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Biomedical subjects

Nutthapong Tangsinmankong

Publications and source records attributed to Nutthapong Tangsinmankong.

12 recordsLinked to original sources

Validation of current joint American Academy of Allergy, Asthma & Immunology and American College of Allergy, Asthma and Immunology guidelines for antibody response to the 23-valent pneumococcal vaccine using a population of HIV-infected children.

BACKGROUND: Measuring antibody responses to 23-valent pneumococcal polysaccharide vaccines (PPV) is crucial to evaluation of humoral immune function. However, data are limited comparing responses in immunodeficient subjects. OBJECTIVE: A case-controlled study comparing changes in PPV antibody titer in immunocompetent and immunodeficient children was performed to validate current guidelines. METHODS: A cohort of 95 immunocompetent children and 22 HIV-infected children, ages 2 to 15 years, was vaccinated with PPV, and before and after vaccination, IgG titers against capsular polysaccharides for 12 pneumococcal serotypes were measured. Results were used to calculate the receiver operator characteristic curve, sensitivity, and specificity of various interpretation criteria for their accuracy in detecting suboptimal responders. RESULTS: Immunodeficient subjects had lower CD4%, antidiphtheria, antitetanus titers, and mean post-PPV titers (2.5 +/- 1.7 vs 4.5 +/- 2.1 mug/mL; P < .001) compared with immunocompetent subjects. The interpretation, using individual post-PPV titer of > or =4-fold increase over prevaccination as a positive response, yielded the highest accuracy as measured by area under the curve value (receiver operator characteristic curve = .755). For this criterion, the numbers of serotypes with positive responses of < or =5 of 12 serotypes measured yielded 72.7% sensitivity and 56.8% specificity in detecting antibody-deficient subjects. CONCLUSION: Current guidelines using > or =4-fold increase in post-PPV titers has sufficient sensitivity and specificity to identify antibody deficiency. The minimal positive responses should be at least 50% of serotypes tested. CLINICAL IMPLICATIONS: Measurement of PPV antibody response based on the current guidelines accurately identify children with humoral immunodeficiency.

Acquired Immunodeficiency Syndrome↗

LMP-420, a small-molecule inhibitor of TNF-alpha, reduces replication of HIV-1 and Mycobacterium tuberculosis in human cells.

BACKGROUND: Co-infections of human immunodeficiency virus (HIV) and Mycobacterium tuberculosis (M. Tb) are steadily increasing and represent a major health crisis in many developing countries. Both pathogens individually stimulate tumor necrosis factor-alpha (TNF) release from infected cells and TNF, in turn, enhances the replication of each. A recent report on a Phase I clinical trial suggested that etanercept (soluble TNF receptor) might be beneficial in treating HIV/M. Tb co-infected patients. We sought to determine if a small molecule inhibitor of TNF synthesis and activity could block replication of either organism and thus be a potential adjunct to existing drugs targeting these agents. RESULTS: LMP-420, a novel anti-inflammatory agent that inhibits TNF, was tested for HIV-1 inhibition both alone and in combination with AZT (3' -azido-3-deoxythymidine). LMP-420 alone was tested against M. Tb. HIV-1 infected human peripheral blood mononuclear cells (PBMC) or M. Tb-infected human alveolar macrophages (AM) were treated with a single dose of LMP-420 and viral or bacterial replication determined after 7 or 5 days respectively. Viral replication was determined from supernatant p24 levels measured by ELISA. M. Tb replication was determined by bacterial culture of macrophage lysates. LMP-420 alone inhibited HIV replication over 7 days with an IC50 of approximately 300 nM. Combination of LMP-420 with AZT doubled the level of HIV inhibition observed with AZT alone. LMP-420 alone inhibited the replication of virulent M. Tb by >80%, more than that observed with anti-TNF antibody alone. CONCLUSION: Inhibition of TNF with inexpensive, small-molecule, orally-active drugs may represent a useful strategy for enhancing the activity of currently-available antiviral and anti-M. Tb agents, particularly in those areas where co-infections with these pathogens act to synergistically enhance each other.

Journal Article↗

Acrodermatitis enteropathica-like eruption and food allergy.

BACKGROUND: Acrodermatitis enteropathica-like eruption (AE) is a distinct rash associated with profound zinc deficiency. It is seen in a variety of conditions but has not been reported as a presentation of food allergy. OBJECTIVE: To report AE as an unusual presentation of food allergy in infants. METHODS: Acrodermatitis enteropathica-like eruption was diagnosed by a characteristic rash and a low serum zinc level. The diagnosis of food allergy was made by history, serum total IgE and food specific IgE levels, or oral challenge with suspected foods. RESULTS: Two infants with AE, diarrhea, and low serum zinc levels were evaluated. Food allergy was found in both infants. The first infant had a serum IgE level of 4642 IU/mL. Specific IgE levels to milk, soybean, wheat, and peanut were 39.04, 10.14, 5.65, and 102.61 kU/L, respectively. Oral challenges to milk and peanut were positive and to soybean were negative. The second infant had a serum IgE level of 991 IU/mL; specific IgE levels to soybean and milk were 36.9 and 0.53 kU/L, respectively. Evaluation for other possible causes of diarrhea revealed homozygous delta F508 in the first infant, confirming the coexistence of cystic fibrosis; findings in the second infant were negative. CONCLUSIONS: Undiagnosed food allergy can lead to profound zinc deficiency. Food allergy should be suspected in a child with acquired AE.

Acrodermatitis↗

Varicella zoster as a manifestation of immune restoration disease in HIV-infected children.

BACKGROUND: Exacerbation of opportunistic infections in HIV-infected patients shortly after initiation of highly active antiretroviral therapy (HAART) has been named immune restoration disease (IRD). Thus far, IRD has not been reported in children. OBJECTIVE: We describe the clinical and immune characteristics of IRD in HIV-infected children treated with HAART. METHODS: A historical cohort study was conducted in a tertiary HIV center in perinatally HIV-infected children who were started on a first stable HAART between January 1996 and July 2002. The incidence of opportunistic infections, newly AIDS-defining events or death after initiation of HAART, and virologic and immunologic information was evaluated at baseline and every 3 months post-HAART. RESULTS: Sixty-one perinatally HIV-infected children were started and maintained on HAART for >6 months. Seven episodes of IRD occurred. All were cutaneous herpes zoster (HZ). Children who developed HZ had significantly lower baseline CD4+ and CD8+ T-cell numbers compared with children who did not. HZ occurred only in children (7 of 34 subjects) with virological and immunological success to HAART. In children with a previous history of varicella infection, the risk of developing HZ after HAART was higher in those without a protective level of varicella-specific IgG (50%, or 5 of 10 subjects) compared with those with seroprotection (10%, or 2 of 20). CONCLUSION: Herpes zoster is a common manifestation of IRD in HIV-infected children after the initiation of HAART. Risks for developing HZ include no protective varicella-specific antibody despite previous varicella infection, severe immunodeficiency at baseline, and vigorous immunologic and virologic responses to HAART.

Antiretroviral Therapy, Highly Active↗

Interleukin receptor-associated kinase (IRAK-4) deficiency associated with bacterial infections and failure to sustain antibody responses.

We previously described a girl with recurrent episodes of pneumococcal pneumonia with septicemia and other infections,(1) found to have interleukin-1 receptor-associated kinase 4 deficiency (IRAK-4) deficiency.(2) In this report, we show that our patient is unable to sustain antibody responses either to polysaccharide or protein antigens or to a neoantigen-bacteriophage.

Antibodies, Bacterial↗

Effect of influenza virus vaccine on the expression of human immunodeficiency virus co-receptor CCR5.

BACKGROUND: Administration of influenza vaccine to human immunodeficiency virus (HIV)-infected children can lead to increased viral load. CCR5 and CXCR4 are known to play an important role in HIV cell entry and viral replication. OBJECTIVE: To determine the effects of influenza vaccine on chemokine receptors and on viral load in HIV-infected children. METHODS: Eight HIV-infected children receiving stable therapy and 11 healthy adults were enrolled. Chemokine expression and immune activation were determined before and 48 hours after influenza vaccination. CCR5 and beta-chemokine gene expression were analyzed using real-time polymerase chain reaction. Viral load was measured at baseline, 48 hours, and 6 to 12 weeks. RESULTS: Forty-eight hours after influenza vaccination, mean CCR5 expression was significantly decreased on the CD3 (21.1% vs 11.3% in HIV-infected children; P = .02; and 18.3% vs 10.7% in controls; P = .008) and CD4 (13.0% vs 3.6% in the HIV group; P = .04; and 13.6% vs 6.5% in controls; P = .02) lymphocytes. This was observed in conjunction with an increase in HLA-DR expression on T lymphocytes in HIV-infected children (P = .046). No significant changes were observed in HIV viral load, CD3 and CD8 lymphocyte counts, expression of interleukin 2 receptor and CXCR4, or gene expression of CCR5 and beta-chemokines 48 hours after vaccination. CONCLUSIONS: Influenza virus vaccine markedly decreased chemokine receptor CCR5 expression on CD4 T lymphocytes. However, this immunomodulatory effect does not seem to affect overall viral replication in HIV-infected children who received highly active antiretroviral therapy.

Antiretroviral Therapy, Highly Active↗

Immunogenicity of 23-valent pneumococcal polysaccharide vaccine in children with human immunodeficiency virus undergoing highly active antiretroviral therapy.

BACKGROUND: The 23-valent pneumococcal polysaccharide vaccine (23PSV) has been recommended for children infected with human immunodeficiency virus (HIV); however, the efficacy of this vaccination in HIV-infected children undergoing highly active antiretroviral therapy (HAART) has not been studied. OBJECTIVE: To study the immunogenicity and immunologic protection of 23PSV in HIV-infected children after stable HAART. METHODS: Serotype-specific IgG antibodies to 12 pneumococcal capsular polysaccharides were analyzed before and after 23PSV vaccination in 41 HIV-infected children undergoing HAART and compared with 95 HIV-negative control children. Seropositivity, clinical protection, and additional clinical protection from 23PSV were calculated based on serotype specific IgG antibody levels and on the known incidence of these serotypes for causing invasive disease. RESULTS: Children with HIV infection undergoing HAART developed a significant increase in specific IgG levels to Streptococcus pneumoniae after 23PSV vaccination (0.95 vs 1.84 micro/gmL, P < .001). The HIV-infected children with CD4+ cell counts of 25% or higher at the time of vaccination developed a higher additional clinical protection gain from 23PSV vaccination than did children with a lower percentage of CD4+ cells. CONCLUSIONS: HIV-infected children undergoing stable HAART develop a significant immunologic response to 23PSV, especially those with higher T-cell counts and lower viral loads at the time of vaccination.

Adolescent↗

Different mechanisms are utilized by HIV-1 Nef and staphylococcal enterotoxin A to control and regulate interleukin-10 production.

Interleukin-10 (IL-10) plays an important immunopathogenic role in immunologic diseases, especially in HIV infection and atopic dermatitis. The control and regulatory mechanisms of IL-10 production have not been described in these diseases. Recently, we demonstrated that HIV-1 Nef induces IL-10 production in monocytes and that staphylococcal enterotoxin A (SEA) induces IL-10 production in T-lymphocytes. Here we show that Nef-induced IL-10 production and mRNA expression are strongly blocked by rapamycin, but are not blocked by cyclosporin (CsA) or FK506. Conversely, we show that CsA and FK506 completely inhibit SEA-induced IL-10 protein production and mRNA expression. The results of this study demonstrate that IL-10 production by Nef and SEA is controlled and regulated by different mechanisms.

Cells, Cultured↗

Improving care of HIV-infected patients in the outpatient setting with patient data flow sheets.

Medical management of pediatric/adolescent HIV has become increasingly complex, requiring a multidisciplinary approach to care. Close clinical monitoring is needed to minimize opportunistic infections, initiate appropriate antiretroviral therapy, and ensure optimal health care to the patient. Monitoring should include evaluation of efficacy and side effects of therapy, early detection and treatment of HIV-associated complications, and maintenance of current immunizations. Tracking clinical data in chronically ill patients is a difficult task without an effective monitoring system. A patient data flow sheet was created to assist in planning care and monitoring disease progression by consolidating clinical information into an organized, one-page summary for each patient. One year after the patient data flow sheets were instituted, there was a significant improvement in the consistency of obtaining and monitoring routine HIV labs as well as serologies, and other recommended tests. The flow sheets have increased effectiveness of patient care and have been used to assist with quality assurance monitoring and quality improvement in the clinic setting.

Adolescent↗