Evidence of Health Effects Associated With Exposure to Cyanobacteria in Water Used For Recreation or At Workplaces

While reported concentrations of cyanotoxins in drinking-water are rarely found above the low microgram per litre range (see section 5.1), contact with scums through recreational activities more frequently results in exposure to cyanotoxin concentrations in a range of up to milligrams per litre (see Chapter 2), and acutely hazardous exposure is a realistic scenario if site users ingest scum. Evidence of health effects from recreational exposure has been published mainly as anecdotal reports, case studies and from epidemiological studies.

Case Reports of Short-Term Health Effects from Acute Exposure

A number of published case reports of illness after exposure to cyanobacteria during recreation have been widely quoted to illustrate the relevance of this pathway. As discussed at the beginning of this chapter, in most of the published cases, the presence of infectious pathogens cannot be unambiguously excluded, and it is typically unclear whether the symptoms reported were caused by the known cyanotoxins or by other components of the bloom, including the possibility of yet unknown cyanobacterial metabolites. For example, enteritic viral or parasite pathogens may well have been present even where bacterial indicators were reported to have been absent. The case in Box 5.4 shows that later availability of new analytical methods can support or exclude cyanotoxins as cause if sample material is still available.

BOX 5.4: HUMAN MORTALITY FROM ACCIDENTAL INGESTION OF TOXIC CYANOBACTERIA - A CASE RE-EXAMINED

Wayne W. Carmichael

In July 2002, a 17 year-old male was taken to a local hospital emergency department in full cardiopulmonary arrest following an episode of vomiting and diarrhoea followed by seizure at his home. The patient, an athletic otherwise healthy individual, had no previous history of seizures, syncope or diarrhoeal illness. Extensive resuscitation efforts failed and the patient expired in the emergency department. An autopsy was performed the following day to determine the cause of death. After ruling out several possible aetiologies for death, including toxic chemicals and pathogenic microbes, the possible role of cyanotoxins was pursued since the youth was reported to have accidentally ingested water while swimming in a local golf course pond, about 2h prior to symptoms, that was described as “dirty and scummy”. Unfortunately, because cyanotoxins were considered as possible cause only late in the course of the investigation, no samples were taken from the pond. Samples of the youth’s blood, liver and vitreous fluid were tested for MCs, STX, ATX and CYN. In addition, stool collected from autopsy was examined for the presence of cyanobacterial cells. ELISA was negative for microcystins and LC/MS analyses was negative for STX and CYN. ESI LC/ MS did reveal a strong peak with mlz 166 with a retention time of 9.08 min, “similar”’ to that of anatoxin-a, 8.51 min. This evidence allowed an initial listing of this cyanotoxin as a possible cause of death. Further analyses showed, however, that this peak with mlz 166 is not anatoxin-a but the ubiquitous amino acid phenylalanine.

In consequence, this example of a false-positive investigation of mortality from anatoxin-a should now be considered one of unknown cause.

A number of reports contain substantial evidence of the uptake of cyanobacteria and a likely connection to the symptoms observed:

• • Dillenberg and Dehnel (1960) reported a case series of illness in 13 persons after swimming at various bloom-affected Canadian lakes (despite warnings posted following animal deaths); symptoms included headache, nausea, vomiting, painful diarrhoea, arthralgia and myalgia (i.e., pain in joints and muscles). Stool samples from two of the more severely affected individuals, one of whom was hospitalised overnight, were sent to the Saskatchewan public health laboratories, where Microcystis cells were identified in the specimens.
• • Turner et al. (1990) reported that 10 out of 18 army recruits fell ill after training exercises involving canoeing - including practicing Eskimo rolls - in a waterbody affected by a Microcystis bloom, with two soldiers needing hospitalisation for a week because of severe atypical pneumonia and generalised illnesses. The authors suggested that inhalational exposure to cyanotoxins, especially to microcystin, may have been the probable cause, although that assertion has been challenged by others. This was the incident that first triggered wider attention to cyanobacterial toxicity in humans.

• • In Argentina, a teenage jet-ski rider was hospitalised for several weeks, including an 8-day period in an intensive care unit during which time he required artificial ventilation. Acute respiratory symptoms were followed by hepatic insufficiency, which was essentially self-limiting. The presumed aetiologic agent was a microcystin-pro- ducing bloom of Microcystis, which was present as heavy scum in the dam at the time the young man spent several hours on and in the water (Giannuzzi et al., 2011).
• • In Uruguay, a 20-month-old child suffered acute liver failure after repeated recreational activity at a beach of the Rio de La Plata River (Vidal et al., 2017) in January 2015. During this month, the river had a pronounced bloom of Microcystis sp. and microcystin concentrations up to 25 700 pg/L were reported in scum material. The child and her family first showed gastrointestinal symptoms a few hours after the final exposure, but she also developed jaundice and increased serum levels of liver enzymes as well as a need for mechanical respiratory support. A liver transplant was performed after 20 days, and microcystins were detected in the removed liver in concentrations up to 78 ng/g of tissue, which is in the range of the concentrations found in livers of the Caruaru victims (discussed in section 5.4). While the authors explicitly do not exclude other factors, for example, autoimmune hepatitis type II as cause (possibly triggered by the exposure to microcystins), they identify a high plausibility of direct damage through the repeated exposure to an estimated total of at least 1.78 L of microcystin containing water over a few days.
• • In a review of CDC’s Waterborne Disease and Outbreak Surveillance System in the USA in 2009-2010, 11 outbreaks were associated with cyanobacteria. In 70% of cases, health effects were associated with the major exposure route: rash, irritation, swelling or sores were reported in those outbreaks where exposure occurred mainly through dermal contact while gastrointestinal symptoms were reported after water ingestion. The outbreak with the more severe gastrointestinal and neurologic symptoms (one of the two hospitalisation cases) was characterised by the highest levels of MCs (>2000 pg MC-LR eq/L) and 9, 15 and 0.09 pg/L of CYN, ATX and STX. In the three cases in which ATX and STX were present, neurologic symptoms or confusion/visual disturbance were reported in addition to fever, headache and eye irritation. However, in all three cases, microcystins were also detected at often substantially higher concentrations (0.3->2000 pg/L), and in one of them, CYN and STX were also present (Hilborn et al., 2014).

For assessing cases such as these, it is important that mere co-occurrence

of cyanotoxins and unspecific symptoms (skin irritation, gastrointestinal, etc., see above) is not indicative of the known cyanotoxins having caused the symptoms; more likely the cyanobacteria 1 biomass contains both toxins and other, yet unknown agents causing such general symptoms. In contrast, cause-effect relationships are likely if symptoms or analytical results are toxin-specific (e.g., for hepatotoxins elevated serum enzyme levels such as gamma glutamyl transferase; for neurotoxins respiratory difficulties, tingling of extremities, confusion or visual disturbance). While finding cyanotoxins in body fluids of patients and/or cyanobacterial cells in their stool confirms exposure, even this does not allow the conclusion that these were the cause of symptoms, as it is currently unknown how concentrations in serum relate to damage in the liver, for example.

Regarding occupational exposure, two studies have been undertaken by the mining industry in Australia. The Australian Coal Association Research Programme projects (Fabbro et ah, 2008; Fabbro et ah, 2010) investigated cyanobacteria and their toxicity in various waterbodies available to industry in Central Queensland, Australia, a semiarid region with a history of cyanobacterial blooms. Of the 180 samples tested for toxin, 17% contained CYN and 3% contained microcystin. Total CYN concentrations (CYN plus deoxycylindrospermopsin) ranged from 0.2 to 22.1 pg/L. Microcystin concentrations ranged from 1.7 to 3200 pg/L. Concentrations of toxin- producing cyanobacteria (Dolichospermum circinale) as high as 500 000 cells/mL were recorded from pit water (Fabbro et ah, 2008). Workers can potentially have direct contact with pit water when installing pump facilities or when it is used for dust suppression, cooling or wash down. This research also provided the initial identification of novel toxicity associated with Limnothrix/Geitlerinema (Fabbro et ah, 2010; Bernard et ah, 2011; Humpage et ah, 2012).

Other anecdotal and case reports of varying reliability describe acute gastrointestinal and respiratory illnesses associated with activities such as waterskiing (likely forming aerosols and spray) in recreational waters contaminated by cyanobacteria (reviewed in Stewart et ah, 2006d), including a report of a windsurfer in the UK with hepatic dysfunction diagnosed by liver function tests and liver biopsy (Probert et ah, 1995). In only a small proportion of such anecdotal reports documented in the biomedical literature were the subjects examined by medical practitioners. Anecdotal reports of illness are occasionally reported in local broadcast or print media, and some descriptions of the number and type of complaints received by public health authorities can be found in overview publications (see, e.g., Backer et ah, 2015). A report from the US State of Nebraska recorded more than 50 complaints of skin eruptions, vomiting, diarrhoea and headache after swimming or waterskiing at a cyanobacteria-affected lake over a single summer weekend (Walker et ah, 2008).

Severe skin reactions have been reported from contact with marine cyanobacteria, particularly with Lyngbya majuscula (now termed Moorea producens), which causes deep blistering particularly when trapped under bathing suits and where blooms have contained the toxins lyngbyatoxin A and debromoaplysiatoxin (see section 2.6). Severe dermatitis, resembling skin burns, has been reported from marine bathing in the presence of cyanobacteria dislodged from rocks, particularly after storms in tropical seas (Hashimoto et ah, 1976; Moore et ah, 1993). Lyngbya/Moorea has been recorded in many marine ecosystems worldwide, but is most common in tropical/subtropical locations. Intoxication events have been reported primarily in midsummer when both numbers of people engaged in recreational activities and the potential for bloom formation are high. Reports are chiefly from economically more developed countries, potentially due to a recording bias, and often include multiple morbidities.

Complaints of acute skin reactions have been associated with exposure to freshwater cyanobacteria as well as with eukaryotic microalgae; however, cyanobacteria are the focus of the majority of these reports (Stewart et ah, 2006c) with clinical investigations suggesting allergic responses (Cohen &C Reif, 1953; Stewart et ah, 2006a; Stewart et ah, 2006b; Geh et ah, 2016). Two reports focus on the pigment phycocyanin as a suspect allergen (Cohen &c Reif, 1953), and indeed a case investigation of anaphylaxis following consumption of Spirulina in tablet form (Petrus et ah, 2009) and clinical laboratory allergy studies identified phycocyanin as an allergen (Geh et ah, 2015; Lang-Yona et ah, 2018). However, this requires further clarification as it would contradict other reports assigning antiallergic, anti-inflammatory and antioxidant properties to phycocyanins (Strasky et ah, 2013; Liu et ah, 2015; Wu et ah, 2016). Investigators conducting epidemiological fieldwork at cyanobacteria-affected waters have received a small number of anecdotal reports from individuals with a history of allergy, though the association between anticipated symptom occurrence and cyanobacteria in such cases remains speculative. The possibility of serious anaphylactic reactions has been raised for some benthic cyanobacteria (Stewart et ah, 2011). Thus, while allergic responses to some cyanobacteria are discussed in the literature, their relevance remains unclear.

A widespread problem that case studies, such as those discussed above, face is that in the course of steps taken to elucidate the possible cause of the observed symptoms, cyanobacteria are typically considered only rather late. If many days pass between symptom observation and sampling the water to which patients were exposed, a bloom may already have disappeared and the chance for establishing a causal connection is missed. This is true in particular for surface blooms or scums which can disperse within a few hours, for example, due to increased wind. Informing the medical community about toxic cyanobacteria may help to reduce the time between exposure and water sampling as well as to document the situation at the time of possible exposure, for example, with images taken with mobile phones.