Long-Term Consequences of Puumala Hantavirus Infection

Mustonen, Jukka; Vaheri, Antti; Pörsti, Ilkka; Mäkelä, Satu

doi:10.3390/v14030598

Cited by 8 publications

(5 citation statements)

References 45 publications

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“…At the one-month follow-up control, our patients did not report major complaints and their creatinine levels were normal. However, past hantavirus infection can be associated with long-term chronic cardiovascular, renal, and endocrine disorders [ 27 , 30 ]. This implies a serious approach to patients with HFRS paired with studious follow-up.…”

Section: Discussionmentioning

confidence: 99%

Epidemiology and Clinical Course of Haemorrhagic Fever with Renal Syndrome in New Endemic Area for Hantavirus Infection in Croatia

Cekinović Grbeša,

Zahirović,

Flego

et al. 2023

Life

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Background: Hantaviruses remain an important case of emerging and re-emerging infections in human medicine. This study aimed to analyse the epidemiology, clinical presentation, and outcome of hantavirus infections in the western part of Republic of Croatia, a new geographical area for hantavirus infections. Methods: Retrospective analysis of medical records of patients treated for hemorrhagic fever with renal syndrome (HFRS) at the infectious diseases Clinic of the Clinical Hospital Center in Rijeka, Croatia, from 1 January 2014, to 31 December 2021. Results: During the eight-year period, 251 patients were hospitalized and treated for HFRS, with epidemic outbreaks in years 2014 and 2021. Most patients had a typical clinical course of HFRS and received supportive care. Serological analysis revealed the Puumala Virus (PUUV) as the predominant etiology of the disease. Epidemiological analysis revealed clustering of infections in the region of Gorski Kotar and spread to the area on the Mediterranean coast (Adriatic Sea), which was previously considered an area free from hantavirus infections. Conclusions: The presented results indicate the spread of hantavirus infections in Croatia from the central low-lying parts of the country to the tourist-attractive western area adjacent to the Mediterranean coast, which was previously considered free of hantavirus infections.

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Section: Discussionmentioning

confidence: 99%

Epidemiology and Clinical Course of Haemorrhagic Fever with Renal Syndrome in New Endemic Area for Hantavirus Infection in Croatia

Cekinović Grbeša,

Zahirović,

Flego

et al. 2023

Life

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“…This has been performed with two aims: (i) to understand better the pathogenesis of NE [ 4 ] and (ii) to use the biomarkers to predict the disease severity and long-term consequences of the disease [ 63 , 64 , 65 , 66 ]. As summarized in our recent review [ 67 ], cardiovascular, nephrological, and endocrinological consequences have been found in some patients, but severe complications are rare.…”

Section: Role Of Different Factors In the Variationmentioning

confidence: 99%

Puumala Hantavirus Infections Show Extensive Variation in Clinical Outcome

Vaheri

Smura

Vauhkonen

et al. 2023

Viruses

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The clinical outcome of Puumala hantavirus (PUUV) infection shows extensive variation, ranging from inapparent subclinical infection (70–80%) to severe hemorrhagic fever with renal syndrome (HFRS), with about 0.1% of cases being fatal. Most hospitalized patients experience acute kidney injury (AKI), histologically known as acute hemorrhagic tubulointerstitial nephritis. Why this variation? There is no evidence that there would be more virulent and less virulent variants infecting humans, although this has not been extensively studied. Individuals with the human leukocyte antigen (HLA) alleles B*08 and DRB1*0301 are likely to have a severe form of the PUUV infection, and those with B*27 are likely to have a benign clinical course. Other genetic factors, related to the tumor necrosis factor (TNF) gene and the C4A component of the complement system, may be involved. Various autoimmune phenomena and Epstein-Barr virus infection are associated with PUUV infection, but hantavirus-neutralizing antibodies are not associated with lower disease severity in PUUV HFRS. Wide individual differences occur in ocular and central nervous system (CNS) manifestations and in the long-term consequences of nephropathia epidemica (NE). Numerous biomarkers have been detected, and some are clinically used to assess and predict the severity of PUUV infection. A new addition is the plasma glucose concentration associated with the severity of both capillary leakage, thrombocytopenia, inflammation, and AKI in PUUV infection. Our question, “Why this variation?” remains largely unanswered.

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“…In addition, PUUV often results in complications and long-term hormonal, renal or cardiovascular consequences. (3) In Finland, PUUV has a significant impact on public health. The reported average incidence rate of diagnosed PUUV infections in Finland is 31-39 cases per 100,000 inhabitants.…”

Section: Introductionmentioning

confidence: 99%

“…In addition, PUUV often results in complications and long-term hormonal, renal or cardiovascular consequences. (3)…”

Section: Introductionmentioning

confidence: 99%

Genetic analysis implicatesERAP1and HLA as risk factors for severe Puumala virus infection

Haapaniemi,

Strausz,

Tervi

et al. 2024

Preprint

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Puumala virus (PUUV) infections can cause severe illnesses such as Hemorrhagic Fever with Renal Syndrome in humans. However, human genetic risk factors contributing to disease severity are still poorly understood. Our goal was to elucidate genetic factors contributing to PUUV infections and understand the biological mechanisms underlying individual vulnerability to the disease. Leveraging data from the FinnGen study, we conducted a genome-wide association study on severe Hemorrhagic Fever with Renal Syndrome caused by PUUV with 2,227 cases. We identified associations at the Human Leukocyte Antigen (HLA) locus andERAP1with severe PUUV infection. HLA molecules are canonical mediators for immune recognition and response.ERAP1facilitates immune system recognition and activation by cleaving viral proteins into smaller peptides which are presented to the immune system via HLA class I molecules. Notably, we identified that the lead variant (rs26653, OR = 0.84, p = 2.93×10-8) in theERAP1gene was a missense variant changing amino acid arginine to proline. From the HLA region, we showed independent and significant associations with both HLA class I and II genes. Furthermore, we showed independent associations with nine HLA alleles and severe PUUV infection using conditional HLA fine-mapping. The strongest association was found with theHLA-C*07:01allele (OR = 1.5, p = 4.0×10−24) followed by signals atHLA-B*13:02, HLA-DRB1*01:01, andHLA-DRB1*11:01alleles (p<5×10−8). Our findings suggest that viral peptide processing withERAP1and antigen presentation through HLA alleles contribute to the development of severe PUUV disease.

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Long-Term Consequences of Puumala Hantavirus Infection

Cited by 8 publications

References 45 publications

Epidemiology and Clinical Course of Haemorrhagic Fever with Renal Syndrome in New Endemic Area for Hantavirus Infection in Croatia

Epidemiology and Clinical Course of Haemorrhagic Fever with Renal Syndrome in New Endemic Area for Hantavirus Infection in Croatia

Puumala Hantavirus Infections Show Extensive Variation in Clinical Outcome

Genetic analysis implicatesERAP1and HLA as risk factors for severe Puumala virus infection

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