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The hemorrhagic fevers of Southern Africa with special reference to studies in the South African Institute for Medical Research.

In this review of studies on the hemorrhagic fevers of Southern Africa carried out in the South African Institute for Medical Research, attention has been called to occurrence of meningococcal septicemia in recruits to the mining industry and South African Army, to cases of staphylococcal and streptococcal septicemia with hemorrhagic manifestations, and to the occurrence of plague which, in its septicemic form, may cause a hemorrhagic state. "Onyalai," a bleeding disease in tropical Africa, often fatal, was related to profound thrombocytopenia possibly following administration of toxic witch doctor medicine. Spirochetal diseases, and rickettsial diseases in their severe forms, are often manifested with hemorrhagic complications. Of enterovirus infections, Coxsackie B viruses occasionally caused severe hepatitis associated with bleeding, especially in newborn babies. Cases of hemorrhagic fever presenting in February-March, 1975 are described. The first outbreak was due to Marburg virus disease and the second, which included seven fatal cases, was caused by Rift Valley fever virus. In recent cases of hemorrhagic fever a variety of infective organisms have been incriminated including bacterial infections, rickettsial diseases, and virus diseases, including Herpesvirus hominis; in one patient, the hemorrhagic state was related to rubella. A boy who died in a hemorrhagic state was found to have Congo fever; another patient who died of severe bleeding from the lungs was infected with Leptospira canicola, and two patients who developed a hemorrhagic state after a safari trip in Northern Botswana were infected with Trypanosoma rhodesiense. An illness manifested by high fever and melena developed in a young man after a visit to Zimbabwe; the patient was found to have both malaria and Marburg virus disease.

Adult↗

Leptospira interrogans serovar hardjo is not a major cause of bovine abortion in Victoria.

The aim of this study was to determine whether evidence could be obtained of foetal infection with Leptospira interrogans serovar hardjo in aborted foetuses collected from dairy farms. Material from 197 abortions occurring over a wide area of Victoria was collected over 3 years. None of 195 foetal kidney cultures or 7 cultures from membranes was positive for leptospiral organisms. Immunogold silver staining for leptospires was performed on sections of kidneys, lungs or heart from 156 foetuses, with negative results. Evidence of transient leptospiral infection in 11 of 123 foetuses was obtained by foetal heart blood serology. Two isolates of L. interrogans serovar hardjo were obtained from the urine of milking cows. These strains were examined by restriction endonuclease analysis and both were shown to be of the genotype Hardjobovis, as have been all Australian isolates studied so far. It appears that foetal infection with serovar hardjo is not associated with any substantial proportion of bovine abortions in Victoria, in contrast to the situation in Northern Ireland. The apparent absence from Victoria of the pathogenic genotype Hardjoprajitno is a possible explanation.

Abortion, Veterinary↗

Proinflammatory and immunomodulatory cytokine mRNA time course profiles in hamsters infected with a virulent variant of Leptospira interrogans.

In order to quantify in vivo the mRNAs of cytokines which play important roles in leptospirosis, we have developed quantitative real-time PCR assays for interleukin-2 (IL-2), IL-4, IL-10, IL-12p40, tumor necrosis factor alpha (TNF-alpha), gamma interferon (IFN-gamma), transforming growth factor beta, and two housekeeping genes (encoding beta-actin and hypoxanthine phosphoribosyltransferase). We used a lethal hamster model reflecting severe leptospirosis in humans. The LightCycler system was used to quantify the gene expression levels with the SYBR green I detection format using external standard curves for each target. We compared the expression levels of cytokine mRNA in the peripheral blood mononuclear cells of both control (uninfected) hamsters and Leptospira interrogans-inoculated hamsters from 1 to 24 h and then 1 to 4 days postinfection. In this kinetic study, there was pronounced expression of Th1 cytokine mRNA (TNF-alpha, IFN-gamma, and IL-12), with transcripts being detected as early as 1 h postinfection. Expression of anti-inflammatory cytokines, such as IL-4 and IL-10, was prominent in delayed samples from 1 to 4 days postinfection in response to infection with Leptospira interrogans. Our data are the first to establish that pathogenic leptospires can stimulate in vivo the production of type 1 cytokines involved in cellular immunity by using this informative animal model. Measuring and assessing cytokine profiles may provide a useful method for accurate study of the mechanisms of anti-Leptospira immunity, indications of prognosis factors, and prospective evaluation of leptospirosis vaccine efficacy in humans.

Animals↗

Role of the coypu (Myocastor coypus) in the epidemiology of leptospirosis in domestic animals and humans in France.

The coypu (Myocastor coypus), a rodent whose natural habitat is stagnant freshwater, has become a widespread pest in France within the last decade. This study investigated the prevalence of seropositivity and the renal carriage of leptospires in coypus in order to evaluate their role in terms of the risk of infection by Leptospira interrogans in domestic animals and humans. The study involved the application of serological and bacteriological methods to identify leptospires infection and/or carriage in 738 coypus trapped from 1996 to 1999 in six areas of France. Seroprevalence in samples ranged from 16.5 to 66%, and three field strains were isolated (two L. interrogans Icterohaemorrhagiae and one L. interrogans Sejroe). This first report on the isolation of leptospires from coypus in France emphasises the role of this animal in the epidemiology of leptospirosis.

Animals↗

Severe disease in a dairy herd associated with acute infection with bovine virus diarrhoea virus, Leptospira harjo and Coxiella burnetii.

Between November 1984 and February 1985, a serious outbreak of pyrexia, diarrhoea, agalactia, metritis and severe weight loss affected most of the recently calved cows in a 183-cow dairy herd in Norfolk. Fifteen cows died and 20 were culled. Forty cows aborted during or after the outbreak, and many of them produced mummified fetuses; 18 calves were stillborn and three others died soon after birth. Necropsy of three affected cows revealed ulceration of the gastrointestinal tract similar to that seen in cases of mucosal disease. Bovine virus diarrhoea virus was isolated from the intestines of one cow that died soon after the onset of illness. The virus was also isolated from the blood of four acutely ill cows and seroconversion was demonstrated in three of those that survived. The virus was isolated from three aborted fetuses, a stillborn calf and a live neonatal calf. Body fluids from two aborted fetuses were seropositive for the virus as were sera from all the aborting cows tested. In addition to widespread seroconversion to bovine virus diarrhoea virus during the outbreak, there was serological evidence of recent infection with Leptospira interrogans serovar hardjo and Coxiella burnetii in a high proportion of cows. It was concluded that this was primarily an acute outbreak of bovine virus diarrhoea but its unprecedented clinical severity was probably associated with the concurrent introduction of L hardjo and C burnetii into an immunologically naive herd during the main calving period. Epidemiological analysis suggested that the source of the virus and L hardjo was down-calving heifers returning from communal marsh grazing.

Abortion, Veterinary↗

Determination of specific anti-leptospiral immunoglobulins M and G in sera of experimentally infected dogs by solid-phase enzyme-linked immunosorbent assay.

The development and evaluation of an enzyme-linked immunosorbent assay (ELISA) to detect specific anti-leptospiral IgM and IgG in sera of dogs experimentally infected with Leptospira interrogans serotype canicola are reported. In all dogs specific anti-leptospiral IgM was detected from the second half of the first week after infection, the maximum being attained during the second week. Subsequently the IgM titre gradually decreased. Specific anti-leptospiral IgG was detected later and increased gradually to reach almost the same level as the IgM titre after two to three months. During the initial stage of the infection, when the microscopic agglutination titre was still negative or very low, a high IgM titre was accompanied by a negative or very low IgG titre in every case. After the initial stage a substantial IgG titre was also detectable. It is suggested that the test is suitable for serodiagnostic purposes, particularly for the diagnosis of a current infection in an individual.

Animals↗

Prevention of renal infection and urinary shedding in dogs by a Leptospira vaccination.

Prevention of urinary shedding of Leptospira interrogans spp. by chronically infected dogs remains a key objective of the vaccination in dogs against leptospirosis which is a zoonotic disease. An inactivated bivalent vaccine composed of Leptospira interrogans serovars icterohaemorrhagiae [L. icterohaemorrhagiae] and canicola [L. canicola] bacterins was tested for its ability to protect puppies against a challenge exposure with L. icterohaemorrhagiae. The vaccine was administered twice at a 3-week interval to six puppies aged from 8 to 9 weeks. Six other puppies were used as unvaccinated controls. All puppies were challenged 2 weeks after the second vaccine injection by intraperitoneal (IP) administration of L. icterohaemorrhagiae (day 0). Clinical signs, haematological and biochemical changes and evidence of Leptospira in blood, urine and kidney were monitored for 4 weeks after the challenge exposure (days 0-28). Puppies were euthanised on day 28 for post-mortem and histological examinations of liver and kidney. Control group presented clinical pictures of severe or subclinical infection. One dog developed severe clinical signs (hypothermia, depression, anorexia, abdominal pain, dehydration, icterus, weight loss) and died on post-infection day (PID) 7 due to an acute renal failure. Gross and microscopic lesions were in accordance with this clinical pattern. In the five remaining control dogs, the challenge exposure induced mainly a systemic infection including leptospiraemia, leptospiruria and renal carriage. The vaccinated group remained healthy throughout the study period. In conclusion, immunisation with a Leptospira vaccine was shown to protect dogs against symptomatology and leptospiraemia, urine shedding and renal infection.

Animals↗

Leptospira outer membrane protein activates NF-kappaB and downstream genes expressed in medullary thick ascending limb cells.

Tubulointerstitial nephritis is the main manifestation of acute renal damage caused by leptospirosis, but the mechanism remains unexplored. Patients infected with LEPTOSPIRA: shermani in Taiwan disclosed tubular dysfunction particularly in the medullary thick ascending limb of loop of Henle (mTAL), and the related renal damage seems to be underestimated. To elucidate the mechanism of tubular damage, outer membrane protein extract from LEPTOSPIRA: was administered to a model of cultured mTAL cells derived from normal mice. The addition of outer membrane protein extract from L. shermani to cultured mTAL cells induced a significant nuclear DNA binding of the NF-kappa B transcription factor by electrophoresis mobility shift assay. Forty-eight h after adding the outer membrane protein extract (0.2 microg/ml) to the cultured cells, the expression of inducible nitric oxide mRNA increased by 4.2-fold, monocyte chemoattractant protein-1 by 3-fold, and tumor necrosis factor-alpha by 2.4-fold when compared with untreated cells examined by reverse transcription competitive-PCR. Supernatant nitrite, monocyte chemoattractant protein-1, and tumor necrosis factor-alpha protein levels also increased by 1.8-, 7.1-, and 5-fold, respectively. An antiserum raised against L. shermani largely prevented these effects. Outer membrane protein extract from L. bratislava induced fewer effects than L. shermani, and the avirulent nonpathogenic L. biflexa serovar patoc did not induce significant effects in the mTAL cells. In conclusion, L. shermani infection may cause mTAL cell damage and inflammation through the NF-kappa B-associated pathway. Findings of this study may be important in understanding the pathogenesis of tubulointerstitial nephritis caused by these organisms.

Animals↗

Leptospirosis associated with serovars hardjo and pomona in red deer calves (Cervus elaphus).

Four red deer calves (Cervus elaphus) died with severe nephritis apparently associated with infection by Leptospira interrogans serovar pomona. The sera of 12 in-contact red deer calves were examined for leptospiral agglutinins and nine showed titres to pomona consistent with recent infection. Two also showed titres of 1:100 to serovar hardjo. The urine of five of these in-contact calves was examined periodically over a period of nine months. All were initially leptospiruric, four being infected with pomona and one with hardjo. In four animals leptospiruria could only be detected for up to six months, but one animal infected with pomona was leptospiruric for at least eight months. The apparent source of infection was from infected cattle, and it is suggested that deer are unlikely to act as maintenance hosts for serovar pomona.

Journal Article↗

Central nervous system leptospirosis in the Philippines.

One hundred hospitalized patients in Manila, Philippines with aseptic meningoencephalitis were screened for leptospirosis. On the basis of a microscopic agglutination titer of 1:1,600 or greater, the diagnosis was made in five cases, yet in no instance had leptospirosis been included in the differential diagnosis on admission to the hospital. Four of the five patients first noted neurologic symptoms during the second week of illness; two patients presented with encephalitis, two with meningitis and the fifth with hemiparesis. No case was complicated by renal dysfunction or jaundice. By the time of discharge from the hospital, two patients had recovered completely and the other three had markedly improved. Our data show that leptospirosis is an important but overlooked cause of aseptic meningoencephalitis in the Philippines. This is probably also the case in other parts of the tropics where Leptospira interrogans infection remains a significant public health problem.

Adult↗

The role of macrophages in the protection of mice against leptospirosis: in vitro and in vivo studies.

Balb/c mice are naturally resistant to infection with Leptospira interrogans serovar copenhageni, but leptospires were not phagocytosed by mouse peritoneal macrophages in vitro without added specific antibody. Similar results were obtained irrespective of whether leptospires were viable or killed, virulent or avirulent, or whether macrophages were obtained from normal mice, immunized mice or mice previously infected with BCG. Suppression or stimulation of macrophage function in vivo did not affect the outcome of infection of immunosuppressed mice with leptospires; specific antibody was essential for protection from infection.

Animals↗

[Risk factors and frequency of positive antibodies for leptospirosis in a sub urban population near Santiago].

BACKGROUND: Leptospirosis is a zoonotic disease and its incidence is known in Chile since 2002, when it was incorporated as a disease that must be reported to health authorities. A serologic survey for leptospirosis was performed in humans and animals from a farm in a semi urban area in Santiago Chile, after the death of a farmer due to Weil disease in that place. AIM: To report the prevalence of antibodies against leptospirosis and to determine exposure to infection risk factors in the humans and domestic animals studied in this survey. MATERIAL AND METHODS: Antibodies were detected by IgM immunodot and indirect haemagglutination test in 61 humans (43 male, aged 5 to 70 years) and by microscopic agglutination test (MAT) in 44 animals. A questionnaire was applied to determine their exposure to risk factors for infection with Leptospira. RESULTS: Seventy two percent of the studied population were farm workers and 70% had activities that required contact with water from canals, 41% cleaned closed places where rodents were present. Other risk factors detected were lack of sewage and waste disposal, high level of rodent infestation and disposal of faeces into canals used for watering. Two humans (3.3%) and six animals (1 bovine and 5 rodents) had positive antibodies. Among animals, antibodies against Leptospira serovar pomona and icterohaemorragiae were detected. CONCLUSIONS: In Chile, leptospirosis exists not only in rural areas but semi urban ones close to Santiago, although the prevalence is low. Education is necessary among semi urban population to avoid infection.

Adolescent↗

Canine leptospirosis. A retrospective study of 17 cases.

Seventeen dogs were diagnosed with leptospirosis on the basis of clinical findings, laboratory abnormalities, and serology. This article summarizes and characterizes the historical and physical findings, laboratory data, serology, treatment, and outcome of these dogs. All of the dogs had serologic evidence of infection with interrogans serovars pomona and grippotyphosa. These findings are compared with previous reports of canine infection with Leptospira interrogans serovars icteroaemorrhagiae and canicola. The clinical presentation of these dogs did not correspond to the classic description of the disease in dogs in which concurrent renal and hepatic diseases are present. This may be due to infection with different serovars than those previously reported. In addition, this article suggests that canine leptospirosis should be considered in the differential diagnosis of dogs with acute or subacute renal failure.

Animals↗

[Morphology of a natural focus of Pomona leptospirosis in a steppe area].

The natural focus of Leptospira pomona infection has been found to include areas of the forest-meadow flood plain where the circulation of leptospires is constantly maintained among small mammals (the nucleus of the focus). A high level of Leptospira carriership (17.7%) among the animals has been registered in the central part of the flood plain and near the terraces, these areas having the most favorable conditions for the development of epizootic leptospirosis.

Animals↗

Serological survey of pre-weaned New Zealand fur seals (Arctocephalus forsteri) for brucellosis and leptospirosis.

AIM: To conduct a longitudinal serological survey for evidence of Brucella spp and Leptospira spp infection of pre-weaned New Zealand fur seals in a colony on the Otago Peninsula. METHODS: Seal pups were repeatedly captured on a monthly basis from February through to July 2001. Pups were tagged at first capture and a blood sample was taken at each capture event. A total of 163 sera were collected from 118 seal pups. Where sufficient volume was collected, the sera were tested for leptospirosis using the microscopic agglutination test (MAT), and for brucellosis using the competitive enzyme-linked immunosorbent assay (ELISA) for Brucella abortus. RESULTS: None of 128 sera from 101 seals tested positive to the ELISA for B. abortus. All tests for Leptospira interrogans serovars Grippotyphosa, Copenhageni, Bratislava and Leptospira borgpetersenii serovar Ballum were negative at a cut-off of <1/100 dilution. Positive or suspicious titres were found to L. interrogans serovars Canicola and Pomona and L. borgpetersenii serovar Hardjo. The highest titres (12,800) were found to serovar Pomona. The titre to serovar Pomona in one seal rose from <1/50 in March to 12,800 in April and was <1/50 when re-sampled in July. The titre to serovar Pomona in another seal dropped from 12,800 in May to <1/50 in June. These seals also had titres to serovar Hardjo, which rose or fell in the same manner. All suspicious or positive titres occurred in late April and early May, when the pups were approximately 4-5 months old. In June and July, all seals tested were negative. CONCLUSIONS: There was no serological evidence of Brucella infection in the pre-weaned fur seals at the colony. Positive titres to serovars Pomona, Hardjo, or Canicola suggest that a Leptospira species was present at the colony, however isolation or visualisation of the organism is required to confirm this. Care should be exercised when handling New Zealand fur seals to prevent human infection or inadvertent transfer of leptospirosis to another marine mammal species.

Age Factors↗