Academic journal article Bulletin of the World Health Organization

Presumptive Diagnosis of Severe HIV Infection to Determine the Need for Antiretroviral Therapy in Children Less Than 18 Months of age/Diagnostic Presomptif D'une Infection Grave Par le VIH Pour Determiner le Besoin D'une Therapie Antiretrovirale Chez Les Enfants De Moins De 18 mois/Diagnostico Provisional De la Infeccion Grave Por El VIH Para Determinar la Necesidad del Tratamiento

Academic journal article Bulletin of the World Health Organization

Presumptive Diagnosis of Severe HIV Infection to Determine the Need for Antiretroviral Therapy in Children Less Than 18 Months of age/Diagnostic Presomptif D'une Infection Grave Par le VIH Pour Determiner le Besoin D'une Therapie Antiretrovirale Chez Les Enfants De Moins De 18 mois/Diagnostico Provisional De la Infeccion Grave Por El VIH Para Determinar la Necesidad del Tratamiento

Article excerpt

Introduction

Important strides have been made in recent years in the prevention of mother-to-child transmission (PMTCT) of the human immunodeficiency virus (HIV). Donor investment in PMTCT programmes has been substantial and governments have made a commitment to roll out the programmes. Yet despite these advances, in developing countries approximately 15% of all new cases of HIV infection are diagnosed in children. (1) Between one half and two thirds of the children who become infected with HIV will die before their second birthday: unless they are diagnosed and placed on antiretroviral therapy (ART). (3) In sub-Saharan Africa, only around 15% of HIV-exposed infants are tested for HIV in the first two months of life, and the majority of infected children less than 2 years of age die without having their HIV status definitively confirmed through virologic tests. (4,5)

The World Health Organization (WHO) recommends giving ART to all infants less than 24 months of age with a confirmed diagnosis of HIV infection (i.e. with positive virologic tests results), even if they have no symptoms. (4) Antibody tests cannot provide the definitive diagnosis of HIV infection in very young children because maternal IgG antibodies cross the placenta into the fetal circulation during pregnancy and remain detectable for up to 18 months after birth. (6) Thus, a virologic method, typically nucleic acid testing to detect viral desoxyribonucleic acid (DNA) or ribonucleic acid (RNA), is required. Such tests are much more complex and costly than more common HIV laboratory assays and have proven difficult to implement in national treatment programmes worldwide. (7-10)

In resource-constrained settings, lack of access to virologic tests leads to reliance on the presumptive diagnosis of HIV infection for case management. In fact, in its revised 2010 guidelines WHO recommends initiating ART in all children less than 18 months of age with a presumptive clinical diagnosis of severe HIV disease, established on the basis of a defined set of clinical symptoms in infants with antibodies against HIV. (4) Historically, however, health-care providers have been reluctant to treat children with a presumptive diagnosis due to various concerns, including but not limited to: initiating HIV negative infants on potentially toxic antiretrovirals, stigma for infants with unclear HIV status, or physician comfort with moderately predictive diagnostic tools. Clinical screening parameters alone, without antibody testing, have demonstrated low sensitivity (20-23%), although their specificity is reasonably high (92-94%). (11-15) Thus, efforts to improve the management of children with a presumptive diagnosis of severe HIV disease have focused on two goals: (i) identifying a set of clinical criteria with high enough sensitivity to detect severe HIV disease so that more affected children receive ART, and (ii) identifying HIV-positive children at high risk of death (15) and in need of ART without delay.

In our model we have used a set of modified clinical criteria developed by Iliff et al. to define severe HIV disease. The criteria include the following: pneumonia, current diarrhoea, ear discharge, very low weight, generalized lymphadenopathy, oral thrush, and tuberculosis in either the infant or in a sibling or parent of the infant. These criteria, based on the results of a clinical trial of approximately 14 000 infants in Zimbabwe, have shown a sensitivity and specificity ranging from 19.8% to 67.7% and from 94.0% to 90.4%, respectively, depending on the child's age. They are "modified" in the sense that they resemble WHO's criteria for the Integrated Management of Childhood Illness15 but exclude persistent diarrhoea (> 14 days) and parotid swelling and include underweight (i.e. weight below the median for age). By adding underweight to the algorithm, Iliff et al. achieved a sensitivity of 65% at 6 weeks, 79% at 6 months and 86% at 12 months, respectively. …

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