ASYMPTOMATIC MONKEY POX VIRUS INFECTION: A SELF-SAMPLING SCREENING INTERVENTION ADRESSED TO GAY, BISEXUAL AND OTHER MEN WHO HAVE SEX WITH MEN AND TRANS WOMEN IN SPAIN
Project description:Computational designing of four different series (D-G) of thiazolidinone was done starting from different amines which was further condensed with various aldehydes. These underwent in silico molecular investigations for density functional theory (DFT), molecular docking, and absorption, distribution metabolism, excretion, and toxicity (ADMET) studies. The different electrochemical parameters of the compounds are predicted using quantum mechanical modeling approach with Gaussian. The docking software was used to dock the compounds against choosing PDB file for chickenpox, human immunodeficiency, hepatitis, and monkeypox virus as 1OSN, 1VZV, 6VLK, 1RTD, 3I7H, 3TYV, 4JU3, and 4QWO, respectively. The molecular interactions were visualized with discovery studio and maximum binding affinity was observed with D8 compounds against 4QWO (-13.383 kcal/mol) while for compound D5 against 1VZV which was -12.713 kcal/mol. Swiss ADME web tool was used to assess the drug-likeness of the designed compounds under consideration, and it is concluded that these molecules had a drug-like structure with almost zero violations.
Project description:The recent monkeypox virus (MPXV) outbreak was of global concern and has mainly affected gay, bisexual and other men who have sex with men (GBMSM). Here we assess prevalence of MPXV in high-risk populations of GBMSM, trans women (TW) and non-binary people without symptoms or with unrecognized monkeypox (Mpox) symptoms, using a self-sampling strategy. Anal and pharyngeal swabs are tested by MPXV real-time PCR and positive samples are tested for cytopathic effect (CPE) in cell culture. 113 individuals participated in the study, 89 (78.76%) were cis men, 17 (15.04%) were TW. The median age was 35.0 years (IQR: 30.0-43.0), 96 (85.02%) individuals were gay or bisexual and 72 (63.72%) were migrants. Seven participants were MPXV positive (6.19% (95% CI: 1.75%-10.64%)). Five tested positive in pharyngeal swabs, one in anal swab and one in both. Six did not present symptoms recognized as MPXV infection. Three samples were positive for CPE, and showed anti-vaccinia pAb staining by FACS and confocal microscopy. This suggests that unrecognized Mpox cases can shed infectious virus. Restricting testing to individuals reporting Mpox symptoms may not be sufficient to contain outbreaks.
Project description:The mpox outbreak of 2022–2023 involved rapid global spread in men who have sex with men. We infected 18 rhesus macaques with mpox by the intravenous, intradermal, and intrarectal routes and observed robust antibody and T cell responses following all three routes of infection. Numerous skin lesions and high plasma viral loads were observed following intravenous and intradermal infection. Skin lesions peaked on day 10 and resolved by day 28 following infection. On day 28, we re-challenged all convalescent and 3 naive animals with mpox. All convalescent animals were protected against re-challenge. Transcriptomic studies showed upregulation of innate and inflammatory responses and downregulation of collagen formation and extracellular matrix organization following challenge, as well as rapid activation of T cell and plasma cell responses following re-challenge. These data suggest key mechanistic insights into mpox pathogenesis and immunity. This macaque model should prove useful for evaluating mpox vaccines and therapeutics.
Project description:Monkeypox is an emerging infectious disease, which has a clinical presentation similar to smallpox. In the two past decades, Central Africa has seen an increase in the frequency of cases, with many monkeypox virus (MPXV) isolates detected in the Democratic Republic of Congo (DRC) and the Central African Republic (CAR). To date, no complete MPXV viral genome has been published from the human cases identified in the CAR. The objective of this study was to sequence the full genome of 10 MPXV isolates collected during the CAR epidemics between 2001 and 2018 in order to determine their phylogenetic relationships among MPXV lineages previously described in Central Africa and West Africa. Our phylogenetic results indicate that the 10 CAR isolates belong to three lineages closely related to those found in DRC. The phylogenetic pattern shows that all of them emerged in the rainforest block of the Congo Basin. Since most human index cases in CAR occurred at the northern edge of western and eastern rainforests, transmissions from wild animals living in the rainforest is the most probable hypothesis. In addition, molecular dating estimates suggest that periods of intense political instability resulting in population movements within the country often associated also with increased poverty may have led to more frequent contact with host wild animals. The CAR socio-economic situation, armed conflicts and ecological disturbances will likely incite populations to interact more and more with wild animals and thus increase the risk of zoonotic spillover.
Project description:OBJECTIVES:Recent outbreaks of anorectal lymphogranuloma venereum (LGV) among men who have sex with men (MSM) have been characterised by proctocolitis requiring extended antibiotic treatment compared with infections caused by other serovars of Chlamydia trachomatis (CT). We describe the prevalence and clinical features of LGV among Nigerian MSM diagnosed with anorectal CT. METHODS:MSM were recruited for this observational cohort in Lagos, Nigeria, using respondent-driven sampling and screened for HIV and bacterial STIs every three?months for up to 18 months. Nucleic acid amplification tests for CT were performed on rectal swab specimens. Prevalent and incident cases of anorectal CT underwent additional testing to identify LGV using novel real-time PCR assays specific for the L-serovars of CT. RESULTS:From April 2014 to July 2016, 420 MSM underwent testing for rectal STIs, of whom 66 (15.7%) had prevalent anorectal CT. Among those without prevalent disease, 68 developed incident infections during 208 person-years of follow-up. Of 134 prevalent and incident cases of anorectal CT, 7 (5.2%) were identified as LGV. None of the seven participants with LGV reported any symptoms. Two of the participants with LGV were simultaneously coinfected with rectal gonorrhoea. HIV coinfection was common among participants with both LGV (n=5, 71%) and non-LGV (n=98, 77%) serovars of CT (P=0.66). CONCLUSIONS:Anorectal LGV was uncommon but present among Nigerian MSM in this study. Consistent screening for L-serovars of CT, or presumptive treatment for LGV in cases with a high suspicion for this diagnosis, could potentially improve patient outcomes and decrease transmission.
Project description:We investigated prevalence of lymphogranuloma venereum (LGV) among men who have sex with men who were tested for chlamydia at 12 clinics in the United Kingdom during 10 weeks in 2012. Of 713 men positive for Chlamydia trachomatis, 66 (9%) had LGV serovars; 15 (27%) of 55 for whom data were available were asymptomatic.
Project description:The human nasopharynx is the main reservoir for Streptococcus pneumoniae. We applied conventional and molecular methods to determine the prevalence of S. pneumoniae nasopharyngeal colonization in adults. Paired trans-orally and trans-nasally obtained nasopharyngeal samples from 268 parents of 24-month-old children were assessed for pneumococcal presence. Parents were classified as colonized when live pneumococci were recovered from either sample cultured on medium selective for S. pneumoniae. Of the 52 (19%) colonized parents 49 (18%) were culture-positive in trans-nasal and 10 (4%) in trans-oral samples. Bacterial growth was harvested from these cultures, DNA isolated and tested by quantitative-PCR (qPCR) targeting lytA and piaA genes specific for S. pneumoniae. A sample was considered positive if signals for both genes were detected. Altogether 105 (39%) individuals were classified as positive for pneumococcus by qPCR including 50 (19%) in trans-nasal and 94 (35%) in trans-oral settings. Although significantly more trans-nasal compared to trans-oral samples were culture-positive for S. pneumoniae at the primary diagnostic step (p<0.001) the opposite was observed in qPCR results (p<0.001). To confirm the presence of live pneumococcus in samples positive by qPCR but negative at the initial diagnostic step, we serially-diluted cell harvests, re-cultured and carefully examined for S. pneumoniae presence. Live pneumococci were recovered from an additional 43 parents including 42 positive in trans-oral and 4 in trans-nasal samples increasing the number of individuals culture- and qPCR-positive to 93 (35%) and positive by either of two methods to 107 (40%). There were significantly more trans-oral than trans-nasal samples positive for pneumococcus by both culture and qPCR (n = 71; 27%; vs. n = 50; 19%; p<0.05). Our data suggest that pneumococcal colonization is more common in adults than previously estimated and point towards the superiority of a trans-oral over a trans-nasal approach when testing adults for colonization with S. pneumoniae.
Project description:Improved knowledge of factors that promote outbreaks of enteric pathogens among men who have sex with men (MSM) could enable targeted public health interventions. We detected enteric pathogens in 57 of 519 (11%) asymptomatic MSM, and we found that enteric pathogen detection was associated with both oroanal sex (rimming) and group sex.
Project description:Strongyloides stercoralis infection is frequently underdiagnosed since many infections remain asymptomatic. To estimate the prevalence and characteristics of asymptomatic S. stercoralis infection in Latin American migrants attending a community-based screening program for Chagas disease in Spain. Three community-based Chagas disease screening campaigns were performed in Alicante (Spain) in 2016, 2017, and 2018. Serological testing for S. stercoralis infection was performed using a non-automatized IVD-ELISA detecting IgG (DRG Instruments GmbH, Marburg, Germany). Of the 616 migrants from Central and South America who were screened, 601 were included in the study: 100 children and adolescents (<18 years of age) and 501 adults. Among the younger group, 6 participants tested positive (prevalence 6%, 95% confidence interval [CI] 2.5% to 13.1%), while 60 adults did so (prevalence 12%, 95% CI 9.3% to 15.3%). S. stercoralis infection was more common in men than in women (odds ratio adjusted [ORa] 2.28, 95% CI 1.289 to 4.03) and in those from Bolivia (ORa 2.03, 95% CI 1.15 to 3.59). Prevalence increased with age (ORa 1.02, 95% CI 0.99 to 1.05). In contrast, a university education had a protective effect (ORa 0.29, 95% CI 0.31 to 0.88). Forty-one (41/66; 62.1%) of the total cases of S. stercoralis infection were treated at the health care center. Positive stool samples were observed in 19.5% of the followed-up positive cases. Incorporating serological screening for S. stercoralis into community-based screening for Chagas disease is a useful intervention to detect asymptomatic S. stercoralis infection in Central and South American migrants and an opportunity to tackle neglected tropical diseases in a transversal way. The remaining challenge is to achieve patients' adherence to the medical follow-up.