Organophosphate poisoning temporal trends and spatial distribution, Uganda, 2017─2022

doi:10.21203/rs.3.rs-3903010/v1

Introduction:

Organophosphates (OP) are toxic chemical agents used as agricultural pesticides and insecticides and are one of the commonest agents of poisoning worldwide, responsible for > 3,000,000 poisonings and 300,000 deaths globally per year. As a country with an agriculture-based economy, Uganda has widespread use of pesticides, creating an elevated risk for OP poisoning. We assessed the distribution and temporal and spatial trends of OP poisoning admissions in Uganda during 2017─2022 to guide control and prevention interventions.

Methods

We analysed OP poisoning surveillance data from the District Health Information System version 2 (DHIS2). As per DHIS2, OP poisoning admissions were defined as a hospital stay due to suspected OP poisoning while deaths were defined as inpatient deaths with OP poisoning listed as the cause of death. We calculated annual incidence of OP poisoning admissions per 100,000 population and case-fatality rates per patient admitted with OP at national, regional, and health facility levels. We used the Mann-Kendall (MK) test to determine the strength and direction of the trend.

Results

A total of 37,883 (average: 6,314 per year) OP admissions and 1,599 (average: 267 per year) deaths were reported (case-fatality rate [CFR] = 4.2%) during 2017─2020. Males (incidence = 18/100,000), children < 5 years (incidence = 20/100,000), and residents of Ankole Region (incidence = 26/100,000) were the most affected. CFRs increased with the increasing healthcare level of the admitting health facility. The incidence of OP declined by over 3-fold over the study period (MK=-13, p = 0.02). Kiruhura and Bukwo Districts had consistently high incidences (> 50/100,000) throughout the study period.

Conclusion

There was a significant reduction in incidence of OP poisoning in Uganda during 2017─2020. Males, children < 5 years, and residents in Ankole Region were the most affected. Strengthening sensitization among agricultural and livestock farming communities about the risks of pesticide poisoning and building capacity of health workers and equipping lower-level health facilities to effectively manage medical emergencies including OP poisoning could reduce the OP burden and mortality in Uganda.

Toxicology

Organophosphate poisoning

pesticides

Uganda

Organophosphates are a group of highly toxic chemical compounds that are commonly used as agricultural pesticides and insecticides[1]. They are one of the main agents of poisoning, responsible for over 3,000,000 poisonings and an estimated 300,000 deaths per year worldwide [2]. These poisonings, which lead to substantial morbidity and mortality among the exposed, may occur due to occupational or accidental exposure, deliberate ingestion in cases of suicide, or during chemical warfare [3, 4]. Most organophosphate poisonings have involved exposures to agricultural pesticides [5]. The major routes of exposure for organophosphates are the respiratory tract, gastrointestinal tract, skin, and eyes [6].The clinical features of organophosphate poisoning are based in the central nervous system and include salivation, lacrimation, urination, defecation, abdominal pain, general body weakness, vomiting, loss of consciousness, anxiety, tremors, and convulsions [7]. Once exposed, symptoms occur within minutes to hours depending on the type of organophosphate poison, route of exposure, and dose [8].

In low and middle-income countries (LMIC), the significant reliance on pesticides for agricultural production results in an elevated risk of exposure to organophosphates [4]. The widespread availability and indiscriminate use of pesticides in such settings, coupled with poor storage and handling practices and lack of awareness about the consequences of poisoning make LMIC particularly vulnerable [9].

Uganda has a largely agricultural economy [10] and a development strategy hinged on rapid industrialization in agriculture [11], which results in the widespread use of pesticides among agricultural farmers [12]. In Uganda, pesticides, including organophosphates, are widely available in animal drug shops and shops that sell general merchandise, and can be found on farms and in homes [13]. There have been previous reports of organophosphate poisoning in Uganda linked to both intentional and unintentional pesticide exposures. [12–14]. Prevention efforts for pesticide poisoning in Uganda have included health education and sensitization on proper use of pesticides among farming communities [15]. There are other measures which the limit the availability and toxicity of pesticides, such as regulation to limit sales to trained and licensed vendors [16]. Additionally, the replacement of highly toxic pesticides with less toxic and equally potent ones has also been implemented [17]. Despite the risk potential, little is known about the burden of organophosphate poisoning in Uganda. We assessed the distribution, temporal, and spatial trends of organophosphate poisoning in Uganda 2017─2022, to guide targeted control and prevention interventions.

Study design and data source

We analysed organophosphate poisoning surveillance data captured in the District Health Information System version 2 (DHIS2). The DHSI2 is an open-source web based platform that is used to collect, report, and analyse aggregate data that is routinely generated across health facilities in Uganda[18]. Uganda has 146 districts which are distributed across the 15 regions as designated by the Ministry of Health. The healthcare system comprises government and privately owned health facilities which are organized in a hierarchical order [19] from Health Centre (HC) II (found at parish level), HCIII (found at sub-county level), HCIV (found at county/health sub-district level), district hospital (found at district level), regional referral hospital found at regional level), and the national referral hospital (found at national level).

The DHIS2 collects data on priority diseases, conditions, and events of public health importance including organophosphate poisoning from the Health Management Information system (HMIS). All cases suspected of organophosphate poisoning are recorded in HMIS as admissions/in-patient occurrences. The HMIS is a paper-based system in which health facilities record patient data on conditions of interest. These data are later entered into the electronic DHIS2 and aggregated from all health centres in the country.

Study variables, data abstraction, analysis, and management

We abstracted aggregate data on organophosphate poisoning admissions and

deaths from the inpatient monthly reports in the Health Management Information System (HMIS) from 2017 to 2022. As per HMIS, organophosphate poisoning admissions were defined as a hospital stay due to suspected organophosphate poisoning as a primary diagnosis. Organophosphate poisoning deaths were defined as inpatient deaths with organophosphate poisoning listed as the cause of death in DHIS2.

Data were imported into Stata version 16 software (Stata Corporation, College Station, Texas, USA) for analysis. We calculated the annual incidence of OP poisoning as annual admissions due to OP poisoning per 100,000 population. Population data was obtained from the Uganda Bureau of Statistics population estimates[20]. Additionally, we calculated the case fatality rate (CFR) of OP poisoning as a percentage of number of deaths due to OP poisoning divided by the number of OP admissions. We calculated annual incidence of organophosphate poisoning and the overall case fatality rates at national, regional, and health facility level. We used line graphs to describe national trends of OP admissions and CFR. The Mann-Kendall test was used to determine the significance of the trends. Choropleth maps were drawn using QGIS software to show the spatial distribution of organophosphate incidence in the country. To further contextualize the findings, we also abstracted data on reporting rates, calculated as the percentage of complete submitted monthly reports over the study period divided by the number of expected reports.

Incidence and case fatality rate of organophosphate poisoning, Uganda, 2017–2022

Overall, a total of 37,883 (average: 6,314 per year) organophosphate poisoning cases.

The overall average incidence was 15 organophosphate admissions per 100,000 persons. Residents of Ankole Region were more affected while those in Lango Region were least affected. (Incidence: 26/100,000 vs 7/100,000 persons). (Table 1). Males had a higher incidence of organophosphate poisoning than females (18 vs 13/100,000, p = 0.03). Children < 5 years had a higher incidence than persons ≥ 5 years (20 vs 14/100,000, p = 0.01). Overall, 1,599 (average: 267 per year) deaths were reported (CFR) = 4.2% during 2017–2022. Residents in Kampala Region had the highest overall CFR while those in Teso Region had the lowest (CFR: 8.5% vs 2.2%) (Table 1).

Table 1

Incidence and case fatality rate of organophosphate poisoning, Uganda, 2017─2022
	Cases	Average population	Incidence /100,000	Deaths	Case fatality rate (%)
Sex
Female	2,772	20,951,652	13	75	2.7
Male	3,542	20,100,565	18	192	5.4
Age group
< 5 years	1,570	7,715,064	20	48	3.1
≥ 5 years	4,744	33,337,153	14	219	4.6
*Health facility level
Health Centre III	1,253	-	-	29	2.3
Health Centre IV	1,374	-	-	37	2.7
District Hospital	2,911	-	-	141	4.8
Regional Referral	684	-	-	52	7.6
National Referral	92	-	-	9	9.7
*Ownership
Government	3,769	-	-	163	4.3
Private	2,545	-	-	104	4.0
Region
Ankole	871	3,308,524	26	38	4.4
Bukedi	511	2,269,307	23	12	2.3
Tooro	677	3,030,632	22	33	4.8
Teso	613	2,877,800	21	14	2.2
Bugisu	431	2,124,113	20	15	3.4
Acholi	332	1,890,706	18	22	6.6
Kigezi	290	1,637,823	18	17	5.8
North Central	624	4,869,437	13	32	5.1
Bunyoro	327	2,638,612	12	15	4.6
Kampala	222	1,848,566	12	19	8.5
Karamoja	118	1,168,481	10	4	3.3
South Central	536	5,782,964	9	20	3.7
West Nile	278	3,202,789	9	10	3.8
Busoga	323	4,227,008	8	12	3.7
Lango	162	2,444,762	7	7	4.3
Total	6,314	41,052,217	15	267	4.2
*Population data for health facility level and ownership was not available to calculate incidence

There was no difference between in CFR by age or sex. CFRs increased with increasing admitting health care level of the health facility. Lower-level health facilities like HCIII had low CFR and compared to high level health facilities-the National Referral Hospitals (CFR: 2.3% Vs 9.7%) (Table 1).

Overall trend of incidence of organophosphate poisoning admissions, Uganda 2017─2022

There was a 350% (more than 3-fold) decline (MK=-13, p = 0.02) in incidence of OP poisoning admissions per 100,000 population from 2017─2022. The greatest decline was between 2019 and 2020 (Fig. 1). Reporting rates were high and stable over the study period (Range: 86–94%).

Trend of case fatality rate of organophosphate poisoning, Uganda 2017─2022

There was no significant change (MK=-9, p = 0.13) in the incidence of organophosphate poisoning deaths from 2017─2022 (Fig. 2). The greatest decline was between 2018 and 2019 (Fig. 2).

Spatial distribution of organophosphate poisoning admission incidence, district level, Uganda, 2017─2022

Overall, the incidence of organophosphate poisoning admissions declined across all districts. The number of districts reporting > 100 cases per 100,000 admissions reduced from seven districts in 2017 to one district in 2022. Spatial clustering of high-incidence districts was observed in the east and south-western parts of the country. The incidences in Kiruhura and Bukwo districts remained high every year over the study period (Fig. 3).

We assessed the trends and spatial distribution of organophosphate poisoning admissions incidence and deaths in Uganda, 2017─2022. The incidence of organophosphate poisoning admissions declined over the study period with an overall CFR of4.2%. Males, children < 5 years, and residents of Ankole Region were the most affected. Two districts (Kiruhura and Bukwo) had the highest incidences throughout the study period.

The incidence of organophosphate poisoning admissions declined throughout the study period. Since 2014, Uganda has implemented periodic public awareness campaigns about safe use of pesticides for small-holder farmers and pesticide dealers [21]. These campaigns have included sensitization about responsible handling to reduce risk of poisoning and environmental pollution. Additional campaigns targeting government pesticide regulators, non-governmental organisations, and media have also been implemented to address the dangers of organophosphate poisoning [22]. These have included information about safe handling and use of pesticides and sensitization about banned and counterfeit pesticides. Similar health education and hazard assessment programs have been shown to have contributed to a reduction in organophosphate incidences amongst livestock farmers in Zambia [23]. Additionally, in 2008, Uganda ratified the Rotterdam Convention, which banned the importation and use of highly toxic pesticides [24]; Uganda has also implemented the Agricultural Chemical Control Act to use less toxic pesticides [25]. Together, these may be contributing to the reduction in the incidence of organophosphate poisonings. To continue this decline, it is important to monitor and strengthen these interventions.

The overall CFR was 4.2%. This is lower than the CFR in two other Uganda studies on organophosphate poisonings done in hospital emergency centres in Uganda in 2022 (18%; 11/61) and 2018 (7.3%; 7/96) [26, 27]. Mortality in organophosphate poisoning depends on the route of administration, the exposure dose, obtaining early diagnosis, and availability of appropriate medical care [28, 29]. It is possible that since patients included in this study were inpatients, they may have had access to appropriate treatment, including activated charcoal and atropine, which are known to decrease mortality after organophosphate ingestion [3, 30]. High CFRs were reported in a retrospective study; CFR = 7.8% (51/656) and a prospective study CFR = 5.6% (13/230) conducted in Tanzania[31]. This was attributed to challenges in clinical management of patients due to lack of specific details on the OP chemicals responsible for poisoning during hospital care. Ensuring that hospitals are stocked with equipment and antidotes for organophosphate could help further reduce the mortality associated with this exposure.

Males in our study were more affected than females. In Uganda, men are more involved than women in agricultural activities which involve spraying of pesticides and these put them at high risk of occupational exposure [32–34]. Occupational exposures can occur through unintentional ingestion, inhalation, and skin and eye contact [35]. Studies in India have similarly identified higher incidence of organophosphate poisoning among men than women [36, 37]. There is need to sensitize the public, especially men involved in agricultural work, about the importance of wearing personal protective gear like gloves, boots, and gloves during pesticide application.

Children below 5 years were more affected by organophosphate poisoning than persons who were above 5 years. Studies in Uganda and China in 2017 also found that children were more affected than adults [38–40]. Globally, most organophosphate poisoning cases in children are accidental and occur after they ingest pesticide that was poorly stored in households [41, 42]. In Uganda, there is often poor storage practices of pesticides in the households [38], leading to easy access by children. The exploratory and inquisitive behaviour together with frequent hand-mouth movements puts children at a risk of pesticide poisoning through the oral route [43]. Interventions that facilitate further reduction in the incidence of organophosphate poisoning amongst children are advisable. For instance, care takers to safely keep pesticides away from reach of children and packaging pesticides in containers that cannot easily be breached by children.

Residents in Ankole Region were the most affected by organophosphate poisonings. Additionally, the incidences of Kiruhura and Bukwo districts remained high every year during the study period. Ankole Region (which includes Kiruhura District) is one of several regions engaged in both agriculture and livestock farming [44]. This region implements the intensive mixed farming model of growing of crops (banana-coffee) and rearing of cattle unlike other regions which exclusively apply either the crops (banana, coffee, millet, tea, cotton, millet, maize and cassava) or rearing animals (cattle-goats) only models[45]. This may lead to increased circulation of organophosphate agro-chemicals in Ankole Region as opposed to other regions. Additionally, poor handling likely plays a role. A study in Ankole Region about the usage of pesticides amongst dairy livestock farmers revealed that most farmers handled highly toxic agrochemicals without following proper instructions or having personal protective equipment [46]. However, similar data are not available for other regions. Like Kiruhura District, Bukwo District is also heavily involved in agriculture and livestock farming [47, 48]. Further investigation is needed to understand the reason for persistently elevated levels of organophosphate poisoning in these districts, compared to other districts with similarly agricultural and livestock-based economies.

Higher-level admitting health facilities recorded a higher CFR compared to lower-level health facilities. Lower-level health facilities (which act as the first point of care) may not have the staff, stock, or equipment to handle emergency poisoning cases [49, 50] and often refer cases to higher-level facilities, which can incur treatment delays. In addition, more severe cases may be more likely to attend the higher-level facilities as their first point of care. Together, these may contribute to the higher CFRs in higher-level facilities. These findings are consistent with those in the Tanzanian study which showed that higher level health level facilities had a higher CFR than lower level primary health facilities [31]. This was attributed to lack of clinical capacity amongst healthcare workers to diagnose and treat such cases at primary healthcare level. It is important that rapid referrals are done from lower-level health facilities to higher level health facilities. In areas in which organophosphate poisonings comprise a high proportion of patient visits, it may be worthwhile to stock antidotes and train staff to manage such cases until they can reach higher-level facilities. Higher-level health facilities should additionally be equipped to handle organophosphate poisoning emergencies.

Limitation

Our study only utilized secondary data from the DHIS2, which are limited in terms of variables available for analysis. Secondly, the study utilized information of only admitted patients, and thus outpatients and persons who did not seek care from the health facilities were excluded, resulting in an under-estimation of the incidence of organophosphate poisoning in Uganda. Community-level studies using primary data to determine the factors associated with organophosphate poisoning may be beneficial in understanding the trends of organophosphate poisoning in Uganda.

There was a reduction in both incidence and mortality of organophosphate poisoning among admitted persons in Uganda during 2017–2022. Males, children < 5 years, and residents of highly agricultural districts were most affected. CFRs increased with increasing administrative level of the health facility. A detailed study into the reasons for the decline and strengthening interventions that can be directly linked to the decline nationally could facilitate continued reductions in organophosphate poisoning burden in Uganda. It is also important to build the capacity of health workers and equip lower-level health facilities to appropriately manage organophosphate poisoning incidents.

CFR

Case Fatality Rate

DHIS2

District Health Information System-2

HC

Health Centre

HMIS

Health Management Information System

LIC

Low-income country

MK

Mann-Kendall

OP

Organophosphate

Acknowledgements

The authors thank the staff of the Uganda Public Health Fellowship Program for the technical support and guidance offered during this study. The authors also extend their appreciation to the Ministry of Health, National Public Health Emergency Operations Centre for the technical support they offered during this study. Finally, we appreciate the biostatisticians and surveillance officers who ensure reporting of surveillance data from their respective districts, as well as the team managing the DHIS2 platform; your hard work enabled the availability of data we used for this analysis.

Authors’ Contributions

RZ: participated in the conception, design, analysis, interpretation of the study and wrote the draft manuscript; MWW, GZ, PK, RM, DK, BK, PEO, RM, LB and FLA reviewed the report, reviewed the drafts of the manuscript for intellectual content and made multiple edits to the draft manuscript; RM, DK, FLA, BK, LB, JK, IM and ARA reviewed the manuscript to ensure intellectual content and scientific integrity. All authors read and approved the final manuscript.

Funding

The project was supported by the President’s Emergency Plan for AIDS (PEPFAR) through the United States Centers for Disease Control and Prevention Cooperative Agreement number GH001353-01 through Makerere University School of Public Health to the Uganda Public Health Fellowship Program, Ministry of Health. The contents of this manuscript are solely the responsibility of the authors and do not necessarily represent the official views of the US Centers for Diseases Control and Prevention, the Department of Health and Human Services, Makerere University School of Public Health, or the Ministry of Health.

The funders had no role in the study design, data collection, data analysis and decision to publish or preparation of the manuscript

Availability of data and materials

The datasets upon which our findings are based belong to the Uganda Public Health Fellowship Program. For confidentiality reasons, the datasets are not publicly available. The datasets can be availed upon reasonable request from the corresponding author with permission from the Uganda Public Health Fellowship Program.

Ethics approval and consent to participate

Because our study used routinely collected surveillance data reported by health facilities in the DHIS2 which were also aggregated with no individual patient identifiers, we did not seek for ethical approval. However, we sought permission to use the data from the Uganda MoH. The US Centers for Disease Control and Prevention (CDC) also provided the non-research determination (NRD) for non-human subjects which is equivalent to a waiver. Data were only accessed by the study team.

Consent to publication

Not applicable

Competing interests

The authors declare that they have no competing interests.

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The authors declare no competing interests.

Organophosphate poisoning temporal trends and spatial distribution, Uganda, 2017─2022

Status:

Version 1

Abstract

Introduction:

Methods

Results

Conclusion

Figures

Introduction

Methods

Study design and data source

Study variables, data abstraction, analysis, and management

Results

Incidence and case fatality rate of organophosphate poisoning, Uganda, 2017–2022

Overall trend of incidence of organophosphate poisoning admissions, Uganda 2017─2022

Trend of case fatality rate of organophosphate poisoning, Uganda 2017─2022

Spatial distribution of organophosphate poisoning admission incidence, district level, Uganda, 2017─2022

Discussion

Limitation

Conclusion

Abbreviations

Declarations

References

Additional Declarations

Status:

Version 1