The Role of Cyano-HAB (Cyanobacteria Harmful Algal Blooms) in the One Health Approach to Global Health

Abstract

Harmful algal bloom events occur in salt, brackish, and fresh water. In bodies of water such as oceans and estuaries, diatoms or dinoflagellates form “tides” that produce toxins associated with seafood poisoning, including paralytic shellfish poisoning, or respiratory distress from inhalation of aerosolized toxins. Cyanobacteria predominantly bloom in fresh water; they can produce microcystins; cylindrospermopsin; and other toxins that humans or animals might be exposed to through water contact, inhalation, or ingestion. Animals that become ill or die can be sentinels for harmful algal bloom events. In a One Health approach, information about harmful algal bloom exposures and health effects support efforts to detect these events and mitigate and prevent associated illnesses. Human, animal, and environmental health partners can work together to document the occurrence and impacts of harmful algal bloom events and characterize associated illnesses.

1. Introduction

One Health is a term increasingly used at the beginning of the 21st century to highlight how the concept of health is based on interdependent collaborations among human and animal health professionals, wildlife, and environmental sciences [1,2]. However, the concept of One Health as a more inclusive way to study and maintain health within an interspecies continuum is ancient. The authors of [3] provided overviews of the origins, scope, systems thinking, and value of One Health, including how the Chinese Zhou dynasty (11th–13th century) organized public health systems involving both physicians and veterinarians. In 1960, Rachel Carson made connections between the application of highly toxic pesticides and negative effects on human, domestic, terrestrial, and aquatic wildlife health. A One Health approach would have benefited all those involved in a methylmercury poisoning incident in Japan in 1950 [4]. Prolonged industrial release of methylmercury into waters off the coast of Minamata first poisoned fish and then birds, followed by cats, and then thousands of humans fell ill as the toxin spread throughout the food chain. Insights into infectious diseases have been explained by scientists such as Edward Jenner when, in developing a vaccine against smallpox (a human disease), he demonstrated the cross-reactivity of human antibodies between smallpox and the less pathogenic cowpox (an animal disease). Countless other scientists, physicians, and public health professionals worked within the One Health to address zoonotic diseases food and water safety and environmental protection to optimize the health and well-being of people on Earth.

In short, One Health is a paradigm that recognizes the interdependence of human, animal, plant, microbial, and ecosystem health (The One Health Initiative). Effective multidisciplinary research, surveillance, and management are essential for synchronous improvements in the health of humans, other animals, plants, and ecosystems [1] The One Health framework provides an interdisciplinary paradigm that seeks to optimize fitness with the aid of using leveraging present assets and talents amongst human, veterinary, and air quality professionals to deal with some of the most complex multidisciplinary challenges that define the 21st century. Reports on human health and animal health tend to be published separately and discussed separately. However, harmful cyanobacteria impact both humans and animals. Animals often suffer direct and high-intensity exposures to harmful cyanobacteria that cause disease and death. Animal diseases or deaths associated with cyanobacteria can therefore be used to warn of risks and, with due attention, can enable the implementation of actions to avoid negative effects on human health [5].

2. Cyanobacteria Characteristics and Their Toxins

Algae are autotrophic organisms typically found in aquatic environments, classified (as of 2023) into the following divisions:

Cyanobacteria; Chlorophyta; Chromophyta; Euglenophyta; Pyrrophyta; Rhodophyta; Cryptophyta, and a final group encompassing all uncertain attributions. Approximately 6000 species have been identified, with 300 species (comprising phytoplankton) capable of blooming in concentrations sufficient to color the water. In their metabolism, many species can produce biologically active molecules, or biotoxins. While cyanobacteria are a natural presence in the environment, anthropogenic activities now contribute to the global increase in cyano-HABs [6].

Nutrient pollution from human and animal waste, extensive use of fertilizers, combustion of plant material, excessive grazing, warmer climates, drought conditions reducing nutrient absorption by terrestrial plants, and the depth and flow of water bodies are all factors contributing to algal bloom formation [7]. In 2002, bloom incidence was detected in all countries worldwide, including Antarctica [8]. Conditions favoring cyanobacterial presence are expected to increase based on projections of future human population growth, land use patterns, and climate changes [9]. Many cyanobacterial genera produce potent toxins as secondary metabolites (cyanotoxins), some of which are released before and others largely after the cyanobacteria lyse, causing large-scale deaths of fish and domestic animals, as well as human poisoning cases worldwide. Furthermore, they lead to bioaccumulation in fish, shellfish, and crops [10,11], resulting in toxicity to humans and poisoning in animals. Some of these biotoxins (microcystins, β-N-methylamino-L-alanine BMAA) are capable of forming an odorless aerosol that can reach surrounding areas during bloom periods [12,13,14]. Blooms can increase cell density and toxic concentration within hours; during their decline, water may appear clean again, yet toxin levels can be at their highest. The incidence of minor symptoms (nausea, vomiting, diarrhea) associated with recreational exposure are likely underestimated since some bathers with more severe illnesses seek emergency medical facilities, most refer to their family doctor, or do not seek medical attention at all, managing the illness at home. This leads to a lack of awareness about the health phenomenon’s extent and its real impact on the bathing population. Additionally, the medical inexperience of emergency facilities regarding algal toxin poisoning and its epidemiology can lead to misdiagnosis and inadequate medical care. This issue can be addressed through the development of medical information and epidemiological systems, the establishment of training courses, and the creation of web medical sites on algal toxins, guiding primary care physicians towards the concept of prevention and proper aquatic ecology management. During a bloom event, children and individuals with existing conditions should be considered at-risk groups.

It should also be noted that not all toxic species have been identified, and not all toxins discovered. New findings are periodically under scientific scrutiny, as are new reports in geographical areas previously considered safe. For instance, in Italy, over ten years (1993–2003), reports of algal blooms tripled, and within these, reports of toxic blooms quintupled on average. Biotoxins are not produced exclusively by one species but are often common products across many species: for example, anatoxin-a is produced by several species of the genera Anabaena Bory ex Bornet and Flahault 1886, Oscillatoria Schaffner 1922, Aphanizomenon Morren ex Bornet and Flahault 1888, and Planktothrix Anagnostidis and Komárek 1988; microcystins are produced by Microcystis Kützing ex Lemmermann 1907 M. aeruginosa, M. viridis, M. botrys, Oscillatoria limosa, Anabaena flos-aquae, A. lemmermannii, A. circinalis, Planktothrix agardhii, P. rubescens, P. mougeotii, various Nostoc Agardh ex Kirchner 1890 species, Anabaenopsis milleri, Haphalosiphon hibernicus, and Gleotrichia sp.; Cylindrospermopsin is produced by Cylindrospermopsis raciborskii, Aphanizomenon ovalisporum, Aph. flos-aquae, Aph. gracile, Umezakia natans, Anabaena bergii, Anabaena lapponica, Raphidiopsis curvata, and Lyngbya wollei [15].

Microcystins, in particular, are cyclic peptides made up of seven amino acids, are hydrophobic, and have many structural variants (over 250 microcystins have been isolated and characterized worldwide so far) [16].

Microcystins are present in freshwater, brackish water, and even marine waters (e.g., cases of hepatic poisoning in net-pen-reared salmon). The proportion of individual microcystin (MC) variants in a single strain depends on time, light intensity, and temperature: for example, Planktothrix spp. prefer low light intensity, while Anabaena spp. prefer moderate light intensity. High and low pH levels favor toxin production. In addition to and concurrent with microcystins, cyanobacteria essentially produce four groups of toxins [17]: -peptides containing the Ahp group, -linear peptides, -anabaenopeptilides-aeruginosins, to which, over time, have been added: aeruginopeptins, microginins, microviridins, cyanopeptolins, planktopeptins, largamides, oscillamides, micropeptins, along with other major toxins anatoxin-a, cylindrospermopsin, and saxitoxin analogs. Microcystins and cylindrospermopsins are very stable in water and resistant to boiling; they degrade slowly in nature, more rapidly in sunlight than under ultraviolet (UV) rays; moreover, beached blooms that dry in the sun may contain high levels of microcystins for months. Cyanobacteria often produce, during their life cycle, senescence, and decomposition, compounds with unpleasant taste and odor, such as geosmin and 2-methylisoborneol [18,19]. Generally, these odor-causing compounds are not considered to pose serious health risks, but their potential toxicity has been little studied. It is important to emphasize that they may indicate the need to prevent human and animal exposure to water that may also contain potentially lethal cyanotoxins [18]. Cyanobacterial blooms have negatively impacted human and animal health for thousands of years. However, reports of human and animal diseases or deaths associated with harmful cyanobacterial blooms tend to be studied and reported separately. As a result, professionals working in human or animal health fields do not always communicate their findings related to these events. Figure 1 illustrates the diversified production of cyanotoxins and other cyanopeptides in blooms analyzed in eutrophic reservoirs across almost all Italian regions.

Utilizing the One Health concept, which is the integrated and collaborative approach across health disciplines, a 2015 study [20] reviewed all existing literature to uncover instances where diseases and deaths among livestock, dogs, fish, and other animals associated with toxic blooms served as sentinel events to warn of potential risks to human health. It was found that diseases or deaths among livestock, dogs, and fish all served as useful indicators of potential human health risks from toxic blooms.

Efficient monitoring of environmental conditions and animal health within a One Health framework can provide vital warnings of the human health risks associated with toxic cyanobacterial blooms. The incorporation of the One Health approach emphasizes the interconnectedness of human, animal, and environmental health, underscoring the importance of a multi-disciplinary response to the challenges posed by cyanobacterial blooms. This approach not only aids in the early detection and mitigation of risks but also fosters a comprehensive understanding of the ecological dynamics contributing to the proliferation of cyanobacteria and their toxins. Such an understanding is crucial for developing strategies to prevent and manage harmful algal blooms, thereby safeguarding public health and preserving aquatic ecosystems.

3. Cases of Health Effects on Animals

In the year 1672, English merchant-naturalist Christopher Kirkby published an article in the scientific journal “Philosophical Transactions of the Royal Society”, in which he reported a peculiar phenomenon observed during one of his travels: the surface of Lake Tucholskie (near Gdańsk, in present-day Poland) had turned a brilliant greenish-yellow due to a “filamentous inflorescence”, and domestic animals drinking from it died from poisoning. Kirkby’s account is considered the first scientific testimony of a harmful algal bloom (HAB), a bloom potentially harmful to humans and their activities.

Toxic blooms and their adverse health consequences on associated animals have been recorded for over 180 years; the first published report believed to document a harmful cyanobacterial bloom was by Hald to the Danish government in 1833. Hald described the death of cattle and fish associated with “sick” lakes where green material covered the water’s surface. The bloom material was not characterized. Hald wrote of not knowing whether the green substance was caused by aquatic plants, insects, or minerals [21].

Initially, waters were suspected to be harmful due to the temporal and spatial proximity of dead or dying animals observed within and around a bloom. Although the toxicity of these aquatic “plant” materials was hypothesized from the observation of animal deaths associated with them, the toxicogenic organisms and the toxic principles themselves were not characterized.

Francis was the first to scientifically investigate the toxic effects of a cyanobacterial bloom [22]. Following a mass death of livestock around Lake Alexandrina in Australia, he administered a sample of the bloom material from Nodularia spumigena in the lake to a sheep. He then compared the results of the experimentally exposed animal’s autopsy with sheep that had died following natural exposure to the bloom and concluded that cyanobacteria were the source of the toxic effects.

Toxic cyanobacteria can negatively affect wildlife, livestock, and pets. Schwimmer and Schwimmer (1968) [23] collected and summarized over 65 wildlife, livestock, and pet mortality events associated with cyanobacteria for the period 1878–1960. Animal deaths associated with harmful cyanobacteria have been reported in Europe, North America, South America, Australia, Africa, and Asia [22,24,25,26,27,28,29], providing a selective review of published reports of animal morbidity and mortality events associated with cyanobacteria worldwide, with case studies representative of livestock, pet, and wildlife deaths.

Reports of livestock deaths following exposures to cyanobacteria have been reported from every inhabited continent and have involved ruminants, pigs, horses, poultry, farmed fish, and even honeybees [30,31,32,33,34]. Livestock with access to agricultural ponds and lake sections can be at risk during a bloom, especially when surface blooms driven by wind accumulate at the water access site for animals. Overflow of bloom material from farm ponds, contaminating the grazing area for animals, can also be a source of poisoning for livestock [35]. Antemortem signs of intoxication vary and depend on the cyanotoxins, dose, and exposure timing; therapeutic interventions employed; and the individual characteristics of the exposed animals. Acute effects often include hypersalivation, agitation, anorexia, pale mucous membranes, weakness, dyspnea, recumbency, depression, ataxia, diarrhea, muscle tremors and fasciculations, convulsions, apparent blindness, and sudden death [36,37,38]. Birds may show weakness and neurological signs such as ataxia and hyperextended neck (opisthotonos) before death. Cyanobacteria have been associated with mass mortality events in farmed catfish and carp; microcystins in the water were accompanied by clinical signs of disease and macroscopic lesions in the liver [32,33,34,39] Due to microcystin residues, the latter authors cautioned against human consumption of tissues from contaminated fish.

Reports of poisonings and deaths of pets associated with cyanobacteria have more frequently involved dogs. Dogs can be in contact with cyanobacterial blooms that accumulate near the shore, drink contaminated water, and lick bloom material from their fur after swimming [38]. A recent summary of dog deaths associated with cyanobacteria in the United States compiles over 100 reports over the last 80 years [40]. The frequency of reporting such events has significantly increased since the 1970s; however, reporting biases, attribution, and detection have all influenced the number of events confirmed to be associated with cyanobacteria. Acute effects among pets include vomiting, diarrhea, excessive salivation, weakness, seizures, hemorrhages, and sudden death [41,42].

Wild animal deaths associated with toxic freshwater cyanobacterial blooms are commonly reported, but undoubtedly many occur unreported due to a lack of human observation of the event. Several types of vertebrates can be harmed, from fish to birds to mammals [43,44,45,46]. In some cases, it is not always possible to attribute wildlife deaths to harmful cyanobacteria because when animals are found, the bodies are too decomposed for reliable pathological and toxicological analyses. Fish and aquatic birds run a particularly high risk of harmful effects associated with cyanobacteria and have been reported in mass mortality events on most continents [25,28,39,44,47,48]. Cyanobacterial blooms can have both direct and indirect negative effects on fish and aquatic birds: intoxication may occur after direct exposure to cyanobacteria or food and water contaminated by cyanotoxins; indirect effects of cyanobacterial blooms include a decrease in dissolved oxygen and the proliferation of Clostridium botulinum [49]. Large mortality events have occurred when birds were poisoned by botulinic toxin in aquatic environments [50,51].

Cyanotoxins accumulate in aquatic organisms like phytoplankton, zooplankton, gastropods, copepods, crab larvae, mollusks (hepatopancreas), crustaceans (hepatopancreas and muscle), and fish (liver and muscle) and thus travel up the freshwater food chain [51]. Irrigation with contaminated water can cause the presence of cyanobacteria and the accumulation of cyanotoxins in vegetables, such as lettuce (in the leaves), turnips, and rice seeds; the consumption of foods or vegetables grown with irrigation water contaminated by cyanobacteria and cyanotoxins poses a health issue for consumers [52,53,54].

Routes of contamination in fish include ingestion and absorption through the gill epithelium [55]. The main target organs are the liver, kidneys, and gills, with pathologies caused by the inhibition of protein phosphatases (PP), effects on the development of juvenile stages, and changes in behavior [56,57]. The toxicity of microcystins in fish depends on the balance between accumulation and metabolism; the detoxification capacity through the glutathione-S-transferase pathway is species-specific, as is the sensitivity to toxins [58]. Tissue concentrations indicate that even the consumption of the muscle tissue of contaminated fish can pose a risk to human health [59] The concentration in fish is also a direct consequence of several factors, whose variation can be responsible for the differing results obtained in field studies. In our studies, we found that ELISA (enzyme-linked immunosorbent assay) measurements of total microcystins in water are significantly higher if, instead of analyzing the whole sample, the extracellular and intracellular toxin are quantified separately and then the results are added together. High toxin concentrations can also be detected even in the presence of low cell counts because the release into the water occurs during the senescence of the bloom and cellular lysis [60]. Therefore, the mere microscopic counting of cells often does not provide a reliable indication of the amount of toxin in the water. The presence of microcystins in the tissues of valuable fish stock also implies toxic effects exerted during growth and normal development of individuals, which under these conditions present fish stocks with reduced average weight and decreased adaptability [55,56,57,58,59,60,61].

4. Cases of Human Health Effects

Human health can be adversely affected by toxin-producing cyanobacteria from multiple sources and through various exposure pathways. The most impactful outbreaks of intoxications and deaths associated with cyanobacteria have been reported when patients requiring hemodialysis were directly exposed to cyanotoxins intravenously through dialysis prepared from contaminated water [62,63]. This exposure route to cyanotoxins has caused toxic hepatitis, multi-organ damage, and death [62,63,64,65]. Humans are more commonly exposed to harmful cyanobacteria through the oral and dermal route, as well as occasionally through inhalation exposure to cyanobacterial cells and mixtures of cyanotoxins during recreational activities on or in untreated surface waters [66,67,68,69,70]. Occasionally, these exposures have caused severe respiratory compromise characterized by pneumonia and acute respiratory distress syndrome [60,63].

Short-term effects caused by microcystins include gastroenteritis (also periodic); nausea; vomiting; visual disturbances; muscle pains; allergic reactions; conjunctivitis; dermatitis; mouth ulcers; inhibition of protein phosphatases 1 (PP-1) and 2A (PP-2A) leading to hyperphosphorylation of cellular proteins and disruption of important cellular mechanisms; and structural and functional liver damage resulting in hepatotoxicity and nephrotoxicity, both acute and chronic. Microcystins [71] also act as tumor promoters, double insulin release in rat RINm5F cells, derepress progesterone synthesis in rat corpus luteum cells, decrease aldosterone production in rat ZG cortex cells, reduce iron uptake in rabbit reticulocytes, cause up to a 28% increase in primary adherence in human polymorphonuclear leukocytes, depress immune activity, cause apoptosis in human lymphocytes, and induce colon cancer in initiated mice. The most famous mass intoxication events detected were due to the consumption of water contaminated by toxic blooms, caused in Brazil by the eutrophication of the reservoir created by the Itaparica dam (Bahia), with 2000 cases of gastroenteritis, of which 88 were fatal (affecting elderly, children, and adults), and the use of contaminated water in dialysis fluid at the Caruaru hospital in Pernambuco, with 117 cases of poisoning, of which 65 were fatal. Less severe intoxication effects include fever; other respiratory illnesses, symptoms of respiratory and skin allergies; and dermatological, gastrointestinal, neurological, otic, and ocular symptoms [70,71,72,73,74,75,76,77,78]. Toxic levels measured in various countries have revealed the onset of acute effects between 0.1 and 0.5 µg/L of microcystin in drinking water (Finland, 1989) and up to 0.82 µg/L in Sweden in 1994 [79], with chronic effects from an intake of 2.2–3.9 µg/day/adult and 0.4–2.0 µg/day/child in China [80].

The first European case of periodic contamination of the water supply network was documented in Riga. This city, the capital of Latvia, is surrounded by many lakes made eutrophic by numerous discharges of domestic and industrial wastewater. One of these, Lake Mazais Baltezers, is used for the artificial recharge of groundwater (Quaternary aquifer) through infiltration basins. The water quality of this lake is crucial as the groundwater is used as a source of drinking water, but by the end of summer, significant toxic cyanobacterial blooms occur in this lake, with the presence of microcystin-LR. The toxins were analyzed in samples of surface water and drinking water to assess the purification efficiency of the geological layers traversed by the recharged aquifers. A study by Eynard et al. [81] demonstrated that Lake Mazais Baltezers was vulnerable due to human activities and the water quality could rapidly vary because of cyanobacteria, with microcystin contamination detected up to 250 ng/L in groundwater around lakes used as water reservoirs, and up to 1470 ng/L in pumping stations. The soil in this area was not sufficiently effective to protect groundwater and drinking water from toxins during the bloom period (August–September), and it seemed that toxins were not degraded in the soil, which created concern because the consumption of subacute levels could be harmful to human health. The concentrations of toxins detected indicated that the water source should have been monitored and measures should have been introduced to control blooms and remove toxins from the water. In microcystins, the dose–response curve is steep: acute damage manifests as soon as the threshold is reached; the linear form (product of breakdown or precursor) is still toxic, although 100 times less toxic compared to the cyclic toxin. Occupational exposure to harmful cyanobacteria has been reported after routine work on an accidentally contaminated surface water body, in relation to the investigation of a cyanobacterial bloom, and following an investigation into diseases and deaths in animals associated with cyanobacteria. Microcystins induce high-level activation of the proto-oncogenes c-fos, c-jun, and c-myc, and through the inhibition of protein phosphatases by means of subacute doses, also causing inactivation of DNA repair enzymes [82].

Combined with the action of a mutagen, or alone, this activity can promote the development of neoplastic alterations, activating tumor growth. Drinking water contaminated by harmful cyanobacteria has been associated with liver and kidney damage [83,84] with severe manifestations, prolonged hospitalizations, and deaths [84,85,86]. Acute health effects such as gastroenteritis, muscle pains, and dermatitis associated with the domestic use of contaminated drinking water have been reported [78,87]. If municipal systems are contaminated, a large number of people can be exposed and become ill [88,89,90,91]. The incidence of tumors from the presence of microcystins in drinking waters has been investigated by various research groups around the world, starting from 1996 [92] for the correlation between primary liver cancer and consumption of water contaminated with microcystins from surface reservoirs and wells with depths < 200 m by Fleming et al. (2002) [93] for increased risk of primary liver carcinoma in Florida due to water from untreated aqueducts, by Zhou et al. [94] in the city of Haining for the incidence of colorectal cancer seven times higher for consumption of water from river or lake compared to tap or well water, by Svircev et al. [95] for the increased incidence of primary liver carcinoma in Serbia due to consumption of water from untreated aqueducts, and by Gorham et al. [96] also on the increased incidence of hepatocarcinoma in cities in Ohio served by drinking waters from sources contaminated by cyanobacteria.

In China, the district of Qi-Dong, where the detected incidence of liver carcinoma was eight times higher than in areas where well water is consumed instead of pond or lake water, has been a field of experimentation in territorial prevention for thirty-one years to successfully decrease the cancer incidence rate by acting with mass vaccinations against hepatitis B, changing dietary habits to block exposure to aflatoxins, and purifying drinking waters, as well as changing their sources of supply [80]. Furthermore, involuntary exposure through inhalation of cyanotoxins during activities on or in contaminated waters has been documented [97]. As for exposure through recreational activities, numerous reports exist worldwide. In Saskatchewan, Canada, 10 children fell ill with diarrhea after swimming in a lake covered in cyanobacteria. Anabaena cells were found in the feces of one child [98]. Since then, it has been shown that Anabaena (many of which now belong to the genus Dolichospermum) is a significant producer of MC in Canada [99]. In the United Kingdom, 10 out of 18 army recruits during a military exercise in a basin with a Microcystis aeruginosa bloom reported abdominal pain, nausea, vomiting, diarrhea, sore throat, dry cough, mouth blisters, and headache. Two were hospitalized and developed atypical pneumonia. Serum enzymes indicative of liver damage were elevated. MC-LR was identified in the bloom material [100]. In Argentina in 2007, an acute intoxication caused by a cyanobacterial bloom producing MC in waters used for recreational purposes occurred [69]. A 19-year-old individual bathed in a Microcystis bloom for at least 2 h. A concentration of 48.6 μg/L (total MCs—cell-bound and free) was detected in the water within 4 h of exposure. Hours after exposure, the patient exhibited fever, nausea, and abdominal pain and was admitted to a medical center. Initially, the patient suffered from hypoxemia and renal failure with reduced platelet count and increased leukocytes, but within 3 days from admission developed signs of liver damage (increase in aspartate aminotransferase [AST], alanine aminotransferase [ALT], and GGT, but normal bilirubin and alkaline phosphatase [ALP]). Tests for HIV, Epstein–Barr virus, Chlamydia pneumoniae, and Mycoplasma were negative. The patient fully recovered after 20 days. In Montevideo, Uruguay, a 20-month-old child was admitted to the hospital following repeated recreational exposures to Microcystis blooms containing MCs up to 8200 µg/L [101]. Over 5 days, the child developed fatigue and jaundice before being admitted to intensive care. ALT, AST, and serum bilirubin were elevated. The patient tested negative for hepatitis A, B, and C viruses; Epstein–Barr virus; and cytomegalovirus. The initial diagnosis was type II autoimmune hepatitis, but the patient did not respond to immunosuppressants (methylprednisolone and cyclosporine). Twenty days after admission, a liver transplant was performed, after which the child recovered. Histopathological examination of the removed liver showed extensive hepatocellular damage, hemorrhage, and nodular regeneration without inflammation. A methanolic extract of a 20 g liver sample contained MC-LR at 2.4 ng/g and [D-Leu1]MC-LR at 75.4 ng/g. Zhou [94] reported that the use of drinking water reserves contaminated by microcystins was associated with higher rates of colorectal cancer in human populations in some parts of China. These findings were confirmed by the epidemiological study of Gorham et al. [96] on the water supply sources of five large cities in Ohio. The conventional treatment of drinking water, which involves filtration, flocculation, and disinfection, reduces but does not always eliminate cyanobacteria and cyanotoxins; more sophisticated methods are needed to reduce cyanotoxins in drinking water to acceptable concentrations [102]. However, drinking water treatment processes can still be compromised or rendered ineffective when large amounts of cyanobacterial biomass enter the water source intake. Some poorly characterized human health risks also include repeated voluntary exposure to cyanotoxins through the ingestion of cyanobacteria as food or supplements [103,104,105], with contaminations of health food products (algae-based supplements) and cosmetics also recorded, as a consequence of accidental contamination of Aphanizomenon flos-aquae lyophilisate with microcystin-producing cyanobacteria (M. aeruginosa).

In 1996, a monitoring in the United States revealed that 97% of such samples were contaminated by microcystins. The International Agency for Research on Cancer (IARC) established in 2010 that the promotion of liver tumors by these toxins is plausible [105]. Unlike the World Health Organization (WHO), which proposed in 1999 [79] and subsequently maintained a single threshold value (tolerable daily intake, TDI) of 0.04 µg/kg, the U.S. Environmental Protection Agency (US EPA) has proposed a TDI to avert acute effect of 0.006 µg/kg since November 2006, as well as a threshold value to prevent chronic effect of 0.003 µg/kg [106]. The same US EPA in 2015 set the health advisory level for a maximum of 10 days of intake, i.e., the maximum intake level considered protective against non-carcinogenic adverse effects (TDHA), at 0.3 µg/L for infants and 1.6 µg/L for all others, including adults [107].

5. Italian Cases

Several cases of Italian lakes (Figure 1) have been studied by our group over the course of several years, revealing widespread contamination in the environment due to cyanotoxins originating from periodic toxic blooms that occur in these water bodies. Here, we present three emblematic cases: Lake Vico (Lazio, Viterbo, Italy), Lake Albano (Lazio, Rome, Italy), and Lake Occhito (Molise, Campobasso, Italy).

5.1. Lake Vico

Lake Vico (Figure 2) is an extensive basin of volcanic origin located within a crater depression of the Cimino Volcano complex, 60 km from Rome. The surface area is 12.09 km², the volume is 260.7 million m³, and the depth reaches 48.5 m (average depth 21.6 m); the turnover time is 17 years [108,109]. Situated within a Regional Park, the lake is classified as a wetland of international importance by the Ramsar Convention.

The lake’s surroundings host large hazelnut monocultures; its waters serve the potable uses of 10,000 inhabitants of two municipalities, Ronciglione and Caprarola; and it is a bathing area frequented year-round. Lake Vico (Viterbo, Italy) was monitored for about 11 years (2005–2009, 2012–2013, 2018–2019, 2021–2022), investigating the species of cyanobacteria present, population dynamics, and contamination in fish fauna in the lake’s aquifer where artesian wells deepened, as well as in public drinking water fountains. Blooms of the cyanobacterium Planktothrix rubescens regularly took place in this lake during the autumn–winter months, and during the study period reached maximum values of 72.5 million cells/L (January 2007) [110], with microcystin production (maximum value of 350 µg/L in March, 2008) [111] and, following recent analyses, also of BMAA toxin (maximum detected value 718 µg/L, November 2019). Ten artesian wells within the caldera and tapping into the lake’s aquifer were analyzed for the presence of microcystins, presenting a maximum value of 123 ng/L of toxins (September 2005); analyzing some samples of potabilized water, a public utility (fountain in the municipality of Caprarola) showed a presence of 350 ng/L (January 2008), and two private utilities in Caprarola showed a presence up to 340 (February 2008) and 500 ng/L (March 2009). From March 2006 to March 2009, the study of the lake also included toxic contamination in fish fauna with particular attention to the most commercially appreciated species, the whitefish (Coregonus lavaretus).

Out of 59 fish tissue samples analyzed, 6.8% tested negative. In the remaining 93.2%, values ranged from 0.21 to 39.19 ng of microcystins/g of fresh tissue (

Table 1. P. rubescens blooms and cyanotoxins detected in Vico, Albano, and Occhito lakes.

Location	Matrix	P. rubescens Bloom (Max n, Cells/L)	MCST Max Value	BMAA Max Value	Reference
Vico	Lake water	72.5 × 106 (Jan 2007)	350 μg/L (March 2008)	718 μg/L Nov 2009	[111]
	Wells water		350 ng/L (Jan 2008 Caparola)
	Fish (Coregonus lavaretus)		26.56 ng/g
	Hazelnuts		2.3 ng/g (2010)
Albano	Lake water	298 × 106 (Jan 2008)			[114]
	Fish (Salmo trutta lacustris)		2.41 ng/g (Aug 2006)		[115]
Occhito	Lake water	14 × 109 (April 2009)	298 μg/L (March 2009)	24.14 ppb (March 2014)	[116]
	Fish		2.98 ng/g (May 2009)	0.95 μg/g (Nov 2014)	[116]
	Mussels (Mytilus galloprovincialis)		256 ng/g (May 2009)
	Mussels (Chamelea galina)		2.3 ng/g (May 2009)
	Vegetables (Asparagus)		1.5 ng/g (Oct 2015)		[117,118]

). Values in the muscle tissue (specifically subject to human consumption) were found from 0.21 to 26.56 ng/g of fresh tissue. According to the scientific literature, the average level of fish portions generally ingested by an adult human of about 70 kg varies between 100 and 300 g [112,113]; according to this prediction, 32% of the samples examined exceeded the microcystin intake threshold recommended by US EPA (up to 38 times more).

The EDI (edible daily intake) values, calculated in 2008–2009 for the commercial fish species of Vico based on the TDI value proposed by the WHO, ranged from 4.8 to 122.4 μg (2 to 51 times higher than the threshold). In 2010, a strong and spectacular bloom occurred in the lake, which for this species of cyanobacteria presents a particularly recognizable blood-red color due to the high cellular quantity of the phycobilin phycoerythrin; the bloom lasted until May 2010, and on this occasion, a brief study was conducted on the possible contamination of microcystins in garden or orchard plants whose roots were on the lake’s aquifer. Specifically, broccoli (Brassica oleracea) grown in a garden near the lake’s shore and hazelnuts (Corylus avellana) from monocultures surrounding the shores were examined. Hazelnut production is the main agricultural activity of the Viterbo district and the Cimino Complex; hazelnuts are not only exported but also used locally to produce ice cream, cakes, cookies, and chocolate creams, and they are widely consumed by the local population. Harvests are carried out at the end of August, but the fruits start to form on the bushes towards the beginning of May. In the analysis conducted, the broccoli, whose root system does not reach a meter in depth, and whose irrigation was carried out with public aqueduct water, were found not to be contaminated; green hazelnuts picked at the beginning of June and dry ones fallen at the end of August were found to have concentrated 2.3 ng of microcystins/g of fresh weight. Similar samples collected 20 km away from the lake’s shores were found not to be contaminated.

5.2. Lake Albano

Lake Albano is a volcanic basin in Lazio within an ellipsoidal crater depression, whose major axis, oriented Northwest–Southeast, is 3.5 km long, while the minor is 2.3 km long [119]. The lake’s perimeter is 12 km, and its depth reaches 175 m. The average water renewal time exceeds 67 years. Lacking outlets, the lake is characterized by an ancient Roman channel carved into the lava rock through the crater, used to regulate the lake level. The lake is made eutrophic by human activities, which in the past led to the development of algal blooms; the first manifestations of these phenomena were highlighted by Cannicci [120]. Since 1960, the lake level dropped about four meters below the outflow, accelerating the transformation from an oligotrophic to a eutrophic state. Studies conducted over two decades on the dynamics of populations of toxic cyanobacteria present in the lake and the presence of biotoxins they produced have led to the detection of periodic winter blooms of P. rubescens [114], with peaks usually in January (maximum value reached 298 × 10⁶ cells/L, January 2008) (Figure 3), and concurrent presence of microcystins and BMAA (Figure 4). Two of thirteen artesian wells analyzed inside the lake’s caldera showed contamination by microcystins, specifically the Albano well (60 m deep) throughout the bloom period from December 2004 to March 2005, and Sforza Cesarini (100 m deep, a well for potable uses) in March 2005, the end period of the blooms. The total microcystin contamination detected reached up to 67 ng/L (Albano well, January 2005). As documented in other lakes, also in Albano, two fish (Salmo trutta lacustris) sampled in August 2006 revealed microcystin contamination not in the muscle tissue anymore, but still in the viscera (up to 2.41 ng/g) (Table 1), although the P. rubescens population had receded during the summer season. This evidence proved that complete detoxification in fish fauna could require more than three months [114]. This detailed examination of Lake Albano and Lake Vico demonstrates the complex challenges posed by cyanobacterial blooms in Italian water bodies, highlighting the importance of continuous monitoring and analysis to safeguard both environmental health and public safety. Through these efforts, researchers can better understand the dynamics of harmful blooms and the potential for toxin contamination in water and food sources, and thus they can develop strategies to mitigate their impacts. This knowledge is crucial for informing public health advisories, guiding policy decisions, and enhancing the overall management of water resources in affected regions.

5.3. Lake Occhito

Lake Occhito, situated on the border between the regions of Puglia and Molise, is Italy’s largest artificial lake. Created for potable purposes by damming the Fortore River, it has a depth of 90 m and a surface area of 13 km². The river’s course to the sea after the dam is about 67 km. The mouth on the northern Pugliese coast is close to significant mussel farms, also present in two coastal lagoons, the so-called Lesina and Varano lakes. During the winter of 2009, an extensive bloom of Planktothrix rubescens completely covered the surface of Lake Occhito with dense red foams from January to April. In past years, eyewitnesses had occasionally observed red blooms in the lake. By January, the bloom had covered the entire lake surface, and in the following months, it reached the entire water network of the surrounding territories. In March and April 2009, after a series of heavy rains, the gates of the Fortore dam were opened to allow water to flow into the river below, lowering the dangerously high lake level. However, this caused the bloom to reach the river mouth and spread to the mussel farms along the coast of Manfredonia.

Three surface water samples taken in March 2009 from three lake stations during the P. rubescens bloom and analyzed using the ELISA immunoassay gave values from 120 to 298 µg/L for total microcystins and from 0.5 to 0.7 µg/L for the content of extracellular microcystins. In April 2009, in a surface sample of the bloom, 14 × 10⁹ cyanobacterial cells/L were counted (Table 1).

In the Occhito water supply network, continuous presences of oscillating cells between 3 and 35 million cells/L were detected for months in 2009 by ARPA Puglia. The incidence of gastroenteritis reported in the territorial hospitals of the province of Foggia was studied to verify any anomalies in epidemiological trends (Figure 5). The trend did not follow the typical influenza-like (with gastroenteric syndromes) season of 2008–2009, which peaked in the last week of January, declining in subsequent periods [121]. In conclusion, based on the evidence we possess, it is possible that the higher incidence of gastroenteritis in the province of Foggia in March 2009 was linked to a higher level of microcystins in the network water, not entirely stopped by the water treatment plant, and derived from a peak reached in the lake bloom.

Fish muscle samples from the lake, collected in May 2009 and analyzed using the ELISA immunoassay, showed microcystin contamination from 0.42 to 2.98 ng/g. Sea water samples at the mouth of the Fortore River, analyzed with the ELISA immunoassay, gave values from 0 to 0.61 µg/L (May 2009).

Three samples out of 36 analyzed (8%) were negative. In 2009, the average monthly values of the total concentration of microcystins in sea water showed a peak of 0.38 µg/L (May 2009), progressively decreasing to 0.03 µg/L in July. In 2010, the average monthly values showed a peak of 0.16 µg/L (January 2010) dropping to 0.01 µg/L by April. Mussels (M. galloprovincialis) from marine farms along the coast were sampled and analyzed from April 2009. ELISA analyses showed a maximum concentration of microcystin at 256 ng/g in 2009 (May 6), with a gradual decrease to a minimum of 1.73 ng/g on July 1.

The average monthly values showed the highest concentration at 63.15 ng/g in May, then dropping to 2.7 ng/g in July. In 2010, the highest value was detected in January (27.75 ng/g). The average monthly values reached a maximum of 19.1 ng/g in January, with a slow decrease to 1.38 ng/g in April and a slow rise to 2.5 ng/g in June. Benthic clams Chamelea gallina gave values from 1 to 2.3 ng/g (May 2009). A total of 8 out of 75 mussel samples analyzed (10.5%) were not contaminated [117]. From June 2015 to May 2016, 73 samples of vegetable crops were collected from fields between San Severo, Lesina, and Lucera, where agricultural crops are irrigated with water from three collection and distribution tanks (Tavoliere, Finocchito, and Vasca D) whose water directly comes from the lake. ELISA screening results of the crop samples showed concentrations of microcystins above the detectability limit (0.1 ppb) in 31 samples, with concentration ranges between 0.2 and 1.5 ppb. In everyday vegetables like tomatoes, a minimum value of 0.2 ppb and a maximum value of 1 ppb were detected during the summer period (June 2015). The highest value was detected in asparagus in October 2015 (1.5 ppb), a month when many other vegetables also showed their highest concentration of microcystins, measured through ELISA tests: cabbage 1.3 ppb, fennel 1.1 ppb, kale 1.3 ppb. In cabbage, a minimum concentration of 0.2 ppb and a maximum of 1.0 ppb were detected; in fennel, a minimum concentration of 0.5 and a maximum of 0.8 ppb in May 2016, a period when spinach registered 0.6 ppb [118].

BMAA (β-N-methylamino-L-alanine) is a potent neurotoxin associated with ALS, Parkinson’s disease, and Alzheimer’s dementia, produced by all species of cyanobacteria (aquatic and terrestrial) as well as some diatoms and dinoflagellates. The toxin concentrates in plant and animal tissues but also has volatile properties and can be inhaled [14,122].

In a study conducted during the years 2013–2014, water and fish samples from Lake Occhito were analyzed for the presence of BMAA. In the water samples, the highest levels of the toxin were found in March 2014 (24.14 ppb), with a higher concentration at the sampling site identified as the right bend of the Occhito basin. Spring samples from 2013 (March–April) and the same period in 2014 detected overlapping toxin levels, slightly higher in the latter year (averaging, respectively, 12.20 and 16.37 ppb), especially for the month of March. Fish samples were evaluated solely through the ELISA immunoassay technique. Analysis of this matrix recorded levels between 1.44 and 3.93 µg/g of dry weight muscle (equivalent to 0.30–0.95 µg/g of fresh weight muscle). The highest toxin levels were detected in the September–November 2014 period with average concentration values of 2.01 µg/g of dry weight [116].

International epidemiological studies suggest the influence of BMAA presence on the neuronal pathology of human populations surrounding bodies of water with toxic-producing blooms [14].

Epidemiological data up to 2013 related to the incidence of diseases such as Alzheimer’s disease and dementia were provided by epidemiological centers of the regions of Puglia and Molise, covering municipalities in the provinces of Foggia and Campobasso as reported in Figure 6. Considering the larger municipalities of the province of Foggia (Foggia, Lucera, Manfredonia, San Severo), a higher number of cases were detected in the capital municipality, and incidence percentages similar to those recorded in Foggia in recent years were also observed in municipalities closer to the Occhito reservoir (Figure 6). The first municipalities presented in the legend are located close to the Occhito basin.

Furthermore, in the capital city, a sharp increase in the incidence of neurological diseases was noted starting from 2007. As for the epidemiological data of the province of Campobasso, data were only found for the year 2010. In municipalities closer to the reservoir, a larger number of neurological disease cases were highlighted, with percentage values higher than those of other municipalities (Figure 7).

BMAA can be removed from water intended for potable use with treatment systems comparable to those effective against microcystins (e.g., activated carbon filters), and it is therefore highly recommended that waters from Lake Occhito undergo specific treatments before being introduced into the relevant water supply networks.

This precautionary approach emphasizes the need for rigorous water quality management and monitoring to ensure the safety of drinking water and the protection of public health from the potential adverse effects of BMAA and other toxins associated with harmful algal blooms. The implementation of such measures is critical, especially for communities reliant on water bodies like Lake Occhito for their water supply.

6. Discussion

The findings from Lake Occhito highlight the broader implications of cyanobacterial blooms on water safety, food security, and public health. The presence of toxins in water supplies and food sources such as fish and mussels necessitates ongoing vigilance and responsive strategies to mitigate risks. Moreover, the potential long-term health impacts underscored by the epidemiological data on neurological diseases in areas affected by water contamination with BMAA and microcystins call for comprehensive research and policy initiatives.

Efforts to address these challenges involve a multifaceted approach, including:

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Enhanced monitoring: implementing advanced and continuous monitoring of water bodies for early detection of harmful algal blooms and toxin levels, utilizing both traditional sampling methods and emerging technologies like remote sensing.

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Public awareness and education: raising awareness among local communities, fishermen, and farmers about the risks of algal toxins and promoting safe practices to reduce exposure.

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Water treatment innovations: investing in and applying effective water treatment solutions that can remove a broad range of algal toxins, ensuring the safety of drinking water and irrigation supplies.

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Regulatory and policy frameworks: developing and enforcing regulations and guidelines for water quality management, including acceptable levels of algal toxins in water and food products, to protect public health and the environment.

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Research and collaboration: encouraging interdisciplinary research on the impacts of harmful algal blooms and fostering collaboration among scientists, policymakers, water managers, and public health officials to share knowledge and develop integrated solutions.

The case of Lake Occhito serves as a reminder of the complex interplay between environmental factors, human activity, and public health, highlighting the importance of a proactive and collaborative approach to managing the risks associated with harmful algal blooms. By prioritizing water safety and public health, communities can better navigate the challenges posed by these environmental phenomena and work towards sustainable water management and health outcomes.

Continuing from the management and response to harmful algal blooms (HABs), it is important to emphasize the role of community engagement and stakeholder involvement in developing effective strategies:

Engaging local communities, including residents, businesses, and recreational users of water bodies, in the conversation about HABs can lead to better understanding and more effective actions. This includes participation in monitoring programs, adherence to public health advisories, and support for environmental conservation efforts that reduce nutrient runoff into water bodies.

Leveraging technology and innovation can significantly improve the detection, monitoring, and management of HABs. This includes the development of more sensitive and rapid testing methods for toxins, the use of drones and satellite imagery for monitoring bloom development, and the application of advanced water treatment technologies that can effectively remove toxins. Innovations in data analysis, such as machine learning algorithms that predict bloom occurrences, can also play a vital role in early warning systems.

Given the variability and unpredictability of HABs, adaptive management approaches that can evolve based on new scientific findings and monitoring data are crucial. Policymakers and water managers should be prepared to update guidelines, policies, and management strategies as more is learned about the triggers and impacts of HABs. This might include revising nutrient management plans, updating water treatment protocols, and modifying public health advisories to better protect communities and ecosystems.

HABs are a global issue affecting both developed and developing countries. International collaboration and knowledge sharing can enhance the global response to HABs, facilitating the exchange of best practices, research findings, and technologies. Collaborative efforts through international organizations, research consortia, and bilateral partnerships can strengthen the capacity of nations to address the challenges posed by HABs and protect water resources and public health on a global scale.

A variety of techniques have been employed to combat the cause of HABs, the eutrophication of water bodies, including hydrological management, P reduction or immobilization, complementary ecological management, biomanipulation, and top-down control of the food web [123].

Yang et al. [124] predicted that all urban lakes and most medium-sized lakes in urban-rural fringe areas in China may be eutrophic or hyper-eutrophic by 2030.

Jin et al. [125] indicated that both nutrient pollution control and lake ecological restoration should be carried out for eutrophic control of lakes in China.

Over the last three decades, eutrophication management has undergone a transformation from simple direct elimination of algae for the reduction of endogenous nutrient concentrations to multiple technologies for the restoration of lake ecosystems.

In a recent work by Zhang [126], the development and revolution of three remediation methods, namely, physical, chemical, and biological methods, are examined and their possible improvements and future directions are outlined. A combination of these three management techniques can be used to synthesize short- and long-term management strategies that control the development of cyanobacterial blooms and aquatic ecosystem restoration.

The definitive strategy for the restoration of water bodies involves the general diversion and control of point and diffuse sources of pollution, a strategy often requiring a long time, measured in years if calculated for large volumes. In cases involving small bodies of water that for particular reasons (conservation of special biodiversity, environmental and health protection needs, etc.) must be quickly recovered, the use of symptomatic methods that accelerate recovery can be used in association with the control of nutrient input. Bruno et al. [127] reported two cases in Italy in which remediation has been successfully addressed through the only management of nutrient inflow, resulting in the elimination of the problem of recurrent HABS.

7. Conclusions

Ensuring increased public awareness of cyano-HAB episodes and enhancing the effectiveness of monitoring and management of toxic blooms are vital to recognize the phenomena, understand their causes, anticipate their manifestations, and mitigate their effects. An ongoing One Health approach to surveillance, coupled with outcomes from scientific research (e.g., environmental sciences and studies on human and animal health) and improved access to testing for samples, will enhance the robustness and usefulness of the system. This comprehensive strategy not only aids in immediate response and mitigation efforts but also contributes to long-term preventive measures against the adverse impacts of HABs on public health, local economies, and the environment.

Incorporating this comprehensive strategy requires a multidisciplinary approach that leverages expertise across environmental science, public health, veterinary medicine, and economic analysis. This cross-sectoral collaboration under the One Health umbrella facilitates a more effective and cohesive response to the complex challenge posed by HABs, enabling stakeholders to address both the symptoms and root causes of these events.

Monitoring and predictive modeling of HABs are critical components of this strategy, allowing for early warning systems that can inform water management practices and public health advisories. By integrating satellite imagery, water quality data, and climate models, authorities can anticipate HAB occurrences and implement measures to protect public and animal health as well as mitigate economic impacts.

Public education campaigns play a pivotal role in raising awareness about the risks associated with HABs and promoting safe practices among water users, including recreational visitors, anglers, and communities reliant on affected water bodies for their livelihood. These campaigns should provide clear guidelines on identifying HABs, avoiding exposure, and reporting sightings to local environmental or health authorities. Economic analysis of HAB impacts, including direct costs to healthcare, fisheries, and tourism, as well as indirect costs such as decreased property values and long-term environmental degradation, is vital for understanding the full scope of these events. Such analysis supports the allocation of resources for HAB prevention, monitoring, and response efforts, and it can guide policy development aimed at reducing nutrient pollution and other contributing factors. Investments in research and technology development are essential for improving HAB detection methods, understanding toxin pathways in ecosystems, and developing treatments for toxin exposure. Advancements in water treatment technologies can help ensure safe drinking water supplies and protect aquatic life, contributing to the overall resilience of communities to HABs. The holistic approach embodied in the One Health framework emphasizes the interconnectedness of human, animal, and environmental health, advocating for collaborative efforts to effectively address HABs. Through continued partnership, innovation, and commitment to public education and awareness, it is possible to reduce the frequency and severity of HAB events, safeguarding public health, preserving biodiversity, and ensuring the economic vitality of affected regions.

8. Future Directions

Some nations in Europe have developed One Health guidelines to reduce health risks associated with harmful cyanobacteria. For instance, in Scotland, a series of guidelines for assessing the risk posed by waters affected by cyanobacterial blooms has been developed and updated with the aim of protecting both human and animal health (Scottish Government Health and Social Care Directorates). In this case, the responsibility to initially assess potential health risks from harmful cyanobacteria has been assigned to water quality officials and workers, public and environmental health officials, and concerned individuals. Guidelines have been developed for incident investigation, reporting, and distributing public alerts. France has developed SAGIR (Surveiller les maladies de la faune sauvage pour AGIR, https://www.ofb.gouv.fr/le-reseau-sagir), a surveillance network for zoonotic diseases and environmental toxins that includes the Fédérations des chasseurs and the Office national de la chasse et de la faune sauvage. Hunters report wildlife mortality events to SAGIR, which then sends wildlife surveillance staff to investigate the death of animals and surrounding environmental conditions. This helps maximize early detection of emerging health threats, informs risk assessment, and ultimately contributes to the protection of animal and human health.

In the United States, the CDC and the National Center for Environmental Health had historically provided funding to states to collect reports on human and animal health associated with cyanobacteria, but funding has ended, and not all states are able to continue related activities [128]. Currently, efforts are underway to incorporate reports of animal and human diseases associated with harmful algal blooms into the CDC National Outbreak Reporting System (NORS), a voluntary national system that receives reports of human diseases from food, water, and other sources [129]. While incorporating human and animal diseases and deaths into NORS will increase general awareness about harmful cyanobacteria among some state health authorities, it is too early to see if these efforts will succeed in promoting integration and communication among human and animal populations and environmental health specialists that will lead to a collaborative One Health framework for integrated health protection.

Preventing the environmental and health consequences of blooms also involves controlling the aquatic environment through which goods or live animals are transported. Almost all unicellular algae, under adverse conditions, have the ability to form resistant cysts that fall to the bottom and can withstand years in a quiescent state until environmental conditions become favorable again; these cysts can undergo passive transport into new waters. Marine algal species typically travel in the form of resistant cysts in the empty ballast tanks of cargo ships filled with seawater. Freshwater species can be transported, for example, in fish tanks purchased in countries with water bodies affected by blooms; tropical or polar species may find themselves in temperate latitudes, and if environmental conditions are sufficiently favorable, the result can be the establishment of the new species. In the case of species with toxic production, this occurs in the form of mixtures, but the general and assumed presence, in the case of cyanobacteria, is that of the neurotoxin BMAA [130]. Microcystins, for example, may be associated with the presence of other compounds like BMAA whose widespread production in cyanobacterial species represents a new potential long-term danger to human health [131,132]. The cyanobacterium P. rubescens also produces anabaenopeptins and aeruginosins [133], cyanopeptides characterized by lower toxicity compared to microcystins, whose synergistic effect has yet to be assessed in relation to the total toxicity of this species. The presence of these toxins is generally not investigated when microcystins are present, so it is not possible to make an estimate of the total health risk. Moreover, the ability of these classes of toxins to concentrate as mixtures along the food chain through different routes, and thus reach not only humans but also plant and animal species [46,84], makes research and reporting of their associated presence, as well as the registration of originating or related events in general databases of quick and public access, increasingly indispensable. Similar evidence in Italian lakes [115,116,134] has led to considering that the risks associated with the consumption of potable water, aquatic products, and contaminated agricultural products must be systematically evaluated in relation to the annual population dynamics of the examined toxic species, but also in relation to variations in total toxin production over multi-year series, as well as to the trophic evolution of the water body. Therefore, it might be more correct to think of the risk evaluation from cyanobacterial toxins as a dynamic variable, to which human and animal epidemiological conditions are not foreign. The establishment of a public control body with a One Health approach cannot do without as comprehensive knowledge as possible of the ecological and toxicological characteristics of all the species affecting the territory under surveillance. In this regard, as already emerged from the investigations by the US EPA, the collaboration between local populations, experts in environmental health and management, specialists in epidemiological sciences and in human and animal medicine, and local authorities is of vital importance. To this end, an important role can be played by the creation of formal agreements with non-profit civic associations that act as sentinels and, when necessary, as suppliers of samples collected in the immediacy of suspicious or unusual events, to allow the technical sectors of the control body to carry out real-time investigations and usefully report any situations susceptible to evolving into risk. Organizing a national structure for early warning and control in a One Health key should analytically foresee the study of the synergistic effects that different biotoxin mixtures can have on toxicity (e.g., microcystins together with other cyanobacterial toxins), the evaluation of the possible presence of non-peptidic toxins, and of course the typing of blooms based on the production of specific toxins. The development of integrated systems for rapid, efficient, and global detection of anomalies is another fundamental aspect to allow valid countermeasures in risk management: phytoplanktonic field monitoring must include continuous and regular sampling campaigns, with related broad-spectrum chemical, biological, and toxicological analyses. The use of satellite systems in remote sensing, originally created for military espionage, is a technology that has been experimented for more than forty years with projects like SEAWIFT (Sea-viewing Wide Field-of-view-Sensor), AVHRR (Advanced Very High Resolution Radiometers), NEMO (Noise and Emissions MOnitoring and radical mitigation), MODIS (Moderate Resolution Imaging Spectroradiometer), MERIS (Medium Resolution Imaging Spectrometer), and Sentinel for the detection of algal blooms in marine and freshwater bodies. The advantage offered by this approach is the vastness of geographical areas that can be covered by a satellite image; the quantitative analyses that the recorded information can offer; and, most usefully, the direct reading of the conditions of the water body.

This approach not only enhances our understanding of the immediate impacts of harmful algal blooms but also contributes to long-term environmental and health strategies. By integrating satellite technology with ground-based monitoring, authorities can develop a more comprehensive and responsive strategy for managing the risks associated with cyanobacterial blooms [135]. Moreover, the incorporation of advanced technologies and methodologies should be paralleled by the development of public awareness campaigns and education programs. Informing the public about the risks associated with harmful algal blooms, the importance of reporting sightings, and ways to minimize exposure can significantly contribute to community health and safety. Such efforts can empower individuals and communities to take proactive steps in bloom prevention, including reducing nutrient runoff through sustainable agricultural practices and responsible waste management. An essential component of a successful One Health approach is the establishment of a multidisciplinary task force that includes representatives from environmental protection agencies, public health departments, wildlife conservation organizations, agricultural sectors, and community groups. This task force can facilitate the sharing of information, coordinate response efforts, and develop integrated strategies to address the complex challenges posed by harmful algal blooms. Investing in research is crucial for advancing our understanding of cyanobacterial blooms, their triggers, and their impacts on ecosystems and human health. Research efforts should focus on identifying the conditions that lead to blooms, developing more effective methods for detecting and mitigating toxins, and exploring new treatment technologies for contaminated water and affected agricultural products. Finally, policy initiatives at both the national and international levels can provide the framework for a coordinated and effective response to harmful algal blooms. This could include setting standards for water quality, establishing guidelines for the safe consumption of fish and shellfish from affected areas, and creating emergency response plans for bloom events. International cooperation, through the sharing of best practices and collaborative research projects, can enhance global efforts to combat the threat posed by cyanobacterial blooms. By adopting a dynamic, multidisciplinary, and proactive One Health approach, society can better manage the risks associated with harmful algal blooms, protect public health and the environment, and ensure the sustainable use of precious water resources. The integration of scientific research, public engagement, policy development, and international collaboration is key to addressing this global challenge.