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Health burden of skin lesions at low arsenic exposure through groundwater
in Pakistan. Is river the source?
$
Zafar Fatmi
, Iqbal Azam, Faiza Ahmed, Ambreen Kazi, Albert Bruce Gill, Muhmmad Masood Kadir,
Mubashir Ahmed, Naseem Ara, Naveed Zafar Janjua, Core Group for Arsenic Mitigation in Pakistan
1
Department of Community Health Sciences, Aga Khan University, Stadium Road, P.O. Box 3500, Karachi, Pakistan
article info
Article history:
Received 21 July 2008
Received in revised form
9 March 2009
Accepted 8 April 2009
Available online 5 May 2009
Keywords:
Arsenicosis
Epidemiology
Groundwater
Skin lesions
Pakistan
abstract
A significant proportion of groundwater in south Asia is contaminated with arsenic. Pakistan has low
levels of arsenic in groundwater compared with China, Bangladesh and India. A representative multi-
stage cluster survey conducted among 3874 persons X15 years of age to determine the prevalence of
arsenic skin lesions, its relation with arsenic levels and cumulative arsenic dose in drinking water in a
rural district (population: 1.82 million) in Pakistan. Spot-urine arsenic levels were compared among
individuals with and without arsenic skin lesions. In addition, the relation of age, body mass index,
smoking status with arsenic skin lesions was determined. The geographical distribution of the skin
lesions and arsenic-contaminated wells in the district were ascertained using global positioning system.
The total arsenic, inorganic and organic forms, in water and spot-urine samples were determined by
atomic absorption spectrophotometry. The prevalence of skin lesions of arsenic was estimated for
complex survey design, using surveyfreq and surveylogistic options of SAS 9.1 software.The prevalence of
definitive cases i.e. hyperkeratosis of both palms and soles, was 3.4 per 1000 and suspected cases i.e. any
sign of arsenic skin lesions (melanosis and/or keratosis), were 13.0 per 1000 among X15-year-old persons
in the district. Cumulative arsenic exposure (dose) was calculated from levels of arsenic in water and
duration of use of current drinking water source. Prevalence of skin lesions increases with cumulative
arsenic exposure (dose) in drinking water and arsenic levels in urine. Skin lesions were 2.5-fold among
individuals with BMI o18.5 kg/m
2
. Geographically, more arsenic-contaminated wells and skin lesions
were alongside Indus River, suggests a strong link between arsenic contamination of groundwater with
proximity to river.This is the first reported epidemiological and clinical evidence of arsenic skin lesions
due to groundwater in Pakistan. Further investigations and focal mitigation measures for arsenic may be
carried out alongside Indus River.
&2009 Elsevier Inc. All rights reserved.
1. Introduction
Drinking arsenic-contaminated water for long duration results
in typical skin lesions characterized by symmetrical bilateral
hyperkeratosis (hardening) of palms and soles and/or hyperpig-
mentation or hypopigmentation (typically both) of parts of skin
unexposed to sunlight (Kadono et al., 2002). Arsenic skin lesions
have propensity to turn into cancers (Karagas et al., 2001;Chen
and Ahsan, 2004). Arsenic exposure through drinking water may
also lead to increased blood pressure (Lee et al., 2005), decreased
lung function (Zaldivar and Ghai, 1980;Smith et al., 1998;
Mazumder et al., 2000;von Ehrenstein et al., 2005;Pervez et al.,
2008), risk of cancers of lung and bladder (Morales et al., 2000;
S.C. Mukherjee et al., 2003;S.B. Mukherjee et al., 2003;Michaud
et al., 2004), decreased intellectual functions and peripheral
neuropathy (S.C. Mukherjee et al., 2003;S.B. Mukherjee et al.,
2003;Wasserman et al., 2004).
The frequency and severity of arsenic skin lesions depend on
both the concentration of arsenic in drinking water and duration
of use. Furthermore, toxicity of arsenic is enhanced by malnutri-
tion (Valentine et al., 1992, 1994;Mitra et al., 2004;Maharjan et
al., 2007) and smoking (Hossain et al., 2005). Relation of arsenic
with sex is unclear, with some claims that it is more severe and
common among females (Ahmad et al., 1999), while other studies
refute such claims and report that it is more common among
males (Watanabe et al., 2001;Kadono et al., 2002;Maharjan et al.,
2005).
Groundwater is the main source of drinking in South Asia
and arsenic skin lesions due to groundwater arsenic have
been reported in Bangladesh, India, Myanmar and Nepal (Guha
Mazumder et al., 1998;Chakraborti et al., 2003;Department
of Public Health Engineering Government of Bangladesh, British
ARTICLE IN PRESS
Contents lists available at ScienceDirect
journal homepage: www.elsevier.com/locate/envres
Environmental Research
0013-9351/$ - see front matter &20 09 Elsevier Inc. All rights reserved.
doi:10.1016/j.envres.2009.04.002
$
Funding source: Water and Sanitation (WES) Programme, UNICEF, Pakistan.
Corresponding author. Fax: +9221 4934295/4932095.
E-mail address: zafar.fatmi@aku.edu (Z. Fatmi).
1
Sikandar Ali Panhwar, Aslam Tahir, Tameez Ahmad, Athar Dil, Aftab Shahbaz,
Col. Shahbaz Ahmed.
Environmental Research 109 (2009) 575–581
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Geologic Survey, 1999;Rahman et al., 2001, 2005;Sengupta
et al., 2003;von Ehrenstein et al., 2005). However, many of these
studies were conducted on convenient sampling such as selected
heavily arsenic-contaminated villages (Guha Mazumder et al.,
1998;Chakraborti et al., 2003;Sun, 2004;Rahman et al., 2005).
Evidence is accumulating that arsenic may lead to adverse health
effects even at lower concentrations (Mazumder et al., 2000;
Rahman et al., 2006a, b;McDonald et al., 2007). Therefore, few
well-designed population-based estimates on arsenic skin lesions
(arsenicosis) were available, especially at low arsenic concentra-
tion in groundwater (Rahman et al., 20 06a, b). However, for
appropriate allocation of resources an accurate population-based
estimate of health burden for arsenic was warranted.
UNICEF with government of Pakistan conducted a national
survey in 2004 on arsenic levels in groundwater. From one-third
of the total districts of the country (35/104), 8712 drinking water
samples were collected. Of them 9% had arsenic 410
m
g/L and
0.7% were 450
m
g/L. Most of these groundwater sources were
affected in the range of 0–500
m
g/L (Ahmad et al., 2004a, b ).
No assessment has been conducted to determine the burden
of skin lesions due to drinking arsenic-contaminated groundwater
in Pakistan. A mitigation measure requires an assessment of the
magnitude of the health effects of arsenic. Therefore, this study
was designed to estimate the prevalence of arsenic skin lesions
and determine its relationship with arsenic levels in water and
cumulative exposure to arsenic in water, relation with spot-urine
levels of arsenic and potential risk factors in one of the arsenic-
contaminated district of Pakistan. The study also determined the
geographical distribution of skin lesion of arsenic and contami-
nated wells in the district.
2. Materials and methods
2.1. Study design and setting
This cross-sectional survey was conducted between January
and June 2006 in seven talukas (subdistricts) of the district
Khairpur, situated in northeast of Sindh province of Pakistan. One
subdistrict (Nara) was not included because it is a desert and
sparsely populated. The total population of Khairpur excluding
Nara taluka was 1.82 million: 77% rural (Population Census
Organization, Ministry of Economic Affairs and Statistics, Govern-
ment of Pakistan, 2006). Majority relies on agriculture and speaks
Sindhi language in Khairpur.
2.2. Selection of participants
Multi-stage cluster sampling was done. In the first stage, using
previous survey data (Ahmad et al., 2004), the villages of Khairpur
district were divided into low, medium and high contami-
nated villages, based on the levels of arsenic concentration and
proportion of affected wells in each village. In ‘low’ category
villages none (0%) of the water sources had arsenic at X100
m
g/L,
in ‘medium’ category villages 0.01–59.9% water sources had
X100
m
g/L and in ‘high’ category villages X60% of water sources
had X100
m
g/L of arsenic. According to this survey (Ahmad
et al., 2004), of the total 1858 villages, 20 (1%) were in ‘high’, 185
(10%) were in ‘medium’ and 1653 (89%) villages were in ‘low’
contaminated category.
We randomly selected 216 villages from the above three
categories. Of these, 70% (14/20) of ‘high’ contaminated villages,
50% (93/185) of ‘medium’ and only 7% (109/1653) of ‘low’
contaminated villages were randomly selected. Therefore, pro-
portionately, we oversampled ‘high’ and ‘medium’ contaminated
villages and undersampled ‘low’ contaminated villages to effi-
ciently utilize the resources and also to have adequate number of
arsenic skin lesion cases to fulfill the secondary objectives. Arsenic
level of X100
m
g/L as cut off was kept to further enhance the
probability of detection of arsenic skin lesions. Ten households
were selected systematically from each village and one male and a
female adult X15 years were selected randomly from the listing
of the household members. Four persons, two males and two
females including two health personnel, conducted interviews
and examination with the respective male and female study
participants after taking informed consent.
2.3. Skin examination and definition of cases
A ‘manual of diagnosis and mitigation’ was developed after a
series of consultation meetings with dermatologists. All study
personnel were given 1 week training in the field. Skin lesions
were examined by trained health personnel and reconfirmed
(validated) by trained expert (PI) with digital photographs and
revisits.
Suspected cases: Any arsenic skin manifestations i.e. hypo and/
or hyperpigmentation of skin unexposed to sunlight, or symme-
trical bilateral hyperkeratosis of palms and/or soles. Definitive
cases: Hyperkeratosis on both palms and soles with or without
hypo and/or hyperpigmentation on skin unexposed to sunlight
(Fig. 1).
Differential diagnosis: Health personnel were trained for
differential diagnosis based on history and physical examination.
In this respect, album of photographs of lesions mimicking arsenic
lesions was also provided to field team for reference. The
following lesions were excluded mimicking keratosis: seborrheic
keratosis, hereditary palmo-plantar hyperkeratosis, epidermodys-
plasia verruciformis, eczema, verruca (warts), lichen planus, corns
and calluses, occupational keratosis, verruca vulgaris, tinea pedis,
candidal hyperkeratosis/pitted keratolysis, pityriasis rubra pilaris
and psoriasis. The following lesions were excluded related
to melanosis: melasma, drug-induced pigmentation, actinic derma-
toses, xeroderma pigmentosum, familial progressive dyschromatosis,
ARTICLE IN PRESS
Fig. 1. Bilaterally symmetrical advanced hyperkeratosis of both palms and soles (arsenicosis).
Z. Fatmi et al. / Environmental Research 109 (2009) 575–581576
Author's personal copy
pitryasis versicolor, idiopathic guttate hypomelanosis, pityriasis
lichenoides and leprosy.
2.4. Field sampling and laboratory procedures for arsenic exposure
measurement
2.4.1. Water sampling
Water samples were taken from all the current drinking water
sources, and also past sources if available within the same village.
Duration of drinking (number of years) from the same source was
inquired based on recall. Cumulative exposure (dose) to arsenic
was calculated, based on recall, by multiplying the average
concentration of arsenic in current drinking water sources
(weighted according to the proportion of water taken from each
source) with the average amount of water taken per day (average
drinking water and tea in winters and summers) and duration
of water taken (number of years water taken from the same
source) per body weight. Persons who had eaten any seafood such
as fish or prawns within the last 3 days were excluded from
the analysis. Exposure of arsenic through occupation, food and
medicinal sources were also inquired.
2.4.2. Urine samples: suspected cases and controls
Spot-urine samples were taken from all individuals who had
any sign of arsenic skin lesions (suspected cases) and also from
two individuals, one male and a female, without any arsenic skin
lesions (controls) from each village.
2.4.3. Laboratory procedures
The water and urine samples were obtained in arsenic-free
(pre-acid washed and rinsed with de-ionized water) polyethylene
containers. The Pakistan Council for Research in Water Resources,
Laboratory, Islamabad conducted arsenic level testing. The total
arsenic in water and urine by Mercury/Hydride System Atomic
Absorption Spectrophotometer (HG-AAS) with an arsenic detec-
tion limit of 0.1
m
g/L was conducted. For quality control, 10% of
duplicate samples of water were tested for reliability, for which
99% agreement was found.
2.5. Geographical distribution of skin lesions and arsenic
contamination
Using global positioning system (GPS), the geographical
distribution of patients with arsenic skin lesions and affected
drinking water sources with Indus River was analyzed. Relation of
arsenic levels in water with the depth of wells was also
determined.
2.6. Anthropometry
Weight and height were also measured using bathroom scales
and height meter, respectively.
2.7. Statistical analysis
Statistical analysis was done using SAS 9.1 software. The
analysis considered complex survey design (multi-stage cluster
sampling), using surveyfreq and surveylogistic options. Prevalence
of arsenic skin lesions was determined separately for definitive
and suspected cases after adjusting for differential sampling of
villages, application of weights of population.
For determining the relation between arsenic levels in water
and urine and other factors, we used all arsenic skin lesions
(suspected cases). Prevalence of arsenic skin lesions by cumulative
arsenic exposure (dose) and arsenic concentration in urine were
estimated. Prevalence of arsenic skin lesions according to age,
gender, smoking status and body mass index (BMI) and its
association with these factors were determined. Prevalence of
arsenic skin lesions according to various taluka (subdistricts)
of Khaipur district was also determined.
2.8. Sample size
A minimum of 3254 persons were required to estimate an
anticipated prevalence of 1.3% of arsenic skin lesions, taking
desired precision of 0.55%, 95% confidence interval and a design
effect of 2. Keeping 15% for incomplete information a total of 3742
persons were needed to fulfill the objectives. Post-hoc power
calculations were also done for determining the adequacy of
sample size for association studies.
2.9. Ethical approval
The study was reviewed and approved by Ethics Review
Committee of Aga Khan University.
3. Results
A total of 3874 individuals (51.5% females) were interviewed
and examined in 216 villages and 2517 samples of drinking water
sources were collected for these individuals. Some individuals had
multiple drinking water sources while others had combined
source for both males and females in the household. While 505
urine samples were collected: 63 for cases with skin lesions and
432 controls.
The mean age of the participants was 36.8 years. Approxi-
mately 42% (SE ¼1.3) were between 15 and 30 years, 35%
(SE ¼1.2) were 31–45 years and the rest 23% (SE ¼0.9) were
445 years of age. Fifty-nine percent (SE ¼1.7) had no schooling.
While 16.7% (SE ¼0.4) had more than 10 years of schooling.
Approximately, 16% (SE ¼1.0) had BMI of o18.5 kg/m
2
. More
than 18% (SE ¼0.9) ever smoked cigarettes: 28% (SE ¼1.5) males
and 9.1% (SE ¼1.1) females.
Most of the population (98.5%) was using groundwater for
drinking purposes; 85% of the population owned a hand-pump,
installed within the household premises (82%). Seventy-one
percent of the sources were between 31 and 50 ft deep and the
average depth was 37.3 (SD ¼11.3) ft. Average duration of hand-
pumps, time since it is being used, was 15.1 (SD ¼19.3) years.
Approximately, 10% of the X15-year-old population of the
district was drinking water at arsenic levels between 10 and
49
m
g/L, 2% were using X50
m
g/L while 1% X100
m
g/L.
The prevalence of definitive cases of arsenicosis was 3.4
(SE ¼1.4) per 1000 population of X15 years in the district
Khairpur (Table 1). Extrapolated to population of district Khairpur
(Population Census Organization, Statistics Division, Ministry of
Economic Affairs and Statistics, Government of Pakistan, 2006), an
estimated 6528 person X15 years of age had definitive arsenic
skin lesions. Any manifestation on the skin related to arsenic
(suspected cases) was 13.0 (SE ¼2.4) per 1000 among persons
X15 years. Distribution of the type of arsenic skin lesions
(arsenicosis) is given in Table 1.
We used the suspected cases of arsenicosis for determining the
association with age, gender, nutritional and smoking status. Age,
gender and smoking status were not significantly related with
arsenic skin lesions. Individuals with o18.5 kg/m
2
were 2.5 times
more likely to have skin lesions compared with those who were
X18.5kg/m
2
(Table 2).
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Z. Fatmi et al. / Environmental Research 109 (2009) 575–581 577
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The prevalence of skin lesions increased with increasing levels
of arsenic in drinking water. The significant increase in the
prevalence of skin lesions was found with cumulative arsenic
exposure (dose) (Fig. 2). The prevalence of skin lesions also
increased with increasing levels of arsenic in urine (Fig. 3). Mean
arsenic levels in drinking water, urine and cumulative arsenic
exposure (dose) were significantly higher among cases (persons
with skin lesions) than controls (persons without skin lesions).
We did not find any significant association between arsenic levels
and depth of hand-pumps.
Greater proportion of water sources had arsenic concentrations
that were unsafe for human consumption in subdistricts which
were closer to River Indus namely Gambat, Kingri and Sobho Dero
(Fig. 4a). Respectively, we found higher prevalence of arsenic skin
lesions in three subdistricts that were in proximity to the River
Indus (Fig. 4b).
4. Discussion
This paper provides first epidemiological and clinical evidence
of arsenic skins lesions due to groundwater contamination in a
district in Pakistan. Few research studies provide systematic and
quantitative information regarding prevalence of arsenic skin
lesions and its relation with arsenic concentration in water and
urine (Rahman et al., 2006a, b). Most of the studies were
conducted in areas where groundwater has high levels of arsenic
(Guha Mazumder et al., 1998;Chakraborti et al., 2003;Sun, 2004;
Rahman et al., 2005).
This study further adds to the evidence that lower levels
of arsenic exposure in water lead to arsenic skin lesions. The
prevalence of skin lesions in West Bengal at lower levels of arsenic
exposure was similar to this study; zero among females and 2 per
1000 among males at o50
m
g/L (Mazumder et al., 2000). Most of
the arsenic exposed population in Khairpur was between 10 and
50
m
g/L. Comparison of mean arsenic levels in drinking water and
urine also suggests that exposure levels in this study was lower
than studies conducted in Bangladesh and West Bengal (Nabi
et al., 2005).
Arsenic skin lesions may serve as an indicator for arsenic
affected population as it is a convenient method of ascertainment.
Epidemiological studies of populations exposed to low doses
of arsenic have documented increased risks of numerous and
diverse human health effects, including several types of cancers,
type 2 diabetes, vascular disease, cardiovascular disease and
reproductive and developmental problems. Studies claimed to
ARTICLE IN PRESS
Table 2
Prevalence of arsenic skin lesions (arsenicosis) by age, gender, BMI and smoking
status
a
Variables Number
of cases
Cases per
100 0
SE P
Age categories (years)
15–30 (n¼1612) 20 10.8 3.5 NS
31–45 (n¼1342) 19 12.8 3.8
445 (n¼920) 24 17.0 5.0
Gender
Female (n¼1985) 37 14.0 3.4 NS
Male (n¼1884) 26 11.7 3.3
Body mass index (kg/m
2
)
o18.5 (n¼596) 17 25.3 7.9 o0.01
X18.5 (n¼3278) 46 10.5 2.5
Ever smoker
Yes 15 14.1 5.2 NS
No 48 12.6 2.7
NS ¼not significant (40.05).
a
Weighted analysis was done to adjust for variable sampling (oversampling/
undersampling), therefore, numbers may not correspond with the proportions in
the table.
P <0.01
Skin lesions per 1000 population
5.7 11.8
56.5
38.5
0
10
20
30
40
50
60
70
80
90
100
<10
Cumulative arsenic exposure (dose)* in drinking water
(µg/L-years/kg)
10-<50 50-<100 100 or more
Fig. 2. Prevalence of arsenic skin lesions (arsenicosis) by cumulative arsenic
exposure (dose). *Cumulative arsenic exposure (dose) is calculated by arsenic
levels in water sources (weighted with proportion drinking from each source)
multiplied by average daily drinking from water and tea (summers and winters)
multiplied with duration of drinking (number of years) from same source per body
weight.
P 0.06
Skin lesions per 1000 population
As levels in urine (µg/L)
36.6
99.5
123.6
186
0
50
100
150
200
250
300
350
<10 10-<50 50-<100 100 or more
Fig. 3. Prevalence of arsenic skin lesions (arsenicosis) by arsenic levels in urine.
Table 1
Prevalence of arsenic skin lesions (arsenicosis)
a
Variables Number of
cases
Cases per
100 0
SE
Arsenicosis (hyperkeratosis of both palms and
soles) (n¼3874)
9 3.4 1.4
Any manifestation of arsenicosis (n¼3874) 63 13.0 2.4
Hyperpigmentation (melanosis) 42 8.7 2.1
Keratosis of soles 18 4.0 1.3
Hypopigmentation 19 3.7 1.4
Keratosis of palms 8 3.4 1.4
Scaly crusted lesion 9 1.4 0.7
Fungating lesion 4 1.1 0.7
Ulcerated lesion 3 0.6 0.5
a
Weighted analysis was done to adjust for variable sampling (oversampling/
undersampling), therefore, numbers may not correspond with the proportions in
the table.
Z. Fatmi et al. / Environmental Research 109 (2009) 575–581578
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have observed adverse human health effects at arsenic levels far
below 10
m
g/L in cell culture and at or below this level in several
in-vivo models (Bodwell et al., 2006). Arsenic enhances the
mutagenicity of other DNA-damaging agents, impair DNA repair,
aberration in gene expression by DNA hypomethylation, and
induce chromosome abnormalities and cell proliferation (Roy and
Saha, 2002). Therefore, the health consequences are much graver
than are estimated by skin lesions of arsenic alone.
Variable definitions have been used by studies to determine
the burden of arsenic skin lesions. It was particularly noted in the
literature that the estimates of arsenic skin lesions vary widely
when pigmentation of the skin is included in the definition. First
of all, it is difficult to ascertain pigmentation in a dark complexion
skin, particularly for studies conducted in Bangladesh and West
Bengal India (Khan et al., 1997;Ahmad et al., 1997), and secondly,
the studies have used variable definitions for pigmentation (Tseng
et al., 1968;Wong et al., 1998). Additionally, the characteristics of
arsenic skin lesions may also vary from one place to another
(Tseng et al., 1968;Wong et al., 1998). This study estimated the
prevalence for definitive cases of arsenicosis, hyperkeratosis of
palms and/or soles excluding skin pigmentation, and suspected
cases, any manifestation of arsenicosis on skin including pigmen-
tation, of skin lesions of arsenic. Alongside, it also utilized
laboratory criteria, exposure to arsenic in drinking water, for
diagnosis of arsenic cases to validate its findings.
Due to variable definitions used for arsenic skin lesions in
different studies it may make the comparison difficult; however
the burden of arsenic health effects seems lower in Pakistan
(0.34–1.3%) than regional countries. The studies have found
9.8–20.6% prevalence of skin lesions in Bangladesh and West
Bengal, India (Rahman et al., 2001, 2005). A study conducted in
Nepal found 8.9% prevalence of skin lesions (Ahmad et al.,
2004a, b). The prevalence of skin lesions in four affected provinces
of China ranged between 2.08% and 13.7% (Sun, 2004). Similarly,
the levels and proportion of arsenic-contaminated water sources
were lower in the district Khairpur than studies conducted in
regional countries (Rahman et al., 2001, 2005;Ahmad et al.,
2004a, b;Sun, 2004). Even low to moderate level of arsenic
exposure lead to skin lesions of arsenic if the duration of exposure
is sufficiently long as shown in this survey. Approximately, 12% of
drinking water sources in Khairpur district had arsenic X10
m
g/L
and 2% had X50
m
g/L. These results were consistent with UNICEF
survey conducted earlier in this area (Ahmad et al., 2004a, b).
UNICEF used arsenic testing kits (Merck) while this survey utilized
HG-AAS. In comparison in Bangladesh and West Bengal, respec-
tively, 56% and 52% drinking water sources contained arsenic
X10
m
g/L and 37% and 25% X50
m
g/L (Rahman et al., 2001).
Groundwater sources tested in Nepal showed that 23% and 5% of
the sources had X10
m
g/L and X50
m
g/L arsenic, respectively
(Shrestha et al., 2003). Studies in six provinces of China showed a
range of 1.06–52.35% of the drinking water sources contaminated
with arsenic at X50
m
g/L (Sun, 2004). The highest recorded
arsenic value in water sources in Khairpur district was 350
m
g/L.
However, studies conducted in Bangladesh and Nepal has found
much higher levels (1700–2500
m
g/L) of arsenic in drinking water
(Ahmad et al., 2004a, b;Anawar et al., 2002). The arsenic dose is
a function of concentration of arsenic in water and duration
of consumption. The study showed that prevalence of arsenic
skin lesion increases with increasing levels of arsenic in current
drinking water sources. This study found a stronger association
with cumulative arsenic exposure and arsenic skin lesions than
found with current arsenic water levels.
Geographically, greater proportion of arsenic-contaminated
wells and high prevalence of arsenic skin lesions were found
alongside River Indus (Fig. 4). Further investigations for arsenic may
be carried out along the course of the River Indus in Pakistan. This is
similar to findings in Bangladesh and West Bengal where most of
the severely contaminated wells were along the bank of river
Ganges (Chakraborti et al., 2003). The reason for high concentration
of arsenic along the river course is still unexplained. In both the
rivers of Indus and Ganges, the concentration of arsenic is very low.
However, geologists hypothesize that river alluvial soil along the
bank attract and concentrate arsenic over a period. The concen-
trated arsenic leach into the groundwater and its level of arsenic
rises (Acharyya et al., 1999;Nickson et al., 1998).
The prevalence ratio (or risk) of skin lesions was 2.4 among
malnourished. Studies in Bangladesh have found similar findings
and prevalence ratio of and around 2 among malnourished than
healthy individuals (Islam et al., 2004;Milton et al., 2004).
Age, gender and smoking were not associated with arsenic skin
lesions. The differences of prevalence in categories of age, gender
and smoking are very small and range only from 0.1% to 0.6%
ARTICLE IN PRESS
Fig. 4. (a) Proportion of groundwater sources contaminated with arsenic at
X10
m
g/L in talukas (subdistricts) in district Khairpur, Pakistan. (b) Prevalence of
arsenic skin lesions (arsenicosis) according to subdistricts (talukas) and its relation
with River Indus in district Khairpur, Pakistan.
Z. Fatmi et al. / Environmental Research 109 (2009) 575–581 579
Author's personal copy
(Table 2). In some studies smokers have been found to be at more
risk of developing arsenic skin lesion than non-smokers (Hossain
et al., 2005). However, studies have also found ambiguous
association of arsenic skin lesions with smoking (Hadi and
Parveen, 2004). The relation of smoking with skin lesions needs
further investigation. A study conducted in Bangladesh found
increased prevalence of skin lesions of arsenic with age (Bodwell
et al., 2006). Some research studies have found that males were
more likely to have arsenic skin lesion than females (Ahmad et al.,
2004a, b;Hadi and Parveen, 2004). However, females were more
susceptible to skin lesions in another study (Ahmad et al., 1999).
In the wake of these findings, efforts should be directed to
provide arsenic-free water to the identified villages. Most of the
heavily affected villages are alongside Indus River. Operational
research should be conducted to test various options. Most of the
villages (99%) can avail the option of switching to safe wells. A few
villages (less than 1%) have most of its sources with the unsafe
levels of arsenic. In these villages, arsenic removal technologies
and deep wells may be a viable option (Van Geen et al., 2002,
2003;Shrestha et al., 2003;Mead, 2005). The answer lies in
multidisciplinary team with health, behavioral and earth scien-
tists working together to solve this problem.
5. Limitations
This study included population X15 years because lower
prevalence of skin lesions was expected among younger popula-
tion (Ahmad et al., 2004a, b;Chowdhury et al., 2003). This
estimation would have required a much larger sample. This study
measured total arsenic in water and urine. Total arsenic includes
organic and inorganic forms of arsenic. However, groundwater
contains mostly inorganic arsenic that is more toxic than organic
forms (Schulman, 2000;Mandal and Suzuki, 2002). The seafood
such as fishes also contains organic form of arsenic (Schulman,
2000;Mandal and Suzuki, 2002). Therefore, analysis excluded
those individuals who ate fishes during the last 3 days.
The probability of type II error always remains when we fail to
reject null hypothesis. The sample size for this study was not
calculated for testing the hypothesis. However, we could still use
the test of hypotheses for certain bound on error (difference in the
proportions). In our case for the variables of age, gender and
smoking status that we test hypotheses, the actual difference
in proportions is very small between the two groups, therefore, in
order to minimize the type II error at that level, a very large
sample was required. It is for the same reason we did not go for
multivariable analysis as very few variables would have such
bound on the error of estimation.
The study used water and urine samples as an indicator of
exposure to arsenic. These mainly describe the acute exposures.
Inorganic arsenic has strong affinity to bind with sulphydryl
group, therefore keratin-rich tissues such as skin, hairs and nails
have high concentrations of arsenic and are also used as
biomarkers for chronic exposure. However, processing these
biological samples is technologically challenging. Furthermore,
24-h urine is a more reliable indicator of arsenic exposure than
spot urine. However, speciation of arsenic is technologically
difficult and collection of 24-h urine logistically challenging in
rural areas. Therefore, many studies have used spot-urine samples
for reliable results (Calderon et al., 1999).
6. Conclusions
This paper presents the epidemiological and clinical evidence
of adverse health effects (skin lesions) of groundwater arsenic
contamination in a low to moderately affected area. Most of the
studies have focused its attention to high concentration arsenic
affected areas. There is significant burden of skin lesions at
relatively low concentration of arsenic in Khairpur district of
Pakistan. Levels of arsenic contamination in groundwater in this
study were less compared with Bangladesh and West Bengal.
Several districts in Pakistan have similar concentration of arsenic
in groundwater. There is significant relation of both arsenic skin
lesions and groundwater contamination of wells with proximity
to Indus River. Further studies of health effects of arsenic should
be carried out particularly among the population living alongside
River Indus. The goal of eliminating arsenic from drinking water
should be tackled with great diligence. Population awareness and
health workers training, alongside availability of arsenic testing
kits, to take mitigation measures, are needed.
Ethical review: This research study was reviewed by Aga Khan
University Ethics Review Committee (Human Subject Assurance
Number: FWA00001177).
Acknowledgments
We would like to thank UNICEF for providing financial support,
and department of Local Government, Sindh for facilitating this
survey. Not least, we wish to thank the people of Khairpur,
villagers and households visited, for their hospitality and
cooperation.
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