III

A Field Guidefor Detection, Management andSurveillance of Arsenicosis Cases

WORLD HEALTH ORGANIZATIONRegional Office for South-East Asia

Edited by Deoraj Caussy, New Delhi, 2005

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This guide was conceived, designed and technically supervised by Dr Deoraj

Caussy, Environmental Epidemiologist, World Health Organization, working in

collaboration with a consortium of experts listed in Appendix B.

The technical contributions of the participants of various workshops listed in

Appendix B are gratefully acknowledged. Thanks are also due to the countless

number of patients whose clinical findings and photographs have been used

in this guide. Finally, thanks for the photographs are gratefully acknowledged

to the following persons: 1) Professor AZM Maidul Islam, Professor and

chairman, Department of Dermatology, Bangabandhu Sheikh Mujib Medical

College, Dhaka, Bangladesh, 2) Professor Akthar Ahmad, Department of

Occupational and Environmental Health, National Institute of Preventive and

Social Medicine, Dhaka, Bangladesh, 3) Dr Zakir Hussain, office of the

Directorate General of Health, Dhaka Bangladesh, 4) Dr Vandana Chatrath,

Dermatologist, New Delhi, India, 5) Dr Siriluck Thaicharoen, Dermatologist,

Nakhorn Si Thamarat Province, Thailand and, 6) Dr Thada Piamphongsant,

Senior Consultant Dermatologist, Institute of Dermatology, Nonthaburi,

Thailand.

Acknowledgments

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Preface

Globally, arsenicosis, also referred to as arsenism, is an important non-

communicable disease resulting from the ingestion of groundwater containing

an unsafe level of arsenic. Groundwater contamination, in excess of the WHO

guideline value, has been observed in some countries of the South-East Asia

Region. The affected countries are Bangladesh, India, Myanmar, Nepal and

Thailand. Over 10 million tubewells are in use in the Region, potentially

exposing between 40 and 50 million persons to unsafe levels of arsenic.

To mitigate the health effects of arsenic in the South-East Asia Region, in 2003,

WHO prepared this Field Guide for Detection, Management and Surveillance

of Arsenicosis Cases. The materials were developed and field-tested in regional

and national workshops in Bangladesh, India and Thailand.

This guide is primarily for human resource development in the area of arsenic

mitigation in the Region.

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Section 1 Introduction1.01 Background and Purpose of This Module . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 011.02 The Role of WHO in Arsenic Mitigation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 021.03 Programme Strategy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 02

Section 2 Epidemiology of Arsenicosis in South-East Asia2.01 Forms and Occurrence of Arsenic . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 042.02 Pathway for Exposure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 042.03 Health Impact of Exposure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 04

Section 3 Clinical Aspects3.01 Pathogenesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 053.02 Skin Manifestations of Chronic Arsenic Ingestion . . . . . . . . . . . . . . . . . . . . . . . . . 063.03 Differential Dermal Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 083.04 Other Non-dermal Manifestations of Chronic Arsenicosis . . . . . . . . . . . . . . . . 09

Section 4 Case Definitions4.01 Definition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 104.02 Rationale for Case Definition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 104.03 Criteria for Case Definition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 104.04 Clinical Criteria . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 114.05 Laboratory Criteria . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 114.06 Algorithm . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 114.07 Suspected Case . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 114.08 Probable Case . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 114.09 Clinically Confirmed Case . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 114.10 Laboratory Confirmed Case . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 154.11 Clinically and Laboratory Confirmed Case . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 154.12 Non-arsenic Case . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 154.13 Sensitivity and Specificity of Case Definition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 154.14 Role of National Expert Committee . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15

Section 5 Laboratory Support5.01 Types of Specimen . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 165.02 Collection, Storage and Shipment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 165.03 Analytical Procedures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 175.04 Quality Control . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17

Table of Contents

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5.05 Interpretation of Laboratory Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 175.06 Laboratory Network . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18

Section 6 Case Management6.01 Basic Principles for Management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 196.02 Available Management Strategies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19

6.02.1 Cessation of Exposure to Drinking Water . . . . . . . . . . . . . . . . . . . . . . . . . 206.02.2 Administration of Nutritional Supplements . . . . . . . . . . . . . . . . . . . . . . . 206.02.3 Provision of Non-Specific Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 206.02.4 Secondary Prevention of Latent Effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . 206.02.5 Counselling and Education . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20

6.03 Patient Management Flow Chart . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22

Section 7 Case Surveillance7.01 Rationale of Surveillance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 237.02 Suggested Format of Surveillance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24

Section 8 Illustrations of Skin Manifestations 25

Section 9 Further Discussions on Differential Diagnosis 31

Appendix A: Working Methods Adopted for Formulation of the Field Guide 34

Appendix B: Members of the Expert Committees 35Appendix C: Key References 38

List of TablesTable 1 : Characteristic Cutaneous Lesions of Arsenicosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 06Table 2 : Common Conditions to be Considered for Differential

Diagnosis of Non-cancer Skin Lesions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14Table 3 : Checklist of Suggested Case Management for Systemic

Manifestation of Arsenicosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19

List of Figures and ChartsFigure 1 : Strategic Goals for Arsenic Mitigation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 02Figure 2 : Components of Surveillance Tasks at Each Administrative Level . . . . . . . . . . . . . . . . 23Flowchart 1: Arsenicosis Case Definition Algorithm . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12Flowchart 2 : Management of Arsenicosis Cases at Various Levels of Health Services . . . . 21

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Section 1. Introduction

1.01 BACKGROUND AND PURPOSE OF THEMODULE

Drinking water contaminated with an unsafe level ofarsenic is known to result in adverse health outcomes.In many parts of the world, the source of drinkingwater is groundwater. While groundwater is relativelysafe as regards bacterial contamination and otherimpurities, it is prone to chemical contamination suchas arsenic. Arsenic contamination of groundwater mayoccur in two ways: drawing of water from aquifers thatnaturally contain arsenic or contamination fromanthropogenic activities such as mining. Groundwatercontamination in excess of the World HealthOrganization guideline value of 0.01 mg/L has beenobserved in parts of USA, Canada, Argentina, Chile,Mexico, Hungary and many countries of the South-EastAsia Region. The most affected countries in the South-East Asia Region are in the river basins of the Ganga-Brahmaputra or the Mekong Delta. Affected countriesinclude India, Bangladesh, Nepal, Myanmar, Vietnam,Cambodia, Laos and China.

Until now there have been no internationally acceptedcriteria for the diagnosis and management ofarsenicosis or diseases associated with arsenicexposure. The purpose of this document is to serve asa guideline for the diagnosis, surveillance andmanagement of arsenicosis. It is recognized thatarsenicosis may manifest with or without skinmanifestation. However, generally skin manifestationis the primary condition leading a patient to seekmedical care. Therefore, the emphasis in this documentis the diagnosis of arsenicosis based on dermalmanifestations.

The use of this document will ensure consistency in thediagnosis and management of arsenicosis cases, trainingof health workers and provide a set of objective criteriafor the evaluation of any intervention measures. Theultimate aims are to set the norm, standards andguidelines for a harmonized protocol on case detection,management and surveillance. These criteria weredeveloped by an expert group working in the field ofarsenic taking into account the best available evidencefor action that is currently available. It is envisaged thatnational authorities, sister agencies and developmentpartners will use this document to manage arsenic

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contamination in their respective countries and mayfurther translate it into the local language.

1.2 ROLE OF WHO IN ARSENIC MITIGATION

WHO first assessed the risk of arsenic in drinkingwater in 1958 by producing the InternationalStandards for Drinking Water. In 1981, in collaborationwith other UN agencies, WHO published the“Environmental Health Criteria on Arsenic” toevaluate the health risks to humans from exposure toarsenic. The Environmental Health Criteria on arsenicwas updated in 2001. Globally, the WHO Guidelinesfor Drinking Water Quality, published in 1993, havebeen used as the basis for the development ofnational standards for arsenic.

Realizing the serious health impact of arseniccontamination in the South-East Asia Region of WHO,the Regional Office for South-East Asia, since 1996, hasprovided policy and technical support to nationalgovernments of the affected countries. In 1997, theRegional Office held a regional consultation of expertsand made 20 key recommendations for arsenicmitigation. These recommendations have been used asthe basis for designing projects and implementingprogrammes by national governments, donor agenciesand NGOs alike. However, on reviewing the progress of

implementation, it was evident that critical gaps in casereporting and case management remained to beremedied. In 2002, the Regional Office launched anarsenic mitigation initiative which was founded onpolicy support stemming from the recommendations ofthe High-Level Task Force, the Regional Committee andthe Advisory Committee on Health Research.

1.3 PROGRAMME STRATEGY

The programme strategy focuses on WHO’s normativerole in applying the health risk assessment paradigmfor the mitigation of the health impact of arsenicexposure. As shown in Figure 1, the arsenic mitigationinitiative is implemented through a strategic planfocusing on three main goals, namely:

(1) responding to arsenic hazard through consistentapplication of health risk paradigm of exposureassessment, risk characterization and riskmanagement,

(2) strengthening infrastructure for arsenicmitigation through promotion of a network ofcentres of excellence, and

(3) building capacity through human resourcedevelopment.

Figure 1STRATEGIC GOALS FOR ARSENIC MITIGATION

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Section 2. Epidemiology of Arsenicosis in S-E Asia

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The South-East Asia Region contains a naturalarsenic-rich eco-belt formed by arsenic-ladenalluvium or sediments deposited in theBrahmaputra-Gangetic river basins millions ofyears ago. Countries of South-East Asia that are inthis belt include Bangladesh, parts of India,Myanmar and Nepal. Anthropogenic miningactivities in one province of Thailand have alsobeen responsible for arsenic contamination.Groundwater from tubewells is a predominantsource of drinking water in many of the MemberCountries in which contamination of groundwateroften exceeds either the WHO guideline valuesor the respective prevailing national standards.It is estimated that some 30 million personsmay be at risk for arsenic-related diseases byvirtue of consuming arsenic contaminated waterin the region.

2.01 FORMS AND OCCURRENCE OF ARSENIC

Arsenic is an element that can combine with bothmetals and non-metals to form inorganic and organiccompounds. The inorganic forms are toxic to humanhealth and consist mostly of arsenite and arsenatecompounds. The organic forms are comparatively non-toxic and are mostly present in sea foods.

2.02 PATHWAY FOR EXPOSURE

Humans may be exposed to inorganic arsenic fromall four environmental matrices of air, water, foodand soil. General environmental exposures includeingestion of soil by children, ingestion of certaintraditional medicines and various food items andingestion of water. Arsenic is present at levelsranging from 0.2 to 40 µg/g of soil while in urban airthe concentration of arsenic is at levels around0.02 µg/m3 of air. The levels of arsenic in food itemsin the affected countries vary but they currently posea lesser threat than drinking water.

2.03 HEALTH IMPACT OF EXPOSURE

The health impact of exposure to arsenic depends onthe dose, the modality and duration of exposure aswell as the source and type of arsenic. Prolongedexposure to non-lethal doses of 0.005 to 0.09-mg/kg-body weight/day results in arsenicosis, a disease thatis characterized by dermatological features ofpigmentation and keratosis. Arsenicosis is also calledarsenicism, and is also referred to as black footdisease, black skin fever etc. in various parts of theworld. Cancers of the lungs, bladder, kidney and skinhave been consistently observed in subjects drinkingarsenic-contaminated water. Presently, inconclusiveevidence exists for linking arsenic to cardiovasculardisease, diabetes or negative reproductive healthoutcomes.

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Section 3. Clinical Aspects

3.01 PATHOGENESIS

Both organic and inorganic arsenic are absorbed fromthe gastrointestinal tract; however, arsenic toxicityresults from absorption of trivalent and pentavalentinorganic arsenic.

After absorption, arsenic is cleared rapidly from theblood and during its “first-pass” phase it reaches theliver where it is detoxified by conversion into MMAand DMA. Arsenic metabolism is characterized by twosequential reactions:

(a) First, the reduction of pentavalent arsenic totrivalent arsenic in the presence of gluthathione,

(b) The second is oxidative methylation reaction inwhich the trivalent forms of arsenic aresequentially methylated to form mono, di andtrimethylated products using s-adenosylmethionine (SAM) as methyl donor and GSH asan essential co-factor. Arsenic methylationoccurs primarily in the liver.

Urine is the primary route for elimination of bothpentavalent and trivalent inorganic arsenicals, 45-75%of the administered dose being excreted in the urinewithin a few days to a week. Arsenate can uncoupleoxidative phosphorylation in mitochondria bysubstituting for inorganic phosphate in the synthesisof ATP, the main energy source of cellular metabolism.Arsenite reacts readily with vicinal sulphydryl groupsof many essential enzymes and proteins within thecell. It is the affinity of arsenite for the sulphydrylgroup that accounts for its accumulation in keratin-rich tissues such as skin, hair and nails.

Chronic arsenic toxicity produces various dermal andsystemic manifestations including cancer. Trivalentarsenic is believed to be a carcinogen that induceschromosomal abnormalities including changes in thestructure and number of chromosomes and sisterchromatid exchanges. The exact molecular mechanismof arsenic induced carcinogenesis is less understood.

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Table 1CHARACTERISTIC CUTANEOUS LESION OF ARSENICOSIS

3.02 SKIN MANIFESTATIONS OF CHRONICARSENIC INGESTION

The skin manifestations of chronic arsenicosis,resulting from ingestion of arsenic, can be eithernon-malignant or malignant. The hallmarks ofnon-malignant manifestations are dermal changesconcomitantly characterized by increasedpigmentation and hardening of the skin, that is acombination of melanosis and keratosis. Thecharacteristic cutaneous lesions of arsenicosis areillustrated in Table 1. The most common sequence isthe gradual development of spotted or “raindroppigmentation”, followed by the gradual emergence ofhyper-keratotic changes. Both conditions take severalyears ranging from 6 to 9 years depending on theexposure dose and other host factors.

The hyper-pigmentation commonly appears in a finelyfreckled, “raindrop” pattern that is particularlypronounced on the trunk and extremities and issymmetrically distributed bilaterally. Mucousmembranes such as the undersurface of tongue orbuccal mucosa may also be involved. Other patterns

MILDSlightthickening,or minutepapules(less than2 mm) ofpalms and soles, oftenassociated with a grit-liketexture, that may beprimarily detectable bypalpation

KERATOSES

Characterized by thickening of the skin and appearance ofpapules or nodules that can both be further sub-categorizedas follows:

MODERATEMultiple, raised keratosis(>2 to 5 mm), appearing

Fine-freckled or spottedpattern on trunk andextremities (rain-droppigmentation)

MELANOSES

Diffused or generalized hyperpigmentation

Rounded hypo-pigmented orde-pigmented macules on anormal or hyper-pigmentedbackground (leukomelanosis)

Localized or patchypigmentation generallyon the body

Pigmentation of mucousmembranes (e.g. oral mucosa),usually in combination withother changes listed above(less common)

MELANOSISPalm of a man sufferingfrom melanosis

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BOWEN’S DISEASE

May appear as multiple macules, papule, or plaque (1mm to manycm) in non-sun exposed areas. Usually a scaly, crustederythematous plaque. They are usually sharply demarcated andseldom indurated (pic overleaf). If the crust is removed, theunderlying surface may be red and oozing.

In situ squamous cell carcinoma / intra-epidermal carcinoma

Both these cancers have highly variable clinical appearances,depending in part on the stage of the malignancy. Squamous CellCarcinoma is characterized by ulcerated or fungating growth (picoverleaf). Basal cell carcinoma is initially characterized by pearlytranslucent nodules leading to ulcerations.

SQUAMOUS CELL & BASAL CELL CARCINOMA

include diffused hyper-pigmentation (melanosis);localized or patchy pigmentation and so-calledleukodermia or leukomelanosis in which the hypo-pigmented macules take a spotty, white appearance.

Arsenical hyper-keratosis predominantly appears onpalms and the plantar aspect of the feet, althoughinvolvement of the dorsum of the extremities andtrunk has also been described. In the early stages, theinvolved skin might have an indurated, grit-likecharacter that can be best appreciated by palpation;however, the lesions usually advance to form raised,punctuated, 2-4 mm wart-like keratosis that arereadily visible. Occasional lesions might be larger(approximately 1 cm) and have a nodular or hornyappearance. In severe cases, the hands and solespresent with diffused verrucous lesions. Cracks andfissures may be severe in the soles.

The most common type of malignancy followingchronic exposure are skin cancer such as Bowen’sdisease, squamous cell carcinomas or basal cellcarcinomas, although internal malignancies areprobably related as well.

KERATOSISMostly characterized bythickening of palms and soles,alone or in combination withnodules

mainly or exclusively in asymmetric distribution onpalms and soles

SEVERELarge discrete or confluent

keratotic elevations(> 5 mm) on palms andsoles, with nodular, wart-likeor horny appearance.

Less commonly, there mayalso be involvement of thedorsum of the extremities,and trunk. Diffusedthickening of the palms andsoles may occur alone or incombination with thekeratotic nodules.

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Bowen’s disease, or in situ squamous cell carcinoma /intra-epidermal carcinoma may appear as multiplemacules, papule, or plaque (1mm to many cm) innon-sun exposed areas. It usually presents as a scaly,crusted erythematous plaque that are sharplydemarcated and seldom indurated.

Squamous cell and basal cell carcinoma have highlyvariable clinical appearances, depending in part onthe stage of the malignancy. Squamous Cell Carcinomais characterized by ulcerated or fungating growth.Basal cell carcinoma is initially characterized by pearlytranslucent nodules leading to ulcerations.

3.03 DIFFERENTIAL DERMAL DIAGNOSIS

The classic pattern of rain-drop pigmentation isrelatively specific for arsenic, and its occurrencetogether with palmar-plantar hyperkeratosis ispathognomonic for arsenicosis. Nonetheless, some ofthe skin changes associated with arsenic may appearthe same or similar to those encountered in othermedical conditions. Table 2 lists at least five categoriesof dermal manifestations mimicking arsenicaldermatosis and include diffused melanosis, spottedmelanosis, leukomelanosis, diffused keratosis, andnodular keratosis. Clinicians and paramedicalpersonnel practising in primary care settings can betrained to screen patients for the possible presence ofcharacteristic arsenic-related skin lesions, but adifferential diagnosis examination using the criteria ofSection 9 by an experienced dermatologist or otherphysician with relevant expertise is recommended forconfirmation of the diagnosis.

BOWEN’S DISEASEIn situ squamous cell carcinoma / intra-epidermalcarcinoma seen here as a sharply demarcated plaque.

SQUAMOUS CELL CARCINOMAUlcerated growth, peculiar to the condition, seen on thefinger of a patient.

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3.04 OTHER NON-DERMAL MANIFESTATIONSOF CHRONIC ARSENICOSIS

The most common systemic manifestations includeneurological, haematological, gastrointestinal andrespiratory complications.

Complications of the central and peripheral nervoussystems are neuropathy characterized by paresthesiasand numbness. Studies from Taiwan havedocumented the presence of black-foot disease, aunique peripheral arterial disease characterized bysevere systemic arteriosclerosis as well as drygangrene and spontaneous amputations of affectedextremities at end stages. Though the incidence of legpain or intermittent cramp in the leg muscles is notuncommon, dry gangrene is less frequently seen inthe Indo-Gangetic Basin.

Haematological complications include leukopenia,anaemia and spleenomegaly.

Gastrointestinal complications include symptoms likeanorexia, vague abdominal pain or chronic diarrhoea;liver enlargement with or without non-cirrhotic portalfibrosis are also seen.

Respiratory complications include chronic cough orbronchitis.

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Section 4. Case Definitions

4.02 RATIONALE FOR CASE DEFINITION

The accurate detection of arsenic cases is thecornerstone for case management and reporting. Indisease surveillance, a case is usually defined byclinical signs, symptoms, or laboratory measures. Inapplying this approach for arsenic case definition, twopractical difficulties arise. First, there are several skinconditions in South-East Asia that share majorfeatures with arsenic-defining conditions and,secondly, the use of laboratory measures is notuniformly available under all local conditions.Therefore, the selection of case definition forarsenicosis ultimately depends on the objective of thepublic health programme. The present objectives informulating a case definition are to:

(a) achieve consistent case detection and reportingin the Region,

(b) provide an objective way to evaluate the efficacyand effectiveness of any interventions,

(c) attain consistency in the training of health careworkers in the Region, and

(d) enable valid comparison of studies.

4.03 CRITERIA FOR CASE DEFINITION

In formulating a working case definition, it isgenerally prudent not to include any clinicalinformation or diagnostic test which might not beuniformly available under conditions of local medicalpractice. The case criteria should be appropriate forthe diagnostic resources available to the communitywhere the problem exists. However, this may makethe case definition less precise. Therefore, a balancebetween scientific precision and field practicalityhas been maintained in devising an algorithmwhereby a case can be either clinically confirmed onlyor clinically and laboratory confirmed depending onthe availability of resources or clinical expertise or thepurpose for which the case definition is needed. Thus,the recommended case definition algorithm uses twomajor diagnostic criteria, namely:

Arsenicosis is defined as a chronic healthcondition arising from prolongedingestion of arsenic above the safe dosefor at least six months, usuallymanifested by characteristic skin lesionsof melanosis and keratosis, ocurringalone or in combination, with or withoutthe involvement of internal organs.

4.01 DEFINITION

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(a) the presence of pigmentary and keratotic skinlesions, and

(b) evidence of exposure to elevated levels ofarsenic established by history of intake ofarsenic contaminated water, or by arsenicconcentration in hair or nails.

4.04 CLINICAL CRITERIA

The first diagnostic criterion requires the presence onphysical examination of any of the pigmentary orkeratotic skin signs listed in Table 1. These signsencompass a spectrum of non-cancerous and cancercutaneous findings that are well-recognized featuresof chronic arsenic ingestion.

4.05 LABORATORY CRITERIA

A reliable history of consuming drinking water withan elevated concentration of arsenic for at least sixmonths is sufficient to establish exposure. See Box 1.In the absence of adequate information regarding asubject’s exposure history, the finding of elevatedlevels of arsenic in a subject’s hair or nails could offerpresumptive evidence of elevated arsenic exposure.Arsenic testing should be conducted usingstandardized sample collection methods andacceptable laboratory techniques as elaborated inSection 5.

4.06 ALGORITHM

A diagnostic algorithm for case detection provides asimplified scheme for implementing the casedefinition and classifying patients under fieldconditions and in various levels of health carefacilities. The suggested algorithm is shown inFlowchart 1.

4.07 SUSPECTED CASE

A “suspected case” is a subject who showscharacteristic skin lesions or pigmentary changes orkeratosis on first presentation and who has notundergone in-depth medical examination orlaboratory testing. The list of skin lesions forsuspecting a case is detailed in Table 1.

The classification of “suspected case” is temporary. Itshould be reclassified as “probable”, “confirmed” or“non-arsenic” after further clinical examination and orlaboratory testing.

4.08 PROBABLE CASE

A “probable case” is a suspected case that hasundergone further clinical examination and belongsto one of the two categories as below:

EITHER(a) a suspected case showing melanosis AND bilateralkeratosis involving palms and soles

OR(b) a suspected case showing unilateral melanosis orkeratosis after excluding other skin lesions mimickingarsenicosis.

Probable cases whose arsenic tests are subsequentlyfound to be negative maintain the status of probablecase.

4.09 CLINICALLY CONFIRMED CASE

A “clinically confirmed case” is a “probable case” inwhom the presence of other arsenicosis-simulatingskin lesions has been ruled out by differential in-depthskin examination by either a trained dermatologistor an arsenic expert. The differential features to beused are given in Table 2 and further elaborated inSection 9.

< flip for gatefold: Flowchart 1

Laboratory Confirmedis a Probable Case classified on thebasis of differential skin diagnosisbut in whom subsequentlaboratory tests for arsenic proveto be positive

Clinically Confirmedis a “probable case” in whom thepresence of other arsenicosis-simulating skin lesions has beenruled out by differential in-depthskin examination.

Clinically andLaboratoryConfirmed

Suspected Caseis a subject who shows characteristicskin lesions of pigmentary changesor keratosis on first presentation andwho have not undergone in-depthmedical examination

Probable Caseis a “suspected case” that

has undergone furtherclinical examination and

belongs to two categoriesmentioned in 4.08

A clinically confirmed case maybe further confirmed bylaboratory testing of arsenic inspecial circumstances

Primary Level

Secondary Level

Tertiary Level

Flowchart 1 :Arsenicosis Case Definition Algorithm

Arsenic exposure can be established by testing either water or biomarker (see box 1)+ As per table 1 and differential diagnosis of Section 9*

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Table 2COMMON CONDITIONS TO BE CONSIDERED FORDIFFERENTIAL DIAGNOSIS OF NON-CANCER SKIN LESIONS

Actinic dermatosis

Melasma

Ashy dermatosis

Found on exposed part of the body

Found mainly on face

Diffused pigmented macules mainly on trunk

DiffusedKeratosis

CATEGORY MAJOR CONDITIONS FORCONSIDERATION

DISTINGUISHING FEATURES

NodularKeratosis

DiffusedMelanosis

SpottedMelanosis

Leuco-Melanosis

Pityriasis versicolor

Freckle

Lichen planus

Idiopathic guttate hypomelanosis

Pityriasis versicolor

Pityriasis – lichenoides chronica

Leprosy

Psoriasis (palms and soles)

Eczema

Occupational keratosis

Tinea pedis

Pitted keratolysis

Hyperpigmented macules with fine scale on trunk, face and neckextremities.

Mottled pigmentation on face and trunk increases with sun exposure.

Starts with violaceous pruritic papular lesion on trunk andextremities and produces spotty pigmentation on resolution.

Multiple depigmented macules on trunk and extremities.

Hyper and hypo-pigmented macules with scales on trunk, face, neckand extremities.

Erythematous papular lesion followed by hypo-pigmented macules

Macular hypo-pigmented or erythematous lesions, usually with lossof sensation. There may be involvement of peripheral nerves whichare usually thickened and tender.

Diffused keratoderma on palms and soles, with or without scalypsoriatic patches on the other sites.

Lichenified lesions with pruritus and occasional oozing.

Keratotic lesions corresponding to site of friction.

Scaly fissured keratotic lesion, with or without fissures on webs.

Multiple pitted (depressed) and keratotic lesions on soles.

Occupational keratosis

Verruca vulgaris

Corns/calluses

Seborrheic keratosis

Same as above.

Multiple verrucous pigmented papules and nodules on trunk,extremities and dorsum of hands and feet.

Localized keratotic lesions at the site of friction.

Discrete well-defined pigmented papules and plaques on sun-exposedareas.

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4.10 LABORATORY CONFIRMED CASE

A probable case classified on the basis of differentialskin diagnosis becomes a “laboratory confirmed case”when subsequent laboratory tests for arsenic proveto be positive.

4.11 CLINICALLY AND LABORATORYCONFIRMED CASE

A “clinically and laboratory confirmed case” is a“clinically confirmed case” in whom the arsenic testis also positive by the criteria recommended in Box 1.

4.12 NON-ARSENIC CASE

A “non-arsenic case” is a “suspected” or “probable”case in which the medical specialist finds that thepatient’s skin condition is due to a cause other thanarsenic exposure.

4.13 SENSITIVITY AND SPECIFICITY OF CASEDEFINITION

The rigor and complexity of a case definition and itssensitivity and specificity vary depending on thepurpose for which the definition will be applied. Inclinical settings, it is appropriate to use a broader andsimpler case definition that will apply to capture allpossible spectrums of clinical presentations. Thepresent case definition algorithm for non-cancerousskin lesions shows acceptable sensitivity (>80%) andspecificity (>80%) for the prevalent arsenic-associatedskin lesions.

It must be remembered that all arsenicosis cases maynot necessarily show dermal manifestations at theoutset. Hence those cases will not be captured by thepresent algorithm. However, clinical evaluation formanagement of suspected cases described in Section6 will pick up such cases that will have to beappropriately followed up medically.

4.14 ROLE OF NATIONAL EXPERT COMMITTEE

There may be instances where the application of thepresent algorithm does not lend itself to some clinicalcases. In such cases it is advisable to refer these typesof cases to a nationally constituted expert committeefor advice. If such a committee does not exist in aparticular country, then referral for advice from aregional centre of expertise is recommended.

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Box 1LABORATORY CRITERIA FOR ESTABLISHINGEXPOSURE HISTORY OF ARSENICOSIS CASES

Section 5. Laboratory Support

Consumption ofdrinking water with anarsenic concentration inexcess of prevailingnational standards forat least six months.

If data on the arsenicconcentration ofpreviously consumedwater is unavailable, anelevated concentrationof arsenic in hair(> 1 mg/Kg of hair)or in nail clippings(> 1.5 mg/Kg of hair)may serve aspresumptive evidenceof elevated arsenicexposure.

TESTING BIOMARKER

TESTING WATER

THE ARSENIC CONCENTRATION should be determinedusing a validated method performed by trainedpersonnel in a laboratory meeting national standardsand practising standard operating procedures.

Laboratory support provides ancillary informationin instances where probable cases cannot beclinically confirmed or in instances or countrieswhere a laboratory diagnosis is required for finalconfirmation.

5.01 TYPES OF SPECIMEN

WATER: Arsenic exposure can be established bytesting the water that is currently being consumed.

HAIR AND NAIL: Hair or nails provide circumstantialevidence for history of past exposure within thepreceding nine months.

URINE: Both organic and inorganic forms of arsenicare excreted in the urine which will test positive forarsenic. Thus, recent exposure to arsenic can beestablished from urine samples provided the subjectshave not been consuming sea-food in the precedingfour days. Alternatively, the chemical form of arsenicmust be differentiated by laboratory methods.

BLOOD: Blood is of no value in establishing chronicarsenic exposure because of the short half-life ofarsenic in blood.

5.02 COLLECTION, STORAGE AND SHIPMENT

WATER AND URINE: For water and urine samples itis advisable to collect 50 ml of samples. Care must betaken to avoid contamination and prevent speciationchanges during sample collection and storage. Plasticcontainers should be acid washed and traces ofoxidizing agents avoided to preserve the oxidationstate of the arsenic compounds, in instances wherespeciation is required. The container should also becompletely filled to prevent oxidation from the air inthe bottle.

Concentrated hydrochloric acid (1 ml of acid to100 ml of urine) can be used to prevent bacterialgrowth for urine samples. The samples are stableat room temperature for at least a week and at –20°Cfor 6 months. For longer periods it is recommendedthat the samples be frozen at –80°C.

17

Urine and water samples can be shipped at roomtemperature. Avoid shipment before a weekend orholidays. All specimens must be accompanied by aduly filled request form containing information on thepatient’s name, referring doctor, clinical diagnosis andan address for sending results. The request formshould be packed in a separate plastic bag forprotection in the event of specimen leakage.

HAIR AND NAILS: Care should be taken to avoidsuperficial arsenic contamination. The hair must bewashed with arsenic-free shampoo and also be free ofcolouring chemicals containing arsenic. For a femalesubject, collect 30 hairs 6 cm. long from the base ofthe hair, discard the hair beyond 6 cm. For males,collect 60 short hairs from the base. For nails, let themgrow for one month then clip every finger and toenail—this represents 9 months of exposure.

Specimens of hair and nails can be stored at 4°C untiltested. Prolonged storage may lead to endogenousfungal growth in some instances. Hair and nails canbe shipped at room temperature.

5.03 ANALYTICAL PROCEDURES

Historically, colorimetric and gravimetric methodshave been used for determining arsenic. However,these methods are either semi-quantitative or lacksensitivity. In recent years, the technique of atomicabsorption spectrometry (AAS) has become themethod of choice due to its selectivity and sensitivityin the detection of arsenic. Thus, AAS may beconsidered as the standard reference method (“goldstandard”) for the evaluation of other test methods.A commonly-used variant of the AAS technique is thehighly sensitive hydride generation atomic absorptionspectrometric method (HGAAS).

For mass screening under field conditions, or in asituation where no laboratory facilities exist, it is oftenpractical to use a reliable test-kit for testing arsenic.A number of such test kits are commercially available.However, the validity of these kits in comparison toother test methods must be established. It is alsorecommended that Member Countries develop policyand guidelines for the selection, import and use of

these kits in consultation with their respectivenational control authorities (NCA).

Before using a test kit, all instructions and materialsafety data sheet must be read and understood.The persons performing the analysis must also betrained in a laboratory which meets nationalstandards and practices standard operatingprocedures. The range and limitations of the kitmust be established. Chemicals such as sulfite andselenium or other impurities can interfere with theperformance of some kits and these must beestablished for each instance.

5.04 QUALITY CONTROL

Testing of arsenic should be undertaken bylaboratories that have been nationally recognized andin which appropriate quality control measures areroutinely performed. Such laboratories shouldincorporate both internal and external quality controlsand follow accepted Standard Operating Procedures(SOP). The person performing the testing must also beappropriately trained in this area. It is advisable fornational authorities to have policy and guidelines onthe introduction and use of SOP in laboratoriesperforming arsenic testing, including the use of kitsand also to maintain a list of laboratories meetingthese standards.

5.05 INTERPRETATION OF LABORATORYRESULTS

WATER: The current WHO guideline value of arsenicin water is 0.01 mg/L (or 10 µg/L also expressed as 10part per billion (ppb). Thus, any sample containingarsenic concentration of greater than 10 µg/litre isconsidered positive. Some countries may havenational standards of arsenic that are 50 µg/litre. Insuch instances arsenic concentration in excess of50 µg/litre is considered positive.

URINE: A urine sample showing more than 50 µg/litremay be taken as evidence of recent exposure providedthe subject has not consumed sea food during theprevious four days.

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HAIR AND NAILS: The value in hair and nails is notknown with certainty. On review of the literature itcan be assumed that arsenic concentration of greaterthan 1 mg/kg of dry hair and arsenic concentrationof more than 1.5 mg/kg of nail may be considered asindicative of exposure to an unsafe dose of arsenicwithin the preceding 11 months.

5.06 LABORATORY NETWORK

In many countries there is a network of laboratoriesthat can perform tests to detect arsenic. Usually,testing of water is the responsibility of the PublicHealth Engineering Department or appropriate waterauthorities of the respective countries. In manycountries, testing can also be done by institutions,universities or private laboratories. However, onlyspecialized laboratories can distinguish the chemicalform or species of arsenic. For a list of reliablelaboratories in your country, consult your nationalauthorities. In countries where such facilities do notexist, it is suggested that specimens be tested in areference laboratory in the Region.

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6.01 BASIC PRINCIPLES FOR MANAGEMENT

Drugs used in the management of arsenicosis shouldbe ideally based on solid evidence generated throughrandomized controlled clinical trials. However, moreoften, recommendations have to be made withoutsuch evidence. In those circumstances it is a mixtureof less than adequate evidence and the consensus ofexperts in the area. The management of arsenicosisfalls into this category.

Management approaches for arsenicosis utilized inthe Region to-date have included the use of manydrugs, agents and nutrients. Therefore, therapies thathave not been validated in arsenicosis throughrandomized double-blinded controlled clinical trials,or have not been part of standard medical treatment,cannot be recommended at this point.

6.02 AVAILABLE MANAGEMENT STRATEGIES

Future studies will inevitably bring about major changesin management. Presently, the management ofarsenicosis focuses on five key approaches:

(1) Cessation of exposure to drinking water orother items with elevated concentration ofarsenic;

(2) Administration of drugs or nutrients directed athastening recovery or averting diseaseprogression;

(3) Provision of non-specific supportive care toimprove physical symptoms or treat selectedcomplications;

(4) Secondary prevention of latent effects throughmedical surveillance, and

(5) Counselling and education to addresspsychosocial sequelae of the illness andprovision of appropriate rehabilitation.

Section 6. Case Management

Table 3CHECKLIST OF SUGGESTED CASEMANAGEMENT FOR SYSTEMICMANIFESTATION OF ARSENICOSIS

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6.02.1 CESSATION OF EXPOSURE TO DRINKINGWATER

As there is no known specific treatment forarsenicosis, the prudent intervention is to stopconsumption of arsenic-contaminated water.Appropriate counselling for safe water options andhealth consequences of consuming arsenic-contaminated water should be supported throughstandard Information, Education and Communication(IEC) strategies. In general, the water supply optionfor an area will depend on the availability, quality anddevelopment potentials of available alternative watersources in a given area. A single option may not besuitable or affordable for people with different socialand economic conditions. Some of the main strategiesfor safe water should include:

(1) Treatment of surface water. Treatment of surfacewater can be an option in areas with perennialsurface water of adequate quantity and good quality.Some of the options include slow sand filters or pondsand filters; pressure filtration followed bydisinfection; small-scale conventional or prototypetreatment plants, and conventional surface watertreatment plants.

(2) Rainwater harvesting. Rainwater harvesting hasgood potential for safe water supply in mostparts where there is rainfall. It can be combinedwith household-based technology withprovision for adequate storage tanks. Thismethod is particularly useful in areas whereadequate quantity and good quality of surfacewater sources are limited.

(3) Deep tubewell. In some areas, deep tubewells canprovide water of acceptable quality. Beforeboring a deep tubewell it is important to ensurethat the deep aquifers are separated from theshallow contaminated aquifers by relativelyimpermeable layers. The quality of the watermust be monitored for arsenic and other heavymetals that pose health risks.

(4) Treatment of arsenic contaminated water. In someareas, the only available option may be to treatthe arsenic contaminated water. A variety of

options are available depending on technologies,cost and acceptability and range from filter unitsfor domestic use, through filter units forcommunity level use to piped supply of arsenictreated-water.

6.02.2 ADMINISTRATION OF NUTRITIONALSUPPLEMENTS

Administration of non-specific nutritionalsupplements or anti-oxidants directed at hasteningrecovery or averting disease progression has beenundertaken in many countries. Some commonly usedanti-oxidants include beta carotene, vitamin E andvitamin C. Presently, there is no large-scalerandomized-controlled double-blinded trial to evaluatethe efficacy of these treatment regimens. Their usedepends on the national policy and therecommendations of the concerned medical bodies inrespective countries.

6.02.3 PROVISION OF NON-SPECIFIC THERAPY

Symptomatic treatment for patients with keratosis orkeratosis and melanosis includes the application ofkeratolytic agents. Presently, 5-10% of salicylic acidand 10-20% of urea-based ointment for the treatmentof keratotic lesions is the most common prevailingpractice, as evidenced by literature review. Higherdoses need further evaluation.

6.02.4 SECONDARY PREVENTION OF LATENTEFFECTS

Secondary prevention of latent effects should be donethrough medical surveillance. The management ofarsenic-associated cancer patients should follow theprevailing national standards and practice for themanagement of cancer patients in general.

6.02.5 COUNSELLING AND EDUCATION

Counselling and education address the psychosocialsequelae of the illness and provide appropriate

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MANAGEMENT of skin and other cancers

MANAGEMENT OF OTHER systemiccomplications listed in Table 3

REHABILITATION services to be provided

RESEARCH on case managementincluding epidemiology, natural historyand therapeutic regimens andinterventions

TRAINING of trainers.

RECORD keeping and reporting

MONITORING of the surveillance system

CONFIRMATION of diagnosis accordingto standard criteria based on the case-classification algorithm

MANAGEMENT of Bowen’s disease andskin cancer. Management of systemicdisorders.

MONITORING of biological and watersamples as needed

REFERRAL of complications

REHABILITATION services to be provided.

RECORD keeping and reporting of cases.

TRAINING and support for primaryhealth care providers

District Hospitals etc.

State Hospitals etc.

HISTORY and physical examinationfor detection of arsenicosis.

TREATMENT of symptoms ofsystemic manifestations listed inTable 3.

COUNSELLING to stop consumptionof arsenic-contaminated water, andprovision of information on arsenic-safe water supplies.

ADVICE on adequate nutrition

PROVISION of supportive care bytopical keratolytic agents for

patients with keratosis. Presently5-10% of salicylic acid and 10-20%of urea based ointment is used.

SURVEILLANCE of arsenicosispatients on a periodic basis

EDUCATION of patients andcommunity: counseling for recogni-tion and management of systemicmanifestation of arsenicosis

FOLLOW-UP of cases and referral tohigher levels as indicated

REHABILITATION services to bearranged

RECORD keeping and reporting.

For instance, PHC etc.

Flowchart 2MANAGEMENT OF ARSENICOSIS CASES AT VARIOUS LEVELS OF HEALTH SERVICES

22

rehabilitation. Programs should be implemented oneducating patients and other community membersabout basic public health aspects of arsenicosis andto dispel misconceptions that may lead tostigmatization, family and occupational disruptionand other social hardsdhip.

6.03 PATIENT MANAGEMENT FLOW CHART

A suggested patient management schedule isillustrated in Flowchart 2. The implementation of thisflowchart will depend on both the guiding nationalpolicy and the existing infrastructure in a particularcountry. The first step, examination of the patient forthe presence of non-cancer arsenic-related skin lesions,may be conducted by trained health care personnelsuch as medical doctors or other skilled health careproviders at the primary care level. These personnelshould receive standardized training in therecognition of characteristic arsenic-related skinlesions. In order to maximize sensitivity of the casedetection process at the primary health care level, thepersonnel are instructed to exercise an inclusive andnon-stringent approach when identifying arsenic-related skin lesions.

Patients who are designated “probable cases” should bereferred for a second evaluation by a dermatologist orother physician with specialized expertise in therecognition and diagnosis of arsenic-related skin lesionsand other abnormal conditions of the skin. Thisevaluation, which should include a complete physicalexamination and a review of the patient’s medical andexposure history, may be conducted at either theprimary or secondary care level. The purpose of thesecondary examination is two-fold:

(a) The criteria outlined in Table 2 and Section 9 shouldbe used to perform a differential diagnosis to eitherconfirm or rule out the presence of skin lesionsconsistent with chronic arsenic exposure;

and

(b) The patient should be evaluated for the presenceof other medical conditions potentially related toarsenic exposure (Table 3). All patients should be

referred, as appropriate, for further evaluation ortreatment of any medical conditions detected by themedical specialist.

If the patient’s clinical presentation is such that themedical specialist cannot confirm or rule out thepresence of characteristic skin lesions, the patientshould retain the diagnosis of “suspected/probablecase”, and be referred for re-evaluation by the medicalspecialist in 6 to 12 months.

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7.01 RATIONALE OF SURVEILLANCE

Surveillance is the routine collection, analysis,interpretation and distribution of data relevant forcontrol and prevention. Two types of surveillancecan be recognized: active and passive. An activesurveillance is solicited by the health agency and thecases are actively sought using a variety of methodssuch as case-search or calling up the health careprovider. A passive surveillance is one which isinitiated by the health care providers and cases areroutinely sent to the health agency. There are threeprerequisites to public health surveillance: (1) anorganized health system, (2) a classification systemof the disease or conditions under surveillance and,(3) measurement techniques.

Each Member Country has a health system. Forsustainability, arsenicosis surveillance should beincluded in the routine reporting format that can begrafted into the disease surveillance system of eachcountry.

The WHO classification provides a broad system forclassifying arsenic cases, and can be accordinglyadapted to the specific needs of a country.

The measurement techniques pertain to the processof surveillance consisting of collecting data forinformation and action. For this purpose, data iscollected, collated, analysed and interpreted. Theresults are then disseminated to facilitate preventionand control measures.

The goals of arsenic surveillance must be defined bythe respective national authorities as these willdepend on the availability of resources andinfrastructure for implementation. Since resource is aconstraint, active search for arsenicosis cases shouldonly be undertaken where the magnitude of theproblem needs to be assessed. Furthermore,arsenicosis is a chronic condition and is not targetedfor eradication. Therefore, passive surveillance orsentinel surveillance from arsenic clinics may besufficient from a public health point of view. The maingoal of arsenicosis surveillance then becomes follow-up and management of cases, especially “probable”cases that cannot be easily classified. Surveillance can

Section 7. Case Surveillance

Figure 2COMPONENTS OF SURVEILLANCE TASKS ATEACH ADMINISTRATIVE LEVEL

Analysis,Feedback

& Response

24

also be used to monitor the effectiveness of anintervention programme such as behaviour change orintroduction of safe water options.

7.02 SUGGESTED FORMAT OF SURVEILLANCE

Clarity of purpose is essential for effectivesurveillance. The following criteria are recommendedfor surveillance:

(1) Clear objectives of the programme;

(2) Specification of the target population undersurveillance;

(3) Realistic programme indicators of surveillance;

(4) Specification of the minimum data set to beused;

(5) Clear guidelines on the tasks and role of eachhealth care provider in the chain of surveillance;and

(6) Enabling tools and guidelines to be used inperforming surveillance tasks.

Each country must decide whether the objective ofthe arsenic surveillance programme is to monitor thetrend of the arsenicosis or to follow up patients forclinical management. These two goals are notmutually exclusive but the associated tasks aredifferent. Depending on the surveillance objectivesone can select the appropriate target population to beeither all subjects at risk for arsenic diseases or onlysubjects at high risk. The indicator for the surveillanceprogramme will also be contingent on the objectivesof the programme. Thus, if all subjects are undersurveillance, then one can express the indicator as thenumber of new cases of arsenic per 100,000population for a given period.

A minimum core data set should be collected. Thedata may consist of who is a case, specified by ageand sex. What type of case is it, classified accordingto the WHO algorithm of suspected, probable,clinically confirmed, clinically and laboratory

confirmed or unclassified. Where is the case located,based on the geographical location. How is the case,depending on whether it is alive, dead, or has othermajor complications.

The surveillance tasks must be defined for eachadministrative level of the health service. Figure 2shows the surveillance tasks for each level of thehealth care delivery. Thus, at the peripheral levels ofhealth care, the focus should be to detect “suspected”and “probable” cases as well as to report and providesymptomatic treatment of systemic infections.Therefore, surveillance information may be kept caseby case at the primary level.

At the intermediate, administrative level of healthcare, the focus would be to clinically confirm all“suspected” and “probable” cases as well as to provideclinical management of Bowen’s disease and systemicdisorders. The surveillance data must be analysed tomonitor trends and provide feedback to the primarylevels for programme implementation. The data maybe kept in an aggregate form at this level.

At the central level, the focus should be on confirmingall categories of cases and monitoring the overallperformance and trends of the surveillance system bythe use of graphs, maps, charts and trends. The datashould be kept in aggregate form at this level andreporting should include submission of periodicreports to WHO and other relevant agencies.

Each Member Country should formulate appropriatetools, guidelines and protocols for reporting cases.This will allow data flow from the primary to thetertiary level and specify how frequently the data willbe reported and in what formats (electronic, paper, ortelephone). The data will flow from one administrativelevel to another. Case detection to be used must beclearly specified. It is recommended that detection andreporting of cases be implemented using the WHOhierarchical case classification system as discussed inSection 4 of this module and the flowchart shown onpage 12-13 (Gatefold).

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DIFFUSED ARSENICAL MELANOSIS

Chest

DIFFUSED ARSENICAL MELANOSISHands

NON-ARSENICAL DIFFUSED MELANOSISActinic Dermatosis is confined to exposed part of the body

NON-ARSENICAL DIFFUSED MELANOSISMelasma is usually confined to face to person with hormonaldysfunction

NON-ARSENICAL DIFFUSED MELANOSISAshy Dermatosis is confined to the face and trunk

NON-ARSENICAL DIFFUSED MELANOSISIcthyosis is confined to the back

Section 8. Illustrations of Skin ManifestationsDIFFUSED MELANOSIS

Nearly all arsenicosis patient first show diffused melanosis that gradually appears over the palms, soles, face and skin. Thiscondition has to be distinguished from melanosis of genetic or environmental origin, for further details see Table 2 and section 9.

26

ARSENICAL-LEUKOMELANOSISChest

ARSENICAL-LEUKOMELANOSISPalm

NON-ARSENICAL-LEUKOMELANOSISIdiopathic guttate hypomelanosis is characterized by discrete,slightly depressed macules of white porcelain color

ARSENICAL-LEUKOMELANOSISThigh

NON-ARSENICAL-LEUKOMELANOSISPityriasis versicolor of the back is characterized by hypopigmentedmacules with fine scales

NON-ARSENICAL-LEUKOMELANOSISXeroderma pigmentosa is characterized by freckling and atropicdepigmentation

LEUCO-MELANOSIS

Some arsenicosis patients show Leukomelanosis appearing as “rain-drops”, usually consisting of a mixture of pigmented darkcells and white, de-pigmented cells that occur in the chest, backs and legs. Arsenical Leukomelanosis has to be distinguishedfrom leuko-melanosis of genetic or environmental origin, for further details see Table 2 and section 9.

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SPOTTED ARSENICAL MELANOSISRain-drop pigmentation chest

NON-ARSENICAL SPOTTED MELANOSISPityriasis versicolor is charcterized by hyper-pigmented papules

NON-ARSENICAL SPOTTED MELANOSISLichen amyloidosis is characterized by angular melanosis ofthe trunks

SPOTTED ARSENICAL MELANOSISRain-drop pigmentation legs

NON-ARSENICAL SPOTTED MELANOSISLichen planus is characterized by violaceous pigmentation

NON-ARSENICAL SPOTTED MELANOSISFreckles is characterized by mottled pigmentation

SPOTTED MELANOSIS

Many arsenicosis patients show spotted melanosis that appears mainly on the chest, backs and thigh. This conditionhas to be distinguished from other types of spotted melanosis of genetic or environmental origin, for further details seeTable 2 and section 9.

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DIFFUSED KERATOSIS

Arsenical diffused keratosis are hyperkeratotic lesions that have diffused in all parts of the sole and palms giving a grittyfeeling to the touch and have to be distinguished from other non-arsenical keratosis of genetic or environmental origin, forfurther details see Table 2 and section 9.

DIFFUSED ARSENICAL KERATOSISHands

NON-ARSENICAL DIFFUSED KERATOSISPsoriasis is characterized by kerato-derma giving scaly patches(hand)

NON-ARSENICAL DIFFUSED KERATOSISPsoriasis is charcterized by kerato-derma giving scaly patches(back)

NON-ARSENICAL DIFFUSED KERATOSISEczema is characterized by oozing lichenified lesions

NON-ARSENICAL DIFFUSED KERATOSISPitted Keratolysis is characterized by pitted or depressed lesions

NON-ARSENICAL DIFFUSED KERATOSISTinea Pedis is characterized by scaly, fissured, keratotic lesions

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ARSENICAL NODULAR KERATOSISHand

NON-ARSENICAL NODULAR KERATOSISVerruca vulgaris appears as verrucous papules (hands)

NON-ARSENICAL NODULAR KERATOSISCallus are corns occuring at sites of friction

ARSENICAL NODULAR KERATOSIS (WITH MELANOSIS)Feet

NON-ARSENICAL NODULAR KERATOSISVerruca vulgaris appears as verrucous papules (feet)

NON-ARSENICAL NODULAR KERATOSISOccupational keratosis, showing lesions at sites of friction

NODULAR KERATOSIS

Many arsenicosis patients show hyperkeratotic, pin-headed lesions that occur as localized lesions in parts of the palms andsoles. This condition has to be distinguished from other non-arsenical nodular keratosis of genetic or environmental origin, forfurther details see Table 2 and section 9.

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BOWENS DISEASEBowens disease occur as multiple-crusted, erythematouspapules and plaques (back)

NON-BOWEN DISEASEIn psoriasis, the lesions are sharply demarcated with silvery scales

NON-BOWENS DISEASELichen planus of legs showing violaceous papules (thighs)

NON-BOWEN DISEASELichen planus of hands showing flat-topped violaceous papules

NON-BOWEN DISEASEIn Superficial Actinic Prokeratosis, the lesions are ill defined andreddish brown in color

SQUAMOUS CELL CARCINOMASquamous cell carcinoma is characterized by crusted plaques withill-defined borders

PRE-MALIGNANT AND MALIGNANT CUTANEOUS CONDITIONS

Pre-malignant and malignant cutaneous conditions associated with arsenic exposure have to be distinguished from othersimilar conditions.

31

Brown patches typically on the malar prominencesof face and forehead. The pigmented patches aresharply demarcated. Mainly in women, particularlyin pregnancy, on birth control pills or with ovariandysfunction.

Post inflammatory hyper-pigmentation inindividuals with past history of taking an offendingdrug. The sites and morphology of the lesions varyaccording to the responsible drug. Commonly,pigmentation occurs on sun-exposed areas of skin,and also on mucous membranes, particularly thegingiva and hard palate. The pigmentation variesfrom blue black, muddy brown, pink, brown, orslate-grey colour depending on the drugs used.There may be changes on the nails. Pigmentationusually fades away after withdrawal of the drug.

Darkening of sun-exposed areas of the skinfollowing exposure to sunlight. The increasedpigmentation occurs over hours to days, and fadesgradually over the course of days to weeks whenUV exposure is discontinued.

Genetic disorder, found mostly in children.Characterized by intensive freckling, with atrophicdepigmented skin changes, photophobia and kerato-conjunctivitis, leading to blindness. A positivefamily history is of diagnostic value.

i) Lesions run in familiesii) Lesions are either spotted, freckle-like

melanosis or symmetrical diffuse melanosisiii) Predominantly involve extremitiesiv) May also involve trunk.

Hyper and hypo-pigmented macules with fine scalesand raised margins, usually on trunk, proximalextremities, face, and neck. The scales are dusk-likeor furfuracious. May be exacerbated by sunlight.Wood’s lamp examination is helpful for diagnosis,showing yellowish fluorescence. Skin scrapingsobtained for microscopy and mycological culturereveal fungal elements.

Porcelain-white macules with distinct margins maybe slightly depressed without any obvious cause.

i) Disease of adolescents and young adultsii) Starts as non-pruritic erythematous papules,

becomes covered with pigmented scales

Patchy pigmentation in arsenicosis isuncommon on the face, and does not varywith pregnancy.

Hyper-pigmentation in arsenicosis is notlocalized or concentrated in sun-exposedareas, and rarely involves the mucousmembranes. Presence of keratosis inArsenicosis.

Hyper-pigmentation in arsenicosis is notlocalized or concentrated in sun-exposedareas, and does not increase or decreasewith changes in the intensity of UVexposure.

Arsenicosis is not associated with ocularsigns or symptoms, except in earlytransient conjunctival injection.

Arsenicosis does not run in generationsand is associated with keratosis.

Pigmented macules in arsenicosis are notraised, and do not vary with sunlight.Fungal elements are absent.

Pigmented macules are not depressed inarsenicosis. No keratosis or melanosis ispresent in Idiopathic guttatehypomelanosis.

Scales are distinctive and absent inarsenicosis; there is no keratosis inPityriasis lichenoides chronica.

Melasma

Drug-induced

UV inducedPigmentation/Actinic dermatosis

Xerodermapigmentosum

Familial progressivedyschromatosis

Pityriasis versicolor

Idiopathic guttatehypomelanosis

Pityriasis lichenoideschronica

DISEASE ASSOCIATED WITHPIGMENTARY CHANGES

MAIN CUTANEOUS MANIFESTATIONS KEY FEATURES THAT DISTINGUISHTHE CONDITION FROM ARSENICOSIS

Section 9. Further Discussions onDifferential Diagnosis

32

DISEASE ASSOCIATED WITHPIGMENTARY CHANGES

MAIN CUTANEOUS MANIFESTATIONS KEY FEATURES THAT DISTINGUISHTHE CONDITION FROM ARSENICOSIS

DISEASE ASSOCIATED WITHKERATOTIC CHANGES

MAIN CUTANEOUS MANIFESTATIONS KEY FEATURES THAT DISTINGUISHTHE CONDITION FROM ARSENICOSIS

i) Pigmented keratotic lesions found mostly onphoto exposed areas. Covered site may also beinvolved

ii) Asymptomatic in natureiii) Stuck on skin surfaceiv) Old age group commonly involved.

Dominantly inherited disorder presenting withmarked congenital thickening of the palms andsoles, usually symmetrical and diffuse. There isfrequently hyper-hydrosis and occasional nailthickening.

a) Hypo-pigmented macular lesions interspersedbetween keratotic lesions, asymptomatic.

b) Keratotic papular lesion mainly in trunk sparingpalm, sole, asymptomatic.

Transform into:a) Cutaneous hornb) Bowen’s diseasec) Squamous cell Ca

Usually, but not always associated with history ofcontact with household or occupational allergen.Manifested by papulo-vesicular, oozy, crustedlesions in acute stage, progressing to lichenified,thickened, scaly lesions in chronic stages. Pruritusis common. Withdrawal of allergen may beassociated with remission.

In arsenicosis there is presence ofspeckled, diffuse or leuco-melanosisand keratosis of palm and sole.

Arsenical keratosis is not a congenitalcondition, but appears gradually over aperiod of years to decades.

Arsenical keratoses do not sparekeratosis of palm and sole.

Arsenical keratosis occurspredominantly on palms and soles, andlacks an acute, papulo-vesicular stage.Pruritus is not a common feature.

Seborrheic keratosis

Hereditary Palmo-plantarhyperkeratosis

Epidermodysplasiaveruciformis

Eczema

Pityriasis lichenoideschronica (contd.)

Leprosy

iii) Scales are lid-likeiv) Lesions resolute with hypo-pigmented

macular lesions (like pityriasis versicolor)v) Trunk and extremities are common sites of

involvementvi) Recalcitrant in nature.

Macular hypo-pigmented or erythematous lesions,usually with loss of sensation. There may beinvolvement of peripheral nerves which are usuallythickened and enlarged.In advanced stage there may be muscle atrophyand deformities. Slit skin smear and skin biopsywill confirm the diagnosis.

Dermatological lesions of arsenicosisare rare on the face, and are notassociated with atrophy or deformityand loss of sensation.

33

Usually occurs on the dorsal surface of hands andfeet, particularly on the periungual region. Causedby a human papillomavirus, trimming the papularrough surface keratin makes the capillaries moreprominent and visible, which may help in diagnosis.Spontaneous resolution may occur.

i) Generally localized lesion, sometimes may belinear or involve scalp

ii) Lesions are papules, mostly on extremities andfollicular in nature

iii) Heals with pigmentation, atrophy or loss ofhair.

Keratotic thickening that occurs on pressure pointsin hands and feet. May be painful to palpation.

Related with nature of occupation. Occurs on palmand sole on areas that come in contact withoccupational tools, usually sparing the mid portion.

Maceration, scaling, thickening and fissuring, usuallyin front part of the soles and intertriginous regions.Pruritus is a prominent feature. Fungal elementsmay be detectable on microscopy or mycologicalculture.

Discrete, erythematous, dry scaly papulo pustularlesions or plaque type lesions, usually on the middleportion of palm and sole with or without itching.Typical silvery white scaly patches may be presentelsewhere on the skin. Nails are also affected withpitting, subungual hyperkeratosis or onycholysis.Characterized by relapse and remission.

Characterized by symmetrical and diffuse spikypapular eruptions on extensor surface of skinparticularly on elbows, knees and hands (Nutmeggrater). Frequently leads to exfoliative dermatitis.Hyperkeratosis in palms and sole is remarkable. Onsole hyperkeratosis extends up the sides called“Sandal”. There may also be nail changes.

i) Diffuse keratosisii) Sieve-shaped depressed lesion, exclusively on

the solesiii) Found in barefooted persons with excessive

water users.

i) Solitary or multiple discrete papulonodularlesion with rough or verrucous surface

ii) Generally unilateraliii) Multiple black dots at the centreiv) Bleeds on cutting / paring

Arsenical keratosis occurs as multiple ordiffuse lesions, predominantly on palmsand soles. Lesions are pinpoint in earlystages, but may form wart-like nodulesin advanced cases.

Absence of keratotic follicular lesions inarsenicosis.

Arsenical keratosis of palms and soles isnot confined to pressure points.

Arsenic keratoses are distributed evenly.

Arsenical keratosis is not prominent inintertriginous areas, and is usuallywithout prominent pruritus.

Arsenical keratosis is withouterythematous or papulo pustularfeatures.

Arsenical keratosis occurspredominantly on the palms and soles,and lacks exfoliate features.

In arsenicosis the keratotic soles are notpitted, and there will be associated withskin pigmentation.

Verruca (warts)

Lichen Planus

Corns and calluses

Occupationalkeratosis

Tinea pedis and othermycoses

Psoriasis

Pityriasis rubrapilaris

Candidialhyperkeratosis/pittedkeratolysis

DISEASE ASSOCIATED WITHKERATOTIC CHANGES

MAIN CUTANEOUS MANIFESTATIONS KEY FEATURES THAT DISTINGUISHTHE CONDITION FROM ARSENICOSIS

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The accompanying flowchart illustrates the processand fundamental approaches that were used indeveloping this Field guide on the basis of the bestavailable evidence.

Starting in 2000, the literature was extensivelyreviewed for all explicit and implicit case definitionsand patient management strategies used so far andthe most commonly occurring features were selected.These were used as the basis to formulate a workingcase definition and management protocol. At least 33different published studies from around the worldwere used.

In 2002, Member Countries were supported to developnational case definition and management protocols.For this purpose, meetings of national expertcommittees consisting of dermatologists, oncologists,internists, toxicologists and epidemiologists wereconvened to arrive at a consensus.

In 2003, these national expert committees met in theRegional Office to reach a regional consensus basedon the respective national protocols. The consensusversion was field-tested in high and low prevalenceareas. A committee of regional experts examined theresults of the validation and prepared the presentversion of the protocol.

In 2004, this module was officially launched inComilla, Bangladesh.

Appendix A: Working Methods Adopted forFormulation of the Field Guide

Figure 3SUMMARY OF WORKING METHODS

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CASE DEFINITION

Dr SK Akhtar Ahmad, Associate Professor, Departmentof Occupational and Environmental Health, NIPSOM,Mohakhali, Dhaka, Bangladesh

Dr Farzana Begum, Project Officer, Dhaka CommunityHospital, 190/1, Boromoghbazar, Wireless Railgate,Dhaka-1217, Bangladesh

Dr Deoraj Caussy, Regional Epidemiologist, Departmentof Evidence and Information for Policy, RegionalOffice for South-East Asia, World HealthOrganization, I.P. Estate, Ring Road, New Delhi, India

Dr Virasakdi Chongsuvivatwong, Epidemiology Unit,Faculty of Medicine, Prince Songkla University, HatYai, Thailand

Dr Anton Fric, Medical Officer, Office of the WHORepresentative, Nepal, Kathmandu

Dr Alakendu Ghosh, Associate Professor, Department ofMedicine, Institute of Post Graduate MedicalEducation and Research, Kolkata-700020, India

Dr Myint Myint Gyi, Lecturer/Head, Department ofDermatology, Yangon General Hospital, Yangon,Myanmar

Prof. AZM Maidul Islam, Professor and Chairman,Department of Dermatology, Bangabandhu SheikhMujib Medical University, Dhaka, Bangladesh

Dr Saima Khan, Assistant Project Officer, Arsenic Healthand Nutrition Section, United Nations Children’sFund, GPO Box 58, Dhaka, Bangladesh

Dr Peera Kongthong, Director, Ronpiboon Hospital,Nakon Si Thammarat Province, Thailand

Dr Keshar Man Malla, Dermatologist, BhaktapurHospital, Bhaktapur, Nepal

Dr D N Guha Mazumder, Professor of Medicine andGastroenterology (Retired), Institute of Post Graduate

Medical Education and Research, Kolkata, India

Dr Thada Piamphongsant, Senior Consultant, Institute ofDermatology, Department of Medical Services,Ministry of Public Health, Nonthaburi, Thailand

Dr Md Siddiqur Rahman, Deputy Programme Manager(Arsenic), Directorate General of Health Services,Mohakhali, Dhaka, Bangladesh

Dr Sujit Ranjan Sengupta, Professor, Department ofDermatology, Institute of Post Graduate MedicalEducation and Research, Kolkata-700 020, India

Dr Siriluk Thaicharoen, Director of Leprosy Unit -Dermatologist, Department of Disease ControlRegion II, Nakorn Si Thammarat Province,Thailand

CASE VALIDATION

Dr H Firdaus Adam, Chief of Section of Data Analysisand Dissemination, Directorate General, CD & CEH,Ministry of Health, Jakarta, Indonesia

Dr Ugen Dophu, Deputy Medical Superintendent, JigmeDorji Wangchuck National Referral Hospital,Thimphu, Bhutan

Dr Anton Fric, Medical Officer, Office of the WHORepresentative, Nepal, Kathmandu

Dr A K Harit, Chief Medical Officer, National Institute ofCommunicable Diseases, 22 Sham Nath Marg, NewDelhi, India

Dr Rachel Kaufmann, Senior Public Health Specialist,World Bank Liaison for Environmental Health, MSNMC11-1108, 1818 H Street, Washington DC 20433USA

Dr Saima Khan, Assistant Project Officer, Arsenic Healthand Nutrition Section, United Nations Children’sFund, GPO Box 58, Dhaka, Bangladesh

Dr D N Guha Mazumder, Professor of Medicine and

Appendix B: Members of Expert Committees

List of members of Expert Committees that contributed to the formulation of this Field Guide

36

Gastroenterology (Retired), Institute of Post GraduateMedical Education and Research, Kolkata, India

Prof Mir Misbahuddin, Head, Department of Toxicology,Bangabandhu Sheikh Mujib Medical University,Dhaka, Bangladesh

Dr. D.K Raut, Professor and Head of Department ofEpidemiology, All India Institute of Hygiene andPublic Heath, Kolkata-700-073, India

Dr Sabai Nyi, Research Officer, Department of MedicalResearch, No 5, PO Dagon, Ziwaka Road, Yangon,Myanmar

Dr Soe Tint, Assistant Director, Occupational Health,Department of Health, Ministry of Health, Yangon,Myanmar

CASE SURVEILLANCE

Dr Kusum Adhikary, United Nations Children’s Fund,219/2, A.J.C. Bose Road, Kolkata-700017, India

Dr Deoraj Caussy, Regional Epidemiologist, Department ofEvidence and Information for Policy, Regional Office forSouth-East Asia, World Health Organization, I.P. Estate,Ring Road, New Delhi, India

Dr Ranjit Kumar Dey, Director, Planning, Research andEnvironmental Health, Directorate General of HealthServices, Mohakhali, Dhaka, Bangladesh

Dr R.S. Dhaliwal, Assistant Director, Indian Council ofMedical Research, Ansari Nagar, New Delhi-110 029,India

Dr Manen Prashad Gorkhali, Health Consultant,Environment and Public Health Organization, POBox 4102, New Baneshwar, Kathmandu, Nepal

Dr A K Harit, Chief Medical Officer, National Institute ofCommunicable Diseases, 22 Sham Nath Marg, NewDelhi, India

Dr Shamsul Huda, Environmental Health Adviser, Officeof the WHO Representative, Kathmandu, Nepal

Dr Saima Khan, Assistant Project Officer, Arsenic Healthand Nutrition Section, United Nations Children’sFund, GPO Box 58, Dhaka, Bangladesh

Dr Kunal Kanti Majumdar, Consultant, ArsenicMitigation Programmeme, UNICEF, 219/2, AJC BoseRoad, Kolkata-700017, India

Dr Thada Piamphongsant, Senior Consultant, Institute ofDermatology, Department of Medical Services,Ministry of Public Health, Nonthaburi, Thailand

Dr Wilaiwan Puttapruk, Academic of Public Health,Ronpiboon Hospital, Nakon Si Thammarat Province,Thailand

Dr Kamjad Ramakul, Director, Bureau of Occupationaland Environmental Diseases, Department of Health,Ministry of Public Health, Nonthaburi, Thailand

Dr D K Raut, Professor and Head of Department ofPublic Health, All India Institute of Hygiene andPublic Health Kolkata 700-073, India

Dr S K Saha, Joint Director of Health Services (PH & CD),Directorate of Health Services, Government of WestBengal, Writer’s Building, Kolkata, India

Dr Kokila Devi Shrestha, Chief of Epidemiology,Department of Health Services, Epidemiology andDisease Control Division, Ministry of Public Health,Kathmandu, Nepal

Dr Anchalee Siripitayakunkit, Disease Control Officer,Bureau of Epidemiology, Department of DiseaseControl, Ministry of Public Health, Nonthaburi,Thailand

Dr Phanompun Siriwatananukul, Deputy Director,Bureau of Occupational and Environmental Diseases,Department of Disease Control, Nonthaburi-11000,Thailand

37

Dr Khin Myat Tun, Applied Medical Research Division,Department of Medical Research (Lower Myanmar),Myanmar

Mrs Sutida U-tapan, Health Technical Officer, Bureau ofOccupational and Environmental Diseases,Nonthaburi-11000, Thailand

Dr Pranay Kumar Upadhyay, Senior Public HealthAdministrator, Department of Health Services,Ministry of Health, Kathmandu, Nepal

CASE MANAGEMENT

Dr Shah Mohammad Keramat Ali, Professor, ClinicalNutrition, Institute of Nutrition and Food Science,University of Dhaka, Dhaka, Bangladesh

Dr Deoraj Caussy, Regional Epidemiologist, Department ofEvidence and Information for Policy, Regional Office forSouth-East Asia, World Health Organization, I.P. Estate,Ring Road, New Delhi, India

Prof. A.Z.M. Maidul Islam, Professor and Chairman,Department of Dermatology, Bangabandhu SheikhMujib Medical University, Dhaka, Bangladesh

Dr Salamat Khandker, Medical Officer, DPHE Bhaban,Fourth Floor, Shaheed Capt. Monsur Ali Sarani,Dhaka-1000, Bangladesh

Dr Md Abdur Rahman Khan, Director (Planning),Directorate General of Health Services, Mohakhali,Dhaka, Bangladesh

Dr Kunal Kanti Majumdar, Consultant, ArsenicMitigation Programmeme, UNICEF, 219/2, AJC BoseRoad, Kolkata-700017, India

Prof Mir Misbahuddin, Head, Department of Toxicology,Bangabandhu Sheikh Mujib Medical University,Dhaka, Bangladesh

Dr Mahmuder Rahman, Principal and Professor ofMedicine, Dhaka National Medical College and

Hospital, Magbazar, Waiken Rail Gali, Dhaka,Bangladesh

Prof. Mahmudur Rahman, Director, National Institute ofPreventive and Social Medicine (NIPSOM), Dhaka,Bangladesh

Dr KC Saha, Ex Professor of Dermatology, Calcutta Schoolof Tropical Medicine, Kolkata, India

Dr M.H. Salim Ullah Sayed, Assistant Professor,Department of Occupational and EnvironmentalHealth, NIPSOM, Mohakhali, Dhaka-1212,Bangladesh

Dr Sujit Ranjan Sengupta, Professor, Institute of PostGraduate Medical Education and Research, Kolkata,India

Dr Cherian Varghese, National Professional Officer, Officeof the WHO Representative to India, New Delhi,India

Dr Krisantha Weerasuriya, Regional Adviser, EssentialDrugs and Medicines Policy, Department of Familyand Community Health, Regional Office for South-East Asia, World Health Organization, New Delhi,India

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1. Agency For Toxic Substance and Disease Registry(ARSDR), Toxocological Profile for Arsenic: USDepartment of Health and Human Services, 1998

2. Bangladesh Medical Association: (Akram-HussainS editor) Easy Diagnosis and Management ofArsenicosis, 2004

3. Caussy, D., Normative Role of WHO in MitigatingHealth Impacts of Chronic Arsenic Exposure in theSouth-East Asia Region 2003. pp 439-447 In Arsenicand Health Effects V, Editor Chappell WR,Abernathy CO and Thomas DJ. Elsevier Science Ltd,New York

4. Caussy, D., Gochfeld, M., Gurzau, E., Neagu, C.,Ruedel, H., 2003. Lessons from Case Studies ofMetals: investigating exposure, bioavailability, andrisk. Ecotoxicology and Environmental Safety. 56(2003), 45-51.

5. Caussy, D., Case Study of the Impact of Under-standing Bioavailability: Arsenic. Ecotoxicology andEnvironmental Safety. 56 (2003), 164-173.

6. Dinman B D, Arsenic, Chronic Human Intoxication,March 1960. Journal of Occupational Medicine.2: 137-142.

7. Guha Mazumder DN, Criteria for Case Definition ofArsenicosis, 2003. pp117-133. In Arsenic and HealthEffects V, Editor Chappell WR, Abernathy CO andThomas DJ. Elsevier Science Ltd., New York.

8. Kosnett M and Kreiss K, Case Studies inEnvironmental Medicine: Arsenic Toxicity. AgencyFor Toxic Substance and Disease Registry (ATSDR).Toxocological Profile for Arsenic: US Department ofHealth and Human Services, 1990

9. National Research Council (NRC), NationalAcademy Press, Washington DC, Arsenic in DrinkingWater, 2000.

10. Saha KC, Arsenicosis in West Bengal, 2002.Sandanada Prakashani Publisher, Kolkata, India.

Appendix C: Key References

11. Rashid HA, Research Studies on Health Impact ofArsenic Exposure, 2002. Bangladesh MedicalResearch Council, Dhaka, Bangladesh.

12. Rossman TG, Arsenic in Environmental andOccupational Medicine, Third edition, edited byWilliam N. Rom. Lippincott-Raven Publishers,Philadelphia, 1998

13. Sams MW and Lynch PJ (editors) In Principles andPractice of Dermatology, second edition 1996,Churchill Livingstone, New York.

14. World Health Organization, Arsenic and ArsenicCompounds (second edition). Geneva; InternationalProgramme on Chemical Safety, EnvironmentalHealth Criteria, P 224, 2001.

15. World Health Organization, Regional Office forSouth-East Asia (SEARO), Report of a RegionalConsultation on Arsenic Contamination andrecommendations for action, 1997, New Delhi,India.

16. World Health Organization Regional Office forSouth-East Asia (SEARO), Report of a RegionalConsultation on Arsenicosis Case-Detection,Management and Surveillance 2002, New Delhi,India.

17. World Health Organization, Regional Office forSouth-East Asia (SEARO), Report of an Inter-countryWorkshop on Development of Regional Policy andGuidelines for Arsenic Testing, 2003, Kolkata, India.

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