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1.
J Infect Dis ; 229(4): 1189-1199, 2024 Apr 12.
Article in English | MEDLINE | ID: mdl-37740551

ABSTRACT

BACKGROUND: High-resolution metabolomics (HRM) is an innovative tool to study challenging infectious diseases like leprosy, where the pathogen cannot be grown with standard methods. Here, we use HRM to better understand associations between disease manifestations, nutrition, and host metabolism. METHODS: From 2018 to 2019, adults with leprosy and controls were recruited in Minas Gerais, Brazil. Plasma metabolites were detected using an established HRM workflow and characterized by accurate mass, mass to charge ratio m/z and retention time. The mummichog informatics package compared metabolic pathways between cases and controls and between multibacillary (MB) and paucibacillary (PB) leprosy. Additionally, select individual metabolites were quantified and compared. RESULTS: Thirty-nine cases (62% MB and 38% PB) and 25 controls were enrolled. We found differences (P < .05) in several metabolic pathways, including fatty acid metabolism, carnitine shuttle, retinol, vitamin D3, and C-21 steroid metabolism, between cases and controls with lower retinol and associated metabolites in cases. Between MB and PB, leukotrienes, prostaglandins, tryptophan, and cortisol were all found to be lower in MB (P < .05). DISCUSSION: Metabolites associated with several nutrient-related metabolic pathways appeared differentially regulated in leprosy, especially MB versus PB. This pilot study demonstrates the metabolic interdependency of these pathways, which may play a role in the pathophysiology of disease.


Subject(s)
Leprosy , Micronutrients , Adult , Humans , Fatty Acids , Pilot Projects , Vitamin A , Mycobacterium leprae
2.
Emerg Infect Dis ; 30(11): 2447-2451, 2024 Nov.
Article in English | MEDLINE | ID: mdl-39419762

ABSTRACT

We describe the case of a returned traveler to the United States from Ecuador who had an acute febrile illness, initially diagnosed as Oropouche fever. This illness was later confirmed to be a rare infection with Iquitos virus, a related bunyavirus that shares 2 of 3 genome segments with Oropouche virus.


Subject(s)
Bunyaviridae Infections , Orthobunyavirus , Phylogeny , Travel , Humans , Ecuador , United States , Orthobunyavirus/genetics , Orthobunyavirus/isolation & purification , Orthobunyavirus/classification , Bunyaviridae Infections/diagnosis , Bunyaviridae Infections/virology , Male , Adult
3.
Curr Opin Rheumatol ; 2024 Aug 12.
Article in English | MEDLINE | ID: mdl-39120541

ABSTRACT

PURPOSE OF REVIEW: Systemic sclerosis (SSc)-associated heart involvement (SHI) is a significant cause of both morbidity and mortality in individuals with SSc. SHI can take many different forms, and likely is a spectrum of fibroinflammatory cardiac disease. Presenting features include arrhythmia, ventricular systolic or diastolic dysfunction, pericardial disease, and exercise intolerance. Risk of sudden cardiac death in SSc is likely 10-30-fold greater than general population estimates. In this review, we explore what is known about the pathogenesis of SHI, its prevention and management, and discuss available strategies for screening for SHI in light of new recommendations for the routine screening of SHI in all SSc patients. RECENT FINDINGS: We describe the spectrum, clinical features, and pathogenesis of SHI. Furthermore, we review the new recommendations for screening for SHI in individuals with SSc. SUMMARY: There is a large, under-recognized burden of SHI in people living with SSc, which likely contributes to the significant increase in sudden cardiac death observed in SSc. However, a broad-based screening approach, including asymptomatic, low-risk patients should be viewed with caution given the lack of evidence-based treatments and interventions for SHI particularly in this group.

4.
Article in English | MEDLINE | ID: mdl-38548670

ABSTRACT

OBJECTIVES: To quantify the frequency and impact of malnutrition in systemic sclerosis (SSc), as diagnosed by the Global Leadership Initiative on Malnutrition (GLIM) criteria, based on weight loss, body mass index (BMI) and muscle atrophy. METHODS: Australian Scleroderma Cohort Study participants meeting ACR/EULAR criteria for SSc with ≥1 concurrent weight and height measurement were included. Chi-squared tests, two-sample t-tests or Wilcoxon rank-sum tests were used for between-group comparison as appropriate. Multivariable logistic regression models were used to establish the determinants of malnutrition diagnosis. Kaplan-Meier and Cox proportional hazard models were used for survival analyses, based on malnutrition diagnosis, and individual GLIM criteria (% weight loss, BMI thresholds and presence of muscle atrophy). RESULTS: In this study of 1903 participants, 43% were diagnosed with malnutrition according to GLIM criteria, of whom 33% had severe malnutrition. Participants diagnosed with malnutrition were older, and more likely to have dcSSc, higher SSc severity scores and RNA polymerase-3 positivity. Gastrointestinal (GI) involvement, multimorbidity, cardiopulmonary disease, raised inflammatory markers, hypoalbuminaemia and anaemia were more common in malnourished participants (p< 0.01). Multimorbidity (OR1.6, 95%CI1.2-2.0, p< 0.01), pulmonary arterial hypertension (OR2.1, 95%CI1.4-2.0, p< 0.01) and upper GI symptoms (OR1.6, 95%CI1.3-2.0, p< 0.01) were all associated with malnutrition.Health-related quality-of-life (HRQoL) and physical function were poorer in malnourished participants. Survival was worse in those with malnutrition after adjusting for age, sex and dcSSc (HR 1.4, 95%CI1.1-1.7, p< 0.01). CONCLUSIONS: Malnutrition is common in SSc and confers poorer survival, HRQoL and physical function.

5.
J Rheumatol ; 51(5): 495-504, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38224991

ABSTRACT

OBJECTIVE: To explore the effect of left ventricular (LV) diastolic dysfunction (LVDD) in systemic sclerosis (SSc)-associated interstitial lung disease (ILD), and to investigate SSc-specific associations and clinical correlates of LVDD. METHODS: There were 102 Australian Scleroderma Cohort Study participants with definite SSc and radiographic ILD included. Diastolic function was classified as normal, indeterminate, or abnormal according to 2016 American Society of Echocardiography/European Association of Cardiovascular Imaging guidelines for assessment of LV diastolic function. Associations between clinical features and patient- and physician-reported dyspnea were evaluated using logistic regression. Survival analyses were performed using Kaplan-Meier survival estimates and Cox regression modeling. RESULTS: LVDD was identified in 26% of participants, whereas 19% had indeterminate and 55% had normal diastolic function. Those with ILD and LVDD had increased mortality (hazard ratio 2.4, 95% CI 1.0-5.7; P = 0.05). After adjusting for age and sex, those with ILD and LVDD were more likely to have severe dyspnea on the Borg Dyspnoea Scale (odds ratio [OR] 2.6, 95% CI 1.0-6.6; P = 0.05) and numerically more likely to record World Health Organization Function Class II or higher dyspnea (OR 4.2, 95% CI 0.9-20.0; P = 0.08). Older age (95% CI 1.0-6.4; P = 0.05), hypertension (OR 5.0, 95% CI 1.8-13.8; P < 0.01), and ischemic heart disease (OR 4.8, 95% CI 1.5-15.7; P < 0.01) were all associated with LVDD, as was proximal muscle atrophy (OR 5.0, 95% CI 1.9-13.6; P < 0.01) and multimorbidity (Charlson Comorbidity Index scores ≥ 4, OR 3.0, 95% CI 1.1-8.7; P = 0.04). CONCLUSION: LVDD in SSc-ILD is more strongly associated with traditional LVDD risk factors than SSc-specific factors. LVDD is associated with worse dyspnea and survival in those with SSc-ILD.


Subject(s)
Dyspnea , Lung Diseases, Interstitial , Scleroderma, Systemic , Ventricular Dysfunction, Left , Humans , Female , Dyspnea/etiology , Dyspnea/physiopathology , Scleroderma, Systemic/complications , Scleroderma, Systemic/mortality , Scleroderma, Systemic/physiopathology , Lung Diseases, Interstitial/mortality , Lung Diseases, Interstitial/physiopathology , Lung Diseases, Interstitial/etiology , Lung Diseases, Interstitial/complications , Male , Middle Aged , Ventricular Dysfunction, Left/physiopathology , Ventricular Dysfunction, Left/diagnostic imaging , Ventricular Dysfunction, Left/mortality , Aged , Australia/epidemiology , Adult , Echocardiography , Diastole , Cohort Studies
6.
Clin Exp Rheumatol ; 42(8): 1581-1589, 2024 08.
Article in English | MEDLINE | ID: mdl-39152747

ABSTRACT

OBJECTIVES: To identify the trajectories and clinical associations of functional disability in systemic sclerosis (SSc). METHODS: Australian Scleroderma Cohort Study (ASCS) participants meeting ACR/EULAR criteria for SSc recruited within 5 years of disease onset, with ≥2 Health Assessment Questionnaire-Disability Index (HAQ-DI) scores were included. Group based trajectory modelling (GBTM) was used to identify the number and shape of HAQ-DI trajectories. Between group comparisons were made using the chi-squared test, two-sample t-test or Wilcoxon rank-sum test as appropriate. Multiple logistic regression was used to identify features associated with trajectory group membership. Survival analyses were performed using Kaplan Meier and Cox proportional hazard modelling. RESULTS: We identified two HAQ-DI trajectory groups within 426 ASCS participants with incident SSc: low-stable disability (n=221, 52%), and high-increasing disability (n=205, 48%). Participants with high-increasing disability were older at disease onset, more likely to have diffuse SSc (dcSSc), cardiopulmonary disease, multimorbidity, digital ulcers, and gastrointestinal involvement (all p≤0.01), as was use of immunosuppression (p<0.01). Multimorbidity was associated with high-increasing trajectory group membership (OR3.1, 95%CI1.1-8.8, p=0.04); independently, multiple SSc features were also strongly associated including dcSSc (OR2.3, 95%CI1.3-4.2, p<0.01), proximal weakness (OR7.3, 95%CI2.0-27.1, p<0.01) and joint contractures (OR2.7, 95%CI1.3-5.3, p<0.01). High-increasing physical disability was associated with an almost two-fold increased risk of mortality (HR1.9, 95%CI1.0-3.8, p=0.05), and higher symptom burden. CONCLUSIONS: Two trajectories of functional disability in SSc were identified. Those with high-increasing functional disability had a distinct clinical phenotype and worse survival compared to those with low-stable functional disability. These data highlight the pervasive nature of physical disability in SSc, and its prognostic importance.


Subject(s)
Disability Evaluation , Scleroderma, Systemic , Humans , Female , Male , Middle Aged , Scleroderma, Systemic/physiopathology , Scleroderma, Systemic/complications , Scleroderma, Systemic/mortality , Scleroderma, Systemic/diagnosis , Scleroderma, Systemic/epidemiology , Australia/epidemiology , Adult , Aged , Surveys and Questionnaires , Functional Status , Proportional Hazards Models , Disease Progression , Prognosis , Health Status , Time Factors , Risk Factors , Predictive Value of Tests , Multimorbidity , Severity of Illness Index , Kaplan-Meier Estimate
7.
Clin Exp Rheumatol ; 42(8): 1669-1674, 2024 08.
Article in English | MEDLINE | ID: mdl-39152749

ABSTRACT

OBJECTIVES: To investigate the burden and clinical associations of fatigue in systemic sclerosis (SSc) as measured by FACIT-Fatigue scores. METHODS: Australian Scleroderma Cohort Study participants with ≥1 FACIT-Fatigue score were included. Participants were divided into those with incident SSc (≤5 years SSc duration at recruitment and FACIT-Fatigue score recorded within 5 years of disease onset) or prevalent SSc (first FACIT-Fatigue score recorded >5 years after SSc onset). Generalised estimating equations were used to model change in FACIT-Fatigue scores over time, expressed as an increasing (improving) or decreasing (worsening) score. RESULTS: Of 859 participants, 215 had incident SSc and 644 prevalent SSc. First-recorded FACIT-Fatigue scores were similar in those with incident (37 units, IQR 25-45.5) and prevalent SSc (36 units, IQR 23-44; p=0.17), as were lowest-ever recorded FACIT-Fatigue scores (incident 23 units; prevalent 22 units, p=0.75). In incident SSc, higher skin scores (regression coefficient (RC) -1.5 units, 95%CI -2.3 to -0.8), PAH (RC -8.2, 95%CI -16.5 to 0.1) and reduced left ventricular function (RC -10.6, 95%CI -18.3 to -2.8) were associated with more severe fatigue. In prevalent SSc, higher skin scores (RC -0.6, 95%CI -1.3 to 0), gastrointestinal symptoms (RC -6.6, 95%CI -9.0 to -4.2), hypoalbuminaemia (RC -2.8, 95%CI -5.0 to -0.7), BMI<18.5kg/m2 (RC -6.3, 95%CI -10.3 to -2.2), raised CRP (RC -3.1, 95%CI -4.7 to -1.5), and anaemia (RC -1.7, 95%CI -3.5 to 0.1) were associated with more severe fatigue. CONCLUSIONS: The burden of fatigue is substantial in both incident and prevalent SSc. Cardiopulmonary and gastrointestinal involvement are associated with worse fatigue.


Subject(s)
Fatigue , Scleroderma, Systemic , Humans , Scleroderma, Systemic/epidemiology , Scleroderma, Systemic/complications , Scleroderma, Systemic/diagnosis , Scleroderma, Systemic/physiopathology , Fatigue/epidemiology , Fatigue/physiopathology , Fatigue/diagnosis , Fatigue/etiology , Female , Middle Aged , Male , Incidence , Prevalence , Australia/epidemiology , Adult , Aged , Cost of Illness , Risk Factors , Severity of Illness Index , Time Factors
8.
Intern Med J ; 53(3): 311-317, 2023 03.
Article in English | MEDLINE | ID: mdl-35969110

ABSTRACT

Hydroxychloroquine (HCQ) and its close relative chloroquine (CQ) were initially used as antimalarial agents but are now widely prescribed in rheumatology, dermatology and immunology for the management of autoimmune diseases. HCQ is considered to have a better long-term safety profile than CQ and is therefore more commonly used. HCQ has a key role in the treatment of connective tissue diseases including systemic lupus erythematosus (SLE), where it provides beneficial immunomodulation without clinically significant immunosuppression. HCQ can also assist in managing inflammatory arthritis, including rheumatoid arthritis (RA). Debate around toxicity of HCQ in COVID-19 has challenged those who regularly prescribe HCQ to discuss its potential toxicities. Accordingly, we have reviewed the adverse effect profile of HCQ to provide guidance about this therapeutic agent in clinical practice.


Subject(s)
Antirheumatic Agents , COVID-19 , Lupus Erythematosus, Systemic , Humans , Hydroxychloroquine/adverse effects , Antirheumatic Agents/adverse effects , Friends , COVID-19 Drug Treatment , Chloroquine/adverse effects , Lupus Erythematosus, Systemic/drug therapy
9.
Intern Med J ; 53(10): 1919-1924, 2023 10.
Article in English | MEDLINE | ID: mdl-37772776

ABSTRACT

Cardiopulmonary complications of connective tissue diseases (CTDs), particularly pulmonary arterial hypertension (PAH) and interstitial lung disease (ILD), are major determinants of morbidity and mortality. Multidisciplinary meetings may improve diagnostic accuracy and optimise treatment. We review the literature regarding multidisciplinary meetings in CTD-ILD and PAH and describe our tertiary centre experience of the role of the multidisciplinary meeting in managing CTD-PAH.


Subject(s)
Connective Tissue Diseases , Lung Diseases, Interstitial , Humans , Prognosis , Connective Tissue Diseases/complications , Connective Tissue Diseases/diagnosis , Connective Tissue Diseases/therapy , Lung Diseases, Interstitial/diagnosis , Lung Diseases, Interstitial/etiology , Lung Diseases, Interstitial/therapy , Patient Care Team
10.
BMC Musculoskelet Disord ; 23(1): 113, 2022 Feb 03.
Article in English | MEDLINE | ID: mdl-35114987

ABSTRACT

BACKGROUND: Pain sensitisation plays a major role in musculoskeletal pain. However, effective treatments are limited, and although there is growing evidence that exercise may improve pain sensitisation, the amount and type of exercise remains unclear. This systematic review examines the evidence for an effect of aerobic exercise on pain sensitisation in musculoskeletal conditions. METHODS: Systematic searches of six electronic databases were conducted. Studies were included if they examined the relationship between aerobic physical activity and pain sensitisation in individuals with chronic musculoskeletal pain, but excluding specific patient subgroups such as fibromyalgia. Risk of bias was assessed using Cochrane methods and a qualitative analysis was conducted. RESULTS: Eleven studies (seven repeated measures studies and four clinical trials) of 590 participants were included. Eight studies had low to moderate risk of bias. All 11 studies found that aerobic exercise increased pressure pain thresholds or decreased pain ratings in those with musculoskeletal pain [median (minimum, maximum) improvement in pain sensitisation: 10.6% (2.2%, 24.1%)]. In these studies, the aerobic exercise involved walking or cycling, performed at a submaximal intensity but with incremental increases, for a 4-60 min duration. Improvement in pain sensitisation occurred after one session in the observational studies and after 2-12 weeks in the clinical trials. CONCLUSIONS: These findings provide evidence that aerobic exercise reduces pain sensitisation in individuals with musculoskeletal pain. Further work is needed to determine whether this translates to improved patient outcomes, including reduced disability and greater quality of life.


Subject(s)
Fibromyalgia , Musculoskeletal Pain , Exercise , Exercise Therapy , Humans , Musculoskeletal Pain/diagnosis , Musculoskeletal Pain/epidemiology , Musculoskeletal Pain/therapy , Quality of Life
11.
Rheumatology (Oxford) ; 61(1): 103-120, 2021 12 24.
Article in English | MEDLINE | ID: mdl-34273157

ABSTRACT

OBJECTIVE: Recent advances in cardiac MRI (CMR) and other diagnostic techniques have made it easier to identify subclinical cardiac inflammation and dysfunction in the idiopathic inflammatory myopathies (IIM). Herein, we systematically review the literature regarding cardiac involvement in IIM. METHODS: We searched Medline and EMBASE from 1990 to 2020 using keywords related to IIM and cardiac disease. We included English language studies in adults with any immune-mediated, inflammatory muscle pathology. RESULTS: We identified 10 425 potentially relevant abstracts, of which 29 were included. Most frequently these included patients with PM or DM without symptomatic myocarditis. Five categories of cardiac investigation were used in these patients: cardiac enzyme testing, ECG, transthoracic echocardiography, CMR and nuclear medicine testing. Patients with clinical myocarditis had universally abnormal cardiac troponin levels and ECG. Elevated cardiac troponin T was more common than cardiac troponin I and may correlate with disease activity, whereas cardiac troponin I was more specific for cardiac involvement. Non-specific ECG changes were common. The major finding on transthoracic echocardiography was abnormal ejection fraction. Gross systolic dysfunction was unusual, but subclinical systolic dysfunction was reported in several studies. Abnormal diastolic function was common and may be associated with disease duration. Late gadolinium enhancement (reflecting regional necrosis or scarring) and abnormal myocardial mapping parameters (reflecting myocardial inflammation, fibrosis and oedema) were frequently identified on CMR, suggesting significant subclinical myocardial pathology (despite typically normal ejection fraction). CONCLUSION: Abnormal cardiac investigations are commonly found in asymptomatic IIM patients, which has potential prognostic and treatment implications.


Subject(s)
Myocarditis/etiology , Myositis/complications , Echocardiography , Electrocardiography , Humans , Magnetic Resonance Imaging , Myocarditis/blood , Myocarditis/diagnostic imaging , Troponin I/blood , Troponin T/blood
12.
BMC Musculoskelet Disord ; 22(1): 341, 2021 Apr 09.
Article in English | MEDLINE | ID: mdl-33836697

ABSTRACT

BACKGROUND: Arthritis, regardless of cause, has significant physical, social and psychological impacts on patients. We aimed to identify the non-healthcare needs perceived by patients with inflammatory arthritis (IA) and osteoarthritis (OA), and to determine if these differ. METHODS: We electronically searched MEDLINE, PsycINFO, EMBASE and CINAHL (1990-2020) systematically to identify non-healthcare-related needs of people with IA or OA. All citations were screened and quality appraised by two reviewers. Data was extracted by a single reviewer. RESULTS: The search identified 7853 citations, with 31 studies included (12 for OA, 20 for IA). Six areas of need emerged and these were similar in both group These were: 1) Assistance with activities of daily living especially related to a lack of independence; 2) Social connectedness: need for social participation; 3) Financial security: worry about financial security and increased costs of health-seeking behaviours; 4) Occupational needs: desire to continue work for financial and social reasons, facilitated by flexibility of workplace conditions/environment; 5) Exercise and leisure: including limitation due to pain; 6) Transportation: limitations in ability to drive and take public transport due to mobility concerns. Many areas of need were linked; e.g. loss of employment and requiring support from family was associated with a sense of "failure" and loss of identity, as social isolation. CONCLUSIONS: This review highlights the pervasive impact of arthritis on peoples' lives, regardless of aetiology, albeit with a limited evidence base. Improved identification and targeting of non-healthcare needs of people with arthritis is likely to improve person-centred care.


Subject(s)
Activities of Daily Living , Osteoarthritis , Delivery of Health Care , Employment , Humans , Osteoarthritis/diagnosis , Osteoarthritis/epidemiology , Osteoarthritis/therapy , Workplace
13.
J Clin Microbiol ; 59(1)2020 12 17.
Article in English | MEDLINE | ID: mdl-33067270

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of an ongoing pandemic that has infected over 36 million and killed over 1 million people. Informed implementation of government public health policies depends on accurate data on SARS-CoV-2 immunity at a population scale. We hypothesized that detection of SARS-CoV-2 salivary antibodies could serve as a noninvasive alternative to serological testing for monitoring of SARS-CoV-2 infection and seropositivity at a population scale. We developed a multiplex SARS-CoV-2 antibody immunoassay based on Luminex technology that comprised 12 CoV antigens, mostly derived from SARS-CoV-2 nucleocapsid (N) and spike (S). Saliva and sera collected from confirmed coronavirus disease 2019 (COVID-19) cases and from the pre-COVID-19 era were tested for IgG, IgA, and IgM to the antigen panel. Matched saliva and serum IgG responses (n = 28) were significantly correlated. The salivary anti-N IgG response resulted in the highest sensitivity (100%), exhibiting a positive response in 24/24 reverse transcription-PCR (RT-PCR)-confirmed COVID-19 cases sampled at >14 days post-symptom onset (DPSO), whereas the salivary anti-receptor binding domain (RBD) IgG response yielded 100% specificity. Temporal kinetics of IgG in saliva were consistent with those observed in blood and indicated that most individuals seroconvert at around 10 DPSO. Algorithms employing a combination of the IgG responses to N and S antigens result in high diagnostic accuracy (100%) by as early as 10 DPSO. These results support the use of saliva-based antibody testing as a noninvasive and scalable alternative to blood-based antibody testing.


Subject(s)
Antibodies, Viral/analysis , Antibodies, Viral/blood , COVID-19/diagnosis , SARS-CoV-2/immunology , Saliva/immunology , COVID-19 Nucleic Acid Testing/methods , Coronavirus Nucleocapsid Proteins/immunology , Female , Humans , Immunoglobulin A/blood , Immunoglobulin G/blood , Immunoglobulin M/blood , Male , Spike Glycoprotein, Coronavirus/immunology
14.
South Med J ; 112(1): 45-51, 2019 01.
Article in English | MEDLINE | ID: mdl-30608632

ABSTRACT

OBJECTIVES: Zika virus is an emerging infection that has posed vexing challenges to the US public health system. Improved characterization of patients with possible and confirmed infection is needed to better understand risks for infection in US travelers and to inform evolving evaluation guidelines. METHODS: We performed a retrospective electronic health record review of patients evaluated for Zika virus infection at an academic travel clinic in Atlanta, Georgia, from January 1 through August 31, 2016. We evaluated 46 patients who presented to the clinic during this period for evaluation of possible Zika virus infection, including patients with Zika virus symptoms, asymptomatic patients with possible exposure to Zika virus, and referral visits for Zika virus testing. RESULTS: Among the 46 patients evaluated, 30 (65.2%) were tested for Zika virus, 8 of whom (17.4%) had laboratory evidence of infection (7 confirmed, 1 probable). Cases, including confirmed and probable infections, most commonly had fever, rash, conjunctivitis, headache, and myalgia, although differences compared with noncases were not statistically significant. Many patients evaluated were not tested because of stringent testing criteria. CONCLUSIONS: Our findings may help inform improvements in timely clinical decision making for Zika virus testing. This may assist clinicians and public health agencies. Wider access to accurate screening modalities will help providers evaluate and advise patients.


Subject(s)
Travel , Zika Virus Infection/diagnosis , Adult , Ambulatory Care Facilities , Asymptomatic Infections , Conjunctivitis/etiology , Conjunctivitis/physiopathology , Exanthema/etiology , Exanthema/physiopathology , Female , Fever/etiology , Fever/physiopathology , Georgia/epidemiology , Headache/etiology , Headache/physiopathology , Humans , Male , Middle Aged , Myalgia/etiology , Myalgia/physiopathology , Referral and Consultation , Retrospective Studies , Zika Virus Infection/complications , Zika Virus Infection/physiopathology
15.
Clin Infect Dis ; 66(1): 1-10, 2018 01 06.
Article in English | MEDLINE | ID: mdl-29020226

ABSTRACT

Background: There is an urgent need for studies of viral persistence and immunity during human Zika infections to inform planning and conduct of vaccine clinical trials. Methods: In 5 returned US travelers with acute symptomatic Zika infection, clinical features, viral RNA levels, and immune responses were characterized. Results: Two pregnant, flavivirus-experienced patients had viral RNA persist in plasma for >44 and >26 days. Three days after symptom onset, transient increases in proinflammatory monocytes began followed at 5 days by transient decreases in myeloid dendritic cells. Anti-Zika virus immunoglobulin M was detected at day 7 after symptom onset, persisted beyond 103 days, and remained equivocal through day 172. Zika virus-specific plasmablasts and neutralizing antibodies developed quickly; dengue virus-specific plasmablasts and neutralizing antibodies at high titers developed only in flavivirus-experienced patients. Zika virus- and dengue virus-specific memory B cells developed in both flavivirus-naive and -experienced patients. CD4+ T cells were moderately activated and produced antiviral cytokines after stimulation with Zika virus C, prM, E, and NS5 peptides in 4/4 patients. In contrast, CD8+ T cells were massively activated, but virus-specific cells that produced cytokines were present in only 2/4 patients assessed. Conclusions: Acute infections with Zika virus modulated antigen-presenting cell populations early. Flavivirus-experienced patients quickly recalled cross-reactive MBCs to secrete antibodies. Dengue virus-naive patients made little dengue-specific antibody but developed MBCs that cross-reacted against dengue virus. Zika virus-specific functional CD4+ T cells were readily detected, but few CD8+ T cells specific for the tested peptides were found.


Subject(s)
Adaptive Immunity , B-Lymphocytes/immunology , Immunity, Innate , T-Lymphocyte Subsets/immunology , Zika Virus Infection/immunology , Zika Virus Infection/pathology , Zika Virus/immunology , Adult , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , Female , Humans , Immunoglobulin M/blood , Male , Pregnancy , RNA, Viral/blood , Time Factors , Viral Load , Zika Virus Infection/virology
16.
Malar J ; 17(1): 198, 2018 May 15.
Article in English | MEDLINE | ID: mdl-29764439

ABSTRACT

BACKGROUND: Malaria chemoprophylaxis options in pregnancy are limited, and atovaquone-proguanil (AP) is not recommended because of insufficient safety evidence. An anonymous, internet-based survey was disseminated to describe outcomes of pregnancies accidentally exposed to AP. Outcomes of interest included miscarriage (defined as pregnancy loss before 20 weeks), stillbirth (defined as pregnancy loss at or after 20 weeks), preterm birth or live birth prior to 37 weeks, and the presence of congenital anomalies. RESULTS: A total of 487 women responded and reported on 822 pregnancies. Of the 807 pregnancies with information available on exposure and outcomes, 10 (1.2%) had atovaquone-proguanil exposure, all in the first trimester, and all resulted in term births with no birth defects. CONCLUSIONS: Use of an anti-malarial not recommended in pregnancy is likely to occur before the woman knows of her pregnancy. This study adds to the limited evidence of the safety of AP in pregnancy. Further study on use of AP in pregnancy should be a high priority, as an alternative option for the prevention of malaria in pregnancy in non-immune travellers is urgently needed.


Subject(s)
Antimalarials/adverse effects , Atovaquone/adverse effects , Chemoprevention/adverse effects , Chloroquine/adverse effects , Mefloquine/adverse effects , Pregnancy Outcome/epidemiology , Proguanil/adverse effects , Abnormalities, Drug-Induced/epidemiology , Abnormalities, Drug-Induced/etiology , Abortion, Spontaneous/chemically induced , Abortion, Spontaneous/epidemiology , Adult , Drug Combinations , Female , Humans , Live Birth/epidemiology , Middle Aged , Pregnancy , Premature Birth/chemically induced , Premature Birth/epidemiology , Stillbirth/epidemiology , United States/epidemiology , Young Adult
17.
J Cardiothorac Vasc Anesth ; 32(3): 1289-1294, 2018 06.
Article in English | MEDLINE | ID: mdl-29169799

ABSTRACT

OBJECTIVE: To investigate the pharmacokinetics of a 20 mmol magnesium bolus in regards to serum and urinary magnesium concentration, volume of distribution, and half-life. DESIGN: Prospective, experimental study. SETTING: A university-affiliated teaching hospital. PARTICIPANTS: Twenty consecutive cardiac surgery patients treated with magnesium bolus therapy for prevention of arrhythmia. INTERVENTIONS: A 20-mmol bolus of magnesium sulfate was administered intravenously. MEASUREMENTS AND MAIN RESULTS: Median magnesium levels increased from 1.04 (interquartile range 0.94-1.23) mmol/L to 1.72 (1.57-2.14) mmol/L after 60 minutes of magnesium infusion (p < 0.001) but decreased to 1.27 (1.21-1.36) and 1.16 (1.11-1.21) mmol/L after 6 and 12 hours, respectively. Urinary magnesium concentration increased from 6.3 (4.2-14.5) mmol/L to 19.1 (7.4-34.5) mmol/L after 60 minutes (p < 0.001), followed by 22.7 (18.4-36.7) and 15 (8.4-19.7) mmol/L after 6 and 12 hours, respectively. Over the 12-hour observation period, the cumulative urinary magnesium excretion was 19.1 mmol (95.5% of the dose given). The median magnesium clearance was 10 (4.7-15.8) mL/min and increased to 14.9 (3.8-20.7; p = 0.934) mL/min at 60 minutes. The estimated volume of distribution was 0.31 (0.28-0.34) L/kg. CONCLUSION: Magnesium bolus therapy after cardiac surgery leads to a significant but short-lived increase of magnesium serum concentration due to renal excretion and distribution, and the magnesium balance is neutral after 12 hours.


Subject(s)
Cardiac Surgical Procedures , Magnesium/pharmacokinetics , Thoracic Surgical Procedures , Aged , Female , Humans , Magnesium/administration & dosage , Male , Prospective Studies
18.
Mem Inst Oswaldo Cruz ; 112(4): 275-280, 2017 Apr.
Article in English | MEDLINE | ID: mdl-28327791

ABSTRACT

BACKGROUND: Despite public health efforts to reduce the global burden of leprosy, gaps remain in the knowledge surrounding transmission of infection. Helminth co-infections have been associated with a shift towards the lepromatous end of the disease spectrum, potentially increasing transmission in co-endemic areas. OBJECTIVES: Using this biologically plausible association, we conducted a geographic information systems (GIS) study to investigate the spatial associations of schistosomiasis and leprosy in an endemic area of Minas Gerais (MG), Brazil. METHODS: Data on new cases of Mycobacterium leprae and Schistosoma mansoni infections from 2007-2014 were retrieved from the Brazilian national notifiable diseases information system for seven municipalities in and surrounding Vespasiano, MG. A total of 139 cases of leprosy and 200 cases of schistosomiasis were mapped to a municipality level. For one municipality, cases were mapped to a neighborhood level and a stratified analysis was conducted to identify spatial associations. FINDINGS: A relative risk of 6.80 [95% confidence interval (CI) 1.46 - 31.64] of leprosy was found in neighborhoods with schistosomiasis. Incidence rates of leprosy increased with corresponding incidence rates of schistosomiasis, and the temporal trends of both infections were similar. CONCLUSIONS: The associations found in this project support the hypothesis that helminth infections may influence the transmission of leprosy in co-endemic areas.


Subject(s)
Coinfection/epidemiology , Leprosy/epidemiology , Neglected Diseases/epidemiology , Schistosomiasis mansoni/epidemiology , Adolescent , Adult , Aged , Aged, 80 and over , Brazil/epidemiology , Child , Child, Preschool , Endemic Diseases , Female , Geographic Information Systems , Humans , Incidence , Infant , Infant, Newborn , Male , Middle Aged , Risk Factors , Spatio-Temporal Analysis , Young Adult
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