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Orthopoxvirus-specific T-cell responses were analyzed in 10 patients who had recovered from Mpox including 7 people with human immunodeficiency virus (PWH). Eight participants had detectable virus-specific T-cell responses, including a PWH who was not on antiretroviral therapy and a PWH on immunosuppressive therapy. These 2 participants had robust polyfunctional CD4+ T-cell responses to peptides from the 121L vaccinia virus (VACV) protein. T-cells from 4 of 5 HLA-A2-positive participants targeted at least 1 previously described HLA-A2-restricted VACV epitope, including an epitope targeted in 2 participants. These results advance our understanding of immunity in convalescent Mpox patients.
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Mpox , Orthopoxvirus , Humanos , Antígeno HLA-A2 , Vaccinia virus , Epitopos , Proteínas ViraisRESUMO
The Baltimore City Health Department (Baltimore, MD) promoted IWantTheKit for chlamydia, gonorrhea, and HIV testing to city residents and clinic patients when COVID-19 restricted in-person clinic services. From April to October 2020, monthly online IWantTheKit orders increased by 645%. A high prevalence of chlamydia and gonorrhea was detected, and 96% of users who tested positive for chlamydia and gonorrhea were successfully contacted for treatment. Uptake by Baltimore City Health Department priority populations and excellent treatment linkage demonstrated how a public health-academic partnership successfully addressed a service gap during the pandemic. (Am J Public Health. 2022;112(7):985-989. https://doi.org/10.2105/AJPH.2022.306835).
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COVID-19 , Infecções por Chlamydia , Chlamydia , Gonorreia , Infecções por HIV , COVID-19/diagnóstico , COVID-19/epidemiologia , Infecções por Chlamydia/diagnóstico , Infecções por Chlamydia/epidemiologia , Gonorreia/diagnóstico , Gonorreia/epidemiologia , Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , HumanosRESUMO
BACKGROUND: Chloroquine-azithromycin is being evaluated as combination therapy for malaria. It may provide added benefit in treating or preventing bacterial infections that occur in children with malaria. OBJECTIVE: We aim to evaluate the effect of treating clinical malaria with chloroquine-azithromycin on the incidence of respiratory-tract and gastrointestinal-tract infections compared to treatment with chloroquine monotherapy. METHODS: We compared the incidence density and time to first events of respiratory-tract and gastrointestinal-tract infections among children assigned to receive chloroquine-azithromycin or chloroquine for all symptomatic malaria episodes over the course of 1 year in a randomized longitudinal trial in Blantyre, Malawi. RESULTS: The incidence density ratios of total respiratory-tract infections and gastrointestinal-tract infections comparing chloroquine-azithromycin to chloroquine monotherapy were 0.67 (95% confidence interval [CI], .48, .94) and 0.74 (95% CI, .55, .99), respectively. The time to first lower-respiratory-tract and gastrointestinal-tract infections were significantly longer in the chloroquine-azithromycin arm compared to the chloroquine arm (P = .04 and P = .02, respectively). CONCLUSIONS: Children treated routinely with chloroquine-azithromycin had fewer respiratory and gastrointestinal-tract infections than those treated with chloroquine alone. This antimalarial combination has the potential to reduce the burden of bacterial infections among children in malaria-endemic countries.
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Antimaláricos/uso terapêutico , Azitromicina/uso terapêutico , Cloroquina/uso terapêutico , Gastroenteropatias/prevenção & controle , Malária/tratamento farmacológico , Malária/microbiologia , Infecções Respiratórias/prevenção & controle , Pré-Escolar , Quimioterapia Combinada/métodos , Feminino , Gastroenteropatias/epidemiologia , Gastroenteropatias/parasitologia , Humanos , Incidência , Estudos Longitudinais , Malária/epidemiologia , Malaui/epidemiologia , Masculino , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/parasitologia , RiscoRESUMO
Syphilis serology interpretation can be challenging even for experienced providers. This article reviews the staging of syphilis and the principles of syphilis serology testing, the algorithms used in diagnosis, and guidance for their use in monitoring the response to treatment. The authors illustrate these principles through a series of clinical scenarios and describe the rationale behind the management approaches.
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Sífilis , Humanos , Sífilis/diagnóstico , Sífilis/tratamento farmacológico , Sorodiagnóstico da Sífilis , Algoritmos , Atenção Primária à SaúdeRESUMO
BACKGROUND: Since July 23, 2022, global mpox cases reached 92,546, with over 31,000 in the United States. Asymptomatic carriage is a critical mechanism influencing the global dissemination of mpox. Seroprevalence studies are crucial for determining the epidemic's true burden, but uncertainties persist in serologic assay performance and how smallpox vaccination may influence assay interpretation. OBJECTIVES: Our study aimed to assess the performance of several diagnostic assays among mpox-positive, vaccinated, and pre-outbreak negative control samples. This investigation sought to enhance our understanding and management of future mpox outbreaks. STUDY DESIGN: Serum samples from 10 mpox-positive, five vaccinated uninfected, and 137 pre-outbreak controls were obtained for serological testing. The mpox-positive samples were obtained around 100 days post symptom onset, and vaccinated patients were sampled approximately 90 days post-vaccination. Multiple diagnostic assays were employed, including four commercial ELISAs (Abbexa, RayBioTech, FineTest, ProteoGenix) and a multiplex assay (MesoScale Diagnostics (MSD)) measuring five mpox and five smallpox antigens. RESULTS: Three commercial ELISA kits had low specificity (<50â¯%). The Proteogenix ELISA targeting the E8L antigen had a 94â¯% sensitivity and 87â¯% specificity. The E8L antigen on the MSD assay exhibited the greatest distinction between exposure groups, with 98â¯% sensitivity and 93â¯% specificity. CONCLUSIONS: None of the assays could distinguish between mpox-positive and vaccinated samples. The MSD assay targeting the MPXV E8L antigen demonstrated the greatest differentiation between mpox-positive and pre-outbreak negative samples. Our findings underscore the imperative to identify sensitive and specific assays to monitor population-level mpox exposure and infection.
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Background: During the 2022 mpox outbreak most patients were managed as outpatients, but some required hospitalization. Uncontrolled human immunodeficiency virus (HIV) has been identified as a risk factor for severe mpox. Methods: Patients with mpox diagnosed or treated within the Johns Hopkins Health System between 1 June and 15 December 2022 were included. The primary outcome of interest was risk of hospitalization. Demographic features, comorbid conditions, treatment, and clinical outcomes were determined. Results: A total of 353 patients were tested or treated for mpox; 100 had mpox diagnosed or treated (median age, 35.3 years; 97.0% male; 57.0% black and 10.0% Hispanic; 46.0% people with HIV [PWH]). Seventeen patients (17.0%) required hospitalization, 10 of whom were PWH. Age >40 years, race, ethnicity, HIV status, insurance status, and body mass index >30 (calculated as weight in kilograms divided by height in meters squared) were not associated with hospitalization. Eight of 9 patients (88.9%) with immunosuppression were hospitalized. Immunosuppression was associated with hospitalization in univariate (odds ratio, 69.3 [95% confidence interval, 7.8-619.7]) and adjusted analysis (adjusted odds ratio, 94.8 [8.5-1060.1]). Two patients (11.8%) who were hospitalized required intensive care unit admission and died; both had uncontrolled HIV infection and CD4 T-cell counts <50/µL. Median cycle threshold values for the first positive mpox virus sample did not differ between those who were hospitalized and those who were not. Conclusions: Immunosuppression was a significant risk factor for hospitalization with mpox. PWH with CD4 T-cell counts <50/µL are at high risk of death due to mpox infection. Patients who are immunosuppressed should be considered for early and aggressive treatment of mpox, given the increased risk of hospitalization.
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BACKGROUND: Distinguishing new from recrudescent infections in post-treatment episodes of malaria is standard in anti-malarial drug efficacy trials. New infections are not considered malaria treatment failures and as a result, the prevention of subsequent episodes of malaria infection is not reported as a study outcome. However, in moderate and high transmission settings, new infections are common and the ability of a short-acting medication to cure an initial infection may be outweighed by its inability to prevent the next imminent infection. The clinical benefit of preventing new infections has never been compared to that of curing the initial infection. METHODS: Children enrolled in a sulphadoxine-pyrimethamine efficacy study in Blantyre, Malawi from 1998-2004 were prospectively evaluated. Six neutral microsatellites were used to classify new and recrudescent infections in children aged less than 10 years with recurrent malaria infections. Children from the study who did not experience recurrent parasitaemia comprised the baseline group. The odds of fever and anaemia, the rate of haemoglobin recovery and time to recurrence were compared among the groups. RESULTS: Fever and anemia were more common among children with parasitaemia compared to those who remained infection-free throughout the study period. When comparing recrudescent vs. new infections, the incidence of fever was not statistically different. However, children with recrudescent infections had a less robust haematological recovery and also experienced recurrence sooner than those whose infection was classified as new. CONCLUSIONS: The results of this study confirm the paramount importance of providing curative treatment for all malaria infections. Although new and recrudescent infections caused febrile illnesses at a similar rate, recurrence due to recrudescent infection did have a worsened haemological outcome than recurrence due to new infections. Local decision-makers should take into account the results of genotyping to distinguish new from recrudescent infections when determining treatment policy on a population level. It is appropriate to weigh recrudescent malaria more heavily than new infection in assessing treatment efficacy.
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Antimaláricos/administração & dosagem , Malária/tratamento farmacológico , Malária/patologia , Pirimetamina/administração & dosagem , Sulfadoxina/administração & dosagem , Anemia/epidemiologia , Anemia/patologia , Criança , Pré-Escolar , Ensaios Clínicos como Assunto , Combinação de Medicamentos , Febre/epidemiologia , Humanos , Lactente , Malária/diagnóstico , Malaui , Masculino , Repetições de Microssatélites , Plasmodium/classificação , Plasmodium/genética , Plasmodium/isolamento & purificação , RecidivaRESUMO
Effective treatment of sexually transmitted infections (STIs) is limited by diagnostics that cannot deliver results rapidly while the patient is still in the clinic. The gold standard methods for identification of STIs are nucleic acid amplification tests (NAATs), which are too expensive for widespread use and have lengthy turnaround times. To address the need for fast and affordable diagnostics, we have developed a portable, rapid, on-cartridge magnetofluidic purification and testing (PROMPT) polymerase chain reaction (PCR) test. We show that it can detect Neisseria gonorrhoeae, the pathogen causing gonorrhea, with simultaneous genotyping of the pathogen for resistance to the antimicrobial drug ciprofloxacin in <15 min. The duplex test was integrated into a low-cost thermoplastic cartridge with automated processing of penile swab samples from patients using magnetic beads. A compact instrument conducted DNA extraction, PCR, and analysis of results while relaying data to the user via a smartphone app. This platform was tested on penile swab samples from sexual health clinics in Baltimore, MD, USA (n = 66) and Kampala, Uganda (n = 151) with an overall sensitivity and specificity of 97.7% (95% CI, 94.7 to 100%) and 97.6% (95% CI, 94.1 to 100%), respectively, for N. gonorrhoeae detection and 100% concordance with culture results for ciprofloxacin resistance. This study paves the way for delivering accessible PCR diagnostics for rapidly detecting STIs at the point of care, helping to guide treatment decisions and combat the rise of antimicrobial resistant pathogens.
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Gonorreia , Infecções Sexualmente Transmissíveis , Baltimore , Gonorreia/diagnóstico , Gonorreia/tratamento farmacológico , Humanos , Neisseria gonorrhoeae/genética , Sensibilidade e Especificidade , Infecções Sexualmente Transmissíveis/diagnóstico , Infecções Sexualmente Transmissíveis/tratamento farmacológico , UgandaRESUMO
BACKGROUND: Early palliative care addresses biopsychosocial needs for people living with HIV in an outpatient setting. We sought to describe patients referred to a palliative care program and compare the medical outcomes of emergency department (ED) visits, hospitalizations, primary care visits, and viral load suppression among patients enrolled in the program, to patients who did not enroll (no-show group). SETTING: We completed a retrospective cohort study at an urban, academically affiliated HIV primary care clinic. METHODS: Data were collected from electronic medical records. Descriptive statistics characterized patient demographics at baseline, comorbidities, and reasons for referral to palliative care. Viral load suppression, rates of ED visits, hospitalizations, primary care visits, and retention in care were compared between the palliative and no-show groups. RESULTS: The most common reasons for referral were chronic pain management and medication/appointment adherence. Median percent of viral load measurements suppressed increased over time, but did not differ statistically between groups (pre: 28.6% and 15.5%, post: 70.8% and 50.0%, palliative and no-show groups, respectively). Median rates of ED visits and hospitalizations were low and were not impacted by palliative care. Rates of primary care visit attendance remained stable in the palliative group (4.6/year) but declined in the no-show group (3.5/year), P < 0.05. Retention in care improved significantly after the palliative intervention (palliative: 85.4%-96.1%, no-show: 94.4%-82.5%), and at high and low palliative engagement, suggesting a threshold effect of the intervention. CONCLUSION: Outpatient early palliative care is a promising intervention that might impact retention in HIV care.
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Infecções por HIV/tratamento farmacológico , Cuidados Paliativos , Encaminhamento e Consulta , Retenção nos Cuidados , Adulto , Fármacos Anti-HIV/uso terapêutico , Contagem de Linfócito CD4 , Serviço Hospitalar de Emergência/estatística & dados numéricos , Feminino , Infecções por HIV/complicações , Infecções por HIV/psicologia , Humanos , Masculino , Adesão à Medicação , Pessoa de Meia-Idade , Visita a Consultório Médico/estatística & dados numéricos , Estudos Retrospectivos , Carga ViralRESUMO
Background: Given the lack of new antimicrobials to treat Neisseria gonorrhoeae (NG) infections, reusing previously recommended antimicrobials has been proposed as a strategy to control the spread of multi-drug-resistant NG. We assessed ciprofloxacin susceptibility in a large sample set of NG isolates and identified correlates associated with ciprofloxacin-resistant NG infections. Methods: NG isolates collected in Baltimore, Maryland between 2014 and 2016 were evaluated by Gyrase A (gyrA) PCR and E-test for susceptibility to ciprofloxacin. Clinical characteristics and demographics were evaluated by multivariate regression analysis to identify correlates of ciprofloxacin-resistant NG infections. Results: 510 NG isolates from predominately African American (96.5%), heterosexual (85.7%), and HIV-negative (92.5%) male subjects were included in the study. The overall percentage of isolates with mutant gyrA sequences, indicative of ciprofloxacin resistance, was 32.4%, and significantly increased from 24.7% in 2014 to 45.2% in 2016 (p < 0.001). Participants older than 35 years of age were 2.35 times more likely to have a gyrA mutant NG infection than younger participants (p < 0.001). Race, sexual orientation, symptomology, or co-infection the HIV or syphilis were not associated with a particular NG gyrA genotype. Conclusions: Resistance to ciprofloxacin in Baltimore is lower than other regions and indicates that in this environment, use of ciprofloxacin may be appropriate for targeted treatment provided utilization of enhanced surveillance tools. The targeted use of ciprofloxacin may be more beneficial for individuals under 35 years of age. Point-of-care tests for NG diagnosis and susceptibility testing are urgently needed to identify individuals who can be treated with this targeted approach.
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This article discusses muscle pain concepts in the context of myofascial pain syndrome (MPS) and summarizes microdialysis studies that have surveyed the biochemical basis of this musculoskeletal pain condition. Though MPS is a common type of non-articular pain, its pathophysiology is only beginning to be understood due to its enormous complexity. MPS is characterized by the presence of myofascial trigger points (MTrPs), which are defined as hyperirritable nodules located within a taut band of skeletal muscle. MTrPs may be active (spontaneously painful and symptomatic) or latent (non-spontaneously painful). Painful MTrPs activate muscle nociceptors that, upon sustained noxious stimulation, initiate motor and sensory changes in the peripheral and central nervous systems. This process is called sensitization. In order to investigate the peripheral factors that influence the sensitization process, a microdialysis technique was developed to quantitatively measure the biochemical milieu of skeletal muscle. Biochemical differences were found between active and latent MTrPs, as well as in comparison with healthy muscle tissue. In this paper we relate the findings of elevated levels of sensitizing substances within painful muscle to the current theoretical framework of muscle pain and MTrP development.