Section 3 -

AIDS In Children Cecilia Ridaura Sanz

Children were latecomers in the global awareness of the disease. The western world first perceived AIDS as a disease of a particular group of male adults with specific risk factors. The spread of the disease from the original at risk group to a more diversified population brought the problem of pediatric AIDS to the forefront. AIDS IN CHILDREN AS DIFFERENT FROM AIDS IN ADULTS Children acquire AIDS in their own particular way. What is in adults a disease transmitted by sexual contact or anomalous intravenous entry and as we later understood, with transfused blood, becomes in children an infection usually contracted through maternal intermediation. Regardless of the mode of infection in the mother, the child can become infected in utero, at the moment of birth or during lactation. The same microorganism, through different pathogenic mechanisms and in a different host, produces different biologic, clinical and pathological components of the disease. This produces a different disease. The following table illustrates differences in the pathological expression: CHILDREN ADULTS Thymic involution No HIV encephalitis Infrequent Lymphoid interstitial pneumonia Lymphoma Smooth muscle tumors Kaposi Arteriopathy Seldom Progressive encephalopathy Seldom Growth arrest Wasting syndrome Hyperglobulinemia Lymphopenia Bacterial infections Opportunistic infections. Tuberculosis infrequent Tuberculosis frequent Differences also arise in the infectious complications. Published reports from several sources including series from Latin America and from Africa underscore a low frequency of tuberculosis, acknowledgly frequent in adults. Children infected perinatally with HIV have a higher frequency of encephalopathy during the first year of life whereas the frequency after the age of three years is similar to that in the adult. It has been proposed that this early encephalopathy in infants has a different pathogenic mechanism from that occurring in late survivors. THE ROLE OF THE AUTOPSY The autopsy offers a perspective on the causes and circumstances of mortality of a disease, reveals associated pathology that could not be supported clinically and is able to formulate questions and answers that were not possible in the living patient. In the case of the Human Immunodeficiency virus (HIV) and its clinical expression as Acquired Immunodeficiency Syndrome (AIDS), an important component of mortality is infection, often by opportunistic microorganisms present in the environment and which usually do not give rise to disease in the immunologically intact population. A reasonable assumption would be that a patient with a compromised immune system will become infected with germs present in his particular surroundings and therefore information obtained from a particular geographic and ecologic context are not necessarily applicable to a different context. It is therefore imperative to document carefully the prevailing infections in AIDS patients in each site. Populations at risk vary in different geographical contexts by virtue of particular social en economic determinants. The examination of a subset of pediatric patients with HIV/AIDS that die and undergo autopsy can provide information that becomes a reference point for the evaluation and management of the diseased population and in the definition of the local biology of the disease. It must be emphasized that opportunistic infections were first described at autopsy and even at present these complications are clinically under diagnosed in as much as 50% as compared with autopsy findings. The autopsy continues to describe new pathological states such as HIV infection related pulmonary emphysema and provides accurate correlation and reference for new imaging studies. The autopsy also monitors the impact of therapy with highly active antiretroviral therapy (HAART). As a result of longer survival of patients with AIDS and their exposure to different treatment regimens, new pathologic expressions of the disease have been described. Early autopsy studies demonstrated the high prevalence of HIV encephalitis and of opportunistic central nervous system infections. After the introduction of nucleoside reverse transcriptase inhibitors, the prevalence of opportunistic infections decreased but a concurrent increase in HIV encephalitis was noted. With the subsequent introduction of protease inhibitors a decline in both was observed. Or more recent emergence are descriptions of severe forms of encephalitic disease with massive infiltration of HIV infected cells and with white matter destruction that are currently attributed the interaction of the infection with the drugs used in therapy. THE PATHOLOGY OF AIDS IN CHILDREN. THE LITERATURE Children develop a gamut of primary lesions directly derived from infection with HIV: Lymphohematopoietic disturbances. Germinal center hyperplasia. Lymphoid depletion. Multinucleated giant cells. Extreme thymic atrophy (pseudodysplasia) Cardiovascular disturbances Idiopathic myocarditis. Myocardiopathy with left ventricular dysfunction. Vasculitis. Central nervous system disturbances. Encephalitis with multinucleated giant cells. Diffuse poliodystrophy. Mineralized vessels in basal ganglia. The infectious complications reported from autopsy series of children (177 cases from 6 selected publications) list among those more frequent: Bacterial infections, Pneumocystis pneumonia, cytomegalovirus, Candida infections, herpes, non tuberculous mycobacterioses and histoplasmosis. Isolated cases include tuberculosis, aspergillosis, toxoplasmosis, measles, adenovirus infection and cryptococcosis. THE MEXICAN EXPERIENCE Between 1986 and 2005, thirty six autopsies were performed on children dying with AIDS or with evidence of HIV infection at the National Institute of Pediatrics in Mexico City. These were 18 boys and 18 girls ranging form four months to 19 years of age. The disease was contracted by maternal transmission in 25, in 7 it was secondary to transfusion and one patient appears to have been infected by sexual contact. No source of infection was identified in three cases. Of the 25 cases of maternal transmission, the mother was infected by blood traansfusion in 10 and probably by sexual contact in 13. In two cases the source was not identified. Specific AIDS related pathology was identified in 27 cases. Twenty one had central nervous system involvement with a diverse combination of changes including foci of gliosis, multi nucleated giant cells, necrosis and demyelination. In the immune and hemopoietic system, 21 had lymphoid depletion of the thymus with a dysplastic appearance and bone marrow depletion in different combinations. Interstitial nephritis was present in one case and another had glomerular disease. Two cases showed large vessel vasculopathy (coronary 2, aorta 1). Bacterial infection was the main pathology in a majority of cases, we found it in 20 of 36 patients. Other infections were present as follows: cytomegalovirus 15, Candida species in 8, Pneumocystis infection in 9, herpes/varicella was present in 6, histoplasmosis in 5 and non-tuberculous mycobacteria in 3. Adenovirus infection was present in 2 patients. Single cases of measles, respiratory syncitial virus infections and toxoplasmosis were detected. Neoplasia arose in two patients, Hodgkin lymphoma and angiocentric non-Hodgkin lymphoma post renal transplantation. However in both cases the HIV infection was acquired from blood transfusion in the course of management of the primary disease. Worth noting is the absence of tuberculosis in our material and the fact that in none of the five cases of histoplasmosis was this microorganisms suspected clinically. Readings Anthony IC, Ramage SN, Carnie FW, Simmonds P, Bell JE. 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