Underrecognition of leptospirosis during a dengue fever outbreak in Hawaii, 2001-2002

During the 10-year period from 1997 through 2006, the reported mean annual incidence rate of leptospirosis in the state of Hawaii was 3.3/100,000 with a range of 22-60 infections reported each year. Because the clinical presentation is highly variable, however, leptospirosis illness is challenging to recognize and may be underdiagnosed. To assess whether the incidence may be substantially higher than reported figures indicate, we retrospectively studied the prevalence of anti-Leptospira IgM antibodies among specimens obtained over a 12-month period (May 2001 to April 2002) from patients presenting with febrile illness during a dengue fever outbreak in Hawaii. Of 1206 patients testing negative or indeterminate for dengue, 54 (4.5%; 95% confidence interval: 3.3%-5.7%) were positive for anti-Leptospira IgM antibodies using a commercially available dipstick enzyme-linked immunosorbent assay (ELISA). The most common clinical symptoms reported by laboratory-positive leptospirosis patients were fever (92%), headache (88%), and myalgia (83%). Three clinical symptoms were significantly less common among persons laboratory positive for leptospirosis when compared with the 122 patients who had been diagnosed with dengue fever during the outbreak: rash (p < 0.0001), chills (p = 0.05), and petechiae (p = 0.0005). Laboratory-positive leptospirosis infections were identified in persons exposed on each of the 5 most populous islands and illness onsets spanned a 10-month period, reflecting an endemic pattern of disease. If added to the figures obtained via routine passive surveillance, the number of leptospirosis infections identified through this study would more than double the annual incidence rate for Hawaii during 2001. These findings indicate that many leptospiral infections in Hawaii go undiagnosed. Physicians should maintain a high index of suspicion for leptospirosis when assessing patients presenting with acute febrile illness among residents and visitors to Hawaii.     

Leptospirosis among hospitalized febrile patients in northern Tanzania

We enrolled consecutive febrile admissions to two hospitals in Moshi, Tanzania. Confirmed leptospirosis was defined as a ≥ 4-fold increase in microscopic agglutination test (MAT) titer; probable leptospirosis as reciprocal MAT titer ≥ 800; and exposure to pathogenic leptospires as titer ≥ 100. Among 870 patients enrolled in the study, 453 (52.1%) had paired sera available, and 40 (8.8%) of these met the definition for confirmed leptospirosis. Of 832 patients with ≥ 1 serum sample available, 30 (3.6%) had probable leptospirosis and an additional 277 (33.3%) had evidence of exposure to pathogenic leptospires. Among those with leptospirosis the most common clinical diagnoses were malaria in 31 (44.3%) and pneumonia in 18 (25.7%). Leptospirosis was associated with living in a rural area (odds ratio [OR] 3.4, P < 0.001). Among those with confirmed leptospirosis, the predominant reactive serogroups were Mini and Australis. Leptospirosis is a major yet underdiagnosed cause of febrile illness in northern Tanzania, where it appears to be endemic.     

Leptospirosis in Malaysia: a common cause of short-term fever.

A study of 1,437 unselected febrile patients in rural Malaysia yielded a diagnosis of leptospirosis in 86 (6.0%). The clinical syndrome was mild to moderate in all cases, jaundice was observed in only 2 (2.3%) and no deaths were documented. The diagnosis was not clinically obvious in most cases, and it is apparent that many infections must be going unnoticed at present.     

The etiology of febrile illness in adults presenting to Patan hospital in Kathmandu, Nepal

In Nepal, many infections remain poorly characterized, partly due to limited diagnostic facilities. We studied consecutive febrile adults presenting to a general hospital in Kathmandu, Nepal. Of the 876 patients enrolled, enteric fever and pneumonia were the most common clinical diagnoses. Putative pathogens were identified in 323 (37%) patients, the most common being Salmonella enterica serotype Typhi and S. enterica serotype Paratyphi A (117), Rickettsia typhi (97), Streptococcus pneumoniae (53), Leptospira spp. (36), and Orientia tsutsugamushi (28). Approximately half of the Salmonella isolates were resistant to nalidixic acid. No clinical predictors were identified to reliably distinguish between the different infections. These findings confirm the heavy burden of enteric fever and pneumonia in Kathmandu, and highlight the importance of murine typhus, scrub typhus, and leptospirosis. Given the lack of reliable clinical predictors, the development of cheap and accurate diagnostic tests are likely to be of great clinical utility in this setting.     

An outbreak of leptospirosis among Peruvian military recruits

Acute undifferentiated febrile illnesses are common in tropical developing countries but are difficult to diagnose on clinical grounds alone. Leptospirosis is rarely diagnosed, despite evidence that sporadic cases and epidemics continue to occur worldwide. The purpose of this study was to diagnose an outbreak of acute undifferentiated febrile illness among Peruvian military recruits that developed after a training exercise in the high jungle rainforest of Peru. Of 193 military recruits, 78 developed an acute febrile illness with varied manifestations. Of these, 72 were found to have acute leptospirosis by a microscopic agglutination test (MAT). An enzyme-linked immunosorbent assay using Leptospira biflexa antigen was insensitive for the detection of anti-leptospiral IgM antibodies compared with the MAT (20 of 72, 28%). This outbreak of acute undifferentiated febrile illness among Peruvian military recruits was due to leptospirosis. High clinical suspicion, initiation of preventative measures, and performance of appropriate diagnostic testing is warranted in similar settings to identify, treat, and prevent leptospirosis.     

Leptospirosis: A clinical review of evidence based diagnosis,treatment and prevention

Leptospirosis is a zoonotic disease with worldwide distribution and increasing prevalence. Infection is caused by the spirochete Leptospira, with common exposure being contaminated fresh water. Most infections are asymptomatic, but symptoms range from a mild, self-limiting, non-specific febrile illness to fulminant respiratory and renal failure with a high mortality rate. The combination of jaundice, renal failure, and hemorrhage is known as Weil’s disease and is the most characteristic pattern associated with severe leptospirosis. Clinical suspicion alone may be enough to warrant empiric antibiotic treatment in many cases. Serological methods are the most commonly used means of confirming a diagnosis of leptospirosis. The “gold standard” is the microscopic agglutination test. Typical treatment for mild causes is oral doxycycline, though azithromycin and oral penicillins are reasonable alternatives. Intravenous penicillin G has long been the standard of care for severe cases though limited studies show no benefit compared to third generation cephalosporins. We review the clinical presentation, diagnosis, treatment and prevention of leptospirosis.     

From prolonged febrile illness to fever of unknown origin: the challenge continues

BACKGROUND: Epidemiological changes and the ongoing expansion of the diagnostic armamentarium warrant a regular update of the spectrum of diseases that present as prolonged febrile illnesses. METHODS: We prospectively collected a series of 290 immunocompetent patients referred to our university hospital between 1990 and 1999 with a febrile illness (temperature >38.3 degrees C) of uncertain cause, lasting at least 3 weeks. Patients were categorized in 4 groups according to the timing of diagnosis: early diagnosis (within 3 in-hospital days or 3 outpatient visits), intermediate diagnosis (between days 4 and 7), late diagnosis (after day 7), and no diagnosis during index contact or follow-up. RESULTS: A final diagnosis was established early in 67 patients (23.1%), intermediate in 38 (13.1%), and late in 87 (30.0%). In the remaining 98 (33.8%), no diagnosis was made. The cause of the fever remained obscure in 50 (47.6%) of 105 patients with episodic fever vs 48 (25.9%) of 185 patients with continuous fever (P<.001). Among the 192 patients with a final diagnosis, noninfectious inflammatory diseases represented the most prevalent diagnostic category (35.4%), surpassing infections (29.7%), miscellaneous causes (19.8%), and malignancies (15.1%). Fourteen disorders accounted for over 59% of diagnoses, whether diagnosis was reached early, intermediate, or late. Hematological malignancies made up 11.5% of diagnoses, but were responsible for 14 (58.3%) of the 24 fatalities related to the febrile illness. Of the 80 patients discharged alive without diagnosis and for whom follow-up was available, 3 died, but the deaths were considered to be unrelated to the feverish illness. CONCLUSIONS: Prolonged febrile illnesses remain a diagnostic challenge. Despite the technological progress of the late 20th century, the origin of the fever remains elusive in many patients, especially in those with episodic fevers. Noninfectious inflammatory diseases emerge as the most prevalent diagnostic category.     

Leptospirosis on Oahu: an outbreak associated with flooding of a university campus

On October 31, 2004, a stream overflowed, flooding the University of Hawaii (UH) campus. On November 19, 2004, a possible flood-related leptospirosis case (Patient 1) was reported to the Hawaii State Department of Health (HDOH). Surveillance for febrile illness was established through an Internet questionnaire. Active case finding was conducted among groups involved in the flood clean-up. Free leptospirosis testing was offered by HDOH. Patient 1's illness was confirmed as leptospirosis by microscopic agglutination testing. A total of 271 persons responded to the Internet survey, of whom 90 (33%) reported a febrile illness within 30 days of contact with flood water. Forty-eight respondents (18%) were tested for leptospirosis. One additional acute leptospirosis case was identified. Patient 2 was epidemiologically linked to Patient 1. Health care providers should maintain a high level of suspicion for leptospirosis after flooding events, and local public health officials should promote leptospirosis awareness among flood-affected populations.     

Etiologies of Illness among Patients Meeting Integrated Management of Adolescent and Adult Illness District Clinician Manual Criteria for Severe Infections in Northern Tanzania: Implications for Empiric Antimicrobial Therapy

We describe the laboratory-confirmed etiologies of illness among participants in a hospital-based febrile illness cohort study in northern Tanzania who retrospectively met Integrated Management of Adolescent and Adult Illness District Clinician Manual (IMAI) criteria for septic shock, severe respiratory distress without shock, and severe pneumonia, and compare these etiologies against commonly used antimicrobials, including IMAI recommendations for emergency antibacterials (ceftriaxone or ampicillin plus gentamicin) and IMAI first-line recommendations for severe pneumonia (ceftriaxone and a macrolide). Among 423 participants hospitalized with febrile illness, there were 25 septic shock, 37 severe respiratory distress without shock, and 109 severe pneumonia cases. Ceftriaxone had the highest potential utility of all antimicrobials assessed, with responsive etiologies in 12 (48%) septic shock, 5 (14%) severe respiratory distress without shock, and 19 (17%) severe pneumonia illnesses. For each syndrome 17–27% of participants had etiologic diagnoses that would be non-responsive to ceftriaxone, but responsive to other available antimicrobial regimens including amphotericin for cryptococcosis and histoplasmosis; anti-tuberculosis therapy for bacteremic disseminated tuberculosis; or tetracycline therapy for rickettsioses and Q fever. We conclude that although empiric ceftriaxone is appropriate in our setting, etiologies not explicitly addressed in IMAI guidance for these syndromes, such as cryptococcosis, histoplasmosis, and tetracycline-responsive bacterial infections, were common.     

Complicated malaria and other severe febrile illness in a pediatric ward in Libreville, Gabon

ABSTRACT: BACKGROUND: Although a substantial decline of Plasmodium falciparum infection is observed in Africa following implementation of new control strategies, malaria is still considered as the major cause of febrile illness in hospitalized African children. The present study was designed to assess the management of febrile illness and to determine the proportion of children with febrile illness hospitalized for primary diagnosis of malaria who had confirmed complicated malaria after implementation of new malaria control strategies in Libreville, Gabon. METHODS: Demographic, clinical and biological data from hospitalized children with fever or a history of fever with a primary diagnosis of clinical malaria, aged less than 18 years old, who benefited from hematological measurements and microscopic malaria diagnosis were recorded and analyzed during a prospective and observational study conducted in 2008 in the Centre Hospitalier de Libreville. RESULTS: A total of 418 febrile children were admitted at hospital as malaria cases. Majority of them (79.4%) were aged below five years. After medical examination, 168 were diagnosed and treated as clinical malaria and, among them, only 56.7% (n = 95) had Plasmodium falciparum positive blood smears. Age above five years, pallor, Blantyre Coma Score <=2 and thrombocytopenia were predictive of malaria infection. Respiratory tract infections was the first leading cause of hospitalization (41.1%), followed by malaria (22.7%); co-morbidities were frequent (22%). Less than 5% of suspected bacterial infections were confirmed by culture. Global case fatality rate was 2.1% and 1% for malaria. Almost half (46%) of the children who received antimalarial therapy had negative blood smears. Likewise, antibiotics were frequently prescribed without bacteriological confirmation. CONCLUSIONS: The use of clinical symptoms for the management of children febrile illness is frequent in Gabon. Information, training of health workers and strengthening of diagnosis tools are necessary to improve febrile children care.     

Water and sodium disturbances predict prognosis of acute disease in long term cared frail elderly

Elderly patients are at increased risk for developing infections and fever. We aimed to investigate the incidence, causes and outcome of hypernatemia and hyponatremia among elderly long-term care patients with febrile illness. This is a prospective study conducted in a 110 beds, nursing department for dependent elderly in geriatric long-term care facility during 20 months period. Changes in plasma sodium concentrations were found in 48% (132/270) of the febrile illness: during the acute illness in 38% (102/270) of the events and during the follow-up period after acute febrile event, in 30% (59/198) of the events. Upper respiratory tract, bronchial, lung, and urinary tract infections were the most common causes for the fever. Hypernatremia was more prevalent on acute febrile illness (63%). Hyponatremia was more common before the febrile illness (10%) and during the follow-up period (69%). The most common causes of hypernatremia were inadequate hydration or correction (57%) and continuous diuretic treatment (38%). The most common causes of hyponatremia were: Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH) (38%), incorrect hydration (19%), and continuous diuretic treatment (30%). During the study, 60% (28/47) of the patients died, and hypernatremia was detected in 82% (20/28). Disturbances in sodium concentrations were predictors of bad outcomes, related to the underlying diseases burden, and were not related to the magnitude of the changes in plasma sodium, time of its development, advanced age, gender and coexisting changes in plasma potassium level.     

Viral Isolates of a Novel Putative Phlebovirus in the Marche Region of Italy

Co-infection with pathogens that cause acute febrile illness creates a diagnostic challenge as a result of overlapping clinical manifestations. Here, we describe four fatal cases of Leptospira species/dengue virus co-infection in Puerto Rico. Although all patients sought care early, antibiotic administration was delayed for most. Steroids were administered to all patients, in most cases before antibiotics. These cases show the need for clinicians evaluating patients in or recently returned from the tropics with acute febrile illness to consider both dengue and leptospirosis. Furthermore, they illustrate the need for nucleic acid- or antigen-based rapid diagnostic tests to enable timely patient diagnosis and management. In particular, antibiotic therapy should be initiated early for patients with suspected leptospirosis, and steroids should not be administered to patients with suspected dengue.     

Asymptomatic infection and risk factors for leptospirosis in Nicaragua.

As part of an investigation of a 1995 outbreak of leptospirosis in Nicaragua, a cross-sectional serologic survey was conducted in the town of El Sauce. Of 566 persons, 85 (15%) were positive for IgM anti-Leptospira antibodies, indicating recent leptospirosis infection. Asymptomatic leptospirosis infection was common, with only 25 (29.4%) of the 85 seropositive inhabitants reporting a febrile illness in the 2 months before the survey. Multivariable analysis revealed that having an indoor water source remained independently protective against leptospirosis. Gathering wood was independently associated with infection. These findings suggest that asymptomatic infection with Leptospira is common in endemic areas of Leptospira transmission. Improvement in water sanitation and behavioral modifications to reduce environmental exposure may reduce the risk of leptospirosis in endemic regions.     

Human leptospirosis in Denmark 1970-1996: an epidemiological and clinical study

Epidemiological and clinical aspects of 118 laboratory confirmed cases of human leptospirosis in Denmark from 1970 to 1996 were reviewed. Icterohaemorrhagiae (72%) and sejroe (20%) were the most frequent serovars. The incidence of leptospirosis was 0.09/100,000 inhabitants/y. 93% of the patients were 18-64 y old, 90% were men and 72% of the cases occurred from July to November. Occupational exposure was present in 63% (74/118) of the cases (41% fish farmers, 28%, farmers). Eight percent of the patients had travelled abroad, 7% had been exposed to sewers and 4%, had been exposed through recreational activities (fishing). Initial symptoms were generally non-specific. Weil's disease developed in 63%, of the patients, more often in patients infected with the serovar icterohaemorrhagiae (73%) compared to patients infected with serovars sejroe or saxkoebing (25%). The fatality rate was 7%, all due to icterohaemorrhagiae. Though a rare disease in Denmark, leptospirosis should be considered in certain risk groups as a possible diagnosis in patients with acute febrile illness.     

Retrospective serosurvey of leptospirosis among patients with acute febrile illness and hepatitis in Egypt

The epidemiologic status of leptospirosis in Egypt has not been well defined because of difficulties in disease diagnosis. A retrospective study was conducted to detect leptospiral antibodies among undiagnosed acute febrile illness (AFI) and hepatitis cases. Approximately 16% of both AFI (141/886) and acute hepatitis (63/392) cases showed seroreactivity to Leptospira IgM by ELISA and microscopic agglutination test (MAT). Canicola, Djasiman, Grippotyphosa, Pyrogenes, Icterohemorrhagiae, and Pomona were the most commonly reactive serovars among patients with AFI. Djasiman, Grippotyphosa and Icterohemorrhagiae were the most reactive among patients with acute hepatitis. This study represents the first systematic report of Leptospira associated with patients with AFI and hepatitis in Egypt. Physicians need to have increased awareness about the importance of leptospirosis in the differential diagnosis of AFI and acute hepatitis in Egypt. In addition, laboratory capacity should be developed at fever hospitals to diagnose leptospirosis.     

Mild, self-resolving acute leptospirosis in an HIV-infected patient in the Peruvian Amazon

We report a case of acute, self-resolving leptospirosis presenting in a HIV-positive patient from the Peruvian Amazon. The patient presented with an undifferentiated acute febrile illness that resolved without treatment, diagnosed retrospectively as leptospirosis by serology and real-time polymerase chain reaction. Five months later, he was admitted because of a febrile illness with jaundice, hepatosplenomegaly, peripheral edema, and oral candidiasis. Because of the clinical suspicion of AIDS, stored sera of the previous admission were tested, and HIV seropositivity was confirmed, proving that the condition was present at the first admission. Acute leptospirosis in HIV coinfection is not inevitably severe, and there is probably a wide variation in clinical manifestations similar to what occurs in immuno-competent hosts.     

Epidemiology,clinical and laboratory features of 24 consecutive cases of leptospirosis at a German infectious disease center

To determine epidemiological, clinical and laboratory characteristics of leptospirosis, 24 consecutive patients diagnosed with the infection between 2011 and 2017 at the University Medical Center Hamburg-Eppendorf were retrospectively analyzed. The majority of patients were male travelers who returned from Southeast Asia and had a history of freshwater-associated activities. Considering the lack of discriminatory clinical or clinical chemistry parameters, leptospirosis should be regarded as differential diagnosis in any patient with acute febrile illness, especially with a history of travel to tropical and subtropical regions or freshwater exposure.     

Significance of fever in hospital employees

Hospital employees are exposed to a variety of occupationally related hazards that can be categorized as infectious or noninfectious. Lost work time often results from these problems. Infection control practitioners receive many telephone calls of inquiry about these employees in terms of their transmissible infections. Little has been written concerning fever in the employee health setting. To determine the frequency of febrile illness in hospital employees, we conducted a prospective study of the employee health service from January to December 1987. Winthrop-University Hospital is a 533-bed community teaching hospital with approximately 2400 employees. During 1987, 2974 visits were made to the employee health service. Of these, 879 (30%) were for occupationally related illness or injury. Oral temperatures of greater than or equal to 100 degrees F were noted in 25 (2.8%) of the 879 visits. Fever occurred predominantly in employees with infections. Upper respiratory tract infection accounted for 268 of 544 (49%) visits for infection. In addition, 11 of 22 (50%) febrile episodes were related to upper respiratory tract infections. A total of 963 work days were lost because of illness or injury. Of these, 743 (77%) were related to an infectious illness; 67 sick days (7%) were attributed to infections with a febrile response. We conclude that fever is uncommon in our employee health care population and that upper respiratory tract infections were the single most common cause of fever. When an employee had a febrile illness, the lost work time was 9% of the total time loss because of infection.