Magnus Evander - Academia.edu (original) (raw)

Papers by Magnus Evander

Research paper thumbnail of Acetowhitening of the cervix and vulva as a predictor of subclinical human papillomavirus infection: Sensitivity and specificity in a population-based study

Obstetrics and Gynecology, 1997

To evaluate acetowhite changes of the cervix and vulva as a predictor of human papillomavirus (HP... more To evaluate acetowhite changes of the cervix and vulva as a predictor of human papillomavirus (HPV) infection.In this population-based study all women aged 19, 21, 23, and 25 years and registered as living in a primary health care area within the city of Ume, Sweden were eligible for inclusion. Each participant underwent a gynecologic examination with sampling of epithelial cells for HPV-DNA detection and Papanicolaou smear. Colposcopy was performed 5 minutes after application of 5% acetic acid. A two-step polymerase chain reaction (PCR) technique was employed for HPV-DNA detection.Colposcopy and sampling of epithelial cells could be performed in 535 women. The sensitivity of detection of HPV infection by the acetowhitening of the cervix was 22% (95% confidence interval [CI] 18%, 26%). The specificity of detection of HPV infection by the acetowhitening of the cervix was 90% (95% CI 87%, 93%). The sensitivity of detection of HPV infection by cytology was 13% (95% CI 10%, 16%), and the specificity was 99% (95% CI 98%, 100%). The combination of acetowhitening and cytology did not improve the diagnostic value.Acetowhitening of the cervix and vulva has low sensitivity as a predictor of HPV infections as determined by PCR.

Research paper thumbnail of The Influence of Sexual and Social Factors on the Risk of Chlamydia trachomatis Infections: A Population-Based Serologic Study

Sexually Transmitted Diseases, 1995

Genital chlamydia infections often are asymptomatic, which promotes their spread in the populatio... more Genital chlamydia infections often are asymptomatic, which promotes their spread in the population. In women, the possible consequences of infection are pelvic inflammatory disease and infertility. Most studies on the prevalence of Chlamydia trachomatis have been based on clinical series, and prevalences tend to vary with the clinical setting. Few seroepidemiologic studies have emerged from industrialized countries. To assess the prevalence of Chlamydia trachomatis using culture and serology, and its relationship with possible risk factors. This was a population-based study involving completion of a self-administered questionnaire, analysis of cervical samples for Chlamydia trachomatis, and serologic tests for Chlamydia trachomatis antibodies. The prevalence of Chlamydia trachomatis infection was 2.7%, and the seroprevalence was 24.7% among the sexually active women. Seropositivity was correlated with sexual behavior variables, and the incidence of serologic cross-reactivity with respiratory infections (strain TWAR) was low. Multivariate logistic regression analysis showed the number of sexual partners, age at first coitus, history of therapeutic abortion, and previous pelvic inflammatory disease to be independently correlated with seropositivity. Early sexual experience and multiple lifetime sexual partners are independent risk factors for Chlamydia trachomatis infection.

Research paper thumbnail of Lifetime Number of Partners As the Only Independent Risk Factor for Human Papillomavirus Infection: A Population-Based Study

Sexually Transmitted Diseases, 1995

Previous studies of relationships between genital human papillomavirus infection and tentative ri... more Previous studies of relationships between genital human papillomavirus infection and tentative risk factors have yielded conflicting results, possibly because of inaccuracy of the viral detection methods used and differences in selection criteria. To determine human papillomavirus prevalence and identify risk factors in a group of young Swedish women. This was a population-based study involving completion of a structured questionnaire, analysis of cervical scrapings for human papillomavirus and Chlamydia trachomatis, and serologic tests for C. trachomatis and herpes simplex virus antibodies. The prevalence of human papillomavirus infection was 22% among the sexually active women and 4% among the virgins. A number of factors were associated with human papillomavirus prevalence in univariate analysis, but logistic regression analysis showed that lifetime number of male sexual partners was the only independent risk factor for human papillomavirus infection (adjusted odds ratio, 7.45; 95% CI, 2.79-19.92 for six or more partners vs. one partner). Human papillomavirus infection is a prevalent sexually transmitted disease among young Swedish women, and the lifetime number of male sexual partners is a major risk factor.

Research paper thumbnail of The geographic distribution of mosquito species in Sweden

Journal of the American Mosquito Control Association

Surveillance of the actual distribution of mosquito species in Northern Europe is fundamental for... more Surveillance of the actual distribution of mosquito species in Northern Europe is fundamental for evaluating risk for emerging pathogens, and for research on potential vectors. The Swedish mosquito fauna composition and geographic distribution, originally described by Professor Christine Dahl in the 1970´s, included 43 species. We have compiled the information published from 1978 to 2012, and our own surveillance data from 2001 to 2013, and compared this with the species list and geographic distribution provided in “Taxonomy and geographic distribution of Swedish Culicidae” by Dahl (1977). New species detected during these 36 years were Culiseta (Culicella) ochroptera (Peus, 1935) published 1984, Aedes (Aedes) rossicus Dolbeskin, Goritzkaja & Mitrofanova, 1930 published 1986, Anopheles (Anopheles) beklemishevi published 1986, Aedes (Ochlerotatus) euedes (Howard, Dyar & Knab, 1912) published 2001, Aedes (Ochlerotatus) nigrinus (Eckstein, 1918) first recorded in 2012, and Anopheles (A...

Research paper thumbnail of A Novel and Rapid PCR-based Method for Genotyping Human Papillomaviruses in Clinical Samples

Many human papillomavirus (HPV) genotypes are associated with cervical carcinoma. We demonstrate ... more Many human papillomavirus (HPV) genotypes are associated with cervical carcinoma. We demonstrate the utility of an innovative technique for genotyping of HPV in cervical tissue samples. This method provides an accurate means of identification of the specific HPV genotypes present in clinical specimens. By using the MY09-MY11 and the GP5+-GP6+ consensus primer pairs, HPV sequences were amplified by nested PCR

Research paper thumbnail of The Importance of Bank Vole Density and Rainy Winters in Predicting Nephropathia Epidemica Incidence in Northern Sweden

PLoS ONE, 2014

Pathogenic hantaviruses (family Bunyaviridae, genus Hantavirus) are rodent-borne viruses causing ... more Pathogenic hantaviruses (family Bunyaviridae, genus Hantavirus) are rodent-borne viruses causing hemorrhagic fever with renal syndrome (HFRS) in Eurasia. In Europe, there are more than 10,000 yearly cases of nephropathia epidemica (NE), a mild form of HFRS caused by Puumala virus (PUUV). The common and widely distributed bank vole (Myodes glareolus) is the host of PUUV. In this study, we aim to explain and predict NE incidence in boreal Sweden using bank vole densities. We tested whether the number of rainy days in winter contributed to variation in NE incidence. We forecast NE incidence in July 2013-June 2014 using projected autumn vole density, and then considering two climatic scenarios: 1) rain-free winter and 2) winter with many rainy days. Autumn vole density was a strong explanatory variable of NE incidence in boreal Sweden in 1990-2012 (R 2 = 79%, p,0.001). Adding the number of rainy winter days improved the model (R 2 = 84%, p,0.05). We report for the first time that risk of NE is higher in winters with many rainy days. Rain on snow and ground icing may block vole access to subnivean space. Seeking refuge from adverse conditions and shelter from predators, voles may infest buildings, increasing infection risk. In a rainy winter scenario, we predicted 812 NE cases in boreal Sweden, triple the number of cases predicted in a rain-free winter in 2013/2014. Our model enables identification of high risk years when preparedness in the public health sector is crucial, as a rainy winter would accentuate risk.

Research paper thumbnail of A need for One Health approach – lessons learned from outbreaks of Rift Valley fever in Saudi Arabia and Sudan

Infection Ecology & Epidemiology, 2014

Research paper thumbnail of Vaccination with virus-like particles protects mice from lethal infection of Rift Valley Fever Virus

Research paper thumbnail of Presentation of the HPV16E7 protein by skin grafts is insufficient to allow graft rejection in an E7-primed animal

The E7 transforming protein of Human Papillomavirus type 16 (HPV16) is expressed in the skin of a... more The E7 transforming protein of Human Papillomavirus type 16 (HPV16) is expressed in the skin of a line of FVB mice transgenic for the E6 and E7 open reading frames of HPV16 driven from the alpha A crystallin promoter (FVB alpha AcryHPV16E6E7). We have transferred skin from FVB alpha AcryHPV16E6E7 mice to naive or E7-primed syngeneic FVB recipients to assess whether the E7 protein of HPV16 can function as a minor transplantation antigen (MTA) and promote skin graft rejection. FVB mice did not reject E7 expressing tail or flank skin grafts. E7 immunized FVB x C57BL/6J mice recipients of FVB alpha-AcryHPV16E6E7 x C57BL/6J skin generated humoral and DTH responses to E7 in vivo and E7-specific CTL precursors in the spleen, but failed to reject E7 expressing tail skin grafts by 100 days posttransfer. Thus although HPV16 E7 + ve mesenchymal and endodermal tumors can be eliminated by an E7-specific immune response, the same protein is unable to act as a MTA and promote graft rejection when expressed in skin cells. Lack of rejection of grafts expressing MTAs such as E7 may be relevant to the immunology of epithelial tumors expressing tumor-specific antigens and to our understanding of the immunology of diseases of the skin.

Research paper thumbnail of Milder winters in northern Scandinavia may contribute to larger outbreaks of haemorrhagic fever virus

Global Health Action, 2009

The spread of zoonotic infectious diseases may increase due to climate factors such as temperatur... more The spread of zoonotic infectious diseases may increase due to climate factors such as temperature, humidity and precipitation. This is also true for hantaviruses, which are globally spread haemorrhagic fever viruses carried by rodents. Hantaviruses are frequently transmitted to humans all over the world and regarded as emerging viral diseases. Climate variations affect the rodent reservoir populations and rodent population peaks coincide with increased number of human cases of hantavirus infections. In northern Sweden, a form of haemorrhagic fever called nephropathia epidemica (NE), caused by the Puumala hantavirus (PUUV) is endemic and during 2006Á2007 an unexpected, sudden and large outbreak of NE occurred in this region. The incidence was 313 cases/100,000 inhabitants in the most endemic areas, and from January through March 2007 the outbreak had a dramatic and sudden start with 474 cases in the endemic region alone. The PUUV rodent reservoir is bank voles and immediately before and during the peak of disease outbreak the affected regions experienced extreme climate conditions with a record-breaking warm winter, registering temperatures 6Á98C above normal. No protective snow cover was present before the outbreak and more bank voles than normal came in contact with humans inside or in close to human dwellings. These extreme climate conditions most probably affected the rodent reservoir and are important factors for the severity of the outbreak.

Research paper thumbnail of Lifetime Number of Partners As the Only Independent Risk Factor for Human Papillomavirus Infection

Sexually Transmitted Diseases, 1995

Previous studies of relationships between genital human papillomavirus infection and tentative ri... more Previous studies of relationships between genital human papillomavirus infection and tentative risk factors have yielded conflicting results, possibly because of inaccuracy of the viral detection methods used and differences in selection criteria. To determine human papillomavirus prevalence and identify risk factors in a group of young Swedish women. This was a population-based study involving completion of a structured questionnaire, analysis of cervical scrapings for human papillomavirus and Chlamydia trachomatis, and serologic tests for C. trachomatis and herpes simplex virus antibodies. The prevalence of human papillomavirus infection was 22% among the sexually active women and 4% among the virgins. A number of factors were associated with human papillomavirus prevalence in univariate analysis, but logistic regression analysis showed that lifetime number of male sexual partners was the only independent risk factor for human papillomavirus infection (adjusted odds ratio, 7.45; 95% CI, 2.79-19.92 for six or more partners vs. one partner). Human papillomavirus infection is a prevalent sexually transmitted disease among young Swedish women, and the lifetime number of male sexual partners is a major risk factor.

Research paper thumbnail of The 2007 Rift Valley Fever Outbreak in Sudan

PLoS Neglected Tropical Diseases, 2011

Rift Valley fever (RVF) is a neglected, emerging, mosquito-borne disease with severe negative imp... more Rift Valley fever (RVF) is a neglected, emerging, mosquito-borne disease with severe negative impact on human and animal health and economy. RVF is caused by RVF virus (RVFV) affecting humans and a wide range of animals. The virus is transmitted through bites from mosquitoes and exposure to viremic blood, body fluids, or tissues of infected animals. During 2007 a large RVF outbreak occurred in Sudan with a total of 747 confirmed human cases including 230 deaths (case fatality 30.8%); although it has been estimated 75,000 were infected. It was most severe in White Nile, El Gezira, and Sennar states near to the White Nile and the Blue Nile Rivers. Notably, RVF was not demonstrated in livestock until after the human cases appeared and unfortunately, there are no records or reports of the number of affected animals or deaths. Ideally, animals should serve as sentinels to prevent loss of human life, but the situation here was reversed. Animal contact seemed to be the most dominant risk factor followed by animal products and mosquito bites. The Sudan outbreak followed an unusually heavy rainfall in the country with severe flooding and previous studies on RVF in Sudan suggest that RVFV is endemic in parts of Sudan. An RVF outbreak results in human disease, but also large economic loss with an impact beyond the immediate influence on the directly affected agricultural producers. The outbreak emphasizes the need for collaboration between veterinary and health authorities, entomologists, environmental specialists, and biologists, as the best strategy towards the prevention and control of RVF.

Research paper thumbnail of Kinetics of Rift Valley Fever Virus in experimentally infected mice using quantitative real-time RT-PCR

Journal of Virological Methods, 2008

Rift Valley Fever (RVF) is an important viral zoonosis in Africa affecting animals and humans. Si... more Rift Valley Fever (RVF) is an important viral zoonosis in Africa affecting animals and humans. Since no protective vaccines or effective treatments are available for human use, accurate and reliable diagnostic methods are essential for surveillance of the disease in order to implement adequate public health actions. To study the kinetics of the RVF Virus (RVFV) infection, a SYBR Green-based quantitative real-time RT-PCR assay was developed. By using primers targeting the S-segment of RVFV, the detection limit of this assay was estimated to 30 RNA templates. Blood and organs of experimentally infected mice were sampled at different time points and RVFV RNA was quantified. High amounts of RVFV RNA were found in blood, brain, and liver samples shortly after infection with a 1-4 days post infection window for viral RNA detection. Mice developed symptoms after the appearance of serum antibodies, indicating that the host response plays an important role in the outcome of the disease. The RVFV quantitative RT-PCR proved to be a valuable diagnostic tool during the first days of infection, before detectable antibody levels and visual symptoms of RVF were observed.

Research paper thumbnail of Hantavirus-specific IgA in saliva and viral antigen in the parotid gland in patients with hemorrhagic fever with renal syndrome

Journal of Medical Virology, 2011

The Hantavirus genus comprises rodent borne, zoonotic viruses of the Bunyaviridae family that cau... more The Hantavirus genus comprises rodent borne, zoonotic viruses of the Bunyaviridae family that cause hemorrhagic fever with renal syndrome (HFRS) in Eurasia and hantavirus cardiopulmonary syndrome (HCPS) in the Americas. Rodent saliva contains infectious hantavirus and evidence suggests that hantavirus is also shed in human saliva, but person-to-person transmission is rare. In saliva, immunoglobulin (Ig) A is the predominant immunoglobulin class. Secretory IgA serves as an important first line of defence on epithelial surfaces and the binding of secretory IgA to pathogens can inhibit adherence of microorganisms to mucosal cells and neutralize viruses. This study investigated the presence and importance of salivary IgA in relation to viral antigen in the saliva by testing Puumala hantavirus (PUUV) specific IgA, and RNA in saliva in acutely ill patients with HFRS. In saliva samples, PUUV specific IgA was detected in 12 of 33 (36%) patients with HFRS and 20 (61%) were PUUV RNA positive. There was a statistically significant inverse association between the presence of salivary IgA antibodies and PUUV RNA in the saliva. PUUV-specific IgA in saliva was not found in a long-term follow-up, while PUUV IgA in serum was detected in three patients, 28-32 months after the initial study. Notably, both PUUV RNA and PUUV nucleocapsid antigen were detected in endothelial cells within the parotid gland of a deceased patient with HFRS.

Research paper thumbnail of Puumala Hantavirus Viremia Diagnosed by Real-Time Reverse Transcriptase PCR Using Samples from Patients with Hemorrhagic Fever and Renal Syndrome

Journal of Clinical Microbiology, 2007

(NE), a milder form of hemorrhagic fever with renal syndrome. There is a need for fast and reliab... more (NE), a milder form of hemorrhagic fever with renal syndrome. There is a need for fast and reliable diagnostics to differentiate the disease from other infections. By aligning virus RNA sequences isolated from 11 different bank voles and one human patient, we designed a real-time reverse transcriptase (RT) PCR method for detection of PUUV RNA. The real-time RT-PCR assay showed linearity from 20 to 2 ؋ 10 6 virus copies with a correlation coefficient above 0.98 to 0.99 for all experiments. The detection threshold for PUUV cDNA was two copies per reaction. A two-step qualitative RT-PCR to detect PUUV RNA showed 100% concordance with the real-time RT-PCR assay. PUUV RNA viremia was detected in 33 of 34 PUUV immunoglobulin M (IgM)positive patients with typical clinical NE disease from the region of endemicity. One PUUV IgM-negative sample had PUUV RNA, and 4 days later, the patient was IgM positive. Of samples with indeterminate IgM, 43% were PUUV RNA positive. The kinetics of antibody titers and PUUV viremia were studied, and five of six NE patients displayed a decrease in PUUV viremia a few days after disease outbreak coupled with an increase in PUUV IgM and IgG. In one patient with continuously high PUUV RNA levels but low IgM and no IgG response, the infection was lethal. These findings demonstrated that real-time RT-PCR is a useful method for diagnosis of PUUV viremia and for detecting PUUV RNA at early time points, before the appearance of IgM antibodies. . Samples were handled according to routine instructions and analyzed by IF within 1 to 2 days after sampling. A qualitative two-step RT-PCR and a quantitative one-step real-time RT-PCR analysis were performed later on samples stored at Ϫ80°C. The project was approved by the Construction of synthetic standard PUUV RNA. Standard PUUV RNA was constructed from a pT7Blue-3 vector (Novagen, Darmstadt, Germany) with a cloned 501-bp cDNA fragment of the S gene (strain Umeå/hu; accession no. AY526219). The insert was sequenced to locate the 5Ј-to-3Ј direction and to certify 100% homology to the primers and probe. This was important to ensure the same efficiency in quantitation of the standard curve and the patient samples. The plasmid was linearized with the restriction enzyme SacI and used as a template for RNA transcription using the MEGAscript High Yield Transcription Kit (Ambion, Austin, TX) according to the manufacturer's protocol. The synthesized RNA was incubated with DNase at 37°C for 15 min, purified by phenolchloroform extraction and isopropanol precipitation, and finally resuspended in 40 l of nuclease-free water with 40 U recombinant RNasin RNase inhibitor (Promega, Madison, WI). RNA dilutions of 10 Ϫ4 to 10 Ϫ9 were analyzed by real-time PCR with and without a prior RT reaction step to ensure a DNA template concentration of less than 0.2%. DNA contamination equal to or above 0.2% required DNase treatment of the RNA. The RNA concentration was measured spectrophotometrically, and RNA at Ն1 ϫ 10 8

Research paper thumbnail of The anti-papillomavirus activity of human and bovine lactoferricin

Antiviral Research, 2007

Human papillomavirus (HPV) cause common warts, laryngeal papilloma and genital condylomata and is... more Human papillomavirus (HPV) cause common warts, laryngeal papilloma and genital condylomata and is necessary for the development of cervical cancer. We have previously found that lactoferrin has antiviral activity against HPV-16 and others have demonstrated that lactoferricin, an N-terminal fragment of lactoferrin, has inhibitory activities against several viruses. Two cell lines and two virus types, HPV-5 and HPV-16, were used to study if lactoferrin and lactoferricin could inhibit HPV pseudovirus (PsV) infection. We demonstrated that bovine lactoferrin (bLf) and human lactoferrin (hLf) were both potent inhibitors of HPV-5 and -16 PsV infections. Among the four lactoferricin derivatives we analyzed, a 15 amino acid peptide from bovine lactoferricin (bLfcin) 17-31 was the most potent inhibitor of both HPV-5 and HPV-16 PsV infection. Among the other derivatives, the human lactoferricin (hLfcin) 1-49 showed some antiviral activity against HPV PsV infection while bLfcin 17-42 inhibited only HPV-5 PsV infection in one of the cell lines. When we studied initial attachment of HPV-16, only bLfcin 17-42 and hLfcin 1-49 had an antiviral effect. This is the first time that lactoferricin was demonstrated to have an inhibitory effect on HPV infection and the antiviral activity differed depending on size, charge and structures of the lactoferricin.

Research paper thumbnail of Relation between the presence of human papillomavirus type 16 deoxyribonucleic acid in cervicovaginal cells and general health condition

American Journal of Obstetrics and Gynecology, 1993

Cervicovaginal cell samples were analyzed for the presence of human papillomavirus type 16 deoxyr... more Cervicovaginal cell samples were analyzed for the presence of human papillomavirus type 16 deoxyribonucleic acid. All 99 women included in the study had normal Papanicolaou smear results, normal findings on wet smear, and no clinical signs of genital papillomavirus or any other genital infection. Deoxyribonucleic acid polymerase chain reaction was performed with three different human papillomavirus type 16-specific primer pairs from the early 6, early 7, and upstream regulatory regions. Human papillomavirus type 16 was detected in 21% of the 99 women. Seven of 69 women (10%) who were not taking any medication except for cyclic estrogen or progestin replacement therapy were carriers of human papillomavirus type 16. Seven of 19 women (37%) who used hormonal contraceptives or who sought early pregnancy termination were carriers of human papillomavirus type 16. All 7 women with diseases that required frequent hospital care were carriers of human papillomavirus type 16. The 4 women who had never had sexual intercourse were not carriers of human papillomavirus type 16. Our results indicate that the human papillomavirus type 16 prevalence in women may reflect to some extent the general health conditions of the patients.

Research paper thumbnail of Papilloma Virus Infection of the Vulva

Acta Obstetricia et Gynecologica Scandinavica, 1989

Analyses of the possible presence of human papilloma virus (HPV) DNA were performed on 84 biopsie... more Analyses of the possible presence of human papilloma virus (HPV) DNA were performed on 84 biopsies from 50 women with clinically and histopathologically suspected HPV infection of the vulva. The colposcopic criteria for inclusion in the study were: acetowhite flat lesions with or without fissures and/or diffuse hyperplastic mucosa with a granulated or filamental surface. Directed biopsies for histopathology and DNA hybridization (dot-blot and Southern-blot) were taken. All women had histopathological evidence of HPV infection. Twelve women had cervical and/or vulvar neoplasia. HPV DNA could be demonstrated in the vulvar biopsies from 24 women; 13 women had HPV 16, 3 had HPV 18, HPV 31 and HPV 33, respectively. In addition, 10 biopsies contained HPV DNA of unknown types. Fifty-five percent of granulated and filamental lesions and 43% of flat lesions with or without fissures were positive for HPV DNA. 34 women had one or more of the following symptoms: itching, burning, dyspareunia, discharge, fissures, dryness and dysuria. Papillomavirus vulvitis is a sexually transmitted disease which may cause recalcitrant symptoms and/or concomitant neoplasia. It is thus important to recognize the different symptoms and signs of this disease.

Research paper thumbnail of Dynamics and Drivers of Hantavirus Prevalence in Rodent Populations

Vector-Borne and Zoonotic Diseases, 2014

Human encroachment on wildlife habitats has contributed to the emergence of several zoonoses. Pat... more Human encroachment on wildlife habitats has contributed to the emergence of several zoonoses. Pathogenic hantaviruses are hosted by rodents and cause severe diseases in the Americas and Eurasia. We reviewed several factors that potentially drive prevalence (the proportion of infected rodents) in host populations. These include demography, behavior, host density, small mammal diversity, predation, and habitat and landscape characteristics. This review is the first to include a quantitative summary of the literature investigating hantavirus prevalence in rodents. Demographic structure and density were investigated the most and predation the least. Reported effects of demographic structure and small mammal diversity were consistent, whereby reproductive males were most likely to be infected and prevalence decreased with small mammal diversity. The influences of habitat and landscape properties are often complex and indirect. The relationship between density and prevalence merits more investigation. Most hantavirus hosts are habitat generalists and their control is challenging. Incorporating all potential factors and their interactions is essential to understanding and controlling infection in host populations.

Research paper thumbnail of Acetowhitening of the cervix and vulva as a predictor of subclinical human papillomavirus infection: Sensitivity and specificity in a population-based study

Obstetrics and Gynecology, 1997

To evaluate acetowhite changes of the cervix and vulva as a predictor of human papillomavirus (HP... more To evaluate acetowhite changes of the cervix and vulva as a predictor of human papillomavirus (HPV) infection.In this population-based study all women aged 19, 21, 23, and 25 years and registered as living in a primary health care area within the city of Ume, Sweden were eligible for inclusion. Each participant underwent a gynecologic examination with sampling of epithelial cells for HPV-DNA detection and Papanicolaou smear. Colposcopy was performed 5 minutes after application of 5% acetic acid. A two-step polymerase chain reaction (PCR) technique was employed for HPV-DNA detection.Colposcopy and sampling of epithelial cells could be performed in 535 women. The sensitivity of detection of HPV infection by the acetowhitening of the cervix was 22% (95% confidence interval [CI] 18%, 26%). The specificity of detection of HPV infection by the acetowhitening of the cervix was 90% (95% CI 87%, 93%). The sensitivity of detection of HPV infection by cytology was 13% (95% CI 10%, 16%), and the specificity was 99% (95% CI 98%, 100%). The combination of acetowhitening and cytology did not improve the diagnostic value.Acetowhitening of the cervix and vulva has low sensitivity as a predictor of HPV infections as determined by PCR.

Research paper thumbnail of The Influence of Sexual and Social Factors on the Risk of Chlamydia trachomatis Infections: A Population-Based Serologic Study

Sexually Transmitted Diseases, 1995

Genital chlamydia infections often are asymptomatic, which promotes their spread in the populatio... more Genital chlamydia infections often are asymptomatic, which promotes their spread in the population. In women, the possible consequences of infection are pelvic inflammatory disease and infertility. Most studies on the prevalence of Chlamydia trachomatis have been based on clinical series, and prevalences tend to vary with the clinical setting. Few seroepidemiologic studies have emerged from industrialized countries. To assess the prevalence of Chlamydia trachomatis using culture and serology, and its relationship with possible risk factors. This was a population-based study involving completion of a self-administered questionnaire, analysis of cervical samples for Chlamydia trachomatis, and serologic tests for Chlamydia trachomatis antibodies. The prevalence of Chlamydia trachomatis infection was 2.7%, and the seroprevalence was 24.7% among the sexually active women. Seropositivity was correlated with sexual behavior variables, and the incidence of serologic cross-reactivity with respiratory infections (strain TWAR) was low. Multivariate logistic regression analysis showed the number of sexual partners, age at first coitus, history of therapeutic abortion, and previous pelvic inflammatory disease to be independently correlated with seropositivity. Early sexual experience and multiple lifetime sexual partners are independent risk factors for Chlamydia trachomatis infection.

Research paper thumbnail of Lifetime Number of Partners As the Only Independent Risk Factor for Human Papillomavirus Infection: A Population-Based Study

Sexually Transmitted Diseases, 1995

Previous studies of relationships between genital human papillomavirus infection and tentative ri... more Previous studies of relationships between genital human papillomavirus infection and tentative risk factors have yielded conflicting results, possibly because of inaccuracy of the viral detection methods used and differences in selection criteria. To determine human papillomavirus prevalence and identify risk factors in a group of young Swedish women. This was a population-based study involving completion of a structured questionnaire, analysis of cervical scrapings for human papillomavirus and Chlamydia trachomatis, and serologic tests for C. trachomatis and herpes simplex virus antibodies. The prevalence of human papillomavirus infection was 22% among the sexually active women and 4% among the virgins. A number of factors were associated with human papillomavirus prevalence in univariate analysis, but logistic regression analysis showed that lifetime number of male sexual partners was the only independent risk factor for human papillomavirus infection (adjusted odds ratio, 7.45; 95% CI, 2.79-19.92 for six or more partners vs. one partner). Human papillomavirus infection is a prevalent sexually transmitted disease among young Swedish women, and the lifetime number of male sexual partners is a major risk factor.

Research paper thumbnail of The geographic distribution of mosquito species in Sweden

Journal of the American Mosquito Control Association

Surveillance of the actual distribution of mosquito species in Northern Europe is fundamental for... more Surveillance of the actual distribution of mosquito species in Northern Europe is fundamental for evaluating risk for emerging pathogens, and for research on potential vectors. The Swedish mosquito fauna composition and geographic distribution, originally described by Professor Christine Dahl in the 1970´s, included 43 species. We have compiled the information published from 1978 to 2012, and our own surveillance data from 2001 to 2013, and compared this with the species list and geographic distribution provided in “Taxonomy and geographic distribution of Swedish Culicidae” by Dahl (1977). New species detected during these 36 years were Culiseta (Culicella) ochroptera (Peus, 1935) published 1984, Aedes (Aedes) rossicus Dolbeskin, Goritzkaja & Mitrofanova, 1930 published 1986, Anopheles (Anopheles) beklemishevi published 1986, Aedes (Ochlerotatus) euedes (Howard, Dyar & Knab, 1912) published 2001, Aedes (Ochlerotatus) nigrinus (Eckstein, 1918) first recorded in 2012, and Anopheles (A...

Research paper thumbnail of A Novel and Rapid PCR-based Method for Genotyping Human Papillomaviruses in Clinical Samples

Many human papillomavirus (HPV) genotypes are associated with cervical carcinoma. We demonstrate ... more Many human papillomavirus (HPV) genotypes are associated with cervical carcinoma. We demonstrate the utility of an innovative technique for genotyping of HPV in cervical tissue samples. This method provides an accurate means of identification of the specific HPV genotypes present in clinical specimens. By using the MY09-MY11 and the GP5+-GP6+ consensus primer pairs, HPV sequences were amplified by nested PCR

Research paper thumbnail of The Importance of Bank Vole Density and Rainy Winters in Predicting Nephropathia Epidemica Incidence in Northern Sweden

PLoS ONE, 2014

Pathogenic hantaviruses (family Bunyaviridae, genus Hantavirus) are rodent-borne viruses causing ... more Pathogenic hantaviruses (family Bunyaviridae, genus Hantavirus) are rodent-borne viruses causing hemorrhagic fever with renal syndrome (HFRS) in Eurasia. In Europe, there are more than 10,000 yearly cases of nephropathia epidemica (NE), a mild form of HFRS caused by Puumala virus (PUUV). The common and widely distributed bank vole (Myodes glareolus) is the host of PUUV. In this study, we aim to explain and predict NE incidence in boreal Sweden using bank vole densities. We tested whether the number of rainy days in winter contributed to variation in NE incidence. We forecast NE incidence in July 2013-June 2014 using projected autumn vole density, and then considering two climatic scenarios: 1) rain-free winter and 2) winter with many rainy days. Autumn vole density was a strong explanatory variable of NE incidence in boreal Sweden in 1990-2012 (R 2 = 79%, p,0.001). Adding the number of rainy winter days improved the model (R 2 = 84%, p,0.05). We report for the first time that risk of NE is higher in winters with many rainy days. Rain on snow and ground icing may block vole access to subnivean space. Seeking refuge from adverse conditions and shelter from predators, voles may infest buildings, increasing infection risk. In a rainy winter scenario, we predicted 812 NE cases in boreal Sweden, triple the number of cases predicted in a rain-free winter in 2013/2014. Our model enables identification of high risk years when preparedness in the public health sector is crucial, as a rainy winter would accentuate risk.

Research paper thumbnail of A need for One Health approach – lessons learned from outbreaks of Rift Valley fever in Saudi Arabia and Sudan

Infection Ecology & Epidemiology, 2014

Research paper thumbnail of Vaccination with virus-like particles protects mice from lethal infection of Rift Valley Fever Virus

Research paper thumbnail of Presentation of the HPV16E7 protein by skin grafts is insufficient to allow graft rejection in an E7-primed animal

The E7 transforming protein of Human Papillomavirus type 16 (HPV16) is expressed in the skin of a... more The E7 transforming protein of Human Papillomavirus type 16 (HPV16) is expressed in the skin of a line of FVB mice transgenic for the E6 and E7 open reading frames of HPV16 driven from the alpha A crystallin promoter (FVB alpha AcryHPV16E6E7). We have transferred skin from FVB alpha AcryHPV16E6E7 mice to naive or E7-primed syngeneic FVB recipients to assess whether the E7 protein of HPV16 can function as a minor transplantation antigen (MTA) and promote skin graft rejection. FVB mice did not reject E7 expressing tail or flank skin grafts. E7 immunized FVB x C57BL/6J mice recipients of FVB alpha-AcryHPV16E6E7 x C57BL/6J skin generated humoral and DTH responses to E7 in vivo and E7-specific CTL precursors in the spleen, but failed to reject E7 expressing tail skin grafts by 100 days posttransfer. Thus although HPV16 E7 + ve mesenchymal and endodermal tumors can be eliminated by an E7-specific immune response, the same protein is unable to act as a MTA and promote graft rejection when expressed in skin cells. Lack of rejection of grafts expressing MTAs such as E7 may be relevant to the immunology of epithelial tumors expressing tumor-specific antigens and to our understanding of the immunology of diseases of the skin.

Research paper thumbnail of Milder winters in northern Scandinavia may contribute to larger outbreaks of haemorrhagic fever virus

Global Health Action, 2009

The spread of zoonotic infectious diseases may increase due to climate factors such as temperatur... more The spread of zoonotic infectious diseases may increase due to climate factors such as temperature, humidity and precipitation. This is also true for hantaviruses, which are globally spread haemorrhagic fever viruses carried by rodents. Hantaviruses are frequently transmitted to humans all over the world and regarded as emerging viral diseases. Climate variations affect the rodent reservoir populations and rodent population peaks coincide with increased number of human cases of hantavirus infections. In northern Sweden, a form of haemorrhagic fever called nephropathia epidemica (NE), caused by the Puumala hantavirus (PUUV) is endemic and during 2006Á2007 an unexpected, sudden and large outbreak of NE occurred in this region. The incidence was 313 cases/100,000 inhabitants in the most endemic areas, and from January through March 2007 the outbreak had a dramatic and sudden start with 474 cases in the endemic region alone. The PUUV rodent reservoir is bank voles and immediately before and during the peak of disease outbreak the affected regions experienced extreme climate conditions with a record-breaking warm winter, registering temperatures 6Á98C above normal. No protective snow cover was present before the outbreak and more bank voles than normal came in contact with humans inside or in close to human dwellings. These extreme climate conditions most probably affected the rodent reservoir and are important factors for the severity of the outbreak.

Research paper thumbnail of Lifetime Number of Partners As the Only Independent Risk Factor for Human Papillomavirus Infection

Sexually Transmitted Diseases, 1995

Previous studies of relationships between genital human papillomavirus infection and tentative ri... more Previous studies of relationships between genital human papillomavirus infection and tentative risk factors have yielded conflicting results, possibly because of inaccuracy of the viral detection methods used and differences in selection criteria. To determine human papillomavirus prevalence and identify risk factors in a group of young Swedish women. This was a population-based study involving completion of a structured questionnaire, analysis of cervical scrapings for human papillomavirus and Chlamydia trachomatis, and serologic tests for C. trachomatis and herpes simplex virus antibodies. The prevalence of human papillomavirus infection was 22% among the sexually active women and 4% among the virgins. A number of factors were associated with human papillomavirus prevalence in univariate analysis, but logistic regression analysis showed that lifetime number of male sexual partners was the only independent risk factor for human papillomavirus infection (adjusted odds ratio, 7.45; 95% CI, 2.79-19.92 for six or more partners vs. one partner). Human papillomavirus infection is a prevalent sexually transmitted disease among young Swedish women, and the lifetime number of male sexual partners is a major risk factor.

Research paper thumbnail of The 2007 Rift Valley Fever Outbreak in Sudan

PLoS Neglected Tropical Diseases, 2011

Rift Valley fever (RVF) is a neglected, emerging, mosquito-borne disease with severe negative imp... more Rift Valley fever (RVF) is a neglected, emerging, mosquito-borne disease with severe negative impact on human and animal health and economy. RVF is caused by RVF virus (RVFV) affecting humans and a wide range of animals. The virus is transmitted through bites from mosquitoes and exposure to viremic blood, body fluids, or tissues of infected animals. During 2007 a large RVF outbreak occurred in Sudan with a total of 747 confirmed human cases including 230 deaths (case fatality 30.8%); although it has been estimated 75,000 were infected. It was most severe in White Nile, El Gezira, and Sennar states near to the White Nile and the Blue Nile Rivers. Notably, RVF was not demonstrated in livestock until after the human cases appeared and unfortunately, there are no records or reports of the number of affected animals or deaths. Ideally, animals should serve as sentinels to prevent loss of human life, but the situation here was reversed. Animal contact seemed to be the most dominant risk factor followed by animal products and mosquito bites. The Sudan outbreak followed an unusually heavy rainfall in the country with severe flooding and previous studies on RVF in Sudan suggest that RVFV is endemic in parts of Sudan. An RVF outbreak results in human disease, but also large economic loss with an impact beyond the immediate influence on the directly affected agricultural producers. The outbreak emphasizes the need for collaboration between veterinary and health authorities, entomologists, environmental specialists, and biologists, as the best strategy towards the prevention and control of RVF.

Research paper thumbnail of Kinetics of Rift Valley Fever Virus in experimentally infected mice using quantitative real-time RT-PCR

Journal of Virological Methods, 2008

Rift Valley Fever (RVF) is an important viral zoonosis in Africa affecting animals and humans. Si... more Rift Valley Fever (RVF) is an important viral zoonosis in Africa affecting animals and humans. Since no protective vaccines or effective treatments are available for human use, accurate and reliable diagnostic methods are essential for surveillance of the disease in order to implement adequate public health actions. To study the kinetics of the RVF Virus (RVFV) infection, a SYBR Green-based quantitative real-time RT-PCR assay was developed. By using primers targeting the S-segment of RVFV, the detection limit of this assay was estimated to 30 RNA templates. Blood and organs of experimentally infected mice were sampled at different time points and RVFV RNA was quantified. High amounts of RVFV RNA were found in blood, brain, and liver samples shortly after infection with a 1-4 days post infection window for viral RNA detection. Mice developed symptoms after the appearance of serum antibodies, indicating that the host response plays an important role in the outcome of the disease. The RVFV quantitative RT-PCR proved to be a valuable diagnostic tool during the first days of infection, before detectable antibody levels and visual symptoms of RVF were observed.

Research paper thumbnail of Hantavirus-specific IgA in saliva and viral antigen in the parotid gland in patients with hemorrhagic fever with renal syndrome

Journal of Medical Virology, 2011

The Hantavirus genus comprises rodent borne, zoonotic viruses of the Bunyaviridae family that cau... more The Hantavirus genus comprises rodent borne, zoonotic viruses of the Bunyaviridae family that cause hemorrhagic fever with renal syndrome (HFRS) in Eurasia and hantavirus cardiopulmonary syndrome (HCPS) in the Americas. Rodent saliva contains infectious hantavirus and evidence suggests that hantavirus is also shed in human saliva, but person-to-person transmission is rare. In saliva, immunoglobulin (Ig) A is the predominant immunoglobulin class. Secretory IgA serves as an important first line of defence on epithelial surfaces and the binding of secretory IgA to pathogens can inhibit adherence of microorganisms to mucosal cells and neutralize viruses. This study investigated the presence and importance of salivary IgA in relation to viral antigen in the saliva by testing Puumala hantavirus (PUUV) specific IgA, and RNA in saliva in acutely ill patients with HFRS. In saliva samples, PUUV specific IgA was detected in 12 of 33 (36%) patients with HFRS and 20 (61%) were PUUV RNA positive. There was a statistically significant inverse association between the presence of salivary IgA antibodies and PUUV RNA in the saliva. PUUV-specific IgA in saliva was not found in a long-term follow-up, while PUUV IgA in serum was detected in three patients, 28-32 months after the initial study. Notably, both PUUV RNA and PUUV nucleocapsid antigen were detected in endothelial cells within the parotid gland of a deceased patient with HFRS.

Research paper thumbnail of Puumala Hantavirus Viremia Diagnosed by Real-Time Reverse Transcriptase PCR Using Samples from Patients with Hemorrhagic Fever and Renal Syndrome

Journal of Clinical Microbiology, 2007

(NE), a milder form of hemorrhagic fever with renal syndrome. There is a need for fast and reliab... more (NE), a milder form of hemorrhagic fever with renal syndrome. There is a need for fast and reliable diagnostics to differentiate the disease from other infections. By aligning virus RNA sequences isolated from 11 different bank voles and one human patient, we designed a real-time reverse transcriptase (RT) PCR method for detection of PUUV RNA. The real-time RT-PCR assay showed linearity from 20 to 2 ؋ 10 6 virus copies with a correlation coefficient above 0.98 to 0.99 for all experiments. The detection threshold for PUUV cDNA was two copies per reaction. A two-step qualitative RT-PCR to detect PUUV RNA showed 100% concordance with the real-time RT-PCR assay. PUUV RNA viremia was detected in 33 of 34 PUUV immunoglobulin M (IgM)positive patients with typical clinical NE disease from the region of endemicity. One PUUV IgM-negative sample had PUUV RNA, and 4 days later, the patient was IgM positive. Of samples with indeterminate IgM, 43% were PUUV RNA positive. The kinetics of antibody titers and PUUV viremia were studied, and five of six NE patients displayed a decrease in PUUV viremia a few days after disease outbreak coupled with an increase in PUUV IgM and IgG. In one patient with continuously high PUUV RNA levels but low IgM and no IgG response, the infection was lethal. These findings demonstrated that real-time RT-PCR is a useful method for diagnosis of PUUV viremia and for detecting PUUV RNA at early time points, before the appearance of IgM antibodies. . Samples were handled according to routine instructions and analyzed by IF within 1 to 2 days after sampling. A qualitative two-step RT-PCR and a quantitative one-step real-time RT-PCR analysis were performed later on samples stored at Ϫ80°C. The project was approved by the Construction of synthetic standard PUUV RNA. Standard PUUV RNA was constructed from a pT7Blue-3 vector (Novagen, Darmstadt, Germany) with a cloned 501-bp cDNA fragment of the S gene (strain Umeå/hu; accession no. AY526219). The insert was sequenced to locate the 5Ј-to-3Ј direction and to certify 100% homology to the primers and probe. This was important to ensure the same efficiency in quantitation of the standard curve and the patient samples. The plasmid was linearized with the restriction enzyme SacI and used as a template for RNA transcription using the MEGAscript High Yield Transcription Kit (Ambion, Austin, TX) according to the manufacturer's protocol. The synthesized RNA was incubated with DNase at 37°C for 15 min, purified by phenolchloroform extraction and isopropanol precipitation, and finally resuspended in 40 l of nuclease-free water with 40 U recombinant RNasin RNase inhibitor (Promega, Madison, WI). RNA dilutions of 10 Ϫ4 to 10 Ϫ9 were analyzed by real-time PCR with and without a prior RT reaction step to ensure a DNA template concentration of less than 0.2%. DNA contamination equal to or above 0.2% required DNase treatment of the RNA. The RNA concentration was measured spectrophotometrically, and RNA at Ն1 ϫ 10 8

Research paper thumbnail of The anti-papillomavirus activity of human and bovine lactoferricin

Antiviral Research, 2007

Human papillomavirus (HPV) cause common warts, laryngeal papilloma and genital condylomata and is... more Human papillomavirus (HPV) cause common warts, laryngeal papilloma and genital condylomata and is necessary for the development of cervical cancer. We have previously found that lactoferrin has antiviral activity against HPV-16 and others have demonstrated that lactoferricin, an N-terminal fragment of lactoferrin, has inhibitory activities against several viruses. Two cell lines and two virus types, HPV-5 and HPV-16, were used to study if lactoferrin and lactoferricin could inhibit HPV pseudovirus (PsV) infection. We demonstrated that bovine lactoferrin (bLf) and human lactoferrin (hLf) were both potent inhibitors of HPV-5 and -16 PsV infections. Among the four lactoferricin derivatives we analyzed, a 15 amino acid peptide from bovine lactoferricin (bLfcin) 17-31 was the most potent inhibitor of both HPV-5 and HPV-16 PsV infection. Among the other derivatives, the human lactoferricin (hLfcin) 1-49 showed some antiviral activity against HPV PsV infection while bLfcin 17-42 inhibited only HPV-5 PsV infection in one of the cell lines. When we studied initial attachment of HPV-16, only bLfcin 17-42 and hLfcin 1-49 had an antiviral effect. This is the first time that lactoferricin was demonstrated to have an inhibitory effect on HPV infection and the antiviral activity differed depending on size, charge and structures of the lactoferricin.

Research paper thumbnail of Relation between the presence of human papillomavirus type 16 deoxyribonucleic acid in cervicovaginal cells and general health condition

American Journal of Obstetrics and Gynecology, 1993

Cervicovaginal cell samples were analyzed for the presence of human papillomavirus type 16 deoxyr... more Cervicovaginal cell samples were analyzed for the presence of human papillomavirus type 16 deoxyribonucleic acid. All 99 women included in the study had normal Papanicolaou smear results, normal findings on wet smear, and no clinical signs of genital papillomavirus or any other genital infection. Deoxyribonucleic acid polymerase chain reaction was performed with three different human papillomavirus type 16-specific primer pairs from the early 6, early 7, and upstream regulatory regions. Human papillomavirus type 16 was detected in 21% of the 99 women. Seven of 69 women (10%) who were not taking any medication except for cyclic estrogen or progestin replacement therapy were carriers of human papillomavirus type 16. Seven of 19 women (37%) who used hormonal contraceptives or who sought early pregnancy termination were carriers of human papillomavirus type 16. All 7 women with diseases that required frequent hospital care were carriers of human papillomavirus type 16. The 4 women who had never had sexual intercourse were not carriers of human papillomavirus type 16. Our results indicate that the human papillomavirus type 16 prevalence in women may reflect to some extent the general health conditions of the patients.

Research paper thumbnail of Papilloma Virus Infection of the Vulva

Acta Obstetricia et Gynecologica Scandinavica, 1989

Analyses of the possible presence of human papilloma virus (HPV) DNA were performed on 84 biopsie... more Analyses of the possible presence of human papilloma virus (HPV) DNA were performed on 84 biopsies from 50 women with clinically and histopathologically suspected HPV infection of the vulva. The colposcopic criteria for inclusion in the study were: acetowhite flat lesions with or without fissures and/or diffuse hyperplastic mucosa with a granulated or filamental surface. Directed biopsies for histopathology and DNA hybridization (dot-blot and Southern-blot) were taken. All women had histopathological evidence of HPV infection. Twelve women had cervical and/or vulvar neoplasia. HPV DNA could be demonstrated in the vulvar biopsies from 24 women; 13 women had HPV 16, 3 had HPV 18, HPV 31 and HPV 33, respectively. In addition, 10 biopsies contained HPV DNA of unknown types. Fifty-five percent of granulated and filamental lesions and 43% of flat lesions with or without fissures were positive for HPV DNA. 34 women had one or more of the following symptoms: itching, burning, dyspareunia, discharge, fissures, dryness and dysuria. Papillomavirus vulvitis is a sexually transmitted disease which may cause recalcitrant symptoms and/or concomitant neoplasia. It is thus important to recognize the different symptoms and signs of this disease.

Research paper thumbnail of Dynamics and Drivers of Hantavirus Prevalence in Rodent Populations

Vector-Borne and Zoonotic Diseases, 2014

Human encroachment on wildlife habitats has contributed to the emergence of several zoonoses. Pat... more Human encroachment on wildlife habitats has contributed to the emergence of several zoonoses. Pathogenic hantaviruses are hosted by rodents and cause severe diseases in the Americas and Eurasia. We reviewed several factors that potentially drive prevalence (the proportion of infected rodents) in host populations. These include demography, behavior, host density, small mammal diversity, predation, and habitat and landscape characteristics. This review is the first to include a quantitative summary of the literature investigating hantavirus prevalence in rodents. Demographic structure and density were investigated the most and predation the least. Reported effects of demographic structure and small mammal diversity were consistent, whereby reproductive males were most likely to be infected and prevalence decreased with small mammal diversity. The influences of habitat and landscape properties are often complex and indirect. The relationship between density and prevalence merits more investigation. Most hantavirus hosts are habitat generalists and their control is challenging. Incorporating all potential factors and their interactions is essential to understanding and controlling infection in host populations.