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New Zealand Veterinary Journal 50(3) Supplement, 61-63, 2002 Fifty years of leptospirosis research in New Zealand: a perspective
RB Marshall*‡ and BW Manktelow†§
Introduction
hyos (later renamed tarassovi) and 5% had similar titres to serovar pomona. It was not until 1975 that Ryan and Marshall reported It is not known when pathogenic leptospires fi rst became estab- the fi rst isolation in culture of serovar tarassovi in the course of lished in New Zealand. The fi rst land mammals to arrive in this a survey for leptospirosis in pigs being submitted to an abattoir. country about 1,200 years ago were human beings, dogs and the The survey was of 80 pigs and from these, one isolation of serovar kiore, Rattus exulans. It cannot be determined if leptospirosis tarassovi was made, in contrast to serovar pomona which was re- also arrived at that time. It is more likely that most, if not all covered from 38. As indicated by both serological and cultural pathogenic leptospires arrived with intentional and unintentional studies in this country the overall level of infection of serovar mammalian imports in the late 18th and 19th centuries.
tarassovi in deer, goats and horses is of the order of 1–6%. It has The history of leptospirosis research in New Zealand is one which also been isolated from dogs (Mackintosh et al 1980) and cases of has traced the pattern of infection from overt animal and human human infections with this serovar have also been reported (Wilks disease through to the epidemiology of inapparent carrier states in both domestic and feral animals. We now know that these carriers represent reservoirs of infection. The causal organisms are fragile Human leptospirosis
and can be diffi cult to grow. Serological testing has sometimes been useful in diagnosis but in earlier days serology created con- Even in the early days of interest in leptospirosis as an animal fusion because of cross-reactions among types (serovars) of lep- disease, the phenomenon of zoonotic infection of human subjects tospires. For example early studies suggested that the hedgehog, was fully appreciated. The advent of the Accident Compensation Erinaceus europaeus occidentalis, might be a carrier of infection by Scheme, under which leptospirosis was classifi ed as an occupa- serovar pomona, but subsequent work showed that serovar ballum tional disease of farmers and meat industry workers, gave research was the most common serovar in that host. Another very practical in this fi eld considerable impetus. Blood cultures of the organism defi ciency of reliance on serological diagnosis was the absence of became promoted as the “gold standard” for diagnosis of hu- antibody in the early stages of acute disease.
man leptospirosis but that required good clinical skills and early suspicion of the disease during differential diagnoses. It also re- The fi rst confi rmed occurrence of leptospirosis in domesticated quired ready access to laboratories with the ability to provide the animals in New Zealand was in 1950 when Leptospira pomona specialised services needed for the culture and identifi cation of (later known as L. interrogans serovar pomona) was isolated from leptospires. The septicaemic phase of the disease is relatively short a calf with haemoglobinuria at Wallaceville Animal Research Sta- (4–7 days) and more data were needed on the dynamics of anti- tion (Anonymous 1951), but 1953 was the seminal year for pub- body levels in patients if serology was to be useful in diagnostic lications on leptospirosis. At a meeting of the Northland Branch and epidemiological studies. Serum antibody begins to be detect- of the New Zealand Veterinary Association, Ensor (1953) report- able during the second week of illness and should peak about 2 ed that in Northland during the 1952 season, 76 farms reported weeks later but treatment with antibiotics can confuse the clarity outbreaks of redwater which were attributed to leptospirosis. At of both serological and cultural approaches to diagnosis. In spite the same meeting McClure (1953) reported the clinical and post- of this potential diffi culty, in suspect cases it is important to insti- mortem characteristics of the disease in young calves. He also gave tute antibiotic treatment at high dosage as early as possible. The the opinion that “Investigation into the relationship of Leptospira antibiotic of choice is penicillin, given intravenously at the rate pomona and bovine abortion in New Zealand would be of value.” of 2 mega-units 6-hourly for 7 days. Oral doxycycline, 100 mg There was not long to wait because 7 months later Te Punga and 12-hourly, is an effective alternative in patients who are allergic to Bishop (1953) recorded an outbreak of bovine abortion in the penicillin (Wilks and Humble 1997). In epidemiological studies Waikato district which was established as being due to serovar po- the rate of decline or half-life of leptospiral antibodies becomes an mona. Interestingly, the paper contains the earliest colour illustra- important theoretical variable to be accounted for in population tions to appear in the New Zealand Veterinary Journal, including studies. However, studies over 53 months of 69 meat inspectors an excellent photomicrograph showing a silver-stained leptospiral with a range of leptospiral titres showed considerable variation organism in a foetal kidney. The colour plates also illustrate the in magnitude and rates of decay. Furthermore, some individuals contrast between the clear-cut severe lesions of placentitis due to with previously confi rmed leptospirosis had titres of 1:192, seven Brucella abortus, which was present in New Zealand at that time, years after infection (Blackmore et al 1984). Cross-reactivity and the mildness of changes in the placenta associated with lepto- between serovars can also create diffi culty in establishing which spiral abortion. We now know that the latter “lesions” are largely serovars a host may have experienced.
autolytic or putrefactive in nature and associated with intrauter-ine death of the bovine conceptus.
Taxonomy of serovars present
In 1958 Russell and Hansen extended interest in leptospirosis from cattle to pigs. They examined the sera of 1,125 healthy in New Zealand
adult pigs and found 4% had titres of 1:200 or higher to serovar The taxonomy of leptospiral organisms has been improved con-siderably since the fi rst reports in this journal of the diseases they caused. Although internationally there are some 180 serovars recognised within the seven species of pathogenic leptospires, * Infobrok, 110A Linton Street, Palmerston North, New Zealand.
‡ only eight of these serovars within two species have been isolated Editor’s note: This paper was completed by the second author using notes and confi rmed as being present in this country. These are serovars prepared by Dr Roger Marshall before his untimely death.
† 79 Jickell Street, Palmerston North, New Zealand.
australis, canicola, copenhageni and pomona within the species L. § Author for correspondence. Email: [email protected] interrogans, as well as serovars balcanica, hardjobovis, tarrasovi New Zealand Veterinary Journal 50(3) Supplement, 2002 and ballum within the species L. borgpetersenii. Serovars canicola of serovar pomona. One of these was a formalinised, alum-pre- and australis have only been isolated from human patients in this cipitated vaccine, the other was freeze-dried. The former induced country and thus cannot be ascribed endemic status.
the highest and most persistent antibody response. Vaccination was successfully used to prevent leptospirosis of young calves by Important to the understanding of the epidemiology of the a double dose vaccination of their dams in late pregnancy. Since various leptospiral types was the advent of typing by using endo- the early work on vaccination there have been improvements in nucleases to study the genomes of isolates (Marshall et al 1981; vaccines but more importantly an improved understanding of the epidemiology of the various serovars. This understanding has greatly facilitated the elaboration of effective vaccination strate- Maintenance hosts and renal localisation of infection
gies. Such strategies are now fi rmly established for both cattle and pig industries.
The presence of maintenance hosts is pivotal to the endemic ex-istence of the disease. For the optimum persistence of leptospiral In countries where the major maintenance hosts are among wild- infection in a maintenance host the infection should not kill the life, control of human leptospirosis by control of the disease in host and the shedding of viable organisms in the urine should animals is not a feasible option and aggressive reduction of hosts last for a relatively long period. Recognised maintenance hosts for such as rodents, plus possible vaccination of at-risk persons, is ac- various serovars are cattle for serovar hardjobovis, pigs for serovars cepted as the best approach. In New Zealand, the vast majority of pomona and tarassovi, brushtail possums (Trichosurus vulpecula) cases of human infection are derived from domestic animals and for serovar balcanica, the black rat (Rattus rattus) for serovar bal- as a consequence there is a golden opportunity to control the eco- lum, and the brown or Norway rat (Rattus norvegicus) for serovar nomic effects of disease in animals and concurrently reduce the copenhageni. Wilson et al (1998) have also suggested that farmed exposure to infection of people, especially those in high-risk oc- deer may act as maintenance hosts for some serovars. Charac- cupations. Members of the Women’s Division of Federated Farm- teristically the maintenance relationship between organism and ers saw the toll that was caused by leptospirosis in rural workers host is most evident in sexually mature animals. In this context and raised a considerable amount of money to fund research into horses, dogs, human beings, goats, sheep and camelids have not the problem at Massey University. The main research priorities been identifi ed as regular maintenance hosts and usually become were the identifi cation of maintenance hosts and the elaboration infected by direct contact with infected maintenance host species, of the best strategies for control. The majority of human cases of their urine, or effl uent. The common natural routes of infection leptospirosis were in dairy farmers. The belief that the number of are believed to be via the conjunctiva, oral or nasal mucosae, or organisms required to infect a human being was less if the route was through abraded skin or mucous membranes, as opposed to intact skin, had long been a basis for public health recommenda- The signifi cance of localisation of infection in the kidney cannot tions for workers at risk from infected animals. Application of be over-emphasised because of the importance of this phenom- these theoretical measures aimed at protecting people milking enon as a stage of the disease that follows the septicaemic compo- cows from urine splashes, and shielding skin and mucosae by nent. The duration and intensity of leptospiruria are key factors. mechanical barriers, or appropriate changes in work practices, The localisation of leptospires in the proximal convoluted tubules were considered unlikely to be widely adopted. After dairy farm- of the kidney is assumed to afford them some degree of protection ers, meat industry workers and pig keepers were the next most from humoral antibody. This protection permits replication and commonly affected groups. Vaccination of maintenance hosts persistence of the organisms within the tubular lumen. Nonethe- using an appropriate strategy to control animal infection and less there is an interstitial cellular reaction in infected kidneys that thereby human disease, was soon identifi ed as the best approach. in some cases may give rise to focal lesions which, if severe, may There became apparent a strong will to tackle the problem on a be seen with the naked eye and are almost always detectable by broad front. The industry, Massey University, government agen- cies, including the Accident Compensation Commission, vaccine In maintenance hosts, leptospiruria persists for long periods, and manufacturers and, most importantly, the veterinary profession may even last for a lifetime. Detection of leptospiruria by either joined in the battle. At the same time steps were taken to increase culture or direct microscopy can be used to confi rm endemicity the awareness of the disease among rural medical practitioners.
of infection in a herd or the diagnosis of subclinical disease in individual animals. Dark fi eld microscopy will detect leptospiral Control programmes
organisms in urine if they are present at a concentration of at least 1,000 organisms per ml of urine. That concentration is common- Improvements in the performance of vaccines allowed industry- ly achieved in maintenance hosts and may go as high as 100,000 wide control programmes based on a full understanding of the per ml. Cultural techniques unfortunately take up to 3 months disease in the maintenance species (Marshall 1987). Vaccination to complete and isolation may be frustrated by the presence of of adult females leads to the acquisition of passive immunity in other bacteria which overgrow leptospires in the non-selective, young animals. This has the advantage of protecting the other- specialised media which they require for growth.
wise susceptible young but may interfere with production of ac-tive immunity if fi rst vaccination occurs while humoral antibody is still present. The period during which the susceptible infected Vaccination and control
host sheds leptospires in the urine, and the concentration of Soon after reports of the disease associated with serovar pomona those organisms, determine the chance of infection being passed in cattle, attempts were made to produce a suitable vaccine, using to another animal of the same or different species. The dose of a heat-killed whole culture (Webster and Reynolds 1955). The organisms required for a new host to become infected depends size and recognition of the problem of serovar pomona infection upon the species being infected, the characteristics of the invading at that time is illustrated by the fact that in the period 1952–5, leptospires and the route of entry. Nevertheless current vaccine- 13,000 bovine sera were examined at the Wallaceville laboratory based control programmes have been extremely successful. Hu- for antibodies to leptospires (McDonald and Rudge 1957). The man beings acquire their leptospiral infections almost exclusively same paper by the latter two authors reported on the preparation from animal sources. They are therefore a very useful sentinel and testing of two vaccines prepared from a virulent fi eld isolate species for success or otherwise of control of infection in animals. New Zealand Veterinary Journal 50(3) Supplement, 2002 A bivalent animal vaccine against serovars pomona and hardjobovis Selected further reading
was vigorously introduced to the market at the end of 1979. No-tifi cations of human infection dropped from 677 in 1979, to 325 Blackmore DK, Schollum LM. The occupational hazards of leptospirosis in the
meat industry. New Zealand Medical Journal 95, 494–7, 1982 in 1981. In the following year the number fell to 179 cases and Blackmore DK, Schollum LM. Risks of contracting leptospirosis on the dairy
remained at <200 for another 5 years with further falls later (Mar- farm. New Zealand Medical Journal 95, 649–52, 1982 shall and Chereshsky 1996). This was a very pleasing outcome.
Blackmore DK, Marshall RB, Mackintosh CG. Alternative strategies for the
control of leptospirosis in dairy herds. New Zealand Veterinary Journal 29, 19–20, 1981 Conclusion
Blackmore DK, Bahaman AR, Marshall RB. The epidemiological interpretation
Confusion and uncertainty have often occurred as a consequence of serological responses to leptospiral serovars in sheep. New Zealand Veterinary of published research, surveillance, and individual diagnosis when Bolt I, Marshall RB. The epidemiology of Leptospira interrogans serovar pomona
they have relied exclusively upon serological data. In spite of the in grower pig herds. New Zealand Veterinary Journal 43, 10–15, 1995 practical diffi culties associated with cultural isolation of patho- Brockie RE. Leptospiral infections of rodents in the North Island. New Zealand
genic leptospires, signifi cant advances in an understanding of the Veterinary Journal 25, 89–91, 1977 epidemiology of leptospiral infections must still rely heavily on Chereshsky A, Cameron G, Marshall RB. A case of human Leptospira canicola
the “gold standard” of isolation and identifi cation of the causal infection in New Zealand. New Zealand Veterinary Journal 41, 101, 1993 organism. The knowledge base so derived may be further en- Day TD, Waas JR, O’Connor CE. Effects of experimental infection with
hanced by the use of more recently developed molecular biologi- Leptospira interrogans serovar balcanica on the health of brushtail possums cal techniques such as those pioneered by Marshall et al in 1981.
(Trichsurus vulpecula). New Zealand Veterinary Journal 45, 4–7, 1997 Fairley R. Porcine leptospirosis in New Zealand. Surveillance 24(4), 15, 1997
The New Zealand experience is that sound and comprehensive Fairley RA, Cooper DR, Guilford WG, Schollum LM. Haemolytic disease
research must precede the formulation of control strategies. associated with Leptospira interrogans serovar pomona in red deer calves (Cervus Multifaceted communication and cooperation between research- elaphus). New Zealand Veterinary Journal 34, 116–7, 1986 ers, veterinary clinicians, and private, voluntary and statutory Flint SH, Corner RJ, Marshall RB. A serological study of leptospirosis in
domestic deer in New Zealand. New Zealand Veterinary Journal 36, 151–2, interests have been key ingredients of the successful control pro- gramme that is in place in this country.
Hathaway SC. Leptospirosis in New Zealand: an ecological point of view. New
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