Abstract
Introduction
Metallophosphide poisoning, mainly due to aluminum phosphide and zinc phosphide, is a growing public health problem in developing countries associated with a high mortality rate, including in Ethiopia, where it is used a fumigant for stored grains and agricultural commodities. Ethiopia lacks a well-organized poison control center, making it difficult to obtain primary data on metallophosphide poisoning cases and outcomes. This systematic review and meta-analysis aim to determine the pooled prevalence and mortality rate from metallophosphide poisoning in Ethiopia.
Methods
As of August 2024, PUBMED, EMBASE, SCOPUS, and GOOGLE SCHOLAR were inclusively searched. Two independent reviewers extracted the data. Quality was assessed using the Modified Newcastle-Ottawa Scale adapted for cross-sectional studies. A random effects model was used to obtain the pooled estimate of the prevalence of and mortality rate from metallophosphide poisoning.
Results
Fourteen studies with a sample size of 3218 were included in the final estimate. The pooled prevalence of metallophosphide poisoning in this systematic review and meta-analysis was 38% (95% CI: 0.14–0.71, I2 = 96.6%, p < 0.0001). In the teen-included studies for the pooled mortality analysis, the sample size was 677 and the pooled mortality rate was 37% (95 % CI: 0.22, 0.55, I2 = 87.8%, P < 0.0001).
Conclusion
We found a high pooled prevalence of metallophosphide poisoning in Ethiopia. This highlights the urgent need for regulatory actions to restrict the sales and distribution of these substances. This is supported by international experiences from similar low-resource settings. We recommend safer alternatives to control insects and rodents, such as mechanical rodent controls and integrated pest management. Public awareness creation and enhancing local management protocols to reduce the burden and improve the outcome of metallophosphide poisoning.
Supplementary Information
The online version contains supplementary material available at 10.1186/s12873-025-01294-w.
Keywords: Metallophosphide Poisoning, Aluminum Phosphide, Zinc Phosphide, Pooled Prevalence, Pooled Mortality Rate, Systematic Review, Meta-Analysis, Ethiopia
Introduction
Metallophosphide poisoning, which includes Aluminum phosphide and Zinc phosphide, is a rising public health problem as a means of committing suicide with increased morbidity and mortality in young adults of agriculturally driven economic societies [1, 2].
Metallophosphide phosphide can be absorbed into the body by oral ingestion, inhalation, and through damaged skin. Following oral ingestion, metallophosphide react in the stomach and intestine with water and hydrochloric acid to liberate phosphine gas [3]. The liberated phosphine gas is then quickly absorbed from both the gastrointestinal (GI) tract and respiratory mucosa [1]. Locally to the gastrointestinal tract, phosphine is corrosive. Once systemically absorbed, phosphine gas causes extensive oxidative damage to multiple organ systems and impedes cellular oxygen consumption, which disrupts aerobic respiration and cellular energy production at the mitochondrial level [1, 4]. It mainly produces an energy crisis in the cells and affects the cardiovascular tissues, lungs, gastrointestinal tract, and kidneys, although all organs can be involved [5].
The symptoms and signs include profound and refractory hypotension, tachycardia or bradycardia, palpitation, cardiac arrhythmias, electrocardiography (ECG) abnormalities, myocarditis, pericarditis and subendocardial infarction, pulmonary edema (tachypnea or dyspnea), disseminated intravascular coagulopathy, severe GI upset like nausea, repeated vomiting, abdominal discomfort or pain, and restlessness [6]. After ingestion, symptoms and signs could start within minutes or, rarely, take up to 24 hours to appear; even in severe cases, cardiovascular collapse and death may occur within hours [7, 8]. It is associated with a high mortality rate with no specific antidote but only supportive measures to save lives. The mainstay of treatments are early notification, diagnosis, resuscitation, intensive monitoring, and supportive care with gastrointestinal decontamination [9].
Ethiopia lacks a well-organized poison control center, making it difficult to obtain primary data on metallophosphide poisoning cases and mortality. Many studies have addressed other poisoning mechanisms like organophosphate [10, 11], but metallophosphide is understudied. Knowing the prevalence, trends and public health impact is important as it is becoming an emerging public health issue in ethiopia. Thus, we aimed to do this systematic review and meta-analysis study to determine the pooled prevalence and mortality rate. This study will assist health professionals, policymakers, programmers, and planners in developing and implementing case management and control strategies, as well as implementing effective interventions, to reduce the prevalence and preventable mortality burden of metallophosphide poisoning in Ethiopia.
Methods
The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA-2020) statement and checklist were followed in the conducting and reporting of this systematic review and meta-analysis.
Eligibility criteria
Inclusion and exclusion criteria; Eligibility criteria were set prior to the search. With no publication year restriction until August 2024, case series and primary research articles on human subjects conducted in Ethiopia that had pertinent data were included. Books, guidelines, case studies, and systematic reviews were not included.
Information source
We systematically searched electronic databases, including PubMed, Scopus, Embase, Google Scholar. and direct Google search, with the last date of August 2024, to find primary studies that are relevant to our study.
Searching strategies
A thorough searching technique was used to search the databases utilizing the Condition, Context, and Population (CoCoPop) criteria. Using a comprehensive searching strategy that includes common Boolean words such as (“Pattern” OR “Incidence” OR “Prevalence” OR “Epidemiology” AND (“Poisoning” OR “Zinc Phosphide” OR “Aluminum Phosphide” OR “Metallophosphide Poisoning” OR “Fumigant” OR “Rodenticide” OR “Rat Poisoning” OR “Insecticide”) AND “Ethiopia”.
Selection of studies
Peer-reviewed prospective or retrospective cohort studies, cross-sectional studies, and case-control studies that address the review question were retrieved. All identified and retrieved studies were exported to EndNote version 20 reference manager to manage and remove duplicates and for text citations. An agreed-upon screening tool was used by three independent reviewers (KDA, AWT, and SMW) to screen the included studies. Whenever there were discrepancies between these reviewers, a fourth reviewer (GBG) was involved.
Data collection process
Definition for data extraction
We developed an Excel sheet of data extraction tools for relevant data capture from the records for our systematic review and meta-analysis. Three review authors (KDA, AWT, and SMW) separately participated in data extraction. The extraction tools included the following data types: author, year of publication, year of data collection, study design, region, study design, sample size, and number of metallophosphide poisonings.
Data items
Risk of bias assessment
The quality of the included studies was evaluated by using the Modified Newcastle-Ottawa Scale for cross-sectional studies. The tool has three main criteria, which includes selection (representativeness of the sample, sample size, non-respondents and ascertainment of exposure) with maximum score of 4 stars; comparability between groups with a maximum score of 2 stars; and outcome assessment (assessment of the outcome and statistical test) with a maximum score of 3. The maximum possible score is 9. Studies with scores of 8 and 9 were labeled high quality, score of 6 and 7 were labeled as fair quality, and scores of ≤ 5 were labeled as poor quality. It was used to assess the quality of the individual and overall quality, and funnel plot visual inspection was done.
Effect measures
The pooled prevalence and pooled mortality rate were used. These were calculated as the number of patients and deaths from metallophosphide divided by the number of acute poisoning cases (sample size) in the studies, then multiplied by 100.
Synthesis methods
R statistical package version 4.4.1 was used for pooled prevalence with a 95 % confidence interval (CI) and forest plot. Test for heterogeneity between studies was assessed by calculating Cochran Q statistics, I2 statics, and P-values of Higgins I2-test statistics values of 25%, 50%, and 75% indicating low, moderate and high heterogeneity testing, respectively, and visually by the forest plot. A funnel plot was done to assess publication bias.
Results
Study selection
With meticulous search of different databases, PUBMED, EMBASE, SCOPUS, and GOOGLE SCHOLAR, 959 studies were retrieved. After duplications were removed and studies were excluded for different reasons as shown in (Fig. 1), fourteen studies were analyzed.
Fig. 1.
PRISMA 2020 flow diagram for new systematic reviews which included searches of databases and registers only
Characteristics of studies
Six of the 14 research studies that made up the final analysis were conducted in the Amhara region, four in the Oromia region, three in Addis Ababa, and one in Harar. Four were released in 2020 or earlier (Table 1). The quality of the included studies was assessed using the Newcastle-Ottawa scale as shown below (Fig. 2 and 3).
Table 1.
Characteristics of fourteen studies selected for systematic review and meta-analysis
| Author | Pub/ year |
Study design | Regions | Sample size | Response rate (number) | Total death | Death (Metallophosphide (number) |
|---|---|---|---|---|---|---|---|
| Chala et.al [9] | 2015 | Descriptive | Oromia, Adama | 292 | 28 | 24 | 4 |
| Asrie et.al [10] | 2024 | Observational | Amhara, Ethiopia | 442 | 141 | 78 | 47 |
| Teym et.al [11] | 2023 | Cross-sectional | Northwest Ethiopia | 315 | 79 | 55 | |
| woyessa et.al [12] | 2020 | Cross-sectional | Western Ethiopia | 211 | 8 | 15 | |
| waktola et.al [13] | 2023 | Cross-sectional | Northwest Ethiopia | 233 | 74 | 26 | 24 |
| Shumet et.al [14] | 2022 | Cross-sectional | Northwest Ethiopia | 121 | 92 | 75 | 72 |
| bogale et.al [15] | 2021 | Cross-sectional | Northwest Ethiopia | 125 | 125 | 39 | 39 |
| tassew et.al [16] | 2023 | Cross-sectional | Northcentral, Ethiopia | 156 | 156 | 68 | 77 |
| reda et.al [17] | 2023 | Cross-sectional | Northwest, Ethiopia | 400 | 129 | 72 | |
| Bereda et.al [18] | 2021 | Cross-sectional | Southwest, Ethiopia | 76 | 15 | 45 | |
| Eyasu et.al [19] | 2017 | Descriptive | Addis Ababa, Ethiopia | 592 | 38 | 7 | 1 |
| Zemedie et.al [20] | 2021 | Cross-sectional | Northeastern, Ethiopia | 98 | 7 | 10 | 2 |
| Nigusse et.al [21] | 2022 | Cross-sectional | Eastern Ethiopia | 150 | 9 | 65 | 5 |
| Mohammed et.al [22] | 2017 | Case series | Addis Ababa | 7 | 7 | 5 | 5 |
Fig. 2.
Risk of bias in individual studies
Fig. 3.
Overall Quality of studies based on Newcastle-Ottawa Scale
Result of synthesis for prevalence
The final analysis includes 14 studies with a total sample size of 3218. The final pooled prevalence of the metallophosphide poisoning in this SRMA was 38% (95% CI: 0.14–0.71, I2 = 96.6%). Since the included studies show high heterogeneity, which was shown by the high I2 test (I2 = 96.6%); the model employed a random effect (I2 = 96.4% [95.2%; 97.3%], p < 0.0001) rather than Fixed effect model, which is used for studies with same true size (no heterogeneity beyond chance) (Fig. 4). To assess publication bias in the included studies, funnel plot visual inspection was done (Figs. 5 and 6), and it shows asymmetry and hence trim and fill analysis was done (Figs. 7 and 8).
Fig. 4.
The pooled prevalence of metallophosphides poisoning in Ethiopia
Fig. 5.
Funnel plot analysis of included studies for pooled prevalence
Fig. 6.
Funnel plot analysis of included studies for mortality
Fig. 7.
Fill and trim funnel plot analysis for pooled prevalence
Fig. 8.
Fill and trim funnel plot analysis for mortality
Result of synthesis for mortality
Ten studies with a sample size of 677 were included in the final analysis. The pooled prevalence was 37 % (95 % CI: 0.22, 0.55, I2 = 87.8 %). The I2 test revealed high heterogeneity among included studies; the model used a random effect (I2 = 87.8 %, P < 0.0001) (Fig. 9).
Fig. 9.
The pooled mortality of metallophosphides poisoning in Ethiopia
Discussion
This systematic review and meta-analysis revealed that the pooled prevalence (38% with 95% CI: 0.14–0.71, I2 = 96.6%) and pooled mortality rate (37 % with 95 % CI: 0.22, 0.55, I2 = 87.8 %, P < 0.0001) of metallophosphide poisoning in Ethiopia are notably high. The findings from this study are much higher than the findings from previous systematic reviews of observational studies on patterns and epidemiology of acute poisoning in Ethiopia, which identified that organophosphates and household cleansing agents were the predominant agents of acute poisoning [11, 12]. Our study found that metallophosphide poisoning is emerging as a public health concern, especially in agriculturally dependent segments of populations.
The pooled mortality rate observed in our study is lower than reports from a study of 418 patients found, a mortality rate of 77.2% [13] and a case fatality ratio of 44% (317/140) reported from Albania [14]. This discrepancy may be because our analysis included zinc phosphide, which is a relatively less toxic form of metallophosphide [15] and exposure to air and humidity, which lessens its toxicity in our cases [16]. Though mortality rates from metallophosphide poisoning vary across the globe, consistently high fatality rates indicate the inherent lethality of these substances [17–19]. Other countries having similar agriculture-dependent economies and challenges related to regulations, such as India and Sri Lanka, face the same high incidence and mortality from metallophosphide poisoning [20–22]. This is often linked to the absence of restricted access to toxic substances and limited healthcare infrastructure [23–25]. Studies show that organophosphate poisoning and therapeutic drug overdose are the commonest forms of poisoning in urban societies, while pesticides and rodenticides are the most common in rural areas [26]. These findings highlight that metallophosphide poisoning is becoming an emerging means of committing suicide in young, productive, agricultural-driven societies.
Several factors contribute to the high prevalence of metallophosphide poisoning in Ethiopia such as a heavy reliance of the country’s economy on agriculture, which forces a high spread use of pesticides and fumigants for crop protection, which in turn leads to both intentional and accidental exposure to poisons especially among the younger, productive age segments [27, 28]. The lack of strong regulations to enforce the sale, distribution, and safe storage of toxic substances also contributes to the higher incidence of metallophosphide poisonings. In addition, the increased mortality rate of metallophosphide poisoning can be attributed to the absence of specific antidotes and limited resources for advanced care in Ethiopia.
Given the lethality and unavailability of antidotes for metallophosphide poisoning, multifaced responses are urgently needed in Ethiopia to tackle this threat to public health including implementation of stringent regulations on the sales and distribution, public awareness creation on handling and storage of pesticides, and the dangers associated with misuse, and even establishment of poison control centers capable of doing surveillance and coordinate emergency responses [29–31]. Capacity-building training should also be delivered to healthcare providers, and standard clinical management protocols should be developed to improve patient outcomes [14]. Nationwide prospective studies incorporating various aspects of poisoning, including socioeconomic, mental health, and environmental factors related to poisoning, should be conducted to better understand the contributing factors and effective interventions.
Limitations
Since this is a systematic review and meta-analysis of published articles that had a high heterogeneity of articles, it missed some important socioeconomic and mental health indicators, and discrepancies in the quality of included primary studies. Future prospective nationwide studies to address these gaps are warranted.
Conclusions
This high pooled prevalence and mortality rate of metallophosphide poisoning in Ethiopia reflects a confluence of agricultural dependency, regulatory gaps, and socioeconomic vulnerability. The Ethiopian burden surpasses the African average, necessitating context-specific interventions with multisectoral strategies.
Recommendations
This study revealed the emergence of metallophosphides as a major public health threats in Ethiopia, which needs to be addressed through multifaceted approaches, including policy-level interventions to restrict the sales and distribution of the substances, and the use of safer alternative fumigants and rodenticides should be promoted. National Toxicology and Poison Control Center must be established for coordinated responses. We also recommend the development of specialized poison management units within hospitals equipped with trained personnel, standardized protocols and guidelines, equipment, and drugs, including antidotes. Targeted educational campaigns to rural and agricultural populations to create awareness about the dangers of metallophosphides, safe handling, and storage must be delivered. Wider future research to determine the true prevalence and mortality rates, as well as to evaluate the effectiveness of current management approaches, and suggest newer approaches, must be conducted. Treatment outcome and mortality rate.
Electronic supplementary material
Below is the link to the electronic supplementary material.
Acknowledgments
We would like to acknowledge the authors of the primary studies.
Abbreviations
- ALP
Aluminum phosphide
- CoCoPop
Condition, Context and Population
- ECG
Electrocardiography
- GI
Gastro-Intestinal (GI) tract
- PH3
Phosphine gas
- PRISMA
Preferred Reporting Items for Systematic Reviews and Meta-Analyses
- Zn3P2
zinc phosphide
Author contributions
Conceptualization: Kassaye Demeke Altaye, Adina Worku Teka, Saron Mulugeta Worku, Data curation: Kassaye Demeke Altaye, Adina Worku Teka, Saron Mulugeta Worku, Bikis Liyew Methodology: Kassaye Demeke Altaye, Geta Bayu Genet, Nahom Worku Teshager Data analysis: Kassaye Demeke Altaye, Geta Bayu Genet, Bikis Liyew, Nahom Worku Teshager Writing-original draft: Kassaye Demeke Altaye, Bethelhem Yenenew Assefa, Nahom Worku Teshager Writing-proofreading: Kassaye Demeke Altaye, Bethelhem Yenenew Assefa, Bikis Liyew, Nahom Worku Teshager.
Funding
No funding received.
Data availability
The dataset used to support the findings of this study is available from the corresponding author upon request.
Declarations
Ethics, consent to participate, and consent to publish declarations
Not applicable.
Competing interests
The authors declare that there are no conflicts of interests.
Footnotes
Registered on PROSPERO: https://www.crd.york.ac.uk/PROSPERO/view/CRD42025640032.
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Data Availability Statement
The dataset used to support the findings of this study is available from the corresponding author upon request.