This study aimed to assess the likelihood of an outbreak or epidemic of emerging infectious diseases (EIDs) in Shaoxing city, China, and its resulting impact to provide decision makers with quantitative, directive results. Factors related to the risk of EIDs were selected through meeting with experts and were arranged in a hierarchical structure. These evaluation factors were also weighted to allow the use of a point system for evaluation. As a result, 14 evaluation factors comprising a 3-layer hierarchy were generated. The riskiest top 10 EIDs were HIV/AIDS (consistency index [CI] = 3.206), cholera (CI = 3.103), SARS (CI = 2.804), acute schistosomiasis (CI = 2.784), malaria (CI = 2.777), legionellosis (CI = 2.743), avian influenza A/H5N1 (CI = 2.734), dengue fever (CI = 2.702), Escherichia coli O157:H7 enteritis (CI = 2.593), and plague (CI = 2.553). The risk assessment was specifically intended to support local and national government agencies in the management of high risk EIDs in their efforts to (i) make resource allocation decisions, (ii) make high-level planning decisions, and (iii) raise public awareness of the EID risk. The results showed that the EID risk in Shaoxing could be effectively assessed through an analytic hierarchy process.
Severe fever with thrombocytopenia syndrome (SFTS) is a disease with a high case fatality rate that is caused by infection with the recently identified tick-borne SFTS virus (SFTSV), for which there are no specific countermeasures. We examined the effects of ribavirin and mizoribine, which are nucleoside analogue drugs with broad antiviral activities, on SFTSV proliferation in vitro. When 3 cell lines were treated with these drugs before and during infection with a Chinese SFTSV strain, the 99% effective concentrations (EC99) of ribavirin were 19–64 μg/ml (78–262 μM); in contrast, the EC99 of mizoribine was >500 μg/ml (1,929 μM). Similar levels of inhibitory effects of ribavirin were observed with 4 Japanese SFTSV strains. However, when Vero cells were treated with ribavirin 3 days after inoculation, the inhibitory effect was dramatically decreased, indicating that ribavirin did not effectively reduce virus production in pre-infected cells. These results suggest that ribavirin could be used as post-exposure prophylaxis for the prevention of SFTS.
To compare the clinical features of patients with tuberculous meningitis (TBM) and bacterial meningitis (BM) and to validate Thwaites' diagnostic scoring system for the differential diagnosis of TBM and BM, a retrospective review of 211 patients with TBM or BM who were admitted to Huashan Hospital, Fudan University, from 2007 to 2012 was conducted. The clinical characteristics and laboratory data were compared, and Thwaites' diagnostic scores were assessed at the time of admission for the differential diagnosis of TBM and BM. Significant differences were observed between the 2 groups in general information, clinical features, and cerebrospinal fluid characteristics. The sensitivity and specificity of Thwaites' diagnostic scoring system for the differential diagnosis of TBM and BM were found to be 98.2% and 43.6%, respectively, with positive and negative predictive values being 65.9% and 95.8%, respectively. The sensitivity and specificity for the differential diagnosis of TBM and initially treated BM were 98.2% and 82.9%, respectively, but were only 98.2% and 24.2% for that of TBM and partially treated BM, respectively. Thus, Thwaites' diagnostic scoring system was found to be highly effective for the differential diagnosis of TBM and initially treated BM but was found to be less effective for that of TBM and partially treated BM.
The Oka blood group antigen basigin (BSG or CD147) is an erythrocyte receptor for the PfRh5 protein from Plasmodium falciparum. A recent study has shown that the PfRh5–BSG interaction is essential for erythrocyte invasion by P. falciparum. In this study, 6 SNPs in the BSG gene were investigated in 312 adult patients with P. falciparum malaria (109 cerebral malaria and 203 mild malaria patients) living in northwest Thailand. To examine the association between BSG SNPs and cerebral malaria, the allele and haplotype frequencies were compared in cerebral and mild malaria patients. Nonsynonymous SNPs were not assessed in the association analysis. The results showed that common BSG polymorphisms and haplotypes were not significantly associated with cerebral malaria. In conclusion, common SNPs in BSG do not influence the risk of cerebral malaria in the Thai population.
Burkholderia pseudomallei is an intracellular pathogenic bacterium that causes melioidosis in humans. On infection, neutrophils eliminate the majority of intracellular B. pseudomallei. Previous reports on the risk factors for melioidosis have shown that host factors, particularly age and diabetes mellitus, increase susceptibility to B. pseudomallei; however, whether these factors influence neutrophil functions in response to infection remains unknown. In this study, whole blood samples were collected from healthy Thai blood donors and co-cultured with B. pseudomallei, and phagocytic and respiratory burst functions of neutrophils were then measured by flow cytometry. The results show reduced neutrophil functions in older donors or those with poor glycemic control. Furthermore, the levels of antibody against B. pseudomallei showed a positive correlation with neutrophil functions. This study therefore indicated the importance of age, glycemic control, and antibody levels in the activity of neutrophils in melioidosis.
In this study, 2 methods of DNA extraction were evaluated for use in conjunction with the screening system Rapid Foodborne Bacterial Screening 24 (RFBS24), which employs multiplex real-time SYBR Green polymerase chain reaction (SG-PCR) and can simultaneously detect 24 target genes of foodborne pathogens in fecal DNA samples. The QIAamp DNA Stool mini kit (Qkit) and Ultra Clean Fecal DNA Isolation Kit (Ukit) were used for bacterial DNA extraction from fecal samples artificially inoculated with Clostridium perfringens, Staphylococcus aureus, Salmonella Typhimurium, and Campylobacter jejuni. SG-PCR and simplex real-time quantitative PCR (S-qPCR) analyses revealed higher copy numbers (8–234 times) of DNA in samples obtained using Ukit compared with those obtained using Qkit, resulting in lower cycle threshold values for the Ukit samples of the 4 bacteria on SG-PCR analysis. Fecal DNA samples from patients infected during foodborne outbreaks of Salmonella and Campylobacter were also prepared by Qkit and Ukit methods and subjected to RFBS24 analyses. Higher numbers of RFBS24 bacterial target genes were detected in DNA samples obtained using Ukit compared with those obtained using Qkit. Thus, the higher DNA extraction efficiency of the Ukit method compared with Qkit renders the former more useful in achieving improved detection rates of these 4 bacteria in fecal samples using SG-PCR.
A strong dependency of rubella and measles epidemics on population size was confirmed by 2 types of plots: the cumulative frequency distribution of number of cases per prefecture and the slope of the log–log plots of number of cases per prefecture on the y-axis vs. prefecture population size on the x-axis. These parameters were found to be constant and unique to each infectious agent. The broader cumulative frequency distribution and steeper slope of the log–log plots were characteristic to measles and rubella, i.e., a higher population size was correlated with a disproportionate high incidence of measles and rubella. No such tendency was found in other infections with possible exceptions of pertussis and keratoconjunctivitis. The dependency of rubella and measles on population density was examined by log–log plots of patient number/population vs. population density, which revealed strong population density dependency of rubella; the dependency of measles on population density was equivocal.
In South Korea, scrub typhus is the most common acute febrile illness in autumn. We analyzed scrub typhus cases reported from 2008 to 2012 to describe the epidemiology of scrub typhus as well as eschar patterns. A total of 30,478 cases were reported from 2008 to 2012; the incidence rates were higher in the southern and western regions of South Korea. The common clinical symptoms of confirmed scrub typhus cases from 2010 to 2012 were fever/chills (95.2%), eschars (78.9%), and myalgia (61.7%). The primary sites of eschars were the lower extremities (19.0%), abdomen/waist (13.4%), and axilla (11.5%) in men and the shoulder/frontal chest (15.1%), lower extremities (14.5%), and abdomen/waist (13.6%) in women. Regardless of gender, eschars tended to be more on the lower extremities among the leisure activities group. Among the occupational farm work group, who usually lived in rural areas, eschars appeared most frequently on the abdomen/waist in men and on the shoulder/frontal chest in women. Eschar patterns were influenced by gender and activities. These results could facilitate the prevention of scrub typhus and clarify the current status of scrub typhus in South Korea.
Rotavirus is the most common cause of severe gastroenteritis in children worldwide. This retrospective, cross-sectional study was undertaken in a sentinel hospital that provides the only pediatric beds for the local population with an average of 4,400 children aged <5 years and determined the incidence of rotavirus hospitalizations. Medical charts that recorded acute gastroenteritis cases occurring in children aged <5 years living in the cites of Yuri-Honjo or Nikaho, Akita, Japan between 2001 and 2011 were retrieved and examined to enumerate rotavirus antigen-positive hospitalizations. Of the 1,596 acute gastroenteritis cases retrieved, antigen detection was performed in 834 cases, and 387 were positive; hence, the crude annual incidence rate of rotavirus hospitalizations was 8.8 per 1,000 person-years. The adjusted annual incidence rate of rotavirus hospitalizations was 13.7 per 1,000 person-years when untested samples collected during the peak season were extrapolated to the same rotavirus detection proportion as the tested samples (58.9%). We confirmed a high incidence of rotavirus hospitalizations in Akita Prefecture and revealed a considerable degree of annual fluctuation in the rotavirus hospitalization rates, which exceeded the degree of stochastic fluctuation. Thus, caution must be exercised when interpreting the impact of a rotavirus vaccine on the reduction of the number of rotavirus hospitalizations.
Viruses are the major etiological agents of acute respiratory infections (ARIs) in young children. Although respiratory virus co-detections are common, analysis of combinations of co-detected viruses has never been conducted in Japan. Nineteen respiratory viruses or subtypes were surveyed using multiplex real-time PCR on 1,044 pediatric (patient age < 6 years) ARI specimens collected in Osaka City, Japan between January 2010 and December 2011. In total, 891 specimens (85.3%) were virus positive (1,414 viruses were detected), and 388 of the virus-positive specimens (43.5%, 388/891) were positive for multiple viruses. The ratio of multiple/total respiratory virus-positive specimens was high in children aged 0–35 months. Statistical analyses revealed that human bocavirus 1 and human adenovirus were synchronously co-detected. On the other hand, co-detections of human parainfluenza virus type 1 (HPIV-1) with HPIV-3, HPIV-3 with human metapneumovirus (hMPV), hMPV with respiratory syncytial virus A (RSV A), hMPV with influenza virus A (H1N1) 2009 (FLUA (H1N1) 2009), RSV A with RSV B, and human rhinovirus and FLUA (H1N1) 2009 were exclusive. These results suggest that young children (<3 years) are highly susceptible to respiratory viruses, and some combinations of viruses are synchronously or exclusively co-detected.
Central to the paradigm of the pathogenesis of Mycobacterium tuberculosis is its ability to attach to, enter, and subsequently survive in host macrophages. However, little is known regarding the bacterial adhesins and invasins involved in this interaction with host macrophages. Pili are cell-surface structures produced by certain bacteria and have been implicated in adhesion to and invasion of phagocytes in several species. M. tuberculosis pili (MTP) are encoded by the Rv3312A (mtp) gene. In the present study, we assessed the ability of a Δmtp mutant and an mtp-complemented clinical strain to adhere to and invade THP-1 macrophages in comparison with the parental strain by determining colony-forming units. Both adhesion to and invasion of macrophages, although not reaching significance, were markedly reduced by 42.16% (P = 0.107) and 69.02% (P = 0.052), respectively, in the pili-deficient Δmtp mutant as compared with the wild-type. The pili-overexpressing complemented strain showed significantly higher levels of THP-1 macrophage adhesion (P = 0.000) and invasion (P = 0.040) than the mutant. We, thus, identified a novel adhesin and invasin of M. tuberculosis involved in adhesion to and invasion of macrophages.
We report the epidemiology and laboratory diagnostic results of rubella cases from 2011 to 2013 in Hokkaido district, Japan. A total of 150 cases were officially reported as rubella; 102 (68%) involved males and 48 (32%) involved females. The highest proportion of cases were notified in 40–49-year-old age group among males and the 20–29-years-old age group among females. Forty-six cases (25 males and 21 females) had not been vaccinated, and 17 had been vaccinated, whereas 87 had the unknown vaccination status. Eighty-three cases (55.3%) showed the 3 typical principal rubella symptoms (fever, rash, and lymphadenopathy). Seven, 11, 92, and 40 cases were identified in the northern, eastern, central, and southern areas of Hokkaido district, respectively. In the central and southern areas of Hokkaido district, endemic rubella transmissions were indicated by both the epidemiological survey and molecular analyses. However, these outbreaks terminated spontaneously and did not expand to other areas of Hokkaido district. Fortunately, no congenital rubella syndrome (CRS) cases were reported during this observation period. However, to control virus transmission, prevent CRS, and maintain the routine vaccination program, the immediate introduction of an immunization strategy is required for susceptible individuals, particularly young adults.
Sulfonylureas have been regarded as potential drug candidates against tuberculosis (TB) because they can inhibit the biosynthesis of branched-chain amino acids by targeting acetohydroxyacid synthase (AHAS). We demonstrated previously that novel monosubstituted sulfonylureas showed potent in vitro activities against TB. In the current study, we further explored the anti-TB activity of monosubstituted sulfonylureas in a mouse model. Compounds 30 and 31 exhibited the most efficacy: a single intragastric administration at a dose of 250 mg/kg led to a reduced lung bacterial count, and the dose of 500 mg/kg achieved a >99% reduction in bacterial load for both H37Rv and extensively drug-resistant isolates. These results indicate that these compounds are more potent than commercial sulfonylureas in vivo and may provide insight into the potential implications for the design of novel drugs to combat TB by targeting AHAS.
A 76-year-old Japanese male presenting with high fever, headache, and disturbance of consciousness was hospitalized. Contrast computed tomography revealed thrombophlebitis in the internal jugular vein and abscesses in the posterior neck region, pharynx, and pterygoid muscle. Streptococcus constellatus infection was confirmed by culture of blood samples, and the patient was diagnosed with Lemierre syndrome. In addition to the administration of antibiotics and anticoagulants, abscess drainage was performed. S. constellatus should be considered as a causative bacterium in elderly patients with Lemierre syndrome.
Forty domestic and travel-associated Campylobacter jejuni isolates were analyzed by profiling 7 pathogenic genes (cdtB, cadF, Cj0131, ciaB, racR, wlaN, and virB11) along with multilocus sequence typing (MLST) and antimicrobial susceptibility testing. cdtB, cadF, and Cj0131 were present in all isolates, whereas virB11 was not detected in either domestic or travel-associated isolates. ciaB was present in all domestic isolates and 94% of travel-associated isolates. The respective detection rates of racR and wlaN in domestic and travel-associated isolates were 94% and 71% and 35.3% and 23%, respectively. MLST analyses of the 40 isolates generated 25 different sequence types (STs). ST-443 (12 isolates) and ST-21 (8 isolates) were dominant among the domestic isolates; however, STs varied among travel-associated isolates. Nalidixic acid, tetracycline, and ciprofloxacin resistance rates of the 40 isolates were 100% (40/40), 95% (38/40), and 88% (35/40), respectively. Domestic isolates exhibited 2-fold higher ciprofloxacin, telithromycin, and chloramphenicol resistance rates than travel-associated isolates. These results indicate a diverse genetic background for travel-associated C. jejuni and suggest that this pathogen may be an important emerging public health threat to travelers.
A number of novel recombinant human adenoviruses (HAdVs) have recently been identified through sequencing of the complete genomes. The recombinant HAdV sequences share similarity with other types in the major capsid genes, namely the hexon, penton base, and fiber genes, implying recombination events, which may result in escape from the immune response and the acquisition of different organotropisms. Therefore, a surveillance system of HAdVs that considers the effect of frequent recombination on genetic evolution in these genes must be constructed. In this study, we designed new primer sets that can amplify the partial penton base and fiber genes from species HAdV-A to HAdV-F and proteotype HAdVs on the basis of sequence analyses, including previously reported primers that amplify loop 1 of the hexon. Phylogenetic analysis through sequencing with these primers correctly classified clinical HAdV isolates in loop 1 of the hexon gene, the Arg-Gly-Asp (RGD) loop of the penton base gene, and the knob of the fiber gene, which contain neutralizing, hemagglutination, and receptor binding epitopes associated with immunogenicity and tissue tropisms of HAdVs. This study contributes to the accumulation of correct information regarding genetic diversity and evolution in the worldwide HAdV surveillance.