Cholera outbreak Haiti 2010 2013 www annarbor com
Cholera outbreak Haiti 2010 -2013 www. annarbor. com
Diarrheal Diseases in Tropical Medicine MED/GH 561 April 10, 2013 Frederick S. Buckner, MD
Topics to be discussed • Epidemiology of diarrheal disease • Clinical presentations, pathophysiology, etiologic agents • Diarrhea in children in developing countries – Watery diarrhea – Dysentery – Persistent diarrhea • Rotavirus • Cholera
Major causes of death among children under five years of age - World 2008 8. 8 M deaths worldwide* 68% due to infectious dz 15% due to diarrhea #1 respiratory: 1. 575 M #2 diarrhea: 1. 336 M #3 malaria: 0. 732 Black RE, Lancet, 2010 *7. 7 M deaths worldwide, 2010
Center for Vaccine Development M. Levine, Univ. Maryland Millenium Declaration adopted by all 189 United Nations Member States, 2000
Approaches to understanding diarrhea • Diarrheal syndromes – Acute diarrhea • Watery • Bloody (dysentery) – Chronic diarrhea (persistent): >14 days • Etiologies: viruses, bacteria, parasites • Host factors – Children (malnourished) – HIV infected – Travelers
How much fluid does your intestine absorb in a day? ~10 liters
FIC-NIH
Case 1 You are working in a clinic in rural Thailand. A mother brings in a 4 month baby with diarrhea and lethargy. How long has the diarrhea been going on? “ 2 days” Can you describe the diarrhea? “Like water” Is it bloody? “No” Is the baby breastfeeding or drinking water? “She stopped feeding earlier today” Seattle Times
Case 1 continued What is this syndrome? Acute watery diarrhea Is it important to determine the etiology? Probably not. (Rotavirus, Enterotoxigenic E. coli, etc. ) Exception: suspected cholera What is the urgency of the problem? How to Rx? Possibly fatal unless treated urgently with fluids
Diarrhea in children: focus on developing countries • 2008: 1. 3 million deaths/year • 1 billion episodes/year in children – 6 -7 episodes/child/year in developing countries – 1 -2 episodes/child/year in developed countries Darfur orphanage (Sudan) http: //www. thewe. cc/contents/more/archiv e/darfur_sudan. html
Worldwide distribution of deaths caused by diarrhea in children under 5 years of age in 2000
Contributing factors • Malnutrition: ¼ of children in developing countries are malnourished • 1. 1 billion people do no have access to safe drinking water • 2. 4 billion are without adequate sanitation • Social unrest (war zones, refugee camps) Kenya www. scoop. co. nz/stories/PO 0703/S 00273. htm
Death rate from diarrhea is declining • 1980’s: 4 -6 million deaths/year • 2000: 2. 5 million deaths • 2008: 1. 3 million deaths An estimated 50 million lives have been saved due to use of oral rehydration therapy (ORT) (WHO 2009) “ORT was probably the greatest medical innovation of the 20 th century”* Lancet
ORS
Composition of various solutions ORS (WHO) Pedialyte Gatorade Sodium 75 m. Eq/L 45 m. Eq/L 20 m. Eq/L Potassium 20 m. Eq/L 3. 2 m. Eq/L Sugar 20 g/L 25 g/L 59 g/L
Coupled sodium and glucose transport in the intestine JAMA 291: 2628 -31, 2004
Standard vs. new ORS solutions m. Eq/L Standard (1975) Glucose 111 Reduced osmolarity ORS (2002) 75 Sodium 90 75 Chloride 80 65 Potassium 20 20 Citrate 10 10 Osmolarity 311 245
Amylase resistant starch - ORS J. Ped. Gastro. Nutr. 42: 362, 2006 NEJM 342: 308, 2000 Appears to decrease fecal fluid loss and shorten duration of diarrhea.
What is the typical acid-base disturbance resulting from diarrhea? a) b) c) d) Non-anion gap metabolic acidosis Anion gap metabolic acidosis Metabolic alkalosis No acid-base disturbance Answer: a (which is why ORS has base)
Acute diarrhea in children: Etiologic treatment is usually not necessary • Assessment and management of dehydration is essential
Decreased skin turgor Center for Vaccine Development M. Levine, Univ. Maryland
Assessment of dehydration in children with diarrhea • Severe dehydration: – – Lethargy or unconsciousness Not able to drink or drinks poorly Sunken eyes Skin pinch goes back very slowly (>2 sec) • Some dehydration: – – Restless/irritability Thirsty and drinks eagerly Sunken eyes Skin pinch goes back slowly • No dehydration
Treatment of watery diarrhea* • Severe dehydration: – Immediate intravenous fluids – If IV treatment unavailable within 30 min, consider ORS by nasogastric tube • Some dehydration: – ORS in the clinic with monitoring for 4 hours • No dehydration: – Extra-fluids at home *WHO/UNICEF Guidelines: Integrated Management of Childhood illnesses, 2000
Intravenous or intraosseous infusion
Center for Vaccine Development M. Levine, Univ. Maryland
Case 2 www. nomadslandfilms. com
Case 2 You are working in a refugee camp in Chad. A woman brings a 6 month boy with watery diarrhea of 1 day duration. The child is breastfeeding well. On physical exam, the baby appears well nourished and alert. He has no abdominal tenderness. What is your medical advice?
Administer ORS
Treatment of diarrhea with no dehydration • Treat the child as an outpatient • Counsel the mother on 3 rules of home Rx – Give extra fluid ( breastfeeding or ORS) • Teach mother how to mix and give ORS (mother’s card) – Up to 2 years: give 50 -100 ml after each loose stool – Older than 2 years: give 100 -200 ml after each loose stool – Continue feeding (soup, rice water, yogurt drinks) – Return immediately if: • Child becomes unable to drink or breastfeed • Child develops fever • Child develops blood in stool
Mother’s card www. who. int/child-adolescent-health/publications/referral_care/chap 11/chart 17. htm
ORS
WHO and UNICEF See references
IMCI
Adjunctive therapy in children? • Anti-motility agents? No • Anti-emetics? No • Zinc supplements? Yes, in malnourished populations. Zinc given during an episode of diarrhea and for 10 -14 days after reduces the severity of the episode and the incidence of diarrhea for the following 4 to 6 months. – Administer 10 -20 mg per day x 10 -14 days – Syrup (20 mg/5 m. L) or Tablets (20 mg)
Administration of zinc* Use of zinc was found to be safe, with few side effects reported, and did not affect the use of oral rehydration solution. <6 mo: ½ tablet/day x 10 d >6 mo: 1 tablet per day x 10 d *Zinc sulfate 20 mg http: //centre. icddrb. org/news/index. jsp? id. Details=194
AUG. 2009
Dysentery Campylobacter jejuni 15 -60 u. M Very active Ingested RBCs sometimes visible www. unc. edu Salmonella enteritidis
Dysentery in children (loose frequent stools containing blood) • Most cases are due to Shigella and require antibiotic therapy (5 days) – TMP/SMX (issues with resistance) – Azithromycin, cefixime, ceftriaxone, cipro (? ) • Check stool for E. histolytica trophozoites • When to hospitalize: – Infants < 2 mo old (IM ceftriaxone) – Malnourished children • Supportive care: – Prevent dehydration. Continue feeding – Never give narcotic analgesics or antimotility drugs
Amebic dysentery Entamoeba histolytica Trophozoite 15 -60 u. M Very active Ingested RBCs sometimes visible 3. 5 -20 u. M 1 -4 nuclei Chromidial bars http: //www. medicine. cmu. ac. th/dept/parasite/framepro. htm
Persistent diarrhea Nepal P. Buckner
Persistent diarrhea in children Diarrhea lasting >14 days • Assess for signs of dehydration and Rx – ORS is sufficient for rehydration in most cases • Evaluation: – Examine the child for non-intestinal infections: • Pneumonia, sepsis, UTI, otitis media – Examine stool (wet mount): • Giardia lamblia trophozoites – MTZ 5 mg/kg TID x 5 days – Cryptosporidium (GEMS study) – Consider HIV infection
Giardia lamblia Trophozoite 14 x 7 u. M 2 nuclei Parabasal body Motile with jerky movements Cyst 8 -12 u. M 2 -4 nuclei Thick wall Granular cytoplasm
Persistent diarrhea Importance of diet • Good nutrition is essential for recovery of the gut and for prevention • Breast feeding should be continued • For children > 4 mo – First diet*: Starch based, reduced milk (low lactose) diet – Second diet* (if no improvement on first diet): A no-milk (lactose free) diet with reduced cereal (starch) Iraqi child homepages. stmartin. edu/orgs/sac * www. who. int/child-adolescent-health/publications/referral_care/chap 42. htm
Rotavirus infection • Responsible for ~500, 000 child deaths/yr and 2 million hospitalizations worldwide (1400 deaths/day) • Almost all morbidity and mortality in age <5
Rotarix (GSK) vaccine trial in developing countries
Rotavirus vaccine program PATH = Program for Appropriate Technology in Health Rotavirus movie GAVI = Global Alliance for Vaccines and Immunisations
Cholera Death comes through the water for the people of 19 th century London. Kew Bridge Steam Museum. www. 24 hourmuseum. org. uk
Cholera • Vibrio cholerae: – Gram negative, comma shaped rods – Serovar 01 causes cholera • “Classical” biotype: caused 1 st six cholera pandemics in south Asia during the 19 th and 20 th centuries • El Tor biotype: started spreading in 1960 s – Now the predominant biotype (e. g. Haiti) – Serovar 0139 causes cholera like illness • First appeared in India in 1992 • Tends to affect adults
V. cholerae • Killed by heating at 55°C for 15 min • Killed by most disinfectants • Survives saline conditions for two weeks at ambient temperatures • Can survive on/in shellfish for 2 wks if refrigerated
Cholera: Transmission • Humans are the only known natural host • Infection requires a large infective dose via contaminated food or water • Incubation period: hours to 5 days • Symptomatic vs. asymptomatic carrier – Classical biotype: 1: 5 – El Tor biotype: 1: 40 Refugee camp in Najaf, Iraq dancewater. blogspot. com
Cholera in Haiti • Oct, 2010– Jan, 2013 – >500, 000 cases – 7900 deaths Dec, 2012: • 2, 300 hospitalizations/week • 40 deaths/week Following Hurricane Sandy: spread to Dominican Republic, Cuba, and Venezuela
2008 -09 cholera outbreak in Zimbabwe August 2008 – February 2009 • 88, 000 cases • Overall, 4% fatality rate • Remote areas, fatality 20 -30% http: //doctorswithoutborders. org/publications/alert/article. cfm? id=3477&cat=alert-article
Cholera: clinical features • Rice-water stools: up to 30 L/day • Usually painless diarrhea • Fever is usually absent • Vomiting in 80% (shortly after diarrhea begins) • Hypovolemia and shock within 12 hr – Electrolyte disturbances Cl-, Ca++ – Hypoglycemia – Renal failure, cardiac arrythmias
Cholera cot
Cholera: diagnosis • In epidemics, the diagnosis is made on clinical grounds • Dark-field microscopy of stool shows comma-shaped “darting” bacteria • Stool should be submitted to a reference lab for culture. Transportation in alkaline peptone water and kept cool.
Cholera: treatment • Rehydration: – IV lactated Ringer’s (LR) – ORS: by mouth or by NG tube • Antibiotics: only beneficial in most severe cases – Adults: Doxycycline 300 mg PO x 1 – Children or pregnant women: TMP-SMX x 3 d
Cholera: prevention • Public health measures: – Improved food and water hygiene – Improved sanitation • Vaccines? – Not recommended during outbreaks • Health education
Diarrheal disease Primary Prevention The F-Diagram Sanitation Fluids Water Quality Fields Food Feces Flies Fingers Water Quantity Hand Washing Source: Wagner and Lanois, 1958 New Host
Recommended reading • Clinical Management of Acute Diarrhoea. WHO/UNICEF Joint Statement. 2004* • Handbook IMCI. Integrated Management of Childhood Illness. World Health Organization. 2005. * • Practice guidelines for the management of infectious diarrhea. 2001. Clin Infect Dis. 32: 331 -51. • Enteric infections, diarrhea, and their impact on function and development. 2008. J Clin Invest. 118: 1277 -90. • Water, sanitation and hygiene for the health of developing nations. 2003. Public Health. 117: 452 -56.
The end
Appendix materials
Millenium Development Goals Millenium Declaration adopted by all 189 United Nations Member States, 2000
http: //www. un. org/millenniumgoals/pdf/2012_Progress_E. pdf
Is the pathology in the small bowel or colon? Small Bowel Colon Symptoms Nausea, bloating, cramping, gas, weight loss Fever, rectal pain, frequent painful stools Physical signs Dehydration, orthostasis, Fever, abdominal pain decreased skin tugor Diarrhea Large volume, watery Small volume, pasty, and/or blood, mucous Microscopic exam of stool Without inflammatory cells or blood, with/without mucous Inflammatory cells, blood, mucous
Agents of diarrhea based on localization within the intestine Small Bowel Colon Bacteria E. coli (ETEC, EPEC), Staphylococcus aureus, Clostridium perfringens, Bacillus cereus, Vibrio cholera, Salmonella sp. Campylobacter sp. , Shigella sp. , Salmonella sp. , Clostridium difficile, Yersinia sp. , EHEC (0157: H 7), Vibrio parahemolyticus, Plesiomonas shigelloides, Aeromonas hydrophila Viruses Rotavirus Norovirus Astroviruses Caliciviruses Cytomegalovirus Adenovirus Parasites Giardia lamblia, Cyclospora cayatenensis, Cryptosporidium parvum, Microsporidium sp. , Dientamoeba fragilis, Isospora belli Entamoeba histolytica, Balantidium coli
Case 3 • A 55 y/o business man is traveling to Lima, Peru, for a week. He is healthy except for reflux disease for which he takes omeprazole. He wants to be prepared for the possibility of getting traveler’s diarrhea. – Causes? – Prophylaxis? – Treatment of traveler’s diarrhea? picasaweb. google. com
Traveler’s diarrhea • Causes: ETEC, Salmonella, Shigella, Campylobacter, viruses, Giardia • Prevention: – Dietary discretion: avoid raw, uncooked foods – Water: boiled or carbonated. (Bottled) • Treatment of water: boil x 1 min, treat with iodine, or filter – Pepto-bismol tablets • Treatment: – Antimotility agents (symptomatic for mild cases) – Antibiotics: quinolones, azithromycin, rifaximin – Seek medical attention with dysentery
Rifaximin (Xifaxan) • Non-absorbed rifampin-like antibiotic – Active against E. coli strains, but not Shigella – Expensive • Prevention: 200 mg PO once daily • Treatment: 200 mg tid x 3 days ($32)
The 1854 cholera epidemic in London and the beginning of modern epidemiology and public health
Center for Vaccine Development M. Levine, Univ. Maryland
Center for Vaccine Development M. Levine, Univ. Maryland
ERI = Excess Rate of Isolation Center for Vaccine Development M. Levine, Univ. Maryland
ERI = Excess Rate of Isolation Center for Vaccine Development M. Levine, Univ. Maryland
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