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Re: Penicillin prophylaxis for sickle cell disease

Dear Editor

Asplenia predisposes to serious infections due to polysaccharide encapsulated organisms.[1] Young children with sickle cell disease are at risk of pneumococcal bacteremia at a rate approximating 100 times that observed in normal infants and young children.[2] In 1986, Gaston et al. reported reduced pneumococcal infection and related deaths in children with sickle cell disease given twice-daily prophylactic oral penicillin V by 84 percent compared with placebo.[3] This approach is still recommended nowadays,[4] for children with sicke cell disease at least under 5 years of age,[5] despite vaccination with pneumococcal vaccine.[6] However, instead of oral penicillin V, the benzathine penicillin G has being used in several places all over the world for the same purpose. According to Reese et al., the blood levels of benzathine penicillin G ranges from 0.10 to 0.15 units/ml, which are equivalent to 0.06 to 0.09ug/ml, and of oral penicillin V ranges from 3 to 5 ug/ml.[7]

Since the 1980s, the frequency of penicillin non-susceptible pneumococcal strains at intermediate or absolute level has been increasing at different levels in many countries.[8] According to NCCLS, 2000, the MIC standards for pneumococcal resistance to penicillin is < 0.06 ug/ml (susceptible), 0.125-1 ug/ml (intermediate resistance), > 2ug/ml (absolute resistance).[9] Therefore, it is improbable to have success on prophylaxis for invasive pneumococcal disease by using benzathine G penicillin. Pediatricians should be alert to this issue.

References

(1) Wong WY. Prevention and management of infection in children with sickle cell anaemia. Paediatr Drugs 2001; 3:793-801.

(2) Wong WY, Powars DR, Chan L et al . Polysaccharide encapsulated bacterial infection in sickle cell anemia: a thirty-year epidemiologic experience. Am J Hematol 1992; 39 : 176-182.

(3) Gaston MH, Verter JI, Woods G et al. Prohylaxis with oral penicillin in children with sickle cell anemia: a randomized trial. N Engl J Med 1986; 314 : 1593-1599.

(4) American Academy of Pediatrics. Pneumococcal Infections. In Red Book: Report of the Committee on Infectious Diseases, 25th ed. Pickering LK, Ed. 2000 Elk Grove Village, IL: American Academy of Pediatrics; 2000: 460.

(5) Falletta JM, Woods GM, Verter JL et al . Discontinuing penicillin prophylaxis in children with sickle cell anemia. J Pediatr 1995; 127 : 685- 690.

(6) Finn A, Booy R, Moxon R, Sharland M, Heath P. Should the new pneumococcal vaccine be used in high-risk children? Arch Dis Child 2002; 87 : 18-21.

(7) Reese RE, Betts RF and Gumustop B. Handbook of Antibiotics, 3rd ed. Philadelphia: Lippincott Williams & Wilkins, 2000.

(8) Applebaum PC. World-wide development of antibiotic resistance in pneumococci. Eur J Clin Microbiol 1987; 6 : 367-377.

(9) National Committee for Clinical Laboratory Standards. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically, 7th ed. M7-A2. Villanova, PA: NCCLS, 2000.

Cristiana Nascimento-Carvalho, MD, PhD
Department of Pediatrics, Faculty of Medicine
Federal University of Bahia
Rua Prof. Aristides Novis
No. 105/1201B – Salvador,
Bahia, Brazil

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Re: Conflicting advice

Dear Editor

As a follow up to this article, the most recent CMO letter [1] sent out in August 2002, updates the recommendations issued by the Dept. of Health (DoH) in January 2002[2] by making the recommendations for "at risk" under 2 year old children coincide with the manufacturer's recommendations for immunisation of normal healthy children in their Summary of Product Characteristics for their European product licence.

These schedules differ a little bit from those set out in our paper[3] which was subsequently cited in the recent RCPCH guidelines for immunisation of immunocompromised children.[4] In particular, the DoH advice does not draw any distinction between different risk groups, whereas our advice is to give extra doses to children with hyposplenism and various forms of immunocompromise. The DoH does not, at present, advocate use of the conjugate vaccine in any children over the age of two, whereas we do, conscious that many experts feel that there are good theoretical reasons to use the conjugate vaccine in this way (just as conjugate meningococcal C vaccine has replaced polysaccharide vaccine use in older children). Finally, the DoH suggests all recipients in the second year of life should receive 2 doses of conjugate pneumococcal vaccine, whereas we suggest only one for "at risk" children outwith the very high risk groups mentioned above.

The differences between the two sets of advice have led to some enquiries from colleagues as to how best to proceed and why the two documents differ.

>We think it is important to emphasise that both sets of recommendations have been drawn up in the absence of much data as to how best to protect these groups of children. What evidence there is, is summarised in our paper. Further immunogenicity studies in children with HIV and other groups are in progress. In addition, it was reassuring to hear the preliminary results of a large efficacy study in children in South Africa at the International Symposium on Pneumococci and Pneumococcal Diseases in May 2002 which suggested that conjugate pneumococcal vaccine is protective in children with HIV infection, albeit less so than in uninfected children. However, most pre-licensure studies were done in normal healthy infants, since that was the target group for the license. In the absence of more data, it is not surprising that different expert groups have come up with slightly differing advice. In addition, presumably, as a government agency, the DoH must be constrained to some extent against issuing recommendations which go beyond or which differ from those contained within an official product license - even if that license relates to healthy rather than "at risk" individuals.

Consistently following either set of recommendations seems reasonable under the circumstances – no doubt further modifications to this advice will follow in due course as further evidence emerges.

Adam Finn
Robert Booy
Mike Sharland
Paul Heath

References

(1) CMO letter. August 2002. http://www.doh.gov.uk/cmo/letters/cmo0204.htm#iii (accessed 18th Sept 2002)

(2) CMO letter. January 2002. http://www.doh.gov.uk/cmo/cmo0201.htm(accessed 18th Sept 2002)

(3) Finn A, Booy R, Moxon R, Sharland M, Heath P. Should the new pneumococcal vaccine be used in high-risk children? Arch Dis Child 2002;87:18-21

(4) RCPCH best practice statement. Immunisation of the immunocompromised child. http://www.rcpch.ac.uk/publications/recent_publications/Immunocomp.pdf (accessed 18th Sept 2002)