Ben Zion Krieger

Bio: Ben Zion Krieger is an academic researcher from Yeshiva University. The author has contributed to research in topics: Abscess & Cellulitis. The author has an hindex of 2, co-authored 2 publications receiving 323 citations.

Simian immunodeficiency virus-induced mucosal interleukin-17 deficiency promotes Salmonella dissemination from the gut

Abstract: Salmonella typhimurium causes a localized enteric infection in immunocompetent individuals, whereas HIV-infected individuals develop a life-threatening bacteremia. Here we show that simian immunodeficiency virus (SIV) infection results in depletion of T helper type 17 (TH17) cells in the ileal mucosa of rhesus macaques, thereby impairing mucosal barrier functions to S. typhimurium dissemination. In SIV-negative macaques, the gene expression profile induced by S. typhimurium in ligated ileal loops was dominated by TH17 responses, including the expression of interleukin-17 (IL-17) and IL-22. TH17 cells were markedly depleted in SIV-infected rhesus macaques, resulting in blunted TH17 responses to S. typhimurium infection and increased bacterial dissemination. IL-17 receptor-deficient mice showed increased systemic dissemination of S. typhimurium from the gut, suggesting that IL-17 deficiency causes defects in mucosal barrier function. We conclude that SIV infection impairs the IL-17 axis, an arm of the mucosal immune response preventing systemic microbial dissemination from the gastrointestinal tract.

Effect of Continuous Intravenous Infusion of Zidovudine (AZT) in Children with Symptomatic HIV Infection

Abstract: To produce concentrations of zidovudine (AZT) in plasma and cerebrospinal fluid that would provide constant inhibition of the replication of human immunodeficiency virus (HIV), we gave AZT by continuous intravenous infusion to 21 children ranging in age from 14 months to 12 years who had acquired HIV infection through transfusions or perinatally. All patients were symptomatic before AZT treatment (Class P2 of the Centers for Disease Control); 13 (62 percent) had evidence of neurodevelopmental abnormalities. The mean CD4/CD8 ratio was 0.18; 11 patients had CD4 counts below 0.2 x 10(9) per liter. We administered AZT at four dose levels: 0.5, 0.9, 1.4, and 1.8 mg per kilogram of body weight per hour. The plasma drug concentrations achieved at the respective dose levels were 1.9 +/- 0.3, 2.8 +/- 1.4, 3.1 +/- 1.1, and 4.5 +/- 1.0 microM. The steady-state cerebrospinal fluid:plasma ratio was 0.24 +/- 0.07. The only evidence of toxicity was bone marrow suppression. Transfusion was required in 14 patients because of low levels of hemoglobin (5 mmol per liter [less than 8 g per deciliter]). Dose-limiting neutropenia (less than 0.5 x 10(9) polymorphonuclear leukocytes per cubic millimeter) occurred in most patients who received doses of 1.4 mg per kilogram per hour or more. Improvement in neurodevelopmental abnormalities occurred in all 13 children who had presented with encephalopathy before treatment. Serial measurements of IQ before therapy and after three and six months of continuous therapy with AZT showed that IQ scores, including those for verbal and performance IQ, rose in these 13 patients and in 5 other children who had no detectable evidence of encephalopathy before treatment. Most patients also had increased appetite and weight, decreased lymphadenopathy and hepatosplenomegaly, decreased immunoglobulin levels, and increased numbers of CD4 cells. In some patients the improvement in the features of encephalopathy occurred despite the absence of immunologic improvement. We conclude that AZT is beneficial in children with symptomatic HIV infection, especially those with encephalopathy (which may be subclinical), and that the optimal continuous intravenous dose of AZT in children is between 0.9 and 1.4 mg per kilogram per hour.

Pneumococcal disease during HIV infection. Epidemiologic, clinical, and immunologic perspectives.

Abstract: Objective To characterize the epidemiology, clinical manifestations, and immunologic risk factors for infections with Streptococcus pneumoniae among persons infected with human immunodeficiency virus (HIV); and to delineate a practical approach for diagnosis, treatment, and prevention of these infections. Data sources English-language articles from Index Medicus and their references as well as abstracts from conference proceedings that compared rates as well as clinical and microbiologic features of S. pneumoniae infections in HIV-infected patients. Study selection All human studies that included denominators, appropriate control groups, or sufficient clinical descriptions and animal studies with key immunologic observations were cited. Data extraction We compared epidemiologic and clinical responses to pneumococcal disease in HIV-infected patients and control subjects and correlated clinical and experimental data on immunologic defects associated with HIV infection with those on regulation of pneumococcal infections. Data synthesis Among patients with HIV infection, the incidence of invasive pneumococcal disease is high, bacteremia is a common complication of pneumonia, and relapses occur frequently. However, the clinical presentation, response to therapy, and serotypes isolated are similar to those in persons without HIV infection, and mortality is similar or lower. Specific local and systemic defects in host defense, particularly humoral immunity, may contribute to the high incidence of invasive pneumococcal disease. Conclusions Streptococcus pneumoniae is the leading cause of invasive bacterial respiratory disease in adults and children with HIV infection. Prompt diagnosis and antimicrobial therapy are associated with a favorable clinical outcome. Characterizing the specific immunologic defects associated with invasive pneumococcal disease in HIV-infected patients may facilitate development of successful, cost-effective strategies for prophylaxis.

Impaired Neutrophil Function in Patients With AIDS or AIDS-Related Complex: A Comprehensive Evaluation

Abstract: We measured the neutrophil function of 6 patients with AIDS and Kaposi's sarcoma (KS); 22 patients with AIDS-related complex (ARC); and 28 healthy, heterosexual controls. Neutrophils from patients with ARC showed significantly less chemotaxis (P less than or equal to .025) than did those from patients with AIDS and KS or from controls. Serum from patients with AIDS and KS or with ARC significantly (P less than or equal to .05) inhibited chemotaxis of neutrophils from controls; heat treatment of the serum abolished this inhibitory effect. Bacterial killing by neutrophils from patients with AIDS and KS or with ARC was also significantly (P less than or equal to .05) less than for neutrophils from controls, as was neutrophil phagocytosis binding of Candida albicans (P less than or equal to .05). Expression of OKM1 antigen was increased in the patients studied. Enzyme degranulation, adherence, and aggregation were also examined. The defects found in neutrophil function are selective and may be important in the increased susceptibility of patients with human immunodeficiency virus infection to bacterial and fungal infections.

Longitudinal study of 94 symptomatic infants with perinatally acquired human immunodeficiency virus infection. Evidence for a bimodal expression of clinical and biological symptoms.

Abstract: • To better define the clinical and biological evolution of infants after vertical human immunodeficiency virus type 1 infection, we analyzed 94 consecutive infected patients followed up after their first clinical symptoms. The expression of clinical symptoms and biological abnormalities followed a bimodal distribution, some patients having an early and severe disease and the others having a slowly progressive one. One third of our patients suffered from early onset of opportunistic infection (OI). These patients had a significantly higher incidence of severe encephalopathy compared with patients without OI. The rate of survival at 3 years was 48% ± 24%. In contrast, the patients without early OI or severe encephalopathy had a probability of survival at 3 years of 97%±3%. This probability was not modified by the occurrence of bacterial infection or lymphoid interstitial pneumonitis. Lymphoid interstitial pneumonitis occurred at a mean age of 29 months, significantly later than OI or severe encephalopathy. Laboratory results at initial examination were correlated with clinical symptoms. Thus, when the number of CD4 lymphocytes was less than 500/mm 3 , children suffered more frequently from life-threatening symptoms (OI and severe encephalopathy): 15 of 22 vs 14 of 69. The same was true when the lymphocytes did not proliferate after antigenic stimulation, when anti-p18 and/or anti-p25 antibodies were absent in the serum, and when p24 antigen was detected in serum. Finally, severe encephalopathy was associated with low anti–human immunodeficiency virus cerebrospinal fluid antibody titer, whereas 88% of patients with moderate or no encephalopathy had signs of intrathecal anti–human immunodeficiency virus antibody synthesis. In conclusion, a subgroup of patients expressed very early signs of severe immunodeficiency and encephalopathy, whereas the majority of patients had a longer survival and less severe clinical symptoms during their first years of life than previously thought. ( AJDC . 1990;144:1210-1215)