Diagnostic value of serum human Galactomannan aspergillus antigen and 1,3‐beta‐D‐glucan in immunocompromised patient suspected fungal infection

BackgroundThe prevalence of fungal infection (FI) in developing countries is high, but the diagnosis of FI is still challenging to determine, so it is needed evaluation of biomarkers other than microbiological culture, because the culture has low sensitivity, high cost, not available in every laboratory and needs a long time. The detection of human galactomannan Aspergillus antigen (GAL) and 1,3‐beta‐D‐glucan (BDG) on the fungal cell wall could be the promising biomarkers for fungal infection. Neutropenia, lymphopenia and CD4T cells in the immunocompromised patients are essential factors, but these cell associations with BDG and GAL levels have not been evaluated yet. The study aimed to evaluate GAL and BDG for detecting fungal infection and their association with total leucocyte count, neutrophil, monocyte, lymphocyte and CD4T cells.MethodA cross‐sectional study was conducted among 86 patient with suspected FI. Fungal infection established using EORTC/MSG criteria. Serology test performed using ELISA. Leucocyte cells were measured using a haematology autoanalyser, and CD4T cells were analysed using BD FACSPresto. Statistical analysis obtained using Spearman''s correlation coefficient, ROC curve analysis and 2 × 2 contingency table.ResultsSerum Galactomannan and BDG had a significant correlation with CD4T cells and total lymphocyte count (p < 0.05). The cut‐off OD GAL >0.3 had sensitivity 54.6%, specificity 87.5% and AUC 0.71; meanwhile, the BDG cut‐off >115.78 pg/ mL had sensitivity 71.2%, specificity 52.4% and AUC 0.63 for detecting fungal infection.ConclusionsThe immunocompromised patients can undergo GAL for determining the diagnose of FI. The lower the CD4T cells and total lymphocyte count, the higher the GAL and BDG serum levels.     

Multicentre laboratory evaluation of Brugia Rapid dipstick test for detection of brugian filariasis

A multicentre evaluation of the Brugia Rapid dipstick test was performed using 1263 serum samples in four international laboratories, i.e. T.D. Medical College (TDMC, India), National Institutes of Health (NIH, USA), Swiss Tropical Institute (STI, Switzerland) and Leiden University Medical Centre (LUMC, Netherlands). In comparison with microscopy, the dipstick demonstrated sensitivities of 97.2% (70 of 72) at TDMC, 91.6% (175 of 191) at LUMC and 100% (six of six) at STI. Sera of chronic patients showed a positivity rate of 11.3% (19 of 168) and 61.2% (71of 116) at TDMC and LUMC, respectively. All 266 sera of non-endemic normals from STI, NIH and LUMC tested negative with the dipstick. At LUMC, sera of 'endemic normals' (amicrofilaraemics with no clinical disease) from an area with approximately 35% microfilaria positivity showed 60.8% positive results (31 of 51), thus demonstrating the likelihood of many cryptic infections occurring in this population. Specificities of the test with Onchocerca volvulus sera were 98.8% (80 of 81) and 100% (10 of 10) at the NIH and STI, respectively; while specificity with Loa loa sera at the NIH was 84.6% (44 of 52). At the STI, the dipstick test also demonstrated 100% specificity when tested with 75 sera from various protozoan and helminthic infections.     

Helminth infection in populations undergoing epidemiological transition: a friend or foe?

Helminth infections are highly prevalent in developing countries, especially in rural areas. With gradual development, there is a transition from living conditions that are dominated by infection, poor sanitation, manual labor, and traditional diet to a situation where burden of infections is reduced, infrastructure is improved, sedentary lifestyle dominates, and processed food forms a large proportion of the calorie intake. The combinations of some of the changes in lifestyle and environment are expected to result in alteration of the landscape of diseases, which will become dominated by non-communicable disorders. Here we review how the major helminth infections affect a large proportion of the population in the developing world and discuss their impact on the immune system and the consequences of this for other infections which are co-endemic in the same areas. Furthermore, we address the issue of decreasing helminth infections in many parts of the world within the context of increasing inflammatory, metabolic, and cardiovascular diseases.     

Comparison of an enzyme linked immunosorbent assay (ELISA) and a radioallergosorbent test (RAST) for detection of IgE antibodies to Brugia malayi

The enzyme linked immunosorbent assay (ELISA) for specific IgE antibodies to Brugia malayi was compared with the radioallergosorbent test (RAST) for use in immunoepidemiological studies of lymphatic filariasis. Sera used were from individuals (aged 5-82 years) living in an area endemic for lymphatic filariasis in South Sulawesi, Indonesia. The percentage of positive IgE ELISA reactions (52.6%) among the population was lower than the percentage of positive RAST (94.5%). Although an overall significant concordance was found between the two assays (P < 0.001), 328 (42.7%) individuals with a positive RAST result were negative in the ELISA, whereas only 6 (0.8%) subjects were positive by ELISA, yet negative by RAST. When the population was divided into those with active infection (positive for anti-filarial IgG4) and those not infected (mf-negative and negative for anti-filarial IgG4), the correlation between the two tests was higher in the IgG4-positive (rho = 0.70) than in the IgG4-negative (rho = 0.52) group. These results indicate that in assessment of B. malayi specific IgE antibody, RAST is superior to ELISA. However, given the use of radioactivity in the RAST method and given our results obtained in subjects with high anti-filarial IgG4, one could consider using the IgE-ELISA in areas with high endemicity for filariasis. In areas with low endemicity or where control programs are implemented, sera will have to be tested by RAST.     

Long-term follow-up of treatment with diethylcarbamazine on anti-filarial IgG4: dosage,compliance, and differential patterns in adults and children

We have followed a population in an area endemic for Brugia malayi for three years after intensive treatment with diethylcarbamazine (DEC). Microfilariae were cleared from the circulation within four months in all eligible study participants (n = 60). There appeared to be a strong correlation between the maximum reduction in specific IgG4 and the number of days drug was taken under supervision (p = 0.41, P < 0.001), indicating that high total dosage of DEC is necessary for optimal reduction of active infection. In individuals with good compliance (at least 180 mg/kg of body weight, n = 34), we observed variable IgG4 patterns. All pre-treatment IgG4+ children (9-14 years old) and 40% of the IgG4+ adult population (> or = 15 years old) showed a gradual decrease in anti-filarial IgG4; 53% of these showed complete clearance of worm burden by the end of the study. In contrast, another group of male IgG4+ adults showed IgG4 patterns that started to increase between nine months and two years after treatment, indicating either a partial efficacy of DEC that allowed recovery of resident adult worms or reinfection.     

Effect of high-dose vitamin A supplementation on the immune response to Bacille Calmette-Guerin vaccine

BACKGROUND: Vitamin A supplementation (VAS) at birth has been associated with decreased mortality in Asia. Bacille Calmette-Guérin (BCG) vaccine is given at birth in tuberculosis-endemic countries. Previous studies suggest that VAS may influence the immune response to vaccines. OBJECTIVE: Our objective was to examine whether VAS influences the immune response to simultaneously administered BCG vaccine. DESIGN: Within a randomized trial of 50,000 IU vitamin A or placebo given with BCG vaccine at birth in Guinea-Bissau, 2710 infants were examined for BCG scar formation and delayed-type hypersensitivity (DTH) to purified protein derivative of Mycobacterium tuberculosis (PPD) at 2 and 6 mo of age. The ex vivo cytokine response to PPD was measured in 607 infants. RESULTS: At 2 mo of age, 39% (43% of the boys and 34% of the girls) responded to PPD. The prevalence ratio of a measurable PPD reaction for VAS compared with placebo recipients was 0.90 (95% CI: 0.80, 1.02) for all infants, 0.81 (95% CI: 0.69, 0.95) for boys, and 1.04 (95% CI: 0.86, 1.26) for girls. At 6 mo of age, 42% of the infants responded to PPD. No difference was observed between VAS and placebo recipients. The prevalence of BCG scar was not affected by VAS. The ex vivo interferon-gamma response to PPD was increased by VAS (means ratio: 1.40; 95% CI: 1.03, 1.91). CONCLUSIONS: VAS with BCG vaccination does not appear to interfere with the long-term immune response to BCG. However, VAS temporarily altered the DTH reaction to PPD in boys at 2 mo of age, suggesting sex differences in the immunologic response to VAS given with BCG. This trial was registered at www.clinicaltrials.gov as #NCT00168597.     

Reversal in microfilarial density and T cell responses in human lymphatic filariasis

This study reports reversals in microfilarial density and the accompanying changes in cellular immune responses to filarial antigens of 39 individuals (11 microfilaria-positives, 22 microfilaria-negatives and six converters) living in an area endemic for brugian filariasis. Microfilarial counts decreased from April, the end of the rainy season to July, middle of the dry season (g.m. 88 mf/ml and 38 mf/ml, respectively; P = 0.001) and subsequently increased in November, the beginning of the rainy season (P = 0.088). Whereas the proliferative responses remained low throughout the study period in microfilaraemic individuals, in amicrofilaraemics these responses changed in the opposite direction to that of microfilarial densities. In three converters, proliferation changed in the opposite direction to the presence or absence of microfilariae. Cytokine analysis in the converters revealed that interferon-gamma was most affected by the shifts in microfilarial densities. In contrast, interleukin-4 responses showed little correlation with changes in parasite densities.     

Clustering of allergic outcomes within families and households in areas endemic for helminth infections

BACKGROUND: Allergy and helminth infections share key immunological features in terms of Th2 responses. Although in industrialized countries clustering of allergic disorders within families has been frequently reported, such information is lacking from areas where helminth infections are endemic. METHODS: A total of 466 subjects from 29 families and 112 households participated in this study. Filarial infection, skin test reactivity and IgE to mite as well as total IgE were measured in all samples. Clustering of the allergy-related outcomes due to genetic and household factors was tested. RESULTS: Genetic factors contributed significantly to the clustering of total IgE and allergen-specific IgE, whereas only household factors contributed to the clustering of SPT positivity. CONCLUSION: Similar to several studies conducted in western populations, total IgE and allergen-specific IgE are influenced by genetic factors in a population resident in a helminth endemic area. However, clustering of SPT positivity due to genetic factors was not significant in the current study raising the question of whether the presence of helminth infections may override genes that are associated with the expression of tissue reactivity to allergens in the west.