Indian Pediatrics 2002; 39: 57-63  

Clinical Manifestations of HIV-1 Infection

From the Departments of Child Health and Clinical Virology*, Christian Medical College Hospital, Vellore 632 004, India.

Correspondence to: Dr. Thomas Cherian, Department of Child Health, Christian Medical College Hospital, Vellore 632 004, India.

E-mail: [email protected]

Manuscript received: June 26, 2000;

Initial review completed: July 27, 2000;

Revision accepted: June 14, 2001.

The global pandemic of acquired immunodeficiency syndrome (AIDS) has already claimed an estimated five million lives(1). Pediatric AIDS threatens much of the progress made in child survival in developing countries over the past ten to fifteen years. The earliest reports of AIDS in Indian children have come from multi-transfused thalassemic children(2). More recent reports have described the clinical manifestations in children with perinatally acquired infection(3,4). This report describes the mode of transmission, clinical manifestations and outcome of HIV/AIDS among children diagnosed at our hospital, to add to the emerging description of clinical manifestation of HIV infection among children in India.

The clinical case records of children diagnosed to have HIV infection at our hospital from January 1988 to March 2001 were reviewed. All children had a detailed history and clinical examination performed at the first visit. Serological testing was performed in 45 children because of symptoms suggestive of HIV infection, in 35 children because their parents had positive HIV ELISA tests, and in 8 children as part of preoperative screening. HIV infection was defined using the revised surveillance case definition for HIV infection(5), and children were classified into clinical categories using the revised CDC classification of 1994(6). Children younger than 18 months were considered HIV-infected if they tested posi-tive on HIV RNA-PCR assay, or, in addition to positive serology (repeatedly reactive ELISA and confirmatory Western Blot), they had increased serum immunoglobulins, depressed CD4 lymphocyte count and mani-fested evidence of symptomatic HIV infec-tion (AIDS-indicator conditions diagnosed definitively or presumptively, or recurrent bacterial infections) that met criteria included in the 1987 pediatric AIDS surveillance case definition(7).

Serological diagnosis of HIV infection was made on repeatedly reactive ELISA testing (UBI HIV 1/2 EIA, Beijing United Biomedical Ltd., China; DETECT HIV, Biochem Immunosystems Inc., Canada; ABBOTT EIA PLUS, Abbott, USA) and confirmed by Western blot (HIV Blot 2.2 Gene Labs, Singapore; IMMUNOBLOT INNOLIA, Immunogenetics, Belgium). HIV RNA testing was done using an RT-PCR assay (Amplicor HIV 1 Monitor Test Version 1.5, Roche Diagnostics, NJ, U.S.A.). CD4 lymphocyte subset testing was done using a flowcytometer (Becton Dickinson Facscan, USA) or using an ELISA test (Capcellia CD4/8, Sanofi Diagnostics Pasteur, France). Addtional investigations were done as clinically indicated.

Microbiological confirmation of diag-nosis of tuberculosis and Pneumocystis carinii pneumonia (PCP) was not always possible. In such cases guidelines from the 1987 CDC surveillance case definition were used. PCP was diagnosed based on findings of persistent cough and/or tachypnea with minimal findings on auscultation, hypoxemia on pulse oximetry or arterial blood gas monitoring, elevated serum lactate dehydrogenase (LDH), presence of diffuse infiltrates on the chest radiograph and response to co-trimoxazole(7,8); in one child who failed to respond to co-trimoxazole, diagnosis was confirmed by post-morterm lung biopsy. Lymphoid interstitial pneumonia (LIP) was diagnosed on the basis of chronic cough and presence of reticulonodular opacities on the chest radiograph, with or without hilar lymphadenopathy, persisting for more than 2 months and unresponsive to antimicrobial or antituberculous therapy(7). Esophageal candidiasis was diagnosed in the presence of recent onset of retrosternal pain on swallowing and oral candidiasis(7) and resolution of symptoms with fluconazole therapy; diagnosis was confirmed with a barium swallow in one of the 4 patients. Tuberculosis was diagnosed on the basis of chronic cough and fever, failure to thrive and weight loss, persistent radiographic findings despite adequate antibiotic therapy; and clinical and radiological improvement with antituberculous therapy(9). Encephalopathy was diagnosed using CDC criteria(6).

Only 7 children were started on anti-retroviral therapy owing to cost constraints. Coexisting infections were treated using appropriate antimicrobial drugs. All severely immunosuppressed children and, after 1995, all HIV-exposed infants aged 6 weeks to 12 months received prophylaxis against Pneumocystis carinii (10). Data from the questionnaires and clinical case records was entered and analyzed using the software SPSS for Windows (Version 7.5).

Eighty-eight children, 50 boys and 38 girls, were included in the study. Seventy-seven (87%) of the 88 had acquired infection by perinatal transmission. Nine children (10%) acquired infection following blood transfusion. Three children with thalassemia, one with Fanconi anemia and one with classical hemophilia developed infection following multiple blood transfusions that started between 1986 to 1993; of these, one child acquired the infection as late as 1998. Three children were transfused with their fathers’ blood in the neonatal period in 1989, 1990 and 1994, respectively; the fathers were later found to be HIV positive and the mothers HIV negative. The ninth child was transfused with an unrelated donor’s blood in 1994 following a road traffic accident; both parents were HIV negative. In two children the mode of transmission could not be ascertained. In a 15 month old child infection was proved by HIV RNA testing but both parents were negative on repeated testing using both ELISA and Western Blot and there was no definite history of blood or blood product transfusion. In another 10-year-old asympto-matic girl whose mother was HIV negative sexual abuse was considered. Her father had died a year previously reportedly with tuberculosis and genital ulcers.

The median duration of follow up was 8 months (range 1 to 156 months). Twenty-seven children are still on regular follow up. Ten children died, and 51 children were lost to follow up at varying periods following diagnosis of HIV infection.

Twelve children were asymptomatic (category N). Seventy-six children were symptomatic, with 18 children in category A, 27 in category B and 31 in category C. The age at onset of symptoms ranged from 1 month to 10 years. Thirty six of the 76 (47%) became symptomatic before 12 months of age; all but 3 were infected perinatally. The remaining 40 became symptomatic at 20 to 120 months of age; 35 were infected perinatally.

Table I enumerates the various clinical manifestations seen in these children. Organisms isolated from pus culture from abscesses and suppurative foci were Group A beta-hemolytic streptococci, enterococci, coagulase-negative staphylococci and Staphylococcus aureus, and from ear pus in children with recurrent otitis media were Pseudomonas aeruginosa, E. coli and Proteus mirabilis.

Of the 23 children with recurrent diarrhea, enteric pathogens were isolated in only five (Salmonella typhimurium, enteropathogenic E.coli, Vibrio cholerae (2 children) and Shigella sonnei). The organisms isolated in blood culture from the six children with documented septicemia were Staphylococcus aureus (2 children), coagulase-negative staphylococci, Enterococcus faecalis (2 children), Salmonella typhimurium, and Pseudomonas aeruginosa. In all three children with meningitis no organisms were isolated on CSF culture, and antigen detection for H. influenzae type b, pneumococcus and cryptococcus were negative.

All 12 children diagnosed to have tuberculosis (11 pulmonary and 1 miliary) had parents with pulmonary tuberculosis. The Mantoux test was positive (10 × 10 mm) in only two; induration was less than 5 mm in the remaining children. Acid fast bacilli (AFB) were seen in smear and isolated in culture from fasting gastric juice in only 4 children though at least three specimens were collected from each child with suspected tuberculosis. Radiographic findings in the 11 children with pulmonary tuberculosis revealed only a right hilar node in 1 child, diffuse infiltrates in 4 children, and segmental or lobar lesions in 6 (of whom 2 had pleural effusions and 2 had hilar adenopathy in addition). Of the 12 children, 3 have completed therapy, 4 are still on treatment and regular follow up and are responding, 4 children were lost to follow up and one child died due to fulminant hepatitis 2 weeks after initiating anti-tuberculous therapy.

Table I– Frequency of Clinical Manifestations of HIV Infection

Six children were presumptively diagnosed to have PCP; CD4 counts done in 4 of these children showed evidence of severe immunosuppression in 3. All six had oral candidiasis. Two died in hospital; one was 4½ months old and the other 2½ years old; post-mortem lung biopsy done in one showed presence of P. carinii cysts in the alveolar spaces.

Of the 21 children with evidence of encephalopathy by CDC criteria, 11 had progressive encephalopathy, with regression of milestones, spasticity and hyperreflexia; one had dysarthric speech, two had ataxia, two had hemiplegia and two had well-controlled seizures in addition. We were able to obtain CT scans in only two children; both showed evidence of cortical atrophy and one child had basal ganglia calcifications in addition.

Ten children died. Six of the ten were younger than 12 months, and the oldest was 50 months old at death. Documented (by post-mortem biopsy) causes of death in 4 of the 6 children who died in hospital were Pneumocystis carinii pneumonia in one, cytomegaloviral (CMV) pneumonia in one, dilated cardiomyopathy in one, and fulminant hepatitis in one. The fifth child died in hospital following an attack of cholera with persistent acidosis and hypokalemia, and in the sixth a clinical diagnosis of PCP was made, but we were unable to confirm the diagnosis as the parents refused permission for post-mortem lung biopsy. Four children died at home; one had acute watery diarrhea, two died of bronchopneumonia that did not respond to oral antibiotics, and the fourth died at home with severe progressive ence-phalopathy.

Though our data show that the mode of acquisition and clinical manifestations of pediatric HIV/AIDS in India are not substantially different from that reported in other countries, there are several important aspects of the disease that we would like to highlight.

Transfusion-associated transmission of HIV continues to occur in India despite regulations requiring screening of donors, either because screening procedures are not being followed or because transmission may occur despite screening. The former is likely in the case of the children infected from transfusions from their fathers. Many small hospitals without access to blood banks may transfuse patients with blood from a close relative without screening in the mistaken belief that the blood would be safe. Our data shows that this is not necessarily true and that unscreened blood must not be used, irrespective of the donor.

Our data also shows that a bimodal progression occurs in Indian children, as described in other countries(11). A significant proportion of patients present in infancy and have severe disease and early death, while children surviving beyond 5 years of age tend to have only moderate signs and symptoms and have longer survival.

The common clinical manifestations of HIV infection such as hepatomegaly, generalized lymphadenopathy and spleno-megaly, and skin infections, recurrent diarrhea, and failure to thrive are the same as in studies of HIV-infected children in both Western(12) and tropical countries(13), and in recent reports from India(3,4). Papular urticaria, thought to be due to a hyper-sensitivity reaction to environmental factors or allergens such as insect saliva or mosquito bites, was commonly seen in our patients. This condition has been described as one of the initial manifestations of HIV infection in Haitian adults and children(13,14).

Respiratory infections were a common problem in our series. Microbiological confirmation of tuberculosis and Pneumo-cystis carinii penumonia was not always possible, and diagnosis was often pres-umptive, based on clinical criteria and response to therapy. As in other studies from India and other tropical countries(4,13), bacterial pneumonia occurred more fre-quently than PCP and LIP. This may reflect the greater importance of bacterial infections in tropical countries as well as limited diagnostic options for the diagnosis of PCP and LIP. A recent Indian study has shown a 4% incidence of PCP when confirmed with bronchoalveolar lavage(4). In India, where definitive diagnosis using bronchoalveolar lavage or lung biopsy are seldom feasible, using presumptive criteria for early diagnosis of Pneumocystis carinii pneumonia and PCP prophylaxis in infants of HIV-positive mother may prevent one of the major causes of death in infancy.

Our experience is similar to other studies showing that HIV-infected children with tuberculosis often have a negative tuberculin test(3,15), the proportion of children with positive smears or cultures is low(16), and that clinical and radiological features do not differ from children without HIV infection.

The high incidence of encephalopathy in this series of children is comparable to other studies in both developed(17) and developing countries(4,18), and highlights the need for developmental and neurological assessment of the HIV-infected child at each visit.

Among the 10 children who died, the predominant causes of death were respiratory. Since a proportion of these could be due to PCP, prophylaxis for all HIV-exposed infants from 6 weeks to 12 months of age may be important in reducing mortality.

Contributors: VPV and TC designed the study, enrolled the patients, carried out follow up, analyzed the data and prepared the manuscript. AJC helped with patient enrolment and follow up. PGB performed the serology. TJJ, CK and PR assisted in patient enrollment, data analysis and manuscript preparation.

Funding: None.

Competing interests: None stated.

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