WASH Impacts on Maternal and Child Mortality, Malnutrition and Impaired Development
Water, Sanitation & Hygiene (WASH) Impacts on Maternal and Child Mortality, Malnutrition and Impaired Development Tom Mahin – Centre for Affordable Water & Sanitation Technology Rachel Peletz - London School of Hygiene & Tropical Medicine CAWST Learning Exchange June 28, 2010 By Pierre Holtz UNICEF
Situation in 2010 in Sub-Saharan Africa “Over 13,000 mothers,newborns, and children die every day in sub-Saharan Africa” - Friberg et al. (2010) Sub-Saharan Africa’s Mothers, Newborns, and Children: How Many Lives Could Be Saved with Targeted Health Interventions? PLOS Medicine Vol 7, Issue 6, e1000295
Deaths for Children < 5 Years Old & Malnutrition From: Müller and Krawinkel (2005) “Malnutrition and health in developing countries” CMAJ 173 (3)
Diarrhea May Increase Acute Lower Respiratory Infections“In this analysis, we found that diarrhoea may increase the risk of ALRI (Acute Lower Respiratory Infections) … in malnourished child populations. The results suggest that prevention of diarrhoea may contribute to a reduction in ALRI, the leading immediate cause of death in children.” Schmidt et al. (2009) “Recent diarrhoeal illness and risk of lower respiratory infections in children under the age of 5 years” International Journal of Epidemiology 38:766–772
Diarrhea and Pneumonia - Infants• “For example, comorbidity of pneumonia and diarrhea is high, suggesting shared risk “ factors and exacerbation of risk due to coexistence of multiple morbidities” From: Nutrition and Health in Developing Countries 2nd Edition, Humana Press, Chapter 4 “Infant Mortality” by Parul Christian
Risk of Acute Respiratory Infections for Children vs. Diarrhea Days over Last 14 Days (Ghana) Schmidt et al. (2009) “Recent diarrhoeal illness and risk of lower respiratory infections in children under the age of 5 years” International Journal of Epidemiology 38:766–772
Waterborne Infections, Malnutrition and Impaired Development• “A rate-limiting step in achieving normal nutrition may be impaired absorptive function due to multiple repeated enteric infections. This is especially problematic in children whose diets are marginal.”• “In malnourished individuals, the infections are even more devastating…Malnutrition is a major contributor to mortality and is increasingly recognized as a cause of, potentially lifelong, functional disability.” - Guerrant et al. (2008) “Malnutrition as an enteric infectious disease with long-term effects on child development” Nutr Rev. 66(9): 487–505.
Enteric Pathogens Impair Absorption of Nutrients • ”The morbidity impact of enteric pathogens is related to their ability to directly impair intestinal absorption as well as their ability to cause diarrhea, both of which impair nutritional status” • “The absorptive function of a healthy intestinal tract is especially critical in the first few formative years of life. This is because, unlike many other species, the predominant brain and synapse development in humans occurs in the first 2 years after birth.” - Petri et al. (2008) “Enteric infections, diarrhea, and their impact on function and development” J Clin Invest. April 1; 118(4): 1277–1290.
Modified from Caulfield and Black Chapter 5 - Zinc deficiency inComparative Quantification of Health Risks WHO 2004
Kinney et al.(2010) “Sub-Saharan Africa’s Mothers, Newborns, and Children: Where and Why Do They Die?” PLOS Medicine Vol 7, Iss 6 e1000294
Kinney et al.(2010) “Sub-Saharan Africa’s Mothers, Newborns, and Children: Whereand Why Do They Die?” PLOS Medicine Vol 7, Iss 6 e1000294
Key After Birth InterventionsRecommended by Friberg et al. Friberg et al. (2010) Sub-Saharan Africa’s Mothers, Newborns, and Children: How ManyLives Could Be Saved with Targeted Health Interventions? PLOS Medicine Vol 7, Issue 6,
Part I Diarrhea & Waterborne Pathogens asContributors to Maternal and Child Malnutrition
Definitions• Malabsorption – reduced absorption of nutrients• Persistent diarrhea – diarrhea lasting > 14 days• Stunting – a longer-term measure of malnutrition. Defined as the height/length for age (HAZ) below minus two standard deviations from the standard median height for age• Weight for age - weight for age (WAZ) or “underweight” is a shorter-term measurement of malnutrition• Protein–energy malnutrition - measurements that fall below 2 standard deviations under the normal HAZ, WAZ or WHZ (weight for height or wasting)
Malnutrition• Malnutrition has two constituents: 1. Protein–energy malnutrition 2. Micronutrient deficiencies - e.g. iron (anemia), vitamin A and zinc• Malnutrition - “It is globally the most important risk factor for illness and death, with hundreds of millions of pregnant women and young children particularly affected.” – from Müller and Krawinkel (2005) “Malnutrition and health in developing countries” Canadian Medic. Assoc. Journ. 173 (3)
Malnutrition and Pathogens - Persistent Infections“Not only are the effects of malnutrition complex,its causes are as well. Worrisome food insecurityis obviously critical, but a factor that ispotentially even more important (especially forchildren with marginal intake) is the inability toabsorb what they do take in because ofrepeated or persistent intestinal infections.”– Guerrant et al. (2008) Malnutrition as an enteric infectious disease with long-term effects on child development Nutr Rev. September; 66(9): 487–505.
A Substantial Proportion of Malnutrition is Due to Repeated Enteric Infections• “A substantial proportion of global malnutrition is due to impaired intestinal absorptive function resulting from multiple and repeated enteric infections”• “These include recurrent acute … as well as persistent infections, even those without overt liquid diarrhea.” - Guerrant et al. (2008) “Malnutrition as an enteric infectious disease with long-term effects on child development” Nutr Rev.
Nutrient Malabsorption“Impaired … host immune responses and disruptedintestinal barrier function due to malnutrition anddiarrheal illnesses likely combine to renderweaning children susceptible to repeated boutsof enteric infections leading to intestinal injury andconsequently, nutrient malabsorption duringthe developmentally critical first 2 years of life.”- Guerrant et al. (2008) “Malnutrition as an enteric infectious disease with long-term effects on child development” Nutr Rev.
Malnutrition and Developing Countries• “The high prevalence of bacterial and parasitic diseases in developing countries contributes greatly to malnutrition there. Similarly, malnutrition increases one’s susceptibility to and severity of infections, and is thus a major component of illness and death from disease.”• “Malnutrition is …the most important risk factor for the burden of disease in developing countries. It is indirectly responsible for about half of all deaths in young children. The risk of death is directly correlated with the degree of malnutrition.” - Müller and Krawinkel (2005) “Malnutrition and health in developing countries” Canadian Medic. Assoc. Journ. 173 (3)
Malnutrition – Waterborne Pathogens Cycle Modified from Guerrant et al. (2008) “Malnutrition as an enteric infectious disease with long-term effects on child development” Nutr Rev.
Reduced Weight Gain vs. % of Days with Diarrhea for Malnourished Children Petri et al. (2008) “Enteric infections, diarrhea, and their impact on function and development” The Journal of Clinical Investigation
Adapted from: “Tackling the silent killer, The case for sanitation” by WaterAid (2008)
Weight-for-age (WAZ) as a Proxy for Diarrhea in Last 14 Days Schmidt et al. (2009) “Weight-for-age z-score as a proxy marker for diarrhoea in epidemiological studies” J Epidemiol Community Health. Dec 1 (Epub)
Lack of Full Success of Dietary Approaches• “Under the plausible assumption that children grow poorly because they do not eat enough of the right foods, research efforts have focused on identifying dietary solutions. Numerous studies have tested many nutrient-dense foods and supplements, nutrition education interventions, and infant feeding behavioural change strategies.”• “A recent review of 38 of these studies showed that …none of these interventions achieved normal growth: the growth effect of even the most successful of these studies (~ +0·7 Z) is equivalent to about 1/3 of the average deficit of Asian & African children (~ –2·0 Z).” – Humphrey J H (2009) Lancet 374: 1032-35
Maternal Undernutrition Low Birthweight - Infant Mortality• “Low birthweight is related to maternal undernutrition; it contributes to infections and asphyxia, which together account for 60 per cent of neonatal deaths”.• “An infant born weighing between 1,500 and 2,000 grams is eight times more likely to die than an infant born with an adequate weight of at least 2,500 grams.” – UNICEF 2009
From: Müller and Krawinkel(2005) “Malnutrition andhealth in developing countries”CMAJ 173 (3)
Malnutrition, Children and Water• “Severe malnutrition ... occurs almost exclusively in children.”• “…in order to address infectious diseases as a cause of protein–energy malnutrition it is likewise important to promote breast- feeding, improve the water supply and sanitation, and educate people about hygiene.” - from: Müller and Krawinkel (2005) “Malnutrition and health in developing countries” Canadian Medic. Assoc. Journ. 173 (3)
Protein–energy Malnutrition and Diarrhea • “Protein–energy malnutrition and diarrhea typically interact in a vicious cycle…” Modified from: Müller and Krawinkel (2005) “Malnutrition and health in developing countries” CMAJ” 173 (3)
Diarrhea as a Major Risk Factor forSevere Malnutrition in South Africa Saloojee et al. (2007) “What’s new? Investigating risk factors for severe childhood malnutrition in a high HIV prevalence South African setting” Scandinavian Journal of Public Health, 35(Suppl 69): 96–106
UnderweightAdapted from Shrimpton et al. (2001) “Worldwide Timing of Growth Faltering:Implications for Nutritional Interventions” PEDIATRICS Vol. 107 No. 5 May
StuntingAdapted from Shrimpton et al. (2001) “Worldwide Timing of Growth Faltering:Implications for Nutritional Interventions” PEDIATRICS Vol. 107 No. 5 May
Once Children are Stunted, It’s Difficult to Catch Up Later On• “Whether a child has experienced chronic nutritional deficiencies and frequent bouts of illness in early life is best indicated by the infant’s growth in length and the child’s growth in height. Day-to- day nutritional deficiencies over a period of time lead to diminished, or stunted, growth.• “Once children are stunted, it is difficult for them to catch up in height later on, especially if they are living in conditions that prevail in many developing countries.” - TRACKING PROGRESS ON CHILD AND MATERNAL NUTRITION, A survival and development priority” (2009) UNICEF
Mortality Risksfor 2,446 Hospitalized Children (Uganda) TUMWINE et al. (2003) “CRYPTOSPORIDIUM PARVUM IN CHILDREN WITH DIARRHEA IN MULAGO HOSPITAL, KAMPALA, UGANDA” Am. J. Trop. Med. Hyg., 68(6),, 710–715
Cryptosporidium Infection Rates in Infants in India and Jamaica Das et al. (2006) “Molecular Characterization of Cryptosporidium spp. from Children in Kolkata, India” LINDO et al. (1998) “EPIDEMIOLOGY OF JOURNAL OF CLINICAL GIARDIASIS AND CRYPTOSPORIDIOSIS IN MICROBIOLOGY,, 44, No. 11 JAMAICA” Am. J. Trop. Med. Hyg., 59(5), 717–721
Cryptosporidium – High Infection Rates in Children < 24 Months (Pakistan) IQBAL et al. (1999) “CRYPTOSPORIDIUM INFECTION IN YOUNG CHILDREN WITH DIARRHEA IN RAWALPINDI, PAKISTAN” Am. J. Trop. Med. Hyg., 60(5), 868–870
CDC Study of Pathogen Antibodies in Children (Guatemala) STEINBERG et al. (2004) “PREVALENCE OF INFECTION WITH WATERBORNE PATHOGENS: A SEROEPIDEMIOLOGIC STUDY IN CHILDREN 6–36 MONTHS OLD IN S JUAN” SACATEPEQUEZ, GUATEMALA Am. J. Trop. Med. Hyg., 70(1), pp. 83–88
Common Waterborne Protozoan Pathogens Young Children (Pakistan) Adapted from IQBAL et al. (1999) “CRYPTOSPORIDIUM INFECTION IN YOUNG CHILDREN WITH DIARRHEA IN RAWALPINDI, PAKISTAN” Am. J. Trop. Med. Hyg., 60(5), 868–870
Impact of Cryptosporidium Infection onAbility of Intestines to Absorb Nutrients Guerrant et al. (2008) “Malnutrition as an enteric infectious disease with long-term effects on child development” Nutr Rev.
Relative Risk Factors for Acute Malnutrition (Botswana) Mach et al. (2009) “Population-Based Study of a Widespread Outbreak of Diarrhea Associated with Increased Mortality and Malnutrition in Botswana, January – March, 2006” Am. J. Trop. Med. Hyg., 80(5),pp. 812-818
Asymptomatic Cryptosporidium Infection and Malnutrition• Cryptosporidium infection can be associated with malnutrition with or without overt diarrhea (symptomatic or asymptomatic).
Impact of Asymptomatic Cryptosporidiosis on Monthly Weight Gain in Peruvian Infants Checkleyet al. (1997). "Asymptomatic and symptomatic cryptosporidiosis: their acute effect on weight gain in Peruvian children." Am J Epidemiol 145(2): 156-163.
Repeated Enteric Infections Reduce Availability of NutrientsRepeated enteric pathogen infections reduce availability of nutrients due to:• Intestinal malabsorption - studies show that damage to the small intestine mucosa (resulting in decreased permeability) occurs as a result of pathogen infection and resulting diarrhea.• Increased losses due to diarrhea• Increased metabolic needs
Diarrhea Outbreak Followed bySevere Acute Malnutrition (Botswana) Mach et al. (2009) “Population-Based Study of a Widespread Outbreak of Diarrhea Associated with Increased Mortality and Malnutrition in Botswana, January – March, 2006” Am. J. Trop. Med. Hyg., 80(5), 812-818
HIV Negative Patients With Malabsorption Syndrome Adapted from: Behera et al. Parasites in Patients with Malabsorption Syndrome: A Clinical Study in Children and Adults Dig Dis Sci (2008) 53:672–679
Top 3 Pathogens Associated with Malnourished Zambian Children with Persistent Diarrhea Amadi et al. (2001) “Intestinal and Systemic Infection, HIV, and Mortality in Zambian Children With Persistent Diarrhea and Malnutrition” Journal of Pediatric Gastroenterology and Nutrition
Giardia Infection and Zinc Malabsorption Quihui et al. (2010) “Could giardiasis be a risk factor for low zinc status in schoolchildren from northwestern Mexico? A cross-sectional study with longitudinal follow-up” BMC Public Health 10:85
Reduced Blood Levels of Zinc & Iron Turkish Children with Giardia = children with Giardia = children without Giardia Modified from Ertan et al. (2002) “Serological levels of zinc, copper and iron elements among Giardia lamblia infected children in Turkey” Pediatrics International 44, 286–288
Reduced Blood Levels of Zinc & Iron Egyptian Children with Giardia Modified from Abou-Shady et al. Impact of Giardia lamblia on Growth, Serum Levels of Zinc, Copper, and Iron in Egyptian Children (2010) Biol Trace Elem Res
Waterborne Protozoa Infection Levels inChildren with “Malabsorption Syndrome” (India) Behera et al.
Some of the Impacts of Maternal Zinc Deficiency• Preterm delivery• Low birth weight• Maternal and infant mortality
Zinc and DiarrheaSome possible mechanisms of the effect of zinc on the duration and severity of diarrhea include:• Improved absorption of water and electrolytes by the intestines,• Regeneration of gut lining,• Improved immunity
Zinc Deficiencies, Children & Multiple Diseases• “A systematic review of relevant epidemiological research involved meta-analysis from 11 intervention trials. Results of our review indicate that zinc deficiency in children aged <5 years increases the risk of incidence for diarrhoeal disease by 1.28 (28%), pneumonia by 1.52 (52%) and malaria by 1.56 (56%)”. - from Caulfield and Black “Chapter 5 - Zinc deficiency” in Comparative Quantification of Health Risks WHO
Zinc Deficiencies and Stunting Black et al. (2008) “Maternal and child undernutrition: global and regional exposures and health consequences” Lancet
Some Impacts of Maternal Anemia • Increased maternal deaths • Low birth weight • Neonatal mortality • Impaired cognition
Anemia, Children and Chronic Infection • Anemia is highly prevalent among children in developing countries • SE Asia has the highest prevalence of anemia in children, affecting approximately 2/3 of children • Anemia caused by chronic infection may account for a substantial proportion of anemia among children
EcuadorAdapted from Sackey et al. (2003) “Predictors and Nutritional Consequences of IntestinalParasitic Infections in Rural Ecuardorian Children” Journal of Tropical Pediatrics; Feb; 49
Adapted from: Sackey et al. (2003) “Predictors and Nutritional Consequences of IntestinalParasitic Infections in Rural Ecuardorian Children Journal of Tropical Pediatrics; Feb; 49
Key Messages WASH and Malnutrition• Waterborne pathogens cause “enteric infections” that significantly contribute to malnutrition by either (a) recurring or persistent diarrhea (b) asymptomatic impacts to the intestines that interfere with nutrient absorption (malabsorption)• Cryptosporidium and Giardia appear to particularly result in malabsorption/malnutrition
Key Messages Part I (cont.)• Diarrhea and/or “asymptomatic” enteric infections significantly contribute to or cause zinc deficiencies, iron deficiencies (anemia) and likely Vitamin A deficiencies
Part IIWaterborne Pathogens, Malnutrition and Maternal/Child Mortality Rates
Introductory QuoteWhen a woman dies in childbirth, amid theshock is the haunting question of “why? Whatwent wrong?”Answering the question of “what went wrong?”is .. critical to strengthening health systems. – Quote from “Unaccountable - Addressing Reproductive Health CareGaps” (2010) Human Rights Watch
Definitions• Anemia – is a decrease in normal number of red blood cells (RBCs) or less than the normal quantity of hemoglobin in the blood• Bacteremia - is the presence of bacteria in the blood• Perinatal - the period occurring "around the time of birth", up to 7 completed days after birth
Hepatitis E & Maternal Mortality Adapted from Purcell & Emerson (2008) “Hepatitis E: an emerging awareness of an old disease” J Hepatol. Mar;48(3):494-503
Percent of Hepatitis Due to Hep E Purcell & Emerson (2008) “Hepatitis E: an emerging awareness of an old disease” J Hepatol. Mar;48(3):494-503
Hepatitis E• Because diagnostic tests vary greatly in specificity, sensitivity and availability, Hepatitis E is probably underdiagnosed.• “Most outbreaks have occurred following monsoon rains, heavy flooding, contamination of well water, or massive uptake of untreated sewage into city water treatment plants.” - WHO
Diarrhea and AnemiaFrom: “Maternal Anemia: A Preventable Killer” USAID
Anemia - From USAID• “Anemia is one of the most widely prevalent disorders, affecting the lives of almost half a billion women of reproductive age. Iron deficiency anemia, alone, contributes to over 100,000 maternal and almost 600,000 perinatal deaths each year… impacts include increased risk of infant mortality, pre-term delivery, low birth weight, and reduced cognitive development in children.• Anemia has multiple causes: increased iron requirements during pregnancy, inadequate intake of micronutrients… and malaria, hookworm, HIV, diarrhea and other infections.”
% Anemia & Low Birthweight - Nepal % TRACKING PROGRESS ON CHILD AND MATERNAL NUTRITION, A survival and development priority” (2009) UNICEF
> 600% Increase in Maternal Mortality Rate (MMR) Due to Anemia (Gambia) ANYA S. A. (2004) “SEASONAL VARIATION IN THE RISK AND CAUSES OF MATERNAL DEATH IN THE GAMBIA: MALARIA APPEARS TO BE AN IMPORTANT FACTOR” Am. J. Trop. Med. Hyg., 70(5)
IDA = Iron Deficiency AnemiaFrom: “Maternal Anemia: A Preventable Killer” USAID
Anemia - Mechanisms of Maternal/Child Mortality • “Women do not die in childbirth as a direct effect of iron deficiency, but rather die of heart failure due to blood loss, which is made more precipitous by iron deficiency anaemia.” • “Similarly, babies do not die in the perinatal period from iron deficiency, but rather die of other causes, some of which are related to preterm birth, for which maternal iron deficiency is a risk factor.” Stoltzfus et al. (2004) “Chapter 3 – Iron deficiency anaemia” in Comparative Quantification of Health Risks Global and Regional Burden of Disease Attributable to Selected Major Risk Factors
Zinc and Mortality in Young Children• Zinc deficiency contributes substantially to and mortality of young children throughout the world.
Zinc, Vitamin A and Malaria• “Although the association is complex and requires additional research, ….Existing evidence strongly suggests that micronutrient deficiencies and general undernutrition increase the burden of malaria morbidity and mortality.”• “Large numbers of children less than five years old suffer and die of malaria due to nutritional inadequacies in terms of protein energy, zinc, and vitamin A.” CAULFIELD et al. (2004) “UNDERNUTRITION AS AN UNDERYING CAUSE OF MALARIA MORBIDITY AND MORTALITY IN CHILDREN LESS THAN FIVE YEARS OLD” Am. J. Trop. Med. Hyg.71(Suppl 2), 55–63
Pakistan Railway Hospital Rawalpindi (2004 to 2005) Modified from Bakhtiar et al. (2007) “Relationship between maternal hemoglobin and perinatal outcome” The Journal of the Pakistan Medical Association
Brabin et al. (2001) “Analysis of Anemia and Child Mortality” The Journal of Nutrition
Brabin et al. (2001) “Analysis of Anemia and Child Mortality” The Journal of Nutrition
Maternal Anemia and Stillbirths“It has been suggested that lowhemoglobin (iron) concentrations cancause a state of chronic hypoxia, which ispresumably exacerbated in pregnancywhen oxygen demands are particularlyhigh because of the metabolism of themother and the fetus, and that oxygentransfer to the fetus is probably reduced inanemic women.” - Yatich et al. (2010) “Malaria, Intestinal Helminths and Other Risk Factors for Stillbirth in Ghana” Infectious Diseases in Obstetrics and Gynecology Article ID 350763
Stillbirths and Anemia• “Of the 130 million babies born worldwide every year, approximately 4 million are stillborn, more than 98% of these occur in developing countries. Stillbirth accounts for more than half of perinatal mortality in developing countries.”• “Stillbirths have not been widely studied, have been under-reported, and rarely have been considered in attempts to improve birth outcomes in developing countries.” - Yatich et al. (2010) “Malaria, Intestinal Helminths and Other Risk Factors for Stillbirth in Ghana” Infectious Diseases in Obstetrics and Gynecology Article ID 350763
Modified from Yatich et al. (2010) “Malaria, Intestinal Helminths andOther Risk Factors for Stillbirth in Ghana” Infectious Diseases inObstetrics and Gynecology Article ID 350763
Zupan J “Perinatal Mortality in Developing Countries” (2005) N Engl J Med 352;20
Schistosomiasis & Maternal/Infant Mortality• “Approximately, 10 million women in Africa have schistosomiasis in pregnancy. Pregnant women infected with schistosomiasis develop severe anemia, have low birth weight infants, and an increased infant and maternal mortality rate. Schistosomiasis has been detected in the placenta and newborns”• “Data suggest that infected women have a higher rate of spontaneous abortions and a higher risk for ectopic pregnancies.” - N. M.Nour (2010) “Schistosomiasis: Health Effects on Women” REVIEWS IN OBSTETRICS & GYNECOLOGY VOL. 3 NO. 1
Countries at High Risk of Schistosomiasis (in red)
Reduction in Schistosomiasis & Trachoma from Watsan Interventions Esrey et al. (1991) “Effects of improved water supply and sanitation on ascariasis, diarrhoea, dracunculiasis, hookworm infection, schistosomiasis, and trachoma” Bulletin of the World Health Organization, 69 (5): 609-621
Mortality Risks for Cryptosporidiosis2,446 Hospitalized Children (Uganda) TUMWINE et al. (2003) “CRYPTOSPORIDIUM PARVUM IN CHILDREN WITH DIARRHEA IN MULAGO HOSPITAL, KAMPALA, UGANDA” Am. J. Trop. Med. Hyg., 68(6), 710–715
Cryptosporidiosis in Infancy and Mortality Molbak et al. (1993) “Cryptosporidiosis in infancy and childhood mortality in Guinea Bissau, West Africa” British Medical Journal;307:417-20
Chlorinating Water is Not Enough!• “Our findings demonstrate a high incidence of acute Cryptosporidium infection in children in Mexico City with no immune disorders and apparently adequate sanitary conditions at home and in the surrounding environment.• The families of the children in this study had chlorinated water....The parents of these children washed their hands before preparing and eating meals …” - SANCHEZ-VEGA et al. (2006) “CRYPTOSPORIDIOSIS AND OTHER INTESTINAL PROTOZOAN INFECTIONS IN CHILDREN - LESS THAN ONE YEAR OF AGE IN MEXICO CITY” Am. J. Trop. Med. Hyg., 75(6), pp. 1095–1098
Non-typhoid Salmonella & African Children• “Nontyphoidal salmonellae (NTS) have long been a common but relatively neglected cause of invasive disease in children living in tropical Africa especially during rainy seasons.”• “NTS bacteraemia has consistently been associated with young age (most cases present between 6 months and 3 years of age), anaemia, malnutrition and more recently with HIV infection, with reported case-fatality rates of over 20%.”• “NTS are also a common and frequently fatal cause of meningitis.” Graham and English (2009) “Nontyphoidal salmonellae: a management challenge for children with community acquired invasive disease in tropical African countries” Lancet. January 17; 373(9659): 267–269
Non-Typhoid Salmonella Infections in Children & Rainfall (Malawi)
NTS Increasingly Common Cause of Severe Bacterial Disease in Africa• “As immunisation with Haemophilus influenzae type b (Hib) vaccine becomes more widely available, NTS together with Streptococcus pneumoniae are the major causes of severe bacterial disease in African children from 2 months to 5 years of age.”• “Future implementation of pneumococcal vaccines is likely to further emphasise their (NTS) relative importance as a pathogen …” – Graham and English (2009) “Nontyphoidal salmonellae: a management challenge for children with community acquired invasive disease in tropical African countries” Lancet 373(9659): 267–269
Non-typhoid Salmonella Bacteremia vs. Age MacLennan et al. (2008) “The neglected role of antibody in protection against bacteremia caused by nontyphoidal strains of Salmonella in African children” The Journal of Clinical Investigation
Anti-Salmonella Antibodies are Lower in Infants MacLennan et al. (2008) “The neglected role of antibody in protection against bacteremia caused by nontyphoidal strains of Salmonella in African children” J. Clin. Invest. 118:1553–1562
Bacteremia Prevention (e.g. safe water and food)• “The considerable mortality associated with community- acquired bacteremia and the short interval between admission and death, despite careful implementation of the WHO recommendations for treatment, highlight the need for prevention.”• “Even where microbiologic facilities exist, causative organisms can be identified only after 24 to 48 hours, by which time most deaths in children with bacteremia have already occurred.” Berkely et al. (2005) N Engl J Med;352:39-47.
Morpeth et al. (2009) “Invasive Non-Typhi Salmonella” Disease in AfricaClin Infect Dis. Aug 15;49(4)
Reddy et al. (2010)“Community-acquiredbloodstream infectionsin Africa: a systematicreview and meta-analysis” LancetInfectious Disease Vol10 June
Bacterial Contamination of Water Can Also Contaminate Food Adapted from: “Tackling the silent killer, The case for sanitation” by WaterAid (2008)
Reduced Risk of Neonatal Mortalityfor Maternal Handwashing (Nepal) Days Since Delivery Modified from Rhee et al. (2008) “Impact of Maternal and Birth Attendant Hand-washing on Neonatal Mortality in Southern Nepal” Arch Pediatr Adolesc Med. July ; 162(7): 603–608
Key Messages Maternal and Child Mortality and WASH• Waterborne Hepatitis E infections during pregnancy result in high mortality rates to mothers (up to 20%)• Cryptosporidium contributes to high mortality rates in children < 5 particularly where malnutrition rates are high• Diarrhea contributes to anemia which results in significantly higher mortality rates for mothers, and infants
Key Messages Part II (cont.)• Diarrhea and/or reoccurring or persistent “enteric infection” driven zinc deficiency results in increased child mortality rates• Schistosomiasis results in significantly higher maternal and infant mortality rates• Non-typhoid Salmonella commonly originates from water or food and in sub-Saharan Africa can spread from the gut (becomes invasive) to becomes a common cause of fatal blood infections in children
Part IIIWaterborne Pathogens-Malnutrition- Impaired Development in Children
Definitions• Cognitive – the “process of thought”• Schizophrenia – a mental disorder characterized by abnormalities in the perception or expression of reality.
Long-Term Impacts of Malnutrition “Malnutrition is well recognized as a widespread health problem with consequences that are both acute and, even more often, long-term. However, the long-term effects, especially from nutritional deficits early in life, on children who dont die, but have their development impaired, may exceed even the troubling mortality.”- Guerrant et al. (2008) “Malnutrition as an enteric infectious disease with long- term effects on child development” Nutr Rev. September; 66(9): 487–505.
Weight of Child at 4-5 Years Old Can Mask Earlier Deficiencies• “Whereas a deficit in height (stunting) is difficult to correct, a deficit in weight (underweight) can be recouped if nutrition and health improve later in childhood.”• “The weight of a child at 4–5 years old, when it is adequate for the child’s age, can therefore mask deficiencies that occurred during pregnancy or infancy, and growth and development that have been compromised.” - TRACKING PROGRESS ON CHILD AND MATERNAL NUTRITION, A survival and development priority” (2009) UNICEF
Chronic Undernutrition in Early Childhood & Diminished Cognitive Development•“Chronic undernutrition in early childhood alsoresults in diminished cognitive and physicaldevelopment, which puts children at adisadvantage for the rest of their lives. They mayperform poorly in school, and as adults they maybe less productive, earn less and face a higherrisk of disease than adults who were notundernourished as children.” - “TRACKING PROGRESS ON CHILD AND MATERNAL NUTRITION, A survival and development priority” (2009) UNICEF
Diarrhea and AnemiaFrom: “Maternal Anemia: A Preventable Killer” USAID
Anemia as a “Direct” Cause of Impaired Child Development“Decreased work productivity and alteredchild development (or intelligence) wereconsidered to be direct sequelae (result)of iron deficiency, the assumption beingthat iron deficiency directly causesdecreased oxygen delivery to muscles andthe brain.” Stoltzfus et al. (2004) “Chapter 3 – Iron deficiency anaemia” in Comparative Quantification of Health Risks Global and Regional Burden of Disease Attributable to Selected Major Risk Factors WHO
Low Birthweight & Impaired Development “Some reviews also suggest high rates of cognitive impairment, learning disability, and behavioural problems among children who were born with lower birthweight, which is likely to be caused by sub-optimum development of the brain”. - Desai et al. (2007) “Epidemiology and burden of malaria in pregnancy” Lancet Infect Dis; 7:93–104
Child Underweight and Stunting• “Of the 555 million preschool children in developing countries, 32% are stunted and 20% are underweight …and leads to long-term cognitive deficits, poorer performance in school and fewer years of completed schooling, and lower adult economic productivity.• Child underweight state or stunting mainly develops during the first 2 years of life, when mean weight-for-age and length-for-age Z scores of children in Africa and Asia drop to about –2.0, with little or no recovery thereafter.” Humphrey (2009) “Child undernutrition, tropical enteropathy, toilets, and handwashing” Lancet; 374: 1032–35
Giardia and Cryptosporidium & Impaired Development• “Giardia and Cryptosporidium are ubiquitous enteric protozoan pathogens…Both pathogens are significant causes of diarrhea and nutritional disorders …”• “In developing regions of the world, Giardia and Cryptosporidium constitute part of the complex group of parasitic, bacterial and viral diseases that impair the ability to achieve full potential and impair development and socio-economic improvements.” - from article by the WHO Coordinator, Parasitic Diseases and Vector Control - Savioli et al. (2006) “Giardia and Cryptosporidium join the ‘Neglected Diseases Initiative” Trends in Parasitology Vol.22 No.5 May
Guerrant et al. (2008) “Malnutrition as an enteric infectious disease with long-term effects on child development” Nutr Rev. September; 66(9): 487–505.
Impact of Giardia on Cognitive Development“Giardiasis can lead to zinc and other micronutrient deficiencies that have been associated with deficits in cognitive development.”- Berkman et al. (2002) The Lancet
Impact of Giardia and Severe Stunting on Test Scores Berkman et al. (2002) “Effects of stunting, diarrhoeal disease, and parasitic infection during infancy on cognition in late childhood: a follow-up study” The Lancet
Impact of Early Childhood Persistent Diarrhea on IntelligenceNIEHAUS et al.EARLYCHILDHOODDIARRHEA ISASSOCIATED WITHDIMINISHEDCOGNITIVEFUNCTION 4 TO 7YEARS LATER INCHILDREN IN ANORTHEASTBRAZILIANSHANTYTOWN Am.J. Trop. Med. Hyg.,66(5), 2002
Early Cryptosporidiosis and Lasting Impairments in Growth and Development• “Without question, cryptosporidiosisconstitutes a leading cause of persistentdiarrhea in tropical, developing areas, …amongchildren, in whom it often signals a period ofincreased diarrhea burden or nutrition shortfalls…• The impact and consequences ofcryptosporidiosis may well be far greater thangenerally appreciated, because of the lastingimpairments in growth and development thatmay follow, especially with early childhoodinfections in impoverished areas” - From Dillingham et al. (2002) “Cryptosporidiosis: epidemiology and impact” Microbes and Infection 4 1059–1066–
Diarrhea and Growth in Children• “Cryptosporidial infections and persistent diarrhoea predispose to increased diarrhoea morbidity and nutritional shortfalls for up to 18 months”.• “Cryptosporidial infections at <6 months of age and in stunted children predispose to 0.95–1.05 cm growth deficits one year later.”• “Early childhood diarrhoea (at 0–2 years old) associates with lasting growth shortfalls, persisting at 3.6 cm at seven years old, and additive to 8.2 cm with intestinal helminths at 0–2 years old”. – Guerrant et al. (2002) “Updating the DALYs for diarrhoeal disease” TRENDS in Parasitology Vol.18 No.5
Malnutrition, Loss of Cognitive Function and Specific Pathogens “Studies linking specific microbes with malnutrition are limited, but currently there are data linking malnutrition and attendant loss of cognitive function to infection with EAEC, ETEC, Shigella, Ascaris, Cryptosporidium, E. histolytica, Giardia, and Trichuris trichiura” - Petri et al. (2008) “Enteric infections, diarrhea, and their impact on function and development” J Clin Invest. April 1; 118(4): 1277–1290
Waterborne Toxoplasma InfectionsImpacts on Pregnant Women & Offspring From CDC
Toxoplasma Infection DuringPregnancy and Impaired Development• “Acute infection with Toxoplasma during pregnancy and its potentially tragic outcome for the fetus and newborn continue to occur … worldwide”• “Transmission to the fetus occurs almost solely in women who acquire their primary infection during gestation and can result in visual and hearing loss, mental and psychomotor retardation, seizures, …. or death. Toxoplasmosis in pregnant women most often goes unrecognized.” – from Montoya and Remington (2008) “Management of Toxoplasma gondii Infection during Pregnancy” Clinical Infectious Diseases 47:554–66
Pregnancy, Immunity and Toxoplasma InfectionProduction of progesterone duringpregnancy leads to downregulation ofimmune functions, and thereforeincreases the risk of Toxoplasmainfection in pregnant women.
Toxoplasma Infection During Pregnancy Impacts on Offspring Adapted from: McLeod et al. (2006) “Outcome of Treatment for Congenital Toxoplasmosis, 1981–2004: The National Collaborative Chicago- Based, Congenital Toxoplasmosis Study” Clinical Infectious Diseases 42:1383–94
Toxoplasma Infection and Risk of Infection and Clinical Signs Adapted from: Montoya and Remington (2008) “Management of Toxoplasma gondii Infection during Pregnancy” Clinical Infectious Diseases; 47:554–66
Toxoplasma Contamination by Water Source (Polish Farms) Sroka et al. (2006) “OCCURRENCE OF TOXOPLASMA GONDII IN WATER FROM WELLS LOCATED ON FARMS” Ann Agric Environ Med, 13, 169–175
Toxoplasma and Lack of ProtectiveAntibodies in Pregnant Women (cont.) Elsheikha H.M, (2008) “Review Paper Congenital toxoplasmosis: Priorities for further health promotion action” Public Health 122, 335–353
Toxoplasma - CDC“If you are newly infected with Toxoplasma while you are pregnant, or just before pregnancy, then you can pass the infection on to your baby. You may not have any symptoms from the infection. Most infected infants do not have symptoms at birth but can develop serious symptoms later in life, such as blindness or mental disability.” CDC (2008)
Toxoplasma, Pregnancy & Schizophrenia• “Previous studies have shown that maternal antibodies to Toxoplasma measured during pregnancy are associated with an increased risk of schizophrenia and other psychoses in adult offspring.”• “Recently, it has been recognized that different genotypes of Toxoplasma have distinct neuropathogenic potential.” – Xiao et al. (2009) “Serological pattern consistent with infection with type I Toxoplasma gondii in mothers and risk of psychosis among adult offspring” Microbes and Infection 11 1011-1018
Toxoplasma and Schizophrenia• From 1953 - 2003, 19 studies reported of Toxoplasma antibodies in persons with schizophrenia and other severe psychiatric disorders• 18 of the 19 reported a higher percentage of Toxoplasma antibodies in the affected patients; in 11 studies the difference was statistically significant. Source - Torrey and Yolken (2003) “Toxoplasma gondii and Schizophrenia” Emerging Infectious Diseases
Chlorine is Not Effective for Toxoplasma• “Toxoplasma is increasingly recognized as a waterborne pathogen. Infection can be acquired by drinking contaminated water …..• Oocysts were exposed to 100 mg/L of chlorine for 30 min, or for 2, 4, 8, 16, and 24 hr.• Results of the chemical exposure experiments indicate that neither sodium hypochlorite nor ozone effectively inactivate T. gondii oocysts, even when used at high concentrations.” Wainwright et al. (2007) “CHEMICAL INACTIVATION OF TOXOPLASMA GONDII OOCYSTS IN WATER” J. Parasitol., 93(4)
Trachoma• “6 million people worldwide are blind because of trachoma—the leading cause of preventable blindness—and more than 150 million people need treatment.”• “Improving access to water and better hygiene can reduce trachoma morbidity by 27%”– Bartram et al. (2005) “Focusing on improved water and sanitation for health” The Lancet
Trachoma Prevalence by Age Burton et al. (2003) “Which Members of a Community Need Antibiotics to Control Trachoma? Conjunctival Chlamydia trachomatis Infection Load in Gambian Villages” Investigative Ophthalmology & Visual Science, 44, 10
Trachoma Risk and Latrines (Villages in Gambia)Note that since “Water supply was equally good in all villages, watercould not be assessed as a risk factor” in this study. Burton et al. (2003) “”Which Members of a Community Need Antibiotics to Control Trachoma? Conjunctival Chlamydia trachomatis Infection Load in Gambian Villages” Investigative Ophthalmology & Visual Science,, 44, 10
Key Messages Part IIIImpaired Development & Waterborne Pathogens• Giardia and Cryptosporidium likely negatively impact cognitive development in children• Toxoplasma infection (from water or certain undercooked meats) usually has very serious development impacts on offspring
Key Messages Part III (cont.)• Diarrhea contributes to anemia which can have impacts on child development due to reduced oxygen to the fetus• Trachoma is a common cause of blindness in children in some countries significantly impacting child development. WASH interventions such as hygiene can significantly lower Trachoma rates