Possible acute coinfections in Thai malaria patients

We conducted serodiagnostic testing for dengue virus infection, murine typhus, scrub typhus and leptospirosis in Plasmodium falciparum-infected individuals in Thailand. Sera from 194 malaria patients with a median age of 24 years were tested. No antibody titers diagnostic of dengue virus infection were demonstrated, but 29 (15%) of patients had serological evidence of scrub typhus, 45 (23.2 %) patients had evidence of murine typhus, and 15 (7.7%) sera tested positive for leptospirosis. Our serological results suggested that duel infections are not uncommon in malaria that is acquired in Thailand. However, our results must be confirmed by prospective studies aimed at describing the causative organisms. Mixed infections would have multiple implications for clinicians, including unexpected clinical findings and apparent poor responses to antimalarial treatment in patients thought only to have malaria.     

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

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

Coinfection with leptospirosis and scrub typhus in Taiwanese patients

We retrospectively analyzed patients with leptospirosis (n = 35), scrub typhus (n = 45), and coinfection (leptospirosis and scrub typhus [n = 7]) to facilitate the detection of coinfection. Our data showed that factors favoring these disease entities included animal contact, an aspartate aminotransferase/alanine aminotransferase ratio > 2 (for leptospirosis); outdoor exposure, lymphadenopathy, splenomegaly, eschar, and elevated alkaline phosphatase levels (for scrub typhus and coinfection); calf tenderness, conjunctival suffusion, jaundice, oliguria, elevated total bilirubin levels and serum creatinine levels (for leptospirosis and coinfection); and maculopapular rash (for scrub typhus). Patients at risk for leptospirosis are often at increased risk for scrub typhus and vice versa. Lack of knowledge of coinfection may jeopardize the health of affected patients. Our study serves as a reminder of potential coinfection and provides clues for its detection.     

Molecular Confirmation of Co-Infection by Pathogenic Leptospira spp. and Orientia tsutsugamushi in Patients with Acute Febrile Illness in Thailand

Leptospirosis and scrub typhus are major causes of acute febrile illness in rural Asia, where co-infection is reported to occur based on serologic evidence. We re-examined whether co-infection occurs by using a molecular approach. A duplex real-time polymerase chain reaction was developed that targeted a specific 16S ribosomal RNA gene of pathogenic Leptospira spp. and Orientia tsutsugamushi. Of 82 patients with an acute febrile illness who had dual infection on the basis of serologic tests, 5 (6%) had polymerase chain reaction results positive for both pathogens. We conclude that dual infection occurs, but that serologic tests may overestimate the frequency of co-infections.Leptospirosis and scrub typhus are major causes of acute febrile illness in the Asia-Pacific region.^1,2 Leptospirosis is caused by pathogenic Leptospira spp., and scrub typhus is caused by the gram-negative obligate intracellular bacterium Orientia tsutsugamushi. Because both infections affect agricultural workers and have similar clinical features, including fever, myalgia, headache, and lymphadenopathy, they are difficult to distinguish on clinical grounds alone. Co-infection with leptospirosis and scrub typhus was first reported in rice farmers who were hospitalized with leptospirosis in northeastern Thailand; with 9 (40%) of 22 patients were also seropositive for scrub typhus.³ Dual infection has also been reported in Taiwan and India.^4–6 A study from Thailand reported that 103 (12.2%) of 845 patients with an acute febrile illness had dual infection, of which 33 were attributed to leptospirosis and scrub typhus.² All previous studies have relied on serologic tests, and the possibility remains that co-infection represents cross-reactivity between serologic assays, or an acute infection by one pathogen after a recent infection by another pathogen. The aim of this study was to determine if dual infection in Thai patients on the basis of serologic testing could be confirmed by a molecular method.The study protocol was approved by the Ethics Committee of the Faculty of Tropical Medicine, Mahidol University, Thailand (MUTM 2010-033-01). A duplex real-time polymerase chain reaction (PCR) was developed for the 16S ribosomal RNA (rRNA) gene. Primers and hydrolysis probe targeting the 16S rRNA gene of pathogenic Leptospira spp. were based on a reported TaqMan assay.⁷ These primers generated an 88-basepair product (positions 205–220 and 240–263 of L. interrogans 16S rRNA gene sequence; GenBank accession no. {"type":"entrez-nucleotide","attrs":{"text":"AY631894","term_id":"54112255","term_text":"AY631894"}}AY631894). Primers and hydrolysis probe targeting the 16S rRNA gene of O. tsutsugamushi were modified from those of a previous study⁸ and were as follows: forward 5′-GGCATACGGTATTAGCACTTA-3′, reverse 5′-GCATTAATTAGTGGCAAACG-3′, and probe ROX-5′-TAAA TGTTATTCCGTACTGATGGGCAG-3′-BHQ2. The hydrolysis probe for O. tstsugamushi was labeled with ROX so that this probe could be used in a single reaction with the hydrolysis probe for Leptospira spp. (6-FAM). The modified primers amplified a 92-basepair product (positions 53–72 and 125–145 of the 16S rRNA gene of O. tsutsugamushi strain Boryong; GenBank sequence accession no. {"type":"entrez-nucleotide","attrs":{"text":"NC_009488","term_id":"148283997","term_text":"NC_009488"}}NC_009488). The assay was optimized and performed in a 20-μL single reaction containing 5 μL DNA, 1× QUANTIPROBES (QuantiMix Easy Probes Kit; Biotools, Madrid, Spain), 8 mM MgCl₂, 0.15 μM of each primer, and 0.1 μM of each probe. Cycling conditions were at 95°C for 8 minutes (1 cycle), followed by 50 cycles at 95°C for 10 sec and 60°C for 1 minute.The PCR amplification efficiencies and detection limits of the assay were determined by using a linearized plasmid pG16S described for scrub typhus⁸ and genomic DNA of L. interrogans serovar Lai for leptospirosis. DNA concentration was determined by using the Quanti-it™ High-Sensitivity DNA Assay Kit (Invitrogen, Carlsbad, CA) and the Rotor-Gene 3000 by using the DNA concentration measurement mode. Serially diluted DNA for each pathogen was used as a template in four triplicate calibration curves.The mean PCR efficiency was 0.88 (95% confidence interval [CI] = 0.81–0.93) for L. interrogans and 0.97 (95% CI = 0.96–0.99) for O. tsutsugamushi. The calibration curve for Leptospira spp. had a mean slope of −3.7 (95% CI = −3.8 to −3.48) and a y intercept of 38.2 (95% CI = 36.1–40.2), and that for O. tsutsugamushi had a mean slope of −3.3 (95% CI = −3.5 to −3.2) and a y intercept of 37.5 (95% CI = 36.4–38.8). Cycle quantification ranged from 19.9 to 36 (interquartile range = 22.7–34.5) for O. tsutsugamushi, and from 14.5 to 32.2 (interquartile range = 18.7–35.9) for Leptospira spp. The calibration curve showed a linear dynamic range over five orders of magnitude (5×10⁵ to 5 copies/μL) for both pathogens. The limit of detection of a duplex quantitative PCR was five genome equivalents for Leptospira genomic DNA and five copies for the O. tsutsugamushi plasmid. The mean coefficient of variation for the quantification calibrator for leptospirosis and scrub typhus was 0.1%.The analytical specificity of the duplex PCR was evaluated by using genomic DNA isolated from one clinical isolate of each of the following species: Rickettsia typhi, Staphylococcus aureus, Enterococcus sp., Escherichia coli, Salmonella enterica serovar Typhi, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Burkholderia pseudomallei. These species were selected because they represent common causes of serious infection in Southeast Asia. Genomic DNA of O. tsutsugamushi and R. typhi was extracted from infected laboratory tissue cultures by using the Wizard^® SV Genomic DNA Purification Kit (Promega, Madison, WI). Genomic DNA was extracted from the remaining species from laboratory cultures by using the Wizard^® Genomic DNA Extraction Kit (Promega) with the addition of 5 μL (10 mg/mL) of lysostaphin during the extraction of S. aureus DNA. None of the isolate tests showed a false-positive result.Diagnostic sensitivities and specificities of the assay were determined by using patients selected from a cohort study of acute febrile illness conducted at a hospital in northeastern Thailand during October 2000–December 2001, which has been described.⁹ Blood samples were obtained at admission for Leptospira spp. culture, serologic testing, and molecular diagnostic tests, and a second (convalescent) sample was obtained for serologic testing approximately two weeks later.Diagnosis of leptospirosis was based on a positive Leptospira culture and/or positive microscopic agglutination test (MAT) result (defined as a four-fold increase in MAT titer between acute-phase and convalescence-phase samples or a single titer ≥ 1:400). Diagnosis of scrub typhus was based on a positive fluorescent antibody assay (IFA) result (defined as a four-fold increase in IgM and IgG titer in a scrub typhus IFA between acute-phase and convalescence-phase samples or an IgM titer ≥ 1:400 and an IgG titer ≥ 1:800).A case–control study was conducted from the original cohort and consisted of 100 patients with laboratory confirmed leptospirosis alone (24 of whom were culture positive for Leptospira spp.), 100 patients with scrub typhus alone, and 150 controls. The controls were randomly selected from patients with negative laboratory test results for both infections, and had the following diagnoses: dengue fever (n = 16); murine typhus (n = 7); bacterial septicemia caused by Escherichia coli (n = 5), Klebsiella pneumoniae (n = 2), Klebsiella oxytoca (n = 1), Corynebacterium jeikeium (n = 1), Enterococcus sp. (n = 1), or Pseudomonas aeruginosa (n = 1); melioidosis (n = 1); human immunodeficiency virus–related infection (n = 1); Japanese encephalitis (n = 1); Q fever (n = 1); other diagnoses (n = 19); or an unknown diagnosis (n = 93).DNA was extracted from 5 mL of admission blood samples (containing EDTA) obtained during the clinical fever study as described.⁹ Each sample was assayed in duplicate in the duplex PCR. A positive result for one or both duplicate samples for a given species was interpreted as positive. The PCR result was positive for 59 of 100 leptospirosis monoinfection cases (diagnostic sensitivity = 59.0, 95% CI = 48.7–68.7) and for 62 of 100 scrub typhus monoinfection cases (diagnostic sensitivity = 62.0, 95% CI = 51.7–71.5). The PCR result was negative for leptospirosis for 138 of 150 controls (diagnostic specificity = 92.0, 95% CI = 86.4–95.8) and negative for scrub typhus for 139 of 150 controls (diagnostic specificity = 92.7, 95% CI = 87.3–96.3).The assay was then applied to all patients in the acute febrile illness cohort study who had been defined as having dual infections and had samples available for testing (n = 82). A four-fold increase in scrub typhus IFA titer was observed for 64 patients (78%), and a high single titer was observed for 18 patients (22%). Leptospirosis was diagnosed on the basis of positive results for culture and MAT for five patients (6%), positive results for culture and negative results for MAT for three patients (4%), and negative culture results and positive results for MAT for 74 patients (90%). The duplex PCR results for these 82 patients were as follows: 43 (52%) were positive for leptospirosis, 9 (11%) were positive for scrub typhus, 5 (6%) were positive for leptospirosis and scrub typhus, and 25 (30%) were negative for leptospirosis and scrub typhus.Our findings confirm that co-infection occurs, albeit at a low frequency (6%). Possible explanations for the difference observed between serologic and molecular results include low sensitivity of the molecular assay, failure to test a sample obtained during the window of bacteremia in leptospirosis, serologic cross-reactivity, and acute infection caused by one pathogen in the background of a recent but not active infection caused by the second pathogen. The assay described could represent a useful diagnostic assay to detect both pathogens in a single test.     

Imported rickettsial disease: clinical and epidemiologic features

PURPOSE AND METHODS: The rickettsioses continue to constitute major health problems in many parts of the world. With increasing international travel, recognition of rickettsial diseases by physicians is becoming more important. The clinical features of four cases of rickettsial disease imported into Canada over a five-year period are presented; two patients with tick typhus (Rickettsia conorii), one patient with scrub typhus (R. tsutsugamushi), and one patient with murine typhus (R. typhi). We also present the North American data over the past 10 years from the Centers for Disease Control (CDC) (Atlanta). RESULTS: Since 1983 in the United States, three cases of imported scrub typhus, all after travel to India, were confirmed, as well as six cases of murine typhus after travel to southeast Asia. At the CDC, 67 imported cases of tick typhus have been confirmed by indirect fluorescent antibody test since 1976; most illnesses occurred after travel to Africa. CONCLUSION: Rickettsial diseases are underrecognized by physicians, who should consider these diagnoses in travelers returning from endemic areas. Since effective treatment is available, prompt diagnosis and treatment are important. In all cases, specific serologic confirmation should be obtained.     

Rickettsial meningitis and encephalitis

Nine of 72 patients with scrub typhus and three of 137 with murine typhus presented with meningitis and/or encephalitis syndromes. Focal neurologic signs were rare, and cerebrospinal fluid profiles were similar to those of leptospirosis and viral and tuberculous meningitis. One patient had papilledema, and another had cerebellitis. Other major organ involvement (renal, liver, or lungs) occurred in five patients. One patient died and four spontaneously recovered, while the conditions of the rest responded well to either chloramphenicol or doxycycline. Scrub and murine typhus should be included in the differential diagnoses of aseptic meningitis and encephalitis in patients exposed to endemic areas, especially when accompanied by renal insufficiency and/or jaundice. They are treatable forms of virallike meningoencephalitis.     

Rickettsia serosurvey in Kimberley, Western Australia.

To determine if antibodies to rickettsiae (scrub typhus, spotted fever, and typhus group rickettsiae) occur among persons living in the Kimberley (northern tropical) region of Western Australia, 920 sera collected in a non-random manner in 1996 from patients in Kununurra, Broome, Fitzroy Crossing, Wyndham, Derby, and Halls Creek were tested by micro-immunofluorescence for antibodies to a panel of rickettsial antigens. Of 920 sera examined, 52 (5.6%) were positive for antibodies to one or more of the three groups of rickettsial microorganisms. The largest group of sera (24; 2.6%) were positive for scrub typhus (Orientia tsutsugamushi). Eleven other sera (1.2%) were positive for scrub typhus and spotted fever group rickettsiae and four (0.4%) were positive for scrub typhus, spotted fever group, and typhus group rickettsiae. In addition 13 sera (1.4%) were positive only for spotted fever group rickettsiae. In this study, only titers > or = 1:256 were considered significant. Thus, there is serologic evidence for scrub typhus and spotted fever group rickettsial infections in the Kimberley region of Western Australia. Because of the method of serum collection, it is not possible to determine the prevalence of seropositivity, but the data support the need for a proper epidemiologic study of rickettsial diseases in this region of Australia.     

Scrub Typhus-Associated Hemophagocytic Syndrome

Summary A patient was admitted to our hospital with fever of unknown origin, lymphadenophathy and moderate anemia. The diagnosis of scrub typhus (tsutsugamushi disease) was established on specific serologic demonstration of antibodies to the cross-reacting proteins OX-K antigen and reaffirmed by successful treatment with doxycycline. The diagnosis of hemophagocytic syndrome (HPS) was made on the cytologic findings of many histiocytes containing phagocytosed blood cells in the marrow aspirate. The hemophagocytosis phenomenon disappeared after the scrub typhus was successfully treated, thus suggesting the relationship between scrub typhus and hemophagocytosis. In a patient with rickettsial diseases including scrub typhus, associated with HPS, it is important to understand the relationship between the two disorders since the prognosis for HPS, if untreated, is very poor. Received: December 8, 1999 · Revision accepted: January 30, 2000     

Short report: prospective evaluation of a multi-test strip for the diagnoses of scrub and murine typhus, leptospirosis, dengue Fever, and Salmonella typhi infection

A multi-test strip dotblot immunoassay for the diagnosis of typhoid fever, scrub typhus, murine typhus, dengue virus infection and leptospirosis was evaluated in Thai adults presenting to hospital with acute, undifferentiated fever. The kit gave multiple positive test results in 33 of 36 patients with defined infections and was therefore not a useful admission diagnostic tool.     

Laboratory diagnosis of two scrub typhus outbreaks at Camp Fuji,Japan in 2000 and 2001 by enzyme-linked immunosorbent assay,rapid flow assay,and Western blot assay using outer membrane 56-kD recombinant proteins

Two scrub typhus outbreaks occurred among U.S. Marines training at Camp Fuji, Japan, between October 25 and November 3, 2000 and October 17 and November 30, 2001. Nine cases in approximately 800 Marines in 2000 and eight cases in approximately 900 Marines in 2001 (approximate attack rates = 1.1% and 0.9%, respectively) reported with signs and symptoms of fever, rash, headache, lymphadenopathy, myalgia, and eschar. Serologies and rapid response to doxycycline treatment indicated they had scrub typhus. Sixty-four convalescent serum samples (18 suspected cases and 46 negative controls) from U.S. Marines training at Camp Fuji during the outbreaks were assessed by enzyme-linked immunosorbent assay (ELISA), rapid flow assay (RFA), and Western blot assay for evidence of infection with Orientia tsutsugamushi, the causative agent of scrub typhus. All but one suspected case had serologic evidence of scrub typhus and all 46 control sera were non-reactive to O. tsutsugamushi antigens. The recombinant 56-kD antigen (r56) from the Karp, Kato and Gilliam strains of O. tsutsugamushi in an ELISA format provided better results than Karp r56 alone (ELISA and RFA) or whole cell antigen preparation from Karp, Kato and Gilliam (ELISA).     

Usefulness of nested PCR for the diagnosis of scrub typhus in clinical practice: A prospective study

The aims of this study were to determine the diagnostic accuracy and clinical usefulness of using nested polymerase chain reaction (PCR) for the diagnosis of scrub typhus through a prospective comparison of nested PCR and indirect immunofluorescent antibody assay (IFA). We conducted a multi-center prospective study of patients who were suffering with possible scrub typhus infection. Whole blood samples were collected for PCR testing, and sera were obtained for serology evaluation using the indirect IFA and the passive hemagglutination assay (PHA). We prospectively studied 135 patients with possible scrub typhus. One hundred eighteen patients were confirmed as having scrub typhus, 7 patients were undetermined, and 10 patients were confirmed as having other diseases. The results of nested PCR assay showed a sensitivity of 82.2% and a specificity of 100%. Ninety-six of the 118 patients were positive for IgM on their admission day. Of the 22 patients who were negative for IgM antibody at admission, 19 had positive results for nested PCR of the buffy coat. The nested PCR assay of the buffy coat is useful as a rapid and reliable test for confirming the diagnosis of scrub typhus.     

Murine typhus identified as a major cause of febrile illness in a camp for displaced Khmers in Thailand

Scrub and murine typhus have been identified as causes of illness among the 238,000 displaced Khmer people residing in temporary settlements on the Thai side of the Thai-Cambodian border. Still, the true extent of the problem and the relative frequency of infection with scrub typhus as compared to murine typhus are unknown. We evaluated consecutive patients with unexplained pyrexia (documented fever, no exclusionary diagnosis, and constitutional symptoms) in 1 temporary settlement over 1 month. Laboratory studies included culture of blood and assay of paired sera for rickettsial IgM and IgG antibody, for dengue IgM and IgG antibody, and for leptospiral IgM and IgG antibody. Among 37 patients (27 adults and 10 children), 28 (75%) had a rickettsiosis (26 cases of murine typhus and 2 cases of scrub typhus). No case of enteric fever, dengue, or leptospirosis was diagnosed. The illnesses of 9 patients were not identified. Signs and symptoms did not distinguish confirmed rickettsial infections from undiagnosed illnesses. The 1 month attack rate of rickettsial infection was 29/100,000 for children and 185/100,000 for adults. Murine typhus was a major cause of febrile illness in this settlement.     

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

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

Scrub typhus and leptospirosis co-infection in Himalayan region

Scrub typhus and leptospirosis are both zoonosis and systemic febrile illnesses with diverse clinical manifestations and they may present with similar signs and symptoms. We present a case of co-infection of scrub typhus and leptospirosis from Himachal Pradesh in the Himalayan region of India.     

Fatal septicemic melioidosis in a young military person possibly co-infected with Leptospira interrogans and Orientia tsutsugamushi

Concurrent melioidosis, leptospirosis, and scrub typhus after rural activities is rarely reported. A 19-year-old previously healthy man had fever onset after 2 weeks of military training. Pneumonia became evident on the fifth day of fever under intravenous penicillin and oral minocycline therapy. Acute respiratory failure developed the next day with shock and acute renal and liver function deterioration, which resulted in death. Blood cultures on the third and fifth days grew Burkholderia pseudomallei. Serology revealed leptospirosis and scrub typhus. The emergence of melioidosis in Taiwan and this death without antibiotic treatment for melioidosis alert us that B. pseudomallei should be included as a possible pathogen of pneumonia and sepsis, especially after rural activities.     

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

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

Prevalence of relative bradycardia in Orientia tsutsugamushi infection

We investigated 100 febrile patients infected with Orientia tsutsugamushi (the etiologic agent of scrub typhus) for the presence of relative bradycardia, defined as in increase in heart rate of < 10 beats/minutes/1 degree C increase in temperature. The median heart rate response for the entire febrile scrub typhus population was 9.3 beats/minute/degrees C and the prevalence of relative bradycardia was 53%. The occurrence of relative bradycardia was independent of patient age or gender. There were no differences in median basal temperature or febrile temperature between those patients exhibiting relative bradycardia and those with a normal febrile pulse increase. However, febrile patients with relative bradycardia had a significantly higher resting pulse rate following recovery from infection than did patients who had a normal pulse increase during their illness. These data demonstrate that relative bradycardia frequently accompanies mild infection with O. tsutsugamushi and that baseline cardiovascular parameters may affect the febrile heart rate response to scrub typhus.     

Gastrointestinal manifestations of septic patients with scrub typhus in Maharat Nakhon Ratchasima Hospital

Scrub typhus is an acute febrile illness caused by Orientia induced vasculitis, which is common in Asia and the Pacific Islands and is sometimes also encountered in Western countries. Even though it can cause multi-organ dysfunctions, there is limited information regarding the relationship between scrub typhus infection and gastrointestinal dysfunction. Therefore, a cross-sectional study was conducted to discover the gastrointestinal manifestations of septic patients with scrub typhus infection. During the study period, 80 septic cases were recruited, and according to the results of immunofluorescent antibody testing (IFA), 20 (25%) were found to have scrub typhus infection. The most common gastrointestinal symptoms of scrub typhus patients were vomiting 13 (65%), nausea 12 (60%), diarrhea 9 (45%), and hametamesis or melena 5 (25%). Gastrointestinal signs included hepatomegaly 8 (40%), jaundice 7 (35%), and abdominal pain 4 (20%). Elevation of SGOT, SGPT, and alkaline phosphatase were 16 (80%), 14 (70%), and 16 (80%), respectively. Direct bilirubin was elevated in 19 (95%) of the cases and half of the cases had a low serum protein level. Of scrub typhus cases, 8 (40%) had eschars. The sites of eschars were mostly in hidden areas, such as on the back, genitalia and abdomen. Three of the five patients with eschar had hepatomegaly on ultrasound examination. The significant findings of the scrub typhus septic patients with eschar on endoscopic examination were gastritis in two cases, gastritis with gastric erosion in two cases, and one case showed a duodenal ulcer and erosion. The differentiating point for endoscopic findings in scrub typhus compared to the other causes was that the stomach lesions were more frequent and severe than the duodenal lesions. According to our endoscopic findings, physicians should be aware of gastric and duodenal lesions in febrile patients with gastrointestinal symptoms, such as abdominal pain or discomfort and indigestion. Scrub typhus can cause gastrointestinal and liver dysfunction.     

Granulomatous hepatitis associated with scrub typhus

A 56 year old patient with scrub typhus infection having unusual presentation of hepatic injury resembling acute hepatitis is described. The clinical features of fever, headache, eschar, lymphadenopathy, lymphocytosis and high Rickettsia tsutsugamushi immunofluorescence titres confirmed the diagnosis of scrub typhus. Acute hepatitis was proven by hepatic biochemical tests and liver biopsy. The patient had a complete recovery soon after antibiotic treatment. The presentation of this case suggests that scrub typhus infection should be included in the list of differential diagnosis of acute hepatitis or granulomatous hepatitis, at least in the Asian Pacific region where scrub typhus still prevails.