137: International Perspectives on Medical Toxicology

Poisoning is a worldwide problem, but the major effects are felt in the developing world. At least 250,000 to 350,000 people die every year from acute pesticide poisoning,⁷² and an estimated 20,000 to 94,000 humans die each year from snake bites,⁹⁷ the vast majority of whom lives in rural farming areas of lower and middle income countries. Hundreds of thousands of people are affected by groundwater arsenic contamination in Bangladesh and India,¹⁴⁹ and outbreaks of poisoning from contaminated food⁴⁰ and environmental pollution from poorly regulated industrial activity^49,135 affect whole communities throughout the developing world.

The resources for dealing with these problems are limited in many countries. Public health education about poisons and infrastructure limiting access and exposure to the most highly toxic chemicals are practically absent in much of the developing world. Access to medical care is often limited for financial, cultural, and geographic reasons. Medical toxicology is frequently not a recognized specialty and patients are evaluated by general physicians with little training—although often with great experience. Diagnostic facilities are few, effective treatment options even more rare. Where antidotes exist, there is rarely enough knowledge or experience to use them effectively.³⁰ Intensive care beds for invasive monitoring and long-term ventilation are scarce. This chapter outlines some of the major poisoning risks and challenges for medical toxicology in the developing world.

The World Health Organization (WHO) has ranked injury, including poisoning, among the top 15 causes of death worldwide for persons aged 5 to 44 years.^114,174 Recent reanalysis of data from the Global Burden of Disease project estimated that acute and chronic exposure to chemicals caused over 4.9 million deaths and 86 million disability-adjusted life years (DALYs) worldwide in 2004—more than cancer, sexually transmitted diseases, or diabetes.^135,179 Children younger than 15 years of age bore more than one half of this burden.

Tremendous regional disparities in the health impact of poisoning are apparent. The global mortality burden from poisoning is disproportionately shouldered by lower and middle income countries. Overall, as much as 75% or more of all poisoning related deaths occur in the developing world,⁸¹ and an estimated 95% of children who die each year from acute poisoning live in low- and middle-income countries.¹⁷⁴ Children living in Sub-Saharan Africa are at highest risk, with an estimated annual mortality rate of four children per 100,000 population. This is double the global average and higher than that in any other region.¹⁴²

These figures are striking, yet most likely underestimate the contribution of poisoning to the global burden of disease and disability. Much of the existing data on poisoning epidemiology from lower income countries reflects the experience in larger hospital centers. By contrast, most of the population lives in rural areas, and many patients with poisoning may never reach such facilities for a variety of financial, cultural, or geographic reasons. For example, logistical difficulty with accessing health care facilities was responsible in part for the high mortality from snakebite noted in one community-based study in Nepal.¹⁴⁶ Social or economic barriers often contribute to “healer shopping” within traditional or spiritual systems, with allopathic medical care delayed or avoided in many African countries.^52,86,128

Unintentional poisoning risks from occupational, environmental, food, or medication sources may also be poorly recognized in commu­nities, or by health care workers.¹²³ The diagnosis of poisoning may not be suspected if a clear history of exposure is not given, because symptoms can mimic infectious or other processes and few medical centers have ready access to laboratory tests for specific poisons. When poisoning is suspect, many countries lack detailed injury surveillance systems or other standardized reporting mechanisms. The WHO has undertaken several initiatives to improve global poisoning surveillance, including support for poison center (PC) development in under represented regions worldwide, and the international efforts of the IPCS/INTOX programs to harmonize data collection and reporting terminology represent an important step toward this goal. However, the interpretation of PC data as evidence of epidemiologic trends must be approached with some caution (Chap. 136).

Agents commonly involved in acute poisoning differ substantially between communities, both within and among countries. For example, a comparison of poisoning cases seen at a major public teaching hospital in New York City with two large rural hospitals in Sri Lanka found striking differences in the classes of xenobiotics involved. A total of 70% of the patients in New York City were poisoned with pharmaceuticals, and 90% of patients in the Sri Lankan cohort were poisoned with nonpharmaceuticals, primarily pesticides and botanicals, such as yellow oleander, with a 10 times higher case fatality rate.⁸¹ A study comparing poisoning epidemiology in district (rural) and regional (urban) hospitals in Zimbabwe found that poisoning from pesticides was equally common in both settings, but animal envenomation was seen nearly twice as often at the district facilities compared to regional centers, and poisoning with pharmaceuticals was a problem seen uniquely at the regional hospital.¹⁵⁶

Understanding the local patterns and specific risks for poisoning in particular communities is of critical importance since it provides an evidence base for designing and prioritizing strategies to prevent or limit harm. This section reviews some of the more common xenobiotics implicated in poisoning in developing countries worldwide.

Pesticides

A systematic review suggested that at least 250,000—but more likely 350,000—deaths occur each year from acute pesticide self-poisoning around the world.⁷² The WHO now considers pesticide poisoning to be the single most important means of suicide, accounting for more than one-third of all suicides worldwide.²⁵ Most of these deaths occur in Asia, particularly in China and India.⁷² The annual number of deaths from occupational or unintentional pesticide poisoning is unknown but was estimated 20 years ago at 20,000.⁹⁰

While many classes of pesticides are implicated (Chap. 113), organic phosphorous (OP) pesticides appear to be responsible for the majority of pesticide-related deaths in the developing world.⁵⁶ Deliberate self-poisoning with OP pesticides puts a high cost on the health care system. In one study examining the experience in Sri Lanka, OP pesticide poisoning was responsible for 943 of 2559 (36%) admissions to a secondary hospital for poisoning.⁶⁰ The case fatality for OP poisoning was 21%, and pesticide poisoned patients occupied 41% of all medical intensive care beds. Similar situations have been reported from across the world.⁵⁶ In all likelihood, such studies underestimate the mortality associated with intentional pesticide ingestion as most are hospital based and do not include patients who die prior to hospital presentation.²

Factors contributing to the high mortality of self-poisoning with pesticides in the developing world include the intrinsic lethality of many pesticides, and health care systems that are poorly prepared to handle such critically ill patients (Table 137–1). Pesticides are often easily available in highly concentrated preparations in rural communities throughout the developing world. The ease of drinking liquid pesticides is also a factor facilitating massive intentional ingestions, as are inadequate pesticide storage systems.⁹⁹ Outbreaks of unintentional poisoning from contaminated flour or old pesticide containers used to store food still occur in rural areas.⁵⁴ The extraordinarily high human, economic, and social costs of pesticide-related mortality worldwide reinforce the importance of developing simple, economical, and evidence based strategies specifically designed to care for acutely poisoned patients in resource limited environments.^26,32

Envenomation

Envenomation by snakes and other animals represents another significant cause of morbidity and mortality in the developing world. Few countries mandate the reporting of animal bites, making it difficult to estimate global incidence, severity, and outcome. Current data estimates that about 20,000 to 94,000 deaths occur globally each year from snakebite.⁹⁷ The vast majority of deaths and serious envenomations occur in the developing world, with less than 100 snakebite deaths per year estimated to occur in Europe, the United States, Canada, and Australia combined.^42,97

Because most rural people in the developing world may first consult traditional healers, hospital based studies of mortality and morbidity associated with snakebites likely underestimate the scope of the problem.^42,150 For example, a study of rural Philippine rice farmers found that only 8% of cobra (Naja philippinensis) bite victims reached a hospital in the 1980s.¹⁷⁰ However, changes in treatment seeking can occur. Studies over the last decade in Sri Lanka have shown that patients have started going to the hospital rapidly after common krait (Bungarus caeruleus) snakebite, bypassing traditional healers.¹⁰³ A study in Ghana found that the incidence of snakebite victims at a district hospital increased significantly after the introduction of a new treatment protocol, possibly reflecting increased confidence in the ability of the health care system to manage these cases.¹⁶⁸

Snakebites are most commonly occupational hazards in the rural tropics. Victims are just as likely to be women as men, reflecting rural farming practices. Working in large plantations and subsistence farms places rural people in frequent contact with venomous snakes. With simultaneous changes in global climate and expansion of human settlements, it is likely that the range of venomous snakes will enlarge to include urban areas and regions previously considered too temperate to support them.^82,121 Snakebites from members of the Elapidae and Viperidae families are responsible for the majority of deaths worldwide, although several other families are also medically important (Colubridae and Atractaspididae species, in particular; Chap. 122 and Special Considerations: SC8).^169,172

The burden of snake envenomation on local resources can be substantial. During the rainy season in Benin, snakebites account for up to 20% of all hospital admissions, with an estimated case fatality rate of 3% to 6%.⁴³ In this region, the annual incidence of snake envenomation ranges from 200 to 100,000 in rural villagers to 1300 to 100,000 in sugar cane plantation workers.⁴³ One study conducted in Nigeria in the late 1970s noted an incidence of 497 per 100,000 and a 12% case fatality (primarily due to envenomation by the carpet viper, Echis occelatus).¹³⁶

After snakebites, the second most common cause of mortality and morbidity from venomous animals is scorpion stings^88,169 (Chap. 118). Medically important scorpion species are widely distributed throughout the tropics, being particularly common causes of morbidity in North Africa, Mexico, India, and Brazil.⁴⁴ The total number of medically significant ­scorpion stings that occurs annually is unknown; a recent review estimated 1.2 million stings, leading to more than 3250 deaths (case fatality 0.27%).⁴⁴ Other venomous insects, such as Arachnida (spiders) and Hymenoptera (bees, ants, and wasps), are rarely sources of significant mortality on a global scale⁸⁸ (Chap. 118).

Herbal and Traditional Medicines

The use of traditional medicine (TM) to treat or prevent health problems is widespread. The WHO estimates that around 80% of the world’s population consults traditional healers regularly.¹⁷⁷ Frequently cited reasons for this preference or reliance on TM include financial considerations, sociocultural preferences, beliefs about the relative safety and efficacy of TM compared to allopathic medicines, and mistrust or relative inaccessibility of doctors.^86,128 Traditional practitioners still greatly outnumber medical professionals in many regions. For example, in 2004 there was one traditional healer but only 0.04 physicians per 500 inhabitants in Mali.⁷¹

Although TM also encompasses a variety of spiritual, religious, or physical manipulation therapies, it often includes administration of “herbal” remedies (muti) either orally or via enema. These are typically prepared using a combination of aqueous plant materials, sometimes mixed with insect or other animal parts, metallic salts, or both. While traditional medicinal preparations have usually been tested by generations of practitioners and the concentrations of active ingredients are generally low, both intentional and unintentional poisonings are common.^{38,94,153,157} In a 2-year retrospective review of acutely poisoned patients from South Africa, TM was the second most common cause of admission (15.8% of cases) and had the highest mortality rate (15.2%), accounting for over half of all deaths in the series.¹⁶⁷ TM was the most common cause of admission (23% of cases) for acute poisoning in another 10-year retrospective review of cases from Zimbabwe, with a 6% mortality rate.⁹⁵

The specific chemical constituents responsible for TM poisoning may vary widely between geographic and cultural areas. Laboratory analysis and ethnopharmacologic surveys in a number of countries have begun to elucidate some of the chemical constituents of commonly prescribed recipes. Interestingly, a review of 41 autopsies in South Africa for which the causative agent was presumed to be an herbal medicine found that cardiac glycosides were present in 44% of cases.¹⁰⁹ Adulterants are also implicated in poisoning from TM formulations. For example, these are common in traditional Ayurvedic medicines (particularly heavy metals⁶³ and corticosteroids⁷⁵) and Asian medicines (particularly synthetic pharmaceuticals and heavy metals³⁶ Chap. 45). A Taiwanese study of 2609 samples found that 23% were adulterated with pharmaceutical products such as caffeine, NSAIDs, acetaminophen, and diuretics.⁸⁴

Pharmaceuticals

In many lower income countries, pharmaceuticals are relatively uncommon causes of acute poisoning. However, the incidence appears to be rising in conjunction with larger global demographic shifts toward increased urbanization and industrialization. Access to a wider array of medications is relatively greater among urban dwellers than in rural ones, and more people in urban communities may have the financial means to buy them. In a retrospective review of poisoning cases admitted to urban versus rural health centers in Zimbabwe, poisoning with pharmaceuticals was uniquely seen at the urban facilities, accounting for more than 15% of poisoning cases at regional hospitals surveyed and none of the cases presenting for care at the district level.¹⁵⁶ The relative importance of pharmaceuticals in global poisoning trends is likely to continue over the next decades as the number of therapeutic drugs available for use in lower income countries expands, and more and more societies shift toward a “dual burden of disease” pattern, including chronic illnesses that require long-term drug therapy.^21,120

The pharmacopeia available in low-income countries is often more restricted than in higher income countries, and this is reflected in the types of medications implicated in acute poisoning cases. The most common xenobiotics seen in the developing world are those used to treat tropical diseases. For example, self-poisoning with the antimalarial chloroquine (Chap. 59) has been widely reported in Sub-Saharan Africa,^{20,27,116,137} although this medication is now rarely used so the incidence may soon decrease. Intentional and unintentional poisoning with the leprosy drug dapsone, as well as the tuberculosis drug isoniazid (Chap. 58), are also well reported.^{132,158,159,165}

Criminal poisoning of commuters to facilitate robbery is a common problem across South Asia.^89,117,133 In the 1970s and 1980s, drinks containing extracts of Datura stramonium were given to unsuspecting commuters, resulting in anticholinergic poisoning.⁹⁸ Practice has changed recently and benzodiazepines are now more commonly given for this purpose.¹⁰⁸ As many as 300 people are admitted unconscious with this problem to a single university medical unit in Dhaka each year.¹⁰⁸

A more general issue of toxicologic concern is the prevalence of poor-quality medicines in use worldwide. Although data estimating the extent of the problem and its impact on health are limited, recent estimates suggest that more than one-third of all medicines on sale in Southeast Asia and Sub-Saharan Africa are substandard or counterfeit.^23,118,119 The major problem with these medications is an absence or subtherapeutic concentration of active ingredient, leading to treatment failures and an increase in drug-resistant pathogens where antimicrobials are involved. However, substandard medications may sometimes contain more active ingredient than stated, leading to adverse drug effects,¹⁶¹ or contain harmful adulterants or contaminants.

Epidemic poisonings from such poor quality medicines underscore the dangers of inadequate regulation and oversight of pharmaceutical manufacture and sales. Recent examples include the deaths of more than 120 patients in Karachi from exposure to a batch of isosorbide mononitrate contaminated with pyrimethamine,¹⁵ the hospitalization of more than 50,000 infants in China with melamine poisoning from adulterated formula,⁸⁷ and the numerous epidemics of diethylene glycol poisoning in multiple countries over the past few decades from contaminated glycerine, paracetamol syrups, cough syrups, toothpastes, teething mixtures, and other medications.^{22,79,125,127,140,148}

Household Products and Chemicals

Poisoning with common household products, such as fuels, cleansing products, rat poisons, insecticides, body care products, and cosmetics, is a global problem. This general category of diverse xenobiotics is consistently implicated as a significant source of unintentional childhood poisoning worldwide. The PC movement that began in the 1950s in North America grew out of an increasing recognition of the child health risks associated with exploratory household poison ingestions. Household chemicals are a similarly well recognized risk for unintentional childhood poisoning in Sub-Saharan Africa, accounting for up to 80% of all pediatric admissions for poisoning.^{21,41,45,96,126} Internationally, the specific risks are remarkably consistent, including age younger than 6 years (with toddlers younger than 3 years of age most affected), male sex, low socioeconomic status, and unsafe storage practices in the home.

Among specific household products, hydrocarbon poisoning from unintentional ingestion of kerosene (paraffin) is widely reported as the most common cause of pediatric admissions in low-income countries around the world.^{41,45,96,102,173} Kerosene is a common fuel used to power stoves and lamps in many relatively poor communities. It is pale in color with an appearance similar to water, and it is often purchased or stored in used beverage containers making it easy to misidentify (Chap. 108).⁶² In Sub-Saharan Africa, kerosene poisoning accounts for some 25% to 75% of all poisoning-related hospital visits among children younger than 6 years of age.¹²² Several studies document an increase in poisoning related admissions during the warmer months of the year, when children are more likely to become thirsty and to drink from any beverage container at hand.^101,102

Caustics are another group of household products frequently implicated in poisoning in the developing world. The common form of caustic ingested varies between countries. In many countries, alkaline substances are most frequently implicated, whereas in others, such as Taiwan and Morocco, poisoning with hydrochloric or sulfuric acids may be more common.^{3,105,154,180} Acute poisoning carries substantial mortality risk, usually more than 10%. If the acute phase of caustic poisoning is survived, there also is a high rate of delayed complications, primarily esophageal strictures. Delayed complications may require surgical intervention, balloon dilatation of the esophagus (bougienage), or feeding tube placement. These treatments are expensive, require significant hospital resources, and have inherent morbidity and mortality (Chap. 106).

As with other categories of poison, patterns of self-harm using domestic products tend to demonstrate regional particularities. For example, in Hong Kong there is significant morbidity reported in association with self-poisoning using common household detergent products such as dettol (4.8% chloroxylenol, pine oil, and isopropyl alcohol) and savlon (cetrimide).^34,37,39,46 Frequent use of potassium permanganate for self-harm has also been reported from Hong Kong.^129,181 Fatal poisoning with hair dye (paraphenylenediamine) is known in the Middle East and North Africa.^29,61,80,151 Barium sulfide, arsenic sulfide, and calcium oxide are contained in hair removal preparations¹⁴⁶; poisoning from ingestion of these preparations has been reported from India and Iran.⁴ Rubigine is a domestic cleansing product containing hydrofluoric acid and ammonium difluoride that is used for self-harm in the Caribbean,⁸⁵ while ingestion of sodium hydroxide is common in Malaysia.¹⁹

Plants

Poisonous plants have been used therapeutically to induce abortion, for recreational intoxication, in homicidal acts, and for self-harm throughout human history (Chap. 121). This section briefly mentions select toxic plants that are most commonly used in self-poisoning, or that have caused epidemic poisoning in the developing world.

Self-poisoning with seeds of two plants containing cardioactive steroids are important clinical problems in Asia. Yellow oleander (Thevetia peruviana) kills hundreds of people each year in Sri Lanka and India^28,57 (Chap. 65). Sea mango (Cerbera manghas) has killed hundreds of people in Kerala, India,⁶⁸ and is a focal problem in eastern Sri Lanka.⁵⁸ Oduvan (Cleistanthus collinus) leaf contains the glycosides cleistanthin A and B, which produce severe hypokalemia and cardiac dysrhythmias.¹³ Self-poisoning has killed hundreds of people in Tamil Nadu, India.^12,155 The superb lily (Gloriosa superba) contains colchicine alkaloids and has also been used for self harm in South Asia^5,9,111 (Chap. 36).

Ackee tree fruit (Blighia sapida), which contains hypoglycin when unripe, is widely consumed as a food source. Epidemics of fatal poisoning with unripe Ackee fruit have occurred throughout the Caribbean and in Africa.^{64,92,110,112} Poisoning by castor beans (Ricinus communis) or other lectin containing plants such as Jatropha spp (African purging nut) is well reported from Africa and South Asia^1,65,78,93 (Chap. 121).

Numerous plant species contain atropine like alkaloids, causing an anticholinergic syndrome when ingested. Reports of intentional ingestion of Datura species have been reported from Africa, Asia, and Latin America.^78,143,152 Most commonly, the seeds are ingested as a recreational drug for their hallucinatory effects,^67,138 or as part of traditional medical preparations.³⁵

Occupational and Environmental Sources

Poisoning from occupational and environmental sources is a significant global health problem, with disproportionate effects on persons living in lower income communities around the world. Exposure to “traditional” environmental health hazards, such as indoor air pollution from the combustion of solid fuels, and naturally occurring contaminants in groundwater, soil, and food, is still a major cause of morbidity and mortality in much of the world. Around 50% of the world’s people rely on solid fuels such as coal, dung, wood, or crop residues for cooking and heating.³¹ Resultant indoor air pollution was estimated to cause 1,965,000 deaths and 41,009,000 DALYs from lower respiratory tract infections, cancers, and COPD in 2004.¹⁷⁸ In Bangladesh, arsenic contaminated groundwater contributed to 9100 deaths and 125,000 DALYs in 2001.¹⁰⁷ Dental and skeletal fluorosis from excessive fluoride in drinking water is endemic in at least 17 countries worldwide.⁶⁶

Increasingly, modern environmental health hazards (MEHHs) also play a large role in global poisoning risks.^49,124 MEHHs include outdoor air pollution from automobiles and factories, soil and water contamination by plastics, heavy metals, pesticides and other industrial chemicals and wastes, radiation hazards, land degradation, and climate change produced by rapid urbanization and industrial development in the absence of strong regulatory controls.⁴⁹ These are important sources of both occupational and environmental exposure to a wide range of toxins with acute and chronic health effects. Inadequate safeguards to control the selection, sale, and application of pesticides in parts of Africa and Asia are linked to pesticide poisoning both as an occupational hazard^53,91 and from residues left on food.^11,48,123 Occupational lead poisoning has largely been controlled in developed countries through improved working conditions and occupational health screens, but remains an enormous problem in developing countries where occupational and environmental health protection measures are often underdeveloped or practically nonexistent.^164,171

Industrial factories are often placed in urban areas, or the areas around factories are rapidly urbanized, placing large numbers of people at risk not only from pollution but from industrial errors as well. The 1984 Bhopal tragedy in which a Union Carbide pesticide plant malfunctioned, releasing isocyanate gas into the surrounding community and causing an estimated 3787 deaths and 558,125 injuries, is emblematic of such disasters.^14,145

Several international agreements on chemical safety provide legal frameworks to mitigate the human and environmental impact of global industrialization; however, the actual implementation of regulatory controls has lagged behind the expansion of toxic exposures. For example, at the level governance a total of 39 Sub-Saharan African countries have ratified the Rotterdam Convention on chemical safety. Yet industrial pollution is now becoming so highly concentrated in growing urban areas that the continent’s pollution intensity (pollution generated per unit of production output) is now rated among the world’s highest, attesting to significant regional difficulties in enforcing such regulations.¹⁶⁶

The predominance of informal sector activity in agricultural and industrial work in lower income countries poses serious regulatory challenges. Fumes and dusts from small-scale domestic businesses involved in smelting, battery recycling or manufacture, welding, pottery, ceramic production, and artisanal mining are common sources of exposure to lead and other heavy metals in developing countries, and put not only workers but whole communities at risk.¹⁶⁴ More recently, unregulated electronic waste (e-waste) recycling, in which salable metals are reclaimed from old electronics by burning, has emerged as a significant human and environmental health hazard in parts of China, West Africa, and India.^7,104,160 Workers are often aware of the health risks, yet economic hardship and lack of alternative employment make them unwilling or unable to change.

Easy access to industrial chemicals from inadequate regulation of packaging and sales may also facilitate their use for intentional self-harm. For example, formic and acetic acids are used in the manufacture of rubber, and case series are reported from areas surrounding rubber factories in India and Sri Lanka.¹³⁹ Copper sulfate is widely used for self-poisoning in parts of South Asia, and carries a high mortality rate due to direct damage to the gastrointestinal tract, hepatorenal failure, and hemolysis^6,144 (Chap. 95). Cyanide has become a commonly used method in Korea over the last 20 years¹⁰⁶ (Chap. 126).

Regulatory science and the coordinated actions of agencies and programs across multiple sectors play a vital role in preventing or reducing the impact of poisoning in society. Within the health sector, significant inter- and intraregional disparities in access to health care have a major impact on poisoning outcomes. Lack of human resources to provide acute care is an enormous problem in many parts of the developing world. In Mozambique, there is only one trained medical doctor for every 33,000 individuals, compared with 1 in 390 persons in the United States. Tanzania has a nurse to population ratio of 1:2700 individuals compared with 1:107 individuals in the United States. Policies and programs encouraging sustainable and equitable health workforce development are needed foundation to improve health care access globally.⁵⁰

Beyond rectifying the raw numbers deficit, clinical training programs in many low and middle income countries must be upgraded to promote broad exposure and specialist development in clinical toxicology and acute care. Increasing local and international commitment to the growth of emergency medicine in low- and middle-income countries promises to support the dissemination of scientific knowledge and improve provider competence in advanced resuscitation techniques.^8,16,70 Significant gaps in infrastructure and resources to provide basic critical care interventions and meet WHO minimum standards for essential emergency supplies must also be addressed.^17,18,83

In addition to global disparities in acute care infrastructure generally, access to antidotes for specific poisons is either lacking or inadequate in much of the world.^10,131,176 Poor antidote availability is not unique to the developing world,⁵¹ and many antidotes may be considered either adjunctive or unnecessary therapies. However, in certain cases they can significantly reduce the need for other medical interventions, and this may be particularly important in rural or underdeveloped areas where critical care facilities are not readily available.¹³⁴ For example, the most important challenge to improving the treatment of patients with snakebite worldwide is poor antivenom availability, particularly in rural areas where it is most needed to reduce critical delays in administration.^162,163 Currently, many available antivenoms are prohibitively expensive, ineffective, or have a high rate of adverse reactions. Equally important, some antivenoms must be refrigerated, making storage impractical in many rural areas where the need is most acute. Critical evaluation of existing antivenoms and development of new products are thus desperately needed^{24,30,76,77,105,162,163,172,175} (Special Considerations: SC8).

Where antidotes are available, knowledge and experience to know how to use them safely and effectively is often lacking.³² Input from experts in medical toxicology improves outcomes, reduces hospital stays and health care costs associated with acute poisoning,^33,47,69 but practitioners in many parts of the world have limited or no access to consultation with such specialists. The mission of the International Union of Toxicology is to foster international scientific cooperation, ensure the development of toxicologists, and promote the dissemination of knowledge in toxicology worldwide.⁵⁵ Through the collaborative efforts of this and other regional professional societies, an increasing number of online, regional, and international forums now offer educational and professional development opportunities in clinical toxicology around the globe. More work is needed to promote awareness and the growth of the specialty in all regions.

Improving health care access and health system preparedness is only one aspect of the coordinated, multilevel, national, and international public health responses needed to reduce the global impact of poisoning. Prevention and risk reduction efforts must involve locally appropriate community level education and awareness raising, strong governance to support the design, implementation, and monitoring of regulatory controls, and the involvement of multiple stakeholders and sectors including water, waste management, energy, agriculture, transportation, industry, and civil society. Effective legislative frameworks developed in countries with more advanced public health infrastructure have been successfully disseminated in some cases. For example, between 2000 and 2004 the proportion of people with blood lead concentrations above 10 μg/dL globally decreased from 20% to 14%, largely due to the widespread phase out of leaded gasoline.¹³⁵ Other strategies, such as pharmaceutical and food safety regulations enacted through the US Food and Drug Administration, have influenced “duplicative legislation” in other countries but continue to pose significant implementation challenges in low and middle income countries that lack the necessary financing, human resources, and infrastructure to enforce them well.¹³⁰

Many public health measures with proven efficacy, such as routine lead testing during childhood, the regulation of vehicle emissions, the detection of carbon monoxide, and the incorporation of childproof containers may seem prohibitively resource intensive in many parts of the world. The development of new, low-cost technologies such as solar heating and electrical sources, chemical assays and residue detectors, and electronic devices to identify and track pharmaceuticals hold some promise to reduce global risks for unintentional poisoning. More research is needed to propose and evaluate the effectiveness, acceptability, and sustainability of new and proven poison prevention techniques in resource-limited environments.

Recognizing that self-harm from pesticide ingestion is responsible for a majority of acute poisoning deaths worldwide, public health interventions specifically designed to limit access are an important goal. A minimum pesticide list, based on the WHO essential xenobiotic list initiative, has been proposed.⁵⁹ Such a list would provide policy makers and farmers with unbiased information about relative risks. However, voluntary initiatives such as international policy statements and industry sponsored programs often suffer from a lack of resources, a shortage of political will, and nonexistent enforcement mechanisms.^100,115 A dramatic illustration of an effective national program to reduce pesticide poisoning risks is the ban of all WHO high-risk OP insecticides and the organic chlorine endosulfan in Sri Lanka, which effectively arrested a previously exponential increase in the incidence of pesticide poisoning and halved the national suicide rate between 1995 and 2005.⁷³ This program is estimated to have saved more than 20,000 lives in 10 years.⁷³

Ironically, some programs to remove the most environmentally persistent and toxic chemicals from use have inadvertently replaced them with agents highly toxic to humans. The replacement of persistent organic chlorine compounds with carbamates in malaria control programs is an example. The opposite effect has also occurred, for example, by replacing OP insecticides with pyrethroids to reduce human toxicity.¹⁰⁰ Coordinated pesticide harm reduction strategies should take into account concerns regarding both environmental and human toxicity, and anticipate which xenobiotics will enter into use as replacements as specific chemicals are phased out.¹⁴¹ A strategy based on industrial hygiene models of a hierarchy of controls has been proposed by several authors^115,141

(Table 137–2).

• Poisoning is a common worldwide. Fatal poisoning is disproportionately concentrated in lower and middle income countries, where public health systems and acute care resources to detect, manage, prevent, and collect data on poisoning are often less well developed.

• Global poisoning estimates are mostly derived from health care sources in a minority of developing world countries; current data may underrepresent the true burden and distribution of injuries from poisoning.

• Efforts to develop international poisoning surveillance systems and establish harmonized definitions of poisoning cases will help generate a more complete picture to inform local, national, and international policies and interventions.

• Pesticides are the most important cause of death from acute poisoning worldwide, with a majority of cases attributable to acts of deliberate self harm.

• Improving access to health care and health system preparedness to provide acute care is essential to reduce global disparities in poisoning outcomes.

• Randomized controlled trials and cost effectiveness research are needed to critically evaluate the utility of specific public health and treatment interventions in resource limited settings.

Acknowledgments

Michael Eddleston, MD, and Aaron Hexdall, MD, contributed to this chapter in previous editions.

References