Cytotoxic immune responses in the lungs correlate to disease severity in patients with hantavirus infection.

Hantavirus infections may cause severe and sometime life-threatening lung failure. The pathogenesis is not fully known and there is an urgent need for effective treatment. We aimed to investigate the association between pulmonary viral load and immune responses, and their relation to disease severity. Bronchoscopy with sampling of bronchoalveolar lavage (BAL) fluid was performed in 17 patients with acute Puumala hantavirus infection and 16 healthy volunteers acting as controls. Lymphocyte subsets, granzyme concentrations, and viral load were determined by flow cytometry, enzyme-linked immunosorbent assay (ELISA), and quantitative reverse transcription polymerase chain reaction (RT-PCR), respectively. Analyses of BAL fluid revealed significantly higher numbers of activated CD8(+) T cells and natural killer (NK) cells, as well as higher concentrations of the cytotoxins granzymes A and B in hantavirus-infected patients, compared to controls. In patients, Puumala hantavirus RNA was detected in 88 % of BAL cell samples and correlated inversely to the T cell response. The magnitude of the pulmonary cytotoxic lymphocyte response correlated to the severity of disease and systemic organ dysfunction, in terms of need for supplemental oxygen treatment, hypotension, and laboratory data indicating renal failure, cardiac dysfunction, vascular leakage, and cell damage. Regulatory T cell numbers were significantly lower in patients compared to controls, and may reflect inadequate immune regulation during hantavirus infection. Hantavirus infection elicits a pronounced cytotoxic lymphocyte response in the lungs. The magnitude of the immune response was associated with disease severity. These results give insights into the pathogenesis and possibilities for new treatments.

Time to revise the paradigm of hantavirus syndromes? Hantavirus pulmonary syndrome caused by European hantavirus.

Hantaviruses have previously been recognised to cause two separate syndromes: hemorrhagic fever with renal syndrome in Eurasia, and hantavirus pulmonary syndrome (HPS) in the Americas. However, increasing evidence suggests that this dichotomy is no longer fruitful when recognising human hantavirus disease and understanding the pathogenesis. Herein are presented three cases of severe European Puumala hantavirus infection that meet the HPS case definition. The clinical and pathological findings were similar to those found in American hantavirus patients. Consequently, hantavirus infection should be considered as a cause of acute respiratory distress in all endemic areas worldwide.

Blood lead and erythrocyte protoporphyrin levels in Kazakhstan.

A pilot study was conducted to examine the extent of lead exposure and prevalence of iron deficiency in 3 major cities of Kazakhstan. Blood lead (B-Pb.) and erythrocyte protoporphyrin (ZnPP) levels of 475 children, age range 6 months to 7 yeas were measured. The mean B-Pb. levels in the different cities ranged from 4-7 micrograms/dl (minimum 1 to max 29 micrograms/dl) and similarly the mean ZnPP levels ranged from 26-32 micrograms/dl (minimum 12 and maximum 95 micrograms/dl), thus confirming low level lead poisoning of children at some sites. One to four year olds had greater than 10 micrograms/dl B-Pb in 18-27% cases compared with 3-7% cases in five to seven year olds. Prevalence of iron deficiency in 6 months to 4 year old children was the highest ranging from 28-86% compared with 4 to 15% in 4-7 year olds. However, there was remarkably low prevalence (4%) of iron deficiency in a group of 5-6 years olds. This study suggests that a targeted B-Pb and ZnPP monitoring together with an iron supplementation programme in the 3 cities of Kazakhstan is essential. Environmental education appears to have had a positive impact in lowering B-Pb at one site and should thus be expanded nationwide.