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PLoS Neglected Tropical Diseases Sep 2020Murine typhus is an acute febrile, flea-borne disease caused by the bacteria Rickettsia typhi. The disease occurs worldwide but is likely underrecognized due to its...
Murine typhus is an acute febrile, flea-borne disease caused by the bacteria Rickettsia typhi. The disease occurs worldwide but is likely underrecognized due to its non-specific symptoms, causing significant morbidity. A systematic review found disease complications in one-fourth of all patients and a long fever duration in those untreated. Although mortality in treated cases is estimated to be very low, some case series have shown a notably higher mortality in untreated patients. This study aimed to describe the outcomes and estimate the mortality of untreated murine typhus through a comprehensive systematic literature review. We systematically searched the literature for articles describing untreated murine typhus patients, excluding cases with no laboratory assay confirmed diagnosis, those who received efficacious treatment, had incomplete information on primary outcome and articles describing less than 10 patients and performed a narrative synthesis of the study findings. The study protocol followed the PRISMA guidelines and was part of a more extensive protocol registered at PROSPERO (CRD42018101991). Twelve studies including a total of 239 untreated patients matched the eligibility criteria. Only a single study reported one death in 28 patients, giving a patient series mortality of 3.6% and an overall mortality of 0.4% in 239 untreated patients. Complications were reported in 10 of the 12 studies and included involvement of the central nervous system, kidney and lung, with a hospitalisation rate of 70% and ICU admission rate of 27% in one study. The mean duration of fever in untreated patients was 15 days in two and 12.7 days in one study. Although the untreated mortality in this study was low, the sample size was small. Murine typhus caused significant morbidity when untreated, leading to high hospitalisation rates and highlighting the importance of early diagnosis and treatment of this neglected disease to reduce disease burden and health-care related costs.
Topics: Databases, Factual; Fever; Hospitalization; Humans; Mortality; Rickettsia typhi; Treatment Outcome; Typhus, Endemic Flea-Borne
PubMed: 32925913
DOI: 10.1371/journal.pntd.0008641 -
The American Journal of Tropical... Jul 2020Murine typhus is a neglected but widespread infectious disease that results in acute fever. The immunofluorescence assay (IFA) is the "gold standard" to identify IgM or...
Murine typhus is a neglected but widespread infectious disease that results in acute fever. The immunofluorescence assay (IFA) is the "gold standard" to identify IgM or IgG antibodies, although there is a lack of standardization in methodologies. The objective of this review is to summarize 1) the differences in published methodologies, 2) the diagnostic cutoff titers, and 3) the justification of diagnostic cutoffs. Searches were performed by combining the following search terms: "murine typhus," "," "immunofluorescence," "IFA," and "serologic" with restrictions (i.e., "" or "murine typhus," and "IFA" or "immunofluorescence," or "serologic*"). The search identified 78 studies that used IFA or immunoperoxidase assay (IIP) antibody cutoffs to diagnose murine typhus, 39 of which were case series. Overall, 45 studies (57.7%) provided little to no rationale as to how the cutoff was derived. Variation was seen locally in the cutoff titers used, but a 4-fold or greater increase was often applied. The cutoffs varied depending on the antibody target. No consensus was observed in establishing a cutoff, or for a single-value diagnostic cutoff. In conclusion, there is a lack of consensus in the establishment of a single-value cutoff. Further studies will need to be executed at each distinct geographic location to identify region-specific cutoffs, while also considering background antibody levels to distinguish between healthy and infected patients.
Topics: Antibodies, Bacterial; Fluorescent Antibody Technique; Humans; Immunoglobulin G; Immunoglobulin M; Neglected Diseases; Predictive Value of Tests; Rickettsia typhi; Typhus, Endemic Flea-Borne
PubMed: 32274984
DOI: 10.4269/ajtmh.19-0818 -
Acta Tropica Feb 2017Murine or endemic typhus, a febrile disease caused by Rickettsia typhi, is often misdiagnosed due to its non-specific presentation. We sought to evaluate all available... (Review)
Review
Murine or endemic typhus, a febrile disease caused by Rickettsia typhi, is often misdiagnosed due to its non-specific presentation. We sought to evaluate all available evidence in the literature regarding the clinical and laboratory manifestations, epidemiological characteristics, and outcomes of murine typhus. Pubmed was searched for all articles providing available data. In an effort to incorporate contemporary data, only studies from 1980 were included. Thirty-three case series including 2074 patients were included in final analysis. Available evidence suggests that the classic triad of fever, headache and rash is encountered in only one-third of patients. Other frequent symptoms were chills, malaise, myalgia, and anorexia. A tetrad of reported laboratory abnormalities consisting of elevated liver enzymes, lactate dehydrogenase, erythrocyte sedimentation rate and hypoalbuminemia was detected. Complications were observed in one-fourth of patients, reported mortality was extremely low, but untreated patients had notably longer duration of fever. Among epidemiological characteristics, a seasonal distribution with most cases reported during warmer months, was the most prominent finding. Murine typhus in children exhibits several different characteristics, with abdominal pain, diarrhea, and sore throat reported more commonly, higher frequency of anemia, lower frequency of hypoalbuminemia, hematuria and proteinuria and a much lower rate of complications. This systematic review of published evidence provides a thorough description of the clinical and laboratory features of murine typhus and highlights important differences in children.
Topics: Animals; Child; Exanthema; Fever; Headache; Humans; Treatment Outcome; Typhus, Endemic Flea-Borne
PubMed: 27983969
DOI: 10.1016/j.actatropica.2016.10.018 -
Vector Borne and Zoonotic Diseases... Jul 2016In high-income countries, homeless individuals in urban areas often live in crowded conditions with limited sanitation and personal hygiene. The environment of... (Review)
Review
INTRODUCTION
In high-income countries, homeless individuals in urban areas often live in crowded conditions with limited sanitation and personal hygiene. The environment of homelessness in high-income countries may result in intensified exposure to ectoparasites and urban wildlife, which can transmit infections. To date, there have been no systematic evaluations of the published literature to assess vector-borne and zoonotic disease risk to these populations.
OBJECTIVES
The primary objectives of this study were to identify diversity, prevalence, and risk factors for vector-borne and zoonotic infections among people experiencing homelessness and extreme poverty in urban areas of high-income countries.
METHODS
We conducted a systematic review and narrative synthesis of published epidemiologic studies of zoonotic and vector-borne infections among urban homeless and very poor people in the United States and Europe from 1990 to 2014.
RESULTS
Thirty-one observational studies and 14 case studies were identified (nā=ā45). Seroprevalence to the human louse-borne pathogen Bartonella quintana (seroprevalence range: 0-37.5%) was identified most frequently, with clinical disease specifically observed among HIV-positive individuals. Seropositivity to Bartonella henselae (range: 0-10.3%) and Rickettsia akari (range: 0-16.2%) was noted in multiple studies. Serological evidence of exposure to Rickettsia typhi, Rickettsia prowazekii, Bartonella elizabethae, West Nile virus, Borellia recurrentis, lymphocytic choriomeningitis virus, Wohlfartiimonas chitiniclastica, Seoul hantavirus (SEOV), and Leptospira species was also identified in published studies, with SEOV associated with chronic renal disease later in life. HIV infection, injection drug use, and heavy drinking were noted across multiple studies as risk factors for infection with vector-borne and zoonotic pathogens.
CONCLUSIONS
B. quintana was the most frequently reported vector-borne infection identified in our article. Delousing efforts and active surveillance among HIV-positive individuals, who are at elevated risk of complication from B. quintana infection, are advised to reduce morbidity. Given documented exposure to rodent-borne zoonoses among urban homeless and marginalized people, reducing human contact with rodents remains an important public health priority.
Topics: Animals; Bacterial Infections; Europe; Ill-Housed Persons; Humans; Social Marginalization; United States; Zoonoses
PubMed: 27159039
DOI: 10.1089/vbz.2015.1863 -
Expert Opinion on Drug Safety 2016Doxycycline is highly effective, inexpensive with a broad therapeutic spectrum and exceptional bioavailability. However these benefits have been overshadowed by its... (Comparative Study)
Comparative Study Review
INTRODUCTION
Doxycycline is highly effective, inexpensive with a broad therapeutic spectrum and exceptional bioavailability. However these benefits have been overshadowed by its classification alongside the tetracyclines - class D drugs, contraindicated in pregnancy and in children under 8 years of age. Doxycycline-treatable diseases are emerging as leading causes of undifferentiated febrile illness in Southeast Asia. For example scrub typhus and murine typhus have an unusually severe impact on pregnancy outcomes, and current mortality rates for scrub typhus reach 12-13% in India and Thailand. The emerging evidence for these important doxycycline-treatable diseases prompted us to revisit doxycycline usage in pregnancy and childhood.
AREAS COVERED
A systematic review of the available literature on doxycycline use in pregnant women and children revealed a safety profile of doxycycline that differed significantly from that of tetracycline; no correlation between the use of doxycycline and teratogenic effects during pregnancy or dental staining in children was found.
EXPERT OPINION
The change of the US FDA pregnancy classification scheme to an evidence-based approach will enable adequate evaluation of doxycycline in common tropical illnesses and in vulnerable populations in clinical treatment trials, dosage-optimization pharmacokinetic studies and for the empirical treatment of undifferentiated febrile illnesses, especially in pregnant women and children.
Topics: Age Factors; Animals; Anti-Bacterial Agents; Bacterial Infections; Child; Child, Preschool; Contraindications; Doxycycline; Female; Humans; Infant; Infant, Newborn; Pregnancy; Pregnancy Complications, Infectious; Pregnancy Outcome
PubMed: 26680308
DOI: 10.1517/14740338.2016.1133584 -
Vector Borne and Zoonotic Diseases... Jun 2013Urban Norway and black rats (Rattus norvegicus and Rattus rattus) are the source of a number of pathogens responsible for significant human morbidity and mortality in... (Review)
Review
Urban Norway and black rats (Rattus norvegicus and Rattus rattus) are the source of a number of pathogens responsible for significant human morbidity and mortality in cities around the world. These pathogens include zoonotic bacteria (Leptospira interrogans, Yersina pestis, Rickettsia typhi, Bartonella spp., Streptobacillus moniliformis), viruses (Seoul hantavirus), and parasites (Angiostrongylus cantonensis). A more complete understanding of the ecology of these pathogens in people and rats is critical for determining the public health risks associated with urban rats and for developing strategies to monitor and mitigate those risks. Although the ecology of rat-associated zoonoses is complex, due to the multiple ways in which rats, people, pathogens, vectors, and the environment may interact, common determinants of human disease can still be identified. This review summarizes the ecology of zoonoses associated with urban rats with a view to identifying similarities, critical differences, and avenues for further study.
Topics: Animals; Bacterial Infections; Cities; Disease Reservoirs; Ecology; Humans; Male; Parasitic Diseases; Public Health; Rats; Risk Factors; Rodent Diseases; Virus Diseases; Zoonoses
PubMed: 23590323
DOI: 10.1089/vbz.2012.1195 -
PloS One 2012An increasing use of point of care diagnostic tests that exclude malaria, coupled with a declining malaria burden in many endemic countries, is highlighting the lack of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
An increasing use of point of care diagnostic tests that exclude malaria, coupled with a declining malaria burden in many endemic countries, is highlighting the lack of ability of many health systems to manage other causes of febrile disease. A lack of knowledge of distribution of these pathogens, and a lack of screening and point-of-care diagnostics to identify them, prevents effective management of these generally treatable contributors to disease burden. While prospective data collection is vital, an untapped body of knowledge already exists in the published health literature.
METHODS
Focusing on the Mekong region of Southeast Asia, published data from 1986 to 2011 was screened to for frequency of isolation of pathogens implicated in aetiology of non-malarial febrile illness. Eligibility criteria included English-language peer-reviewed studies recording major pathogens for which specific management is likely to be warranted. Of 1,252 identified papers, 146 met inclusion criteria and were analyzed and data mapped.
RESULTS
Data tended to be clustered around specific areas where research institutions operate, and where resources to conduct studies are greater. The most frequently reported pathogen was dengue virus (n = 70), followed by Orientia tsutsugamushi and Rickettsia species (scrub typhus/murine typhus/spotted fever group n = 58), Leptospira spp. (n = 35), Salmonella enterica serovar Typhi and Paratyphi (enteric fever n = 24), Burkholderia pseudomallei (melioidosis n = 14), and Japanese encephalitis virus (n = 18). Wide tracts with very little published data on aetiology of fever are apparent.
DISCUSSION AND CONCLUSIONS
This mapping demonstrates a very heterogeneous distribution of information on the causes of fever in the Mekong countries. Further directed data collection to address gaps in the evidence-base, and expansion to a global database of pathogen distribution, is readily achievable, and would help define wider priorities for research and development to improve syndromic management of fever, prioritize diagnostic development, and guide empirical therapy.
Topics: Asia, Southeastern; Fever; Geography; Humans
PubMed: 22970193
DOI: 10.1371/journal.pone.0044269