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ARTICLES: Stephen Miles Hughes, Beatrice Amadi, Mwiya Mwiya, Hope Nkamba, Georgina Mulundu, Andrew Tomkins, and David Goldblatt CD4 Counts Decline Despite Nutritional Recovery in HIV-Infected Zambian Children With Severe Malnutrition Pediatrics 2009; 123: e347-e351 [Abstract] [Full text] [PDF]

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CD4 cells and cellular immune deficiency-a paradox

Eleni Papadopulos-Eleopulos, Valendar F. Turner, John Papadimitriou and, David Causer   (10 February 2009)

CD4 cells and cellular immune deficiency-a paradox 10 February 2009
Eleni Papadopulos-Eleopulos, Biophysicist Royal Perth Hospital Western Australia, Valendar F. Turner, John Papadimitriou and, David Causer Send letter to journal: Re: CD4 cells and cellular immune deficiency-a paradox vturner{at}iinet.net.au Eleni Papadopulos-Eleopulos, et al.	The study by Hughes et al1 amply confirms what Chandra has termed the “causal relationship between the conjugal pair of famine and pestilence”.2 However, the study also raises a significant question in regard to the role CD4 cells play in cellular immunity. According to Hughes et al and all other HIV experts, HIV infection impairs cellular immunity by causing decreased numbers of CD4 cells (acquired immune deficiency=AID) and the more severe the AID the higher the probability of developing bacterial, mycobacterial and fungal infections. In regard to malnutrition they state “the unusual frequent, and severe infections in children with severe malnutrition (SM) have been attributed to impairment in cell-mediated immunity”. Chandra states “It is recognized that malnutrition and infection are two major obstacles for health, development and survival worldwide, and that poverty and ignorance are the most significant contributing factors…malnutrition is the commonest cause of immunodeficiency worldwide.2 Furthermore, malnourished, immunodeficient children also have high frequencies of bacterial and fungal infections including tuberculosis and Pneumocystis carinni pneumonia.3 4 Yet, although the clinical pictures of malnutrition and AIDS are uncanningly similar, the Hughes study reported a totally dissimilar picture in regard to “cell-mediated immunity”. This is a paradox the authors did not address. In their study 56 children were hospitalised for SM, 24 HIV-infected and 32 uninfected. Both groups were treated with milk powder feedings, micronutrients and “parenteral antibiotics on admission”. Of the 56 children whose CD4 cells were determined at admission, 40 had samples measured at discharge but only “27 on full nutritional recovery”. They reported “HIV-uninfected children with SM had normal CD4 counts…Critically, we showed that CD4 percentages tended to fall rather than rise on nutritional recovery among the HIV-uninfected children…We propose that the CD4 counts had risen as a result of infection and returned to baseline after antimicrobial treatment”. In the HIV-infected group “the prevalence of severe immunosuppression [AID]…rose (from 17% on admission to 63% by the time of full nutritional recovery)”. This study raises the following questions: 1. Why are these children’s cellular immune deficiencies disparate in terms of the numbers of CD4 cells? 2. Why were infections associated with an increase in CD4 cells in one group but a decrease in the other? 3. Why was the treatment of infections successful in the HIV-infected individuals at the time their cause, AID, was worsening? We can think of three possible explanations: 1. Problems in the design of this study. 2. The nature of the “cell-mediated immunity” is different in the two groups. 3. The numbers of CD4 cells is not an indicator of “cell-mediated immunity” in any group of patients, including HIV-infected individuals.5-7 We would be grateful for an alternative, more plausible explanation. REFERENCES 1. Hughes SM, Amadi B, Mwiya M, Nkamba H, Mulundu G, Tomkins A, et al. CD4 counts decline despite nutritional recovery in HIV-infected Zambian children with severe malnutrition. Pediatrics 2009;123:e347-51. Epub 2009 Jan 5. 2. Chandra RK. Nutrition and immunology: from the clinic to cellular biology and back again. Proc Nutr Soc 1999;58:681-3. 3. Dutz W, Post C, Vessal K, Kohout E. Endemic infantile pneumocystis carinii infection: the Shiraz study. NCI Monogr 1976;43:31-40. 4. Hughes WT, Price RA, Sisko F, Havron WS, Kafatos AG, Schonland M, et al. Protein-calorie malnutrition. A host determinant for Pneumocystis carinii infection. Am J Dis Child 1974;128:44-52. 5. Goodwin JG. OKT3, OKT4, and all that. JAMA 1981;246:947-948. 6. Papadopulos-Eleopopulos E, Turner VF, Papadimitriou JM, Hedland- Thomas B, Causer D, Page B. A critical analysis of the HIV-T4-cell-AIDS hypothesis. Genetica 1995;95:5-24. 7. Pandrea IV, Gautam R, Ribeiro RM, Brenchley JM, Butler IF, Pattison M, et al. Acute loss of intestinal CD4+ T cells is not predictive of simian immunodeficiency virus virulence. J Immunol 2007;179:3035-46. Conflict of Interest: None declared