CURICULUM VITAE Job Description (History) : Name :Suharyo Hadisaputro, Prof.Dr.dr..Sp.PD-KPTI, FINASI Borne : Juana, March 10 , 1945; Position : Professor in Medicine Medical Faculty Diponeoro Univ Education : Doctoral in Medical (Public Helath),1990; Cosultan of Tropical Infectious Disease, 1986; Internal Medicine Spesialist, 1981; Medical Doctor, 1972; Job Description (History) : Chief I of Researcher Tropical Infectious Disease Jkt; Chief of Researcher Tropical Infectious Disease Semg Chief of Program of Doctoral Medical & Health Undip. Chief Program of Magister Epidemiologiy Undip. Director of Postgraduate Program Diponegoro Univ; Interest of Science : Field and Clinical Epidemiology Tropical I nfectious Disease; Epidemiology of Communicable Disease; Epidemiologiy of Non Communicable Disease; Epidemiology of Iodine Disorder Deficiency

(Food & Water Borne Disease) INFECTIOUS DIARRHEA (Food & Water Borne Disease) Suharyo Hadisaputro International Seminar of Food and Water Borne Disease September 17, 2012 in Semarang, Indonesia

Outline of Presentation Introduction Significance & prevalence High Risk Circumstances & Populations Pathogenesis Etiologic Agents Diagnostic Approach & Differential Management

FACTORS INFLUENCED TO INCREASED OF INFECTIOUS DISEASES IN INDONESIA (1) Economic Development, Changed of Demografic and Life Style in Community; (2) Development of Transportation  Increased of Traveller inter-region, island, and city in Indonesia. (3) Environmental changed  Disaster in many areas in Indonesia, and many projects irigations ? (4) Limitation of manpower and health sevices in community; Non hygiene of foodhandling  transmission of bacteriae (Salmonella typhi); Mutation and Evolution of organism  new strain emerge and antibiotics resistancy.

EMERGING INFECTIOUS DISEASES IN INDONESIA Vector borne Disease : (1) DF/DHF (2) Chikungunya (3) Japanese Encephalitis (4) Malaria (5) Filariasis (6) Leptospirosis (7) Toxoplasmosis; Sexual Transmitted Disease (STD); Airborne Disease : (1) Tuberculosis (2) Influenza. Food and Water borne Disease : (1) Typhoid Fever (2) Diarrhoae.

FOOD AND WATER BORNE DISEASES. (1) TYPHOID DAN SALMONELLOSIS : The sanitary factor and hygienic food and water take was responsibility on the increase of the morbidity of typhoid fever. DIARRHOEA : Many causes of diarrhoea, and the strain of Cholera Vibrio O 139 from Bangladesh was a potentially factor to increase the case of diarrhoea in Indonesia.

Causes of Death Worldwide Pneumonia 8.5% Diarrhea 5.8% TB 3.9% Measles 2.1% • Infections - 24.4% • Ischemic Heart Disease - 12.5% Malaria 1.7% Tetanus 1.1% Pertussis 0.7% HIV 0.6% 2 4 6 8 Percent Lancet 1997;349:1269

TEN MAIN DISEASES IN INDONESIA URBAN/RURAL AREA

TEN MAIN DISEASES OF CAUSED OF DEATH IN INDONESIA

Risks in 3rd World Lack of safe water supply Contaminated foods Poor sanitation Overcrowding Malnutrition

Global Risks in the World Traveller Diarrhoea HIV infection & immunosuppression Day Care Centers: fomite spread Also affects staff, household contacts Nursing Home/Chronic Care Facilities Antibiotics Achlorhydria/H2 blocker

Factors in Emergencies Lack of safe, clean water supply Contamination of food supply Poor sanitation Overcrowding Malnutrition HIV infection & immunosuppression

Overall Significance One of most common diseases in world 3-5 billion cases of acute infectious diarrhea annually Kills 5-10 million people/year In the U.S., more than 8 million seek medical attention for diarrhea; costs $23 billion in medical expenses & lost wages

DIARRHEA Diarrhea is a common symptom that can range in severity from an acute, self-limited annoyance to a severe, life-threatening illness. Patients may use the term "diarrhea" to refer to increased frequency of bowel movements, increased stool liquidity, a sense of fecal urgency, or fecal incontinence

Definition διάρροια; literally meaning "through-flowing" Stool looses its normal consistence Weight usually increases: >235g/d (♂), >175g/d (♀)‏ Frequency increases: >2/d Often associated with imperative urge to defecate Can contain blood, pus and mucous

Definition In the normal state, approximately 10 L of fluid enter the duodenum daily, of which all but 1.5 L are absorbed by the small intestine. The colon absorbs most of the remaining fluid, with only 100 mL lost in the stool. From a medical standpoint, diarrhea is defined as a stool weight of more than 250 g/24 h

Input Absorption Fecal Water 100-200 mL/d Diet/Saliva : 3 L/d Stomach : 2 L Jejunum : 5 L/d Bile : 1 L Pancreas : 2 L Bowel : 1 L Ileum : 2-3 L Colon : 1-2 L Total 9 L Total 8.8 L Fecal Water 100-200 mL/d Thus, diarrhea is defined as >200 mL liquid excretion per day. In extremus, the gastrointestinal tract can both absorb and secrete 20 L of water per day.

ACUTE DIARRHEA Diarrhea that is acute in onset and persists for less than 3 weeks is most commonly caused by infectious agents, bacterial toxins (either ingested preformed in food or produced in the gut), or drugs

Causes of acute infectious diarrhea Viral - Norwalk virus, Norwalk-like virus, Rotavirus Protozoal - Giardia lamblia, Cryptosporidium Bacterial - Preformed enterotoxin production Staphylococcus aureus, Bacillus cereus, Clostridium perfringens Enterotoxin production; Enterotoxigenic E coli (ETEC), Vibrio cholerae

Toxicogenic/Secretory Other classifacation Viral Protozoan CMV, Rota, adeno, enterovirus, Norwalk Giardia, Amy the Ameba, Cryptosporidium “Invasive” Toxicogenic/Secretory E. Coli 0157:H7, Shigella Salmonella, Vibrios, Campy Low-Backed Her, Staph, noninvasive E. Coli, Be Serious, C. Difficile, Cholera *lumps together invasive, inflammatory, non-amebic dysenteries, etc.

Pathogenesis Stimulation of net fluid secretion Mucosal destruction with increased permeability Nutrient malabsorption Increased propulsive contraction

Etiologic Agents Toxin-producing bacteria Invasive Bacteria Parasites Viruses

Toxin-producing bacteria Cholera Shigella ETEC (enterotoxigenic E. Coli) EHEC (Enterohemorrhagic/EC 0157 Clostridium difficile Bacillus cereus

Vibrio Cholera Spread in water, undercooked seafood Secretion of fluid in small intestine Malabsorption of fluid in large intestine Rice water stools—large volume, high electrolyte content More info: Cholera

Shigella Spread by contaminated food, water Bloody diarrhea characteristic Fever common Some carriers asmptomatic; symptoms usually occur in 2-3 days More info: Shigella

ETEC (Enterotoxigenic EC) Major cause of diarrhea in developing countries & travelers Two toxins, one cholera-like Causes watery diarrhea, nausea, cramps, low-grade fever Rx: TMP-SMX or Bismuth salicylate More info: ETEC

EHEC (Enterohaemorrhagic EC) Toxin from undercooked food, especially beef May be mild or asx, but fever, severe cramps & bloody diarrhea common Cause of hemolytic uremic syndrome More info: EHEC-O157

C. difficile Antibiotics facilitate overgrowth of normal bowel inhabitant Watery diarrhea +/- blood, cramps, fever Treatment: oral vancomycin or Flagyl More info: C. difficile

Invasive Bacteria EIEC (enteroinvasive E. coli) Salmonella Campbylobacter Yersinia

Enteroinvasive E. coli Symptoms mimic Shigella: bloody diarrhea, fever, cramps Thought to be spread by food contamination Therapy supportive, usually self-limited without requiring antibiotics More info: EIEC

Salmonella Contaminates raw eggs, dairy products, poultry, other meats Fever, diarrhea, +/- vomiting, can enter bloodstream More common in children, in summer More info: Salmonella

Enteric Fever A severe systemic illness manifested initially by prolonged high fevers, prostration, confusion, respiratory symptoms followed by abdominal tenderness, diarrhea, and a rash is due to infection with Salmonella typhi or Salmonella paratyphi, which causes bacteremia and multiorgan dysfunction

Campylobacter Spread by contaminated water or raw milk Causes patchy destruction of walls of small and large intestines Diarrhea +/- blood, fever, vomiting, HA, abd pain More info: Campylobacter

Yersinia Contaminates dairy products, poultry, & other meat Multiple syndromes, including sepsis in immunosuppressed; appendicitis-like; fever/diarrhea/abd pain in children; & extra-intestinal infections More info: Yersinia

Parasites Giardia lamblia Entamoeba histolytica Cryptosporidium

Giardia Zoonosis, animals contami- nated Water Diarrhea, abdominal pain, gas Treat w/ Flagyl

Entamoeba histolytica Diarrhea, often Bloody, fever, abd cramps Onset usually 2-4 wks, range days-mos Treat w/ Flagyl More info: Amoeba

Cryptosporidium Watery diarrhea, emesis, cramps, fever Transmitted in water or fecal-oral More pathogenic in immunosupressed, especially AIDS Best treatment is restoring immune fn, (e.g., several drugs for HIV), azithromycin shows some efficacy More info: Cryptosporidium

Viruses Rotavirus Norwalk Agent Calciviruses

Rotavirus Epidemiology Most common cause of acute gastro-enteritis in children worldwide Infects almost all children by age 4 Kills nearly one million annually Fecal-oral transmission, lasts for days on toys & countertops More common in winter

Rotavirus features Ranges from asymptomatic to severe 3-9 days’ fever, abd. pain, diarrhea Wheel-shaped RNA virus, seen in stool on EM, or diagnosed by ELISA Prevent w/ handwashing & hygiene Rx severe cases w/ ORS or IV fluids More info: Rotavirus

Calciviruses Known as Norwalk-like viruses—small, single-stranded RNA viruses Associated with ingestion of raw shellfish, fecal-oral transmission Cause diarrhea, vomiting, fever, headache

DIAGNOSTIC APPROACH Often based on clinical grounds alone Diagnostic studies often unavailable Symptoms often resolve, or require prompt treatment, before results can be obtained Clinical features that may be helpful include exposure/risk factors; stool volume, presence of blood, associated symptoms

DIAGNOSTIC STUDIES If available, may include: Fecal leukocytes Stool culture Ova and parasites C. difficile titer Amoeba titers

MANAGEMENT OF DIARRHOAE Treatment often empiric Oral rehydration therapy (ORT) IV hydration Anti-diarrheals: anti-motility, absorbent, and anti-secretory agents Antibiotics

Oral Rehydration Safe, simple, cheap 1st use: Bangladesh, 1971—dramatic reduction in mortality Premix, or use H2O, salt, sugar Treats and prevents diarrhea Sodium-glucose co-transport Mothers can administer ORT

Oral Rehydration Glucose-based ORT may paradoxically increase fecal fluid loss Rice-based ORT may more quickly relieve symptoms, ? More available High amylose maize (amylase-resistant) based ORT shortens diarrhea duration and reduces stool volume

Indications for IV hydration Severe dehydration (hypotension, shock, stupor, coma) Ileus—abd distention a/o absent BS Persistent severe vomiting Excessive stool output (10cc/kg/hr) Severe glucose malabsorption

More on IV hydration Replace fluid deficit as well as continuing losses Transition to ORT as soon as dehydration improves and/or gut seems to be working again

Antimotility Agents Increase segmental & decrease propulsive contractions Prolong transit time Loperamide better than diphenoxylate in clinical trials Opiates have similar effect on motility Limit to 48 hours; may prolong illness & can cause ileus or toxic megacolon

Absorbent agents Nonabsorbable resins, e.g. cholestyramine Bind C. difficile toxin Speed toxin clearance, promote mucosal recovery—for multiple pathogens Stop 5 days after symptoms resolve

Antisecretory agents Decrease propulsive contractions Increase mucosal absorption Decrease mucosal secretion Enhance electrolyte & H20 reabsorption Most useful in AIDS-associated diarrhea Ex.: octreotide

Antibiotics in Diarrhoae Not indicated for most cases of simple, watery diarrhea Most helpful for: Shigella, ETEC, ameobiasis, giardia, cholera, S. typhi May help for cryptosporidium, other salmonella Not useful for viral, EIEC

Special treatment of cholera Oral Rehydration Therapy Antibiotics Limit spread of disease by reducing volume & duration of diarrhea Adults: Doxycycline, 300 mg once Children: 6 mg/kg once Alternatives: TTC, Chloramphenicol, Septra, quinolones, erythromycin

CONTROL OF ENTERIC FEVER Applying the principle of hygiene Depend of the improvement of income Cultural changes of personal hygiene Many effort for control of TF, are : (1) Treatment and control of sources infection : Adequate antibiotic treatment for active patients and carriers, special isolation in the hospital ?, desinfections of the excreta, sterilization of the patient’s linen etc.

CONTROL OF ENTERIC FEVER (2) Improved on environment health . To trace the source infection . To investigate of routes transmis . Water purification/chlorination . Control of all exposed foods for sale in the market and store. . Reduction the house-flies density . To avoid of having open garbage pail etc.

CONTROL OF ENTERIC FEVER (3) Supervision on food industries and restaurant . Supervision on sanitation of places work and food processin, equipment etc. . Prohibition to employ people who infected . Routine examination of stool culture . To trace of food, if as medium suspected . All milk and milk products should be pasteurized or boiled.

CONTROL OF ENTERIC FEVER (4) Control of healthy population . Supervision on hygiene of food and drink . Serving the food in hot condition . Health education for community . Providing the places for washing hand . Conducting vaccination of EF in endemic area, however, improvement of sanitation and health system is very important role.

THE WHO GOLDEN RULES FOR SAVE FOOD PREPARATION Choose foods processing for safety. Cook food thoroughly. Eat cooked food immediately. Store cooked food thoroughly. Reheat cooked food thoroughly. Avoid contact between raw and cooked foods. Wash hands repeately. Keep all kitchen surfaces meticolously clean. Protect foods from insects, rodents & animals. Use pure water.

LEVEL OF PREVENTION NO DISEASE ASYMPTOMATIC DISEASE CLINICAL COURSE ORDINARY DETECTION ONSET NO DISEASE ASYMPTOMATIC DISEASE CLINICAL COURSE PREMORD Underlying risk factors PRIMARY Remove of risk factors SECONDARY Early detec-tion & prompt treatment TERTIARY Reduce complications

SUMMARY OF DIARRHEA CONTROL Diarrheal disease most prevalent in developing countries, and costly. In Indonesia incidence still high. Transmission most of direct route. Empiric treatment with ORT most often effective The strategies of Diarrhea Control

SUMMARY OF DIARRHAE CONTROL The strategies of Diarrhea Control are : . Detection and control of source, . Disease surveillance, . Health education in community, . Improvement of hygiene sanitation, . Promotion of water and food borne disease, . Prevention contamination in food/water production, . Conducting vaccination ??.

TERIMA KASIH