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1.
Am J Respir Crit Care Med ; 206(7): 892-900, 2022 10 01.
Article in English | MEDLINE | ID: mdl-35608549

ABSTRACT

Rationale: Although World Health Organization guidelines emphasize contact investigation for tuberculosis (TB)-exposed children, data that support chest radiography as a useful tool are lacking. Objectives: We evaluated the diagnostic and prognostic information of chest radiography in children exposed to TB and measured the efficacy of isoniazid preventive therapy (IPT) in those with relevant radiographic abnormalities. Methods: Between September 2009 and August 2012, we enrolled 4,468 TB-exposed children who were screened by tuberculin skin testing, symptom assessment, and chest radiography. Those negative for TB disease were followed for 1 year for the occurrence of new TB diagnoses. We assessed the protective efficacy of IPT in children with and without abnormal chest radiographs. Measurements and Main Results: Compared with asymptomatic children with normal chest films, asymptomatic children with abnormal radiographs were 25.1-fold more likely to have coprevalent TB (95% confidence interval [CI], 1.02-613.76) and 26.7-fold more likely to be diagnosed with incident TB disease during follow-up (95% CI, 10.44-68.30). Among the 29 symptom-negative and CXR-abnormal child contacts, 20% (3/15) of the isoniazid recipients developed incident TB, compared with 57% (8/14) of those who did not receive IPT (82% IPT efficacy). Conclusions: Our results strongly support the use of chest radiography as a routine screening tool for the evaluation of child TB contacts, which is readily available. Radiographic abnormalities not usually considered suggestive of TB may indicate incipient or subclinical disease, although TB preventive treatment is adequate in most cases.


Subject(s)
Isoniazid , Tuberculosis , Antitubercular Agents/therapeutic use , Child , Humans , Isoniazid/therapeutic use , Radiography , Tuberculin , Tuberculosis/diagnostic imaging , Tuberculosis/drug therapy
2.
J Community Health ; 45(2): 400-406, 2020 04.
Article in English | MEDLINE | ID: mdl-31612368

ABSTRACT

HIV pre-exposure prophylaxis (PrEP) is underutilized among Hispanics, women, and low-income individuals. To better understand PrEP barriers in this population, questionnaires were administered to 500 patients attending public health clinics in southern Arizona which provide family planning and sexually transmitted infections care. Sixty-three percent believed that they had no risk of HIV infection. When asked "Before today, did you know that there was a pill that can prevent HIV infection?" 80% of persons answered no. Among women, 88% answered no to this question. As expected, individuals with a higher perceived HIV risk (OR 1.76) or one HIV risk factor (OR 5.85) had a higher probability of knowledge. Among survey participants 87% would take a daily pill, 91% would visit a health-care provider every 3 months, and 92% would have laboratory testing every 3 months. Fifty-four percent would not be afraid or embarrassed if friends or family knew they were taking PrEP. Seventy-two percent would take PrEP despite temporary nausea. Sixty-two percent would pay ≥ $40 every 3 months for PrEP. Lack of knowledge, rather than patient attitudes, is the more important barrier to wider utilization of PrEP among individuals, especially women, attending public health clinics in Southern Arizona. Future efforts need to focus on education and access to PrEP in underserved populations including women and Hispanics.


Subject(s)
Community Health Services , HIV Infections , Health Knowledge, Attitudes, Practice , Pre-Exposure Prophylaxis , Adult , Arizona , HIV Infections/drug therapy , HIV Infections/prevention & control , Humans , Surveys and Questionnaires
3.
J Clin Immunol ; 37(7): 732-738, 2017 Oct.
Article in English | MEDLINE | ID: mdl-28865061

ABSTRACT

PURPOSE: Mendelian susceptibility to mycobacterial disease is a rare clinical condition characterized by a predisposition to infectious diseases caused by poorly virulent mycobacteria. Other infections such as salmonellosis and candidiasis are also reported. The purpose of this article is to describe a young boy affected with various infectious diseases caused by Mycobacterium tuberculosis complex, Salmonella sp, Klebsiella pneumonie, Citrobacter sp., and Candida sp, complicated with severe enteropathy and transient hypogammaglobulinemia. METHODS: We reviewed medical records and performed flow cytometry staining for lymphocyte populations, lymphocyte proliferation in response to PHA, and intracellular IFN-γ production in T cell PHA blasts in the patient and a healthy control. Sanger sequencing was used to confirm the genetic variants in the patient and relatives. RESULTS: Genetic analysis revealed a bi-allelic mutation in IL12RB1 (C291Y) resulting in complete IL-12Rß1 deficiency. Functional analysis demonstrated the lack of intracellular production of IFN-γ in CD3+ T lymphocytes from the patient in response to rhIL-12p70. CONCLUSIONS: To our knowledge, this is the third patient with MSMD due to IL-12Rß1 deficiency complicated with enteropathy and hypogammaglobulinemia and the first case of this disease to be described in Colombia.


Subject(s)
Agammaglobulinemia/genetics , Candidiasis/genetics , Enteritis/genetics , Gram-Negative Bacterial Infections/genetics , Receptors, Interleukin-12/deficiency , Receptors, Interleukin-12/genetics , Agammaglobulinemia/drug therapy , BCG Vaccine , Candidiasis/drug therapy , Drug Resistance, Bacterial , Enteritis/drug therapy , Genetic Predisposition to Disease , Gram-Negative Bacterial Infections/drug therapy , Humans , Infant , Mutation , Mycobacterium tuberculosis
4.
Clin Infect Dis ; 61Suppl 3: S164-72, 2015 Oct 15.
Article in English | MEDLINE | ID: mdl-26409279

ABSTRACT

Childhood tuberculosis contributes significantly to the global tuberculosis disease burden but remains challenging to diagnose due to inadequate methods of pathogen detection in paucibacillary pediatric samples and lack of a child-specific host biomarker to identify disease. Accurately diagnosing tuberculosis in children is required to improve case detection, surveillance, healthcare delivery, and effective advocacy. In May 2014, the National Institutes of Health convened a workshop including researchers in the field to delineate priorities to address this research gap. This blueprint describes the consensus from the workshop, identifies critical research steps to advance this field, and aims to catalyze efforts toward harmonization and collaboration in this area.


Subject(s)
Biomarkers , Biomedical Research , Tuberculosis/diagnosis , Biological Specimen Banks , Child , Delivery of Health Care , Humans , National Institutes of Health (U.S.) , Pediatrics , Specimen Handling , Tuberculosis/epidemiology , United States
5.
Lancet ; 383(9928): 1572-9, 2014 May 03.
Article in English | MEDLINE | ID: mdl-24671080

ABSTRACT

BACKGROUND: Multidrug-resistant tuberculosis threatens to reverse recent reductions in global tuberculosis incidence. Although children younger than 15 years constitute more than 25% of the worldwide population, the global incidence of multidrug-resistant tuberculosis disease in children has never been quantified. We aimed to estimate the regional and global annual incidence of multidrug-resistant tuberculosis in children. METHODS: We developed two models: one to estimate the setting-specific risk of multidrug-resistant tuberculosis among child cases of tuberculosis, and a second to estimate the setting-specific incidence of tuberculosis disease in children. The model for risk of multidrug-resistant tuberculosis among children with tuberculosis needed a systematic literature review. We multiplied the setting-specific estimates of multidrug-resistant tuberculosis risk and tuberculosis incidence to estimate regional and global incidence of multidrug-resistant tuberculosis disease in children in 2010. FINDINGS: We identified 3403 papers, of which 97 studies met inclusion criteria for the systematic review of risk of multidrug-resistant tuberculosis. 31 studies reported the risk of multidrug-resistant tuberculosis in both children and treatment-naive adults with tuberculosis and were used for evaluation of the linear association between multidrug-resistant disease risk in these two patient groups. We identified that the setting-specific risk of multidrug-resistant tuberculosis was nearly identical in children and treatment-naive adults with tuberculosis, consistent with the assertion that multidrug-resistant disease in both groups reflects the local risk of transmitted multidrug-resistant tuberculosis. After application of these calculated risks, we estimated that around 999,792 (95% CI 937,877-1,055,414) children developed tuberculosis disease in 2010, of whom 31,948 (25,594-38,663) had multidrug-resistant disease. INTERPRETATION: Our estimates underscore that many cases of tuberculosis and multidrug-resistant tuberculosis disease are not being detected in children. Future estimates can be refined as more and better tuberculosis data and new diagnostic instruments become available. FUNDING: US National Institutes of Health, the Helmut Wolfgang Schumann Fellowship in Preventive Medicine at Harvard Medical School, the Norman E Zinberg Fellowship at Harvard Medical School, and the Doris and Howard Hiatt Residency in Global Health Equity and Internal Medicine at the Brigham and Women's Hospital.


Subject(s)
Global Health/statistics & numerical data , Tuberculosis, Multidrug-Resistant/epidemiology , Adolescent , Child , Child, Preschool , Humans , Incidence , Infant , Risk Assessment
6.
Clin Infect Dis ; 58(6): e115-8, 2014 Mar.
Article in English | MEDLINE | ID: mdl-24336756

ABSTRACT

An acquired immune deficiency due to interferon gamma (IFN-γ) autoantibodies was diagnosed in a 78-year-old Japanese man with treatment-refractory disseminated nontuberculous mycobacterial infection. In addition to standard antimycobacterial therapy, he was successfully treated with rituximab to eliminate B cells and thereby the autoantibody. Subsequently, he obtained a sustained remission from infection.


Subject(s)
Antibodies, Monoclonal, Murine-Derived/therapeutic use , Autoantibodies/immunology , Immunologic Factors/therapeutic use , Interferon-gamma/immunology , Mycobacterium Infections, Nontuberculous/drug therapy , Mycobacterium Infections, Nontuberculous/immunology , Aged , Autoantibodies/blood , Humans , Male , Rituximab
7.
Diagn Microbiol Infect Dis ; 109(3): 116302, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38657352

ABSTRACT

For microbiological confirmation of pediatric pulmonary tuberculosis (PTB), gastric aspirates (GA) are often operationally unfeasible without hospitalization, and the encapsulated orogastric string test is not easily swallowed in young children. The Combined-NasoGastric-Tube-and-String-Test (CNGTST) enables dual collection of GA and string specimens. In a prospective cohort study in Kenya, we examined its feasibility in children under five with presumptive PTB and compared the bacteriological yield of string to GA. Paired GA and string samples were successfully collected in 95.6 % (281/294) of children. Mycobacterium tuberculosis was isolated from 7.0 % (38/541) of GA and 4.3 % (23/541) of string samples, diagnosing 8.2 % (23/281) of children using GA and 5.3 % (15/281) using string. The CNGTST was feasible in nearly all children. Yield from string was two-thirds that of GA despite a half-hour median dwelling time. In settings where the feasibility of hospitalisation for GA is uncertain, the string component can be used to confirm PTB.


Subject(s)
Feasibility Studies , Mycobacterium tuberculosis , Tuberculosis, Pulmonary , Humans , Tuberculosis, Pulmonary/diagnosis , Infant , Child, Preschool , Prospective Studies , Male , Female , Mycobacterium tuberculosis/isolation & purification , Kenya , Bacteriological Techniques/methods , Specimen Handling/methods , Specimen Handling/instrumentation
8.
Curr Opin Pediatr ; 24(3): 319-28, 2012 Jun.
Article in English | MEDLINE | ID: mdl-22568943

ABSTRACT

PURPOSE OF REVIEW: To discuss the recommendations pertaining to infants, children, and adolescents in new and updated tuberculosis (TB) guidelines that have been published since 2010 - with emphasis on those from supranational organizations. RECENT FINDINGS: The main developments in the guidelines covered in this article are related to: novel diagnostics for TB infection, disease, and drug resistance; updated treatment regimens for childhood and drug-resistant TB (DR-TB); and primary and secondary prevention of TB disease in HIV-infected children and adolescents. SUMMARY: These new guidelines have significant implications for improving pediatric TB care. Regarding diagnosis, current interferon-gamma release assays should not replace tuberculin skin testing, but may be complementary; a polymerase chain reaction assay has been validated for detecting Mycobacterium tuberculosis and rifampicin resistance in microscopy-negative samples, especially in HIV-infected and DR-TB suspects; and a molecular line probe assay has been validated for detecting DR-TB in microscopy-positive samples and culture isolates in DR-TB suspects. With respect to treatment, there have been certain changes in the recent World Health Organization recommendations for certain clinical syndromes, for multidrug-resistant TB disease, and for HIV/TB disease. Concerning prevention, there are new screening algorithms for case finding, and new recommendations for treating HIV-infected children with presumed TB infection and with TB disease with treatment completed (i.e., secondary prophylaxis).


Subject(s)
Practice Guidelines as Topic , Tuberculosis/diagnosis , AIDS-Related Opportunistic Infections/diagnosis , AIDS-Related Opportunistic Infections/therapy , Antitubercular Agents/therapeutic use , Child , Humans , Interferon-gamma/biosynthesis , Nucleic Acid Amplification Techniques/methods , Tuberculosis/therapy , Tuberculosis, Multidrug-Resistant/diagnosis , Tuberculosis, Multidrug-Resistant/therapy
9.
Hum Vaccin Immunother ; 18(7): 2154506, 2022 12 30.
Article in English | MEDLINE | ID: mdl-36476311

ABSTRACT

While influenza cases in Arizona have nearly tripled since 2018, vaccination rates continue to lag. Statewide, Hispanics and African Americans had the lowest vaccination rates despite having higher influenza infection rates than Whites. Given Arizona's racial influenza vaccination disparity and the general increase in vaccination hesitancy due to COVID-19, the purpose of this study was to better understand the influences of seasonal influenza vaccination in Arizona during the COVID-19 pandemic using qualitative methods. Findings from this study revealed that many participants were motivated to get the influenza vaccine to protect their family and close friends. The heightened concern for COVID-19 prompted some Hispanic/Latino focus group discussion participants to consider getting vaccinated. However, many Hispanic/Latino participants also expressed that they stopped getting influenza vaccine due to negative vaccination experiences or concern about sickness following immunization. African American participants primarily discussed receiving the vaccine as part of their routine health visit. Compared to other races, more White participants believed that vaccination was unimportant because they were healthy, and the people they interacted with never got sick. Distinct factors influence risk perception and vaccination intention across different racial/ethnic groups. Effective interventions can account for these factors and be tailored to the target population to maximize vaccination uptake.


Subject(s)
COVID-19 , Influenza Vaccines , Influenza, Human , Humans , Influenza, Human/prevention & control , Potassium Iodide , Intention , Arizona , Pandemics , White People , Vaccination , Perception
10.
J Am Geriatr Soc ; 70(4): 960-967, 2022 04.
Article in English | MEDLINE | ID: mdl-35141874

ABSTRACT

BACKGROUND: Adult residents of skilled nursing facilities (SNF) have experienced high morbidity and mortality from SARS-CoV-2 infection and are at increased risk for severe COVID-19 disease. Use of monoclonal antibody (mAb) treatment improves clinical outcomes among high-risk outpatients with mild-to-moderate COVID-19, but information on mAb effectiveness in SNF residents with COVID-19 is limited. We assessed outcomes in SNF residents with mild-to-moderate COVID-19 associated with an outbreak in Arizona during January-February 2021 that did and did not receive a mAb. METHODS: Medical records were reviewed to describe the effect of bamlanivimab therapy on COVID-19 mortality. Secondary outcomes included referral to an acute care setting and escalation of medical therapies at the SNF (e.g., new oxygen requirements). Residents treated with bamlanivimab were compared to residents who were eligible for treatment under the FDA's Emergency Use Authorization (EUA) but were not treated. Multivariable logistic regression was used to determine association between outcomes and treatment status. RESULTS: Seventy-five residents identified with COVID-19 during this outbreak met eligibility for mAb treatment, of whom 56 received bamlanivimab. Treated and untreated groups were similar in age and comorbidities associated with increased risk of severe COVID-19 disease. Treatment with bamlanivimab was associated with reduced 21-day mortality (adjusted OR = 0.06; 95% CI: 0.01, 0.39) and lower odds of initiating oxygen therapy (adjusted OR = 0.07; 95% CI: 0.02, 0.34). Referrals to acute care were not significantly different between treated and untreated residents. CONCLUSIONS: mAb therapy was successfully administered to SNF residents with COVID-19 in a large outbreak setting. Treatment with bamlanivimab reduced 21-day mortality and reduced initiation of oxygen therapy. As the COVID-19 pandemic evolves and newer immunotherapies gain FDA authorization, more studies of the effectiveness of mAb therapies for treating emerging SARS-CoV-2 variants of concern in high-risk congregate settings are needed.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Monoclonal/therapeutic use , Antibodies, Monoclonal, Humanized , Antibodies, Neutralizing , Arizona , Humans , Immunotherapy , Pandemics , Skilled Nursing Facilities
11.
Pediatr Infect Dis J ; 41(8): 671-677, 2022 08 01.
Article in English | MEDLINE | ID: mdl-35703284

ABSTRACT

BACKGROUND: Tuberculosis (TB) is a leading cause of illness and death in children globally. Improved bacteriologic and clinical diagnostic approaches in children are urgently needed. METHODS: In a prospective cohort study, a consecutive series of young (<5 years) children presenting with symptoms suggestive of TB and parenchymal abnormality on chest radiograph in inpatient and outpatient settings in Kisumu County, Kenya from October 2013 to August 2015 were evaluated at baseline and over 6 months. Up to 14 specimens per child were tested for the Mycobacterium tuberculosis complex by fluorescence microscopy, Xpert MTB/RIF and mycobacterial culture. Using detailed clinical characterization, cases were retrospectively classified according to standardized research case definitions and the sensitivity and specificity of microbiological tests on different specimen types were determined. RESULTS: Among 300 young children enrolled, 266 had sufficient information to be classified according to the research clinical case definition. Of these, 36% (96/266) had TB disease; 32% (31/96) with bacteriologically confirmed intrathoracic TB. Compared to culture, the sensitivity of a single Xpert test ranged from 60 to 67% and specificity from 97.5 to 100% for different specimen types. CONCLUSIONS: Despite extensive specimen collection and laboratory testing, TB could not be bacteriologically confirmed in almost two-thirds of children with intrathoracic TB classified by research clinical case definitions. Improved diagnostic tests are needed to identify children with TB and to exclude other potential causes of illness.


Subject(s)
Mycobacterium tuberculosis , Tuberculosis , Child , Child, Preschool , Humans , Mycobacterium tuberculosis/genetics , Prospective Studies , Retrospective Studies , Sensitivity and Specificity , Sputum/microbiology , Tuberculosis/diagnosis
12.
JAMA Pediatr ; 175(5): e206069, 2021 05 01.
Article in English | MEDLINE | ID: mdl-33616611

ABSTRACT

Importance: Criterion-standard specimens for tuberculosis diagnosis in young children, gastric aspirate (GA) and induced sputum, are invasive and rarely collected in resource-limited settings. A far less invasive approach to tuberculosis diagnostic testing in children younger than 5 years as sensitive as current reference standards is important to identify. Objective: To characterize the sensitivity of preferably minimally invasive specimen and assay combinations relative to maximum observed yield from all specimens and assays combined. Design, Setting, and Participants: In this prospective cross-sectional diagnostic study, the reference standard was a panel of up to 2 samples of each of 6 specimen types tested for Mycobacterium tuberculosis complex by Xpert MTB/RIF assay and mycobacteria growth indicator tube culture. Multiple different combinations of specimens and tests were evaluated as index tests. A consecutive series of children was recruited from inpatient and outpatient settings in Kisumu County, Kenya, between October 2013 and August 2015. Participants were children younger than 5 years who had symptoms of tuberculosis (unexplained cough, fever, malnutrition) and parenchymal abnormality on chest radiography or who had cervical lymphadenopathy. Children with 1 or more evaluable specimen for 4 or more primary study specimen types were included in the analysis. Data were analyzed from February 2015 to October 2020. Main Outcomes and Measures: Cumulative and incremental diagnostic yield of combinations of specimen types and tests relative to the maximum observed yield. Results: Of the 300 enrolled children, the median (interquartile range) age was 2.0 (1.0-3.6) years, and 151 (50.3%) were female. A total of 294 met criteria for analysis. Of 31 participants with confirmed tuberculosis (maximum observed yield), 24 (sensitivity, 77%; interdecile range, 68%-87%) had positive results on up to 2 GA samples and 20 (sensitivity, 64%; interdecile range, 53%-76%) had positive test results on up to 2 induced sputum samples. The yields of 2 nasopharyngeal aspirate (NPA) samples (23 of 31 [sensitivity, 74%; interdecile range, 64%-84%]), of 1 NPA sample and 1 stool sample (22 of 31 [sensitivity, 71%; interdecile range, 60%-81%]), or of 1 NPA sample and 1 urine sample (21.5 of 31 [sensitivity, 69%; interdecile range, 58%-80%]) were similar to reference-standard specimens. Combining up to 2 each of GA and NPA samples had an average yield of 90% (28 of 31). Conclusions and Relevance: NPA, in duplicate or in combination with stool or urine specimens, was readily obtainable and had diagnostic yield comparable with reference-standard specimens. This combination could improve tuberculosis diagnosis among children in resource-limited settings. Combining GA and NPA had greater yield than that of the current reference standards and may be useful in certain clinical and research settings.


Subject(s)
Specimen Handling/methods , Tuberculosis, Pulmonary/diagnosis , Child, Preschool , Cross-Sectional Studies , Feces/microbiology , Female , Humans , Infant , Kenya , Male , Nasopharynx/microbiology , Prospective Studies , Reference Standards , Sensitivity and Specificity , Urine/microbiology
14.
Lancet Infect Dis ; 20(11): e289-e297, 2020 11.
Article in English | MEDLINE | ID: mdl-32589869

ABSTRACT

Tuberculosis is the leading cause of death globally that is due to a single pathogen, and up to a fifth of patients with tuberculosis in high-incidence countries are children younger than 16 years. Unfortunately, the diagnosis of childhood tuberculosis is challenging because the disease is often paucibacillary and it is difficult to obtain suitable specimens, causing poor sensitivity of currently available pathogen-based tests. Chest radiography is important for diagnostic evaluations because it detects abnormalities consistent with childhood tuberculosis, but several limitations exist in the interpretation of such results. Therefore, other imaging methods need to be systematically evaluated in children with tuberculosis, although current data suggest that when available, cross-sectional imaging, such as CT, should be considered in the diagnostic evaluation for tuberculosis in a symptomatic child. Additionally, much of the understanding of childhood tuberculosis stems from clinical specimens that might not accurately represent the lesional biology at infection sites. By providing non-invasive measures of lesional biology, advanced imaging tools could enhance the understanding of basic biology and improve on the poor sensitivity of current pathogen detection systems. Finally, there are key knowledge gaps regarding the use of imaging tools for childhood tuberculosis that we outlined in this Personal View, in conjunction with a proposed roadmap for future research.


Subject(s)
Mycobacterium tuberculosis/genetics , Mycobacterium tuberculosis/immunology , Tuberculosis, Pulmonary/diagnostic imaging , Adolescent , Child , Child, Preschool , Humans , Magnetic Resonance Imaging/methods , Mass Chest X-Ray/methods , Nucleic Acid Amplification Techniques , Positron Emission Tomography Computed Tomography/methods , Tomography, Emission-Computed, Single-Photon/methods , Tuberculin Test , Tuberculosis, Pulmonary/microbiology , Ultrasonography/methods
15.
Am J Trop Med Hyg ; 99(6): 1534-1536, 2018 12.
Article in English | MEDLINE | ID: mdl-30277208

ABSTRACT

A healthy 16-year-old girl born and raised in Tucson, AZ, had screening and confirmatory testing revealing Chagas disease; clinical evaluation established that she had the indeterminate form of chronic Chagas disease with evidence of likely autochthonous transmission. Trypanosoma cruzi DNA was detected by conventional polymerase chain reaction in Triatoma rubida captured at her home.


Subject(s)
Chagas Disease/transmission , DNA, Protozoan/genetics , Disease Transmission, Infectious , Insect Vectors/parasitology , Triatoma/parasitology , Trypanosoma cruzi/genetics , Adolescent , Animals , Arizona , Chagas Disease/diagnosis , Chagas Disease/parasitology , Female , Humans , Trypanosoma cruzi/isolation & purification
16.
Clin Infect Dis ; 45(8): 950-7, 2007 Oct 15.
Article in English | MEDLINE | ID: mdl-17879907

ABSTRACT

BACKGROUND: Similar to poliovirus, enterovirus type 71 (EV71) causes severe disease, including aseptic meningitis, encephalitis, acute flaccid paralysis, and acute cardiopulmonary dysfunction. Large epidemics of EV71 infection have been reported worldwide. METHODS: After recognition of a cluster of cases of EV71 disease, we reviewed records of patients with EV71 disease who required hospitalization at The Children's Hospital in Denver, Colorado, from 2003 through 2005. The presence of enterovirus was detected by reverse-transcriptase polymerase chain reaction (PCR) and/or viral culture of specimens from multiple sources, and the virus was typed as EV71 using genetic sequencing. RESULTS: Eight cases of EV71 disease were identified in both 2003 and 2005. Fifty-six percent of patients with EV71 disease were < or = 6 months of age (range, 4 weeks to 9 years). All 16 patients had EV71 central nervous system infection. Enterovirus PCR (EV-PCR) of cerebrospinal fluid specimens yielded positive results for only 5 (31.2%) of the 16 patients; all of these patients were < 4 months of age and had less severe disease. However, EV-PCR of upper respiratory tract specimens yielded positive results for 8 (100%) of 8 patients, and EV-PCR of lower gastrointestinal tract specimens yielded positive results for 7 (87.5%) of 8 patients. CONCLUSIONS: An outbreak of neurologic EV71 disease occurred in Denver, Colorado, during 2003 and 2005. Likely, EV71 disease remains unrecognized in other parts of the United States, because EV-PCR of cerebrospinal fluid frequently yields negative results. EV-PCR of specimens from the respiratory and gastrointestinal tracts had higher diagnostic yields than did EV-PCR of cerebrospinal fluid. EV71 infection should be considered in young children presenting with aseptic meningitis, encephalitis, acute flaccid paralysis, or acute cardiopulmonary collapse. EV71 infection may be an underrecognized emerging disease in the United States.


Subject(s)
Central Nervous System Viral Diseases/epidemiology , Central Nervous System Viral Diseases/virology , Disease Outbreaks , Enterovirus A, Human/classification , Enterovirus A, Human/isolation & purification , Enterovirus Infections/epidemiology , Enterovirus Infections/virology , Central Nervous System Viral Diseases/diagnosis , Cerebrospinal Fluid/virology , Child , Child, Preschool , Colorado/epidemiology , Encephalitis/etiology , Enterovirus A, Human/genetics , Enterovirus A, Human/growth & development , Enterovirus Infections/diagnosis , Female , Gastrointestinal Tract/virology , Humans , Infant , Infant, Newborn , Male , Meningitis, Aseptic/etiology , Multiple Organ Failure/etiology , Paralysis/etiology , Polymerase Chain Reaction , Respiratory System/virology , Sequence Analysis, DNA , Virus Cultivation
18.
J Infect ; 74 Suppl 1: S74-S83, 2017 06.
Article in English | MEDLINE | ID: mdl-28646966

ABSTRACT

Children suffer a huge and often underappreciated burden of disease in tuberculosis (TB) endemic countries. Major hurdles include limited awareness among health care workers, poor integration of TB into maternal and child health approaches, diagnostic difficulties and a lack of child-friendly treatment options. Accurate disease diagnosis is particularly difficult in young and vulnerable children who tend to develop paucibacillary disease and are unable to produce an expectorated sputum sample. In addition, access to chest radiography is problematic in resource-limited settings. Differentiating between TB exposure and M. tuberculosis infection, and especially between M. tuberculosis infection and TB disease is crucial to guide clinical management. TB represents a dynamic continuum from well-contained "latent" infection to incipient and ultimately severe disease. The clinical spectrum of disease in children is broad and can be confused with a myriad of common infections. We provide a pragmatic 4-step approach to diagnose intra-thoracic TB in children and demonstrate how classifying clinical, radiological and laboratory findings into recognised clinical syndromes may provide a more refined diagnostic approach, even in resource-limited settings.


Subject(s)
Diagnostic Tests, Routine/methods , Disease Management , Tuberculosis, Pulmonary/diagnosis , Tuberculosis, Pulmonary/pathology , Child , Child, Preschool , Humans , Infant , Infant, Newborn
19.
Rev Bras Ter Intensiva ; 29(3): 271-278, 2017.
Article in Portuguese, English | MEDLINE | ID: mdl-28977101

ABSTRACT

OBJECTIVE: This report aimed to describe the outcomes of the patients with severe H1N1 associated acute respiratory distress syndrome who were treated with extracorporeal membrane oxygenation therapy. METHODS: This retrospective review analyzed a single-center cohort of adult patients with H1N1-related acute respiratory distress syndrome who were managed with veno-venous extracorporeal membrane oxygenation during the winter of 2013/2014. RESULTS: A total of 10 patients received veno-venous extracorporeal membrane oxygenation for H1N1 influenza between January 2013 and March 2014. Seven patients were transferred to our center for extracorporeal membrane oxygenation consideration (all within 72 hours of initiating mechanical ventilation). The median patient age was forty years, and 30% were female. The median arterial oxygen partial pressure to fraction of inspired oxygen ratio was 62.5, and the median RESP score was 6. Three patients received inhaled nitric oxide, and four patients were proned as rescue therapy before extracorporeal membrane oxygenation was initiated. The median duration of mechanical ventilation was twenty-two days (range, 14 - 32). The median length of stay in the intensive care unit was twenty-seven days (range, 14 - 39). The median hospital length of stay was 29.1 days (range, 16.0 - 46.9). Minor bleeding complications occurred in 6 of 10 patients. Eight of the ten patients survived to hospital discharge. CONCLUSION: The survivors were relatively young and discharged with good functional status (i.e., enhancing quality-adjusted life-years-saved). Our experience shows that even a relatively new extracorporeal membrane oxygenation program can play an important role in that capacity and provide excellent outcomes for the sickest patients.


OBJETIVO: Descrever os desfechos de pacientes com síndrome do desconforto respiratório agudo associada à influenza subtipo H1N1 grave tratados com oxigenação por membrana extracorpórea. MÉTODOS: Trata-se de revisão retrospectiva de uma coorte de pacientes oriunda de um único centro, constituída por adultos com síndrome do desconforto respiratório agudo relacionada com influenza subtipo H1N1 e tratados com oxigenação venovenosa por membrana extracorpórea durante a temporada de inverno no hemisfério norte de 2013/2014. RESULTADOS: Dez pacientes receberam oxigenação venovenosa por membrana extracorpórea para tratamento de influenza subtipo H1N1 entre janeiro de 2013 e março de 2014. Sete deles foram transferidos para nosso centro visando à utilização de oxigenação por membrana extracorpórea dentro de um período de 72 horas após o início da ventilação mecânica. A idade mediana foi de 40 anos, sendo 30% dos pacientes do sexo feminino. O valor mediano da proporção entre pressão parcial de oxigênio e fração inspirada de oxigênio foi de 62,5, sendo o escore RESP mediano de 6. Três pacientes receberam inalação de óxido nítrico e quatro utilizaram posição prona como tratamento de resgate antes de ser iniciada a oxigenação por membrana extracorpórea. A duração mediana da ventilação mecânica foi de 22 dias (variação de 14 - 32). O tempo mediano de permanência na unidade de terapia intensiva foi de 27 dias (variação de 14 - 39). O tempo mediano de permanência no hospital foi de 29,1 dias (variação de 16,0 - 46,9). Ocorreram complicações não importantes de sangramento em seis dos dez pacientes. Oito dos dez pacientes sobreviveram até a alta hospitalar. CONCLUSÃO: Os sobreviventes eram relativamente jovens e tiveram alta com boas condições funcionais, o que salienta os anos de vida ajustados pela qualidade que foram salvos. Nossa experiência demonstra que mesmo um programa ainda relativamente novo de oxigenação por membrana extracorpórea pode desempenhar um papel importante, e proporcionar resultados excelentes para os pacientes mais graves.


Subject(s)
Extracorporeal Membrane Oxygenation/methods , Influenza, Human/complications , Pneumonia, Viral/complications , Respiratory Distress Syndrome/therapy , Adult , Aged , Blood Gas Analysis , Female , Humans , Influenza A Virus, H1N1 Subtype/isolation & purification , Influenza, Human/therapy , Intensive Care Units , Length of Stay , Male , Middle Aged , Pneumonia, Viral/therapy , Quality-Adjusted Life Years , Respiration, Artificial , Respiratory Distress Syndrome/etiology , Retrospective Studies , Treatment Outcome
20.
Pneumonia (Nathan) ; 8: 23, 2016.
Article in English | MEDLINE | ID: mdl-28702302

ABSTRACT

The accurate diagnosis of tuberculosis (TB) in children remains challenging. A myriad of common childhood diseases can present with similar symptoms and signs, and differentiating between exposure and infection, as well as infection and disease can be problematic. The paucibacillary nature of childhood TB complicates bacteriological confirmation and specimen collection is difficult. In most instances intrathoracic TB remains a clinical diagnosis. TB infection and disease represent a dynamic continuum from TB exposure with/without infection, to subclinical/incipient disease, to non-severe and severe disease. The clinical spectrum of intrathoracic TB in children is broad, and the classification of clinical, radiological, endoscopic, and laboratory findings into recognized clinical syndromes allows a more refined diagnostic approach in order to minimize both under- and over-diagnosis. Bacteriological confirmation can be improved significantly by collecting multiple, high-quality specimens from the most appropriate source. Mycobacterial testing should include traditional smear microscopy and culture, as well as nucleic acid amplification testing. A systematic approach to the child with recent exposure to TB, or with clinical and radiological findings compatible with this diagnosis, should allow pragmatic classification as TB exposure, infection, or disease to facilitate timely and appropriate management. It is important to also assess risk factors for TB disease progression and to undertake follow-up evaluations to monitor treatment response and ongoing evidence supporting a TB, or alternative, diagnosis.

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