Publications by authors named "Renee L Galloway"

44 Publications

Role of Diagnostics in Epidemiology, Management, Surveillance, and Control of Leptospirosis.

Pathogens 2022 Mar 24;11(4). Epub 2022 Mar 24.

Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, CA 90073, USA.

A One Health approach to the epidemiology, management, surveillance, and control of leptospirosis relies on accessible and accurate diagnostics that can be applied to humans and companion animals and livestock. Diagnosis should be multifaceted and take into account exposure risk, clinical presentation, and multiple direct and/or indirect diagnostic approaches. Methods of direct detection of spp. include culture, histopathology and immunostaining of tissues or clinical specimens, and nucleic acid amplification tests (NAATs). Indirect serologic methods to detect leptospiral antibodies include the microscopic agglutination test (MAT), the enzyme-linked immunosorbent assay (ELISA), and lateral flow methods. Rapid diagnostics that can be applied at the point-of-care; NAAT and lateral flow serologic tests are essential for management of acute infection and control of outbreaks. Culture is essential to an understanding of regional knowledge of circulating strains, and we discuss recent improvements in methods for cultivation, genomic sequencing, and serotyping. We review the limitations of NAATs, MAT, and other diagnostic approaches in the context of our expanding understanding of the diversity of pathogenic spp. Novel approaches are needed, such as loop mediated isothermal amplification (LAMP) and clustered regularly interspaced short palindromic repeats (CRISPR)-based approaches to leptospiral nucleic acid detection.
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http://dx.doi.org/10.3390/pathogens11040395DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9032781PMC
March 2022

Molecular Detection and Typing of Pathogenic in Febrile Patients and Phylogenetic Comparison with Detected among Animals in Tanzania.

Am J Trop Med Hyg 2020 10;103(4):1427-1434

Duke Global Health Institute, Duke University, Durham, North Carolina.

Molecular data are required to improve our understanding of the epidemiology of leptospirosis in Africa and to identify sources of human infection. We applied molecular methods to identify the infecting species and genotypes among patients hospitalized with fever in Tanzania and compared these with genotypes detected among animals in Tanzania to infer potential sources of human infection. We performed real-time PCR to detect the presence of pathogenic in acute-phase plasma, serum, and urine samples obtained from study participants with serologically confirmed leptospirosis and participants who had died with febrile illness. blood culture was also performed. In positive specimens, we performed species-specific PCR and compared participant sequences with reference sequences and sequences previously obtained from animals in Tanzania. We detected DNA in four (3.6%) of 111 participant blood samples. We detected (one participant, 25.0%), (one participant, 25.0%), and (one participant, 25.0%) (one [25%] undetermined). Phylogenetic comparison of sequence from the and genotypes detected from participants was closely related to but distinct from genotypes detected among local livestock species. Our results indicate that a diverse range of species is causing human infection. Although our analysis suggests a close relationship between genotypes found in people and livestock, continued efforts are needed to obtain more genetic material from human leptospirosis cases to help prioritize species and genotypes for control.
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http://dx.doi.org/10.4269/ajtmh.19-0703DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7543812PMC
October 2020

Linking longitudinal and cross-sectional biomarker data to understand host-pathogen dynamics: Leptospira in California sea lions (Zalophus californianus) as a case study.

PLoS Negl Trop Dis 2020 06 29;14(6):e0008407. Epub 2020 Jun 29.

Department of Ecology and Evolutionary Biology, University of California, Los Angeles, California, United States of America.

Confronted with the challenge of understanding population-level processes, disease ecologists and epidemiologists often simplify quantitative data into distinct physiological states (e.g. susceptible, exposed, infected, recovered). However, data defining these states often fall along a spectrum rather than into clear categories. Hence, the host-pathogen relationship is more accurately defined using quantitative data, often integrating multiple diagnostic measures, just as clinicians do to assess their patients. We use quantitative data on a major neglected tropical disease (Leptospira interrogans) in California sea lions (Zalophus californianus) to improve individual-level and population-level understanding of this Leptospira reservoir system. We create a "host-pathogen space" by mapping multiple biomarkers of infection (e.g. serum antibodies, pathogen DNA) and disease state (e.g. serum chemistry values) from 13 longitudinally sampled, severely ill individuals to characterize changes in these values through time. Data from these individuals describe a clear, unidirectional trajectory of disease and recovery within this host-pathogen space. Remarkably, this trajectory also captures the broad patterns in larger cross-sectional datasets of 1456 wild sea lions in all states of health but sampled only once. Our framework enables us to determine an individual's location in their time-course since initial infection, and to visualize the full range of clinical states and antibody responses induced by pathogen exposure. We identify predictive relationships between biomarkers and outcomes such as survival and pathogen shedding, and use these to impute values for missing data, thus increasing the size of the useable dataset. Mapping the host-pathogen space using quantitative biomarker data enables more nuanced understanding of an individual's time course of infection, duration of immunity, and probability of being infectious. Such maps also make efficient use of limited data for rare or poorly understood diseases, by providing a means to rapidly assess the range and extent of potential clinical and immunological profiles. These approaches yield benefits for clinicians needing to triage patients, prevent transmission, and assess immunity, and for disease ecologists or epidemiologists working to develop appropriate risk management strategies to reduce transmission risk on a population scale (e.g. model parameterization using more accurate estimates of duration of immunity and infectiousness) and to assess health impacts on a population scale.
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http://dx.doi.org/10.1371/journal.pntd.0008407DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7351238PMC
June 2020

Estimating acute human leptospirosis incidence in northern Tanzania using sentinel site and community behavioural surveillance.

Zoonoses Public Health 2020 08 6;67(5):496-505. Epub 2020 May 6.

Centre for International Health, University of Otago, Dunedin, New Zealand.

Many infectious diseases lack robust estimates of incidence from endemic areas, and extrapolating incidence when there are few locations with data remains a major challenge in burden of disease estimation. We sought to combine sentinel surveillance with community behavioural surveillance to estimate leptospirosis incidence. We administered a questionnaire gathering responses on established locally relevant leptospirosis risk factors and recent fever to livestock-owning community members across six districts in northern Tanzania and applied a logistic regression model predicting leptospirosis risk on the basis of behavioural factors that had been previously developed among patients with fever in Moshi Municipal and Moshi Rural Districts. We aggregated probability of leptospirosis by district and estimated incidence in each district by standardizing probabilities to those previously estimated for Moshi Districts. We recruited 286 community participants: Hai District (n = 11), Longido District (59), Monduli District (56), Moshi Municipal District (103), Moshi Rural District (44) and Rombo District (13). The mean predicted probability of leptospirosis by district was Hai 0.029 (0.005, 0.095), Longido 0.071 (0.009, 0.235), Monduli 0.055 (0.009, 0.206), Moshi Rural 0.014 (0.002, 0.049), Moshi Municipal 0.015 (0.004, 0.048) and Rombo 0.031 (0.006, 0.121). We estimated the annual incidence (upper and lower bounds of estimate) per 100,000 people of human leptospirosis among livestock owners by district as Hai 35 (6, 114), Longido 85 (11, 282), Monduli 66 (11, 247), Moshi Rural 17 (2, 59), Moshi Municipal 18 (5, 58) and Rombo 47 (7, 145). Use of community behavioural surveillance may be a useful tool for extrapolating disease incidence beyond sentinel surveillance sites.
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http://dx.doi.org/10.1111/zph.12712DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7497209PMC
August 2020

Sensitivity of C-reactive protein for the identification of patients with laboratory-confirmed bacterial infections in northern Tanzania.

Trop Med Int Health 2020 03 6;25(3):291-300. Epub 2020 Jan 6.

Kilimanjaro Christian Medical Centre, Moshi, Tanzania.

Objective: Identifying febrile patients requiring antibacterial treatment is challenging, particularly in low-resource settings. In South-East Asia, C-reactive protein (CRP) has been demonstrated to be highly sensitive and moderately specific in detecting bacterial infections and to safely reduce unnecessary antibacterial prescriptions in primary care. As evidence is scant in sub-Saharan Africa, we assessed the sensitivity of CRP in identifying serious bacterial infections in Tanzania.

Methods: Samples were obtained from inpatients and outpatients in a prospective febrile illness study at two hospitals in Moshi, Tanzania, 2011-2014. Bacterial bloodstream infections (BSI) were established by blood culture, and bacterial zoonotic infections were defined by ≥4 fold rise in antibody titre between acute and convalescent sera. The sensitivity of CRP in identifying bacterial infections was estimated using thresholds of 10, 20 and 40 mg/l. Specificity was not assessed because determining false-positive CRP results was limited by the lack of diagnostic testing to confirm non-bacterial aetiologies and because ascertaining true-negative cases was limited by the imperfect sensitivity of the diagnostic tests used to identify bacterial infections.

Results: Among 235 febrile outpatients and 569 febrile inpatients evaluated, 31 (3.9%) had a bacterial BSI and 61 (7.6%) had a bacterial zoonosis. Median (interquartile range) CRP values were 173 (80-315) mg/l in bacterial BSI, and 108 (31-208) mg/l in bacterial zoonoses. The sensitivity (95% confidence intervals) of CRP was 97% (83%-99%), 94% (79%-98%) and 90% (74%-97%) for identifying bacterial BSI, and 87% (76%-93%), 82% (71%-90%) and 72% (60%-82%) for bacterial zoonoses, using thresholds of 10, 20 and 40 mg/l, respectively.

Conclusion: C-reactive protein was moderately sensitive for bacterial zoonoses and highly sensitive for identifying BSIs. Based on these results, operational studies are warranted to assess the safety and clinical utility of CRP for the management of non-malaria febrile illness at first-level health facilities in sub-Saharan Africa.
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http://dx.doi.org/10.1111/tmi.13358DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7265697PMC
March 2020

Distinguishing patients with laboratory-confirmed chikungunya from dengue and other acute febrile illnesses, Puerto Rico, 2012-2015.

PLoS Negl Trop Dis 2019 07 22;13(7):e0007562. Epub 2019 Jul 22.

National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.

Chikungunya, a mosquito-borne viral, acute febrile illness (AFI) is associated with polyarthralgia and polyarthritis. Differentiation from other AFI is difficult due to the non-specific presentation and limited availability of diagnostics. This 3-year study identified independent clinical predictors by day post-illness onset (DPO) at presentation and age-group that distinguish chikungunya cases from two groups: other AFI and dengue. Specimens collected from participants with fever ≤7 days were tested for chikungunya, dengue viruses 1-4, and 20 other pathogens. Of 8,996 participants, 18.2% had chikungunya, and 10.8% had dengue. Chikungunya cases were more likely than other groups to be older, report a chronic condition, and present <3 DPO. Regardless of timing of presentation, significant positive predictors for chikungunya versus other AFI were: joint pain, muscle, bone or back pain, skin rash, and red conjunctiva; with dengue as the comparator, red swollen joints (arthritis), joint pain, skin rash, any bleeding, and irritability were predictors. Chikungunya cases were less likely than AFI and dengue to present with thrombocytopenia, signs of poor circulation, diarrhea, headache, and cough. Among participants presenting <3 DPO, predictors for chikungunya versus other AFI included: joint pain, skin rash, and muscle, bone or back pain, and absence of thrombocytopenia, poor circulation and respiratory or gastrointestinal symptoms; when the comparator was dengue, joint pain and arthritis, and absence of thrombocytopenia, leukopenia, and nausea were early predictors. Among all groups presenting 3-5 DPO, pruritic skin became a predictor for chikungunya, joint, muscle, bone or back pain were no longer predictive, while arthritis became predictive in all age-groups. Absence of thrombocytopenia was a significant predictor regardless of DPO or comparison group. This study identified robust clinical indicators such as joint pain, skin rash and absence of thrombocytopenia that can allow early identification of and accurate differentiation between patients with chikungunya and other common causes of AFI.
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http://dx.doi.org/10.1371/journal.pntd.0007562DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6645456PMC
July 2019

Investigating Possible Infectious Causes of Chronic Kidney Disease of Unknown Etiology in a Nicaraguan Mining Community.

Am J Trop Med Hyg 2019 09;101(3):676-683

Department of Epidemiology, Boston University School of Public Health, Boston, Massachusetts.

A chronic kidney disease of unknown etiology (CKDu) has been killing workers in Central America. Occupational heat stress is thought to play an important role. Leptospirosis and hantavirus have been suggested as additional possible risk factors. In a case-control study in a Nicaraguan mining community, a structured survey was administered to adults, and biological measurements and specimens were taken. Serum was analyzed for antibodies to and hantavirus. Before statistical analysis, a board-certified nephrologist determined final case and control status based on serum creatinine and other laboratory values. Multivariable analysis was by logistic regression. In sensitivity analyses, cases were restricted to those diagnosed with CKDu in the previous 3 years. Of 320 eligible participants, 112 were classified as presumptive cases, 176 as controls and 32 as indeterminant. The risk of CKDu in those ever having worked in mining or construction was 4.4 times higher than in other participants (odds ratio = 4.44, 95% CI: 1.96-10.0, = 0.0003). Eighty-three (26%) of the 320 participants were seropositive for at least one tested strain of . No evidence of a causal link between leptospirosis or hantavirus and CKDu was found. The sensitivity analyses provide some evidence against the hypotheses that leptospirosis or hantavirus leads to CKDu . A major limitation was the impossibility of determining the absolute or relative timing of infection and CKDu onset. A prospective cohort design, with repeated collection of specimens over several years, could yield clearer answers about infections as potential etiologic agents in CKDu.
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http://dx.doi.org/10.4269/ajtmh.18-0856DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6726956PMC
September 2019

Risk factors for human acute leptospirosis in northern Tanzania.

PLoS Negl Trop Dis 2018 06 7;12(6):e0006372. Epub 2018 Jun 7.

Centre for International Health, University of Otago, Dunedin, New Zealand.

Introduction: Leptospirosis is a major cause of febrile illness in Africa but little is known about risk factors for human infection. We conducted a cross-sectional study to investigate risk factors for acute leptospirosis and Leptospira seropositivity among patients with fever attending referral hospitals in northern Tanzania.

Methods: We enrolled patients with fever from two referral hospitals in Moshi, Tanzania, 2012-2014, and performed Leptospira microscopic agglutination testing on acute and convalescent serum. Cases of acute leptospirosis were participants with a four-fold rise in antibody titers, or a single reciprocal titer ≥800. Seropositive participants required a single titer ≥100, and controls had titers <100 in both acute and convalescent samples. We administered a questionnaire to assess risk behaviors over the preceding 30 days. We created cumulative scales of exposure to livestock urine, rodents, and surface water, and calculated odds ratios (OR) for individual behaviors and for cumulative exposure variables.

Results: We identified 24 acute cases, 252 seropositive participants, and 592 controls. Rice farming (OR 14.6), cleaning cattle waste (OR 4.3), feeding cattle (OR 3.9), farm work (OR 3.3), and an increasing cattle urine exposure score (OR 1.2 per point) were associated with acute leptospirosis.

Conclusions: In our population, exposure to cattle and rice farming were risk factors for acute leptospirosis. Although further data is needed, these results suggest that cattle may be an important source of human leptospirosis. Further investigation is needed to explore the potential for control of livestock Leptospira infection to reduce human disease.
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http://dx.doi.org/10.1371/journal.pntd.0006372DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5991637PMC
June 2018

Leptospirosis Cases Infected with Uncommon Serogroups, Puerto Rico, 2013-2015.

Am J Trop Med Hyg 2018 01 1;98(1):258-261. Epub 2018 Jan 1.

Division of Vector-Borne Diseases, Centers for Disease Control and Prevention, San Juan, Puerto Rico.

Leptospirosis is an emerging bacterial zoonosis that is endemic but underrecognized throughout the tropics. Through prospective surveillance for acute febrile illness (AFI) among patients who presented to the emergency department of a hospital located in an urban region of Puerto Rico, four patients with laboratory-confirmed leptospirosis were identified. All patients had signs and symptoms of AFI, including fever, headache, and dehydration. Three patients had leukocytosis with thrombocytopenia and were admitted to the hospital. One hospitalized patient presented with jaundice, icteric sclera, and hematuria and developed rhabdomyolysis, whereas another patient with pulmonary edema was admitted to the intensive care unit. Microscopic agglutination titers among the four patients were highest against serogroups Icterohaemorrhagiae (serovar Mankarso), Australis (serovar Bratislava), Bataviae (serovar Bataviae), and Canicola (serovar Canicola). These case reports demonstrate that infection with these apparently uncommon serogroups can result in illness ranging from mild to life-threatening.
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http://dx.doi.org/10.4269/ajtmh.17-0538DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5928731PMC
January 2018

Clinical and epidemiologic characteristics of dengue and other etiologic agents among patients with acute febrile illness, Puerto Rico, 2012-2015.

PLoS Negl Trop Dis 2017 Sep 13;11(9):e0005859. Epub 2017 Sep 13.

Ponce Health Sciences University/Saint Luke's Episcopal Hospital, Ponce, Puerto Rico, United States of America.

Identifying etiologies of acute febrile illnesses (AFI) is challenging due to non-specific presentation and limited availability of diagnostics. Prospective AFI studies provide a methodology to describe the syndrome by age and etiology, findings that can be used to develop case definitions and multiplexed diagnostics to optimize management. We conducted a 3-year prospective AFI study in Puerto Rico. Patients with fever ≤7 days were offered enrollment, and clinical data and specimens were collected at enrollment and upon discharge or follow-up. Blood and oro-nasopharyngeal specimens were tested by RT-PCR and immunodiagnostic methods for infection with dengue viruses (DENV) 1-4, chikungunya virus (CHIKV), influenza A and B viruses (FLU A/B), 12 other respiratory viruses (ORV), enterovirus, Leptospira spp., and Burkholderia pseudomallei. Clinical presentation and laboratory findings of participants infected with DENV were compared to those infected with CHIKV, FLU A/B, and ORV. Clinical predictors of laboratory-positive dengue compared to all other AFI etiologies were determined by age and day post-illness onset (DPO) at presentation. Of 8,996 participants enrolled from May 7, 2012 through May 6, 2015, more than half (54.8%, 4,930) had a pathogen detected. Pathogens most frequently detected were CHIKV (1,635, 18.2%), FLU A/B (1,074, 11.9%), DENV 1-4 (970, 10.8%), and ORV (904, 10.3%). Participants with DENV infection presented later and a higher proportion were hospitalized than those with other diagnoses (46.7% versus 27.3% with ORV, 18.8% with FLU A/B, and 11.2% with CHIKV). Predictors of dengue in participants presenting <3 DPO included leukopenia, thrombocytopenia, headache, eye pain, nausea, and dizziness, while negative predictors were irritability and rhinorrhea. Predictors of dengue in participants presenting 3-5 DPO were leukopenia, thrombocytopenia, facial/neck erythema, nausea, eye pain, signs of poor circulation, and diarrhea; presence of rhinorrhea, cough, and red conjunctiva predicted non-dengue AFI. By enrolling febrile patients at clinical presentation, we identified unbiased predictors of laboratory-positive dengue as compared to other common causes of AFI. These findings can be used to assist in early identification of dengue patients, as well as direct anticipatory guidance and timely initiation of correct clinical management.
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http://dx.doi.org/10.1371/journal.pntd.0005859DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5597097PMC
September 2017

Fatal spp./Zika Virus Coinfection-Puerto Rico, 2016.

Am J Trop Med Hyg 2017 Oct 19;97(4):1085-1087. Epub 2017 Jul 19.

Division of Vector-Borne Diseases, Centers for Disease Control and Prevention, San Juan, Puerto Rico.

Coinfection with pathogens that cause acute febrile illness (AFI) can complicate patient diagnosis and management. This report describes a fatal case of spp./Zika virus (ZIKV) coinfection in Puerto Rico. The patient presented with a 5-day history of AFI; reported behavioral risk factors for leptospirosis; was diagnosed with possible leptospirosis, dengue, chikungunya, or ZIKV disease; and received appropriate treatment for leptospirosis and dengue. Following a 3-day hospitalization, the patient died due to acute gastrointestinal hemorrhage, and kidney and liver failure. Serologic diagnostic testing for leptospirosis and ZIKV disease was negative; however, molecular diagnostic testing performed postmortem was positive for detection of spp. and ZIKV nucleic acid. This case demonstrates the need for continued clinical awareness of leptospirosis in areas experiencing outbreaks of pathogens that cause AFI and the need for evaluation of coinfection with AFI-causing pathogens as a risk factor for increased severity of disease.
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http://dx.doi.org/10.4269/ajtmh.17-0250DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5637617PMC
October 2017

Leptospira seropositivity as a risk factor for Mesoamerican Nephropathy.

Int J Occup Environ Health 2017 01 17;23(1):1-10. Epub 2017 Feb 17.

a Department of Epidemiology , Boston University School of Public Health , Boston , MA , USA.

Background: Leptospirosis is postulated as a possible cause of Mesoamerican Nephropathy (MeN) in Central American workers.

Objectives: Investigate job-specific Leptospira seroprevalence and its association with kidney disease biomarkers.

Methods: In 282 sugarcane workers, 47 sugarcane applicants and 160 workers in other industries, we measured anti-leptospiral antibodies, serum creatinine, and urinary injury biomarkers, including neutrophil gelatinase-associated lipocalin (NGAL), interleukin-18 (IL-18), and N-acetyl-D-glucosaminidase (NAG).

Results: Leptospira seroprevalence differed among job categories and was highest among sugarcane cutters (59%). Seropositive sugarcane workers had higher NGAL concentrations (relative mean: 1.28; 95% CI: 0.94-1.75) compared to those who were seronegative, with similar findings among field and non-field workers.

Conclusions: Leptospira seroprevalence varied by job category. There was some indication that seropositivity was associated with elevated biomarker levels, but results were inconsistent. Additional studies may help establish whether Leptospira infection plays any role in MeN among Central American workers.
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http://dx.doi.org/10.1080/10773525.2016.1275462DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6060841PMC
January 2017

Prevalence and clinical presentation of Rickettsia, Coxiella, Leptospira, Bartonella and chikungunya virus infections among hospital-based febrile patients from December 2008 to November 2009 in Bangladesh.

BMC Infect Dis 2017 02 13;17(1):141. Epub 2017 Feb 13.

International Centre for Diarrheal Diseases Research, Bangladesh (icddr,b), Dhaka, Bangladesh.

Background: We conducted a study to identify Rickettsia, Coxiella, Leptospira, Bartonella, and Chikungunya virus infections among febrile patients presenting at hospitals in Bangladesh.

Methods: We collected blood samples from patients at six tertiary hospitals from December 2008 to November 2009 and performed laboratory tests at the United States Centers for Disease Control and Prevention (CDC).

Results: Out of 720 enrolled patients, 263 (37%) were infected with Rickettsia; 132 patients had immunofluorescence antibody titer >64 against spotted fever, 63 patients against scrub typhus fever and 10 patients against typhus fever. Ten patients were identified with Coxiella. We isolated Leptospira from two patients and Bartonella from one patient. Ten patients had antibodies against Chikungunya virus. The proportion of patients who died was higher with rickettsial fever (5%) compared to those without a diagnosis of rickettsial infection (2%). None of the patients were initially diagnosed with rickettsial fever.

Conclusions: Rickettsial infections are frequent yet under-recognized cause of febrile illness in Bangladesh. Clinical guidelines should be revised so that local clinicians can diagnose rickettsial infections and provide appropriate drug treatment.
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http://dx.doi.org/10.1186/s12879-017-2239-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5307764PMC
February 2017

Comparison of the Estimated Incidence of Acute Leptospirosis in the Kilimanjaro Region of Tanzania between 2007-08 and 2012-14.

PLoS Negl Trop Dis 2016 12 2;10(12):e0005165. Epub 2016 Dec 2.

Centre for International Health, University of Otago, Dunedin, New Zealand.

Background: The sole report of annual leptospirosis incidence in continental Africa of 75-102 cases per 100,000 population is from a study performed in August 2007 through September 2008 in the Kilimanjaro Region of Tanzania. To evaluate the stability of this estimate over time, we estimated the incidence of acute leptospirosis in Kilimanjaro Region, northern Tanzania for the time period 2012-2014.

Methodology And Principal Findings: Leptospirosis cases were identified among febrile patients at two sentinel hospitals in the Kilimanjaro Region. Leptospirosis was diagnosed by serum microscopic agglutination testing using a panel of 20 Leptospira serovars belonging to 17 separate serogroups. Serum was taken at enrolment and patients were asked to return 4-6 weeks later to provide convalescent serum. Confirmed cases required a 4-fold rise in titre and probable cases required a single titre of ≥800. Findings from a healthcare utilisation survey were used to estimate multipliers to adjust for cases not seen at sentinel hospitals. We identified 19 (1.7%) confirmed or probable cases among 1,115 patients who presented with a febrile illness. Of cases, the predominant reactive serogroups were Australis 8 (42.1%), Sejroe 3 (15.8%), Grippotyphosa 2 (10.5%), Icterohaemorrhagiae 2 (10.5%), Pyrogenes 2 (10.5%), Djasiman 1 (5.3%), Tarassovi 1 (5.3%). We estimated that the annual incidence of leptospirosis was 11-18 cases per 100,000 population. This was a significantly lower incidence than 2007-08 (p<0.001).

Conclusions: We estimated a much lower incidence of acute leptospirosis than previously, with a notable absence of cases due to the previously predominant serogroup Mini. Our findings indicate a dynamic epidemiology of leptospirosis in this area and highlight the value of multi-year surveillance to understand leptospirosis epidemiology.
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http://dx.doi.org/10.1371/journal.pntd.0005165DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5135036PMC
December 2016

Investigation of a Guillain-Barré syndrome cluster in the Republic of Fiji.

J Neurol Sci 2017 Jan 1;372:350-355. Epub 2016 Sep 1.

Fiji Ministry of Health and Medical Services, Suva, Fiji.

Background: In 2014, we investigated a cluster of Guillain-Barre syndrome (GBS) in Fiji that occurred during a dengue epidemic. We designed a case-control study to determine the etiology.

Methods: Cases were patients meeting Brighton Collaboration criteria for GBS with onset from February 2014 to May 2014. Controls were persons without symptoms of GBS who were matched by age group and location. We collected information on demographics and potential exposures. Serum samples were tested for evidence of recent arboviral or Leptospira spp. infections.

Results: Nine cases of GBS were identified for an incidence of five cases per 100,000 population/year. Median age of cases was 27years (range: 0.8-52); five (56%) were male. Six (67%) reported an acute illness prior to GBS onset. Among the 9 cases and 28 controls enrolled, odds ratios for reported exposures or antibodies against various arboviruses or Leptospira spp. were not statistically significant.

Conclusions: No clear etiologies were identified for this unusual GBS cluster. There was a temporal association between the GBS cluster and a dengue epidemic, but we were unable to substantiate an epidemiologic or laboratory association. Further study is needed to explore potential associations between arboviral infections and GBS.
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http://dx.doi.org/10.1016/j.jns.2016.08.064DOI Listing
January 2017

Human Leptospirosis in Malaysia: Reviewing the Challenges After 8 Decades (1925-2012).

Asia Pac J Public Health 2016 05 3;28(4):290-302. Epub 2016 Apr 3.

University of Malaya, Kuala Lumpur, Malaysia

The history and epidemiology of human leptospirosis in Malaysia from 1925 to 2012 are described. Previous studies have demonstrated that leptospirosis is an endemic disease in Malaysia occurring in both urban and rural locations. The number of cases has risen dramatically since the Ministry of Health Malaysia highlighted leptospirosis as a notifiable disease in 2010, with reported cases increasing from 248 cases in 2004 to 3604 in 2012. The incidence of infection among the population suggests that occupation, sex, age, ethnic background, water recreational activities, and sporting events are risk factors. A robust surveillance system is now in place to monitor temporal and spatial changes in the incidence and prevalence of infection and to identify risk areas and disease behavior. Despite extensive studies over the past decade, there is a still a need to describe local serovars in host carriers and the human population, with the view to develop an effective vaccine against leptospirosis.
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http://dx.doi.org/10.1177/1010539516640350DOI Listing
May 2016

Serological Evidence of Infection with Endemic Human Pathogens Among Free-Ranging Old World Monkeys in Puerto Rico.

Am J Trop Med Hyg 2016 05 21;94(5):1095-9. Epub 2016 Mar 21.

Dengue Branch, Centers for Disease Control and Prevention, San Juan, Puerto Rico; Fish and Wildlife Bureau, Puerto Rico Department of Natural and Environmental Resources, San Juan, Puerto Rico; Epidemiology and Research Office, Puerto Rico Department of Health, San Juan, Puerto Rico; Zoonoses and Select Agent Laboratory, Bacterial Special Pathogens Branch, Centers for Disease Control and Prevention, Atlanta, Georgia.

Serum specimens from free-ranging but nonnative patas monkeys (Erythrocebus patas) and rhesus macaques (Macaca mulatta) in southwestern Puerto Rico (PR) were tested for antibodies to infection with dengue viruses (DENVs), West Nile virus (WNV), Leptospira species, and Burkholderia pseudomallei by microneutralization, plaque reduction neutralization, microscopic agglutination, and indirect hemagglutination, respectively. Of 23 animals (21 E. patas and two M. mulatta) tested, all had evidence of prior DENV infection, and of 17 animals tested for WNV, nine (53%) had evidence of prior infection. Of 24 (22 E. patas, two M. mulatta) tested for Leptospira spp., 10 (42%) had evidence of prior exposure, and one patas monkey had antibodies against B. pseudomallei The acquisition of pathogens endemic among humans in PR by resident nonhuman primates merits further study to define modes of acquisition.
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http://dx.doi.org/10.4269/ajtmh.15-0262DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4856609PMC
May 2016

Determination of Leptospira borgpetersenii serovar Javanica and Leptospira interrogans serovar Bataviae as the persistent Leptospira serovars circulating in the urban rat populations in Peninsular Malaysia.

Parasit Vectors 2016 Mar 1;9:117. Epub 2016 Mar 1.

Institute of Biological Sciences, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia.

Background: Leptospirosis is an emerging infectious disease of global significance, and is endemic in tropical countries, including Malaysia. Over the last decade, a dramatic increase of human cases was reported; however, information on the primary vector, the rat, and the Leptospira serovars circulating among the rat population is limited. Therefore, the present study was undertaken to isolate Leptospira and characterise the serovars circulating in the urban rat populations from selected main cities in Peninsular Malaysia.

Methods: Rat trappings were carried out between October 2011 to February 2014 in five urban cities which were chosen as study sites to represent different geographical locations in Peninsular Malaysia. Microscopic agglutination test (MAT) and PCR were carried out to identify the Leptospiral serogroup and determine the pathogenic status of the isolates, respectively while pulsed-field gel electrophoresis (PFGE) and random amplified polymorphic DNA (RAPD)-PCR were used to characterize the isolates.

Results: Three rat species were identified from the three hundred and fifty seven rats captured with Rattus rattus, being the dominant rat species (285, 80 %) followed by Rattus norgevicus (53, 15 %) and Rattus exulans (19, 5 %). Only 39 samples (11.0 %) were positive by culture and further confirmed as pathogenic Leptospira by PCR. Significant associations were shown between host infection with locality, season, host-age and species. Based on MAT, two serogroups were identified in the population namely; L. borgpetersenii serogroup Javanica (n = 16) and L. interrogans serogroup Bataviae (n = 23). Pulsed-field gel electrophoresis (PFGE) distinguished the two serovars in the urban rat populations: L. borgpetersenii serovar Javanica (41 %), and L. interrogans serovar Bataviae (59 %). RAPD-PCR yielded 14 distinct patterns and was found to be more discriminative than PFGE.

Conclusions: This study confirms two Leptospira serovars circulating among the urban rats population in Peninsular Malaysia namely; L. borgpetersenii serovar Javanica and L. interrogans serovars Bataviae. Despite the low number of isolates obtained from the rat population, this study suggests that rodent control programs and disease surveillance may help to reduce the possible risk of disease transmission.
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http://dx.doi.org/10.1186/s13071-016-1400-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4772511PMC
March 2016

Early Indicators of Fatal Leptospirosis during the 2010 Epidemic in Puerto Rico.

PLoS Negl Trop Dis 2016 Feb 25;10(2):e0004482. Epub 2016 Feb 25.

Bacterial Special Pathogens Branch, Division of High Consequence Pathogens, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.

Background: Leptospirosis is a potentially fatal bacterial zoonosis that is endemic throughout the tropics and may be misdiagnosed as dengue. Delayed hospital admission of leptospirosis patients is associated with increased mortality.

Methodology/principal Findings: During a concurrent dengue/leptospirosis epidemic in Puerto Rico in 2010, suspected dengue patients that tested dengue-negative were tested for leptospirosis. Fatal and non-fatal hospitalized leptospirosis patients were matched 1:1-3 by age. Records from all medical visits were evaluated for factors associated with fatal outcome. Among 175 leptospirosis patients identified (4.7 per 100,000 residents), 26 (15%) were fatal. Most patients were older males and had illness onset during the rainy season. Fatal case patients first sought medical care earlier than non-fatal control patients (2.5 vs. 5 days post-illness onset [DPO], p < 0.01), but less frequently first sought care at a hospital (52.4% vs. 92.2%, p < 0.01). Although fatal cases were more often diagnosed with leptospirosis at first medical visit (43.9% vs. 9.6%, p = 0.01), they were admitted to the hospital no earlier than non-fatal controls (4.5 vs. 6 DPO, p = 0.31). Cases less often developed fever (p = 0.03), but more often developed jaundice, edema, leg pain, hemoptysis, and had a seizure (p ≤ 0.03). Multivariable analysis of laboratory values from first medical visit associated with fatal outcome included increased white blood cell (WBC) count with increased creatinine (p = 0.001), and decreased bicarbonate with either increased WBC count, increased creatinine, or decreased platelet count (p < 0.001).

Conclusions/significance: Patients with fatal leptospirosis sought care earlier, but were not admitted for care any earlier than non-fatal patients. Combinations of routine laboratory values predictive of fatal outcome should be considered in admission decision-making for patients with suspected leptospirosis.
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http://dx.doi.org/10.1371/journal.pntd.0004482DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4767218PMC
February 2016

What Makes a Bacterial Species Pathogenic?:Comparative Genomic Analysis of the Genus Leptospira.

PLoS Negl Trop Dis 2016 Feb 18;10(2):e0004403. Epub 2016 Feb 18.

Division of Infectious Diseases, Department of Medicine, University of California San Diego School of Medicine, La Jolla, California, United States of America.

Leptospirosis, caused by spirochetes of the genus Leptospira, is a globally widespread, neglected and emerging zoonotic disease. While whole genome analysis of individual pathogenic, intermediately pathogenic and saprophytic Leptospira species has been reported, comprehensive cross-species genomic comparison of all known species of infectious and non-infectious Leptospira, with the goal of identifying genes related to pathogenesis and mammalian host adaptation, remains a key gap in the field. Infectious Leptospira, comprised of pathogenic and intermediately pathogenic Leptospira, evolutionarily diverged from non-infectious, saprophytic Leptospira, as demonstrated by the following computational biology analyses: 1) the definitive taxonomy and evolutionary relatedness among all known Leptospira species; 2) genomically-predicted metabolic reconstructions that indicate novel adaptation of infectious Leptospira to mammals, including sialic acid biosynthesis, pathogen-specific porphyrin metabolism and the first-time demonstration of cobalamin (B12) autotrophy as a bacterial virulence factor; 3) CRISPR/Cas systems demonstrated only to be present in pathogenic Leptospira, suggesting a potential mechanism for this clade's refractoriness to gene targeting; 4) finding Leptospira pathogen-specific specialized protein secretion systems; 5) novel virulence-related genes/gene families such as the Virulence Modifying (VM) (PF07598 paralogs) proteins and pathogen-specific adhesins; 6) discovery of novel, pathogen-specific protein modification and secretion mechanisms including unique lipoprotein signal peptide motifs, Sec-independent twin arginine protein secretion motifs, and the absence of certain canonical signal recognition particle proteins from all Leptospira; and 7) and demonstration of infectious Leptospira-specific signal-responsive gene expression, motility and chemotaxis systems. By identifying large scale changes in infectious (pathogenic and intermediately pathogenic) vs. non-infectious Leptospira, this work provides new insights into the evolution of a genus of bacterial pathogens. This work will be a comprehensive roadmap for understanding leptospirosis pathogenesis. More generally, it provides new insights into mechanisms by which bacterial pathogens adapt to mammalian hosts.
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http://dx.doi.org/10.1371/journal.pntd.0004403DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4758666PMC
February 2016

Epidemiology of human leptospirosis in Malaysia, 2004-2012.

Acta Trop 2016 May 1;157:162-8. Epub 2016 Feb 1.

Institute of Biological Sciences, Faculty of Science, University of Malaya, Malaysia. Electronic address:

Leptospirosis is an emerging disease, especially in countries with a tropical climate such as Malaysia. A dramatic increase in the number of cases has been reported over the last decade; however, information on the epidemiological trends of this disease is lacking. The objective of this study is to provide an epidemiological description of human leptospirosis cases over a 9-year period (2004-2012) and disease relationship with meteorological, geographical, and demographical information. A retrospective study was undertaken to describe the patterns of human leptospirosis cases and their association with intrinsic (sex, age, and ethnicity) and extrinsic (location, rainfall, and temperature) factors. Data was grouped according to age, sex, ethnicity, seasonality and geographical distribution, and analyzed using statistical tools to understand the influence of all the different factors on disease incidence. A total of 12,325 cases of leptospirosis were reported between 2004 and 2012 with an upward trend in disease incidence, with the highest in 2012. Three hundred thirty-eight deaths were reported with an overall case fatality rate of 2.74%, with higher incidence in males (9696; 78.7%) compared with female patients (2629; 21.3%), and overall male to female ratio of 3.69:1. Patients aged cohorts between 30-39 years old (16.22 per 100,000 population) had the highest disease incidence while the lowest incidence occurred between <1 to 9 years old (3.44 per 100,000 population). The average incidence was highest amongst Malays (10.97 per 100,000 population), followed by Indians (7.95 per 100,000 population). Stratification according to geographical distribution showed that the state of Malacca had the highest average disease incidence (11.12 per 100,000 population) followed by Pahang (10.08 per 100,000 population). The states of Terengganu, Kelantan, and Perak recorded similar rates of incidence (≈8.00 per 100,000 population), while Johor with the least number of reported cases (1.80 per 100,000 population). Positive relationships were recorded between the number of reported cases with the number of raining days per month and monthly average temperature (p-value<0.05). However, no significant association was noted between rainfall volume and number of reported Leptospirosis cases. This collaborative efforts between medical, academic and governmental institutions has enabled the construction of this comprehensive database that is essential to understand the disease trends in Malaysia and add insights into the prevention and control of this disease.
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http://dx.doi.org/10.1016/j.actatropica.2016.01.031DOI Listing
May 2016

Optimization of LipL32 PCR assay for increased sensitivity in diagnosing leptospirosis.

Diagn Microbiol Infect Dis 2015 Jul 9;82(3):199-200. Epub 2015 Apr 9.

Bacterial Special Pathogens Branch, Division of High-Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, 1600 Clifton Road NE, Atlanta, GA, USA.

Early diagnosis of leptospirosis in humans is critical with regard to initiation of appropriate treatment; however, the gold standard serological test cannot detect antibodies until nearly a week after symptom onset. PCR has been shown to be sensitive and specific in the early phase of leptospirosis. Previously, we developed and validated a TaqMan PCR assay targeting lipL32. We reoptimized and validated this assay using PerfeCTa® qPCR ToughMix®, Low ROX™ (Quanta Biosciences, Gaithersburg, MD, USA). For optimization with the new mix, the final primer concentrations were increased from 0.5 μmol/L to 0.9 μmol/L compared to our previous assay, and the probe concentration increased from 0.1 μmol/L to 0.125 μmol/L. This newly optimized assay resulted in a lower limit of detection and increased diagnostic sensitivity. Here, we present the performance data of the improved assay and describe several clinical cases that were initially negative but tested positive using the optimized assay.
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http://dx.doi.org/10.1016/j.diagmicrobio.2015.03.024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6452440PMC
July 2015

Antibiotic Efficacy in Eliminating Leptospiruria in California Sea Lions () Stranding with Leptospirosis.

Aquat Mamm 2015 26;41(2):203-212. Epub 2015 May 26.

Department of Ecology and Evolutionary Biology, University of California, Los Angeles, CA 90095, USA,

Stranded California sea lions () along the California coast have been diagnosed with leptospirosis every year since at least the 1980s. Between September 2010 and November 2011, we followed 14 stranded California sea lions that survived to release and evaluated antibiotic efficacy in eliminating leptospiruria (urinary shedding of leptospires). Leptospiruria was assessed by real-time PCR of urine and urine culture, with persistence assessed using longitudinally collected samples. Serum chemistry was used to assess recovery of normal renal function. Microscopic agglutination testing (MAT) was performed to assess serum anti- antibody titers, and the MAT reactivity patterns were consistent with serovar Pomona infection frequently observed in this population. Animals were initially treated for 6 to 16 d (median = 10.5; mean = 10.8) with antibiotics from the penicillin family, with some receiving additional antibiotics to treat other medical conditions. All urine cultures were negative; therefore, the presence of leptospiruria was assessed using PCR. Leptospiruria continued beyond the initial course of penicillin family antibiotics in 13 of the 14 sea lions, beyond the last antibiotic dose in 11 of the 14 sea lions, beyond recovery of renal function in 13 of the 14 sea lions, and persisted for at least 8 to 86 d (median = 45; mean = 46.8). Five animals were released with no negative urine PCR results detected; thus, their total shedding duration may have been longer. Cessation of leptospiruria was more likely in animals that received antibiotics for a greater duration, especially if coverage was uninterrupted. Real-time PCR results indicate that an antibiotic protocol commonly used to treat leptospirosis in rehabilitating California sea lions does not eliminate leptospiruria. It is possible that antibiotic protocols given for a longer duration and/or including other antibiotics may be effective in eliminating leptospiruria. These results may have important human and animal health implications, especially in rehabilitation facilities, as transmission may occur through contact with animals with persistent leptospiruria.
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http://dx.doi.org/10.1578/AM.41.2.2015.203DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6379896PMC
May 2015

Contact investigation of melioidosis cases reveals regional endemicity in Puerto Rico.

Clin Infect Dis 2015 Jan 30;60(2):243-50. Epub 2014 Sep 30.

Bacterial Special Pathogens Branch, Centers for Disease Control and Prevention, Atlanta, Georgia.

Background: Melioidosis results from infection with Burkholderia pseudomallei and is associated with case-fatality rates up to 40%. Early diagnosis and treatment with appropriate antimicrobials can improve survival rates. Fatal and nonfatal melioidosis cases were identified in Puerto Rico in 2010 and 2012, respectively, which prompted contact investigations to identify risk factors for infection and evaluate endemicity.

Methods: Questionnaires were administered and serum specimens were collected from coworkers, neighborhood contacts within 250 m of both patients' residences, and injection drug user (IDU) contacts of the 2012 patient. Serum specimens were tested for evidence of prior exposure to B. pseudomallei by indirect hemagglutination assay. Neighborhood seropositivity results guided soil sampling to isolate B. pseudomallei.

Results: Serum specimens were collected from contacts of the 2010 (n = 51) and 2012 (n = 60) patients, respectively. No coworkers had detectable anti-B. pseudomallei antibody, whereas seropositive results among neighborhood contacts was 5% (n = 2) for the 2010 patient and 23% (n = 12) for the 2012 patient, as well as 2 of 3 IDU contacts for the 2012 case. Factors significantly associated with seropositivity were having skin wounds, sores, or ulcers (odds ratio [OR], 4.6; 95% confidence interval [CI], 1.2-17.8) and IDU (OR, 18.0; 95% CI, 1.6-194.0). Burkholderia pseudomallei was isolated from soil collected in the neighborhood of the 2012 patient.

Conclusions: Taken together, isolation of B. pseudomallei from a soil sample and high seropositivity among patient contacts suggest at least regional endemicity of melioidosis in Puerto Rico. Increased awareness of melioidosis is needed to enable early case identification and early initiation of appropriate antimicrobial therapy.
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http://dx.doi.org/10.1093/cid/ciu764DOI Listing
January 2015

Development of a real-time PCR for the detection of pathogenic Leptospira spp. in California sea lions.

Dis Aquat Organ 2014 Aug;110(3):165-72

Hollings Marine Laboratory, National Centers for Coastal Ocean Science, National Ocean Service, National Oceanic Atmospheric Administration, Charleston, South Carolina 29412, USA.

Several real-time PCR assays are currently used for detection of pathogenic Leptospira spp.; however, few methods have been described for the successful evaluation of clinical urine samples. This study reports a rapid assay for the detection of pathogenic Leptospira spp. in California sea lions Zalophus californianus using real-time PCR with primers and a probe targeting the lipL32 gene. The PCR assay had high analytic sensitivity-the limit of detection was 3 genome copies per PCR volume using L. interrogans serovar Pomona DNA and 100% analytic specificity; it detected all pathogenic leptospiral serovars tested and none of the non-pathogenic Leptospira species (L. biflexa and L. meyeri serovar Semaranga), the intermediate species L. inadai, or the non-Leptospira pathogens tested. Our assay had an amplification efficiency of 1.00. Comparisons between the real-time PCR assay and culture isolation for detection of pathogenic Leptospira spp. in urine and kidney tissue samples from California sea lions showed that samples were more often positive by real-time PCR than by culture methods. Inclusion of an internal amplification control in the real-time PCR assay showed no inhibitory effects in PCR negative samples. These studies indicated that our real-time PCR assay has high analytic sensitivity and specificity for the rapid detection of pathogenic Leptospira species in urine and kidney tissue samples.
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http://dx.doi.org/10.3354/dao02752DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6423441PMC
August 2014

Isolation of Leptospira from a phocid: acute renal failure and mortality from Leptospirosis in rehabilitated northern elephant seals (Mirounga angustirostris), California, USA.

J Wildl Dis 2014 Jul 7;50(3):621-7. Epub 2014 May 7.

1  University of Illinois Zoological Pathology Program, Loyola University Medical Center, 2160 South First Avenue, Maywood, Illinois 60153, USA.

During rehabilitation, acute renal failure due to leptospirosis occurred in eight male northern elephant seals (Mirounga angustirostris) that stranded along the central California coast in 2011. Characteristic histologic lesions including renal tubular degeneration, necrosis, and mineralization, and mild lymphoplasmacytic interstitial nephritis were noted in the six animals examined. Immunohistochemistry, bacterial culture, and PCR were positive in 2/3, 2/3, and 3/4 seals, respectively, and 6/8 had high serum antibody titers to Leptospira interrogans serovar pomona. Pulsed-field gel electrophoresis confirmed one isolate as serovar pomona. Variable number tandem repeat (VNTR) analysis showed both elephant seal isolates were identical to each other but distinct from those isolated from California sea lions (Zalophus californianus). The time from stranding to onset of azotemia was 1 to 38 (median=24) days, suggesting some seals were infected at the rehabilitation facility. Based on temporal and spatial incidence of infection, transmission among elephant seals likely occurred during rehabilitation. Molecular (VNTR) analysis of the two isolates indicates there is a unique L. interrogans serovar pomona genotype in elephant seals, and sea lions were not the source of infection prior to or during rehabilitation. This study confirms the susceptibility of northern elephant seals to leptospirosis, indicates intraspecies transmission during rehabilitation, and reports the first isolation and preliminary characterization of leptospires from elephant seals.
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http://dx.doi.org/10.7589/2013-08-195DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6397957PMC
July 2014

Estimating leptospirosis incidence using hospital-based surveillance and a population-based health care utilization survey in Tanzania.

PLoS Negl Trop Dis 2013 5;7(12):e2589. Epub 2013 Dec 5.

Division of Infectious Diseases, Department of Medicine, Duke University Medical Center, Durham, North Carolina, United States of America.

Background: The incidence of leptospirosis, a neglected zoonotic disease, is uncertain in Tanzania and much of sub-Saharan Africa, resulting in scarce data on which to prioritize resources for public health interventions and disease control. In this study, we estimate the incidence of leptospirosis in two districts in the Kilimanjaro Region of Tanzania.

Methodology/principal Findings: We conducted a population-based household health care utilization survey in two districts in the Kilimanjaro Region of Tanzania and identified leptospirosis cases at two hospital-based fever sentinel surveillance sites in the Kilimanjaro Region. We used multipliers derived from the health care utilization survey and case numbers from hospital-based surveillance to calculate the incidence of leptospirosis. A total of 810 households were enrolled in the health care utilization survey and multipliers were derived based on responses to questions about health care seeking in the event of febrile illness. Of patients enrolled in fever surveillance over a 1 year period and residing in the 2 districts, 42 (7.14%) of 588 met the case definition for confirmed or probable leptospirosis. After applying multipliers to account for hospital selection, test sensitivity, and study enrollment, we estimated the overall incidence of leptospirosis ranges from 75-102 cases per 100,000 persons annually.

Conclusions/significance: We calculated a high incidence of leptospirosis in two districts in the Kilimanjaro Region of Tanzania, where leptospirosis incidence was previously unknown. Multiplier methods, such as used in this study, may be a feasible method of improving availability of incidence estimates for neglected diseases, such as leptospirosis, in resource constrained settings.
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http://dx.doi.org/10.1371/journal.pntd.0002589DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3855074PMC
July 2014

Etiology of severe non-malaria febrile illness in Northern Tanzania: a prospective cohort study.

PLoS Negl Trop Dis 2013 18;7(7):e2324. Epub 2013 Jul 18.

Division of Infectious Diseases and International Health, Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA.

Introduction: The syndrome of fever is a commonly presenting complaint among persons seeking healthcare in low-resource areas, yet the public health community has not approached fever in a comprehensive manner. In many areas, malaria is over-diagnosed, and patients without malaria have poor outcomes.

Methods And Findings: We prospectively studied a cohort of 870 pediatric and adult febrile admissions to two hospitals in northern Tanzania over the period of one year using conventional standard diagnostic tests to establish fever etiology. Malaria was the clinical diagnosis for 528 (60.7%), but was the actual cause of fever in only 14 (1.6%). By contrast, bacterial, mycobacterial, and fungal bloodstream infections accounted for 85 (9.8%), 14 (1.6%), and 25 (2.9%) febrile admissions, respectively. Acute bacterial zoonoses were identified among 118 (26.2%) of febrile admissions; 16 (13.6%) had brucellosis, 40 (33.9%) leptospirosis, 24 (20.3%) had Q fever, 36 (30.5%) had spotted fever group rickettsioses, and 2 (1.8%) had typhus group rickettsioses. In addition, 55 (7.9%) participants had a confirmed acute arbovirus infection, all due to chikungunya. No patient had a bacterial zoonosis or an arbovirus infection included in the admission differential diagnosis.

Conclusions: Malaria was uncommon and over-diagnosed, whereas invasive infections were underappreciated. Bacterial zoonoses and arbovirus infections were highly prevalent yet overlooked. An integrated approach to the syndrome of fever in resource-limited areas is needed to improve patient outcomes and to rationally target disease control efforts.
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http://dx.doi.org/10.1371/journal.pntd.0002324DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3715424PMC
February 2014

Interlaboratory agreement of pulsed-field gel electrophoresis identification of Leptospira serovars.

Am J Trop Med Hyg 2013 Aug 1;89(2):380-4. Epub 2013 Jul 1.

Department of Medicine, San Antonio Military Medical Center, Fort Sam Houston, Texas, USA.

Leptospirosis may be caused by > 250 Leptospira serovars. Serovar classification is a complex task that most laboratories cannot perform. We assessed the interlaboratory reproducibility of a pulsed-field gel electrophoresis (PFGE) identification technique developed by the Centers for Disease Control and Prevention (CDC). Blinded exchange of 93 Leptospiraceae strains occurred between San Antonio Military Medical Center (SAMMC) and the CDC. PFGE was performed and gel images were analyzed and compared with patterns present in each laboratory's database (CDC database: > 800 strain patterns; SAMMC database: > 300 strain patterns). Overall, 93.7% (74 of 79) of strains present in each receiving laboratory's database were correctly identified. Five isolates were misidentified, and two isolates did not match serovar PFGE patterns in the receiving laboratory's database. Patterns for these seven isolates were identical between laboratories; four serovars represented misidentified reference strains. The PFGE methodology studied showed excellent interlaboratory reproducibility, enabling standardization and data sharing between laboratories.
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http://dx.doi.org/10.4269/ajtmh.12-0768DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3741266PMC
August 2013
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