Occupy Medicine Vaccines for versus profits for the

Occupy Medicine Vaccines for versus profits for the 99% 1% Jacob M. Puliyel St Stephens Hospital, Delhi puliyel@gmail. com

Raffle of a dead donkey Cost 500 tickets @ $2 each Refund Profit $ 1000 $2 $ 898

250, 000 death in India each year due to Hepatitis B Miller et al Health Economics 2000; 9: 19 -35 ICMR data suggests about 5000 die Dhir et al Ind J of Gastroenterol 1998; 17: 100 -3

Model Used Model ‘stratified by income group and geographic region’ was used and it was available on the CDC web site: http: // nihfic. cit. nih. gov No model on web site /research

Model using data from Taiwan Males 25% Male hepatitis B carriers die in Taiwan World Record 300% of mortality in Taiwanese female carriers Beasley Cancer 1988; 61: 1942 -56 It is 17 times higher than mortality in Canadian carriers Villeneuve et al Gastroenterology 1994: 106: 1000 -5

Extrapolation Taiwan Male Mortality 4% population are carriers in India If 1 in 4 carriers die of the disease 1% of deaths in India must be due to Hepatitis B 1% of deaths among India’s 1 billion population is 250, 000! Puliyel JM. Lancet 2004; 363: 659

Health Economics publishes call for retraction of paper Model used by Miller must be published or the paper retracted Puliyel JM Health Economics 2004; 13: 1147 Miller has replied that the model was lost Miller MA Health Economics 2004; 13: 1147 -8 The paper has NOT been retracted yet

Invasive H. Influenza B (Hib ) disease Incidence of invasive disease with Hib is very low. Incidence: 9/100, 000 Asia 109 /100, 000 Western Pacific Levine Pediatr Infect Dis J 1998; 17: S 95113

Is Hib really needed in Asia? Editorial in Bulletin of WHO Lau YL Bulletin WHO 1999; 77: 867 -8

Natural Immunity in Asia 1. High antibody levels pre-vaccination at 6 weeks 2. Not passive immunity Without immunization: Increasing antibody titers with increasing age Tastan Ind Pediatr 2000; 37: 414 -7

Natural Immunity in Asia: Vaccine Booster Effect 3. After vaccination, antibody levels increase ten times higher than normal suggesting that child was immune before vaccination Acharya Ind Pediatr 1997; 34: 9 -15 Kumar Ind J Pediatr 1997; 64: 839 -47

Natural Immunity to Hib Animal model: E coli cross-reactive antigens against Hib Schneerson Inf and Immunol 1971; 4: 397401 Bradshaw Lancet 1971; 1095 -98 Petrie Br J Exp Path 1971; 13: 380 -94 Infection with organisms like E Coli may protect Asians against Hib Puliyel Vaccine 2001; 19: 4592 -4

Inappropriate-Media Hypothesis for Low Culture Rate Chocolate agar supplemented with Isovitalex Gellert Lancet. 1994 ; 344: 959

• • Invasive Bacterial Infection Surveillance Group (IBIS) Study Continuous surveillance for 4 years 6 of the largest hospitals in 6 cities Appropriate culture techniques Findings: 125 cases in 4 years! Small numbers? Access to the hospital is perhaps a problem Solution: Community studies needed. IBIS Group Clinical Infect. Dis 2002; 34: 949 -57

WHO Prospective Community Study Hib Meningitis Incidence Hib meningitis 7/100, 000 (Levine had estimated 9/100, 000 invasive disease) Low rate of Hib in children in this region: (a) genetic factors (b) early exposure to bacteria with cross-reacting antigens (c) low bacterial virulence Minz et al IJMR 2008; 128: 57 -64

New Ideas Low Incidence of • Culture media not the problem: IBIS Study • Access to hospital not the issue: Mitz Community Study Perhaps prior antibiotic use problem Hib

Probe study for areas with Low Culture Rate Probe studies to identify reduction in clinical disease after immunization No culture proof needed The Hib initiative. www. hibaction. org/research. php#vaccine _probe.

Indonesia Lambok Study 55000 children: • Double blind • Hamlet randomized • Active case surveillance Gessner Lancet 2005; 365: 43 -52

Vaccine Effectiveness (Vaccine preventable Hib disease) Disease manifestation Vaccine Effectiveness (Incidence Unvaccinated – Vaccinated) Alveolar Consolidation/ Effusion - 43 (95% CI -185 to 98

Bangladesh Probe 2007 • Not randomized. No blinding • Incident case-control study • Population 68, 000 • 35% received Hib vaccine • 475 Pneumonia. Baqui Ped Infect Dis 2007; 26: 565 -71

Bangladesh Probe Vaccine Effectiveness - 3 doses Baqui Ped Infect Dis 2007; 26: 565 -71 Disease Community Controls (matched for age , sex, season and distance from hospital) Meningitis 40% (95% CI -138 to 85) Pneumonia (WHO protocol) 20% (95% CI -10 to 43)

Press release WHO Dhaka , 28 June 2007 New study shows Hib vaccine protects children from significant burden of life -threatening pneumonia and meningitis Press release signed by WHO, GAVI, USAID, Johns Hopkins Puliyel Demanding Accountability. BMJ 2010; c 4081 Puliyel Eu tu WHO. IJMR 2010; 131: 588 -9

No Hidden Agenda • Cost of Hib in the USA is $5. 60 (1998 prices) • Price can come down only if Hib is part of EPI internationally Nossal Nature Medicine 1988; 5: 475 -6 Steinhoff Lancet 1993 ; 342: 630 -1 Poor countries must use the vaccine so the price of the vaccine in the West can come down Puliyel Vaccine 2001; 19: 4592 -4

Hib eliminated: Replacement by other invasive strains of H. influenza Proportional increase in non-B H. influenza strains, including non- serotypeable strains, causing invasive H influenza disease in the post- Hib vaccine era in Canada Tsang et al Clin Infect Dis. 2007; 44: 1611 -4. Brown et al Clin Infect Dis 2009; 49: 1240– 1243

Pneumococcal vaccine Cost Rs 12, 000 per child Benefit Reduce 3. 6 cases of pneumonia /1000 children vaccinated Madhi WHO Bull 2008; 86

Pneumococcal Vaccine Harm: Risk of Asthma Doubled 1. 4 additional cases of Asthma for every 3. 6 cases pneumonia avoided (per 1000 children vaccinated) Klugman K. NEJM 2003; 349: 1341 -8

Spending Rs 12 million to save Rs 40 • Vaccine costs Rs 12, 000 per child • Vaccinating 1000 children costs Rs 12 million • Treating 4 cases of pneumonia will cost Rs 40 if WHO recommended Septran is used Dabade Lancet 2009; 373: 2195 -6 If prices come down to Rs 1200/child you will spend Rs 1. 2 million to save Rs 40

Cure is Worse than Disease Strain Replacement Invasive pneumococcal infections increased after PCV 7 Serotype 19 A isolated, one third of which were resistant to multiple antibiotics. Kaplan Pediatrics 2010; 125: 429 -436

Rota Virus in India • Continuous reassortment bovine and human strains. of Ramani S. IJMR 2007; 125: 619 -32 • No study on reduction in diarrhoea among vaccinated in India

Community Perspective: Allocative Efficiency Hypothetical Case Study 1. Rota virus control costs Rs 200 crores Saves 1 life year per Rs 20, 000 2. Polio control costs Rs 350 crores Saves 1 life year per Rs 10, 000 3. TB control costs Rs 700 crores

Rank Incremental Cost-Utility Ratios Budgetary Constraint: Rs 1000 crores 1. TB control costs Rs 700 crores Saves 1 life per Rs 5000 2. Polio control costs Rs 350 crores Saves 1 life per Rs 10, 000 3. Rota virus control costs Rs 200 crores Saves 1 life per Rs 20, 000

50% of the population don’t receive the basic EPI vaccines costing Rs 30 • HPV Rs 9000/child • Rotavirus Rs 2000/child • Pneumococcal vaccine 12000/child Rs

Pneumococcal Vaccine: Perspective of the Individual Exorbitantly expensive Cost per child Rs 12, 000 MRP includes incentive to doctor Rs 3000 • Very small benefits (3. 6/1000 pneumonia) • Individual risks - Asthma (1. 4/1000) • Community risks - Antibiotic Resistant Strains Can it be prescribed ethically to rich?

Half Truths and Lies • 10. 6 million children under five years of age die each year • Pneumonia, leading cause of mortality among children in developing countries SAGE WHO www. who. int/immunization/SAGE_wg_detailedr eview_pneumo. Vaccine. pdf Pneumonia is a vaccine preventable disease

The Unsaid Truth • Vaccine is against only one bacterial pathogen and that against only a limited number of strains of that bacteria. • It is dishonest to pretend the vaccine can prevent all pneumonia

Another Half Truth Pneumococcal vaccine protection against vaccine-strain invasivedisease (VS-IPD) 80% (CI 58% to 90%, P < 0. 0001) Cochrane meta analysis. Lucero 2009

The other half of the truth No reduction in all-cause mortality [OR 11% (95% CI -1% to 21%, P = 0. 08)] Incidence of vaccine strain invasive disease was so low - the absolute risk difference (ARR) is only -0. 002 (CI: 0. 004 to -0. 000) Number Needed to Prevent One Case 500. Puliyel Microbiology and Infection 2011

Misleading Statistics • Risk reduction (RR) of 50% good for a vaccine Patients and doctors are easily convinced sounds Suppose Risk comes down from 4% to 2% • RR is 50% • It affords 2% reduction in absolute risk.

Yellow fever • 100% Protection • ARR ZERO (As disease non-existent India)

RR and ARR RR = R 2/R 1 = (0. 0001/0. 0002) = ARR = R 1 – R 2 = 0. 0002 - 0. 0001 = 50% 0. 0001 NNT = 1/ARR = 1/0. 0001 = 1000 Die Live Total Contr ol 2 998 100 0 Vacci ne 1 999 100 0 Total 3 1997 200 0

Efficacy as 'absolute risk reduction' to calculate cost benefits easily • Impressive sounding reductions in relative risk can mask much smaller reductions in absolute risk. • Clinical decisions based on absolute risk (AR) rather than relative risk (RR). Godlee F 2008. Absolute risk please. BMJ

How to avoid buying a dead donkey What the MSF can do

Resolution for WHA: Intervention to enhance child survival Efficacy must ALWAYS be reported in terms of 'absolute risk reduction' NOT Relative risk (RR) so that Member States can calculate cost benefits easily