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Clinical Course of Avian Influenza A(H5N1) in Patients at the Persahabatan Hospital, Jakarta, Indonesia, 2005-2008
1. Priyanti Z. Soepandi, MD, FCCP,
2. Erlina Burhan, MD,
3. Hadiarto Mangunnegoro, MD, FCCP,
4. Arifin Nawas, MD,
5. Tjandra Yoga Aditama, MD,
6. Lia Partakusuma, MD,
7. Fathiyah Isbaniah, MD,
8. Mukhtar Ikhsan, MD,
9. Boedi Swidarmoko, MD,
10. Agung Sutiyoso, MD,
11. Suhud Malik, MD,
12. Rachel Benamore, MBBChir,
13. J. Kevin Baird, PhD and
14. Walter R. J. Taylor, MD
+ Author Affiliations
1.
From the Rumah Sakit Persahabatan (Drs Soepandi, Burhan, Mangunnegoro, Nawas, Aditama, Partakusma, Isbaniah, Ikhsan, Swidarmoko, and Sutiyoso), Jakarta timur, Indonesia; the Center for Biomedical and Pharmaceutical R&E (Dr Malik), National Institutes of Health Research and Development, and the Eijkman-Oxford University Clinical Research Unit (Dr Baird), Jakarta, Indonesia; the Department of Radiology (Dr Benamore), Churchill Hospital, and the Nuffield Department of Clinical Medicine (Drs Baird and Taylor), University of Oxford, Oxford, England; and the Mahidol Oxford University Clinical Research Unit (Dr Taylor), Bangkok, Thailand.
1. Correspondence to:
Erlina Burhan, MD, Rumah Sakit Persahabatan, Jalan Persahabatan raja 1, Jakarta timur, Indonesia; e-mail: eburhan@yahoo.com
Abstract
Background: Limited understanding of the presentation and course of influenza A(H5N1) infection in humans hinders evidence-based management.
Methods: We reviewed the case records of patients admitted to the Persahabatan Hospital (RSP), Jakarta, Indonesia, with influenza A(H5N1) confirmed by real-time polymerase chain reaction.
Results: Twenty-two previously well patients, aged 3 to 47 years (median 24.5 years), were identified. All attended a clinic or hospital after a median of 2 days of illness (range 0-7). Times to first dose of oseltamivir (three died before receiving oseltamivir) were 2 to 12 days (median 7 days), administered mostly (n = 15) at RSP. Nineteen patients required mechanical ventilation. Deaths numbered 18 (case fatality = 82%) occurring within hours to 6 days of RSP admission, corresponding to 6 to 16 days of illness. Admission hyperglycemia ( ≥ 140 mg/dL), unrelated to steroids or known underlying diabetes mellitus, and elevated D-dimer levels (0.81-5.2 mg/L, upper limit of normal < 0.5 mg/L) were present in 14/21 (67%) and 20/21 (95%) patients, respectively. Fibrinogen concentrations were mostly low/normal at 129.9 to 517.9 mg/dL (median 241.1, normal 200-400 mg/dL), whereas C-reactive protein (9/11) and ferritin (6/8) levels were increased. Risk factors for death (univariate analysis) included: (1) increased D-dimers, (2) hyperglycema, (3) increased urea, (4) more extensive chest radiograph shadowing, and (5) lower admission oxygen saturation.
Conclusions: Early diagnosis and effective treatment of human influenza A(H5N1) infection remains challenging. Most patients were referred late with advanced disease. Oseltamivir had limited clinical impact. Elevated D-dimer levels, consistent with fibrinolysis, and hyperglycemia warrant more research to determine their underlying mechanisms and optimal treatment.
1. Priyanti Z. Soepandi, MD, FCCP,
2. Erlina Burhan, MD,
3. Hadiarto Mangunnegoro, MD, FCCP,
4. Arifin Nawas, MD,
5. Tjandra Yoga Aditama, MD,
6. Lia Partakusuma, MD,
7. Fathiyah Isbaniah, MD,
8. Mukhtar Ikhsan, MD,
9. Boedi Swidarmoko, MD,
10. Agung Sutiyoso, MD,
11. Suhud Malik, MD,
12. Rachel Benamore, MBBChir,
13. J. Kevin Baird, PhD and
14. Walter R. J. Taylor, MD
+ Author Affiliations
1.
From the Rumah Sakit Persahabatan (Drs Soepandi, Burhan, Mangunnegoro, Nawas, Aditama, Partakusma, Isbaniah, Ikhsan, Swidarmoko, and Sutiyoso), Jakarta timur, Indonesia; the Center for Biomedical and Pharmaceutical R&E (Dr Malik), National Institutes of Health Research and Development, and the Eijkman-Oxford University Clinical Research Unit (Dr Baird), Jakarta, Indonesia; the Department of Radiology (Dr Benamore), Churchill Hospital, and the Nuffield Department of Clinical Medicine (Drs Baird and Taylor), University of Oxford, Oxford, England; and the Mahidol Oxford University Clinical Research Unit (Dr Taylor), Bangkok, Thailand.
1. Correspondence to:
Erlina Burhan, MD, Rumah Sakit Persahabatan, Jalan Persahabatan raja 1, Jakarta timur, Indonesia; e-mail: eburhan@yahoo.com
Abstract
Background: Limited understanding of the presentation and course of influenza A(H5N1) infection in humans hinders evidence-based management.
Methods: We reviewed the case records of patients admitted to the Persahabatan Hospital (RSP), Jakarta, Indonesia, with influenza A(H5N1) confirmed by real-time polymerase chain reaction.
Results: Twenty-two previously well patients, aged 3 to 47 years (median 24.5 years), were identified. All attended a clinic or hospital after a median of 2 days of illness (range 0-7). Times to first dose of oseltamivir (three died before receiving oseltamivir) were 2 to 12 days (median 7 days), administered mostly (n = 15) at RSP. Nineteen patients required mechanical ventilation. Deaths numbered 18 (case fatality = 82%) occurring within hours to 6 days of RSP admission, corresponding to 6 to 16 days of illness. Admission hyperglycemia ( ≥ 140 mg/dL), unrelated to steroids or known underlying diabetes mellitus, and elevated D-dimer levels (0.81-5.2 mg/L, upper limit of normal < 0.5 mg/L) were present in 14/21 (67%) and 20/21 (95%) patients, respectively. Fibrinogen concentrations were mostly low/normal at 129.9 to 517.9 mg/dL (median 241.1, normal 200-400 mg/dL), whereas C-reactive protein (9/11) and ferritin (6/8) levels were increased. Risk factors for death (univariate analysis) included: (1) increased D-dimers, (2) hyperglycema, (3) increased urea, (4) more extensive chest radiograph shadowing, and (5) lower admission oxygen saturation.
Conclusions: Early diagnosis and effective treatment of human influenza A(H5N1) infection remains challenging. Most patients were referred late with advanced disease. Oseltamivir had limited clinical impact. Elevated D-dimer levels, consistent with fibrinolysis, and hyperglycemia warrant more research to determine their underlying mechanisms and optimal treatment.
