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1.
Immunity ; 56(4): 879-892.e4, 2023 04 11.
Artículo en Inglés | MEDLINE | ID: mdl-36958334

RESUMEN

Although the protective role of neutralizing antibodies against COVID-19 is well established, questions remain about the relative importance of cellular immunity. Using 6 pMHC multimers in a cohort with early and frequent sampling, we define the phenotype and kinetics of recalled and primary T cell responses following Delta or Omicron breakthrough infection in previously vaccinated individuals. Recall of spike-specific CD4+ T cells was rapid, with cellular proliferation and extensive activation evident as early as 1 day post symptom onset. Similarly, spike-specific CD8+ T cells were rapidly activated but showed variable degrees of expansion. The frequency of activated SARS-CoV-2-specific CD8+ T cells at baseline and peak inversely correlated with peak SARS-CoV-2 RNA levels in nasal swabs and accelerated viral clearance. Our study demonstrates that a rapid and extensive recall of memory T cell populations occurs early after breakthrough infection and suggests that CD8+ T cells contribute to the control of viral replication in breakthrough SARS-CoV-2 infections.


Asunto(s)
COVID-19 , Humanos , SARS-CoV-2 , Linfocitos T CD8-positivos , Infección Irruptiva , ARN Viral , Anticuerpos Neutralizantes , Anticuerpos Antivirales , Vacunación
2.
Immunity ; 55(7): 1316-1326.e4, 2022 07 12.
Artículo en Inglés | MEDLINE | ID: mdl-35690062

RESUMEN

Vaccination against SARS-CoV-2 protects from infection and improves clinical outcomes in breakthrough infections, likely reflecting residual vaccine-elicited immunity and recall of immunological memory. Here, we define the early kinetics of spike-specific humoral and cellular immunity after vaccination of seropositive individuals and after Delta or Omicron breakthrough infection in vaccinated individuals. Early longitudinal sampling revealed the timing and magnitude of recall, with the phenotypic activation of B cells preceding an increase in neutralizing antibody titers. While vaccination of seropositive individuals resulted in robust recall of humoral and T cell immunity, recall of vaccine-elicited responses was delayed and variable in magnitude during breakthrough infections and depended on the infecting variant of concern. While the delayed kinetics of immune recall provides a potential mechanism for the lack of early control of viral replication, the recall of antibodies coincided with viral clearance and likely underpins the protective effects of vaccination against severe COVID-19.


Asunto(s)
COVID-19 , Vacunas Virales , Anticuerpos Neutralizantes , Anticuerpos Antivirales , Humanos , SARS-CoV-2 , Vacunación
3.
Immunity ; 55(7): 1299-1315.e4, 2022 07 12.
Artículo en Inglés | MEDLINE | ID: mdl-35750048

RESUMEN

As the establishment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific T cell memory in children remains largely unexplored, we recruited convalescent COVID-19 children and adults to define their circulating memory SARS-CoV-2-specific CD4+ and CD8+ T cells prior to vaccination. We analyzed epitope-specific T cells directly ex vivo using seven HLA class I and class II tetramers presenting SARS-CoV-2 epitopes, together with Spike-specific B cells. Unvaccinated children who seroconverted had comparable Spike-specific but lower ORF1a- and N-specific memory T cell responses compared with adults. This agreed with our TCR sequencing data showing reduced clonal expansion in children. A strong stem cell memory phenotype and common T cell receptor motifs were detected within tetramer-specific T cells in seroconverted children. Conversely, children who did not seroconvert had tetramer-specific T cells of predominantly naive phenotypes and diverse TCRαß repertoires. Our study demonstrates the generation of SARS-CoV-2-specific T cell memory with common TCRαß motifs in unvaccinated seroconverted children after their first virus encounter.


Asunto(s)
COVID-19 , SARS-CoV-2 , Linfocitos T CD4-Positivos , Linfocitos T CD8-positivos , Epítopos de Linfocito T , Humanos , Memoria Inmunológica , Receptores de Antígenos de Linfocitos T , Receptores de Antígenos de Linfocitos T alfa-beta/genética , Glicoproteína de la Espiga del Coronavirus
4.
Clin Microbiol Rev ; 37(1): e0009423, 2024 03 14.
Artículo en Inglés | MEDLINE | ID: mdl-38226640

RESUMEN

Neisseria gonorrhoeae infection is an important public health issue, with an annual global incidence of 87 million. N. gonorrhoeae infection causes significant morbidity and can have serious long-term impacts on reproductive and neonatal health and may rarely cause life-threatening disease. Global rates of N. gonorrhoeae infection have increased over the past 20 years. Importantly, rates of antimicrobial resistance to key antimicrobials also continue to increase, with the United States Centers for Disease Control and Prevention identifying drug-resistant N. gonorrhoeae as an urgent threat to public health. This review summarizes the current evidence for N. gonorrhoeae vaccines, including historical clinical trials, key N. gonorrhoeae vaccine preclinical studies, and studies of the impact of Neisseria meningitidis vaccines on N. gonorrhoeae infection. A comprehensive survey of potential vaccine antigens, including those identified through traditional vaccine immunogenicity approaches, as well as those identified using more contemporary reverse vaccinology approaches, are also described. Finally, the potential epidemiological impacts of a N. gonorrhoeae vaccine and research priorities for further vaccine development are described.


Asunto(s)
Antiinfecciosos , Gonorrea , Vacunas , Recién Nacido , Humanos , Neisseria gonorrhoeae , Gonorrea/tratamiento farmacológico , Gonorrea/epidemiología , Gonorrea/prevención & control
5.
J Infect Dis ; 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38877763

RESUMEN

While ceftriaxone remains the first-line treatment for gonorrhoea, the US CDC recommended cefixime as a second-line treatment in 2021. We tested 1176 Neisseria gonorrhoeae isolates among clients attending the Melbourne Sexual Health Centre in 2021-2022. The prevalence of cefixime resistance was 6.3% (74/1176), azithromycin resistance was 4.9% (58/1176) and ceftriaxone resistance was 0% (0/1176). Cefixime resistance was the highest among women (16.4%, 10/61), followed by men-who-have-sex-with-women (6.4%, 7/109), and men-who-have-sex-with-men (5.8%, 57/982). The prevalence of cefixime-resistant N. gonorrhoeae exceeds the threshold of the 5% resistance level recommended by the World Health Organization; and thus, cefixime treatment would have limited benefits in Australia.

6.
Sex Transm Infect ; 100(1): 48-51, 2024 Jan 17.
Artículo en Inglés | MEDLINE | ID: mdl-38050184

RESUMEN

OBJECTIVES: To ensure accurate diagnosis of infectious diseases, preanalytical factors should be considered when assessing specimen quality and subsequent test result. Accordingly, we aimed to systematically assess the effect of storage time, temperature and buffer on the analytical sensitivity of detecting the sexually transmitted pathogen, Neisseria gonorrhoeae across multiple molecular diagnostic platforms. METHODS: Cultured N. gonorrhoeae was spiked into generic and commercial storage buffers and stored at four temperatures and five time points, ranging from -20°C to 37°C, over 30 days. Samples were processed using the Alinity m STI, Xpert CT/NG and Aptima Combo 2 nucleic acid amplification assays and an in-house quantitative PCR assay. A reduction in analytical sensitivity was defined as a significant (p<0.05) increase in cycle threshold (Ct) value relative to control samples. RESULTS: In total, 2756 samples were processed, with N. gonorrhoeae detected in 99.2% of samples. With respect to time, analytical sensitivity was maintained from day 2 (113/120; 94.2%) up to day 30 (110/120; 91.7%) relative to baseline samples. With respect to temperature, analytical sensitivity was maintained from -20°C (147/150; 98.0%) up to 37°C (136/150; 90.7%) relative to baseline samples. Generic buffers, Viral Transport Medium and Amies Liquid Media showed a reduction in analytical sensitivity compared with their commercial counterparts, Aptima Multitest Swab Transport Media and Abbott Alinity transport buffer using select diagnostic assays; this reduction appeared temperature dependent, with the largest differences in median Ct values observed at 37°C (p<0.05). CONCLUSIONS: Increased prevalence of sample self-collection for sexually transmitted infections (STIs) warrants an evaluation of preanalytical sample storage variables on diagnostic testing performance. Here, across a range of time points, temperatures and storage buffers, N. gonorrhoeae was successfully detected, supporting flexibility in sample storage, and by extension the feasibility of analysing self-collected samples to improve access to STI testing.


Asunto(s)
Infecciones por Chlamydia , Gonorrea , Ácidos Nucleicos , Enfermedades de Transmisión Sexual , Humanos , Neisseria gonorrhoeae/genética , Técnicas de Amplificación de Ácido Nucleico/métodos , Chlamydia trachomatis/genética , Sensibilidad y Especificidad , Infecciones por Chlamydia/diagnóstico , Gonorrea/diagnóstico
7.
Med J Aust ; 220(11): 566-572, 2024 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-38803004

RESUMEN

OBJECTIVES: To investigate the distribution and prevalence of Japanese encephalitis virus (JEV) antibody (as evidence of past infection) in northern Victoria following the 2022 Japanese encephalitis outbreak, seeking to identify groups of people at particular risk of infection; to investigate the distribution and prevalence of antibodies to two related flaviviruses, Murray Valley encephalitis virus (MVEV) and West Nile virus Kunjin subtype (KUNV). STUDY DESIGN: Cross-sectional serosurvey (part of a national JEV serosurveillance program). SETTING: Three northern Victorian local public health units (Ovens Murray, Goulburn Valley, Loddon Mallee), 8 August - 1 December 2022. PARTICIPANTS: People opportunistically recruited at pathology collection centres and by targeted recruitment through community outreach and advertisements. People vaccinated against or who had been diagnosed with Japanese encephalitis were ineligible for participation, as were those born in countries where JEV is endemic. MAIN OUTCOME MEASURES: Seroprevalence of JEV IgG antibody, overall and by selected factors of interest (occupations, water body exposure, recreational activities and locations, exposure to animals, protective measures). RESULTS: 813 participants were recruited (median age, 59 years [interquartile range, 42-69 years]; 496 female [61%]); 27 were JEV IgG-seropositive (3.3%; 95% confidence interval [CI], 2.2-4.8%) (median age, 73 years [interquartile range, 63-78 years]; 13 female [48%]); none were IgM-seropositive. JEV IgG-seropositive participants were identified at all recruitment locations, including those without identified cases of Japanese encephalitis. The only risk factors associated with JEV IgG-seropositivity were age (per year: prevalence odds ratio [POR], 1.07; 95% CI, 1.03-1.10) and exposure to feral pigs (POR, 21; 95% CI, 1.7-190). The seroprevalence of antibody to MVEV was 3.0% (95% CI, 1.9-4.5%; 23 of 760 participants), and of KUNV antibody 3.3% (95% CI, 2.1-4.8%; 25 of 761). CONCLUSIONS: People living in northern Victoria are vulnerable to future JEV infection, but few risk factors are consistently associated with infection. Additional prevention strategies, including expanding vaccine eligibility, may be required to protect people in this region from Japanese encephalitis.


Asunto(s)
Anticuerpos Antivirales , Brotes de Enfermedades , Virus de la Encefalitis Japonesa (Especie) , Encefalitis Japonesa , Humanos , Estudios Transversales , Virus de la Encefalitis Japonesa (Especie)/inmunología , Persona de Mediana Edad , Estudios Seroepidemiológicos , Encefalitis Japonesa/epidemiología , Encefalitis Japonesa/inmunología , Adulto , Femenino , Masculino , Anticuerpos Antivirales/sangre , Anciano , Victoria/epidemiología , Inmunoglobulina G/sangre , Adulto Joven , Virus de la Encefalitis del Valle Murray/inmunología , Adolescente , Factores de Riesgo
8.
Euro Surveill ; 29(3)2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38240057

RESUMEN

Under International Health Regulations from 2005, a human infection caused by a novel influenza A virus variant is considered an event that has potential for high public health impact and is immediately notifiable to the World Health Organisation. We here describe the clinical, epidemiological and virological features of a confirmed human case of swine influenza A(H1N2)v in England detected through community respiratory virus surveillance. Swabbing and contact tracing helped refine public health risk assessment, following this unusual and unexpected finding.


Asunto(s)
Subtipo H1N1 del Virus de la Influenza A , Gripe Humana , Infecciones por Orthomyxoviridae , Enfermedades de los Porcinos , Animales , Humanos , Porcinos , Subtipo H1N2 del Virus de la Influenza A , Subtipo H1N1 del Virus de la Influenza A/genética , Enfermedades de los Porcinos/diagnóstico , Enfermedades de los Porcinos/epidemiología , Gripe Humana/diagnóstico , Gripe Humana/epidemiología , Inglaterra/epidemiología
9.
Clin Infect Dis ; 76(5): 795-799, 2023 03 04.
Artículo en Inglés | MEDLINE | ID: mdl-36285535

RESUMEN

BACKGROUND: We compared the rapid plasma reagin (RPR) titer on the day of initial presentation with that on the day of syphilis treatment to inform clinical practice as to whether a repeated RPR test should be recommended. METHODS: We undertook a retrospective study between 1 March 2011 and 31 December 2020 at the Melbourne Sexual Health Centre in Australia among individuals who underwent syphilis serology on the day of initial presentation and the day of treatment, if the latter were within 14 days after initial presentation. We calculated the percentage of individuals with a ≥4-fold change in RPR titer, stratified by the time between initial presentation and treatment and by syphilis stage. RESULTS: Among the 766 included syphilis cases, the median duration between initial presentation and treatment was 6 days (interquartile range, 5-7 days). Of these cases, 14.8% (n = 113) had a ≥4-fold increase or decrease during this interval. The number of cases with a ≥4-fold increase or decrease in RPR titer increased with increasing time between initial presentation and treatment, from 5.7% (n = 6) 1-3 days after initial presentation to 26.2% (n = 27) at 10-14 days (Ptrend < .001). There was no significant difference in the number of cases with a ≥4-fold increase or decrease in RPR titer between syphilis stages (P = .66). CONCLUSIONS: Our data support the recommendation of repeating the RPR titer if the day of initial presentation and the day of treatment are different, even when treatment is within a few days after initial presentation.


Asunto(s)
Sífilis , Humanos , Sífilis/diagnóstico , Sífilis/tratamiento farmacológico , Treponema pallidum , Reaginas , Estudios Retrospectivos , Serodiagnóstico de la Sífilis
10.
Emerg Infect Dis ; 29(10): 2083-2092, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37703891

RESUMEN

We investigated Treponema pallidum PCR positivity at mucosal sites (oral, anal, and vaginal sites) among adults who had sexual contact with a person with syphilis (syphilis contacts). All syphilis contacts had oral rinse and swab samples collected for testing. Men who have sex with men had anal swab and women had vaginal swab samples collected for testing, regardless of the presence of lesions. Of 407 persons tested, 42 (10%) had early syphilis diagnosed; of those, 19 (45%) tested positive by PCR from any anatomic site and had a positive serologic test. T. pallidum was positive from vaginal samples in 3 women, anal samples in 3 men, and oral cavity samples in 2 women and 3 men, without symptoms at those sites. Three women had no prior syphilis serologic test. T. pallidum detection at asymptomatic mucosal sites suggests early syphilis infections, particularly in cases that would conventionally be staged as latent syphilis of unknown duration.


Asunto(s)
Minorías Sexuales y de Género , Sífilis , Masculino , Adulto , Femenino , Humanos , Treponema pallidum , Sífilis/diagnóstico , Sífilis/epidemiología , Homosexualidad Masculina , Vagina
11.
Artículo en Inglés | MEDLINE | ID: mdl-33593834

RESUMEN

Topical antibiotic preparations, such as fusidic acid (FA) or mupirocin, are used in the prevention and treatment of superficial skin infections caused by staphylococci. Previous genomic epidemiology work has suggested an association between the widespread use of topical antibiotics and the emergence of methicillin resistant Staphylococcus aureus in some settings. In this study, we provide experimental proof of co-selection for multidrug resistance in S. aureus following exposure to FA or mupirocin. Through targeted mutagenesis and phenotypic analyses, we confirmed that fusC carriage confers resistance to FA, and mupA carriage confers high-level resistance to mupirocin in multiple S. aureus genetic backgrounds. In vitro experiments demonstrated that carriage of fusC and mupA confer a competitive advantage in the presence of sub-inhibitory concentrations of FA and mupirocin, respectively. Further, we used a porcine skin colonisation model to show that clinically relevant concentrations of topical antibiotics can co-select for presence of unrelated antimicrobial resistance determinants, such as mecA, blaZ, and qacA, in fusC or mupA harbouring S. aureus These findings provide valuable insights on the role of acquired FA or mupirocin resistance in co-selecting for broader antibiotic resistance in S. aureus, prompting greater need for judicious use of topical antibiotics.

12.
J Med Virol ; 95(1): e28429, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36571266

RESUMEN

Mpox is a zoonotic disease caused by monkeypox virus (MPXV) from the Orthopoxvirus genus. Unprecedented transmission events have led to more than 70 000 cases reported worldwide by October 2022. The change in mpox epidemiology has raised concerns of its ability to establish endemicity beyond its traditional geographical locations. In this review, we discuss the current understanding of mpox virology and viral dynamics that are relevant to mpox diagnostics. A synopsis of the traditional and emerging laboratory technologies useful for MPXV detection and in guiding "elimination" strategies is outlined in this review. Importantly, development in MPXV genomics has rapidly advanced our understanding of the role of viral evolution and adaptation in the current outbreak.


Asunto(s)
Mpox , Orthopoxvirus , Animales , Humanos , Mpox/diagnóstico , Mpox/epidemiología , Monkeypox virus , Zoonosis , Brotes de Enfermedades
13.
J Med Virol ; 95(8): e29029, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37565686

RESUMEN

The impact and frequency of infectious disease outbreaks demonstrate the need for timely genomic surveillance to inform public health responses. In the largest known outbreak of mpox, genomic surveillance efforts have primarily focused on high-incidence nations in Europe and the Americas, with a paucity of data from South-East Asia and the Western Pacific. Here we analyzed 102 monkeypox virus (MPXV) genomes sampled from 56 individuals in Melbourne, Australia. All genomes fell within the 2022 MPXV outbreak lineage (B.1), with likely onward local transmission detected. We observed within-host diversity and instances of co-infection, and highlight further examples of structural variation and apolipoprotein B editing complex-driven micro-evolution in the current MPXV outbreak. Updating our understanding of MPXV emergence and diversification will inform public health measures and enable monitoring of the virus' evolutionary trajectory throughout the mpox outbreak.


Asunto(s)
Monkeypox virus , Mpox , Humanos , Monkeypox virus/genética , Mpox/epidemiología , Genómica , Brotes de Enfermedades , Australia/epidemiología
14.
Sex Transm Infect ; 99(3): 162-166, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-35732476

RESUMEN

OBJECTIVES: Condylomata lata are a less common but distinctive syphilitic lesion. Variable theories as to their nature and origin exist. The aim of this study was to determine the clinical and laboratory characteristics of condylomata lata by determining (1): the most closely aligned stage of syphilis, based on the rapid plasma reagin (RPR) titre; (2) symptom duration and (3) Treponema pallidum PCR cycle threshold (CT) values, as an indicator of organism load. METHODS: This was a retrospective study of patients with T. pallidum PCR-positive condylomata lata lesions, attending a clinic in Melbourne, Australia, between 2011 and 2021. Syphilis serology was undertaken and RPR titres compared between condylomata lata, primary and secondary syphilis cases. RESULTS: 51 cases with T. pallidum PCR-positive condylomata lata were included. 41 cases were in men, 40 of whom were men who have sex with men (MSM), and 10 in women. Twelve of 51 (24%) cases were in HIV-positive MSM. Thirty-three of 51 (65%) had other mucocutaneous signs of secondary syphilis; 18 (35%) had no other signs of secondary syphilis. The median RPR titre among the 51 condylomata lata cases was 1:128, compared with the median RPR titre of primary syphilis (1:4) and of secondary syphilis (1:128). The median duration of lesions was 24 (IQR 10-60) days, with no significant difference between those with and without other signs of secondary syphilis (p=0.75). Median CT values for condylomata lata (CT=31) and primary syphilis (CT=31) were significantly lower than for other secondary syphilis lesion types (CT=33), indicating higher T. pallidum loads for condylomata lata and primary lesions compared with other secondary syphilis lesion types. DISCUSSION: These findings support condylomata lata as lesions that occur during the secondary stage of syphilis and which are likely to be highly infectious.


Asunto(s)
Enfermedades Gastrointestinales , Minorías Sexuales y de Género , Sífilis Cutánea , Sífilis , Masculino , Humanos , Femenino , Sífilis/complicaciones , Homosexualidad Masculina , Estudios Retrospectivos , Treponema pallidum , Serodiagnóstico de la Sífilis
15.
Intern Med J ; 53(5): 835-840, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-37134258

RESUMEN

Prior to January 2022, only a single case of infection with Japanese encephalitis virus (JEV) had been reported on the Australian mainland, acquired in the northern extremity on Cape York. We report the clinical characteristics of the sentinel cluster of cases that confirmed the local acquisition of JEV in southern Australia along the Murray River bordering New South Wales and Victoria.


Asunto(s)
Culex , Virus de la Encefalitis Japonesa (Especie) , Encefalitis Japonesa , Animales , Humanos , Australia del Sur , Victoria
16.
Sex Health ; 20(5): 390-402, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37423606

RESUMEN

BACKGROUND: The first mpox case was reported in May 2022 in Australia. Most cases have been diagnosed in men who have sex with men (MSM). This study aimed to examine community understanding of mpox, attitudes towards vaccination, and potential changes in sexual practices surrounding the mpox outbreak among MSM and transgender people in Victoria, Australia. METHODS: Participants were recruited from sexual health clinics and communities in Victoria, Australia, in August-October 2022. Participants were asked about their understanding and knowledge of mpox, vaccination uptake and intentions to change sexual practices. Univariable and multivariable logistic regression was performed to examine the factors associated with mpox vaccine uptake. RESULTS: Most participants (97.8%, 525/537) had heard about mpox and 10.5% (55/525) knew someone who had had mpox. Of the 12 mpox knowledge questions, the median score of correct answers was 10 (IQR=8-11) out of a maximum of 12. More than a third (36.6%, 191/522) had been vaccinated against mpox. MSM who had a good knowledge of mpox had the highest odds of receiving mpox vaccine compared with those who had poor knowledge (aOR=4.05; 95% CI: 1.54-10.61). To prevent mpox, half reported they would reduce having sex with casual partners, stop having chemsex (used drugs for the purpose of sex), stop attending sex-on-premises-venues, and stop having group sex. A quarter reported they would increase condom use for anal sex. CONCLUSIONS: One-third of high-risk participants and a substantial proportion of participants intended to reduce or stop certain practices, which may explain the large reduction in mpox cases.

17.
J Infect Dis ; 226(1): 167-176, 2022 08 12.
Artículo en Inglés | MEDLINE | ID: mdl-35134931

RESUMEN

BACKGROUND: Group A Streptococcus (GAS) causes superficial pharyngitis and skin infections as well as serious autoimmune sequelae such as acute rheumatic fever (ARF) and subsequent rheumatic heart disease. ARF pathogenesis remains poorly understood. Immune priming by repeated GAS infections is thought to trigger ARF, and there is growing evidence for the role of skin infections in this process. METHODS: We utilized our recently developed 8-plex immunoassay, comprising antigens used in clinical serology for diagnosis of ARF (SLO, DNase B, SpnA), and 5 conserved putative GAS vaccine antigens (Spy0843, SCPA, SpyCEP, SpyAD, Group A carbohydrate), to characterize antibody responses in sera from New Zealand children with a range of clinically diagnosed GAS disease: ARF (n = 79), GAS-positive pharyngitis (n = 94), GAS-positive skin infection (n = 51), and matched healthy controls (n = 90). RESULTS: The magnitude and breadth of antibodies in ARF was very high, giving rise to a distinct serological profile. An average of 6.5 antigen-specific reactivities per individual was observed in ARF, compared to 4.2 in skin infections and 3.3 in pharyngitis. CONCLUSIONS: ARF patients have a unique serological profile, which may be the result of repeated precursor pharyngitis and skin infections that progressively boost antibody breadth and magnitude.


Asunto(s)
Faringitis , Fiebre Reumática , Enfermedades Cutáneas Infecciosas , Infecciones Estreptocócicas , Formación de Anticuerpos , Niño , Humanos , Faringitis/prevención & control , Streptococcus pyogenes
18.
Clin Infect Dis ; 75(5): 813-823, 2022 09 14.
Artículo en Inglés | MEDLINE | ID: mdl-34984438

RESUMEN

BACKGROUND: Mycoplasma genitalium (MG) infection is challenging to cure because of rising antimicrobial resistance and limited treatment options. METHODS: This was a prospective evaluation of the efficacy and tolerability of resistance-guided combination antimicrobial therapy for MG treatment at Melbourne Sexual Health Centre (August 2019-December 2020). All patients received 7 days of doxycycline before combination therapy based on the macrolide-resistant profile. Macrolide-susceptible infections received combination doxycycline + azithromycin (1 g, day 1; 500 mg, days 2-4) and macrolide-resistant infections combination doxycycline + moxifloxacin (400 mg daily for 7 days). Adherence and adverse effects were recorded at test-of-cure, recommended 14-28 days after antimicrobial completion. Sequencing was performed to determine the prevalence of single nucleotide polymorphisms (SNPs) in the parC gene and their association with moxifloxacin treatment outcomes in macrolide-resistant infections. RESULTS: Of 100 patients with macrolide-susceptible MG treated with doxycycline + azithromycin, 93 were cured (93.0%; 95% confidence interval [CI], 86.1-97.1). Of 247 patients with macrolide-resistant MG receiving doxycycline + moxifloxacin, 210 were cured (85.0%; 95% CI, 80.0-89.2). parC sequencing was available for 164 (66%) macrolide-resistant infections; 29% had SNPs at parC S83 or D87 (23% S83I). The absence of SNPs at parC S83/D87 was associated with 98.3% cure (95% CI, 93.9-99.8) following doxycycline + moxifloxacin. The presence of the parC S83I-SNP was associated with failure in 62.5% (95% CI, 45.8-77.3). Side effects were common (40%-46%) and predominantly mild and gastrointestinal. CONCLUSIONS: Combination doxycycline + azithromycin achieved high cure for macrolide-susceptible infections. However, in the context of a high prevalence of the parC S83I mutation (23%) in macrolide-resistant infections, doxycycline + moxifloxacin cured only 85%. Infections that were wild-type for S83/D87 experienced high cure following doxycycline + moxifloxacin, supporting the use of a parC-resistance/susceptibility testing strategy in clinical care.


Asunto(s)
Farmacorresistencia Bacteriana , Infecciones por Mycoplasma , Mycoplasma genitalium , Antibacterianos/efectos adversos , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Azitromicina/efectos adversos , Doxiciclina/efectos adversos , Farmacorresistencia Bacteriana/genética , Humanos , Macrólidos/efectos adversos , Moxifloxacino/farmacología , Moxifloxacino/uso terapéutico , Infecciones por Mycoplasma/tratamiento farmacológico , Mycoplasma genitalium/efectos de los fármacos , Mycoplasma genitalium/genética
19.
Sex Transm Infect ; 98(8): 570-574, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-35618414

RESUMEN

OBJECTIVES: We aimed to characterise patterns of anal and oral detection of Treponema pallidum among men who have sex with men (MSM) with early syphilis. METHODS: 200 MSM with serologically confirmed primary, secondary and early latent syphilis were tested with T. pallidum polA PCR using an anal canal swab, oral rinse, plus swabs from any anal and oral lesions in a prospective, cross-sectional study. Anal and oral T. pallidum cycle threshold values were compared between subsets of men and according to rapid plasma reagin (RPR) titre. RESULTS: Of 200 men with early syphilis, 45 and 48 had anal and oral T. pallidum detected, respectively. Cycle threshold values were lower with anal compared with oral T. pallidum whether lesions were present or not. Among 27 and 42 men with anal and oral T. pallidum detected, respectively, and no anal or oral primary lesion, frequency of detection increased with increasing RPR titre, with 95% (25/27) and 98% (41/42) of shedding from respective sites occurring with RPR titres ≥1:16. 6.5% (13/200) of men with syphilis had concurrent detection of T. pallidum from both anal and oral sites: 9/13 with secondary syphilis, 7/9 of whom had anal lesions with a median duration of 30 days (range 7-180 days). CONCLUSIONS: These data suggest T. pallidum load at the anus is higher than at the oral cavity and that a subset of men with secondary syphilis and prolonged anal lesions may be relatively infectious. Earlier detection and treatment of syphilis, when RPR titres are lower than 1:16, could potentially reduce infectiousness from anal and oral sites.


Asunto(s)
Minorías Sexuales y de Género , Sífilis , Masculino , Humanos , Treponema pallidum/genética , Homosexualidad Masculina , Canal Anal/patología , Estudios Transversales , Estudios Prospectivos
20.
Sex Transm Infect ; 98(8): 582-585, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-35217591

RESUMEN

BACKGROUND: Lymphogranuloma venereum (LGV) is caused by Chlamydia trachomatis serovars L1-L3. This study determined the positivity for LGV testing before and after introduction of universal LGV testing of positive rectal Chlamydia trachomatis samples in men who have sex with men (MSM). METHODS: From March 2015 to February 2018, MSM with rectal C. trachomatis were not routinely tested for LGV at the Melbourne Sexual Health Centre unless they had HIV or symptoms of proctitis. From February 2018, universal testing for LGV of all positive rectal C. trachomatis specimens in men over the age of 25 years, regardless of symptoms was undertaken. LGV positivity was defined as the detection of LGV-associated C. trachomatis serovars. RESULTS: There were 3429 and 4020 MSM who tested positive for rectal chlamydia in the selective and universal LGV-testing periods, respectively. Of the total 3027 assessable specimens in both periods, 97 (3.2%; 95% CI 2.6% to 3.9%) specimens tested positive for LGV. LGV positivity in the selective testing period was higher than in the universal testing period (6.6% (33/502) vs 2.5% (64/2525), p<0.001). The proportion of LGV cases that were asymptomatic increased from 15.2% (5/33) in the selective testing period to 34.4% (22/64) in the universal testing period (p=0.045). Of the 70 symptomatic LGV cases symptoms included rectal discharge (71.4%, n=45) and rectal pain (60.0%, n=42). CONCLUSION: Universal LGV testing of all positive rectal chlamydia samples in MSM compared with selective testing led to the detection of asymptomatic rectal LGV, which constituted 34% of rectal LGV cases.


Asunto(s)
Linfogranuloma Venéreo , Enfermedades del Recto , Minorías Sexuales y de Género , Masculino , Humanos , Adulto , Linfogranuloma Venéreo/diagnóstico , Linfogranuloma Venéreo/epidemiología , Homosexualidad Masculina , Chlamydia trachomatis , Enfermedades del Recto/diagnóstico , Enfermedades del Recto/epidemiología
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