These three diseases are all spread by rats.

Leptospirosis is due to infection with the organism Leptospira interrogans. This organism is a highly motile spirochaete. The species leptospira interrogans can be divided into a number of different serovars based upon the organisms’ ability to react with different antibodies. This characteristic enables different serovars to exist preferentially in different species, so, for example, L canicola tends to occur in dogs, L. pomona and L bratislava in swine, L hardjo in cattle, L icterohaemorrhagica in rats, and L gryppotyphosa in field mice. However these relationships are not entirely specific, may be different in different environments and may even change over time.

The links between certain animal hosts and their infecting serovars in the Pacific have been examined in the Federated States of Micronesia (FSM). In FSM, L. australis tends to be associated with rats , L australis, L Bratislava and L copenhageni are associated with dogs, and a large range of serovars (particularly L Bratislava). are associated with swine (Simms, 1998).

Serovars occur more often in some species (‘host-adapted serovars’). because a special type of immunologic relationship exists between infecting serovars and host species. The relationship results in an infected animal becoming an asymptomatic carrier of Leptospirosis, and the animal periodically sheds millions of organisms in the urine over extended periods of time. This creates a maintenance cycle of exposure leading to widespread infection among animals in the area, and marked leptospire contamination of the environment.

Human infection is considered to be a ‘non-host-adapted infection, as the organism cannot be maintained in humans for long periods of time. Non-host -adapted Leptospirosis is considered an accidental infection, which occurs when exposed to leptospires adapted to, and spread, by, another species of animal. Non host-adapted infection is limited to sporadic cases and will not be maintained in a group of animals as long as the source of the non-adapted leptospires is removed (Simms, 1998).

Leptospira can survive for weeks in soil or water. The optimum temperature for their survival is 28-32 degrees Celsius and they survive best in an alkaline environment. Tropical, unpolluted, non-saline waters provide the best environment, and where there is the presence of limestone, as in Fiji, their lifespan is prolonged even further. Flooding after tropical rain is particularly favorable.

In Fiji, there are a large number of animals that are capable of being hosts to Leptospirosis. These include the common rats (Rattus norvegicus, Rattus rattus, Rattus exulans). and mice (Mus musculis), mongooses  (Herpestes auropunctatus), the cane toad (Bufo marinus), cattle, dogs, bats, reptiles and some birds (Faine, 1982). Such organisms infect their environment with large quantities of leptospira.

In Fiji, the main people who develop Leptospirosis-like syndromes are farmers. According to Faine:

Wet soil and heavy early morning dew, mixed with urine vided at night by nocturnal rodents or infected livestock in pastures represent a serious hazard to early morning field workers, particularly in the tropics where field work is done before the heat of the day. The cutting and handling of crops like sugar cane and pineapples frequently causes skin abrasions, which may increase the possibility of leptospiral infection, since strong protective clothing is not always available to workers in low-income groups. Cane cutters are often bare-footed or poorly shod, and scratches on the feet and legs are particularly likely to come in contact with animal urine. However boots into which water has seeped (as when working in deep rice fields). may be more hazardous then protective, and gloves that are wet by rain or dew permit continued contact of leptospires with moist and softened skin… Although the burning of ripe cane  prior to harvesting has many disadvantages, and mechanical harvesting may be undesirable in labour-intensive areas, burning not only facilitates the cutting but also drives out rodents, snakes and amphibians, kills leptospires on the soil, in surface waters and on damp vegetation, and helps to dry the ground surface. Both the burning and mechanical harvesting of cane should be seriously considered in areas of high endemicity where rodent damage is excessive and surface moisture is abundant.  (Faine, 1982)

Foot abrasions in patient with leptospirosis

The primary lesions in leptospirosis are areas of damage to the endothelium of small blood vessels, leading to extravasation of blood, emigration of leptospires into the tissues, and relative anoxia, these then leading to ischaemic damage to organs such as kidneys, liver and adrenals.

Patients originally present with a febrile illness, headache, prostration and severe myalgia—particularly in the lower limbs. They then go on to develop jaundice, renal failure and mental depression. There is a wide range of complicating conditions that can occur in Leptospirosis including pulmonary haemorrhage, gastrointestinal haemorrhage, meningism, mania, iritis and pancreatitis. Severe cases of Leptospirosis have a high mortality if they are not treated early.

Jaundice in a patient with leptospirosis

Diagnosis of Leptospirosis is based upon evidence of a single high titre of antibodies, or a rise in antibody titer. Antibodies do not generally become detectable until the second week of illness. They can be tested for in a number of ways. In Fiji, it has generally been done using the macroscopic slide agglutination test. This is less specific than the microscopic agglutination test (MAT). Recently an ELIZA test has also been used in Fiji, and other serological tests are also available elsewhere

Leptospires can be isolated in the blood/CSF during the first 10 days of the illness, and from urine for several weeks from about 1 week. Specimens need to be cultured on special media, but this can be done at reference laboratories, since the leptospira remain alive in uncoagulated blood for up to 11 days.

Leptospirosis has been known to exist in Fiji for a long time. In 1952 a Fijian soldier died shortly after arriving in Singapore. This is thought to be the first recorded case of Leptospirosis contracted in Fiji (Ram, 1978).  In 1958, Edmonds and Hawley found that almost 25% of people at Nabua had leptospiral antibodies (Ram, 1974). Leptospirosis was first diagnosed clinically in Fiji in 1969.

Between 1965 and 1966, the Fiji Veterinary Laboratory carried out a survey of Leptospiral antibodies in cattle and dogs. Of 55 normal cattle, leptospiral antibodies were found in 22 (4.4%). These were predominantly L pomona. Serology was also tested in 20 dogs that showed signs of hepatitis or nephritis, and antibodies to L canicola were found in 3, and L icterohaemorrhagica were found in 7. In 1970, Sparrow quoted the prevalence of leptospiral antibodies in dogs as 19%. Between 1971 and 1974, L pomona antibodies were found in pigs, and in a later study of pigs, L pomona continued to be the most common serovars, but L icterohaemorrhagiae, L wolfii, L autumnalis and L bataviae were also found.  Leptospiral antibodies were found in only 1 out of 58 rat sera tested in 1971-4 and none of 80 mongoose sera (Ram, 1974).

After the initial reports, the numbers of patients diagnosed with Leptospirosis in the years 1972-1977 fluctuated between 25-57.The cases occurred mostly in men, mostly in the rainy  season, and mostly in ethnic Fijians. The predominant infecting serovar was icterohaemorrhagica (46%), followed by australis (23.8%). and canicola (31%). and cynopteri (19%). The major presenting syndromes were hepatorenal syndrome (66%), septicaemia (23%), aseptic meningitis (10%). and bilateral uveitis (0.7%). There were 13 deaths, all of which were due to hepatorenal syndrome (Ram, 1978). Pneumonitis was found in 25% and haemoptysis in 8.3%  (Ram, 1978). By 1974, 445 cases were diagnosed at CWM Hospital over the next 15 years. There were 36 deaths—a case fatality of 8%. Autopsies were performed on 18 cases. Severe pulmonary haemorrhages were found in four cases (Singh et al. 1986).

A severe epidemic of what was thought to be Leptospirosis occurred in Labasa in 2000. Between January and August 67 cases were diagnosed, of which 31 died. Many of these cases died of pulmonary haemorrhage. Leptospira serology was only positive in a minority of these cases.  

Pulmonary haemorrhage in leptospirosis 

Table 19.3.  Leptospirosis in Fiji

Source: Buadromo, 2001

  The results of investigations for Leptospirosis for 1995-2000 are shown in Table 19.3. These appear to show a marked change in the serovars infecting humans in Fiji since the earlier reported cases, but some of this can be explained by cross-reactivity of some serological tests for copenhageni and icterohaemorrhagica. This has led laboratories to stop testing for icterohaemorrhagica and to test only for copenhageni. It is apparent that many of those who are thought to have Leptospirosis in Fiji test negative for leptospiral serology. There may be a number of reasons for this.

Firstly, it maybe that inappropriate testing is being ordered. However many patients who have tested negative do appear to have syndromes indistinguishable from those who have tested positive.

A second reason might be if patients were tested before antibodies develop. Antibodies tend to develop after one week, and although many patients present late, it is possible that blood samples are done before this time. The use of paired samples would prevent this from occurring, although they can be hard to arrange, especially as many patients are from remote, rural areas.

A final reason might be if some of the patients actually suffer from a different disease. The differential diagnosis of Leptospirosis includes malaria, enteric fever, viral hepatitis, dengue, Hantavirus and Rickettsia (Speelman ). Studies are needed to see which of these organisms might be implicated in Fijian disease patterns.

Leptospirosis is treated with antibiotics and supportive care. The usual antibiotic used in Fiji is penicillin. The more severe cases are also treated with steroids, and H2 receptor blockers.  Patients with severe disease frequently require inotropic agents, peritoneal dialysis, ICU admission, CVP monitoring and intubation and ventilation. In 1985 it was reported that Leptospirosis was the most cause of acute renal failure in Fiji at CWM hospital, being responsible for 202 out of 5551 cases of acute renal failure seen at CWM between 1968 and 1984. In the Leptospirosis patients with renal failure, there was a case fatality of 17.8%.  

Peritoneal dialysis in leptospirosis

In the early reports of Leptospirosis in Fiji, the main cause of death was hepatorenal syndrome. More recently, an increasing number of deaths due to pulmonary haemorrhage appear to be occurring, and in 1999-2000, all deaths in those with leptospirosis occurred due to pulmonary haemorrhage. This is a worldwide trend, but the cause is currently uncertain. Possibilities include changes in infecting serovars, co-infection with other organisms such as Hantaviruses, or changes in immunological responses such as if people had repeat infections with different serovars.

A case series from Australia has reported that steroid therapy is effective in treating pulmonary haemorrhage in patients with Leptospirosis (Med Jn Aust, 1998). and steroids have also been reported to be effective in the treatment of severe Leptospirosis in Pohnpei (Malani et al. 1996). However in practice, few patients with massive pulmonary haemorrhage in Leptospirosis survive despite treatment with steroids. There is one case history documented of a patient with Leptospirosis who had oliguric renal failure and massive pulmonary haemorrhage but who survived after treatment with nitric oxide inhalation and haemofiltration (Borere et al. 1999). At present this form of treatment is not available in Fiji, but it may become possible in the future.

It should also be noted that a number of patients in Fiji present with pulmonary haemorrhage alone, without the other symptoms of Leptospirosis. These patients have an extremely high early mortality. It is uncertain whether this syndrome represents a limited form of Leptospirosis, or is due to a separate disease.

Simms (1998). has made the following suggestions for formulating a leptospirosis control program

1.The systematic reduction of the number of leptospires in the environment through:

a. Vaccination of animals;

b. Periodic administration of antibiotics to the animal population; and

c. Eradication of the rodent population;

2.A public education campaign, to increase public awareness of:

a. The risk of infections

b. The symptoms; and

c. The benefits of early treatment.

He also noted that vaccination of humans is occasionally undertaken, but is limited by the side effects of the vaccine.  Animal vaccines would cost $US360 to produce 1500 doses of a trivalent leptospirosis vaccine, and both dogs and pigs would need to be vaccinated twice yearly. In the Fijian context, this may decrease the disease to some extent, but many dogs would be simply un-catchable, and animals like rats are unlikely to be suitable candidates.

There is some potential for an education campaign. The syndrome of ‘muscle aches and pains’ is one of the leading causes of consultation and may turn out to be due to anything from influenza to osteoarthritis. Because of its ubiquity, early treatment of patients with penicillin might not be economically viable. This is also an area that would benefit from further research.

Hantaviruses  are single-stranded RNA viruses belonging to the family Bunyaviridae. There are a number of different Hantaviruses, each associated with a single host species of rodent. When a Hantavirus infects a rodent from its host species, the infection is life-long, and the host rodent continues to shed virus asymptomatically in saliva, urine and faeces for a variable period of time after infection. These viruses may cause further colonisation of other members of the host species, or they may infect other species of rodent or other animals such as man. In non-host species viruses may be asymptomatic or may cause disease, but they will be unable to be maintained for long periods (Butler & Peters, 1994).

Hantaviruses are found in rodents all over the world, and appear to have spread around the world at the same time as their rodent hosts. Hantaviruses are adapted to particular hosts; so new host species do not become colonized with Hantaviruses that colonise other rodents. The importance of this in the Pacific is that there are limited numbers of rodent species, so the number and type of Hantaviruses that might occur are also limited.

There are two main groups of Hantavirus—those that affect the old-world rodents of Europe, Asia and Africa, and those that infect the new-world rodents of North and South America. Hantaviruses that infect old-world rodents cause  ‘Haemorrhagic fever with renal syndrome’ (HFRS), whereas the new-world rodents cause Hantavirus pulmonary syndrome (HPS). The delineation between these two illnesses is not always straightforward.

There are four main viruses that infect old-world rodents and are pathogenic in humans.—Hantaan virus (Striped field mouse—Apodemus agrarius), Seoul virus (Norway rat—Rattus  norwegicus), Puumala virus (bank vole—Clethrionomys glariolus). and Dobrava virus (Yellow necked field mouse—Apodemus flavicollis). (Butler & Peters, 1994). Serological evidence of infection with these agents may be found in other rodents, but this would not usually reflect colonisation.  Of the hosts of these viruses, only Rattus norwegicus is present in Fiji.

There are a large number of new-world Hantaviruses associated with American rodents (Levis et al. 1998; Young et al. 1998). yet none of these hosts are found in the Pacific. The exception to this is that there is a single report of a Hantavirus known as Leakey virus from the old-world house mouse Mus musculis obtained in Texas (Childs et al. 1994). The significance of this finding is not known.

In the Pacific, there are only four species of rodent—Rattus Norwegicus (Norway rat), Rattus rattus  (roof rat), Rattus exulans (Polynesian rat), and Mus domesticuls or Mus musculis (house or musk mouse). (Simms, 1998). Of these, all except Rattus exulans are widely spread around the world including Europe, Asia, the America and the Pacific. In Russian studies, antibodies to Hantaviruses have been identified in the three widely spread species, though it is probable that only Rattus Norwegicus and possibly Rattus rattus are colonised—by Seoul type viruses (Tkachenko et al. 1998). 

Rattus exulans, the Polynesian rat, has been in the Pacific from pre-colonial times where it is thought to have been brought with early human settlers from Asia. It is therefore an old-world rat, and any Hantaviruses that use it as a host will probably share old-world characteristics. As yet, there are no reported Hantaviruses found in this host, but it has not yet been well studied. In Fijian studies in which rats are captured in urban environments, Rattus exulans is not commonly seen.

Hantaviruses are associated with two main medical syndromes. The old-world viruses such as Seoul virus cause ‘Haemorrhagic fever with renal syndrome’ (HFRS), whereas the new-world viruses cause Hantavirus pulmonary syndrome (HPS). From the discussion above, it seems likely that Fiji should only see cases of HFRS, since the host for Seoul virus is present here. There is also the possibility of other, as yet undescribed Hantaviruses infecting Rattus exulans, but these are also likely to cause HFRS rather than HPS, since they would also be old-world type viruses.

Many patients with HFRS follow a typical course of illness which follows five main stages:

1. Febrile phase (days 1-4). The onset is abrupt with retro-orbital headache, eye pain, photophobia and mild myalgia. Gastrointestinal symptoms (abdominal pain, nausea and vomiting). are common. There is typically an erythematous rash, which may become petechial on the face, neck, shoulders and upper thorax.

2. Hypotensive phase (days 5-8). This starts about the fifth day of illness with marked proteinuria, haemoconcentration, hypotension and occasionally shock

3. Oliguric phase (days 9-11). This starts about the ninth day with increased urinary output and signs of renal failure. Haemorrhagic manifestations appear with haematuria, serious haemorrhage is unusual, but may take the form of haematemesis, melaena, and cerebrovascular complications.

4. Diuretic phase (Days 12-14). The patient improves with diuresis.

5. Convalescent phase (15^th day onwards). This phase is protracted, lasting up to 4 months. Sequelae are rare, except those resulting from CNS complications.’ (Simpson, 1996).

The following findings are useful in making the diagnosis of HFRS: sudden onset of high fever, chills, myalgia, anorexia, nausea and vomiting and severe pain in the retro-orbital area, eyeball, abdomen and flank; flushing of the face, neck and anterior cheat area, injections of conjunctiva and pharynx, petechial in axilla, soft palate and conjunctivae, and costovertebral angle tenderness; laboratory findings of leukocytosis with a left shift, haemoconcentration, thrombocytopenia, and atypical lymphocytes, urinary findings of microscopic haematuria and proteinuria, and biochemical findings of increased creatinine and blood urea nitrogen, increased transaminase, hypoalbuminaemia, decrease cholesterol level with decreased HDL cholesterol. Confirmation of the disease is based on demonstration of specific IgM antibodies on Elisa, or fourfold or greater rise in anti-hantavirus antibody titre in paired sera by any serological tests (Lee, et al. 1998).

There are also some long-term sequelae of Hantavirus infection. Studies of HFRS in USA have shown that there are a number of cases of this disease that were previously overlooked. In Baltimore, Seoul virus is associated with Rattus norwegicus, and researchers have identified a number of cases associated with chronic hypertensive renal diseases (Butler & Peters, 1994).

In 1982, 82 human sera and 58 sera from rats were sent to the institute of viral studies in Korea as part of an investigation of an outbreak of glomerulonephritis. Three of the human sera showed positive titres (1:160, 1:160, 1:20). for Hantaan virus. There were five positive rat sera with titres ranging from 1:20 to 1:80. A further batch of 44 human sera and 45 rat sera were sent in 1984. Three human and one rat sera showed positive titres against Hantaan virus (Ram et al. 1986).

In 1992, Dr Andrew Ajdukiewicz from the Fiji School of Medicine sent specimens from 39 patients presenting with a range of diseases. A number of patients with different disease presentations were found to have antibodies to Hantavirus (Table 19.4).

Table19.4 Presentations of cases with positive Hantavirus serology.

   A typical case history for one of these patients is as follows: an 18-year-old male was admitted with a 6-day history of severe muscle pain, vomiting and nausea. No diarrhoea, cough, haemoptysis or haematuria. On examination he was conscious, toxic, jaundiced with conjunctival injection and liver tenderness. HB 13.8, WCC 12,800, platelets 63,000. His creatinine rose to 849, and bilirubin to 587. His LDH rose to 843, CK to 1009, but Alkaline phosphatase max was 171, ALT max was 294. His presumptive diagnosis was Leptospirosis although serology was not done. Hantavirus was only diagnosed in retrospect when serology was performed.

In 2000 Dr Adjukiwiecz sent a further 16 specimens of which two were positive for Hantavirus.  

Leptospirosis and Hantavirus are both spread by rodents, and both present with similar syndromes. The clinical histories of most of the cases found by Dr Adjukiwiecz are entirely consistent with leptospirosis, although serology was either not done, or was negative for all of them. 

When evidence of Hantavirus infection is found in people with leptospirosis—type syndromes, it is important then to distinguish whether the Hantavirus serology is simply a marker of the patient’s contact with rodents, or represents actual Hantavirus disease.

Acute infections with Hantavirus can be demonstrated either by the presence of Hantavirus in tissues, by an increase in Titre of IgG, or by IgM as demonstrated by IgM capture ELIZA. IgM antibodies appear by the 5^th to seventh day of the illness, specific titres rising to 1/64 and falling again after 6-8 weeks. Other immunoflourescent IgG and neutralizing antibodies persist at high titre for more than three decades (Simpson, 1996).

Unfortunately, because of the high mortality, patients often die. before serological markers appear. In this case other methods of diagnosis are required. In a Chilean series of cases, infection was confirmed via genetic sequencing of material amplified from autopsy tissue (MMWR, 1997). A German series has shown that is possible to detect the presence of Hantavirus in kidney biopsy specimens using the polymerase chain reaction (Heiske et al. 1999).

The differential diagnosis of HFRS includes scrub typhus, leptospira, other viruses, ITP, TTP, and the cause of ARF. The differential diagnosis of  HPS includes pneumococcal pneumonia, pneumonic plague, psittacosis, histoplasmosis, mycoplasma pneumonia, influenza, tularemia, legionellosis, meningococcemia, Leptospirosis, disseminated fungi, and  rickettsia (Butler & Peters, 1994). Other agents of interest that can cause overwhelming pulmonary syndromes include meiloidosis and equine morbilliform virus.  

Eosinophillic meningitis is a disease caused by the parasite Angiostrongylus cantonensis —the rat  lung worm. According to Kliks et al.:

…Angiostrongylus  cantonensis, was first detected in rats in Canton, China in 1933... During and just after WWII the parasite was introduced, and/or spread passively from South and Southeast Asia into the Western Pacific islands and eastward and southward through Micronesia, Melanesia, Australia and into Polynesia, sequestered in shipments of war material and facilitated by post-war commerce. In the 1950s numerous cases were identified for the first time on Sumatra, the Philippines, Taiwan, Saipan, New Caledonia, and as far east as Rarotonga and Tahiti. Then cases were detected in Vietnam, Thailand, Cambodia, Java, Sarawak, the New Hebrides, Guam and Hawaii during the 1960s..’ (Kliks et al. 1992).

As well as occurring in rats, this parasite may also occur in aquatic creatures such as shrimp, fish and snails. The parasite can be ingested by children eating snails, or eating raw fish or vegetables contaminated by snails .

Although the disease is usually mild, there are a number of case reports of fatalities from this condition, including cases that have occurred in Fiji (Paine et al. 1994). The disease should be suspected in patients with headaches and eosinophilia in their CSF. It is often associated with paraesthesias and itch. Most patients recover without treatment (Pungyagupta et al. 1975). Treatment with either  prednisone, mebendazole, or albendazole have been recommended by some authorities although it has also been suggested that vermicidal agents may make the disease worse by suddenly killing the parasites. In Fiji, most cases are managed conservatively .

 Borer A, Metz I, Gilad J, Riesenberg K, et al (1999). Massive pulmonary haemorrhage caused by Leptospirosis successfully treated with nitric oxide inhalation and hemofiltration. J Infect. 38(1).: 42-5.

 Buadromo E (2000). Private communication.

Butler JG, Peters CJ (1994). Hantaviruses and hantavirus pulmonary syndrome. Clin Inf Dis. 19: 387-95.

 Childs JE, Ksiazek TG, Spiropolou CF, Krebs JW et al (1994). Serologic and Genetic identification of Peromyscus maniculatus as the primary rodent resevoir for a new hantavirus in the South-Western United States. Jn Inf Dis. 169: 1271-80.

 Heiske A, Anheier B, Pilaski J, Klenk HD, Grone HJ, Feldmann H (1999).  Polymerase chain reaction detection of Puumala virus RNA in formaldehyde-fixed biopsy material. Kidney Int. 55(5).: 2062-9

 Kay BH, Prakash G, Andre RG (1995). Aedes albopictus and other Aedes (Stegomyia). species in Fiji. J Am Mosq Control Assoc. 11(2 Pt 1).: 230-4 

Kliks MM, Palumbo NE. Eosinophilic meningitis beyond the Pacific Basin: the global dispersal of a peridomestic zoonoses caused by Angiostrongylus cantonensis, the nematode lungworm of rats. Soc-Sci-Med. 1992 Jan; 34(2).: 199-212. 

Lee JS, Lahdevirta J, Koster F, Levy H (1998). Clinical manifestations and treatment of HFRS and HPS. in Lee HW, Calisher C, Schmaljohn C. Manual of Haemorrhagic fever with renal syndrome and  Hantavirus pulmonary syndrome. WHO, Seoul.1998. 

Levis S, Morzunov SP, Rowe JE, Enria D, et al (1998). Genetic diversity and epidemiology of Hantaviruses in Argentina. Jn Infect Dis 177: 529-38. 

Malani J, Pryor J, Lusangulira K (1996). Leptospirosis in Pohnpei (1986-1995).: a case series on the use of dopamine/steroid for Weil’s syndrome. Pacific Health Dialog. 2).: 153-161. 

Med Jn Aust (1998).Leptospirosis associated with severe pulmonary haemorrhage in Far North Queensland. Med Jn Aust.  169: 151-3. 

MMWR (1997). 46(40).: 949-50. 

Paine M, Davis S. Brown G (1994).  Severe forms of infection with  Angiostrongylus cantonensis acquired in Australia and Fiji.  Aust NZ J Med. 24:415- 416. 

Punyagupta S, Juttijudata P, Bunnag T (1975).  Eosinophilic meningitis in Thailand: Clinical studies of 484 cases probably caused by Angiostrongylus cantonensis. Am J Trop Med Hygiene 24:921-931. 

Ram P (1974). Leptospirosis. Fiji Medical Journal.  2: 171-5 

Ram P, Beg MF, Rao, U, Nadiri P, et al (1986). Acute glomerulonephritis in Fiji 1981-1982. Fiji Med Jn. 14(5&6). 123-132. 

Ram P (1978a). Epidemiology of Leptospirosis in Fiji. Fiji Med Jn. 6: 70-72. 

Ram P (1978b). History of Leptospirosis in Fiji. Fiji Med Jn. 6:68-9. 

Ram P (1978c). Leptospira icterohaemorrhagiae infections. Fiji Med Jn. 6: 73-8. 

Simms JR (1998). Animal Leptospirosis in the Federated States of Micronesia. Pacific Health Dialog. 5(1).: 30-37. 

Simpson DIH (1996). Arbovirus infections. In Cook GC. Manson’s Tropical Disease. WB Saunders, London.  

Singh KP, Seruvatu LM, Ram P (1986). Autopsy findings in human leptospirosis. Fiji Med Jn. 14 (1&2).17-19. 

Speelman P (1997). Leptospirosis. In  Harrison’s principles of Internal medicine. 14th Edition. 

Tkachenko RA, Ivanidze EA, Zagidullin I, Dekonenko AE (1998). HFRS in Eurasia: Russia and the republics of the former USSR. In Wang Lee H, Calisher C, Schmaljohn C (eds). Manual of haemorrhagic fever with renal syndrome and hantavirus pulmonary syndrome. WHO. 

Young JC, Mills JN, Enria DA, Dolan NE, Khan AS, Ksiazek TG (1998). New-world Hantaviruses.  Brit Med Bull. 54(3).: 659-73.