RESUMEN
BACKGROUND: Autoantibodies against interleukin-12 (anti-interleukin-12) are often identified in patients with thymoma, but opportunistic infections develop in only some of these patients. Interleukin-12 (with subunits p40 and p35) shares a common subunit with interleukin-23 (subunits p40 and p19). In a patient with disseminated Burkholderia gladioli infection, the identification of both anti-interleukin-23 and anti-interleukin-12 prompted further investigation. METHODS: Among the patients (most of whom had thymoma) who were known to have anti-interleukin-12, we screened for autoantibodies against interleukin-23 (anti-interleukin-23). To validate the potential role of anti-interleukin-23 with respect to opportunistic infection, we tested a second cohort of patients with thymoma as well as patients without either thymoma or known anti-interleukin-12 who had unusual infections. RESULTS: Among 30 patients with anti-interleukin-12 who had severe mycobacterial, bacterial, or fungal infections, 15 (50%) also had autoantibodies that neutralized interleukin-23. The potency of such neutralization was correlated with the severity of these infections. The neutralizing activity of anti-interleukin-12 alone was not associated with infection. In the validation cohort of 91 patients with thymoma, the presence of anti-interleukin-23 was associated with infection status in 74 patients (81%). Overall, neutralizing anti-interleukin-23 was detected in 30 of 116 patients (26%) with thymoma and in 30 of 36 patients (83%) with disseminated, cerebral, or pulmonary infections. Anti-interleukin-23 was present in 6 of 32 patients (19%) with severe intracellular infections and in 2 of 16 patients (12%) with unusual intracranial infections, including Cladophialophora bantiana and Mycobacterium avium complex. CONCLUSIONS: Among patients with a variety of mycobacterial, bacterial, or fungal infections, the presence of neutralizing anti-interleukin-23 was associated with severe, persistent opportunistic infections. (Funded by the National Institute of Allergy and Infectious Diseases and others.).
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Autoanticuerpos , Síndromes de Inmunodeficiencia , Interleucina-23 , Infecciones Oportunistas , Adulto , Humanos , Autoanticuerpos/inmunología , Síndromes de Inmunodeficiencia/inmunología , Interleucina-12/antagonistas & inhibidores , Interleucina-12/inmunología , Interleucina-23/antagonistas & inhibidores , Interleucina-23/inmunología , Micosis/inmunología , Infecciones Oportunistas/inmunología , Timoma/inmunología , Neoplasias del Timo/inmunología , Anticuerpos Neutralizantes/inmunología , Infecciones Bacterianas/inmunologíaRESUMEN
BACKGROUND: Autoimmune polyendocrine syndrome type 1 (APS-1) is a life-threatening, autosomal recessive syndrome caused by autoimmune regulator (AIRE) deficiency. In APS-1, self-reactive T cells escape thymic negative selection, infiltrate organs, and drive autoimmune injury. The effector mechanisms governing T-cell-mediated damage in APS-1 remain poorly understood. METHODS: We examined whether APS-1 could be classified as a disease mediated by interferon-γ. We first assessed patients with APS-1 who were participating in a prospective natural history study and evaluated mRNA and protein expression in blood and tissues. We then examined the pathogenic role of interferon-γ using Aire-/-Ifng-/- mice and Aire-/- mice treated with the Janus kinase (JAK) inhibitor ruxolitinib. On the basis of our findings, we used ruxolitinib to treat five patients with APS-1 and assessed clinical, immunologic, histologic, transcriptional, and autoantibody responses. RESULTS: Patients with APS-1 had enhanced interferon-γ responses in blood and in all examined autoimmunity-affected tissues. Aire-/- mice had selectively increased interferon-γ production by T cells and enhanced interferon-γ, phosphorylated signal transducer and activator of transcription 1 (pSTAT1), and CXCL9 signals in multiple organs. Ifng ablation or ruxolitinib-induced JAK-STAT blockade in Aire-/- mice normalized interferon-γ responses and averted T-cell infiltration and damage in organs. Ruxolitinib treatment of five patients with APS-1 led to decreased levels of T-cell-derived interferon-γ, normalized interferon-γ and CXCL9 levels, and remission of alopecia, oral candidiasis, nail dystrophy, gastritis, enteritis, arthritis, Sjögren's-like syndrome, urticaria, and thyroiditis. No serious adverse effects from ruxolitinib were identified in these patients. CONCLUSIONS: Our findings indicate that APS-1, which is caused by AIRE deficiency, is characterized by excessive, multiorgan interferon-γ-mediated responses. JAK inhibition with ruxolitinib in five patients showed promising results. (Funded by the National Institute of Allergy and Infectious Diseases and others.).
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Proteína AIRE , Interferón gamma , Inhibidores de las Cinasas Janus , Poliendocrinopatías Autoinmunes , Adulto , Animales , Femenino , Humanos , Masculino , Ratones , Proteína AIRE/deficiencia , Proteína AIRE/genética , Proteína AIRE/inmunología , Autoanticuerpos/sangre , Autoanticuerpos/inmunología , Quimiocina CXCL9/genética , Interferón gamma/genética , Interferón gamma/inmunología , Inhibidores de las Cinasas Janus/uso terapéutico , Ratones Noqueados , Nitrilos/uso terapéutico , Poliendocrinopatías Autoinmunes/genética , Poliendocrinopatías Autoinmunes/tratamiento farmacológico , Poliendocrinopatías Autoinmunes/inmunología , Pirazoles/uso terapéutico , Pirazoles/farmacología , Pirimidinas/uso terapéutico , Linfocitos T/inmunología , Factores de Transcripción/genética , Factores de Transcripción/inmunología , Proyectos Piloto , Modelos Animales de Enfermedad , Niño , Adolescente , Persona de Mediana EdadRESUMEN
More frequent among adults, phenocopies may be caused by somatic mutations or anti-cytokine autoantibodies, mimicking the phenotypes of primary immunodeficiencies. A fourteen-year-old girl was referred for a two-year history of weight loss and multiple recurrent abscesses, complicated recurrent pneumonia, pyelonephritis, osteomyelitis, and septic shock, without fever. She had started with nausea, hyporexia, and weight loss, then with abscesses in her hands, knee, ankle, and spleen. She also developed a rib fracture and left thoracic herpes zoster. The patient was cachectic, with normal vital signs, bilateral crackles on chest auscultation, tumefaction of the knee joint, and poorly healed wounds in hands and chest, oozing a yellowish fluid. Chest computed tomography revealed multiple bilateral bronchiectases. Laboratory workup reported chronic anemia, leukocytosis, neutrophilia, mild lymphopenia, thrombocytosis, pan-hypergammaglobulinemia, and elevated acute serum reactants. Lymphocyte subsets were low but present. Mycobacterium tuberculosis was detected via polymerase chain reaction in a bone biopsy specimen from ankle osteomyelitis. Whole-exome sequencing failed to identify a monogenic defect. Interleukin-12 was found markedly elevated in the serum of the patient. Phosphorylation of STAT4, induced by increasing doses of IL-12, was neutralized by patient serum, confirming the presence of anti-IL12 autoantibodies. IL-12 and IL-23 are crucial cytokines in the defense against intracellular microorganisms, the induction of interferon-gamma production by lymphocytes, and other inflammatory functions. Patients who develop neutralizing serum autoantibodies against IL12 manifest late in life with weight loss, multiple recurrent abscesses, poor wound healing, and fistulae. Treatment with anti-CD20 monoclonal antibodies was effective.
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Absceso , Autoanticuerpos , Humanos , Femenino , Autoanticuerpos/inmunología , Autoanticuerpos/sangre , Adolescente , Absceso/inmunología , Subunidad p40 de la Interleucina-12/inmunología , Recurrencia , Osteomielitis/inmunologíaRESUMEN
BACKGROUND: Single-dose benzathine penicillin G (BPG) is the preferred therapy for early syphilis, but poorer serologic responses have been observed among people with HIV (PWH). No enhanced regimen has previously been shown to improve serologic outcomes of early syphilis. METHODS: We conducted a retrospective study to compare the treatment responses to single-dose BPG combined with 7-day doxycycline versus BPG alone in PWH who presented with early syphilis. Rapid plasma reagin (RPR) titers were determined every 3-6 months for all included PWH. Serologic response was defined as at least a fourfold decline in RPR titers at month 12. RESULTS: During January 2018 to March 2022, 223 PWH with 307 episodes of early syphilis received single-dose BPG plus doxycycline and 347 PWH with 391 episodes received BPG alone. The median age was 36 years and baseline CD4 count was 600 cells/mm3. In the intention-to-treat with last-observation-carried-forward analysis, PWH receiving BPG plus doxycycline had a significantly higher serologic response rate at 12 months of treatment than those receiving BPG alone (79.5% vs 70.3%, respectively; P= .006). The factors associated with 12-month serologic response were RPR titer (per 1-log2 increase, adjusted odds ratio [AOR], 1.25; 95% CI, 1.15-1.35) and receipt of BPG plus doxycycline (AOR, 1.71; 95% CI, 1.20-2.46). In the subgroup analyses, BPG plus doxycycline was consistently associated with a better serologic response than BPG alone at month 12. CONCLUSIONS: Among PWH with early syphilis, single-dose BPG plus doxycycline achieved higher serologic responses than BPG alone during a 12-month follow-up period.
RESUMEN
BACKGROUND: For people with human immunodeficiency virus (PWH) who have no serological responses to their primary hepatitis A virus (HAV) vaccination or have seroreversion after successful primary vaccination, the optimal revaccination strategy remains unclear. METHODS: In this open-label, randomized clinical trial, PWH who tested negative for anti-HAV antibodies after receiving a standard 2-dose series of primary HAV vaccination were enrolled and assigned in a 1:1 ratio to receive either 1 dose (the 1-dose group) or 2 doses of HAV vaccine administered 4 weeks apart (the 2-dose group). Serological response rates and anti-HAV antibody titers were compared at weeks 24 and 48. RESULTS: Of the 153 participants (77 in the 1-dose group and 76 in the 2-dose group), the overall serological response rates at week 48 after revaccination were similar between the 2 groups (2- vs 1-dose, 80.2% vs 71.4%, P = .20). However, anti-HAV antibody titers were consistently higher in the 2-dose group than in the 1-dose group. In subgroup analysis, PWH who were nonresponders to primary HAV vaccination were significantly more likely to mount a serological response after 2-dose HAV revaccination (68.4% vs 44.1%, P = .038). No severe adverse events were reported throughout the study. CONCLUSIONS: Two-dose HAV revaccination administered 4 weeks apart yielded similar serological responses as 1-dose revaccination among PWH who were nonresponders or had seroreversion after primary HAV vaccination. The 2-dose revaccination schedule generated significantly higher anti-HAV antibody titers and was more likely to elicit serological responses at week 48 among PWH who were nonresponders to primary HAV vaccination. Clinical Trials Registration. NCT03855176.
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Virus de la Hepatitis A , Hepatitis A , Humanos , Inmunización Secundaria , VIH , Anticuerpos de Hepatitis A , Vacunación , Vacunas contra la Hepatitis A , Hepatitis A/prevención & controlRESUMEN
BACKGROUND: Studies correlating reactogenicity and immunogenicity of COVID-19 vaccines are limited to BNT162b2, with inconsistent results. We investigated whether adverse reactions after other COVID-19 vaccines reliably predict humoral responses. METHODS: Adult volunteers were recruited for homologous or heterologous prime-boost vaccinations with adenoviral (ChAdOx1, AstraZeneca) and/or mRNA (mRNA-1273, Moderna) vaccines administered either 4 or 8 weeks apart. Adverse effects were routinely solicited and recorded by subjects in a standard diary card for up to 84 days post booster vaccination. Anti-SARS-CoV-2 IgG titers were measured pre- (visit 1), and post-booster dose at days 14 (visit 2) and 28 (visit 3). RESULTS: A total of 399 participants (75% women) with a median age of 41 (interquartile range, 33-48 IQR) years were included. Vaccine-induced antibody titers at days 14 and 28 were significantly higher among subjects who reported local erythema, swelling, pain, as well as systemic fever, chills, headache, myalgia, arthralgia, fatigue compared to those who did not experience local or systemic reactogenicity. Post-vaccination humoral responses did not correlate with the occurrence of skin rash and correlated weakly with gastrointestinal symptoms. A significant correlation between post-vaccination peak body temperature and anti-SARS-CoV-2 spike IgG at Day 14, independent of vaccine type and schedule, was found. CONCLUSION: Specific symptoms of reactogenicity such as post-vaccination injection site pain, swelling, erythema and fever, myalgia and fatigue are significantly predictive of the magnitude of the anti-SARS-CoV-2 antibody response.
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COVID-19 , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Adulto , Femenino , Humanos , Persona de Mediana Edad , Masculino , Vacunas contra la COVID-19/efectos adversos , Formación de Anticuerpos , Mialgia/etiología , Vacuna BNT162 , COVID-19/prevención & control , Vacunación/efectos adversos , Fatiga , Fiebre/etiología , Anticuerpos AntiviralesRESUMEN
BACKGROUND: COVID-19 rebound is usually reported among patients experiencing concurrent symptomatic and viral rebound. But longitudinal viral RT-PCR results from early stage to rebound of COVID-19 was less characterized. Further, identifying the factors associated with viral rebound after nirmatrelvir-ritonavir (NMV/r) and molnupiravir may expand understanding of COVID-19 rebound. METHODS: We retrospectively analyzed clinical data and sequential viral RT-PCR results from COVID-19 patients receiving oral antivirals between April and May, 2022. Viral rebound was defined by the degree of viral load increase (ΔCt ≥ 5 units). RESULTS: A total of 58 and 27 COVID-19 patients taking NMV/r and molnupiravir, respectively, were enrolled. Patients receiving NMV/r were younger, had fewer risk factors for disease progression and faster viral clearance rate compared to those receiving molnupiravr (All P < 0.05). The overall proportion of viral rebound (n = 11) was 12.9%, which was more common among patients receiving NMV/r (10 [17.2%] vs. 1 [3.7%], P = 0.16). Of them, 5 patients experienced symptomatic rebound, suggesting the proportion of COVID-19 rebound was 5.9%. The median interval to viral rebound was 5.0 (interquartile range, 2.0-8.0) days after completion of antivirals. Initial lymphopenia (<0.8 × 109/L) was associated with viral rebound among overall population (adjusted odds ratio [aOR], 5.34; 95% confidence interval [CI], 1.33-21.71), and remained significant (aOR, 4.50; 95% CI, 1.05-19.25) even when patients receiving NMV/r were considered. CONCLUSION: Our data suggest viral rebound after oral antivirals may be more commonly observed among lymphopenic individuals in the context of SARS-CoV-2 Omicron BA.2 variant.
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Antivirales , COVID-19 , Humanos , Antivirales/uso terapéutico , Estudios Retrospectivos , SARS-CoV-2RESUMEN
Anticytokine autoantibodies can cause immunodeficiency or dysregulate immune responses. They may phenocopy genetically defined primary immunodeficiencies. We review current anti-type 1 and anti-type 2 interferon; anti-IL-12/23, anti-IL-17, and anti-GM-CSF autoantibodies; HLA associations; disease associations; and mechanistically based treatment options. Suspecting the presence of these autoantibodies in patients and identifying them at the onset of symptoms should ameliorate disease and improve outcomes.
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Autoanticuerpos/inmunología , Citocinas/inmunología , Autoinmunidad , HumanosRESUMEN
Binding levels and neutralization activity of anti-type 1 interferon autoantibodies peaked during acute coronavirus disease 2019 and markedly decreased thereafter. Most patients maintained some ability to neutralize type 1 interferon into convalescence despite lower levels of binding immunoglobulin G. Identifying these autoantibodies in healthy individuals before the development of critical viral disease may be challenging.
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COVID-19 , Interferón Tipo I , Autoanticuerpos , Humanos , Inmunoglobulina G , Interferón-alfaRESUMEN
BACKGROUND: Anti GM-CSF autoantibodies (aAb) have been related to acquired pulmonary alveolar proteinosis (PAP) and described in cases of severe infections such as cryptococcosis and nocardiosis in previously healthy subjects. Whether there are different anti-GM-CSF autoantibodies corresponding to these phenotypes is unclear. Therefore, we examined anti-GM-CSF autoantibodies to determine whether amount or neutralizing activity could distinguish between groups. METHODS: Plasma samples gathered in the National Institute of Health from patients with anti GM-CSF aAb and either PAP (n = 15), cryptococcal meningitis (n = 15), severe nocardiosis (n = 5) or overlapping phenotypes (n = 6) were compared. The relative amount of aAb was assessed using a particle-based approach, reported as a mouse monoclonal anti-human GM-CSF as standard curve and expressed in an arbitrary Mouse Monoclonal Antibody Unit (MMAU). The neutralizing activity of the plasma was assessed by inhibition of GM-CSF-induced intracellular phospho-STAT5 (pSTAT5) in monocytes. RESULTS: Anti-GM-CSF aAb relative amounts were higher in PAP patients compared to those with cryptococcosis (mean 495 ± 464 MMAU vs 197 ± 159 MMAU, p = 0.02); there was no difference with patients with nocardiosis (430 ± 493 MMAU) nor between the two types of infections. The dilution of plasma resulting in 50% inhibition of GM-CSF-induced pSTAT5 (approximate IC50) did not vary appreciably across groups of patients (1.6 ± 3.1%, 3.9 ± 6% and 1.8 ± 2.2% in PAP patients, cryptococcosis and nocardiosis patients, respectively). Nor was the concentration of GM-CSF necessary to induce 50% of maximal GM-CSF-induced pSTAT5 in the presence of 10 MMAU of anti-GM-CSF aAb (EC50). When studying longitudinal samples from patients with PAP or disseminated nocardiosis, the neutralizing effect of anti-GM-CSF aAb was relatively constant over time despite targeted treatments and variations in aAb levels. CONCLUSIONS: Despite different clinical manifestations, anti-GM-CSF antibodies were similar across PAP, cryptococcosis and nocardiosis. Underlying host genetics and functional analyses may help further differentiate the biology of these conditions.
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Criptococosis , Meningitis Criptocócica , Nocardiosis , Proteinosis Alveolar Pulmonar , Animales , Anticuerpos Monoclonales , Autoanticuerpos , Ratones , Proteinosis Alveolar Pulmonar/diagnóstico , Factor de Transcripción STAT5RESUMEN
BACKGROUND: Patients with adult-onset immunodeficiency syndrome due to anti-interferon-γ autoantibodies (AIGAs) are susceptible to disseminated Mycobacterium avium complex (MAC) infections. M. chimaera, a newly identified MAC species, is distinguished from the others due to the reduced virulence. Previous cases of disseminated M. chimaera infection have been linked to cardiothoracic surgery. Reports of disseminated M. chimaera in patients without a history of cardiothoracic surgery are rare. CASE PRESENTATION: A 57-year-old Asian man, previously healthy, presented with fever, dry cough, exertional dyspnea, and decreased appetite. The delayed resolution of pneumonia despite antibiotic treatment prompted further imaging studies and biopsies from the lung and lymph node. The fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) demonstrated intense uptake in lung consolidations and diffuse lymphadenopathy. Cultures of the specimens obtained from sputum, blood, stool, lung tissue, and lymph node grew M. chimaera. Further immunological evaluation disclosed the presence of neutralizing AIGAs, which possibly led to acquired immunodeficiency and disseminated M. chimaera infection. CONCLUSIONS: We herein present the first case of adult-onset immunodeficiency due to AIGAs complicated with disseminated M. chimaera infection. Further immunological evaluation, including AIGAs, may be warranted in otherwise healthy patients who present with disseminated mycobacterial infection.
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Síndromes de Inmunodeficiencia , Infecciones por Mycobacterium no Tuberculosas , Mycobacterium , Adulto , Quimera , Humanos , Síndromes de Inmunodeficiencia/complicaciones , Masculino , Persona de Mediana Edad , Infecciones por Mycobacterium no Tuberculosas/microbiología , Tomografía Computarizada por Tomografía de Emisión de PositronesRESUMEN
BACKGROUND: Beginning from 2015-2016, unprecedented large outbreaks of acute hepatitis A that predominantly affected men who have sex with men (MSM) reemerged across the continents. We assessed the impact of an early initiated hepatitis A virus (HAV) vaccination campaign that targeted MSM living with human immunodeficiency virus (HIV) during the 2015-2017 hepatitis A outbreak in Taiwan. METHODS: First, we ascertained the effectiveness of HAV vaccination for MSM living with HIV using a nested case-control study of 1470 persons living with HIV who were initially HAV-seronegative. We then fitted a model of HAV transmission among MSM, risk-structured by HIV status, to the actual epidemic curve of reported acute hepatitis A cases in Taiwan during 2015-2017. RESULTS: Fifty-five cases of acute hepatitis A were matched to 220 controls. Single-dose and 2-dose HAV vaccination provided protection rates of 96.1% and 97.8% among recipient MSM living with HIV, respectively. Model fitting yielded basic reproductive number estimates of 7.26 (MSM living with HIV) and 3.04 (MSM not living with HIV). In a counterfactual scenario without an HAV vaccination campaign, the outbreak would have involved 7153 hepatitis A cases during 2015-2017 in contrast to the 1352 that were observed. We therefore estimated that the HAV vaccination campaign averted 80.7% (sensitivity analysis, 48.8%-92.7%) of acute hepatitis A cases that would otherwise have occurred by the end of 2017. CONCLUSIONS: The early initiated HAV vaccination campaign, which targeted MSM living with HIV, very effectively curtailed the 2015-2017 hepatitis A outbreak in Taiwan.
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Infecciones por VIH , Hepatitis A , Minorías Sexuales y de Género , Estudios de Casos y Controles , Brotes de Enfermedades/prevención & control , Infecciones por VIH/epidemiología , Infecciones por VIH/prevención & control , Hepatitis A/epidemiología , Hepatitis A/prevención & control , Homosexualidad Masculina , Humanos , Programas de Inmunización , Masculino , Taiwán/epidemiología , VacunaciónRESUMEN
Infections caused by the difficult-to-treat bacterium Mycobacterium abscessus are increasing in frequency. Rifabutin, in contrast to rifampin, appears to be active in vitro against M. abscessus, especially against clarithromycin-resistant strains. However, explorations for potential synergy between rifabutin and available antimicrobials are currently limited. In vitro synergism between rifabutin and 10 antimicrobials was evaluated in 31 mycobacterial strains by the checkerboard method. The fractional inhibitory concentration index (FICI) was calculated for each rifabutin-based combination. The colony morphology was recorded. Molecular methods for determination of the M. abscessus subspecies and analysis of macrolide resistance were performed by sequencing of the secA1, rpoB, hsp65, erm(41), and rrl genes. Rifabutin yielded an MIC50 of 16 mg/liter (range, 2 to 32 mg/liter) against 26 clinical M. abscessus isolates (comprising 13 M. abscessus subsp. abscessus and 13 M. abscessus subsp. massiliense isolates) and 5 reference strains, including M. abscessus subsp. abscessus ATCC 19977, M. abscessus subsp. bolletii BCRC 16915, M. abscessus subsp. massiliense BCRC 16916, M. chelonae ATCC 35752, and M. peregrinum ATCC 700686. Significant synergism, classified by an FICI of ≤0.5, was demonstrated for the combinations of rifabutin and imipenem in 100% of M. abscessus subsp. abscessus and 69% of M. abscessus subsp. massiliense isolates, and significant synergism for rifabutin and tigecycline was demonstrated in 77% of M. abscessus subsp. abscessus and 69% of M. abscessus subsp. massiliense isolates. Among the 6 clarithromycin-resistant (MICs ≥ 8 mg/liter) M. abscessus subsp. abscessus isolates, the combination of rifabutin and clarithromycin was 100% synergistic. Rifabutin showed promising in vitro synergism with first-line anti-M. abscessus agents, especially for macrolide-resistant M. abscessus subsp. abscessus isolates.
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Antibacterianos/farmacología , Claritromicina/farmacología , Imipenem/farmacología , Infecciones por Mycobacterium no Tuberculosas/tratamiento farmacológico , Mycobacterium abscessus/efectos de los fármacos , Rifabutina/farmacología , Tigeciclina/farmacología , Farmacorresistencia Bacteriana/efectos de los fármacos , Sinergismo Farmacológico , Humanos , Macrólidos/farmacología , Pruebas de Sensibilidad Microbiana , Infecciones por Mycobacterium no Tuberculosas/microbiologíaRESUMEN
Outbreaks of infections by Mycobacterium abscessus, particularly subspecies massiliense, are increasingly reported worldwide. Several multilocus sequence typing (MLST) protocols for grouping international outbreak strains have been developed but not yet directly compared. Using the three-gene (hsp65, rpoB, and secA1), seven-gene (argH, cya, glpK, gnd, murC, pta, and purH) and thirteen-gene (all of the preceding genes plus gdhA, pgm, and pknA) MLST schemes, we identified 22, 38, and 40 unique sequence types (STs), respectively, among a total of 139 nonduplicated M. abscessus isolates. Among subspecies massiliense, three-gene MLST not only clustered all outbreak strains together (in 100% agreement with the seven-gene and thirteen-gene schemes), but it also distinguished between two new STs that would have been grouped together by the seven-gene MLST but were distinct by the thirteen-gene MLST owing to differences in hsp65, rpoB, and pknA Here, we show that an abbreviated MLST may be useful for simultaneous identification of M. abscessus the subspecies level and screening M. abscessus subsp. massiliense isolates with outbreak potential.
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Tipificación de Secuencias Multilocus , Infecciones por Mycobacterium no Tuberculosas/diagnóstico , Infecciones por Mycobacterium no Tuberculosas/microbiología , Mycobacterium abscessus/genética , Proteínas Bacterianas/genética , ADN Bacteriano , Brotes de Enfermedades , Humanos , Tipificación de Secuencias Multilocus/métodos , Infecciones por Mycobacterium no Tuberculosas/epidemiología , Filogenia , Análisis de Secuencia de ADNRESUMEN
Outbreaks of hepatitis A virus (HAV) infection have been occurring among men who have sex with men in the Asia-Pacific region, the United States, and several European countries since June 2015 and recently among persons who are homeless and use illicit drugs in the United States. We evaluated the serologic responses and effectiveness of HAV vaccination in human immunodeficiency virus (HIV)-positive individuals during the outbreak in Taiwan. From June 1, 2015, to September 30, 2016, anti-HAV immunoglobulin G was prospectively determined among all HIV-positive individuals. We prospectively observed 1,533 HAV-seronegative, HIV-positive individuals (94.1% being men who have sex with men with a median cluster of differentiation 4 (CD4) count of 550 cells/µL) who were advised to receive two doses of HAV vaccine administered 6 months apart. Of them, 1,001 individuals (65.3%) received at least one dose of HAV vaccine during the study period and 532 (34.7%) declined to receive vaccine. The primary endpoints were serologic response at weeks 28-36 and acquisition of HAV infection during follow-up. The incidence rate of acute HAV infection was 3.7 and 99.3 per 1,000 person-years of follow-up in the vaccinated and unvaccinated groups, respectively, resulting in a vaccine effectiveness of 96.3%. At weeks 28-36, the seroconversion rates were 63.8% and 93.7% in the intention-to-treat and per-protocol analyses, respectively. The factors associated with seroconversion at weeks 28-36 were younger age (per 1-year decrease, adjusted odds ratio, 1.08; 95% confidence interval, 1.02-1.12) and undetectable plasma HIV RNA load (adjusted odds ratio, 3.19; 95% confidence interval, 1.32-7.68). CONCLUSION: During the outbreak of acute hepatitis A, two-dose HAV vaccination is effective at preventing HAV infection among HIV-positive individuals receiving combination antiretroviral therapy; our data highlight the importance of HAV serologic screening and vaccination to prevent outbreaks of acute hepatitis A in at-risk populations. (Hepatology 2018;68:22-31).
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Infecciones por VIH/inmunología , Vacunas contra la Hepatitis A/inmunología , Hepatitis A/epidemiología , Adulto , Brotes de Enfermedades , Femenino , Hepatitis A/prevención & control , Humanos , Masculino , Estudios Prospectivos , Taiwán/epidemiologíaRESUMEN
BACKGROUND: Higher rates of hepatitis C virus (HCV) reinfection after viral clearance have been well described among HIV-positive men who have sex with men (MSM) in Europe. The epidemiology of HCV reinfection, however, has rarely been investigated among HIV-positive patients in Asia-Pacific region. METHODS: We retrospectively identified HIV-positive patients with recent HCV infection who had cleared their primary infection, either spontaneously or via treatment, between January 2011 and May 2018. All included patients were observed until 31 March 2019. HCV reinfection was defined as recurrent HCV viraemia after achieving viral clearance with anti-HCV treatment or after spontaneous clearance. RESULTS: During the study period, 219 HIV-positive patients (90.4% MSM) were diagnosed with recent HCV infection. Viral clearance with successful treatment was achieved in 108 patients (49.3%) and spontaneous clearance occurred in 20 (9.1%); of them, 18 (14.1%) acquired HCV reinfections, resulting in an incidence rate of 8.2 per 100 person-years of follow-up (95% CI 5.2-13.1). With the adjusted Cox proportional hazards model, we found a higher reinfection risk in patients with syphilis (adjusted hazard ratio 10.3, 95% CI 1.4-77.8, P = .023) compared to those without syphilis. HCV RNA testing, if performed only following syphilis and elevated aminotransferases, might miss 44.4% and 33.3% of HCV reinfections, respectively. CONCLUSIONS: Similar to the findings in Europe, we observed a high incidence of HCV reinfection among HIV-positive Taiwanese with recent HCV infection, which was significantly associated with syphilis. To identify HCV reinfections, annual HCV RNA testing should be instituted instead of testing driven by symptoms, syphilis or elevated aminotransferases.
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Infecciones por VIH/epidemiología , Infecciones por VIH/virología , Hepatitis C/tratamiento farmacológico , Hepatitis C/epidemiología , Hepatitis C/virología , Adulto , Antivirales/uso terapéutico , Coinfección/epidemiología , Control de Enfermedades Transmisibles , Femenino , Seropositividad para VIH/epidemiología , Hepacivirus/aislamiento & purificación , Humanos , Incidencia , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Estudios Retrospectivos , Minorías Sexuales y de Género , Taiwán/epidemiologíaRESUMEN
BACKGROUND: Tenofovir disoproxil fumarate (TDF) is active against both HBV and HIV. Whether the introduction of TDF-containing combination antiretroviral therapy (cART) has improved the outcome of HIV/HBV-coinfected patients remains unclear in areas of higher HBV endemicity. METHODS: We retrospectively reviewed medical records of newly diagnosed antiretroviral-naïve HIV-infected patients between 2007 and 2015. Four groups of patients were defined, according to the HBV status and availability of TDF for HIV treatment in Taiwan in 2011. The primary outcome was all-cause mortality. RESULTS: During the 9-year study period, 1,723 HIV-infected patients were included, with a median age of 31 years and baseline CD4 count of 273 cells per µL. The HBV seroprevalence had declined from 18.1% (125/692) in the pre-TDF era to 10.1% (104/1031) in the post-TDF era. The respective mortality rate for HIV/HBV-coinfected and HIV-monoinfected patients in the pre-TDF era was 23.2 (95% CI, 12.5-43.1) and 9.6 (95% CI, 6.1-15.0) deaths per 1000 person-years of follow-up [PYFU], and the respective mortality rate in the post-TDF era was 15.7 (95% CI, 7.0-34.8) and 8.0 (95% CI, 5.5-11.6) deaths per 1000 PYFU. The adjusted hazard ratio for mortality in multivariate Cox proportional-hazards regression analysis among HIV/HBV-coinfected patients compared to HIV-monoinfected patients was 2.79 (95% CI, 1.25-6.22) in pre-TDF era and 1.11 (95% CI, 0.45-2.72) in post-TDF era. CONCLUSIONS: In this country of high HBV endemicity, the adverse impact of chronic HBV infection on the survival observed in the pre-TDF era has significantly diminished among HIV/HBV-coinfected patients compared to HIV-monoinfected patients in the era of TDF-containing cART.
Asunto(s)
Adenina/análogos & derivados , Antirretrovirales/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Hepatitis B/tratamiento farmacológico , Ácidos Fosforosos/uso terapéutico , Adenina/uso terapéutico , Adulto , Coinfección/tratamiento farmacológico , Coinfección/virología , Femenino , Infecciones por VIH/complicaciones , Infecciones por VIH/mortalidad , Hepatitis B/complicaciones , Hepatitis B/mortalidad , Humanos , Masculino , Estudios Retrospectivos , Taiwán/epidemiologíaRESUMEN
BACKGROUND: The outcomes of deep-seated abscesses attributed to chronic disseminated candidiasis (CDC) in patients with hematological malignancies have rarely been reported in recent years. METHODS: We retrospectively reviewed and analyzed the data of patients with hematological malignancies who received a diagnosis of CDC at a medical center in Taiwan between 2008 and 2013. RESULTS: Sixty-one patients (32 men and 29 women) were diagnosed with CDC. The median age was 51 years (range: 18-83). The overall incidence of CDC was 1.53 per 100 patient-years in patients with hematological malignancies between 2008 and 2013. The highest incidence of CDC was 4.3 per 100 patient-years for acute lymphoblastic leukemia, followed by 3.6 for acute myeloid leukemia. We detected 3 (4.9%) proven, 13 (21.3%) probable, and 45 (73.8%) possible cases of CDC. A total of 13 patients had positive blood cultures for Candida species: C. tropicalis (8), C. albicans (2), C. glabrata (2), and C. famata (1). The median duration of antifungal treatment was 96 days (range: 7-796 days). Serial imaging studies revealed that the resolution rate of CDC was 30.0% at 3 months and 54.3% at 6 months. Five patients (8.2%) had residual lesions that persisted beyond one year. A multivariate analysis of the 90-day outcome revealed that shock was the only independent prognostic factor of 90-day survival in patients with CDC. CONCLUSION: The incidence of CDC did not decrease between 2008 and 2013. Patients with acute leukemia had a higher risk of CDC than those with other hematological malignancies. Imaging studies conducted at 6 months after diagnosis revealed that only half of the patients showed complete resolution. CDC requires prolonged treatment, and serial imaging at 6 months interval is suggested. Shock is the only independent prognostic factor of 90-day survival in patients with CDC.
Asunto(s)
Candidiasis/etiología , Neoplasias Hematológicas/complicaciones , Absceso Hepático/microbiología , Enfermedades del Bazo/microbiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antifúngicos/uso terapéutico , Candida/patogenicidad , Candidiasis/diagnóstico por imagen , Candidiasis/tratamiento farmacológico , Candidiasis/epidemiología , Enfermedad Crónica , Femenino , Neoplasias Hematológicas/microbiología , Humanos , Absceso Hepático/etiología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Enfermedades del Bazo/etiología , Tasa de Supervivencia , Taiwán/epidemiologíaRESUMEN
We evaluated the serologic responses to different 2-dose combinations of the inactivated hepatitis A virus (HAV) vaccines Havrix and Vaqta among human immunodeficiency virus-positive individuals during an acute hepatitis A outbreak in Taiwan. In this 16-month retrospective study, one group received 1 dose of Havrix followed by 1 dose of Vaqta, and another group received 2 doses of Vaqta. The Havrix-Vaqta and Vaqta-Vaqta groups achieved similar seroconversion rates at weeks 28-36 (82.3% and 80.9%, respectively; absolute difference, 1.3% [95% confidence interval {CI}, -6.3%-3.7%]) and week 48 (94.7% and 94.4%, respectively; absolute difference, 0.3% [95% CI, -2.6%-3.2%]), suggesting the interchangeability of different combinations of HAV vaccines. The significantly higher seroconversion rate after the first dose of Vaqta, compared with the dose of Havrix (53.0% vs 32.4%) may provide potential benefits in preventing HAV infection during the outbreak.