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PubMed2003

Possible scrub typhus coinfections in Thai agricultural workers hospitalized with leptospirosis.

Possible coinfections with Orientia tsutsugamushi the causative agent of scrub typhus, were prospectively evaluated in rice farmers hospitalized with leptospirosis in Northeast Thailand. Of 22 adults with leptospirosis diagnosed by the microscopic agglutination test, 9 also had serologic evidence of scrub typhus. Of 9 individuals with possible coinfections, 5 had signs or symptoms typical of scrub typhus and atypical of leptospirosis. Patients who appeared to have mixed infections had significantly higher median platelet counts and significantly lower median serum bilirubin and creatinine concentrations (P < 0.05, Mann-Whitney U test) than did individuals with leptospirosis alone. One patient with serologic evidence of scrub typhus and leptospirosis was treated only with penicillin, to which scrub typhus is not sensitive. Respiratory distress worsened during therapy, and the patient died of respiratory failure. Physicians should consider the possibility of scrub typhus infection in leptospirosis patients who respond poorly to treatment or who have atypical disease manifestations.

Adult↗
PubMed1992

[Abdominal typhus today].

Abdominal typhus is all the rearer disease among acute infectious diseases in Vojvodina. In the last ten years (1981-1990) 16 patients with abdominal typhus were treated at the Department of Infectious Diseases in Novi Sad, mostly young individuals from 6 to 30 years of age (13 patients). Positive epidemiologic features were found in 13 patients. In 80% of the cases the source of infection was outside Vojvodina. They usually were admitted at the Department on the first and second week of the disease (11 patients), and 3 patients were admitted on the third week. None of the patients was suspected of having abdominal typhus at the time of admittance. Delayed hospitalization and unrecognized abdominal typhus were most likely due to the atypical onset and course of the disease. Atypical features in the clinical picture occurred in all the patients with a sudden onset of the disease. The abrupt temperature elevation in 50% of the patients was followed by shivering, fever and shaking. Hepatosplenomegaly was found in 12 patients, abdominal meteorism in 10, typical typhus tongue in none. Typhus state was not found in any of the patients. Normal leucocyte count was found in 7 patients, positive Widal's agglutination reaction in 13, coproculture in 8 and hemoculture in 15 patients. The atypical clinical picture was the result of early administration of broad-spectrum antibiotics before the established etiology of the febrile state.

Adolescent↗
PubMed1991

Murine and scrub typhus at Thai-Kampuchean border displaced persons camps.

Rickettsial infections are considered a major cause of illness among inmates of Thai-Kampuchean border displaced persons camps. In the absence of sophisticated laboratory support, it had become common practice to treat patients with obscure fevers with tetracycline as a 'diagnostic' test for typhus. This study evaluated a group of 67 randomly selected camp inmates who presented with fever and had findings that indicated a specific diagnosis. Differential blood counts, malaria smears, hemoglobin determinations, blood cultures, dengue and Japanese encephalitis virus and rickettsial IgM and IgG antibody titers were determined. Patients were then treated with tetracycline and followed. They could be divided into six groups after data were analyzed. Those with no final diagnosis comprised 14 cases (21%), 4 patients (6%) were found to have dengue fever, 6 (9%) scrub typhus and 39 (58%) had murine (endemic) typhus. None of the bacterial blood cultures drawn from this group grew any organisms and no tick typhus or Japanese encephalitis was diagnosed. Analysis of symptoms and signs did not allow clinical differentiation between groups. All patients became afebrile and well within 1-5 days of starting tetracycline therapy. We conclude that rickettsial disease is a major health problem in the Thai-Kampuchean border camps. The incidence of murine typhus increased during the dry season and was more prevalent among males. The use of tetracycline as a 'therapeutic test' did not distinguish between rickettsial, viral and undiagnosed febrile diseases.

Cambodia↗
PubMed1986

Characterization of human cytotoxic lymphocytes directed against cells infected with typhus group rickettsiae: evidence for lymphokine activation of effectors.

An in vitro culture and assay system was used to determine whether cytotoxic lymphocytes are generated in humans after rickettsial infection. Peripheral blood mononuclear cells (PBMC) were obtained from six individuals with serologic evidence of prior infection with typhus group rickettsiae and from six nonimmune individuals. After PBMC from immune individuals were stimulated in vitro for 7 days with rickettsial antigen, they were capable of lysing typhus group rickettsia-infected, autologous phytohemagglutinin (PHA)-induced blasts, but not uninfected PHA-blasts. No cytotoxic effector cells were generated when either PBMC from immune individuals were placed in culture for 7 days without antigenic stimulation, or when PBMC from nonimmune individuals were stimulated in vitro with antigen for 7 days. Freshly isolated PBMC from immune donors were also unable to lyse typhus group rickettsia-infected autologous PHA-blasts or an autologous rickettsia-infected lymphoblastoid cell line (LCL). Neither supernatants from antigen-stimulated cultures of PBMC from immune donors nor recombinant human interferon-gamma were capable of significantly lysing typhus group rickettsia-infected PHA blasts by this assay. Populations of cytotoxic effector cells depleted of OKT3, OKT4, or OKT8-positive cells by treatment with the respective monoclonal antibodies and complement were assayed for their cytotoxic capacity. The results suggest that the cytotoxic effector cell population is predominantly OKT3 and OKT8-positive, but OKT4-negative. Positive selection with the use of a fluorescence-activated cell sorter also suggested that most of the cytotoxic effector cells are OKT8-positive. PBMC from immune donors after in vitro stimulation with rickettsial antigen were capable of significantly lysing infected autologous LCL or infected HLA-mismatched LCL as compared with the respective uninfected controls. In addition, PBMC from either immune donors or nonimmune donors after stimulation in vitro for 7 days with media containing purified lymphokines were capable of significantly lysing autologous infected LCL as compared with the uninfected autologous control. We conclude that lysis of cells infected with typhus group rickettsiae is mediated by a lymphokine-activated killer.

Antigens, Bacterial↗
PubMed2005

Clinical and laboratory features of murine typhus in central Tunisia: a report of seven cases.

INTRODUCTION: Murine or endemic typhus, caused by Rickettsia typhi, has been reported in all continents. In the 1970s, no cases of murine typhus were diagnosed in Tunisia. METHODS: The clinico-epidemiological characteristics of seven cases of murine typhus diagnosed at our hospitals since 1993 are reported. Diagnosis was confirmed by indirect fluorescence assay detecting specific R. typhi antibodies. RESULTS: Murine typhus occurred in all ages from 18-80 years during the hot season in rural areas. Clinical features were: sudden onset of fever and absence of eschar in all cases, with maculo-papular rash (five cases), prostration (four cases), meningism (three cases) and pneumonia (four cases). Frequent laboratory findings were moderate thrombopenia (four cases) and elevated transaminases (four cases). Before the results of serology, clinical diagnoses were Mediterranean Spotted Fever (four cases), Q fever (one case), pneumonia (one case), and lymphocytic meningitis (one case). Serology confirmed all diagnoses with cross-reactivity with Rickettsia conorii. CONCLUSION: Murine typhus exists in Tunisia and its prevalence is underestimated. Further, more specific studies are needed to evaluate the true prevalence.

Adolescent↗
PubMed2000

Doxycycline and rifampicin for mild scrub-typhus infections in northern Thailand: a randomised trial.

BACKGROUND: Some strains of scrub typhus in northern Thailand are poorly responsive to standard antirickettsial drugs. We therefore did a masked, randomised trial to compare rifampicin with standard doxycycline therapy for patients with scrub typhus. METHODS: Adult patients with strictly defined, mild scrub typhus were initially randomly assigned 1 week of daily oral treatment with 200 mg doxycycline (n=40), 600 mg rifampicin (n=38), or doxycycline with rifampicin (n=11). During the first year of treatment, the combined regimen was withdrawn because of lack of efficacy and the regimen was replaced with 900 mg rifampicin (n=37). Treatment outcome was assessed by fever clearance time (the time for oral temperature to fall below 37.3 degrees C). FINDINGS: About 12,800 fever patients were screened during the 3-year study to recruit 126 patients with confirmed scrub typhus and no other infection, of whom 86 completed therapy. Eight individuals received the combined regimen that was discontinued after 1 year. The median duration of pyrexia was significantly shorter (p=0.01) in the 24 patients treated with 900 mg daily rifampicin (fever clearance time 22.5 h) and in the 26 patients who received 600 mg rifampicin (fever clearance time 27.5 h) than in the 28 patients given doxycycline monotherapy (fever clearance time 52 h). Fever resolved in a significantly higher proportion of patients within 48 h of starting rifampicin (900 mg=79% [19 of 24], 600 mg=77% [20 of 26]) than in patients treated with doxycycline (46% [13 of 28]; p=0.02). Severe gastrointestinal events warranted exclusion of two patients on doxycyline. There were two relapses after doxycycline therapy, but none after rifampicin therapy. INTERPRETATION: Rifampicin is more effective than doxycycline against scrub-typhus infections acquired in northern Thailand, where strains with reduced susceptibility to antibiotics can occur.

Adolescent↗
PubMed2003

Scrub typhus: a frequently overlooked cause of acute renal failure.

Acute renal failure associated with scrub typhus infection is not rare as previously thought. The possibility of scrub typhus should be borne in mind when patients present with fever and varying degrees of acute renal failure, particularly if an eschar exists, along with a history of environmental exposure in an area like Taiwan, where scrub typhus is endemic. Prompt diagnosis and the use of appropriate antibiotics can rapidly alter the clinical course of the disease and prevent the development of serious or fatal complications. To illustrate the above point, this study reports 3 cases of scrub typhus associated with acute renal failure. They were seen at Chang Gung Memorial Hospital in a 2-year interval. Case 1 was referred from district hospital with clinical features of multiple organ dysfunctions, including shock, fever, acute respiratory failure, acute renal failure, and acute hepatitis. Case 2 was admitted with the chief problems of shock, fever, acute renal failure, and DIC. Case 3 visited our outpatient clinic due to fever, maculopapular rash and acute renal failure. In all these patients, the diagnosis was confirmed using immunofluorescence techniques, which showed that Orientia tsutsugamushi had an IgM titer of 1:80 or greater. Notably, despite having varying degrees of acute renal deterioration, the patients responded very well to doxycycline therapy and recovered completely. Additionally, a total of 4 similar cases of scrub typhus associated with acute renal failure were reviewed from the past literature.

Acute Kidney Injury↗
PubMed2006

Clinical usefulness of eschar polymerase chain reaction for the diagnosis of scrub typhus: a prospective study.

BACKGROUND: The aim of this study was to determine the diagnostic utility of performing eschar polymerase chain reaction (PCR) for the diagnosis of scrub typhus through a prospective comparison of eschar PCR results with indirect immunofluorescent antibody assay (IFA) results. METHODS: We conducted a multicenter prospective study involving patients with possible scrub typhus. Whole-blood samples and eschars were obtained for serological evaluation and PCR. A new crust was formed several days later at the site of the removed eschar. The newly formed crust was taken for performance of the second eschar PCR. Additional blood samples and eschars were collected, if possible, at 1-week intervals for 1 month after antibiotic treatment. RESULTS: We prospectively studied 135 patients with possible scrub typhus. Of these patients, 118 had scrub typhus confirmed on the basis of either a single indirect immunofluorescent specific immunoglobulin M titer against Orientia tsutsugamushi of > or = 1:10 or a > or = 4-fold increase in the follow-up titer. The results of nested PCR assay of the eschars demonstrated a sensitivity of 0.86 (95% confidence interval, 0.78-0.92) and a specificity of 1 (95% confidence interval, 0.05-1). Among the 50 patients who showed positive results of eschar PCR at admission, 46 (92%) also showed positive results for the follow-up PCR test of the newly formed eschar after the treatment with antibiotics. CONCLUSIONS: The eschar PCR assay was useful as a rapid and reliable test to confirm the diagnosis of scrub typhus, even though the patients received treatment with appropriate antibiotics, such as macrolides, quinolones, and tetracycline, which are all active against Orientia and Rickettsia species.

Adult↗
PubMed1982

Doxycycline propylaxis for human scrub typhus.

The use of doxycycline, as a prophylactic antibiotic against scrub typhus was investigated in a prospective, randomized, double-blind study. Twenty volunteers were divided into two similar groups. Beginning three days before exposure to Leptotrombidium fletcheri chiggers infected with Rickettsia tsutsugamushi, and continuing for six weeks after exposure, one group received weekly 200-mg oral doses of doxycycline and the other group received a placebo. Nine of 10 doxycycline-treated subjects remained well during prophylaxis but developed antibody to scrub typhus, whereas nine of 10 subjects given the placebo required treatment for scrub typhus. Therefore, the efficacy of the regimen in preventing scrub typhus was 89% (eight cases prevented of nine expected). Ten days after successfully completing prophylaxis, eight of nine subjects reported minor self-limiting symptoms. A single dose of doxycycline was given on day 3 of illness to volunteers who developed scrub typhus. Such therapy was initially effective but was frequently followed by relapse and cannot be recommended.

Adult↗
PubMed2001

Passive transfer of scrub typhus plasma to patients with AIDS: a descriptive clinical study.

We examined the HIV-inhibitory effects previously found to be associated with scrub typhus infection. Individual 500 ml units of plasma from donors with mild scrub typhus were safety-tested, subjected to virucidal heat treatment, and administered to 10 HIV-1-infected recipients who were not receiving antiretroviral drugs. HIV-1 copy number fell three-fold or more in two recipients, and virus burden was reduced for 8 weeks in 70% (7/10) of recipients of a single plasma infusion, compared with the mean of three pre-infusion measurements. Scrub typhus donor plasma inhibited HIV-1 in vitro compared with normal human plasma and media controls. In the clearest in vivo response, reduction in viral load was accompanied by clinical improvement, a switchback from the syncytia-inducing to the non-syncytia-inducing phenotype, and decreases in CD8 cells and IL-6 levels. Scrub typhus infections can generate heat-stable, transferable plasma factors that exert prolonged anti-HIV effects. Whether variability in the results is due to different scrub typhus infections, different HIV infections or different individual responses, is unclear.

Acquired Immunodeficiency Syndrome↗
PubMed2003

Outbreak of scrub typhus in southern India during the cooler months.

Orientia tsutsugamushi, the agent of scrub typhus, is a strict intracellular bacterium which is found in many parts of Asia including India. During the past few years, the number of patients with rickettsial infection and scrub typhus has increased, especially during the cooler months. We report in this study a recent outbreak of scrub typhus recorded during the cooler months (October 2001 to February 2002) in patients admitted to our hospital with acute febrile illness associated with diverse signs and symptoms. Overall, 28 patients were clinically and serologically confirmed to have scrub typhus. Fever for more than one week was the only common manifestation. Myalgias was the next most common feature (52%), and rash was observed in only 22% of the cases. Seventeen patients treated with doxycycline recovered in 1 to 3 days, as well as two patients who received chloramphenicol. In five patients who received ciprofloxacin, fever subsided only after five days. Finally three patients (10.7%) died, including one patient treated with doxycycline. These data indicate that scrub typhus is a reemerging infectious disease in India with a possibility of drug resistance. This reemergence emphasizes the need for further prospective studies to design effective control measures.

Adolescent↗
PubMed2001

[Tsutsugamushi disease (scrub typhus) in Japan: clinical features].

Clinical features of tsutsugamushi disease (scrub typhus) were analyzed, based on 416 cases reported in Japan in 1998. Three major clinical symptoms: eschar, fever and rash were found in 87%, 98% and 92% of the cases, respectively. Elevated levels of CRP, GOT, GPT and LDH were observed in 96%, 85%, 78% and 91%, respectively. These clinical and laboratory findings were observed in the majority of the cases and considered important for diagnosis. Disseminated intravascular coagulation developed in 21 cases, indicating that scrub typhus can be life threatening. Lymphadenopathy was observed in 51% of the cases. Enlarged lymph nodes were limited to the local sites in 75% of these lymphadenopathy cases and most of these sites were adjacent to eschars. Most eschars were scabbed and located in the abdomen and the lower half of the body, especially the feet. This suggests that these parts are frequently exposed to tsutsugamushi mites. Furthermore, the skin is soft in these parts and covered by cloth. These factors may make it possible for mites to keep biting without being noticed for several hours, long enough for rickettsial transmission. Interestingly, eschar and rash were absent in 14% and 8% of the cases, respectively. This result suggests that the cases without the unique symptoms may have been misdiagnosed as common cold or other febrile illnesses. One hundred and fifty-four suspected cases were not scrub typhus cases by the serological tests. The three major clinical symptoms were present in approximately a half of these negative cases, eschar being observed in approximately 70%. This may suggest the presence of new type of scrub typhus can not be diagnosed by the present laboratory tests. Clinical features of scrub typhus in Japan were well revealed, and information obtained in the present study is useful for improving clinical diagnosis. It should, however, be stressed that there were cases that could not be correctly diagnosed only by the clinical symptoms, suggesting that it is important to improve the serological tests.

Diagnosis, Differential↗
PubMed1974

Mechanisms of immunity in typhus infections. IV. Failure of chicken embryo cells in culture to restrict growth of antibody-sensitized Rickettsia prowazeki.

Rickettsia prowazeki, pretreated with typhus immune human serum, readily infects, and grows in, chicken embryo cells in culture. This finding is similar to those of previous studies which showed that typhus rickettsiae, pretreated with immune serum, grow in cells of the yolk sac of embryonated hen eggs and in the cells of the midgut of the human body louse. In contrast, identically treated typhus rickettsiae were destroyed by human macrophages in culture. Collectively, these observations seem to support an emerging concept that the fate of antibody-sensitized typhus rickettsiae depends upon the presence or absence of certain specialized properties of the host cell into which they gain entrance-nonphagocytic cells or "nonprofessional" phagocytic cells versus certain kinds of "professional" phagocytes. The phenomena involved probably have an important bearing on the mechanisms of the persisting infection and the nonsterile immunity which characterizes convalescence from typhus fever in man. They also form the basis for certain practical technical innovations in the laboratory.

Adult↗
PubMed2006

Eradication of typhus exanthematicus in Bosnia and Herzegovina.

Typhus exanthematicus in Bosnia and Herzegovina held in endemic areas from which especially quickly began spread after 1945. That year, in 1945, one hundred epidemics of typhus fever appeared, with the highest incidence rate in Europe of 215.04 per 1,000. Directions of unique program in the world were to eradicate lice of the body, but also establish monitoring of the recidivism, Brill-Zinsser disease. Since 1971, typhus exanthematicus (classical typhus) hasn't appeared in Bosnia and Herzegovina, so epidemic typhus can considered as an eradicated communicable disease.

Animals↗
PubMed2004

Clinical role of interstitial pneumonia in patients with scrub typhus: a possible marker of disease severity.

Interstitial pneumonia (IP) frequently occurs in patients with scrub typhus, but its clinical significance is not well known. This study was designed to evaluate interstitial pneumonia as a marker of severity of the disease for patients with scrub typhus. We investigated clinical parameters representing the severity of the disease, and the chest radiographic findings for 101 patients with scrub typhus. We then compared these clinical factors between patients with and without IP. We also studied the relationship between IP and other chest radiographic findings. The chest radiography showed IP (51.4%), pleural effusion (42.6%), cardiomegaly (14.9%), pulmonary alveolar edema (20.8%), hilar lymphadenopathy (13.8%) and focal atelectasis (11.8%), respectively. The patients with IP (n=52) had higher incidences in episode of hypoxia (p=0.030), hypotension (p=0.024), severe thrombocytopenia (p=0.036) and hypoalbuminemia (p=0.013) than the patients without IP (n=49). The patients with IP also had higher incidences of pleural effusion (p<0.001), focal atelectasis (p=0.019), cardiomegaly (p<0.001), pulmonary alveolar edema (p=0.011) and hilar lymphadenopathy (p<0.001) than the patients without IP. Our data suggest that IP frequently occurs for patients with scrub typhus and its presence is closely associated with the disease severity of scrub typhus.

Adult↗
PubMed1999

[Epidemic typhus in Africa].

Epidemic typhus is caused by a small strictly intracellular virus named Rickettsia prowazekii, a member of the Rickettsial family. It is transmitted to man by the body louse, Pediculus humanus. Although now rare in Western countries, exanthematic typhus remains common in the Southern hemisphere due to poverty, inadequate clothing hygiene, and poor socioeconomic conditions. In Africa, outbreaks have historically occurred in Burundi, Rwanda, southwest Ouganda, and Ethiopia. The largest outbreak of epidemic typhus since the World War II was reported in Burundi where ongoing civil war since October 1993 has forced 10 p. 100 of the population of Burundi to live in cold, promiscuity, and malnutrition of makeshift refugee camps. The purpose of this report based on our two-year experience working with this unfortunate population is to describe the characteristics of this disease in Africa where the epidemic form had become rare until recently. Indeed political unrest as well as numerous civil wars are now epidmiological factors favorizing outbreaks of epidemic typhus at any time. This overview also provides an opportunity to recall epidemiological, bacteriological, and clinical aspects of typhus as well as diagnosis and treatment of the disease in the context of Africa.

Africa↗
PubMed1999

[Poland: cholera to typhus, 1831-1950].

In this article devoted to Poland's direct and indirect role in the elaboration of contemporary international health structures and to her reputation as an epidemic reservoir of Europe, we consider how Poland came to be perceived as the cordon sanitaire of the West. Traditionally seen as upholding Western values, in the 19th and 20th centuries the country became increasingly associated with "Eastern plagues"-cholera and then typhus-coming from Russia and which could spread to the rest of Europe if Poland did not manage to contain them. When Poland was reconstituted as a nation-state in 1918, the new country won international recognition through her successful attempts to contain a typhus epidemic sweeping westwards from Russia. The Polish government convened the first European, League sponsored, health conference following the First World War. A Polish doctor, L. RAJCHMAN, was chosen to head up the League of Nations Health Organisation (forerunner of the WHO) and later (1946) founded UNICEF. Finally, we examine the key issue of exanthematous typhus in both world wars, exemplifying how a disease can come to be "ideologized", in this case by Nazi Germany. Typhus was the pretext used- in the name of "public health"-for segregating Polish citizens of Jewish origin and even killing them. Paradoxically, typhus was in the process of being eradicated when the war began and German policy of mass resettlements, sequestration, and starvation only spurred the epidemic they supposedly wished to control.

Cholera↗
PubMedDate not supplied

[Epidemic typhus in tropical Africa. A reemerging disease that is severe but curable].

In tropical regions of Africa, frequently subject to social and political upheavals, there is an ever-present threat of typhus epidemics, as shown by the recent typhus outbreak in Burundi in 1997. Epidemic typhus should be systematically suspected in certain epidemiological conditions: famine, war, high-density populations (refugee camps, prisons), the presence of body louse in the clothing, and in the presence of certain clinical findings: severe infectious syndrome (temperature above 38 C), severe pain and muscle weakness, with coughing and severe neurological signs. The rapid diagnosis and treatment of typhus are essential. The prognosis has improved, thanks to the specific antibiotics that are currently available, particularly doxycycline, prescribed as a single oral dose of 200 mg for adults or of 100 mg for children. However, the prognosis still depends to a large extent on the speed of diagnosis. Typhus epidemics could be effectively predicted and limited if the measures for control of the body louse recommended by the World Health Organization were applied in the areas with the most favorable epidemiological conditions.

Adult↗