OBJECTIVE: To assess usefulness of WHO clinical case definitions for diagnosis of AIDS in children in developing countries in developing countries.
METHODS: A prospective study was conducted in the department of Pediatrics at Maharaja Yashwant Rao Hospital, MGM Medical College, Indore .133 cases between 18months-12 yrs of age satisfying WHO case definitions of AIDS were included in study group. Informed consent was taken from the parents. A Biotest Anti HIV Tetra ELISA test detecting antibodies to both HIV1& HIV2 was applied in all cases to confirm the diagnosis of HIV infection. All observations were statistically analyzed
RESULTS: Our study detected 5.26%(7) of HIV prevalence in hospitalized children. 31 (23.3%)cases of total 133 cases manifested 3major signs. The sensitivity & specificity of 3 major signs of WHO criteria were 14.28% & 76.19% respectively. Cases showing 2major & 2 minor signs were 48 (36%). The sensitivity & specificity of 2 major& 2 minor signs of WHO criteria were 28.57% & 63.49% respectively. Cases manifesting 2major & 1 minor signs were 54(40.6%). The sensitivity & specificity of 2 major& 1 minor signs of WHO criteria were 57.14 & 60.31% respectively.
CONCULSION: Due to low sensitivity of detecting positive cases, the WHO Clinical Case Definition criteria for AIDS may not be appropriate in developing countries where signs included in WHO Clinical Case Definition criteria for AIDS are otherwise common due to other prevalent diseases. Thus multicentric studies are further required to modify these criteria in Indian set up.

KEY WORDS: Sensitivity, Specificity, WHO AIDS clinical case definitions

HIV infection is assuming alarming proportions in developing countries, especially in urban India. At present, India is in an exponential phase of the HIV epidemic. National AIDS Control Organization (1) reported 2.5% prevalence of HIV seropositivity in August 1999.Of the 35,20,179 persons screened, 88,604 were seropositive. Of the 8220 AIDS cases in India, 319(3.8%) were below 14 years of age. Currently ministry of Public Health & Family Welfare (2), Govt. of MP reported 1290 AIDS cases in November 2004, including 47 cases in 0-10 years age group. WHO (3) proposed a clinical case definition for diagnosis of AIDS in countries where diagnostic resources are limited .The definitions are believed to be sensitive but have not been formally evaluated. There may be differences in clinical features among different countries. Therefore, there is an urgent need to carefully evaluate clinical diagnostic criteria in different settings Moreover there is scarcity of data on the seroprevalence of HIV infections in hospitalized children. Hence this study was planned to determine the prevalence of HIV infection in hospitalized children and to assess the usefulness of WHO Clinical Case Definition criteria for diagnosis of AIDS in children in developing countries.

MATERIAL & METHOD: This prospective study was conducted at Maharaja Yashwant Rao Hospital & Chacha Nehru Bal Chikitsalaya, Avam Anusandhan Kendra lndore, in the department of pediatrics attached to Mahatma Gandhi Memorial College during July 2002-Sept 2003.The cases were selected from 18months –12yrs of age group. The selection of case was based on the WHO clinical criteria (2) for diagnoses for AIDS in children in developing countries. Table 1 presents WHO clinical case definition criteria for diagnosis of AIDS. We did not use confirmed maternal HIV infection criteria because of limitation of availability of laboratory tests in our set up. Inclusion criteria were presence of one of the followings (a) 3major (b) 2 major & 2minor (c) 2 major & 1minor criteria. We attempted to find sensitivity and specificity for 2 major and 2 minor signs. We also evaluated 3 major & 2major and 1 minor criteria to know the suitability for the diagnosis of AIDS. All cases who received any kind of parenteral injection or infusion were excluded from the study. After written consent from parents, the children were subjected to detailed history, physical relevant investigation and HIV screening. Both the parents were questioned separately in the vernacular and any discrepancy led to combined questioning. Those who had not heard of AIDS were regarded as unaware of HIV. Separated serum (from 4 ml of the venous blood) was stored at 2o-8o C. Samples were tested for HIV 1and HIV 2 antibodies by Biotest Anti HIV Tetra ELISA test. If tested negative, the child was labeled as HIV negative and if tested positive then it was confirmed by a second ELISA using a different kit. If the first EISA was equivocal then a second ELISA was performed. If his ELISA was equivocal, then the child was labeled as HIV negative

Presence of 2 major and 2 minor signs in the absence of other known cause of immunosuppression is diagnostic of AIDS
MAJOR:
1 Weight loss or abnormally slow growth
2 Chronic diarrhea > 1 month
3 Prolonged fever > 1 month
MINOR:
1 Generalized lymphadenopathy
2 Oropharyngeal candiadiasis
3 Recurrent common bacterial infections
4 Generalized dermatitis
5 Persistent cough > 1 month
6 Confirmed maternal HIV infection

Of the133 children screened, only 7 children were seropositive. The majority of these children belonged to 19 months to 5 years age group with male to female ratio of 2.5:1.Parents of all 7 HIV positive cases belonged to lower socioeconomic status, and none of their parents were aware of HIV. Fathers of all 7 cases were involved in high-risk occupation or behavior .Out of the 133 cases, 31(23.3%) cases had 3 major criteria, 48(36%)) cases had 2 major and 2 minor criteria and 54(40.6%)) cases had 2 major and 1 minor criteria. Tuberculosis was confirmed in 60 cases out of which 17(12.7%) cases had pulmonary tuberculosis, 13(9.41%) cases had disseminated tuberculosis, 30(22.5%) cases had tuberculosis meningitis and 41(68.3%) gave history of contact with Tuberculosis. All 133 cases were malnourished, of which 19(17.2%), 22(16.5%), 49(36.8%), and 43(32.3%) cases belonged to Protein Energy Malnutrition grade I, II, III, & IV respectively. (Based on Indian Academy of Pediatrics classification of Malnutrition).

Legend:

1 Loss of weight

2 Chronic diarrhea >1 months

3 Chronic Pyrexia >1 months

4 Repeated common infection

5 Generalized lymphadenopathy

6 Oral Candidiasis

7 Persistent cough>1 months

National AIDS Control Organization (1) reported 2.5 % prevalence in the general population .In our study we find incidence of 5.26% in hospitalized children. While a study by Agarwal M et al (4) reported prevalence of 15% in clinically suspected hospitalized children from Mumbai. In our study, all the mothers of 7 HIV seropositive cases were HIV positive and 5 cases had their fathers positive for HIV and one father died of some unknown cause. None of our 7 HIV positive cases received any kind of parenteral infusions and injections in the past. Hence the most probable route of transmission was vertical. Several studies have demonstrated that the rate of mother to child transmission of HIV ranges from 15 to 40%(5,6,7).

The major WHO clinical criteria of failure to thrive, fever>1month, diarrhea>1 month are widely prevalent due to endemic diseases. Tuberculosis and malnutrition that are rampant in India can also produce similar clinical findings. If the presence of WHO clinical criteria are diagnostic of AIDS our data should have revealed higher rates of seropositivity. But in our study only 7cases, out of 133 cases that came under WHO AIDS case definition criteria were HIV seropositive. A report from Mumbai by Daga (8) showed that out of 28 confirmed cases of HIV, only 6 fulfilled WHO criteria.

There are conflicting reports regarding sensitivity and specificity of WHO criteria. Even in Africa with 30% seroprevalence, Nikole et al (9) reported a sensitivity of 37-40% and specificity between 26-59% while in another recent study from Bloemfontein South Africa (10) reported a sensitivity of 14.5% and specificity of 98.6%. They proposed a new clinical case definition based on criteria marasmus, hepatosplenomegaly, oropharyngeal candiadiasis & generalized lymphadenopathy with a sensitivity of 63.2% and specificity of 96%. In Our study, the sensitivity & specificity of 3 major signs of WHO AIDS criteria were 14.28% & 76.19% respectively. The sensitivity & specificity of 2 major & 2 minor signs of WHO AIDS case definition criteria were 28.57% & 63.49% respectively. The sensitivity & specificity of 2 major& 1 minor signs of WHO AIDS case definition criteria were 57.14 & 60.31% respectively.

Due to low sensitivity of detecting positive cases, The WHO AIDS clinical case definition criteria may not be appropriate in developing countries where signs included in WHO AIDS clinical case definition criteria are otherwise common due to other prevalent diseases. Multicentric studies are required to evaluate the effectiveness and to suggest modifications in these criteria so as to increase their sensitivity in the diagnosis of AIDS.

1. WHO AIDS clinical case criteria has low sensitivity & low specificity in developing countries
          2. Vertical transmission route is major route for acquiring HIV in pediatric age group.
          3. Antenatal HIV screening of mothers should be done to prevent vertical transmission.

1. National AIDS Control Organization. Ministry of Health and Family Welfare, Government of India. Surveillance for HIV infection/AIDS Cases in India (Period of report since inception, i.e. 1986 to 31st August 1999), 1999.
   
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3. World Health Organization. Acquired Immunodeficiency Syndrome (AIDS). WHO/CDC case definition for AIDS. Wkly Epid Rec 1986; 61: 69-76
   
4. Agarwal M, Koppikar GV, Ghildiyal R, Charvakar M, Joshi SM, Lahiri KR. Seropositivity rate for HIV infection in hospitalized children on selective screening. Indian Pediatr 2001; 38: 267-271.
   
5. Oxtoby MJ. Vertically acquired HIV infection in the United States. In: Pediatric AIDS: The Challenge of HIV Infection in Infants, Children, and Adolescents, 2nd edn. Eds. Pizzo PA, Wilfert CM, Baltimore, Williams and Wilkins, 1994; pp 3-20.
   
6. Mofenson L. Epidemiology and determinants of vertical HIV transmission. Semin Pediatr Infect Dis 1994; 5: 252-265.
   
7. Mofenson LM, Volinsky SM. Current insight regarding vertical transmission. In: Pediatric AIDS: The Challenge of HIV Infection in Infants, Children, and Adolescents, 2nd edn. Eds. Pizzo PA, Wilfert CM, Baltimore, Williams and Wilkins, 1994; pp 179-203
   
8. Daga SR, Verma B, Gosavi DV. HIV infection in children. Indian Pediatr 1999; 36: 1250-1253
   
9. Nicole A, Timaeus 1, Kigadye RN, Walraven G, Killewo J. The impact of HIV 1 infection on mortality in children under 5 years of age in sub-Saharan Africa: A demographic and epidemiological analysis. AIDS 1994, 8: 995-1005
   
10. Christine L.van Gend, Maaike L.Haadsma, Pieter J.J. Sauer, and Cornelius J. Schoeman.Evaluation of the WHO Clinical Case Definition for Pediatric HIV infection in Bloemfontein, South Africa.journal of tropical Pediatrics June2003; 49:143-147
    

Last Updated on 01-11-2005

Preeti Raikwar, S. Thora, Liladhar Kashyap. TO ASSESS USEFULNESS OF WHO CLINICAL CASE DEFINITIONS FOR DIAGNOSIS OF AIDS IN CHILDREN IN DEVELOPING COUNTRIES . Pediatric Oncall [serial online] 2005 [cited 2005 October 1];2. Available from:
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