Public health concerns and remedies

Mass use of insecticide-treated bednets in malaria endemic poor countries: public health concerns and remedies

Ehiri, John E

INTRODUCTION

OVER the last two decades, morbidity and mortality from malaria have increased in sub-Saharan Africa due to civil unrest, resistance to available drugs, human migration, population displacements, deteriorating health systems, and the HIV/AIDS epidemic which consumes much of the resources for disease prevention. In response to this growing challenge, international development agencies, spearheaded by the World Health Organization (WHO), founded the Roll Back Malaria (RBM) initiative, a global partnership for prevention and control of malaria (1). The primary goal of RBM is to achieve a 50% reduction in the global malaria burden by 2010, and the period 2001-2010 has been tagged the “United Nations Decade to Roll Back Malaria” (2). RBM has adopted use of insecticide-treated mosquito nets as a major tool for the achievement of its malaria control objectives.

Treatment of mosquito nets with insecticide was probably introduced for the first time during World War II, when nearly half a million American servicemen were stricken with malaria (3). Wider use of insecticide treated nets began in the 19805 following the development in the early 1970s of photostable synthetic pyrethroids which are fastacting, effective in small quantities, relatively stable, adhere to fabric, and relatively safe to humans (4). Based on a series of field studies of the effect of insecticide-treated nets (ITNs) on malaria morbidity and mortality in sub-Saharan Africa (5-7), promotion of use of ITNs has emerged as a key intervention for malaria control. RBM’s target is to have 60% of the world’s population at risk of malaria sleeping under ITNs by 2005 (1). Realization of this goal could see tens of millions of doses of pesticides for net impregnation entering thousands of homes in malaria endemic poor countries annually (8). Thus, strategies to ensure a fuller understanding of their health risks and to minimize actual and potential adverse effects on human health are urgently needed.

THE SAFETY OF INSECTICIDES

All pesticides are toxic in nature. There are 795 chemical and biological pest control agents in current use globally (9). According to the World Health Organization (10), thirty-three of these are classified as extremely hazardous to human health, 48 as highly hazardous, 118 as moderately hazardous, and 239 as slightly hazardous. Only 149 were considered to be unlikely to cause acute hazard in normal use. In addition, the Council of the European Community has classified 149 of the chemical pesticides included in the manual as ‘dangerous to the environment’ (11). Insecticides recommended by the WHO Pesticide Evaluation Scheme (WHOPES) for the treatment of mosquito nets to prevent malaria are presented in Table 1. All products are pyrethroid insecticides, which are presently the only group of insecticides recommended for this use (4).

In one of WHO’s statements regarding the safety of pyrethroidtreated mosquito nets (4), it was asserted that if prescribed precautions are followed, field use of these products at concentrations recommended for treatment of mosquito nets poses little or no hazard to people treating the nets or to users of the treated nets. Although other risk assessment of the use of deltamethrin on ITNs largely supports this view of the WHO, a relatively high chronic risk (beyond the US EPA standard of 100) was shown to exist for newborns sleeping under ITNs (13). Toxicity refers to the inherent poisonous potency of a compound under experimental conditions, and chronic toxicity refers to the potential for adverse effects from long-term exposure (8). The toxicity of pyrethroids is due to their affinity for, and intrinsic effect on, receptors or targets within the sodium channels for nerve conduction. Given that pyrethroids are highly lipophilic, they pass through cell membranes and are absorbed through the skin, by inhalation and by ingestion. Thus, individuals are at risk of exposure to pyrethroid insecticides through accidental swallowing or drinking of the product, inhaling solvent vapors of emulsifiable concentrate (EC) solutions (e.g., permethrin), splashing the product into the eyes or onto the skin during net treatment, and insecticide residues during net use (4).

Chronic effects from exposure to chemicals usually occur at much lower concentrations than is needed to produce acute effects. As such, exposure to a certain concentration level might have no adverse health effect if it is brief, but may have an effect if that exposure persists over a long period of time (8). Table 2, presents data on chronic toxicity of pyrethroid products used for treatment of mosquito nets.

As shown in Table 2, the chronic toxicity of insecticide products is expressed as “no observed adverse effect level” (NOAEE) and “acceptable daily intake” (ADI). NOAEL is the dosage of an insecticide that results in no discernible harm to experimental animals in chronic toxicity studies that include the close examination of all body organs for abnormalities (4). The ADI is the daily exposure level of the insecticide residue, expressed as mg/kg body weight that, over the entire lifetime of a human being, appears to be without appreciable risk, on the basis of all facts known at a given time, calculated from the relevant NOAEL, with a safety factor of 100.

Use of ITNs also predisposes individuals to acute pesticide poisoning. Table 3 shows the acute oral and dermal toxicity of insecticide formulations commonly used for treatment of mosquito nets as reported by manufacturers in the material safety data sheets of their products. LD5O is a statistical estimate of the amount of substance required to kill 50% of a population of test animals (usually rats); the higher the LD50, the lower the toxicity (8).

Acute toxicity refers to the adverse effect that may result from single or multiple exposures to a chemical over a relatively short period of time (4). Acute toxicity may occur through treatment and handling of insecticides for treatment of nets. As would be expected, individuals involved in dipping large numbers of nets are most at risk, whereas those who occasionally treat their own nets are less exposed to this level of risk (4). Acute effects reported by net dippers include tingling and burning sensations (paraesthesia), eye pain and irritation, swelling of the face, headache and dizziness (4). Transitory side effects have also been reported by householders mainly during the first few days after net treatment, including skin itching, eye burning, nasal irritation and sneezing.

Impregnation of mosquito nets with insecticides is carried out by dipping the nets in basins or plastic bags containing the insecticide mixed with water. The general procedures can be any of the following (14): 1) Do-It-Yourself (DIY) kits, where anyone can treat nets using treatment kits available through shops and health centers. The availability of insecticides over the counter poses a significant safety concern. Analyses by the WHO Pesticide Evaluation Scheme (WHOPES) show that ingestion of the contents of even a single application pack of permethrin 10% EC could be lethal to a child (4), and without adequate precaution the potential for realization of this risk is high in settings with limited awareness of the hazards of insecticide products. 2) Pre-treated, long-lasting nets, whereby the manufacturer treats the net prior to packaging and sale. Since currently available pre-treated long-lasting nets lose their efficacy over time, and from washing, they require re-treatment every 6 months to one year to maintain their efficacy over their life span. Washing large quantities of treated nets in bodies of water could be hazardous to both humans and the aquatic environment, and regular re-treatment of nets increases the risk of acute toxicity among net dippers. 3) Mass treatment, which can be done by trained personnel at dipping centers, where people bring their nets for treatment and re-treatment. Persons who dip large quantities of nets are exposed to acute toxicity of insecticide products, especially if prescribed precautions are not followed.

THE GAP IN EVIDENCE

In summary, the limited risk assessments undertaken so far with regard to the safety of ITNs suggest that they are relatively safe, if due precaution is observed. In interpreting results of these assessments, however, it is important to note that whereas the use of mosquito nets is not new, mass use of ITNs as a population-based malaria control tool is a relatively new technology, and some uncertainty remains about the potential for problems as their use expands (8). The fact that DDT was heralded as a panacea for vector-related problems several decades ago, and now found to be extremely hazardous to human health and environment, and was subsequently banned in industrialized countries including the US, calls for caution in widespread use of ITNs in uncontrolled settings.

Efforts should be directed toward accumulation of data on potential health and environmental risks of long-term use and misuse, especially where ‘dip-it-yourself is the dominant practice. So far, research attention to potential adverse health effects has been meager, and data on acute and chronic health effects related to toxic exposures are generally lacking (15) apart from a few recent reviews (12,13). For example, although it is known that there are people who are sensitive to deltamethrin, no data exists on the extent of this problem in less developed countries since prior studies focused on dead mosquitoes and reduction in malaria morbidity and mortality.

While the transitory nature of acute effects from pyrethroids is typical of the vast majority of poisonings (8), some reports of poisoning incidents involving these products point to the potential for serious, irreversible effects, particularly from exposure to highly concentrated products, and thus, underscores the need for investment in research, education and training. For example, Miiller-Mohnssen (16) reports on 144 adults who fell ill after indoor pyrethroid exposure and experienced lengthy recovery periods, with permanent damage in some cases. In one case study, a woman spilled a concentrated permethrin solution on her leg and hand, and afterward, bathed the area with an oil solution (16). Oil greatly enhances the skin’s permeability to lipophilic pesticides like pyrethroids, and this was the main reason why she sustained painful, permanent and debilitating damage to the exposed areas (8,16). In addition, when insecticide-treated nets are washed, a certain amount of insecticide is lost from the net into the water. The amount of insecticide lost on washing varies but can be estimated at around 50% loss on first wash (17). Most ITN programs are in developing countries where domestic activities that require water (e.g., bathing and laundry) are carried out in local streams. The effect that the lost insecticide from washing large quantities of insecticide-treated nets may have on aquatic life could potentially be serious, but this has yet to be investigated.

THE NEED FOR PESTICIDE SAFETY PROGRAMS IN MALARIA ENDEMIC POOR COUNTRIES

Safe use of insecticides requires adequate appreciation of the toxicity of these products, and strict adherence to cautionary advice, both on the part of public health professionals and the general public. However, there are a plethora of socioeconomic factors that present significant challenges to safe use of insecticides in less developed countries. These include (18):

* Lack of appropriate pest control legislation and a lack of modern pesticide approval/registration procedures

* Lack of monitoring of pollutants in food, drinking water and the environment

* Lack of poisoning surveillance systems and regional or national poison information/control centers

* High rates of illiteracy and inability to read complex label instruction

* Use of labels in foreign language

* Lack of capacity (human and financial) to advice on, and enforce, regional and national insecticide use and safety regulations

* Poor information provision leading to a lack of knowledge of the risks associated with use and misuse of insecticides

* Lack of facilities for proper waste management, resulting in indiscriminate disposal of used insecticides in the environment

* Lack of clean water for washing

* Re-use of pesticide containers for food and water storage

Recent case studies of potential health risks associated with widespread use of insecticides conducted by the UK Pesticide Action Network (PAN) in Africa provide some insight into the potential for problems. In the Gambia, for example, PAN selected permethrin, the insecticide used to treat bednets in the country’s malaria control program (19). Permethrin is imported into the Gambia by the government and a number of aid agencies, and over 1,300 villages are involved in the program. Evaluation studies show that the use of the permethrinimpregnated bednets has reduced mortality from cerebral malaria (20). However, comparatively little information exists on health risks and training needs for safe use of insecticides by both health workers and the communities. Permethrin is a neuro-poison which acts on the nervous system and can cause itching and burning sensations on exposed human skin. It is also toxic to aquatic organisms and to bees (19). The PAN case study showed that relevant data needed for risk assessment and training needs analyses were hard to extract or unavailable. Although poisoning data are kept by hospitals, the identities of particular chemicals involved in the cases were usually not recorded. Records kept by importers were also found to be unsatisfactory due to lack of trained staff in these organizations. There was no monitoring data for pesticides in various environmental compartments (air, water, and soil). The case study revealed a number of significant risks of exposure at several stages of the chemical’s life cycle. These included when the pesticide is decanted from the large imported drums into smaller containers, when the bednets are dipped by either the village health worker or by individuals in their own homes, when unlabeled containers of insecticides are brought into the home, and deliberate misuse of the chemical. It was agreed that most of the risks associated with permethrin could be avoided if the users were fully aware of the dangers and were trained in safe handling of the product. Investment in training and monitoring of adverse health and environmental effects were identified as crucial (19).

THE WAY FORWARD

Proper product selection

The massive scale-up of acquisition and use of ITNs in malaria endemic poor countries is a major operation that would involve unprecedented use of insecticides in these countries. Thus, a reassessment of the health risks associated with ITNs is needed in order to form the basis for policy and practice. At the national level, appropriate selection of products is essential, and this must be based on local assessment of the product’s effectiveness and risks. Unfortunately, in many less developed countries, decision regarding selection of pesticides is often made on the basis of cost and effectiveness, with minimal emphasis on safety (21). Countries embarking on interventions to increase use of ITNs should endeavor to select pesticide active ingredient and formulation that present the least overall risk. They should be aware of the facts that water-dispersible tablets eliminate the potential for poisoning through accidental exposure to concentrated liquid product; large containers necessitate the transfer of hazardous products into smaller, often poorly labeled containers; unit-dose products for do-it-yourself treatment of nets at home predispose individuals, especially children, to accidental exposure.

Effective monitoring of adverse effects

Procedures for identifying adverse human and environmental exposure should be instituted at national, regional, and local levels, so that monitoring could be carried out on a regular basis, and so as to facilitate assessment of impacts and changes over time. Human behavior and the potential for unapproved misuse of insecticides should be monitored and addressed. An important issue for observation in this regard is whether users will restrict themselves to the WHO-recommended ITN products, once they have become accustomed to treating their own nets, or whether they will substitute these with more readily available or cheaper, but more hazardous products (8). Risk analyses should be based on actual levels of health and environmental exposure under observed conditions of use. The results of studies done to determine effects on human health and the environment are inconclusive. Studies of this nature should be intensified and ongoing. Other studies should seek to determine if mosquitoes are developing resistance to current insecticides being used; the possibility of pesticides becoming a part of the food chain through biomagnification in fish; and also whether there was use of unauthorized pesticide for treating bednets and their health and environmental effects. In the meantime, householders should be encouraged to report illnesses associated or suspected to be associated with pesticide use; health personnel in health care institutions such as hospitals should be encouraged to improve record-keeping system to be able to report on illnesses associated with pesticide use.

Legislation

Given the toxic nature of insecticides, national authorities should attempt to regulate the use of these chemicals especially at the wholesale and retail levels. It is going to be difficult to regulate household use of these chemicals even though it is at the household level that most of the risks will be present. However, if regulations are promulgated and the capacity for enforcement exists, then this could reduce some of the dangers posed by the distribution and use of insecticides for treating bednets. It should be noted, however, that one couldn’t pass a regulation requiring householders to use the right amount of insecticide or to recognize signs and symptoms of poisoning. This has got to be the role of education.

Training and education

Training (including training-of-trainers) in safe use and management of insecticides is important at all levels, and locally appropriate methods for disseminating information and knowledge about insecticides need to be instituted. Public awareness of potential risks associated with use and misuse of insecticides is essential in malaria endemic countries. A comprehensive education program is needed not only to inform individuals and families of the benefits of ITNs, but also their associated health and environmental risks. This education program should target those involved in the production, distribution and sale of insecticides, householders and health personnel. The priority target group for education should be householders. The programs should be developed with inputs from those it will target and should reflect the cultural context in which they are developed and the literacy level of the population. Surveys to determine the knowledge, attitudes and practices of householders with respect to the use of insecticides and mosquito control in general should provide useful data on which meaningful education programs can be developed. Community members can be trained to conduct community self-surveys. Available community resources should be utilized and the mass media incorporated as a partner. Educational materials should be pre-tested before they are put into general use. Any educational intervention should seek to address the following: choosing the right insecticide product, reading the product label, determining the right amount to purchase and use, using the product safely and correctly (22); routes of entry of insecticide into the human body system and the environment, signs and symptoms of poisoning, emergency measures; personal protective clothing such as chemical-resistant gloves which cover up to the elbow, working in well-ventilated areas, hand washing, avoiding unnecessary exposure, proper storage and disposal of insecticide and containers (23). Educational programs should be ongoing and evaluated periodically.

Emphasis on health and environmental impact assessment (HEIA)

Good practice procedures require that every development project be preceded by an assessment of its health and environmental impacts. This requirement should be an essential element of all ITN promotion programs in malaria endemic poor countries. Fortunately, steps for conducting such assessments have been described and documented (24-26), and several useful documents relating to the safety of ITNs are readily available (27-29) to guide agencies embarking on ITN promotion programs. A few international health agencies currently undertake programmatic assessment of the use of insecticide-treated materials in their development activities (8). Other agencies, national governments and non-governmental organizations (NGOs) involved in the promotion of ITNs in less developed countries should avail themselves of useful resource material on assessment of risks associated with ITNs. The pesticide management guidelines produced by the United Nations’ Food and Agricultural Organization (30), available at no cost on the internet, provide valuable reference material for countries wishing to establish national regulation and guidelines for safe use of pesticides.

Finally, the promotion of ITNs should be done within the context of an integrated approach to vector control and consequently other components of mosquito control such as environmental management, larvicidal and biological control should be incorporated where possible to ensure sustainability. Only by reducing malaria-related morbidity and mortality through use of bednets and at the same time, mitigating the potential adverse environmental and health impacts associated with long-term use and misuse of insecticides, can we ensure sustainability in efforts to prevent malaria through use of bednets.

REFERENCES

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4. World Health Organization. Safety of pyrethroid-treated mosquito nets. 1999. WHO Pesticide Evaluation Scheme (WHOPES). WHO Document: WHO/CDS/CPE/WHOPES/99.5. http://www.who.int/ctd/whopes/sptmn_ eng.pdf (Accessed: December 5, 2003).

5. Habluetzel A, Cuzin N, Diallo DA, et al. Insecticide-treated curtains reduce the prevalence and intensity of malaria infection in Burkina Faso. Tropical Medicine and International Health 1999; 4:8; 557-564.

6. CuzinQuattara N, Van den Broek AH, Habluetzel A, et al. Wide-scale installation of insecticide-treated curtains confers high levels of protection against malaria transmission in a hyper-endemic area of Burkina Faso. Transactions of the Royal Society of Tropical Medicine and Hygiene 1999;93:5; 473-479.

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SUMMARY

Epidemiological evidence arising mainly from studies undertaken in subSaharan Africa suggests that sleeping under insecticide-treated mosquito nets is a cost-effective and efficacious method of controlling malaria. For this reason, promotion of use of insecticide-treated nets (ITNs) has become a key malaria control strategy. In 1999, the United Nations Children’s Fund (UNICEF) and WHO set the goal of providing 32 million nets and 320 million net treatments a year for the next 10 years to protect 80% of African households against malaria. All pesticides are toxic by nature and are associated with adverse health risks that depend on the toxicity of each chemical, as well as the type and degree of exposure. Thus, massive scale-up of use of ITNs in malaria endemic poor countries can be expected to present tangible risks to health, especially where the insecticides for net treatment and re-treatment are handled mostly by untrained persons in uncontrolled settings. This paper examines potential health risks of mass use of ITNs in malaria endemic poor countries and calls for the implementation of strategies to minimize potential risks through careful selection of products, appropriate labeling (including labeling in the local languages of the user communities), pesticide safety education of the public and training of health personnel, and active monitoring of adverse health effects to document actual and potential hazards, and to facilitate planning of mitigation efforts.

Key words: insecticide-treated bednets, malaria control, health and environmental impact, exposure, safety education.

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