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Seasonality of influenza in humans: a conundrum across latitudes Wladimir J. Alonso Fogarty International Center NIH.

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Presentation on theme: "Seasonality of influenza in humans: a conundrum across latitudes Wladimir J. Alonso Fogarty International Center NIH."— Presentation transcript:

1 Seasonality of influenza in humans: a conundrum across latitudes Wladimir J. Alonso Fogarty International Center NIH

2 This talk: Influenza and … 1) The conundrum of human influenza seasonality 2) Causative explanations 3) Examples of contributions from Brazil in: Describing the phenomenon Understanding the dynamics of influenza pandemics Public health policy implications

3 Current understanding of influenza seasonality “Infectious disease dynamics offer a wide variety of intriguing and unexplained phenomena, yet none is as consistently observed while still remaining so poorly understood as the seasonality of influenza” Lofgren et al (2007) Influenza Seasonality: Underlying Causes and Modeling Theories J Virol 81:

4 Maps of influenza peak timing Based on the literature search in Pubmed between May 2009 and February 2010 for influenza and RSV articles published between 1990 and all hospital and community-based studies using one or more laboratory tests, with a minimum average of 2 virus-positive specimens per month Bloom-Feshbach et al. (2013). PLoS ONE 8(2)

5 Maps of influenza peak timing Based on the literature search in Pubmed between May 2009 and February 2010 for influenza and RSV articles published between 1990 and all hospital and community-based studies using one or more laboratory tests, with a minimum average of 2 virus-positive specimens per month

6 So, how do astronomical seasons trigger influenza epidemics in different latitudes

7 Influenza and … 1) The conundrum of influenza seasonality 2) Causative explanations 3) Examples of contributions from Brazil in: Describing the phenomenon Understanding the dynamics of influenza pandemics Public health policy implications

8 Diana Marques

9 Practical application in recommendations for preventing the transmission in a pandemic

10 Global influenza seasonality: Reconciling patterns across temperate and tropical regions J Tamerius, MI Nelson, SZ Zhou, C Viboud, MA Miller, WJ Alonso Environmental health perspectives 119 (4), 439 J Tamerius, MI Nelson, SZ Zhou, C Viboud, MA Miller, WJ Alonso Environmental health perspectives 119 (4), 439 A framework for addressing seasonality of influenza in humans

11 Putative relationship and causal connections among key seasonal stimuli, mediating mechanisms, and influenza epidemics.

12 Mediating mechanisms

13 Seasonal Factors

14 Hemmers et al Harper G 1961 Hood 1963 Loosli et al RelativeH umidity Virus survival Shechmeister 1950, Schaffer et al RelativeH umidity Virus survival would explain better current data better Shaman & Kohn 2009 anomalously ▼AH associated with the onset of wintertime influenza in US Shaman et al 2010 Absolute Humidity Virus survival

15 RelativeH umidity Virus survival Absolute Humidity Virus survival Problems: -Does not explain circulation in the tropics Shechmeister 1950, Schaffer et al RelativeH umidity Virus survival

16 Sensitivity of influenza viruses to UV radiation (Tamm and Fluke 1950, Powell and Setlow 1956, Jensen 1964) Low inactivation rates during low sun seasons Sagripanti and Lytle 2007 Problems: - the amount of UV indoors (where a large proportion of influenza transmission possibly occurs) is constant

17 Vitamin D (dependent upon exposure to UVB) acts as an immune system modulator (Cannel et al 2006) Clinical trial (Urashima et al 2009): Tested if vitamin D supplements affected the incidence of influenza in school-aged children. Yes for Influenza A (and Asthma) but No for Influenza B

18 Problems: -Still poor evidence -It might act as a facilitator, but would still need additional mechanisms to explain why changes in weather trigger epidemics

19 Influenza di freddo (influence of the cold) Italy circa 1530

20 Lowen et al 2007 Experience with guinea-pigs Temperature Aerosol transmission 5oC 30 o C Polozov et al 2008 Virus stability Temperature (<21 o C) Ordering of phospolipids

21 Problems: -Hard to explain circulation in the tropics

22 Cold winter weather causes people to crowd indoors (one of the most accepted hypothesis)

23 Individuals spend on average 1–2 hours more indoors during cold weather in the USA (Graham and McCurdy 2004)

24 Photo: Bart Pogoda It would also be valid for precipitation, as people spend about 0.5 hours more indoors during rainy weather conditions.

25 Problems: -These differences seem minimal in the 24 hours of the day (mainly in the current crowded conditions of urban areas) -No empirical data has shown an association between increased contact rates due to weather conditions and increases in influenza transmission (Lofgren et al. 2007)

26 School schedules, calendar festivities, etc could drive influenza Holidays reduced transmission among children in France by 20–29% (Cauchemez et al. 2008)

27 Problems: - Influenza peaks during the winter in temperate locations, and not during the fall or spring (when children are also in school) - tropical epidemics do not overlap with school calendar - crowding also occurs year-round at festivals, sporting events, and conferences without consistent outbreaks of infection

28 Exposure to cool (and dry) temperatures can affect host immunity: - vasoconstriction in the nose and respiratory tract (Le Merre et al. 1996) - mucociliary function (Salah et al. 1988) - increases energetic demand (Lochmiller and Deerenberg 2000) -abrupt changes in temperature are also implied in a broad range of diseases, including influenza (Bull and Morton, 1978)

29 Problems: -Hard to explain circulation in the tropics (although the hypothesis of increases in energetic demand is consistent with the requirement for thermoregulation during damp conditions of rainy season in the tropics)

30 2) large territorial extension ranging from equatorial to semi-temperate climates Brazil 1) good epidemiological data is available

31 Estimating the circulation of influenza based on hospitalizations and deaths is not straightforward in temperate countries, and it is even less so in tropical countries. Severe clinical outcomes are often caused by secondary bacterial infections, and a primary influenza infection may be unrecognized. Additionally, laboratory confirmation of influenza infection is rarely conducted. As a result, most influenza-related hospitalizations and deaths are not attributed to influenza on discharge forms and death certificates Problems in describing influenza seasonality

32 1) We investigated monthly pneumonia and influenza mortality data, from all Brazilian states, in a period comprising 22 years 2) We obtained independent confirmation of our findings with virus surveillance data from available years ( ) Study in Brazil

33 Phase of the major peak (months of the year) J F M A M J J A S O N D Latitude (degrees) Peak timing was found to be structured spatio-temporally, with annual peaks being earlier in the north, and gradually later in the south of Brazil Colors indicate the same regions in both figures and sizes correspond to (log) of population of each state

34 Confirmation with virus surveillance data

35 Monthly climatic data obtained from worldwide climate maps generated by the interpolation of climatic information from ground-based meteorological stations Climatologic factors Mitchell TD, Jones PD. An improved method of constructing a database of monthly climate observations and associated high-resolution grids. International Journal of Climatology 2005;25: (data at:

36 … precipitation discriminates much better influenza seasons in the equatorial regions While temperature seems important in the South… Plots of periods (averages of 3 months) of high- (circles) and low-influenza incidence (triangles)

37 This talk: Influenza and … 1) The conundrum of influenza seasonality 2) Causative explanations 3) Examples of contributions from Brazil in: Describing the phenomenon Understanding the dynamics of influenza pandemics Public health policy implications

38 Influenza vaccination in Brazil Previous weeks of southern cold were not necessarily in the right timing of vaccination for the entire country da Cunha, Camacho et al 2005 Influenza vaccination in Brazil: rationale and caveats. Revista de Saúde Pública 39(1):129-36

39 Recommendation of optimization of influenza vaccination in Brazil as a by-product of the studies of influenza seasonality

40 Inferring time-dependent connections between influenza strains detected in Belém and São Paulo and vaccination timing São Paulo’s data from Adolfo Lutz Institute and Belém data from Evandro Chagas Institute Virus of influenza detected at the Evandro Chagas Institute (IEC) and Adolfo Lutz Institute (IAL) in the period from I991 to year Month of detection at IEC Detected vírus at IEC Month of detection at IAL Detected vírus at IALVírus vacinais 1991 June A/England/427/88 (H3N2) A/Beijing/353/89 (H3N2) October July September B/Gingdao/102/91 A/Washinghton/15/91 (H3N2) A/Beijing/358/89 (H3N2) 1992Sem detecção 1993Sem detecçãoApril A/Beijing/32/92 (H3N2) 1994 April A/Guan Dong/25/93 (H3N2) B/Guan Dong/8/93 Februrary B/Brazil/216/ May Februrary B/Guan Dong/8/93 A/Shang Dong/9/93 (H3N2) March A/Johannesburg/33/94 (H3N2) 1996Sem detecção January April June A/Wuhan/359/95 (H3N2) A/Johannesburg/33/94 (H3N2) A/Taiwan/1/86 (H1N1) A/Bayern/07/95(H1N1) B/Beijing/184/ Sem detecção May June March A/Wuhan/359/95 (H3N2) A/Bayern/07/95(H1N1) B/Beijing/184/ March August A/Sydney/05/97 (H3N2) B/Beijing/184/93 April A/Sydney/05/97 (H3N2) B/Beijing/184/ March Februrary A/Sydney/5/97 (H3N2) B/Beijing/184/93 March July A/Sydney/5/97 (H3N2) B/Beijing/184/93 A/Beijing/262/95 (H1N1) A/Sydney/5/97 (H3N2) B/Beijing/184/ MarchA/NewCaledonia/20/99(H1N1) March A/NewCaledonia/20/99(H1N1) A/Sydney/05/97 (H3N2) A/Panamá/2007/99 (H3N2) A/NewCaledonia/20/99(H1N1) A/Sydney/05/97 (H3N2) B/Beijing/184/ May March May A/NewCaledonia/20/99 (H1N1) A/Panama/2007/99 (H3N2) B/Sichuan/379/99 April June B/Sichuan/379/99 A/NewCaledonia/20/99 (H1N1) A/Panama/2007/99 (H3N2) A/NewCaledonia/20/99 (H1N1) A/Panama/2007/99 (H3N2) B/Sichuan/379/ April A/Panama/2007/99 (H3N2) B/Hong Kong/330/2001 May June A/Panama/2007/99 (H3N2) B/Hong Kong/330/2001 A/NewCaledonia/20/99 (H1N1) A/Panama/2007/99 (H3N2) B/Sichuan/379/ January March December A/Newcaledonia/20/99 (H1N2) A/Panama/2007/99 (H3N2) A/Fujian/411/2002 (H3N2) April A/Newcaledonia/20/99 (H1N2) A/Panama/2007/99 (H3N2 A/NewCaledonia/20/99 (H1N1) A/Panama/2007/99 (H3N2) B/Hong Kong/330/ January March A/Fujian/411/2002 (H3N2) January March April June A/Fujian/411/2002 (H3N2) B/Hong Kong/330/2001 B/Hong Kong/1434 B/Brisbane/ A/NewCaledonia/20/99 (H1N1) A/Fujian/411/2002 (H3N2) B/Hong Kong/330/ JanuaryB/Shanghai/361/2002 January Februrary A/NewCaledonia/20/99 (H1N1) B/Shanghai/361/2002 H3 A/NewCaledonia/20/99 (H1N1) A/Wellington/1/2004 (H3N2) B/Shanghai/361/ May October A/California/7/2004 (H3N2) A/Wisconsin/67/2005 (H3N2) B/Malaysia/2506/2004 May October A/California/7/2004 (H3N2) A/Wisconsin/67/2005 (H3N2) B/Malaysia/2506/2004 A/NewCaledonia/20/99 (H1N1) A/California/7/2004 (H3N2) B/Malaysia/2506/ April January A/NewCaledonia/20/99 (H1N1) A/Wisconsin/67/2005 (H3N2) B/Malaysia/2506/2004 May A/Wisconsin/67/2005 (H3N2)A/NewCaledonia/20/99 (H1N1) A/Wisconsin/67/2005 (H3N2) B/Malaysia/2506/2004 Belém São Paulo

41 Southern Hemisphere Flu vaccine not good for Brazil? Mello et al (2010) influenza viruses isolated monthly from 1999 to 2007 in Belém and São Paulo Belém São Paulo

42 Immunity based on hypothetical scenario where the Northern Hemisphere vaccination recommendations and schedule are used in both cities. Immunity based on historic vaccination strategy adopted by Brazilian authorities, relying on the Southern Hemisphere vaccine recommendations and schedule. Southern Hemisphere Flu vaccine not good for Southern tropics?

43 Southern and Northern Hemisphere recommendation

44 Matches with Southern Hemisphere recommendations 11 matches

45 Matches with Northern Hemisphere recommendations 24 matches

46 Influenza vaccination in Brazil Previous weeks of southern cold were not necessarily in the right timing of vaccination for the entire country da Cunha, Camacho et al 2005 Influenza vaccination in Brazil: rationale and caveats. Revista de Saúde Pública 39(1):129-36

47 This talk: Influenza and … 1) The conundrum of influenza seasonality 2) Causative explanations 3) Examples of contributions from Brazil in: Describing the phenomenon Understanding the dynamics of influenza pandemics Public health policy implications

48

49 Data Mortality from two publicly available and independent sources: Records from the Mortality Information System of the vital statistics agency of the Brazilian Ministry of Health ( ) Laboratory-confirmed H1N1pdm deaths from the National Surveillance Information System of Notifiable Diseases (SINAN) as of March 12 (2012)

50 Laboratory-confirmed H1N1pdm deaths High diagnostic specificity Relatively straightforward to obtain the parameters However, it does not capture deaths caused by secondary complications

51 Pneumonia and influenza coded records from the Mortality Information System No attempt to estimate all deaths caused by H1N1pdm strain. Instead, we estimate mortality in the pandemic period above that expected in a non-pandemic year (and attributed causes)

52 Geographical patterns in the timing of pandemic mortality: week of the first lab-confirmed death by state. The size of the data points is proportional to the population of each state. The same colors are used to show each state on the graph and map.

53 Overall, there was an excess of 2,273 P&I associated deaths and 2,787respiratory- associated deaths No excess of circulatory deaths 95% confidence threshold was obtained

54 Geographical patterns in the severity of pandemic mortality

55 Lessons learned from the 2009 Pandemic in Brazil Timing more similar to seasonal influenza (therefore putativelly constrained by climate) – different therefore from 1918 pandemic Gradient of impact from the south to the equator, where pandemic had nearly no impact (confirmed by recent studies in Africa) No excess mortality from secondary causes in Brazil (other than respiratory, pneumonia or influenza)

56 Importance of external drivers in influenza Importance of climate Immunity of the population No seasonal at all Totally seasonal

57 Prediction: more lethal and transmissible -> less seasonal Reed et al 2013 Novel Framework for Assessing Epidemiologic Effects of Influenza Epidemics and Pandemics, Emerg Infect Dis Totally seasonal No seasonal at all (pigs as Mentioned by Martha - Pigs in a constant pandemic?) Totally seasonal No seasonal at all (pigs as Mentioned by Martha - Pigs in a constant pandemic?) Totally seasonal

58 Alonso et al 2011 The 1918 influenza pandemic in Florianopolis, a subtropical city in Brazil. Vaccine 1918 pandemic Schuck-Paim et al. (2012) Exceptionally high mortality rate of the 1918 influenza pandemic in the Brazilian naval fleet. Influenza and Other Respiratory Viruses

59 Alonso & McCormick BMC public health 12 (1), 1-9 Alonso & McCormick BMC public health 12 (1), 1-9

60 Ministry of Health (Brazil) Adolfo Lutz Institute (Brazil) Evandro Chagas Institute (Brazil) Oswaldo Cruz Foundation (Brazil) Federal University of Ceara (Brazil) National Autonomous University of Mexico (Mexico) Arizona State University (USA) Fogarty International Center/NIH (USA) Collaboration on the studies presented: Cécile Viboud Mark A Miller Rodolfo Acuña-Soto Martha Nelson Fernanda E Moura Francielle Nascimento Lone Simonsen James Tamerius Mirleide C dos Santos Terezinha Paiva Maria Akiko Ishida Margarete A Benega Roberto M. Fernandes Marcia L. Carvalho Luciane Z Daufenbach Gerardo Chowell Cynthia Schuck-Paim Thanks!


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