Acute kidney injury requiring hemodialysis in patients with anicteric leptospirosis.

BACKGROUND: Leptospirosis is an infrequent disease in the US, with most cases reported in the state of Hawaii. Renal involvement is common (44 - 67%), ranging from a mild prerenal azotemia in anicteric disease to renal failure requiring dialysis in Weil's syndrome (severe leptospirosis with jaundice, renal failure, and hemorrhage). METHODS: To describe the pattern of leptospiral renal disease at our institution, we performed a retrospective analysis (1992 - 2004) of all hospitalized cases of laboratory confirmed leptospirosis presenting with acute kidney injury (AKI), defined as a presenting serum creatinine > 1.5 mg/dl. RESULTS: During this time period, 18 patients were hospitalized with laboratory confirmed leptospirosis. Among these patients, 12 had AKI on presentation, and hemodialysis was required in 3 patients. Renal biopsies were performed in 2 of these patients, revealing acute tubulointerstitial nephritis. Interestingly, the patients who required dialysis did not have Weil's syndrome. They did not exhibit jaundice or hemorrhage, and serum AST (mean 51.7 U/l (range 36 - 60)), ALT (mean 51.0 U/l (range 38 - 64)), and total bilirubin (mean 1.2 mg/dl (range 0.8 - 1.8)) were either within normal limits or only slightly elevated, despite having the worst renal disease. CONCLUSIONS: This series adds to other evidence that severe AKI (requiring dialysis) can complicate anicteric leptospirosis in contrast to the notion that the AKI in anicteric disease is typically mild and prerenal. Leptospirosis should be considered in all patients who present with fever and AKI, especially if associated with thrombocytopenia or travel to an endemic area.

Assessment of the clinical presentation and treatment of 353 cases of laboratory-confirmed leptospirosis in Hawaii, 1974-1998.

Leptospirosis is frequently misdiagnosed as a result of its protean and nonspecific presentation. Leptospirosis, a zoonosis with global distribution, commonly occurs in tropical and subtropical regions; most reported cases in the United States occur in Hawaii. All laboratory-confirmed leptospirosis cases in the State of Hawaii from 1974 through 1998 (n=353) were clinically evaluated. The most common presentation involved nonspecific signs or symptoms, including fever, myalgia, and headache. Jaundice occurred in 39% of cases; conjunctival suffusion was described in 28% of these cases. Initiation of antibiotics before the seventh day of symptoms was associated with a significantly shortened duration of illness. Because early recognition and initiation of antibiotic therapy are important, clinicians should familiarize themselves with the clinical presentation of leptospirosis, and when evaluating a patient with a febrile illness, they should obtain exposure and travel histories and entertain the possibility of leptospirosis in the differential diagnosis.

Of mice and mongooses ... a history of leptospirosis research in Hawaii.

A history of leptospirosis research in Hawaii is presented, beginning with the first published work in 1937. This account traces the leading researchers who described the organism and the disease, the diagnostic tests developed and used, the reservoir animals identified, methods of disease transmission discovered, prevention programs developed in the state, and research into more effective disease detection and prevention.

Clinical and epidemiological observations regarding the 1998 Kauai murine typhus outbreak.

Five cases of murine typhus occurring on southwestern Kauai in 1998 are described, following an investigation by the Department of Health. Two cases also had concurrent leptospirosis. Recent habitat changes of peridomestic animals and their fleas may have increased the risk for developing murine typhus. Increased suspicion of typhus by island physicians and more aggressive rodent control activities are recommended.

Evaluation of the indirect hemagglutination assay for diagnosis of acute leptospirosis in Hawaii.

Timely diagnosis of leptospirosis is important to ensure a favorable clinical outcome. The definitive serologic assay, the microscopic agglutination test (MAT), requires paired sera and is not useful for guiding early clinical management. The only screening test approved for use in the United States, the indirect hemagglutination assay (IHA), has not undergone extensive field evaluation. To assess the performance of the leptospirosis IHA in Hawaii, serum from patients evaluated for leptospirosis between 1992 and 1997 were tested with the IHA at the Hawaii State Laboratories Division and with the MAT at the Centers for Disease Control and Prevention. Leptospirosis was considered confirmed by a fourfold rise in MAT titer and/or a positive culture. A total of 92 (41%) of 226 specimens from 114 persons with confirmed leptospirosis were found positive by IHA. Only 18 (15%) of 119 specimens obtained within 14 days of onset were IHA positive, compared to 74 (69%) of 107 specimens collected more than 14 days after onset (P <0.001). Repeat testing ultimately resulted in 78 (68%) of the confirmed cases having at least one specimen found positive by IHA. Thirteen different presumptive infecting serogroups were identified among 251 specimens with an MAT titer of >/=200 and obtained from persons with confirmed or probable leptospirosis. Fifty (68%) of 73 specimens with Icterohaemorrhagiae as the presumptive infecting serogroup were found positive by IHA, compared to 44 (47%) of 93 specimens with Australis as the presumptive infecting serogroup (P, 0.01). The IHA test was positive for 3 (1%) of 236 specimens from 154 persons without leptospirosis. The sensitivity of the leptospirosis IHA in Hawaii was substantially below figures reported previously, particularly early in the course of illness, limiting its usefulness for diagnosing acute infection. Since the presumptive infecting serogroup affected IHA results and the prevalence of serovars varies with geography, the performance of the IHA should be assessed locally. More sensitive leptospirosis screening tests are needed in Hawaii.

Simple latex agglutination assay for rapid serodiagnosis of human leptospirosis.

A newly developed latex agglutination assay for the detection of genus-specific Leptospira antibodies in human sera was evaluated. The assay is performed by mixing, on an agglutination card, serum with equal volumes of stabilized antigen-coated, dyed test and control latex beads and is read within 2 min. The latex agglutination test was evaluated with groups of serum samples from patients with leptospirosis and control patients from Hawaii, the Seychelles, Thailand, and The Netherlands. The mean overall sensitivity was 82.3%, and the mean overall specificity was 94.6%. The assay is easy to perform and does not require special skills or equipment. The reagents have a long shelf life, even at tropical temperatures. Together, these factors make the assay suitable for use even at the peripheral level of a health care system as a rapid screening test for leptospirosis.

International multicenter evaluation of the clinical utility of a dipstick assay for detection of Leptospira-specific immunoglobulin M antibodies in human serum specimens.

We performed a multicenter evaluation of a robust and easily performed dipstick assay for the serodiagnosis of human leptospirosis. The assay is aimed at the detection of Leptospira-specific immunoglobulin M (IgM) antibodies. The study involved 2,665 serum samples collected from 2,057 patients with suspected leptospirosis in 12 countries on five continents with different levels of endemicity and different surveillance systems. The patients were grouped as laboratory-confirmed leptospirosis case patients and noncase patients based on the results of culturing and the microscopic agglutination test. Paired samples from 27.7% of the subjects were tested. Of the 485 case patients, 87.4% had a positive dipstick result for one or more samples. Of the 1,513 noncase patients, only 7.2% had a positive result. Whereas most (88.4%) of the positive samples from the case patients showed moderate to strong (2+ to 4+) staining in the dipstick assay, most (68.1%) of the positive samples from the noncase patients showed weak (1+) staining. The sensitivity of the dipstick assay increased from 60.1% for acute-phase serum samples to 87.4% for convalescent-phase samples. The specificities for these two groups of samples were 94.1 and 92.7%, respectively. The dipstick assay detected a broad variety of serogroups. The results of the dipstick assay were concordant (observed agreement, 93.2%; kappa value, 0.76) with the results of an enzyme-linked immunosorbent assay for the detection of specific IgM antibodies, a test which is often used in the laboratory diagnosis of current or recent leptospirosis. This study demonstrated that this easily performed dipstick assay is a valuable and useful test for the quick screening for leptospirosis; has a wide applicability in different countries with different degrees of endemicity; can be used at all levels of the health care system, including the field; and will be useful for detecting and monitoring outbreaks of leptospirosis.

Leptospirosis on Oahu: an outbreak among military personnel associated with recreational exposure.

In December 1992, a common-source waterborne outbreak of leptospirosis occurred on the island of Oahu in the state of Hawaii. Two male service persons were hospitalized with culture-confirmed leptospirosis. Eighteen others had similar histories of exposure to the same freshwater swimming site. Although six men developed signs and symptoms comparable to those of the two confirmed cases, none manifested culture or serologic evidence of leptospirosis. The increased incidence of leptospirosis in Hawaii coupled with an increased risk in young males characterize the military population in Hawaii as a high-risk population with respect to leptospirosis.

Ciguatera on Kauai: investigation of factors associated with severity of illness.

Epidemiologic characterization of ciguatera fish poisoning has been limited by lack of laboratory confirmation, absence of prospective follow-up, and incomplete analysis of age-related factors. A 1985 outbreak on the island of Kauai in the state of Hawaii that involved 15 persons of various ages was investigated to determine factors associated with disease severity. The presence of ciguatoxin was detected in leftover portions of the implicated fish by enzyme immunoassay. All cases were medically and epidemiologically investigated and followed prospectively. Ten of the 15 cases demonstrated bradycardia; seven were hospitalized, including two requiring placement in intensive care. Bradycardia was associated with increasing age and body weight (P < 0.01 and < 0.05, respectively) as well as the amount of toxic fish consumed (P < 0.01). Duration of illness ranged from two to 132 days. Increasing duration of illness was correlated with both increasing age and weight (rs = 0.64 and rs = 0.72, respectively, both P < 0.01) and was independent of amount and components of toxic fish consumed. The correlation between increasing age and weight with duration and severity of symptoms may be explained by prior subclinical toxin exposure and is consistent with the observation that repeated ciguatoxin exposures are associated with more severe illness. The association between amount of toxic fish consumed and bradycardia is consistent with an increased dose of ciguatoxin. The findings of this outbreak investigation support previously unconfirmed observations.

Active surveillance and risk factors for leptospirosis in Hawaii.

A clinic-hospital-based leptospirosis surveillance program was conducted to determine the morbidity and risk factors in nonepidemic settings. The study was conducted on two islands, Kauai and Hawaii (Big Island), in the state of Hawaii for one year during 1988 and 1989. An active, more comprehensive case detection system was used on the Big Island that enabled us to determine the incidence of clinical disease. Subjects from both islands were used to conduct a case-control study for risk factors. One hundred seventy-two subjects from the Big Island (who presented with any two of the following symptoms: fever, headache, myalgia, or nausea/vomiting) were enrolled in the study. Twenty cases were diagnosed by culture, serology, or fluorescent antibody tissue staining at autopsy. Six cases required hospitalization and two succumbed to fatal infections. We estimated that these cases represented an annual incidence rate of 128 per 100,000 person-years in our target population. For 33 cases, 77 controls were matched for island, age, sex, and time of onset of illness. Interviews were conducted retrospectively in a double-blinded fashion with cases and controls and evaluated approximately 30 risk factors. Factors that were associated most strongly with development of leptospirosis were household use of rainwater catchment systems (P = 0.003), presence of skin cuts during the incubation period (P = 0.008), contact with cattle or the urine of cattle (P = 0.05 and P = 0.03, respectively), and handling of animal tissues (P = 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

Rabid bat diagnosed in Hawaii.

Since 1966, the Hawaii State Government has been conducting Fluorescent Rabies Antibody (FRA) testing on animal brains as part of a statewide rabies-surveillance program. On April 3, 1991, the Department of Health (DoH) laboratory diagnosed the first case of rabies detected in the State. A large brown bat, Eptesicus fuscus fuscus, captured in a transport container that had just been off-loaded from a ship at Honolulu harbor, was caught. It's brain was examined and showed typical fluorescent staining patterns for rabies virus. The USPHS Centers For Disease Control (CDC) rabies laboratory confirmed the diagnosis 2 days later. The successful interception of this rabid animal was the result of close cooperation between the private sector (Sea Land Service, Hawaiian Stevedores) and the Hawaii State Government Departments of Health and of Agriculture.

Leptospirosis on Kauai: investigation of a common source waterborne outbreak.

During the summer of 1987, a common source waterborne outbreak of leptospirosis occurred on the island of Kauai in the state of Hawaii. Eight leptospirosis cases were identified using the microscopic agglutination test. Methodologic weaknesses in this technique were responsible for the initial missed diagnosis on six of the eight cases. All cases had repeated exposure to the Waimea River. A wide array of animal reservoirs and optimal water conditions may have been factors in this outbreak.

Salmonella egg survey in Hawaii: evidence for routine bacterial surveillance.

One hundred and six dozen eggs, representing 12 brands, were purchased from Oahu supermarkets and cultured for Salmonella using standard FDA (Food and Drug Administration) microbiological techniques. Two enrichment incubation temperatures were used to improve culture sensitivity. Ten cartons (9.4 percent) of the 106 dozen samples had shells positive for Salmonella. Seven of the 10 were traced to a single egg processor. Inspection of the facility led to the discovery of malfunctioning equipment used in the egg washing and sanitation process.

Rabies prevention in Hawaii.

The scientific basis of Hawaii's public health rabies prevention program is discussed, as is a proposed minor modification offered to assist Hawaii residents who use guide dogs and who want to travel out of state. Hawaii's current quarantine program has successfully prevented the introduction of the disease. Alternative programs involve risks that are not easily evaluated.

A semisynthetic bovine pancreatic ribonuclease containing a unique nitrotyrosine residue.

A fully active semisynthetic ribonuclease, RNase 1-118:111-124, may be prepared by enzymatically removing six residues from the COOH terminus of the protein (positions 119-124) and then complementing the inactive RNase 1-118 with a chemically synthesized peptide containing the COOH-terminal 14 residues of the molecule (RNase 111-124) [M. C. Lin, B. Gutte, S. Moore, and R. B. Merrifield (1970) J. Biol. Chem. 245, 5169-5170]. Nitration of tyrosine-115 in the peptide followed by complex formation with RNase 1-118 affords a fully active enzyme containing a unique nitrotyrosine residue in a position which is known and which is very likely to be completely exterior to the active site region. The binding constant between the tetradecapeptide and RNase 1-118 (5 X 10(6) M-1 at pH 6.0) is not changed by the nitration. Crystals of the nitrated complex are isomorphous with those of RNase 1-118:111-124, for which a refined 1.8-A structure has recently been obtained.