Pandemic influenza: certain uncertainties

Abstract

For at least five centuries, major epidemics and pandemics of influenza have occurred unexpectedly and at irregular intervals. Despite the modern notion that pandemic influenza is a distinct phenomenon obeying such constant (if incompletely understood) rules such as dramatic genetic change, cyclicity, "wave" patterning, virus replacement, and predictable epidemic behavior, much evidence suggests the opposite. Although there is much that we know about pandemic influenza, there appears to be much more that we do not know. Pandemics arise as a result of various genetic mechanisms, have no predictable patterns of mortality among different age groups, and vary greatly in how and when they arise and recur. Some are followed by new pandemics, whereas others fade gradually or abruptly into long-term endemicity. Human influenza pandemics have been caused by viruses that evolved singly or in co-circulation with other pandemic virus descendants and often have involved significant transmission between, or establishment of, viral reservoirs within other animal hosts. In recent decades, pandemic influenza has continued to produce numerous unanticipated events that expose fundamental gaps in scientific knowledge. Influenza pandemics appear to be not a single phenomenon but a heterogeneous collection of viral evolutionary events whose similarities are overshadowed by important differences, the determinants of which remain poorly understood. These uncertainties make it difficult to predict influenza pandemics and, therefore, to adequately plan to prevent them.

Figure 1

European epidemics of probable influenza during the period of European monastic and court chronicles, 876–1491ad.On the y-axis, influenza activity is recorded according to apparent degree of geographic extension, as determined by historians and historical documents [–,,,,,–,–,–,–,–,,–,–,,,–,,,,,,–,–,,,,–238]. Such determinations may only be rough approximations. Disease severity as reported by contemporary observers is characterized as “mild” () or “severe” (). In most instances, these designations have not been established by either reliable mortality or case-fatality data. Unlettered epidemics/pandemics reflect insufficient information about disease severity. Also plotted is the first sweate epidemic of 1485

Figure 2

Old World (top panel) and New World (bottom panel) pandemics and epidemics of probable influenza, 1492–1728. On the y-axis, influenza activity is recorded according to apparent degree of geographic extension, as determined by historians and historical documents [–,,,,,–,–,–,–,–,–,,–,–,,,–,,,,,,–,–,,,,–238]. Such determinations may only be rough approximations. Disease severity as reported by contemporary observers is characterized as “mild” (M) or “severe” (S). In most instances, these designations have not been established by either reliable mortality or case-fatality data. Unlettered epidemics/pandemics reflect insufficient information about disease severity. Also plotted are the sweate epidemics of the early 16th century

Figure 3

Old World (top panel) and New World (bottom panel) pandemics and epidemics of probable influenza, 1729 to 1888. On the y-axis, influenza activity is recorded according to apparent degree of geographic extension, as determined by historians and historical documents [–,,,,,–,–,–,–,–,–,,–,–,,,–,,,,,,–,–,,,,–238]. Such determinations may only be rough approximations. Disease severity as reported by contemporary observers is characterized as “mild” (M) or “severe” (S). In most instances, these designations have not been established by either reliable mortality or case-fatality data. Unlettered epidemics/pandemics reflect insufficient information about disease severity

Figure 4

The 1889 influenza pandemic was tracked globally as it first appeared and then spread quickly, in this case from East to West (Asia to Europe), similar to the rapid spread of modern pandemics [104,105]. Figure adapted from Clemow [5]

Figure 5

Genetic relationships between human and swine influenza viruses, 1918–2010; adapted from Morens et al. [10]

Figure 6

Secular patterns of mortality increases over the first 5 years after pandemic appearance, in four influenza pandemics appearing between 1889 and 1968. The four panels are adapted from different data sources and cannot be compared for purpose other than examining appearance/recurrence patterns. The top panel represents data from Germany [239]. The second panel represents data from Breslau (now Wrocław, Poland), from Lubinski [187]. In the bottom two panels, representing the 1957 [240] and 1968 [241] pandemics in America, data on mortality increases are displayed as rising above the expected background

Figure 7

Pandemic occurrence by estimated global population, 800–2009 ad. European-wide epidemics are included for the period when pandemics may not have been recorded, from 800–1491 ad (see text). *For 1833, see text discussion on different pandemics versus “waves” between 1830 and 1837