August 22, 2013
By Lisa Petrison, Ph.D.
Aflatoxin in foods appears to be a major driver in the AIDS epidemic in Africa, as a result of immune system damage from the poisons making people more susceptible to the HIV virus, reports a series of published papers by University of Alabama professor Pauline Jolly and co-authors.
Following is a list of peer-reviewed articles looking at the apparent ability of mold toxicity to prevent individuals’ immune systems from keeping the HIV virus in check, along with links to media coverage.
Jolly PE, Inusah S, Lu B, Ellis WO, Nyarko A, Phillips TD, Williams JH. Association Between High Aflatoxin B1 Levels and High Viral Load in HIV-Positive People. World Mycotoxin Journal, 2013 (in press).
Since both aflatoxin and the human immunodeficiency virus (HIV) cause immune suppression, chronic exposure to aflatoxin in HIV-positive people could lead to higher levels of virus replication. This study was conducted to examine the association between aflatoxin B1 albumin adduct (AF-ALB) levels and HIV viral load. Antiretroviral naive HIV-positive people (314) with median CD4 count of 574 cells/μl blood (mean ± standard deviation = 630±277) were recruited in Kumasi, Ghana. Sociodemographic and health data, and blood samples were collected from participants. The plasma samples were tested for AF-ALB and HIV viral load. Univariate logistic regression analysis was conducted using viral load (high/low) as the outcome and AF-ALB quartiles as exposure. Multivariable logistic regression analysis was performed between quartile AF-ALB, viral load and CD4 adjusting for sex, age, and year of HIV diagnosis. Both univariate and multivariable logistic regression showed that viral load increased as AF-ALB levels increased. By univariate analysis, high viral load was 2.3 times more likely among persons in the third AF-ALB quartile (95% confidence interval (CI): 1.13, 4.51), and 2.9 times more likely among persons in the fourth AF-ALB quartile (CI: 1.41, 5.88), compared to persons in the first quartile. In the multivariable model, persons in the fourth AF-ALB quartile were about 2.6 times more likely to have high viral loads than persons in the first quartile (CI: 1.19-5.69). When AF-ALB and viral load were log transformed and linear regression analysis conducted, the univariate linear regression analysis showed that for each pg/mg increase in AF-ALB, viral load increased by approximately 1.6 copies/ml (P=0.0006). The association was marginally significant in the adjusted linear regression model (i.e. for each pg/mg increase in AF-ALB, the mean viral load increased by approximately 1.3 copies/ml, P=0.073). These data show strong and consistent increases in HIV viral load with increasing AF-ALB levels. Since the median and mean CD4 were greater than 500 cells for participants in each AF-ALB quartile, the results indicate that the immune modulating and virus transcription effects of aflatoxin may occur quite early in HIV infection, even while the CD4 count is still above 500, resulting in higher viral loads.
Here is some media coverage of this article.
July 22, 2013
The New York Times
Mold Toxins Tied to AIDS Epidemic
July 23, 2013
Is a Common Food Fungus Worsening the AIDS Epidemic?
July 23, 2013
Infection Control Today
Is a Common Food Fungus Worsening the AIDS Epidemic?
July 23, 2013
Food Quality News
Nut Mould May Spread AIDS
July 23, 2013
Study Reveals Fungus Coating on Stored Food May Worsen AIDS Epidemic
Obuseh FA, Jolly PE, Kulczycki A, Ehiri J, Waterbor J, Desmond RA, Preko PO, Jiang Y, Piyathilake CJ. Aflatoxin levels, plasma vitamins A and E concentrations, and their association with HIV and hepatitis B virus infections in Ghanaians: a cross-sectional study. J Int AIDS Soc. 2011 Nov 11;14:53. PMID: 22078415
Micronutrient deficiencies occur commonly in people infected with the human immunodeficiency virus. Since aflatoxin exposure also results in reduced levels of several micronutrients, HIV and aflatoxin may work synergistically to increase micronutrient deficiencies. However, there has been no report on the association between aflatoxin exposure and micronutrient deficiencies in HIV-infected people. We measured aflatoxin B1 albumin (AF-ALB) adduct levels and vitamins A and E concentrations in the plasma of HIV-positive and HIV-negative Ghanaians and examined the association of vitamins A and E with HIV status, aflatoxin levels and hepatitis B virus (HBV) infection.
METHODS: A cross-sectional study was conducted in which participants completed a demographic survey and gave a 20 mL blood sample for analysis of AF-ALB levels, vitamins A and E concentrations, CD4 counts, HIV viral load and HBV infection.
RESULTS: HIV-infected participants had significantly higher AF-ALB levels (median for HIV-positive and HIV-negative participants was 0.93 and 0.80 pmol/mg albumin, respectively; p <0.01) and significantly lower levels of vitamin A (-16.94 μg/dL; p <0.0001) and vitamin E (-0.22 mg/dL; p <0.001). For the total study group, higher AF-ALB was associated with significantly lower vitamin A (-4.83 μg/dL for every 0.1 pmol/mg increase in AF-ALB). HBV-infected people had significantly lower vitamin A (-5.66 μg/dL; p = 0.01). Vitamins A and E levels were inversely associated with HIV viral load (p = 0.02 for each), and low vitamin E was associated with lower CD4 counts (p = 0.004).
CONCLUSIONS: Our finding of the significant decrease in vitamin A associated with AF-ALB suggests that aflatoxin exposure significantly compromises the micronutrient status of people who are already facing overwhelming health problems, including HIV infection.
Jolly PE, Shuaib FM, Jiang Y, Preko P, Baidoo J, Stiles JK, Wang JS, Phillips TD, Williams JH. Association of high viral load and abnormal liver function with high aflatoxin B1-albumin adduct levels in HIV-positive Ghanaians: preliminary observations. Food Addit Contam Part A Chem Anal Control Expo Risk Assess. 2011 Sep;28(9):1224-34. PMID: 21749228
We examined the association between certain clinical factors and aflatoxin B(1)-albumin adduct (AF-ALB) levels in HIV-positive people. Plasma samples collected from 314 (155 HIV-positive and 159 HIV-negative) people were tested for AF-ALB levels, viral load, CD4+ T-cell count, liver function profile, malaria parasitaemia, and hepatitis B and C virus infections. HIV-positive participants were divided into high and low groups based on their median AF-ALB of 0.93 pmol mg(-1) albumin and multivariable logistic and linear regression methods used to assess relationships between clinical conditions and AF-ALB levels. Multivariable logistic regression showed statistically significant increased odds of having higher HIV viral loads (OR=2.84; 95% CI=1.17-7.78) and higher direct bilirubin levels (OR=5.47; 95% CI=1.03-22.85) among HIV-positive participants in the high AF-ALB group. There were also higher levels of total bilirubin and lower levels of albumin in association with high AF-ALB. Thus, aflatoxin exposure may contribute to high viral loads and abnormal liver function in HIV-positive people and so promote disease progression.
Williams JH, Grubb JA, Davis JW, Wang JS, Jolly PE, Ankrah NA, Ellis WO, Afriyie-Gyawu E, Johnson NM, Robinson AG, Phillips TD. HIV and hepatocellular and esophageal carcinomas related to consumption of mycotoxin-prone foods in sub-Saharan Africa. Am J Clin Nutr. 2010 Jul;92(1):154-60. PMID: 20484447
Promotion of the HIV epidemic by aflatoxin is postulated but not yet established. Sub-Saharan populations commonly consume food contaminated by mycotoxins, particularly aflatoxins (predominantly found in peanut, maize, rice, and cassava) and fumonisins, which occur primarily in maize. Aflatoxin promotes hepatocellular cancer, and fumonisin may promote esophageal cancer.
OBJECTIVES: This analysis was undertaken to test the hypotheses that consumption of mycotoxin-prone staple foods is 1) related to the incidence of HIV infection in Africa and 2) related to “signature” cancer rates confirming exposure to aflatoxins and fumonisins.
DESIGN: World Health Organization data for causes of death and the Food and Agriculture Organization per capita consumption data for commodities in sub-Saharan Africa were used. Per capita Gross Domestic Product and the percentage of Muslims (%Muslim) were the socioeconomic data sets exploited. Relations between causes of mortality, consumption of mycotoxin-prone foods, and socioeconomic variables were evaluated. Models for HIV transmission as a function of maize consumption and %Muslim were estimated.
RESULTS: HIV and esophageal cancer deaths were significantly related to maize but were inversely related to %Muslim and rice consumption. HIV infections were minimized (74 compared with 435/100,000 people; odds ratio: 2.41; 95% CI: 1.73, 3.24; P < or = 0.0001) by the combination of low maize consumption and above-median % Muslim. Hepatocellular cancer deaths were positively related to rice but negatively related to maize consumption.
CONCLUSIONS: HIV transmission frequency is positively associated with maize consumption in Africa. The relation between cancer and food suggests that fumonisin contamination rather than aflatoxin is the most likely factor in maize promoting HIV. Changes to the quality of maize may avoid up to 1,000,000 transmissions of HIV annually.
Kew MC. Hepatocellular carcinoma in African Blacks: Recent progress in etiology and pathogenesis. World J Hepatol. 2010 Feb 27;2(2):65-73. PMID: 21160975
Occult hepatitis B virus (HBV) infection was shown to be present in 75% of Black Africans with hepatocellular carcinoma (HCC) in whom the tumor was hitherto not thought to be caused by chronic HBV infection. The association between chronic HBV infection and the development of the tumor is thus even closer than was originally thought. HBV viral load was found to be significantly higher in patients with HCC than in Black African controls. As in other populations, HBV e antigen-positive patients with hepatocellular carcinoma had significantly higher viral loads than patients negative for this antigen. The significance of this finding is discussed. The risk for HCC development with genotype A of HBV, the predominant genotype in African isolates, has not been investigated. Genotype A was shown to be 4.5 times more likely than other genotypes to cause HCC in Black Africans, and tumours occurred at a significantly younger age. Increasing numbers of patients with human immunodeficiency virus (HIV) and HBV co-infection are being reported to develop HCC. A preliminary case/control comparison supports the belief that HIV co-infection enhances the hepatocarcinogenic potential of HBV. A study from The Gambia provides the first evidence that dietary exposure to aflatoxin B(1) may cause cirrhosis and that this may play a contributory role in the pathogenesis of aflatoxin-induced HCC. An animal model has provided experimental support for the clinical evidence that dietary iron overload in the African is directly hepatocarcinogenic, in addition to causing the tumor indirectly through the development of cirrhosis.
Jiang Y, Jolly PE, Preko P, Wang JS, Ellis WO, Phillips TD, Williams JH. Aflatoxin-related immune dysfunction in health and in human immunodeficiency virus disease. Clin Dev Immunol. 2008;2008:790309. PMID: 18695741
Both aflatoxin and the human immunodeficiency virus (HIV) cause immune suppression and millions of HIV-infected people in developing countries are chronically exposed to aflatoxin in their diets. We investigated the possible interaction of aflatoxin and HIV on immune suppression by comparing immune parameters in 116 HIV positive and 80 aged-matched HIV negative Ghanaians with high (> or =0.91 pmol/mg albumin) and low (<0.91 pmol/mg albumin) aflatoxin B1 albumin adduct (AF-ALB) levels. AF-ALB levels and HIV viral load were measured in plasma and the percentages of leukocyte immunophenotypes and cytokine expression were determined using flow cytometry. The cross-sectional comparisons found that (1) among both HIV positive and negative participants, high AF-ALB was associated with lower perforin expression on CD8+ T-cells (P = .012); (2) HIV positive participants with high AF-ALB had significantly lower percentages of CD4+ T regulatory cells (Tregs; P = .009) and naive CD4+ T cells (P = .029) compared to HIV positive participants with low AF-ALB; and (3) HIV positive participants with high AF-ALB had a significantly reduced percentage of B-cells (P = .03) compared to those with low AF-ALB. High AF-ALB appeared to accentuate some HIV associated changes in T-cell phenotypes and in B-cells in HIV positive participants.
Williams JH, Phillips TD, Jolly PE, Stiles JK, Jolly CM, Aggarwal D. Human aflatoxicosis in developing countries: a review of toxicology, exposure, potential health consequences, and interventions. Am J Clin Nutr. 2004 Nov;80(5):1106-22. PMID: 15531656
Aflatoxins are well recognized as a cause of liver cancer, but they have additional important toxic effects. In farm and laboratory animals, chronic exposure to aflatoxins compromises immunity and interferes with protein metabolism and multiple micronutrients that are critical to health. These effects have not been widely studied in humans, but the available information indicates that at least some of the effects observed in animals also occur in humans. The prevalence and level of human exposure to aflatoxins on a global scale have been reviewed, and the resulting conclusion was that approximately 4.5 billion persons living in developing countries are chronically exposed to largely uncontrolled amounts of the toxin. A limited amount of information shows that, at least in those locations where it has been studied, the existing aflatoxin exposure results in changes in nutrition and immunity. The aflatoxin exposure and the toxic affects of aflatoxins on immunity and nutrition combine to negatively affect health factors (including HIV infection) that account for >40% of the burden of disease in developing countries where a short lifespan is prevalent. Food systems and economics render developed-country approaches to the management of aflatoxins impractical in developing-country settings, but the strategy of using food additives to protect farm animals from the toxin may also provide effective and economical new approaches to protecting human populations.
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