Epidemiological Studies of Acute Health Risks from Short-Term Recreational Exposure
Several epidemiological studies investigating acute illness following recreational exposure to freshwater cyanobacteria have been conducted between 1990 and 2011. These studies utilised various retrospective and prospective designs capable of detecting relative differences in commonly reported symptoms between exposed and unexposed groups; however, levels of exposure were usually poorly characterised, and hence, these studies are inadequate for risk assessment purposes. Symptoms assessed included both cutaneous and systemic reactions - the statistical analyses of the studies do not differentiate between both.
- • Philipp and coworkers conducted the first three formal epidemiological investigations into recreational exposure to cyanobacteria: These comprised a series of cross-sectional studies conducted in 1990 at inland waters in the UK, affected some weeks earlier by cyanobacteria blooms. They found only minor illnesses, with no statistically significant differences between symptoms reported by exposed and unexposed groups (Philipp, 1992; Philipp & Bates, 1992; Philipp etal., 1992).
- • A retrospective study conducted in Australia in response to an extensive bloom of Anabaena circinalis in the River Murray in South Australia also did not detect any statistically significant increase in symptoms between those exposed to river water during recreational activities and nonexposed controls (El Saadi et al., 1995).
- • Pilotto et al. (1997) conducted a prospective cohort study in 1995 at recreational waters in southern and south-east Australia and reported a statistically increased likelihood of symptom reporting compared to unexposed controls after 7 days (but not after 2 days) following exposure to low levels of cyanobacteria (5000 cells/mL) for more than 1 h. The cohort size for the statistically significant finding was small, comprising 93 exposed and 43 unexposed subjects.
- • Stewart et al. (2006c) conducted a larger prospective cohort study in Australia and the USA and detected a statistically significant increase in symptom reporting, particularly respiratory symptoms, three days following exposure. These authors used multivariable analysis after adjusting for confounding variables such as age, smoking, geographic region and a prior history of allergic disease. Increased symptom reporting rates were seen only at higher cyanobacterial densities, using a biomass estimate of exposure, and symptom severity was rated as mild by most study subjects. These associations were linked to cyanobacterial cell densities higher than 100 000 cells/mL
- • Two prospective cohort studies conducted in the USA by Backer et al. (2008; 2010) found no relationship to symptom reporting and exposure to microcystins, as measured by ELISA and LC-MS in lake water, aerosols and blood.
- • Levesque et al. (2014) conducted a prospective cohort study of residents living near three lakes in Quebec, Canada, which had a history of being impacted by cyanobacteria, one of which is also used as source for drinking-water. Exposure to cyanobacteria included a range of recreational water activities, drinking-water (for residents living near the lake with drinking-water abstraction from the lake) and consumption of fish from study lakes. Recreational exposure to cyanobacteria was associated with increased reporting of gastrointestinal symptoms; 466 individuals were enrolled in the study, although the number of subjects that engaged in recreational activities was not reported. The authors reported a strong statistically significant relationship between gastrointestinal illness and exposure to cyanobacte- rial cells above 100 000 cells/mL.
Most of the symptoms reported in these studies are mild and self-limiting. In contrast, the toxicological considerations discussed in section 5.2.3 show that serious morbidity or death through oral uptake of toxin is a realistic scenario in recreational water settings, if larger amounts of a highly toxic bloom are ingested. While the case study from Uruguay (Vidal et al., 2017) provides supporting evidence that they may occur, such events are, however, probably rare, and with the possible exception of the case-control design adopted by El Saadi et al. (1995), the prospective and retrospective epidemiological studies discussed above were not designed to detect the impact of massive oral exposure to high toxin concentrations.
The “gold standard” epidemiological design, a randomised controlled trial, could in theory be employed to investigate exposures and outcomes from oral consumption of cyanotoxin-contaminated recreational water, but this could not be done in practice on ethical grounds and would be logistically challenging. Future epidemiological investigations that seek to document events of severe acute illness following oral ingestion of cyanotoxin-contaminated waters would probably need to employ a case-control design. An advantage of these studies is that outcome data is ascertained by medical practitioners; however, disadvantages include exposure recall bias and recruitment of appropriate control groups (Stewart et al., 2006c). El Saadi et al. (1995) also alluded to difficulties in gaining cooperation of diagnosing practitioners.
In contrast to the limitations of field epidemiology, clinical studies overcome the reliance on self-reporting of symptom occurrence, severity and duration. The diagnosis and history of acute intoxication or allergic response to cyanobacteria and/or cyanotoxins is likely to be more reliable when conducted by expert clinicians, particularly when clinical histories and examinations can be supported by confirmatory or complementary diagnostic tests. Early clinical investigations, and in some cases desensitisation treatments, were concerned with allergic reactions to cyanobacteria in recreational waters (reviewed in Stewart et al., 2006c), and more recent clinical studies have addressed the topic of cutaneous and respiratory reactivity to cyanobacteria (Pilotto et al., 2004; Stewart et al., 2006a; Bernstein et al., 2011). The results of these clinical investigations confirm the case study reports discussed above that certain freshwater cyanobacteria can elicit hypersensitivity reactions in some individuals.
Responses to Presumed Cyanotoxin-Related Acute Illness Following Exposure
With increasing public information and awareness of cyanotoxin occurrence, it is possible that more individuals will consult medical services if they develop symptoms after exposure - symptoms which not necessarily are caused by cyanobacteria and their toxins. However, particularly where symptoms set in rapidly, that is, within only a few hours after exposure, intoxication should be a diagnostic consideration. Medical consultation will primarily serve to clarify and treat symptoms. Although very few cases are known to date, patients may present with concerns of intoxication after exposure to scums or high concentrations of suspended cyano- bacterial cells. For neurotoxins, these would be associated with symptoms of respiratory distress, and urgent respiratory support, including supplementary oxygen therapy, would be the appropriate response. Concerns about possible liver damage from microcystins or cylindrospermopsin after exposure can be met by surveillance of serum parameters reflecting liver function, particularly markers of acute injury such as hepatic transaminases.
Beyond this primary function, however, reporting such cases to public health authorities is helpful for promoting the understanding of the public health impact of recreational exposure to (toxic) cyanobacteria. As discussed above, analysis of water samples for cyanobacteria and cyanotoxins very soon after exposure would be most useful, and to make this happen, it is important that medical services or public health authorities trigger such action. Specific biomarkers of exposure to cyanotoxins are not routinely available, but a range of diagnostic criteria may be applied to support the identification of possible cyanobacterial intoxication (Box 5.5).
BOX 5.5: DIAGNOSTIC CRITERIA TO SUPPORT THE IDENTIFICATION OF POSSIBLE CYANOBACTERIAL INTOXICATION
- • Routine diagnostic tests used by clinicians in fields such as clinical microbiology and clinical biochemistry, to investigate whether other causes may explain presenting signs and symptoms;
- • a recent history of engaging in recreational water activity, with ingestion of water at a site contaminated by a planktonic bloom, scum material or detached benthic mats of cyanobacteria;
- • the confirmation of cyanotoxins and/or cyanotoxin-producing cyanobacteria in water samples or benthic mats collected at or close to the time and location of exposure;
- • signs and symptoms of acute hepatic toxicity, supported by findings of hepatic impairment at clinical examination and abnormal liver function tests;
- • signs and symptoms of motor nerve deficit, which may or may not manifest in acute respiratory insufficiency, seen at clinical examination where the clinical history indicates recent exposure to cyanobacteria;
- • cyanobacterial cells and trichomes in vomitus and stool samples identified by microscopy; although this procedure is a simple, low-tech method for identifying a biomarker of exposure to cyanobacteria, it seems to have been scarcely reported in human case investigations since the 1960s (Dillenberg & Dehnel, I960; Schwimmer & Schwimmer, 1964).
When allocating symptoms to cyanotoxins, it is important to realise that mere co-occurrence is insufficient for establishing a causal connection: even if cyanotoxins are found in patients’ serum, it remains possible that other components of the bloom caused the symptoms, particularly if symptoms are unspecific. If, however, they relate to the mode of action and exposure to high toxin concentrations, this is indicative of the respective toxin to be a likely cause. To support diagnosis, awareness and networking of laboratories involved in microbiological and chemical analyses is important so that they too can trigger a timely sampling campaign at the site where patients were exposed - within a short reaction time to capture the situation in situ as close to the potential exposure event as possible.