ArticleLiterature Review

Scrub typhus during pregnancy and its treatment: A case series and review of the literature

Authors:
To read the full-text of this research, you can request a copy directly from the authors.

Abstract

Although scrub typhus is uncommon in pregnant women, when present, it can have serious repercussions for the mother and developing fetus. Since it is uncommon, the clinical impact of scrub typhus on pregnancy has not been elucidated and an effective and safe therapeutic regimen has not been validated. The medical records of pregnant women whose scrub typhus were treated at Chungnam National University Hospital were reviewed and their clinical outcomes were evaluated. A review of the literature was also performed on pregnant women with scrub typhus and their clinical outcomes. Eight pregnant women with scrub typhus were treated successfully with a single 500-mg dose of azithromycin, and no relapses were reported. They all delivered healthy babies at term, without congenital or neonatal complications. In the reviews, azithromycin was effective against scrub typhus and had favorable pregnancy outcomes. Ciprofloxacin and cefuroxime failed to treat scrub typhus and fetal loss resulted. A single 500-mg dose of azithromycin may be a reasonable treatment regimen for pregnant women with scrub typhus. Ciprofloxacin might not be advisable for the treatment of scrub typhus during pregnancy. Scrub typhus itself seems to have serious adverse effects on pregnancy if not appropriately controlled.

No full-text available

Request Full-text Paper PDF

To read the full-text of this research,
you can request a copy directly from the authors.

... gambiae mosquitoe was more attracted to pregnant women than non-pregnant women [3], have not been performed with the vectors of ST (mites) and MT (fleas). There is a scatter of small case series and reports on ST and MT [4][5][6][7][8][9][10][11][12][13][14][15][16] which tend to suggest serious repercussions for the mother and fetus, and congenital transmission has also been reported [10,11]. There is a definitive lack of new studies or data in the published literature with a four year gap between the two latest publications [16,17]. ...
... Congenital malformation has not been associated with doxycycline use [19,20] but the class effect ascribed to tetracyclines including possible effects on the musculoskeletal development of the fetus [21] and staining of teeth in young children [22] precludes its use. While short courses of doxycycline are probably safe there is insufficient evidence to support their use as first line therapy [5,23]. Macrolide antibiotics such as azithromycin, are safe in pregnancy and reported to be equally effective to doxycycline for the treatment of scrub typhus [24]. ...
... The pooling of data into a single data set includes the aforementioned fever cohort women, additional unpublished cases, and data reported from case reports or case series in 16 different publications [5][6][7]9,10,12,[15][16][17]34] (Supporting Information S1). As the population birth weight percentiles were unknown for these publications, low birth weight (,2500 g) replaced fetal growth restriction in the definition of poor neonatal outcome. ...
Article
Full-text available
There is a paucity of published reports on pregnancy outcome following scrub and murine typhus despite these infections being leading causes of undifferentiated fever in Asia. This study aimed to relate pregnancy outcome with treatment of typhus. Data were analyzed from: i) pregnant women with a diagnosis of scrub and/or murine typhus from a fever cohort studies; ii) case series of published studies in PubMed using the search terms "scrub typhus" (ST), "murine typhus" (MT), "Orientia tsutsugamushi", "Rickettsia tsutsugamushi", "Rickettsia typhi", "rickettsiae", "typhus", or "rickettsiosis"; and "pregnancy", until February 2014 and iii) an unpublished case series. Fever clearance time (FCT) and pregnancy outcome (miscarriage and delivery) were compared to treatment. Poor neonatal outcome was a composite measure for pregnancies sustained to 28 weeks or more of gestation ending in stillbirth, preterm birth, or delivery of a growth restricted or low birth weight newborn. There were 26 women in the fever cohort. MT and ST were clinically indistinguishable apart from two ST patients with eschars. FCTs (median [range] hours) were 25 [16-42] for azithromycin (n = 5), 34 [20-53] for antimalarials (n = 5) and 92 [6-260] for other antibiotics/supportive therapy (n = 16). There were 36.4% (8/22) with a poor neonatal outcome. In 18 years, 97 pregnancies were collated, 82 with known outcomes, including two maternal deaths. Proportions of miscarriage 17.3% (14/81) and poor neonatal outcomes 41.8% (28/67) were high, increasing with longer FCTs (p = 0.050, linear trend). Use of azithromycin was not significantly associated with improved neonatal outcomes (p = 0.610). The published ST and MT world literature amounts to less than 100 pregnancies due to under recognition and under diagnosis. Evidence supporting the most commonly used treatment, azithromycin, is weak. Collaborative, prospective clinical trials in pregnant women are urgently required to reduce the burden of adverse maternal and newborn outcomes and to determine the safety and efficacy of antimicrobial treatment.
... Approximately 14-28% of infected people have evidence of hepatomegaly or splenomegaly, and in severe cases, pulmonary and cardiac compromise can occur [2][3][4][5]. Several case reports and series of murine typhus infec-tion in pregnant women have been published with varying reports of adverse perinatal outcomes, ranging from a mild self-limited disease course to a 40% incidence of preterm birth and low birth weight [6][7][8][9][10][11][12][13][14][15][16][17][18]. This current report would total the number of published cases reported in pregnancy to 100 and is only the second published case report of murine typhus infection during pregnancy in women living in the southwestern region of the United States [6][7][8][9][10][11][12][13][14][15][16][17][18]. ...
... Several case reports and series of murine typhus infec-tion in pregnant women have been published with varying reports of adverse perinatal outcomes, ranging from a mild self-limited disease course to a 40% incidence of preterm birth and low birth weight [6][7][8][9][10][11][12][13][14][15][16][17][18]. This current report would total the number of published cases reported in pregnancy to 100 and is only the second published case report of murine typhus infection during pregnancy in women living in the southwestern region of the United States [6][7][8][9][10][11][12][13][14][15][16][17][18]. Diagnosis in pregnancy is often challenging given the overlap of initial hematologic results with other infectious diseases and critical obstetrical conditions that are more common [3][4][5][6][7][8]. ...
... Laboratory results demonstrate elevated liver enzymes, thrombocytopenia, leukopenia, elevated lactate dehydrogenase, and hypoalbuminemia [4,5]. Significant overlap exists in the symptomatology of this infection with other Rickettsial diseases, viral syndromes, and even critical obstetrical complications such as preeclampsia, where transaminitis and thrombocytopenia are common [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18]. Approximately 25% of infected people may have more severe manifestations of disease including respiratory or renal failure, aseptic meningitis, and shock, requiring aggressive management in the intensive care unit setting [4,5]. ...
Article
Full-text available
Flea-borne (murine) typhus is caused by Rickettsia typhi. Infection in pregnant women can lead to adverse outcomes when diagnosis and treatment is delayed. We describe how next-generation sequencing (NGS) using the Karius® test was used to rapidly diagnose murine typhus in two pregnant women admitted to a large tertiary care center in Houston, Texas, when all initial testing was nondiagnostic. 1. Background Murine typhus is a Rickettsial disease caused by the bacteria Rickettsia typhi (R. typhi) or possibly R. felis and can be transmitted by infected fleas harbored by rats, cats, dogs, and other small mammals [1–5]. In the United States, Texas reports the highest numbers of flea-borne typhus cases annually with the majority of cases occurring in the southern coastal region [2–5]. In 2018, there were 738 reported cases in the state of Texas, representing a 2-fold increase compared to 2016 [1]. Clinical presentation often includes fever, headache, rash, nausea, vomiting, and myalgias accompanied by abnormal hematologic indices including anemia (18–75%), thrombocytopenia (19–48%), elevated aminotransferase levels (38–90%), and an elevated erythrocyte sedimentation rate (59–89%) [3–5]. Approximately 14-28% of infected people have evidence of hepatomegaly or splenomegaly, and in severe cases, pulmonary and cardiac compromise can occur [2–5]. Several case reports and series of murine typhus infection in pregnant women have been published with varying reports of adverse perinatal outcomes, ranging from a mild self-limited disease course to a 40% incidence of preterm birth and low birth weight [6–18]. This current report would total the number of published cases reported in pregnancy to 100 and is only the second published case report of murine typhus infection during pregnancy in women living in the southwestern region of the United States [6–18]. Diagnosis in pregnancy is often challenging given the overlap of initial hematologic results with other infectious diseases and critical obstetrical conditions that are more common [3–8]. In addition, initial serologic titers using indirect immunofluorescence assay (IFA) IgM testing are often inconclusive, as only 50% of patients will have serologic evidence of disease one week after onset of infection [5]. Often, the diagnosis is delayed, as most infected people demonstrate seroconversion two weeks after onset of illness; therefore, repeat testing is recommended [3–7, 19]. A single titer of 1 : 128 is considered diagnostic for infection [3–5]. Similar to other published manuscripts describing this infection during pregnancy, we report two cases presenting with a potentially life-threatening disease course, supporting the need for prompt diagnosis and treatment. Cell-free next-generation sequencing using the Karius® test was used to rapidly diagnose R. typhus in both patients, prompting directed therapy to eradicate infection with doxycycline. The Karius® test, performed in a Clinical Laboratory Improvement Amendments- (CLIA-) licensed, College of American Pathologists- (CAP-) accredited laboratory (Karius Inc., Redwood City, CA), is a test that utilizes next-generation sequencing (NGS) to detect circulating microbial cell-free DNA (mcfDNA) in plasma. Blood plasma from a routine draw is isolated and shipped overnight at ambient temperature to the Karius CLIA/CAP laboratory. Sample-specific controls are added on receipt, and an automated liquid-handling platform performs cfDNA extraction and NGS library preparation [20]. The NGS libraries are multiplexed, inspected for quality, and sequenced. A custom-built analysis pipeline uses a clinical-grade database to identify microbial DNA fragments found in plasma [20]. Pathogens with plasma DNA levels that are significantly higher than real-time background thresholds are listed on the patient report, along with the concentration of the microbial cfDNA in plasma reported as molecules per microliter (MPM). In the largest validation study of this platform, the simulated organism was correctly identified in 121 of 125 simulations for a sensitivity of 97.5%. The positive predictive value (PPV) was 99% (121 of 122), consistent with the expected 95% sensitivity at the level of detection. These findings have been validated with research published in the clinical setting using appropriate comparetors [20–23]. 2. Case Presentation 2.1. Case 1 The patient is a 34-year-old pregnant white female who presented at 31 4/7 weeks gestation to an outside emergency department (ED) with complaints of unrelenting headaches, rash, and a fever of 103.1°F. She was experiencing these symptoms for two days at home. She reported the rash was limited to her trunk and arms, mainly characterized by small red bumps that were nonpruritic. She reported her headache to be mainly frontal and mildly relieved with acetaminophen. She was employed as a veterinarian technician and left work early that day due to her symptoms. She was discharged with an antipyretic and instructed to follow up with her obstetrician. After 24 hours, she represented to the same ED with continued complaints of malaise, fever, and arthralgia. At that visit, her laboratory results demonstrated elevated liver enzymes and thrombocytopenia. The diagnosis of a nonspecific viral syndrome was made, and the patient was discharged to home. On the third day, after the initial presentation to the ED, the patient presented to the obstetrical triage unit with worsening symptoms and a fever of 103.4°F. Results of her blood work at that time revealed elevated liver enzymes, proteinuria, thrombocytopenia, and a significantly decreased white blood count (Table 1). She was transferred to the intensive care unit, and vancomycin, piperacillin/tazobactam, and azithromycin were initiated for broad antimicrobial coverage. Fetal ultrasound revealed an appropriately grown nonanomalous fetus with normal amniotic fluid. Blood and urine cultures along with a respiratory PCR panel for respiratory syncytial virus, adenovirus, influenza A/B, and parainfluenza virus were performed. Serology testing for pathogens including viral hepatitis, syphilis, human immunodeficiency virus, cytomegalovirus, herpes simplex virus, Epstein-Barr virus (EBV), coccidioidomycosis, histoplasmosis, and parvovirus was ordered (Table 1). After 48 hours, all results were negative, including the IFA serologic IgM testing for Rickettsia typhi. On her third hospital stay, she began experiencing dyspnea and desaturations to 88-91%. A chest film was ordered and revealed bilateral opacities in then lower lung fields, and emergent computed tomography (CT) demonstrated similar findings with no evidence of thrombus. An echocardiogram revealed normal cardiac function with an ejection . With impending respiratory failure and continued febrile morbidity, the multidisciplinary team ordered the Karius® test. Twenty-four hours after sample receipt, the test reported the detection of Rickettsia typhi at 147 cfDNA MPM with no other pathogens identified. After a thorough discussion with the patient and her family about risks and benefits, oral doxycycline 100 mg twice daily for 7 days was initiated per the Centers for Disease Control and Prevention recommendations for the treatment of murine typhus and all other antibiotics were discontinued [19]. Within 24 hours, the patient demonstrated symptomatic improvement, her oxygen requirement was improved, and labs began to normalize. The patient required physical therapy and aggressive pulmonary care for several days before she was discharged to home to complete the course of doxycycline. Although preliminarily negative, murine typhus was confirmed with IFA serologic IgM and IgG titer values of >1 : 256 and >1 : 128, respectively, three weeks after admission. Follow-up studies demonstrated clearance of Rickettsia typhi using these standard serologic testing platforms. She delivered a full-term male infant with a reassuring newborn assessment without any complications. Parameter Case 1 Case 2 Age (years) 34 29 Pregnancy details G3P2, 31 3/7 wks GA G1P0, 13 1/7 wks GA Associated conditions Initial suspected diagnosis Viral syndrome Viral syndrome, UTI Fever 103.1 F→103.4 F 102.7 F→102.9 F Septic shock Yes Yes ICU admission Hospital day 3 Hospital day 3 Headache Yes Yes Confusion No No Rash Yes No Myalgia/arthralgia Yes No Malaise Yes Yes Respiratory symptoms Dyspnea, hypoxia Dyspnea, cough GI symptoms Yes No Hepatomegaly/splenomegaly Imaging not performed Hepatomegaly Myocarditis No No Laboratory analysis Hgb (Ref: 9.6-12.4 g/dL) 9 12 WBC (Ref: 6.00-13.32 cells/mm³) 2.5 11.6 %PMNs (Ref: 10.9-76.0%) 33.1 61.4 %Bands 43.7 11.8 Platelet count (10³/μL) (Ref: 244-580 10³/μL) 91 354 Na (Ref: 133-142 mEq/L) 136 135 BUN (Ref: 2–23 mg/dL) 10 13 Cr (Ref: 0.15-0.4 mg/dL) 0.51 0.62 AST (Ref: 20-60 U/L) 651 95 ALT (Ref: 12-45 U/L) 429 146 Alk Phos (Ref: 60-330 U/L) 79 62 Lactate dehydrogenase (313-618 U/L) 860 774 Hematuria Yes No Proteinuria Yes No Lumbar puncture Not performed Not performed Imaging U/S: normal fetus CXR: bibasilar opacities U/S: normal fetus CXR: bibasilar infiltrates Abd U/S: hepatomegaly Karius® test result Rickettsia typhi cfDNA MPM (RR 0 MPM) EBV cfDNA MPM (RR 1.38 MPM) 147 6 242 Rickettsia typhi indirect immunofluorescence assay (IFA) serology IgG and IgM Negative day 3 IgM (<1 : 64) Positive day 28 IgM 1 : 256 IgG 1 : 128 Negative day 3 IgM (<1 : 64) Positive day 10 IgM 1 : 128 IgG 1 : 1024 Blood, throat, stool, urine Cxs Negative Negative Rapid plasma reagin Negative Negative Hepatitis panel serology IgG and IgM Negative Negative Human immunodeficiency virus 1/2 Ag/Ab 4th gen with reflex Negative Negative Herpes simplex virus PCR direct assay Negative Negative Epstein-Barr virus antibody panel IgM and IgG to EBV VCA Negative Positive—EBV VCA VCA IgG 1 : 544 EBNA Cytomegalovirus IgG and IgM Negative Negative Parvovirus IgM Negative Negative Toxoplasma gondii IgG and IgM Negative Negative Coccidioides IgM to DTP antigen Negative Negative QuantiFERON®-TB Negative Negative Histoplasma immunodiffusion of ant M/H Negative Negative Brucella Ab (total) by agglutination Negative Negative Legionella pneumophila urine antigen Negative Negative Coxiella burnetii (Q fever) IgG Negative Negative Empiric antibiotic coverage Vancomycin, piperacillin/tazobactam, azithromycin Vancomycin, meropenem, azithromycin Hospital Day KT ordered 3 2 KT time to diagnosis 1 day from sample receipt 3 days from collection 1 day from sample receipt 2 days from collection Impact of KT on therapy Narrow to doxycycline Narrow to doxycycline Hospital day of doxycycline initiation 4 3 Outcome Full recovery, delivery of a full-term male infant Full recovery, currently 32 wks GA wks = weeks; RP = rapid respiratory panel; CSF = cerebrospinal fluid; Cx = culture. MPM refers to molecules of microbial cell-free DNA/microliter (of a particular pathogen). RR refers to the reference range in MPM of a particular pathogen which is the 97.5%ile of the Karius® test result for that particular pathogen across a cohort of 609 asymptomatic healthy adults. indicates detection under the Karius® test commercial threshold.
... Only few case reports and case series have been published so far. Diagnosis of scrub typhus during pregnancy is the same as in nonpregnant women There has been reports that scrub typhus may lead to spontaneous abortion, stillbirth, preterm delivery and small for gestational age infants but still exact impact in final maternal and fetal outcome is still unclear [4,5]. Doxycycline continues to be the standard therapy for scrub typhus in nonpregnant adults; however, being a class D drug according to the U.S. Food and Drug Administration (FDA), it is contraindicated in pregnant women. ...
... Doxycycline continues to be the standard therapy for scrub typhus in nonpregnant adults; however, being a class D drug according to the U.S. Food and Drug Administration (FDA), it is contraindicated in pregnant women. Azithromycin has been reported to effectively cure scrub typhus in pregnant women and showed favorable pregnancy outcomes [5][6][7]. Till date, no other study based on IgM ELISA from sub-Himalayan region has described the clinical profile and outcome of scrub typhus in pregnant females. ...
... Complication rates were also similar. This is in accordance with other studies [3,5,8] No mortality was found in these patients. ARDS, severe sepsis, MODS, and septic shock were present more in patients presenting in the second trimester. ...
Article
Full-text available
Background Scrub typhus is rare in pregnancy, but it has now become an important cause of febrile illness in pregnancy in sub-Himalayan region of India. Only a few case reports have been published so far, and they show adverse maternal and fetal outcomes. No consensus has been reached till now regarding treatment. Methodology All the pregnant patients irrespective of period of gestation admitted with febrile illness with positive IgM ELISA for scrub typhus with or without eschar were included. The clinical profile was observed using a detailed history of symptoms, travel, recreation, agricultural activities, treatment record prior to admission, and a detailed examination, and the treatment outcome was noted. Fever workup including cultures, CXR, CSF analysis, serology for scrub was done. IgM scrub typhus was done by kit method manufactured by InBios Intertational, Inc. Results We observed in total 14 pregnant patients out of which eight were in the the second trimester and six were in the third trimester. The clinical features of the disease observed for pregnant females were the same as for nonpregnant females. There was no difference in the severity of scrub typhus between pregnant and nonpregnant women. No mortality was found in these patients. On follow-up, they had normal peripartum and postpartum periods. All were treated with azithromycin 500 mg once a day for 5 days. Conclusion Although rare, scrub typhus should be considered in differential diagnosis of fever in pregnant patients especially in scrub season. Azithromycin should be the drug of choice in pregnancy as it has no adverse effect on fetus and pregnancy outcome.
... 4 Scrub typhus is not so common during pregnancy, when present can be associated with adverse maternal and foetal outcomes. 5,6,7 Case Report A 20 year old primigravida at 24 weeks of gestation presented with high grade fever with chills and rigors and shortness of breath for two days. On examination she was febrile (temperature-104 0 F), with tachycardia (pulse rate-130/min) and high respiratory rate (RR-30/min). ...
... 3 In pregnancy, it may be associated with adverse maternal and foetal outcomes. 5,6,7 Early diagnosis and treatment are essential in order to reduce the mortality and the complications associated with the disease. 3 In the present case, both history and examination supported the preliminary diagnosis of Scrub typhus which was confirmed after laboratory investigations. ...
... Pre-term delivery, miscarriages, small for gestational age babies, and neonatal death have been reported in women with scrub typhus infection during pregnancy. [153][154][155][156][157][158] Pregnancy outcomes appear to be better in those who are treated early and appropriately, and there is some evidence to suggest that the choice of antibiotic matters, with azithromycin generally considered the favoured antibiotic in pregnancy. [155][156][157] There are a few reports of vertical transmission of scrub typhus. ...
... [153][154][155][156][157][158] Pregnancy outcomes appear to be better in those who are treated early and appropriately, and there is some evidence to suggest that the choice of antibiotic matters, with azithromycin generally considered the favoured antibiotic in pregnancy. [155][156][157] There are a few reports of vertical transmission of scrub typhus. 159,160 Multi-organ dysfunction syndrome Multi-organ dysfunction syndrome is a commonly reported life threatening complication of scrub typhus. ...
Article
Full-text available
The mite-borne rickettsial zoonosis scrub typhus is widely prevalent in parts of Southeast and Far East Asia, and northern Australia. The disease is an acute febrile illness, associated with rash and often an eschar, which responds dramatically to treatment with antibiotics. In some cases it results in a serious illness leading to multiple organ involvement and death. The disease manifestations are thought to result from a systemic vasculitis, caused by both direct effects of the organisms as well as an exaggerated immune response, although little is understood about its pathogenesis. A wide spectrum of clinical manifestations, affecting nearly every organ system, have been described with scrub typhus. Some of these manifestations are serious and life threatening. In this systematic review, we summarise the typical and atypical manifestations of scrub typhus reported in the literature. Awareness of these unusual manifestations will hopefully guide clinicians towards diagnosing the condition early, and initiating early appropriate antibiotics and other supportive measures.
... 5 However, the exact impact of this infection on fetal outcome is still unclear. 6,7 The mortality rate in untreated individuals can be as high as 30%. 3,4 but we were able to achieve a good foetomaternal outcome in our patient. ...
... 3 Some studies have reported successful treatment with 500 mg single dose. 3,[5][6][7]9 However, our patient required a higher dose of 1 gram per day for a longer duration for her fever to subside. It could be because the diagnosis was delayed in our case by almost two weeks from the onset of symptoms. ...
Article
Full-text available
Scrub typhus is an acute febrile illness rarely diagnosed in pregnancy. Here we report a case of scrub typhus in the third trimester of pregnancy, its associated complications and its management to ensure a favourable fetomaternal outcome. Mrs X, a 22- year old primigravida, was diagnosed with scrub typhus at 38 weeks of pregnancy after developing high- grade fever for 12 days. An atypical eschar was seen on one foot. Her ultrasonography revealed foetal tachycardia and severe oligohydramnios. She was started on tab azithromycin 500 mg OD but remained febrile even after two days. Fever subsided at dose of 1gm/day. When she was afebrile for 48 hours and adequately hydrated, labour was induced and she delivered vaginally a full-term alive baby of 2.2 kg. Vertical transmission was not observed in the baby. Scrub typhus is an easy-to-treat cause of acute undifferentiated febrile illness in the Indian subcontinent, and should always be a differential diagnosis even in the absence of a pathognomic eschar. Timely treatment ensures a favourable fetomaternal outcome.
... Data on pregnancy outcomes in conjunction with a scrub typhus infection are scarce. However, scrub typhus was linked to poor pregnancy outcomes; this was also reported in a fever cohort study in a nearby district [21][22][23]. The number of pregnant women presenting with obstetric complications (e.g., preterm labor or contraction and fetal loss) related to scrub typhus was very high. ...
... Considering these findings, it must be emphasized that pregnant women need special attention. Azithromycin is an alternative that can be safely prescribed during pregnancy [21,24]. If clinical presentation is the only diagnostic tool, empiric treatment should not be delayed if there is suspicion of a scrub typhus infection in a pregnant woman. ...
Article
Full-text available
Introduction: Scrub typhus is endemic in rural Southeast Asia. The district of Umphang in northwestern Thailand is a prototype environment for this disease. We report the clinical manifestations and outcomes of patients diagnosed with scrub typhus in this area. Methodology: Patients diagnosed with scrub typhus between 2011 and 2014 were analyzed. Diagnosis was based on clinical symptoms in conjunction with a positive rapid test or a pathognomonic eschar lesion. Results: A total of 857 patients were included, of which 488 were adults and 369 were children. Most patients (728; 84.9%) were included via a positive serology on rapid test, 86 patients (10.0%) had eschar only, and 43 patients (5.0%) had both sero-confirmation and presence of eschar. The most common symptom was fever (93.8%), followed by headache (48.1%) and cough (33.1%). Eschars were reported in 129 patients, with a significantly higher percentage in children (p < 0.001), and a different anatomical distribution was found when adults and children were compared. Common complications were elevated transaminases, acute kidney injury, and pneumonia. Most patients recovered from the disease. Conclusions: Scrub typhus in Umphang district is common. Patients can present with a variety of clinical symptoms, regardless of the presence of fever. Standard treatment led to a favorable outcome in most patients.
... Azithromycin is an alternative in children, pregnant women and in doxycycline-resistant cases. [9] Therapeutic trial with antibiotic therapy is also preferred, if specific tests are not available and the index of suspicion is high. ...
Article
Full-text available
A. Abstract: Scrub typhus fever is an acute febrile illness caused by an obligate intracellular organism Orientia tsutsugamushi. In many rural areas of Asia, this disease has a great importance in public health. It affects all ages of people and since it is uncommon in pregnant women, it increases foetal mortality and pre-term delivery. The symptoms are mild and clinical course is uneventful. Further complications for this disease are renal failure, respiratory distress, jaundice, myocarditis and thrombocytopenia. Early diagnosis and treatment is essential to reduce mortality and further complications. The authors have reported a 40-year old female patient with scrub typhus who recovered completely with antibiotic treatment of azithromycin and doxycycline.
... When using doxycycline, it is important to choose its dose and duration of treatment carefully. Azithromycin is an FDAapproved drug for use in pregnant women and children (34)(35)(36). It has a better CR and a lower probability of AD. ...
Article
Full-text available
Background To explore the efficacy and safety of drugs in patients with scrub typhus. Methods For this systematic review and network meta-analysis, we searched PubMed, Embase, Web of Science, Cochrane Central Register of Clinical Trials, China National Knowledge Infrastructure (CNKI), and Wanfang data (WF) up to December 2021. All randomized controlled trials (RCTs) of antibiotics used to treat scrub typhus were included without language or date restrictions. The overall effectiveness was evaluated from 4 perspectives: cure rate (CR), defervescence time (DT), gastrointestinal symptoms–adverse events (GS-AD), and abnormal blood count–adverse events (ABC-AD). The quality of evidence was evaluated using the Cochrane Risk of Bias tool and GRADE system. Results Sixteen studies involving 1,582 patients were included to evaluate 7 drugs, namely, azithromycin, doxycycline, chloramphenicol, tetracycline, rifampin, moxifloxacin, and telithromycin. In this network meta-analysis, rifampicin (82%) and chloramphenicol (65%) were more effective in terms of CR, and moxifloxacin (3%) from the quinolone family was the worst. Azithromycin caused the fewest events in terms of ABC-AD. No differences were found in this network meta-analysis (NMA) in terms of DT and GS-AD. Conclusions Rifampicin was associated with the highest CR benefit and the lowest risk of DT when used to treat patients with scrub typhus, except in areas where tuberculosis (TB) was endemic. Azithromycin was found to be better in CR and was associated with a lower probability of GS-AD and ABC-AD; therefore, it may be considered to treat pregnant women and children. Moxifloxacin had a much lower CR than other drugs and is, therefore, not recommended for the management of scrub typhus. Systematic Review Registration https://www.crd.york.ac.uk/PROSPERO/ , identifier: CRD42021287837.
... 5 In pregnant women infected with scrub typhus incidences of increased foetal loss, pre-term delivery and small for gestational age infants are reported. 6 The drug of choice in non-pregnant individuals include oral tetracycline (500mg four times daily) or doxycycline (200mg OD) for seven days. 5 As per United States Food and Drug administration categories of drug safety during pregnancy, tetracyclines come under Category D (evidence of human foetal risks exists but benefit s may outweigh risks in cert ain situations) and hence are contraindicated in pregnant women. Chloramphenicol, a category C drug (animal reproduction studies have shown an adverse effect on the foetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks) is also effective against scrub typhus in both pregnant and nonpregnant women. ...
Article
Full-text available
Scrub typhus is an uncommon cause of acute febrile illness during pregnancy. If not diagnosed early and treated appropriately it can lead to adverse maternal and foetal outcome. We report the case of a 27-year-old woman, gravida 2, para 1, live birth 1, with 29 weeks gestation who presented to the hospital with high grade fever, chills, severe headache and body pains of 9 days duration. The diagnosis of scrub typhus was confirmed by serum immunochromatography. She was successfully treated with azithromycin, and discharged. There were no foetal complicatons.
... The dose of Azithromycin used to treat scrub typhus in pregnancy has varied from a single 500 mg dose to 1-2 g for three to five days. 6 With suboptimal reproductive health services in rural areas, the burden of morbidity and mortality due to scrub typhus is bound to increase among the low-and middle-income countries. Urbanization combined with deforestation in semi-arid regions expose increasing numbers to these vectors and low level of awareness among practitioners may add to the disease burden. ...
Article
Full-text available
Scrub typhus is an important unrecognized cause for undifferentiated acute febrile illness in India associated with poor fetal outcomes. Maternal and fetal outcomes among pregnant patients with scrub typhus presenting to a tertiary care university teaching hospital from January 2010 to July 2012 were studied. Scrub typhus was diagnosed by clinical criteria along with scrub ELISA positivity or an eschar. In total, 33 of 738 patients (4.5%) who were diagnosed with scrub typhus were pregnant; 57.6% were in the third trimester, 27.3% in the second, and only 15.2% in the first trimester; 69.7% required admission to intensive care. Mortality was low (3%, n = 1) compared to 12.2% mortality reported previously. All patients were treated with Azithromycin. Poor fetal outcome was observed in 51.5% of these pregnancies with fetal loss occurring in 42.4% and preterm childbirth in 9.1%. Scrub typhus complicating pregnancy is associated with a poor fetal outcome despite treatment with Azithromycin. A majority require intensive care treatment for survival.
... In recent decades, with the economic development [2], population movement, urbanization [13], climatic changes and the overutilization of natural resources, the epidemic focus is expanding continuously [14]. The incident population have spread from occupational population to general population such as the elderly, children, pregnant women and tourists [2,[15][16][17]. ...
Article
Full-text available
Scrub typhus is an important public health problem in China, especially in Guangzhou city. Typical outbreaks of scrub typhus have been previously reported in rural areas, affecting mainly farmers. We describe an atypical outbreak of the disease with case fatalities, from a park in Haizhu District, Guangzhou, that could turn out to be a potential scrub typhus epidemic site.Methods From May 2012 to June 2012, a case?control study was conducted to identify source and risk factors of this outbreak. Reported cases of scrub typhus in Xiaogang Park were confirmed by Weil?Felix test or a nested polymerase chain reaction (NPCR). Controls were matched with their neighbors by gender and age. Multivariate conditional logistic regression was used to identify risk factors and protective factors.ResultsA total of 29 cases were confirmed by Weil?Felix test, including 4 deaths by both Weil?Felix test and NPCR. All patients presented with fever (100%), while 28 (96.6%) cases had eschars, 10 (34.5%) headache, 10 (34.5%) chills, 6 (20.7%) lymphadenopathy, 5 (17.2%) rash, 2 (6.9%) vomiting and 1 (3.5%) presented with conjunctival congestion. The proportion of cases with activity history in Xiaogang Park was much higher than the control group (72.4% vs 24.1%, P?<?0.001), and morning exercise in park or field was also as a risk factor for scrub typhus (adjusted OR =3.0, 95% CI: 1.1 - 8.2). Four factors were significantly associated with the risk of developing scrub typhus: sitting on the lawn (adjusted OR =8.0, 95% CI: 1.4 - 44.5), close contact with rats (adjusted OR =3.3, 95% CI: 1.2 -9.6), sitting near the rat holes (OR =6.8, 95% CI: 1.2 - 38.1) and wearing long-sleeved clothing when outside (adjusted OR =0.3, 95% CI: 0.1 - 0.7).Conclusions We confirmed an atypical outbreak of scrub typhus in a park in Guangzhou city, which has the potential to develop into an important epidemic site. This public health risk should not be neglected and requires more attention from authorities.
... Therapuetic management of rickettsioses (based on 9,[16][17][18][19][20][21][22][23] ...
... Only 22 cases were reported in the English literature [2]. Though the presence of coinfection of scrub typhus and malaria has been reported in Thai patients with fever, It is also common in India but is apparently grossly underreported [3] scrub typhus is a re-emerging disease in South-East Asia and the South-Western Pacific region with a case fatality rate of up to 30% in untreated cases.To the best of our knowledge there is no case report on anaesthetic management of such patient for LSCS.We report this case due to rarity of this disease in pregnancy. ...
Article
Full-text available
Scrub typhus is a rick ettsial disease that is uncommon during pregnancy, however fetal jeopardy associated with it may necessitate caesarean section. Anaesthetic management of such parturients is not documented in the published medical literature. To the best of our knowledge, we are reporting the first case on the successful anaesthetic management of a parturient who was diagnosed to have a scrub typhus along with co-infection with malaria from the Garhwal region of Uttarakhand state in India, which was previously not known to harbour the vector. She underwent successful elective cesarean section under low dose spinal anaesthesia. The fetal outcome was also excellent without vertical transmission of infection.
... Reducing mortality over a 4-year period was reported in this study. Favourable maternal and fetal outcome may be expected in appropriately managed patients with scrub typhus complicating pregnancy [82] . ...
Article
Full-text available
Scrub typhus infection is an important cause of acute undifferentiated fever in South East Asia. The clinical picture is characterized by sudden onset fever with chills and non-specific symptoms that include headache, myalgia, sweating and vomiting. The presence of an eschar, in about half the patients with proven scrub typhus infection and usually seen in the axilla, groin or inguinal region, is characteristic of scrub typhus. Common laboratory findings are elevated liver transaminases, thrombocytopenia and leukocytosis. About a third of patients admitted to hospital with scrub typhus infection have evidence of organ dysfunction that may include respiratory failure, circulatory shock, mild renal or hepatic dysfunction, central nervous system involvement or hematological abnormalities. Since the symptoms and signs are non-specific and resemble other tropical infections like malaria, enteric fever, dengue or leptospirosis, appropriate laboratory tests are necessary to confirm diagnosis. Serological assays are the mainstay of diagnosis as they are easy to perform; the reference test is the indirect immunofluorescence assay (IFA) for the detection of IgM antibodies. However in clinical practice, the enzyme-linked immuno-sorbent assay is done due to the ease of performing this test and a good sensitivity and sensitivity when compared with the IFA. Paired samples, obtained at least two weeks apart, demonstrating a ≥ 4 fold rise in titre, is necessary for confirmation of serologic diagnosis. The mainstay of treatment is the tetracycline group of antibiotics or chloramphenicol although macrolides are used alternatively. In mild cases, recovery is complete. In severe cases with multi-organ failure, mortality may be as high as 24%.
... Other drugs that have successfully used are azithromycin, clarithromycin and rifampicin. In pregnant women, azithromycin can be safely used (28). A large majority of our patients (96%) were treated with doxycycline 100 mg bid for 12-14 days. ...
Article
Full-text available
Objective: We undertook this study in view of sudden outbreak of acute febrile illness, with associated thrombocytopenia and multiorgan failure, to assess the underlying etiological agent in these cases occurring in the district of Haryana, Northern India. Methods: Adult patients with acute febrile illness who visited out-patient and emergency department, from July to November 2012 were examined. Suspected cases were tested for specific IgM antibodies against Orientia tsutsugamushi. Results: Among 25 seropositive cases, 22 (88%) presented from July to September, while 3 (12%) during October and November. Mostly patients presented with fever (88%), hypotension (40%), maculopapular rash (28%) mostly on face and trunk, eschar (12%) predominantly over lower limbs and pleural effusion (12%). Abnormal liver function tests were seen in the form of elevated transaminases (84%) and serum alkaline phosphatase (72%). Anemia (36%), leukocytosis (32%) and thrombocytopenia (72%) were also detected. Proteinuria was found in 64% of patients while 40% had increased blood urea on presentation. The most common complications were shock in 32% and acute respiratory distress syndrome (ARDS) in 20% of the patients, eventually requiring ventilator support. Patients were treated with doxycycline 100 mg bid for 12-14 days. Three patients could not recover despite the addition of azithromycin and injectable chloramphenicol apart from doxycycline, and succumbed to the illness giving a mortality rate of 12%. Conclusions: Scrub typhus forms one of the most differentials in patients of acute febrile illness presenting with thrombocytopenia, shock, abnormal liver function tests, renal dysfunction, ARDS and multiorgan dysfunction. Measures avoiding direct contact with infected mites and reducing the time of contact of mites with the body coupled with early diagnosis and treatment should be considered to prevent the development of fatal complications.
... Late recognition, delay in initiating antiviral treatment, and the presence of comorbid conditions, such as asthma and diabetes, were found to increase morbidity and mortality (37). Scrub typhus is a zoonosis that is endemic to the Asia-Pacific region (38). It is poorly studied in the Indian subcontinent and its contribution to maternal death remains unmeasured. ...
Article
Full-text available
Objective: Infections significantly contribute to maternal mortality. There is a perceived change in the spectrum of such infections. This study aims to estimate the contribution of various types of infections to maternal mortality. Material and methods: We retrospectively reviewed records of maternal death cases that took place between 2003 and 2012 in the Christian Medical College, Vellore, India. The International Classification of Diseases-Maternal Mortality was used to classify the causes of deaths and World Health Organization near-miss criteria were used to identify organ dysfunction that occurred before death. Infections during pregnancy were divided into three groups, i.e., pregnancy-related infections, pregnancy-unrelated infections, and nosocomial infections. Results: In this study, 32.53% of maternal deaths were because of some type of infection as the primary cause. The contribution of pregnancy-related infections was comparable with that of pregnancy-unrelated infections (16.03% vs. 16.50%). Metritis with pelvic cellulitis, septic abortions, tuberculosis, malaria, scrub typhus, and H1N1 influenza (influenza A virus subtype) were among the most commonly encountered causes of maternal death due to infections. Another 7.07% of cases developed severe systemic infection during the course of illness as nosocomial infection. A significant majority of mothers were below 30 years of age, were primiparae, had advanced gestational age, and had operative delivery. Cardiovascular and respiratory system dysfunctions were the most common organ dysfunctions encountered. Conclusion: The contribution of pregnancy-unrelated infections to maternal deaths is significant. Control of these diverse community-acquired infections holds the key to a reduction in maternal mortality along with the promotion of clean birthing practices. Nosocomial infections should not be underestimated as a contributor to maternal mortality.
... It is noteworthy that both the spotted fever group rickettsioses and scrub typhus can include an inoculation eschar at the bite site, adding an additional challenge to differential diagnosis. The drug of choice for the treatment of diseases within the order Rickettsiales is doxycycline (tetracycline, chloramphenicol, and azithromycin have also been used successfully) [74][75][76][77]; however, the emergence of antibiotic-resistant strains of O. tsutsugamushi is of current/future concern [78]. Additionally, there are no long-lasting, broadly-protective vaccines available against scrub typhus (or the rickettsial diseases), despite a long, rich history of research attempts (killed, live, attenuated, subunit vaccines) aimed at the successful development of such [79]. ...
Article
Full-text available
Scrub typhus and the rickettsial diseases represent some of the oldest recognized vector-transmitted diseases, fraught with a rich historical aspect, particularly as applied to military/wartime situations. The vectors of Orientia tsutsugamushi were once thought to be confined to an area designated as the Tsutsugamushi Triangle. However, recent reports of scrub typhus caused by Orientia species other than O. tsutsugamushi well beyond the limits of the Tsutsugamushi Triangle have triggered concerns about the worldwide presence of scrub typhus. It is not known whether the vectors of O. tsutsugamushi will be the same for the new Orientia species, and this should be a consideration during outbreak/surveillance investigations. Additionally, concerns surrounding the antibiotic resistance of O. tsutsugamushi have led to considerations for the amendment of treatment protocols, and the need for enhanced public health awareness in both the civilian and medical professional communities. In this review, we discuss the history, outbreaks, antibiotic resistance, and burgeoning genomic advances associated with one of the world’s oldest recognized vector-borne pathogens, O. tsutsugamushi.
... All patients responded well to the treatment and no relapses were reported. Finally pregnancy showed good maternal and fetal outcome [15]. ...
Article
Full-text available
Scrub typhus is endemic and re-emerging in eastern and southern Asia. Illness varies from mild and self-limiting to fatal. Only few studies were published about its effect in maternal and neonatal outcome. A retrospective analysis was done in six prenatal and two postnatal women with scrub typhus. Details about clinical presentation, investigations, treatment given, response to treatment and pregnancy outcome were collected. The common symptoms were fever with chills, vomiting, myalgia, headache and abdominal pain. Typical features of eschar and lymphadenopathy were noted in only two cases. Two patients presented with jaundice and altered liver function test. Two patients presented with breathlessness. One patient developed oligohydramnios. Two postnatal women developed scrub typhus following blood transfusion for postpartum haemorrhage. Because of its high prevalence, scrub typhus should be included in fever investigations in endemic areas, even in the absence of eschar. Early diagnosis of cases will help in less severe organ damage and easy recovery with antibiotics. Few evidences state that scrub typhus can spread through blood transfusion. Correlation between blood transfusion and scrub typhus has to be further evaluated.
... An eschar at the site of chigger feeding is a classic clinical feature of scrub typhus; however, the spotted fever group of rickettsioses can also include an inoculation eschar at the bite site, adding an additional challenge during differential diagnosis [1]. The drug of choice for the treatment of scrub typhus is doxycycline (tetracycline, chloramphenicol, and azithromycin have also been used successfully) [6][7][8]; however, the emergence of antibiotic-resistant strains of O. tsutsugamushi is of concern [9]. Additionally, there are no long-lasting, broadly protective vaccines available against scrub typhus [10]. ...
Article
Full-text available
Background The emergence and re-emergence of scrub typhus has been reported in the past decade in many global regions. In this study, we aim to identify potential scrub typhus infection risk zones with high spatial resolution in Qingdao city, in which scrub typhus is endemic, to guide local prevention and control strategies. Methodology/Principal findings Scrub typhus cases in Qingdao city during 2006–2018 were retrieved from the Chinese National Infectious Diseases Reporting System. We divided Qingdao city into 1,101 gridded squares and classified them into two categories: areas with and without recorded scrub typhus cases. A boosted regression tree model was used to explore environmental and socioeconomic covariates associated with scrub typhus occurrence and predict the risk of scrub typhus infection across the whole area of Qingdao city. A total of 989 scrub typhus cases were reported in Qingdao from 2006–2018, with most cases located in rural and suburban areas. The predicted risk map generated by the boosted regression tree models indicated that the highest infection risk areas were mainly concentrated in the mid-east and northeast regions of Qingdao, with gross domestic product (20.9%±1.8% standard error) and annual cumulative precipitation (20.3%±1.1%) contributing the most to the variation in the models. By using a threshold environmental suitability value of 0.26, we identified 757 squares (68.7% of the total) with a favourable environment for scrub typhus infection; 66.2% (501/757) of the squares had not yet recorded cases. It is estimated that 6.32 million people (72.5% of the total population) reside in areas with a high risk of scrub typhus infection. Conclusions/Significance Many locations in Qingdao city with no recorded scrub typhus cases were identified as being at risk for scrub typhus occurrence. In these at-risk areas, awareness and capacity for case diagnosis and treatment should be enhanced in the local medical service institutes.
... A few clinical studies have shown that azithromycin is as effective as doxycycline for the treatment of mild to moderate scrub typhus (5)(6)(7). For this reason, azithromycin is considered an appropriate alternative for mild to moderate scrub typhus in areas where doxycycline-resistant scrub typhus is prevalent (8), and also for children under 8 years of age or in women during pregnancy (9), where doxycycline is contraindicated. However, there are few clinical data on the efficacy of different antibiotics for the treatment of severe, life-threatening scrub typhus (10), despite the fact that complicated cases of scrub typhus are not uncommon (11)(12)(13). ...
Article
Full-text available
There are no well-matched, controlled studies comparing azithromycin with doxycycline for the treatment of complicated scrub typhus. A retrospective propensity score-matched case-control study was performed for patients who presented with complicated scrub typhus and were treated with doxycycline or azithromycin between 2001 and 2011. Data on comorbidities, clinical manifestations, laboratory studies, treatments, and outcomes were extracted for analysis. The clinical characteristics and outcomes of the azithromycin-treated group (n = 73) were compared to those of the doxycycline-treated group (n = 108). Of 181 patients, 73 from each group were matched by propensity scores. There were no significant differences in baseline characteristics between the matched groups. The treatment success and survival rates were not significantly different (89% [65/73 patients] versus 96% [70/73 patients] and 96% [70/73 patients] versus 96% [70/73 patients], respectively [P > 0.05]). No difference was observed in the time to defervescence or length of hospital stay between the two groups (P > 0.05). In complicated scrub typhus patients (n = 181), multivariate analysis showed that only APACHE II score was an independent risk factor for mortality (95% confidence interval, 1.11 to 1.56; P < 0.001). Our data suggest that outcomes of azithromycin therapy are comparable to those of doxycycline therapy in patients with complicated scrub typhus.
... [9,10] When contracted during pregnancy, it may lead to adverse feto-maternal outcomes like preterm labor, small for gestational age baby, increased fetal loss, increased maternal mortality due to sepsis, multiorgan dysfunction, etc., up to 50% of the patients. [12][13][14] Our case report highlights the need to consider the diagnosis of scrub typhus in pregnant women with unexplained fever especially since the disease is quite common in India. The other important point to note is that timely and appropriate management of this patient was delayed due to the ongoing COVID-19 crises since her clinical presentation overlapped with COVID-19 features closely. ...
Article
Full-text available
Coronavirus disease 2019 (COVID-19) pandemic has emerged as the major public health threat in recent times. Although associated with high morbidity and mortality affecting all age groups across populations, “pregnant women” represent a subgroup that needs extra surveillance. We present the case of a primigravida in her advanced pregnancy presenting with acute febrile illness with flu-like symptoms. The clinico-radiological picture was suspicious for COVID-19; however, she tested negative for COVID-19 on two occasions. On further investigations, she tested positive for Scrub typhus (IgM-ELISA) and responded to treatment with doxycycline. However, due to the ongoing COVID-19 pandemic, much time was lost before suspecting and reaching the final diagnosis. Therefore, the patient had to suffer due to delayed medical intervention and intrauterine fetal death. Despite the unprecedented rise of COVID-19 in pregnant women in recent times, we should not forget about other tropical illnesses, which can mimic COVID-19 in clinical presentation and affect feto-maternal outcomes adversely.
... In endemic areas, the risk of infection is mainly associated with farming and outdoor activities, posing a high disease burden (Park et al., 2015;Wangrangsimakul et al., 2020). Human scrub typhus incidence is not only reported from occupational-related groups such as farmers in the countryside but also occurred in the others such as the elderly, children, pregnant women, tourists and even in the urban population (Kim et al., 2006;Wei et al., 2014;Weitzel et al., 2018). In Bangkok, a rapid increase in population, capital investment and employment has expanded the city to surrounding areas. ...
Article
Full-text available
Chiggers are recognized as vectors of scrub typhus disease caused by the bacteria, Orientia tsutsugamushi. The risk of disease exposure is mainly related to chigger bites when humans or animals roam into vector-infested habitats. In big cities, urban public parks could provide areas for the animal-human interface and zoonotic pathogen transmission. The ecology and epidemiology of urban scrub typhus are still poorly understood in Thailand. Small mammals were trapped and examined for chigger infestation in urban public parks across metropolitan Bangkok, Thailand. We found a high prevalence of infestation (76.8%) with surprisingly low diversity. Two chigger species, Leptotrombidium deliense and Ascoschoengastia indica, were identified using morphological characteristics and molecular confirmation. The generalized linear model identified host intrinsic variables (i.e. body mass index) with host density, habitat composition and open field as the extrinsic factors explaining the abundance of chigger infestation. The bacteria O. tsutsugamushi was not detected in chiggers (90 chigger-pooled samples) and animal host tissues (164 spleen samples). However, the existence of chigger vectors calls for the Bangkok Metropolitan Administration and public health authorities to develop a comprehensive scrub typhus monitoring and prevention strategy in the parks and nearby communities.
... It can be associated with constitutional symptoms like headache, fatigue and generalised body pains. 2 Fever in pregnancy has been associated with adverse outcomes. 3 Hence early diagnosis and management can prevent the same. An acute rise in body temperature usually occurs when there is an in increase in hormone levels of adrenocorticotrophic hormone, growth hormone and in increase in neutrophils, muscle proteolysis and lipogenesis. ...
Article
BACKGROUND This study was conducted to evaluate the maternal and fetal outcome of fever in pregnancy. METHODS The present study was a prospective observational study conducted from April 2012 – March 2014 among patients in the Department of Obstetrics and Gynaecology, Sri Ramachandra Institute of Higher Education and Research Institute, and they were followed up to the time of delivery to determine the maternal and foetal outcome. This is a prospective study and sample size was 120 patients. All patients admitted with fever irrespective of the gestational age and parity were included in the study. The ethical committee of Ramachandra Medical College and Hospital approved the study. Reference CSP-MED / 13 / AUG / 08 / 47. RESULTS Fever in pregnancy nearing term has been associated with adverse outcomes. Even elevated temperature in the first trimester can lead to fetal loss. Urinary tract infection was the most common infection during pregnancy. E. coli was the most common organism isolated. Other aetiologies encountered were dengue, malaria, scrub typhus, leptospirosis, enteric fever, H1N1, Influenza A viral fever, respiratory tract infections, and chicken pox. The most frequently seen adverse outcome in this study was abortion. There was one maternal mortality due to H1N1 and one neonatal mortality due to dengue haemorrhagic fever which was transmitted to the fetus. There was one fetus with multiple anomalies and the mother had a history of chicken pox in the first trimester. There were 15 cases of premature rupture of membrane and 12 cases had preterm labour. Intrapartum fever was associated with postpartum haemorrhage and meconium-stained liquor in some mothers. CONCLUSIONS Fever during pregnancy can potentially lead to adverse maternal and perinatal outcomes even at a low-grade temperature of a short duration of less than a week. Even elevated temperature in the first trimester can lead to fetal loss. Fever in pregnancy nearing term has been associated with adverse perinatal outcomes. Some virulent organisms can lead to fetal anomalies and maternal death. KEY WORDS Fever in Pregnancy, Maternal Outcome, Foetal Outcome
... Although cases of resistance have been reported and are potentially increasing (20,21), AZ has been shown to be effective for eradicating intrauterine U. parvum infection in nonhuman primates (22), with a MIC of 0.5 to 4 g/ml (23). AZ has been used extensively in pregnancy to treat a host of infections, including chlamydia (24), scrub typhus (25), and malaria (as part of combination therapy) (26). AZ is a readily available generic drug with an excellent safety profile; cases of hepatotoxicity are quite rare (27), and the small risk of Q-T interval prolongation identified in highrisk patients (28) is not significant in young or middle-aged individuals (29), the demographics into which most pregnant women fall. ...
Article
Full-text available
Intrauterine infection with Ureaplasma spp. is strongly associated with preterm birth and adverse neonatal outcomes. We assessed whether combined intra-amniotic (IA) and maternal intravenous (IV) treatment with one of two candidate antibiotics, azithromycin (AZ) or solithromycin (SOLI), would eradicate intrauterine Ureaplasma parvum (UP) infection in a sheep model of pregnancy.
... Azithromycine, is classified in category B by the US Food and Drug Administration (US FDA) Pregnanancy Category and is the suggested alternative drug in these patients and young children under 8 years-old [5]. Routine ECG, serum level of electrolytes, liver and renal function should be carefully checked in the patients of ST treated with azithromycin that prolong QT intervals. ...
... Furthermore, Orientia spp. are sensitive to antibiotics including doxycycline and azithromycin [14,15]. ...
Article
Full-text available
Scrub typhus is an important arthropod-borne disease causing significant acute febrile illness by infection with Orientia spp. Using a risk-based approach, this review examines current practice, the evidence base and regulatory requirements regarding matters of biosafety and biosecurity, and presents the case for reclassification from Risk Group 3 to Risk Group 2 along with recommendations for safe working practices of risk-based activities during the manipulation of Orientia spp. in the laboratory. We recommend to reclassify Orientia spp. to Risk Group 2 based on the classification for RG2 pathogens as being moderate individual risk, low community risk. We recommend that low risk activities, can be performed within a biological safety cabinet located in a Biosafety Level (BSL) 2 core laboratory using standard personal protective equipment. But when the risk assessment indicates, such as high concentration and volume, or aerosol generation, then a higher biocontainment level is warranted. For, the majority of animal activities involving Orientia spp., Animal BSL 2 (ABSL2) is recommended however where high risk activities are performed including necropsies, Animal BSL (ABSL3) is recommended.
... However, this antibiotic is generally not recommended for the following conditions: pregnancy, young children, inability to take oral medicine, and doxycycline resistance. The use of doxycycline for several days in pregnant women and children does not cause major problems, but macrolide antibiotics are safe even in this case, and therefore it can be a safe alternative [48,49]. Moreover, azithromycin has an injectable form and thus can be used in people who have difficulty in oral administration. ...
Article
Full-text available
Tsutsugamushi disease or scrub typhus in Korea was first officially reported in foreign soldiers in 1951 and in indigenous persons in 1986. However, the history is further prolonged. The book Dong Ui Bo Gam, published in 1613, described “Soo Dok” (water poisoning), which is similar to tsutsugamushi disease. Further, the term was mentioned in the book Hyang Yak Gu Geup Bang, first published in 1232–1251. During the Japanese colonial rule (1910-1945), Trombicula akamushi was identified in Suwon, Korea, in 1917. Although cases of tsutsugamushi disease in Korea with a murine typhus-like illness and OXK-positivity were reported in 1935, such atypical presentation was not recognized as tsutsugamushi disease. During the Korean War, in 1951, tsutsugamushi disease developed in two British soldiers stationed in the Imjin River, who presented typical features and positive OXK reactions. Indigenous cases have re-emerged since 1986. Thereafter, there were many studies on various aspects of tsutsugamushi disease: epidemiology, vector, small mammals, clinical features and complications, diagnosis, and treatment. Persistence of Orientia tsutsugamushi and its possible recrudescence with pneumonia were reported in 2012 and 2014, respectively.
... As with all human pathogens, culture of Orientia spp or Rickettsia spp in vitro or in vivo carries the intrinsic hazard of infection of laboratory and ancillary staff (known as laboratory-acquired infections [LAIs]) via parental inoculation by accidental self-inoculation or needle-stick incident, animal bite, or inhalation of infectious aerosols generated during laboratory procedures or incidents [21][22][23][24]. Importantly, Orientia spp and Rickettsia spp are susceptible to antibiotic therapy with doxycycline as first-line treatment, and azithromycin as an alternative treatment such as in the case of infections during pregnancy [25,26] although there have been treatment failures with azithromycin in murine typhus (Newton et al [27]). ...
Article
Full-text available
This study examined the literature on laboratory-acquired infections (LAIs) associated with scrub typhus (Orientia tsutsugamushi) and murine typhus (Rickettsia typhi) research to provide an evidence base for biosafety and biocontainment. Scrub typhus LAIs were documented in 25 individuals, from 1931-2000 with 8 (32%) deaths during the pre-antibiotic era. There were 35 murine typhus LAI reports and no deaths. Results indicated that highest risk activities were working with infectious laboratory animals involving significant aerosol exposures, accidental self-inoculation or bite related infections. A risk-based biosafety approach for in vitro and in vivo culture of O. tsutsugamushi and R. typhi would require only high-risk activities (animal work or large culture volumes) be performed in high containment BSL3 laboratories. We argue that relatively low risk activities including inoculation of cell cultures or the early stages of in vitro growth using low volumes/low concentrations of infectious materials can be performed safely in BSL2 laboratories within a biological safety cabinet.
Article
Arthropod-borne bacterial diseases affect more than 25,000 Americans every year and thousands more around the world. These infections present a diagnostic dilemma for clinicians because they mimic many other pathologic conditions and are often low on or absent from the differential diagnosis list. Diagnosis is particularly challenging during pregnancy, as these infections may mimic common pregnancy-specific conditions, such as typical and atypical preeclampsia, or symptoms of pregnancy itself. Concerns regarding the safety in pregnancy of some indicated antibiotics add a therapeutic challenge for the prescriber, requiring knowledge of alternative therapeutic options for many arthropod-borne bacterial diseases. Physicians, especially those in endemic areas, must keep this class of infections in mind, particularly when the presentation does not appear classic for more commonly seen conditions. This article discusses presentation, diagnosis, and treatment of the most common of these arthropod-borne bacterial diseases, including Lyme disease, Rocky Mountain spotted fever, tick-borne relapsing fever, typhus, plague, cat-scratch disease, and Carrión disease.
Article
Full-text available
Treatment of intrauterine infection is likely key to preventing a significant proportion of preterm deliveries before 32 weeks' gestation. Azithromycin (AZ) may be an effective antimicrobial in pregnancy; however, few gestation-appropriate data are available to inform the design of AZ-based treatment regimens in early pregnancy. We aimed to determine whether a single intraamniotic AZ dose, or repeated maternal IV AZ doses, would safely yield therapeutic levels of AZ in an 80 d gestation (term=150 d) ovine fetus.
Article
Full-text available
Pregnancy is a state of double danger i.e. any drug that a pregnant woman takes can easily cross placenta and can produce a teratogenic effects on fetus. It can interfere with normal embryonic or fetal development and induce abnormal post natal structure or function. Teratogens alter the genetic function of fetus. This review provides practitioners with summary of information regarding teratology risks for drugs, chemical exposure during pregnancy. INTRODUCTION: Pregnancy is the term used to describe when a woman has a growing fetus inside of her. In most cases, the fetus grows in the uterus. Human pregnancy lasts about 40 weeks or just more than 9 months, from the start of the last menstrual period to childbirth. Each pregnancy is divided into three trimesters. These three trimesters have different emotional and physical happenings that make them unique.
Article
Rickettsioses (also called typhus) are associated with arthropods, including ticks, mites, fleas, and lice, although Q fever is acquired through the inhalation of contaminated aerosols or the consumption of milk. These zoonoses first emerged in the field of travel medicine 20 years ago. Here, we review rickettsioses and Q fever in travelers, highlighting cases reported in the past decade. African tick bite fever and Mediterranean spotted fever are the two most frequent spotted fevers. While the presentation of these fevers is typically benign, cardiac and neurological complications due to African tick bite fever have been reported, and Mediterranean spotted fever has been complicated by multi-organ failure and death in a few cases. Murine typhus and Q fever remain difficult to recognize and diagnose because these illnesses often present with only fever. New molecular tools, particularly when deployed with samples obtained from eschar swabs, might be easily implemented in laboratories with PCR facilities. Doxycycline must be introduced upon clinical suspicion of rickettsioses or Q fever and should be considered in cases of fever of unknown origin in travelers who are returning from at-risk geographic areas.
Article
Purpose: To detect and identify the aetiological agent in the peripheral blood from the cases of neonatal sepsis. Materials and methods: Four neonates from geographically different regions of South India presented with signs of neonatal sepsis and all the routine clinical and laboratory investigations were performed. Blood culture by Bac T Alert 3D was negative. To establish the aetiology, polymerase chain reaction (PCR) for eubacterial genome and subsequent amplification with Gram positive and Gram negative primers were performed followed by deoxyribonucleic acid (DNA) sequencing. Results: PCR for the detection of eubacterial genome was positive in all the four neonates and further amplification with designed Gram positive and Gram negative primers revealed the presence of Gram negative bacteria. The amplicons were identified as Orientia tsutsugamushi in three neonates and Coxiella burnetti in the other neonate. Multalin analysis was done to further characterise the strain variation among the three strains. Conclusion: PCR-based DNA sequencing is a rapid and reliable diagnostic tool to identify the aetiological agents of neonatal sepsis. This is the first case series of emerging Rickettsial neonatal sepsis in India .
Article
抄録 日本紅斑熱とツツガムシ病はともにダニ類を介して発症するリケッチア感染症であり,両者とも発熱,皮疹,肝障害を呈するなど類似点の多い疾患である。我々は同時期に発症した日本紅斑熱とツツガムシ病の各1例を経験したので,臨床的相違点を主眼に症例報告を行う。症例1:59歳,女。2009年7月末より微熱と倦怠感あり。8月上旬より39℃台の発熱と手掌を含む全身に淡紅色の小型の紅斑が出現した。右背部に,中央に壊死を伴う小豆大の丘疹あり。血液検査では血小板減少と肝・腎機能障害を認めた。表在リンパ節は触知しなかった。臨床所見より日本紅斑熱を疑い,ミノサイクリンおよびレボフロキサシンを投与した。血清中の特異的抗体価は初診時に比べ,2週間後のペア血清でIgGとIgMの上昇を認め,日本紅斑熱と診断した。症例2:59歳,男。2009年7月末より38℃台の発熱があった。8月上旬に全身の紅斑が出現した。左背部に,周囲に発赤を伴う爪甲大の黒色壊死あり。表在リンパ節はすべて腫大しており,CT画像では縦隔,腹部など全身にリンパ節腫大を認めた。臨床所見よりツツガムシ病を疑い,ミノサイクリンを投与した。血清抗体は初診時採血でKato,Karp,およびGilliam株のIgMの上昇を認め,ツツガムシ病と診断した。2症例とも比較的典型例であり,刺し口の大きさや手掌の紅斑,全身性リンパ節腫大の有無で両疾患の鑑別が可能であった。
Chapter
Full-text available
Viral hemorrhagic fevers (VHFs) are a group of etiologically diverse viral diseases unified by common underlying pathophysiology. VHFs describe a severe febrile syndrome with multisystem organ involvement. Characteristically the vascular system is damaged with attendant impairment of the body’s ability to regulate itself leading to vascular instability and decreased integrity. Damage to the microvasculature, generally in accompaniment of reduced platelet function, results in its disruption and local hemorrhage. Bleeding is common and is generally a manifestation of the widespread vascular damage. Life threatening loss of blood volume is rare.
Article
ABSTRACT Rickettsial diseases and scrub typhus constitute a group of the oldest known vector-borne diseases. The cosmopolitan distribution of the vectors that transmit rickettsiae and orientiae leads to a worldwide prevalence of these diseases. Despite their significant historical status, detection and diagnosis of these diseases are still evolving today. Serological methods remain among the most prevalent techniques used for the detection/diagnosis of rickettsial diseases and scrub typhus. Molecular techniques have been instrumental in increasing the sensitivity/specificity of diagnosis, identifying new Rickettsia and Orientia species and have enhanced epidemiological capabilities when used in combination with serological methods. In this review, we discuss these techniques and their associated pros and cons.
Article
Six cases of scrub typhus (tsutsugamushi disease) were reported to the Shizuoka Prefecture Hamamatsu City public health center during the seven years from 2001 to 2007. The content of the clinical record of the five cases were investigated. High serum titers of antibody to Gilliam-type Orientia tsutsugamushi were detected by immunofluorescense assay in most of these patients. Fever, rash, headache and relative bradycardia seen at a high frequency. On peripheral blood smear examination, atypical lymphocytes were detected in 3 cases. Serum electrolyte examination revealed hyponatremia in 4 (80%) patients; SIADH was suspected in one of these cases. All the patients improved promptly following start of therapy with intravenous or oral minocycline.
Chapter
The obligate intracellular bacterium Orientia tsutsugamushi is responsible for more than one million cases of scrub typhus annually throughout the Asia-Pacific region. Human infection occurs via the bite of the larval form (chigger) of several species of trombiculid mites. While in some patients the result of infection is a mild, febrile illness, others experience severe complications, which may even be fatal. This review discusses the genome and biology of the causative agent, the changing epidemiology of scrub typhus, the challenges of its diagnosis, and current treatment recommendations.
Article
Background: Scrub typhus is a zoonotic disease that remains an important health threat in endemic areas. Appropriate anti-rickettsial treatment ensures a successful recovery. Doxycycline is a recommended drug, but it is contraindicated in pregnant women and young children. Azithromycin is a safer alternative drug, but its effectiveness remains largely unclear. Herein, we conducted a systematic review and meta-analysis to determine the effectiveness of azithromycin. Methods: Studies that investigated azithromycin in treating scrub typhus were systematically identified from electronic databases up to December 2016. Information regarding study population, disease severity, treatment protocols, and responses was extracted and analyzed. Results: In this review, 5 studies were included, which comprised a total of 427 patients. When comparing the treatment failure rate, we observed a favorable outcome in patients treated with azithromycin (risk ratio [RR] 0.83, 95% confidence interval [CI] 0.23-2.98). However, patients in the azithromycin group had longer time to defervescence (mean difference 4.38 hours, 95% CI -2.51 to 11.27) and higher rate of fever for more than 48 hours (RR 1.31, 95% CI 0.81-2.12). Moreover, patients treated with azithromycin had less adverse effects (RR 0.8, 95% CI 0.42-1.52). Conclusions: Azithromycin is as effective as other anti-rickettsial drugs with higher treatment success rates, lower frequency of adverse effects, and longer time to defervescence (GRADE 2B). Therefore, it is reasonable to use azithromycin as the first-line treatment against scrub typhus. Further studies are warranted to elucidate the effectiveness of azithromycin in specific patient groups, at high dose and influence of drug resistance.
Article
Background: Scrub typhus, an emerging rickettsial disease caused by Orientia tsutsugamushi, is a clinically important endemic disease on Taiwan. Methods: From January 1, 2007, to December 31, 2013, 156 patients diagnosed with scrub typhus were admitted to Taitung MacKay Memorial Hospital. Demographic data, clinical features, laboratory results, and outcomes of patients were retrospectively analyzed. Results: Among 156 cases, 150 survived (96%) and six died (4%). There were 111 males (71%) and 45 females (29%) with a mean age of 47.8 years. The most common clinical features were fever (100%), general malaise (77%), chill (74%), headache (59%), and eschar (55%). No seasonal pattern was observed, with peaks in November and January. The average time to defervescence after appropriate antibiotics for the 150 surviving patients was 2.45 days. The significant risk factors were a delay of initial appropriate antibiotics use within 24 hrs, increased C-reactive protein (CRP), and liver cirrhosis. Conclusion: Scrub typhus, a growing and emerging disease, is considered in the differential diagnosis of fever of unknown origin, and its diagnosis may be missed if it is not considered owing to its nonspecific clinical presentation. It is important to have a high index of suspicion and to increase awareness in endemic areas. Prompt diagnosis and early treatment with appropriate antibiotics are vital.
Chapter
Infectious dermatoses are the major burden of skin diseases prevalent in tropics. Some fungal, protozoal, and helminthic infestations are exclusively seen in tropical regions. Endemic pemphigus and few nutritional deficiencies account for majority of noninfectious tropical dermatoses. Basically, the climatic conditions and inhabiting human’s culture and behavior are the chief attributable factors in acquiring and perpetuation of these diseases. Besides, migration and/or tourism further augment the risk of dissemination of tropical skin diseases to other regions of the world.
Article
Full-text available
Scrub typhus is an infectious disease caused by Orientia tsutsugamushi, carried by mites. It is endemic in Southeast Asia, including India, Pakistan, and Sri Lanka. It has a broad spectrum of clinical manifestations ranging from sub-clinical disease to organ failure to fatal disease. We are reporting the case of a 22yr old primigravida at 33 weeks of gestation with acute febrile illness, burning micturition, breathlessness, raised bilirubin and hepatomegaly which lead to a diagnostic dilemma between pyelonephritis and scrub typhus. After her evaluation, acute pyelonephritis with the features of sepsis with scrub typhus infection was found. The characteristic eschar of scrub typhus was absent in our patient. IgM antibody for scrub typhus came positive in our case. Azithromycin, a macrolide, is the drug of choice for treatment in pregnant women owing to its safety prole and our patient too responded well to 5 days treatment of 500 mg of Azithromycin
Article
Full-text available
Ecology and epidemiology. Scrub typhus is a life-threatening infectious disease that presents as an acute undifferentiated febrile illness. Its agent, Orientia tsutsugamushi, is an obligately intracytosolic bacterium that is transmitted by feeding larval trombiculid mites, which are the reservoir of the agent and the only life stage that feeds on a vertebrate host.
Article
Full-text available
A nurse experience a needlestick during the care of a patient with scrub typhus, treated with pefloxacin (400 mg twice daily) and cefazolin. Seven days after the needlestick, pain and erythematous swelling developed at the tip of her left fourth finger, the site of the needlestick. Fever and headache developed 10 days later, and her skin lesion became a small vesicle surrounded by a dark erythematous area. The diagnosis of scrub typhus was made by a rising indirect immunofluorescent antibody titre, and her illness was improved with doxycycline.
Article
Full-text available
Concerns regarding the teratogenicity of fluoroquinolones have resulted in their restricted use during gestation. This is despite an increasing need for their use due to emerging bacterial resistance. The objectives of the present investigation were to evaluate pregnancy and fetal outcomes following maternal exposure to fluoroquinolones and to examine whether in utero exposure to quinolones is associated with clinically significant musculoskeletal dysfunctions. We prospectively enrolled and followed up 200 women exposed to fluoroquinolones (norfloxacin, ciprofloxacin, ofloxacin) during gestation. Pregnancy outcome was compared with that for 200 controls matched for age and for smoking and alcohol consumption habits. Controls were exposed to nonteratogenic, nonembryotoxic antimicrobial agents matched by indication, duration of therapy (+/- 3 days), and trimester of exposure. Rates of major congenital malformations did not differ between the group exposed to quinolones in the first trimester (2.2%) and the control group (2.6%) (relative risk, 0.85; 95% confidence interval, 0.21 to 3.49). Women treated with quinolones had a tendency for an increased rate of therapeutic abortions compared with the rate among women exposed to nonteratogens (relative risk, 4.50; 95% confidence interval, 0.98 to 20.57), resulting in lower live-birth rates (86 versus 94%; P = 0.02). The rates of spontaneous abortions, fetal distress, and prematurity and the birth weight did not differ between the groups. Gross motor developmental milestone achievements did not differ between the children of the mothers in the two groups. We concluded that the use of fluoroquinolones during embryogenesis is not associated with an increased risk of major malformations. There were no clinically significant musculoskeletal dysfunctions in children exposed to fluoroquinolones in utero. The higher rate of therapeutic abortions observed in quinolone-exposed women compared to that for their controls may be secondary to the misperception of a major risk related to quinolone use during pregnancy.
Article
Full-text available
Azithromycin was given to mice and humans infected with strains of Orientia tsutsugamushi from northern Thailand, where drug-resistant scrub typhus occurs. Azithromycin and doxycycline yielded comparable mouse survival rates (73 and 79%, respectively; P > 0.5). Symptoms, signs, and fever in two pregnant women abated rapidly with azithromycin. Prospective human trials are needed.
Article
Full-text available
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.
Article
Full-text available
Scrub typhus, caused by Orientia tsutsugamushi, is a rural is 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.
Article
Scrub typhus is still prevalent on Penghu Islands. We herein report a case in a pregnant woman who had been to Yi-Lan County in Taiwan. The patient responded well to Minocycline (Minocin) therapy without complication. Her newborn baby was found not complicated with the disease. The relative literature is reviewed.
Article
Scrub typhus called tsutsugamushi disease, is a mite-born acute febrile disease caused by Rickettsia tsutsugamushi. To our knowledge, neonatal scrub typhus has not been reported in the literature. We report on a 26-day-old newborn with aseptic meningitis. The newborn showed an increased specific 1gM antibody to R.tsutsugamushi conjointly with his mother's 1gM titer to the organism. This is the first case in the literature documenting neonatal scrub typhus and may be related to infection in the mother. CASE REPORT A 26-day-old male newborn was well until 4 days prior to this admission. He suffered from intermittent high fever, abdominal distention, and skin pallor.
Article
Ciprofloxacin (120 mg/kg of body weight per day), chloramphenicol (300 mg/kg per day), and gentamicin (30 mg/kg per day) were compared with placebo in a BALB/cj mouse model of scrub typhus. All animals treated with ciprofloxacin and chloramphenicol survived. All animals treated with gentamicin or placebo died. All surviving animals showed evidence of seroconversion. Ciprofloxacin and chloramphenicol were statistically more effective in preventing death than gentamicin or placebo.
Article
With the use of indirect fluorescent antibody or mouse inoculation methods, scrub typhus was diagnosed in 109 of 1650 febrile American servicemen in Vietnam. The fluorescent antibody test was positive in all 32 patients from whom Rickettsia were recovered, but a rising antibody titer to Proteus OXK occurred in only 47%, which included only 5 of 27 patients infected with Gilliam strain. The diagnosis was clinically suspected in only 51 patients. Generalized lymphadenopathy and lymphocytosis were commoner than either eschar or rash, and, in the absence of the latter findings, the illness was frequently mistaken for infectious mononucleosis. Early treatment with tetracycline shortened the duration of illness and suppressed the convalescence indirect fluorescent antibody titer. No relapses occurred in those patients who received tetracycline for at least 7 days.
The changes in plasma sodium, potassium, chloride and osmolality levels have been examined in primigravidae and multigravidae. Plasma sodium and potassium concentrations decrease significantly from 10 to 28 weeks in multigravidae but not in primigravidae. Both groups show a significant increase in plasma potassium concentration between 28 and 37 weeks, when there is no change in sodium concentration. Plasma sodium and potassium levels rise significantly following delivery in primigravidae but, with multigravidae, only the rise in the latter is statistically significant. There is no change in the plasma levels of chloride and osmolality during normal pregnancy, irrespective of parity; osmolality increases significantly after delivery in each group. The results appear consistent with the hypothesis that the expansion of plasma volume is an important factor in the observed changes.
Article
Female mice were inoculated with either a virulent or avirulent strain of Rickettsia tsutsugamushi before (1 month and 1 week) or after (approximately 10 days) impregnation. From each group, two pregnant mothers were killed on day 20 post-impregnation, and fetuses and placentas were examined for rickettsiae. Organisms were isolated from 80% of placentas but not from the fetuses. Immediately following parturition, litters from 50% of the infected mothers were exchanged with litters from uninfected mothers. In all cases, no scrub typhus rickettsiae were found in the litters examined on days 1, 7, and 30 postpartum, and no antibody was found in sera collected 1 and 2 months postpartum.
Article
Sera of 111 mother/cord pairs were tested for IgG and IgM antibodies to Rickettsia tsutsugamushi. Thirty-two (29%) of the mothers had positive IgG titers that indicated previous infections. Evidence of fetal infection was not found, since IgM antibodies were not detected in corresponding cord sera.
Article
Scrub typhus is a rickettsian disease which is seldom found in pregnancy. A 31-year-old, 34 weeks pregnant woman presented with fever, chill and cough for 6 weeks. Fetal jeopardy was found then a cesarean section was performed to deliver a 2,200 g male with hepatosplenomegaly. The mother's diagnosis was confirmed by positive Weil-Felix (OXK titer 1:320) and scrub typhus (titer 1:1600) tests. Vertical transmission was also demonstrated by a positive scrub typhus IgM in her child.
Article
In addition to erythromycin, macrolides now available in the United States include azithromycin and clarithromycin. These two new macrolides are more chemically stable and better tolerated than erythromycin, and they have a broader antimicrobial spectrum than erythromycin against Mycobacterium avium complex (MAC), Haemophilus influenzae, nontuberculous mycobacteria, and Chlamydia trachomatis. All three macrolides have excellent activity against the atypical respiratory pathogens (C. pneumoniae and Mycoplasma species) and the Legionella species. Azithromycin and clarithromycin have pharmacokinetics that allow shorter dosing schedules because of prolonged tissue levels. Both azithromycin and clarithromycin are active agents for MAC prophylaxis in patients with late-stage acquired immunodeficiency syndrome (AIDS), although azithromycin may be the preferable agent because of fewer drug-drug interactions. Clarithromycin is the most active MAC antimicrobial agent and should be part of any drug regimen for treating active MAC disease in patients with or without AIDS. Although both azithromycin and clarithromycin are well tolerated by children, azithromycin has the advantage of shorter treatment regimens and improved tolerance, potentially improving compliance in the treatment of respiratory tract and skin or soft tissue infections. Intravenously administered azithromycin has been approved for treatment of adults with mild to moderate community-acquired pneumonia or pelvic inflammatory diseases. An area of concern is the increasing macrolide resistance that is being reported with some of the common pathogens, particularly Streptococcus pneumoniae, group A streptococci, and H. influenzae. The emergence of macrolide resistance with these common pathogens may limit the clinical usefulness of this class of antimicrobial agents in the future.
Article
Three pharmacokinetic/pharmacodynamic parameters--(i) the peak concentration to the minimum inhibitory concentration ratio (C(max)/MIC); (ii) the area under the concentration-time curve to MIC ratio (AUC(24h)/MIC); and (iii) the time the concentration exceeds the MIC (T>MIC)--are important predictors of the clinical efficacy of antibiotics. For antibiotics with pronounced concentration-dependent killing, such as the fluoroquinolones or the aminoglycosides, C(max)/MIC and AUC(24)/MIC are the main factors that establish efficacy. Antibiotics with a weak, or no, concentration dependency generally have their efficacy linked to T>MIC, and these include the beta-lactams and the conventional macrolides. Antibiotics with weak concentration-dependent effects, but with prolonged persistent effects, such as tetracyclines and azithromycin, have their activity mostly related to the AUC(24)/MIC. By applying these concepts to current antibiotics, and also to the development of novel agents, it is possible to optimise their dosages and administration schedules. This will maximise therapeutic efficacy, may prevent or delay the emergence of bacterial resistance to antibiotics, and can certainly minimise side-effects.
Article
A 49-year-old travel guide fell ill during his return from a 6-week-stay in Vietnam, Myanmar and Thailand. He developed high fever and severe headache. On admission, the body temperature was at 39.5 degrees C with relative bradycardia. A black, crusted skin lesion of approximately 5 mm diameter was noted on the chest wall and was interpreted as an insect bite. CRP and liver enzymes were elevated. Total leucocyte count was normal but the differential count showed a left shift and aneosinophilia. Imaging procedures revealed splenomegaly and small pleural effusions on both sides. The patient was treated with a parenteral quinolone based on the initial suspicion of typhoid fever. Failure of this treatment and negative blood cultures raised concerns about the possibility of Tsutsugamushi fever, based on travel history and a re-evaluation of the skin lesion as an eschar. Tsutsugamushi fever was suspected on epidemiological and clinical grounds and was confirmed by the detection of specific IgM to Orienta tsutsugamushi and by seroconversion of IgG antibodies during follow-up. Even before immunodiagnostic confirmation was available, a course of doxycycline was started. This led to rapid improvement of the patient's condition. In febrile travellers returning from Southeast Asia, Tsutsugamushi fever has to be considered in the differential diagnosis. The causative agent, Orienta tsutsugamushi is transmitted by larvae of trombiculid mites (chiggers). Leading symptoms are fever continua, cephalgia, and a primary lesion (eschar) at the site of cutaneous inoculation. The Eschar is easily overlooked and has to be searched carefully. Diagnosis is confirmed by the detection of specific antibodies. However, serology may be negative in the beginning. Therefore, treatment with doxycycline should be initiated on clinical grounds.
Article
Scrub typhus is one of the most important endemic infections in the Asia-Pacific region. Although tetracyclines or chloramphenicol are the recommended drugs of choice for the treatment of scrub typhus, reports of doxycycline-resistant strains have prompted a search for alternative treatments. We conducted a prospective, open-label, randomized trial from September 2002 through November 2003 to compare azithromycin with doxycycline for the treatment of mild scrub typhus. The time to defervescence was assessed to compare the efficacy of the 2 treatment regimens. A total of 93 patients were randomly assigned to receive either a single 500-mg dose of azithromycin or a 1-week course of daily oral 200-mg dose of doxycycline. Cure was achieved in 47 (100%) of 47 patients in the azithromycin-treated group and in 43 (93.5%) of 46 patients in the doxycycline-treated group (P=.117). The median time to defervescence was 21 h for the azithromycin-treated group and 29 h for the doxycycline-treated group (P=.097). There were no serious adverse events during the study. No relapses occurred in either group during a 1-month follow-up period. The single 500-mg dose of azithromycin was as effective as the 1-week course of daily 200-mg doses of doxycycline for the treatment of mild scrub typhus acquired in South Korea.
Scrub typhus is a rickettsial disease that is uncommon during pregnancy. We report a case of a 33-year-old woman, G1P0, 29 weeks pregnancy who presented to hospital with high fever, chill and headache for two weeks. Her diagnosis of scrub typhus was confirmed by serum immunofluorescent assay. She was successfully treated with chloramphenicol, but preterm delivery occurred. Her infant died from respiratory distress syndrome. No vertical transmission was demonstrated in this case. Scrub typhus should be listed in the differential diagnosis of acute febrile illness in pregnant women, who either live in, or return from, endemic areas. Chloramphenicol can be used safely during pregnancy if it is not circulating at the time of delivery.
Scrub Ty-phus. Bulletin No. 21
  • Oaks
  • Jr
  • Rl Ridgway
  • A Shirai
  • Twartz
Oaks SC Jr, Ridgway RL, Shirai A, Twartz JC, 1983. Scrub Ty-phus. Bulletin No. 21. Kuala Lampur, Malaysia: Institute for Medical Research.