John P. Johnson

Respiratory syncytial virus illnesses in human immunodeficiency virus- and noninfected children.

Respiratory syncytial virus (RSV) lower respiratory tract and febrile upper respiratory tract illnesses were prospectively assessed in cohorts of 83 infants born to human immunodeficiency virus (HIV)- and of 48 infants born to non-HIV-infected mothers. Of the infants born to HIV-infected mothers, 18 were themselves infected with HIV, 26 were indeterminant and 39 were free from HIV. Ten RSV illnesses occurred in 8 HIV-infected, 2 illnesses in 2 indeterminant and 17 illnesses occurred in 17 non-HIV-infected children. RSV shedding was prolonged in HIV class P2- vs. non-HIV-infected children, at medians of 30 days (range, 1 to 199 days) and 6 days (range, 1 to 21 days), respectively (P = 0.02). Ribavirin and intravenous immunoglobulin failed to eradicate RSV from one child who shed virus for 199 days. Wheezing occurred in 1 of 4 vs. 9 of 10 episodes of lower respiratory tract illness in HIV-infected and non-HIV-infected children, respectively (P = 0.04). No differences were noted in duration of illness, temperature, respiratory rate or oxygen saturation between HIV- and non-HIV-infected children. Infection control and public health concerns regarding prolonged shedding of RSV in HIV-infected children must be recognized.

Detection of salivary immunoglobulin A antibodies to HIV-1 in infants and children.

Secretory immunoglobulin A (slgA) antibodies of non-maternal origin are present in newborns and slgA to HIV-1 antigens has been detected in infected adults. In this study we investigated the presence of HIV-1-specific IgA in saliva from 41 children (aged 1 day–46 months) born to women at risk for HIV-1 infection. Saliva samples were assayed for HIV-1 antibodies with IgA-specific Western blot. The samples from 10 out of 11 children with subsequently proven infection, including one aged 6 months, demonstrated IgA antibodies to HIV-1 envelope antigens. Samples from infants under 15 months, who were born to infected mothers and subsequently shown to be uninfected, were slgA negative. Of the 12 children with continued indeterminate HIV-1 status, eight showed neither slgA nor serologic evidence of infection and four showed slgA antibodies. HIV-1-specific slgA was detectable before the age of 15 months and may prove to be valuable in the diagnosis of HIV-1 infection in infants.

Rotavirus rna variation during chronic infection of immunocompromised children

Polyacrylamide gel electrophoresis was performed on RNA from rotaviruses isolated from two immunocompromised patients with prolonged rotavirus diarrhea. Extensive variations were observed in the genomes of rotaviruses isolated from each patient during a 16-week period of their illness. An animal model of rotavirus infection was used to help evaluate the results found in our patients. Individual mouse rotavirus strains were found to be stable during serial passage, but individual animals could be coinfected with more than one viral strain. The changes found in the rotavirus RNA from our patients possibly represented reinfection by different viral strains. Appropriate precautions should be observed to prevent such reinfections in immunocompromised patients.

Surgical intervention in children with human immunodeficiency virus infection

Twenty-one children with human immunodeficiency virus (HIV) infection required surgical intervention during the course of their disease. There were 11 females and 10 males (age range, 3 months to 6 years). The children underwent 54 operative procedures after diagnosis of their disease. These included placement of central venous catheter (23 patients), open lung biopsy (11), incision and drainage of perirectal abscess (4), incision and drainage of soft tissue abscess (5), myringotomy (2), diverting colostomy (3), Nissen fundoplication (1), and other (5). All 21 patients had clinical AIDS by the Centers for Disease Control CDC classification. To date, there have been 12 deaths in the 21 patients (57%) due to progressive deterioration with the patients disease. Most procedures were adjuncts for diagnostic and therapeutic intervention in a population of children with a uniformly fatal disease. The knowledge of various high risk groups for AIDS must heighten the surgeons awareness to the growing and significant pediatric segment of the HIV population, the complications of their disease, and the surgeons limited role in treating these problems.

Phytohemagglutinin-inducible p24 in peripheral blood mononuclear cells as a predictor of human immunodeficiency virus type 1 vertical transmission and infant clinical status.

We sought to determine whether the detectability of phytohemagglutinin-inducible p24 (PHA-p24) in short term cultures of peripheral blood mononuclear cells correlates with an increased risk of vertical transmission among human immunodeficiency virus type 1 (HIV-1)-infected pregnant women and more severe symptomatology among HIV-1-infected infants. The assay for PHA-p24 was performed on specimens obtained from HIV-1-infected women during their pregnancy and from infants during the first 6 months of life. Infants were followed prospectively to determine HIV-1 infection outcome and symptomatology. Among PHA-p24 positive women 9 of 19 (47.4%) gave birth to HIV-1-infected infants compared with 4 of 25 (16.0%) of PHA-p24-negative women (P = 0.02). Among women who tested PHA-p24-positive and had a CD4+ lymphocyte count < 500 cells/mm3, 8 of 15 (53.3%) gave birth to HIV-1-infected infants compared with 4 of 26 (15.4%) not meeting these conditions (P = 0.01). Among HIV-1-infected infants 4 of 5 (80%) of those testing PHA-p24-positive by one month of age developed an opportunistic infection or encephalopathy by 12 months of age, compared with none of the 11 infants testing PHA-p24-negative (P = 0.003). We conclude that PHA-p24 may be a useful in vitro measure for increased risk of vertical transmission among HIV-1-infected pregnant women and increased risk for rapid development of severe disease among HIV-1-infected infants.

Vertical Transmission of Human Immunodeficiency Virus From Seronegative or Indeterminate Mothers

UNLABELLED OBJECTIVE--To describe the identification of human immunodeficiency virus (HIV)-infected infants born to women who were seronegative or indeterminate during pregnancy. RESEARCH DESIGN--Longitudinal cohort study. SETTING--Inner-city medical center. PARTICIPANTS A series of children born to women with histories of risk factors for HIV infection were followed up for studies of the natural history of HIV-infected infants. These children were identified through risk factor assessment of pregnant women presenting for obstetric care. INTERVENTIONS--Counseling and testing to detect HIV. RESULTS--Three women were retrospectively identified who were infected with HIV during pregnancy but whose test results showed them to be either seronegative or indeterminate. Two of these women transmitted HIV infection to their children. Subsequently, all three women were confirmed to be infected. CONCLUSIONS--Standard serologic testing to detect HIV infection will not identify all infected pregnant women. Perinatal transmission of HIV can occur in women with negative results of enzyme-linked immunosorbent assay or indeterminate results of Western blot analysis during pregnancy.

1010 LABORATORY FINDINGS IN VARIOUS CONGENITAL IMMUNODEFICIENCIES

57 patients with suspected or proven immunodeficiency disorders were evaluated. Clinical diagnoses using WHO criteria included common variable immunodeficiency (6), DiGeorge Syndrome (6), X-linked hypogammaglobulinemia (5), IgA deficiency (5), ataxia-telangiectasia (4), mucocutaneous candidiasis (4), transient hypogammaglobulinemia (4), chronic granulomatous disease (3), severe combined immunodeficiency (2), and miscellaneous disease states (18). Immunological evaluation included CBC and differential, lymphocyte subset analysis with monoclonal antibodies, in vitro responses to mitogens, in vitro immunoglobulin production, serum immunoglobulin profiles and serological titers to tetanus toxoid, pneumococcal polysaccharide antigen, and EBV. Despite homogenous clinical findings in each group, laboratory results showed marked variability. For example, in patients clinically diagnosed as DiGeorge Syndrome, representation of OKT3+ lymphocytes ranged from 3-73%, OKT4+ 3-64%, OKT8+ 3-33% and sIg+ 10-56%. Four children with recurrent infections, but fitting no clinically defined immune deficiency disorder, and six first degree relatives of immunodeficiency patients performed normally in all the above assays (supplemented where appropriate with in vitro studies of PMN function. While laboratory studies complement the clinical findings and may exclude certain immunodeficiency disorders, they should not be used as the primary basis for diagnosis.

SERUM INHIBITOR OF GRANULOCYTE COLONY FORMATION ASSOCIATED WITH NEUTROPENIA IN TYPE I DYSGAMMAGLOBULINEMIA

A sixteen year old white male with X-linked Type I Dysgammaglobulinemia developed persistent neutropenia (total neutrophils < 500/mm3) which was unresponsive to broad spectrum antibiotics, prednisone, or a single infusion of one liter of fresh frozen plasma. His plasma agglutinated neutrophils in a microagglutination assay. His plasma (or serum) inhibited colony formation in a dose dependent fashion in a granulocyte/macrophage colony forming assay using human bone marrow cells. Complete inhibition was obtained when the patients serum reached a final concentration of 5%. This effect was similar when either the patients or normal bone marrow cells were used. Heating the patients serum to 56°C for 30 minutes did not destroy the inhibitor. Bone marrow cells cultured in a medium containing 5% of the patients serum and 5% of normal serum were also completely inhibited. Seven total plasma exchange procedures were performed over three weeks during which time the peripheral neutrophil count returned to normal and no serum inhibitor could be demonstrated. Upon completion of the plasma exchange procedures, the peripheral neutrophil count fell within three days to less than 500/mm3 and the serum inhibitor of colony formation reappeared. Three weeks after the plasma exchange procedures, the neutrophil count spontaneously returned to normal while on broad spectrum antibiotic therapy.

Genetically determined deficiency of the third component of complement in the dog

A genetically determined deficiency of the third component of complement (C3) has been identified in a colony of Brittany spaniels. Immunochemical methods show no detectable C3 in the serum of the affected dogs, and there is no evidence of an inhibitor of C3 in the serum. The C3 deficiency appears to be transmitted as an autosomal recessive trait.