About the Author(s)


Somasundram Pillay Email symbol
Department of Internal medicine, Faculty of Health Sciences, University of KwaZulu-Natal, Durban, South Africa

Nombulelo Magula symbol
Department of Internal medicine, Faculty of Health Sciences, University of KwaZulu-Natal, Durban, South Africa

Citation


Pillay S, Magula N. A trio of infectious diseases and pulmonary embolism: A developing world’s reality. S Afr J HIV Med. 2021;22(1), a1192. https://doi.org/10.4102/sajhivmed.v22i1.1192

Case Report

A trio of infectious diseases and pulmonary embolism: A developing world’s reality

Somasundram Pillay, Nombulelo Magula

Received: 05 Nov. 2020; Accepted: 11 Dec. 2020; Published: 28 Jan. 2021

Copyright: © 2021. The Author(s). Licensee: AOSIS.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Introduction: Human immunodeficiency virus (HIV), Tuberculosis (TB) and coronavirus disease (COVID-19) infections independently possess the ability to trigger formation of venous thromboembolism (VTE) and pulmonary embolism (PE). To the authors’ knowledge, this is the first case report describing the presence of PE in a patient with all three aforementioned infectious co-morbidities.

Presentation: A patient living with HIV with virological failure secondary to defaulting antiretroviral therapy (ART) presented with hypoxia, clinical and radiological features suggestive of community-acquired pneumonia (CAP) with raised inflammatory markers and D-dimer levels.

Management: She was commenced on prophylactic anticoagulation, supplemental oxygen and empirical antibiotics targeting CAP and pneumocystis jiroveci pneumonia, swabbed for COVID-19 infection and had sputa sent for Gene Xpert® TB testing. A day later, COVID-19 results returned positive and the patient was transferred to isolation and added onto dexamethasone and therapeutic anticoagulation. Sputa returned positive for mycobacterium TB a day later, and anti-tuberculosis therapy was added. She remained persistently hypoxic, with a Well’s score of 3 placing her at moderate risk for PE, which prompted for a computed tomography pulmonary angiogram (CTPA) being ordered, which demonstrated left lower lobe subsegmental PE. Warfarin was added to her regimen. She was discharged on day 18 with a therapeutic international normalised ratio (INR) and not requiring oxygen therapy.

Conclusion: This scenario is relevant in low to middle-income countries. The utilisation of a raised D-Dimer in the setting of all four coexisting conditions in arriving at a definite diagnosis remains uncertain. We noted that despite our index patient being on thrombo-prophylaxis, she developed PE highlighting the need for increased vigilance in all COVID-19 patients, even those on prophylactic anticoagulation.

Keywords: HIV; tuberculosis; COVID-19; pulmonary embolism; middle-income countries.

Introduction

Coronavirus disease (COVID-19) infection is associated with increased prevalence of venous thromboembolism and pulmonary embolism (PE).1,2,3,4,5 Pulmonary embolism carries a high morbidity and mortality burden, and a high index of suspicion for underlying PE must be maintained in all COVID-19 infected patients. Hypercoagulability in COVID-19 infection occurs either because of altered haemostasis, severe inflammation, endothelial dysregulation or disseminated intravascular coagulation.1

The risk of venous thromboembolism (VTE) in patients living with HIV (PLHIV) is increased in patients who are antiretroviral therapy (ART)-naïve, those with a low cluster of differentiation (CD4) counts and virally unsuppressed.6

Dentan and colleagues showed that tuberculosis is significantly associated with VTE. They, however, found no link between TB and PE but postulated that the occurrence of PE in patients with TB (PWTB) could be explained by hypercoagulability.7 Reports of PE in PWTB in Africa are scarce. Kwas et al. have described three cases of TB associated with PE in patients from Tunisia,8 whilst Ekukwe and colleagues described another case of bilateral PE in a PWTB.9

Clinical and therapeutic challenges exist in PLHIV presenting with community-acquired pneumonia (CAP). Depending on the patient’s ART compliance, viral load, certain differentials arise – especially if the patient is viral unsuppressed where in addition to COVID-19 pneumonia, one considers pneumocystis jiroveci pneumonia (PJP) and/or pulmonary TB as differentials. Empirical therapy is commenced with an antibiotic (containing a combination of trimethoprim and sulfamethoxazole) plus corticosteroid therapy for PJP with amoxicillin-clavulanic acid and azithromycin for CAP.10

We describe the following typical patient encountered in clinical practice to demonstrate the need for maintaining a high level of clinical vigilance for PE in patients with coexistent HIV, TB and COVID-19 infection. No data exists, describing the occurrence of PE in such a patient co-infected with all three infectious conditions.

Case report

Miss B.N.S., a 44-year-old female living with HIV since 1997, had defaulted ART since 2012 and was virologically unsuppressed (viral load of 23 358 copies/mL, CD4 = 66 cells/µL). She presented on 22/09/2020 with a 1-week history of constitutional symptoms (poor appetite, night sweats and easy fatigability) associated with a non-productive cough and shortness of breath. No symptoms of fever, sore throat, anosmia or dysgeusia were elicited. Clinical examination revealed a chronically ill-looking patient, tachycardia (133 beats/min), tachypnoea (22 breaths/min) and hypoxic at room air (oxygen saturation of 88%). Chest auscultation revealed crepitations in the mid and lower zones of her right lung. Chest radiograph (Figure 1) showed bilateral central and peripheral ground-glass opacification (GGO), greater involvement of the right lung.

FIGURE 1: Chest radiograph (postero-anterior view).

Blood investigations revealed results as per Table 1. Based on the patient’s history, clinical, radiological and biochemical findings, a diagnosis of CAP was made, and she was started empirically on amoxicillin-clavulanic acid, azithromycin, oral trimethoprim/sulfamethoxazole, prednisone and prophylactic clexane® 60 mg daily. Nasopharyngeal swab and sputa were sent for COVID-19 and TB polymerase chain reaction (PCR). A day later, the COVID-19 PCR result returned as positive. She was initiated onto dexamethasone, vitamin D, zinc, thiamine, ascorbic acid and therapeutic anticoagulation (enoxaparin 60 mg BD). Whilst in the ward she remained hypoxic requiring 100% rebreather mask to maintain an oxygen saturation of over 90%. The sputa TB PCR test returned positive on 24/09/2020, and the patient was initiated onto anti-tuberculosis treatment (Rifafour® 3 tablets with pyridoxine 25 mg daily).

TABLE 1: Results of laboratory investigations.

However, despite being on treatment for PJP, pulmonary TB and CAP, the patient remained hypoxic with a Wells’ score of 3 (heart rate > 100 bpm and prolonged immobilisation) putting her at moderate risk of developing a PE.11 A CTPA was ordered and revealed bilateral GGO and left lower lobe subsegmental pulmonary emboli (Figure 2).

FIGURE 2: Computed tomography pulmonary angiogram showing filling defect in left lower lobe subsegmental pulmonary artery.

No evidence of deep vein thrombosis was found. Warfarin 5 mg daily was added to her existing anticoagulation regimen.

The final diagnosis made in Miss B.N.S. was that of a PLHIV, virologically unsuppressed, who defaulted ART with a CD4 of 66 with confirmed:

  • Severe COVID-19:12,13,14
  • Pulmonary tuberculosis
  • Pulmonary embolism
  • Pneumocystis iirovecii pneumonia (clinical diagnosis plus a positive serum B-D-glucan).

She remained hypoxic needing prolonged oxygen supplementation until Day 17 post-admission. On Day 18, she was transferred to a step-down facility off oxygen to continue with her anticoagulation and TB treatment with a view to restarting ART in 6–8 weeks.

Discussion

Individually, HIV, TB and COVID-19 can predispose to thromboembolism. This case report describes the presence of PE in a patient with all aforementioned infectious diseases and the complexities associated with diagnosis in a developing country. No literature could be found on the combination of HIV, TB, COVID-19 and the development of PE in a single patient.

Daily clinical patient re-evaluation is a necessity even in the times of COVID-19. This is often neglected as clinical staff are afraid of their well-being and resort to making notes without careful patient re-examination. Together with clinical examination, review of blood investigations and patient’s oxygen consumption needs, a management plan could be formulated.

The plasma D-dimer test has a low specificity and can be raised in a multitude of conditions including HIV-infection, TB, VTE, PE, COVID-19, pneumonia and increased age.15,16,17,18 This limited its use in differentiating between the four coexistent medical conditions in our patient, all of which are known to cause elevations in D-dimer levels. This highlights the complexity of diagnosing PE in the context of HIV, TB and COVID-19 infection.

The debate on the use of thromboprophylaxis in patients hospitalised with COVID-19 is ongoing with most studies currently advocating for its use.19,20,21 Prophylactic anticoagulation has long been recommended for at-risk in-patients with medical conditions such as HIV and/or TB.22,23 Despite being on prophylactic enoxaparin, our patient still developed a PE. This is similar to what Klok et al. and Tang et al. showed in their studies.9,24

Pulmonary embolism remains a great masquerader and clinicians must maintain a level of vigilance for diagnosing this life-threatening medical condition, more especially during the COVID-19 infection era.

Acknowledgements

Competing interests

The authors have declared that no competing interest exists.

Authors’ contributions

The principal author (S.P.) made substantial contributions to conception and design of the work, writing of the article and final approval and agreed to be accountable for all aspects of the research. The co-author (N.M.) made substantial contributions to conception of the work, critically reviewed and edited the draft and final approval and agreed to be accountable for all aspects of the research.

Ethical consideration

Approval was obtained from the patient, King Edward VIII Hospital and the KwaZulu-Natal Department of Health.

Funding information

This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.

Data availability statement

Data sharing is not applicable to this article as no new data were created or analysed in this study.

Disclaimer

The views and opinions expressed in this article are those of the authors and do not necessarily reflect the official policy or position of any affiliated agency of the authors.

References

  1. Allen, F. & Michaely, R., 2003, ‘Payout policy’, in G.M. Constantinides, M. Harris & R.M. Stulz (eds.), Handbook of the economics of finance, vol. 1, pp. 337–429, Elsevier, Amsterdam.
  2. Alzahrani, M. & Lasfer, M., 2012, ‘Investor protection, taxation, and dividends’, Journal of Corporate Finance 18(4), 745–762. https://doi.org/10.1016/j.jcorpfin.2012.06.003
  3. Andres, C., Doumet, M., Fernau, E. & Theissen, E., 2015, ‘The Lintner model revisited: Dividends versus total payouts’, Journal of Banking & Finance 55, 56–69. https://doi.org/10.1016/j.jbankfin.2015.01.005
  4. Arko, A.C., Abor, J., Adjasi, C.K.D. & Amidu, M., 2014, ‘What influence dividend decisions of companies in Sub-Saharan African?’, Journal of Accounting in Emerging Economies 4(1), 57–78. https://doi.org/10.1108/JAEE-12-2011-0053
  5. Badenhorst, W.M., 2017, ‘Tax preferences, dividends and lobbying for maximum value’, South African Journal of Economic and Management Sciences 20(1), 1–10. https://doi.org/10.4102/sajems.v20i1.1476
  6. Baker, H.K. & Weigand, R., 2015, ‘Corporate dividend policy revisited’, Managerial Finance 41(2), 126–144. https://doi.org/10.1108/MF-03-2014-0077
  7. Bidvest Group Limited, 2016, Integrated report for the year ended 30 June 2016, Bidvest Group Limited, Johannesburg.
  8. Bird, A., 2013, Dividends and shareholder taxation: Evidence from Canada, unpublished paper, Tepper School of Business, Carnegie Mellon University, Pittsburgh.
  9. Cassim, F.H., 2010, ‘The challenge of treasury shares’, Acta Juridica 2010(1), 151–164.
  10. Coetzee, S. & De Wet, J., 2014, ‘Dividend tax, dividend payments and share values: A South African perspective’, Corporate Ownership and Control 11(3), 242–252. https://doi.org/10.22495/cocv11i3c2p3
  11. David, T. & Ginglinger, E., 2016, ‘When cutting dividends is not bad news: The case of optional stock dividends’, Journal of Corporate Finance 40, 174–191. https://doi.org/10.1016/j.jcorpfin.2016.07.008
  12. Farre-Mensa, J., Michaely, R. & Schmalz, M.C., 2014, ‘Payout policy’, Annual Review of Financial Economics 6, 75–134. https://doi.org/10.1146/annurev-financial-110613-034259
  13. Feito-Ruiz, I., Renneboog, L. & Vansteenkiste, C., 2018, Elective stock and scrip dividends, Finance Working Paper No. 574/2018, European Corporate Governance Institute, Brussels.
  14. Filen, C., 2011, ‘STC change to dividend withholding tax’, Moneyweb, viewed 02 July 2019, from http://www.moneyweb.co.za/archive/stc-change-to-dividend-withholding-tax/.
  15. Geiler, P. & Renneboog, L., 2015, ‘Taxes, earnings payout, and payout channel choice’, Journal of International Financial Markets, Institutions and Money 37, 178–203. https://doi.org/10.1016/j.intfin.2015.01.005
  16. Graham, M., 1999, ‘The effect of STC on earnings retention’, South African Journal of Accounting Research 13(1), 63–75. https://doi.org/10.1080/10291954.1999.11435085
  17. Hanlon, M. & Hoopes, J.L., 2014, ‘What do companies do when dividend tax rates change? An examination of alternative payout responses’, Journal of Financial Economics 114(1), 105–124. https://doi.org/10.1016/j.jfineco.2014.06.004
  18. IASB (International Accounting Standards Board), 2018, IAS 10 events after the reporting period, IASB, London.
  19. Jacob, M. & Jacob, M., 2013, ‘Taxation, dividends, and share repurchases: Taking evidence global’, Journal of Financial and Quantitative Analysis 48(4), 1241–1269. https://doi.org/10.1017/S0022109013000367
  20. JSE (Johannesburg Stock Exchange), 2016, Glossary of investment and stock market terms – JSE, viewed 18 August 2018, from https://www.jse.co.za/investor-type/individual/glossary.
  21. JSE (Johannesburg Stock Exchange), 2017, JSE listing requirements, Service issue no. 25, LexisNexis Butterworths, Johannesburg.
  22. JSE (Johannesburg Stock Exchange), 2019, Small, medium and large caps – JSE, viewed 18 March 2019, from https://www.jse.co.za/grow-my-wealth/small-medium-and-large-caps.
  23. Korkeamaki, T., Liljeblom, E. & Pasternack, D., 2010, ‘Tax reform and payout policy: Do shareholder clienteles or payout policy adjust?’, Journal of Corporate Finance 16(4), 572–587. https://doi.org/10.1016/j.jcorpfin.2009.12.003
  24. KPMG, 2016, South Africa’s Economic Misery Index – Not as bad as during previous crises, viewed 17 December 2019, from https://home.kpmg/za/en/home/home/press-releases/2016/08/south-africa-economic-misery-index.html.
  25. Lasfer, M.A., 1997, ‘On the motivation for paying scrip dividends’, Financial Management 26(1), 62–80. https://doi.org/10.2307/3666240
  26. Lie, E. & Lie, H.J., 1999, ‘The effect of personal taxes in payout policy decisions: An empirical analysis of share repurchases and dividends’, Journal of Financial and Quantitative Analysis 34(4), 533–552. https://doi.org/10.2307/2676233
  27. Mans-Kemp, N. & Viviers, S., 2015, ‘The relationship between corporate governance and dividend payout ratios: A South African study’, Management Dynamics: Journal of the Southern African Institute for Management Scientists 24(2), 20–35.
  28. Marcus, M. & Gore, T., 2008, ‘Crackdown on treasury share repurchases’, Business Day, Business Law & Tax Review, May 2008, p. 6.
  29. Marcus, M. & Toerien, F., 2014, ‘The relative cost of internal vs. external equity in South Africa: The impact of capital gains and dividend taxes’, South African Journal of Accounting Research 28(1), 97–116.
  30. Mix Telematics Limited, 2008, Annual report for the year ended 31 March 2008, Mix Telematics Limited, Stellenbosch.
  31. Montgomery, L.A., 2015, ‘The relationship between the dividend payout ratio and the subsequent earnings growth’, Master’s thesis, University of Cape Town, Cape Town.
  32. Mthanti, T., 2017, ‘Political turmoil in 2016 can be traced back to the 2008 financial crisis’, Mail & Guardian, viewed 17 December 2019, from https://mg.co.za/article/2017-01-02-political-turmoil-in-2016-can-be-traced-back-to-the-2008-financial-crisis.
  33. Munzhelele, F., 2019, ‘Distribution policy and creation of shareholders’ wealth: A study of firms listed on the Johannesburg Stock Exchange’, PhD thesis, University of Pretoria, Pretoria.
  34. Nel, R., 2018, ‘Investor tax-driven preferences for dividends and share repurchases of listed companies’, South African Journal of Accounting Research 32(1), 71–87. https://doi.org/10.1080/10291954.2017.1414349
  35. Nyere, L. & Wesson, N., 2019, ‘Factors influencing dividend payout decisions: Evidence from South Africa’, South African Journal of Business Management 50(1), 1–16. https://doi.org/10.4102/sajbm.v50i1.1302
  36. Oosthuizen, G., 2009, ‘Analysing cash retained by companies declaring scrip dividend on the Johannesburg Stock Exchange’, Master’s thesis, Stellenbosch University, Stellenbosch.
  37. Osborne, J., 2010, ‘Improving your data transformations: Applying the Box-Cox transformation’, Practical Assessment, Research, and Evaluation 15(12), 1–9.
  38. Republic of South Africa, 1962, Income Tax Act, No. 58 of 1962 (as amended), Government Printer, Pretoria.
  39. South African Revenue Service, 2008, Legal & Policy Income Tax: Taxation Laws Amendment Act No. 3 of 2008, viewed 24 April 2017, from www.sars.gov.za.
  40. Statistics South Africa, 2017, CPI history, viewed 18 August 2017, from http://www.statssa.gov.za/publications/P0141/CPIHistory.pdf?
  41. Steenkamp, G. & Wesson, N., 2020, ‘Post-recession share repurchase behaviour by JSE-listed companies: Transparent or not?’, Journal of Accounting in Emerging Economies 10(3), 465–486. https://doi.org/10.1108/JAEE-02-2020-0040
  42. Van der Linde, K., 2008, ‘Aspects of the regulation of share capital and distributions to shareholders’, PhD thesis, University of South Africa, Pretoria.
  43. Venter, S., 2014, ‘The impact of the introduction of dividends tax in South Africa on foreign and local investors’, Master’s thesis, University of Pretoria, Pretoria.
  44. Wesson, N. & Hamman, W.D., 2012, ‘The repurchase by a holding company of treasury shares held by subsidiaries: A South African perspective’, South African Journal of Business Management 43(4), 33–44. https://doi.org/10.4102/sajbm.v43i4.480
  45. Wesson, N., Hamman, W.D. & Bruwer, B.W., 2015, ‘Share repurchase and dividend payout behaviour: The South African experience’, South African Journal of Business Management 46(3), 43–54. https://doi.org/10.4102/sajbm.v46i3.100
  46. Wesson, N., Smit, E., Kidd, M. & Hamman, W.D., 2018, ‘Determinants of the choice between share repurchases and dividend payments’, Research in International Business and Finance 45, 180–196. https://doi.org/10.1016/j.ribaf.2017.07.150
  47. Williams, L.J. & Abdi, H., 2010, ‘Fisher’s least significant difference (LSD) test’, in N. Salkind (ed.), Encyclopedia of research design, pp. 840–853, Sage, California.
  48. World Bank, 2020, World Development Indicators – GDP growth (annual %), viewed 18 May 2020, from https://databank.worldbank.org/source/world-development-indicators.