#18,464
On the heels of announcing their plan to buy 5 million doses of H5 vaccine, yesterday the UKHSA published 3 Rapid Evidence Reviews on the avian H5 virus. These internal reviews are conducted by the Clinical and Public Health Response Evidence Review team and the Science Evidence Review team within UKHSA.
Incubation and infectious period of influenza A (H5): A rapid evidence summary - Dec 4th
These reviews are all based on published evidence on-or-before April 26th of this year, and so they may not reflect some of the more recent changes to the panoply of H5 viruses. Each review runs approximately 30 pages, and is heavily annotated.
Two of these studies are closely related; looking at the incubation and infectious period for A(H5) in humans and non-humans. The first review also discusses several probable cases of human-to-human transmission going back as much as 20 years.
Remarkably, more than 20 years after H5 reappeared in Southeast Asia and began its world tour, there remain significant gaps in our understanding of how this virus spreads in human and non-human hosts.
Follow the links top read these reviews in their entirety.
Research and analysis
Influenza A (H5)
This rapid evidence summary identified and summarised evidence relating to the infectious and incubation period of influenza (H5).
Incubation and infectious period of influenza A (H5): A rapid evidence summary
Ref: Published December 2024 GOV-17586
PDF, 423 KB, 27 pages
Main messages
1. The purpose of this rapid evidence summary was to identify and summarise the available evidence on the infectious period (the timeframe in which an individual may transmit the infection to others) and incubation period (the time between contracting an infection and symptom onset) of influenza A (H5) (search up to 26 April 2024), including 11 studies in total.
2. One retrospective cohort study of 8 cases estimated the probable range of the infectious period to be between 5 and 13 days (2), and one retrospective cohort study of 11 secondary cases estimated serial interval to be 8 days (range: 2 to 11 days) (1). The case series that presented evidence for human-to-human transmission reported that the 2 index cases likely infected 3 secondary cases (individuals infected through direct contact with an index case) 3 to 5 days after their symptom onset (9, 10).
3. Three retrospective cohort studies including up to 59 cases (assuming no overlap in cases between studies) (2 to 4) and 7 case series and case reports including up to 30 cases (assuming no overlap in cases between studies) (5 to 11) were identified that provided evidence for the incubation period of H5 influenza.
4. Almost all cases were exposed to poultry prior to symptom onset, although there was evidence of human-to-human transmission in several cases (2, 9, 10).
5. Estimates of the incubation period varied between 2 and 10 days across studies, although in the 2 retrospective cohort studies estimating the mean and median incubation periods,the mean was estimated as 3.3 days (3) and a median as 5 days (4).
6. Overall, there was very limited evidence estimating the infectious period and limited evidence estimating the incubation period of influenza A (H5). Additionally, almost all cases were identified in Asia between 2003 and 2014, potentially limiting generalisability of the results to a contemporary UK population, as both the circulating H5N1 influenza virus and demographics of potential cases may be different in ways that could affect the infectious and incubation periods.
Summary
There was extremely limited evidence estimating the infectious period of influenza A (H5) cases. One study of 8 cases estimated the probable range of the infectious period to be between 5 and 13 days, and one study of 11 secondary cases estimated the median interval between illness onset of serial cases in infection clusters with inconclusive exposure to a zoonotic source of virus to be 8 days (range: 2 to 11 days).
Additionally, in the case series presenting evidence for human-to-human transmission, the 2 index cases likely infected the other 3 cases 3 to 5 days after their symptom onset. There was also limited evidence estimating the incubation period of influenza A (H5) cases (a maximum of 89 cases if there was no overlap between studies). Most cases were exposed to poultry prior to symptom onset, although there was evidence of human-to-human transmission in some cases.
Estimates of the incubation period varied between 2 and 10 days across studies. In the 2 retrospective cohort studies estimating the mean and median incubation periods, the mean was estimated as 3.3 days (3) and the median as 5 days (4).
Incubation and infectious period of influenza A (H5) in non-human mammals: A rapid evidence summary
Ref: December 2024 GOV-17588
PDF, 417 KB, 31 pages
This rapid evidence summary identified and summarised evidence relating to the timeframe of transmitting an infection between 2 non-human mammals (the infectious period). It also identified and summarised time between contracting an infection and symptom onset (incubation period) of influenza A (H5) in non-human mammals.
Main messages
1. The purpose of this rapid evidence summary was to identify and summarise the available evidence on the infectious period (the timeframe in which an individual may transmit the infection to others) and incubation period (the time between contracting an infection and symptom onset) of influenza A (H5) in non-human mammals (search up to 15 May 2024) (1 to 8).
2. Eight studies were included in this review. Seven studies were experimental animal studies (including ferrets, guinea pigs, dogs, and cats), where non-human mammals were inoculated with H5 influenza, and a total of 46 healthy non-human mammals were exposed between one and 2 days later to the infected animals to examine transmission (1 to 7). One study was an observational study reporting on an outbreak of H5N1 influenza among 147 tigers in Thailand (8).
3. Six of the 7 experimental studies reported on infectious period of H5 influenza by repeat testing of healthy, exposed non-human mammals (1 to 6). One experimental study (7) and the one observational study (8) provided evidence for the incubation period.
4. In 6 of the experimental studies reporting on infectious period, the time from exposure to testing positive for H5 influenza for non-human mammals was between 2 and 8 days, although most non-human mammals tested positive 5 or fewer days after exposure (1 to 6). The time from exposure to the last positive test was between 4 and 12 days across the 6 studies, although not all studies continued to test until there were no more positive tests, meaning some non-human mammals could have tested positive for longer.
5. The 2 studies reporting on the incubation period suggested the incubation period of H5 influenza was around 3 days for 147 tigers (8), and 3 to 4 days for one cat (7).
6. In the experimental studies inoculating non-human mammals with more than one strain ofH5 influenza, there were differences in the proportion of non-human mammals testing positive and the time to first and last positive tests. This may be due to chance given the low number of non-human mammals examined, but this may also suggest different strains of H5 influenza could have different infectious periods.
7. The studies included a variety of non-human mammal species, and there were differences in how the contact non-human mammals were exposed to the inoculated non-human mammals, which may have contributed to differences in the results between studies.
8. Overall, there was limited evidence estimating both the infectious period and the incubation period of influenza A (H5) in non-human mammals, with evidence from 46 nonhuman mammals exposed to inoculated non-human mammals (many of the exposed nonhuman mammals did not become infected) for the infectious period (time from exposure to first and last positive test), and evidence from up to 147 tigers and one cat for the incubation period.
Summary
In 6 studies, the time from exposure to the first non-human mammal testing positive for H5 influenza was between 2 and 8 days, although the majority of non-human mammals tested positive 5 or fewer days after exposure. The time to the last positive test in each study was between 4 and 12 days after exposure across the 6 studies, although not all studies continued to test until there were no more positive tests, meaning some non-human mammals could have tested positive for longer.
The 2 studies reporting on the incubation period suggested the incubation period of H5 influenza was around 3 days for tigers, and 3 to 4 days in one cat. In the experimental studies inoculating non-human mammals with different strains of H5 influenza, there were differences between studies in the proportion of non-human mammals testing positive and the time from exposure to first and last positive tests. The studies experimented or reported on a variety of non-human mammals, and there were differences in how the healthy non- human mammals were exposed to the inoculated non-human mammals, which could have contributed to differences in results between studies.
The third study, on conjunctivitis related to H5 or H7 infection, focuses primarily on past H7Nx outbreaks, as this symptom was only rarely reported with H5N1 prior to this year. Given its limited H5 data, I've just posted their summary below.
Conclusion
This rapid evidence summary on the clinical and epidemiological characteristics of people with conjunctivitis caused by influenza A (H5 or H7) included 12 studies reporting approximately 93 human conjunctivitis cases. These were caused by 3 influenza A subtypes: H5N1 (1 case), H7N7 (approximately 87 cases) and H7N3 (5 cases). There were 12 included studies (1 to 12): 2 retrospective cohort studies (5, 7), one cross-sectional study (3), one case series (6), and 8 case reports with between one and 3 cases per report (1, 2, 4, 8 to 12). There was overlap in reporting of cases between some studies (2, 3, 5 to 8, 11, 12).
Most of the evidence was in working-age adults in the context of occupational exposure during poultry outbreaks (2, 3, 5 to 12). Comorbidities of those affected were not reported. For the majority there were no co-existing influenza-like-illness symptoms (6, 7). For the single case of conjunctivitis caused by influenza A H5N1 there were no reported eye swab test results (4), however for the influenza A H7N7 and H7N3 conjunctivitis cases there was evidence of positive test results from eye swabs (2, 6 to 10, 12).
In most cases the suspected source of the infection was occupational poultry exposure (2, 3, 6 to 12). In 2 cases it was suspected to be non-occupational poultry exposure (1, 4). The influenza A H7N7 outbreak in the Netherlands in 2003 also provided some evidence of possible human-to-human transmission from index cases who worked with poultry to their household contacts (5 to 7). However, it was not possible to determine whether transmission had occurred during the period of conjunctivitis symptoms. The conjunctivitis-specific incubation period was only available for 2 influenza A H7N3 conjunctivitis cases occurring in Canada in 2004, and was 3 days and 1 to 2 days for the 2 cases respectively (11).
There was very limited evidence describing the clinical and epidemiological characteristics of people with conjunctivitis caused by influenza A (H5). The numbers of people with conjunctivitis caused by influenza A (H7) in the included studies were small, most cases were in working age adults, and comorbidities of cases were not reported. This means we have limited information on the clinical and epidemiological characteristics of people with conjunctivitis caused by influenza A (H5 or H7).
