Clinical short communication| Volume 425, 117447, June 15, 2021

Download started.


Tuberculosis in Myasthenia Gravis patients on immunosuppressive therapy in a high-risk area: Implications for preventative therapy

Published:April 13, 2021DOI:


      • MG patients on immune therapy are not at higher risk of developing tuberculosis.
      • Consider tuberculosis preventative therapy when higher prednisone doses are used.
      • Consider tuberculosis preventative therapy in those with scarring on chest X-ray.


      Data regarding the risk of tuberculosis (TB) in myasthenia gravis (MG) patients receiving immunosuppressive therapy is limited, and the benefit of TB preventative therapy in these patients is uncertain. We audited observational data collected at an MG clinic in South Africa over a ~ 10-year period, of cases who received immunosuppressive therapy. The total time that the cohort was at risk (patient-years) was used as the denominator to calculate TB incidence after immunosuppressive therapy initiation. Multivariate logistic regression analysis was performed to identify differences between patients who did, and those who did not, develop TB. Of 480 cases, only two received TB preventative therapy when starting immunotherapy. Seventeen of 282 (6%) patients tested, were HIV-infected. With a median follow-up of 3.6 years (interquartile range 1;7.5), 13 (3%) patients (all HIV-uninfected) developed TB (38% within 12 months of starting immunosuppressive therapy). The incidence rate of TB in the study population (≤401/100000 person-years) was not higher than that for the hospital's catchment area during the same period (>500/100000 population). The maximum dose of prescribed prednisone was higher in patients who developed TB compared to those who did not (median: 0.6 mg/kg/day vs 0.4; 0.002); Odds ratio for TB increased 1.26-fold for every 0.1 mg/kg/day increase in maximum dose (p = 0.001). In our TB endemic setting, receiving immunosuppressive therapy was not associated with excess TB in MG patients. Preventative therapy may be considered in those who are at greatest risk of developing TB and receiving high-dose prednisone.



      TB (tuberculosis), PT (preventative therapy), MG (myasthenia gravis), HIV (human immune deficiency virus), PET-CT (positron emission tomography-computerized tomography)
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Journal of the Neurological Sciences
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • World Health Organization
        Global Tuberculosis Report 2020, Geneva.
        • Wood R.
        • Liang H.
        • Wu H.
        • Middelkoop K.
        • Oni T.
        • Molebogeneg R.
        Changing prevalence of TB infection with increasing age in high TB burden townships in South Africa.
        Int. J. Tuberc. Lung. Dis. 2010; 14 (PMID: 1932–6203): 406-412
        • Dheda K.
        • Barry C.E.
        • Maartens G.
        Lancet. 2016; 387: 1211-1226
        • Cobelens F.
        • Kik S.
        • Esmail H.
        • Cirillo D.M.
        • Lienhardt C.
        • Matteelli A.
        From latent to patent: rethinking prediction of tuberculosis.
        Lancet Respir. Med. 2017; 5: 243-244
        • Sterling T.R.
        • Njie G.
        • Zenner D.
        • Cohn D.L.
        • Reves R.
        • Ahmed A.
        • et al.
        Guidelines for the treatment of latent tuberculosis infection: recommendations from the National Tuberculosis Controllers Association and CDC, 2020.
        Am. J. Transplant. 2020; 20: 1196-1206
        • Horsburgh C.R.
        • Rubin E.J.
        Latent tuberculosis infection in the United States.
        N. Engl. J. Med. 2011; 364: 1441-1448
        • Heckmann J.M.
        • Rawoot A.
        • Bateman K.
        • Renison R.
        • Badri M.
        A single-blinded trial of methotrexate versus azathioprine as steroid-sparing agents in generalized myasthenia gravis.
        BMC Neurol. 2011; 11: 1-9
        • Huda S.
        • Woodhall M.R.
        • Vincent A.
        • Heckmann J.M.
        Characteristics of acetylcholine-receptor-antibody–negative myasthenia gravis in a south African cohort.
        Muscle Nerve. 2016; 54: 1023-1029
        • Wolfe G.I.
        • Kaminski H.J.
        • Aban I.B.
        • Minisman G.
        • Kuo H.-C.
        • Marx A.
        • et al.
        Randomized trial of Thymectomy in myasthenia gravis.
        N. Engl. J. Med. 2016; 375: 511-522
        • Heckmann J.M.
        • Owen E.P.
        • Little F.
        Myasthenia gravis in south Africans: racial differences in clinical manifestations.
        Neuromuscul. Disord. 2007; 17: 929-934
        • Europa T.A.
        • Nel M.
        • Heckmann J.M.
        Myasthenic ophthalmoparesis: time to resolution after initiating immune therapies.
        Muscle Nerve. 2018; 58: 542-549
        • Jaretzki A.
        • Barohn R.J.
        • Ernstoff R.M.
        • Kaminski H.J.
        • Keesey J.C.
        • Penn A.S.
        • et al.
        Myasthenia gravis: recommendations for clinical research standards.
        Neurology. 2000; 70: 16-23
        • King G.
        • Zeng L.
        Logistic regression in rare events data.
        J. Stat. Softw. 2003; 8: 137-163
        • Guns M.
        • Vanacker V.
        Logistic regression applied to natural hazards: rare event logistic regression with replications.
        Nat. Hazards Earth Syst. Sci. 2012; 12: 1937-1947
        • Imai K.
        • King G.
        • Lau O.
        Toward a common framework for statistical analysis and development.
        J. Comput. Graph. Stat. 2008; 17: 892-913
        • Choirat C.
        • Gandrud C.
        • Honaker J.
        • Kosuke I.
        • King G.
        • Lau O.
        Relogit: Rare Events Logistic Regression for Dichotomous Dependent Variables, “Zelig Everyone’s Stat. Software.”.
        2013: 102-103
        • Sahai H.
        • Khurshid A.
        Confidence intervals for the mean of a Poisson distribution: a review.
        Biom. J. 1993; 35: 857-867
        • Heckmann J.M.
        • Marais S.
        Management issues in myasthenia gravis patients living with HIV: a case series and literature review.
        Front. Neurol. 2020; 11: 1-6
        • Keane J.
        • Gershon S.
        • Wise R.P.
        • Mirabile-Levens E.
        • Kasznica J.
        • Schwieterman W.D.
        • et al.
        Tuberculosis associated with infliximab, a tumor necrosis factor α–neutralizing agent.
        N. Engl. J. Med. 2001; 345: 1098-1104
        • Malherbe S.T.
        • Shenai S.
        • Ronacher K.
        • Loxton A.G.
        • Dolganov G.
        • Kriel M.
        • et al.
        Persisting PET-CT lesion activity and M. tuberculosis mRNA after pulmonary tuberculosis cure.
        Nat. Med. 2016; 22: 1094-1100
        • Steinbrück P.
        • Dănkovã D.
        • Edwards L.B.
        • Doster B.
        • Livesay V.T.
        Tuberculosis risk in persons with “fibrotic” x-ray lesions.
        Bull. Int. Union Tuberc. 1972; 47 (PMID: 5077112): 135-159
        • Fox G.J.
        • Dobler C.C.
        • Marais B.J.
        • Denholm J.T.
        Preventative therapy for latent tuberculosis infection- the promise and the chalennges.
        Int. J. Infect. Dis. 2017; 56: 68-76
        • Sester M.
        • Kampmann B.
        What defines latent infection with Mycobacterium tuberculosis in patients with autoimmune disease?.
        Thorax. 2016; 71: 3-4
        • Narisimhan P.
        • Wood J.
        • MacIntyre C.R.
        • Mathai D.
        Pulm. Med. 2013; : 1-11
        • van der Watt J.J.
        • Harrison T.B.
        • Benatar M.
        • Heckmann J.M.
        Polyneuropathy, anti-tuberculous treatment and the role of pyridoxine in the HIV/AIDS era: a systematic review.
        Int. J. Tuberc. Lung. Dis. 2011; 15: 722-728