The effects of exposures to mycotoxins on immunity in children: a systematic review

The majority of childhood deaths occur in low-income countries, with vaccine-preventable infections contributing greatly. Of the many possible environmental factors that could hamper a child's immune response, mycotoxins rank among the least studied in spite of the high exposure in vulnerable populations. Aflatoxin crosses the placenta, is secreted in breast milk and is consumed widely in weaning diets by children with developing organ systems. This review describes the effects of mycotoxin exposure on immunity in children that may contribute to sub-optimal vaccine effectiveness. We searched electronic databases and references of identified articles for relevant studies on the effects of mycotoxins on the immune system in children. Geographical location, publication year, study design, sample selection, sample size, mean age, route of exposure were extracted on a standard template. Quality was assessed using Joanna Briggs Institute tool for appraisal of systematic reviews for prevalence studies. Our analyses and reporting were conducted in accordance with the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. Out of 806 articles screened, 5 observational studies met criteria for inclusion for review. The definition of exposures to mycotoxins and outcomes varied across the studies. Exposure to mycotoxins was positively associated with low birth weight and concentration of antibodies to asexual malaria parasites and hepatitis B surface antigen, and negatively associated with death and sIgA, antibodies to pneumococcal antigen 23. Despite the far-reaching clinical and public health effects of mycotoxin exposure among children, studies on the effects of mycotoxin exposure on immunity in children were few, small and mostly of low quality. There is an urgent need for carefully designed prospective studies in this neglected field to inform policy interventions for child health in settings where exposure to mycotoxins is high

Approaching quality improvement at scale: a learning health system approach in Kenya.

In 2002, we identified major shortcomings in the management of sick newborns and children at the first referral or district hospital level in Kenya. Failure in the dissemination of knowledge and skills (and thus of translation of evidence informed policy) was a fundamental problem. To address this challenge between 2005 and 2012 we developed, implemented and studied: i. the national evidence-based clinical practice guidelines in the form of protocol booklets that can be disseminated at scale (and have recently described how this process matured over more than a decade); ii. the Emergency Triage Assessment and Treatment plus Admission Care course (that has been updated over time); iii. the standardised medical record forms including checklists of key symptoms and signs that are key elements of the protocols and help define the nature and severity of common illnesses (also updated over time). The effect of implementing these tools as part of a multifaceted strategy including outreach, audit and feedback to improve guideline adherence was tested between 2006 and 2009 and proven effective in a cluster randomised trial.6 In recent years, we have been able to document wider adoption of the protocols, training and record forms (including uptake outside Kenya) with some evidence of improvements in the quality of district hospital care, measured as adherence to guidelines, beyond centres directly engaged in research.</p

The effects of aflatoxin exposure on Hepatitis B-vaccine induced immunity in Kenyan children

Background: Globally, approximately three million children die each year from vaccine preventable infectious diseases mainly in developing countries. Despite the success of the expanded immunization program, not all infants and children around the world develop the same protective immune response to the same vaccine. A vaccine must induce a response over the basal immune response that may be driven by population-specific, environmental or socio-economic factors. Mycotoxins like aflatoxins are immune suppressants that are confirmed to interfere with both cell-mediated and acquired immunity. The mechanism of aflatoxin toxicity is through the binding of the bio-activated AFB1-8, 9-epoxide to cellular macromolecules. Methods: We studied Hepatitis B surface antibodies [anti-HBs] levels to explore the immune modulation effects of dietary exposure to aflatoxins in children aged between one and fourteen years in Kenya. Hepatitis B vaccine was introduced for routine administration for Kenyan infants in November 2001. To assess the effects of aflatoxin on immunogenicity of childhood vaccines Aflatoxin B1-lysine in blood serum samples were determined using High Performance Liquid Chromatography with Fluorescence detection while anti-HBs were measured using Bio-ELISA anti-HBs kit. Results: The mean ± SD of AFB1-lysine adducts in our study population was 45.38 ± 87.03 pg/mg of albumin while the geometric mean was 20.40 pg/mg. The distribution of AFB1-lysine adducts was skewed to the right. Only 98/205 (47.8%) of the study population tested positive for Hepatitis B surface antibodies. From regression analysis, we noted that for every unit rise in serum aflatoxin level, anti-HBs dropped by 0.91 mIU/ml (−0.9110038; 95% C.I −1.604948, −0.21706). Conclusion: Despite high coverage of routine immunization, less than half of the study population had developed immunity to HepB. Exposure to aflatoxin was high and weakly associated with low anti-HBs antibodies. These findings highlight a potentially significant role for environmental factors that may contribute to vaccine effectiveness warranting further research

Approaching quality improvement at scale: a learning health system approach in Kenya.

In 2002, we identified major shortcomings in the management of sick newborns and children at the first referral or district hospital level in Kenya. Failure in the dissemination of knowledge and skills (and thus of translation of evidence informed policy) was a fundamental problem. To address this challenge between 2005 and 2012 we developed, implemented and studied: i. the national evidence-based clinical practice guidelines in the form of protocol booklets that can be disseminated at scale (and have recently described how this process matured over more than a decade); ii. the Emergency Triage Assessment and Treatment plus Admission Care course (that has been updated over time); iii. the standardised medical record forms including checklists of key symptoms and signs that are key elements of the protocols and help define the nature and severity of common illnesses (also updated over time). The effect of implementing these tools as part of a multifaceted strategy including outreach, audit and feedback to improve guideline adherence was tested between 2006 and 2009 and proven effective in a cluster randomised trial.6 In recent years, we have been able to document wider adoption of the protocols, training and record forms (including uptake outside Kenya) with some evidence of improvements in the quality of district hospital care, measured as adherence to guidelines, beyond centres directly engaged in research.</p

Treatment of Burkitt lymphoma in equatorial Africa using a simple three-drug combination followed by a salvage regimen for patients with persistent or recurrent disease.

Prior to the introduction of the International Network for Cancer Treatment and Research (INCTR) protocol INCTR 03-06, survival of patients with Burkitt lymphoma at four tertiary care centres in equatorial Africa was probably no more than 10-20%. The results reported here for 356 patients have demonstrated marked improvement in survival through the use of a uniform treatment protocol consisting of cyclophosphamide, methotrexate, vincristine, and intrathecal therapy, and the introduction of non-cross resistant second-line (salvage) therapy, consisting of ifosfamide, mesna, etoposide and cytarabine, when patients failed to achieve a complete response to first-line therapy or relapsed early. Overall survival rates of 67% and 62% were observed at 1 and 2 years (relapse is rare after 1 year of remission). Of interest was the small impact of cerebrospinal fluid (CSF) and bone marrow involvement on outcome. However, the presence or absence of abdominal involvement clearly defined two prognostic groups. An additional finding was the association between CSF pleocytosis and orbital tumours, suggesting that spread of tumour cells to the central nervous system may sometimes occur via direct involvement of cranial nerves in the orbit. Survival rates may be increased in patients with abdominal involvement by combining first- and second-line therapy, but verification will require a further clinical study