On-line version ISSN 2078-5135
SAMJ, S. Afr. med. j. vol.100 n.10 Cape Town Oct. 2010
Solubility tests and the peripheral blood method for screening for sicklecell disease
To the Editor: We refer to the paper by Okwi et al.1 Cost benefit analysis of screening for sickle cell disease (SCD) using different methods cannot be done in isolation, and the following are important principles to take into account.
1. Reasons for screening: (i) early detection of the disease for timely intervention to minimise morbidity and mortality; (ii) patient and family education on SCD; (iii) genetic counselling as part of a long-term strategy to prevent live homozygous SCD (SS) births; and (iv) short-and long-term cost saving by means of (i), (ii) and (iii) above.
2. The method of detection needs to be very sensitive. Subjects with false-negative results will remain undiagnosed and may well present with an acute crisis or organ damage, with major cost implications.
The sensitivities of the sickling and solubility tests for detection of the sickle cell trait (AS) as reported by the authors were 65% and 45%, respectively, essentially translating to high 35% and 65% false-negative rates, an unacceptable scenario regardless of cost saving.
Clearly the methodologies need to be questioned, since the sickling test is sensitive enough to detect AS.1,2 In addition, the article advocates that negative sickling tests be regarded as negative for the disease, evidently with no further testing required. This means that 35% of the subjects tested will walk around with undiagnosed AS despite having been tested, which defeats the objectives of screening as stated above.
The recommendation by the group that the sickling test be the preferred and sole method for screening, purely on the basis of economics, is disconcerting, while with its observed shortcomings the proposed screening method would be of short-term benefit.
We conclude that a cost benefit analysis of methods with such low sensitivities is ineffective and futile.
N A Alli
S B Loonat
Department of Molecular Medicine and Haematology
School of Pathology
University of the Witwatersrand/National Health Laboratory Service
1. Okwi AL, Ocaido M, Byarugaba W, Ndugwa CM, Parkes A. Solubility tests and the peripheral blood film method for screening for sickle cell disease: A cost benefit analysis. S Afr Med J 2009;99(12):887-891. [ Links ]
2. Dacie JV, Lewis SM. Practical Haematology. 5th ed. Edinburgh: Churchill Livingstone, 1975. [ Links ]
3. Chanarin J. Laboratory Haematology. 1st ed. Edinburgh: Churchill Livingstone, 1989. [ Links ]
Okwi et al. reply: Our cost benefit analysis was not done in isolation, as suggested above. The paper was published together with others that appeared elsewhere and addressed the issues raised. Sensitisation of communities (patient and family education on SCD) and timely intervention were covered in a publication in the East African Medical Journal.1 Another paper addressing some of these issues was published in BMC Blood Disorders.2
All the false negatives with the sickling test were cases of AS (carriers), not SS. The sickling test demonstrated all SS cases, as did Hb electrophoresis - i.e. sickling was sensitive in SS detection but not in AS detection. The sickling test would therefore be sensitive enough to detect all the children with SS, who would benefit most since they suffer from crisis, while carriers (AS) do not.
Lastly, the authors state that our article advocated interpreting a negative sickling test as the patient being negative for the disease, with no further testing required. We did not assume or recommend this. Our assumption was that all the children who might accidentally be missed by the sickling test and develop symptoms later would be tested by Hb electrophoresis.
We concluded that although the sickling test was not highly sensitive, it was more sensitive than solubility and the peripheral blood film method.
1. Okwi AL, Byarugaba W, Ndugwa CM, Parkes A, Ocaido M, Tumwine JK. Knowledge gaps, attitude and beliefs of the communities about sickle cell disease in eastern and western Uganda. East Afr Med J 2009;86(9):442-449. [ Links ]
2. Okwi AL, Byarugaba W, Ndugwa CM, Parkes A, Ocaido M, Tumwine JK. An update on the prevalence of sickle cell trait in Eastern and Western Uganda. BMC Blood Disorders 2010;10: 5doi:10. [ Links ]1186/1471-2326-10-5.