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PAPERS: Shahadat Hossain, Rabi Biswas, Iqbal Kabir, Shafique Sarker, Michael Dibley, George Fuchs, and Dilip Mahalanabis Single dose vitamin A treatment in acute shigellosis in Bangladeshi children: randomised double blind controlled trial BMJ 1998; 316: 422-426 [Abstract] [Full text]

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Vitamin A treatment in acute shigellosis: are the conclusions valid?

Michael L Bennish   (9 January 1999)

Vitamin A treatment in acute shigellosis: are the conclusions valid? 9 January 1999
Michael L Bennish Send response to journal: Re: Vitamin A treatment in acute shigellosis: are the conclusions valid?	Dear Sir; Hossain et al, in their report on vitamin A treatment of shigellosis, conclude, that "....vitamin A along with standard antibiotic reduces the severity of acute shigellosis...", and "...vitamin A supplementation should be added to the standard treatment for acute shigellosis". [1] We do not agree with those conclusions. The benefit of vitamin A as adjunctive therapy, for shigellosis can only be judged in a study in which patients receive adequate antimicrobial therapy. [2] In the Hossain study 64% of patients were infected with strains of Shigella resistant to the antimicrobial agent - nalidixic acid - used for treatment of study patients. It is unclear how many patients had an alternative effective antimicrobial agent provided, and when this change of therapy occurred. The inadequacy of antimicrobial treatment in this study is reflected in clinical cure rates of less than 50% in both the vitamin A supplemented and non-supplemented groups. That is not an acceptable cure rate in shigellosis, in which adequate antimicrobial treatment routinely achieves a cure rate of 65% or more.[3,4] Indeed, Hossain and colleagues predicated their sample size calculation on a 98% cure rate in the vitamin A supplemented group. [1] The definition of cure used in this study included the absence of any mucus or blood in stool, measures which, are not good indicators of overall clinical status, and the determination of which can vary between observers. It is important to know which component of the definition of clinical cure (three or fewer formed stools, no visible stool blood or mucus, afebrile) used in the study accounted for the difference in cure rates between groups and if there were any differences in more objective outcome measures, such as total number of stools during the study or, duration of fever. [3,5] The authors contend that the differences in reported outcome between groups may have been because vitamin A supplementation stimulated "...phagocytosis and cell mediated killing of pathogens". The similar rate of clearance of Shigella observed in the two groups would seem to directly contradict this contention. The rapid divergence (by 24 hours) between groups in the proportion of patients with clinical cure suggests a more rapid response than could reasonably be expected to be achieved by vitamin A "...enhanced repair of the micro-ulcers in the gut epithelium". Vitamin A has an important role to play in public health in developing countries. The rationale for that use, however, must come from well-conducted studies in which children receive effective primary therapy for their illness (in this case effective antimicrobial therapy), and for which there are clear, reproducible and clinically relevant definitions of treatment outcome. Sincerely Mohammed Abdus Salam, M.B.B.S Chief Physician Wasif Ali Khan, M.B.B.S Physician Ujjwal Dhar Physician International Center for Diarrhoeal Disease Research, Bangladesh GPO Box 128 Dhaka, 1000 BANGLADESH Anne Ronan, DCH, MRCP, FRACP, MMedSci (Epid) Child and Family Health Services Wallsend Campus, Newcastle, NSW AUSTRALIA Nigel C. Rollins, MD MRCP Department of Paediatrics and Child Health University Natal Private Bag 7 Congella 4013 SOUTH AFRICA Michael L. Bennish, M.D. Associate Professor Division of Geographic Medicine and Infectious Diseases New England Medical Center Tufts University School of Medicine Boston, MA UNITED STATES REFERENCES 1. Hossain S, Biswas R, Kabir I, Sarker S, Dibley M, Fuchs G, Mahalanabis D. Single-dose vitamin A treat MA, Bennish ML. Antimicrobial therapy of shigellosis. Rev Infect Dis 1991;13:(suppl 4):S332-41. 2. Salam C, Khan WA, Bennish ML. Treatment of shigellosis, IV: cefixime ineffective in shigellosis in adults. Ann Intern Med 1995;123:505-8. 3. Salam MA, Bennish ML. Therapy for shigellosis, I. Randomized, double blind trial of nalidixic acid in childhood shigellosis. J Pediatr 1988;113:901-7. 4. Salam MA, Dhar U, Khan WA, Bennish ML. Randomised comparison of ciprofloxacin suspension and pivmecillinam for childhood shigellosis. Lancet 1998. In press. 5. Salam MA, Seas ment in acute shigellosis in Bangladeshi children: randomised double blind controlled trial. BMJ 1998;316:422-6.