Published on March 13, 2014
Recurring outbreaks of Acute Encephalopathy in Children in Bangladesh Is Unintentional Acute Pesticide Poisoning a hidden cause? Dr. Pritimoy Das MBBS, MPH Research Investigator, CCD, icddr,b firstname.lastname@example.org March 12, 2014 1
Background • Encephalitis is a very dreadful disease in children with high mortality rate • It is endemic throughout the year with occasional epidemics in various localities in Bangladesh 2
2004 – 2005 • 14,726 children were admitted in the Department of Paediatric of Rangpur Medical College Hospital (RMCH) • 225 children were suffering from encephalitis Mortality rate 53.8%(121 in number) 3 Department of Paediatrics, RMCH. Annual Report 2005.
2006 - 2008. • 285 encephalitis cases • The mean age was 4 ± 2.4 years • Death rate was 44.56%. 4 Wahed MA, Sarker PC, Hossain MA (2010)
Pesticide use: Bangladesh situation • Pesticide use in Bangladesh started in 1960s and tremendously increased over last fifty years. 7 Sanzidur Rahman (2013)
Bangladesh: Pesticide consumption 8 Sanzidur Rahman (2013)
Pesticide consumption • Consumption of pesticides grew by 1340% from 1977 to 2009. • Pesticide use grew at an alarming rate of 10% per annum 9 Sanzidur Rahman (2013)
Kg/hectare Year Bangladesh: Pesticide use per hectare 10 Sanzidur Rahman (2013)
Pesticide use per hectare • The use rate of pesticides has increased by 1103% from only 0.26 kg of active ingredients per hectare (of gross cropped area) in 1977 to 3.13 kg per hectare in 2009. 11 Sanzidur Rahman (2013)
Death Toll • In Bangladesh, pesticide poisoning related deaths represented 8% of all hospital deaths for people aged 15-49 years in 2009 Islam (2012), Health bulletin (2009) 12
? Children • However, pesticide poisoning among children may be under reported in Bangladesh since many poisonings are unintentional and the exposure to pesticides may be unrecognized 13
Outbreaks of unintentional pesticide poisoning in Bangladesh: Since 2008- • Institute for Epidemiology, Disease Control and Research (IEDCR), in collaboration with • icddr,b has identified 3 clusters of unintentional pesticide poisoning among children 14
Outbreaks of unintentional pesticide poisoning in Bangladesh: 2008 2012 2009 15
The first outbreak • Two villages of Atrai and Badalgachi sub- districts of Naogaon District • March to June, 2008; 16
Second outbreak • Two villages of the Dhamrai sub-district of Dhaka District • April-May in 2009 17
Third outbreak • Dinajpur district • Thakurgaon district • June-July in 2012 18
2008, 2009 outbreaks at a glance • 23 cases were identified • 12 (52%) died. • All were between 7 months and 7.5 years of age. • The cases and their families did not report any known exposures to pesticides, and the local physicians initially diagnosed them as cases of encephalitis or pneumonia. 19
2008, 2009 outbreaks at a glance Clinical features • Onset of illness was very sudden • Frothy discharge from mouth, inability to hold up the neck, weakness of limbs, respiratory distress, and unconsciousness. • In general, the condition of the patient rapidly deteriorated with deaths occurring within a median of two hours (range 30 minutes to 21 hours) from the onset 20
2009 outbreak: Case definition • Case-patients were children aged 1–10 years who presented to healthcare facilities with at least 2 symptoms characteristic of cholinergic inhibition (ie, difficulty breathing, excessive sweating, frothy discharge, loss of consciousness, convulsions, urinary incontinence, vomiting, weakness in arms or legs) 21
Laboratory evidence: 2009 outbreak • Among total 8 case patients, 3 case-patients demonstrated plasma cholinesterase activity within 10 hours of illness onset that was at least 20% lower than specimens tested 30 days after recovery. • Serum carbofuran and its metabolite, 3-hydroxy carbofuran, were detected in 2 case-patients and in none of the controls; these specimens had been collected within 6 hours of illness onset. • Six case-patients had a higher median level of urinary creatinine-corrected carbofuran than 18 controls. 22 Martin J. (2011)
2012 Outbreak 23
2012 outbreak: Case definition • Suspected cases, defined as children who had been admitted to the hospital with convulsions with or without fever, altered mental status and unconsciousness • 14 meet case definition • 13 (93%) died 24
The most common symptoms were • Convulsions (100%), • Unconsciousness (86%), • Frothy discharge from the mouth (86%) • Altered mental status (71%) 25
2012 outbreak: Clinical features In the majority of cases (64%), the illness started with • Sudden outcry in the early morning • Fatigue, • Convulsions and • Unconsciousness. 26
2012 outbreak: cont. Median time from onset of illness to- • Unconsciousness - 2.5 hours (range: 30 minutes to 15 hours) • Death -20 hours (range: 6-130 hours) 27
2012 outbreak: Linked to pesticide? Most of the cases entered nearby orchards to- Play Collect dropped or cracked lychees Eat, or collect lychees from small branches Etiology still unknown 28
Outbreaks of acute encephalitis of unknown origin during the litchi harvest period, Vietnam, 2004–2009 Case definition: Clinical diagnosis of suspected acute viral encephalitis, age <15 years, onset date during May 1–July 31, (2004-2009) and negative serology for JEV IgM or full immunization against JEV [Termed as Ac Mong encephalitis (AME)] Paireau J (2012) 29
Outbreaks of acute encephalitis of unknown origin during the litchi harvest period, Vietnam, 2004–2009 • 239 children met the inclusion criteria • Their median age was 5 years (inter quartile range 2–7.5) Paireau J (2012) 30
Outbreaks of acute encephalitis of unknown origin during the litchi harvest period, Vietnam, 2004–2009 A) Annual number of AME cases B) annual litchi production Findings strengthens the hypothesis: Litchis might play a role in these outbreaks Litchi cultivation was spatially and temporally associated with AME. Litchis might play a role in these outbreaks Litchi cultivation was spatially and temporally associated with AME. Paireau J (2012) 31
2013-2014: Ongoing pesticide poisoning surveillance in Bangladesh • Surveillance of Unintentional Acute Pesticide Poisoning due to Carbamate and Organophosphate among Young Children in Bangladesh (UAPP). • Started from October 2013 32
Objectives (UAPP) 1. To identify the cases and/or clusters of unintentional carbamate and organophosphate acute pesticide poisoning in hospitals of Bangladesh 2. To determine the type(s) of pesticides responsible for clusters of unintentional acute carbamate and organophosphate pesticide poisoning in children (≤ 10 years) 33
UAPP: Media surveillance system • Currently in Bangladesh, surveillance for pesticide poisoning is done through word-of- mouth as well as scanning newspapers daily for reports of clusters of unusual illness that resemble the signs of APP (sudden onset of convulsions, unconsciousness, and death among children in the same village) 34
UAPP: Active surveillance in 3 Hospitals • Atrai Upazilla Health Complex (UHC), in Naogaon district under Rajshai Division. This is the outbreak sub-district in 2008. • Dhamrai UHC under Dhaka Division. This was the outbreak sub-district in 2009 • Bashkhali UHC in Chitagong district under Chitagong Division. Many cases were reported from this sub-district in 2009 where children presented with sudden onset of illness and unconsciousness (Hossain MS Sazzad, personal communication). The routine laboratory tests of their cerebrospinal fluids (CSF) were normal, and Nipah and Japanese tests were also negative. 35
Need to exclude infectious encephalitis Poisoning/encephalopathy Encephalitis Onset Sudden Gradual Fever Uncommon/absent Common Depressed mental status Steady deterioration Fluctuating Types of seizure Generalized Generalized/Focal Vision Blurred vision Photophobia Pupil Pin point Usually not pinpoint 36
Case definition: Unintentional Acute Pesticide Poisoning (UAPP) surveillance Suspect All children ≤ 10 years of age seen in a health facility with- • Sudden onset of illness without fever AND • History of possible exposure to agricultural fields and/or eating agricultural products in last 24 of hours of illness onset where pesticides are commonly used AND • At least THREE of the following CONCURRENT features: Onset of illness with a sudden cry, excessive respiratory secretions, excessive salivation, diarrhea, vomiting, abdominal cramp, loss of bladder/bowel control, excessive sweating, cold extremity, slower pulse rate, pupil constriction, headache, muscle fasciculation/twitching, generalized weakness/paralysis, chest tightness, respiratory fatigue/failure, unexplained lacrimation, convulsions, altered mental status, loss of consciousness, coma AND • No other obvious explanation for symptoms. 37
Probable • Meets “suspect” case definition AND symptoms improved following clinical treatment with atropine or pralidoxime. Confirmed • Meets “suspect” case definition AND one of the following: 1) laboratory evidence of plasma cholinesterase levels that were severely depressed (<20% of the mid values of laboratory reference range) OR 2) laboratory evidence of a parent pesticide compound or metabolite in concentrations (in biological specimens) consistent with poisoning. Case definition: Unintentional Acute Pesticide Poisoning (UAPP) surveillance 38
Identification of clusters • For this study, an APP cluster will be defined as two or more persons living within a 15 minutes’ walk of each other all of whom meet the case definition of UAPP within 10 days of each other. 39
Findings: From October 2013 Hospital (Upazila Health Complex) Children attended in emergency room Meet UAPP case definition % Atrai 193 0 0 Dhamrai 2339 0 0 Bashkhali 1576 1 0.06 Total 4108 1 0.02 40
When a case patient is identified • Collect of Serum and Urine samples from suspect case • Encourage treating physician to use specific antidot (Atropin, pralidoxime) to treat patient • Collect exposure related data • Store sample at icddr,b lab for – Cholinesterase test (Dhaka) – Test for pesticides in CDC lab/ALS lab (Canada) 41
Seasons in Bangladesh we should care Lychee: June -July Mango: May - September (Increased risk of UAPP) 42
12 Hospital Based Influenzae Surveillance (HBIS) hospitals: 3 Meningoencephalitis (ME) surveillance hospitals- Rajshahi MCH Rangpur MCH Faridpur MCH 43 Courtesy to HBIS team for the Original map Future plan: To extend this surveillance
Each of all 14 surveillance hospital has- • 1 Field Assistant (recruited by icddr,b) • 1 Surveillance physician (Govt.) • They are trained to screen patients for other surveillance activities • Established system of sample collection/ processing/transport Strength 44
Limitation • Staffs are loaded with other surveillances • Delay between sample collection time and getting test result-rapid diagnosis not possible • Current UAPP case definition is not suitable for Field Assistant who does initial screening • Limited resource: Testing samples for pesticide(s) is costly 45
Recommendation: Refining the case definition • Make an unique case definition for surveillance in Asia region • Should be easy, suitable for non-technical person (FA) to screen patients • Should be able to excludes infectious causes of encephalitis at the screening time 46
So…to move forward Further Discussion needed… 47
References • The World Bank, 2006. Toxic Pollution from Agriculture - An Emerging Story. The World Bank. Available at: http://econ.worldbank.org/WBSITE/EXTERNAL/EXTDEC/0,,contentMDK:21139876~pagePK:64165401~piP K:64165026~theSitePK:469372,00.html [Accessed February 12, 2014]. • Rahman, S., 2013. Pesticide consumption and productivity and the potential of IPM in Bangladesh. The Science of the total environment, 445-446, pp.48–56. Available at: http://www.ncbi.nlm.nih.gov/pubmed/23314122 [Accessed February 3, 2014] • Islam S, Borak Z. Attitude and behavior towards suicide: role of counseling as prevention. JALRB 2012;3:224-62. • Ministry of Health and Family Welfare. Government of Bangladesh. Health Bulletin 2009. Dhaka: Ministry of Health and Family Welfare. Government of Bangladesh. 2009, 20 p • Martin J, (2011). Investigation of an Outbreak of Unintentional Acute Pesticide Poisoning: Assessment of Exposure to Carbamate and Organophosphate Insecticides, Rural Bangladesh, 2009. http://journals.lww.com/epidem/Fulltext/2011/01001/Investigation_of_an_Outbreak_of_Unintentional.3 28.aspx • Paireau J, Tuan NH, Lefrançois R, Buckwalter MR, Nghia ND, Hien NT et al. Litchi-associated Acute Encephalitis in Children, Northern Vietnam, 2004-2009. Emerg Infect Dis 2012;18:1817-24. 48
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