22 August 2007
WHO Updates Clinical Advice on Human H5N1 Virus Infections
This week the World Health Organization (WHO) released new guidance on practical clinical issues in the care of patients with H5N1 avian influenza infections. The 22-page document, including 95 references, builds on the WHO Consultation conferences on Human H5N1 infections convened in Antalya, Turkey in March 2007 and in Hanoi, Viet Nam in May 2005. Annex 1 lists the nine international members of the “Document drafting group” and the 12 international external reviewers.
This document, posted on the WHO website at: www.who.int/csr/disease/avian_influenza/guidelines/clinicalmanage07/en/index.html, also includes two quite useful standardization documents. These are a “WHO H5N1 Clinical Case Summary Form” and a lab form that includes space for data on virus detection results (RT-PCR and Virus Culture), virus susceptibility testing, and plasma antiviral concentration.
Among the multiple clinical “pearls” for this emerging disease are:
1. “The duration of A (H5N1) viral replication in humans appears to be prolonged and has been documented to last up to 15-17 days after illness onset (see references 4, 12, 13). In the absence of corticosteroid administration, immuno-competent A (H5N1)-infected persons probably cease to excrete the infectious virus 3 weeks after illness onset, but further virological shedding data are needed to verify this.” (Page 2 “Site of Care” section).
2. “In contrast to uncomplicated seasonal influenza, oseltamivir treatment is also warranted for patients presenting late with A (H5N1) virus infection because viral replication is more prolonged than with seasonal influenza”. (Page 5 “Antiviral Treatment” section).
3. “Continued fever and clinical deterioration may suggest ongoing viral replication, although the possibilities of bacterial superinfection and other nosocomial complications should be evaluated. If no clinical improvement has been observed after a standard 5-day course, the oseltamivir therapy may be extended for a further 5 days” (page 6).
4. Regarding potential inhaled therapy with the neuraminidase inhibitor zanamivir (Relenza), “stringent hospital infection control measures must be adhered to if any drugs are administered by a nebulizer to patients with human A (H5N1) illness to prevent possible transmission of A (H5N1) viruses by aerosol.”
5. Regarding potential combination antiviral therapy with an adamantine drug (rimantidine or amantidine) plus a neuraminidase inhibitor (oseltamivir or zanamivir), this should only be considered if there is “pneumonic disease or clinical progression” and when locally circulating A (H5N1) viruses (such as Clade 2.2 and Clade 2.3) are likely to be susceptible to adamantanes (but NOT Clade 1 viruses as found so far in Cambodia, Thailand, or Viet Nam). Preferably, serial respiratory samples should also be collected for serial virological monitoring” (page 7 “Other viral agents” section).
6. Regarding “virological monitoring: “When possible, collection of serial respiratory samples (throat swabs and , if available, tracheal aspirates) for detection of A (H5N1) virus (before treatment, day 4-5, and day 7-8 after treatment is initiated) should be considered to analyze viral clearance or persistence and antiviral resistance” (pages 7-8).
7. A detailed section on ventilatory support is provided (pages 12-14) including the observation that “There appears to be a high incidence of pneumothorax in critically ill A (H5N1) virus-infected patients.” (Page 12).
8. Regarding infection control, it is noted emphasized that “Administration of supplemental oxygen via mask may also contribute to dispersion of potentially infectious aerosols. Oxygen masks with an expiratory port and HEPA filter will reduce aerosol production” (page 14).
Hospitals, health care clinics, and public health agencies would benefit by reviewing and discussing this document with all persons and departments that could become involved with the care of a patient (e.g., a traveler in August 2007 to the USA from an H5N1 endemic area of the world) in order to have an updated standard operating protocol (SOP) for the optimal care of such patients and to minimize the infection control risk to persons providing this medical care.
Daniel R. Lucey, MD, MPH
Director, Center for Biologic Counterterrorism and Emerging Diseases
EROne Institutes, Department of Emergency Medicine,
Washington Hospital Center
Adjunct Professor of Microbiology and Immunology
Georgetown University Medical Center
Website for this document: www.BePast.org