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

Introduction

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

Maternal Mortality Ratios

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

“

• “For example, comorbidity of pneumonia and

diarrhea is high, suggesting shared risk

factors and exacerbation of risk due to

coexistence of multiple morbidities”

Diarrhea and Pneumonia - Infants

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 in

Comparative 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: Where

and Why Do They Die?” PLOS Medicine Vol 7, Iss 6 e1000294

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,

Key After Birth Interventions

Recommended by Friberg et al.

Part I Diarrhea & Waterborne Pathogens as

Contributors 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 insecurity

is obviously critical, but a factor that is

potentially even more important (especially for

children with marginal intake) is the inability to

absorb what they do take in because of

repeated 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 disrupted

intestinal barrier function due to malnutrition and

diarrheal illnesses likely combine to render

weaning children susceptible to repeated bouts

of enteric infections leading to intestinal injury and

consequently, nutrient malabsorption during

the 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 and

health 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 for

Severe 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

Underweight

Adapted from Shrimpton et al. (2001) “Worldwide Timing of Growth Faltering:

Implications for Nutritional Interventions” PEDIATRICS Vol. 107 No. 5 May

Stunting

Adapted 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

UNICEF 2009

Mortality Risks

for 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

Das et al. (2006) “Molecular

Characterization of Cryptosporidium

spp. from Children in Kolkata, India”

JOURNAL OF CLINICAL

MICROBIOLOGY,, 44, No. 11

Cryptosporidium Infection Rates in Infants

in India and Jamaica

LINDO et al. (1998) “EPIDEMIOLOGY OF

GIARDIASIS AND CRYPTOSPORIDIOSIS IN

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 SAN

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 on

Ability 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 Nutrients

Repeated 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 by

Severe 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

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

= children with Giardia

= children without Giardia

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 in

Children 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 Diarrhea

Some 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

Adapted from Sackey et al. (2003) “Predictors and Nutritional Consequences of Intestinal

Parasitic Infections in Rural Ecuardorian Children” Journal of Tropical Pediatrics; Feb; 49

Ecuador

Adapted from: Sackey et al. (2003) “Predictors and Nutritional Consequences of Intestinal

Parasitic 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 II

Waterborne Pathogens, Malnutrition and

Maternal/Child Mortality Rates

Introductory Quote

When a woman dies in childbirth, amid the

shock is the haunting question of “why? What

went wrong?”

Answering the question of “what went wrong?”

is .. critical to strengthening health systems.

– Quote from “Unaccountable - Addressing Reproductive Health Care

Gaps” (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

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

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 Anemia

From: “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)

From: “Maternal Anemia: A Preventable Killer” USAID

IDA = Iron Deficiency

Anemia

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

Modified from Bakhtiar et al. (2007) “Relationship between maternal hemoglobin

and perinatal outcome” The Journal of the Pakistan Medical Association

Pakistan Railway Hospital Rawalpindi (2004 to 2005)

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 low hemoglobin (iron) concentrations can cause a state of chronic hypoxia, which is presumably exacerbated in pregnancy when oxygen demands are particularly high because of the metabolism of the mother and the fetus, and that oxygen transfer to the fetus is probably reduced in anemic 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 and

Other Risk Factors for Stillbirth in Ghana” Infectious Diseases in

Obstetrics 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 Cryptosporidiosis

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

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 Africa Clin Infect Dis. Aug

15;49(4)

Reddy et al. (2010)

“Community-acquired

bloodstream infections

in Africa: a systematic

review and meta-

analysis” Lancet Infectious Disease Vol

10 June

Adapted from: “Tackling the silent killer, The case for sanitation” by WaterAid (2008)

Bacterial Contamination of Water Can Also Contaminate Food

Reduced Risk of Neonatal Mortality

for 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 III

Waterborne 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 don't 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 also results in diminished cognitive and physical development, which puts children at a disadvantage for the rest of their lives. They may perform poorly in school, and as adults they may be less productive, earn less and face a higher risk of disease than adults who were not undernourished as children.”

- “TRACKING PROGRESS ON CHILD AND MATERNAL NUTRITION, A survival

and development priority” (2009) UNICEF

Diarrhea and Anemia

From: “Maternal Anemia: A Preventable Killer” USAID

Anemia as a “Direct” Cause of

Impaired Child Development

“Decreased work productivity and altered child development (or intelligence) were considered to be direct sequelae (result) of iron deficiency, the assumption being that iron deficiency directly causes decreased oxygen delivery to muscles and the 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 Intelligence

NIEHAUS et al.

EARLY

CHILDHOOD

DIARRHEA IS

ASSOCIATED WITH

DIMINISHED

COGNITIVE

FUNCTION 4 TO 7

YEARS LATER IN

CHILDREN IN A

NORTHEAST

BRAZILIAN

SHANTYTOWN Am.

J. Trop. Med. Hyg.,

66(5), 2002

Early Cryptosporidiosis and Lasting

Impairments in Growth and Development

• “Without question, cryptosporidiosis constitutes a leading cause of persistent diarrhea in tropical, developing areas, …among children, in whom it often signals a period of increased diarrhea burden or nutrition shortfalls…

• The impact and consequences of cryptosporidiosis may well be far greater than generally appreciated, because of the lasting impairments in growth and development that may follow, especially with early childhood infections 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 Infections

Impacts on Pregnant Women & Offspring

From CDC

Toxoplasma Infection During

Pregnancy 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 Infection

Production of progesterone during

pregnancy leads to downregulation of

immune functions, and therefore

increases the risk of Toxoplasma

infection 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 Protective

Antibodies 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, water

could 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 III

Impaired 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