Secondary choriocapillaritis in infectious chorioretinitis.

PURPOSE: To analyse the indocyanine green angiography (ICGA) patterns of hypofluorescence that are compatible with choriocapillaritis that occur secondarily to toxoplasmic retinochoroiditis (ToRC), ocular tuberculosis (including tuberculous choroiditis, TuCR and multifocal serpiginoid choroiditis, TMSC) and syphilitic chorioretinitis (SyCR). METHODS: This was a single centre, retrospective case review study. Patients with a diagnosis of ToRC, TuCR, TMSC or SyCR were identified, their charts were reviewed and fundus photographs, fluorescein angiography (FA) and ICGA pictures were assessed. RESULTS: Indocyanine green angiography was performed at the initial presentation in 63 of the 105 patients with ToRC, in 37 of the 38 patients with TuCR, in six of six patients with TMSC and in two of four patients with SyCR. The following four ICGA patterns indicated choriocapillaritis: extension of hypofluorescence beyond the hypofluorescence of the actual infectious focus as seen on fundus photography or FA (seen only in ToRC and TuCR); small dark dots around the infectious focus (seen only in ToRC); multiple 'confetti-like' hypofluorescent areas or hypofluorescent geographical confluent areas (seen only in TMSC); and widespread areas of nonperfusion visible only in ICGA (seen only in SyCR). CONCLUSIONS: Patients with secondary choriocapillaritis have distinct typical ICGA findings. ICGA is thus an important diagnostic tool that can provide an explanation for otherwise obscure visual loss and that might have diagnostic value for specific conditions like ToRC and SyCR.

Transmission and diagnosis of equine babesiosis in South Africa

The transmission and prevalence of Babesia equi and B. caballi are being studied. Rhipicephalus evertsi mimeticus an ixodid tick from Namibia was identified as a new vector of B. equi, however, R. turanicus, previously reported to be a vector, failed to transmit both B. equi and B. caballi in the laboratory. The accurate diagnosis of B. caballi is being investigated because the nature of its low level parasitaemia does not allow easy detection in thin blood smears, routinely used for diagnosis, by clinicians. Consequently its role as a pathogen remains obscure. The importance of identifying infected horses, destined for export to Babesia-free coutries, is also stressed. Thock and thin blood smears, serology (IFAT) and DNA probes are currently employed to study disease prevalence. To date 293 healthy, adult, throughbred horses have been screened by all three methods. The percentage positives are as follows: B. equi 4.4%, 70.6%, 13% and B. caballi 0.7%, 37%, 18.4% respectively. The DNA probes were more sensitive than blood smear examination for diagnosing carrier infections but are probably not sensitive enough to identify all carrier infections. A poor correlation was found between detection of the parasites' DNA and seropositivity. However, polymerase chain reaction could be used to amplify parasite DNA in a particular sample and its could result in more accurate diagnosis.

Molecular detection and identification of zygomycetes species from paraffin-embedded tissues in a murine model of disseminated zygomycosis: a collaborative European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Fungal Infection Study Group (EFISG) evaluation.

The present study was performed to assess the interlaboratory reproducibility of the molecular detection and identification of species of Zygomycetes from formalin-fixed paraffin-embedded kidney and brain tissues obtained from experimentally infected mice. Animals were infected with one of five species (Rhizopus oryzae, Rhizopus microsporus, Lichtheimia corymbifera, Rhizomucor pusillus, and Mucor circinelloides). Samples with 1, 10, or 30 slide cuts of the tissues were prepared from each paraffin block, the sample identities were blinded for analysis, and the samples were mailed to each of seven laboratories for the assessment of sensitivity. A protocol describing the extraction method and the PCR amplification procedure was provided. The internal transcribed spacer 1 (ITS1) region was amplified by PCR with the fungal universal primers ITS1 and ITS2 and sequenced. As negative results were obtained for 93% of the tissue specimens infected by M. circinelloides, the data for this species were excluded from the analysis. Positive PCR results were obtained for 93% (52/56), 89% (50/56), and 27% (15/56) of the samples with 30, 10, and 1 slide cuts, respectively. There were minor differences, depending on the organ tissue, fungal species, and laboratory. Correct species identification was possible for 100% (30 cuts), 98% (10 cuts), and 93% (1 cut) of the cases. With the protocol used in the present study, the interlaboratory reproducibility of ITS sequencing for the identification of major Zygomycetes species from formalin-fixed paraffin-embedded tissues can reach 100%, when enough material is available.

Is the thymus a target organ in infectious diseases?

The thymus is a central lymphoid organ, in wich T cell precursors differentiale and generate most of the so-called T cell reprtoire. Along with a variety of acute infectious diseases, we and others determined important changes in both microenvironmental and lymphoid compartments of the organ. For example, one major and common feature observed in acute viral, bacterial and parasitic diseases, is a depletion of cortical thymocytes, mostly those bearing the CD4-CD8 double positive phenotype. This occurs simmultaneously to the relative enrichment in medullary CD4 or CD8 single positive cells, expressing high densities of the CD3 complex. Additionally we noticed a variety of changes in the thymic microenvironment (and particularly is epithelial component), comprising abnormal location of thymic epithelial cell subsets as well has a denser Ia-bearing cellular network. Moreover, the extracellular matrix network was altered with an intralobular increase of basement membrane proteins that positively correlated with the degree of thymocyte death. Lastly, anti-thymic cell antibodies were detected in both human and animal models of infectious diseases, and in some of them a phenomenon of molecular mimicry could be evidenced. Taken together, the data receiwed herein clearly show that the thymus should be regarded as a target in infectious diseases.

A model for intra-familial distribution of an infectious disease (Chagas' disease)

A probabilistic model for intra-familial distribution of infectous disease is proposed and applied to the prevalence of positive serology for Trypanosoma cruzi infection in Northeastern Brazilian sample. This double with one tail excess model fits satisfactorily to the data and its interpretation says that around 51% of these 982 families are free of infection risk; among those that are at risk, 3% have a high risk (0.66), probably due to high domestic infestation of the vector bug; while 97% show a small risk (0.11), probably due to accidental, non-domestic transmission.

Recombinant erythropoietin in acute chemotherapy-induced anemia of children with cancer.

Chemotherapy-induced anemia in children with cancer is usually of acute onset. To investigate an alternate treatment to transfusion (Tx), we undertook a phase I-II clinical trial of daily administrations of recombinant erythropoietin (rHuEPO). Patients with a hemoglobin (Hgb) value < 75 g/l were treated for 14 days in cohorts of 3 at escalating daily doses of 25, 50, 70, 80, 90, and 100 U/kg respectively. The maximum-tolerated dose was not encountered. Of 18 courses given to 15 children aged 0.5-18 years, 7 (39%) were associated with increased or stable Hgb levels (courses without Tx), while 11 (61%) were terminated by a Tx, without evidence of a dose-response relationship. Changes in mean Hgb levels and absolute reticulocyte counts were paralleled by those of mean white blood cell, platelet, and absolute neutrophil counts during the first 7 days and when the end-points of the study were reached. Numbers of circulating burst-forming units-erythroid remained low throughout courses without Tx. No cumulative increase of serially determined serum EPO levels was observed and serum ferritin levels were elevated in both groups of courses. We conclude that daily administration of rHuEPO were safe but ineffective in our trial. Recovery of chemotherapy-induced myelosuppression appeared to be the rate-limiting factor for the outcome, without evidence of an enhanced stimulation of erythropoiesis. The lack of a proliferative response of specific progenitor cells suggested a mechanism of transient primary resistance to rHuEPO.

Survey of Infectious Etiologies of Bovine Abortion during Mid- to Late Gestation in Dairy Herds.

Bovine abortion of unknown infectious etiology still remains a major economic problem. Thus, we investigated whether Brucella spp., Listeria monocytogenes, Salmonella spp., Campylobacter spp. and Coxiella burnetii are associated with abortion and/or stillbirth in Tunisian dairy cattle. Using a pan-Chlamydiales PCR, we also investigated the role of Chlamydiaceae, Waddlia chondrophila, Parachlamydia acanthamoebae and other members of the Chlamydiales order in this setting. Veterinary samples taken from mid to late-term abortions from twenty dairy herds were tested. From a total of 150 abortion cases collected, infectious agents were detected by PCR in 73 (48.66%) cases, 13 (8.66%) of which represented co-infections with two infectious agents. Detected pathogens include Brucella spp (31.3%), Chlamydiaceae (4.66%), Waddlia chondrophila (8%), Parachlamydia acanthamoebae (5.33%), Listeria monocytogenes (4.66%) and Salmonella spp. (3.33%). In contrast, Campylobacter spp. and Coxiella burnetii DNA were not detected among the investigated veterinary samples. This demonstrates that different bacterial agents may cause bovine abortion in Tunisia. This is the first report suggesting the role of Parachlamydia acanthamoebae in bovine abortion in Africa. Further studies with a larger number of samples are necessary to confirm whether this emerging pathogen is directly linked to abortion in cattle.

Evolutionary Control of Infectious Disease: Prospects for Vectorborne and Waterborne Pathogens

Evolutionary theory may contribute to practical solutions for control of disease by identifying interventions that may cause pathogens to evolve to reduced virulence. Theory predicts, for example, that pathogens transmitted by water or arthropod vectors should evolve to relatively high levels of virulence because such pathogens can gain the evolutionary benefits of relatively high levels of host exploitation while paying little price from host illness. The entrance of Vibrio cholerae into South America in 1991 has generated a natural experiment that allows testing of this idea by determining whether geographic and temporal variations in toxigenicity correspond to variation in the potential for waterborne transmission. Preliminary studies show such correspondences: toxigenicity is negatively associated with access to uncontaminated water in Brazil; and in Chile, where the potential for waterborne transmission is particularly low, toxigenicity of strains declined between 1991 and 1998. In theory vector-proofing of houses should be similarly associated with benignity of vectorborne pathogens, such as the agents of dengue, malaria, and Chagas' disease. These preliminary studies draw attention to the need for definitive prospective experiments to determine whether interventions such as provisioning of uncontaminated water and vector-proofing of houses cause evolutionary reductions in virulence

Integrated Genetic Epidemiology of Infectious Diseases: The Chagas Model

Genetic typing of pathogenic agents and of vectors has known impressive developments in the last 10 years, thanks to the progresses of molecular biology, and to the contribution of the concepts of evolutionary genetics. Moreover, we know more and more on the genetic susceptibility of man to infectious diseases. I propose here to settle a new, synthetic field of research, which I call `integrated genetic epidemiology of infectious diseases' (IGEID). I aim at evaluating, by an evolutionary genetic approach, the respective impact, on the transmission and pathogenicity of infectious diseases, of the host's, the pathogen's and the vector's genetic diversity, and their possible interactions (co-evolution phenomena). Chagas' disease constitutes a fine model to develop the IGEID methodology, by both field and experimental studies.

Environmental determinants of infectious and parasitic diseases

A review of the role of the environment as a determinant of infectious and parasitic diseases is presented. Historical considerations and the several environmental classifications of diseases are introduced. In a broader perspective the subject is analyzed in view of the emergence of the environmental health area, with its new paradigms. A review of epidemiological studies about environmental sanitation conditions and measures is presented, analyzing the conclusions derived from 256 studies. Finally, an epidemiological study carried out in Betim, Minas Gerais is briefly described, in order to illustrate the potentiality of this kind of study. Setting priorities of interventions regarding diarrhea control was the aim of this investigation. Conclusion about the role of this approach to optimize preventive measures for the control of infectious and parasitic diseases, of sound importance to the reality of the developing world, is stated.