The aim of this paper was to systematically review the literature on the prevalence of UAPP and to estimate the annual global distribution. In total, we estimate that about 385 million cases of UAPP occur annually world-wide including about 11,000 fatalities. This estimation depends on the quality and validity of data as well as the estimation procedure.
Our extrapolations follow a step-wise approach. The effects of the different estimation steps are highlighted in Table 9. For fatal UAPP, almost no difference is seen between the reported numbers from eligible publications and the national estimations, as the data were already on a national level and WHO Mortality Database added very little. The world-wide extrapolation added some 3000 cases over all regions. In contrast, for non-fatal UAPP, a steep increase occurs by extrapolating from numbers in extracted publications to the national level. That is because non-fatal UAPP was mostly recorded by surveys on study populations and the national estimates resulted from applying the poisoning ratios to larger national at-risk populations. So, the estimation of non-fatal country-wise UAPP is a crucial step in our review and depends upon the reliability of assessed incidence of UAPP. We found a median ratio of 47% of respondents suffering from UAPP from all included surveys (Table 5), with a span between zero and 100% showing high variability across studies, countries, and populations studied. This variability was lower when countries were compared using studies with the same study design. This matches the results of an international survey in 11 countries and different populations in the year 2006 [169]. The ratio of UAPP was lowest for Spain (30%) and highest for Morocco (85%), pointing to a possible influence of the study designs.
Table 9 Fatal and non-fatal annual UAPP according to different estimation stepsFull size table
Our estimation considerably exceeds the pervasive 1990 WHO figure of about 1 million annual cases of UAPP. This figure, however, was understood to refer to poisonings with severe manifestations only and relied mostly on hospital data. WHO concluded that the numbers of “poisonings may be matched by a greater number of unreported, but mild, intoxications and acute conditions such as dermatitis” [5]. In revisiting the WHO assessments Jeyaratnam provided an estimate for those unreported, mild intoxications as 25 million cases in developing countries [6]. His estimate was an extrapolation from surveys of self-reported symptoms undertaken in just two countries in Asia, in which 6.7% of agricultural workers in Malaysia were poisoned per year and 2.7% in Sri Lanka. We were unable to arrive at an occupational estimate for either of these countries because of a lack of recent data, but our estimate for developing countries is higher, with an overall global farming/occupational estimate for a yearly UAPP incidence of 44% (Table 10). Our estimates ranged from a low of 0.05% in the USA to a high of 84% in Burkina Faso. Consistently high rates of UAPP were found in South Asia and South East Asia, mostly in the 54–65% range. High rates were also found in Africa, ranging from 21% in Cote d’Ivoire to 84% in Burkina Faso.
Table 10 Incidence of yearly non-fatal UAPP among the farming/occupational population by regions and countriesFull size table
Apart from the USA, the only other country to register below 1% was Australia. However, for both of these countries, the data came from registers and did not include farmer/worker surveys. The respective underestimation of non-fatal UAPP is visible from the low number of cases for North America. Only 1078 cases were reported for the occupational population in this region (Table 8) whereas in the USA alone, more than 70,000 cases of non-fatal UAPP occurred annually among the general population (Table A2). Unfortunately, the register-based data do not allow for differentiation between subpopulations, and the share of the farming/occupational population in the UAPP total is therefore not available.
In conclusion, our world-wide estimates of UAPP follow from a better coverage of countries and data sources compared to earlier studies. An increase of pesticide poisoning might have resulted from the increase in global pesticide use between 1990 and 2017. Whereas the world-wide tonnage increase in pesticide use was about 80%, this includes a 484% increase in South America and a 97% increase in Asia, compared to a decrease in Europe of 3% [12]. So, many more farmers and workers are likely to be exposed to pesticides now globally, or more exposed through more frequent use. Our estimates are based on the size of the agriculture population provided by the World Bank, which is calculated by a given share of the total employment. It has to be pointed out that these estimates are probably too low because “employment” is for some countries too narrow a definition, as it might not include informal employment and people engaged in subsistence farming.
There is no generally agreed understanding of what constitutes acute pesticide poisoning. Studies often refer to a classification tool provided by the Intergovernmental Forum on Chemical Safety (IFCS), which was hosted by the WHO [185]. An acute pesticide poisoning by the IFCS definition is any illness or health effect resulting from suspected or confirmed exposure to a pesticide within 48 h. Clinical presentations and symptoms of poisoning were tabulated by this tool. The chosen latency period from exposure to onset of symptoms is decisive for case identification and comes as a trade-off, especially as unspecific symptoms like headache or nausea are also recognized as exposure effects. A too-short period might exclude symptoms with longer latency, while a too-long period could lead to the recognition of poisoning by symptoms that might have resulted from other causes.
Besides the case definition, the studied at-risk-time when exposure might have taken place is also crucial for identification of acute poisoning.
Figures of UAPP in this review originated from registers (e.g. mortality or hospital discharge) or from surveys. Registers usually provide data by ICD codes based on medical records of all defined cases and time span, whereas the surveys identify UAPP by questionnaires applied cross-sectionally to a selected population. Usually, persons are the observation units in surveys and person characteristics are related to the poisonings, whereas cases are reported from registers and monitoring of poisoning is the aim. As a person can suffer from repeated poisonings in a given time span, the incidence of cases usually exceeds the incidence of poisoned persons.
Studies included in this review varied with respect to case definition and at-risk time. Several referred to the IFCS definition with differing at-risk-times e.g. a week [31], or even lifetime “… whether any of 12 listed symptoms had ever been experienced within 48 h of using such pesticides …” [157]. Other studies used their own definitions focused on symptoms, which can show up immediately after spraying [58], within 24 h [53], or have delayed latency for up to a month [149]. Furthermore, some studies refrained from mentioning any latency time and left it to the respondents to link symptoms to exposure, such as “during application last year” [35], or “had ever experienced incidents related to agrochemicals” [169]. Such differences among surveys might lead to different results. For example, Choudhary et al. [53] studied poisoning symptoms with respect to different exposure times. Prevalence of skin related problems was highest in the 18 months exposure group (50%), in contrast to those exposed for 12 months (13%) or for 6 months of exposure (8%). However, no information was given on how often or to what extent pesticides were used in those periods. Kofod et al. [186] question the validity of self-reported symptoms as a proxy for acute organophosphate poisonings. The authors found a high prevalence of nonspecific symptoms, taken from a standardized list of clinical presentations, in the intervention group (chlorpyrifos application) as well as in the placebo group (neem application). The study also found no difference in biomarker plasma cholinesterase (PchE) activity between the groups and after intervention. A surprisingly high percentage of the farmers reported symptoms for a seven-day period which was thought to be a “washout” period without any pesticide exposure.”
In summary, it is difficult to assess the influence of different study characteristics on our estimations because most studies gave no clear case definitions and timeframes. In general, we aimed at annual figures and averaged figures when data for more than 1 year was provided by registers. However, we made use of survey results as annual prevalence, even when the at-risk time was considered longer. Furthermore, for our analysis we did not account for different latency periods in case definitions, nor for some surveys requiring two symptoms as a determination of poisoning while most only required one. We acknowledge that extrapolations might lead to an overestimation of country-wide UAPP by surveys directed to regions with high pesticide usage or high-risk populations, and by studies using non-specific symptoms as case indicators.
Data from registers like the WHO Mortality Database or hospital discharge statistics rely on the utilisation of health services and effectiveness of reporting systems. Both are limited in many countries. Utilisation is hampered as individuals suffering from acute pesticide poisoning may not seek medical care for various reasons, such as access to transportation or lack of medical facilities, lack of financial capacity, inability to take time off from work or fear of losing paid work, language and cultural barriers, or lack of health insurance [187]. The country specific reporting systems might give further causes for underreporting [188] including:
lack of a universal, mandatory legal duty to report incidents,
lack of a central reporting point for all incidents,
similarity of symptoms associated with pesticide poisonings to other causes,
misdiagnosis by physicians because of a lack of familiarity with pesticide effects,
inadequate investigation of incidents to identify the pesticide that caused the effects,
difficulty in identifying and tracking chronic effects,
reluctance or inability of physicians to report incidents,
limited geographic coverage of individual poisoning databases.
Studies have examined the number of counted deaths or poisonings against what is likely an underlying and greater number of poisonings. A survey conducted in a potato-producing province in Ecuador reported a pyramid of estimated pesticide health impacts with 4 deaths per year translated to 10 hospitalisations per year, with 40 poisonings that reached medical care per year, 400 possible poisonings with no clinical care, and 4000 cases of prevalent subclinical neurotoxicity with important performance deficits [189]. A recent study calculated a factor of up to 71 to correct for underestimation of occupational pesticide poisoning in routine community based surveillance [101].
Finally, we expect a considerable underreporting of fatal occupational UAPP because the respective ICD10 codes were not used or WHO cause of death data were not available. For example, a Government of India document [123] reported about 6500 fatalities, many of them probably resulting from occupational exposure, but India did not transfer these data to the WHO Mortality database nor did the government identify the number of occupational poisonings in its report.
Realizing that the conditions of use in developing countries are such that toxic pesticides cannot be used safely, the FAO/WHO International Code of Conduct on Pesticide Management [190] states that “Pesticides whose handling and application require the use of personal protective equipment that is uncomfortable, expensive or not readily available should be avoided, especially in the case of small-scale users and farm workers in hot climates”. In 2006, the FAO Council recommended that consideration be given to the progressive ban of highly hazardous pesticides [8], a call that was supported by the 2015 International Conference on Chemicals Management (ICCM4) [10], and by a FAO/WHO Guideline to the International Code of Conduct on Pesticide Management [190]. The lack of action on FAO’s 2006 recommendation and the ongoing problems with pesticides led the UN Special Rapporteur on the Right to Food to recommend to the UN Human Rights Council in 2017 that there needs to be a comprehensive binding treaty to regulate pesticides throughout their life cycle [11]. Implementing these recommendations, especially encouraging all stakeholders to implement agro-ecologically based alternatives to highly hazardous pesticides, also recommended by ICCM4, would drastically reduce the unacceptably high level of UAPP. Several studies have indicated that phasing out highly hazardous pesticides does not need to result in reduced agricultural productivity [191, 192].
In addition to the above mentioned challenges for estimating world-wide UAPP, our study has some limitations. First, the search strategy might have been too restrictive in order to identify all relevant publications. We therefore carried out some sensitivity tests, e.g. by deleting items or by extending to more specific terms like e.g. “organophos*” or to active ingredients in pesticides, but these appeared to barely change our results. Further, we might have missed relevant contributions in the grey literature and surely from national or regional poison control centres.
Second, our world-wide estimate of UAPP is partly based on a weak database. Some countries were covered by only one publication or by data on small samples sizes of specific study populations. For example, Venezuela was covered by one study with 50 workers fumigating against dengue fever- related mosquitoes using organophosphate pesticides. We therefore subjected those countries with limited data (Albania, Australia, Bahrain, Cote d’Ivoire, Malawi, South Africa, Venezuela) to a sensitivity analysis by exclusion from the world-wide extrapolation. However, this reduced the global estimate by just 1 %. Furthermore, for Greece and Tunisia, mortality data from the WHO Mortality database was available only for 2 and 3 years respectively. However, we do not expect this to bias the 5-years average annual UAPP in comparison to the many countries reporting on more years.
We have grouped countries in regions and sub-regions according to FAO’s determination, with the understanding that consistency in types of agriculture, pesticides used and conditions of use that influence exposure is likely to be greater across sub-regions than regions. Overall, studies reported too heterogeneously for global extrapolations to be based on pesticide use pattern.
Finally, although deaths from pesticides in food are known to still occur [193], we did not try to estimate them, nor was there anything in the publications we reviewed that could lead to such an estimate.