| 1. |
- Alaridah, Nader, et al.
(författare)
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Transmission dynamics study of tuberculosis isolates with whole genome sequencing in southern Sweden
- 2019
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Epidemiological contact tracing complemented with genotyping of clinical Mycobacterium tuberculosis isolates is important for understanding disease transmission. In Sweden, tuberculosis (TB) is mostly reported in migrant and homeless where epidemiologic contact tracing could pose a problem. This study compared epidemiologic linking with genotyping in a low burden country. Mycobacterium tuberculosis isolates (n = 93) collected at Scania University Hospital in Southern Sweden were analysed with the standard genotyping method mycobacterial interspersed repetitive units-variable number tandem repeats (MIRU-VNTR) and the results were compared with whole genome sequencing (WGS). Using a maximum of twelve single nucleotide polymorphisms (SNPs) as the upper threshold of genomic relatedness noted among hosts, we identified 18 clusters with WGS comprising 52 patients with overall pairwise genetic maximum distances ranging from zero to nine SNPs. MIRU-VNTR and WGS clustered the same isolates, although the distribution differed depending on MIRU-VNTR limitations. Both genotyping techniques identified clusters where epidemiologic linking was insufficient, although WGS had higher correlation with epidemiologic data. To summarize, WGS provided better resolution of transmission than MIRU-VNTR in a setting with low TB incidence. WGS predicted epidemiologic links better which could consolidate and correct the epidemiologically linked cases, avoiding thus false clustering.
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| 2. |
- Alsved, Malin, et al.
(författare)
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Aerosolization and recovery of viable murine norovirus in an experimental setup
- 2020
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Noroviruses are the major cause for viral acute gastroenteritis in the world. Despite the existing infection prevention strategies in hospitals, the disease continues to spread and causes extensive and numerous outbreaks. Hence, there is a need to investigate the possibility of airborne transmission of norovirus. In this study, we developed an experimental setup for studies on the infectivity of aerosolized murine norovirus (MNV), a model for the human norovirus. Two aerosol generation principles were evaluated: bubble bursting, a common natural aerosolization mechanism, and nebulization, a common aerosolization technique in laboratory studies. The aerosolization setup was characterized by physical and viral dilution factors, generated aerosol particle size distributions, and the viral infectivity after aerosolization. We found a lower physical dilution factor when using the nebulization generator than with the bubble bursting generator. The viral dilution factor of the system was higher than the physical dilution; however, when comparing the physical and viral dilution factors, bubble bursting generation was more efficient. The infectivity per virus was similar using either generation principle, suggesting that the generation itself had a minor impact on MNV infectivity and that instead, the effect of drying in air could be a major reason for infectivity losses.
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| 3. |
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| 5. |
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| 6. |
- Alsved, Malin, et al.
(författare)
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Droplet, aerosol and SARS-CoV-2 emissions during singing and talking
- 2021
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Konferensbidrag (refereegranskat)abstract
- IntroductionAs the pandemic continues to spread, more knowledge is needed about the viral transmission routes. Several super spreading events during the Covid-19 pandemic have been linked to singing in choirs and talking loud. However, in the beginning of the pandemic there was only one study about emitted aerosols and droplets from singing, published in 1968, and only a handful on emissions from talking. Therefore, we conducted a study to measure the aerosol and droplet emissions from talking and singing. We also evaluated the emissions from singing when wearing a face mask.We have further developed our setup so that we collect the aerosol particles from Covid-19 infected patients that are talking and singing, and analyze our samples for SARS-CoV-2, the virus causing Covid-19.MethodTwelve healthy singers (7 professionals, 5 amateurs) were included in the first study part on quantifying the amount of emitted aerosols and droplets. The singers were singing or talking a short consonant rich text repeatedly at a constant pitch with their face in the opening of a funnel. The aerosol particle size and concentration was measured from the other end of the funnel using an aerodynamic particle sizer (APS, 3321, TSI Inc). In addition, the amount of un-evaporated droplets were captured with a high-speed camera and quantified using image analysis.During February and March 2021 we will collect aerosol particles from patients with confirmed Covid-19 that are singing and talking into a funnel. We will use a growth tube condensation collector, a BioSpot (Aerosol Devices), operating at 8 L min-1, and a NIOSH BC-251 cyclone sampler operating at 3.5 L min-1 (TISCH Environmental). The BioSpot collects the whole range of exhaled aerosol particles with high (95%) efficiency into liquid, and the NIOSH cyclone sampler collects particles into three size fractions: <1 µm (filter), 1-4 µm (liquid), >4 µm (liquid). The APS is again used to measure size and concentration of the emitted aerosol particles, so that emissions from infected test subjects can be compared with those of the healthy test subjects. Air samples will be analyzed for detection of SARS-CoV-2 genes, and if possible, SARS-CoV-2 infectivity in cell cultures.ResultsAerosol particle emissions from healthy test subjects were significantly higher during normal singing (median 690, range [320–2870] particles/s) than during normal talking (270 [120–1380] particles/s) (Wilcoxon’s signed rank test, p=0.002). Loud singing produced even more aerosol particles (980 [390–2870] particles/s) than normal singing (p=0.002). The amount of non-evaporated droplets detected by the high-speed camera setup showed similar results: more droplets during loud singing or talking. For both aerosol particle concentrations and droplet numbers, the levels were reduced by on average 70-80% when wearing a surgical face mask.ConclusionsSinging and talking give rise to high aerosol and droplet emissions from the respiratory tract. This is likely an important transmission route for Covid-19. In our upcoming part of the study we hope to determine how much SARS-CoV-2 that is emitted during these social activities.
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| 7. |
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| 8. |
- Alsved, Malin, et al.
(författare)
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Exhaled respiratory particles during singing and talking
- 2020
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Ingår i: Aerosol Science and Technology. - : Informa UK Limited. - 1521-7388 .- 0278-6826. ; 54:11, s. 245-1248
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Tidskriftsartikel (refereegranskat)abstract
- Choir singing has been suspended in many countriesduring the Covid-19 pandemic due to incidental reportsof disease transmission. The mode of transmission has been attributed to exhaled droplets, but with the exception of a study on tuberculosis from1968, there is presently almost no scientific evidence ofincreased particle emissions from singing. A substantial number of studies have,however, investigated aerosols emitted from breathing,talking, coughing and sneezing. It has also been shown that justnormal breathing over time can generate more viablevirus aerosol than coughing, since the latter is a less fre-quent activity.Compared to talking, singing often involves continu-ous voicing, higher sound pressure, higher frequencies,deeper breaths, higher peak airflows and more articu-lated consonants. All these factors are likely to increaseexhaled emissions.The aim of this study was to investigate aerosol anddroplet emissions during singing, as compared to talking and breathing. We also examined the presence of SARS-CoV-2 in the air from breathing, talking and singing,and the efficacy of face masks to reduce emissions. In this study we defined aerosol particles as having a drysize in the range 0.5–10mm. Although debatable from anaerosol physics point of view, a cutoff diameter between5 and 10mm is normally used in medicine for classifica-tion of aerosol versus droplet route of transmission. Droplets are here defined as exhaled particles, frommicron size with no upper size limit, and measured dir-ectly at the mouth before complete evaporation, thuspartly in liquid phase.
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| 9. |
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| 11. |
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| 13. |
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| 14. |
- Alsved, Malin, et al.
(författare)
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Infectivity of exhaled SARS-CoV-2 aerosols is sufficient to transmit covid-19 within minutes
- 2023
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Ingår i: Scientific Reports. - 2045-2322. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Exhaled SARS-CoV-2-containing aerosols contributed significantly to the rapid and vast spread of covid-19. However, quantitative experimental data on the infectivity of such aerosols is missing. Here, we quantified emission rates of infectious viruses in exhaled aerosol from individuals within their first days after symptom onset from covid-19. Six aerosol samples from three individuals were culturable, of which five were successfully quantified using TCID50. The source strength of the three individuals was highest during singing, when they exhaled 4, 36, or 127 TCID50/s, respectively. Calculations with an indoor air transmission model showed that if an infected individual with this emission rate entered a room, a susceptible person would inhale an infectious dose within 6 to 37 min in a room with normal ventilation. Thus, our data show that exhaled aerosols from a single person can transmit covid-19 to others within minutes at normal indoor conditions.
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| 15. |
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| 16. |
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| 17. |
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| 18. |
- Alsved, Malin, et al.
(författare)
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SARS-CoV-2 in aerosol particles exhaled from COVID-19 infected patients during breathing, talking and singing
- 2021
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Konferensbidrag (refereegranskat)abstract
- In the beginning of the COVID-19 pandemic, several super spreader events occurred during singing in choirs, which lead to an increased attention to airborne transmission of SARS-CoV-2, the virus causing COVID-19. Since then, aerosol generation from singing has been studied in more detail, however, only from healthy subjects. In this study, we collected aerosol particles in the exhaled breath of 40 COVID-19 infected patients during breathing, talking and singing, respectively, and analysed the samples for detection of SARS-CoV-2.MethodPatients that were contacted by the COVID-19 testing service due to a positive test result were asked to volunteer for the study. A team of researchers drove a small truck hosting a mobile laboratory to the home address of the patient to perform exhaled breath aerosol collection using a condensational particle collector (BioSpot, Aerosol Devices) and a two-stage cyclone sampler (NIOSH bc-251, Tisch Environmental). Samples were collected for 10 min each when the patient was breathing, talking and singing, respectively.All samples were stored at -80°C until RNA extraction and analysis by reverse transcription quantitative polymerase chain reaction (RT-qPCR) targeting the N-gene.ResultsA first screening of air samples collected with the BioSpot showed that SARS-CoV-2 could be detected in the exhaled aerosols from three of nine patients during singing or talking. Two of these samples contained 103 and 104 viral RNA copies, corresponding to a viral emission rate of approximately 4 and 25 viruses per second, respectively. Samples from the remaining 31 patients are to be analysed during the spring. We hope to contribute to quantifying and understanding the Covid-19 transmission via the airborne route.This study was approved by the Swedish Ethics Review Authority (2020-07103). This work was supported by AFA Insurances and the Swedish Research Council FORMAS.
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| 19. |
- Alsved, Malin, et al.
(författare)
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SARS-CoV-2 in aerosol particles exhaled from COVID-19 infected patients during breathing, talking and singing
- 2021
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Konferensbidrag (refereegranskat)abstract
- In the beginning of the COVID-19 pandemic, several super spreader events occurred during choir singing, which lead to an increased attention to airborne transmission of SARS-CoV-2. Since then, aerosol generation from singing has been studied in detail, however, mainly from healthy subjects. In this study, we collected aerosol particles in the exhaled breath of 38 COVID-19 infected patients during breathing, talking and singing, respectively, and analyzed the samples for detection of SARS-CoV-2.MethodPatients that were contacted by the COVID-19 testing service due to a positive test result early in the phase of their infection (median 2, range: 0-6 days from symptom onset) were asked to volunteer for the study. A team of researchers drove a small truck hosting a mobile laboratory to the home address of the patient to perform exhaled breath aerosol collection using a condensational particle collector (BioSpot, Aerosol Devices) and a two-stage cyclone sampler (NIOSH bc-251, Tisch Environmental). Samples were collected for 10 min each when the patients were breathing, talking and singing, respectively. In addition, patient samples from nasopharynx and saliva were collected, and patients filled out a questionnaire about symptoms. All samples were stored at -80 °C until RNA extraction and analysis by reverse transcription quantitative polymerase chain reaction (RT-qPCR) targeting the N-gene.ResultsA first preliminary screening of air samples collected with the BioSpot showed that SARS-CoV-2 could be detected in the exhaled aerosols from 14 of 38 (37%) patients during respiratory activities. 50% of patients in the early phase of the infection, day 0-1 from symptom onset, emitted detectable levels of airborne SARS-CoV-2 RNA, 35% of patients on day 2-3, and 0% of patients on day 4-6. The highest viral RNA concentrations in aerosol samples were found in those collected during singing. Further analysis is ongoing and we hope that our results will contribute to quantifying and understanding the Covid-19 transmission via the airborne route.This study was approved by the Swedish Ethics Review Authority (2020-07103). This work was supported by AFA Insurances and the Swedish Research Council FORMAS.
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| 20. |
- Alsved, Malin, et al.
(författare)
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SARS-CoV-2 in exhaled aerosol particles from covid-19 cases and its association to household transmission
- 2022
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Ingår i: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. - : Oxford University Press (OUP). - 1537-6591. ; 75:1, s. 50-56
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Covid-19 transmission via exhaled aerosol particles has been considered an important route for the spread of infection, especially during super-spreading events involving loud talking or singing. However, no study has previously linked measurements of viral aerosol emissions to transmission rates.METHODS: During Feb-Mar 2021, covid-19 cases that were close to symptom onset were visited with a mobile laboratory for collection of exhaled aerosol particles during breathing, talking and singing, respectively, and of nasopharyngeal and saliva samples. Aerosol samples were collected using a BioSpot-VIVAS and a NIOSH bc-251 two-stage cyclone, and all samples were analyzed by RT-qPCR for SARS-CoV-2 RNA detection. We compared transmission rates between households with aerosol-positive and aerosol-negative index cases.RESULTS: SARS-CoV-2 RNA was detected in at least one aerosol sample from 19 of 38 (50%) included cases. The odds ratio of finding positive aerosol samples decreased with each day from symptom onset (OR 0.55, 95CI 0.30-1.0, p=0.049). The highest number of positive aerosol samples were from singing, 16 (42%), followed by talking, 11 (30%), and the least from breathing, 3 (8%). Index cases were identified for 13 households with 31 exposed contacts. Higher transmission rates were observed in households with aerosol-positive index cases, 10/16 infected (63%), compared to households with aerosol-negative index cases, 4/15 infected (27%) (Chi-square test, p=0.045).CONCLUSIONS: Covid-19 cases were more likely to exhale SARS-CoV-2-containing aerosol particles close to symptom onset and during singing or talking as compared to breathing. This study supports that individuals with SARS-CoV-2 in exhaled aerosols are more likely to transmit covid-19.
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| 21. |
- Alsved, Malin, et al.
(författare)
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Size distribution of exhaled aerosol particles containing SARS-CoV-2 RNA
- 2023
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Ingår i: Infectious Diseases. - : Informa UK Limited. - 2374-4235 .- 2374-4243. ; 55:2, s. 158-163
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Tidskriftsartikel (refereegranskat)abstract
- Background: SARS-CoV-2 in exhaled aerosols is considered an important contributor to the spread of COVID-19. However, characterizing the size distribution of virus-containing aerosol particles has been challenging as high concentrations of SARS-CoV-2 in exhaled air is mainly present close to symptom onset. We present a case study of a person with COVID-19 who was able to participate in extensive measurements of exhaled aerosols already on the day of symptom onset and then for the following three days. Methods: Aerosol collection was performed using an eight-stage impactor while the subject was breathing, talking and singing, for 30 min each, once every day. In addition, nasopharyngeal samples, saliva samples, room air samples and information on symptom manifestations were collected every day. Samples were analyzed by RT-qPCR for detection of SARS-CoV-2 RNA. Results: SARS-CoV-2 RNA was detected in seven of the eight particle size fractions, from 0.34 to >8.1 µm, with the highest concentrations found in 0.94–2.8 µm particles. The concentration of SARS-CoV-2 RNA was highest on the day of symptom onset, and declined for each day thereafter. Conclusion: Our data showed that 90% of the exhaled SARS-CoV-2 RNA was found in aerosol particles <4.5 µm, indicating the importance of small particles for the transmission of COVID-19 close to symptom onset. These results are important for our understanding of airborne transmission, for developing accurate models and for selecting appropriate mitigation strategies.
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| 22. |
- Alsved, Malin, et al.
(författare)
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Sources of Airborne Norovirus in Hospital Outbreaks
- 2020
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Ingår i: Clinical Infectious Diseases. - : Oxford University Press (OUP). - 1537-6591 .- 1058-4838. ; 70:10, s. 2023-2028
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Noroviruses are the major cause of viral gastroenteritis. Disease transmission is difficult to prevent and outbreaks in healthcare facilities commonly occur. Contact with infected persons and contaminated environments are believed to be the main routes of transmission. However, noroviruses have recently been found in aerosols and airborne transmission has been suggested. The aim of our study was to investigate associations between symptoms of gastroenteritis and presence of airborne norovirus, and to investigate the size of norovirus carrying particles.METHODS: Air sampling was repeatedly performed close to 26 patients with norovirus infections. Samples were analysed for norovirus RNA by RT-qPCR. The times since the patients' last episodes of vomiting and diarrhoea were recorded. Size separating aerosol particle collection was also performed in ward corridors.RESULTS: Norovirus RNA was found in 21 (24%) of 86 air samples from 10 different patients. Only air samples during outbreaks, or before a succeeding outbreak, tested positive for norovirus RNA. Airborne norovirus RNA was also strongly associated with a shorter time period since the last vomiting episode (odds ratio 8.1, p=0.04 within 3 hours since the last vomiting episode). The concentration of airborne norovirus ranged from 5-215 copies/m3, and detectable amounts of norovirus RNA were found in particles <0.95 µm and >4.51 µm.CONCLUSIONS: The results suggest that recent vomiting is the major source of airborne norovirus and imply a connection between airborne norovirus and outbreaks. The presence of norovirus RNA in submicrometre particles indicates that airborne transmission can be an important transmission route.
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| 23. |
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| 24. |
- Andersson, Marie-Louise, et al.
(författare)
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Differential expression of human endogenous retroviral sequences similar to mouse mammary tumor virus in normal peripheral blood mononuclear cells
- 1996
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Ingår i: AIDS Research and Human Retroviruses. - 0889-2229 .- 1931-8405. ; 12:9, s. 833-40
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Tidskriftsartikel (refereegranskat)abstract
- Mouse mammary tumor virus (MMTV) is a retrovirus that causes breast cancer in certain strains of mice. In a previous study we identified, by sequencing clones from human lymphocytes, six groups with similarities to MMTV. Using a primer pair derived from pol sequences conserved within types A, B, and D retroviruses and probes from the six human MMTV-like (HML-1 to HML-6) groups in an internally controlled hybridization assay we investigated the normal variation of expression in PBMCs. Variations occurred within all groups but was most significant within group HML-1, where hybridization signals differed by more than 500-fold between individuals. Groups HML-2 and HML-3 showed consistently stronger hybridization signals than groups HML-1 and HML-5, while group HML-6 resulted in weak signals for all individuals. Stringent hybridization of the amplified cDNA to 20 individual HML clones also demonstrated a marked heterogeneity of expression. Hybridization signals from some groups and sequences were found to be correlated, either in a positive or negative fashion. RNA isolated from PBMCs collected from two donors at four different time points (in the morning and in the afternoon on the same day, repeated 1 week later) was also analyzed using the six hml probes. A small variation in hybridization signals was seen in samples collected on the same day, but a larger difference was observed in samples taken 1 week later. The correlations and the differences in the expression of HMLs between individuals implicate a complex transcriptional regulation system of these sequences.
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| 25. |
- Arimide, Dawit Assefa, et al.
(författare)
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High Level of HIV Drug Resistance and Virologic Nonsuppression among Female Sex Workers in Ethiopia : A Nationwide Cross-Sectional Study
- 2022
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Ingår i: Journal of Acquired Immune Deficiency Syndromes. - 1525-4135. ; 89:5, s. 566-574
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Tidskriftsartikel (refereegranskat)abstract
- Objective:To determine viral load (VL) nonsuppression (VLN) rates, HIV drug resistance (HIVDR) prevalence, and associated factors among female sex workers (FSWs) in Ethiopia.Methods:A cross-sectional biobehavioral survey was conducted among FSWs in 11 cities in Ethiopia in 2014. Whole blood was collected, and HIVDR genotyping was performed. Logistic regression analysis was performed to identify factors associated with VLN and HIVDR.Results:Among 4900 participants, 1172 (23.9%) were HIV-positive and 1154 (98.5%) had a VL result. Participants were categorized into antiretroviral therapy (ART) (n = 239) and ART-naive (n = 915) groups based on self-report. From the 521 specimens (ART, 59; ART-naive, 462) with VL ≥1000 copies/mL, genotyping was successful for 420 (80.6%) and 92 (21.9%) had drug resistance mutations (DRMs). Pretreatment drug resistance (PDR) was detected in 16.5% (63/381) of the ART-naive participants. Nucleoside reverse transcriptase inhibitor (NRTI), non-NRTIs (NNRTIs), and dual-class DRMs were detected in 40 (10.5%), 55 (14.4%), and 35 (9.2%) of the participants, respectively. Among 239 participants on ART, 59 (24.7%) had VLN. Genotyping was successfully performed for 39 (66.1%). DRMs were detected in 29 (74.4%). All 29 had NNRTI, 23 (79.3%) had NRTI or dual-class DRMs. VLN was associated with age 35 years or older, CD4+T-cell count <350 cells/mm3, and being forced into selling sex. PDR and acquired drug resistance were associated with CD4+T-cell count <350 cells/mm3(P < 0.001).Conclusions:The high VLN and HIVDR rates among FSWs underscore the need for targeted interventions to improve ART access and virologic monitoring to maximize the benefit of ART and limit the spread of HIV and HIVDR.
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| 26. |
- Arimide, Dawit Assefa, et al.
(författare)
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HIV-genetic diversity and drug resistance transmission clusters in Gondar, Northern Ethiopia, 2003-2013
- 2018
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 13:10
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Tidskriftsartikel (refereegranskat)abstract
- Background The HIV-1 epidemic in Ethiopia has been shown to be dominated by two phylogenetically distinct subtype C clades, the Ethiopian (C'-ET) and East African (C-EA) clades, however, little is known about the temporal dynamics of the HIV epidemic with respect to subtypes and distinct clades. Moreover, there is only limited information concerning transmission of HIV-1 drug resistance (TDR) in the country. Methods A cross-sectional survey was conducted among young antiretroviral therapy (ART)-naïve individuals recently diagnosed with HIV infection, in Gondar, Ethiopia, 2011-2013 using the WHO recommended threshold survey. A total of 84 study participants with a median age of 22 years were enrolled. HIV-1 genotyping was performed and investigated for drug resistance in 67 individuals. Phylogenetic analyses were performed on all available HIV sequences obtained from Gondar (n = 301) which were used to define subtype C clades, temporal trends and local transmission clusters. Dating of transmission clusters was performed using BEAST. Result Four of 67 individuals (6.0%) carried a HIV drug resistance mutation strain, all associated with non-nucleoside reverse transcriptase inhibitors (NNRTI). Strains of the C-EA clade were most prevalent as we found no evidence of temporal changes during this time period. However, strains of the C-SA clade, prevalent in Southern Africa, have been introduced in Ethiopia, and became more abundant during the study period. The oldest Gondar transmission clusters dated back to 1980 (C-EA), 1983 (C-SA) and 1990 (C'-ET) indicating the presence of strains of different subtype C clades at about the same time point in Gondar. Moreover, some of the larger clusters dated back to the 1980s but transmissions within clusters have been ongoing up till end of the study period. Besides being associated with more sequences and larger clusters, the C-EA clade sequences were also associated with clustering of HIVDR sequences. One cluster was associated with the G190A mutation and showed onward transmissions at high rate. Conclusion TDR was detected in 6.0% of the sequenced samples and confirmed pervious reports that the two subtype C clades, C-EA and C'-ET, are common in Ethiopia. Moreover, the findings indicated an increased diversity in the epidemic as well as differences in transmission clusters sizes of the different clades and association with resistance mutations. These findings provide epidemiological insights not directly available using standard surveillance and may inform the adjustment of public health strategies in HIV prevention in Ethiopia.
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| 27. |
- Arimide, Dawit Assefa, et al.
(författare)
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Molecular Epidemiology and Transmission Dynamics of the HIV-1 Epidemic in Ethiopia : Epidemic Decline Coincided With Behavioral Interventions Before ART Scale-Up
- 2022
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Ingår i: Frontiers in Microbiology. - : Frontiers Media SA. - 1664-302X. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Background: Ethiopia is one of the sub-Saharan countries hit hard by the HIV epidemic. Previous studies have shown that subtype C dominates the Ethiopian HIV-1 epidemic, but the evolutionary and temporal dynamics of HIV-1 in Ethiopia have not been closely scrutinized. Understanding the evolutionary and epidemiological pattern of HIV is vital to monitor the spread, evaluate and implement HIV prevention strategies. Methods: We analyzed 1,276 Ethiopian HIV-1 subtype C polymerase (pol sequences), including 144 newly generated sequences, collected from different parts of the country from 1986 to 2017. We employed state-of-art maximum likelihood and Bayesian phylodynamic analyses to comprehensively describe the evolutionary dynamics of the HIV-1 epidemic in Ethiopia. We used Bayesian phylodynamic models to estimate the dynamics of the effective population size (Ne) and reproductive numbers (Re) through time for the HIV epidemic in Ethiopia. Results: Our analysis revealed that the Ethiopian HIV-1 epidemic originated from two independent introductions at the beginning of the 1970s and 1980s from eastern and southern African countries, respectively, followed by epidemic growth reaching its maximum in the early 1990s. We identified three large clusters with a majority of Ethiopian sequences. Phylodynamic analyses revealed that all three clusters were characterized by high transmission rates during the early epidemic, followed by a decline in HIV-1 transmissions after 1990. Re was high (4–6) during the earlier time of the epidemic but dropped significantly and remained low (Re < 1) after the mid-1990. Similarly, with an expected shift in time, the effective population size (Ne) steadily increased until the beginning of 2000, followed by a decline and stabilization until recent years. The phylodynamic analyses corroborated the modeled UNAIDS incidence and prevalence estimates. Conclusion: The rapid decline in the HIV epidemic took place a decade before introducing antiretroviral therapy in Ethiopia and coincided with early behavioral, preventive, and awareness interventions implemented in the country. Our findings highlight the importance of behavioral interventions and antiretroviral therapy scale-up to halt and maintain HIV transmissions at low levels (Re < 1). The phylodynamic analyses provide epidemiological insights not directly available using standard surveillance and may inform the adjustment of public health strategies in HIV prevention in Ethiopia.
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| 28. |
- Arimide, Dawit Assefa, et al.
(författare)
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Pre-Treatment Integrase Inhibitor Resistance and Natural Polymorphisms among HIV-1 Subtype C Infected Patients in Ethiopia
- 2022
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Ingår i: Viruses. - : MDPI AG. - 1999-4915. ; 14:4
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Tidskriftsartikel (refereegranskat)abstract
- Dolutegravir-based antiretroviral therapy (ART) has been scaled up in many developing countries, including Ethiopia. However, subtype-dependent polymorphic differences might influence the occurrence of HIV-drug-resistance mutations (HIVDRMs). We analyzed the prevalence of pre-treatment integrase strand transfer inhibitor (INSTI) HIVDRMs and naturally occurring polymorphisms (NOPs) of the integrase gene, using plasma samples collected as part of the national HIVDR survey in Ethiopia in 2017. We included a total of 460 HIV-1 integrase gene sequences from INSTI-naïve (n = 373 ART-naïve and n = 87 ART-experienced) patients. No dolutegravir-associated HIVDRMs were detected, regardless of previous exposure to ART. However, we found E92G in one ART-naïve patient specimen and accessory mutations in 20/460 (4.3%) of the specimens. Moreover, among the 288 integrase amino acid positions of the subtype C, 187/288 (64.9%) were conserved (<1.0% variability). Analysis of the genetic barrier showed that the Q148H/K/R dolutegravir resistance pathway was less selected in subtype C. Docking analysis of the dolutegravir showed that protease-and reverse-transcriptase-associated HIVDRMs did not affect the native structure of the HIV-1 integrase. Our results support the implementation of a wide scale-up of dolutegravir-based regimes. However, the detection of polymorphisms contributing to INSTI warrants the continuous surveillance of INSTI resistance.
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| 29. |
- Azadi, Seifollah, et al.
(författare)
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Up-regulation and increased phosphorylation of protein kinase C (PKC) delta, mu and theta in the degenerating rd1 mouse retina.
- 2006
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Ingår i: Molecular and Cellular Neuroscience. - : Elsevier BV. - 1044-7431. ; 31:4, s. 759-773
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Tidskriftsartikel (refereegranskat)abstract
- The rd1 mouse serves as a model for inherited photoreceptor degeneration: retinitis pigmentosa. Microarray techniques were employed to compare the transcriptomes of rd1 and congenic wild-type retinas at postnatal day 11, when degenerative processes have started but most photoreceptors are still present. Of the several genes that were differentially expressed, focus was put on those associated with the protein kinase C (PKC) signaling pathway, in particular PKCδ, μ and θ. Microarray identified these as being up-regulated in the rd1 retina, which was confirmed by QRT-PCR. Western blotting and immunostaining, using antibodies against either total or phosphorylated variants of the PKC isoforms, revealed increased expression and phosphorylation of PKCδ, μ and θ in the rd1 retina at the protein level as well. Our results suggest that these PKC isoforms are involved in rd1 degeneration.
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| 30. |
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| 31. |
- Buggert, Marcus, et al.
(författare)
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CD4+ T cells with an activated and exhausted phenotype distinguish immunodeficiency during aviremic HIV-2 infection
- 2016
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Ingår i: AIDS. - 0269-9370. ; 30:16, s. 2415-2426
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE:: HIV-2 represents an attenuated form of HIV, where many infected individuals remain “aviremic” without antiretroviral therapy (ART). However, aviremic HIV-2 disease progression exits, and in the current study we therefore aimed to examine if specific pathological characteristics of CD4+ T cells are linked to such outcome. DESIGN:: HIV-seronegative (n=25), HIV-1 (n?=?33), HIV-2 (n?=?39, of whom 26 were aviremic), and HIV-1/2 dually (HIV-D) (n?=?13) infected subjects were enrolled from an occupational cohort in Guinea-Bissau. METHODS:: CD4+ T cell differentiation, activation, exhaustion, senescence, and transcription factors were assessed by polychromatic flow cytometry. Multidimensional clustering bioinformatic tools were used to identify CD4+ T cell subpopulations linked to infection type and disease stage. RESULTS:: HIV-2-infected individuals had early- and late-differentiated CD4+ T cell clusters with lower activation (CD38+HLA-DR+) and exhaustion (PD-1) than HIV-1 and HIV-D-infected subjects. We also noted that aviremic HIV-2-infected individuals possessed fewer CD4+ T cells with pathological signs compared to other HIV-infected groups. Still, compared to HIV-seronegatives, aviremic HIV-2-infected subjects had T-bet+ CD4+ T cells that showed elevated immune activation/exhaustion, and particularly the frequencies of PD-1+ cells were associated with suboptimal percentage of CD4+ T cells. CONCLUSIONS:: Increased frequencies of CD4+ T cells with an activated/exhausted phenotype correlate with exacerbated immunodeficiency in aviremic HIV-2-infected individuals. Thus, these findings encourage studies on the introduction of ART also to individuals with aviremic HIV-2 infection.
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| 32. |
- Bächle, Susanna M., et al.
(författare)
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Elevated levels of iNKT cell and NK cell activation correlate with disease progression in HIV-1 and HIV-2 infections
- 2016
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Ingår i: AIDS. - 0269-9370. ; 30:11, s. 1713-1722
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE:: In this study we aimed to investigate the frequency and activation of invariant natural killer T (iNKT) cells and natural killer (NK) cells among HIV-1, HIV-2, or dually HIV-1/HIV-2 (HIV-D)-infected individuals, in relation to markers of disease progression. DESIGN:: Whole blood samples were collected from treatment-naïve HIV-1 (n?=?23), HIV-2 (n?=?34) and HIV-D (n?=?11) infected individuals, as well as HIV-seronegative controls (n?=?25), belonging to an occupational cohort in Guinea-Bissau. METHODS:: Frequencies and activation levels of iNKT and NK cell subsets were analysed using multi-colour flow cytometry and results were related to HIV-status, CD4+ T cell levels, viral load, and T cell activation. RESULTS:: HIV-1, HIV-D, and viremic HIV-2 individuals had lower numbers of CD4+ iNKT cells in circulation compared to seronegative controls. Numbers of CD56 NK cells were also reduced in HIV-infected individuals as compared to control subjects. Notably, iNKT cell and NK cell activation levels, assessed by CD38 expression, were increased in HIV-1 and HIV-2 single, as well as dual, infections. HIV-2 viremia was associated with elevated activation levels in CD4+ iNKT cells, CD56 and CD56 NK cells, as compared to aviremic HIV-2 infection. Additionally, disease markers such as CD4+ T cell percentages, viral load, and CD4+ T cell activation were associated with CD38 expression levels of both iNKT and NK cells, which activation levels also correlated with each other. CONCLUSIONS:: Our data indicate that elevated levels of iNKT cell and NK cell activation are associated with viremia and disease progression markers in both HIV-1 and HIV-2 infections.
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| 33. |
- Dunn, Cathrine A, et al.
(författare)
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An endogenous retroviral long terminal repeat is the dominant promoter for human beta 1,3-galactosyltransferase 5 in the colon
- 2003
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Ingår i: Proceedings of the National Academy of Sciences. - : Proceedings of the National Academy of Sciences. - 1091-6490 .- 0027-8424. ; 100:22, s. 12841-12846
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Tidskriftsartikel (refereegranskat)abstract
- LTRs of endogenous retroviruses are known to affect expression of several human genes, typically as a relatively minor alternative promoter. Here, we report that an endogenous retrovirus LTR acts as one of at least two alternative promoters for the human beta1,3-galactosyltransferase 5 gene, involved in type 1 Lewis antigen synthesis, and show that the LTR promoter is most active in the gastrointestinal tract and mammary gland. Indeed, the LTR is the dominant promoter in the colon, indicating that this ancient retroviral element has a major impact on gene expression. Using colorectal cancer cell lines and electrophoretic mobility-shift assays, we found that hepatocyte nuclear factor 1 (HNF-1) binds a site within the retroviral promoter and that expression of HNF-1 and interaction with its binding site correlated with promoter activation. We conclude that HNF-1 is at least partially responsible for the tissue-specific activation of the LTR promoter of human beta1,3-galactosyltransferase 5. We demonstrate that this tissue-specific transcription factor is implicated in the activation of an LTR gene promoter.
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| 34. |
- Elvstam, Olof, et al.
(författare)
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All-Cause Mortality and Serious Non-AIDS Events in Adults with Low-Level HIV Viremia during Combination Antiretroviral Therapy: Results from a Swedish Nationwide Observational Study.
- 2021
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Ingår i: Clinical Infectious Diseases. - : Oxford University Press (OUP). - 1058-4838 .- 1537-6591. ; 72:12, s. 2079-2086
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Tidskriftsartikel (refereegranskat)abstract
- The impact of low levels of HIV RNA (low-level viremia; LLV) during combination antiretroviral therapy (cART) on clinical outcomes is unclear. We explored the associations between LLV and all-cause mortality, AIDS, and serious non-AIDS events (SNAE).We grouped individuals starting cART 1996-2017 (identified from the Swedish InfCare HIV register) as virologic suppression (VS; <50 copies/mL), LLV (repeated viral load 50-999 copies/mL), and non-suppressed viremia (NSV; ≥1000 copies/mL). Separately, LLV was subdivided into 50-199 and 200-999 copies/mL (reflecting different definitions of virologic failure). Proportional-hazard models (including sex, age, pre-ART CD4 count and viral load, country of birth, injection drug use, treatment experience and interruptions, and an interaction term between viremia and time) were fitted for the study outcomes.6,956 participants were followed for a median of 5.7 years. At the end of follow-up, 60% were categorized as VS, 9% as LLV, and 31% as NSV. Compared with VS, LLV was associated with increased mortality (adjusted hazard ratio [aHR] 2.2, 95% confidence interval [CI] 1.3-3.6). This association was also observed for LLV 50-199 copies/mL (aHR 2.2, 95% CI 1.3-3.8), but was not statistically significant for LLV 200-999 copies/mL (aHR 2.1, 95% CI 0.96-4.7). LLV 50-999 copies/mL was not linked to increased risk of AIDS or SNAE, but in subanalysis, LLV 200-999 copies/mL was associated with SNAE (aHR 2.0, 95% CI 1.2-3.6).In this population-based cohort, LLV during cART was associated with adverse clinical outcomes.
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| 35. |
- Elvstam, Olof, et al.
(författare)
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Associations Between Plasma Human Immunodeficiency Virus (HIV) Ribonucleic Acid Levels and Incidence of Invasive Cancer in People With HIV After Initiation of Combination Antiretroviral Therapy.
- 2021
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Ingår i: Open forum infectious diseases. - : Oxford University Press (OUP). - 2328-8957. ; 8:6
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Tidskriftsartikel (refereegranskat)abstract
- Human immunodeficiency virus (HIV) viremia could be involved in the increased risk of cancer in people with HIV (PWH) receiving combination antiretroviral therapy (cART). We analyzed the association between plasma HIV ribonucleic acid levels in PWH starting cART and incident invasive cancer using the Swedish cohort InfCare HIV linked with national registers.Adults starting cART in 1996-2017 were included if they had ≥1 viral load (VL) measurement before receiving any antiretroviral agent (pre-ART VL) and ≥2 VLs ≥6 months after start of cART. Viremia during cART was analyzed both as viremia-copy-years and categorized as suppression (<50 copies/mL), low-level viremia ([LLV] 50-999 copies/mL), and nonsuppression (≥1000 copies/mL). The main outcome was a composite of invasive malignancies with increased incidence among PWH. We fitted proportional subhazard models (including sex, age, pre-ART CD4 count, and injection drug use) for both pre-ART VL and viremia during cART.After 32 105 person-years, 3254 of 4931 participants (66%) were classified as suppressed, 438 (9%) were classified as LLV, and 1221 (25%) were classified as nonsuppressed. Neither viremia category nor cumulative viremia during cART had a statistically significant association with cancer. Higher pre-ART VL was associated with cancer (adjusted subhazard ratio, 1.4; 95% confidence interval, 1.0-1.8); this remained statistically significant with viremia during cART in the model. In subanalysis, the association with pre-ART VL was statistically significant for acquired immune deficiency syndrome (AIDS)-defining and infection-related non-AIDS-defining cancer, but not for other malignancies.In this nationwide cohort, pre-ART VL was an independent predictor of invasive cancer, whereas viremia profile during cART was not associated with cancer incidence.
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| 36. |
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| 37. |
- Elvstam, Olof, et al.
(författare)
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Virological failure and all-cause mortality in HIV-positive adults with low-level viremia during antiretroviral treatment
- 2017
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 12:7
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Tidskriftsartikel (refereegranskat)abstract
- Objective Although most HIV-infected individuals achieve undetectable viremia during antiretroviral therapy (ART), a subset have low-level viremia (LLV) of varying duration and magnitude. The impact of LLV on treatment outcomes is unclear. We investigated the association between LLV and virological failure and/or all-cause mortality among Swedish patients receiving ART. HIV-infected patients from two Swedish HIV centers were identified from the nationwide register InfCare HIV. Subjects aged >= 15 years with triple agent ART were included at 12 months after treatment initiation if >= 2 following viral load measurements were available. Patients with 2 consecutive HIV RNA values >= 1000 copies/mL at this time point were excluded. Participants were stratified into four categories depending on viremia profiles: permanently suppressed viremia (<50 copies/mL), LLV 50-199 copies/mL, LLV 200-999 copies/mL and viremia >= 1000 copies/mL. Association between all four viremia categories and all-cause death was calculated using survival analysis with viremia as a time-varying covariate, so that patients could change viremia category during follow-up. Association between the three lower categories and virological failure >= 2 consecutive measurements >= 1000 copies/mL) was calculated in a similar manner. LLV 50-199 copies/mL was recorded in 70/1015 patients (6.9%) and LLV 200-999 copies/mL in 89 (8.8%) during 7812 person-years of follow-up (median 6.5 years). LLV 200-999 copies/mL was associated with virological failure (adjusted hazard ratio 3.14 [95% confidence interval 1.41-7.03, p<0.01]), whereas LLV 50-199 copies/mL was not (1.01 [0.34-4.31, p = 0.99]; median follow-up 4.5 years). LLV 200-999 copies/mL had an adjusted mortality hazard ratio of 2.29 (0.98-5.32, p = 0.05) and LLV 50-199 copies/mL of 2.19 (0.90-5.37, p = 0.09). In this Swedish cohort followed during ART for a median of 4.5 years, LLV 200-999 copies/mL was independently associated with virological failure. Patients with LLV had higher rates of all-cause mortality, although not statistically significant in multivariate analysis.
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| 38. |
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| 39. |
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| 40. |
- Esbjörnsson, Joakim, et al.
(författare)
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Frequent CXCR4 tropism of HIV-1 subtype A and CRF02_AG during late-stage disease - indication of an evolving epidemic in West Africa
- 2010
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Ingår i: Retrovirology. - : Springer Science and Business Media LLC. - 1742-4690. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Background: HIV-1 is one of the fastest evolving pathogens, and is distinguished by geographic and genetic variants that have been classified into different subtypes and circulating recombinant forms (CRFs). Early in infection the primary coreceptor is CCR5, but during disease course CXCR4-using HIV-1 populations may emerge. This has been correlated with accelerated disease progression in HIV-1 subtype B. Basic knowledge of HIV-1 coreceptor tropism is important due to the recent introduction of coreceptor antagonists in antiretroviral therapy, and subtype-specific differences regarding how frequently HIV-1 CXCR4-using populations appear in late-stage disease need to be further investigated. To study how frequently CXCR4-using populations appear in late-stage disease among HIV-1 subtype A and CRF02_AG, we evaluated the accuracy of a recombinant virus phenotypic assay for these subtypes, and used it to determine the HIV-1 coreceptor tropism of plasma samples collected during late-stage disease in Guinea-Bissau. We also performed a genotypic analysis and investigated subtype-specific differences in the appearance of CXCR4 tropism late in disease. Results: We found that the recombinant virus phenotypic assay accurately predicted HIV-1 coreceptor tropism of subtype A and CRF02_AG. Over the study period (1997-2007), we found an increasing and generally high frequency of CXCR4 tropism (86%) in CRF02_AG. By sequence analysis of the V3 region of our samples we developed a novel genotypic rule for predicting CXCR4 tropism in CRF02_AG, based on the combined criteria of the total number of charged amino acids and net charge. This rule had higher sensitivity than previously described genotypic rules and may be useful for development of future genotypic tools for this CRF. Finally, we conducted a literature analysis, combining data of 498 individuals in late-stage disease, and found high amounts of CXCR4 tropism for all major HIV-1 subtypes (60-77%), except for subtype C (15%). Conclusions: The increase in CXCR4 tropism over time suggests an evolving epidemic of CRF02_AG. The results of the literature analysis demonstrate the need for further studies investigating subtype-specific emergence for CXCR4-tropism; this may be particularly important due to the introduction of CCR5-antagonists in HIV treatment regimens.
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| 41. |
- Esbjörnsson, Joakim, et al.
(författare)
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HIV-1 Molecular Epidemiology in Guinea-Bissau, West Africa: Origin, Demography and Migrations
- 2011
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 6:2
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Tidskriftsartikel (refereegranskat)abstract
- The HIV-1 epidemic in West Africa has been dominated by subtype A and the recombinant form CRF02_AG. Little is known about the origins and the evolutionary history of HIV-1 in this region. We employed Maximum likelihood and Bayesian methods in combination with temporal and spatial information to reconstruct the HIV-1 subtype distribution, demographic history and migration patterns over time in Guinea-Bissau, West Africa. We found that CRF02_AG and subsubtype A3 were the dominant forms of HIV-1 in Guinea-Bissau and that they were introduced into the country on at least six different occasions between 1976 and 1981. These estimates also corresponded well with the first reported HIV-1 cases in Guinea-Bissau. Migration analyses suggested that (1) the HIV-1 epidemic started in the capital Bissau and then dispersed into more rural areas, and (2) the epidemic in Guinea-Bissau was connected to both Cameroon and Mali. This is the first study that describes the HIV-1 molecular epidemiology in a West African country by combining the results of subtype distribution with analyses of epidemic origin and epidemiological linkage between locations. The multiple introductions of HIV-1 into Guinea-Bissau, during a short time-period of five years, coincided with and were likely influenced by the major immigration wave into the country that followed the end of the independence war (1963-1974).
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| 42. |
- Esbjörnsson, Joakim, et al.
(författare)
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HIV-2 as a model to identify a functional HIV cure
- 2019
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Ingår i: AIDS Research and Therapy. - : Springer Science and Business Media LLC. - 1742-6405. ; 16:1
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Forskningsöversikt (refereegranskat)abstract
- Two HIV virus types exist: HIV-1 is pandemic and aggressive, whereas HIV-2 is confined mainly to West Africa and less pathogenic. Despite the fact that it has been almost 40 years since the discovery of AIDS, there is still no cure or vaccine against HIV. Consequently, the concepts of functional vaccines and cures that aim to limit HIV disease progression and spread by persistent control of viral replication without life-long treatment have been suggested as more feasible options to control the HIV pandemic. To identify virus-host mechanisms that could be targeted for functional cure development, researchers have focused on a small fraction of HIV-1 infected individuals that control their infection spontaneously, so-called elite controllers. However, these efforts have not been able to unravel the key mechanisms of the infection control. This is partly due to lack in statistical power since only 0.15% of HIV-1 infected individuals are natural elite controllers. The proportion of long-Term viral control is larger in HIV-2 infection compared with HIV-1 infection. We therefore present the idea of using HIV-2 as a model for finding a functional cure against HIV. Understanding the key differences between HIV-1 and HIV-2 infections, and the cross-reactive effects in HIV-1/HIV-2 dual-infection could provide novel insights in developing functional HIV cures and vaccines.
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| 43. |
- Esbjörnsson, Joakim, et al.
(författare)
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Increased survival among HIV-1 and HIV-2 dual-infected individuals compared to HIV-1 single-infected individuals
- 2014
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Ingår i: AIDS. - 1473-5571. ; 28:7, s. 949-957
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To compare survival times of HIV-1 single and HIV-1 and HIV-2 dual-infected individuals. Design: Prospective open cohort study. Methods: We analysed data from 259 HIV-1-seroincident cases (either HIV-1 single or HIV-1 and HIV-2 dual-infected) from a cohort with long follow-up (similar to 20 years) in order to study the influence of type of infection and infection order on mortality. Sex and age at HIV-1 infection date was controlled for in a Cox proportional-hazards model. Results: Dual-infected individuals had a 42% longer time from HIV-1 infection to death compared with single-infected individuals, adjusting for age asymmetries between groups. Dual-infected individuals with an HIV-2 infection preceding the HIV-1 infection had a more than two-fold lower mortality risk during follow-up than HIV-1 single-infected individuals. Conclusion: Survival time is longer and the risk of progression to death is lower among HIV-1 and HIV-2 dual-infected individuals compared to HIV-1 single-infected individuals. This natural inhibition could have implications for the development of future HIV-1 vaccines and therapeutics.
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| 44. |
- Esbjörnsson, Joakim, et al.
(författare)
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Inhibition of HIV-1 disease progression by contemporaneous HIV-2 infection.
- 2012
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Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 367:3, s. 224-232
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Progressive immune dysfunction and the acquired immunodeficiency syndrome (AIDS) develop in most persons with untreated infection with human immunodeficiency virus type 1 (HIV-1) but in only approximately 20 to 30% of persons infected with HIV type 2 (HIV-2); among persons infected with both types, the natural history of disease progression is poorly understood. METHODS: We analyzed data from 223 participants who were infected with HIV-1 after enrollment (with either HIV-1 infection alone or HIV-1 and HIV-2 infection) in a cohort with a long follow-up duration (approximately 20 years), according to whether HIV-2 infection occurred first, the time to the development of AIDS (time to AIDS), CD4+ and CD8+ T-cell counts, and measures of viral evolution. RESULTS: The median time to AIDS was 104 months (95% confidence interval [CI], 75 to 133) in participants with dual infection and 68 months (95% CI, 60 to 76) in participants infected with HIV-1 only (P=0.003). CD4+ T-cell levels were higher and CD8+ T-cell levels increased at a lower rate among participants with dual infection, reflecting slower disease progression. Participants with dual infection with HIV-2 infection preceding HIV-1 infection had the longest time to AIDS and highest levels of CD4+ T-cell counts. HIV-1 genetic diversity was significantly lower in participants with dual infections than in those with HIV-1 infection alone at similar time points after infection. CONCLUSIONS: Our results suggest that HIV-1 disease progression is inhibited by concomitant HIV-2 infection and that dual infection is associated with slower disease progression. The slower rate of disease progression was most evident in participants with dual infection in whom HIV-2 infection preceded HIV-1 infection. These findings could have implications for the development of HIV-1 vaccines and therapeutics. (Funded by the Swedish International Development Cooperation Agency-Swedish Agency for Research Cooperation with Developing Countries and others.).
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| 45. |
- Esbjörnsson, Joakim, et al.
(författare)
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Long-term follow-up of HIV-2-related AIDS and mortality in Guinea-Bissau : a prospective open cohort study
- 2019
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Ingår i: The Lancet HIV. - : The Lancet Publishing Group. - 2405-4704 .- 2352-3018. ; 6:1, s. E25-E31
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: HIV type 2 (HIV-2) is considered more benign and has fewer pathogenic consequences than HIV type 1 (HIV-1) for most infected individuals. However, reliable estimates of time to AIDS and mortality among those with HIV-2 infection are absent. We therefore aimed to compare the time to AIDS and mortality, and the CD4 T-cell dynamics between those infected with HIV-1 and HIV-2.METHODS: We did a prospective open cohort study. We included all police officers with regular employment from police stations in both urban and rural areas of Guinea-Bissau since Feb 6, 1990. We continued to include participants until Sept 28, 2009, and follow-up of HIV-1-positive and HIV-2-positive individuals continued until Sept 28, 2013. We collected blood samples at enrolment and at scheduled annual follow-up visits at police stations. We analysed longitudinal data from individuals infected with HIV-1 and HIV-2 according to time to AIDS, time to death, and T-cell dynamics. Time of HIV infection was estimated as the mid-timepoint between last HIV-seronegative and first HIV-seropositive sample. Data from an additional 2984 HIV-uninfected individuals from the same population were analysed to assess the effect of natural mortality on HIV-related mortality.FINDINGS: 872 participants tested HIV positive during the 23-year study period: 408 were infected with HIV-1 (183 infected before and 225 infected after enrolment) and 464 were infected with HIV-2 (377 before and 87 after enrolment). The median time from HIV infection to development of AIDS was 6·2 years (95% CI 5·4-7·1) for HIV-1 infection and 14·3 years (10·7-18·0) for HIV-2 infection (p<0·0001). The median survival time after HIV infection was 8·2 years (95% CI 7·5-8·9) for HIV-1 infection and 15·6 years (12·0-19·2) for HIV-2 infection (p<0·0001). Individuals who were infected with HIV-1 or HIV-2 before enrolment showed similar results. Comparison with uninfected individuals indicated limited confounding contribution from natural mortality. Mean CD4 percentages were higher in individuals with HIV-2 than in those with HIV-1 during early infection (28·0% [SE 1·3] vs 22·3% [1·7]; p=0·00094) and declined at a slower rate (0·4% [0·2] vs 0·9% [0·2] per year; p=0·028). HIV-2-infected individuals developed clinical AIDS at higher mean CD4 percentages (18·2%, IQR 7·2-25·4) than HIV-1-infected individuals (8·2%, 3·0-13·8; p<0·0001).INTERPRETATION: Our results show that both HIV-1-infected and HIV-2-infected individuals have a high probability of developing and dying from AIDS without antiretroviral treatment.
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| 46. |
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| 47. |
- Fenyö, Eva Maria, et al.
(författare)
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Human immunodeficiency virus type 1 biological variation and coreceptor use: from concept to clinical significance.
- 2011
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Ingår i: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 270, s. 520-531
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Tidskriftsartikel (refereegranskat)abstract
- There is ample evidence for intra-patient evolution of the human immunodeficiency virus type 1 (HIV-1) biological phenotype during the pathogenic process. Evolution often involves switch of coreceptor use from CCR5 to CXCR4, but change to more flexible use of CCR5 occurs over time even in patients with maintained CCR5 use. The increasing use of entry inhibitors in the clinic, often specific for one or the other HIV-1 coreceptor or with different binding properties to CCR5, calls for virus testing in patients prior to treatment initiation. Cell lines expressing CCR5/CXCR4 chimeric receptors are tools for testing viruses for mode of CCR5 use. It is conceivable that small-molecule entry inhibitors that differentially bind to CCR5 can be matched for best effect against HIV-1 with different modes of CCR5 use, thereby allowing an individualized drug choice specifically tailored for each patient.
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| 48. |
- Flockerzi, Aline, et al.
(författare)
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Expression pattern analysis of transcribed HERV sequences is complicated by ex vivo recombination
- 2007
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Ingår i: Retrovirology. - : Springer Science and Business Media LLC. - 1742-4690. ; 4
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Tidskriftsartikel (refereegranskat)abstract
- Background: The human genome comprises numerous human endogenous retroviruses ( HERVs) that formed millions of years ago in ancestral species. A number of loci of the HERV-K(HML-2) family are evolutionarily much younger. A recent study suggested an infectious HERV-K(HML-2) variant in humans and other primates. Isolating such a varian t from human individuals would be a significant finding for human biology. Results: When investigating expression patterns of specific HML-2 proviruses we encountered HERV-K(HML-2) cDNA sequences without proviral homologues in the human genome, named HERV-KX, that could very well support recently suggested infectious HML-2 variants. However, detailed sequence analysis, using the software RECCO, suggested that HERV-KX sequences were produced by recombination, possibly arising ex vivo, between transcripts from different HML-2 proviral loci. Conclusion: As RT-PCR probably will be instrumental for isolating an infectious HERV-K(HML2) variant, generation of "new" HERV-K(HML-2) sequences by ex vivo recombination seems inevitable. Further complicated by an unknown amount of allelic sequence variation in HERV-K(HML-2) proviruses, newly identified HERV-K(HML-2) variants should be interpreted very cautiously.
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| 49. |
- Holmdahl, Torsten, et al.
(författare)
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Hydrogen Peroxide Vapor Decontamination in a Patient Room Using Feline Calicivirus and Murine Norovirus as Surrogate Markers for Human Norovirus.
- 2016
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Ingår i: Infection Control & Hospital Epidemiology. - : Cambridge University Press (CUP). - 0899-823X .- 1559-6834. ; 37:5, s. 561-566
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE To determine whether hydrogen peroxide vapor (HPV) could be used to decontaminate caliciviruses from surfaces in a patient room. DESIGN Feline calicivirus (FCV) and murine norovirus (MNV) were used as surrogate viability markers to mimic the noncultivable human norovirus. Cell culture supernatants of FCV and MNV were dried in triplicate 35-mm wells of 6-well plastic plates. These plates were placed in various positions in a nonoccupied patient room that was subsequently exposed to HPV. Control plates were positioned in a similar room but were never exposed to HPV. METHODS Virucidal activity was measured in cell culture by reduction in 50% tissue culture infective dose titer for FCV and by both 50% tissue culture infective dose titer and plaque reduction for MNV. RESULTS Neither viable FCV nor viable MNV could be detected in the test room after HPV treatment. At least 3.65 log reduction for FCV and at least 3.67 log reduction for MNV were found by 50% tissue culture infective dose. With plaque assay, measurable reduction for MNV was at least 2.85 log units. CONCLUSIONS The successful inactivation of both surrogate viruses indicates that HPV could be a useful tool for surface decontamination of a patient room contaminated by norovirus. Hence nosocomial spread to subsequent patients can be avoided. Infect. Control Hosp. Epidemiol. 2016;1-6.
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| 50. |
- Holmdahl, Torsten, et al.
(författare)
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Hydrogen peroxide vapour treatment inactivates norovirus but has limited effect on post-treatment viral RNA levels
- 2019
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Ingår i: Infectious Diseases. - : Informa UK Limited. - 2374-4235 .- 2374-4243. ; 51:3, s. 197-205
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Tidskriftsartikel (refereegranskat)abstract
- Background: Hydrogen peroxide vapour is used as a room disinfectant. Its activity against murine norovirus, a surrogate viability marker for human norovirus, indicates that it is also active against human norovirus. Aim: The aim of this study is to assess how this effect on viability is reflected in measurements of RNA by quantitative PCR (qPCR). Methods: Faeces suspensions of two human norovirus field strains, genogroup I and II and one cultured murine norovirus strain, (genogroup V) were dried on plastic plates, and underwent hydrogen peroxide vapour treatment or were mock treated. The influence of hydrogen peroxide on RNA was measured on genogroups I, II and V by qPCRs and for the cultivable murine norovirus also for viability by cell culture. Virucidal activity on murine norovirus was measured by endpoint titrations as the 50% tissue culture infectious dose, based both on cytopathic effect and on presence of replicating intracellular minus strand RNA. Results: The mean impact on the human norovirus qPCRs was 0.4 log10. The murine norovirus qPCR changed by 1.7 log10 but by an alternative qPCR only by 0.4 log10. These minor changes contrasted the 4.5-5.0 log10 murine norovirus viability reduction after treatment measured by cytopathic effect or intracellular negative-strand RNA. Conclusion: Inactivation of murine norovirus viability by hydrogen peroxide vapour was not reflected in qPCR levels. This finding might be extrapolated to the related human norovirus genogroups. We further found that cellular minus strand murine norovirus PCR was an observer-independent marker to study reduction of murine norovirus viability.
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