A total of 160 autochthonous dengue cases transmitted by Aedes albopictus were reported between August and October of 2014 in Tokyo Metropolis, Japan. Ae. albopictus is a medically important vector of dengue virus, which has expanded its geographic distribution in temperate regions. Understanding the distribution and biting density of Ae. albopictus during the 2014 dengue outbreak in Tokyo is important to evaluate the epidemic risks of dengue fever in other highly populated cities in Europe and Asia. Of the 160 patients, 134 visited the same park (Yoyogi park) located in central Tokyo. Mosquitoes infected with dengue virus were collected from this park, suggesting that it was the exclusive location for the transmission of dengue. This study aimed to collect referential data to estimate the transmission threshold of dengue virus in terms of biting density of Ae. albopictus and determined high transmission risk areas of dengue virus in Yoyogi Park and its vicinity. The overall mean density of biting Ae. albopictus (7.13/man/8 min) was sufficiently high for successful transmission of dengue virus, and areas with biting densities higher than the overall mean density were classified as high risk areas for the transmission of dengue virus in Yoyogi Park.
The influenza pandemic in 2009/2010 shifted public awareness to respiratory tract infections caused by the influenza virus. A prospective study was conducted during the influenza pandemic from November 2009 through April 2010 to determine the causative pathogens and clinical symptoms present in all children and adolescents admitted to the University Children's Hospital, Duesseldorf, Germany, with signs and symptoms of respiratory tract infection. A total of 272 children and adolescents were admitted with symptomes of acute respiratory tract infection (ARI) or influenza-like illness. Viral pathogens were detected in 80% (218/272). However, influenza A pH1N1 infection was only detected in 11% (30/272) of children. Human metapneumovirus (HMPV) and respiratory syncytial virus (RSV) were the predominant identified pathogens that led to the admission of young tachypneic children with pneumonia in the post pandemic phase and the requirement for more intense treatment. During the pandemic and early post-pandemic phase the clinical impact of other respiratory viruses, such as HMPV and RSV, led to a higher clinical disease burden than pH1N1. Consequently, HMPV testing should be performed as routinely as RSV testing in patients hospitalized for ARI. Even while preparing for pandemics, the awareness of other respiratory viruses must be maintained.
Official records show that the Japanese influenza death toll in 1918–1920 was 385 thousand. However, a recently published study claims that the records are skeptical, claiming the figure to be “an anomaly by Asian standard,” and re-estimated the number to be about 2 million by its unique demographical calculation. However, it is not sound from the following socio-historical and statistical perspectives: i) Japan had developed accurate registration and surveillance systems which might not have existed in other developing countries; ii) there were unique socio-economic situations that claim that the relatively low mortality rate in Japan was not a “myth”; iii) the proposed re-estimation was an overestimation, because if it was a fact, about 1.6 million influenza deaths should have not been detected nationwide, i.e., about 3% of the population. Also, the influenza death toll was unrealistically large compared to the all-causes mortality of that period; iv) Japan started census in 1920 and it should have significantly affected the demographic data analysis. However, the effect by this artifact was not taken into account. Consequently, it caused the severe overestimation of the death; v) we recalculated the mortality using the same method and dataset but we could not reach an estimated figure similar to that claimed in the paper.
The prevalence of hepatitis in South Korea is relatively high compared to that in other high-income countries. For this reason, viral hepatitis infection not only affects the population's health, but also impacts national healthcare costs. This study was performed in order to estimate the individual economic costs of the hepatitis A, B, and C viruses as well as to determine, using nationally representative data, the trends in South Korea with respect to these viruses during the 2008–2011 period. The study found that the prevalence of hepatitis A had decreased, but those of hepatitis B and C had increased overall. The mortality rate of hepatitis C was higher than that of the other two types. The mortality rate of hepatitis B had changed little, whereas that of hepatitis C had risen. The total cost of hepatitis A had decreased, from US $62.2 million to US $45.7 million, although a notable exception occurred in 2009, when the cost was US $126.6 million. Conversely, the total cost of hepatitis B had increased rapidly during the same period, from US $501.4 million to US $607.8 million. Finally, the total cost of hepatitis C had also increased from US $63.9 million to US $90.7 million. The direct costs of hepatitis A, B, and C were estimated to account for approximately 35.5%, 46.6%, and 58.0% of the total, respectively. These findings demonstrate the economic burden associated with hepatitis A, B, and C, and demonstrate the need to establish an effective prevention and management policy for future planning in South Korea.
Vibrio parahaemolyticus is an important pathogen that causes gastroenteritis in humans, generally associated with the consumption of contaminated seafood, particularly raw shellfish. There are many serotypes in V. parahaemolyticus resulting from a combination of O and K antigens. Among them, O3:K6 and their variants, which represent the pandemic clone, are the most widespread strains worldwide. In this study, we examined V. parahaemolyticus isolated from a gastroenteritis patient's stool at a hospital in Saitama City, Japan in 2013. Serotyping of the O and K antigens identified the strain as O10:K60. To our knowledge, this is the first reported case of a V. parahaemolyticus strain with this antigen combination in Japan. Subsequently, we used PCR to assay for pathogenicity-associated genes, and found that it was positive for tdh, T3SS1, and T3SS2α genes. Antibiotic susceptibility tests showed that the strain was susceptible to all selected antibiotics except ampicillin. Moreover, we detected specific marker genes for the pandemic clone with two kinds of PCR assay. Our results suggest that the isolate O10:K60 is a newly emerging serotype that belongs to the pandemic clone.
Abacavir/lamivudine (ABC/3TC) is a nucleoside reverse transcriptase inhibitor used for treating human immunodeficiency viral (HIV) infections. Hypersensitivity reactions such as skin eruptions caused by ABC are well-known, but rarely occur in Asians. Raltegravir (RAL) is an integrase strand transfer inhibitor, that is now increasingly, used for treating HIV infections because it has few adverse effects. This retrospective analysis assessed the efficacy and safety of combined ABC/3TC and RAL in both treatment-naïve and -experienced Japanese patients with HIV infections. In all 11 treatment-naïve patients (100%), virological suppression to undetectable level was achieved. Liver transaminases, renal function, and serum lipid profiles showed no exacerbations up to 48 weeks of treatment. In 12 patients who were switched from previous regimens to ABC/3TC and RAL, HIV viral load was undetectable in 11 patients (91.6%), but remained detectable in 1 patient with poor adherence. Major reasons for switching regimens to ABC/3TC and RAL were hyperlipidemia and nausea. After switching, these adverse effects improved, and no new adverse effects were observed. Despite the small number of participants in this study, the results support the combination of ABC/3TC and RAL as a possible treatment choice in Japanese individuals with HIV-infection.
Suitable methods for clinical monitoring of HIV-infected patients are crucial in resource-poor settings. Demographic data, clinical staging, and laboratory findings for 112 asymptomatic subjects positive for HIV were assessed at the first admission and the last visit from 2002 to 2010. Cox regression analysis showed hemoglobin (Hb) (HR = 0.643, P = 0.021) to be a predictive indicator for disease progression, while CD4, CD8, and platelet counts showed low HRs, despite having significant probability values. Hb and total lymphocyte count (TLC) rapidly declined from stage II to III (10.9 and 29.6%, respectively). Reduced CD4 and platelet counts and Hb during stage I were associated with disease progression, and TLC was correlated with CD4 counts at the last follow-up (P < 0.001). However, WHO TLC cutoff of 1,200 cell/mm3 had 26.1% sensitivity and 98.6% specificity. ROC curve analysis suggested that a TLC cutoff of 1,800 cell/mm3 was more reliable in this region. Statistical analysis and data mining findings showed that Hb and TLC, and their rapid decline from stage II to III, in addition to reduced platelet count, could be valuable markers for a surrogate algorithm for monitoring of HIV-infected subjects and starting anti-viral therapy in the absence of sophisticated detection assays.
Dengue virus infections are mostly asymptomatic but can produce a mild, self-limiting acute febrile illness, dengue fever, or a life threatening severe illness, dengue hemorrhagic fever. Dengue hemorrhagic fever is associated with increased vascular permeability partly as a result of elevated levels of matrix metalloproteinases (MMPs). We characterized MMP-2 and MMP-9 production in mosquito and mammalian cells after infection with three strains of dengue virus type-2 (D2-) ranging in virulence: 16681, the prototype New Guinea C (NGC), and PDK-53 vaccine strain. These strains were used to test variations in viral properties in vaccine candidates and confirm the production of MMP as a possible marker for virulence. A zymogram gelatinolytic activity assay was used to assess MMP-2 and MMP-9 production. We found that dengue-infected mosquito and mammalian cell lines had unique MMP-2 and MMP-9 production patterns depending on the virulence of the infecting dengue strain and the duration infection. MMP levels were highest after infection with the most virulent strain D2-16681, followed by the prototype NGC strain, in both cell lines. The MMP levels appeared to correspond with the relative amounts of infectious virions produced later in infection. Our findings improve our understanding of dengue pathogenesis and may facilitate the selection of markers to further the development of dengue vaccines.
We aimed to determine the relationship between leukocyte counts and the survival of patients with Crimean-Congo hemorrhagic fever (CCHF), a life-threatening illness. This is the first study to do so. A total of 220 patients with CCHF were evaluated retrospectively. The mortality rate was 16.4%. Analysis of the relationship between leukocyte counts and mortality rates provided insight into the pathogenesis of CCHF. Receiving operating curve analysis revealed that leukocyte counts ≥2,950/mm3 on the day of admission predicted mortality rate with 62.1% sensitivity. The mean hospitalization stay in patients with fatal disease was 4.3 days; therefore, leukocyte counts were compared on the day of admission and day 3 of the hospital stay. Increases in neutrophil levels and decreases in lymphocyte and monocyte levels were identified as significant risk factors for mortality (P = 0.01, 0.037, and 0.001, respectively). The mortality risk was 7–12 fold higher in patients whose levels of leukocytes (2,950 μL), lactate dehydrogenase (967.5 U/L), and alanine aminotransferase (>119.5 U/L) and activated partial thromboplastin time (42.4 s) exceeded the cut-off values; these were identified as independent predictors of mortality. Depletion of monocytes and lymphocytes and accumulation of neutrophils correlated with poor outcome. These results highlight the importance of the mononuclear immune response for the survival of patients with CCHF.
In the current study we explored the occurrence of adverse drug reactions (ADRs) to antiretroviral therapy among human immune-deficiency virus (HIV)/AIDS patients. We concluded an observational retrospective study in all patients who were diagnosed with HIV infection and were receiving highly active antiviral therapy from Jan. 2007 to Dec. 2012 at Hospital Pulau Pinang, Malaysia. Patient socio-demographic details along with clinical features and susceptible ADRs were observed during the study period. Out of 743 patients, 571 (76.9%) were men, and 172 (23.1%) were women. Overall 314 (42.2%) patients experienced ADRs. A total of 425 ADRs were reported, with 311 (73.1%) occurring in men and 114 (26.8%) in women, with a significant statistical relationship (P value (P) = 0.02, OR = 1.21). Overall 239 (56.2%) ADRs were recorded among Chinese, 94 (22.1%) in Malay, and 71 (16.7%) in Indian patients, which had a statistically significant association with ADRs (P = 0.05, OR = 1.50). Out of a total 425 among ADRs, lipodystrophy was recorded in 151 (35.5%) followed by skin rashes in 80 (18.8%), anemia in 74 (17.4%), and peripheral neuropathy in 27 (6.3%) patients. These findings suggest a need of intensive monitoring of ADRs in HIV treatment centres across Malaysia.
After returning from Bali, Indonesia, in February 2014, a 72-year-old man was hospitalized in Okinawa owing to a high fever and rash. Dengue was clinically suspected, and the patient tested positive for IgM against dengue using a commercial kit. Serologically, the patient showed secondary seroreactivity. Significant increases in neutralization titers (N-titers) against all 4 serotypes of dengue virus (DENV) and Japanese encephalitis virus (JEV) strains were recognized in convalescent-phase sera comparing to acute phase sera. The N-titer against DENV serotype 1 (DENV-1) was the highest among all DENV serotypes. Interestingly, the N-titers against JEV strains were significantly higher than those against all types of DENV comparing to acute phase sera. The virus was isolated from the acute-phase serum and identified as DENV-1 and designated RD14/Okinawa. The patient's symptoms were due to DENV-1 infection. Phylogenetic sequencing analysis indicated that the isolate RD14/Okinawa belonged to genotype I of DENV-1, which is closely related to the Southeast Asian strains and isolates found during the dengue outbreak in Japan in 2014. We should undertake control measures against dengue in Okinawa, which is a subtropical area with Aedes albopictus activity throughout year.
Enterovirus 71 (EV71) and coxsackievirus A16 (CVA16) are members of the Picornaviridae family and are considered the main causative agents of hand, foot and mouth disease (HFMD). In recent decades large HFMD outbreaks caused by EV71 and CVA16 have become significant public health concerns in the Asia-Pacific region. Vaccines and antiviral drugs are unavailable to prevent EV71 and CVA16 infection. In the current study, a chimeric antibody targeting a highly conserved peptide in the EV71 VP4 protein was isolated by using a phage display technique. The antibody showed cross-neutralizing capability against EV71 and CVA16 in vitro. The results suggest that this phage display-derived antibody will have great potential as a broad neutralizing antibody against EV71 and CVA16 after affinity maturation and humanization.
We asked 14 professional cleaners (laundry services) to clean various unused (new) linen and clothing items with a microbial contamination level of <1 cfu/cm2 and then evaluated the bacterial/fungal contamination of the laundered or dry-cleaned items. After laundering, 6 (21.4%) of the 28 samples from 4 of the 14 cleaners (28.6%) were contaminated (1–1,200 cfu/cm2). After dry-cleaning, 2 (7.1%) of the 28 samples from 2 (14.3%) of the 14 cleaners were contaminated (7–10 cfu/cm2). The main contaminant was Bacillus cereus. No sample of the laundered or dry-cleaned items showed Staphylococcus aureus, Escherichia coli, or Pseudomonas aeruginosa contamination. All 14 cleaners investigated in this study used batch-type washing machines. Therefore, batch-type washing machines can cause contamination of linen and clothing items with B. cereus.
A total of 29 Campylobacter jejuni and C. coli strains were isolated from Thai and Japanese children with diarrhea using the Loop-mediated Isothermal Amplification method. The samples were evaluated for mutations in gyrA and 23S rRNA in order to assess resistance against fluoroquinolones and macrolides, respectively. Among the isolated strains, 9 (8 C. jejuni and 1 C. coli) were from Thai children, and the other 20 (C. jejuni) were isolated from Japanese children. High fluoroquinolone resistance rates were observed in Thai (66.7%) and Japanese (90%) children. Macrolide resistance was not observed in Japanese children but was observed at a considerable rate of 12.5% of C. jejuni isolated in the Thai cohort. The results indicate that continuous monitoring of resistance of Campylobacter strains to fluoroquinolones and macrolides is definitely necessary.
We previously reported that progression of liver cirrhosis is quicker and survival is dismal in patients with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) coinfection, especially when acquired in childhood through contaminated blood products. Recently, we performed the first deceased donor liver transplantation (DDLT) for an HIV/HCV-coinfected hemophilic patient in Japan. A 40-year-old man was referred to our hospital for liver transplantation. Regular DDLT was performed using the piggyback technique with a full-sized liver graft. Cold ischemia time was 465 min, and the graft liver weighed 1,590 g. The antiretroviral therapy (ART) was switched from darunavir/ritonavir to raltegravir before the transplant for flexible usage of calcineurin inhibitors postoperatively; tenofovir was used as the baseline treatment. The postoperative course was uneventful, and the patient was discharged home on day 43. He started receiving anti-HCV treatment on day 110 with pegylated interferon, ribavirin, and simeprevir after the DDLT. Herein, we report the first case of DDLT in Japan. Meticulous management of ART and clotting factors could lead to the success of DDLT.