In this study, we have reviewed an old problem – severe malnutrition in children – by using modern techniques for assessing the immunocompetence that has developed over the last decades in response to the HIV/AIDS pandemic. We have used the up-to-date laboratory techniques for the assessment of lymphocyte subsets in recognised laboratories. Since some of the severely malnourished children are also HIV positive, it is now possible to describe the clinical and laboratory features of the two groups of patients: severely malnourished children with HIV infection and those without HIV infection. We have noticed the well-known fact that the clinical features of severe malnutrition and HIV/AIDS overlap in young children. This affects the possibility of an accurate clinical diagnosis of HIV infection in settings with poor resources and often with inadequate HIV-testing facilities, particularly in cases wherein the two conditions, namely, malnutrition and HIV infection co-exist . Therefore, a question that arises is whether there are any clinical differences that may raise a suspicion of HIV infection in cases of severe malnutrition?
In our study in Uganda, both the groups showed a high prevalence of multiple infections, including pneumonia, diarrhoea, bacteraemia, malaria, urinary tract infection and oral thrush. For respiratory, blood stream or urinary tract infections, no significant difference was observed with regard to the HIV status. The only two conditions that were over-represented among the HIV-positive children were persistent diarrhoea and oral thrush. In view of the remarkable difficulties encountered while clinically differentiating between malnutrition and HIV infection, we strongly support the establishment of routine counselling and testing for HIV-1 infection among paediatric patients with severe malnutrition in settings where HIV infection is an existing problem. In our study, we observed that there was a high acceptability of counselling and testing for HIV-1 infection; another reason for the absence of hesitation in organising routine counselling and testing for HIV-1 infection is that the study subjects were in the paediatric age group.
The drop-out cases in this study were mostly due to random factors, and we believe that these did not affect the selection of the study subjects in any systematic manner. In addition, the basic characteristics of the 315 of the 450 severely malnourished children analysed in this study were the same as those of the drop-out cases.
The median CD4+ cell counts and percentages observed in this study were compared to the recently reported median CD4+ counts and percentages of healthy Ugandan children younger than 5 years . Among the HIV-uninfected children without oedema, as many as one-third had signs of immunosuppression with a CD4+ percentage below 25%; this number was 1 in 12 in the HIV-uninfected children with oedema. Almost 80% of the HIV-positive children without oedema had signs of immunosuppression that was revealed as a CD4+ cell percentage below 25%. Approximately half the HIV-positive children with oedema had CD4+ counts below 25%. Very low CD4+ cell percentages consistent with a laboratory diagnosis of AIDS have rarely been described in HIV-uninfected children with or without mixed infections. Reports on the proportions of T cell and CD4+ cell percentages in severely malnourished children have shown inconsistent findings [3, 4, 19, 20]. The difference in the results may be influenced by the differences in study designs and sample size.
Alterations in the haematological functions in malnutrition have been documented . A recent study has reported cases of 5 malnourished children with mixed infection in whom the monocyte counts were higher than those in 4 malnourished children with only respiratory infection although their HIV status was not reported . Therefore, both granulocyte and lymphocyte suppression observed in this study is an indication of reduced haemopoietic function, and the additional burden of HIV-1 infection appears to further reduce this function.
The CD4+ cell percentages in this study were lower in children who presented with non-oedematous severe malnutrition, and this finding was consistent in both HIV-infected and uninfected groups. Earlier studies reported that oedematous malnutrition had lower T cell counts [19, 21], while others found no difference in the T cell count with regard to the type of malnutrition . The reason for these controversies is unclear. The only known fact is that severe malnutrition alters the immunological competence through a number of mechanisms, including apoptosis of the thymus gland [22, 23] and micronutrient deficiencies . Likewise, the rapid destruction of the CD4+ T lymphocytes by the HIV-1 virus has been well established. However, mechanisms leading to cellular immunological alterations in cases wherein severe malnutrition and HIV-1 virus infection co-exist are yet unclear.
It is interesting to notice that the HIV-positive children less often present with oedema, that is, oedema was present in just over 40% of the HIV-positive children, while it was seen in over 60% of the HIV-negative children. Severe wasting in the absence of oedema is a common feature observed in severe malnutrition with concurrent HIV infection [6, 11, 13–15]. The novel observation of this study was that the CD4+ percentages were lower in both HIV-positive and HIV-negative children without oedema than in children with oedema. Both the above-mentioned observations appear to imply that the development of oedema requires a certain degree of immunocompetence, which is an interesting clue to the pathophysiology of oedema in severe malnutrition.