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. 2000 Apr 1;320(7239):938.

Unexpected beneficial effects of measles immunisation

Measles vaccination may be marker for other health seeking behaviours

Craig Dalton 1
PMCID: PMC1117851  PMID: 10742016

Editor—The hypothesis presented by Shann in his editorial that measles immunisation provides non-specific immune stimulation sufficient to decrease mortality from other diseases is interesting.1 However, I don't really believe that the studies have ruled out the more likely explanation that measles immunisation is just a marker for other socioculturally determined health seeking behaviours. The fact that similar effects are not seen for other vaccines does not exclude measles immunisation from being correlated with health seeking behaviours.

Measles vaccination is different from other vaccinations in its timing, and it is often associated with national campaigns (including in some of the studies Shann references). Are there any data that rule out the confounding effect of sociocultural determinants?

References

BMJ. 2000 Apr 1;320(7239):938.

Socioeconomic confounding may also play a part

David Emerton 1

Editor—Shann in his editorial on measles1-1 discusses the hypothesis that standard dose Schwartz measles vaccine reduces mortality from conditions other than measles. He refers to the observation that measles causes only 10% of child mortality whereas the vaccine reduces mortality in developing countries by at least 30%1-2 and that immunised children who have not had measles have a much lower mortality than unimmunised children who have not had measles.1-2,1-3

When I worked at Murgwanza Hospital in Tanzania from 1984 to 1991 measles vaccination was generally available in the community through the maternal child health programmes. These programmes included an educational component relating to nutrition, prevention of disease, and early treatment of febrile illnesses such as malaria. As the primary healthcare programme gained momentum after the Alma Ata declaration, which aimed for health for all by the year 2000, efforts to improve health awareness intensified. It was distressing that children were not all immunised and that outbreaks of measles still occurred. Often children with measles presented late and had signs of other illnesses. We always assumed that children who were not immunised against measles when vaccination was available were more likely to be poorly nourished and less likely to be brought for early medical care if they had life threatening illnesses such as malaria or gastroenteritis.

A study in Benin failed to show that vaccination for diphtheria, tetanus, pertussis, and polio was associated with reduced mortality from other conditions.1-2,1-4 This study was, however, relevant to only a narrow age band, until the children were given measles vaccination. Measles immunisation could be an indicator that parents in developing countries are trying to give their children optimum care. The improved mortality is therefore not necessarily a result of the vaccine itself.

References

  • 1-1.Shann F. A little bit of measles does you good. BMJ. 1999;319:4–5. doi: 10.1136/bmj.319.7201.4. . (3 July.) [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 1-2.Aaby P, Samb B, Simondon F, Coll Seck AM, Knudsen K, Whittle H. Non-specific beneficial effect of measles immunisation: analysis of mortality studies from developing countries. BMJ. 1995;311:481–485. doi: 10.1136/bmj.311.7003.481. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 1-3.Samb B, Aaby P, Whittle H, Coll Seck AM, Simondon F. Decline in measles case fatality ratio after the introduction of measles immunisation in rural Senegal. Am J Epidemiol. 1997;145:51–57. doi: 10.1093/oxfordjournals.aje.a009031. [DOI] [PubMed] [Google Scholar]
  • 1-4.Velema JP, Alihonou EM, Gandaho T, Hounye FH. Childhood mortality among users and non-users of primary health care in a rural West African community. Int J Epidemiol. 1991;20:474–479. doi: 10.1093/ije/20.2.474. [DOI] [PubMed] [Google Scholar]
BMJ. 2000 Apr 1;320(7239):938.

Other conditions with reduced mortality could have been specified

Clinton Buckoke 1

Editor—I have read Shann's editorial on immunisation against measles and was interested to learn that the vaccine itself may reduce mortality from conditions other than measles.2-1 After reading the rest of the article I do not know whether the reduction in mortality is from all conditions other than measles, all infective conditions other than measles, specific infective conditions other than measles, or specific non-infective conditions other than measles.

Although I work as a hospital specialist, I enjoy reading the BMJ as it is a great help in keeping my knowledge base broad. Perhaps Shann could have been more specific for the sake of those readers who do not have the time to seek out all the articles cited as references.

References

BMJ. 2000 Apr 1;320(7239):938.

Number of squint operations in Britain has decreased

Robin Finlay 1

Editor—Shann in his editorial on measles immunisation3-1 highlights several unexpected effects of mass measles vaccination. No more satisfactory explanation has been advanced for an apparently marked decline in the incidence of childhood esotropia (convergent squint) than that it may be the result of a large reduction in the incidence of measles. Figures for the incidence of childhood esotropia, with a peak at age 3-4 years, are difficult to gather, but there is general agreement that fewer cases present in the United Kingdom than a generation ago. More easily verified is a marked decrease in the past 25 years in the number of squint operations performed.

Previously about two squint corrections were done on a typical “general” ophthalmic operating list; now these operations are becoming something of a rarity, though increased awareness of consecutive divergence as a consequence of overzealous squint correction has also contributed to the decline in the number of operations. The principal factors determining the onset of childhood esotropia are genetic influences, refractive errors (usually hyperopia) and a high accommodative convergence to accommodation ratio.3-2 The precipitating cause of a child with normal, though fragile, binocular function developing a squint has often been considered to be a systemic illness. Measles used to be common at this age; now it is rare. Whether it is the stress induced by the illness or, more specifically, a subclinical encephalitis is unknown,3-3 but the decline in measles and that of concomitant esotropia may be connected.

References

  • 3-1.Shann F. A little bit of measles does you good. BMJ. 1999;319:4–5. doi: 10.1136/bmj.319.7201.4. . (3 July.) [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 3-2.Parks MM. Abnormal accommodative convergence in squint. Arch Ophthal. 1958;59:364–380. doi: 10.1001/archopht.1958.00940040070008. [DOI] [PubMed] [Google Scholar]
  • 3-3.Taylor D. Paediatric ophthalmology. Oxford: Blackwell; 1990. p. 625. [Google Scholar]
BMJ. 2000 Apr 1;320(7239):938.

Who brought measles?

Tomas Engler 1

Editor—History has documented well for us the devastating effects of the arrival of the measles virus from Europe several centuries ago—for example, in Iceland and the Americas. Some will also remember that when measles vaccine became available on a large scale in the late 1960s, in the unpublished and published experience (1970s) of several clinicians the relation between measles and susceptibility to other diseases, notably tuberculosis, was well established, at least in Amerindian and other population groups living in poverty and not exposed to measles prior to outbreaks recorded at the time. Studies published then documenting effects of clinical measles on the immune response were accepted as a reasonable explanation.

Thus, Shann's editorial on measles comes as a welcome reminder of things forgotten.4-1 The implications for public health action are clear and not unrelated to the relation between AIDS and susceptibility to other diseases, which has cost so much to “prove.”

The point is one of public policy: how to maintain funding for successful epidemiological activities once their goal has been attained (in this case, the elimination or eradication of measles, hopefully imminent). The history of tuberculosis control, although “glorious” during the years after the second world war related to strong social support (sale of stamps by non-governmental organisations against tuberculosis), has been a glaring example of successive failures in establishing political priority for what once was the “disease of kings.” It is only fair to recognise the renewed efforts being made by the World Health Organization over the past four or five years, and the commitment expressed by its new director general in this regard. Unfortunately, the national response has yet to materialise in the intensity and perspective required. More realistic approaches need to be developed that take into account the financial and logistic barriers still limiting access to general health care across the globe.

Our most successful ventures have been in the pursuit of one disease at a time (such as yellow fever, smallpox, or polio), but how can we deal effectively with the long and growing list? Although there are many reasons to be optimistic, lip service to these causes and to their integration into the mainstream of primary health care is not enough. How long do we need to wait, and how big a price should we all pay for the consequences of our inertia? Have we learned the lessons from our failure in controlling the AIDS epidemic in its early stages? Are we really ready for another epidemic like Ebola? Or is this just a love affair with mycobacteriae and other creatures that share our planet and our bodies? Do we really care at all?

References

BMJ. 2000 Apr 1;320(7239):938.

Authors' reply

Frank Shann 1,2, Peter Aaby 1,2

Editor—Immunisation against measles causes a spectacular reduction of 30% to 86% in child mortality in developing countries.5-1 The benefit is greatest in the six to 12 months after immunisation, and in infancy (44% to 100%). Dalton and Emerton wonder whether the apparent benefit from measles immunisation might be a result of better nutrition and better health care in children who receive measles vaccine (socioeconomic confounding), rather than an effect of the vaccine. In the absence of any large randomised controlled trials of measles vaccine in developing countries, socioeconomic confounding cannot be excluded—but it is unlikely, for several reasons.

Firstly, in the only placebo controlled trial of measles vaccine in a developing country, none of the 23 vaccinated children died compared with 3 (12%) of the 25 unvaccinated children.5-2 Secondly, in a natural experiment in Bissau, some children were accidentally injected with an ineffective vaccine (given on five consecutive vaccination days over three weeks).5-3 There was no selection bias in this study because all the children were immunised. From the time of vaccination to 3 years of age, the death rate was 4.5% in 124 children who seroconverted after active vaccine and 15.1% in 53 children given ineffective vaccine.

Thirdly, in two large studies in Zaire5-4 and Bangladesh,5-5 confounding is unlikely because measles vaccine was made available in half the study area and not in the other. Mortality in the two areas was similar before immunisation. Immunisation reduced mortality by 42% in Zaire and by 46% in Bangladesh.

Fourthly, studies that have controlled for socioeconomic factors have still found that measles immunisation reduced mortality by 36% to 90%.5-1

Fifthly, measles immunisation is unlikely to be merely a marker for better health care because the reduction in mortality is greatest in the 12 months after measles immunisation (and the benefit of better health care should persist), and immunisation against diphtheria, tetanus, and pertussis is not associated with reduced mortality.5-2

Measles immunisation causes a much greater fall in mortality than the proportion of deaths attributed to measles, particularly in girls.5-1 Is this because measles causes many more deaths than we realise (from delayed effects of the disease, or from subclinical infection), or does the vaccine reduce mortality from conditions other than measles? The large reduction in mortality after immunisation is unlikely to be the result of the prevention of delayed deaths from measles because immunised children who have not had measles have a much lower mortality than unimmunised children who have not had measles.5-1 Subclinical measles infection is certainly common in both immunised and unimmunised children in developing countries, but such infections have no effect on nutritional indices or mortality.5-2

In two randomised controlled trials in Guinea-Bissau and Senegal, children were given high titre Edmonston-Zagreb (EZ) vaccine at 4-5 months of age or standard Schwarz vaccine at 9-10 months.5-2 Girls given EZ vaccine had a death rate that was 1.95 and 1.76 times respectively that of girls given Schwarz vaccine. This occurred despite the fact that there is a good antibody response to high titre EZ vaccine at 4-5 months, and there was no increase in measles in the EZ group. Both vaccines protected against measles, but the Schwarz vaccine also protected girls against diseases other than measles. Both trials were randomised, so socioeconomic confounding is unlikely to be the explanation for this remarkable finding.

Buckoke asks which conditions other than measles have a lower mortality after measles immunisation. In a study of 554 children in Bangladesh, immunised children had a lower mortality from measles (95%, 95% confidence interval 79% to 99%), oedema (71%, 29% to 88%) and diarrhoea (46%, 29% to 58%) but little or no protection against respiratory infections, fever, accidents, or other causes of death (P Aaby, unpublished data).

Finlay and Engler point out that measles may have highly undesirable effects, but there is strong evidence that measles immunisation, and mild measles, reduce child mortality. We agree with Engler that the public health issues are of crucial importance. Measles immunisation clearly causes a spectacular reduction in mortality in children in developing countries, and this effect is probably enhanced by a two-dose schedule with immunisation at 6 and 9-12 months. Far greater effort should go into seeing that all children receive measles vaccine, and, if measles is ever eradicated, controlled trials will be needed to see whether the vaccine should still be given to children in countries with high child mortality.

References

  • 5-1.Aaby P, Samb B, Simondon F, Seck AMC, Knudsen K, Whittle H. Non-specific beneficial effect of measles immunisation: analysis of mortality studies from developing countries. BMJ. 1995;311:481–485. doi: 10.1136/bmj.311.7003.481. . (3 July.) [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 5-2.Shann F, Aaby P. Measles immunisation and socioeconomic confounding. bmj.com 1999;319 (bmj.com/cgi/eletters/319/7201/4#EL7)
  • 5-3.Aaby P, Pedersen IBR, Knudsen K, da Silva MC, Mordhorst CH, Helm-Petersen NC, et al. Child mortality related to seroconversion or lack of seroconversion after measles vaccination. Pediatr Infect Dis J. 1989;8:197–200. [PubMed] [Google Scholar]
  • 5-4.Kasongo Project Team. Influence of measles vaccination on survival pattern of 7-35-month-old children in Kasongo, Zaire. Lancet. 1981;1:764–767. [PubMed] [Google Scholar]
  • 5-5.Koenig MA, Khan MA, Wojtyniak B, Clemens JD, Chakraborty J, Fauveau V, et al. Impact of measles vaccination on childhood mortality in rural Bangladesh. Bull WHO. 1990;68:441–447. [PMC free article] [PubMed] [Google Scholar]

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