Trilaciclib prior to gemcitabine plus carboplatin for metastatic triple-negative breast cancer: phase III PRESERVE 2.

Triple-negative breast cancer (TNBC) is an aggressive malignancy for which cytotoxic chemotherapy remains the backbone of treatment. Trilaciclib is an intravenous cyclin-dependent kinase 4/6 inhibitor that induces transient cell cycle arrest of hematopoietic stem and progenitor cells and immune cells during chemotherapy exposure, protecting them from chemotherapy-induced damage and enhancing immune activity. Administration of trilaciclib prior to gemcitabine plus carboplatin (GCb) significantly improved overall survival (OS) compared with GCb alone in an open-label phase II trial in patients with metastatic TNBC, potentially through protection and direct activation of immune function. The randomized, double-blind, placebo-controlled, phase III PRESERVE 2 trial will evaluate the efficacy and safety of trilaciclib administered prior to GCb in patients with locally advanced unresectable or metastatic TNBC. Clinical Trial Registration: NCT04799249 (ClinicalTrials.gov).

ROBUST: A Phase III Study of Lenalidomide Plus R-CHOP Versus Placebo Plus R-CHOP in Previously Untreated Patients With ABC-Type Diffuse Large B-Cell Lymphoma.

PURPOSE: Patients with the activated B-cell-like (ABC) subtype of diffuse large B-cell lymphoma (DLBCL) historically showed inferior survival with standard rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). Phase II studies demonstrated that adding the immunomodulatory agent lenalidomide to R-CHOP improved outcomes in ABC-type DLBCL. The goal of the global, phase III ROBUST study was to compare lenalidomide plus R-CHOP (R2-CHOP) with placebo/R-CHOP in previously untreated, ABC-type DLBCL. METHODS: Histology and cell-of-origin type were prospectively analyzed by central pathology prior to random assignment and study treatment. Patients with ABC-DLBCL received lenalidomide oral 15 mg/d, days 1-14/21 plus standard R-CHOP21 versus placebo/R-CHOP21 for six cycles. The primary end point was progression-free survival (PFS) per independent central radiology review. RESULTS: A total of 570 patients with ABC-DLBCL (n = 285 per arm) were stratified by International Prognostic Index score, age, and bulky disease, and randomly assigned to R2-CHOP or placebo/R-CHOP. Baseline demographics were similar between arms. Most patients completed six cycles of treatment: 74% R2-CHOP and 84% placebo/R-CHOP. The most common grade 3/4 adverse events for R2-CHOP versus placebo/R-CHOP were neutropenia (60% v 48%), anemia (22% v 14%), thrombocytopenia (17% v 11%), and leukopenia (14% v 15%). The primary end point of PFS was not met, with a hazard ratio of 0.85 (95% CI, 0.63 to 1.14) and P = .29; median PFS has not been reached for either arm. PFS trends favoring R2-CHOP over placebo/R-CHOP were seen in patients with higher-risk disease. CONCLUSION: ROBUST is the first DLBCL phase III study to integrate biomarker-driven identification of eligible ABC patients. Although the ROBUST trial did not meet the primary end point of PFS in all patients, the safety profile of R2-CHOP was consistent with individual treatments with no new safety signals.

Direct detection of Corynebacterium striatum, Corynebacterium propinquum, and Corynebacterium simulans in sputum samples by high-resolution melt curve analysis.

BACKGROUND: Pulmonary infections caused by non-diphtheriae corynebacteria are increasing. However, rapid identification of Corynebacterium species poses a challenge due to the low genetic variation within the genus. METHODS: Three reference strains and 99 clinical isolates were used in this study. A qPCR followed by high-resolution melting (HRM) targeting ssrA was performed to simultaneously identify C. striatum, C. propinquum and C. simulans. To further evaluate this assay's performance, 88 clinical sputum samples were tested by HRM and the detection results were compared with those of the traditional culture method and multiple cross-displacement amplification (MCDA) assay. RESULTS: The melting curve produced by a pair of universal primers generated species-specific HRM curve profiles and could distinguish the three target species from other related bacteria. The limit of detection of HRM assay for DNA from the three purified Corynebacterium species was 100 fg. Compared with the culture method, HRM detected 22 additional positive specimens, representing a 23.9% relative increase in detection rate. The HRM assay had 98.4% (95% confidence interval [CI], 90.5-99.9%) sensitivity and 100% (95% CI, 82.8-100%) specificity. Additionally, 95.5% concordance between HRM and MCDA (κ = 0.89 [95% CI, 0.79-0.99]) was noted. CONCLUSIONS: The HRM assay was a simple, rapid, sensitive, and specific diagnostic tool for detecting C. striatum, C. propinquum, and C. simulans, with the potential to contribute to early diagnosis, epidemiological surveillance, and rapid response to outbreak.

Effects of Hot Extrusion Temperature on Mechanical and Corrosion Properties of Mg-Y-Zn-Zr Biological Magnesium Alloy Containing W Phase and I Phase.

The previous study conducted on the as-cast Mg-2Y-1Zn-0.6Zr alloy showed that the tensile strength, yield strength and elongation of the as-cast alloy were 245 MPa, 135 MPa and 14.4%, respectively. In order to further explore the potential of the material, the hot extrusion process of variable temperature (250 °C, 300 °C and 350 °C) was carried out on the basis of the as-cast alloy. After hot extrusion, the mechanical properties of the material have been greatly improved compared with as-cast alloy. The tensile strength, yield strength and elongation of the extruded alloy reached 327 MPa, 322 MPa and 24.9%, respectively. The reason for the significant improvement of material properties is mainly due to the dynamic recrystallization during thermal processing, which greatly fines the grains of as-cast alloy. Moreover, the experimental results shown that the corrosion performance of the alloy after hot extrusion at 300 °C is also optimal.

An immunoproteomic approach to identify antigenic proteins in Nocardia farcinica IFM 10152.

Nocardia farcinica is the etiological agent of nocardiosis, leading to serious pulmonary or systemic infections. To uncover virulence factors and early diagnostic markers, secreted proteins of N. farcinica IFM 10152 were analyzed using an immunoproteome-based approach. A total of 5 proteins were identified by matrix-assisted laser desorption (MALDI-TOF-MS). Bioinformatic analyses showed that the identified proteins were involved in defense against the host innate immune system and required for pathogenesis. All proteins were expressed in E. coli and antigenicity was analyzed with Western blot. To our knowledge, these proteins with antigenicity were identified for the first time in N. farcinica and they may help elucidate the pathogenesis underlying Nocardia and provide potential future diagnostic markers.

Whole-Genome Sequencing Reveals a Prolonged and Persistent Intrahospital Transmission of Corynebacterium striatum, an Emerging Multidrug-Resistant Pathogen.

Corynebacterium striatum is an emerging multidrug-resistant (MDR) pathogen that occurs primarily among immunocompromised and chronically ill patients. However, little is known about the genomic diversity of C. striatum, which contributes to its long-term persistence and transmission in hospitals. In this study, a total of 192 C. striatum isolates obtained from 14 September 2017 to 29 March 2018 in a hospital in Beijing, China, were analyzed by antimicrobial susceptibility testing and pulsed-field gel electrophoresis (PFGE). Whole-genome sequencing was conducted on 91 isolates. Nearly all isolates (96.3%, 183/190) were MDR. The highest resistance rate was observed for ciprofloxacin (99.0%, 190/192), followed by cefotaxime (90.6%, 174/192) and erythromycin (89.1%, 171/192). PFGE separated the 192 isolates into 79 pulsotypes, and differences in core genome single-nucleotide polymorphisms (SNPs) partitioned the 91 isolates sequenced into four clades. Isolates of the same pulsotype were identical or nearly identical at the genome level, with some exceptions. Two dominant subclones, clade 3a, and clade 4a, were responsible for the hospital-wide dissemination. Genomic analysis further revealed nine resistance genes mobilized by eight unique cassettes. PFGE and whole-genome sequencing revealed that the C. striatum isolates studied were the result mainly of predominant clones spreading in the hospital. C. striatum isolates in the hospital progressively acquired resistance to antimicrobial agents, demonstrating that isolates of C. striatum may adapt rapidly through the acquisition and accumulation of resistance genes and thus evolve into dominant and persistent clones. These insights will be useful for the prevention of C. striatum infection in hospitals.

A novel isothermal amplification-based method for detection of Corynebacterium striatum.

Corynebacterium striatum is an emerging multidrug-resistant pathogen causing increasing numbers of infections and nosocomial outbreaks worldwide. Thus, a simple, rapid and accurate method for C. striatum is urgently required for improving diagnosis efficiency. In this study, a C. striatum-multiple cross displacement amplification (MCDA) with visual detection reagent (VR) assay (C. striatum-MCDA-VR), which was a novel isothermal amplification-based method, was established to detect the species-specific ftr1 gene of C. striatum. Amplification was performed at a constant temperature (68 °C) for only 40 min, and the reaction results could be easily elucidated by observation of reaction mixture color when employing the VR. The limit of detection of this method was 10 fg of pure C. striatum DNA. No cross-reaction was observed with non-C. striatum strains. In testing of clinical sputum samples, the C. striatum-MCDA-VR assay showed excellent sensitivity and specificity when compared with sputum smear tests and PCR. The C. striatum-MCDA-VR assay is a simple, rapid and cost-effective approach for identifying C. striatum in microbiological laboratories, especially in resource-limited settings.

Long-term use of lenalidomide and low-dose dexamethasone in Chinese patients with relapsed/refractory multiple myeloma: MM-024 Extended Access Program.

BACKGROUND: The efficacy and safety of lenalidomide plus low-dose dexamethasone (Rd) in Chinese patients with relapsed/refractory multiple myeloma (RRMM) was demonstrated in a phase 2, multicenter trial (MM-021). MM-024 was an Extended Access Program (EAP) that allowed responding patients in the MM-021 trial to continue to receive Rd, and to provide additional safety and efficacy data with longer follow-up. METHODS: Chinese patients with RRMM who completed ≥ 1 year of Rd therapy in MM-021 and who remained progression-free under Rd entered the Treatment Phase of the MM-024 EAP, continuing Rd at the same dose and schedule. Patients in MM-021 who discontinued Rd treatment or progressed were allowed to enroll in the Safety Follow-Up Phase of the MM-024 EAP. Safety data, including the incidence of second primary malignancies (SPMs), were collected for ≥ 5 years from the time the last on-study patient enrolled in the MM-021 trial (primary end point). Efficacy outcomes (time to progression [TTP], progression-free survival [PFS], and overall survival [OS]) were secondary end points. RESULTS: Median follow-up was 38.4 months for the safety population (n = 80) and 43.3 months for the treatment cohort (n = 41). In the safety population, Grade 3-4 adverse events (AEs) occurred in 60.0 % of patients; the most common grade 3-4 AEs were neutropenia (20.0%), decreased neutrophil count (13.8%), and anemia (11.3%). There was no evidence of cumulative toxicity, and no patients discontinued Rd due to AEs; 2 patients had SPMs. In the treatment cohort, median duration of response was 35.1 months, median TTP was 36.9 months, and median PFS was 36.0 months; median OS was not reached due to the low number of deaths (n = 5). CONCLUSION: Long-term treatment with Rd has a predictable and manageable safety profile and provides sustained efficacy in Chinese patients with RRMM. TRIAL REGISTRATION: China State Food and Drug Administration (SFDA) registration (CTA reference numbers: 209L10808; 209L10809; 209L10810; and 209L10811) and ClinicalTrials.gov Identifier: NCT02348528. First received January 23, 2015; last updated November 12, 2015; last verified November 2015; study start date September 2012.

Lenalidomide plus low-dose dexamethasone in Chinese patients with relapsed or refractory multiple myeloma and renal impairment.

Lower starting doses of lenalidomide (LEN) are recommended for patients with renal impairment (RI). In the present study, we conducted a subgroup analysis of the MM-021 registration trial to investigate the efficacy and safety of LEN plus low-dose dexamethasone (LoDEX) in Chinese patients with advanced relapsed or refractory multiple myeloma (RRMM) based on levels of RI. Patients received LEN+LoDEX until disease progression or discontinuation. Patients were divided according to RI: no/mild [creatinine clearance (CrCl) ≥60 mL/min, n = 131], moderate (CrCl ≥30 to <60 mL/min, n = 54), and severe (CrCl <30 mL/min, n = 14). LEN starting dose was 25 mg/day on days 1-21, adjusted for baseline renal function. Best overall response rate was 48 %; in patients with no/mild, moderate, or severe RI, response rates were 50, 42, and 42 %, respectively. Median progression-free survival and overall survival were longer in patients with no/mild RI (9.3 and 22.4 months, respectively) versus those with moderate (6.9 and 16.0 months) or severe RI (4.8 and 11.1 months). LEN+LoDEX was well tolerated, although incidences of grade 3-4 neutropenia, anemia, and thrombocytopenia were higher in patients with severe RI. In Chinese patients with advanced RRMM and RI, adjusting the starting dose of LEN according to renal function did not compromise the efficacy or safety of LEN+LoDEX.

Co-circulation of multiple hemorrhagic fever diseases with distinct clinical characteristics in Dandong, China.

Hemorrhagic fevers (HF) caused by viruses and bacteria are a major public health problem in China and characterized by variable clinical manifestations, such that it is often difficult to achieve accurate diagnosis and treatment. The causes of HF in 85 patients admitted to Dandong hospital, China, between 2011-2012 were determined by serological and PCR tests. Of these, 34 patients were diagnosed with Huaiyangshan hemorrhagic fever (HYSHF), 34 with Hemorrhagic Fever with Renal Syndrome (HFRS), one with murine typhus, and one with scrub typhus. Etiologic agents could not be determined in the 15 remaining patients. Phylogenetic analyses of recovered bacterial and viral sequences revealed that the causative infectious agents were closely related to those described in other geographical regions. As these diseases have no distinctive clinical features in their early stage, only 13 patients were initially accurately diagnosed. The distinctive clinical features of HFRS and HYSHF developed during disease progression. Enlarged lymph nodes, cough, sputum, and diarrhea were more common in HYSHF patients, while more HFRS cases presented with headache, sore throat, oliguria, percussion pain kidney area, and petechiae. Additionally, HYSHF patients displayed significantly lower levels of white blood cells (WBC), higher levels of creations kinase (CK) and alanine aminotransferase (ALT), while HFRS patients presented with an elevation of blood urea nitrogen (BUN) and creatinine (CREA). These clinical features will assist in the accurate diagnosis of both HYSHF and HFRS. Overall, our data reveal the complexity of pathogens causing HFs in a single Chinese hospital, and highlight the need for accurate early diagnosis and a better understanding of their distinctive clinical features.

Factors that influence health-related quality of life in newly diagnosed patients with multiple myeloma aged ≥ 65 years treated with melphalan, prednisone and lenalidomide followed by lenalidomide maintenance: results of a randomized trial.

In the MM-015 trial, melphalan-prednisone-lenalidomide followed by lenalidomide maintenance (MPR-R) significantly prolonged progression-free survival versus melphalan-prednisone (MP) in newly diagnosed patients with multiple myeloma aged ≥ 65 years. Health-related quality of life (HRQoL), a secondary endpoint of MM-015, was also improved with MPR-R. This sub-analysis evaluated the impact of individual predictive factors on HRQoL. Patients completed HRQoL questionnaires at baseline, every third cycle and at progressive disease (PD)/treatment discontinuation. In a mixed-effects model female gender, advanced age and PD negatively affected HRQoL while better treatment responses showed positive effects. Compared to PD, HRQoL during MPR-R treatment was statistically significantly better in two of six preselected domains both of which were also clinically meaningful. HRQoL scores at end of treatment were all either improved or not statistically significantly different versus baseline. In conclusion, continuous treatment with MPR-R, which delays PD, appears to be associated with clinically meaningful improvements in HRQoL.

Identifying high-risk areas of bacillary dysentery and associated meteorological factors in Wuhan, China.

Spatial distribution of bacillary dysentery incidence was mapped at the district level in Wuhan, China. And a generalized additive time series model was used to examine the effect of daily weather factors on bacillary dysentery in the high-risk areas, after controlling for potential confounding factors. Central districts were found to be the high-risk areas. The time series analysis found an acute effect of meteorological factors on bacillary dysentery occurrence. A positive association was found for mean temperature (excess risk (ER) for 1°C increase being 0.94% (95% confidence interval (CI): 0.46% to 1.43% on the lag day 2), while a negative effect was observed for relative humidity and rainfall, the ER for 1% increase in relative humidity was -0.21% (95% CI: -0.34% to -0.08%), and the ER for 1 mm increase in rainfall was -0.23% (95% CI: -0.37% to -0.09%). This study suggests that bacillary dysentery prevention and control strategy should consider local weather variations.

A multicenter, open-label, phase 2 study of lenalidomide plus low-dose dexamethasone in Chinese patients with relapsed/refractory multiple myeloma: the MM-021 trial.

BACKGROUND: There is an unmet need for treatment options in Chinese patients with relapsed or refractory multiple myeloma (RRMM). Lenalidomide plus low-dose dexamethasone is effective and generally well tolerated in Caucasian RRMM patients, but no previous study has evaluated this regimen in Chinese RRMM patients. METHODS: MM-021 is a phase 2, multicenter, single-arm open-label registration trial conducted to assess the efficacy, safety, and pharmacokinetics of lenalidomide plus low-dose dexamethasone in Chinese patients with RRMM. Patients with ≥1 prior antimyeloma therapy received lenalidomide plus low-dose dexamethasone until disease progression or discontinuation. Follow-up of surviving patients continued for ≥1 year after enrollment. The lenalidomide dose was 25 mg/day, and was adjusted according to baseline renal function. Most patients had advanced disease (85.6% had Durie-Salmon stage III) and were heavily pretreated (56.7% had received ≥4 prior regimens; 69.5% prior thalidomide and 63.1% prior bortezomib); 5.3% had immunoglobulin D (IgD) disease. RESULTS: The safety population comprised 199 eligible patients. In the efficacy population (n = 187), the disease control rate (at least stable disease) was 94.7%, and the overall response rate (at least partial response) was 47.6%. High response rates were also achieved in patients who had renal impairment and in those with IgD disease. After a median study follow-up of 15.2 months, the median response duration was 8.8 months (range, 0.4-18.8 months) and median progression-free survival was 8.3 months (95% CI 6.5-9.8). The most common grade 3-4 adverse events (AEs) were anemia (26.1%), neutropenia (25.1%), thrombocytopenia (14.6%), pneumonia (13.1%), leukopenia (9.5%), and decreased neutrophil count (8.5%). AEs led to lenalidomide dose reduction and/or interruption in 40.2% of patients, and treatment discontinuation in about 9% of patients. The pharmacokinetic profile of lenalidomide was similar to that reported in Caucasian and Japanese patients. CONCLUSIONS: Lenalidomide plus low-dose dexamethasone was associated with a high response rate and acceptable safety profile in heavily pretreated Chinese patients with RRMM, including those with renal impairment and IgD subtype. These findings highlight the clinical potential of this regimen in Chinese RRMM patients who have exhausted current treatment options. TRIAL REGISTRATION: China State Food and Drug Administration (SFDA) registration (CTA reference numbers: 209 L10808; 209 L10809; 209 L10810; and 209 L10811) and ClinicalTrials.gov identifier: NCT01593410.

Contribution of follicular dendritic cells to persistent HIV viremia.

HIV-1 infections cannot be completely eradicated by drug therapy, as the virus persists in reservoirs. Low-level plasma viremia has been detected in patients treated for over 7 years, but the cellular compartments that support this low-level viremia have not been identified. The decay of HIV-1 during treatment appears to occur in four phases, with the 3rd and 4th phases occurring when the virus is below the limit of detection of conventional assays. Here, we focus on the 3rd phase of decay, which has been estimated to have a half-life of 39 months. We show that follicular dendritic cells (FDC), which have been identified as an HIV reservoir, can be the main source of the low-level viremia detected during the 3rd phase of decay and contribute to viremia at even longer times. Our calculations show that the kinetics of leakage of virus from FDC is consistent with three types of available clinical data.

Modeling the acute and chronic phases of Theiler murine encephalomyelitis virus infection.

Theiler murine encephalomyelitis virus (TMEV) infection of a mouse's central nervous system is biphasic: first the virus infects motor neurons (acute phase), and this is followed by a chronic phase in which the virus infects glial cells (primarily microglia and macrophages [M]) of the spinal cord white matter, leading to inflammation and demyelination. As such, TMEV-induced demyelinating disease in mice provides a highly relevant experimental animal model for multiple sclerosis. Mathematical models have proven valuable in understanding the in vivo dynamics of persistent virus infections, such as HIV-1, hepatitis B virus, and hepatitis C virus infections. However, viral dynamic modeling has not been used for understanding TMEV infection. We constructed the first mathematical model of TMEV-host kinetics during acute and early chronic infections in mice and fit measured viral kinetic data with the model. The data fitting allowed us to estimate several unknown parameters, including the following: the rate of infection of neurons, 0.5 × 10(-8) to 5.6 × 10(-8) day(-1); the percent reduction of the infection rate due to the presence of virus-specific antibodies, which reaches 98.5 to 99.9% after day 15 postinfection (p.i.); the half-life of infected neurons, 0.1 to 1.2 days; and a cytokine-enhanced macrophage source rate of 25 to 350 M/day into the spinal cord starting at 10.9 to 12.9 days p.i. The model presented here is a first step toward building a comprehensive model for TMEV-induced demyelinating disease. Moreover, the model can serve as an important tool in understanding TMEV infectious mechanisms and may prove useful in evaluating antivirals and/or therapeutic modalities to prevent or inhibit demyelination.

Lenalidomide, melphalan, and prednisone, followed by lenalidomide maintenance, improves health-related quality of life in newly diagnosed multiple myeloma patients aged 65 years or older: results of a randomized phase III trial.

The MM-015 trial assessed the effect of lenalidomide-based therapy on health-related quality of life. Patients (n=459) with newly diagnosed multiple myeloma aged 65 years or over were randomized 1:1:1 to nine 4-week cycles of lenalidomide, melphalan, and prednisone, followed by lenalidomide maintenance; or lenalidomide, melphalan, and prednisone, or melphalan and prednisone, with no maintenance therapy. Patients completed health-related quality of life questionnaires at baseline, after every third treatment cycle, and at treatment end. Health-related quality of life improved in all treatment groups during induction therapy. Patients receiving lenalidomide maintenance had the most pronounced improvements, Global Health Status/Quality of Life (P<0.05), Physical Functioning (P<0.01), and Side Effects of Treatment (P<0.05) out of 6 pre-selected health-related quality of life domains. More patients receiving lenalidomide maintenance achieved minimal important differences (P<0.05 for Physical Functioning). Therefore, lenalidomide, melphalan, and prednisone, followed by lenalidomide maintenance, improves health-related quality of life in patients with newly diagnosed multiple myeloma. (Clinicaltrials.gov identifier NCT00405756).

An outbreak of Mycoplasma pneumoniae caused by a macrolide-resistant isolate in a nursery school in China.

Eighteen out of 45 children were reported to have a respiratory illness during an outbreak at a temporary dormitory in a nursery school in China in 2011. To study the outbreak and to determine the risk factors for infection, an epidemiological investigation was performed. A standardized questionnaire was completed for a total of 45 children with the help of their guardians and parents. In addition, acute- and convalescent-phase serum samples and throat swabs from the children were taken for laboratory diagnosis. The diagnosis of a Mycoplasma-like illness was based on the following clinical criteria. The criteria were onset of illness after 31 May 2011, characterized by a cough, fever(>37.5 °C), or at least 3 of the following symptoms: fever, sore throat, cough or expectoration, and runny or stuffy nose. PCR-restriction fragment length polymorphism (PCR-RFLP), determination of MICs, and sequencing were performed to determine the genotype, antibiotic resistance, and sequence polymorphisms of the isolated strains, respectively. The paired sera revealed that 15 patients were infected with Mycoplasma pneumoniae. Epidemiology confirmed that this was a point source outbreak, characterized by a short incubation period, a high secondary attack rate, and a long period of hospitalization. PCR-RFLP analysis revealed that the 12 isolated strains of M. pneumoniae shared the same subtype P1 gene, and 23S rRNA sequence analysis showed that these strains harbored two macrolide-resistant gene-related point mutations at position 2063 and 2617. In this outbreak, the major risk factor was the distance between the bed of the first patient and the beds of close contacts (beds less than three meters apart). The strains isolated in this study were found to harbor two point mutations conferring macrolide resistance, indicating the importance of pathogen and drug resistance surveillance systems.

Investigation of anaplasmosis in Yiyuan County, Shandong Province, China.

OBJECTIVE: To investigate the situation of anaplasmosis in Yiyuan county, Shandong Province. METHODS: A total of 26 blood samples from febrile patients suspected of anaplasmosis, 48 blood samples from healthy farmers, 8 from dogs, and 10 from goats and 170 ticks were collected in the same area during 2005-2007, and detected by serological and molecular methods. RESULTS: Eight confirmed cases and 6 probable cases were determined using serologic and molecular methods. The seroprevalence of Anaplasma phagocytophilum (A. phagocytophilum) was 26.7% in healthy cases. Nine out of 10 sheep samples and 7 out of 8 dog samples reacted positively to the A. phagocytophilum antigen. PCR amplification and sequencing of the 16SrRNA of A. phagocytophilum gene showed that some samples from patients, goats and ticks were 100% identical. The seroprevalence of Rickettsia typhi was 22.9%, Orientia tsutsugamushi 6.3%, Rickettsia sibirica 27.1%, Coxiella burnetii 18.8%, Bartonella henselae 31.3%, and Borrelia burgdorferi 41.6%. CONCLUSIONS: It is important to make differential diagnosis of febrile patients and to apply treatment with specific antibiotics. It is needed to enforce essential prevention and control measures including tick control and to improve sanitation conditions.