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Mycobacterium tuberculosis (TB) remains a major cause of death worldwide, with central nervous system (CNS) involvement associated with higher mortality.[[1–2]] Paradoxical reactions are rare complications of treatment that are challenging to manage. We describe a patient with neurotuberculosis who developed a fatal paradoxical reaction whilst receiving anti-TB treatment, which led to difficult issues regarding palliative care of a communicable disease.

Case report

A 44-year-old Thai woman living in New Zealand for over 10 years presented to Wellington Hospital with two-week history of headaches, abdominal pain and fevers. At presentation, she was found to have anisocoria, mild left hemiplegia, and ataxia but no confusion. Her medical history was unremarkable, and the initial diagnosis was thought to be an intracerebral bleed. A HIV test was negative. Chest X-ray and brain computerised tomography (CT) were initially unremarkable, but cerebrospinal fluid (CSF) analysis showed 189x10[[6]] white blood cells/L (67% mononuclear cells), an elevated protein of 5.08g/L and low glucose 2.4mmol/L. Initial opening pressures were unfortunately not completed on the first lumbar puncture (LP) but were subsequently measured at 50mmHg. Standard oral four-drug anti-TB treatment with dexamethasone 0.4mg/kg was commenced after acid-fast bacilli detection in the CSF.[[ 3]] Fully susceptible MTB was subsequently cultured in the CSF and sputum.

Her cognition remained normal initially but on day three she became minimally responsive (GCS 8/15) with persistent fevers and new right oculomotor nerve palsy. Hydrocephalus was demonstrated on CT scan, requiring placement of an external ventricular drain. Subsequent magnetic resonance imaging (MRI) revealed leptomeningitis, multiple tuberculomata (left frontoparietal, right temporal, left cerebellar, right medulla), vasculitic infarcts and miliary lung involvement. There were no other pathogens identified. She also developed seizures and was started on levetiracetam. A paradoxical reaction was diagnosed which was managed with five-day course of pulse 1g intravenous methylprednisolone, followed by 5mg/kg infliximab infusions.[[4]] A follow-up CSF culture was negative for growth of MTB four weeks later.

There was no significant improvement in clinical status despite four weeks of anti-TB treatment and management of the paradoxical reaction of the CNS; the patient remained bed bound, minimally responsive, and reliant on nasogastric (NG) tube for feeding and administration of medications. She was fully dependent on nursing care. It was felt that a transition to a palliative approach would be appropriate. Most of her family were overseas with international travel not being possible due to COVID-19 restrictions. Complex family meetings regarding prognosis and withdrawal of treatment were held over video conference with translators.

Withdrawal of treatment decisions were further affected by the communicable nature of TB. A conservative approach was taken for the duration of TB treatment because of the uncertainty about how long she would remain alive, and due to the need for placement in a long-term care facility. Four months of anti-TB treatment had been given, and the infectious disease team and Medical Officer of Health agreed that treatment had been sufficient to no longer pose a transmission threat even if she survived for several weeks—and the NG tube was therefore removed. Nine days following cessation of treatment, the patient passed away in residential care.

View Figure 1.

Discussion

This case demonstrates how severe neurotuberculosis can be at presentation, and of its associated complications. Quantifying and communicating prognosis to patients and family members at baseline may be difficult. This can be guided by bedside scores such as MASH-P (baseline Modified Barthel’s index (M), age (A), stage of TB meningitis (S), hydrocephalus (H), papilledema (P)); this patient had an initial score of 4/10, carrying a 10% predicted six-month mortality.[[ 4]] Paradoxical reactions are often life-threatening, especially with CNS involvement, and remain rare with only a small number of case studies documenting the use of infliximab.[[5]] This inflammatory response occurs in response to dying mycobacteria and can present with fever, hypoxia, lymphadenopathy, and new organ involvement. Tumour necrosis factor alpha (TNF-α) is central to the host response to TB infection. Infliximab is a monoclonal antibody to TNF-α and acts to prevent further formation without the long-term toxicity of systemic corticosteroids.[[6]] Unfortunately, the patient did not significantly recover at any stage despite anti-TB treatment and aggressive management of the paradoxical reaction.

The management of this patient also highlights the complexity that can arise when applying a palliative model of care to communicable disease and differing cultural perspectives. Given the uncertainty of a slow neurological recovery and the slow decline, it was difficult for her family to come to terms with a transition to palliative care, and for the medical team to ascertain the urgency for end-of-life planning. Buddhism is the predominant world view in Thailand, and it is very important within Thai culture for family to be with the patient during death to help ensure a peaceful passing.[[8]] For significant family members to be separated with no chance of visiting, and during a time when active treatment was withdrawn, was distressing to all involved. Removal of an NG tube is routine in terminal care as it can be intrusive and distressing. Continuation of enteral feeding and fluids via NG inappropriately prolongs life where that is no longer the goal.[[7]] However, an NG tube can also be a route of administration for medications for TB and prevention of seizures. Without treatment, a TB patient could become infectious again, develop drug-resistant TB and put others at risk. This would constrain visiting, increase barriers to care and compromise discharge planning.[[9–10]] The patient spent four months in hospital with no improvement but was deemed to have received enough treatment to render her non-infectious. She was transitioned to subcutaneous midazolam for seizure prevention and palliated following discussions with family.

Finally, the management of this case demonstrates the significant indirect impacts COVID-19 can have on patient care. New Zealand has been celebrated for its response to the pandemic with comparatively few deaths and hospital admissions.[[11]] Less obvious have been the indirect impacts of the pandemic on patients and their families. This was just one of numerous examples throughout our healthcare system where a family was prevented from being with their loved one at times of crisis and made repatriation impractical. Although online communication tools have enabled family to see and speak to their relatives, they are a poor substitute for in-person conversation and human touch.

This report highlights the complications that can occur in TB even in the absence of drug resistance. It demonstrates the complexities of palliative care in the context of communicable disease, with impact from both TB and COVID-19 in this case, and the balance that must be struck between public health and personal needs. The ultimately fatal illness of this young woman is also a reminder of how important ongoing global efforts are in the prevention and treatment of infectious disease.

Summary

Abstract

Paradoxical reactions are immune-mediated disease exacerbations that can occur in Mycobacterium tuberculosis (TB) following initiation of treatment. They are rare, challenging to manage and often fatal. We present a case of neurotuberculosis in a young woman, complicated by a paradoxical reaction in which infliximab was trialled without success. This case demonstrates the severity of presentation that can occur in neurotuberculosis, and the complications that paradoxical reactions can present. It also highlights the difficulty of delivering palliative care within the context of communicable disease with challenges posed by both TB and the COVID-19 pandemic.

Aim

Method

Results

Conclusion

Author Information

Grace Chia: Internal Medicine Wellington Regional Hospital, New Zealand. Tait Bartlett: General Medicine Wellington Regional Hospital, New Zealand. Cindy Towns: General Medicine Wellington Regional Hospital, New Zealand. Timothy Blackmore: Infection Services Capital and Coast DHB and Wellington SCL, New Zealand.

Acknowledgements

Correspondence

Cindy Towns: General Medicine Wellington Regional Hospital, New Zealand.

Correspondence Email

cindy.towns@ccdhb.org.nz

Competing Interests

Nil.

1) World Health Organization. Global tuberculosis report. 14 October 2020. 208p. Licence: CC BY-NC-SA 3.0 IGO. Available from https://apps.who.int/iris/bitstream/handle/10665/336069/9789240013131-eng.pdf

2) The Institute of Environmental Science and Research Ltd. Tuberculosis in New Zealand: Annual Report 2017. Porirua, New Zealand: ESR; June 2021. 46p. Report No.: FW19026. Available from https://surv.esr.cri.nz/PDF_surveillance/AnnTBReports/TBAnnualReport2017.pdf

3) Ministry of Health. Guidelines for Tuberculosis Control in New Zealand, 2019. Wellington, New Zealand. Ministry of Health; August 2019. 241p. Available from https://www.health.govt.nz/system/files/documents/publications/guidelines-tuberculosis-control-new-zealand-2019-august2019-final.pdf

4) Rizvi, I, Malhotra, HS, Garg, RK, Kumar, N. Derivation of a Bedside Score (MASH-P) to Predict 6-month Mortality in Tuberculous Meningitis. Journal of Neurological Sciences. 2020;415. https://doi.org/10.1016/j.jns.2020.116877

5) Marais, BJ, Cheong, E, Fernando, S, et al. Use of Infliximab to Treat Paradoxical Tuberculous Meningitis Reactions. Open Forum Infect Dis. 2021;8(1). doi: 10.1093/ofid/ofaa604

6) Blackmore, T, Manning, L, Taylor, WJ, Wallis, RS. Therapeutic Use of Infliximab in Tuberculosis to Control Severe Paradoxical Reaction of the Brain and Lymph Nodes. Clin Infect Dis. 2008;47(10):e83-5. doi: 10.1086/592695

7) Sánchez-Sánchez, E, Ruano-Álvarez, MA, Díaz-Jiménez, J, et al. Enteral Nutrition by Nasogastric Tube in Adult Patients under Palliative Care: A Systematic Review. Nutrients. 2021;13(5):1562. doi: 10.3390/nu13051562

8) Kongsuwan, W, Chaipetch, O, Matchim, Y. Thai Buddhist Families’ Perspectives of a Peaceful Death in ICUs. Nursing in Critical Care. 2012;17: 151-159. doi:10.1111/j.14785153.2012.00495.x

9) Lui, JK, Peterson, J. Barriers to End-of-Life Care from Tuberculosis: A Teachable Moment. Am J Med. 2019;132(9):e701-702. doi: 10.1016/j.amjmed.2019.03.042

10) Ballantyne, A, Rogers WA, Entwistle, V, Towns, C. Revisiting the Equity Debate in COVID-19: ICU is No Panacea. J Med Ethics. 2020;46(10):641-645. doi:10.1136/medethics-2020-106460

11) Jefferies, S, French, N, Gilkison, C, et al. COVID-19 in New Zealand and the Impact of the National Response: A Descriptive Epidemiological Study. Lancet Public Health. 2020;5(11):e612-23. doi:10.1016/S2468-2667(20)30225-5

For the PDF of this article,
contact nzmj@nzma.org.nz

View Article PDF

Mycobacterium tuberculosis (TB) remains a major cause of death worldwide, with central nervous system (CNS) involvement associated with higher mortality.[[1–2]] Paradoxical reactions are rare complications of treatment that are challenging to manage. We describe a patient with neurotuberculosis who developed a fatal paradoxical reaction whilst receiving anti-TB treatment, which led to difficult issues regarding palliative care of a communicable disease.

Case report

A 44-year-old Thai woman living in New Zealand for over 10 years presented to Wellington Hospital with two-week history of headaches, abdominal pain and fevers. At presentation, she was found to have anisocoria, mild left hemiplegia, and ataxia but no confusion. Her medical history was unremarkable, and the initial diagnosis was thought to be an intracerebral bleed. A HIV test was negative. Chest X-ray and brain computerised tomography (CT) were initially unremarkable, but cerebrospinal fluid (CSF) analysis showed 189x10[[6]] white blood cells/L (67% mononuclear cells), an elevated protein of 5.08g/L and low glucose 2.4mmol/L. Initial opening pressures were unfortunately not completed on the first lumbar puncture (LP) but were subsequently measured at 50mmHg. Standard oral four-drug anti-TB treatment with dexamethasone 0.4mg/kg was commenced after acid-fast bacilli detection in the CSF.[[ 3]] Fully susceptible MTB was subsequently cultured in the CSF and sputum.

Her cognition remained normal initially but on day three she became minimally responsive (GCS 8/15) with persistent fevers and new right oculomotor nerve palsy. Hydrocephalus was demonstrated on CT scan, requiring placement of an external ventricular drain. Subsequent magnetic resonance imaging (MRI) revealed leptomeningitis, multiple tuberculomata (left frontoparietal, right temporal, left cerebellar, right medulla), vasculitic infarcts and miliary lung involvement. There were no other pathogens identified. She also developed seizures and was started on levetiracetam. A paradoxical reaction was diagnosed which was managed with five-day course of pulse 1g intravenous methylprednisolone, followed by 5mg/kg infliximab infusions.[[4]] A follow-up CSF culture was negative for growth of MTB four weeks later.

There was no significant improvement in clinical status despite four weeks of anti-TB treatment and management of the paradoxical reaction of the CNS; the patient remained bed bound, minimally responsive, and reliant on nasogastric (NG) tube for feeding and administration of medications. She was fully dependent on nursing care. It was felt that a transition to a palliative approach would be appropriate. Most of her family were overseas with international travel not being possible due to COVID-19 restrictions. Complex family meetings regarding prognosis and withdrawal of treatment were held over video conference with translators.

Withdrawal of treatment decisions were further affected by the communicable nature of TB. A conservative approach was taken for the duration of TB treatment because of the uncertainty about how long she would remain alive, and due to the need for placement in a long-term care facility. Four months of anti-TB treatment had been given, and the infectious disease team and Medical Officer of Health agreed that treatment had been sufficient to no longer pose a transmission threat even if she survived for several weeks—and the NG tube was therefore removed. Nine days following cessation of treatment, the patient passed away in residential care.

View Figure 1.

Discussion

This case demonstrates how severe neurotuberculosis can be at presentation, and of its associated complications. Quantifying and communicating prognosis to patients and family members at baseline may be difficult. This can be guided by bedside scores such as MASH-P (baseline Modified Barthel’s index (M), age (A), stage of TB meningitis (S), hydrocephalus (H), papilledema (P)); this patient had an initial score of 4/10, carrying a 10% predicted six-month mortality.[[ 4]] Paradoxical reactions are often life-threatening, especially with CNS involvement, and remain rare with only a small number of case studies documenting the use of infliximab.[[5]] This inflammatory response occurs in response to dying mycobacteria and can present with fever, hypoxia, lymphadenopathy, and new organ involvement. Tumour necrosis factor alpha (TNF-α) is central to the host response to TB infection. Infliximab is a monoclonal antibody to TNF-α and acts to prevent further formation without the long-term toxicity of systemic corticosteroids.[[6]] Unfortunately, the patient did not significantly recover at any stage despite anti-TB treatment and aggressive management of the paradoxical reaction.

The management of this patient also highlights the complexity that can arise when applying a palliative model of care to communicable disease and differing cultural perspectives. Given the uncertainty of a slow neurological recovery and the slow decline, it was difficult for her family to come to terms with a transition to palliative care, and for the medical team to ascertain the urgency for end-of-life planning. Buddhism is the predominant world view in Thailand, and it is very important within Thai culture for family to be with the patient during death to help ensure a peaceful passing.[[8]] For significant family members to be separated with no chance of visiting, and during a time when active treatment was withdrawn, was distressing to all involved. Removal of an NG tube is routine in terminal care as it can be intrusive and distressing. Continuation of enteral feeding and fluids via NG inappropriately prolongs life where that is no longer the goal.[[7]] However, an NG tube can also be a route of administration for medications for TB and prevention of seizures. Without treatment, a TB patient could become infectious again, develop drug-resistant TB and put others at risk. This would constrain visiting, increase barriers to care and compromise discharge planning.[[9–10]] The patient spent four months in hospital with no improvement but was deemed to have received enough treatment to render her non-infectious. She was transitioned to subcutaneous midazolam for seizure prevention and palliated following discussions with family.

Finally, the management of this case demonstrates the significant indirect impacts COVID-19 can have on patient care. New Zealand has been celebrated for its response to the pandemic with comparatively few deaths and hospital admissions.[[11]] Less obvious have been the indirect impacts of the pandemic on patients and their families. This was just one of numerous examples throughout our healthcare system where a family was prevented from being with their loved one at times of crisis and made repatriation impractical. Although online communication tools have enabled family to see and speak to their relatives, they are a poor substitute for in-person conversation and human touch.

This report highlights the complications that can occur in TB even in the absence of drug resistance. It demonstrates the complexities of palliative care in the context of communicable disease, with impact from both TB and COVID-19 in this case, and the balance that must be struck between public health and personal needs. The ultimately fatal illness of this young woman is also a reminder of how important ongoing global efforts are in the prevention and treatment of infectious disease.

Summary

Abstract

Paradoxical reactions are immune-mediated disease exacerbations that can occur in Mycobacterium tuberculosis (TB) following initiation of treatment. They are rare, challenging to manage and often fatal. We present a case of neurotuberculosis in a young woman, complicated by a paradoxical reaction in which infliximab was trialled without success. This case demonstrates the severity of presentation that can occur in neurotuberculosis, and the complications that paradoxical reactions can present. It also highlights the difficulty of delivering palliative care within the context of communicable disease with challenges posed by both TB and the COVID-19 pandemic.

Aim

Method

Results

Conclusion

Author Information

Grace Chia: Internal Medicine Wellington Regional Hospital, New Zealand. Tait Bartlett: General Medicine Wellington Regional Hospital, New Zealand. Cindy Towns: General Medicine Wellington Regional Hospital, New Zealand. Timothy Blackmore: Infection Services Capital and Coast DHB and Wellington SCL, New Zealand.

Acknowledgements

Correspondence

Cindy Towns: General Medicine Wellington Regional Hospital, New Zealand.

Correspondence Email

cindy.towns@ccdhb.org.nz

Competing Interests

Nil.

1) World Health Organization. Global tuberculosis report. 14 October 2020. 208p. Licence: CC BY-NC-SA 3.0 IGO. Available from https://apps.who.int/iris/bitstream/handle/10665/336069/9789240013131-eng.pdf

2) The Institute of Environmental Science and Research Ltd. Tuberculosis in New Zealand: Annual Report 2017. Porirua, New Zealand: ESR; June 2021. 46p. Report No.: FW19026. Available from https://surv.esr.cri.nz/PDF_surveillance/AnnTBReports/TBAnnualReport2017.pdf

3) Ministry of Health. Guidelines for Tuberculosis Control in New Zealand, 2019. Wellington, New Zealand. Ministry of Health; August 2019. 241p. Available from https://www.health.govt.nz/system/files/documents/publications/guidelines-tuberculosis-control-new-zealand-2019-august2019-final.pdf

4) Rizvi, I, Malhotra, HS, Garg, RK, Kumar, N. Derivation of a Bedside Score (MASH-P) to Predict 6-month Mortality in Tuberculous Meningitis. Journal of Neurological Sciences. 2020;415. https://doi.org/10.1016/j.jns.2020.116877

5) Marais, BJ, Cheong, E, Fernando, S, et al. Use of Infliximab to Treat Paradoxical Tuberculous Meningitis Reactions. Open Forum Infect Dis. 2021;8(1). doi: 10.1093/ofid/ofaa604

6) Blackmore, T, Manning, L, Taylor, WJ, Wallis, RS. Therapeutic Use of Infliximab in Tuberculosis to Control Severe Paradoxical Reaction of the Brain and Lymph Nodes. Clin Infect Dis. 2008;47(10):e83-5. doi: 10.1086/592695

7) Sánchez-Sánchez, E, Ruano-Álvarez, MA, Díaz-Jiménez, J, et al. Enteral Nutrition by Nasogastric Tube in Adult Patients under Palliative Care: A Systematic Review. Nutrients. 2021;13(5):1562. doi: 10.3390/nu13051562

8) Kongsuwan, W, Chaipetch, O, Matchim, Y. Thai Buddhist Families’ Perspectives of a Peaceful Death in ICUs. Nursing in Critical Care. 2012;17: 151-159. doi:10.1111/j.14785153.2012.00495.x

9) Lui, JK, Peterson, J. Barriers to End-of-Life Care from Tuberculosis: A Teachable Moment. Am J Med. 2019;132(9):e701-702. doi: 10.1016/j.amjmed.2019.03.042

10) Ballantyne, A, Rogers WA, Entwistle, V, Towns, C. Revisiting the Equity Debate in COVID-19: ICU is No Panacea. J Med Ethics. 2020;46(10):641-645. doi:10.1136/medethics-2020-106460

11) Jefferies, S, French, N, Gilkison, C, et al. COVID-19 in New Zealand and the Impact of the National Response: A Descriptive Epidemiological Study. Lancet Public Health. 2020;5(11):e612-23. doi:10.1016/S2468-2667(20)30225-5

For the PDF of this article,
contact nzmj@nzma.org.nz

View Article PDF

Mycobacterium tuberculosis (TB) remains a major cause of death worldwide, with central nervous system (CNS) involvement associated with higher mortality.[[1–2]] Paradoxical reactions are rare complications of treatment that are challenging to manage. We describe a patient with neurotuberculosis who developed a fatal paradoxical reaction whilst receiving anti-TB treatment, which led to difficult issues regarding palliative care of a communicable disease.

Case report

A 44-year-old Thai woman living in New Zealand for over 10 years presented to Wellington Hospital with two-week history of headaches, abdominal pain and fevers. At presentation, she was found to have anisocoria, mild left hemiplegia, and ataxia but no confusion. Her medical history was unremarkable, and the initial diagnosis was thought to be an intracerebral bleed. A HIV test was negative. Chest X-ray and brain computerised tomography (CT) were initially unremarkable, but cerebrospinal fluid (CSF) analysis showed 189x10[[6]] white blood cells/L (67% mononuclear cells), an elevated protein of 5.08g/L and low glucose 2.4mmol/L. Initial opening pressures were unfortunately not completed on the first lumbar puncture (LP) but were subsequently measured at 50mmHg. Standard oral four-drug anti-TB treatment with dexamethasone 0.4mg/kg was commenced after acid-fast bacilli detection in the CSF.[[ 3]] Fully susceptible MTB was subsequently cultured in the CSF and sputum.

Her cognition remained normal initially but on day three she became minimally responsive (GCS 8/15) with persistent fevers and new right oculomotor nerve palsy. Hydrocephalus was demonstrated on CT scan, requiring placement of an external ventricular drain. Subsequent magnetic resonance imaging (MRI) revealed leptomeningitis, multiple tuberculomata (left frontoparietal, right temporal, left cerebellar, right medulla), vasculitic infarcts and miliary lung involvement. There were no other pathogens identified. She also developed seizures and was started on levetiracetam. A paradoxical reaction was diagnosed which was managed with five-day course of pulse 1g intravenous methylprednisolone, followed by 5mg/kg infliximab infusions.[[4]] A follow-up CSF culture was negative for growth of MTB four weeks later.

There was no significant improvement in clinical status despite four weeks of anti-TB treatment and management of the paradoxical reaction of the CNS; the patient remained bed bound, minimally responsive, and reliant on nasogastric (NG) tube for feeding and administration of medications. She was fully dependent on nursing care. It was felt that a transition to a palliative approach would be appropriate. Most of her family were overseas with international travel not being possible due to COVID-19 restrictions. Complex family meetings regarding prognosis and withdrawal of treatment were held over video conference with translators.

Withdrawal of treatment decisions were further affected by the communicable nature of TB. A conservative approach was taken for the duration of TB treatment because of the uncertainty about how long she would remain alive, and due to the need for placement in a long-term care facility. Four months of anti-TB treatment had been given, and the infectious disease team and Medical Officer of Health agreed that treatment had been sufficient to no longer pose a transmission threat even if she survived for several weeks—and the NG tube was therefore removed. Nine days following cessation of treatment, the patient passed away in residential care.

View Figure 1.

Discussion

This case demonstrates how severe neurotuberculosis can be at presentation, and of its associated complications. Quantifying and communicating prognosis to patients and family members at baseline may be difficult. This can be guided by bedside scores such as MASH-P (baseline Modified Barthel’s index (M), age (A), stage of TB meningitis (S), hydrocephalus (H), papilledema (P)); this patient had an initial score of 4/10, carrying a 10% predicted six-month mortality.[[ 4]] Paradoxical reactions are often life-threatening, especially with CNS involvement, and remain rare with only a small number of case studies documenting the use of infliximab.[[5]] This inflammatory response occurs in response to dying mycobacteria and can present with fever, hypoxia, lymphadenopathy, and new organ involvement. Tumour necrosis factor alpha (TNF-α) is central to the host response to TB infection. Infliximab is a monoclonal antibody to TNF-α and acts to prevent further formation without the long-term toxicity of systemic corticosteroids.[[6]] Unfortunately, the patient did not significantly recover at any stage despite anti-TB treatment and aggressive management of the paradoxical reaction.

The management of this patient also highlights the complexity that can arise when applying a palliative model of care to communicable disease and differing cultural perspectives. Given the uncertainty of a slow neurological recovery and the slow decline, it was difficult for her family to come to terms with a transition to palliative care, and for the medical team to ascertain the urgency for end-of-life planning. Buddhism is the predominant world view in Thailand, and it is very important within Thai culture for family to be with the patient during death to help ensure a peaceful passing.[[8]] For significant family members to be separated with no chance of visiting, and during a time when active treatment was withdrawn, was distressing to all involved. Removal of an NG tube is routine in terminal care as it can be intrusive and distressing. Continuation of enteral feeding and fluids via NG inappropriately prolongs life where that is no longer the goal.[[7]] However, an NG tube can also be a route of administration for medications for TB and prevention of seizures. Without treatment, a TB patient could become infectious again, develop drug-resistant TB and put others at risk. This would constrain visiting, increase barriers to care and compromise discharge planning.[[9–10]] The patient spent four months in hospital with no improvement but was deemed to have received enough treatment to render her non-infectious. She was transitioned to subcutaneous midazolam for seizure prevention and palliated following discussions with family.

Finally, the management of this case demonstrates the significant indirect impacts COVID-19 can have on patient care. New Zealand has been celebrated for its response to the pandemic with comparatively few deaths and hospital admissions.[[11]] Less obvious have been the indirect impacts of the pandemic on patients and their families. This was just one of numerous examples throughout our healthcare system where a family was prevented from being with their loved one at times of crisis and made repatriation impractical. Although online communication tools have enabled family to see and speak to their relatives, they are a poor substitute for in-person conversation and human touch.

This report highlights the complications that can occur in TB even in the absence of drug resistance. It demonstrates the complexities of palliative care in the context of communicable disease, with impact from both TB and COVID-19 in this case, and the balance that must be struck between public health and personal needs. The ultimately fatal illness of this young woman is also a reminder of how important ongoing global efforts are in the prevention and treatment of infectious disease.

Summary

Abstract

Paradoxical reactions are immune-mediated disease exacerbations that can occur in Mycobacterium tuberculosis (TB) following initiation of treatment. They are rare, challenging to manage and often fatal. We present a case of neurotuberculosis in a young woman, complicated by a paradoxical reaction in which infliximab was trialled without success. This case demonstrates the severity of presentation that can occur in neurotuberculosis, and the complications that paradoxical reactions can present. It also highlights the difficulty of delivering palliative care within the context of communicable disease with challenges posed by both TB and the COVID-19 pandemic.

Aim

Method

Results

Conclusion

Author Information

Grace Chia: Internal Medicine Wellington Regional Hospital, New Zealand. Tait Bartlett: General Medicine Wellington Regional Hospital, New Zealand. Cindy Towns: General Medicine Wellington Regional Hospital, New Zealand. Timothy Blackmore: Infection Services Capital and Coast DHB and Wellington SCL, New Zealand.

Acknowledgements

Correspondence

Cindy Towns: General Medicine Wellington Regional Hospital, New Zealand.

Correspondence Email

cindy.towns@ccdhb.org.nz

Competing Interests

Nil.

1) World Health Organization. Global tuberculosis report. 14 October 2020. 208p. Licence: CC BY-NC-SA 3.0 IGO. Available from https://apps.who.int/iris/bitstream/handle/10665/336069/9789240013131-eng.pdf

2) The Institute of Environmental Science and Research Ltd. Tuberculosis in New Zealand: Annual Report 2017. Porirua, New Zealand: ESR; June 2021. 46p. Report No.: FW19026. Available from https://surv.esr.cri.nz/PDF_surveillance/AnnTBReports/TBAnnualReport2017.pdf

3) Ministry of Health. Guidelines for Tuberculosis Control in New Zealand, 2019. Wellington, New Zealand. Ministry of Health; August 2019. 241p. Available from https://www.health.govt.nz/system/files/documents/publications/guidelines-tuberculosis-control-new-zealand-2019-august2019-final.pdf

4) Rizvi, I, Malhotra, HS, Garg, RK, Kumar, N. Derivation of a Bedside Score (MASH-P) to Predict 6-month Mortality in Tuberculous Meningitis. Journal of Neurological Sciences. 2020;415. https://doi.org/10.1016/j.jns.2020.116877

5) Marais, BJ, Cheong, E, Fernando, S, et al. Use of Infliximab to Treat Paradoxical Tuberculous Meningitis Reactions. Open Forum Infect Dis. 2021;8(1). doi: 10.1093/ofid/ofaa604

6) Blackmore, T, Manning, L, Taylor, WJ, Wallis, RS. Therapeutic Use of Infliximab in Tuberculosis to Control Severe Paradoxical Reaction of the Brain and Lymph Nodes. Clin Infect Dis. 2008;47(10):e83-5. doi: 10.1086/592695

7) Sánchez-Sánchez, E, Ruano-Álvarez, MA, Díaz-Jiménez, J, et al. Enteral Nutrition by Nasogastric Tube in Adult Patients under Palliative Care: A Systematic Review. Nutrients. 2021;13(5):1562. doi: 10.3390/nu13051562

8) Kongsuwan, W, Chaipetch, O, Matchim, Y. Thai Buddhist Families’ Perspectives of a Peaceful Death in ICUs. Nursing in Critical Care. 2012;17: 151-159. doi:10.1111/j.14785153.2012.00495.x

9) Lui, JK, Peterson, J. Barriers to End-of-Life Care from Tuberculosis: A Teachable Moment. Am J Med. 2019;132(9):e701-702. doi: 10.1016/j.amjmed.2019.03.042

10) Ballantyne, A, Rogers WA, Entwistle, V, Towns, C. Revisiting the Equity Debate in COVID-19: ICU is No Panacea. J Med Ethics. 2020;46(10):641-645. doi:10.1136/medethics-2020-106460

11) Jefferies, S, French, N, Gilkison, C, et al. COVID-19 in New Zealand and the Impact of the National Response: A Descriptive Epidemiological Study. Lancet Public Health. 2020;5(11):e612-23. doi:10.1016/S2468-2667(20)30225-5

Contact diana@nzma.org.nz
for the PDF of this article

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