Arsenicosis in Bangladesh

Welcome
Arsenicosis in Bangladesh
Abdul Momin PhD
Associate Professor
Department of Dermatology
Dhaka Medical College, Dhaka,
Bangladesh
‘Rain-drops’ Pigmentation
Warty keratosis
Squamous Cell Carcinoma
Squamous Cell Carcinoma
Genesis of the problem
† In 1960s : In order to combat epidemic of diarrhea
diseases about 4 million tube wells were installed
countrywide.
† In 1980s :arsenic contamination in tube well water
was suspected.
† In 1993 : first case of arsenic poisoning was
detected and was reconfirmed in 1996.
QUOTABLES
„
“Bangladesh is in the midst of a mass
poisoning in history, dangerous level of
arsenic have been found in the ground water,
entering millions of people sip by sip as they
drink from over 4 million tube wells."
-New York Times, 10.11.98 .
QUOTABLES
“If this were the United States, they'd call out the
National Guard and get everyone bottled
water,” said Willard R. Chapel, a physicist who
is one of the world's leading experts on arsenic
contamination (New York Times, 10.11.98) .
“…arsenic in drinking water poses the highest
cancer risk ever found, …we could be talking
about hundreds of thousands of deaths - this is
really a medical emergency.”
Arsenic Poisoning :
Current situation in Bangladesh
zTotal Districts affected
zTotal Upazilas screened
z Contaminated tube wells
:61 out of 64
:270 out of 464
:1.44 million
z Acceptable limit for arsenic
in drinking water
zDetected arsenic levels
in tube well water
z Population exposed
zTotal cases detected
:< 0.05 mg/L
:0.1 to 3.0 mg/L
:About 66 million
:More than 38,000
- NAMIC,2005
Bangladesh Government- British Geological
Survey (Survey BG, 1999)
Population exposed to different levels of
arsenic from drinking water
Arsenic concentration
< 5µg/L
<10µg/L(WHO guideline value)
*<50µg/L(Bangladesh standard)
<100µg/L
<500µg/L
<1000µg/L
Population exposed
( in millions)
67
49
29
18
02
0.1
*This standard was set by NIPSOM group hypothetically
Socio-economic consequences of arsenic
poisoning in Bangladesh
observations from various surveys:
Economic burden of arsenic patient
42%
„
8%
„
„
30%
20%
„
income reduced
rejected from job
less payment
incurred additional expense
58% suffering from mental
agony
13% fear of premature
death
55% girls face difficulties
in getting married
37% patients facing
restriction in sharing
household commodities
Awareness on arsenic contaminated drinking
water in Bangladesh
observations from various surveys:
6%
39%
38%
7%
lack of knowledge
Importance not given
Distance of source
Cheap&free
10%
Easily available
Biotransformation of inorganic arsenic
GSH
(Reduced)
As ( V )
GSSG
(Oxidized)
→
As ( III)
S-adenosyl methionine (SAM)
↓
↓
S-adenosyl homocysteine(SAH)
Methyl arsenate
↓
Monomethyl arsenic acid
↓
Dimethyl arsenic acid
↓
Excreted in urine
→
Important steps of arsenic induced cellular toxicity
Trivalent arsenicals
Pentavalent arsenicals
As V + ADP
↓
Formation of As- ADP (unstable
arsenic ester)
↓
ATP formation decreased
↓
Oxidative phosphorylation
decreased
↓
Oxidative stress occur
↓
Inevitable cell injury
As III +( -SH)
↓
Inhibits (–SH) containing Proteins /
enzymes
↓
Inhibits NAD links Phosphorylation
↓
ATP formation decreased
↓
H 2O 2 production increased
↓
Lipid per oxidation increased
↓
Free radicals/ ROS (Reactive Oxygen Spices)
formed
↓
Oxidative stress occur
↓
Cell injury / cellular death
Effects of arsenicosis
z
The most alarming role of chronic arsenic
exposure is carcinogenicity, which may
affect even after decades of exposure.
z
An expert panel of the National Research
Council in Washington, USA concluded
that chronic ingestion of inorganic arsenic
causes bladder, lungs and skin cancers
(Douglas, 1999) .
Estimated incidence of excess
skin cancer in Bangladesh
Drinking water supply
Projected incidence
• Present arsenic contaminated level
4,15,100
• Satisfying the Bangladesh Standard(50µg/L)
55,200
• Satisfying the WHO guideline value(10µg/L)
15,200
Management of arsenicosis
The present knowledge of the
management of arsenicosis is limited and
specific treatment of chronic poisoning is
not yet identified.
Management of arsenicosis
|
The prevention of further exposure to arsenic is to be
considered at first.
Prevention of accumulation, reversing the affected or
altered biological functions and rapid elimination of arsenic
are the further objectives of treatment in chronic arsenic
toxicity
|
Objectives
1) To determine whether selenium supplement in
arsenicosis patients decreases the arsenic body load,
particularly in hair, nail and urine.
2) To assess whether selenium supplement reverse the
progression of clinical signs of arsenicosis , particularly
a) melanosis and
b) palmo-plantar keratosis without side effects.
Methodology
A randomized double blind placebo
controlled intervention trial was carried
out during the period from November
2004 to November 2006
Prior to data collection , a pilot study was carried
out in the same locality on 10 arsenicosis
volunteer to observe the toxicity of selenium
(Momin et al ; 2004 )
Methodology
z
The subjects of this study were drawn from 11
villages of Shahpur union , highly contaminated
rural area, under Chatkhil upazilla of Noakhali
district (about 170 km south west from Dhaka)
of Bangladesh
z
z
Suspected arsenicosis patients were identified by
clinical examination and confirmed by urine tests.
Recruitment of the subjects was assisted by village leaders,
local NGOs and staff and student of the local college.
Methodology
Total One hundred and seventy four (174)
patients not receiving any drug were
selected from the sampling area and were
assigned randomly into the Group ‘A’ or ‘B’
respectively.
z
87 patients were included in group A
(Selenium) , 87 patients in group B (Placebo).
z
Ethical issue
Each patient was informed about the
purpose of the study and right to withdrawn
from participation was assured .
Voluntary written consents were taken from
each arsenicosis patients.
†
†
„
The study was approved by the ethical review
board of the Bangladesh Medical Research
Council (BMRC)
Intervening agents
z Tablet
selenium containing 200 µg
selenium as high selenium yeast rich
L- selenomethionine.
z Placebo
preparations containing potato
starch in each as tablet form which is
of same color and size to selenium.
Methodology
„
„
„
Urine, and blood samples were collected from
arsenicosis patients at the beginning and at
the end of 4, 8 and 12 months.
Only hair and nail samples were collected at
the beginning and at the end of study period.
Sample of their drinking water was also collected
at the beginning and at the end of first month.
Methodology
|
The specific treatment was provided to the patients,
supervision was strictly maintained at home level
of patient, by the trained field workers over 12
months follow-up.
|
Each patient was instructed to swallow half of the
tablet daily orally with a glass of water.
|
None of the patients were allowed to drink
arsenic contaminated water throughout the
study period.
Methodology
In 10% (17) randomly selected cases, their 24
hours food recall was also noted.
Participants were digitally photographed of
their torso, palms, and soles in the field
every 16 weeks using a high-resolution
digital SLR camera.
Result
Distribution of sex in study subjects
p <0.63
36%
64%
Male
Female
Distribution of age in study subjects
P < 0.83
16%
24%
60%
13-29 years 30-49 years 50+ years
Socio-demographic characteristics of study population
Characteristics
Selenium
(N = 87)
Placebo
(N = 87)
p-value
Number of subjects
Age in years, mean±SD
Body weight, kg, mean±SD
Body height, cm, mean±SD
Literacy in %
a) Upto Primary
b) Secondary
c) HSC+
Monthly household income,
mean±SD
Family size, in %
a) 1-4 (small)
b) 5-6(medium)
c) 7+ (large)
28(M),59( F)
35.9±11.8
47. 6±9.3
153.0±8.3
34(M),53( F)
36.8±13.1
48.2±9.2
153.1±9.2
<0.63
<0.83
<0.09
67.8
19.5
12.7
64.4
14.9
20.7
2781.6±3339.7 2458.6±2809.5
13.8
39.1
47.1
17.2
52.9
29.9
<0.07
<0.17
Distribution of Source and duration of water
intake in the study subjects
Characteristics
Source of drinking water (%)
a) Deep tube well
b)Shallow tube well
c) Pond
d) filter/boil
Duration of drinking water in years,
mean±SD
Source of cooking water (%)
a) Deep tube well
b)Shallow tube well
c) Pond
Duration of cooking water in years,
mean± SD
Selenium
(N = 87)
Placebo
(N = 87)
pvalue
<0.28
6.9
86.2
4.6
2.3
0.3
87.4
2.3
0.0
21.1±11.4
21.9±12.9
3.4
2.3
94.3
1.1
2.3
96.6
25.5±10.6
27.6±11.4
<0.79
<0.45
<0.71
Inorganic arsenic intakes through food intake literature (N= 17)
SL
No
Food item
Intake
(g/day)
Arsenic
conc .(µg/kg)
Total Arsenic
conc .(µg/day)
Inorganic
Fraction
Inorganic As
Intake(µg/day)
1
Cereal
378.2
200
75.64
0.43
32.53
2
Potato
59.3
23
1.36
0.1
0.14
3
Vegetables
108.2
7
0.76
0.05
0.04
4
Pulses
22.5
200
4.5
0.43
1.94
5
Meat
29.3
22
0.65
0.41
0.27
6
Fish
60.9
1662
101.22
0.1
10.12
7
Spices
37.2
7
0.26
0.05
0.01
8
Oils
10.6
19
0.2
1
0.2
9
Fruits
2.4
6.4
0.02
0.1
0.002
10
Sugar
5.6
10.9
0.06
0.43
0.03
11
Milk
23.7
12
0.28
0.75
0.21
12
Misc
9.5
12.5
0.12
0.43
0.05
13
Total
747.4
2181.8
185.07
4.28
45.54
.8
5
2
30
20
10
5
6.
31
.7
.3
2
3
21
.6
40
35
.9
.5
5
3
10
.8
% of the subjects
Distribution of duration of Arsenicosis in study subjects
0
1-3 years
4-6 years
Male
7-9 years
Female
10-12 years
Arsenic concentration in hair µg/L
Co-relation between arsenic in water and hair
1.6
1.4
r =0. 035
P < 0.00
1.2
1.0
.8
.6
-100
0
100
200
Arsenic concentration in water µg/L
300
Co-relation between arsenic in water and nail
Arsenic concentration in Nail µg/L
4.0
3.5
r = 0. 018
P < 0.03
3.0
2.5
2.0
1.5
-100
0
100
200
Arsenic concentration in water µg/L
300
Arsenic concentration in urine µg/L
Co-relation between arsenic in water and urine
200
180
P < 0.00
160
r = 0. 026
140
120
100
80
60
-100
0
100
200
Arsenic concentration in water µg/L
300
2 6 .8
2 1 .1
1 6 .9
20
1 4. 5
30
22.5
56.3
56.3
5 0 .7
40
3 6 .2
3 0 .4
50
13
% of the Subjects
60
5 5 .1
Status of Melanosis in Study subjects
10
0
Severe
Moderate
Mild
Selenium
Before intervention
Severe
Moderate
Placebo
After intervention
Mild
20
19
30
2 1 .2
2 1 .2
3 4 .8
3 4 .8
4 3 .9
3 0 .2
40
4 3 .9
4 9 .2
4 1 .3
50
9 .5
% o f th e Su b jec ts
60
5 0 .8
Status of Keratosis in Study Population
10
0
Severe
Moderate
Mild
Selenium
Before intervention
Severe
Moderate
Placebo
After intervention
Mild
.2
97
10
10
0
0
Status of Symptoms in Study Subjects
80
.9
60
31
% o f th e Su b jects
100
40
20
0
Selenium
Before intervention
Placebo
After intervention
Status of Selenium Concentration in Serum
Se Conc as microgram/L
160
p< 0.00
140
120
100
80
60
40
20
0
0 month
4 month
Selenium
8 month
Placebo
12 month
As conc as microgram/L
Status of Arsenic Concentration in Urine
100
90
80
70
60
50
40
30
20
10
0
0 month
p< 0.00
4 month
Selenium
8 month
Placebo
12 month
Status of Arsenic Concentration in Hair of
Study subjects
Microgram / Kg as mean
1.4
p< 0.01
1.2
1
0.8
0.6
0.4
0.2
0
Before
Af ter
Selenium
Placebo
Status of Arsenic Concentration in Nail of
Study population
Microgram / kg as mean
1.4
p< 0.00
1.2
1
0.8
0.6
0.4
0.2
0
Before
Af ter
Selenium
Placebo
Abnormal Alkaline Phosphatase in Study Subjects
25
% of subjects
23.1
20
15
10
8.5
8.5
6.2
5
0
Before
After
Selenium
Placebo
Selenium group
Before intervention
During intervention
Selenium group
After intervention
Selenium group
Before intervention
During intervention
Selenium group
After intervention
Placebo group
Before intervention
After intervention
We observed no abnormality
in Cardiac, Renal and liver
function test .
Conclusion
Selenium treated arsenicosis patients
showed rapid and sustained improvement
of their clinical signs and symptoms and no
toxicity was observed .
„
„
The concentration of arsenic in hair and
nail also reduced more in selenium
supplementation.
A dose of 100 microgram of selenium as
selenomethionine per day along with use of
arsenic safe water for chronic arsenic toxicity
is safe, effective , cheap and may be the right
choice for combating arsenicosis in
Bangladesh.
Acknowledgement
‡ Prof Dr Shah Mohammad Keramat Ali, Clinical Nutrition
Department , Institute of Nutrition and Food Science, University of
Dhaka.
‡ Prof. Dr Mohammed Alauddin, chairman, Exotics Technology
Center, Ashwuliya, Dhaka.
‡ National Hospital, Chandragonj, Noakhali.
‡ Surjodayshangha, Shahpur union, Chatkhil Upazilla, District
Noakhali .
‡ Environmental unit of World Health Organization (WHO),
Bangladesh.
‡ The Acme Laboratories Limited, Satmasjid Road, Dhanmondi,
Dhaka.
‡ Arsenicosis patients of Shahpur Union for their kind participation
and cooperation.
Thank You