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Scrub and murine typhus in children with obscure fever in the tropics.

Between October, 1985, and February, 1987, 28 (8.7%) cases of scrub and murine typhus were diagnosed among 320 children with greater than or equal to 1 week history of obscure fever. Scrub typhus is a rural disease and characterized by fever, tachypnea and hepatosplenomegaly. Skin rash was rare and eschar was absent. Four patients had pneumonia and two had meningitis. Murine typhus, more an urban disease, was milder and half the patients presented exclusively because of night fever. Slightly enlarged liver and skin rash were the only significant physical signs. Lacking the classical textbook presentations, both rickettsioses often were missed or diagnosed as enteric fever. Recognition is important because patients with either disease respond well to treatment with chloramphenicol or doxycycline.

Child↗

In vitro stimulation of human peripheral blood lymphocytes by soluble and membrane fractions of renografin-purified typhus group rickettsiae.

Cell-free extracts of disrupted Renografin-purified Rickettsia typhi and R. prowazekii were evaluated as antigens in lymphocyte transformation assays for cell-mediated immunity to typhus group rickettsiae in 19 individuals with and 9 without histories of exposure to these organisms. Exposure consisted of clinical disease, vaccination with epidemic typhus vaccine, or occupational exposure to these agents. Both the soluble and membrane fractions of disrupted purified rickettsiae were used, and transformation of peripheral blood lymphocytes (PBL) was determined in microcultures by incorporation of [(3)]thymidine. Of the antigen concentrations tested (1 to 400 mug/ml), 10mug/ml appeared to be the most satisfactory. At this concentration, PBL transformation was highly reproducible and correlated well with donor exposure and the presence of enzyme-linked immunosorbent assay anti-typhus group immunoglobulin G. At higher concentrations, PBL from both exposed and control donors often responded to a lipopolysaccharide-like component present in these preparations. Specific transformation responses to rickettsial fractions were detected in several individuals decades after infection or vaccination, indicating that both fractions contained antigens associated with persisting cell-mediated immunity in humans. Generally, stimulation indexes with the soluble fraction were slightly greater than those obtained with corresponding concentrations of the membrane preparation, and in three individuals transformation was observed only with the soluble fraction. PBL transformation to soluble fractions also appeared to have some species specificity, since PBL from individuals with documented R. typhi infections were more responsive to the homologous soluble preparation than to the soluble fraction of R. prowazekii. PBL transformation also correlated well with homologous but only poorly with heterologous enzyme-linked immunosorbent assay immunoglobulin G titers.

Antibodies, Bacterial↗

Murine typhus and spotted fever in Israel in the seventies.

One hundred and eleven cases of rickettsial disease-100 cases of murine typhus and 11 cases spotted fever--seen over a four year period at the Chaim Sheba Medical Center are reviewed. The clinical picture of murine typhus (caused by Rickettsia mooseri and transmitted by Xenopsylla cheopis) could not be distinguished from that of spotted fever (caused by a Rickettsia similar to Rickettsia conori and transmitted by Rhipicephalus). Some quite severe cases of murine typhus and some relatively mild cases of spotted fever were seen.

Adolescent↗

Murine typhus and spotted fever in Israel in the eighties: retrospective analysis.

One hundred and twenty-one cases of murine typhus and spotted fever in Israel between 1976 and 1985 in the Chaim Sheba Medical Center are reviewed. Clinical manifestations of murine typhus were similar to those described previously, but those of spotted fever were different from classical Mediterranean spotted fever: rash was present in 87% but eschar was noted in only two out of 38 patients. The occurrence of relapse in eight of the 16 patients treated with chloramphenicol (seven cases of murine typhus and one case of spotted fever) was striking, particularly since none occurred in 86 patients treated with tetracycline hydrochloride (p less than 0.01). Relapses were milder than the primary illness, except for one which did not receive specific therapy and was fatal.

Chloramphenicol↗

Murine typhus among Arabs and Jews in Israel 1991--2001.

The aim of this study was to explore the incidence and differences in the epidemiology of murine typhus between Jews and Arabs in Israel. Between 1991 and 2001, 406 cases of murine typhus were diagnosed; 57% of cases occurred between August and November. Differences between Arabs vs. Jews regarding mean yearly incidence (1.84 vs. 0.35/100,000 people; p = 0.003), median age (35 vs. 44 years; p < 0.001), and male:female ratio (1:1 vs. 1.3:1; p = 0.009), were found. Control measures to decrease morbidity of murine typhus should take into consideration the socio-economic and environmental factors influencing the differences observed.

Animals↗

Population indices of chiggers (Leptotrombidium deliense) and incidence of scrub typhus in Chinese military personnel, Pescadores Islands of Taiwan, 1976-77.

Larval Leptotrombidium deliense were recovered from live-trapped Suncus murinus, Rattus rattus and R. norvegicus captured in the Pescadores Islands of Taiwan during 1976 and 1977. Weekly and monthly indices of chigger infestation expressed as a percentage of hosts infested and the number of chiggers per host for S. murinus and Rattus spp. were calculated. Close correlations were observed between monthly indices of L. deliense measured for S. murinus and Rattus spp. and the number of laboratory-confirmed cases of scrub typhus per month. Weekly indices from S. murinus correlated more closely with number of cases than did weekly indices from Rattus spp. The critical level of chigger infestation necessary for a single case of scrub typhus in a month was estimated at 0.69 chigger per S. murinus and 0.68 chigger per Rattus spp. The weekly index of chigger infestation necessary for a single case of scrub typhus during a week was calculated at 0.47 chiggers per shrew. Critical levels of chigger infestations expressed as percentages of hosts infested were not calculated.

Animals↗

Differential expression of interferon-gamma and interferon-gamma-inducing cytokines in Thai patients with scrub typhus or leptospirosis.

Interferon (IFN)-gamma plays an important role in the induction of a type 1 immune response against intracellular pathogens. We compared the plasma levels of IFN-gamma and IFN-gamma-inducing cytokines in adult Thai patients with scrub typhus, caused by the obligate intracellular bacterium Orientia tsutsugamushi, and leptospirosis, caused by extracellular Leptospira interrogans. IFN-gamma, interleukin (IL)-18, and IL-15 levels were elevated only in patients with scrub typhus, whereas IL-12p40 and tumor necrosis factor-alpha concentrations were elevated in both patient groups, although more so in scrub typhus. These data suggest a role for a cell-mediated immune response in host defense against O. tsutsugamushi.

Adolescent↗

Acute myocardial infarction following scrub typhus infection.

Up to recently, a few cases of myocarditis in the cardiac manifestations of scrub typhus have been reported. However, acute myocardial infarction (AMI) associated with scrub typhus has not been previously reported. We presented a case of AMI ensued on scrub typhus, which were successfully treated by percutaneous coronary intervention (PCI).

Humans↗

Evaluation of nested PCR for the diagnosis of scrub typhus among patients with acute pyrexia of unknown origin.

A nested PCR technique was performed to detect a specific 483 bp DNA fragment of Orientia tsutsugamushi, the aetiological agent of scrub typhus, in 53 blood samples from 36 patients with acute pyrexia of unknown origin in southern Thailand. The specific primers could amplify the specific DNA from all 10 prototype strains of O. tsutsugamushi and all nine seropositive patients and three seronegative patients, while no DNA amplification was obtained with DNAs from other rickettsiae or from healthy persons or from patients with murine typhus. The specific PCR product was detectable in the blood for as long as 22 days after the onset of disease in patients without specific treatment and 27 days after receiving a single dose of doxycycline. Thus, nested PCR may be more sensitive than the serological test for diagnosis of scrub typhus and prolonged persistence of O. tsutsugamushi DNA in patients' blood was demonstrated despite clinical recovery of the patients.

Adult↗

Case reports: scrub typhus during pregnancy in India.

Scrub typhus, caused by Orientia tsutsugamushi, is a rural zoonosis endemic in the Asian Pacific region. Doxycycline and chloramphenicol, the recommended drugs for treating this infection, may not be safe during pregnancy. We report on 5 patients with scrub typhus during pregnancy who were seen in India between October 2001 and February 2002. Four of the 5 women were treated initially with ciprofloxacin. Three women had stillbirths, 1 an abortion and 1 a low birthweight baby, which suggests that ciprofloxacin should not be used for treating pregnant women and that scrub typhus leads to severe adverse effects during pregnancy. Randomized controlled trials are urgently needed to ascertain the optimal drug choice, given that currently recommended drugs are contraindicated in pregnant women.

Abortion, Spontaneous↗

Scrub typhus infections poorly responsive to antibiotics in northern Thailand.

BACKGROUND: Rickettsia tsutsugamushi, the aetiological agent of scrub typhus, is common in Asia and readily infects visitors to areas where disease transmission occurs. Rapid defervescence after antibiotic treatment is so characteristic that it is used as a diagnostic test for R tsutsugamushi infection. Reports from local physicians that patients with scrub typhus in Chiangrai, northern Thailand responded badly to appropriate antibiotic therapy prompted us to do a prospective clinical evaluation and antibiotic susceptibility testing of human rickettsial isolates. METHODS: The clinical response to doxycycline treatment in patients with early, mild scrub typhus in northern Thailand was compared with the results of treatment in Mae Sod, western Thailand. Prototype and naturally occurring strains of R tsutsugamushi were tested for susceptibility to chloramphenicol and doxycycline in mice and in cell culture. FINDINGS: By the third day of treatment, fever had cleared in all seven patients from Mae Sod, but in only five of the 12 (40%) from Chiangrai (p < 0.01). Median fever clearance time in Chiangrai (80 h; range 15-190) was significantly longer than in Mae Sod (30 h; range 4-58; p < 0.005). Conjunctival suffusion resolved significantly more slowly in Chiangrai (p < 0.05). Antibiotics prevented death in mice infected by Chiangrai strains of R tsutsugamushi less often than after infection by the prototype strain (p < 0.05). Only one of three Chiangrai strains tested in cell culture was fully susceptible to doxycycline. INTERPRETATION: Chloramphenicol-resistant and doxycycline-resistant strains of R tsutsugamushi occur in Chiangrai, Thailand. This is the first evidence of naturally occurring antimicrobial resistance in the genus Rickettsia.

Administration, Oral↗

The history of epidemic typhus.

Few infectious diseases have influenced human civilization to the same degree as louse-transmitted typhus. Rickettsia prowazekii continues to strikes tens to hundreds of thousands of persons who live with war, famine, crowding, and in squalid conditions associated with social unrest, with mortality rates in excess of 10% to 15%. Historical documents confirm that such devastation has been a continuous feature of human existence to the extent that typhus has been a major determinant in the outcome of many wars, altering human history in its wake-despite incomplete knowledge of its precise origin. In the twenty-first century, circumstances are still conductive for outbreak; the emerging threat of bioterrorism raises justifiable concerns that typhus could affect civilization just as greatly in the future as it has in the past.

Disease Outbreaks↗

Epidemic typhus fever and hearing loss: a histological study (Hallpike collection of temporal bone sections).

Hearing loss as a frequent complication of louse-borne epidemic typhus fever has been well documented in the reports of ENT specialists serving in both the Allied and the German armies in the last war. The present paper describes the characteristic histopathological features as noted in sections of the temporal bones from five British soldiers who died in 1944 of typhus fever during the last war in Eastern Asia. The VIIIth nerve showed multiple 'typhus nodules' and there was extensive interstitial neuritis of the VIIIth nerve and demyelination of the nerve fibres. There were also widely scattered aggregations of mononuclear cells in the inner ear. This unique study was based on the Hallpike collection of temporal bone sections.

Adult↗

Scrub typhus serologic testing with the indirect immunofluorescence method as a diagnostic gold standard: a lack of consensus leads to a lot of confusion.

A review was performed to determine the evidence base for scrub typhus indirect immunofluorescence assay (IFA) methodologies and the criteria for positive results. This review included a total of 109 publications, which comprised 123 eligible studies for analysis (14 publications included 2 substudies). There was considerable underreporting of the IFA methodology and seropositivity criteria used, with most studies using a defined cutoff titer rather than an increase in the titer in paired samples. The choice of positivity cutoff titer varied by country and purpose of the IFA test. This variation limits the comparability of seroprevalence rates between studies and, more seriously, raises questions about the appropriateness of the cutoffs for positive IFA results chosen for diagnosis of acute scrub typhus infection. We suggest that the diagnosis of scrub typhus using IFA should be based on a > or =4-fold increase in the titer in paired serum samples and should only be based on a single sample titer when there is an adequate local evidence base.

Fluorescent Antibody Technique, Indirect↗

Survey of three bacterial louse-associated diseases among rural Andean communities in Peru: prevalence of epidemic typhus, trench fever, and relapsing fever.

Typhus and other louse-transmitted bacterial infections in Peruvian sierra communities are known to occur but have not recently been assessed. In this study, 194 of 1,280 inhabitants of four villages in Calca Province in the Urubamba Valley were included. Thirty-nine (20%) of the 194 volunteers had antibodies to Rickettsia prowazekii, whereas 24 (12%) had antibodies to Bartonella quintana and 2 against Borrelia recurrentis. There was a significant correlation between the presence of infesting ectoparasites and antibodies to R. prowazekii, as well as between antibodies to R. prowazekii and ectoparasite infestation and fever in the previous 6 months. The proportion of inhabitants infested with ectoparasites was significantly higher in the highest-altitude village than in the other three villages. Two volunteers' antibody levels suggested a recent typhus infection, but only B. quintana DNA was amplified from lice. Epidemic typhus remains extant in the area, and B. quintana infections were encountered and documented for the first time in South America.

Adult↗

A clinico-epidemiological study of epidemic typhus in Africa.

Epidemic, louse-borne typhus persists in the rugged, mountainous areas of Ethiopia and much of northeastern and central Africa as well as in the rural highlands of Central and South America, where the conditions of living favor the harboring of body lice and where antibiotic treatment and effective louse-control measures are unavailable. The historical significance and current epidemiology of typhus, including the reservoir of Rickettsia prowazekii in flying squirrels in the United States, are reviewed, and the clinical presentation, laboratory findings, and hospital course in the cases of 60 patients admitted with epidemic, louse-borne typhus to the St. Paul's Hospital in Addis Ababa, Ethiopia, are described. Treatment of this disease with oral doxycycline, tetracycline, or chloramphenicol prevents complications and results in prompt resolution of symptoms.

Adolescent↗

Life-threatening scrub typhus in a traveler returning from Thailand.

Scrub typhus is not one of the more commonly encountered diseases in travelers returning from Asia, but it deserves more consideration in view of its severity and the availability of specific chemotherapy and chemoprophylaxis. We describe a case of scrub typhus that was associated with coma and multiorgan failure in a traveler returning to the United States from Thailand. The diagnosis was made only retrospectively despite a travel history and clinical signs that suggested infection with Rickettsia tsutsugamushi. No specific therapy was given, and marked neurological impairment persisted 6 months after the beginning of the illness. An increased awareness of scrub typhus is a prerequisite for recommending prophylaxis and instituting prompt therapy.

Coma↗

Murine typhus: updated roles of multiple urban components and a second typhuslike rickettsia.

Studies using serologic and polymerase chain reaction-(PCR) facilitated analysis of field samples from southern Texas indicate the presence of Rickettsia typhi and ELB agent infected cat fleas, Ctenocephalides felis (Bouché), and the first observation of ELB infected vertebrates (opossums). The ELB agent is a recently described typhus-like rickettsia that is not distinguished from R. typhi or R. prowazekii by currently available serologic reagents. Restriction digests of PCR products from 399 fleas revealed an ELB agent infection rate of 3.8% and a R. typhi infection rate of 0.8%. Three of nine tested opossums (Didelphis virginiana) were shown to harbor ELB agent infections. No R. typhi infected rats, Rattus norvegicus, or rat-fleas, Xenopsylla cheopis Rothschild, were detected among surveyed samples. The persistence of this murine typhus disease focus appears to be better accounted for by the presence of infected cat fleas, opossums, and other non-rat hosts found in close association with human populations. Involvement of the ELB agent in the biology of murine typhus is suggested by its prevalence among suspected vectors and reservoir hosts.

Animals↗