zithromax and Scrub-Typhus

To explore the efficacy and safety of drugs in patients with scrub typhus.. 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.. 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.. 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.. https://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42021287837.

Topics: Anti-Bacterial Agents; Azithromycin; Child; Chloramphenicol; Female; Humans; Moxifloxacin; Network Meta-Analysis; Rifampin; Scrub Typhus

Scrub typhus is an acute febrile illness caused by intracellular bacteria from the genus Orientia. It is estimated that one billion people are at risk, with one million cases annually mainly affecting rural areas in Asia-Oceania. Relative to its burden, scrub typhus is understudied, and treatment recommendations vary with poor evidence base. These knowledge gaps could be addressed by establishing an individual participant-level data (IPD) platform, which would enable pooled, more detailed and statistically powered analyses to be conducted. This study aims to assess the characteristics of scrub typhus treatment studies and explore the feasibility and potential value of developing a scrub typhus IPD platform to address unanswered research questions.. We conducted a systematic literature review looking for prospective scrub typhus clinical treatment studies published from 1998 to 2020. Six electronic databases (Ovid Embase, Ovid Medline, Ovid Global Health, Cochrane Library, Scopus, Global Index Medicus), ClinicalTrials.gov, and WHO ICTRP were searched. We extracted data on study design, treatment tested, patient characteristics, diagnostic methods, geographical location, outcome measures, and statistical methodology. Among 3,100 articles screened, 127 were included in the analysis. 12,079 participants from 12 countries were enrolled in the identified studies. ELISA, PCR, and eschar presence were the most commonly used diagnostic methods. Doxycycline, azithromycin, and chloramphenicol were the most commonly administered antibiotics. Mortality, complications, adverse events, and clinical response were assessed in most studies. There was substantial heterogeneity in the diagnostic methods used, treatment administered (including dosing and duration), and outcome assessed across studies. There were few interventional studies and limited data collected on specific groups such as children and pregnant women.. There were a limited number of interventional trials, highlighting that scrub typhus remains a neglected disease. The heterogeneous nature of the available data reflects the absence of consensus in treatment and research methodologies and poses a significant barrier to aggregating information across available published data without access to the underlying IPD. There is likely to be a substantial amount of data available to address knowledge gaps. Therefore, there is value for an IPD platform that will facilitate pooling and harmonisation of currently scattered data and enable in-depth investigation of priority research questions that can, ultimately, inform clinical practice and improve health outcomes for scrub typhus patients.

Topics: Anti-Bacterial Agents; Azithromycin; Doxycycline; Feasibility Studies; Female; Humans; Male; Orientia tsutsugamushi; Scrub Typhus

Scrub typhus, caused by Orientia tsutsugamushi, is a widely neglected disease which is gaining global momentum because of its resurgence patterns. The disease is now being reported in newer regions as well as areas previously endemic areas. In this review, we aim to comprehensively review the data available to assist physicians in making an accurate diagnosis and appropriate management of the disease.. Several diagnostic tests have been developed for confirming scrub typhus. However, there is lack of clarity on which tests are most appropriate in a given clinical scenario. A recent study has demonstrated that in early disease (<7 days) when serological tests remain negative, the quantitative polymerase chain reaction is the most sensitive test. Among the serological tests, both IgM enzyme-linked immunosorbent assay as well as rapid diagnostic tests revealed excellent sensitivities and specificities.. With the reemergence of scrub typhus, a high degree of clinical suspicion is required to appropriately diagnose this disease which presents as an acute febrile illness. It can progress to develop various complications leading to multi-organ dysfunction syndrome. Mild illness responds well to antibiotic treatment with doxycycline and azithromycin. Further studies are required to determine the most optimal therapy in severe scrub typhus infections and superiority of one drug over the other.

Topics: Anti-Bacterial Agents; Antibodies, Bacterial; Azithromycin; Doxycycline; Enzyme-Linked Immunosorbent Assay; Female; Global Health; Humans; Male; Neglected Diseases; Orientia tsutsugamushi; Polymerase Chain Reaction; Scrub Typhus; Sensitivity and Specificity; Serologic Tests; Skin; Travel

Scrub typhus, an important cause of acute fever in Asia, is caused by Orientia tsutsugamushi, an obligate intracellular bacterium. Antibiotics currently used to treat scrub typhus include tetracyclines, chloramphenicol, macrolides, and rifampicin.. To assess and compare the effects of different antibiotic regimens for treatment of scrub typhus.. We searched the following databases up to 8 January 2018: the Cochrane Infectious Diseases Group specialized trials register; CENTRAL, in the Cochrane Library (2018, Issue 1); MEDLINE; Embase; LILACS; and the metaRegister of Controlled Trials (mRCT). We checked references and contacted study authors for additional data. We applied no language or date restrictions.. Randomized controlled trials (RCTs) or quasi-RCTs comparing antibiotic regimens in people with the diagnosis of scrub typhus based on clinical symptoms and compatible laboratory tests (excluding the Weil-Felix test).. For this update, two review authors re-extracted all data and assessed the certainty of evidence. We meta-analysed data to calculate risk ratios (RRs) for dichotomous outcomes when appropriate, and elsewhere tabulated data to facilitate narrative analysis.. We included six RCTs and one quasi-RCT with 548 participants; they took place in the Asia-Pacific region: Korea (three trials), Malaysia (one trial), and Thailand (three trials). Only one trial included children younger than 15 years (N = 57). We judged five trials to be at high risk of performance and detection bias owing to inadequate blinding. Trials were heterogenous in terms of dosing of interventions and outcome measures. Across trials, treatment failure rates were low.Two trials compared doxycycline to tetracycline. For treatment failure, the difference between doxycycline and tetracycline is uncertain (very low-certainty evidence). Doxycycline compared to tetracycline may make little or no difference in resolution of fever within 48 hours (risk ratio (RR) 1.14, 95% confidence interval (CI) 0.90 to 1.44, 55 participants; one trial; low-certainty evidence) and in time to defervescence (116 participants; one trial; low-certainty evidence). We were unable to extract data for other outcomes.Three trials compared doxycycline versus macrolides. For most outcomes, including treatment failure, resolution of fever within 48 hours, time to defervescence, and serious adverse events, we are uncertain whether study results show a difference between doxycycline and macrolides (very low-certainty evidence). Macrolides compared to doxycycline may make little or no difference in the proportion of patients with resolution of fever within five days (RR 1.05, 95% CI 0.99 to 1.10; 185 participants; two trials; low-certainty evidence). Another trial compared azithromycin versus doxycycline or chloramphenicol in children, but we were not able to disaggregate date for the doxycycline/chloramphenicol group.One trial compared doxycycline versus rifampicin. For all outcomes, we are uncertain whether study results show a difference between doxycycline and rifampicin (very low-certainty evidence). Of note, this trial deviated from the protocol after three out of eight patients who had received doxycycline and rifampicin combination therapy experienced treatment failure.Across trials, mild gastrointestinal side effects appeared to be more common with doxycycline than with comparator drugs.. Tetracycline, doxycycline, azithromycin, and rifampicin are effective treatment options for scrub typhus and have resulted in few treatment failures. Chloramphenicol also remains a treatment option, but we could not include this among direct comparisons in this review.Most available evidence is of low or very low certainty. For specific outcomes, some low-certainty evidence suggests there may be little or no difference between tetracycline, doxycycline, and azithromycin as treatment options. Given very low-certainty evidence for rifampicin and the risk of inducing resistance in undiagnosed tuberculosis, clinicians should not regard this as a first-line treatment option. Clinicians could consider rifampicin as a second-line treatment option after exclusion of active tuberculosis.Further research should consist of additional adequately powered trials of doxycycline versus azithromycin or other macrolides, trials of other candidate antibiotics including rifampicin, and trials of treatments for severe scrub typhus. Researchers should standardize diagnostic techniques and reporting of clinical outcomes to allow robust comparisons.

Topics: Adult; Anti-Bacterial Agents; Azithromycin; Child, Preschool; Chloramphenicol; Doxycycline; Humans; Macrolides; Randomized Controlled Trials as Topic; Rifampin; Scrub Typhus; Tetracycline

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.. 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.. 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).. 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.

Topics: Anti-Bacterial Agents; Azithromycin; Humans; Scrub Typhus

Scrub typhus is an important febrile disease in Asia, and antibiotics have been used to treat this disease. The purpose of this study was to generate large-scale evidence of the efficacy of different antibiotic regimens for treating scrub typhus using a meta-analysis.. PubMed, Elsevier ScienceDirect, Chinese Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), and Wanfang (Chinese) were searched to identify relevant articles. The data from eligible citations were extracted by two reviewers. All analyses were performed using the Cochrane Collaboration Review Manager 4.2 and Stata 10.0 software programs.. We conducted a meta-analysis of 17 separate studies that evaluated the efficacy of treatment with the different antibiotic regimens for scrub typhus. The median time (h) to clearance of fever in the azithromycin-treated group was longer than that in the chloramphenicol-treated group (weighted mean difference [WMD] = 12.66, 95% confidence interval [CI]: 2.26,23.06). Adverse events were 2.95 (95%CI: 1.32, 6.61) times more likely to occur in the azithromycin-treated group than in the chloramphenicol-treated group. The clearance time (days) for the main symptoms (including fever, headache, rash and lymphadenectasis) in the doxycycline-treated group was shorter than that in the chloramphenicol-treated group (WMD = -0.4, 95%CI: -0.53, -0.26) in five trials. Adverse drug events occurred significantly less frequently in the azithromycin-treated group than in the doxycycline-treated group (relative risk [RR] = 0.47, 95%CI: 0.31,0.71).. Doxycycline was found to act more quickly, but more adverse drug events occur when using this regimen compared to azithromycin and chloramphenicol.

Topics: Anti-Bacterial Agents; Asia; Azithromycin; Chloramphenicol; Doxycycline; Humans; Randomized Controlled Trials as Topic; Scrub Typhus; Treatment Outcome

Scrub typhus is a vector-borne disease caused by the pathogen Orientia tsutsugamushi. We review the published literature for evidence on drug treatment in scrub typhus. Doxycycline has a proven efficacy in several trials and a meta-analysis, although resistance has been documented in parts of northern Thailand. Macrolides are equally efficacious and have less adverse effects, but they are expensive. Azithromycin is the recommended drug in pregnancy and for children. Rifampicin is effective in areas where doxycycline resistance is present. Quinolones have shown some degree of efficacy but the evidence is scant. Most clinical evidence on drug treatment is from cases of mild-to-moderate scrub typhus. Further study is needed on the efficacy of different antibiotics in the treatment of severe, life-threatening scrub typhus.

Topics: Anti-Bacterial Agents; Azithromycin; Child; Clinical Trials as Topic; Doxycycline; Female; Humans; Macrolides; Orientia tsutsugamushi; Pregnancy; Rifampin; Scrub Typhus; Treatment Outcome

The appropriate antibiotic treatment for severe scrub typhus, a neglected but widespread reemerging zoonotic infection, is unclear.. In this multicenter, double-blind, randomized, controlled trial, we compared the efficacy of intravenous doxycycline, azithromycin, or a combination of both in treating severe scrub typhus. Patients who were 15 years of age or older with severe scrub typhus with at least one organ involvement were enrolled. The patients were assigned to receive a 7-day course of intravenous doxycycline, azithromycin, or both (combination therapy). The primary outcome was a composite of death from any cause at day 28, persistent complications at day 7, and persistent fever at day 5.. Among 794 patients (median age, 48 years) who were included in the modified intention-to-treat analysis, complications included those that were respiratory (in 62%), hepatic (in 54%), cardiovascular (in 42%), renal (in 30%), and neurologic (in 20%). The use of combination therapy resulted in a lower incidence of the composite primary outcome than the use of doxycycline (33% and 47%, respectively), for a risk difference of -13.3 percentage points (95% confidence interval [CI], -21.6 to -5.1; P = 0.002). The incidence with combination therapy was also lower than that with azithromycin (48%), for a risk difference of -14.8 percentage points (95% CI, -23.1 to -6.5; P<0.001). No significant difference was seen between the azithromycin and doxycycline groups (risk difference, 1.5 percentage points; 95% CI, -7.0 to 10.0; P = 0.73). The results in the per-protocol analysis were similar to those in the primary analysis. Adverse events and 28-day mortality were similar in the three groups.. Combination therapy with intravenous doxycycline and azithromycin was a better therapeutic option for the treatment of severe scrub typhus than monotherapy with either drug alone. (Funded by the India Alliance and Wellcome Trust; INTREST Clinical Trials Registry-India number, CTRI/2018/08/015159.).

Topics: Administration, Intravenous; Animals; Anti-Bacterial Agents; Azithromycin; Double-Blind Method; Doxycycline; Drug Therapy, Combination; Humans; Middle Aged; Scrub Typhus; Zoonoses

Doxycycline (DX) is the first-line therapeutic agent for scrub typhus. Macrolides, especially azithromycin (AZ), have been found to be equally efficacious as DX for treating scrub typhus in adults. We conducted this study to compare the efficacy of AZ versus DX in pediatric scrub typhus.. Open-label randomized controlled trial.. Children 1-14 years of age suffering from acute febrile illness of ≥5 days and with a positive scrub IgM serology were randomized to receive either DX (2.2 mg/kg/dose twice daily in <40 kg; 100 mg BD in >40 kg for 7 days) or AZ (10 mg/kg/day for 5 days). The primary outcome was defervescence within 7 days of DX or 5 days of AZ.. We had 75 children randomized and analyzed using an intention-to-treat approach and 60 children analyzed via per-protocol analysis. The proportion of children achieving defervescence was comparable in 2 groups [per-protocol analysis: 90.9% in the DX group vs. 96.3% in the AZ group, RR: 0.94 (95% CI: 0.83-1.08)]. On Kaplan-Meier curves, AZ showed a significantly higher probability of defervescence at any time point during treatment as compared with DX (log-rank test P value 0.035).. AZ and DX had comparable rates of defervescence among children with scrub typhus. Trial registration No.: CTRI/2020/01/022991.

Topics: Adult; Anti-Bacterial Agents; Azithromycin; Child; Doxycycline; Humans; Infant, Newborn; Macrolides; Scrub Typhus

To compare the efficacy of azithromycin versus doxycycline in treatment of children with uncomplicated scrub typhus in terms of percentage of children who attained remission of fever after 72 hours of administration of first dose of the study drug, mean time taken to attain fever defervescence, normalization of laboratory parameters, resolution of hepatosplenomegaly and lymphadenopathy.. Interventional, open-labeled randomized controlled trial.. Patients admitted with undifferentiated fever in the In-Patient Department (IPD), Department of Paediatrics, All India Institute of Medical Sciences, Bhubaneswar, India, as per the inclusion criteria were randomized and was treated with azithromycin at 10 mg/kg/d in one group and doxycycline at 4.4 mg/kg/d for 5 days in the other group and was assessed based on the primary and secondary objectives.. There was no statistically significant difference between the percentage of children who attained remission of fever after 72 hours of administration of azithromycin (98.2%) and doxycycline (96.5%) (P value 0.47) and the average time taken for fever defervescence (azithromycin: 24.53 hours; doxycycline: 25.82 hours; P value 0.36). The odds of attaining fever remission in the doxycycline group as compared with the azithromycin group was 1.01 (95% confidence interval -0.60 to -1.71), which was also statistically not significant. There was less incidence of adverse drug events in the azithromycin group (1.78%) as compared with the doxycycline group (8.6%), which was statistically significant (P value 0.02).. Azithromycin is equally efficacious in terms of fever defervescence, resolution of clinical signs and laboratory parameters as doxycycline, is safer and better tolerated in children.

Topics: Anti-Bacterial Agents; Azithromycin; Child, Preschool; Doxycycline; Female; Fever; Humans; India; Infant; Male; Orientia tsutsugamushi; Rickettsiaceae Infections; Scrub Typhus; Treatment Outcome; Vector Borne Diseases

Scrub typhus is an acute febrile illness caused by Orientia tsutsugamushi. We prospectively studied the clinico-laboratory profile and outcome of 358 children aged 1 day to 18 years diagnosed with scrub typhus from Chennai, South India. All children (100%) had fever. Eschar was seen in 67%. All children were treated with oral doxycycline and those with complications were treated with intravenous chloramphenicol/azithromycin. Rapid defervescence (within 48 h) after initiation of doxycline was seen in 306 (85%) and 52 (14.5%) developed complications. Multivariate logistic regression analysis revealed that children who had an elevated aspartate amino transferase (> 120 IU/L) and the presence of thrombocytopenia (platelet count less than 1 lac cells/mm. Our 4-year study highlights the clinico-laboratory profile of Scrub typhus in children from Chennai, South India. Early recognition and prompt treatment reduces the complication and mortality. What is Known: • Scrub typhus is endemic to tsutsugamushi triangle, a geographical triangle extending from northern Japan in the east to Pakistan and Afghanistan in the west and northern Australia in the south. • There is paucity of data regarding its clinico-laboratory profile in neonates as well as its predictors of outcome. What is New: • Children who had an elevated AST and the presence of thrombocytopenia at admission had high risk of developing complications.

Topics: Adolescent; Anti-Bacterial Agents; Azithromycin; Child; Child, Preschool; Chloramphenicol; Doxycycline; Drug Therapy, Combination; Female; Humans; India; Infant; Infant, Newborn; Logistic Models; Male; Prospective Studies; Scrub Typhus; Treatment Outcome

To evaluate the efficacy and safety of azithromycinfor treatment of uncomplicated pediatric scrub typhus.. A randomized controlled trial was performed. We compared azithromycin with doxycycline or chloramphenicol in uncomplicated pediatric scrub typhus from inpatient pediatric department of Chiangrai Prachanukroh Hospital. The primary outcome was cure rate at day 3. The secondary outcomes were timing to defervescence within 72 hours, side effects, and relapsed rate. We compared data between both groups with Fisher's exact test or Mann-Whitney U test, and failure rate was demonstrated by Kaplan-Meier survival curve and Log-rank test.. We included 57 patients, ofwhom, 28 were assigned to doxycycline or chloramphenicol (control group) and 29 to azithromycin (study group). The baseline characteristics of both groups were similar The cure rate was 85.7% in the doxycycline or chloramphenicol group, as compared to 79.3% in the azithromycin group (p = 0.73), and a median time to defervescence was 30 hours (IQR 21, 48) vs. 36 hours (IQR 20, 68) respectively (p = 0.166). There was a little minor side effect in azithromycin group. No relapsed was found in either groups.. Azithromycin was as effective as doxycycline or chloramphenicol in treatment of uncomplicated pediatric scrub typhus.

Topics: Anti-Bacterial Agents; Azithromycin; Child; Child, Preschool; Chloramphenicol; Doxycycline; Female; Humans; Inpatients; Kaplan-Meier Estimate; Male; Recurrence; Scrub Typhus; Time Factors

Leptospirosis and scrub typhus are important causes of acute fever in Southeast Asia. Options for empirical therapy include doxycycline and azithromycin, but it is unclear whether their efficacies are equivalent. We conducted a multicenter, open, randomized controlled trial with adult patients presenting with acute fever (<15 days), without an obvious focus of infection, at four hospitals in Thailand between July 2003 and January 2005. Patients were randomly allocated to receive either a 7-day course of doxycycline or a 3-day course of azithromycin. The cure rate, fever clearance time, and adverse drug events were compared between the two study groups. A total of 296 patients were enrolled in the study. The cause of acute fever was determined for 151 patients (51%): 69 patients (23.3%) had leptospirosis; 57 patients (19.3%) had scrub typhus; 14 patients (4.7%) had murine typhus; and 11 patients (3.7%) had evidence of both leptospirosis and a rickettsial infection. The efficacy of azithromycin was not inferior to that of doxycycline for the treatment of both leptospirosis and scrub typhus, with comparable fever clearance times in the two treatment arms. Adverse events occurred more frequently in the doxycycline group than in the azithromycin group (27.6% and 10.6%, respectively; P = 0.02). In conclusion, doxycycline is an affordable and effective choice for the treatment of both leptospirosis and scrub typhus. Azithromycin was better tolerated than doxycycline but is more expensive and less readily available.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Azithromycin; Doxycycline; Female; Humans; Leptospirosis; Male; Middle Aged; Sample Size; Scrub Typhus; Thailand; Treatment Outcome

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.

Topics: Aged; Anti-Bacterial Agents; Azithromycin; Doxycycline; Female; Humans; Male; Middle Aged; Scrub Typhus

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.

Topics: Adult; Animals; Anti-Bacterial Agents; Azithromycin; Doxycycline; Drug Resistance, Microbial; Female; Humans; Mice; Microbial Sensitivity Tests; Orientia tsutsugamushi; Pregnancy; Scrub Typhus; Tetracycline Resistance; Thailand

Topics: Administration, Intravenous; Anti-Bacterial Agents; Azithromycin; Doxycycline; Humans; Scrub Typhus

Topics: Administration, Intravenous; Anti-Bacterial Agents; Azithromycin; Doxycycline; Humans; Scrub Typhus

Topics: Administration, Intravenous; Anti-Bacterial Agents; Azithromycin; Doxycycline; Humans; Scrub Typhus

Topics: Administration, Intravenous; Anti-Bacterial Agents; Azithromycin; Doxycycline; Humans; Scrub Typhus

Scrub typhus is a re-emerging infectious disease. Though considered as disease of rural areas, this disease has been urbanized and the prevalence has broadened further. Disease has been reported with increasing frequency from various parts of India and has resurgence in north east. It is a disease with multi organ involvement, with or without characteristic eschar and early detection and initial specific treatment is important.. An observational hospital-based study in patients >18years admitted to a tertiary care center in eastern India. Scrub typhus was diagnosed on basis of symptoms with or without eschar and Scrub IgM. Treated with doxycycline (azithromycin in 3 pregnant patients) & clinical course was monitored. An appropriate correlation measure, based on the natures of the variable under study, (e.g.: rank correlation / Pearson correlation/ point biserial correlation) was estimated and subsequently tested at alpha =0.05 level of significance. A p value <0.05 was taken as significant.. A total of 105 patients of scrub typhus were included in present study. It had 66%male and 39% female with the most common age group being 46-60 years. Eschar was found in 33% patients. Neurological manifestation was found in 18% of the patients. Hyponatremia and raised liver enzymes were significantly noticed. 9% patients had Acute respiratory distress syndrome. 4% patients died because of multiorgan dysfunction. Three pregnant patients included in study were treated with azithromycin showed good response and pregnancy outcome was uneventful.. Scrub typhus is no longer a disease of rural India. Physician should have strong suspicion and needs early attempt to diagnose and treat as mostly the disease is featureless and can be treated easily, but delay in starting treatment raises chances of severe complications like encephalitis, ARDS, Macrophage Activation Syndrome. Disease mostly responded with Azithromycin, Doxycycline.

Topics: Anti-Bacterial Agents; Azithromycin; Doxycycline; Female; Humans; Male; Middle Aged; Pregnancy; Scrub Typhus; Tertiary Care Centers

In this prospective study, children from 1-month to 12-years, admitted with positive IgM ELISA testing for scrub typhus, were enrolled over 1-year and administered an empirical single dose of azithromycin (10 mg/kg). All 189 (median age 4.84-years) children had fever with median duration of 8 days at admission. Shortness of breath, altered sensorium, headache, lymphadenopathy, hepatosplenomegaly, pallor, oedema and hypotension were the most prominent symptoms/signs. About 46% of children developed complications, among them hepatic, neurological and cardiovascular were most common. Our study showed a remarkable response to azithromycin, with mean defervescence of 32 h and no mortality. The presence of shortness of breath, headache, altered sensorium, hepatosplenomegaly, meningeal signs, severe anemia, leucocytosis, hyponatremia along with/without any of above mentioned three systemic complications were independent predictors for delayed treatment response by multivariate logistic regression analysis. Hepatic, neurological and cardiovascular complications are an emerging trend. Empiric azithromycin based on clinical suspicion of scrub typhus can be lifesaving.

Topics: Anti-Bacterial Agents; Azithromycin; Child; Child, Preschool; Doxycycline; Dyspnea; Headache; Hepatomegaly; Humans; India; Prospective Studies; Scrub Typhus; Splenomegaly; Treatment Outcome

Scrub typhus is a vector-borne disease caused by Orientia tsutsugamushi. Clinical manifestations generally occur due to vasculitis and inflammation and can have variable degrees of systemic involvement. Meningoencephalitis and cerebellitis are well-known neurological manifestations of scrub typhus, but the occurrence of Guillain-Barré syndrome is extremely rare. The authors report a 7-y-old boy who developed fever followed by rapidly progressive ascending quadriparesis with areflexia and whose etiological workup revealed positive IgM scrub typhus antibody, as well as, a high OXK titer (1:80). Nerve-conduction studies in all four limbs were suggestive of demyelinating neuropathy. He showed complete recovery after treatment with intravenous immunoglobulin (2 g/kg) and azithromycin.

Topics: Azithromycin; Guillain-Barre Syndrome; Humans; Immunoglobulin M; Immunoglobulins, Intravenous; Male; Orientia tsutsugamushi; Scrub Typhus

Previous studies have evaluated treatment efficacy of various antibiotics for patients with mild-to-moderate scrub typhus (ST). However, the efficacy of different antibiotics for treating severe ST remains uncertain.. A retrospective study of patients with severe ST was undertaken in China. The treatment efficacy rates of doxycycline, azithromycin and chloramphenicol were compared, using treatment failure and time to defervescence as primary outcomes.. In total, 876 patients with severe ST who initially received doxycycline, azithromycin or chloramphenicol were recruited. The treatment failure rate did not differ significantly between patients receiving doxycycline and patients receiving azithromycin (6.0% vs 11.4%; P=0.109). However, a higher treatment failure rate was observed for chloramphenicol compared with doxycycline (14.6% vs 6.0%; P=0.004). No significant difference in time to defervescence was observed between patients receiving doxycycline, azithromycin or chloramphenicol. Further subgroup analysis revealed a higher risk of treatment failure for chloramphenicol compared with doxycycline in patients with acute kidney injury, pneumonia and shock; and a higher risk of treatment failure for azithromycin compared with doxycycline in patients with meningitis. Significant correlation was found between azithromycin resistance and meningitis (P=0.009), and between chloramphenicol resistance and acute respiratory distress syndrome (ARDS) (P<0.001) using Cramer's V correlation coefficient. Multi-variate Cox regression analysis revealed significant associations between time to defervescence and presence of ARDS, shock, myocarditis, meningitis and acute kidney injury.. Azithromycin and doxycycline were found to have significant therapeutic effects in patients with severe ST. In contast, chloramphenicol was less efficacious for the treatment of these patients.

Topics: Acute Kidney Injury; Anti-Bacterial Agents; Azithromycin; Chloramphenicol; Doxycycline; Humans; Respiratory Distress Syndrome; Retrospective Studies; Scrub Typhus

Topics: Anti-Bacterial Agents; Azithromycin; Humans; Infant, Newborn; Infant, Newborn, Diseases; Orientia tsutsugamushi; Scrub Typhus

Doxycycline is the drug of choice for pediatric scrub typhus (ST) while azithromycin is considered as an equally effective alternative. This study was undertaken to assess the response to therapy and its predictors in pediatric ST cases treated with doxycycline and azithromycin. Children ≤12 year with fever ≥7 days were screened for ST by IgM ELISA (positive if optical density >0.5). All positive cases were divided into two groups based on whether treated with doxycycline or azithromycin. Fever clearance time (FCT), duration of hospitalization and other clinical characteristics of cases in both groups were compared. Out of 2710 children admitted with fever for more than 7 days, 660 cases (24.35%) tested positive for ST by IgM ELISA. Cases treated with azithromycin and doxycycline were 316 (47.87%) and 344 (52.12%), respectively. In our study, the FCT (p = 0.004), mean duration of hospital stay (p = 0.011), persistence of fever for >48 h after starting antibiotic therapy (p = 0.001) and severe ST requiring ICU admission (p = 0.046) were significantly lower in children who received doxycycline. The logistic regression analysis revealed that the presence of splenomegaly (Adjusted Odds Ratio (AOR) 2.60; 95% Confidence interval (CI) = 1.49-4.53; p = 0.001) and lung crepts (AOR 2.02; 95% CI = 1.06-3.85; p = 0.032) in azithromycin-treated group and presence of meningeal signs (AOR 16.11; 95% CI = 5.47-47.45; p < 0.001), anemia (AOR 2.28; 95% CI = 1.02-5.08; p = 0.044), lung crepts (AOR 2.66; 95% CI = 1.16-6.05; p = 0.020) and absence of eschar (AOR 3.48; 95% CI = 1.70-7.13; p = 0.001) in the doxycycline group was significantly associated with prolonged FCT (>48 h). Doxycycline is superior to azithromycin in defervescing fever, reducing hospital stay and preventing severity in pediatric ST.

Topics: Anti-Bacterial Agents; Azithromycin; Child; Doxycycline; Humans; Prospective Studies; Scrub Typhus

Scrub typhus is an acute febrile disease caused by Orientia tsutsugamushi, which is transmitted through chigger mites. Delayed treatment results in various complications and, in severe cases, death. Granzymes are secreted by cytotoxic T lymphocytes or natural killer cells and are known to play an important role in controlling intracellular pathogens. To date, few studies have been done on granzymes in patients with scrub typhus. In this study, granzymes A and B showed a significant increase during the acute stage of scrub typhus compared with healthy control subjects, and decreased sharply after treatment. In addition, granzymes A and B were significantly high in the moderately elevated liver enzyme group. In conclusion, it appears that the host during the acute phase of scrub typhus increases cytotoxic T-cell activity to control infection.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Azithromycin; Case-Control Studies; Doxycycline; Extracellular Space; Female; Granzymes; Humans; Male; Middle Aged; Scrub Typhus; Young Adult

Topics: Anti-Bacterial Agents; Azithromycin; Child; Doxycycline; Humans; Orientia tsutsugamushi; Scrub Typhus

NA.

Topics: Anti-Bacterial Agents; Azithromycin; Child; Doxycycline; Humans; Intensive Care Units, Pediatric; Nepal; Risk Factors; Scrub Typhus

Scrub typhus is typically associated with a rapid defervescence and clinical improvement within 48 h of initiation of appropriate antibiotics. But increasing reports of resistance to anti-rickettsial medications in scrub typhus are being reported in the literature.. This is a retrospective observational study of children up to the age of 14 years admitted between July 2017 and March 2020, to a private medical college hospital in southern part of India. The aim of this study was to compare the clinical response to antibiotic therapy with doxycycline and azithromycin in pediatric scrub typhus infection.. One hundred thirty-eight children with scrub typhus infection were included for analysis. The median fever control time (h) was 12 (IQR = 6-29) and 24 (IQR = 10-52) with doxycycline and azithromycin respectively (p < 0.001*). Rapid fever control within 48 h was observed in 92% with doxycycline and in 74% with azithromycin (p < 0.001*). The clinical failure rate (defined by the necessity to change the antibiotics due to: (i) worsening of symptoms and signs of scrub typhus despite 48 h of antibiotics or (ii) persistence of fever and other symptoms of scrub typhus beyond 72 h), was significantly less with doxycycline (1%) compared with azithromycin (9.6%).. There has been a significant delayed clinical response to azithromycin in the treatment of scrub typhus in India, when compared to doxycycline. Hence it is preferable to use doxycycline as the first line of antibiotic for undifferentiated fever in scrub typhus endemic areas.. This retrospective study aims to compare the clinical response to doxycycline or azithromycin in the treatment of scrub typhus infection in children. The median fever control time, clinical failure rate and the proportion of children with rapid defervescence of fever within 48 h were significantly superior with doxycycline as compared to azithromycin. The findings of this study and those of similar studies in India represent a spectrum of delayed clinical response of Orientia tsutsugamushi to azithromycin as compared to doxycycline in this region.

Topics: Adolescent; Anti-Bacterial Agents; Azithromycin; Child; Humans; India; Orientia tsutsugamushi; Retrospective Studies; Scrub Typhus

Clinical and laboratory parameters of multisystem inflammatory syndrome in children (MIS-C) mimic Kawasaki disease (KD). KD has been described in association with dengue, scrub typhus and leptospirosis. However, MIS-C with concomitant infection has rarely been reported in literature. A 14-year-old-girl presented with fever and rash with history of redness of eyes, lips and tongue. Investigations showed anemia, lymphopenia, thrombocytosis with elevated erythrocyte sedimentation rate, C-reactive protein, pro-brain natriuretic peptide, Interleukin-6, ferritin and d-dimer. Scrub typhus immunoglobulin M was positive. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunoglobulin G (IgG) level was also elevated. A diagnosis of MIS-C with concomitant scrub typhus was proffered. Child received azithromycin, intravenous immunoglobulin and methylprednisolone. After an afebrile period of 2.5 days, child developed unremitting fever and rash. Repeat investigations showed anemia, worsening lymphopenia, thrombocytopenia, transaminitis, hypertriglyceridemia, hyperferritinemia and hypofibrinogenemia which were consistent with a diagnosis of macrophage activation syndrome (MAS). KD, MIS-C and MAS represent three distinct phenotypes of hyperinflammation seen in children during coronavirus disease pandemic. Several tropical infections may mimic or coexist with MIS-C which can be a diagnostic challenge for the treating physician. Identification of coexistence or differentiation between the two conditions is important in countries with high incidence of tropical infections to guide appropriate investigations and treatment.

Topics: Adolescent; Azithromycin; Biomarkers; Child; COVID-19; Female; Fever; Humans; Immunoglobulin G; Immunoglobulins, Intravenous; Macrophage Activation Syndrome; Methylprednisolone; Pandemics; SARS-CoV-2; Scrub Typhus; Systemic Inflammatory Response Syndrome

A 23-year-old primigravida at 20 weeks of gestation presented to our hospital with undifferentiated febrile illness and severe acute respiratory distress syndrome. She was intubated in the emergency department and transferred to the intensive care unit. Initial treatment included ventilatory care, vasopressor support and broad-spectrum antibiotics. Based on a positive PCR assay for scrub typhus, she was treated with intravenous doxycycline and azithromycin. Despite reduction in fever, her oxygenation further declined. Following a risk-benefits assessment, we decided to ventilate her in prone position for 8 hours a day for three consecutive days using a checklist-based protocol. Her oxygenation indices and lung compliance markedly improved over this period, and she was extubated a day later. She was eventually discharged home after 1 week.

Topics: Adult; Anti-Bacterial Agents; Azithromycin; Doxycycline; Female; Humans; Pregnancy; Respiratory Distress Syndrome; Scrub Typhus; Young Adult

Scrub typhus is an acute febrile illness, which was caused by Orientia tsutsugamushi and transmitted through the bite of chiggers. The diagnosis of scrub typhus could be missed diagnosis due to the absence of the pathognomonic eschar.. A 76-year-old man was hospitalized with fever and kidney injury and was diagnosed of hemorrhagic fever with renal syndrome first. However, the situation of the illness deteriorated into refractory septic shock and multiple organ dysfunction rapidly,although the treatment of anti-sepsis was used in 3rd-5th day. Orientia tsutsugamushi was determined to be the causative pathogen by Next-generation sequencing of his plasma sample in 6th day. Then, the patient was treated with doxycycline and azithromycin and recovered quickly.. Next-generation sequencing was a new diagnostic technology and could identify scrub typhus in accurately and fast without the pathognomonic eschar.

Topics: Aged; Animals; Azithromycin; Bacteremia; Bites and Stings; Communicable Diseases; Data Accuracy; Doxycycline; High-Throughput Nucleotide Sequencing; Humans; Male; Orientia tsutsugamushi; Scrub Typhus; Shock, Septic; Treatment Outcome; Trombiculidae

Scrub typhus, an important cause of unexplained fever, is grossly neglected and often misdiagnosed in low and middle income countries like Nepal. The main aim of this study was to report on the clinical profile and complications of scrub typhus and its outcome in Nepalese children.. A prospective observational study was carried out in children aged 1-16 years, admitted to a tertiary care hospital of central Nepal in between July 2016- Aug 2017. Scrub typhus was diagnosed with IgM ELISA.. All cases of scrub typhus (n = 76) presented with fever and commonly had other symptoms such as headache (75%), myalgia (68.4%), vomiting (64.5%), nausea (59.2%), abdominal pain (57.9%), cough (35.5%), shortness of breath (22.4%), altered sensorium (14.5%), rashes (13.2%) and seizures (11.8%). Important clinical signs noticed were lymphadenopathy (60.5%), hepatomegaly (47.4%), edema (26.3%), jaundice (26.3%), and splenomegaly (15.8%). About 12% (n = 9) had necrotic eschar. Similarly, thrombocytopenia, raised liver enzymes and raised creatinine values were seen in 36.9%, 34.2% and 65.8% respectively. The most common complications were myocarditis (72.4%), hypoalbuminemia (71.1%), severe thrombocytopenia (22.4%), renal impairment (65.8%), hyponatremia (48.7%) and hepatitis (34.2%). Over two-thirds (69.70%) of the cases were treated with doxycycline followed by combination with azithromycin in the remaining 18.4%. Overall, mortality rate in this group was 3.9%.. Scrub typhus should be considered as a differential in any community acquired acute undifferentiated febrile illness regardless of the presence of an eschar. Myocarditis and acute kidney injury are important complications which when addressed early can prevent mortality. Use of doxycycline showed a favorable outcome.

Topics: Adolescent; Anti-Bacterial Agents; Azithromycin; Child; Child, Preschool; Doxycycline; Drug Therapy, Combination; Female; Humans; Infant; Male; Nepal; Prospective Studies; Scrub Typhus; Tertiary Care Centers; Treatment Outcome

Scrub typhus has emerged as an important cause of febrile illness in this Himalayan region of the country. However, it is under considered in the differential diagnoses of febrile illnesses and is not treated and thus, patients often land up with complications in this tertiary care hospital.. It was a retrospective observational study done in department of Medicine from august 2013 to October 2013. All the patients more than or equal to 18 yrs of age admitted during this period with scrub typhus were analysed and their outcome followed. S. ELISA was used to detect scrub typhus.. Total of 106 patients were observed out of which only 10 patients had received anti scrub antibiotics (doxycycline or azithromycin) prior to admission. Seven patients died (6.6%) and none had received anti scrub antibiotics prior to hospitalisation and presented late with average duration of illness of 9.2 days and had more severe form of complications at presentation.Those patients who had received prior anti scrub treatment had fewer and mild complications and none died among that group.. Doxycycline or azithromycin (pregnancy or in child <8 years) should be included in the initial empirical antimicrobial therapy in febrile patients during tick season to treat scrub typhus. The goal is to begin anti-scrub therapy early to reduce the morbidity and mortality associated with this illness.

Topics: Anti-Bacterial Agents; Azithromycin; Child; Doxycycline; Humans; Retrospective Studies; Scrub Typhus

Severe fever with thrombocytopenia syndrome (SFTS) is a tick-borne viral disease with a high mortality rate. Infection can also occur through close contact with an infected patient. Scrub typhus is an acute febrile illness caused by

Topics: Aged; Anti-Bacterial Agents; Azithromycin; Bites and Stings; Bunyaviridae Infections; Ceftriaxone; Coinfection; Female; Genotype; Humans; Leukopenia; Molecular Diagnostic Techniques; Orientia tsutsugamushi; Phlebovirus; Phylogeny; Republic of Korea; Scrub Typhus; Thrombocytopenia; Tick-Borne Diseases; Treatment Outcome

Neonatal hepatitis with acute liver failure due to varied etiology including various infections is reported in the past. Scrub typhus as a cause of neonatal hepatitis has rarely been reported in literature. A high index of clinical suspicion is required for early diagnosis and timely treatment. Severity and prognosis of the disease varies widely because several different strains of Orientia tsutsugamushi exist with different virulence. Delayed diagnosis can result in complication and significant morbidity and mortality. Here, we report three cases of neonatal hepatitis with acute liver failure caused by scrub typhus to increase awareness.

Topics: Anti-Bacterial Agents; Azithromycin; Fatal Outcome; Hepatitis A; Humans; Infant, Newborn; Liver Failure, Acute; Male; Scrub Typhus; Treatment Outcome

Scrub typhus is a re-emerging mite-borne rickettsiosis, which continues to be underdiagnosed, with lethal consequences. The present study was conducted to determine the seasonality, clinical presentation and predictors of mortality in patients with scrub typhus at a tertiary care teaching hospital in northern India.. Scrub typhus was suspected in patients attending the hospital as per the standard case definition and serological evidence was obtained by performing an IgM ELISA.. A total of 284 patients with scrub typhus from urban and rural areas were seen, predominantly from July to November. The most common clinical presentation was a bilateral community-acquired pneumonia (CAP), which resembled pneumonia due to atypical pathogens and often progressed to acute respiratory distress syndrome (ARDS). An acute undifferentiated febrile illness (AUFI) or a febrile illness associated with altered sensorium, aseptic meningitis, shock, abdominal pain, gastrointestinal bleeding or jaundice was also seen. Eschars were seen in 17 per cent of patients, and thrombocytopenia, transaminitis and azotaemia were frequent. There were 24 deaths (8.5%) caused predominantly by ARDS and multi-organ dysfunction. The mortality in patients with ARDS was high (37%). ARDS [odds ratio (OR)=38.29, 95% confidence interval (CI): 9.93, 147.71] and acute kidney injury (OR=8.30, 95% CI: 2.21, 31.21) were the major predictors of death.. The present findings indicate that scrub typhus may be considered a cause of CAP, ARDS, AUFI or a febrile illness with multisystem involvement, in Uttarakhand and Uttar Pradesh, especially from July to November. Empiric therapy of CAP may include doxycycline or azithromycin to ensure coverage of underlying unsuspected scrub typhus.

Topics: Adult; Azithromycin; Community-Acquired Infections; Doxycycline; Female; Humans; India; Male; Middle Aged; Orientia tsutsugamushi; Pneumonia; Respiratory Distress Syndrome; Scrub Typhus

To study the clinical and laboratory profile of pediatric scrub typhus in rural south India.. This is a descriptive study of the clinical and laboratory features of 117 children with IgM ELISA proven scrub typhus out of 448 children, who were admitted in the Pediatric ward of a tertiary care hospital, during the study period of November 2014 through March 2015.. Fever was present in all 117 children, with mean duration of fever at admission as 9 d. Gastrointestinal tract was the most commonly affected system, seen in 51 % of children. Cough (82 %), myalgia (70 %), vomiting (68 %), headache (45 %) and pain abdomen (42 %) were the most common symptoms of scrub typhus. Hepatomegaly (70), splenomegaly (53 %), pallor (50 %) and eschar (41 %) were the common clinical findings in children with scrub typhus. Out of 49 children with eschar, 32 were associated with regional lymphadenopathy, which was commonly seen in axillary, neck and groin regions. Leucocytosis (50 %), anemia (56 %), increased SGOT / SGPT (47 %), thrombocytopenia (41 %), hypoalbuminemia (40 %) and hyponatremia (40 %) were the common lab features. Shock (46 %), myocarditis (24 %) and pneumonia (16 %) were the common complications seen in these children. This study showed that early treatment for scrub typhus results in a good outcome in terms of early recovery and nil mortality.. Regional lymphadenopathy is a marker of hidden or developing eschar. Total count and differential count should be interpreted on the background of the duration of fever. Since IgM ELISA, which is diagnostic of scrub typhus may not be widely available, any febrile child coming from rural area with hepatosplenomegaly, pallor, eschar, generalised / regional lymphadenopathy, anemia, leucocytosis, thrombocytopenia and increased Aspartate transaminase (AST) /Alanine aminotransferase (ALT) should be started on empirical Doxycycline or Azithromycin in order to prevent life threatening complications secondary to delay in therapy.

Topics: Anti-Bacterial Agents; Azithromycin; Child; Doxycycline; Female; Fever; Humans; India; Male; Scrub Typhus

Scrub typhus, caused by Orientia tsutsugamushi, has recently emerged in northern China where the disease had not been known to exist. Although doxycycline and azithromycin are the recommended agents for the treatment of scrub typhus, clinical responses depend both on the susceptibilities of various O. tsutsugamushi strains and the severity of the disease. A retrospective analysis was conducted on patients diagnosed with mild scrub typhus from August 2013 to January 2016 in the Affiliated Hospital of Nantong University, northern China. A total of 40 patients who received minocycline treatment and 34 patients who received azithromycin treatment were included in the analysis. All patients except one defervesced within 120 h after initiating antimicrobial therapy. Kaplan-Meier curves in association with log-rank test showed that the median time to defervescence was significantly shorter for the minocycline-treated group than the azithromycin-treated group (P = 0.003). There were no serious adverse events during treatment. No relapse occurred in either group during the 1-month follow-up period. In conclusion, both minocycline and azithromycin are effective and safe for the treatment of mild scrub typhus, but minocycline is more active than azithromycin against O. tsutsugamushi infection acquired in northern China.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Azithromycin; China; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Male; Middle Aged; Minocycline; Pregnancy; Retrospective Studies; Scrub Typhus; Time Factors; Treatment Outcome; Young Adult

To study the pattern of the clinical presentation, laboratory findings and mortality risk among patients infected by scrub typhus in Western Himalayan region of India.. We studied all serologically confirmed cases of scrub typhus admitted to our hospital from July 2010 through December 2011. Presence of IgM antibodies to scrub typhus antigens by ELISA was considered as serological confirmation of the diagnosis. We observed the symptoms, signs, laboratory findings, risk factors for death from the time of admission till discharge/death. We performed bivariate and logistic regression analysis to look for independent risk factors for death.. Total 253 patients were studied. All patients came from rural areas. More than 2/3rd were women and below 50 years of age each. High grade fever (90%), chills and rigors (68%), conjunctival suffusion (50%), body aches (43%), headache (41%), myalgias (37%), abdominal pain (21%), lymphadenopathy (17%), splenomegaly (17%), cough (16%), altered sensorium (16%), vomiting (15%), hepatomegaly (13%) were main presenting features. Eschar was present in 112 (44%) patients. Transaminitis (49%); and abnormal renal functions (31%) were predominant biochemical abnormalities. All patients were empirically treated with doxycycline/azithromycin. Thirteen (5%) patients died.. In our region, rural women below 50 years of age presenting with high grade fever with or without eschar should be strongly suspected to be having scrub typhus. Renal dysfunction and altered sensorium are significant mortality risk factors (p < 0.05) and need to be identified at early stage to improve the treatment outcomes.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Azithromycin; Doxycycline; Enzyme-Linked Immunosorbent Assay; Female; Fever; Humans; Immunoglobulin M; India; Male; Middle Aged; Orientia tsutsugamushi; Risk Factors; Scrub Typhus; Young Adult

Topics: Aged; Antibodies, Bacterial; Azithromycin; Doxycycline; Drug Therapy, Combination; Female; Fluorescent Antibody Technique, Direct; Gastritis; Gastroscopy; Humans; Orientia tsutsugamushi; Scrub Typhus; Treatment Outcome

We report a case of dual infection of scrub typhus and malaria in a 48-year-old woman.

Topics: Animals; Anti-Bacterial Agents; Azithromycin; Chloroquine; Coinfection; Doxycycline; Enzyme-Linked Immunosorbent Assay; Female; Fever; Humans; Immunoglobulin M; Malaria; Middle Aged; Norepinephrine; Orientia tsutsugamushi; Plasmodium vivax; Scrub Typhus; Sepsis; Severity of Illness Index; Treatment Outcome

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.

Topics: Aged; Anti-Bacterial Agents; Azithromycin; Case-Control Studies; Doxycycline; Female; Humans; Kaplan-Meier Estimate; Male; Propensity Score; Retrospective Studies; Risk Factors; Scrub Typhus; Treatment Outcome

To analyze the clinical manifestations and intervention against fulminant scrub typhus-associated hemophagocytic syndrome.. The medical records for the onset time of hemophagocytic syndrome, the clinical course, the chest radiographic findings, laboratory data, antibiotic therapy, clinical outcome and its prognosis were retrospectively reviewed.. (1) Four patients were diagnosed as scrub typhus based on clinical manifestations only, while 15 patients met the criteria of laboratory diagnosis. All 19 patients with scrub typhus had hemophagocytic syndrome. Eschar lesion was identified in 12 patients, 7 patients were described as an ulcer. A seasonal pattern (78.9% from June through September in 15 patients) was observed. Clinical misdiagnosis was common (all 19 cases). There were 9 patients with admitting diagnosis of scrub typhus, 10 patients were not diagnosed as scrub typhus after admission. In 5 cases within 3 days after admission diagnosis was corrected as scrub typhus. Until discharge from the hospital, 5 cases were not diagnosed with scrub typhus. In this study, the length of time from the illness onset (beginning of fever) to the occurrence of clinical symptoms was (9 ± 4) days. (2) All 19 patients had changed AST levels (149 ± 37) U/L, albumin levels (23 ± 4) g/L, C-reactive protein levels (103 ± 51) mg/L, and platelet count (48 ± 41) × 10⁹/L; bone marrow aspiration revealed in 16 patients marked hemophagocytosis. Weil-Felix agglutination test revealed positive results in 6 of 15 cases. Diagnostic IFA results were positive for 14 patients; 19 patients had interstitial pneumonitis and 17 patients had pleural effusion. (3) Five cases with failure to diagnose the disease had ineffective antibiotics treatment (imipenem or β-lactam-based regimens). These patients did not receive appropriate treatment with antibiotics against scrub typhus. Fourteen patients with admitting diagnosis of scrub typhus were successfully treated with appropriate antibiotics, 8 cases with chloramphenicol, 3 cases with azithromycin, and in 3 patients (2 cases of azithromycin and one case of erythromycin), therapy was then switched to chloramphenicol. Four patients were treated with methylprednisolone and 10 patients with dexamethasone. (4) During their hospitalization, the clinical course in five cases with failure to diagnose the disease rapidly developed and progressed to the life-threatening MODS, four of five cases died. However, the course in 14 patients were relieved and did not progress to MODS.. The diagnosis of scrub typhus was frequently delayed, the early course of scrub typhus could be associated with hemophagocytic syndrome. Serious complications of MODS generally occur without antibiotic treatment. Scrub typhus-associated hemophagocytic syndrome should be taken into consideration among patients with acute systemic febrile illness, significant increases in levels of CRP, hypoalbuminemia, thrombocytopenia, splenomegaly, pneumonitis with pleural effusion, especially those with suspected exposure history. It was not easily recognized without careful observation and was present for a few days in each patient.

Topics: Anti-Bacterial Agents; Azithromycin; C-Reactive Protein; Clinical Laboratory Techniques; Diagnosis, Differential; Erythromycin; Humans; Imipenem; Lymphohistiocytosis, Hemophagocytic; Pneumonia; Retrospective Studies; Scrub Typhus

To study the clinical profile and outcome of scrub typhus cases admitted in an urban referral centre.. This descriptive study describes the clinical profile of 67 children with scrub typhus, who were admitted in an urban referral centre(ICH & HC,Chennai) during the period between October 2010 and March 2011.The diagnosis was confirmed by IgM ELISA.. All children presented with fever. Eschar and rash were present in 46% and 35% cases, respectively. Cough, vomiting, altered sensorium and oliguria were present in 73%,59%,58% and 43%, respectively. Hepatosplenomegaly and pallor were the commonest findings encountered in more than 80% children. Other findings were edema, lymphadenopathy and icterus.Thrombocytopenia, elevated liver enzymes and leukocytosis were seen in 77%, 64% and 49% cases, respectively. Pleural effusion, ascites, shock and respiratory failure were seen in 61%, 47%,45%,34% cases, respectively. Acute renal failure, hepatic failure, multiorgan dysfunction syndrome (MODS), meningoencephalitis and acute respiratory distress syndrome(ARDS) were seen in 10%,10%,7%,6% and 4% cases, respectively. Doxycycline and azithromycin were the antibiotics used. The overall mortality rate was 11.94%. Causes of death were shock, ARDS, acute renal failure(ARF), MODS and disseminated intravascular coagulation(DIVC).. When a child presents with acute febrile illness, maculopapular or erythematous rash, hepatosplenomegaly, lymphadenopathy, thrombocytopenia and features suggestive of capillary leak, diagnosis of Scrub typhus must be considered and the child should be started on empirical therapy with doxycycline or azithromycin which is life saving.

Topics: Anti-Bacterial Agents; Antibodies, Bacterial; Azithromycin; Biomarkers; Child; Child, Preschool; Doxycycline; Enzyme-Linked Immunosorbent Assay; Female; Hospitals, Urban; Humans; Immunoglobulin M; India; Infant; Infant, Newborn; Male; Orientia tsutsugamushi; Scrub Typhus; Tertiary Care Centers; Treatment Outcome

To identify and report a recent outbreak of scrub typhus cases recorded from October 2009 to January 2010 in the state of Meghalaya, India.. The case sheets of all the children were retrieved and reviewed retrospectively. Twenty four (24) patients, who were both clinically and serologically confirmed as scrub typhus cases were included in the study.. Fever for more than 1 wk duration was the most common manifestation (100%) followed by splenomegaly (45.8%), eschar (41.7%), cough (37.5%), hepatomegaly (33.3%), headache and body ache (25%), pain abdomen (25%), vomiting (20.8%), altered sensorium (16.6%), seizures (12.5%) lymphadenopathy (12.5%), and loose stools (8.3%). Meningoencephalitis was the most common complication (29.2%) followed by pneumonia (16.3%) and subconjunctival hemorrhage (8.3%).Cortical blindness, septic shock, peritonitis, myocarditis with CCF, pancytopenia, acute renal failure, coagulopathy, prolonged oxygen dependency and urinary tract infection (UTI) were found in one of each case. Hyponatremia (66.7%), elevated liver enzymes without significant rise of bilirubin (58.3%), hypoalbuminemia (52.2%) and thrombocytopenia (26%) were the other significant laboratory findings. Patients were treated with chloramphenicol, doxycycline and azithromycin. There was no mortality.. This is the first outbreak report from the north eastern region of India with varied clinical presentations, laboratory investigations and complications. Weil Felix test still remains fruitful for diagnosing this disease in a resource limited set up.

Topics: Anti-Bacterial Agents; Azithromycin; Child; Chloramphenicol; Disease Outbreaks; Doxycycline; Female; Humans; India; Male; Meningoencephalitis; Retrospective Studies; Scrub Typhus

Topics: Adult; Anti-Bacterial Agents; Azithromycin; Doxycycline; Female; Gastrointestinal Hemorrhage; Humans; Male; Middle Aged; Scrub Typhus

Orientia tsutsugamushi causes scrub typhus and is a rural zoonosis endemic in the Asia Pacific region. This is the first report of O. tsutsugamushi TA716-like strain in a human in Thailand. The patient was in the 1st trimester of pregnancy when she developed scrub typhus. The O. tsutsugamushi strain TA716 was detected from her admission blood sample, and the pregnancy ended in spontaneous abortion. The effects of scrub typhus in pregnant women and the pregnancy outcome are sparsely documented in the published medical literature. Improved clinical recognition and laboratory diagnosis will be essential to better define the morbidity caused by this zoonosis especially in pregnancy.

Topics: Adult; Animals; Azithromycin; Chlorocebus aethiops; Female; Humans; Orientia tsutsugamushi; Pregnancy; Scrub Typhus; Vero Cells

Topics: Agglutination Tests; Antibodies, Bacterial; Azithromycin; Doxycycline; Enzyme-Linked Immunosorbent Assay; Female; Humans; Immunoglobulin M; India; Middle Aged; Orientia tsutsugamushi; Scrub Typhus; Treatment Outcome

Topics: Adolescent; Adult; Animals; Anti-Bacterial Agents; Azithromycin; Ceftriaxone; Doxycycline; Fatal Outcome; Female; Humans; Pregnancy; Pregnancy Complications, Infectious; Scrub Typhus; Young Adult; Zoonoses

To retrospectively confirm the suspected rickettsial disease (Scrub typhus) using a gold standard diagnostic test i.e. microimmunofluorescence in pediatric patients with acute febrile illness of unknown etiology. Two serological tests, Weil-Felix and Microimmunofluorescence were used to confirm infection. All five children had fever, vomiting and generalized lymphadenopathy, but none had eschar or rash. One was cured with doxycycline, remaining four patients treated with azithromycin and one died despite treatment. Scrub typhus is a cause of fever of unknown origin in Himalayan region of India and azithromycin is an effective alternative to doxycycline in treating this disease.

Topics: Anti-Bacterial Agents; Azithromycin; Child; Child, Preschool; Doxycycline; Fatal Outcome; Female; Fever of Unknown Origin; Fluorescent Antibody Technique; Humans; India; Male; Orientia tsutsugamushi; Retrospective Studies; Scrub Typhus; Treatment Outcome

Scrub typhus, caused by Orientia tsutsugamushi, occurs throughout Southeast Asia. We descript ten cases that occurred in the Torres Strait islands of northern Australia during 2000 and 2001. Preceding heavy rain may have contributed to the outbreak. The successful use of azithromycin in two pediatric patients is also reported.

Topics: Adolescent; Adult; Anti-Bacterial Agents; Azithromycin; Child; Child, Preschool; Female; Humans; Male; Queensland; Scrub Typhus

Topics: Adult; Anti-Bacterial Agents; Azithromycin; Female; Humans; Pregnancy; Pregnancy Complications, Infectious; Scrub Typhus

In an effort to find a potential alternative treatment for scrub typhus, we evaluated the effectiveness of the standard drug doxycycline and the new macrolide azithromycin against a doxycycline-susceptible strain (Karp) and a doxycycline-resistant strain (AFSC-4) of Rickettsia tsutsugamushi. The antibiotics were tested in an in vitro assay system in which infected mouse fibroblast cells (L929) were incubated for 3 days in various concentrations of the drugs. Rickettsial growth was evaluated by direct visual counts of rickettsiae in Giemsastained cells or by flow cytometry. Initial tests were conducted at the concentration of each antibiotic considered to be the upper breakpoint for susceptibility (16 micrograms/ml for doxycycline and 8 micrograms/ml for azithromycin). Growth of both Karp and AFSC-4 was strongly inhibited with both antibiotics, as measured by visual counts, although the percentage of cells infected with AFSC-4 in the presence of doxycycline was three times greater than the percentage of cells infected with Karp but was only 60% as great as the percentage of cells infected with Karp in the presence of azithromycin. Flow cytometry confirmed that rickettsial growth occurred in the absence of antibiotics, but it failed to detect it in the presence of high concentrations of either drug. Visual counts of rickettsial growth at lower concentrations of the antibiotics (0.25 to 0.0078 microgram/ml) showed that the Karp strain was 16 times more susceptible that the AFSC-4 strain to doxycycline. Azithromycin was much more effective than doxycycline against AFSC-4, inhibiting rickettsial growth at 0.0156 microgram/ml to levels below that achieved by 0.25 microgram of doxycycline per ml. Azithromycin was also more effective than doxycycline against the Karp strain, causing greater reductions in the number of rickettsiae per cell at lower concentrations. If in vivo testing confirms the in vitro effectiveness of azithromycin, it may prove to be the drug of choice for the treatment of scrub typhus in children and pregnant women, who should not take doxycycline, and in patients with refractory disease from locations where doxycycline-resistant strains of R. tsutsugamushi have been found. When tested in an in vitro assay system, azithromycin was more effective than doxycycline against doxycycline-susceptible and -resistant strains of R. tsutsugamushi.

Topics: Animals; Anti-Bacterial Agents; Azithromycin; Doxycycline; Fibroblasts; Flow Cytometry; L Cells; Mice; Microbial Sensitivity Tests; Orientia tsutsugamushi; Scrub Typhus; Tetracycline Resistance