The diagnostic accuracy of Th1 (IFN-γ, TNF-α, and IL-2) and Th2 (IL-4, IL-6 and IL-10) cytokines response in AFB microscopy smear negative PTB- HIV co-infected patients.

Acid Fast Bacilli (AFB) microscopy smear remains the most widely used laboratory diagnostic technique for Pulmonary Tuberculosis (PTB) in low-and-middle income countries. Although it is highly specific, the sensitivity varies between 20-80% in immune-competent people, with only 50% case detection among HIV/TB co-infected patients, hence the need to determine the diagnostic accuracy of Th1 and Th2 cytokine response in AFB microscopy smear negative PTB-HIV co-infected patients. A total of 86 participants were recruited; 70 (81.4%) AFB microscopy smear negative and 16 (18.6%) AFB microscopy smear positive. The AFB microscopy smear negative samples were then cultured using Lowenstein Jensen Medium with 46 being culture-negative and 24 being culture-positive. Blood samples were also collected, cultured using QFT-GIT and the supernatant (plasma) harvested to evaluate cytokine profiles using Enzyme-Linked Immunosorbent Assay. IFN-γ (P < 0.001), TNF-α (P = 0.004), IL-2 (P = 0.004) and IL-4 (P = 0.009) median levels were elevated in PTB culture-positive (AFB microscopy smear negative) as compared to PTB culture-negative (AFB microscopy smear negative) participants. Finally, when Th1 cytokines (IFN-γ, TNF-α and IL-2), Th2 cytokines (IL-6 and IL-10) and T cells were included in the logistic regression fit for PTB outcome, the predictive power of discriminating between those who were AFB smear negative in the diagnosis of PTB was good with cross validated area under the curve (AUC) being 0.87 (95% CI: 0.78, 0.96). This study provides evidence for the ability of Th1 and Th2 cytokines to determine PTB status in AFB microscopy smear negative patients co-infected with HIV.

The role of Mycobacterium tuberculosis antigen specific cytokines in determination of acid fast bacilli culture status in pulmonary tuberculosis patients co-infected with human immunodeficiency virus.

INTRODUCTION: The interaction between Mycobacterium tuberculosis and HIV leads to rapid progression of tuberculosis (TB) and human immunodeficiency virus (HIV)-induced immunosuppression. Diagnosis of TB in these patients is more difficult due to its atypical presentations giving contradicting results. The overall aim of this study was to evaluate the ability of pro-inflammatory cytokine (Th1) and anti-inflammatory cytokine (Th2) to discriminate between culture-positive and -negative smear status in HIV-TB co-infected patients. METHODS: In a prospective cohort, a total of 86 study participants were recruited: 46 culture-negative and 40 culture-positive. Blood and sputum samples were collected from all participants. The blood was then analyzed using FACSCalibur flow cytometer to immunophenotype the cells and ELISA performed for cytokine profiles. Sputum samples were analyzed to determine smear status using direct microscopy and Lowenstein Jensen medium. Statistical analyses were performed using R software. Independent samples t-test was used to compare means between the two groups, while the medians were compared using two-sample Wilcoxon rank sum test. Pearson's Chi-square test was used to compare the proportion of male and female participants across the culture and AFB smear status. In order to determine the predictive power of Th1 and Th2 in discriminating Pulmonary Tuberculosis status (PTB) (culture status was used as a confirmatory test), binary logistic regression models were fitted for Th1 covariates [IFN-γ, TNF-α, IL-2 and IL-12(p70)] and Receiver Operating Characteristic (ROC) curves plotted. RESULTS: The overall mean age of the participants was 39 years (SD=12), 42% being male. Although, lymphocytes counts were higher in culture-positive relative to culture-negative, the CD8, CD19, and CD16/CD56 were comparable in the two groups. The CD4 counts differed between the two groups (P=0.012). The Th1 showed a better discrimination between culture-positive and -negative PTB individuals; IFN-γ (P=0.001), TNF-α (P=0.001), IL-2 (P=0.001) and IL-12(p70) (P=0.016). The Th2 cytokines (IL-4, IL-6 and IL-10) were comparable between the culture-positive and -negative groups. However, when the combination of Th1 cytokines [IFN-γ, TNF-α, IL-2 and IL-12(p70)] was fitted in binary logistic regression models, the predictive power was high with area under curve (AUC) being 89.7% in discriminating PTB. CONCLUSION: This study provides evidence for the ability of a combination of Th1 cytokines in discriminating against culture-positive and culture-negative PTB.

Malaria and nutritional status in children living on the coast of Kenya.

BACKGROUND: The relation between malnutrition and malaria is controversial. On the one hand, malaria may cause malnutrition, whereas on the other hand, malnutrition itself may modulate susceptibility to the disease. OBJECTIVE: The objective was to investigate the association between Plasmodium falciparum malaria and malnutrition in a cohort of Kenyan children. DESIGN: The study involved the longitudinal follow-up of children aged 0-95 [corrected] mo for clinical malaria episodes and anthropometric measurements through 4 cross-sectional surveys. We used Poisson regression analysis to investigate the association between malaria and nutritional status. RESULTS: The crude incidence rate ratios (IRRs) for malaria during the 6-mo period before assessment in children defined as malnourished on the basis of low height-for-age or low weight-for-age z scores (<-2) were 1.17 (95% CI: 0.91, 1.50; P=0.21) and 0.94 (0.71, 1.25; P=0.67), respectively, which suggests no association between malaria and the subsequent development of protein-energy malnutrition. However, we found that age acted as an effect modifier in the association between malaria episodes and malnutrition on prospective follow-up. The IRR for malaria in children aged 0-2 y, who were subsequently characterized as underweight, was 1.65 (1.10, 2.20; P=0.01), and a significant overall relation between malaria and stunting was found on regression analysis after adjustment for the interaction with age (IRR: 1.91; 1.01, 3.58; P=0.04). CONCLUSION: Although children living on the coast of Kenya continue to experience clinical episodes of uncomplicated malaria throughout the first decade of life, the effect of malaria on nutritional status appears to be greatest during the first 2 y of life.

Iron deficiency and malaria among children living on the coast of Kenya.

Both iron deficiency and malaria are common in much of sub-Saharan Africa, and the interaction between these conditions is complex. To investigate the association between nutritional iron status, immunoglobulins, and clinical Plasmodium falciparum malaria, we determined the incidence of malaria in a cohort of children between the ages of 8 months and 8 years who were living on the Kenyan coast. Biochemical iron status and malaria-specific immune responses were determined during 2 cross-sectional surveys. We found that the incidence of clinical malaria was significantly lower among iron-deficient children (incidence-rate ratio [IRR], 0.70; 95% confidence interval [CI], 0.51-0.99; P<.05), that the incidence of malaria was significantly associated with plasma ferritin concentration (IRR for log ferritin concentration, 1.48; 95% CI, 1.01-2.17; P<.05), and that iron status was strongly associated with a range of malaria-specific immunoglobulins. We conclude that iron deficiency was associated with protection from mild clinical malaria in our cohort of children in coastal Kenya and discuss possible mechanisms for this protection.