLV-1 viremia and proliferation of poorly functional CD4 cells despite chronicity of infection is a postulated mechanism. Despite good microbiological response to antimycobacterial therapy, the patient remained systemically unwell with refractory anemia. Subsequent initiation of combined antiretroviral therapy led to paradoxical resolution of CD4 T lymphocytosis as well as HIV-1 viral suppression and decreased HTLV-1 proviral load. This is proposed to be the result of attenuation of immune activation post-HIV virological control. This case illustrates the importance of screening for HTLV-1 in HIV-1 patients with appropriate clinical presentation and epidemiological risk factors and explores mechanisms for the complex interactions on HIV-1/HTLV-1 adaptive immunity.

[Role of Chlamydia trachomatis intraocular infection in the development of proliferative vitreoretinopathy (experimental study)].

OBJECTIVE: To study the influence of C. trachomatis infection on proliferative vitreoretinopathy (PVR) stimulation and development in an experimental model. MATERIAL AND METHODS: Intravitreal C. trachomatis injection was performed in 17 rabbits (right eyes) out of which 8 developed minimal chlamydial damage (1 was further subjected to histopathological examination with pathogen detection in ocular structures and other 7 were included in the study group). The control group consisted of 7 rabbits with no laboratory evidence of chlamydial infection. PVR was induced by 4 peripheral retinal punctures with a 19 G needle. Follow-up methods included ophthalmoscopy, ultrasonography, and PVR grading according to the Fastenberg classification. Histopathological examination, supplemented with pathogen detection by direct immunofluorescence in the study group, was performed at weeks 7 and 20. RESULTS: PVR rate and severity were higher in the study group as compared with the controls (5 out of 7 rabbits, grade 2-4 vs. 2 out of 7 rabbits, grade 0-1, p<0.01). In the study group, histopathological examination performed before and after the induction of PVR revealed a pronounced lymphocyte and macrophage infiltration, characteristic of infectious inflammation. Similarly, extra- and intracellular chlamydial inclusions could be found in the retina and/or zones of proliferation throughout the whole study period. Inflammation signs (including those of proliferation) were reliably less significant in the controls. CONCLUSION: C. trachomatis infection of the posterior segment contributes to PVR development due to associated chronic inflammation.

[Role of Chlamydia trachomatis and Chlamydophila pneumoniae in damage of eye posterior segment structures].

AIM: Study the ability of Chlamydia trachomatis and Chlamydophila pneumoniae to damage structures of eye posterior segment, features of development of such infectious process, its morphological and clinical characteristics. MATERIALS AND METHODS: 6 rabbits with confirmed absence of C. trachomatis, C. pneumoniae were used in the study. 3 animals were infected with C. trachomatis culture and 3 animals--with C. pneumoniae culture. Subconjunctival and intravitreal mode of infectious agent introduction were used, as well as instillation of its culture into conjunctival sac. Microbiological diagnostics included microscopy with direct immunofluorescence, culture method and determination of antibody titers. Infectious process was studied by using ophthalmologic methods and histological examination. Observation period was 4 months. RESULTS: In all the animals a development of infectious process at early stages after the infection was confirmed. Conjunctivitis symptoms, inflammatory exudation into vitreous humor, chorioretinal inflammation loci, disorders in transparency of optical media and detachment of retina were clinical manifestations. In 2 animals infected with C. trachomatis severe panuveitis was noted. In 4 animals infectious process assumed subclinical characteristics (infection with both C. trachomatis or C. pneumoniae). In pathomorphologic studies data on the ability of C. trachomatis and C. pneumoniae to cause damage to cells of retina, pigment epithelium and choroid were obtained. CONCLUSION: C. trachomatis and C. pneumoniae may play a significant role in pathology of vitreous humor, retina, pigment epithelium and choroid.

[Dystrophic changes of vitreous in ocular chlamydia infection].

Incidence and character of vitreous changes in ocular chlamydia infection was studied. 312 patients were enrolled into the study (175 males and 137 females) aged from 24 to 52 years old (mean age 38.4 +/- 5.2 years). 165 patients (330 eyes) with laboratory confirmed chlamydia conjunctival infection were included in the experimental group. 147 patients (294 eyes) without chlamydia conjunctival infection were enrolled to the comparison group. Each group was subdivided with regard to the age. Dystrophic changes of vitreous and its posterior detachment are more frequently revealed in eyes with Chlamydia trachomatis infection, besides it happens in a younger age.

[About development of chlamydia multiple organ lesions after primary ocular infection in experiment].

Chlamidia spp. are obligate intracellular pathogens that cause a variety of diseases in humans and animals. Their generalization was proved as hematogenic spreading from the urogenital (C. trachomatis) and the respiratory (C. pneumoniae) systems. The goal was to investigate the possibility of C. trachomatis infection spreading from the primary ocular gate. 6 animals were infected by instillation in the conjunctival sack, subconjunctival and intravitreal injections of C. thachomatis culture. C. trachomatis was detected by direct immunofluorescence method in the retina, retinal pigment epithelium, choroid, brain, the pancreas, the prostate gland and the urethra after primary ocular infection. The results of our study have proved the opportunity of C. trachomatis to cause polyorganic contamination.

[Retinal lesion in experimental chlamydia eye infection].

Until the present time, ophthalmic chlamydiasis has been generally associated with diseases of auxiliary organs of the eye and its anterior segment: conjunctivitis and iridocyclitis. The morphological substrate of eye posterior segment lesion caused by C. trachomatis and C. pneumonia was studied in this investigation. The pathomorphological pattern characteristic of chlamydia-induced rabbit retinal and vitreous body lesions is composed of vitreoretinal lymphocyte-macrophageal infiltrations of varying intensity, posterior hyaloid membrane detachment, peripheral foci or folding of the retina, impaired nuclei of photoreceptors and bipolar neurons, pigment epithelial damage occurring in different concurrences in relation to the species of a causative agent and the clinical picture.

[The clinical and morphological features of Chlamydia pneumoniae-induced chorioretinitis in an experiment].

The clinical and pathomorphological features of vitreous retinochorioidal complex lesion with the pathogen Chlamydia pneumoniae were studied. Three rabbits (6 eyes) were infected with Ch. pneumoniae strain TWAR by instillation, subconjunctivally and 2 eyes were infected by intravitreally. Contamination was controlled by direct immunofluorescence and cultivation (conjunctival scrapes, venous blood). A postmortem study was conducted 128 days later, by employing an immunohistochemical analysis. On days 7-14, all cases showed the signs of a uveal reaction; 4 cases developed chorioretinitis. In 2 cases, the process ran as endophthalmitis with minimal clinical manifestations. The rate of the process was decreased by days 40-50. On the postmortem study, all the cases displayed lymphocytic-macrophageal infiltration in the vitreous body and retina in the presence of retinal focal dystrophic changes. An immunohistochemical study revealed the pathogen in different retinal layers (both inside and outside the chorioretinal foci) in all 6 cases and in the preretinal layers of the vitreous body in 5 cases. The pathogen Ch. pneumoniae is rather highly tropic to the structures of the visual organ and it is able to induce chronic lesion of the structures of the posterior portion of the eye portion with varying clinical manifestations. Dystrophic changes in infected tissues, the vitreous body and chorioretinal complex in particular, are a result of a chronic inflammatory process.

[The specific features of a structural lesion in the ocular posterior segment in experimental chlamydial infection].

The investigation was undertaken to study changes in the structure of the vitreoretinal complex in experimental chlamydial infection. Six rabbits were inoculated with Ch. pneumonia (6 eyes) and Ch. trachomatis (6 eyes) via instillations, subconjunctivally and intravitreally. Clinical and pathomorphological study was conducted during 128 days, by using immunohistochemical techniques. All modes of inoculation resulted in the development of an intraocular infectious process as uveitis, choriorenitis, and vitreitis (endophthalmitis) of varying degrees--from subclinical to severe. Immunohistochemical study revealed the pathogen in the structures of the ocular posterior segment and in venous blood in all cases. When locally inoculated, chlamydial infection becomes disseminated, by afflicting the ocular posterior segment, no matter what the mode of inoculation is applied. The clinical picture of the lesion widely varies from subclinical manifestations to a severe process.

[Local ocular immunity parameters in chronic rhino- or odontogenic infection].

Thirty-four patients with foci of chronic rhino- or odontogenic infection were examined. All the patients underwent physical examination, biochemical blood analysis, immunological test for immunoglobulins A, G, and M, circulating immune complexes, leukocyte migration inhibition test with phytohemagglutinin, Con A, with antigens of the retina, vitreous body, iris, and lens, scrapes from the dentogingival pocket, conjunctival and nasal cavities for Chlamydia, followed by direct immunofluorescence, polymerase chain reaction, and culture. Chronic rhino- or odontogenic infection foci impair local ocular immunity in ophthalmologically healthy patients. The foci of chronic rhinogenic infection cause more pronounced changes in systemic and local ocular immunity than those of chronic odontogenic infection. In half the patients with chronic rhino- or odontogenic infection foci, Chlamydia are detectable in the oral, nasal, and ocular mucosae, which suggests that there is generalized infection and there is a need for complex sanitation of the body. Isolated local treatment for Chlamydia infection is not promising.

[To the detection rate of Chlamydia infection in regmatogenous retinal detachment].

Regmatogenous, or primary, retinal detachment is a vision-threatening condition resulting from retinal rupture. Inflammation and autoimmune processes are of great importance in the pathogenesis of this disease. In this connection, the purpose of the study was to reveal the incidence of Chlamydia infection in regmatogenous retinal detachment. Subretinal fluid (SRF) aspirates and conjunctival scrapes from 50 patients with regmatogenous retinal detachment were studied by direct immunofluorescence test and polymerase chain reaction for Chlamydia trachomatis. The latter was found in 74% of SRF samples and in 90% of conjunctival scapes (in a total of 47 (94%) patients). The findings suggest that regmatogenous retinal detachment is associated with Ch. trachomatis contamination of the organ of vision in most cases. In retinal detachment, it is expedient to include tests for Ch. trachomatis into a complex of diagnostic methods and, when detected, to consider whether antichlamydial therapy is performed.

[To the role of Chlamydia infection in the development of dry eye].

The study deals with the possible etiological role of Chlamydia, Mycoplasma, Ureaplasma, and bacteroid infections in the development of chronic conjunctivitis and dry eye (DE). A hundred and fifty patients with DE and chronic conjunctivitis were examined. Conjunctival scrapes were examined by direct immunofluorescence for evidence of Chlamydia, Mycoplasma, Ureaplasma, and bacteroid infections. DE was verified by the Schirmer test and the Norn test. Ninety-five (63.3%) persons were found to be infected. GE was diagnosed in 84 (56%) of the 150 patients. Analysis of infection rates revealed Chlamydia, Mycoplasma, Ureaplasma as mono- and mixed infection in 63.3, 50.6, and 35.3, respectively, and bacteroids as mixed infection in 32.6%. Chlamydia was detected in the conjunctiva in the vast majority of patients with DE (90.5%). Chlamydia infection of the conjunctiva is one of the causes of artificial DE. Conjunctival Chlamydia affliction is manifested by the clinical picture of chronic slowly progressive inflammation with the progression of DE after a latent period of about 2-3 years.

The radiology of IRIS (immune reconstitution inflammatory syndrome) in patients with mycobacterial tuberculosis and HIV co-infection: Appearances in 11 patients.

AIM: To determine the radiological manifestations of IRIS (immune reconstitution inflammatory syndrome) in patients with HIV and mycobacterium tuberculosis co-infection, in the context of their demographic and clinical data. MATERIALS AND METHODS: The radiological imaging, demographic and clinical data of 11 patients diagnosed with IRIS associated with HIV and mycobacterial tuberculosis co-infection were studied retrospectively. Where available, follow-up imaging studies were also reviewed. RESULTS: The most common radiological feature of IRIS was lymph node enlargement (73%), with central low attenuation centres, in keeping with necrosis, present in most of these cases (88%). Most commonly affected were intra-abdominal nodes (70%), followed by axillary (40%) and mediastinal lymph nodes (36%). Within the lung parenchyma, diffuse, bilateral pulmonary nodules were seen in 55% of cases. Unilateral small volume pleural effusions were seen in two cases with associated parenchymal changes seen in only one. Small volume ascites was seen in two cases. Thirty-six percent of cases presented with new or worsening abscesses despite treatment. In this context, image-guided radiological drainage proved a useful adjunct to the conventional medical therapy for IRIS. The most common clinical signs of IRIS included fever (64%), abdominal pain (36%) and cough (27%). CONCLUSION: We have described the radiological features that are characteristic in IRIS and the importance of putting these into context with the clinical and pathological findings as part of a multidisciplinary approach in making the diagnosis. The role of the radiologist is central in diagnosis, monitoring of disease progression and management of complications in patients with IRIS.

Mycobacterial immune reconstitution inflammatory syndrome in HIV-1 infection after antiretroviral therapy is associated with deregulated specific T-cell responses: beneficial effect of IL-2 and GM-CSF immunotherapy.

BACKGROUND: With the advent of antiretroviral therapy (ART) cases of immune reconstitution inflammatory syndrome (IRIS) have increasingly been reported. IRIS usually occurs in individuals with a rapidly rising CD4 T-cell count or percentage upon initiation of ART, who develop a deregulated immune response to infection with or without reactivation of opportunistic organisms. Here, we evaluated rises in absolute CD4 T-cells, and specific CD4 T-cell responses in 4 HIV-1+ individuals presenting with mycobacterial associated IRIS who received in conjunction with ART, IL-2 plus GM-CSF immunotherapy. METHODS: We assessed CD4 T-cell counts, HIV-1 RNA loads, phenotype for naïve and activation markers, and in vitro proliferative responses. Results were compared with those observed in 11 matched, successfully treated asymptomatic clinical progressors (CP) with no evidence of opportunistic infections, and uninfected controls. RESULTS: Median CD4 T-cell counts in IRIS patients rose from 22 cells/microl before initiation of ART, to 70 cells/microl after 8 months of therapy (median 6.5 fold increase). This coincided with IRIS diagnosis, lower levels of naïve CD4 T-cells, increased expression of immune activation markers, and weak CD4 T-cell responses. In contrast, CP had a median CD4 T-cell counts of 76 cells/microl at baseline, which rose to 249 cells/microl 6 months post ART, when strong T-cell responses were seen in > 80% of patients. Higher levels of expression of immune activation markers were seen in IRIS patients compared to CP and UC (IRIS > CP > UC). Immunotherapy with IL-2 and GM-CSF paralleled clinical recovery. CONCLUSION: These data suggest that mycobacterial IRIS is associated with inadequate immune reconstitution rather than vigorous specific T-cell responses, and concomitant administration of IL-2 and GM-CSF immunotherapy with effective ART may correct/augment T-cell immunity in such setting resulting in clinical benefit.

The prevalence of reduced zidovudine susceptibility in zidovudine-naive, antiretroviral-experienced HIV-1-infected patients.

OBJECTIVES: There is increasing in vitro and in vivo evidence that reduced zidovudine (ZDV) susceptibility is generated by the selective pressure conferred by other nucleoside reverse transcriptase inhibitors (NRTIs). However, the degree to which this occurs in clinical practice remains unclear. We assessed phenotypic and genotypic resistance in ZDV-naive patients with virological failure on stavudine (d4T)-containing regimens, with particular reference to potential cross-resistance between d4T and ZDV. METHODS: Patients were identified from a clinical database. Treatment history was confirmed by case note evaluation and discussion with patients. Genotypic and phenotypic analyses were undertaken by Virco (Virco BVBA, Mechelen, Belgium). RESULTS: Sixty-seven drug-experienced, ZDV-naive patients who underwent a resistance test while failing a d4T-containing regimen were identified. Of these patients, 23% had received three or more NRTIs and 42% at least one non-nucleoside reverse transcriptase (RT) inhibitor; 22% had viruses with reduced d4T susceptibility (>1.8-fold resistance), and 25% had viruses with reduced ZDV susceptibility (>4-fold). The most frequently observed RT mutations were identified. A significant correlation was found between susceptibility to d4T and susceptibility to ZDV (r=0.36; P=0.003), and also between virtual resistance to d4T and that to ZDV (r=0.38; P=0.002). CONCLUSIONS: A significant minority of d4T-treated, ZDV-naive patients were found to have viruses with reduced ZDV susceptibility, with a variable association with classical ZDV resistance mutations. These data suggest that cross-resistance between d4T and ZDV may involve novel constellations of mutations. Correlations between d4T and ZDV susceptibilities and resistances further support cross-resistance between NRTIs.

[Acute chlamydial lesions of the nervous system: etiology, diagnosis, clinical aspects]. / Ostrye khlamidiinye porazheniia nervnoi sistemy: étiologiia, diagnostika, klinika.

The examination of 180 patients with acute neuroinfection (105 males, 75 females at the age from 18 to 45 years) has detected C. trachomatis in 23.8%, C. Pneumoniae in 66.6%, C. psittaci in 9.5% patients. Acute and chlamydial lesions of the central nervous system were characterized by all forms of neuroinfection: serous and purulent meningitides, meningoencephalitides. Development of acute neuroinfection is accompanied by sluggish chlamydial infection of the viscera.

[Laboratory diagnosis of systemic chlamydiosis]. / Osobennosti laboratornoi diagnostiki khlamidiozov s sistemnymi proiavleniiami.

Modern methods for diagnosis of chlamydial infection are compared. In order to detect the total systems' manifestations in patients with chlamydial infection, the authors suggest to extend the list of clinical materials to be collected in patients with suspected chlamydial infection and to use direct immunofluorescent test, polymerase chain reaction, and ligase chain reaction in diagnostic studies.