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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
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 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
Key After Birth Interventions
Recommended by Friberg et al.




 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,
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
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 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




   = 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 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
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
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
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 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)
IDA = Iron Deficiency
                                                 Anemia




From: “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 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
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 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

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WASH Impacts on Maternal and Child Mortality, Malnutrition and Impaired Development

  • 1. 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
  • 3. 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
  • 5. Deaths for Children < 5 Years Old & Malnutrition From: Müller and Krawinkel (2005) “Malnutrition and health in developing countries” CMAJ 173 (3)
  • 6. 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
  • 7. 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
  • 8. 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
  • 9. 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.
  • 10. 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.
  • 11. Modified from Caulfield and Black Chapter 5 - Zinc deficiency in Comparative Quantification of Health Risks WHO 2004
  • 12. 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
  • 13. 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
  • 14. Key After Birth Interventions Recommended by Friberg et al. 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,
  • 15. Part I Diarrhea & Waterborne Pathogens as Contributors to Maternal and Child Malnutrition
  • 16. 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)
  • 17. 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)
  • 18. 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.
  • 19. 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.
  • 20. 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.
  • 21. 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)
  • 22. 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.
  • 23. 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
  • 24. Adapted from: “Tackling the silent killer, The case for sanitation” by WaterAid (2008)
  • 25. 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)
  • 26. 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
  • 27. 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
  • 28. From: Müller and Krawinkel (2005) “Malnutrition and health in developing countries” CMAJ 173 (3)
  • 29. 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)
  • 30. 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)
  • 31. 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
  • 32. Underweight Adapted from Shrimpton et al. (2001) “Worldwide Timing of Growth Faltering: Implications for Nutritional Interventions” PEDIATRICS Vol. 107 No. 5 May
  • 33. Stunting Adapted from Shrimpton et al. (2001) “Worldwide Timing of Growth Faltering: Implications for Nutritional Interventions” PEDIATRICS Vol. 107 No. 5 May
  • 34. 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
  • 36. 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
  • 37. 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
  • 38. 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
  • 39. 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
  • 40. 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
  • 41. 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.
  • 42. 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
  • 43. Asymptomatic Cryptosporidium Infection and Malnutrition • Cryptosporidium infection can be associated with malnutrition with or without overt diarrhea (symptomatic or asymptomatic).
  • 44. 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.
  • 45. 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
  • 46. 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
  • 47. 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
  • 48. 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
  • 49. 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
  • 50. 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
  • 51. 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
  • 52. Waterborne Protozoa Infection Levels in Children with “Malabsorption Syndrome” (India) Behera et al.
  • 53. Some of the Impacts of Maternal Zinc Deficiency • Preterm delivery • Low birth weight • Maternal and infant mortality
  • 54. 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
  • 55. 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
  • 56. Zinc Deficiencies and Stunting Black et al. (2008) “Maternal and child undernutrition: global and regional exposures and health consequences” Lancet
  • 57. Some Impacts of Maternal Anemia • Increased maternal deaths • Low birth weight • Neonatal mortality • Impaired cognition
  • 58. 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
  • 59. 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
  • 60. Adapted from: Sackey et al. (2003) “Predictors and Nutritional Consequences of Intestinal Parasitic Infections in Rural Ecuardorian Children Journal of Tropical Pediatrics; Feb; 49
  • 61. 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
  • 62. 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
  • 63. Part II Waterborne Pathogens, Malnutrition and Maternal/Child Mortality Rates
  • 64. 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
  • 65. 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
  • 66. 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
  • 67. 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
  • 68.
  • 69. 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
  • 70. Diarrhea and Anemia From: “Maternal Anemia: A Preventable Killer” USAID
  • 71. 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.”
  • 72. % Anemia & Low Birthweight - Nepal % TRACKING PROGRESS ON CHILD AND MATERNAL NUTRITION, A survival and development priority” (2009) UNICEF
  • 73. > 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)
  • 74. IDA = Iron Deficiency Anemia From: “Maternal Anemia: A Preventable Killer” USAID
  • 75. 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
  • 76. Zinc and Mortality in Young Children • Zinc deficiency contributes substantially to and mortality of young children throughout the world.
  • 77. 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
  • 78. 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
  • 79. Brabin et al. (2001) “Analysis of Anemia and Child Mortality” The Journal of Nutrition
  • 80. Brabin et al. (2001) “Analysis of Anemia and Child Mortality” The Journal of Nutrition
  • 81. 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
  • 82. 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
  • 83.
  • 84. 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
  • 85. Zupan J “Perinatal Mortality in Developing Countries” (2005) N Engl J Med 352;20
  • 86. 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
  • 87. Countries at High Risk of Schistosomiasis (in red)
  • 88. 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
  • 89. 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
  • 90. 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
  • 91. 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
  • 92.
  • 93. 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
  • 94. Non-Typhoid Salmonella Infections in Children & Rainfall (Malawi)
  • 95. 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
  • 96. 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
  • 97. 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
  • 98. 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.
  • 99. Morpeth et al. (2009) “Invasive Non-Typhi Salmonella” Disease in Africa Clin Infect Dis. Aug 15;49(4)
  • 100. Reddy et al. (2010) “Community-acquired bloodstream infections in Africa: a systematic review and meta- analysis” Lancet Infectious Disease Vol 10 June
  • 101. Bacterial Contamination of Water Can Also Contaminate Food Adapted from: “Tackling the silent killer, The case for sanitation” by WaterAid (2008)
  • 102. 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
  • 103. 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
  • 104. 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
  • 105. Part III Waterborne Pathogens-Malnutrition- Impaired Development in Children
  • 106. Definitions • Cognitive – the “process of thought” • Schizophrenia – a mental disorder characterized by abnormalities in the perception or expression of reality.
  • 107. 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.
  • 108. 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
  • 109. 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
  • 110. Diarrhea and Anemia From: “Maternal Anemia: A Preventable Killer” USAID
  • 111. 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
  • 112. 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
  • 113. 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
  • 114. 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
  • 115. Guerrant et al. (2008) “Malnutrition as an enteric infectious disease with long- term effects on child development” Nutr Rev. September; 66(9): 487–505.
  • 116. 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
  • 117. 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
  • 118. 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
  • 119.
  • 120. 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 –
  • 121. 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
  • 122. 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
  • 123. Waterborne Toxoplasma Infections Impacts on Pregnant Women & Offspring From CDC
  • 124. 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
  • 125. 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.
  • 126. 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
  • 127. 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
  • 128. 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
  • 129. 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
  • 130. 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)
  • 131. 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
  • 132. 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
  • 133. 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)
  • 134. 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
  • 135. 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
  • 136. 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
  • 137. 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
  • 138. 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