Compiled by S K Kabra, Rakesh Lodha
Department of Pediatrics, All India Institute of Medical Sciences, New Delhi
for Pediatric HIV/AIDS, First National Conference (Held on 3^rd & 4^th November, 2001 at Delhi)

A syndrome of immune deficiency with opportunistic infections was first described in 1982 and the first publication of HIV/AIDS in children appeared in 1983. At end of 1999, it is estimated a total of 34.3 million individuals were infected globally, of which 1.3 million (3.8%) were children below 15 years of age¹. Ninety five percent of the infected individuals are staying in the developing countries. Of the 2.8 million deaths due to HIV by 1999, 0.5 million (18%) occurred in children below 15 years¹. Disproportionately higher mortality in children suggests a more aggressive course in children. The estimated numbers of people living with HIV/AIDS in India by end of 1999 were 3.7 million of which 0.16 million (4.3%) were children below 15 years¹. Based on the available data, we estimate that in India, 40,000 children may acquire infection through perinatal route annually. At the All India Institute of Medical Sciences, New Delhi, we have observed increasing trend in the number of children with HIV. The number of children diagnosed to have HIV infection has increased from 2 patients in 1996 to 20 patients in 2000.

Most of the infections in children are vertically transmitted i.e. acquired from mothers. Reports from India and African countries also suggest that vertical transmission remains commonest route^2-5. Blood and blood products, however, remain an important source and are responsible for infection in 10 - 30 % of total cases^3-5. Some of the mothers also acquire HIV through blood transfusion and transmit the infection to their babies⁴.

The rates of transmission of HIV infection from infected mother to child vary from 14% in Europe to 45% in Sub-Saharan Africa^6,7. Factors considered to be associated with higher chances of mother to child transmission (MTCT) include high maternal viral load, low CD 4 cell count in mother, maternal p24 antigenemia, prolonged rupture of membranes (PROM), premature delivery <37 weeks, chorioamnionitis, non-receipt of zidovudine, and non-receipt of caesarian - section before onset of labor⁸. The factors associated with decreased rate of vertical transmission of infections include: presence of high affinity anti gp120 antibodies, high affinity principle neutralizing domain (PND) antibodies, and delivery by caesarian section⁸.

The transmission of infection may occur during intra-uterine period, during delivery, or postnatally. Of these, intrapartum transmission is the most important contributor. The transmission of infection takes place at the time of delivery by mixing of maternal and fetal blood and exposure of fetus to infected maternal blood and cervical secretions during passage through birth canal. Postnatally, the infection may be transmitted through breast-milk. Breastfeeding by an HIV infected mother adds an additional risk of about 14% over and above the usual risk of vertical transmission⁹. Early breast milk, which is more cellular, has a higher risk of transmitting the infection. Presence of secretary IgM in milk is associated with lower rate of transmission¹⁰. It has been observed that mixed feeding (Breastfeeding + top feeding) may further increase risk of transmission¹¹. This may be due to change in gut permeability thereby increasing the risk of passage of the virus across the gut mucosa.

Blood donor screening has made transfusion - transmitted HIV infection a rare event in the developed countries. With appropriate screening, the risk is 1 infection/ 4-6 lakh units transfused¹². Most infections result from blood collection during donor's 'seronegative window'¹³. All blood components carry same risk. Most recipients (90 - 95%) of HIV- positive unit of blood/blood product will develop HIV-infection¹⁴.

Clinical AIDS Definition

Since majority of HIV infection are acquired vertically, the best method for identification of HIV infection would be to screen all mothers and suspect HIV in babies born to HIV positive mothers. Since screening of mothers for HIV is not done universally and some patients get HIV infection through transfusion of blood and blood products, we may see children with clinical manifestations of HIV in majority.

Because of the limited availability of HIV diagnostic testing, attempts have been made to formulate clinical AIDS definitions for adult and children in developing countries. Use of the Centers for Disease Controls and Prevention (CDC) guidelines for clinical classification of HIV infection in children is problematic because they were designed to measure HIV disease progression, not for the identification of children infected with HIV¹⁵. In addition, many category C (or AIDS) diagnoses are beyond the diagnosis capabilities of most of the developing world. Several simple clinical case definitions pertinent to the developing world have been devised and tested, including the WHO clinical case definition (Table I)¹⁶. These definitions detect the presence of symptomatic AIDS and not HIV infection itself and are confounded by prevalent condition such as malnutrition, diarrhoeal disease and tuberculosis. Evaluation of the WHO clinical case definition in hospitalized children in Zaire¹⁷, Rwanda¹⁸, the Ivory Coast¹⁹, and Uganda²⁰ found high specificity rates but low sensitivity rates and low positive predictive values. Lambert et al²¹ found no features that distinguished HIV-negative children from HIV-seropositive children who met the WHO case definition. However, children infected with HIV had poor responses to standard therapy for malnutrition, dehydration, infection, and tuberculosis. Subsequent modification were made in an attempt to increase the usefulness of the definitions. Because of the frequency of respiratory disease in children infected with HIV, a modified WHO clinical case definition was formulated that includes severe or repeated pneumonia as a major criterion and eliminates persistent cough as a minor criterion (Table I)^22,23. In Rwanda¹⁸, use of a sample consisting of only respiratory distress sec ondary to lower respiratory tract infection and generalized lymphadenopathy improved sensitivity, specificity, and positive predictive value. Jean et al²³ evaluated an alternative definition in Haiti that included recurrent or chromic diarrhea and generalized lymphadenopathy as major criteria and failure to thrive, prurigo, candidiasis, tuberculosis, pneumonia and fine hair as minor criteria. The best predictors of HIV infection were generalized lymphadenopathy or prurigo or a combination of recurrent/chronic diarrhea and pneumonia, with a sensitivity of 78 % and specificity of 98%.

There are no published studies in literature to test the sensitivity and specificity of WHO's modified criteria in Indian patients. The reported sensitivity of individual factors including weight loss or failure to thrive is 45-100%, Chronic diarrhea (>1 mo) 15-45%, and severe or repeated pneumonia 8-86%. For minor criteria such as generalized lymphadenopathy is 23-41% and for oro-pharyngeal candidiasis 14-48%. The wide variation in sensitivity is due to different clinical settings. The published studies do not mention about the sensitivity of two major signs associated with at least two minor signs. Risk factors reported from India other than those included in WHO case definition are blood transfusion⁴, disseminated tuberculosis and chronic diarrhoea²⁴. Due to lack od data about the specificity of these risk factors, it is difficult to advice about screening of all these patient for HIV.

To conclude the clinical features suggesting HIV infection includes weight loss or failure to thrive, chronic diarrhea (>1 mo), prolonged fever (> 1 mo), severe or repeated pneumonia, generalized lymphadenopathy, oro-pharyngeal candidiasis, repeated common infections, generalized dermatitis, history of blood transfusion, extrapulmonary tuberculosis and confirmed maternal HIV infection. The sensitivity of these criteria is high but specificity is low. There is need to test these criteria in Indian setting.

References

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