| 1. |
- Asghar, Naveed, 1983-, et al.
(författare)
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Transient Expression of Flavivirus Structural Proteins in Nicotiana benthamiana
- 2022
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Ingår i: Vaccines. - : MDPI. - 2076-393X. ; 10:10
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Tidskriftsartikel (refereegranskat)abstract
- Flaviviruses are a threat to public health and can cause major disease outbreaks. Tick-borne encephalitis (TBE) is caused by a flavivirus, and it is one of the most important causes of viral encephalitis in Europe and is on the rise in Sweden. As there is no antiviral treatment availa-ble, vaccination remains the best protective measure against TBE. Currently available TBE vaccines are based on formalin-inactivated virus produced in cell culture. These vaccines must be delivered by intramuscular injection, have a burdensome immunization schedule, and may exhibit vaccine failure in certain populations. This project aimed to develop an edible TBE vaccine to trigger a stronger immune response through oral delivery of viral antigens to mucosal surfaces. We demonstrated successful expression and post-translational processing of flavivirus structural pro-teins which then self-assembled to form virus-like particles in Nicotiana benthamiana. We performed oral toxicity tests in mice using various plant species as potential bioreactors and evaluated the immunogenicity of the resulting edible vaccine candidate. Mice immunized with the edible vaccine candidate did not survive challenge with TBE virus. Interestingly, immunization of female mice with a commercial TBE vaccine can protect their offspring against TBE virus infection.
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| 2. |
- Ejaz, Muslima, et al.
(författare)
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Anal human papillomavirus infection among men who have sex with men and transgender women living with and without HIV in Pakistan : findings from a cross-sectional study
- 2021
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Ingår i: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 11:11
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: The aim of this study was to determine the prevalence of infection, genotypes and risk factors for human papillomavirus (HPV) among men who have sex with men (MSM) and transgender women living with and without HIV in Pakistan. Anal infection with HPV is very common worldwide among MSM, particularly among MSM living with HIV. The high prevalence of HIV among MSM and male-to-female transgendered individuals in Pakistan is a significant health concern since access to screening and health-seeking is often delayed in this stigmatised key population.DESIGN: This cross-sectional study was conducted between March 2016 and November 2017.PARTICIPANTS, SETTING AND DATA COLLECTION: This study recruited MSM and transgender-women who self-reported to have had anal sex in the last 6 months, and were at least 18 years of age, from the sexual health and antiretroviral therapy centres. Structured questionnaires were administered, and blood samples were obtained to confirm HIV status. Anal swabs were collected for HPV-DNA detection and typing.MAIN OUTCOME MEASURES: The primary outcome was the prevalence of 'HPV-DNA infection'. The prevalence ratios (PR) were calculated using Cox proportional hazard model algorithms to analyse the association between exposure variables and HPV-infection.RESULTS: Complete data were available for 298 MSM and transgender women (HIV +n=131; HIV-n=167). The overall HPV-DNA prevalence was 65.1% and was higher in participants living with HIV as compared with HIV-negative (87% vs 48%; χ2p≤0.001). Likewise, 28.9% of participants living with HIV were infected with two or more than two types of HPV as compared with 18.8% participants without HIV(χ2 p≤0.001). The most frequent HPV type was HPV6/11 (46.9%), followed by HPV16 (35.1%), HPV18 (23.2%) and HPV35 (21.1%). HIV status (PR 2.81, 95% CI 2.16 to 3.82) and never condom use (PR 3.08, 95% CI 1.69 to 5.60)) were independently associated with prevalence of 'anal-HPV16 infection' when adjusting for confounding for age, other sexual and behavioural factors, for example, smoking and alcohol consumption.CONCLUSION: High prevalence of HPV indicates a substantial future risk of anal cancer in Pakistani MSM and transgender women, and particularly in those living with HIV. Current findings support anal Pap-smear HPV screening for this particular group and vaccination efforts for future generations.
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| 3. |
- Ejaz, Muslima, et al.
(författare)
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Human papillomavirus-associated anal squamous intraepithelial lesions in men who have sex with men and transgender women living with and without HIV in Karachi Pakistan : implications for screening and prevention
- 2021
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Ingår i: BMC Infectious Diseases. - : BioMed Central. - 1471-2334. ; 21:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Anal squamous intraepithelial lesions (ASIL), strongly related to human papilloma virus (HPV) infection, is more prevalent among men who have sex with men (MSM). However, no such data are available for Pakistan yet, and neither HPV vaccination nor anal-cytology screening is implemented in Pakistan. The purpose of this first ever study was to assess the prevalence of HPV-related anal cytological abnormalities among MSM and transgender women living with and without HIV infection in Pakistan.METHODS: We conducted a cross-sectional study from March 2016 to November 2017 at sexual health centers run by the Perwaaz Trust and the National AIDS Control Program in Karachi. The study enrolled MSM and transgender women aged greater-than-and-equal-to-18-years who reported anal sex in the preceding 6 months. We collected two anal samples for liquid-based cytology and HPV type testing by PCR, and socio-demographic and behavioral data were collected through face-to face interviews. ASIL and its associations with biological and behavioral risk factors were analyzed through Cox regression for prevalence ratios (PR) and corresponding 95% confidence intervals (CIs).RESULTS: Out of 271 qualifying participants, 79% were MSM and 21% transgender women. The mean age was 28.8 (± 8) years. Almost 35% (93/271) of the study population had ASIL detected, ASIL was significantly more common among participants living with HIV than in HIV negative ((50/118) 42.4%; vs. (43/153) 28.1%) (p ≤ 0.001). Among ASIL, 66% (61/93) had low-grade squamous intraepithelial lesions (LSIL), and 3.6% (3/93) had high-grade squamous intraepithelial lesions (HSIL). The overall, HPV16 positivity was 35.5% (33/93) among all abnormal anal lesions and all 3 HSIL were HPV16 positive, however, HPV16 positivity could show its association with ASIL detection in univariate model only (PRcrude: 2.11(1.39-3.18)). Moreover, any HR-HPV type (PR 3.04; 95% CI 1.75-5.26), concurrent sexually transmitted infection (STI) (2.13; (1.28-3.55)) and HIV + /HPV + coinfection (1.75; (1.07-2.88)) remained independently associated with ASIL in the multivariate model.CONCLUSIONS: Abnormal anal cytology among MSM and transgender is prevalent enough to consider optimal screening regimens. Further studies are required to see if periodic anal cytology can be made part of HIV care and treatment programs among MSM in Pakistan.
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| 4. |
- Holmbom, Martin, 1984-, et al.
(författare)
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Prehospital delay is an important risk factor for mortality in community-acquired bloodstream infection (CA-BSI) : a matched case–control study
- 2021
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Ingår i: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 11:11
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Tidskriftsartikel (refereegranskat)abstract
- Objectives The aim of this study was to identify prehospital and early hospital risk factors associated with 30-day mortality in patients with blood culture-confirmed community-acquired bloodstream infection (CA-BSI) in Sweden.Methods A retrospective case–control study of 1624 patients with CA-BSI (2015–2016), 195 non-survivors satisfying the inclusion criteria were matched 1:1 with 195 survivors for age, gender and microorganism. All forms of contact with a healthcare provider for symptoms of infection within 7 days prior CA-BSI episode were registered. Logistic regression was used to analyse risk factors for 30-day all-cause mortality.Results Of the 390 patients, 61% (115 non-survivors and 121 survivors) sought prehospital contact. The median time from first prehospital contact till hospital admission was 13 hours (6–52) for non-survivors and 7 hours (3–24) for survivors (p<0.01). Several risk factors for 30-day all-cause mortality were identified: prehospital delay OR=1.26 (95% CI: 1.07 to 1.47), p<0.01; severity of illness (Sequential Organ Failure Assessment score) OR=1.60 (95% CI: 1.40 to 1.83), p<0.01; comorbidity score (updated Charlson Index) OR=1.13 (95% CI: 1.05 to 1.22), p<0.01 and inadequate empirical antimicrobial therapy OR=3.92 (95% CI: 1.64 to 9.33), p<0.01. In a multivariable model, prehospital delay >24 hours from first contact remained an important risk factor for 30-day all-cause mortality due to CA-BSI OR=6.17 (95% CI: 2.19 to 17.38), p<0.01.Conclusion Prehospital delay and inappropriate empirical antibiotic therapy were found to be important risk factors for 30-day all-cause mortality associated with CA-BSI. Increased awareness and earlier detection of BSI in prehospital and early hospital care is critical for rapid initiation of adequate management and antibiotic treatment.All data relevant to the study are included in the article or uploaded as supplemental information.
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| 7. |
- Manjate, Alice, 1971-, et al.
(författare)
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Laboratory-based evaluation of the 4th-generation Alere™ HIV Combo rapid point-of-care test
- 2024
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 19:2
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Mozambique is a high-prevalence country for HIV and early detection of new HIV infections is crucial for control of the epidemic. We aimed to evaluate the accuracy of the 4th-generation rapid diagnostic test (RDT) AlereTM HIV Combo in detecting acute and seroconverted HIV-infection, among sexually-active women attending three clinical health centers in Maputo, Mozambique.METHODS: Women aged 14-55 years (n = 920) seeking care at the Mavalane Health Area, Maputo (February 2018-January 2019) were included, and blood specimens sampled. Sociodemographic and sexual behavior data were collected. Point-of-care HIV testing was performed using Alere DetermineTM HIV-1/2 and Uni-GoldTM HIV-1/2. All samples were also tested using Enzygnost® HIV Integral 4 and Innotest® HIV Antigen mAb in laboratory. The 4th-generation RDT AlereTM HIV Combo was evaluated on serum samples in the laboratory. Finally, Innotest® HIV Antigen mAb, Enzygnost® HIV Integral 4 (Ag/Ab), and HIV RNA quantification acted as gold standard assays in the evaluation of AlereTM HIV Combo test for HIV antigen detection (in clinical samples and in three HIV-1 seroconversion panels).RESULTS: The antibody component of the 4th generation AlereTM HIV Combo RDT demonstrated a sensitivity and specificity of 100% examining clinical samples. However, the test did not detect HIV p24 antigen in any clinical samples, while Innotest® HIV Antigen mAb, verified by Enzygnost® HIV Integral 4 (Ag/Ab) and/or HIV RNA quantification, detected HIV antigen in six clinical samples. Furthermore, the AlereTM HIV Combo RDT had a low sensitivity in the detection of HIV p24 antigen in seroconversion panels. The HIV prevalence among the examined women was 17.8%.CONCLUSIONS: The 4th-generation RDT AlereTM HIV Combo showed similar sensitivity to the 3rd-generation RDTs to detect seroconverted HIV-infections. However, the sensitivity for detection of HIV p24 antigen and diagnosing acute HIV infections, before seroconversion, was low. There is an urgent need to develop and evaluate simple and affordable POC tests with high sensitivity and specificity for diagnosing individuals with acute HIV infection in resource-limited settings with high HIV prevalence.
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| 8. |
- Maueia, Cremildo, et al.
(författare)
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Identification of the Human Papillomavirus Genotypes, According to the Human Immunodeficiency Virus Status in a Cohort of Women from Maputo, Mozambique
- 2021
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Ingår i: Viruses. - : MDPI. - 1999-4915. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Human papillomavirus (HPV) infection is now a well-established cause of cervical cancer and other anogenital cancers. An association between human immunodeficiency virus (HIV) infection and higher HPV incidence and prevalence are commonly reported. This study was conducted to demonstrate HPV prevalence, genotypes and its characteristics, according to the HIV status in women from Maputo in Mozambique.METHODS: A total of 233 participants with ages ranging from fourteen to forty-five were included. Cervical samples were collected, DNA extracted, and HPV genotyping was performed using the HPV Direct Flow CHIP Kit.RESULTS: In total, 177 HIV-negative and 56 HIV-positive women were included in the analysis. The overall HPV prevalence was 63% and was significantly higher among HIV-positive women (79% versus 58% among HIV-negative women; p = 0.005). The prevalence of multiple HPV type infections was 32%. High-risk HPV types 52, 68, 35, 18 and 16 were the most frequent. A higher proportion of HIV-positive women had multiple HPV types compared with HIV-negative women.CONCLUSIONS: This study demonstrated a high prevalence of HPV in the study cohort. HIV-positive women were identified as having the highest HPV prevalence and infection with multiple HPV types across all ages. High-risk genotypes were the most commonly found.
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| 9. |
- Maueia, Cremildo, et al.
(författare)
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The relationship between selected sexually transmitted pathogens, HPV and HIV infection status in women presenting with gynaecological symptoms in Maputo City, Mozambique
- 2024
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 19:9
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Tidskriftsartikel (refereegranskat)abstract
- Sexually transmitted infections (STIs) have a profound impact on sexual and reproductive health worldwide. Syphilis, gonorrhea, chlamydia, and trichomoniasis are four currently curable STIs. However, most STI cases are asymptomatic and not detected without laboratory diagnostics. Hepatitis B virus, herpes simplex virus, human immunodeficiency virus (HIV), and human papillomavirus (HPV) are four viral and incurable infections, but they can be mitigated by treatment. We investigated the prevalence of selected sexually transmitted pathogens and their relationship with HPV and HIV infection in women from Maputo, the capital of Mozambique. A cross-sectional study was conducted on 233 non-pregnant women seeking health care relating to gynecological symptoms in Mavalane Health facilities in Maputo, between the 1st of February 2018 and the 30th of July 2019. Cervical brush samples were collected and DNA was extracted. Selected STIs including HPV were detected using multiplex STD and HPV Direct Flow Chip Kits through a manual Hybrispot platform (Vitro, Master Diagnostica, Sevilla, Spain). HIV testing was performed using rapid tests: Determine HIV 1/2 test (Alere Abbott Laboratories, Tokyo, Japan) for screening, and UniGold HIV (Trinity Biotech, Ireland) for confirmation. All women (n = 233) were negative for Haemophilus ducreyi and Herpes Simplex Virus-1 (HSV-1). Among the 233 women, a high prevalence of STIs was found (89%), 63% of the women were positive for HPV and 24% were HIV positive. Treponema pallidum (TP), Trichomonas vaginalis (TV), Herpes Simplex Virus-2 (HSV-2), and Chlamydia trachomatis (CT) were detected in 17%, 14%, 8%, and 8% of the women, respectively. As a common phenomenon, vaginal discharge (90%) was the lower genital tract symptom reported by the majority of the women. Co-infection with any STI and HPV was detected in 56% (130/233) while 45% (59/130) of the co-infections were with high-risk HPV (hrHPV) genotypes. Among the HPV-positive participants, infection by TP was the most prevalent (27%). In total, 28% (66/233) of the participants were positive for any hrHPV genotypes. Co-infection with any STI and HIV was found in 15% (34/233) of the study participants. There was a significant association between HPV infection and TP (p = 0.039) and HSV-2 (p = 0.005). TV, TP, and CT-S1-CT-S2 positivity were significantly more prevalent in HIV-positive participants. Pathobionts Ureaplasma urealyticum/parvum and Mycoplasma hominis were detected in 84.0% (195/233) and 45% (105/233), respectively. This present study describes a high prevalence of STIs. Co-infection between HPV and STIs was found in the majority of the study subjects. The high prevalence of HPV emphasizes the need for HPV vaccination to prevent cervical cancer in this population. Management of STIs is also important in women presenting with gynecological symptoms.
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| 10. |
- Msafiri, Frank, et al.
(författare)
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Vaccine-Induced Seroreactivity Impacts the Accuracy of HIV Testing Algorithms in Sub-Saharan Africa : An Exploratory Study
- 2022
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Ingår i: Vaccines. - : MDPI. - 2076-393X. ; 10:7
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Tidskriftsartikel (refereegranskat)abstract
- The detection of vaccine-induced HIV antibody responses by rapid diagnostic tests (RDTs) may confound the interpretation of HIV testing results. We assessed the impact of vaccine-induced seroreactivity (VISR) on the diagnosis of HIV in sub-Saharan Africa. Samples collected from healthy participants of HIVIS and TaMoVac HIV vaccine trials after the final vaccination were analyzed for VISR using HIV testing algorithms used in Mozambique and Tanzania that employ two sequential RDTs. The samples were also tested for VISR using Enzygnost HIV Integral 4 ELISA and HIV western blot assays. Antibody titers to subtype C gp140 were determined using an in-house enzyme-linked immunosorbent assay (ELISA). The frequency of VISR was 93.4% (128/137) by Enzygnost HIV Integral 4 ELISA, and 66.4% (91/137) by western blot assay (WHO interpretation). The proportion of vaccine recipients that would have been misdiagnosed as HIV-positive in Mozambique was half of that in Tanzania: 26.3% (36/137) and 54.0% (74/137), respectively, p < 0.0001. In conclusion, the HIV RDTs and algorithms assessed here will potentially misclassify a large proportion of the HIV vaccine recipients if no other test is used. Increased efforts are needed to develop differential serological or molecular tools for use at the point of care.
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