Follow-up survey of the prevalence , diagnosis , clinical manifestations and treatment of Spirocerca lupi in South Africa

Copyright: © 2014. The Authors. Licensee: AOSIS OpenJournals. This work is licensed under the Creative Commons Attribution License. Spirocercosis is an important disease in South Africa. The object of this study was to determine if there had been a change in the prevalence, clinical manifestations and treatment of Spirocerca lupi over a 14-year period. A questionnaire was sent to 577 veterinary practices throughout South Africa in 2012. Of responders, 76% indicated that S. lupi occurred in their area, whilst 24% indicated that it did not; 84% considered S. lupi not to be a new phenomenon, whereas 16% considered it to be new. Monthly or seasonal distribution of the disease was not reported, and 76% of responders reported it to occur in no specific breed of dog, whereas 24% reported a breed risk, most considering large breeds to be at greater risk. No specific age or sex was identified as at higher risk. Common owner complaints were vomiting, weight loss, cough, or regurgitation. Reported clinical findings tended to mirror the clinical signs reported by owners. Most common diagnostic methods used were radiology, endoscopy, faecal flotation, and post mortem examination. Forty-four percent did not report seeing asymptomatic cases, 40% reported asymptomatic cases and 16% did not know. Associated complications were reported by 85% of responders, and included oesophageal neoplasia, hypertrophic osteopathy and acute haemothorax. Four different drugs were used as therapy: doramectin, ivermectin, milbemycin and Advocate®, with 9% of the responders using a combination of these four; 85% considered treatment to be effective and 15% ineffective. Treatment was considered more effective if the disease was diagnosed early and there were no complications. Two important conclusions were that more cases are being seen and that efficacy of therapy has increased, with a decrease in the mortality rate.


Introduction
Spirocerca lupi is a nematode parasite of carnivores found primarily in dogs but reported in numerous wild carnivores (Fox, Burns & Hawkins 1988).Natural infections have been reported in man, goats, ponies and a donkey (Ndiritu & Al-Sadi 1976).Spirocercosis occurs throughout the world, having a predominantly tropical and subtropical distribution (Urquhart et al. 1991), although there are colder regions with a high incidence (Ndiritu & Al-Sadi 1976).Infection depends upon canine population density and the degree of contact between definitive, intermediate and transport hosts (Bailey 1963).The adult parasite is most commonly found embedded in a nodule within the host's thoracic oesophagus, although it can occur in the thoracic aorta, stomach, vertebra, pleura, lungs, kidneys, mediastinum and skin (Reinecke 1983).In the oesophagus the adult female worm passes larvated eggs into the lumen, that are finally shed with the faeces and hatch only after having been ingested by an intermediate host (coprophagous beetles) (Fox et al. 1988;Reinecke 1983;Soulsby 1986).Transport hosts (birds, amphibians, reptiles and small mammals) can become infected if they ingest the intermediate host (Fox et al. 1988).
The definitive host becomes infected by ingestion of either the intermediate or transport host.Once ingested, the infective larvae are liberated in the stomach.From there they penetrate the stomach wall, enter an arteriole and migrate in the wall of the gastric and gastric-epiploic arteries to the coeliac artery and then to the thoracic aorta.From the aorta the larvae emerge and migrate to the adjacent oesophagus.This process takes approximately six months (Fox et al. 1988;Reinecke 1983;Soulsby 1986).The pathology of spirocercosis results from larval migration, presence of adult worms in the oesophagus and secondary bacterial infections (Fox et al. 1988).In some cases the oesophageal nodule can undergo malignant transformation to form a sarcoma, with or without metastases (Ivoghli 1978).Hypertrophic osteopathy and spondylitis of the thoracic vertebrae (T6-T12) may also be evident (Fox et al. 1988;Kirberger et al. 2013;Ndiritu & Al-Sadi 1976).
Clinical signs of spirocercosis include vomiting, regurgitation, weight loss, salivation and dysphagia (Evans 1983;Fox et al. 1988).Aortic infection is asymptomatic unless rupture occurs, whereupon haemothorax and sudden death may take place (Soulsby 1986).Aortic thrombo-embolism secondary to aortic aneurysm with sudden-onset hindquarter paralysis can also occur (Gal et al. 2005;Kirberger & Zambelli 2007).Diagnosis is based on survey and contrast radiographs (Evans 1983), oesophagoscopy (Bailey 1963) and finding larvated eggs on faecal flotation (Reinecke 1983;Soulsby 1986).The latter is, however, not a common finding, as the adult female can only shed eggs if there is an opening in the nodule and the eggs are also only shed for an unpredictable, short period of time (Reinecke 1983).As the eggs are heavier than other helminth eggs, a flotation fluid of higher specific gravity is also required (Christie et al. 2011).
One small study reported a prevalence of 74% (Kok et al. 2010), whereas it has been speculated that in endemic areas the prevalence of infection can be 100%, which is probably associated with the many opportunities for acquiring infection from the various intermediate and transport hosts (Urquhart et al. 1991).
In 1998 a questionnaire survey of 716 veterinary practices was undertaken to determine the prevalence of S. lupi in dogs in South Africa (Lobetti 2000).In total 351 (49%) questionnaires were returned, which showed a possible prevalence of 28% with no specific age or sex identified as at higher risk.Large breeds were considered to be at greater risk.The most common complaints by owners and clinical findings were vomiting, weight loss, coughing or regurgitation.Diagnostic methods used were radiology, endoscopy, post mortem examination and faecal flotation.Specific treatments used by 58% of respondents were ivermectin, doramectin, other anthelmintics (benzimidazoles, nitroscanate), and disophenol, whereas 42% of respondents either used no treatment or recommended euthanasia.The majority of respondents considered treatment ineffective and regarded the disease to have a high mortality rate.
The purpose of this study was to repeat the questionnaire survey that was done in 1998 on the prevalence, importance and distribution of S. lupi in South Africa.

Materials and methods
In conjunction with Bayer Animal Health, the same questionnaire (Appendix 1) that was used in 1998 was sent out to 577 veterinary practices throughout South Africa in 2012.The questionnaire was divided into four main sections: (1) presence or absence of S. lupi, and whether the presence was a new phenomenon or not, (2) if S. lupi was associated with time of year, breed, age and sex, (3) presenting features, clinical signs, diagnosis and presence of complications or asymptomatic cases and (4) treatment(s) and effectiveness, and mortality rate of the disease.

Results
In total 316 (55%) questionnaires were returned.Of these, 240 (76%) of the responders indicated that S. lupi occurred in their area, whereas 76 (24%) indicated that it did not.
No specific breed was reported to have been affected by 178 (76%) responders, whereas 55 (24%) reported a breed risk, most considering large breeds to be at greater risk.No specific age or sex was identified to be at higher risk for S. lupi infection.
The most common complaints by owners were vomiting (49%), weight loss (28%), cough (17%) or regurgitation (32%).Reported clinical findings tended to mirror the clinical signs reported by the owners.Other clinical signs reported included salivation, dysphagia, fever, anaemia, dyspnoea or acute death.Only one of the responders reported no abnormal clinical findings.The most common diagnostic methods used were radiology (81%), endoscopy (34%), faecal flotation (9%) and post mortem examination (3%).Other diagnostic methods used were blood smear examination, response to treatment, history and clinical signs.Forty-four percent did not report seeing asymptomatic cases, whilst 40% reported asymptomatic cases and 16% did not know.Complications associated with S. lupi were reported by 85% of responders, and included oesophageal neoplasia (58%), hypertrophic osteopathy (47%) and acute haemothorax (35%).Rare  complications reported were spondylitis, salio-adenitis, oesophagitis, and aortic thrombosis.
The results of the 1998 survey and this survey are summarised in Table 1.

Discussion
This survey indicated that S. lupi is still common in South Africa, having an apparent prevalence of 76%, the highest prevalence still occurring in the provinces of Gauteng and KwaZulu-Natal.This prevalence is similar to that reported by Kok et al. (2010), and higher than in the previous survey (Lobetti 2000), where the reported prevalence was 28%.
The current survey showed that there was an increase in the number of cases seen between 1998 and 2012, which may be as a result of heightened awareness rather than a true increase in prevalence of the disease.
In both this and the previous survey there was no obvious distinction between urban and rural areas.It has previously been reported that S. lupi is common in rural dogs in South Africa (Evans 1983;Reinecke 1983); however, out of 1063 dogs examined for helminths, S. lupi was reported in only three dogs (Verster 1979).Faecal examination is, however, unreliable as only a small percentage of positive dogs can be identified by faecal analysis.In one study 18 of 132 (14%) dogs that were autopsied in South Africa were positive for S. lupi (Minnaar & Krecek 2001).In a Kenyan study, 39 clinical cases and 206 of 1607 (13%) dogs autopsied over a 10-year period were reported to be positive for S. lupi (Wandera 1976).In other studies in Kenya 78% of dogs autopsied were positive for S. lupi, the prevalence being higher in rural than urban dogs (85% versus 38%) (Bradey et al. 1977).In the rural dogs there was a close association with cattle, chickens and dung beetles.
In an Iranian study 76% of sick or stray dogs were infected with S. lupi, with oesophageal lesions present in 58% (Ivoghli 1978).In Malaysia, 23% of dogs autopsied were positive (Retnasalapathy & Khoo-Teik 1976).In India, varying incidences of 20% (Prasad, Singh & Prasad 1971), 58% (Singh, Srivastava & Tewari 1970) and 78% (Ragan & Mohiyuddeen 1974) have been reported.In a study in Southern Texas in the United States of America (USA) it was found that the incidence ranged from 15% to18% (Turk 1960).In Auburn, Alabama, USA, 8% of dogs autopsied were positive (Bailey 1963).It thus appears that the most significant factor involved in the prevalence of S. lupi infection is related to the proximity of the dogs to the intermediate and transport hosts.
The previous survey indicated a tendency towards a summer seasonal prevalence, which was not reported in the current survey.
The previous survey indicated a tendency for large breeds to be at greater risk, with the German shepherd dog at highest risk, which is similar to what has been reported in the literature (Bailey 1972;Lobetti 2012;Wandera 1976).However, this finding was not supported in the current survey.No specific age or sex was identified to be at higher risk for S. lupi infection, although in the literature it has been reported that the most common age group affected with S. lupi is that 1-4 years of age (Chkabra & Singh 1972;Dixon & McGee 1967).In a report from West Africa the age distribution ranged from 1 month to 12 years (Hassan 1982).As this report was based on a faecal survey, the age distribution of dogs less than six months old can be questioned, since the development period of the parasite is 6 months (Fox et al. 1988;Reinecke 1983;Soulsby 1986).Two publications reported male dogs to be more commonly affected (Prasad et al. 1971;Singh et al. 1970), which was not supported in either the previous or the current survey in South Africa.
Complaints by owners and clinical signs (vomiting or regurgitation, weight loss, cough, fever, anaemia, dyspnoea) as well as associated complications (oesophageal neoplasia, hypertrophic osteopathy, acute haemothorax, spondylitis, oesophagitis and aortic thrombosis) were the same as those previously reported (Evans 1983;Fox et al. 1988;Reinecke 1983;Soulsby 1986).The previous survey found that a number of dogs showed no abnormal clinical findings, which was not supported by the current study.
The most common diagnostic methods used in diagnosis of S. lupi were radiology (both survey and contrast), endoscopy and post mortem examination, which is what has been described in the literature (Evans 1983;Fox et al. 1988;Reinecke 1983;Soulsby 1986).In the current survey the use of post mortem diagnosis was greatly reduced over the 14-year period.Although faecal analyses have been used to determine the incidence of S. lupi in other studies (Christie et al. 2011), it was not a commonly used diagnostic method in this survey.This could be attributed to the poor sensitivity of the test as well as the need for a special flotation fluid.In Sierra Leone (West Africa) a faecal survey of dogs showed an infection rate of 3.5% (Hassan 1982), in Kenya 56% (Bradey et al. 1977), in India 37% (Chkabra & Singh 1972), in Malaysia 40% (Retnasalapathy & Khoo-Teik 1976), in rural areas of the south-eastern states of the USA (Alabama and Mississippi) 33.5% (Dixon & McGee 1967), and in Auburn (Alabama), USA 47% (Bailey 1963).It has also been shown that the incidence of the disease can vary, as in a follow-up faecal study done in the same area of Auburn the number of positive cases on faecal examination dropped to 12.7% (Bailey 1972).This was attributed to a decrease in rural areas, and thus rural dogs, and in dung beetle populations as a result of increased use of insecticides.
The mortality rate of spirocercosis in the previous survey was high and probably associated with late diagnosis, presence of complications and no proven available effective anthelmintic.In the current survey the mortality rate was lower, which could be attributed to greater awareness of the disease and increased efficacy of therapy.
The only anthelmintics registered for the therapy of S. lupi are disophenol (Seneviratna, Fernando & Dhanapala 1966), which is no longer available, and Advocate ® (Austin et al. 2013).In this current survey there was a marked reduction in the use of ivermectin and an increase in the use of doramectin.Doramectin has been shown to be effective in the therapy of spirocercosis (Berry 2000;Lavy et al. 2002;Lobetti 2012); however, its use is extra-label, as the product is not registered for use in dogs.The use of Advocate ® was low, which could be attributed to the product having entered the South African market only recently.

Conclusion
In summary, the major changes over the 14 years between the 1998 and 2012 surveys are as follows: • More cases, as well as more asymptomatic cases, are being seen.• Increase in the use of radiographs, oesophagoscopy and faecal analysis in making a diagnosis.• Reduced number of necropsy diagnoses.
• Increased numbers of oesophageal neoplasia and hypertrophy osteopathy being seen as a complication.• Marked reduction in the use of ivermectin as treatment.
• Marked increase in the use of doramectin as treatment.
• Increased efficacy of therapy, with a decrease in high mortality rates.
12. What other treatment(s) do you utilise?

FIGURE
FIGURE 1: Mortality rate reported in the 2012 questionnaire.

TABLE 1 :
1: Mortality rate reported in the 2012 questionnaire.Comparison between the 1998 and 2012 surveys.
†, In the 1998 survey 32% of the responders were unsure as to the outcome of their cases.