Etiology of acute, non-malaria, febrile illnesses in Jayapura, northeastern Papua, Indonesia

We conducted a prospective, inpatient fever study in malaria-endemic Papua, Indonesia to determine non-malaria fever etiologies. Investigations included malaria blood films, blood culture, paired serologic samples analysis for dengue, Japanese encephalitis, leptospirosis, scrub typhus, murine typhus, and spotted fever group rickettsia. During 1997-2000, 226 patients (127 males and 99 females) 1-80 years of age (median age = 25 years) were enrolled. Positive blood cultures (n = 34, 15%) were obtained for Salmonella Typhi (n = 13), Escherichia coli (n = 8), Streptococcus pneumoniae (n = 6), Staphylococcus aureus (n = 5), Streptococcus pyogenes (n = 1), and Klebsiella pneumoniae (n = 1). Twenty (8.8%) patients were positive for leptospirosis by polymerase chain reaction. Eighty (35.4%) of 226 patients had ≥ 1 positive serology, diagnostic for 15 rickettsial and 9 dengue cases. Acid-fast bacilli-positive sputum was obtained from three patients. Most common confirmed (81 of 226, 35.8%)/suspected diagnoses were typhoid fever (n = 41), pneumonia (n = 29), leptospirosis (n = 28), urinary tract infections (n = 20), rickettsioses (n = 19), dengue (n = 17), and meningitis/encephalitis (n = 15). There were 17 deaths, 7 (46.7%) were caused by meningitis/encephalitis. Multiple positive serologic results and few confirmed diagnoses indicate the need for improved diagnostics.     

Increase of leptospirosis in dengue-negative patients after a hurricane in Puerto Rico in 1996 [correction of 1966]

Leptospirosis has rarely been reported in Puerto Rico, although in the period from 1948 to 1952, 208 cases of leptospirosis and an island-wide seroprevalence of antibody to Leptospira of 14% were documented. In Puerto Rico in October 1996, following rainfall and a period of flooding generated by Hurricane Hortense, serum specimens of 4 patients with suspected dengue fever that were negative for dengue tested positive for Leptospira-specific IgM antibodies in a dipstick assay. Subsequently, we used an island-wide dengue laboratory-based surveillance system to determine the increase in leptospirosis after hurricane-generated floods. All anti-dengue IgM-negative patients (n = 142) with disease onset from August 8 to October 6, 1996 from prehurricane and posthurricane groups were investigated for leptospirosis. Laboratory-confirmed leptospirosis cases were defined as microscopic agglutination test titers > or = 1 :400 to 1 or more serovars, or positive immunohistochemistry in autopsy tissues. Four (6%) of 72 prehurricane and 17 (24%) of 70 posthurricane patients had laboratory-confirmed cases of leptospirosis (relative risk [RR] = 4.4, 95% confidence interval [CI] = 1.6-12.4). The mean age of case-patients was 34 years (range = 13-64). Eighteen (86%) of 21 confirmed case-patients were males, including one patient who died (31 years old). Patients were located in 18 (38%) of 48 municipalities that submitted serum samples. Clinical features significantly associated with leptospirosis were eye pain (RR = 1.5, 95% CI = 1.3-1.9), joint pain (RR = 1.4, 95% CI = 1.1-1.6), diarrhea (RR = 1.7, 95% CI = 1.2-2.5), and jaundice (RR = 3.3, 95% CI = 1.5-7.2). This study demonstrates the utility of a dengue laboratory-based surveillance system for the detection of an increase of leptospirosis, which most likely would have gone unrecognized. Leptospirosis is treatable with antibacterial agents; knowledge of this diagnosis may significantly reduce morbidity and mortality.     

Leptospirosis among patients presenting with dengue-like illness in Puerto Rico

Leptospirosis is difficult to distinguish from dengue fever without laboratory confirmation. Sporadic cases/clusters of leptospirosis occur in Puerto Rico, but surveillance is passive and laboratory confirmation is rare. We tested for leptospirosis using an IgM ELISA on sera testing negative for dengue virus IgM antibody and conducted a case-control study assessing risk factors for leptospirosis, comparing clinical/laboratory findings between leptospirosis (case-patients) and dengue patients (controls). Among 730 dengue-negative sera, 36 (5%) were positive for leptospirosis. We performed post mortem testing for leptospirosis on 12 available specimens from suspected dengue-related fatalities; 10 (83%) tested positive. Among these 10 fatal cases, pulmonary hemorrhage and renal failure were the most common causes of death. We enrolled 42 case-patients and 84 controls. Jaundice, elevated BUN, hyperbilirubinemia, anemia, and leukocytosis were associated with leptospirosis (p < .01 for all). Male sex, walking in puddles, rural habitation, and owning horses were independently associated with leptospirosis. Epidemiological, clinical, and laboratory criteria may help distinguish leptospirosis from dengue and identify patients who would benefit from early antibiotic treatment.     

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.     

Rapid diagnostic tests for dengue and leptospirosis: antibody detection is insensitive at presentation

OBJECTIVE: To determine the performance of rapid diagnostic tests for dengue and leptospirosis that rely on detecting antibodies that may not be produced when patients present for medical treatment. METHODS: We prospectively enrolled 723 patients with undifferentiated febrile illness presenting to rural hospitals in northern and northeastern Thailand over a 1-year period. We evaluated rapid antibody detection diagnostic tests for dengue and leptospirosis on these patients. RESULTS: Sensitivity of the tests was low at the acute visit (7.6-21.5%). Sensitivity at the convalescent visit ranged from 25.8% to 81.5% and was significantly higher than at the acute visit for all tests (chi(2), P < 0.001). CONCLUSIONS: Low sensitivity of the rapid tests at presentation suggests that their utility in the acute phase of dengue and leptospirosis is limited.     

Referral pattern of leptospirosis cases during a large urban epidemic of dengue.

During heavy seasonal rainfall in 1996, concurrent epidemics of dengue and leptospirosis occurred in an urban center in northeastern Brazil. We interviewed 110 cases of leptospirosis hospitalized a median of seven days after the onset of illness to evaluate the impact of the dengue epidemic on the triage of suspected leptospirosis from ambulatory clinics to the infectious disease reference hospital. Within the first three days of illness, 46 (42%) cases sought their first medical evaluation, and 28 (61% of 46) received a diagnosis of dengue. Dengue diagnoses were associated with a median of five days delay in referral to the infectious disease hospital. Patients who reported initial diagnoses of dengue were more likely than other patients to have required admission to the intensive care unit (odds ratio [OR] = 2.7, 95% confidence interval [CI] = 0.8-9.5) and to have died during hospitalization (OR = 5.1, 95% CI = 0.8-55.0). These findings indicate that diagnostic confusion between the early symptoms of leptospirosis and dengue may have contributed to the high mortality observed during the leptospirosis epidemic.     

Detection of dengue infection in patients investigated for leptospirosis in Barbados

The annual incidence of leptospirosis in Barbados is approximately 13 severe cases/100,000. The peak incidence occurs in October to December of each year, coinciding with the months of heaviest rainfall. During the second half of 1995, an epidemic of dengue type 1 infection produced almost 1,000 laboratory-confirmed cases. During the same period, leptospirosis mortality was twice the average, suggesting that some cases of leptospirosis were being misdiagnosed and treated inappropriately. Sera from patients investigated for dengue or leptospirosis were analyzed retrospectively to determine the extent of misdiagnosis. During 1995 and 1996, 31 of 139 and 29 of 93 patients, respectively, were confirmed as having leptospirosis. Sera from the remaining leptospirosis-negative patients were tested for IgM antibodies to dengue virus. During 1995 and 1996, 48 of 108 patients and 21 of 64 patients, respectively, were found to have dengue. In 1997, sera from all patients investigated for leptospirosis were also tested prospectively for IgM antibodies to dengue: 38 of 92 leptospirosis-negative patients (41%) were dengue IgM-positive, while 2 of 25 leptospirosis cases also had serologic evidence suggesting acute dengue infection. A second large outbreak of dengue caused by serotype 2 occurred in 1997. During the 1995 and 1997 dengue epidemics in Barbados, dengue cases outnumbered leptospirosis cases investigated in the leptospirosis diagnostic protocol. During 1997, patients investigated but negative for dengue were also tested for anti-leptospiral IgM: 7.3% (19 of 262) were IgM-positive. Substantial misdiagnosis of both dengue and leptospirosis can occur and greater public awareness and clinical suspicion of the similar presentations of these two diseases are necessary.     

Invasive fungal infection in Chinese patients with systemic lupus erythematosus

Invasive fungal infection (IFI) can be a lethal complication in systemic lupus erythematosus (SLE). The aim of this study was to determine the characteristics of hospitalized SLE patients with IFI, and identify the risk factors compared to SLE with other major infections or those with active disease alone. Data from 18 SLE in-patients with IFI at Shanghai Renji Hospital between January 2007 and January 2011 were collected by chart review. SLE patients with either active Mycobacterium tuberculosis (n = 19) or other bacterial infections (n = 17), or active SLE (n = 54) in the same period acted as controls. SLE in-patients with IFI (n = 11) from January 2002 to December 2006 was considered as a historical control group. The most frequent pathogens of SLE-IFI was Cryptococcus neoformans (n = 9, 50.0 %), followed by Aspergillus and Candida (both n = 3, 16.7 %). The infection sites included lung (n = 8, 44.4 %), central nervous system (n = 8, 44.4 %), and disseminated IFI (n = 2, 11.1 %). Three patients (16.7 %) died from IFI. Compared with other major infections, IFI patients were younger, with shorter SLE disease duration, lower C-reactive protein response, higher corticosteroids, and antibiotics exposure. Compared with active SLE, IFI patients had elevated alanine transaminase level, higher corticosteroids and antibiotics exposure. In multivariate analysis, the only significant risk factors for IFI were maximum prednisolone exposure ≥45 mg/day prior to infection or flare within 3 months (OR?=?10.284, 95 %CI (2.877, 36.836)). Compared with the historical SLE-IFI patients, the short-term survival improved over time (63.6 % versus 83.3 %). SLE-IFI is a unique entity that characterized by certain aforementioned parameters compared with other major infections or disease flare in SLE. Familiar with the disease pattern along with appropriate antifungal treatment may lead to a better outcome in SLE-IFI patients.     

Acute myelogenous leukemia patients are at low risk for invasive fungal infections after high-dose cytarabine consolidations and thus do not require prophylaxis

We evaluated the frequency of invasive fungal infections (IFI), the frequency of empirical antifungal use (EAFU), and the efficacy of fluconazole prophylaxis on IFI and EAFU after high-dose cytarabine (HiDAC) consolidations. Twenty-seven acute myelogenous leukemia patients in their first complete remission received 76 cycles of HiDAC (median cycle: n = 3). Fluconazole prophylaxis was administered following 44 cycles (fluconazole group) and not given in 32 cycles (control group). IFI (2 episodes) + EAFU (11 episodes) was observed in 13 of 76 cycles (17%); there was no difference between the fluconazole group and the control group (p = 0.469). Neutropenia duration was <13 days in 89% of the 76 cycles and was similar in the fluconazole and control groups (p = 0.845). Neutropenic fever was observed in 34 of the 76 cycles (45%) and was similar in the fluconazole group and the control group (p = 0.43). Although HiDAC cycle 1 was associated with a shorter neutropenia duration, there was no association between HiDAC cycle numbers and neutropenic fever or IFI + EAFU. HiDAC consolidations resulted in a high rate of neutropenic fever, the lack of an appreciable benefit from EAFU, and rare IFI. Most likely because of the low incidence of IFI, use of fluconazole or another antifungal is not warranted in this setting.     

Penicillin at the late stage of leptospirosis: a randomized controlled trial

There is evidence that an early start of penicillin reduces the case-fatality rate of leptospirosis and that chemoprophylaxis is efficacious in persons exposed to the sources of leptospira. The existent data, however, are inconsistent regarding the benefit of introducing penicillin at a late stage of leptospirosis. The present study was developed to assess whether the introduction of penicillin after more than four days of symptoms reduces the in-hospital case-fatality rate of leptospirosis. A total of 253 patients aged 15 to 76 years with advanced leptospirosis, i.e., more than four days of symptoms, admitted to an infectious disease hospital located in Salvador, Brazil, were selected for the study. The patients were randomized to one of two treatment groups: with intravenous penicillin, 6 million units day (one million unit every four hours) for seven days (n = 125) and without (n = 128) penicillin. The main outcome was death during hospitalization. The case-fatality rate was approximately twice as high in the group treated with penicillin (12%; 15/125) than in the comparison group (6.3%; 8/128). This difference pointed in the opposite direction of the study hypothesis, but was not statistically significant (p = 0.112). Length of hospital stay was similar between the treatment groups. According to the results of the present randomized clinical trial initiation of penicillin in patients with severe forms of leptospirosis after at least four days of symptomatic leptospirosis is not beneficial. Therefore, more attention should be directed to prevention and earlier initiation of the treatment of leptospirosis.     

Invasive fungal infections in patients with hematologic malignancies in a tertiary care cancer center: an autopsy study over a 15-year period (1989-2003)

We evaluated autopsy-proven invasive fungal infections (IFI) in patients with hematologic malignancies over three periods (1989-1993, 1994-1998, and 1999-2003). The autopsy rate declined significantly (67%-34%-26%, respectively p<0.0001). IFI were identified in 314 (31%) of 1017 autopsies. Most IFI (75%) were not diagnosed antemortem. The prevalence of invasive mold infections increased significantly (19%-24%-25% p=0.05) in parallel with the emergence of Zygomycetes (0.9%-4%-3%; p=0.03). The prevalence of all other IFI remained relatively constant. Among patients with invasive pulmonary aspergillosis, those with graft-versus-host disease had a histopathological pattern distinct from those with neutropenia. The complex and evolving epidemiology of IFI in severely immunocompromised patients is not well captured by current diagnostic methods.     

1999～2008年云南省重要自然疫源性疾病疫情分析

目的分析1999～2008年云南省重要自然疫源性疾病疫情,为制定预防控制策略提供依据。方法收集1999～2008年云南省重要自然疫源性疾病相关数据,采用描述流行病学进行分析。结果1999～2008年,云南省发生的重要自然疫源性疾病包括细菌、螺旋体病类的鼠疫、布鲁氏菌病、炭疽、钩端螺旋体病,病毒类的狂犬病、流行性出血热、登革热、流行性乙型脑炎,以及寄生虫病类的疟疾、血吸虫病共10种疾病,病人109445例,死亡795例,病死率为0.73%。疟疾发病人数最多,其次为流行性乙型脑炎和钩端螺旋体病,狂犬病病死率为100%。鼠疫、血吸虫病流行得到有效控制;狂犬病、登革热、钩端螺旋体病和布鲁氏菌病疫情呈现上升趋势。全省16个州（市）中,除迪庆、怒江、曲靖、玉溪外均为重病区。发病群体男性显著高于女性,特别是炭疽、狂犬病、疟疾最为明显。不同疾病发病年龄组不同,高发群体主要为农民、学生、散居儿童和民工,以疟疾发病群体最广泛。结论云南省自然疫源性疾病疫情形势严峻。加强监测与预警、提升应急处置能力和严防大疫发生是防控的主要策略。     

Comparative study of the in-hospital case-fatality rate of leptospirosis between pediatric and adult patients of different age groups

The main objective was to compare the in-hospital case-fatality rate of leptospirosis between pediatric (< 19 years) and adult (>19 years) patients, taking into account gender, renal function, duration of symptoms and jaundice. Medical records of 1016 patients were reviewed. Comparative analysis was restricted to 840 patients (100 pediatric, 740 adults) with recorded information on the variables included in the analysis. Among these patients 81.7% were male and 91.5% were icteric. The case-fatality rate of leptospirosis was 14.4%. The odds of death adjusted for gender, jaundice, duration of symptoms, serum urea and serum creatinine were almost four times higher for the adult than for the pediatric group (odds ratio (OR) = 3.94; 95% confidence interval = 1.19-13.03, p = 0.029). Among adults, increased age was also significantly and independently associated with increased risk of death (p < 0.01). Older patients were also more often treated by dialysis. In conclusion, the data suggest that the in-hospital case fatality rate of leptospirosis is higher for adults than for children and adolescents, even after taking into account the effects of several potential risk factors of death. Among adults, older age was also strongly and independently associated with higher risk of death.     

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.     

Causes of acute, undifferentiated, febrile illness in rural Thailand: results of a prospective observational study

The adult patients who, between July 2001 and June 2002, presented at any of five hospitals in Thailand with acute febrile illness in the absence of an obvious focus of infection were prospectively investigated. Blood samples were taken from all of the patients and checked for aerobic bacteria and leptospires by culture. In addition, at least two samples of serum were collected at different times (on admission and 2-4 weeks post-discharge) from each patient and tested, in serological tests, for evidence of leptospirosis, rickettsioses, dengue and influenza. The 845 patients investigated, of whom 661 were male, had a median age of 38 years and a median duration of fever, on presentation, of 3.5 days. Most (76.5%) were agricultural workers and most (68.3%) had the cause of their fever identified, as leptospirosis (36.9%), scrub typhus (19.9%), dengue infection or influenza (10.7%), murine typhus (2.8%), Rickettsia helvetica infection (1.3%), Q fever (1%), or other bacterial infection (1.2%). The serological results indicated that 103 (12.2%) and nine (1%) of the patients may have had double and triple infections, respectively. Leptospirosis and rickettsioses, especially scrub typhus, were thus found to be major causes of acute, undifferentiated fever in Thai agricultural workers.     

Application of revised dengue classification criteria as a severity marker of dengue viral infection in Indonesia

A prospective study of dengue infected patients at Dr.Soetomo Hospital pediatric ward was carried out from October 2008 to April 2009 to evaluate the revised dengue classification system proposed by the Dengue Control (DENCO), for early detection of severe dengue infected patients using the WHO classification system for comparison, with the addition of clinical interventions as a tool to grade for severity. One hundred forty-five patients were included in the study. Using the WHO classification system, 122 cases (84.1%) were classified as having non-severe dengue, of which 70 (48.3%) were classified as having dengue fever (DF), 39 (26.9%) as having dengue hemorrhagic fever (DHF) grade I, and 13 (9%) as having DHF grade II. Twenty-three (15.9%) were classified as having severe dengue, of which 16 (11%) were classified as having DHF grade III and 7 (4.8%) as having DHF grade IV. With clinical interventions included, 8 cases (6.6%) originally classified as having non-severe dengue infection were reclassified as having severe infection (sensitivity = 74%, specificity = 100%, likelihood ratio (-) = 0.26). Using the new dengue classification system, 117 cases (80.7%) were classified as having non-severe dengue infection, of which 79 (54.5%) were classified as having dengue without warning signs and 38 (26.2%) were classified as having dengue with warning signs, while 28 (19.3%) were classified as having severe dengue infection. Using clinical intervention, 4 cases (3.4%) which were originally classified as having non-severe dengue infection were reclassified as having severe dengue infection (sensitivity = 88%, specificity = 99%, likelihood ratio (+) = 98.88, likelihood ratio (-) = 0.13). Binary logistic regression showed the revised dengue classification system (p = 0.000, Wald:22.446) was better in detecting severe dengue infections than the WHO classification system (p = 0.175, Wald:6.339).     

Etiology of obscure fever in children at a university hospital in northeast Thailand

Obscure fever is not an uncommon problem in Thailand. We studied 25 children with obscure fever admitted to Srinagarind (university) Hospital in Northeast Thailand. The etiology was identified in 52% of the cases: dengue (40%), leptospirosis (8%), and micrococcus septicemia (4%). Two cases with primary dengue infection developed dengue shock syndrome. The case with leptospirosis developed infection-associated, hemophagocytic syndrome. We found no cases of Japanese encephalitis, scrub typhus or murine typhus.     

Serologic evidence of human leptospirosis in and around Kolkata, India: a clinico-epidemiological study

ObjectiveTo investigate the prevalence of leptospirosis among patients from within and outside Kolkata, India, attending the Calcutta School of Tropical Medicine, for treatment during August 2002 to August 2008.MethodsThe leptospirosis cases were determined on the basis of clinical, epidemiological, and biochemical factors, and were tested for leptospiral antibodies using IgM ELISA. Serum samples with absorbance ratio ≥ 1.21 were interpreted as reactive.ResultsThe commonest presentation involved fever, headache and jaundice. The male-female ratio was 61:46. A total of 65(64.20%) cases had abnormal liver and renal functions respectively, and 57.1% had both the abnormalities. The highest incidence (75, 35.04%) was recorded in September-October followed by July-August (53, 24.77%). The reactive cases had absorbance ratios between 1.21 and 8.21, and 53 showed equivocal result, while IgM non reactivity were seen in 90 patients (absorbance ratios 0.10-0.90). The patients responded to treatment with parenteral antibiotics, penicillin, ceftriaxone and cefotaxime; follow up did not reveal case fatality.ConclusionsThe cardinal signs of leptospirosis help in making clinical diagnosis, but in any hyper-endemic situation any patient reporting with acute fever and signs of pulmonary, hepatic or renal involvement should be suspected to have leptospirosis and investigated accordingly. Increased awareness, and early diagnosis and treatment, can reduce mortality due to leptospirosis.     

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.