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BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reinfection is poorly understood, partly because few studies have systematically applied genomic analysis to distinguish reinfection from persistent RNA detection related to initial infection. We aimed to evaluate the characteristics of SARS-CoV-2 reinfection and persistent RNA detection using independent genomic, clinical, and laboratory assessments. METHODS: All individuals at a large academic medical center who underwent a SARS-CoV-2 nucleic acid amplification test (NAAT) ≥45 days after an initial positive test, with both tests between 14 March and 30 December 2020, were analyzed for potential reinfection. Inclusion criteria required having ≥2 positive NAATs collected ≥45 days apart with a cycle threshold (Ct) value <35 at repeat testing. For each included subject, likelihood of reinfection was assessed by viral genomic analysis of all available specimens with a Ct value <35, structured Ct trajectory criteria, and case-by-case review by infectious diseases physicians. RESULTS: Among 1569 individuals with repeat SARS-CoV-2 testing ≥45 days after an initial positive NAAT, 65 (4%) met cohort inclusion criteria. Viral genomic analysis characterized mutations present and was successful for 14/65 (22%) subjects. Six subjects had genomically supported reinfection, and 8 subjects had genomically supported persistent RNA detection. Compared to viral genomic analysis, clinical and laboratory assessments correctly distinguished reinfection from persistent RNA detection in 12/14 (86%) subjects but missed 2/6 (33%) genomically supported reinfections. CONCLUSIONS: Despite good overall concordance with viral genomic analysis, clinical and Ct value-based assessments failed to identify 33% of genomically supported reinfections. Scaling-up genomic analysis for clinical use would improve detection of SARS-CoV-2 reinfections.
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COVID-19 , Humanos , COVID-19/diagnóstico , Teste para COVID-19 , Reinfecção/diagnóstico , Estudos Retrospectivos , SARS-CoV-2/genética , RNARESUMO
PURPOSE OF REVIEW: The risk of nosocomial transmission of mpox during the 2022 global outbreak is not well described. We evaluated reports of exposures to healthcare personnel (HCP) and patients in healthcare settings and risk of transmission. RECENT FINDINGS: Reported nosocomial transmission of mpox has been rare and associated primarily with sharps injuries and breaches in transmission-based precautions. SUMMARY: Currently recommended infection control practices, including the use of standard and transmission-based precautions in the care of patients with known or suspected mpox are highly effective. Diagnostic sampling should not involve the use of needles or other sharp instruments.
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Infecção Hospitalar , Pessoal de Saúde , Mpox , Exposição Ocupacional , Humanos , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/prevenção & controle , Infecção Hospitalar/transmissão , Surtos de Doenças , Instalações de Saúde , Mpox/epidemiologia , Mpox/prevenção & controle , Mpox/transmissão , Saúde Global/estatística & dados numéricos , Exposição Ocupacional/efeitos adversos , Exposição Ocupacional/estatística & dados numéricos , Medição de Risco , Ferimentos Penetrantes Produzidos por AgulhaRESUMO
BACKGROUND: In May 2022, the first case of monkeypox virus (MPXV) infection in the United States in the current global outbreak was identified. As part of the public health and health care facility response, a contact tracing and exposure investigation was done. OBJECTIVE: To describe the contact tracing, exposure identification, risk stratification, administration of postexposure prophylaxis (PEP), and exposure period monitoring for contacts of the index patient, including evaluation of persons who developed symptoms possibly consistent with MPXV infection. DESIGN: Contact tracing and exposure investigation. SETTING: Multiple health care facilities and community settings in Massachusetts. PARTICIPANTS: Persons identified as contacts of the index patient. INTERVENTION: Contact notification, risk stratification, and symptom monitoring; PEP administration in a subset of contacts. MEASUREMENTS: Epidemiologic and clinical data collected through standard surveillance procedures at each facility and then aggregated and analyzed. RESULTS: There were 37 community and 129 health care contacts identified, with 4 at high risk, 49 at intermediate risk, and 113 at low or uncertain risk. Fifteen health care contacts developed symptoms during the monitoring period. Three met criteria for MPXV testing, with negative results. Two community contacts developed symptoms. Neither met criteria for MPXV testing, and neither showed disease progression consistent with monkeypox. Among 4 persons with high-risk exposures offered PEP, 3 elected to receive PEP. Among 10 HCP with intermediate-risk exposures for which PEP was offered as part of informed clinical decision making, 2 elected to receive PEP. No transmissions were identified at the conclusion of the 21-day monitoring period, despite the delay in recognition of monkeypox in the index patient. LIMITATION: Descriptions of exposures are subject to recall bias, which affects risk stratification. CONCLUSION: In a contact tracing investigation involving 166 community and health care contacts of a patient with monkeypox, no secondary cases were identified. PRIMARY FUNDING SOURCE: None.
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Mpox , Humanos , Estados Unidos , Monkeypox virus , Busca de Comunicante , Surtos de Doenças , MassachusettsRESUMO
BACKGROUND: Isolation of hospitalized persons under investigation (PUIs) for coronavirus disease 2019 (COVID-19) reduces nosocomial transmission risk. Efficient evaluation of PUIs is needed to preserve scarce healthcare resources. We describe the development, implementation, and outcomes of an inpatient diagnostic algorithm and clinical decision support system (CDSS) to evaluate PUIs. METHODS: We conducted a pre-post study of CORAL (COvid Risk cALculator), a CDSS that guides frontline clinicians through a risk-stratified COVID-19 diagnostic workup, removes transmission-based precautions when workup is complete and negative, and triages complex cases to infectious diseases (ID) physician review. Before CORAL, ID physicians reviewed all PUI records to guide workup and precautions. After CORAL, frontline clinicians evaluated PUIs directly using CORAL. We compared pre- and post-CORAL frequency of repeated severe acute respiratory syndrome coronavirus 2 nucleic acid amplification tests (NAATs), time from NAAT result to PUI status discontinuation, total duration of PUI status, and ID physician work hours, using linear and logistic regression, adjusted for COVID-19 incidence. RESULTS: Fewer PUIs underwent repeated testing after an initial negative NAAT after CORAL than before CORAL (54% vs 67%, respectively; adjusted odd ratio, 0.53 [95% confidence interval, .44-.63]; Pâ <â .01). CORAL significantly reduced average time to PUI status discontinuation (adjusted difference [standard error], -7.4 [0.8] hours per patient), total duration of PUI status (-19.5 [1.9] hours per patient), and average ID physician work-hours (-57.4 [2.0] hours per day) (all Pâ <â .01). No patients had a positive NAAT result within 7 days after discontinuation of precautions via CORAL. CONCLUSIONS: CORAL is an efficient and effective CDSS to guide frontline clinicians through the diagnostic evaluation of PUIs and safe discontinuation of precautions.
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Antozoários , COVID-19 , Animais , Humanos , Técnicas de Amplificação de Ácido Nucleico , Razão de Chances , SARS-CoV-2Assuntos
Encéfalo/diagnóstico por imagem , Vírus da Encefalite Transmitidos por Carrapatos/isolamento & purificação , Encefalite Transmitida por Carrapatos/diagnóstico , Meningoencefalite/diagnóstico , Idoso , Encefalopatias/etiologia , Diagnóstico Diferencial , Vírus da Encefalite Transmitidos por Carrapatos/imunologia , Encefalite Transmitida por Carrapatos/complicações , Encefalite Transmitida por Carrapatos/diagnóstico por imagem , Feminino , Febre/etiologia , Cefaleia/etiologia , Humanos , Imunoglobulina M/líquido cefalorraquidiano , Imageamento por Ressonância Magnética , Meningoencefalite/complicações , Meningoencefalite/diagnóstico por imagem , Transtornos de Enxaqueca/complicaçõesRESUMO
BACKGROUND: Nonoccupational postexposure prophylaxis (nPEP) is recommended after a sexual or parenteral exposure to human immunodeficiency virus (HIV). Patients frequently seek care in an emergency department (ED) after an exposure and are usually referred to an HIV clinic for further management. There have been few data on determinants of attrition after presentation to EDs for nPEP. METHODS: From July 2010 to June 2011, we prospectively recorded all referrals to nPEP programs from 2 large EDs at 2 academic medical centers in Boston, Massachusetts. Data were recorded on patient demographics, nature of potential HIV exposures, referrals to and attendance at HIV clinics, and reported completion of 28 days of antiretroviral therapy (ART). Multivariable logistic regression was used to evaluate risk factors for (1) patient attrition between the ED and HIV clinic follow-up and (2) documented completion of ART. RESULTS: Of 180 individuals who were referred to clinic follow-up for nPEP care from the ED, 98 (54.4%) attended a first nPEP clinic visit and 43 (23.9%) had documented completion of a 28-day course of ART. Multivariable analysis revealed older age (adjusted odds ratio [aOR], 0.96; 95% confidence interval [CI], .93-.99) and self-payment (aOR, 0.32; 95% CI, .11-.97) were significant predictors for failing to attend an initial HIV clinic appointment. Women were less likely than men to complete a 28-day ART regimen (aOR, 0.34; 95% CI, .15-.79). CONCLUSIONS: Commonly used nPEP delivery models may not be effective for all patients who present with nonoccupational exposures to HIV. Interventions are needed to improve rates of follow-up and completion of nPEP to reduce the risk of preventable HIV infections.
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Assistência Ambulatorial/métodos , Serviços Médicos de Emergência/métodos , Infecções por HIV/prevenção & controle , Adesão à Medicação , Profilaxia Pós-Exposição/métodos , Adulto , Boston , Estudos de Coortes , Feminino , Pesquisa sobre Serviços de Saúde , Humanos , Masculino , Estudos Prospectivos , Adulto JovemAssuntos
Doença de Lyme/complicações , Picadas de Carrapatos/complicações , Dor Abdominal/etiologia , Animais , Diarreia/etiologia , Humanos , Doença de Lyme/etiologia , Doença de Lyme/fisiopatologia , Masculino , Pessoa de Meia-Idade , Picadas de Carrapatos/fisiopatologia , Carrapatos/patogenicidadeRESUMO
Background: For persons with suspected pulmonary tuberculosis, the guidelines of the Centers for Disease Control and Prevention recommend collecting 3 respiratory specimens 8 to 24 hours apart for acid-fast bacilli (AFB) smear and culture, in addition to 1 nucleic acid amplification test (NAAT). However, data supporting this approach are limited. Our objective was to estimate the performance of 1, 2, or 3 AFB smears with or without NAATs to detect pulmonary tuberculosis in a low-prevalence setting. Methods: We conducted a retrospective study of hospitalized persons at 8 Massachusetts acute care facilities who underwent mycobacterial culture on 1 or more respiratory specimens between July 2016 and December 2022. We evaluated percentage positivity and yield on serial AFB smears and NAATs among people with growth of Mycobacterium tuberculosis on mycobacterial cultures. Results: Among 104 participants with culture-confirmed pulmonary tuberculosis, the first AFB smear was positive in 41 cases (39%). A second AFB smear was positive in 11 (22%) of the 49 cases in which it was performed. No third AFB smears were positive following 2 initial negative smears. Of 52 smear-negative cases, 36 had a NAAT performed, leading to 23 additional diagnoses. Overall sensitivity to detect tuberculosis prior to culture positivity was higher in any strategy involving 1 or 2 NAATs (74%-79%), even without AFB smears, as compared with 3 smears alone (60%). Conclusions: Tuberculosis diagnostic testing with 2 AFB smears offered the same yield as 3 AFB smears while potentially reducing laboratory burden and duration of airborne infection isolation. Use of 1 or 2 NAATs increased sensitivity to detect culture-positive pulmonary tuberculosis when added to AFB smear-based diagnostic testing alone.
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OBJECTIVE: The Centers for Disease Control and Prevention reported more than one million people with HIV infection in the United States in 2006, an increase of 11% over 3 years. Worldwide, nearly 34 million people are infected with HIV. Pulmonary disease accounts for 30-40% of acute hospitalizations of HIV-seropositive patients, underscoring the importance of understanding the range of cardiothoracic imaging findings associated with HIV infection. This article will cover extrapulmonary thoracic diseases, chronic lung diseases, and immune reconstitution inflammatory syndrome in HIV-infected patients. Our approach is focused on the radiologist's perspective by recognizing and categorizing key imaging findings to generate a differential diagnosis. The differential diagnosis can be further refined by incorporating clinical data, such as patient demographics, CD4 count, and presenting symptoms. In addition, with prolonged survival of HIV-infected patients in the era of highly active antiretroviral therapy, radiologists can also benefit from awareness of imaging features of a myriad of chronic cardiopulmonary diseases in this patient population. Finally, the change of imaging findings and clinical status in response to treatment provides important diagnostic information, such as in immune reconstitution syndrome. CONCLUSION: Developing a practical approach to key cardiothoracic imaging findings in HIV-infected patients will aid the radiologist in generating a clinically relevant differential diagnosis and interpretation, thereby improving patient care.
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Infecções Oportunistas Relacionadas com a AIDS/diagnóstico por imagem , Doenças Cardiovasculares/diagnóstico por imagem , Infecções por HIV/diagnóstico por imagem , Síndrome Inflamatória da Reconstituição Imune/diagnóstico por imagem , Pneumopatias/diagnóstico por imagem , Pneumopatias/virologia , Doenças Linfáticas/diagnóstico por imagem , Contagem de Linfócito CD4 , Doenças Cardiovasculares/virologia , Doença Crônica , Diagnóstico Diferencial , Humanos , Doenças Linfáticas/virologia , Radiografia Torácica , Tomografia Computadorizada por Raios XRESUMO
OBJECTIVE: The Centers for Disease Control and Prevention reported more than one million people with HIV infection in the United States in 2006, an increase of 11% over 3 years. Worldwide, nearly 34 million people are infected with HIV. Pulmonary disease accounts for 30-40% of acute hospitalizations of HIV-infected patients, underscoring the importance of understanding the pulmonary manifestations in this population. When presented with a chest radiograph or CT image of a patient with the clinical history of HIV infection, one approach is to start by identifying and categorizing key imaging findings. In some instances, the key findings may be further subcategorized to narrow the differential diagnosis, such as distinguishing between perilymphatic distribution and the random distribution of micronodules. The differential diagnosis of these key imaging findings can also be further refined by incorporating clinical data, such as patient demographics, CD4 count, and presenting symptoms. Finally, the change of thoracic disease and clinical status in response to treatment provides important diagnostic information. The purpose of this article is to discuss pulmonary findings in patients with HIV. CONCLUSION: By developing a systematic and practical approach to key pulmonary imaging findings in HIV-infected patients, radiologists can generate clinically relevant and succinct differential diagnoses and thereby improve patient care.
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Infecções Oportunistas Relacionadas com a AIDS/diagnóstico por imagem , Infecções por HIV/diagnóstico por imagem , Pneumopatias/diagnóstico por imagem , Pneumopatias/virologia , Contagem de Linfócito CD4 , Diagnóstico Diferencial , Humanos , Radiografia Torácica , Tomografia Computadorizada por Raios XRESUMO
Transmission risk of monkeypox in healthcare settings outside endemic regions has not been well defined. A rapid review of the literature, including cases outside monkeypox-endemic regions from 2000 to 2022 identified a single reported case of transmission. Available literature is limited by nonstandardized exposure definitions and limited detail describing exposures.
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Mpox , Atenção à Saúde , Humanos , Mpox/epidemiologia , Mpox/transmissão , Monkeypox virusRESUMO
The global spread and continued evolution of SARS-CoV-2 has driven an unprecedented surge in viral genomic surveillance. Amplicon-based sequencing methods provide a sensitive, low-cost and rapid approach but suffer a high potential for contamination, which can undermine laboratory processes and results. This challenge will increase with the expanding global production of sequences across a variety of laboratories for epidemiological and clinical interpretation, as well as for genomic surveillance of emerging diseases in future outbreaks. We present SDSI + AmpSeq, an approach that uses 96 synthetic DNA spike-ins (SDSIs) to track samples and detect inter-sample contamination throughout the sequencing workflow. We apply SDSIs to the ARTIC Consortium's amplicon design, demonstrate their utility and efficiency in a real-time investigation of a suspected hospital cluster of SARS-CoV-2 cases and validate them across 6,676 diagnostic samples at multiple laboratories. We establish that SDSI + AmpSeq provides increased confidence in genomic data by detecting and correcting for relatively common, yet previously unobserved modes of error, including spillover and sample swaps, without impacting genome recovery.
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Primers do DNA/normas , SARS-CoV-2/genética , Análise de Sequência/normas , COVID-19/diagnóstico , Primers do DNA/síntese química , Genoma Viral/genética , Humanos , Controle de Qualidade , RNA Viral/genética , Reprodutibilidade dos Testes , Análise de Sequência/métodos , Sequenciamento Completo do Genoma , Fluxo de TrabalhoRESUMO
Among hospitalized persons under investigation for coronavirus disease 2019 (COVID-19), more repeated severe acute respiratory syndrome coronavirus 2 nucleic acid amplification tests (NAATs) after a negative NAAT were positive from lower than from upper respiratory tract specimens (1.9% vs 1.0%, P = .033). Lower respiratory testing should be prioritized among patients displaying respiratory symptoms with moderate-to-high suspicion for COVID-19 after 1 negative upper respiratory NAAT.
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We describe an approach to the evaluation and isolation of hospitalized persons under investigation (PUIs) for coronavirus disease 2019 (COVID-19) at a large US academic medical center. Only a small proportion (2.9%) of PUIs with 1 or more repeated severe acute respiratory coronavirus virus 2 (SARS-CoV-2) nucleic acid amplification tests (NAATs) after a negative NAAT were diagnosed with COVID-19.
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Teste para COVID-19/estatística & dados numéricos , COVID-19/diagnóstico , Isolamento de Pacientes/estatística & dados numéricos , Padrões de Prática Médica/normas , Centros Médicos Acadêmicos , Boston , Controle de Doenças Transmissíveis/métodos , Hospitalização , Humanos , Técnicas de Amplificação de Ácido Nucleico , Padrões de Prática Médica/organização & administração , Estudos Retrospectivos , SARS-CoV-2RESUMO
BACKGROUND: Concerns about false-negative (FN) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid amplification tests (NAATs) have prompted recommendations for repeat testing if suspicion for coronavirus disease 2019 (COVID-19) infection is moderate to high. However, the frequency of FNs and patient characteristics associated with FNs are poorly understood. METHODS: We retrospectively reviewed test results from 15 011 adults who underwent ≥1 SARS-CoV-2 NAATs; 2699 had an initial negative NAAT and repeat testing. We defined FNs as ≥1 negative NAATs followed by a positive NAAT within 14 days during the same episode of illness. We stratified subjects with FNs by duration of symptoms before the initial FN test (≤5 days versus >5 days) and examined their clinical, radiologic, and laboratory characteristics. RESULTS: Sixty of 2699 subjects (2.2%) had a FN result during the study period. The weekly frequency of FNs among subjects with repeat testing peaked at 4.4%, coinciding with peak NAAT positivity (38%). Most subjects with FNs had symptoms (52 of 60; 87%) and chest radiography (19 of 32; 59%) consistent with COVID-19. Of the FN NAATs, 18 of 60 (30%) were performed early (ie, ≤1 day of symptom onset), and 18 of 60 (30%) were performed late (ie, >7 days after symptom onset) in disease. Among 17 subjects with 2 consecutive FNs on NP NAATs, 9 (53%) provided lower respiratory tract (LRT) specimens for testing, all of which were positive. CONCLUSIONS: Our findings support repeated NAATs among symptomatic patients, particularly during periods of higher COVID-19 incidence. The LRT testing should be prioritized to increase yield among patients with high clinical suspicion for COVID-19.
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Immunomodulating therapies for COVID-19 may carry risks of reactivating latent infections in foreign-born people. We conducted a rapid review of infection-related complications of immunomodulatory therapies for COVID-19. We convened a committee of specialists to formulate a screening and management strategy for latent infections in our setting. Dexamethasone, used in severe COVID-19, is associated with reactivation of latent tuberculosis, hepatitis B, and dissemination/hyperinfection of Strongyloides species and should prompt screening and/ or empiric treatment in appropriate epidemiologic contexts. Other immunomodulators used in COVID-19 may also increase risk, including interleukin-6 receptor antagonist (e.g., tocilizumab) and kinase inhibitors. People with specific risk factors should also be screened for HIV, Chagas disease, and endemic mycoses. Racial and ethnic minorities in North America, including foreign-born persons, who receive immunomodulating agents for COVID-19 may be at risk for reactivation of latent infections. We develop a screening and management pathway for such patients.
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COVID-19 , Tuberculose Latente , Humanos , Imunomodulação , Programas de Rastreamento , SARS-CoV-2RESUMO
The rapid global spread and continued evolution of SARS-CoV-2 has highlighted an unprecedented need for viral genomic surveillance and clinical viral sequencing. Amplicon-based sequencing methods provide a sensitive, low-cost and rapid approach but suffer a high potential for contamination, which can undermine lab processes and results. This challenge will only increase with expanding global production of sequences by diverse research groups for epidemiological and clinical interpretation. We present an approach which uses synthetic DNA spike-ins (SDSIs) to track samples and detect inter-sample contamination through a sequencing workflow. Applying this approach to the ARTIC Consortium's amplicon design, we define a series of best practices for Illumina-based sequencing and provide a detailed characterization of approaches to increase sensitivity for low-viral load samples incorporating the SDSIs. We demonstrate the utility and efficiency of the SDSI method amidst a real-time investigation of a suspected hospital cluster of SARS-CoV-2 cases.
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Paecilomyces variotii is a ubiquitous environmental saprophyte with worldwide distribution. Commonly found in soil and decomposing organic material [1, 2], P. variotii can also be isolated from drinking water [3] and indoor and outdoor air [4-6]. In immunocompetent hosts, P. variotii has been reported as a cause of locally invasive disease including prosthetic valve endocarditis [7, 8], endophthalmitis [9, 10], rhinosinusitis [11, 12], and dialysis-associated peritonitis [13, 14]. In contrast, disseminated infections are more commonly reported in immunocompromised patients, including those with chronic granulomatous disease [15], solid malignancy [16], acute leukemia [17], lymphoma [18], multiple myeloma [19], and after stem cell transplant for myelodysplasia [20]. In 1 case series examining invasive infections by non-Aspergillus molds, P. variotii was the most common cause after Fusarium spp. [21]. Here, we present the case of an immunocompetent patient with extensive intravascular infection involving prosthetic material. We describe successful induction therapy with combination antifungals and extended suppression with posaconazole with clinical quiescence and eventual normalization of serum fungal biomarkers.
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We present the case of an HIV-infected patient with cirrhosis in whom severe neuropsychiatric signs and symptoms developed in the setting of a significantly elevated plasma efavirenz level. Although mild neuropsychiatric symptoms are a well-known adverse effect of this medication, to our knowledge, this is the first report of status epilepticus with routine efavirenz dosing. This case raises several significant questions regarding the adverse effects and dosing of this medication, including which patient characteristics predispose to efavirenz toxicity, the relevance of the CYP2B6 mutation, and indications for therapeutic drug monitoring.