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Article ; Online: Six degrees of separation: use of social network analysis to better understand outbreaks of nosocomial transmission of extensively drug-resistant tuberculosis.

Dharmadhikari, Ashwin S

2012 Volume 207, Issue 1, Page(s) 1–3

MeSH term(s)	Antitubercular Agents/therapeutic use ; Cross Infection/transmission ; Extensively Drug-Resistant Tuberculosis/transmission ; Female ; HIV Infections/complications ; Humans ; Male ; Mycobacterium tuberculosis/classification
Chemical Substances	Antitubercular Agents
Language	English
Publishing date	2012-11-19
Publishing country	United States
Document type	Editorial ; Research Support, N.I.H., Extramural ; Comment
ZDB-ID	3019-3
ISSN	1537-6613 ; 0022-1899
ISSN (online)	1537-6613
ISSN	0022-1899
DOI	10.1093/infdis/jis634
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Article ; Online: Serial acid fast bacilli smear and culture conversion rates over 26 weeks in a cohort of 93 sputum culture–positive tuberculosis (TB).

Dharmadhikari, Ashwin S / Nardell, Edward

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America

2011 Volume 52, Issue 4, Page(s) 554–556

MeSH term(s)	Antitubercular Agents/administration & dosage ; Bacteriological Techniques/methods ; Humans ; Microscopy/methods ; Mycobacterium tuberculosis/isolation & purification ; Sputum/microbiology ; Treatment Outcome ; Tuberculosis/diagnosis ; Tuberculosis/drug therapy
Chemical Substances	Antitubercular Agents
Language	English
Publishing date	2011-01-22
Publishing country	United States
Document type	Comment ; Letter
ZDB-ID	1099781-7
ISSN	1537-6591 ; 1058-4838
ISSN (online)	1537-6591
ISSN	1058-4838
DOI	10.1093/cid/ciq182
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Article ; Online: Meta-Analysis of the Usefulness of Therapeutic Hypothermia After Cardiac Arrest.

Rout, Amit / Singh, Sahib / Sarkar, Sauradeep / Munawar, Immad / Garg, Aakash / D'Adamo, Christopher R / Tantry, Udaya S / Dharmadhikari, Ashwin / Gurbel, Paul A

The American journal of cardiology

2020 Volume 133, Page(s) 48–53

Abstract: Despite current guidelines recommending therapeutic hypothermia (TH) for post cardiac arrest comatose patient, its use remains limited. Randomized controlled trials (RCTs) have also reported conflicting results on the efficacy of TH. Therefore, we ... ...

Abstract	Despite current guidelines recommending therapeutic hypothermia (TH) for post cardiac arrest comatose patient, its use remains limited. Randomized controlled trials (RCTs) have also reported conflicting results on the efficacy of TH. Therefore, we conducted an updated meta-analysis to evaluate the effect of TH in post cardiac arrest patients. We searched electronic databases for RCTs comparing TH (32°C to 34°C) with controls (normothermia or temperature ≥36°C) in comatose patients who sustained cardiac arrest. Mortality and neurological outcomes were the outcomes of interest. We used random effect meta-analysis to estimate risk ratio (RR) with 95% confidence interval (CI). Eight RCTs with a total of 2,026 patients (TH n = 1,025 and control n = 1,001) were included. Irrespective of initial rhythm, TH was associated with significant reduction in poor neurological outcomes (RR 0.87, 95% CI 0.77 to 0.98; p = 0.02) without any difference in mortality (RR 0.94, 95% CI 0.85 to 1.03; p = 0.17). In patients with initial shockable rhythm compared with control, TH reduced mortality (RR 0.85, 95% CI 0.73 to 0.99; p = 0.04) and poor neurological outcomes (RR 0.81, 95% CI 0.67 to 0.99; p = 0.04). Whereas, in patients with initial nonshockable rhythm, TH was associated with decreased poor neurological outcomes after excluding one trial (RR 0.95 95% CI 0.91 to 1.00; p = 0.05). In conclusion, TH is associated with improved neurological outcomes in all patients sustaining cardiac arrest and with decreased mortality in patients with initial shockable rhythm.
MeSH term(s)	Coma/etiology ; Coma/therapy ; Heart Arrest/complications ; Heart Arrest/therapy ; Humans ; Hypothermia, Induced
Language	English
Publishing date	2020-07-24
Publishing country	United States
Document type	Journal Article ; Meta-Analysis ; Systematic Review
ZDB-ID	80014-4
ISSN	1879-1913 ; 0002-9149
ISSN (online)	1879-1913
ISSN	0002-9149
DOI	10.1016/j.amjcard.2020.07.038
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Article ; Online: What animal models teach humans about tuberculosis.

Dharmadhikari, Ashwin S / Nardell, Edward A

American journal of respiratory cell and molecular biology

2008 Volume 39, Issue 5, Page(s) 503–508

Abstract: Animal models have become standard tools for the study of a wide array of human infectious diseases. Although there are no true animal reservoirs for Mycobacterium tuberculosis, many different animal species are susceptible to infection with this ... ...

Abstract	Animal models have become standard tools for the study of a wide array of human infectious diseases. Although there are no true animal reservoirs for Mycobacterium tuberculosis, many different animal species are susceptible to infection with this organism and have served as valuable tools for the study of tuberculosis (TB). The most commonly used experimental animal models of TB are the mouse, rabbit, and guinea pig. Although substantial differences in TB susceptibility and disease manifestations exist between these species, they have contributed significantly to the understanding of TB immunopathogenesis, host genetic influence on infection, efficacy of antimicrobial therapy, and host/pathogen interactions that determine the outcome or severity of infection. Among the three species, mice are relatively resistant to TB infection, followed by rabbits and then guinea pigs, which are extremely vulnerable to infection. Mice are most often used in experiments on immune responses to TB infection and drug regimens against TB. Rabbits, unlike the other two animal models, develop cavitary TB and offer a means to study the factors leading to this form of the disease. Guinea pigs, due to their high susceptibility to infection, have been ideal for studies on airborne transmission and vaccine efficacy. In addition to these three species, TB research has occasionally involved nonhuman primates and cattle models. Current concepts in TB pathogenesis have also been derived from animal studies involving experimentally induced infections with related mycobacteria (e.g., Mycobacterium bovis) whose manifestations in select animal hosts mimic human TB.
MeSH term(s)	Animals ; Disease Models, Animal ; Humans ; Tuberculosis/immunology ; Tuberculosis/metabolism ; Tuberculosis/transmission
Language	English
Publishing date	2008-06-12
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1025960-0
ISSN	1535-4989 ; 1044-1549
ISSN (online)	1535-4989
ISSN	1044-1549
DOI	10.1165/rcmb.2008-0154TR
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Article ; Online: Phase I, single-dose, dose-escalating study of inhaled dry powder capreomycin: a new approach to therapy of drug-resistant tuberculosis.

Dharmadhikari, Ashwin S / Kabadi, Mohan / Gerety, Bob / Hickey, Anthony J / Fourie, P Bernard / Nardell, Edward

Antimicrobial agents and chemotherapy

2013 Volume 57, Issue 6, Page(s) 2613–2619

Abstract: Multidrug-resistant tuberculosis (MDR-TB) threatens global TB control. The lengthy treatment includes one of the injectable drugs kanamycin, amikacin, and capreomycin, usually for the first 6 months. These drugs have potentially serious toxicities, and ... ...

Abstract	Multidrug-resistant tuberculosis (MDR-TB) threatens global TB control. The lengthy treatment includes one of the injectable drugs kanamycin, amikacin, and capreomycin, usually for the first 6 months. These drugs have potentially serious toxicities, and when given as intramuscular injections, dosing can be painful. Advances in particulate drug delivery have led to the formulation of capreomycin as the first antituberculosis drug available as a microparticle dry powder for inhalation and clinical study. Delivery by aerosol may result in successful treatment with lower doses. Here we report a phase I, single-dose, dose-escalating study aimed at demonstrating safety and tolerability in healthy subjects and measuring pharmacokinetic (PK) parameters. Twenty healthy adults (n = 5 per group) were recruited to self-administer a single dose of inhaled dry powder capreomycin (25-mg, 75-mg, 150-mg, or 300-mg nominal dose) using a simple, handheld delivery device. Inhalations were well tolerated by all subjects. The most common adverse event was mild to moderate transient cough, in five subjects. There were no changes in lung function, audiometry, or laboratory parameters. Capreomycin was rapidly absorbed after inhalation. Systemic concentrations were detected in each dose group within 20 min. Peak and mean plasma concentrations of capreomycin were dose proportional. Serum concentrations exceeded 2 μg/ml (MIC for Mycobacterium tuberculosis) following the highest dose; the half-life (t1/2) was 4.8 ± 1.0 h. A novel inhaled microparticle dry powder formulation of capreomycin was well tolerated. A single 300-mg dose rapidly achieved serum drug concentrations above the MIC for Mycobacterium tuberculosis, suggesting the potential of inhaled therapy as part of an MDR-TB treatment regimen.
MeSH term(s)	Administration, Inhalation ; Adolescent ; Adult ; Antitubercular Agents/administration & dosage ; Antitubercular Agents/adverse effects ; Antitubercular Agents/pharmacokinetics ; Antitubercular Agents/therapeutic use ; Capreomycin/administration & dosage ; Capreomycin/adverse effects ; Capreomycin/pharmacokinetics ; Capreomycin/therapeutic use ; Drug Delivery Systems ; Dry Powder Inhalers ; Female ; Humans ; Male ; Middle Aged ; Mycobacterium tuberculosis/drug effects ; Powders/administration & dosage ; Treatment Outcome ; Tuberculosis, Multidrug-Resistant/drug therapy ; Tuberculosis, Multidrug-Resistant/microbiology ; Young Adult
Chemical Substances	Antitubercular Agents ; Powders ; Capreomycin (11003-38-6)
Language	English
Publishing date	2013-03-25
Publishing country	United States
Document type	Clinical Trial, Phase I ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	217602-6
ISSN	1098-6596 ; 0066-4804
ISSN (online)	1098-6596
ISSN	0066-4804
DOI	10.1128/AAC.02346-12
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Article ; Online: Tuberculosis and HIV: a global menace exacerbated via sex trafficking.

Dharmadhikari, Ashwin S / Gupta, Jhumka / Decker, Michele R / Raj, Anita / Silverman, Jay G

International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases

2009 Volume 13, Issue 5, Page(s) 543–546

Abstract: Objective: Global tuberculosis (TB) elimination requires recognition and management of TB/HIV co-infected individuals, including those in marginalized and/or understudied populations. We sought to examine the prevalence of TB among repatriated sex ... ...

Abstract	Objective: Global tuberculosis (TB) elimination requires recognition and management of TB/HIV co-infected individuals, including those in marginalized and/or understudied populations. We sought to examine the prevalence of TB among repatriated sex trafficked Nepalese girls and women in whom a high HIV prevalence was previously reported. Methods: We reviewed case records for cases of TB among 287 sex trafficked girls and women repatriated to a single, rehabilitation non-governmental organization in Kathmandu, Nepal between 1997 and 2005. TB case detection was based on sputum smear results for acid-fast bacilli, radiographs, or histories, as reported in medical tests and/or case records. Results: There were 17 cases of TB that developed after rescue within the sample of girls and women who were aged 7-32 years when they were trafficked. The majority of cases (70%) were likely pulmonary TB. Nearly 9 in 10 individuals who developed TB were HIV co-infected. Conclusions: Although preliminary in nature, our findings highlight the need for more comprehensive exploration of TB prevalence within sex trafficked populations, particularly in light of the large numbers of individuals who are sex trafficked in South Asia, the high prevalence of HIV documented in this group, and the risk of transmission of TB from and to others.
MeSH term(s)	AIDS-Related Opportunistic Infections/diagnosis ; AIDS-Related Opportunistic Infections/epidemiology ; AIDS-Related Opportunistic Infections/transmission ; Adolescent ; Adult ; Child ; Female ; HIV Infections/complications ; HIV Infections/diagnosis ; HIV Infections/epidemiology ; HIV Infections/transmission ; HIV-1 ; Humans ; Mycobacterium tuberculosis/isolation & purification ; Nepal/epidemiology ; Prevalence ; Sex Offenses ; Sputum/microbiology ; Tuberculosis/complications ; Tuberculosis/diagnosis ; Tuberculosis/epidemiology ; Tuberculosis/transmission ; Tuberculosis, Pulmonary/diagnosis ; Tuberculosis, Pulmonary/epidemiology ; Tuberculosis, Pulmonary/microbiology ; Women's Health ; Young Adult
Language	English
Publishing date	2009-01-18
Publishing country	Canada
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	1331197-9
ISSN	1878-3511 ; 1201-9712
ISSN (online)	1878-3511
ISSN	1201-9712
DOI	10.1016/j.ijid.2008.11.010
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Article: Aspiring to zero tuberculosis deaths among southern Africa's miners: is there a way forward?

Dharmadhikari, Ashwin / Smith, Jonathan / Nardell, Edward / Churchyard, Gavin / Keshavjee, Salmaan

International journal of health services : planning, administration, evaluation

2013 Volume 43, Issue 4, Page(s) 651–664

Abstract: Tuberculosis notification rates among South African miners range from 4,000 to 7,000 per 100,000 people. These rates far exceed national tuberculosis notification rates for the general population. Tuberculosis mortality also surpasses deaths caused by ... ...

Abstract	Tuberculosis notification rates among South African miners range from 4,000 to 7,000 per 100,000 people. These rates far exceed national tuberculosis notification rates for the general population. Tuberculosis mortality also surpasses deaths caused by mining accidents. These extraordinarily high rates of disease are unambiguously linked to a series of contributing factors, including exposure to silica dust, HIV infection, and poor working and living conditions. We argue that the only way to stop the transmission of this airborne disease is to treat the mine and its living quarters as one should any other congregate setting with individuals who have high rates of infection with drug-susceptible and drug-resistant strains of tuberculosis. This means implementing interventions that have been demonstrated to stop the spread of tuberculosis over the last 60 years: immediate treatment of active tuberculosis, concurrent treatment of latent tuberculosis disease to reduce the burden of active cases, and appropriate management of patients infected with HIV. Because tuberculosis is also a social disease, biomedical interventions must be coupled with improved living and working conditions. Achieving zero deaths from tuberculosis in the mines is possible if a clear commitment is made to a strategy that recognizes and ameliorates the biological and social antecedents to this epidemic.
MeSH term(s)	Africa, Southern/epidemiology ; Comorbidity ; Disease Progression ; Early Diagnosis ; HIV Infections/drug therapy ; HIV Infections/epidemiology ; HIV Infections/immunology ; Housing/standards ; Housing/statistics & numerical data ; Humans ; Immunocompromised Host ; Latent Tuberculosis/diagnosis ; Latent Tuberculosis/drug therapy ; Latent Tuberculosis/epidemiology ; Male ; Mining/manpower ; Mining/standards ; Mining/statistics & numerical data ; Occupational Diseases/etiology ; Occupational Diseases/mortality ; Occupational Diseases/prevention & control ; Occupational Health Services/standards ; Occupational Health Services/trends ; Secondary Prevention ; Silicosis/epidemiology ; Silicosis/etiology ; Silicosis/immunology ; Social Conditions/statistics & numerical data ; Tuberculosis/diagnosis ; Tuberculosis/mortality ; Tuberculosis/prevention & control ; Tuberculosis, Multidrug-Resistant/diagnosis ; Tuberculosis, Multidrug-Resistant/drug therapy ; Tuberculosis, Multidrug-Resistant/prevention & control
Language	English
Publishing date	2013
Publishing country	United States
Document type	Journal Article
ZDB-ID	184936-0
ISSN	1541-4469 ; 0020-7314
ISSN (online)	1541-4469
ISSN	0020-7314
DOI	10.2190/HS.43.4.d
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Article ; Online: Institutional Tuberculosis Transmission. Controlled Trial of Upper Room Ultraviolet Air Disinfection: A Basis for New Dosing Guidelines.

Mphaphlele, Matsie / Dharmadhikari, Ashwin S / Jensen, Paul A / Rudnick, Stephen N / van Reenen, Tobias H / Pagano, Marcello A / Leuschner, Wilhelm / Sears, Tim A / Milonova, Sonya P / van der Walt, Martie / Stoltz, Anton C / Weyer, Karin / Nardell, Edward A

American journal of respiratory and critical care medicine

2015 Volume 192, Issue 4, Page(s) 477–484

Abstract: Rationale: Transmission is driving the global tuberculosis epidemic, especially in congregate settings. Worldwide, natural ventilation is the most common means of air disinfection, but it is inherently unreliable and of limited use in cold climates. ... ...

Abstract	Rationale: Transmission is driving the global tuberculosis epidemic, especially in congregate settings. Worldwide, natural ventilation is the most common means of air disinfection, but it is inherently unreliable and of limited use in cold climates. Upper room germicidal ultraviolet (UV) air disinfection with air mixing has been shown to be highly effective, but improved evidence-based dosing guidelines are needed. Objectives: To test the efficacy of upper room germicidal air disinfection with air mixing to reduce tuberculosis transmission under real hospital conditions, and to define the application parameters responsible as a basis for proposed new dosing guidelines. Methods: Over an exposure period of 7 months, 90 guinea pigs breathed only untreated exhaust ward air, and another 90 guinea pigs breathed only air from the same six-bed tuberculosis ward on alternate days when upper room germicidal air disinfection was turned on throughout the ward. Measurements and main results: The tuberculin skin test conversion rates (>6 mm) of the two chambers were compared. The hazard ratio for guinea pigs in the control chamber converting their skin test to positive was 4.9 (95% confidence interval, 2.8-8.6), with an efficacy of approximately 80%. Conclusions: Upper room germicidal UV air disinfection with air mixing was highly effective in reducing tuberculosis transmission under hospital conditions. These data support using either a total fixture output (rather than electrical or UV lamp wattage) of 15-20 mW/m(3) total room volume, or an average whole-room UV irradiance (fluence rate) of 5-7 μW/cm(2), calculated by a lighting computer-assisted design program modified for UV use.
MeSH term(s)	Animals ; Disinfection ; Guinea Pigs ; Infection Control/methods ; Tuberculin Test ; Tuberculosis/prevention & control ; Tuberculosis/transmission ; Ultraviolet Rays ; Ventilation
Language	English
Publishing date	2015-04-30
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	1180953-x
ISSN	1535-4970 ; 0003-0805 ; 1073-449X
ISSN (online)	1535-4970
ISSN	0003-0805 ; 1073-449X
DOI	10.1164/rccm.201501-0060OC
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Article: Disseminated histoplasmosis.

Tom, Sabrina / Dharmadhikari, Ashwin

American journal of hematology

2002 Volume 71, Issue 3, Page(s) 223

MeSH term(s)	Blood/microbiology ; Histoplasma/isolation & purification ; Histoplasmosis/blood ; Histoplasmosis/microbiology ; Histoplasmosis/pathology ; Humans ; Male ; Middle Aged
Language	English
Publishing date	2002-11
Publishing country	United States
Document type	Case Reports ; Journal Article
ZDB-ID	196767-8
ISSN	1096-8652 ; 0361-8609
ISSN (online)	1096-8652
ISSN	0361-8609
DOI	10.1002/ajh.10197
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Article ; Online: Surgical face masks worn by patients with multidrug-resistant tuberculosis: impact on infectivity of air on a hospital ward.

Dharmadhikari, Ashwin S / Mphahlele, Matsie / Stoltz, Anton / Venter, Kobus / Mathebula, Rirhandzu / Masotla, Thabiso / Lubbe, Willem / Pagano, Marcello / First, Melvin / Jensen, Paul A / van der Walt, Martie / Nardell, Edward A

American journal of respiratory and critical care medicine

2012 Volume 185, Issue 10, Page(s) 1104–1109

Abstract: Rationale: Drug-resistant tuberculosis transmission in hospitals threatens staff and patient health. Surgical face masks used by patients with tuberculosis (TB) are believed to reduce transmission but have not been rigorously tested.: Objectives: We ... ...

Abstract	Rationale: Drug-resistant tuberculosis transmission in hospitals threatens staff and patient health. Surgical face masks used by patients with tuberculosis (TB) are believed to reduce transmission but have not been rigorously tested. Objectives: We sought to quantify the efficacy of surgical face masks when worn by patients with multidrug-resistant TB (MDR-TB). Methods: Over 3 months, 17 patients with pulmonary MDR-TB occupied an MDR-TB ward in South Africa and wore face masks on alternate days. Ward air was exhausted to two identical chambers, each housing 90 pathogen-free guinea pigs that breathed ward air either when patients wore surgical face masks (intervention group) or when patients did not wear masks (control group). Efficacy was based on differences in guinea pig infections in each chamber. Measurements and main results: Sixty-nine of 90 control guinea pigs (76.6%; 95% confidence interval [CI], 68-85%) became infected, compared with 36 of 90 intervention guinea pigs (40%; 95% CI, 31-51%), representing a 56% (95% CI, 33-70.5%) decreased risk of TB transmission when patients used masks. Conclusions: Surgical face masks on patients with MDR-TB significantly reduced transmission and offer an adjunct measure for reducing TB transmission from infectious patients.
MeSH term(s)	Adult ; Animals ; Female ; Guinea Pigs ; Humans ; Infection Control/instrumentation ; Infectious Disease Transmission, Patient-to-Professional/prevention & control ; Male ; Masks ; Middle Aged ; Prospective Studies ; Treatment Outcome ; Tuberculosis, Multidrug-Resistant/prevention & control ; Tuberculosis, Multidrug-Resistant/transmission ; Tuberculosis, Pulmonary/prevention & control ; Tuberculosis, Pulmonary/transmission
Language	English
Publishing date	2012-02-09
Publishing country	United States
Document type	Controlled Clinical Trial ; Journal Article ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	1180953-x
ISSN	1535-4970 ; 0003-0805 ; 1073-449X
ISSN (online)	1535-4970
ISSN	0003-0805 ; 1073-449X
DOI	10.1164/rccm.201107-1190OC
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