Health effects of chronic aflatoxin exposure Ramou Njie MD, PhD

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1 Health effects of chronic aflatoxin exposure Ramou Njie MD, PhD & MRC Unit The Gambia

2 OUTLINE Aflatoxins Maternal exposure and birth outcomes Impact of exposure on infant growth Impact of exposure in adults Gut health Immune-suppression Hepato-carcinogenesis Summary & conclusions

3 AFLATOXINS Metabolites of Aspergillus flavus and Aspergillus parasiticus fungi Frequent contaminants of staple foods in Africa esp. maize, groundnuts & sorghum Contamination occurs pre- or post-harvest Serious public health hazard to humans

4 Global prediction maps of AFB-1 contamination, 2013 Groundnut-growing areas Maize-growing areas Source: Logrieco, AF, 2016

5 Aflatoxins OUTLINE Maternal exposure and birth outcomes

6 Aflatoxin exposure in pregnant Gambian women Castelino et al, 2014

7 Aflatoxins: maternal exposure & birth outcomes Maternal exposure in animal models linked to: Low birth weight Neural tube defects Skeletal malformations (IARC 1993, 2002)

8 OUTLINE Aflatoxins Maternal exposure and birth outcomes Impact of exposure on infant growth

9 Aflatoxins: impact on infant growth Smith et al, 2012

10 Country prevalence estimates for stunting among children < 5 years Source: UNICEF-WHO-The World Bank (2012)

11 Aflatoxin exposure and child growth: W/Africa, USA and Canada Turner, 2013

12 OUTLINE Aflatoxins Maternal exposure and birth outcomes Impact of exposure on infant growth Impact of exposure in adults Gut health Immune-suppression Hepato-carcinogenesis

13 Aflatoxin exposure and gut health Few Human studies! However, in animal models, exposure resulted in: Reduced intestinal absorptive capacity Inhibition of protein synthesis (Applegate et al, 2009) Modification of gut microbiota by AFB1 in a dose-dependent manner (Wang et al 2016)

14 Aflatoxin exposure: effects on immune function Limited human data + animal studies show that AFB-1 exposure: Leads to upregulation of pro-inflammatory cytokines Is associated with impairment of phagocytosis & bactericidal activity Is associated with increased susceptibility to infections and reduced response to vaccines Jiang, et al 2005 Meissonnier et al, 2006

15 Aflatoxin exposure and hepatocarcinogenesis Aflatoxins classified as group 1 carcinogen (IARC 1993, 2002) AFB1 causally related to development of HCC with M:F of 3:1 Dose-dependent exposure in liver disease with increased 10-fold increase in HCC incidence if HBsAgpositive RR of HCC: Aflatoxin exposure only=3.4 HBsAg-positive only =7.3 Aflatoxin Exp. AND HBsAg+ve =59.4 IARC WGR-no 9, 2015

16 Aflatoxin exposure and hepatocarcinogenesis Hamid, et al, 2013 Kumar, V, 2015

17 Seasonal Variation in TP53 R249S-Mutated Serum DNA with AFP Exposure and HBV infection - Gambia Table 2. Subjects positive for serum R249S mutation by season [n/total (%)]. Period HBsAg negative-a HBsAg positive OR (95% CI) October July 58/236 (25) 106/237 (45) 2.49 (1.68, 3.69)b October March (higher AFB1 exposure) 45/134 (34) 43/134 (32) 0.94 (0.56, 1.57) April July (lower AFB1 exposure) 13/102 (13) 63/103 (61) 10.9 (5.35, 22.34) ORs are adjusted for age and sex. a. Used as reference category for OR determination. b. Adjusted for seasonality Villar, et al, 2011

18 Summary conclusions-1 Long term exposure to food and feeds contaminated with aflatoxins pose serious public health hazards in Africa, leading to high levels of mortality and morbidity Significant reduction in AFP exposure can be achieved through implementation of low-technology approaches at the subsistence farm level in Africa (Turner el al, 2005) Further studies are warranted to correlate mycotoxin exposure and human health possibly via identification and validation of suitable biomarkers

19 Summary conclusions-2 Urgent concerted action by multiple agencies in the agriculture, health, food safety sectors (including regulatory bodies)is necessary to protect human health from mycotoxin exposure. IARC ready to work with WHO and WHO member states to translate knowledge acquired so far through to action at national level in high exposure countries.

20 Acknowledgements Professor Christopher Wild, IARC Director IARC working group on mycotoxin control in LMIC, 2015 Partnership for aflatoxin control in Africa (PACA) African Union Commission (AUC) Global alliance for improved nutrition (GAIN) AMREF health Africa USAID

21 The Gambia