# 4615
On of the great mysteries surrounding human H5N1 infections has been the abysmal survival rate, particularly in Indonesia and parts of South East Asia.
Worldwide (among confirmed cases), 294 of 498 victims have died. That’s roughly a 59% fatality rate. The rate varies, however, with 82% of H5N1 cases dying in Indonesia while less than 32% have succumbed in Egypt.
Sobering numbers, particularly when compared to the 2.5%-5% fatality rate experienced during the 1918 pandemic. Fortunately, the number of cases remains low, and the virus has yet to adapt well enough to human hosts to become a pandemic.
Although human cases have been detected and treated for more than a decade, we rarely get detailed information regarding their course of illness, treatment, or outcome.
In August of 2008 we did get a review of 26 cases out of China, which shed some light on the pathogenesis of the virus (see Clinical Case Review Of 26 Chinese H5N1 Patients)
Today a glimpse, via an abstract for a study (subscription req.) in The Journal CHEST, that outlines the clinical course of 22 patients at one hospital in Indonesia.
A hat tip to Dutchy at FluTrackers for this link.
Clinical course of H5N1 avian influenza in patients at the Persahabatan Hospital, Jakarta, Indonesia, 2005-2008.
Priyanti Z Soepandi, Erlina Burhan, Hadiarto Mangunnegoro, Arifin Nawas, Tjandra Yoga Aditama, Lia Partakusuma, Fathiyah Isbaniah, Suhud Malik, Rachel Benamore, J Kevin Baird, Walter RJ Taylor, and the H5N1 clinical team
Abstract
Background: Limited understanding of the presentation and course of influenza A/H5N1 infection in humans hinders evidence-based management.
Methods: Review of case records of patients with real time, PCR confirmed H5N1 influenza admitted to the Persahabatan Hospital (RSP), Jakarta, Indonesia.
Results: 22 previously well patients, age 3 to 47 years (median 24.5), 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 (3 died before receiving oseltamivir) were 2 to 12 days (median 7), administered mostly (n=15) at RSP. 19 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 raised d-dimers (0.81 – 5.2 mg/L, ULN < 0.5 mg/L) were present in 14/21 (67%) and 20/21 (95%) patients, respectively.
Fibrinogen concentrations were mostly low/normal 129.9-517.9 mg/dL (median 241.1, normal 200-400 mg/dL) whilst CRP (9/11) and ferritin (6/8) were raised. Risk factors for death (univariate analysis) included: (i) raised d-dimers, (ii) hyperglycemia, (iii) raised urea, (iv) more extensive chest X ray shadowing, and (v) lower admission oxygen saturation.
Conclusions: Early diagnosis and effective treatment of human H5N1 infection remains challenging. Most patients were referred late with advanced disease. Oseltamivir had limited clinical impact. Raised d-dimers, consistent with fibrinolysis, and hyperglycemia warrant more research to determine their underlying mechanisms and optimal treatment.
A little interpretation for non-medical readers may be helpful here, particularly regarding the elevated d-dimers readings.
D-dimer is a protein fragment left behind in the blood after a fibrin clot has been degraded. The test is normally used to diagnose thrombosis, but is also diagnostic for DIC (disseminated intravascular coagulation).
DIC (which can present as widespread internal bleeding, hemorrhagic shock, and renal failure) is a condition sometimes seen in severe cases of sepsis and ARDS (Acute Respiratory Distress Syndrome).
Unlike Egypt, which has reported favorably on the efficacy of oseltamivir (Tamiflu) in the treatment of H5N1, this report states that oseltamivir had limited clinical impact.
Whether this has something to do with the clade of virus being encountered in Indonesia, or the delay in starting treatment, or some other unknown variable, isn’t clear.
The d-dimer readings, and hyperglycemia upon admission - which both appear linked to bad outcomes - add new and tantalizing clues to the pathogenesis of this virus in humans.
In February of 2009 we got a look at a study that compared the pathogenesis (disease progression) of non-human primates (macaques) infected with the H5N1 virus, seasonal flu, and with two altered viruses carrying genetic material from the 1918 Spanish Flu.
The study, entitled Early and sustained innate immune response defines pathology and death in nonhuman primates infected by highly pathogenic influenza virus by Carole Baskin et. al. appeared PNAS (The Proceedings of the National Academy of Science).
At the time, I wrote a 3-part essay dissecting this study for the layperson, which some might still find useful.
Dissecting the Influenza Pathogenesis Study Pt. 1
Dissecting the Influenza Pathogenesis Study Pt. 2
Dissecting the Influenza Pathogenesis Study Pt. 3
Despite all we’ve learned from human cases, and lab research, there are plenty of unanswered questions surrounding the virulence of H5N1.
Questions that we would dearly love to have the answers to now, before the virus becomes a graver threat.
