Infants suffering from at least two of the following symptoms - oral thrush, swollen lymph nodes, nappy rash, weight in the bottom ten per cent of all children, enlarged liver or spleen, or gastric reflux – are more likely to be suffering advanced HIV disease, according to a review of clinical symptoms in a South African study of children with confirmed HIV infection designed to help doctors spot children in need of immediate treatment where HIV DNA testing and CD4 counting is not readily available.
The findings were presented by Heather Jaspan of the Faculty of Health Sciences, University of Stellenbosch, South Africa, last week at the Fifteenth Conference on Retroviruses and Opportunistic Infections in Boston.
HIV infection is difficult to diagnose in infants because they can carry their mothers’ antibodies to HIV until they are 18 months old. A direct test for HIV’s genetic material, the HIV-DNA test, must be carried out using specialised laboratory equipment that is not available in many resource-limited settings.
Distinguishing a set of symptoms that reliably predict the presence of advanced HIV infection could help health care workers identify infants in urgent need of testing and treatment.
The CHER study compared immediate versus deferred treatment in infants under the age on one year with a CD4 percentage above 25%. To gain a clinical picture of the course of HIV infection in the first ten weeks of life, researchers in Cape Town and Soweto enrolled nearly 900 infants, ranging in age from 28 to 78 days (median 44 days), into a randomised study.
Observational data from the study were subsequently used by Heather Jaspan and colleagues to test the predictive value of a variety of symptoms of immunodeficiency seen in infants for an immunological state that would warrant immediate antiretroviral treatment (a CD4 percentage below 25%).
The infants in the CHER study (n=540) were compared with exposed but uninfected (125) and unexposed and uninfected infants (125) recruited in other studies in Soweto and Cape Town in order to test the sensitivity and specificity of the indicator conditions for HIV-related immunodeficiency.
Firstly, the researchers looked at the frequency of symptoms according to HIV status (diagnosed by HIV-DNA PCR).
Four symptoms were found to be significantly more common in children with HIV: oral thrush, lymphadenopathy, hepatomegaly and a body weight in the bottom 10% for children in the study (all p
Anaemia, neutropenia, gastroenteritis and gastric reflux (GERD, defined as excessive vomiting, cough and airway obstruction after feeds) were also significantly associated (p
The investigators then analysed the relative risk for each symptom in HIV-infected children by multivariate analysis in which they controlled for age.
Weight in the lowest tenth percentile (RR 3.3), oral thrush (RR 5.6), lymphadenopathy (RR 8.9) and nappy rash (RR2.4) remained strongly predictive, and a sensitivity analysis that also included GERD, splenomegaly and hepatomegaly showed that if any two or three of these symptoms was present, they were 100% specific as predictors of HIV-related immunodeficiency.
This means that the absence of the symptoms is a highly reliable indicator that a child can be expected to test negative for HIV. However, the use of multiple symptoms had much lower sensitivity than the presence of a single symptom from the list above. If only one symptom was present the sensitivity was around 50% - indicating that up to half the infants with the identified symptom would turn out not to have HIV infection
The researchers say that the algorithm will need to be validated in different populations before it can be used more widely, and that many HIV-infected infants will still be missed even if an algorithm can be validated. However Heather
Jaspan noted that in the population studied, the algorithm developed performed as well in infants as the the symptoms used in WHO’s clinical algorithm for presumptive diagnosis of HIV disease in older children.
Jaspan H et al. Clinical and immunological characteristics of very young infants with HIV infection: Children with HIV Early Antiretroviral Study. Fifteenth Conference on Retroviruses and Opportunistic Infections, Boston, abstract 76, 2008.