DIARRHEA & DEHYDRATION - - Get a Free Blog Here
Transcript of DIARRHEA & DEHYDRATION - - Get a Free Blog Here
CURRICULUM VITAE
• Name w/ title : S. Yati Soenarto, MD, Ph.D.Professor ofPediatrics, Consultant for Gastroenterology Place
• DOB : Sukamandi, February 5th 1944 • Home Address : Jalan Sendok CT 8/135 Karanggayam,
Jogjakarta, Indonesia• Office Address : Pediatric Research Office, Department of
Child Health, Faculty of Medicine, Jl.Kesehatan no.1 Sekip Jogjakarta 55281,
RSUP. Dr. Sardjito Teaching Hospital• Phone Number : +62-274-563683 (Home/fax);
+62-274 555455 ; +62-811-256011 • Email : [email protected] PositionChairs• Pediatric Research Office, Department of Child Health,
Faculty of Medicine, Universitas Gadjah Mada (UGM)• Unit of Research Management of Clinical Epidemiology
&Biostatistics, Sardjito Teaching Hospital, Jogjakarta • Health & Medical Researcher Cluster, Universitas Gadjah
Mada (UGM)
UNIVERSITY TRAININGS AND DEGREES HELD
1970 M.D., Faculty of Medicine, Gadjah Mada University, Jogjakarta Indonesia
1975 Pediatrician, Faculty of Medicine, Gadjah Mada University, Jogjakarta, Indonesia
1978 Pediatric Gastroenterology, Wilhelmina Children Hospital, Utrecht, The Netherlands
1985 Pediatric Gastroenterology, Royal Children Hospital-Melbourne University, Australia
1988 Pediatric Consultant for Gastroenterology, Indonesian Pediatric Society, Indonesia
1988 Health Care Evaluation & Management Skills, University of Toronto, Canada
1995 Freeman fellow, Department of Social Medicine, Harvard Medical School, Boston, Massachucets, USA
1997 Ph.D, Faculty of Medicine, Vrije Universitiet, The Netherlands2007 Professor, Gadjah Mada University, Jogjakarta, Indonesia
PRESENT/RECENT APPOINTMENTS• Visiting Professor, Faculty of Medicine,
Melbourne University (2006)• Coordinator, University Research Cluster for
Health and Medicine, UGM Jogjakarta (2007 – present)
• Chair, Clinical Epidemiology & Biostatistics Unit, Faculty of Medicine Gadjah Mada University / Sardjito Teaching Hospital (2007 – 2010)
• Unit of Research Management of Clinical Epidemiology & Biostatistics, SardjitoHospital (2009-present)
AWARDS• 2010 Achmad Bakrie 2010 award for Outstanding Medical field & Highly
respect for the Idea of Freedom. Freedom Institute, Jakarta, Indonesia• 2009 Asia Pacific Pediatrician Assosiation (APPA), Outstanding Asian
Pediatrician Award.• 2008 Indonesian Pediatrics Society, R. Sutedjo Award (Honor for
Exceeding Social Prestige in Health Profession Appliance, Especially in the Field of Child Health).
• 2008 Faculty of Medicine, Gadjah MadaUniversity, Jogjakarta, Prestigious Lecturer.
• 2006 Faculty of Medicine, Gadjah MadaUniversity, Jogjakarta, Dedication for Helping the Sardjito Hospital and Faculty of Medicine Gadjah Mada University Health Reconstruction Project in Nangroe Aceh Darussalam
• 2006 University of Melbourne, Australia, as Visiting Professor at the Faculty of Medicine and Dentistry.
• 2004 Gadjah Mada University, Award for Best Performance in Research and Public Services, Category of International Collaborative Research on Rotavirus Study
PUBLICATION• Siswanto Agus Wilopo, Yati Soenarto, Joseph S. Bresee, Abu Tholib, Sri Aminah, Anton
Cahyono, Jon R. Gentsch, Paul Kilgore, Roger I. Glass. Rotavirus surveillance to determine disease burden and epidemiology in Java, Indonesia, August 2001 through April 2004. Vaccine27S (2009) F61–F66.
• Siswanto Agus Wilopo, Paul Kilgore, Soewarta Kosen, Yati Soenarto, Sri Aminah, Anton Cahyono, Maria Ulfa, Abu Tholib. Economic evaluation of a routine rotavirus vaccination programme in Indonesia. Vaccine 27S (2009) F67–F74.
• Sundari TA, Soetjiningsih, Soenarto Y, Karyana IPG. Efficacy of reduced osmolarity oral rehydration solution, rice-based oral rehydration solution and standard WHO oral rehidration in children with acute diarrhea: a randomized open trial. Paediatrica Indonesiana 2009; 49(3): 169-76
• Soenarto Y, Tholib AT, Bakri A, Waluya H, Firmansyah A, Kadim M, Martiza I, Prasetyo D, Mulyani N, Widowati T, Soetjiningsih, Karyana IPG, Sukadi IW, Widdowson MA. 2008. The Burden of Severe Rotavirus Diarrhea in Indonesia. Journal of Infectious Diaseases 1 November 2009 Volume 200 Supplement 1 hal 188-194
• Putnam SD, Sedyaningsih ER, Listiyaningsih E, Pulungsih SP, Komalarini, Soenarto Y, Salim Och, Subekti D, Riddle MS, Burgess TH, Blair PJ. 2007. Group A Rotavirus – Associated Diarrhea in Children Seeking Treatment in Indonesia. J Clin Virol. 40 (4) : 289-94.
Prof. DR. dr. S. Yati Soenarto, Ph.D., Sp.AK
Pediatric Research Office (PRO),Department of Child Health,
Unifersitas Gadjah Mada /RSUP Dr. Sardjito
Neonatal 38%
Diarrhea18%/28%
Pneumonia14%/20%
Others22%
GLOBAL
CAUSES OF DEATHS IN CHILDREN U5
Bryce J, et.al., 2005
INDONESIAYR 2000 ‐ 2003
WHO,2006/ RISKESDAS
2007
www.who.int.org
ASIA – WHO SEAROYR 2002
“DIARRHEA”
GLOBAL ASIA – WHO SEARYR 2002
Why is diarrhea dangerous?
DIARRHEA DEATH due to LOST (& LACK) of:
WATER & ELECTROLYTE FOOD
Diarrhea
increased loss of water and electrolytes (sodium, potassium
and bicarbonate) in the liquid stool
losses are not adequately replaced and a deficit of water and
electrolytes develops.
Dehydration
decrease in food intake and
nutrient absorption
weight loss and failure to grow
increased nutrient
requirements
Malnutrition
DEATH
SEVERE DEHYDRATION !
1. Signs or symptoms :
Two/more of the follow :• Lethargy/unconsciousness• sunken eyes• unable to drink/drinks
poorly• skin pinch goes back very
slowly ( ≥ 2 seconds )
2. Treatment :
• Give fluid for severedehydration (DiarrheaTreatment Plan C)
SOME DEHYDRATION
1. Signs or symptoms :
Two/more of the follow :
• restlessness, irritability• sunken eyes• drinks eagerly, thirsty• skin pinch goes back
slowly
2. Treatment :
• Give fluid & food for some dehydration (Diarrhea Treatment Plan B)
• After rehydration, advise mother on home treatment & when to return immediately
• Follow up in 5 days ifnot improving
NO DEHYDRATION
1. Signs or symptoms :Not enough signs to
classify as some or severe dehydration
2. Treatment :
• Give fluid & food to treat dehydration diarrhoea at home(Diarrhea Treatment Plan A)
• Advise mother on when to return immediately
• Follow up in 5 days if not improving
WHO Hospital Care for Children, 2006
Classification of the severity of dehydration in children with diarrhea
CLASSIFICATION
DIARRHEA
Based on duration : Based on pathophysiology :
Acute:
Starts suddenly, may continue for several days
Persistent:
starts like acute diarrhea, lasts for >14 days
Osmotic:Caused by luminal substances that induced fluid secretion
Secretoric:endogenous substances (“secretagogues”) induce fluid secretion
I N D O N E S I A
Mortality MorbidityDiarrhea-U5:
Household survey, 2001Basic Health Research (Riskesdas), 2007
ORS
Simpulan: ORS mampu menurunkan angka kematian akibat diare namuntidak pada morbiditasnya
5 LANGKAH TUNTASKAN DIARE
CASE MANAGEMENT
Rehydration: IV oralit 1. NEW ORALIT (REDUCED OSMOLARITY )
2. CONTINUED FEEDING
PHARMACOLOGIC
5. 5. PATIENT-DOCTOR COMMUNICATION
22.ZINC
3. RATIONALANTIMICROBA
1. DEHYDRATION:
2.NUTRITION:
3. ETIOLOGY(commonly infection)
4. SUCCES OF PRACTICE:
5 STEPS OF MANAGEMENT FOR DIARRHEA(PROGRAM)
4. NO ANTIDIARRHEA & ANTIVOMITING
SEVERITY & INCIDENCE
Intravenous“All”
Fasting
AntibioticAntidiarrhea
• ORT: ORS• Limited IV fluid
Feeding: Continue during & increase after diarrhea
Continued feeding
ANTIMICROBES
New formula ORS
ANTIDIARRHEA&ANTIEMETIC&…DRUGS
Patient-Doctor’s Communication!
Incidence,severity &Recurrentdiarrhea
Selective
1970th-1980th
Duration, volume &IV
+ Patient safety
“No” Patient-Doctor’s-
Communication
Zn Suplementation
ANTIMICROBES
ANTIDIARHEA
Development Management of Diarrhea (Program)
-Pre&Probiotics antiemetics -Vaccine ?
ORS Formulas: 1968 - 1977Sodium
mEq/l
Glucose
mmol/l
Osmol
mOsmol/l
ADULTS 101 - 133 40 - 256 274 - 536
CHILDREN 80 - 120 110 - 140 300 - 400
World Health Organization. Implementing the New Recommendations on the Clinical Management of Diarrhoea: Guidelines for Policy Makers and Programme Managers. Geneva: World Health Organization, 2006.
WHO/UNICEF ORS - 1978
• NaCl 3.5 g• NaHCO32.5 g• KCl 1.5 g• Glucose 20 g
• Na+ 90 mEq/l• K+ 20 mEq/l• HCO3 30 mEq/l• Glucose 111 mmol/l• Cl 80 mmol/l• Osmolar.311
mOsmol/l
World Health Organization. Implementing the New Recommendations on the Clinical Management of Diarrhoea: Guidelines for Policy Makers and Programme Managers. Geneva: World Health Organization, 2006.
What is new in ORS?Standard formulation of
ORS• Sodium 90 MEq/L • Osmolarity of 311
mmol/L
New formulation of ORS
• Sodium 75 mEq/L • Osmolarity 245 mmol/L
Reduction of levels of glucose and salt shortens duration of diarrhea
Reduced osmolarity decreases stool output
Improved effectiveness for children with acute, non-cholera diarrhea
Previous Recommendations
• Use of Oral Rehydration Solution and home fluids to correct and prevent dehydration
• Continued feeding including breastfeeding
• Antibiotics for dysentery
• Why Change ? “No effect” on diarrhea duration
New RecommendationsWHO and UNICEF issued a joint policy for the treatment of diarrhea in children in May 2004Treatment should include
Liberal use of low-osmolarity Oral Rehydration Solution and home fluids to correct and prevent dehydrationZinc supplementation for 10-14 days to shorten duration and severity of diarrheaContinued feeding including breastfeedingAntibiotics for dysentery
WHO/UNICEF. Joint statement on the clinical management of acute diarrhea. 2004.
More than A decade of Research Search for
“Super ORS”
Effect of study ORS solutions of different osmolarity on stool output
310 330 360 380
Osmolarity of study ORS solution (mmol/l)
0
40
80
Per
cent
age
diffe
renc
e in
sto
ol
outp
ut c
ompa
red
with
WH
O O
RS
1. New Lo-ORS
AGE AMOUNT OF ORS AFTER EACH LOOSE STOOL
AMOUNT OF ORS TO PROVIDE FOR USE AT
HOME
<12 MONTHS 5O-100 ml 400ml/DAY
1-4 YEARS 100-200 ml 600-800 ml/DAY
> 5 YEARS 200-300 ml 800-1000 ml/DAYADULT 300-400 ml 1200-2800 ML/DAY
200 ml: 1 SACCHETE
Reducing concentration:
-glucose 75 mmol/L
-sodium (NaCl) 75mEq/L
-overall 245 mOsm/Lthe need of IV therapy 33%
stool output 20%
vomiting 30%WHO/UNICEF Joint Statement, 2004
OUTCOME
Multicenter, randomized, double-blind clinical trial to evaluate reduced osmol ORS efficacy & safety in children with acute
watery diarrhea
Therapy with low osmol ORS
A significantly lower proportion of children who required unscheduled intravenous therapy
95% CI:0.4-1.0
Conclusion
Treatment with reduced osmolarity ORS solution was associated with 33% reduction
in the need for unscheduled IV therapyCHOICE Study group, 2001
Systematical review to evaluate reduced osmol ORS for treating dehydration caused by acute diarrhea in children
Therapy with low osmolORS in acute diarrhea
Low osmol ORS was associated with fewer unscheduled intravenous fluid infusions compared with standard WHO ORS (Maentel hanzel OR 0,59, 95% CI 0,45-0,79). Stool output and
vomiting was reduced in reduce osmol ORS.
Conclusion
Reduce osmol ORS is associated with fewer unscheduled IV infusions, lower stool volume
and less vomiting Hahn et al., Cochrane Database of
Systematic Reviews 2002, Issue 1 2009
Systematical review to evaluate reduced osmol ORS for treating Cholera
Therapy with low osmolORS in cholera
There isn’t a significance difference in the need for unscheduled intravenous infusion. The duration for diarrhea is
also shorter in reduced osmol ORS (MD -16,85 hours, CI -21,22 to -12,48; 102 participant, 2 trials). Hyponatremia also occur in reduced osmol ORS but this wasn’t significance in
severe hyponatremia caused by diarrhea.
Conclusion
Treatment with reduced osmolarity ORS solution was effective in treating cholera although
hiponatremia usually occurs.
Murphy et al., Cochrane Database of Systematic Reviews 2004, Issue 4. 2009
2. Continued feeding
Improper beliefs & lack of knowledge
“Resting of bowels”
Malnutrition
Brown, 2003
CONTINUE BREAST FEEDINGIF NO BF, CONTINUE THE PREVIOUS MILK. <6MONTHS: FREQUENT SMALL FEEDING6MONTHS/ >:−PORRIDGE + NUTS, VEGETABLES,MEAT/FISH
+1-2 TEESPOON OIL− FRESH FRUIT/BANANA (POTASIUM)− FRESH FOOD; COOKED AND SOFT FOOD−STIMULATE TO EAT, AT LEAT 6 TIMES−DIARRHEA STOP: CONTINUE FEEDING + EXTRA
MEAL/DAY->2 WEEKS (WHO, 1997)
Breast feeding shortens the duration of acute diarrhea, rotaviral diarrhea, and persistent diarrhea (cit. WHO, 1997)
Early breast feeding (within the first 3 days of life) reduces the risk of diarrhea in the first 6 months of life due to the effects of human colostrum (Clemens et al, 1999)
• Zinc Supplementation WHO/UNICEF recommendations (2004):
Infant – 6 month old : 10 mg/day (10-14 days)
Children older : 20 mg/day (10-14 days)
Micronutrients
3. Micronutrients - Zinc
Establishing Efficacy and Safety of Zinc Supplementation
Before After Zinc Therapy
Impact of Zinc Deficiency
www. www.doctors.ly, 2009
ZINC : Mechanism of Action
Zinc
immune system
intestinal absorptive and/or
secretorytransport process
Antimicrobialeffect
Inhibit growth (3)
S. thyphi, S. parathypiA, V. cholerae, Shigellaflexneri, Shigella sonnei
Humoral and cellular (1)
Anti-diarrheal agent by inhibiting Cl
secretion (2)
1. Cit. Rahman et al. 2005. Am J Clin Nutr2. Hoque et al. 2005. Am J Physiol Gastrointest Liver Physiol3. Surjawidjaja et al. 2004 Medical Principles and Practice
Trials on the Therapeutic Effect of Zinc on Acute Diarrhea
• Countries: Bangladesh (3), Brazil, India (6), Indonesia, Nepal
• Age groups: 3-60 mo
• Dose of zinc: ≈20 mg/d (range 5-45 mg/d)
• Reduces the duration and severity of the episode
Trials in the Pooled Analysis of the Therapeutic Effects of Zinc
Country
No. in Zinc Group
No. in Control Group
Age (mo.)
Zinc Supplement
Indonesia 739 659 3-35 4-5 mg/kg (acetate)
India 456 481 6-35 20 mg (gluconate)
Bangladesh
57 54 3-24 20 mg (acetate)
Am J Clin Nutr. 2000;72:1516-22.
Additional Trials in the Meta-Analysis of the Therapeutic Effects of Zinc in Acute Diarrhea
Trial
No. inZinc Group
No. in Controlgroup
Age (mo)
Zinc Supplement
Bangladesh
341 340 6-23 14.2 or 40.0 mg (acetate)
India 44 36 3-24 40 mg (sulfate)
Brazil 37 37 3-60 22.5 or 45 mg (sulfate)
India 25 25 6-18 40 mg (sulfate)
Additional Trials in the Meta-Analysis of the Therapeutic Effects of Zinc in Acute Diarrhea
Trial
No. in Zinc Group
No. in Control group
Age (mo)
Zinc Supplement
Bangladesh 2001
620 632 3-59 20 mg (acetate)
India 2001a
547 547 3-35 5 or 10 mg (sulfate)
Nepal 442 449 6-35 15 or 30 mg (gluconate)
Additional Trials in the Meta-Analysis of the Therapeutic Effects of Zinc in Acute Diarrhea
Trial
No. in Zinc Group
No. in Control group
Age (mo)
Zinc Supplement
India 2001c
404 401 3-35
15 or 30 mg (gluconate)
India 2001b
132 134 3-36
15 or 30 mg (sulfate)
Effect of Zinc Supplementation on Duration of Acute Diarrhea/Time to Recovery
*Bangladesh, 1999
Pooled
1*Difference in mean and 95% CI
Relative Hazards and 95% CI
*India, 1988
*India, 2000*Brazil, 2000*India, 2001
Indonesia, 1998India, 1995
Bangladesh, 1997India, 2001India, 2001
Nepal, 2001Bangladesh, 2001
Age <12 months Age ≥12 months
Wasted Not Wasted
Male Female
0 0.25 0.5 0.75 1 1.25 1.5 1.75 2Relative Hazard and 95% CI
Relative Hazard of Continuation of Diarrhea inZinc-Supplemented Children With Acute DiarrheaPooled Effect (Stratified Analysis) in Subgroups
Effect of Zinc Supplementation on continuation of Acute Diarrhea for > 7days
Analysis Odds Ratio (95% CI)
Pooled Analysis (n=3)
0.78 (0.56, 1.09)
Meta – Analysis (n=5) 0.73 (0.55, 0.98)
J Pediatr. 1999 ;135:689-97.
Effect of Zinc Supplementation on Duration of persistent Diarrhea Episode
Analysis Effect MeasureEffect Size (95% CI)
Pooled Analysis (n=4)
Lower probability of continuing diarrhea
24% (9%, 38%)
Meta-Analysis (n=5)
Reduction in mean duration
29% (6%, 52%)
J Pediatr. 1999 ;135:689-97.
Lukacik, M, et.al.; 2007
Conclusion
Zinc supplementation
Reported to have a 18.8% reduction in average stool
frequency
(n=4438)
Reported to have a 17.9% reduction of
diarrhea
(n=4438)
zinc supplementation reduces the duration and severity of acute diarrhea
Reported to have a 15.0% shortening of
diarrhea duration
(n=4438)
Conclusion
Zinc supplementation
Reported to have a 12,27% shortening of acute diarrhea duration(13 trials, n=1417)
Reported to have an adverse effect of vomiting
by 1,71 fold(9 trials, n=2390)
zinc supplementation reduces the duration of acute and persistent diarrhea but vomiting is also occurs
Reported to have a 15.84% shortening of
persistent diarrhea duration
(5 trials, n=267)
Lanzerini and Ronfani, Cochrane Database of Systematic Review issue 3, 2008.
Conclusion
Zinc supplementation
Reported to lower average duration of diarrhea (WMD -0,69; 95% CI -0,97 to -0,40)
(13 trials, n=5643)
Reported to have an adverse effect of vomiting
by 1,22 fold(5 trials, n=1384)
zinc supplementation reduces the duration and severity of gastroenteritis but vomiting is also occurs
Significantly reduce the number of episodes of diarrhea lasting longer than 7 days (RR 0,71;
95% CI 0,53-0,96)(8 trials, n=5769)
Patro et al., Aliment Pharmacol Ther 28:713-723, 2008.
Conclusion
Zinc supplementation
Reported to have a 19,70% shortening of acute diarrhea duration
(26 trials)
Reported to have an adverse effect of vomiting
by 2,13 fold(14 trials, n=6779)
zinc supplementation reduces the duration of acute and persistent diarrhea but vomiting is also occurs especially
when given in pre-admission of diarrhea
Reported to have a 15.84% shortening of
persistent diarrhea duration
(5 trials, n=267)
Patel et al., PLoS ONE 5(4): e10386, 2010.
Preventive Effect of Zinc Supplementation on Diarrheal and Pneumonia Incidence with Continuous Supplementation in Subgroups
0 0.25 0.5 0.75 1 1.25 1.5 1.75 2
Odds Ratio and 95% CI
Age < 12 months (4)
Age >= 12 months (3)
Zinc < 60 ug/dl (2)
Zinc >=60 ug/dl (2)
Wasted (4)
Not wasted (2)
Male (4)
Female (3)0 0.25 0.5 0.75 1 1.25 1.5 1.75 2
Odds Ratio and 95% CI
Diarrhea Pneumonia
* Number in parenthesis gives the number of trials contributing to the data
Preventive Effect of Zinc Supplementation on Diarrheal Incidence in Short - Course Supplementation Trials
Bangladesh (I)Bangladesh (II)
Pakistan
Bangladesh (III)
Pooled0 0.25 0.5 0.75 1 1.25 1.5 1.75 2 2.25 2.5
Odds Ratio and 95% CI
•14 days of supplementation (20mg) with surveillance for 2-6 months
Safety of Zinc Supplementation for Diarrhea Treatment
9,100 children <5 y supplemented with zinc or placebo in 18 trials
Vomiting is the only reported adverse effect5/7 trials report no differences between zinc and placebo2 trials report slightly higher vomiting rates in zinc supplemented children
4/4 trials show no adverse effects on copper status after 2 weeks of zinc supplementation
Statement from WHO Meeting, New Delhi, 2001
“There is now enough evidence demonstrating the efficacy of zinc supplementation on the clinical course of acute diarrhea. However, effectiveness studies to address different strategies for delivering zinc supplementation to children with diarrhea should be undertaken. (feasibility, sustainability, cost-effectiveness, consumption of ORS, antibiotic use, non- diarrhea morbidity, overall mortality).”
Zinc Investigators’ Collaborative Group. J Health Pop Nutr, 2001
American Academy of Pediatrics endorsed and accepted as its policy the Centers for Disease Control and Prevention
guideline : “Managing Acute Gastroenteritis Among Children: Oral Rehydration, Maintenance, and Nutritional
Therapy from the Centers for Disease Control and Prevention”, as follows:
Anti-Emetic
Ondansetron, a serotonin antagonist, either by the oral or IV route,
can be effective in decreasing vomiting and limiting hospital admission.
But, antiemetics are usually unnecessary in acute diarrhea management.Because acute diarrhea is a common illness, cost-effective analyses
should be undertaken before routine pharmacologic therapy is recommended
Evaluating Effectiveness
Community-based Trial of Zinc Supplementation During Diarrhea
In rural Bangladesh, 30 health worker areas randomized
8,070 3-59 mo old children, 11,880 child-years
ORT alone vs. ORT and 20 mg/d zinc
Duration of episodes: RH 0.77 (0.69, 0.86)
Diarrhea hospitalization: RR 0.81 (0.65, 1.00)
Mortality: RR 0.49 (0.25, 0.94)
Baqui, Black, Arifeen, et al., BMJ, 2002
Effects of Zinc Supplementation Started During Acute Diarrhea in Bangladesh*
Outcome Zinc (%) Control (%)
Treated with ORS 75 50†
Antibiotic use 13 34†
Other drug use 15 45†
Care from pharmacy 16 33†
Care from village “doctors”
12 27†
Care from homeopaths 6 13†
Baqui, Black, Arifeen et al, J Health Pop Nutr, 2004†All comparisons p<0.01
Multicountry Acceptability Study (INCLEN)
Brazil, Ethiopia, Egypt, India (2 sites), PhilippinesFormative assessment for messagesZinc dispersible tablets along with ORS for outpatient diarrheaPooled results
84% of children consumed >80% of 14 tablets 5 of 6 sites had no decline in ORS use in zinc-supplemented children48% reduction in use of antimicrobial/ anti diarrheal drugs in zinc-supplemented children
INCLEN. J Ped Gastro & Nutr (In Press)
Reasons:-Caretakers felt Zn no longer needed --diarrhea had resolve
- Nausea- Vomiting- Poor palatability- Only given during-
hospitalization72%
28%
Proportion of patients completed Zn 10-day course
Completed Not completed
N= 133
Soenarto et al, unpublished
Cost Benefit Analysis
Introduction of zinc into the standard treatment of diarrhea may cause:
potential reduction in lives lost in Indonesiareduced morbidityimproved nutritional statusPotential financial savings
Assessment for the introduction of zinc in improved maangement of diarrhea in Indonesia. BASICS
4. Pharmacologic
1. Antimicrobial drugsAntimicrobial agents should not be used routinely.
• should be preceded by appropriate stool cultures or pathogen detection tests.
• only few indications for empiric use , e.g. suspected or confirmed shigellosis or cholera, selected cases of inflammatory diarrhea, travelers’ diarrhea and diarrhea due to parasites.
2. Non-antimicrobial drugs• Anti-diarrhoeal drugs and anti-emetics
have no practical benefits for children with acute or persistent diarrhea.
• Antimotility drugs potentially life-threatening adverse effects, including lethargy, ileus, respiratory depression, & coma
4. Pharmacologic
ETIOLOGY of ACUTE DIARRHEA
BACTERIA
VIRUS PARASITES
Generally caused by 3 different agents (individually or as a combination altogether):
• Virus
• Bacteria
• Parasites
Acute gastroenteritis caused by viruses is one of the leading causes of childhood morbidity.
ETIOLOGY OF <5 DIARRHEA IN INDONESIA
80%
5%
1%
5%
3%
1%
1%
1%
2%
1%
5%
RV
Shigella
Aeromonas
Salmonella
Campylobacter
S. Enteritidis
Giardia Lamblia
Mixed (RV+Salmonella)
Mixed (RV+Campylobacter)
Mixed (RV+Ve Inaba)
Study at Sardjito hospital in collaboration with NIH, Ministry of Health, RI & NAMRU2 research, 2005
84% RV; 16% bacterial
<16% need antibiotic
ROTAVIRUS
Global death due to rotaviral diarrhea
ROTAVIRAL DIARRHEA : UNIVERSAL DISEASE
Percentage of rotaviral-diarrhea inpatients in Asia
Breese, 2005
2001-2004
Median = 45%
ROTAVIRAL DIARRHEA IN INDONESIA“Extension for Hospital Based Surveillance & Strain Characterization of Rotavirus Diarrhea in Indonesia”
Bandung 47%Bali 59%
Yogyakarta 35%
N = 2517 (RV: 57%)
2006-2007
Jakarta 67%
Palembang 60%
Mataram 63%
Soenarto et al,2007
CLINICAL MANIFESTATIONS RV DIARRHEA
Clinical presentations
# RV(+) diarrhea N=1435 (%)
# RV (-) diarrheaN=1089 (%)
OR CI
Vomiting 1219 (85) 718 (66) 2.9 2.4 –3.5*
Dehydration 1297 (90) 863 (80) 2.4 1.9 –3.0*
Mucus stool 399 (28) 347 (32) 0.8 0.7 –0.97*
Bloody stool 24 (2) 62 (6) 0.3 0.2 –0.5*
Fever 527 (37) 414 (38) 0.9 0.8 – 1.1
Soenarto et al,2007* p < 0.05
LEVEL OF DEHYDRATION
0
200
400
600
800
1000
1200
1400
Dehydration No dehydration
No.
of s
peci
men
s te
sted
# RV-positive patients# RV-negative patients
p < 0.05
Soenarto et al,2007
TREATMENT PRIOR VISITING HOSPITALS
# Sample tested N=2517 (%)
# RV(+) diarrheaN=1435 (%)
ORS 1416 (56) 865 (60)Antibiotics 689 (27) 398(28)Antivomiting 378 (15) 242 (17)Antidiarrhea 317 (13) 196 (14)Other drugs 668 (27) 395 (28)
Soenarto et al,2007 unpublished
• Research found that viral, especially rotavirus infection are more common for treating diarrhea
• Improving sanitation, hygiene & the availability of clean water may prevent bacterial & parasitic infection, but in rotaviralinfection it may not be the case
• rotavirus dominant vomiting symptoms, ORS may prove less effective
Do 5 STEPS OF MANAGEMENT FOR DIARRHEA (Lintas Diare) are Enough?
Efficacy of Rotarix against RVGE*
DiseaseSeverity
Number of Cases
% Efficacy 95% CIHRV
(N=9009)Placebo
(N=8858)
Severe 12 77 84.771.7, 92.4
Hospita-lized 9 59 85.0
69.6, 93.5
*Ruiz-Palacios G. et al N. Engl. J. Med. 2006; 354: 11-22
Type ofContact
Number of Cases % RateReduction
95% CIVaccine Placebo
Hospitalizations†
ED visits †
Office visits††
6
15
14
144
232
100
95.8
93.5
85.2
90.5, 98.2
88.6, 96.3
73.1, 91.9
Efficacy of RotaTeq to reduce healthcare utilization for rotavirus gastroenteritis*
*Vesikari et al New Engl J Med, 2006Per protocol population (includes only cases that occurred at least 14 days after Dose 3)
† N=34,035 vaccine and 34,003 placebo recipients†† N = 2,834 vaccine and 2839 placebo recipients
• Current therapies for pediatric diarrhea are limited to supportive and symptomatic care.
• Probiotics are especially useful in diseases mediated by the disruption of the normally protective microflora may offer an attractive supportive therapy for acute pediatric diarrhea.
Probiotics & Acute Diarrhea
Meta-analysis: Probiotics & Acute Diarrhea
1. Meta-analysis of probiotics for the prevention and treatment of acute pediatric diarrhea (McFarland, L.V.; Gary W. Elmer, G.W.; and McFarland, M.; 2005)
2. Efficacy of Probiotic Use in Acute Diarrhea in Children: A Meta-Analysis (Huang, J.S.; Bousvaros, A.; Lee, J.W.; Diaz, A.; and Davidson, E.J.; 2002)
3. Probiotic for Pediatric Antibiotic-Associated Diarrhea: a Meta Analysis of Randomized Placebo-Controlled Trials (Johston, B.C.; Supina, A.L.; Vohra, S.; 2006)
18 RCT: treatment of diarrhea by probiotic with diarrhea duration as outcome
8 RCT: treatment of diarrhea by probiotic with percent diarrhea cured as outcome
15 RCT: prevention of diarrhea by probiotic with percent failed as outcome
1. (McFarland, L.V.; Gary W. Elmer, G.W.; and McFarland, M.; 2006)
18 Studies: duration of diarrhea (treatment –control)
18 Studies: duration of diarrhea in days (treatment vs control)
2. (Huang, J.S.; Bousvaros, A.; Lee, J.W.; Diaz, A.; and Davidson, E.J.; 2002)
3. (Johnston, B.C.; Supina, A.L.; Vohra, S.; 2006)
6 RCT (n=707): treatment of diarrhea by probiotic with diarrhea duration as
outcome Subgroup analysis efficacy dose and strain of
probiotics from 6 RCT for treatment AAD
CONCLUSION
1. Pooled estimates found that probiotics offer a safe and effective method to prevent and treat acute pediatric diarrhea. No serious adverse reactions were reported in the trials. (McFarland, L.V.; Gary W. Elmer, G.W.; and McFarland, M.; 2006)
2. In conclusion, bacterial probiotic therapy shortens the duration of acute diarrheal illness in children by approximately one day. (Huang, J.S.; Bousvaros, A.; Lee, J.W.; Diaz, A.; and Davidson, E.J.; 2002)
3. Strain Lactobacillus GG with doses ≥5 billion CFU shows a strong evidence for treatment antibiotic associated diarrhea with no serious adverse effect (Johnston, B.C.; Supina, A.L.; Vohra, S.; 2006)
Probiotic and Traveler’s Diarrhea
Conclusion
Probioticsupplementation
Reported to lower incidence of travelers diarrhea by
85% (RR 0,85; 95% CI 0,79 to 0,91)
(12 trials, n=5643)
No severe adverse effect (bactericimia or fungemia)
were occurred from the supplementation with
probiotic
Probiotic supplementation reduces the incidence of travelers diarrhea and safe
McFarland, L.V.; 2007
(McFarland, L.V., Travel Med&Infec Dis., (2007) 5:97-105)
Funnel plot from 12 RCT: no heterogenity was found (X2=18,9; Z=-0,96, p= 0,34).
Forest plot from 12 RCT: probiotic reduce the incidence of TD by 85% (RR 0,85; 95% CI 0,79-0,91; p<0,001).
Probiotics & RV Diarrhea
• There is ample evidence that probiotics reduce duration & severity of RV diarrhea.
• Clinical trials demonstrated effectiveness of probiotics in treatment and prevention of acute diarrhea, decreasing the severity and duration of rotavirus infections in children as well as diarrhea in adults.
Effective prophylaxis against rotavirus diarrhea using a combination of Lactobacillus rhamnosus GG and antibodies
Lactobacillus rhamnosus strain GG showed a strong anti-rotavirus capacity and reduced the diarrhea prevalence to 41% compared to 93% in infected but untreated mice
(Pant, Marcotte, et.al., 2007)
Application of Probiotics• Future studies on the therapeutic potential of
probiotics are necessary
• Efforts should be made to standardize doses, duration of treatment
• Direct comparisons of probiotics versus placebo are indicated
• Adverse reaction data and cost-effectiveness analyses would be helpful
(McFarland, L.V.; et.al.; 2006)
A New Perspective For Treating Diarrhea
Lintas Diare
Rotavirus Vaccine
Probiotic
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