Experimental evaluation of the potential for crayfish plague transmission through the digestive system of warm-blooded predators.

The crayfish plague pathogen (Aphanomyces astaci) can be transmitted through the digestive system of fish, but its dispersal through mammalian and bird digestive tracts has been considered unlikely, and direct experimental evidence remains scarce. We present a small-scale transmission experiment with European otter and American mink fed with infected crayfish, and experiments testing survival of cultures of five A. astaci strains at temperatures corresponding to those inside mammal and bird bodies. The pathogen was neither isolated from predator excrements nor transmitted to susceptible crayfish exposed to excrements. In agar-based artificial media, it occasionally survived for 15 min at 40.5°C and for 45 min at 37.5°C, but not so when incubated at those temperatures for 45 min and 75 min, respectively. The five tested strains differed in resistance to high temperatures, two (of genotype groups E and D) being more susceptible than other three (of groups A, B and D). Their survival to some extent varied when exposed to the same temperature after several weeks or months, suggesting that some yet-unknown factors may influence A. astaci resistance to temperature stress. Overall, we support the notion that passage through the digestive tract of warm-blooded predators makes A. astaci transmission unlikely.

Treatment-associated polymorphisms in protease are significantly associated with higher viral load and lower CD4 count in newly diagnosed drug-naive HIV-1 infected patients.

BACKGROUND: The effect of drug resistance transmission on disease progression in the newly infected patient is not well understood. Major drug resistance mutations severely impair viral fitness in a drug free environment, and therefore are expected to revert quickly. Compensatory mutations, often already polymorphic in wild-type viruses, do not tend to revert after transmission. While compensatory mutations increase fitness during treatment, their presence may also modulate viral fitness and virulence in absence of therapy and major resistance mutations. We previously designed a modeling technique that quantifies genotypic footprints of in vivo treatment selective pressure, including both drug resistance mutations and polymorphic compensatory mutations, through the quantitative description of a fitness landscape from virus genetic sequences. RESULTS: Genotypic correlates of viral load and CD4 cell count were evaluated in subtype B sequences from recently diagnosed treatment-naive patients enrolled in the SPREAD programme. The association of surveillance drug resistance mutations, reported compensatory mutations and fitness estimated from drug selective pressure fitness landscapes with baseline viral load and CD4 cell count was evaluated using regression techniques. Protease genotypic variability estimated to increase fitness during treatment was associated with higher viral load and lower CD4 cell counts also in treatment-naive patients, which could primarily be attributed to well-known compensatory mutations at highly polymorphic positions. By contrast, treatment-related mutations in reverse transcriptase could not explain viral load or CD4 cell count variability. CONCLUSIONS: These results suggest that polymorphic compensatory mutations in protease, reported to be selected during treatment, may improve the replicative capacity of HIV-1 even in absence of drug selective pressure or major resistance mutations. The presence of this polymorphic variation may either reflect a history of drug selective pressure, i.e. transmission from a treated patient, or merely be a result of diversity in wild-type virus. Our findings suggest that transmitted drug resistance has the potential to contribute to faster disease progression in the newly infected host and to shape the HIV-1 epidemic at a population level.

[30 years since the first AIDS cases were reported: history and the present. Part II]. / Tricet let od popsání prvních prípadu AIDS: historie a soucasnost. Cást II.

HIV taxonomy, morphology, biophysical properties, and replication cycle as well as modes of HIV transmission in humans are described. State of the art laboratory diagnosis of HIV/AIDS, core clinical diagnostic criteria for AIDS, and AIDS treatment guidelines are summarized. Global HIV/AIDS epidemic and relevant prevention activities are discussed.

[30 years since the first AIDS cases were reported: history and the present part III]. / Tricet let od popsání prvních prípadu AIDS - historie a soucasnost Cást III.

The end of the article features the development of HIV/AIDS diagnosis and its implementation in the Czech Republic. The establishment of the National Reference Laboratory for AIDS (NRL AIDS) at the National Institute of Public Health late in 1985 is mentioned and its responsibilities as the methodology centre in the areas of HIV/AIDS laboratory diagnosis and epidemiology are specified. In cooperation with the respective experts, a pilot HIV/AIDS prevalence study was conducted in the Czech Republic. The general criteria for HIV/AIDS laboratory diagnosis were set for both blood transfusion service and microbiology laboratories. Early in 1987, mass screening of blood donors was introduced in blood transfusion centres and in the second half of the same year, the HIV screening program was extended to selected microbiology laboratories. The NRL AIDS established a unified data reporting system, analyzed the results at the national level, and since 1989, has been reporting the outcomes to the international AIDS, and later HIV/AIDS, reporting system. The NRL AIDS also participated in a number of international projects in the areas of the research and development of laboratory techniques and epidemiological surveillance.

[30 years since the first AIDS cases were reported: history and the present. Part I]. / 30 let od popsání prvních prípadi AIDS-- historie a soucasnost Cást I.

The 30-year natural history of AIDS disease is presented from the first clinical cases reported in 1981 to the identification of the HIV as the etiological agent of the disease. The priority dispute between Robert C. Gallo and Luc Montagnier over the discovery of the human immunodeficiency virus is briefly addressed. The final confirmation of the French priority was provided by the fact that the Nobel Prize in Medicine 2008 was awarded to Luc Montagnier and Francoise Barré--Sinoussi from the Pasteur Institute in Paris.

Transmission of drug-resistant HIV-1 is stabilizing in Europe.

The SPREAD Programme investigated prospectively the time trend from September 2002 through December 2005 of transmitted drug resistance (TDR) among 2793 patients in 20 European countries and in Israel with newly diagnosed human immunodeficiency virus type 1 (HIV-1) infection. The overall prevalence of TDR was 8.4% (225 of 2687 patients; 95% confidence interval [CI], 7.4%-9.5%), the prevalence of nucleoside reverse-transcriptase inhibitor (NRTI) resistance was 4.7% (125 of 2687 patients; 95% CI, 3.9%-5.5%), the prevalence of nonucleoside reverse-transcriptase inhibitor (NNRTI) resistance was 2.3% (62 of 2687 patients; 95% CI, 1.8%-2.9%), and the prevalence of protease inhibitor (PI) resistance was 2.9% (79 of 2687 patients; 95% CI, 2.4%-3.6%). There was no time trend in the overall TDR or in NRTI resistance, but there was a statistically significant decrease in PI resistance (P = .04) and in NNRTI resistance after an initial increase (P = .02). We found that TDR appears to be stabilizing in Europe, consistent with recent reports of decreasing drug resistance and improved viral suppression in patients treated for HIV-1 infection.

A study of HIV-1 genetic diversity in the Czech Republic: 1986-2007.

BACKGROUND: The global HIV/AIDS epidemic consists of a number of regional epidemics caused by different HIV-1 subtypes prevailing in different regions. OBJECTIVES: To study changes in genetic diversity of HIV-1 strains isolated in the Czech Republic (CR) over a more than twenty-year period (1986-2007). STUDY DESIGN: HIV-1 strains isolated in CR from 1986 to 2007 were subtyped by pol gene sequencing followed by phylogenetic analysis. The role of HIV-1 subtyping in molecular epidemiology was considered. RESULTS: Awide range of HIV-1 subtypes were found, with subtype B, into which 76.6% of 534 HIV-1 isolates were classified, being predominant during the whole study period. An increasing number of non-B subtypes A1, C, D, F1, G and some recombinant forms (CRF 01_AE, CRF 02_AG and CRF 06_cpx) were identified after 1990. CONCLUSIONS: The absolute predominance of subtype B among HIV-1 strains in the Czech Republic ended in 1991 when different non-B subtypes had been introduced into the country. The East-West migration is responsible for the introduction of HIV-1 subtypes prevalent in Eastern European and some Asian countries. Genetic analysis of HIV-1 isolates from a given region can be helpful in tracing the course of the HIV/AIDS epidemic.

Short report: HIV infection among commercial sex workers and injecting drug users in the Czech Republic.

Since the first HIV case was diagnosed in the Czech Republic in 1985, there is a lack of information regarding the epidemiology of HIV infection in most high-risk groups. To determine the prevalence of, and risk factors for, HIV among female and male commercial sex workers (FCSW and MCSW, respectively) and injecting drug users (IDUs), cross-sectional studies were conducted in the cities of Cheb, Usti nad Labem, Ostrava, and Prague of the Czech Republic. A total of 1,277 subjects were enrolled, which included 585 FCSWs, 230 MCSWs, and 462 IDUs. The HIV prevalences were 0.7% (95% CI: 0.2-1.7%), 0.9% (95% CI: 0.1-3.1%), and 0.2% (95% CI: 0.005-1.2%) among FCSWs, MCSWs, and IDUs, respectively. Although low HIV prevalences were found, ongoing sentinel surveillance studies, which address modifiable behavioral and biologic risk factors among high-risk groups, are necessary to guide strategies to stem the tide of the epidemic in this country.

Response of HIV positive patients to the long-term salvage therapy by lopinavir/ritonavir.

BACKGROUND: The cohort of 19 patients on LPV/r salvage regimen was followed for the period of up to 37.5 months. Patient's virologic response was evaluated with regard to the various baseline characteristics. RESULTS: A 73.7% of patients (14 out of 19) achieved viral suppression during the first three months of treatment, either complete (47.4%) or partial (26.3%). This effect was only transient in five cases (virologic rebound emerged after 9 months of treatment on average) and in nine cases the treatment was successful in the long-term analysis (HIV RNA plasma level still undetectable at 31st month of the therapy on average with maximum of 36 months). We analyzed the link between the virologic response and possible predictive factors of treatment efficiency, such as lopinavir mutation score, various individual mutations, previous PI exposure, etc. We also describe changes in the PR sequence associated with poor response to the salvage therapy to LPV/r. CONCLUSIONS: The results of LPV/r salvage therapy were encouraging. About 47% of patients from our study achieved stable suppression of viral replication for 31 months on average. LPV/r proved to be potent inhibitor despite unfavourable prognosis.