Brian Novick

AIDS Calcification of the basal ganglia in infants and children

CT or postmortem examination demonstrated calcification of the basal ganglia in eight infants and children with acquired immune deficiency syndrome. Serial CT studies documented progression of both bilateral symmetric calcium densities and cerebral atrophy. Clinical features included progressive encephalopathy with dementia, and pyramidal tract signs. Postmortem examination of four children revealed variable degrees of calcific vasopathy of the basal ganglia, involving predominantly the putamen and globus pallidus.

Bacterial infection in the acquired immunodeficiency syndrome of children

We have followed 46 children with acquired immunodeficiency syndrome and acquired immunodeficiency syndrome-related complex. Twenty-six patients had at least one episode of serious bacterial infection. Twenty-seven episodes of sepsis were documented in 21 patients. Soft tissue infection was common in both the presence and the absence of documented bacteremia. Urinary tract infection commonly presented as worsening diarrhea in the absence of sepsis. Organisms commonly isolated included Streptococcus pneumoniae, Haemophilus influenzae and Salmonella sp. Staphylococcal infection accompanied episodes of cellulitis/abscess. Escherichia coli commonly caused urinary tract infection in the absence of sepsis. Enteric and nosocomial sepsis was limited to hospitalized, instrumented patients or to individuals who had received prior antibiotic therapy as outpatients. We conclude that bacterial infection causes serious morbidity in acquired immunodeficiency syndrome and acquired immunodeficiency syndrome-related complex and may be further evidence for altered humoral immunity in the disorder.

DEVELOPMENTAL ABNORMALITIES IN INFANTS AND CHILDREN WITH ACQUIRED IMMUNE DEFICIENCY SYNDROME (AIDS) AND AIDS‐RELATED COMPLEX

Children with acquired immune deficiency syndrome (AIDS) display two types of clinical picture: (1) a fullblown AIDS characterized by the presence of opportunistic infections and/or Kaposis sarcoma and (2) a prodromal stage now identified as AIDS‐related complex (ARC). Neurological complications have been identified in infants and children with the disease. This paper discusses the developmental abnormalities in 16 pediatric patients, seven with AIDS and nine with ARC, ranging in age from six months to six years. In all cases, the mothers of these children either had ARC, AIDS and/or used intravenous drugs. Developmental histories showed delayed acquisition of milestones in most children following the diagnosis of AIDS or ARC, with delayed motor milestones consistently noted in both groups. Several children with AIDS actually lost milestones as their illness progressed; this has not occurred in the ARC group. Psychometric testing revealed more severe cognitive dysfunction in the group with AIDS. Involvement of the central nervous system was documented clinically, radiologically, and/or electrophysiologically in all patients with AIDS. In the ARC group the course of the illness has shown greater variability. Medical and social factors that may contribute to the developmental abnormalities are discussed.

Developmental Abnormalities in Children with Acquired Immunodeficiency Syndrome (AIDS): A Follow-up Study

Developmental abnormalities in 16 pediatric patients with AIDS or AIDS-Related Complex (ARC) were previously described. Neurological deterioration was in evidence on follow-up in 9 of the children, 5 died since the original assessments were performed. Ten patients were reevaluated 14 months later by cognitive testing. Two showed greater progress than expected on the basis of earlier test results; 6 showed the expected level of developmental progress; and the remaining 2 showed regression in cognitive functioning. All patients who exhibited regression in their developmental course showed deterioration in their neurological examinations. Developmental progression was noted in some children who on follow-up serial examinations exhibited a clinically deteriorating neurological picture. Pediatric AIDS patients manifest variable neurodevelopmental courses. As a result, rehabilitative intervention services must be tailored to meet individual needs.

TREATMENT OF AIDS WITH INTRAVENOUS GAMMAGLOBULIN

B cell abnormalities have been reported in adults with AIDS. These abnormalities include poor antibody responses to neo-antigens, and poor in vitro lymphocyte mitogenic responses to Pokeweed Mitogen. Similar abnormalities have been reported by us in infants with AIDS and AIDS related complex. These infants have had multiple bacterial infections including sepsis. 16 patients, 11 infants and 5 adults have been treated with i-v gammaglobulin (Cutter Laboratories) 200mg/kg biweekly for 3 months to 3 years. Clinically, a significant reduction in bacterial infections was noted in all patients. 2 infants developed new opportunistic infections while on treatment. In most patients an increase in the OKT4/T8 ratio and in lymphocyte blasttransformation to phytohemagglutinin and pokeweed mitogen was noted. In 2 out of 4 studied patients suppressor T cell functions were restored. During the first infusions of gamma-globulin transient elevations of serum immune complexes and a drop in total hemolytic complement were sometimes noted. However, with time serum immune complexes decreased to normal levels. None of these changes have been observed in 19 untreated infants with AIDS. I-V gammaglobulin in conjunction with other immunotherapeutic modalities may be of benefit for AIDS patients.

B CELL ABNORMALITIES IN CHILDREN WITH AIDS

B cell abnormalities have recently been described in adults with the Acquired Immunodeficiency Syndrome. Immunological profiles were performed in 19 children with AIDS or its prodromal stage. Opportunistic infections in AIDS patients included disseminated cytomegalovirus, invasive candidiasis, pneumocystis carinii, pneumonia and systemic mycobacterium avium intracellulare. Hypergammaglobulinemia was documented in 6 of 7 children with AIDS and in all prodromes specific antibody responses to tetanus immunization were extremely low or undetectable in 5 of 6 prodromes and in 4 of 5 children with opportunistic infections. Mitogenic responses to phytohemagglutinin were normal in 6 of 7 AIDS infants and 11 of 12 prodromes. Pokeweed mitogen responses were depressed or absent in all patients with prodrome and in 6 of 7 with AIDS. The combination of hypergammaglobulinemia, poor specific antibody responses and depressed pokeweed mitogen responses suggest that B cell abnormalities are found in childhood AIDS, and are similar to those found in adults with the syndrome.Supported by NIH Grant Number: 1 U01 AI 20671-01

957 BACTERIAL INFECTION IN THE ACQUIRED IMMUNODEFICIENCY SYNDROME

We have reviewed the incidence of bacterial infections in 46 children with Acquired Immunodeficiency Syndrome (AIDS). Twenty-five episodes of culture proven sepsis were documented in 20 patients. Twenty patients had at least one episode of serious bacterial infection. Meningitis occurred in 5 instances. Other infections included lobar pneumonia, cellulitis, purulent lymphadenitis, and skin abcesses. Two children had chronically draining otitis media. Urinary tract infection in the absence of sepsis occurred on 9 occasions. Organisms most commonly isolated in outpatients or recently hospitalized patients included pheumococcus, H. Influenza group B, staphylococcus ameus and salmonella. Staph sepsis frequently accompanied skin infection. All episodes of enteric or nosocomial gram negative sepsis occurred in either hospitalized children or in outpatients on extensive antibiotic therapy. E. Coli was the predominant urinary pathogen. Bacterial infection is a major cause of morbidity in pediatric AIDS.

592 IS AIDS TRANSMITTED HORIZONTALLY

To ascertain whether or not there is a risk of horizontal transmission of AIDS, we studied 24 pediatric household contacts of 9 pediatric AIDS index cases. Immune parameters studied included serum immunoglobulins, T4 and T8 cells, in vitro lymphocyte mitogenic responses to phytohemagglutinin, pokeweed mitogen and staph cowan A. Transient immunologic aberrations were noted in four children from three families. These aberrations included elevated IgG levels, reversed T4/T8 ratios and slightly diminished in vitro lymphocyte mitogenic responses to pokeweed mitogen. In no case could antibodies to the lymphadenopathy virus be documented. Clinically, all household contacts remained healthy over a four year follow-up.

THYMULIN (FTS) AND THYMOSIN α 1 - DIAGNOSTIC CRITERIA FOR AIDS IN CHILDREN

Thymosinα1 levels are markedly elevated in homosexual patients with AIDS or AIDS-related complex (prodrome) at a time when their T-cell function and OKT4/T8 ratios are depressed. On the other hand Thymosinα1 and FTS are significantly reduced in patients with primary immunodeficiency diseases affecting cell mediated immunity. We have studied 14 infants with AIDS or AIDS prodrome with reversed OKT4/T8 ratios. FTS levels were diminished in all patients. Thymosinα1 levels were elevated in 12 infants and normal or low in 2 (both treated with steroids, an agent known to depress thymosinα1 levels). It appears that the FTS/thymosinα1 ratio may serve as a diagnostic parameter to discriminate between congenital primary immunodeficiency and AIDS in infants.

NEUROLOGICAL COMPLICATIONS IN INFANTS WITH AIDS

The clinical symptomatology of children with AIDS is similar to that observed in adults including fever, weight loss, diffuse lymphadenopathy and opportunistic infections. In adults, unusual neurological complications including progressive encephalopathy were recently reported. Since 1979, we have noted neurological abnormalities in 6 children with AIDS. 5 patients have not attained appropriate milestones, with severe global delay in areas of gross motor control, fine motor control, social functioning and language. Physical examination revealed spastic diplegia, hyperreflexia and positive Babinski in 4 with diminished muscular tone in 5 infants. 1 had seizures. Cerebrospinal fluid was acellular with normal protein and glucose. Skull X-rays have been negative. CT scans, with and without contrast in 4 children, displayed progressive cerebral atrophy. 1 showed intracerebral calcifications. EEGs showed diffuse slow waves with subsequent studies demonstrating further slowing of electrical activity. 4 of the 6 patients have continued neurologic deterioration with further loss of developmental milestones.