Clinical Infectious Diseases Publishes MAL-ED Goals, Methods and Site-specific Characteristics

December 18th, 2014

Inadequate nutrition has been associated with half of deaths worldwide in children under age five. In addition, write investigators from the MAL-ED Network in a special section of the November 1 edition of Clinical Infectious Diseases, the long-term effects of “undernutrition” in young children “have been associated with cognitive and physical growth deficits across multiple generations and have been thought to suppress immunity to further infections and to reduce the efficacy of childhood vaccines.”

MAL-ED, a project supported by the Bill & Melinda Gates Foundation and led by the Foundation for the National Institutes of Health and the NIH Fogarty International Center, has sites in eight countries with historically high incidence of undernutrition and diarrheal disease. Researchers are studying factors such as enteric infections and other illness indicators, diet and micronutrient levels, socioeconomic status, gut function, and the environment to determine the interrelationships among these factors and their impact on outcomes such as physical growth, cognitive development and vaccine response in the first two years of life, in unprecedented detail. Central to the study is the hypothesis that enteropathogen infection causes intestinal inflammation leading to inadequate functioning of the gut for nutrient absorption, and producing a child that is undernourished and that may suffer from the consequences of undernutrition.

The 19 articles in the special section (freely available at look at the characteristics of each study site in resource-poor environments in Bangladesh, Brazil, India, Nepal, Pakistan, Peru, South Africa and Tanzania along with methods utilized for the project.

MAL-ED Consortium 5th Annual Meeting

July 11th, 2013

The MAL-ED Consortium held its 5th Annual Meeting on May 8-10, 2013 at the Bill & Melinda Gates Foundation Conference Center in Seattle, Washington. Over 130 investigators from around the world were invited to participate in the workshop-like sessions. The meeting’s oral and poster presentations, breakout sessions and panel discussions focused on scientific progress, data analyses, and future plans for the MAL-ED Project – formally titled the Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health Project. Participants included members of the MAL-ED Network (international and national collaborators on the MAL-ED project), investigators representing MAL-ED companion projects, program officials from the Bill & Melinda Gates Foundation (BMGF; the Consortium’s financial supporter) and other invited guests with close ties to the MAL-ED Project, including members of the project’s Scientific Advisory Committee.

The five-year MAL-ED clinical research project is designed to investigate birth cohorts in resource-constrained geographic areas within eight countries where there is a high prevalence of malnutrition (specifically, undernutrition), enteric infections and associated diseases, and shortfalls in physical growth and cognitive development. Staggered enrollment for the birth cohorts began at the end of 2009; follow-up of the children in the study to 24 months of age will conclude at the end of February 2014. The overarching goals of the project are to measure nutritional status and enteric infections; and, to determine their relationship with gut function and inflammation, and their effects on physical and cognitive development as well as on immune responsiveness to scheduled oral and parenteral vaccinations. Individual sessions at the 2013 annual meeting presented results from preliminary analyses of longitudinally collected measures of diarrheal burden, enteric infections (number of different pathogens and duration of fecal shedding), nutrition, and gut function biomarkers; and, their relationship to outcome measures such as physical growth (length, weight and head circumference), cognitive development and responses to vaccinations.

MAL-ED network-wide data analyses may reveal potential intervention approaches that are generalizable across the multiple geographies and cultures involved in the study to improve the health of well-being of all young children living in under resourced areas. However, given the extensive differences across the sites with respect to environmental and cultural factors, individual study site analyses are likely to identify potential site-specific interventions. Preliminary analyses, network-wide and site-specific, examining the effects of nutrition (breastfeeding practices, micronutrients), pathogen exposure, child caregiver interactions, diarrhea, maternal depression, and water, sanitation and child cleanliness on project outcomes (cognitive development, growth, gut function, and vaccine response) were presented during at the three-day annual meeting. Many ideas and strategies on data modeling, for examining associations between measurements and outcomes, and for identifying appropriate statistical methodologies were discussed during the meeting.

Although the annual meeting was primarily focused on MAL-ED project data, there was time devoted to updates from the MAL-ED companion projects – projects funded separately by BMGF that are related to the goals of MAL-ED and that leverage MAL-ED project data, samples and resources. Companion project reporting on their progress included the Quantitative Molecular Diagnostics for Enteropathogens; Breast Milk, Gut Microbiome and Immunity (BMMI); Mycotoxins and Growth Impairment; Performance of Rotavirus and Oral polio Vaccines in Developing Countries (PROVIDE); and a potential new project on genomic sequencing of human Norovirus strains.

At the conclusion of the meeting, the MAL-ED Scientific Advisory Committee acknowledged strengths of the Network, which include the development and implementation of harmonized research protocols, and the interactive nature of the network investigators, while acknowledging that because of the length (in time) of the project and its complexity, scientific papers are only just starting to emerge. In addition, a conversation was started among the MAL-ED Network members to identify ways in which the MAL-ED data and research infrastructure can be used to identify new research hypotheses, to design and implement studies that will utilize the knowledge gained, to test potential intervention strategies, and to develop new funding strategies to accomplish these goals.

Many thanks to everyone who contributed to the success of this meeting – from behind the scenes, the speaker’s podium, and the poster sessions – and especially to those dedicated to finding solutions for improving the health of children worldwide.

MAL-ED site in Vellore, India featured by Bloomberg News

June 18th, 2013

The five-year MAL-ED research project is being conducted in resource-constrained geographic areas within eight countries where there is a high prevalence of malnutrition (specifically, undernutrition), enteric infections and associated diseases (Project Overview). Dr. Gagandeep Kang of Christian Medical College is the Principal Investigator at the Vellore, India MAL-ED site featured in this article in Bloomberg News.  The MAL-ED Network of internationally recognized investigators is executing the study as a collaborative project supported by the Bill & Melinda Gates Foundation, the Foundation for the National Institutes of Health, and the NIH Fogarty International Center.

Markers of Gut Inflammation May Predict Stunting in Infants

May 16th, 2013
Mal-Ed field sites

Mal-Ed field sites

Biological markers – biomarkers – of gut inflammation found in stool may help identify young children at risk for stunted growth and target them for appropriate medical intervention.

In resource poor areas, like those in many regions of the developing world, living conditions can have a negative impact on the growth and development, and the overall health of children. These areas are often characterized by a lack of clean drinking water and poor sanitary conditions leading to an increased risk of intestinal infections and diarrheal disease, as well as other infectious diseases. Children in these areas are particularly at risk during the first two to three years of life when so much of their development (both physical and mental) occurs. When exposure to these conditions is combined with an insufficient diet, either in quantity, quality, or diversity, infants often experience less than optimal growth and development. Chronic undernutrition is not only due to not having enough to eat (caloric content); it is often due to the lack of adequate amounts of needed vitamins, minerals and other micronutrients that are provided by a diverse and balanced diet.

Undernutrition can result in inhibited growth in length (stunted) and/or weight (underweight) when compared to optimal growth as defined by the World Health Organization. In addition to inadequate diet, undernutrition may result in a limited ability to absorb important nutrients through the wall of the intestine. Limited absorption of nutrients may be caused by chronic inflammation of the gut due to repeated and prolonged exposure to enteric infections – viruses, bacteria, parasites – that may damage the intestine and inhibit normal nutrient absorption. Dr. Margaret Kosek of the Johns Hopkins Bloomberg School of Public Health and her colleagues in the MAL-ED Network hypothesized “…that intestinal inflammation, likely resulting from frequent enteric infections, is a prominent contributor to growth failure in infancy.”

The study was designed to determine whether increased gut inflammation at a specific point in time can be used to predict future growth failure. The ability to predict a potentially severe decrease in the rate of growth of a child might enable clinicians to intervene before irreparable damage is done. Linear growth failure (decreased change in height over a defined period of time) was chosen as an outcome growth measure because it is a better marker of a physiologic insult than changes in weight and may be a better predictor of permanent loss of human potential.

Using non-diarrheal stool samples from infants enrolled in the MAL-ED birth cohort project, an eight-site project designed to evaluate the interactions of malnutrition and enteric infections and their effects on growth and cognitive development, the study determined the levels of three indicators of inflammation (biomarkers): alpha-1-antitrypsin (AAT), neopterin (NEO), and myeloperoxidase (MPO). AAT, a protein normally found in the blood stream, can move from blood vessels into stool when the wall of the gut is damaged. Increased production of NEO by immune system cells in the gut is an indicator of an active adaptive immune response associated with inflammation. Similarly, increased levels of MPO indicate increased innate immune response activity.

The research results indicated that elevated levels of AAT, NEO or MPO in the stool of infants were associated with poorer growth over the subsequent six months. Moreover, when a composite score of all three biomarkers combined was used an even greater association with growth shortfalls was observed. The relationship between the levels of these biomarkers and growth outcomes were similar across the diverse conditions found at the eight study sites.

Test kits used to determine the levels of these biomarkers in stool are commercially available, relatively easy to use and affordable. The MAL-ED Network investigators hope that these or other biomarkers of gut inflammation could be used by clinicians to identify children at risk of becoming stunted and who could be targeted for appropriate interventions aimed at reducing gut inflammation, malnutrition and growth shortfalls.

Read the open access full-text scientific article: Kosek M, Haque R, Lima A, Babji S, Shrestha S, Qureshi S, Amidou S, Mduma E, Lee G, Yori PP, Guerrant RL, Bhutta Z, Mason C, Kang G, Kabir M, Amour C, Bessong P, Turab A, Seidman J, Olortegui MP, Quetz J, Lang D, Gratz J, Miller M, and Gottlieb M for the MAL-ED Network. Fecal markers of intestinal inflammation and permeability associated with the subsequent acquisition of linear growth deficits in infants. Am. J. Trop. Med. Hyg., 88(2), 2013, pp.390-396.

MAL-ED Consortium 4th Annual Meeting

June 8th, 2012

The MAL-ED Consortium held its 4th Annual Meeting on May 14-16, 2012 at the Intercontinental Harbor Court in Baltimore, Maryland. Read the rest of this entry »

Keystone Meeting: Malnutrition, Gut-Microbial Interactions and Mucosal Immunity to Vaccines

April 12th, 2011

This meeting, to be held in New Delhi, India from November 7 -11th, 2011 is being organized by two of our MAL-ED investigators, Gagandeep Kang and William Petri among other notable investigators. Read the rest of this entry »

Translational Approaches for Pharmacotherapy Development for Acute Diarrhea Workshop

April 12th, 2011

NIDDK is organizing this workshop which will be held from September 25 – 27th, 2011 in Bethesda Md, USA. Read the rest of this entry »

ASTMH Meeting abstract submission deadline May 17th, 2011

April 7th, 2011

The ASTMH Meeting will take place in Philadelphia this year December 4-8, 2011. The MAL-ED Scientific Administrative core has submitted a proposal for a  MAL-ED related symposium but we encourage all investigators to submit abstracts for presentations and/or posters. The deadline for abstract submission and for the Young Investigators Award is May 17th. Details about the meeting can be found here

3rd Annual Meeting May 2-4, 2011 Seattle, WA

January 3rd, 2011

The 3rd Annual MAL-ED meeting has been scheduled for May 2-4, 2011. Please mark your calendars.

The 2nd Annual MAL-ED Meeting: June 17-19, 2010

June 24th, 2010

The 2nd Annual MAL-ED Meeting was held from June 17 – 19, 2010 at the Hyatt Regency Bethesda hotel in Bethesda, MD, USA. Read the rest of this entry »

MAL-ED Symposium at ASTMH Meeting November 22, 2009

November 24th, 2009

The MAL-ED Network held a symposium at the annual ASTMH meeting in Washington D.C. on November 22, 2009. Although the symposium was scheduled at 8am on the very last day of the meeting, we had a very good turn out. Michael Gottlieb, representing FNIH, and Mark Miller, representing FIC, introduced the MAL-ED Project and set the tone for the other presenters. Read the rest of this entry »

MAL-ED at 2009 ASTMH Meeting

September 23rd, 2009

The American Society of Tropical Medicine and Hygiene (ASTMH) hosted its annual meeting in Washington DC, USA from November 18-22, 2009. Read the rest of this entry »

Inaugural Meeting a Great Success!

February 25th, 2009

From February 15 – 18, 2009, over 70 MAL-ED Consortium members from Africa, Asia and the Americas came to Bethesda, Maryland USA to mark the beginning of the MAL-ED 5 year-funded project and to work on finalizing the standard operating procedures and harmonized protocols that all the research sites will share. Read the rest of this entry »

The Interactions of Malnutrition and Enteric Infections and the Consequences for Child Health is Presented at the ASTMH 57th Annual Meeting

December 22nd, 2008

In December 7-11, 2008 the project was presented at 57th Meeting of The American Society of Tropical Medicine and Hygiene in New Orleans, Louisiana USA.

Inaugural Meeting of the MAL-ED Consortium in February 15-18, 2009 in Washington, DC

December 22nd, 2008

The goals of the meeting are to: Read the rest of this entry »