35. Respiratory Diseases of Adults

Clearly, of even greater concern is the potential for a new influenza A pandemic, as occurred in 1918 and more recently in 1958 and 1968, from a newly altered strain of avian influenza. With each additional bird-to-human case, modest genetic mutation or re-assortment increases the chance for the avian virus to be altered to become established and virulent in mammalian species. This may result in the establishment of sustained transmission among humans. While the pandemics of 1958 and 1968 were together responsible for approximately 3 million deaths, mostly in the very young, the elderly, and in those with comorbid conditions, the 1918 episode is believed to have caused over 40 million deaths, mostly in the age group 15 to 35 years. This potential for greatly increased mortality among such a robust population has fueled recent concern (WHO 2005a).

This concern has become more immediate with the identification of a sub-strain of influenza A, H5N1, first identified in 1997 in Hong Kong when it jumped from poultry to humans and killed six of 18 infected people. Virtually all of the original cases were believed to have been bird-to-human transmission. Since that time there have been a few hundred serologically confirmed cases in Cambodia, Indonesia, Thailand, and Vietnam, with high case fatality but no sustained evidence of ongoing human-to-human transmission (WHO 2005b).

The H5N1 strain is highly pathogenic among poultry. During 2003-2004 it resulted in outbreaks in 8 countries in Asia, with over 100 million birds dying from disease or being culled. More recently, though an additional 150 million birds have been culled, because much of the developing world's poultry economy depends on rural backyard sources, it is not clear how effective these control measures have been. Although these efforts were thought to help control the spread of the virus, permanent ecological reservoirs appear to have become established in wild fowl and domestic chickens over a relatively broad region of Southeast Asia. WHO authorities have expressed concern about the finding that migratory birds that are infected with H5N1 but are relatively asymptomatic have spread viable viruses over large regions with subsequent infection in domestic poultry. Furthermore, more recently there has been evidence of disease in wild and zoo mammals as well as isolated cases of infection in domestic cats. Recent reports from Vietnam include two cases in humans infected through the consumption of uncooked duck blood. Further investigation of possible person-to-person transmission is underway. Recently, WHO (2005b) stated, "The possible spread of H5N1 avian influenza to poultry in additional countries cannot be ruled out. WHO recommends heightened surveillance for outbreaks in poultry and die-offs in migratory birds, and rapid introduction of containment measures, as recommended by FAO and OIE. Heightened vigilance for cases of respiratory disease in persons with a history of exposure to infected poultry is also recommended in countries with known poultry outbreaks. The provision of clinical specimens and viruses, from humans and animals, to WHO and OIE/FAO reference laboratories allows studies that contribute to the assessment of pandemic risk and helps ensure that work towards vaccine development stays on course."

Humans have little natural immunity to the H5N1 viruses. Thus, in contrast to the usual influenza epidemics, which affect the very young, elderly, and those with comorbid conditions, virtually the entire population in an exposed community is at risk. In human cases of avian influenza, following the initial respiratory infection, mortality results from two distinct processes. One process begins with relatively rapid onset of respiratory distress from hypoxia associated with ARDS.^a The alternative process results from secondary bacterial infection with a variety of organisms. In the documented H5N1 influenza infections in humans, respiratory symptoms are most prominent. However, in one case of encephalitis in a child from Vietnam, H5N1 influenza virus was identified in cerebrospinal fluid and fecal matter, and in throat and serum samples. Isolates from several cases were resistant to two commonly used antiviral medications (amantadine and rimantadine), while two other antiviral medications (oseltamivir and zanamivir) still appear to be effective.

There is no way to predict the outcome of these ongoing events. What seems evident is that if human-to-human transmission becomes established, a pandemic will follow. Given the lack of natural immunity, there is considerable concern that even if adequate vaccines were available, distribution on a worldwide basis would be limited by economic considerations as well as distribution problems in the developing world. Efforts are underway to identify the genetic make-up of the strains of H5N1 that will yield the most effective vaccines and to produce such vaccines in a cost-effective manner. Testing H5N1 vaccines based on recently identified viruses in normal healthy volunteers suggests the immunologic response may be adequate, but several months of production would be necessary to produce adequate supplies for one region, let alone for worldwide distribution. Stockpiles of effective antiviral medications are being generated in some countries. In the interim, WHO has encouraged the rapid reporting of cases and the establishment of procedures for better public health intervention strategies before and during a pandemic (WHO 2005c). Many countries have developed pandemic influenza preparedness plans in anticipation of such an event.

Source: Authors.

a. ARDS is defined as Acute Respiratory Distress Syndrome resulting from multiple causes, the most likely in this situation being an immunological reaction to the virus.