Merck's Pnumovax Pulled in Australia with 82 Severe Reactions Since January

Drug watchdog halts injections after adverse reaction in patients
Adam Cresswell From: The Australian April 19, 2011 12:00AM

THE drug regulator has told GPs to stop giving patients a second dose of a vaccine that protects against pneumococcal disease, after more than 80 Australians suffered severe reactions, including severe swelling and abcesses.

The Therapeutic Goods Administration said it was investigating what could have caused 178 reports of reactions to the Pneumovax 23 vaccine, which is meant to protect against a potentially life-threatening bacterial infection that can cause meningitis and death and is mainly given to adults.

Of the 178 reaction reports made from January 1 to April 14, 169 related to reactions at the injection site, of which 82 were deemed severe, and included the skin inflammation cellulitis, swelling from the shoulder to the elbow and abcesses.

In a statement, the TGA said that although such reactions were specifically mentioned as possible side-effects in the information provided with the vaccine, the sheer number had triggered the agency's concern.

The total number of reaction reports is nearly three times the 63 adverse reactions that were reported to the end of April last year, and more than five times the 34 reactions reported in 2009.

The vaccine, made by Merck Sharp and Dohme, is provided free once every five years for adults over 65, indigenous people over 50, tobacco smokers, and people aged 10 and over who are predisposed to invasive pneumococcal disease.

The latest scare follows an earlier incident with the same vaccine in March, when the TGA ordered a recall of one specific batch after a cluster of seven patients reported similar reactions.

Of the 178 reaction reports overall, 57 were among people who received the suspect N3336 batch involved in the earlier NSW incident.

The TGA said in a statement that, out of the 82 severe reactions, 44 were among people receiving their second dose. Another 22 were in people receiving the vaccine for the first time, while it was unclear whether the remainder were first or second shots.

"Analysis of these adverse reactions suggests that the largest number of reactions is occurring in people receiving their second five-yearly dose of Pneumovax," the statement said.

"Further detailed analysis . . . is required and will be undertaken by the TGA and the Australian Technical Advisory Group on Immunisation. Until this analysis is complete, the TGA is recommending as a precautionary measure that patients do not receive a second dose."

Merck Sharp and Dohme said the company was not involved in the TGA's alert and could not "elaborate on the reasons" for the warning.

Pneumococcal Doubles Asthema Incidence

From One Click:

One Click Note: The World Health Organization states that for every 1000 children vaccinated with the pneumococcal vaccine, 1.3 children will develop asthma on account of the vaccine. At the same time only 3.6 cases of pneumonia are prevented by vaccinating 1000 children. Pneumonia is an easily treated condition. Asthma on the other hand may be a lifelong disability:

Publication: Bulletin of the World Health Organization;
Type: Letters
Article DOI: 10.2471/BLT.08.054692

Incidence of pneumonia
is not reduced by pneumococcal conjugate vaccine

Sona Chowdhary & Jacob Puliyel

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

Correspondence to Jacob Puliyel (e-mail: puliyel@gmail.com).
(Published online: 1 September 2008)

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

2. Revised global burden of disease 2002 estimates. Geneva: WHO. Available here [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 vaccinetype 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

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

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/NEJM200102083440602

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