Effect Measure

Do the tropics have a flu season?

The scientific literature is full of specialized papers that on their face would seem to be of little interest. Here’s a title like that: “Prevalence and seasonality of influenza-like illness in children, Nicaragua, 2005-2007″ (Gordon et al., Emerging Infectious Diseases 2009 Mar). Over 4000 Nicaraguan children, aged 2 to 11 years old and living in the capital of Managua were followed for 2 years, April 2005 to April 2007 and observed for development of ILI (influenza-like illness). We know a lot about influenza in major industrialized countries in the northern and southern temperate zones, but very little about the epidemiology of seasonal influenza in tropical regions. Is the pattern of the disease in these populations the same as in temperate climes? Is there a lot of flu or just a low level? Is it still seasonal influenza? The US and Europe have recently set up surveillance systems that help answer these questions but most countries don’t have those resources.

The question of seasonality is especially interesting because we still don’t understand why flu exhibits such a strong seasonal pattern (many hypotheses have been advanced but there is still no agreement). Managua is warm, with a fairly constant temperature between 28 and 32 degrees Celsius. In temperate climates flu season takes place mostly with temperatures below 20 degrees Celsius and low absolute humidity. But in the two years of this study flu peaked in June and July each year, the middle of the rainy season (May to November). Furthermore, this paper also showed a peak in the November – December months during one (2006) but not the other of the two years.

Recent animal studies have suggested cold and dry air is the key to influenza seasonality, but this pattern is not consistent with that finding. The relationship with rainy seasons has been observed before, so the data are far from convincing in view of the epidemiology, scanty as it is. The other interesting finding of this study is that there appears to be a substantial burden of influenza amongst Nicaraguan children.

In other words, it is not the case that influenza in this tropical country is relatively low level and spread throughout the year. In the two years of data in this study there is a lot of it and it shows a characteristic seasonality, peaking in the middle of the rainy season (northern summer). We need to look more closely at other tropical countries, and as this paper shows, it isn’t easy, by any means. I haven’t gone through the details of the study design but it was logistically expensive and time consuming and required an extensive field operation and willing in-country collaborators.But studies like this give us information about how flu is, or is not, transmitted.

Sometimes uninteresting sounding titles are quite interesting.

Comments

  1. #1 Julie Stahlhut
    March 1, 2009

    How about levels of vitamin D? Much less sunlight in the rainy season, no?

  2. #2 revere
    March 1, 2009

    Julie: There’s a modest Vit. D literature on seasonality. I don’t think it has panned out but it has been talked about. Seasonality is still a mystery.

  3. #3 anon
    March 1, 2009

    Here is another paper that discusses the flu “seasonality” in (sub-)tropical region: Cowling BJ, Wong IOL, Ho L-M, Riley S, Leung GM. Methods for monitoring influenza surveillance data. Int J Epidemiol. 2006; 35(5): 1314-1321.

  4. #4 anon
    March 1, 2009

    Or this one: Wong C-M, Chan K-P, Hedley AJ, Peiris JM. Influenza-associated mortality in Hong Kong. Clinical Infectious Diseases. 2004; (39): 1611-1617.

  5. #5 revere
    March 1, 2009

    anon: Yes, there are a few papers, mainly Hong Kong. Measuring incidence is difficult, so it is not surprising there is little to go on. The Commentary by Viboud, which is a link in the post, has a brief review.

  6. #6 M.Randolph Kruger
    March 1, 2009

    Revere, off subject. Hit your gmail acct and tell me what the hell that is…

  7. #7 davidp
    March 2, 2009

    Sounds like kids shut inside with closed windows because of the rain in Mangua, and because of the cold in the temperate zones. Similarly bus and train windows are closed in cold or wet conditions (when they aren’t air conditioned)

  8. #8 dwaly
    March 2, 2009

    Vitamin D! Obviously! I keep seeing all these articles about why the flu happens it the rainy seasons, or the dark seasons all around the world and I cant believe its taking so long for the science community to put 2 and 2 together! And its not modest research either, there’s lots of it. Go to the VitaminDCouncil.org and read to your hearts content.

  9. #10 revere
    March 2, 2009

    In Fluenza: Thank you for reminding me. We posted about it here.

  10. #11 biologist
    March 2, 2009

    dwaly, Julie:

    There is abundant, strong, but almost exclusively circumstantial evidence that vitamin D may play a role. See, e.g., a new paper that has just come out: Ginde AA et al. Association Between Serum 25-Hydroxyvitamin D Level and Upper Respiratory Tract Infection in the Third National Health and Nutrition Examination Survey. Arch Intern Med. 2009;169(4):384-390. See also the literature on vitamin D and cathelicidin/LL-37, especially regarding TB.

    Thoretically, vitamin D should be doing something when it comes to influenza. Influenza is an enveloped virus; vitamin D should matter.

    However, to date, there is no published data looking at any interaction between anything in the vitamin D pathway and the influenza virus itself.

    Thus, we cannot say for certain at this time, really, that vitamin D has an effect on influenza. Various claims are made or suggested in the popular literature that are really more speculation at this point than fact. My personal speculation: I think the data is close to being able to support a statement that vitamin D matters, but I don’t think we’re quite there yet.

  11. #12 Peter Ellis
    May 13, 2009

    If there’s a vitamin D effect, then you should expect a good correlation between skin colour and flu susceptibility in Northern latitudes. I don’t think this has ever been observed or even suggested, which would seem to rule out vitamin D.

  12. #13 PanFluWatch
    May 13, 2009

    Has that connection been demonstrated on a functional level, Peter? (That’s not a hypothetical question; I genuinely don’t pretend to know.)

    I’m far from an expert on vitamin D, but I recently read an article [1] that mentioned that -while circulating vitamin D3 levels differed between blacks and whites, the levels of the related chemical 1alpha,25-dihydroxyvitamin D3 were no different. So the author said that, unless there were processes which required the former and could not proceed with the latter, there should be no adverse physiological differences as a result.

    1. Norman AW. Sunlight, season, skin pigmentation, vitamin D, and 25-hydroxyvitamin D: integral components of the vitamin D endocrine system. Am J Clin Nutr. 1998 Jun;67(6):1108-10. PMID: 9625080

  13. #14 Ken
    June 15, 2009

    Mad dogs and ….

    “How can vitamin-D deficiency exist despite lengthy sun exposure? This apparent paradox was raised in my last post. The medical community now recommends bloodstream vitamin D levels of at least 75-150 nmol/L, yet these levels are not reached by many tanned, outdoorsy people.[…]

    Only mega-doses can overcome what seems to be a homeostatic mechanism that keeps bloodstream vitamin D within a certain range. Indeed, this range falls below the one that is now recommended. Curious isn’t it? Why would natural selection design us the wrong way? […]

    In a wide range of traditional societies, people avoided the sun as much as possible, especially during the hours of peak UV (Frost, 2005, pp. 60-62). Midday was a time for staying in the shade, having the main meal, and taking a nap. Nor is there reason to believe that sun avoidance and clothing were absent among early modern humans. Upper Paleolithic sites have yielded plenty of eyed needles, awls, and other tools for making tight-fitting, tailored clothes.”

  14. #15 Ken
    June 15, 2009

    Mad dogs and ….

    “How can vitamin-D deficiency exist despite lengthy sun exposure? This apparent paradox was raised in my last post. The medical community now recommends bloodstream vitamin D levels of at least 75-150 nmol/L, yet these levels are not reached by many tanned, outdoorsy people.[…]

    Only mega-doses can overcome what seems to be a homeostatic mechanism that keeps bloodstream vitamin D within a certain range. Indeed, this range falls below the one that is now recommended. Curious isn’t it? Why would natural selection design us the wrong way? […]

    In a wide range of traditional societies, people avoided the sun as much as possible, especially during the hours of peak UV (Frost, 2005, pp. 60-62). Midday was a time for staying in the shade, having the main meal, and taking a nap. Nor is there reason to believe that sun avoidance and clothing were absent among early modern humans. Upper Paleolithic sites have yielded plenty of eyed needles, awls, and other tools for making tight-fitting, tailored clothes.”

  15. #16 Hunter
    August 30, 2009

    Ken,
    there are “vitamin d” receptors in every cell of the body, this is an evolutionarily highly conserved mechanism so I doubt natural selection has designed us the wrong way.

    The clothing example is very faulty anyhow as hunter-gatherers do not and did not live inside houses behind perfect UV filters, i.e. glass windows. They did not cover every inch of their body with factor 20 sun screen because of fear of malign melanoma (that btw occurs on the least sun exposed parts of the body). They did also not cover the whole body with clothes (compare with modern day hunter-gatherers).

    And what homeostatic mechanism do you refer too? That the body maxes out at about 10000 IU/day? Anyhow, beach guards have been found to have levels reaching 300 nmol (if I do remember correctly).

  16. #17 tempo dulu
    February 17, 2010

    I doubt that it’s anything to do with vitamin D as many people in the tropics avoid the sun anyway. My guess is that the wetness allowes the virus to spread more easily.

  17. #18 lux
    March 25, 2010

    Hm
    For the rainy season: what about the fact that when you get wet, it’s easier to get sick, and yes people will be locked up more indoors and the air will become more stale, moist and warm.

    For the November-December peak, this sounds like it coincides with the tourist season in the Caribbean, where people who have been exposed to the flu in other countries will now come into contact with the Nicaraguan people.

    I don’t think it could solely be vitamin D deficiency. Perhaps this accelerates it, but it cannot be the entire cause.

  18. #19 biologist
    March 26, 2010

    PanFluWatch:

    1alpha,25(OH)vitD3 is synthesized from 25(OH)vitD3 in the kidney. However, it is also synthesized from 25(OH)vitD3 in cells that need it. So, having a higher concentration of 25(OH)vitD3 around can help. Moreover, recent data appears to suggest that 25(OH)vitD3 itself can bind VDRs and may act synergistically with 1alpha,25(OH)vitD3 (i.e., boosting the effect of 25(OH)vitD3) in at least some circumstances.

    Peter:

    You are correct – a NHANES III study did not find a significant difference between whites and nonwhites for the proportion of each group that had recently had an upper respiratory tract infection (UTRI). There was a slight trend towards nonwhites having more UTRIs that might have come out with more data, but maybe not. But the study did find a significant difference in the frequency of recent UTRI between those with low serum (blood) 25(OH)vitD3 levels and normal/higher levels. That is an important difference for UTRIs as a whole, not race in and of itself.

    Moreover, whether an individual becomes sick may also have a lot to do with what’s going on in “the herd”: if people around you are getting sick, then you’re much more likely to get sick than if they’re not, regardless of your individual vit D status. In other words, it’s possible that “herd” conditions of lower vit D status, in combination with other conditions, permit an illness to circulate in a community as a whole, and then, your particular, individual vit D status may make it more or less likely that you, as an individual, get a UTRI. But having normal vit D levels is certainly not completely protective.

    Vitamin D is certainly not the whole story, but it seems unlikely that it wouldn’t be part. There are lots of variables affecting the host and the pathogen, and it would seem most likely that a combination of both would matter.

    Pardon my 10-month delayed response.

  19. #20 steven zhou
    July 19, 2010

    Great article!

    Please also see a refence below:

    A SEASONAL INFLUENZA THEORY AND MATHEMATICAL MODEL INCORPORATING METEOROLOGICAL AND SOCIO- BEHAVIORAL FACTORS

    http://www.itmm.gov.cn/rdqx/rdqxcn/ch/reader/view_abstract.aspx?file_no=20090101&flag=1

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