Rapid Responses to:

EDITORIALS: Frank Shann Non-specific effects of vaccines in developing countries BMJ 2000; 321: 1423-1424 [Full text]

Rapid Responses: Submit a response to this article

Rapid Responses published:

Confounding Factors.

B M Hegde   (9 December 2000)

Yes, facts support Prof. Hegde ideas!

A López Peña   (11 December 2000)

Concerns about non-specific effects of vaccines in general

Wouter Havinga   (6 January 2001)

Non-specific effects of measles vaccines in rural India

Zubair Kabir   (9 January 2001)

Or is it due to an improved diet

Wouter Havinga   (11 January 2001)

Hypoproteinaemia, and the effects of infections and vaccines

Frank Shann   (2 February 2001)

Confounding Factors. 9 December 2000
B M Hegde, Vice Chancellor Manipal Send response to journal: Re: Confounding Factors.	Dear Sir, It is good that these priliminary data are published. Children in third world countries have a heavy load of hook worm infestations with very low levels of haemoglobin. They also have low protein diet. The combined effect would be lowered serum proteins. Antibody response needs proteins, as antibodies are proteins! To cap it, live polio vaccine given to these children, who may not get the same level of antibody titre as that of the Caucasian children on whom the original controlled studies had been done, would get excreted in the stool of these children and could easily spread by the faecal oral route to other children in the vicinity because of the lack of toilet facilities. Any intramuscular injections (DPT for example) during the time that the faecal oral transmission occurs could attract the onset of poliomyelitis! This could even endanger the lives of adults with immunocompromised state (AIDS etc) and increase total mortality. In the context of overall hypo-proteinaemia could this be one of the contributing factors for the increased total mortality. I had this suspicion about oral polio in India in the very poor segments where toilets are totally lacking! Am I barking up the wrong tree or could there be a grain of truth there? bmhegde
Yes, facts support Prof. Hegde ideas! 11 December 2000
A López Peña Dominican Republic Send response to journal: Re: Yes, facts support Prof. Hegde ideas!	Yes, Professor. You are right. It is perhaps a coincidence but just observe what is happening these days in Dominican Republic. Spread of poliovirus via faeces in countries with lack of sanitary facilities (mainly in rural areas) seems to be a reality. Hopefully adequate measures will be taken in the rest of the Third World countries before detecting cases, not after.
Concerns about non-specific effects of vaccines in general 6 January 2001
Wouter Havinga, General Practitioner St Luke's Medical Centre, Stroud Send response to journal: Re: Concerns about non-specific effects of vaccines in general	Frank Shann is passionate about the need for more research into the effects of the vaccines used in the expanded immunisation programme on mortality from all causes in developing countries (1). Why is it that possible morbidity and mortality due to long-term effects by vaccine regimes in affluent countries is consequently ignored? For some time epidemiological data are showing a noticeable increase in atopic diseases (Th2 related), autoimmune diseases and cancer (Th1 related). Also, despite that it is known that the commensal flora is of great importance in keeping virulent bacteria under control, more and more antibacterial vaccines are being developed and advised to be added to current vaccination regimes. Are other infectious diseases emerging as a result of vaccination programmes? Polio is nearly eliminated but hand foot and mouth disease has been taking its place in Taiwan and Singapore (2,3). Neisseria meningitidis is known (as many other bacteria) for its ability to switch capsule from one serogroup to an other. This might have caused an outbreak due to the serogroup W-135 in travellers vaccinated against the A- and C- serogroup (4). Such a capsular change can also take place in Haemophilus influenzae. I agree with Frank Shann that the long-term effects of vaccines can no longer be ignored. However, I am just as passionate about the need for research into beneficial effects of infectious diseases. There is a steady debate about how microbes can influence the health of a child and his or her health in the future (5). It worries me however that again in this debate, the hygiene hypothesis, the effects of vaccines are ignored. Research into these possible non-specific effects of vaccines needs urgent attention, especially with the current competition to develop vaccines against any virulent bacteria or virus. Or, do we really believe that ultimately man should become a sterile human being and thus be healthy? 1. Shann F. Non-specific effects of vaccines in developing countries. We need evidence about the effect of vaccines on mortality from all causes. BMJ 2000;321:1423-4 2. Dolin R, Enterovirus 71- Emerging infections and emerging questions. Editorial. N Eng J Med 1999;341:984-985 3. Chao-Ching Huang, et al, Neurologic complications in children with enterovirus 71 infection. N Eng J Med 1999;341:936-942 4. Perkins BA. New opportunities for prevention of meningococcal disease. JAMA 2000;283:2842-43 5. Rook GAW, Clean living increases more than just atopic disease. Immunology Today 2000;21:249
Non-specific effects of measles vaccines in rural India 9 January 2001
Zubair Kabir, Research Officer Research & Education Institute, Crest Directorate, St James's Hospital, Dublin 8, Ireland Send response to journal: Re: Non-specific effects of measles vaccines in rural India	EDITOR- Shann in his editorial on "non-specific effects of vaccines" suggests the immediate need for evidence about the effect of vaccines on mortality from all causes in children in developing countries.(1) He refers to the results of Kristensen et al "startling" and "spectacular". It is true that in absence of any large randomised controlled trials of measles vaccine in developing countries, the Guinea-Bissau study is a valuable addition to the existing body of epidemiological literature. Studies have shown that measles immunisation reduces mortality in developing countries by at least 30%.(2 3) As a public health specialist, I worked in a project area of All India Institute of Medical Sciences, New Delhi, India from 1997 to 1999. This is a comprehensive rural health services project covering a population of 74,000 recently in a cohort-wise fashion since 1967. Measles vaccination (the standard Schwartz) was introduced for the whole of project area in 1985 under Universal Immunisation Programme of India. Fourteen peripheral health workers render primary health care services to each household in the project area during their routine domiciliary visits including measles vaccination of infants beyond the ninth month. The area maintains a high vaccination coverage (around 90%) over a period of last ten years. No outbreaks of measles have been reported yet in the project area. Studies in the project area reported 12 measles deaths between 1982- 84 and reducing to only two between 1991-99. The absolute number of child (12-59 months old) deaths from all causes was reduced from 221 between 1982-84 to 85 between 1995-96 (ten years after the introduction of routine measles vaccination in the project area). (4 5) A recent case-control study of the same area revealed a significant association between measles immunisation and child (12-59 months) mortality (odds ratio: 3.0, 95% confidence interval: 1.7, 5.4). The study also showed a valid statistical association between measles immunisation and child mortality, because chance, bias and confounding were evaluated to be unlikely explanations. Finally, the study concluded that measles immunisation was an "independent" risk factor for mortality from all causes in the 12-59 months children of the project area.5 These observations may be due to the non-specific beneficial effects of measles vaccine. Hence, the above finding should be "exploited" to reduce substantially the absolute number of child deaths in developing countries such as India even in areas of high vaccination coverage. Regards, Zubair Kabir 1 Shann F. Non-specific effects of vaccines in developing countries. BMJ 2000; 321: 1423-4. 2 Koenig MA, Khan MA, Wotjtyniak B, Clemens JD, Chakraborty J, Fauveau V, et al. The impact of measles vaccination upon childhood mortality in Matlab, Bangladesh. Bulletin WHO 1990; 68: 441-7. 3 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: 481-5. 4 Reddaiah VP, Lobo J, Kapoor SK, Nath LM. Comprehensive rural health services project Ballabgarh: trends in under-five mortality. Indian J Pediatrics 1988; 55: 287-94. 5 Kabir Z. The relationship between child mortality and primary immunisation in rural India: a case-control study. MSc dissertation (2000). University of Dublin, Ireland. No competing interests
Or is it due to an improved diet 11 January 2001
Wouter Havinga, general practitioner Stroud Send response to journal: Re: Or is it due to an improved diet	It would be interesting to look at what is known about the nutritional state of the children in 1982-84 as compared to the nineties, as suggested by prof Hegde in his reponse on 9 December 2000. If the 14 peripheral health workers also addressed healthy diets (more protein), than perhaps this is the cause for the fall in morbidity/mortality.
Hypoproteinaemia, and the effects of infections and vaccines 2 February 2001
Frank Shann, Director of Intensive Care Royal Children's Hospital, Melbourne, Australia Send response to journal: Re: Hypoproteinaemia, and the effects of infections and vaccines	Professor Hegde wonders whether hypoproteinaemia could explain the apparent increase in mortality after diphtheria-pertussis-tetanus (DPT) and polio vaccines in the study in Guinea-Bissau (1). Although hypoproteinaemia is associated with an impaired immune response to meningococal polysaccharide vaccines in children in West Africa, hypoproteinaemia and malnutrition have little or no effect on the immune response to diphtheria-pertussis-tetanus and polio vaccines (2). Poliomyelitis is rare in Guinea-Bissau, and does not explain the apparent increase in mortality after diphtheria-pertussis-tetanus and polio vaccines. It is important to stress that immunisation did not increase total mortality in the Guinea-Bissau study - but the spectacular reductions in mortality from BCG and measles vaccines were partly offset by the adverse effects of diptheria-pertussis-tetanus vaccine. Dr Havinga may well be correct that some infections have beneficial effects. However, many vaccines offer the best of both worlds - beneficial effects without the dangers of a severe infection. Standard doses of measles vaccine protect against measles, and also appear to cause a substantial reduction in mortality from diseases other than measles (3). Dr Kabir's case-control study provides further evidence that measles vaccine has important beneficial non-specific effects. In addition, the Guinea-Bissau study suggests that BCG vaccine may also have beneficial non -specific effects that substantially reduce mortality, without the dangers of tuberculosis (1). However, the apparent association of diphtheria- pertussis-tetanus vaccine with increased mortality in Guinea-Bissau, suggests that this vaccine may have harmful non-specific effects which offset the many lives saved by the prevention of diphtheria, pertussis and tetanus (1). We need to learn more about the non-specific effects of vaccines and infections, so that we can obtain the benefits while avoiding the harmful effects. 1. Kristensen I, Aaby P, Jensen H. Routine vaccinations and child survival: follow up study in Guinea-Bissau, West Africa. BMJ 2000;321:1-8 2. Greenwood BM, Bradley-Moore AM, Bradley AK, Kirkwood BR, Gilles HM. The immune response to vaccination in undernourished and well- nourished Nigerian children. Ann Trop Med & Parasitol 1986;80:537-44 3. Shann F. A little bit of measles does you good. BMJ 1999;319:4-5