Clinical preparedness for severe pneumonia with highly pathogenic avian influenza A (H5N1): experiences with cases in Vietnam.

BACKGROUND: Avian influenza A (H5N1) in human presents a global pandemic threat, and preparedness is urgently required in high-risk countries. METHODS: A retrospective chart review was conducted on 8 patients with H5N1 infection (aged 2-30 years; 3 fatal) who were hospitalized in Bach Mai Hospital (BMH), Vietnam, or in affiliated hospitals with consultation by physicians in BMH between 2007 and 2010. Demographic background, chest radiographs, and clinical and laboratory data were evaluated to determine the critical issues in relation to clinical outcomes. Treatment of 4 patients with acute respiratory distress syndrome (ARDS) (2 fatal) was assessed for renal replacement therapy using continuous hemodiafiltration (CHDF), polymyxin B-immobilized (PMX) hemoperfusion, or their combination. RESULTS: Patients had direct contact with dead/sick poultry infected with H5N1 virus or lived in areas where H5N1 poultry outbreaks had been reported at the same time as their illness. Time to initiation of oseltamivir from symptom onset was 2-6 days for survivors and 7-9 days for non-survivors. All patients except one had infiltrative shadows on chest radiographs on admission. Patients with delayed treatment developed ARDS. Renal replacement therapy contributed to patient survival, with improvement of oxygenation and a dramatic decrease in serum cytokine levels if initiated earlier. CONCLUSIONS: Understanding local H5N1 poultry outbreaks and chest radiography assist early diagnosis and initiation of antiviral treatment. Developing a network among local and tertiary care hospitals can reduce the time to initiation of treatment. CHDF and PMX hemoperfusion are possible candidates for effective treatment of ARDS with H5N1 if applied earlier.

Oseltamivir is adequately absorbed following nasogastric administration to adult patients with severe H5N1 influenza.

In the absence of a parenteral drug, oral oseltamivir is currently recommended by the WHO for treating H5N1 influenza. Whether oseltamivir absorption is adequate in severe influenza is unknown. We measured the steady state, plasma concentrations of nasogastrically administered oseltamivir 150 mg bid and its active metabolite, oseltamivir carboxylate (OC), in three, mechanically ventilated patients with severe H5N1 (male, 30 yrs; pregnant female, 22 yrs) and severe H3N2 (female, 76 yrs). Treatments were started 6, 7 and 8 days after illness onset, respectively. Both females were sampled while on continuous venovenous haemofiltration. Admission and follow up specimens (trachea, nose, throat, rectum, blood) were tested for RNA viral load by reverse transcriptase PCR. In vitro virus susceptibility to OC was measured by a neuraminidase inhibition assay. Admission creatinine clearances were 66 (male, H5N1), 82 (female, H5N1) and 6 (H3N2) ml/min. Corresponding AUC(0-12) values (5932, 10,951 and 34,670 ng.h/ml) and trough OC concentrations (376, 575 and 2730 ng/ml) were higher than previously reported in healthy volunteers; the latter exceeded 545 to 3956 fold the H5N1 IC(50) (0.69 ng/ml) isolated from the H5N1 infected female. Two patients with follow-up respiratory specimens cleared their viruses after 5 (H5N1 male) and 5 (H3N2 female) days of oseltamivir. Both female patients died of respiratory failure; the male survived. 150 mg bid of oseltamivir was well absorbed and converted extensively to OC. Virus was cleared in two patients but two patients died, suggesting viral efficacy but poor clinical efficacy.