WHO Admits! Pneumonia Vaccine Ineffective, Causes Asthma.

WHO Admits! Pneumonia Vaccine Ineffective, Causes Asthma.

This press alert is
being sent to you as we consider the news important for children. - Dr Jacob Puliyel.



Correspondents are advised to write to Melanie Lauckner at
the Bulletin of the WHO

Laucknerm@who. int (Tel +41 22 791 3439) for their copy of
this item to be published online, in the bulletin on 1/9/08.

http://www.who. int/bulletin/ publish ahead of
print/en/index. html.



Pneumococcal vaccine does not reduce clinical pneumonia and it doubles
the chance of developing asthma



Authors from the WHO admit that the pneumococcal vaccine
does not reduce clinical pneumonia. It reduces a rare type of pneumonia called
radiological pneumonia. This is so rare that 1000 children must be vaccinated
to prevent 3.6 cases of pneumonia.

For every 3.6 cases of
pneumonia prevented 1.3 children will get asthma (reactive airway disease)
because of the vaccine.



Pneumonia is a disease that can be treated and cured with
antibiotics. Asthma is often a life long disability treated with inhaled
bronco-dilator drugs and steroids.

The reply by WHO in the Bull WHO (attached below) admits that pneumococcal
vaccine DOES NOT reduce clinical
pneumonia. It reduces a rare type of pneumonia called radiological pneumonia –
so rare that you have to vaccinate 1000 children (at Rs 12,000 per child) to
prevent 3.6 cases of the pneumonia. Total cost is Rs 12 million to save four
children from pneumonia. Pneumonia, according to WHO protocol is treated with
Septran costing Rs 10. Even if the cost of treatment were 100 times higher, total cost of treatment will be Rs 4000. Cost
of prevention is Rs 12 million.



GAVI is pushing the drug and is
going to provide an introductory offer of vaccine for Rs 50/child. (DBT had recommended the introduction of the
vaccine in India)
Even at this cost, the cost of vaccine alone (no cost added for syringe and
number of nurses needed to give the 3 injections) total cost is Rs 50,000 to
avoid 4 cases of pneumonia.



That is not all. It is not just a waste of money – it is positively harmful. According to the
WHO reply, for every 3.6 cases of pneumonia avoided by vaccination 1.3 children
will develop Asthma (reactive air way disease)!!

Pneumonia is a one-off disease
treated with antibiotics.
Asthma can be life long and never be cured. It
requires repeated use of inhaled drugs and steroids.

Why do doctors prescribe the vaccine to all infants.?

The MRP of Rs 4000 per vial actually includes Rs 1000 for the
doctor/ pharmacy to ensure they promote the vaccine.



Without the patient knowing it, the doctor gets his cut of
Rs 1000 per dose of vaccine dispensed!! No wonder they are all enthusiastic
about the vaccine.

If it increases Asthma; So what?

That will mean many more visits to the doctor and is an
additional incentive.



Patients need to know



Jacob Puliyel MD MRCP M Phil

Department of Pediatrics

St Stephens Hospital

Delhi 110054

puliyel@gmail. com

+ 91 9868035091



ORIGINAL LETTERS

EMBARGOED
till 1 September 2008

Please respect this embargo





http://www.who. int/bulletin/ publish_ahead_ of_print/ en/index. html

Incidence of pneumonia is not reduced by pneumococcal conjugate vaccine

Sona
Chowdharya & Jacob Puliyela

a Department of Pediatrics, St Stephens Hospital, Tis
Hazari, Delhi
110054, India.

Correspondence
to Jacob Puliyel (e-mail: puliyel@gmail. com).

Madhi et al.1
write that the pneumococcal conjugate vaccine (PCV) is an effective instrument
for pneumonia prevention in children. This is not strictly true. WHO data2
suggest that there are 450 million cases of pneumonia each year and that it
causes 3.9 million deaths. In the sub-Saharan region of Africa,
1 022 000 die and 702 000 die in south Asia.1 The
pneumonia referred to is "clinical pneumonia" – a diagnostic syndrome within the
Integrated Management of Childhood Illness – WHO and United Nations Children's
Fund (UNICEF) system for triage and clinical management in developing
countries.3 The Cochrane database4 states that PCV does
not reduce the incidence of clinical pneumonia, although it has been shown to
reduce vaccine-serotype bacteraemic pneumonia and radiological pneumonia. The
benefit of reducing bacteraemic pneumonia and radiological pneumonia is so
minimal that it has no effect on "clinical pneumonia". Poor nations will need
to assess its cost utility carefully.

A
study from the Gambia showed that mortality was 16% lower in a PCV immunized
group compared to placebo recipients (25.2/1000 children years versus
30.1/1000 children years).5 Data are also provided on adverse
effects and deaths within 1 week of receiving any dose of the vaccine or
placebo. The mortality benefit was seen in the first week after injection, well
before vaccine efficacy could have been established. There were 12 deaths in
the vaccine group and 15 among controls (23.8/1000 children years versus
29.8/1000 children years). This suggests that factors other than vaccine
efficacy are responsible for the difference in mortality between the groups
compared.

There
is also another issue that we hope to raise here. The paper states that the
vaccine programme would exceed the WHO threshold in 69 eligible countries. The
authors assert that these findings are conservative in the sense that they did
not assume any herd protection and did not assume protection beyond the age of
2.5 years. Beutels6 has cautioned against this trend of noting the
"positive" uncertainties (herd immunity, protection beyond 2.5 years) without
reporting the "negative" ones (serotype replacement, 7 increased
incidence of asthma),8 which could dampen enthusiasm for the
intervention.



References

1. Madhi SA, Levine OS, Hajjeh R,
Mansoor OD, Cherian T. Vaccines to prevent pneumonia and improve child
survival. Bull World Health Organ 2008;86:365- 372. PMID:18545739 doi:10.2471/ BLT.07.044503< /jrn>

2. Revised global burden of disease
2002 estimates. Geneva: WHO.
Available from: http://www.who. int/healthinfo/ bodgbd2002revise d/en/index. html
[accessed 5
August 2008].

3. Integrated Management of Childhood
Illness. Geneva: WHO;
2000.

4. Lucero MG, Dulalia VE, Parreno RN,
Lim-Quianzon DM, Nohynek H, Makela H, et al. Pneumococcal conjugate vaccines
for preventing vaccine-type invasive pneumococcal disease and pneumonia with
consolidation on x-ray in children under two years of age. Cochrane Database
Syst Rev 2004;CD004977. PMID:15495133< /jrn>

5. Cutts FT, Zaman SM, Enwere G, Jaffar
S, Levine OS, Okoko JB, et al.; Gambian Pneumococcal Vaccine Trial Group.
Efficacy of nine-valent pneumococcal conjugate vaccine against pneumonia and
invasive pneumococcal disease in The Gambia: randomised, double-blind, placebo-controlled
trial. Lancet 2005;365:1139- 46. PMID:15794968 doi:10.1016/ S0140-6736( 05)71876- 6

6. Beutels P. Potential conflicts of
interest in vaccine economics research: a commentary with a case study of
pneumococcal conjugate vaccination. Vaccine 2004;22:3312- 22. PMID:15308354 doi:10.1016/ j.vaccine. 2004.03.001< /jrn>

7. Eskola J, Kilpi T, Palmu A, Jokinen
J, Haapakoski J, Herva E, et al.; Finnish Otitis Media Study Group. Efficacy of
a pneumococcal conjugate vaccine against acute otitis media. N Engl J Med
2001;344:403- 9. PMID:11172176 doi:10.1056/ NEJM200102083440 602

8. Klugman KP, Madhi SA, Huebner RE,
Kohberger R, Mbelle N, Pierce N; Vaccine Trialists Group. A trial of a 9-valent
pneumococcal conjugate vaccine in children with and those without HIV
infection. N Engl J Med 2003;349:1341- 8. PMID:14523142 doi:10.1056/ NEJMoa035060< /jrn>

WHO Reply

Pneumococcal conjugate vaccine is efficacious and effective in reducing
the burden of pneumonia

Shabir
A Madhi,a Orin S Levineb & Thomas Cherianc

a Department of Science and Technology/National
Research Foundation: Vaccine Preventable Diseases, University of the Witwatersrand, Chris Hani Baragwanth Hospital,
Bertsham 2013, South Africa.

b Health Section, United Nations Children's Fund
(UNICEF), New York, NY, USA.

c Department of Immunization, Vaccines and
Biologicals, World Health Organization, Geneva, Switzerland.

Correspondence
to Shabir A Madhi (e-mail: madhis@hivsa. com).

While Chowdhary & Puliyel1 are correct
that there has been a non-significant reduction in clinically diagnosed
pneumonia in the
vaccine-efficacy trials conducted to date, their assertion that pneumococcal
conjugate vaccine (PCV) does not reduce severe pneumonia or reduce mortality in
the Gambia is fundamentally flawed. Updated
estimates indicate that there are 155.8 million clinical episodes of pneumonia
globally, which contribute to approximately 1.9 million deaths, 70% of which
occur in Africa and south-east Asia.2 The major drawback in
evaluating the efficacy of PCV against "clinical pneumonia" is the lack of
specificity of this clinical outcome measure that was designed for case
management of pneumonia. It is therefore biased in favour of higher
sensitivity, at the expense of specificity, rather than for vaccine efficacy
trials. Indeed, a large proportion of the cases that meet the case definitions
for clinical pneumonia have a low positive predictive value and are, therefore,
not pneumonia.3 In the case management strategy, one accepts a level
of over-treatment because of the important mortality reduction benefits.
Nevertheless, that pneumococci contribute to significant pneumonia-related
mortality is evident in the success of the WHO case-management strategy of
pneumonia, which is premised upon early antibiotic therapy especially targeting
S. pneumoniae and is associated with a 36% reduction in
pneumonia-mortality .4

On the other hand,
radiologically- confirmed pneumonia is a relatively more specific measure of
bacterial pneumonia and so efficacy of vaccine on this outcome measure a
better indicator of effect on pneumonia mortality. This outcome was indeed the
primary outcome measure for determining efficacy of the vaccine against
pneumonia, rather than the less specific measure of clinical pneumonia. The
vaccine trials were thus not powered to measure efficacy against clinical
pneumonia and it is not surprising that the efficacy estimate did not reach
statistical significance. Furthermore, low specificity of the outcome measure
leads to misclassification and a substantial underestimation of vaccine
efficacy.5

The
case fatality ratio in the Gambia trial was significantly greater in children
with radiologically- confirmed pneumonia (3%) compared with clinical pneumonia
cases that do not fulfil the criteria of radiologically- confirmed pneumonia
(0.8–1.2%) even with access to antibiotic therapy.6 In the absence
of antibiotics, this difference may have been even greater.
Radiologically- confirmed pneumonia accounts for as much as 16.7–34% of cases of
clinical pneumonia,6–8 The higher case fatality rate of
radiologically- confirmed pneumonia and the higher impact of vaccine on this
clinical outcome suggests that the impact of vaccine is more than a "minimal"
contribution. Additionally, PCV is able to reduce pneumonia with an abnormal
chest x-ray, but not defined as "radiologically- confirmed" , from 1.2–7% to
30–32% when the specificity of this outcome is improved for bacterial pneumonia
by using a C-reactive protein of ≥ 40 mg/l as an adjunctive marker.9,10
Thus, the impact of vaccine on true pneumonia and pneumonia mortality are
substantially greater than is indicated by the efficacy against "clinical
pneumonia".

Additionally,
vaccine-efficacy trials may underestimate the public health benefit of
vaccines, as indicated by the indirect herd-protection observed following
introduction of PCV into the United States of America11 and, more
recently, the 39% reduction in the burden of clinical pneumonia hospitalization
after PCV-introduction, 12 compared to a non-significant 7% reduction
in northern California during the vaccine-efficacy trial.13 It is
only through the phased introduction of PCV, which has been shown to be safe
and efficacious in children from diverse settings, that the true public health
benefit of PCV would be realized in developing countries. This would however
need to be coupled with robust surveillance systems to evaluate changes in the
epidemiology of pneumonia before and after its introduction in representative
populations of different regions of the world.

The
mortality benefit in the Gambian study was not evident only within 1 week
of vaccination, but in fact mainly from 12 months onward when 238 of (72.1%) of
the 330 PCV-recipients' deaths and 289 (73.5%) of the placebo recipients'
deaths occurred.14 The rate of mortality within 7 days of any
dose of study vaccine (n = 12; 0.15%) and placebo (n =
15; 0.18%; P = 0.55) did not differ between the two groups, and
their calculated reported incidence calculations are incorrect. The higher rate of reactive
airway disease observed in the South African study was not evident upon
subsequent analysis following extended follow up of the cohort until an average
of 6.3 years of age (S Madhi, personal communication) . Additionally, the higher initially reported risk (1.3 per
1000 children) needs to be weighed against the net reduction of disease
prevented, which was 3.6 per 1000 child years against radiologically- confirmed
pneumonia alone.15

In
conclusion, while we agree with the assertion that the use of PCV in developing
countries needs to be weighed in relation to its cost and benefit, we believe
that the potential benefit of PCV in developing countries is beyond question,
as indicated by the WHO recommendation on PCV.16 Nevertheless, it is
essential that the introduction of PCV be coupled with adequate surveillance at
least in representative communities of regions in which it is introduced to
fully establish the potential to public health of the vaccine.

Reference

1. Chowdharya S, Puliyela J. Incidence
of pneumonia is not reduced by pneumococcal conjugate vaccine. Bull World
Health Organ 2008;86:XXX.

2. Rudan I, Tomaskovic L, Boschi-Pinto
C, Campbell H. Global estimate of the incidence of clinical pneumonia among
children under five years of age. Bull World Health Organ
2004;82:895- 903. PMID:15654403< /jrn>

3. Cherian T, John TJ, Simoes E,
Steinhoff MC, John M. Evaluation of simple clinical signs for the diagnosis of
acute lower respiratory tract infection. Lancet 1988;2:125-8. PMID:2899187 doi:10.1016/ S0140-6736( 88)90683- 6

4. Sazawal S, Black RE. Effect of
pneumonia case management on mortality in neonates, infants, and preschool
children: a meta-analysis of community-based trials. Lancet Infect Dis
2003;3:547-56. PMID:12954560 doi:10.1016/ S1473-3099( 03)00737- 0

5. Jaffar S, Leach A, Smith PG, Cutts F,
Greenwood B. Effects of misclassification of causes of death on the power of a
trial to assess the efficacy of a pneumococcal conjugate vaccine in The Gambia.
Int J Epidemiol 2003;32:430- 6. PMID:12777432 doi:10.1093/ ije/dyg082< /jrn>

6. Enwere G, Cheung YB, Zaman SM, Akano
A, Oluwalana C, Brown O, et al. Epidemiology and clinical features of pneumonia
according to radiographic findings in Gambian children. Trop Med Int Health
2007;12:1377- 85. PMID:18045264< /jrn>

7. Madhi SA, Kuwanda L, Cutland C,
Klugman KP. The impact of a 9-valent pneumococcal conjugate vaccine on the
public health burden of pneumonia in HIV-infected and -uninfected children. Clin
Infect Dis 2005;40:1511- 8. PMID:15844075 doi:10.1086/ 429828

8. Magree HC, Russell FM, Sa'aga R,
Greenwood P, Tikoduadua L, Pryor J, et al. Chest X-ray-confirmed pneumonia in children
in Fiji. Bull World Health Organ 2005;83:427- 33. PMID:15976893< /jrn>

9. Madhi SA, Klugman KP. World Health
Organisation definition of "radiologically- confirmed pneumonia" may
under-estimate the true public health value of conjugate pneumococcal vaccines.
Vaccine 2007;25:2413- 9. PMID:17005301 doi:10.1016/ j.vaccine. 2006.09.010< /jrn>

10. Cheung YB, Zaman SM, Ruopuro ML,
Enwere G, Adegbola RA, Greenwood B, et al. C-reactive protein and procalcitonin
in the evaluation of the efficacy of a pneumococcal conjugate vaccine in
Gambian children. Trop Med Int Health 2008;13:603- 11. PMID:18331385< /jrn>

11. Direct and indirect effects of
routine vaccination of children with 7-valent pneumococcal conjugate vaccine on
incidence of invasive pneumococcal disease — United States, 1998-2003. MMWR
Morb Mortal Wkly Rep 2005;54:893- 7. PMID:16163262< /jrn>

12. Grijalva CG, Nuorti JP, Arbogast PG,
Martin SW, Edwards KM, Griffin MR. Decline in pneumonia admissions after
routine childhood immunisation with pneumococcal conjugate vaccine in the USA:
a time-series analysis. Lancet 2007;369:1179- 86. PMID:17416262 doi:10.1016/ S0140-6736( 07)60564- 9

13. Black SB, Shinefield HR, Ling S,
Hansen J, Fireman B, Spring D, et al. Effectiveness of heptavalent pneumococcal
conjugate vaccine in children younger than five years of age for prevention of
pneumonia. Pediatr Infect Dis J 2002;21:810- 5. PMID:12352800 doi:10.1097/ 00006454- 200209000- 00005

14. Cutts FT, Zaman SM, Enwere G, Jaffar
S, Levine OS, Okoko JB, et al. Efficacy of nine-valent pneumococcal conjugate
vaccine against pneumonia and invasive pneumococcal disease in The Gambia:
randomised, double-blind, placebo-controlled trial. Lancet
2005;365:1139- 46. PMID:15794968 doi:10.1016/ S0140-6736( 05)71876- 6

15. Klugman KP, Madhi SA, Huebner RE,
Kohberger R, Mbelle N, Pierce N. A trial of a 9-valent pneumococcal conjugate
vaccine in children with and those without HIV infection. N Engl J Med
2003;349:1341- 8. PMID:14523142 doi:10.1056/ NEJMoa035060< /jrn>

16. Pneumococcal conjugate vaccine for
childhood immunization – WHO position paper. Wkly Epidemiol Rec
2007;82:93-104. PMID:17380597< /jrn>





"It is now 30 years since I have been confining myself to the treatment ofchronic diseases. During those 30 years I have run against so many histories of littlechildren who had never seen a sick day until they were vaccinated and who, in the severalyears that have followed, have never seen a well day since. I couldn't put my finger onthe disease they have. They just weren't strong. Their resistance was gone. They wereperfectly well before they were vaccinated. They have never been well since. "---Dr. William Howard Hay

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