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1.
Cell ; 186(21): 4652-4661.e13, 2023 10 12.
Artigo em Inglês | MEDLINE | ID: mdl-37734373

RESUMO

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.


Assuntos
Macaca mulatta , Monkeypox virus , Mpox , Animais , Humanos , Masculino , Homossexualidade Masculina , Mpox/imunologia , Minorias Sexuais e de Gênero , Monkeypox virus/fisiologia
2.
Nature ; 615(7954): 900-906, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36922585

RESUMO

Sex chromosome disorders severely compromise gametogenesis in both males and females. In oogenesis, the presence of an additional Y chromosome or the loss of an X chromosome disturbs the robust production of oocytes1-5. Here we efficiently converted the XY chromosome set to XX without an additional Y chromosome in mouse pluripotent stem (PS) cells. In addition, this chromosomal alteration successfully eradicated trisomy 16, a model of Down's syndrome, in PS cells. Artificially produced euploid XX PS cells differentiated into mature oocytes in culture with similar efficiency to native XX PS cells. Using this method, we differentiated induced pluripotent stem cells from the tail of a sexually mature male mouse into fully potent oocytes, which gave rise to offspring after fertilization. This study provides insights that could ameliorate infertility caused by sex chromosome or autosomal disorders, and opens the possibility of bipaternal reproduction.


Assuntos
Engenharia Genética , Técnicas In Vitro , Oócitos , Cromossomo X , Animais , Feminino , Masculino , Camundongos , Oócitos/metabolismo , Oócitos/fisiologia , Cromossomo X/genética , Cromossomo Y/genética , Células-Tronco Pluripotentes/metabolismo , Síndrome de Down/genética , Síndrome de Down/terapia , Fertilização , Infertilidade/terapia , Homossexualidade Masculina , Transtornos dos Cromossomos Sexuais/complicações , Transtornos dos Cromossomos Sexuais/genética , Transtornos dos Cromossomos Sexuais/terapia , Engenharia Genética/métodos
3.
Nature ; 589(7841): 258-263, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33268894

RESUMO

Animal behaviours that are superficially similar can express different intents in different contexts, but how this flexibility is achieved at the level of neural circuits is not understood. For example, males of many species can exhibit mounting behaviour towards same- or opposite-sex conspecifics1, but it is unclear whether the intent and neural encoding of these behaviours are similar or different. Here we show that female- and male-directed mounting in male laboratory mice are distinguishable by the presence or absence of ultrasonic vocalizations (USVs)2-4, respectively. These and additional behavioural data suggest that most male-directed mounting is aggressive, although in rare cases it can be sexual. We investigated whether USV+ and USV- mounting use the same or distinct hypothalamic neural substrates. Micro-endoscopic imaging of neurons positive for oestrogen receptor 1 (ESR1) in either the medial preoptic area (MPOA) or the ventromedial hypothalamus, ventrolateral subdivision (VMHvl) revealed distinct patterns of neuronal activity during USV+ and USV- mounting, and the type of mounting could be decoded from population activity in either region. Intersectional optogenetic stimulation of MPOA neurons that express ESR1 and vesicular GABA transporter (VGAT) (MPOAESR1∩VGAT neurons) robustly promoted USV+ mounting, and converted male-directed attack to mounting with USVs. By contrast, stimulation of VMHvl neurons that express ESR1 (VMHvlESR1 neurons) promoted USV- mounting, and inhibited the USVs evoked by female urine. Terminal stimulation experiments suggest that these complementary inhibitory effects are mediated by reciprocal projections between the MPOA and VMHvl. Together, these data identify a hypothalamic subpopulation that is genetically enriched for neurons that causally induce a male reproductive behavioural state, and indicate that reproductive and aggressive states are represented by distinct population codes distributed between MPOAESR1 and VMHvlESR1 neurons, respectively. Thus, similar behaviours that express different internal states are encoded by distinct hypothalamic neuronal populations.


Assuntos
Agressão/fisiologia , Hipotálamo/citologia , Hipotálamo/fisiologia , Comportamento Sexual Animal/fisiologia , Animais , Copulação , Receptor alfa de Estrogênio/metabolismo , Feminino , Homossexualidade Masculina , Masculino , Camundongos , Optogenética , Área Pré-Óptica/metabolismo , Proteínas Vesiculares de Transporte de Aminoácidos Inibidores/metabolismo
4.
Annu Rev Med ; 75: 159-175, 2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-37788486

RESUMO

Mpox, previously known as monkeypox, is caused by an Orthopoxvirus related to the variola virus that causes smallpox. Prior to 2022, mpox was considered a zoonotic disease endemic to central and west Africa. Since May 2022, more than 86,000 cases of mpox from 110 countries have been identified across the world, predominantly in men who have sex with men, most often acquired through close physical contact or during sexual activity. The classical clinical presentation of mpox is a prodrome including fever, lethargy, and lymphadenopathy followed by a characteristic vesiculopustular rash. The recent 2022 outbreak included novel presentations of mpox with a predominance of anogenital lesions, mucosal lesions, and other features such as anorectal pain, proctitis, oropharyngeal lesions, tonsillitis, and multiphasic skin lesions. We describe the demographics and clinical spectrum of classical and novel mpox, outlining the potential complications and management.


Assuntos
Mpox , Minorias Sexuais e de Gênero , Masculino , Animais , Humanos , Homossexualidade Masculina , Zoonoses , Surtos de Doenças
5.
N Engl J Med ; 388(26): 2434-2443, 2023 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-37199451

RESUMO

BACKGROUND: In the United States, more than 30,000 cases of mpox (formerly known as monkeypox) had occurred as of March 1, 2023, in an outbreak disproportionately affecting transgender persons and gay, bisexual, and other men who have sex with men. In 2019, the JYNNEOS vaccine was approved for subcutaneous administration (0.5 ml per dose) to prevent mpox infection. On August 9, 2022, an emergency use authorization was issued for intradermal administration (0.1 ml per dose); however, real-world effectiveness data are limited for either route. METHODS: We conducted a case-control study based on data from Cosmos, a nationwide Epic electronic health record (EHR) database, to assess the effectiveness of JYNNEOS vaccination in preventing medically attended mpox disease among adults. Case patients had an mpox diagnosis code or positive orthopoxvirus or mpox virus laboratory result, and control patients had an incident diagnosis of human immunodeficiency virus (HIV) infection or a new or refill order for preexposure prophylaxis against HIV infection between August 15, 2022, and November 19, 2022. Odds ratios and 95% confidence intervals were estimated from conditional logistic-regression models, adjusted for confounders; vaccine effectiveness was calculated as (1 - odds ratio for vaccination in case patients vs. controls) × 100. RESULTS: Among 2193 case patients and 8319 control patients, 25 case patients and 335 control patients received two doses (full vaccination), among whom the estimated adjusted vaccine effectiveness was 66.0% (95% confidence interval [CI], 47.4 to 78.1), and 146 case patients and 1000 control patients received one dose (partial vaccination), among whom the estimated adjusted vaccine effectiveness was 35.8% (95% CI, 22.1 to 47.1). CONCLUSIONS: In this study using nationwide EHR data, patients with mpox were less likely to have received one or two doses of JYNNEOS vaccine than control patients. The findings suggest that JYNNEOS vaccine was effective in preventing mpox disease, and a two-dose series appeared to provide better protection. (Funded by the Centers for Disease Control and Prevention and Epic Research.).


Assuntos
Mpox , Eficácia de Vacinas , Adulto , Humanos , Masculino , Estudos de Casos e Controles , Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle , Homossexualidade Masculina , Mpox/epidemiologia , Mpox/prevenção & controle , Minorias Sexuais e de Gênero/estatística & dados numéricos , Estados Unidos/epidemiologia , Eficácia de Vacinas/estatística & dados numéricos
6.
N Engl J Med ; 388(14): 1296-1306, 2023 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-37018493

RESUMO

BACKGROUND: Interventions to reduce sexually transmitted infections (STIs) among men who have sex with men (MSM) are needed. METHODS: We conducted an open-label, randomized study involving MSM and transgender women who were taking preexposure prophylaxis (PrEP) against human immunodeficiency virus (HIV) infection (PrEP cohort) or living with HIV infection (persons living with HIV infection [PLWH] cohort) and who had had Neisseria gonorrhoeae (gonorrhea), Chlamydia trachomatis (chlamydia), or syphilis in the past year. Participants were randomly assigned in a 2:1 ratio to take 200 mg of doxycycline within 72 hours after condomless sex (doxycycline postexposure prophylaxis) or receive standard care without doxycycline. STI testing was performed quarterly. The primary end point was the incidence of at least one STI per follow-up quarter. RESULTS: Of 501 participants (327 in the PrEP cohort and 174 in the PLWH cohort), 67% were White, 7% Black, 11% Asian or Pacific Islander, and 30% Hispanic or Latino. In the PrEP cohort, an STI was diagnosed in 61 of 570 quarterly visits (10.7%) in the doxycycline group and 82 of 257 quarterly visits (31.9%) in the standard-care group, for an absolute difference of -21.2 percentage points and a relative risk of 0.34 (95% confidence interval [CI], 0.24 to 0.46; P<0.001). In the PLWH cohort, an STI was diagnosed in 36 of 305 quarterly visits (11.8%) in the doxycycline group and 39 of 128 quarterly visits (30.5%) in the standard-care group, for an absolute difference of -18.7 percentage points and a relative risk of 0.38 (95% CI, 0.24 to 0.60; P<0.001). The incidences of the three evaluated STIs were lower with doxycycline than with standard care; in the PrEP cohort, the relative risks were 0.45 (95% CI, 0.32 to 0.65) for gonorrhea, 0.12 (95% CI, 0.05 to 0.25) for chlamydia, and 0.13 (95% CI, 0.03 to 0.59) for syphilis, and in the PLWH cohort, the relative risks were 0.43 (95% CI, 0.26 to 0.71), 0.26 (95% CI, 0.12 to 0.57), and 0.23 (95% CI, 0.04 to 1.29), respectively. Five grade 3 adverse events and no serious adverse events were attributed to doxycycline. Of the participants with gonorrhea culture available, tetracycline-resistant gonorrhea occurred in 5 of 13 in the doxycycline groups and 2 of 16 in the standard-care groups. CONCLUSIONS: The combined incidence of gonorrhea, chlamydia, and syphilis was lower by two thirds with doxycycline postexposure prophylaxis than with standard care, a finding that supports its use among MSM with recent bacterial STIs. (Funded by the National Institutes of Health; DoxyPEP ClinicalTrials.gov number, NCT03980223.).


Assuntos
Anti-Infecciosos , Doxiciclina , Prevenção Primária , Minorias Sexuais e de Gênero , Infecções Sexualmente Transmissíveis , Feminino , Humanos , Masculino , Infecções por Chlamydia/prevenção & controle , Doxiciclina/administração & dosagem , Doxiciclina/uso terapêutico , Gonorreia/prevenção & controle , Infecções por HIV/prevenção & controle , Homossexualidade Masculina , Profilaxia Pré-Exposição , Infecções Sexualmente Transmissíveis/prevenção & controle , Infecções Sexualmente Transmissíveis/transmissão , Sífilis/epidemiologia , Sífilis/prevenção & controle , Prevenção Primária/métodos , Anti-Infecciosos/administração & dosagem , Anti-Infecciosos/uso terapêutico , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Pessoas Transgênero
7.
Proc Natl Acad Sci U S A ; 120(50): e2313284120, 2023 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-38048455

RESUMO

Two separate but related literatures have examined familial correlates of male androphilia (i.e., sexual attraction and arousal to masculine adult males). The fraternal birth order effect (FBOE) is a widely established finding that each biological older brother a male has increased the probability of androphilia 20-35% above baseline rates. Other family demographic variables, such as reproduction by mothers, maternal aunts, and grandmothers, have been used to test evolutionary hypotheses that sexually antagonistic genes lead to androphilia among males, lowering or eliminating reproduction, which is offset by greater reproductive output among their female relatives. These proposed female fecundity effects (FFEs), and the FBOE, have historically been treated as separate yet complementary ways to understand the development and evolution of male androphilia. However, this approach ignores a vital confound within the data. The high overall reproductive output indicative of an FFE results in similar statistical patterns as the FBOE, wherein women with high reproductive output subsequently produce later-born androphilic sons. Thus, examination of the FBOE requires analytic approaches capable of controlling for the FFE, and vice-versa. Here, we present data simultaneously examining the FBOE and FFE for male androphilia in a large dataset collected in Samoa across 10 y of fieldwork, which only shows evidence of the FBOE.


Assuntos
Ordem de Nascimento , Homossexualidade Masculina , Adulto , Masculino , Humanos , Feminino , Estudos Retrospectivos , Comportamento Sexual , Samoa , Mães , Fertilidade
8.
N Engl J Med ; 386(24): 2273-2282, 2022 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-35704479

RESUMO

BACKGROUND: The incidence of anal cancer is substantially higher among persons living with the human immunodeficiency virus (HIV) than in the general population. Similar to cervical cancer, anal cancer is preceded by high-grade squamous intraepithelial lesions (HSILs). Treatment for cervical HSIL reduces progression to cervical cancer; however, data from prospective studies of treatment for anal HSIL to prevent anal cancer are lacking. METHODS: We conducted a phase 3 trial at 25 U.S. sites. Persons living with HIV who were 35 years of age or older and who had biopsy-proven anal HSIL were randomly assigned, in a 1:1 ratio, to receive either HSIL treatment or active monitoring without treatment. Treatment included office-based ablative procedures, ablation or excision under anesthesia, or the administration of topical fluorouracil or imiquimod. The primary outcome was progression to anal cancer in a time-to-event analysis. Participants in the treatment group were treated until HSIL was completely resolved. All the participants underwent high-resolution anoscopy at least every 6 months; biopsy was also performed for suspected ongoing HSIL in the treatment group, annually in the active-monitoring group, or any time there was concern for cancer. RESULTS: Of 4459 participants who underwent randomization, 4446 (99.7%) were included in the analysis of the time to progression to cancer. With a median follow-up of 25.8 months, 9 cases were diagnosed in the treatment group (173 per 100,000 person-years; 95% confidence interval [CI], 90 to 332) and 21 cases in the active-monitoring group (402 per 100,000 person-years; 95% CI, 262 to 616). The rate of progression to anal cancer was lower in the treatment group than in the active-monitoring group by 57% (95% CI, 6 to 80; P = 0.03 by log-rank test). CONCLUSIONS: Among participants with biopsy-proven anal HSIL, the risk of anal cancer was significantly lower with treatment for anal HSIL than with active monitoring. (Funded by the National Cancer Institute; ClinicalTrials.gov number, NCT02135419.).


Assuntos
Neoplasias do Ânus , Infecções por HIV , Lesões Pré-Cancerosas , Lesões Intraepiteliais Escamosas , Conduta Expectante , Adulto , Neoplasias do Ânus/etiologia , Neoplasias do Ânus/patologia , Neoplasias do Ânus/prevenção & controle , Neoplasias do Ânus/terapia , Biópsia , Feminino , Infecções por HIV/complicações , Homossexualidade Masculina , Humanos , Masculino , Infecções por Papillomavirus/complicações , Lesões Pré-Cancerosas/etiologia , Lesões Pré-Cancerosas/patologia , Lesões Pré-Cancerosas/terapia , Estudos Prospectivos , Lesões Intraepiteliais Escamosas/etiologia , Lesões Intraepiteliais Escamosas/patologia , Lesões Intraepiteliais Escamosas/terapia
9.
PLoS Pathog ; 19(5): e1011219, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37253061

RESUMO

Young men who have sex with men (YMSM) are disproportionately affected by HIV and bacterial sexually transmitted infections (STI) including gonorrhea, chlamydia, and syphilis; yet research into the immunologic effects of these infections is typically pursued in siloes. Here, we employed a syndemic approach to understand potential interactions of these infections on the rectal mucosal immune environment among YMSM. We enrolled YMSM aged 18-29 years with and without HIV and/or asymptomatic bacterial STI and collected blood, rectal secretions, and rectal tissue biopsies. YMSM with HIV were on suppressive antiretroviral therapy (ART) with preserved blood CD4 cell counts. We defined 7 innate and 19 adaptive immune cell subsets by flow cytometry, the rectal mucosal transcriptome by RNAseq, and the rectal mucosal microbiome by 16S rRNA sequencing and examined the effects of HIV and STI and their interactions. We measured tissue HIV RNA viral loads among YMSM with HIV and HIV replication in rectal explant challenge experiments among YMSM without HIV. HIV, but not asymptomatic STI, was associated with profound alterations in the cellular composition of the rectal mucosa. We did not detect a difference in the microbiome composition associated with HIV, but asymptomatic bacterial STI was associated with a higher probability of presence of potentially pathogenic taxa. When examining the rectal mucosal transcriptome, there was evidence of statistical interaction; asymptomatic bacterial STI was associated with upregulation of numerous inflammatory genes and enrichment for immune response pathways among YMSM with HIV, but not YMSM without HIV. Asymptomatic bacterial STI was not associated with differences in tissue HIV RNA viral loads or in HIV replication in explant challenge experiments. Our results suggest that asymptomatic bacterial STI may contribute to inflammation particularly among YMSM with HIV, and that future research should examine potential harms and interventions to reduce the health impact of these syndemic infections.


Assuntos
Infecções por Chlamydia , Gonorreia , Infecções por HIV , Minorias Sexuais e de Gênero , Infecções Sexualmente Transmissíveis , Masculino , Humanos , Infecções Sexualmente Transmissíveis/complicações , Infecções Sexualmente Transmissíveis/diagnóstico , Infecções Sexualmente Transmissíveis/terapia , Homossexualidade Masculina , RNA Ribossômico 16S , Infecções por Chlamydia/complicações , Infecções por HIV/complicações , Gonorreia/epidemiologia
10.
Annu Rev Psychol ; 75: 55-85, 2024 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-37722749

RESUMO

Men who have sex with men (MSM) are disproportionately affected by HIV, accounting for two-thirds of HIV cases in the United States despite representing ∼5% of the adult population. Delivery and use of existing and highly effective HIV prevention and treatment strategies remain suboptimal among MSM. To summarize the state of the science, we systematically review implementation determinants and strategies of HIV-related health interventions using implementation science frameworks. Research on implementation barriers has focused predominantly on characteristics of individual recipients (e.g., ethnicity, age, drug use) and less so on deliverers (e.g., nurses, physicians), with little focus on system-level factors. Similarly, most strategies target recipients to influence their uptake and adherence, rather than improving and supporting implementation systems. HIV implementation research is burgeoning; future research is needed to broaden the examination of barriers at the provider and system levels, as well as expand knowledge on how to match strategies to barriers-particularly to address stigma. Collaboration and coordination among federal, state, and local public health agencies; community-based organizations; health care providers; and scientists are important for successful implementation of HIV-related health innovations.


Assuntos
Infecções por HIV , Minorias Sexuais e de Gênero , Masculino , Adulto , Humanos , Estados Unidos , Homossexualidade Masculina , Infecções por HIV/prevenção & controle , Estigma Social
11.
Ann Intern Med ; 177(6): 719-728, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38801778

RESUMO

BACKGROUND: Observational studies suggest that voluntary medical male circumcision (VMMC) may lower HIV risk among men who have sex with men (MSM). A randomized controlled trial (RCT) is needed to confirm this. OBJECTIVE: To assess the efficacy of VMMC in preventing incident HIV infection among MSM. DESIGN: An RCT with up to 12 months of follow-up. (Chinese Clinical Trial Registry: ChiCTR2000039436). SETTING: 8 cities in China. PARTICIPANTS: Uncircumcised, HIV-seronegative men aged 18 to 49 years who self-reported predominantly practicing insertive anal intercourse and had 2 or more male sex partners in the past 6 months. INTERVENTION: VMMC. MEASUREMENTS: Rapid testing for HIV was done at baseline and at 3, 6, 9, and 12 months. Behavioral questionnaires and other tests for sexually transmitted infections were done at baseline, 6 months, and 12 months. The primary outcome was HIV seroconversion using an intention-to-treat analysis. RESULTS: The study enrolled 124 men in the intervention group and 123 in the control group, who contributed 120.7 and 123.1 person-years of observation, respectively. There were 0 seroconversions in the intervention group (0 infections [95% CI, 0.0 to 3.1 infections] per 100 person-years) and 5 seroconversions in the control group (4.1 infections [CI, 1.3 to 9.5 infections] per 100 person-years). The HIV hazard ratio was 0.09 (CI, 0.00 to 0.81; P = 0.029), and the HIV incidence was lower in the intervention group (log-rank P = 0.025). The incidence rates of syphilis, herpes simplex virus type 2, and penile human papillomavirus were not statistically significantly different between the 2 groups. There was no evidence of HIV risk compensation. LIMITATION: Few HIV seroconversions and limited follow-up period. CONCLUSION: Among MSM who predominantly practice insertive anal intercourse, VMMC is efficacious in preventing incident HIV infection; MSM should be included in VMMC guidelines. PRIMARY FUNDING SOURCE: The National Science and Technology Major Project of China.


Assuntos
Circuncisão Masculina , Infecções por HIV , Homossexualidade Masculina , Humanos , Masculino , Adulto , Infecções por HIV/prevenção & controle , Infecções por HIV/epidemiologia , Adulto Jovem , Adolescente , Pessoa de Meia-Idade , China/epidemiologia , Incidência , Comportamento Sexual , Análise de Intenção de Tratamento
12.
Ann Intern Med ; 177(1): 12-17, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38109739

RESUMO

BACKGROUND: Transgender persons are disproportionately affected by HIV, but preexposure prophylaxis (PrEP) use has been low in this population. Clinical encounters for gender-affirming hormone therapy (GAHT) provide opportunities for HIV prevention. OBJECTIVE: To estimate the number of commercially insured transgender women (TGW) and transgender men (TGM) in the United States and their use of HIV prevention services. DESIGN: Retrospective analysis of secondary data. SETTING: Merative MarketScan commercial databases from 2014 to 2021. PARTICIPANTS: TGW and TGM, defined as those with transgender-related diagnoses and prescriptions for feminizing or masculinizing GAHT. MEASUREMENTS: HIV testing and PrEP use. RESULTS: A substantially increasing trend was observed in the prevalence of transgender-related diagnosis codes from 2014 to 2021 and in the proportion of persons who used GAHT. The increases were driven by persons aged 18 to 34 years. In 2021, among 10 613 TGW with a test for or a diagnosis of a sexually transmitted infection (STI) in the previous 12 months, 61.1% had an HIV test; among those, 20.2% were prescribed PrEP. Among 4184 TGM with STI risk, 48.3% had an HIV test; among those, 10.2% were prescribed PrEP. The prevalence of TGW and TGM who had a test for or a diagnosis of an STI, had an HIV test, and were prescribed PrEP increased substantially from 2014 to 2021. LIMITATION: The findings represent only persons with commercial health insurance who sought health care services for GAHT. CONCLUSION: It is important to identify transgender persons to monitor their receipt of HIV prevention services. Encounters for GAHT provide opportunities to offer HIV prevention and other prevention services. Many HIV prevention opportunities were likely missed at clinical encounters for GAHT. PRIMARY FUNDING SOURCE: None.


Assuntos
Infecções por HIV , Profilaxia Pré-Exposição , Infecções Sexualmente Transmissíveis , Pessoas Transgênero , Masculino , Humanos , Feminino , Estados Unidos/epidemiologia , Infecções por HIV/diagnóstico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Homossexualidade Masculina , Estudos Retrospectivos , Prescrições , Teste de HIV
13.
J Infect Dis ; 229(Supplement_2): S121-S131, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-37861379

RESUMO

Orthopoxviruses have repeatedly confounded expectations in terms of the clinical illness they cause and their patterns of spread. Monkeypox virus (MPXV), originally characterized in the late 1950s during outbreaks among captive primates, has been recognized since the 1970s to cause human disease (mpox) in West and Central Africa, where interhuman transmission has largely been associated with nonsexual, close physical contact. In May 2022, a focus of MPXV transmission was detected, spreading among international networks of gay, bisexual, and other men who have sex with men. The outbreak grew in both size and geographic scope, testing the strength of preparedness tools and public health science alike. In this article we consider what was known about mpox before the 2022 outbreak, what we learned about mpox during the outbreak, and what continued research is needed to ensure that the global public health community can detect, and halt further spread of this disease threat.


Assuntos
Mpox , Orthopoxvirus , Minorias Sexuais e de Gênero , Masculino , Animais , Humanos , Homossexualidade Masculina , Surtos de Doenças , Monkeypox virus
14.
J Infect Dis ; 229(Supplement_2): S213-S218, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38019187

RESUMO

The 2022 mpox outbreak primarily involved sexual transmission among men who have sex with men and disproportionately affected persons with human immunodeficiency virus (HIV). We examined viral dynamics and clinical features in a cohort evaluated for mpox infection at a comprehensive HIV clinic in Atlanta, Georgia. Viral DNA was found in 8 oropharyngeal and 5 anorectal specimens among 10 mpox cases confirmed by lesion swab polymerase chain reaction. Within-participant anatomic site of lowest cycle threshold (Ct) value varied, and lower Ct values were found in oropharyngeal and anorectal swabs when corresponding symptoms were present. This provides insight into mpox infection across multiple anatomic sites among people with HIV.


Assuntos
Infecções por HIV , Mpox , Minorias Sexuais e de Gênero , Masculino , Humanos , Homossexualidade Masculina , Instituições de Assistência Ambulatorial
15.
J Infect Dis ; 229(1): 59-63, 2024 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-37402631

RESUMO

Many countries affected by the global outbreak of mpox in 2022 have observed a decline in cases. Our mathematical model accounting for heavy-tailed sexual partnership distributions suggests that mpox epidemics can hit the infection-derived herd immunity threshold and begin to decline, with <1% of sexually active men who have sex with men infected regardless of interventions or behavioral changes. We consistently found that many countries and US states experienced an epidemic peak, with cumulative cases of around 0.1% to 0.5% among men who have sex with men. The observed decline in cases may not necessarily be attributable to interventions or behavioral changes primarily.


Assuntos
Mpox , Minorias Sexuais e de Gênero , Masculino , Humanos , Homossexualidade Masculina , Comportamento Sexual , Surtos de Doenças
16.
J Infect Dis ; 230(1): e121-e130, 2024 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-39052719

RESUMO

BACKGROUND: In the Netherlands, the number of mpox cases started declining before mpox vaccination was initiated. Most cases were men who have sex with men (MSM). We investigated whether the decline in mpox could be attributed to infection-induced immunity or behavioral adaptations. METHODS: We developed a transmission model and accounted for possible behavioral adaptations: fewer casual partners and shorter time until MSM with mpox refrain from sexual contacts. RESULTS: Without behavioral adaptations, the peak in modelled cases matched observations, but the decline was less steep than observed. With behavioral adaptations in the model, we found a decline of 16%-18% in numbers of casual partners in June and 13%-22% in July 2022. Model results showed a halving of the time before refraining from sex. When mpox vaccination started, 57% of MSM with very high sexual activity in the model had been infected. Model scenarios revealed that the outbreak could have waned by November 2022 even without vaccination. CONCLUSIONS: The limited duration of the mpox outbreak in the Netherlands can be ascribed primarily to infection-induced immunity among MSM with high sexual activity levels. The decline was accelerated by behavioral adaptations. Immunity among those most sexually active is essential to impede mpox resurgence.


Assuntos
Surtos de Doenças , Homossexualidade Masculina , Modelos Teóricos , Comportamento Sexual , Humanos , Masculino , Países Baixos/epidemiologia , Parceiros Sexuais , Vacinação/estatística & dados numéricos , Adulto
17.
J Infect Dis ; 229(3): 866-875, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-37769216

RESUMO

BACKGROUND: The incidence of syphilis continues to increase in the United States, yet little is known about Treponema pallidum genomic epidemiology within American metropolitan areas. METHODS: We performed whole-genome sequencing and tprK deep sequencing of 28 T. pallidum-containing specimens, collected mostly from remnant Aptima swab specimens from 24 individuals from Seattle Sexual Health Clinic during 2021-2022. RESULTS: All 12 individuals infected with Nichols-lineage strains were men who have sex with men, while a specific SS14 cluster (mean, 0.33 single-nucleotide variant) included 1 man who has sex with women and 5 women. All T. pallidum strains sequenced were azithromycin resistant via 23S ribosomal RNA A2058G mutation. Identical T. pallidum genomic sequences were found in pharyngeal and rectal swab specimens taken concurrently from the same individuals. The tprK sequences were less variable between patient-matched specimens and between epidemiologically linked clusters. We detected a 528-base pair deletion in the tprK donor site locus, eliminating 9 donor sites, in T. pallidum genomes of 3 individuals with secondary syphilis, associated with diminution of TprK diversity. CONCLUSIONS: We developed an end-to-end workflow for public health genomic surveillance of T. pallidum from remnant Aptima swab specimens. tprK sequencing may assist in linking cases beyond routine T. pallidum genome sequencing. T. pallidum strains with deletions in tprK donor sites currently circulate and are associated with diminished TprK antigenic diversity.


Assuntos
Minorias Sexuais e de Gênero , Sífilis , Masculino , Feminino , Humanos , Treponema pallidum/genética , Homossexualidade Masculina , Sequência de Aminoácidos , Sífilis/epidemiologia , Variação Antigênica , Genômica
18.
J Infect Dis ; 229(Supplement_2): S188-S196, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-37820738

RESUMO

BACKGROUND: Exposures associated with mpox infection remain imperfectly understood. METHODS: We conducted a case-control study enrolling participants who received molecular tests for mpox/orthopoxvirus in California from November 2022 through June 2023. We collected data on behaviors during a 21-day risk period before symptom onset or testing among mpox case patients and test-negative controls. RESULTS: Thirteen of 54 case patients (24.1%) and 5 of 117 controls (4.3%) reported sexual exposure to individuals they identified as potential mpox case patients ("index contacts"; odds ratio [OR], 7.7 [95% confidence interval (CI), 2.5-19.3] relative to individuals who did not report exposure to potential mpox case patients). Among these participants, 10 of 13 case patients (76.9%) and 2 of 5 controls (40.0%) reported that their index contacts were not experiencing symptoms visible to participants during sex (OR, 14.9 [95% CI, 3.6-101.8]). Only 3 of 54 case patients (5.6%) reported exposure to symptomatic index contacts. Case patients reported more anal/vaginal sex partners than did controls (adjusted OR, 2.2 [95% CI, 1.0-4.8] for 2-3 partners and 3.8 [1.7-8.8] for ≥4 partners). Male case patients with penile lesions more commonly reported insertive anal/vaginal sex than those without penile lesions (adjusted OR, 9.3 [95% CI, 1.6-54.8]). Case patients with anorectal lesions more commonly reported receptive anal sex than those without anorectal lesions (adjusted OR, 14.4 [95% CI, 1.0-207.3]). CONCLUSIONS: Sexual exposure to contacts known or suspected to have experienced mpox was associated with increased risk of infection, often when index contacts lacked apparent symptoms. Exposure to more sex partners, including those whom participants did not identify as index contacts, was associated with increased risk of infection in a site-specific manner. While participants' assessment of symptoms in partners may be imperfect, these findings suggest that individuals without visibly prominent mpox symptoms transmit infection.


Assuntos
Infecções por HIV , Mpox , Minorias Sexuais e de Gênero , Feminino , Humanos , Masculino , Estudos de Casos e Controles , Fatores de Risco , Comportamento Sexual , California , Homossexualidade Masculina
19.
J Infect Dis ; 229(3): 707-718, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38012959

RESUMO

BACKGROUND: International data on anogenital HPV infection incidence among men are limited. METHODS: Incidence of incident-persistent (IP) anogenital HPV infections was evaluated among 295 men who have sex with men (MSM) and 1576 heterosexual men (HM) aged 16-27 years in the placebo arm of a global, multicenter 4-valent (4v) HPV vaccine trial. We estimated IP incidence (penile/scrotal, perineal/perianal, anal) for 4vHPV and 9-valent (9v) HPV vaccine types and cumulative IP incidence over 36 months. RESULTS: IP infection incidence per 100 person-years (95% CI) among HM for 4vHPV and 9vHPV types was 4.1 (3.5-4.9) and 6.8 (5.9-7.6) at penile/scrotal, and 1.2 (.8-1.6) and 1.9 (1.5-2.4) at perineal/perianal sites, respectively; and among MSM, IP infection incidence was 2.3 (1.3-3.8) and 3.2 (2.0-4.9) at penile/scrotal, 6.8 (4.9-9.2) and 9.0 (6.9-11.6) at perineal/perianal, and 12.0 (9.4-15.1) and 16.8 (13.7-20.2) at anal sites, respectively. Cumulative IP incidence over 36 months (excluding anal canal; any 9vHPV type) was higher among MSM versus HM (24.1% vs 18.4%). CONCLUSIONS: A substantial proportion of unvaccinated men of catch-up vaccination age developed IP 9vHPV-related infections. Gender-neutral vaccination could decrease male HPV infection, contribute to herd protection, and reduce disease burden. Clinical Trials Registration. NCT00090285.


Assuntos
Infecções por Papillomavirus , Vacinas contra Papillomavirus , Minorias Sexuais e de Gênero , Humanos , Masculino , Homossexualidade Masculina , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/prevenção & controle , Papillomaviridae
20.
J Infect Dis ; 229(Supplement_2): S197-S202, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-37947018

RESUMO

HIV is associated with severe mpox. Sexually transmitted infections (STIs) could facilitate mpox transmission. We estimated HIV and STI frequency among patients with mpox and compared characteristics associated with mpox severity. Mpox cases during 1 June 2022 to 31 March 2023 were matched to Illinois HIV/AIDS surveillance data. Among 1124 patients with mpox, 489 (44%) had HIV and 786 (70%) had prior or concurrent STI; 307 (39%) had ≥3 STI episodes. More patients with mpox who were living with HIV were hospitalized than those without HIV (10.3% vs 4.1%, P < .001). STI screening visits are opportunities to vaccinate against mpox and provide HIV prophylaxis or treatment.


Assuntos
Síndrome da Imunodeficiência Adquirida , Infecções por HIV , Mpox , Infecções Sexualmente Transmissíveis , Humanos , Masculino , Infecções por HIV/complicações , Chicago , Infecções Sexualmente Transmissíveis/diagnóstico , Illinois , Síndrome da Imunodeficiência Adquirida/complicações , Homossexualidade Masculina
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