Severity Biomarkers in Puumala Hantavirus Infection

Annually, over 10,000 cases of hemorrhagic fever with renal syndrome (HFRS) are diagnosed in Europe. Puumala hantavirus (PUUV) causes most of the European HFRS cases. PUUV causes usually a relatively mild disease, which is rarely fatal. However, the severity of the infection varies greatly, and factors affecting the severity are mostly unrevealed. Host genes are known to have an effect. The typical clinical features in PUUV infection include acute kidney injury, thrombocytopenia, and increased vascular permeability. The primary target of hantavirus is the endothelium of the vessels of different organs. Although PUUV does not cause direct cytopathology of the endothelial cells, remarkable changes in both the barrier function of the endothelium and the function of the infected endothelial cells occur. Host immune or inflammatory mechanisms are probably important in the development of the capillary leakage. Several immunoinflammatory biomarkers have been studied in the context of assessing the severity of HFRS caused by PUUV. Most of them are not used in clinical practice, but the increasing knowledge about the biomarkers has elucidated the pathogenesis of PUUV infection.     

Long-Term Consequences of Puumala Hantavirus Infection

Several viral infections are associated with acute and long-term complications. During the past two years, there have been many reports on post-infectious symptoms of the patients suffering from COVID-19 disease. Serious complications occasionally occur during the acute phase of Puumala orthohantavirus caused nephropathia epidemica. Severe long-term consequences are rare. Fatigue for several weeks is quite common. Hormonal insufficiencies should be excluded if the patient does not recover normally.     

Population Ecology of Hantavirus Rodent Hosts in Southern Brazil

In this study we analyze population dynamics of hantavirus rodent hosts and prevalence of infection over a 2-year period in Southern Brazil, a region with a high incidence of hantavirus pulmonary syndrome. The 14 small mammal species captured were composed of 10 rodents and four marsupials, the six most abundant species being Akodon serrensis, Oxymycterus judex, Akodon montensis, Akodon paranaensis, Oligoryzomys nigripes, and Thaptomys nigrita. These species displayed a similar pattern with increasing population sizes in fall/winter caused by recruitment and both, increase in reproductive activity and higher hantavirus prevalence in spring/summer. Specific associations between A. montensis/Jaborá Virus (JABV) and O. nigripes/Juquitiba-like Virus (JUQV-like) and spillover infections between A. paranaensis/JABV, A. serrensis/JABV, and A. paranaensis/JUQV-like were observed. Spillover infection in secondary hosts seems to play an important role in maintaining JABV and JUQV-like in the hantavirus sylvatic cycle mainly during periods of low prevalence in primary hosts.     

Serological Evidence of Hantavirus Infection in Apparently Healthy People from Rural and Slum Communities in Southern Chile

Hantavirus disease in America has been recognizable because of its rapid progression in clinical cases, occurrence in previously healthy young adults, and high case fatality rate. Hantavirus disease has been proposed now to define the diversity of clinical manifestations. Since 1995, a total of 902 cases of hantavirus pulmonary syndrome have been reported in Chile, caused by Andes virus (ANDV), with overall fatality of 32%. This report describes the sero-epidemiology of hantavirus in apparently healthy people in rural and urban slum communities from southern Chile. Ten of 934 samples yielded a positive result resulting in a seroprevalence of 1.07% (95% confidence intervals: 0.05%–2.0%). A higher proportion of positive samples was found among individuals from rural villages (1.3%) and slums (1.5%) compared with farms (0.5%). Seropositivity was associated with age (p = 0.011), low education level (p = 0.006) and occupations linked to the household (homemaker, retired, or student) (p = 0.016). No evidence of infection was found in 38 sigmodontinae rodents trapped in the peri-domestic environment. Our findings highlight that exposure risk was associated with less documented risk factors, such as women in slum and rural villages, and the occurrence of infection that may have presented as flu-like illness that did not require medical attention or was misdiagnosed.     

First Molecular Evidence for Puumala Hantavirus in Poland

Puumala virus (PUUV) causes mild to moderate cases of haemorrhagic fever with renal syndrome (HFRS), and is responsible for the majority of hantavirus infections of humans in Fennoscandia, Central and Western Europe. Although there are relatively many PUUV sequences available from different European countries, little is known about the presence of this virus in Poland. During population studies in 2009 a total of 45 bank voles were trapped at three sites in north-eastern Poland, namely islands on Dejguny and Dobskie Lakes and in a forest near Mikołajki. S and M segment-specific RT-PCR assays detected PUUV RNA in three animals from the Mikołajki site. The obtained partial S and M segment sequences demonstrated the highest similarity to the corresponding segments of a PUUV strain from Latvia. Analysis of chest cavity fluid samples by IgG ELISA using a yeast-expressed PUUV nucleocapsid protein resulted in the detection of two seropositive samples, both being also RT-PCR positive. Interestingly, at the trapping site in Mikołajki PUUV-positive bank voles belong to the Carpathian and Eastern genetic lineages within this species. In conclusion, we herein present the first molecular evidence for PUUV in the rodent reservoir from Poland.     

Infection due to Hantavirus and other rodent-borne viruses

The term "robovirus" (rodent-borne virus) refers to viruses belonging to the Bunyaviridae (genus Hantavirus) and Arenaviridae families, which are occasionally transmitted to human beings from rodents, their natural hosts. Hantaviruses cause two human diseases: hemorrhagic fever with renal syndrome and hantavirus pulmonary syndrome. Arenaviruses produce hemorrhagic fevers or acute central nervous system disease in humans. This article reviews the biology, epidemiology, pathogenesis, clinical features, diagnostic methods, treatment and prevention of hantavirus and, more concisely, arenavirus infections.     

Recent Evidence of Hantavirus Circulation in the American Tropic

Hantaan virus was discovered in Korea during the 1970s while other similar viruses were later reported in Asia and Europe. There was no information about hantavirus human infection in the Americas until 1993 when an outbreak was described in the United States. This event promoted new studies to find hantaviruses in the Americas. At first, many studies were conducted in Brazil, Argentina, Chile, Uruguay and Paraguay, while other Latin American countries began to report the presence of these agents towards the end of the 20th century. More than 30 hantaviruses have been reported in the Western Hemisphere with more frequent cases registered in the southern cone (Argentina, Chile, Uruguay, Paraguay, Bolivia and Brazil). However there was an important outbreak in 2000 in Panama and some rare events have been described in Peru, Venezuela and French Guiana. Since hantaviruses have only recently emerged as a potential threat in the tropical zones of the Americas, this review compiles recent hantavirus reports in Central America, the Caribbean islands and the northern region of South America. These studies have generated the discovery of new hantaviruses and could help to anticipate the presentation of possible future outbreaks in the region.     

Hantavirus pulmonary syndrome in Brazil: clinical aspects of three new cases

Hantavirus pulmonary syndrome (HPS) has been recognized recently in Brazil, where 28 cases have been reported as of September 1999. We report here the clinical and laboratory findings of three cases whose diagnoses were confirmed serologically. All the patients were adults who presented a febrile illness with respiratory symptoms that progressed to respiratory failure that required artificial ventilation in two of them. Laboratory findings were most of the time consistent with those reported in the United States in patients infected with the Sin Nombre virus, and included elevated hematocrit and thrombocytopenia; presence of atypical lymphocytes was observed in one patient. The chest radiological findings observed in all the patients were bilateral, diffuse, reticulonodular infiltrates. Two patients died. Histopathological examination of the lungs of these patients revealed interstitial and alveolar edema, alveolar hemorrhage, and mild interstitial pneumonia characterized by infiltrate of immunoblasts and mononuclear cells. In the epidemiologic investigation of one of the cases, serologic (ELISA) tests were positive in 3 (25%) out of 12 individuals who shared the same environmental exposure. HPS should be included in the differential diagnosis of interstitial pneumonia progressing to acute respiratory failure.     

ABO and Rhesus Blood Groups in Acute Puumala Hantavirus Infection

Puumala hantavirus (PUUV) causes hemorrhagic fever with renal syndrome. We aimed to evaluate whether ABO and rhesus blood groups associate with the susceptibility or the severity of PUUV infection. We analyzed blood groups in 289 adult patients treated in Tampere University hospital due to PUUV infection during the years 1982–2017. Patients’ blood group distribution was compared to that of healthy, voluntary blood donors living in the Tampere University Hospital responsibility area (n = 21,833). The severity of PUUV infection, as judged by the severity of acute kidney injury (AKI), thrombocytopenia, inflammation, capillary leakage, and the length of hospital care, was analyzed across the groups. The ABO and rhesus blood group distributions did not differ between the patients and blood donors. Patients with non-O blood groups had lower systolic blood pressure compared to patients with blood group O, but there was no difference in other markers of capillary leakage or in the severity of AKI. Minor deviations in the number of platelets and leukocytes were detected between the O and non-O blood groups. To conclude, patients with blood group O may be less susceptible to hypotension, but otherwise blood groups have no major influences on disease susceptibility or severity during acute PUUV infection.     

Central Nervous System and Ocular Manifestations in Puumala Hantavirus Infection

Puumala hantavirus (PUUV), carried and spread by the bank vole (Myodes glareolus), causes a mild form of hemorrhagic fever with renal syndrome (HFRS) called nephropathia epidemica (NE). Acute high fever, acute kidney injury (AKI), thrombocytopenia, and hematuria are typical features of this syndrome. In addition, headache, blurred vision, insomnia, vertigo, and nausea are commonly associated with the disease. This review explores the mechanisms and presentations of ocular and central nervous system involvement in acute NE.     

The Prevalence of Viral Pathogens among Bats in Kazakhstan

Bats carry thousands of viruses from 28 different families. To determine the presence of various pathogens in bat populations in Kazakhstan, 1149 samples (393 oropharyngeal swabs, 349 brain samples, 407 guano) were collected. The samples were collected from four species of bats (Vespertilio murinus, Nyctalus noctula, Myotis blythii, Eptesicus serotinus) in nine regions. The Coronavirus RNA was found in 38 (4.75%) samples, and the rabies virus in 27 (7.74%) samples from bats. Coronaviruses and the rabies virus were found in bats in six out of nine studied areas. The RNAs of SARS-CoV-2, MERS, TBE, CCHF, WNF, influenza A viruses were not detected in the bat samples. The phylogeny of the RdRp gene of 12 samples made it possible to classify them as alphacoronaviruses and divide them into two groups. The main group (n = 11) was closely related to bat coronaviruses from Ghana, Zimbabwe and Kenya. The second group (n = 1) was closely related to viruses previously isolated in the south of Kazakhstan. The phylogeny of the N gene sequence from a bat from west Kazakhstan revealed its close relationship with isolates from the Cosmopolitan group of rabies viruses (Central Asia). These results highlight the need for a continuous monitoring of volatile populations to improve the surveillance and detection of infectious diseases.     

Kiwira Virus,a Newfound Hantavirus Discovered in Free-tailed Bats (Molossidae) in East and Central Africa

A novel hantavirus, named Kiwira virus, was molecularly detected in six Angolan free-tailed bats (Mops condylurus, family Molossidae) captured in Tanzania and in one free-tailed bat in the Democratic Republic of Congo. Hantavirus RNA was found in different organs, with the highest loads in the spleen. Nucleotide sequences of large parts of the genomic S and L segments were determined by in-solution hybridisation capture and high throughput sequencing. Phylogenetic analyses placed Kiwira virus into the genus Mobatvirus of the family Hantaviridae, with the bat-infecting Quezon virus and Robina virus as closest relatives. The detection of several infected individuals in two African countries, including animals with systemic hantavirus infection, provides evidence of active replication and a stable circulation of Kiwira virus in M. condylurus bats and points to this species as a natural host. Since the M. condylurus home range covers large regions of Sub-Saharan Africa and the species is known to roost inside and around human dwellings, a potential spillover of the Kiwira virus to humans must be considered.     

The Association between Hantavirus Infection and Selenium Deficiency in Mainland China

Hemorrhagic fever with renal syndrome (HFRS) caused by hantaviruses and transmitted by rodents is a significant public health problem in China, and occurs more frequently in selenium-deficient regions. To study the role of selenium concentration in HFRS incidence we used a multidisciplinary approach combining ecological analysis with preliminary experimental data. The incidence of HFRS in humans was about six times higher in severe selenium-deficient and double in moderate deficient areas compared to non-deficient areas. This association became statistically stronger after correction for other significant environment-related factors (low elevation, few grasslands, or an abundance of forests) and was independent of geographical scale by separate analyses for different climate regions. A case-control study of HFRS patients admitted to the hospital revealed increased activity and plasma levels of selenium binding proteins while selenium supplementation in vitro decreased viral replication in an endothelial cell model after infection with a low multiplicity of infection (MOI). Viral replication with a higher MOI was not affected by selenium supplementation. Our findings indicate that selenium deficiency may contribute to an increased prevalence of hantavirus infections in both humans and rodents. Future studies are needed to further examine the exact mechanism behind this observation before selenium supplementation in deficient areas could be implemented for HFRS prevention.     

Predictable Chikungunya Infection Dynamics in Brazil

Chikungunya virus (CHIKV) was first imported into the Caribbean in 2013 and subsequently spread across the Americas. It has infected millions in the region and Brazil has become the hub of ongoing transmission. Using Seasonal Autoregressive Integrated Moving Average (SARIMA) models trained and validated on Brazilian data from the Ministry of Health’s notifiable diseases information system, we tested the hypothesis that transmission in Brazil had transitioned from sporadic and explosive to become more predictable. Consistency weighted, population standardized kernel density estimates were used to identify municipalities with the most consistent inter-annual transmission rates. Spatial clustering was assessed per calendar month for 2017–2021 inclusive using Moran’s I. SARIMA models were validated on 2020–2021 data and forecasted 106,162 (95%CI 27,303–200,917) serologically confirmed cases and 339,907 (95%CI 35,780–1035,449) total notifications for 2022–2023 inclusive, with >90% of cases in the Northeast and Southeast regions. Comparing forecasts for the first five months of 2022 to the most up-to-date ECDC report (published 2 June 2022) showed remarkable accuracy: the models predicted 92,739 (95%CI 20,685–195,191) case notifications during which the ECDC reported 92,349 case notifications. Hotspots of consistent transmission were identified in the states of Para and Tocantins (North region); Rio Grande do Norte, Paraiba and Pernambuco (Northeast region); and Rio de Janeiro and eastern Minas Gerais (Southeast region). Significant spatial clustering peaked during late summer/early autumn. This analysis highlights how CHIKV transmission in Brazil has transitioned, making it more predictable and thus enabling improved control targeting and site selection for trialing interventions.     

Alcohol Consumption and Its Influence on the Clinical Picture of Puumala Hantavirus Infection

Puumala hantavirus (PUUV) causes hemorrhagic fever with renal syndrome. Characteristic clinical findings include acute kidney injury (AKI), thrombocytopenia, and capillary leakage. Smoking increases the risk of severe AKI, but it is not known whether alcohol consumption predisposes patients to a more severe infection. Liver and pancreatic enzymes, as well as biomarkers of alcohol consumption (gamma-glutamyl transferase, GGT; carbohydrate-deficient transferrin, CDT; GGT-CDT combination; and ethyl glucuronide, EtG), were measured from 66 patients with acute PUUV infection during hospitalization and at the convalescence phase. Alcohol consumption was present in 41% of the study population, 15% showing signs of heavy drinking. Alcohol use did not affect the severity of PUUV induced AKI nor the overall clinical picture of the infection. Liver enzyme levels (GGT or alanine aminotransferase, ALT) were elevated in 64% of the patients, but the levels did not associate with the markers reflecting the severity of the disease. Serum amylase activities at the convalescent stage were higher than those at the acute phase (p < 0.001). No cases with acute pancreatitis were found. In conclusion, our findings indicate that alcohol consumption does not seem to affect the clinical course of an acute PUUV infection.     

Evidence for genetic susceptibility to developing early childhood diarrhea among shantytown children living in northeastern Brazil

To explore the genetic components of susceptibility to early childhood diarrhea (ECD), we used a quantitative genetic approach to estimate the heritability of ECD among children from two Brazilian favelas. Shared environment was used to model common exposure to environmental factors. Genetic relatedness was determined from pedigree information collected by screening household participants (n = 3,267) from two geographically related favelas located in Fortaleza, Brazil. There were 277 children within these pedigrees for whom diarrheal episodes in the first two years of life were recorded. Data on environmental exposure and pedigree relationship were combined to quantitatively partition phenotypic variance in ECD into environmental and genetic components by using a variance components approach as implemented in Sequential Oligogenic Linkage Analysis Routines program. Heritability accounted for 54% of variance in ECD and proximity of residence effect accounted for 21% (P < 0.0001). These findings suggest a substantial genetic component to ECD susceptibility and the potential importance of future genetics studies.     

Evidence for affluence-related hypertension in urban Brazil

Cardiovascular diseases are a leading cause of mortality, and systemic hypertension is a major risk factor. There is an increasing prevalence of hypertension in urban areas of developing countries, due to lifestyle changes associated with economic transition and urbanisation. This study aimed to describe the prevalence and identify risk factors for hypertension in an urban area of South America (Coroa do Meio district in Aracaju, Sergipe State, north-east Brazil) and to examine intraurban hypertension prevalence differences. A cross-sectional survey of 400 adults aged 25 years and over was carried out. Information about health and lifestyle was obtained from a structured interview, followed by assessment of blood pressure (BP) and anthropometry. There were 31.8% (95% confidence interval 27.3-36.6%) participants with hypertension (defined as a systolic BP >140, diastolic BP >90 mmHg, or on antihypertensive medication). Hypertension was independently associated with older age, central obesity (greater waist-to-hip ratio), shorter height and residing in a high socio-economic residential area. Of the four neighbouring areas, hypertension prevalence was 52% in the area of highest income and education, compared with 19, 24 and 34% in the other three areas. The high prevalence of hypertension in this population, and the strong independent association with relative affluence, demonstrates the need for effective primary prevention of hypertension, targeted at modifiable risk factors.     

Overdoses among cocaine users in Brazil

Aims. A survey of cocaine users was undertaken to study (i) the frequency of reported drug overdoses among cocaine users; and (ii) the frequency of witnessing drug overdoses in the same population.
Design and setting. A cross-sectional study as part of the World Health Organization (WHO) Multi-city Study among injecting drug users (IDUs), phase II, was conducted in Santos Metropolitan Region, State of São Paulo, Brazil, in 1999.
Participants. Three hundred and ninety-six exclusive users of cocaine in the Santos Metropolitan Region, São Paulo State, Brazil were surveyed concerning their past experience with drug overdoses.
Findings. Eighty (20%) of the cocaine users reported having experienced one or more overdoses, and 50% reported that they knew one or more other cocaine users who had died of an overdose. On multivariate analysis, being female and having spent time in jail were associated with an increased likelihood of having had one or more overdoses.
Conclusion. Cocaine overdoses are an important and under-recognized health problem in the Santos Metropolitan Region, and possibly in other areas of Brazil.