Tag Archives: Allergy

Three Hits Hypothesis

Quite a lot of diseases are brought about by the conflation of two factors. Mice infected with certain herpes viruses suffer no ill-effect unless a helminth infestation supervenes. Oral allergy syndrome arises when a certain pollen interacts with certain foods (usually raw fruits, vegetables and nuts). The hygiene hypothesis says that lack of exposure to certain gut bacteria sensitises the body to allergic reactions to a range of environmental allergens. The pathway for disease involves three hits:

Genetically predisposed person –> Exposure 1 –> Exposure 2 –> Disease.

An intriguing example of a three-hit condition is the severe disease of children – Burkitt’s lymphoma. This cancer arises in germinal centres of lymph nodes in the neck. It is known that Epstein-Barr (EB) virus infection is necessary for endemic Burkitt’s lymphoma to develop because it prevents apoptosis (cell death) when certain mutations occur in the cell. But endemic Burkitt’s lymphoma only occurs in the malaria belt, and why this is so has been a mystery until the last few years. Now we know that the malaria parasite Plasmodium falciparum ‘upregulates’ an enzyme that causes mutations in DNA in lymph cells. These mutations are a normal part of antibody production since rearrangements of chromosome segments is necessary for antibody specificity. But in people with falciparum malaria, the effect ‘spills over’ to cause mutations of cancer genes. The double hit of EB plus malaria sets the scene for carcinogenesis.[1] Why in the neck – perhaps because lymph cells in the necks of children work particularly hard eradicating throat and ear infections, in which case there is a ‘four hits’ hypothesis!

— Richard Lilford, CLAHRC WM Director


  1. Thorley-Lawson D, Deitsch KW, Duca KA, Torgbor C. The Link between Plasmodium falciparum Malaria and Endemic Burkitt’s Lymphoma—New Insight into a 50-Year-Old Enigma. PLoS Pathog. 2016; 12(1): e1005331.

Early Introduction of Allergenic Foods for Breastfeeding Infants and Risk of Allergy

This is an important question for us all – is the early introduction of allergenic (allergy causing) foods, such as peanuts and egg, associated with higher risk of allergy? The short answer is no.[1] In fact the risk of clinical allergy is lower when peanut and egg is introduced early (at three months) than when introduced later (at six months). It was non-significantly lower by Intention-to-Treat, but significantly lower (p<0.003) in the per protocol analysis (2.4% vs. 7.3%). ‘Compliance’ was poor; less than half of cases in the early introduction group adhered to protocol. The non-adherers had similar rates of allergy to the control (normal practice/delayed introduction) group. There appeared to be a ‘dose’ response with higher intake of allergenic foods associated with greater reductions in the incidence of allergy. Biological testing for allergy gave even stronger protective results for early introduction than did the clinical data reported above. The results are consistent with previous observational and experimental studies. Taken in the round, the results are compelling, shifting probability densities sharply in favour of effectiveness. The World Health Organization recommends exclusive breast feeding to six months of age. Time for change in guidelines in high-income countries?

— Richard Lilford, CLAHRC WM Director


  1. Perkin MR, Logan K, Tseng A, et al. Randomized Trial of Introduction of Allergenic Foods in Breast-Fed Infants. New Engl J Med. 2016; 374: 1733-43.

Exposure of the Baby to a Rich Mixture of Coliform Organisms from the Birth Canal.

Previous research has pointed out that a good draught of such organisms seem to be healthy, as children brought up after delivery by Caesarean have a much higher incidence of atopic allergic reactions than those delivered through the birth canal.[1] Moreover, the colonic microbiome differs across babies born by vaginal vs. abdominal routes. Many have taken this evidence to heart, and have started to paint the baby’s face with a swab marinated in vaginal secretions. A balanced editorial in the BMJ [2] says that such a practice should not be recommended lest the baby be inoculated with less benign organisms called Beta Strep, resident in some vaginas. But if a woman wishes to practice such a procedure, she should not be inhibited from doing so, pending a trial big enough to determine the net long-term effects.

— Richard Lilford, CLAHRC WM Director


  1. Neu J, & Rushing J. Cesarean versus Vaginal Delivery: Long term infant outcomes and the Hygiene Hypothesis. Clin Perinatol. 2011; 38(2): 321-31.
  2. Cunnington AJ, Sim K, Deierl A, et al. “Vaginal seeding” of infants born by caesarean section. BMJ. 2016; 352: i227.