Imported African Tick Bite Fever in Japan: A Literature Review and Report of Three Cases.

African tick bite fever (ATBF) is an acute febrile illness caused by Rickettsia africae. ATBF is an important differential diagnosis of acute febrile illness among returned travelers. However, little information is available on ATBF cases imported to Japan, as only seven have been reported to date. To characterize the epidemiological and clinical profiles of patients diagnosed with ATBF in Japan, we reported three new ATBF cases at our hospital between May 2015 and April 2018 and conducted a literature review.

Surveillance systems for healthcare-associated infection in high and upper-middle income countries: A scoping review.

BACKGROUND: Healthcare-associated infection (HAI) surveillance is useful for improved infection control. To understand the current HAI surveillance systems (HAISS) trend globally, a scoping review was performed. MATERIALS AND METHODS: The search strategy included academic literature review, Google search, and questionnaires by the Embassies of Japan (registration number: UMIN000036035). Eighty-two high and 56 upper-middle income countries defined by country income classification for the World Bank were targeted. The following information was reviewed: name of the system, official website, languages used in the official website, foundation year, operating body, survey type (prevalence or incidence), reporting periodicity, mode of participation (mandatory or voluntary), targeted medical facilities, targeted HAIs and definitions, targeted antimicrobial resistant pathogens, and parameters. Online accessibility of the official websites of the SS was assessed through Google search. RESULTS AND CONCLUSION: Forty-two (30.4%) countries (35 [42.7%] high and 7 [12.5%] upper-middle income countries) had national HAISS. Most systems operated on a voluntary basis, monitored HAI incidence, and used the Center for Disease Control and Prevention definitions. Methicillin-resistant Staphylococcus aureus, surgical site infection, and catheter-related blood stream infection were most commonly monitored. Surveillance for device-associated infections was implemented mainly in intensive care units. Thirty-five countries had at least one official website on their systems, while 7 (20.0%) were identified in the top 30 Google search hits, in English. Approximately half of the academic articles identified through PubMed were from three English-speaking countries. The feasibility and benefits of standardization of the HAI surveillance criteria and efficient feedback methods are future considerations.

Varicella in Adult Foreigners at a Referral Hospital, Central Tokyo, Japan, 2012-2016.

We report a case series of varicella among adult foreigners at a referral hospital in central Tokyo, Japan, during 2012-2016. This series highlights differences in varicella vaccination schedules by country and epidemiology by climate and identifies immigrants and international students as high-risk populations for varicella.

Calcium Pyrophosphate Deposition Disease Involving a Lumbar Facet Joint Following Urinary Tract Infection.

A 75-year-old woman was admitted with urosepsis due to Escherichia coli infection. After improvement with a ureteral stent and antimicrobial agent, she complained of back pain and showed elevated inflammation marker levels. Arthralgia and arthritis of multiple peripheral joints were noted, and radiography indicated cartilage calcification. Magnetic resonance imaging revealed lumbar facet joint effusion. Her symptoms improved with nonsteroidal anti-inflammatory drug administration. Thus, she was diagnosed with calcium pyrophosphate deposition (CPPD)-related facet joint arthritis (FJA) rather than infectious FJA. CPPD-related FJA is an important differential diagnosis in elderly individuals with a risk of CPPD disease who complain of back pain.

Imported Malaria at a Referral Hospital in Tokyo from 2005 to 2016: Clinical Experience and Challenges in a Non-Endemic Setting.

In this study, we reviewed imported malaria cases observed at the National Center for Global Health and Medicine, Tokyo, between 2005 and 2016, to comprehend their demographic and clinical characteristics. Data on 169 cases were used to analyze demographic information; data on 146 cases were used for the analysis of clinical information. The median patients' age was 34 years, and 79.3% of them were male. The proportion of non-Japanese patients increased and surpassed that of Japanese patients after 2015. In 82.2% of the cases, the region of acquisition was Africa, and Plasmodium falciparum was the dominant species (74.0%) followed by Plasmodium vivax (15.4%). We observed 19 (18.4%, 19/103) severe falciparum malaria cases. Mefloquine was the most commonly used drug for treatment until the early 2010s; atovaquone/proguanil was the most commonly used after its licensure in 2013. Although none of the patients died, four recrudescence episodes after artemether/lumefantrine (A/L) treatment and one relapse episode were observed. Overall, malaria was diagnosed on median day 4 of illness, and, thereon, treatment was initiated without delay. Diagnosis on day 5 or later was significantly associated with severe disease in Japanese cases (odds ratio = 4.1; 95% CI = 1.2-14.3). We observed a dominance of falciparum malaria, an increase in the number of non-Japanese cases, late treatment failure after A/L treatment, a low relapse rate, and an association between delayed malaria diagnosis and higher disease severity. Pretravel care and early diagnosis are necessary to reduce malaria-related mortality and morbidity in settings such as ours.

Comparison of the epidemiology and microbiology of peripheral line- and central line-associated bloodstream infections.

We retrospectively studied the epidemiology and microbiology of peripheral line-associated bloodstream infection (PLABSI) in comparison with central line-associated bloodstream infection (CLABSI). Among 2,208 bacteremia episodes, 106 (4.8%) PLABSI and 229 (10.4%) CLABSI were identified. In PLABSI, gram-negative rods, especially Enterobacteriaceae, were more frequently identified than in CLABSI, and infectious disease consultation was more frequently involved. The 7-day mortality rate was similar between the 2 groups, suggesting similar adverse effects of PLABSI and CLABSI on patient outcomes.

Real-time PCR investigation of the prevalence of Fusobacterium necrophorum in patients with pharyngitis in Japan.

PURPOSE: Recent data suggest an association between Fusobacterium necrophorum infection and pharyngotonsillitis among adolescents and adults. However, existing reports are only from North America and Europe. We aimed to identify and compare the prevalence of F. necrophorum among patients with pharyngitis and asymptomatic controls in Japan and clarify the epidemiological characteristics of pharyngitis. METHODS: Patients aged ≥16 years with pharyngitis and asymptomatic controls were prospectively included. F. necrophorum was detected by using both conventional culture methods and real-time F. necrophorum-specific PCR targeting the rpoB gene. The prevalence of ß-hemolytic streptococci was also identified and compared between groups. RESULTS: Forty-four pharyngitis patients and 31 asymptomatic controls were included. F. necrophorum was identified using PCR in 6 (13.6%) pharyngitis cases and 2 (6.5%) controls, with no significant difference (p = 0.457). The median bacterial load of F. necrophorum identified with real-time PCR was significantly higher in pharyngitis cases than in controls (p = 0.046). Patients with a high Centor Score tended to have a higher bacterial load than those with a low Centor Score and controls. In cases of pharyngitis, the prevalence of F. necrophorum was similar to that of Streptococcus pyogenes (F. necrophorum-positive: 6 [13.6%] vs. S. pyogenes-positive: 5 [11.4%], p = 0.99). CONCLUSION: F. necrophorum was similarly prevalent among pharyngitis cases as S. pyogenes in Japan. The association of higher F. necrophorum bacterial load with symptomatic pharyngitis in accordance with the previous findings from a different geographical region suggests that F. necrophorum is an important causative agent of bacterial pharyngitis.

Wohlfahrtiimonas chitiniclastica Bacteremia Hospitalized Homeless Man with Squamous Cell Carcinoma.

We report a case of Wohlfahrtiimonas chitiniclastica bacteremia in an elderly man in Japan who had squamous cell carcinoma. Blood cultures were initially negative for W. chitiniclastica but were positive on day 20. Careful attention needs to be paid to this organism in patients who have chronic wounds with maggots.

Ancylostoma ceylanicum, novel etiological agent for traveler's diarrhea-report of four Japanese patients who returned from Southeast Asia and Papua New Guinea.

BACKGROUND: Countries in the Southeast Asia region have a high prevalence of soil-transmitted helminth, such as roundworm, whipworm, and hookworms [Ancylostoma duodenale, Necator americanus, Ancylostoma ceylanicum]. Recent molecular-based surveys have revealed that A. ceylanicum, a zoonotic hookworm, is likely the second most prevalent hookworm species infecting humans in that part of the world, while others have noted that this infection is an emerging public health risk not only for indigenous people but also for visitors from other countries. CASE PRESENTATION: We recently encountered four cases of A. ceylanicum infection in Japanese individuals who returned from Southeast Asia and Papua New Guinea. Case 1 was a 25-year-old male who stayed in a rainforest in Malaysia for 4 weeks, where he developed abdominal pain and diarrhea in the third week. Eleven adult worms (five males, six females) were expelled after treatment with pyrantel pamoate and identified as A. ceylanicum based on morphological characteristics and DNA sequences of the mitochondrial cytochrome c oxidase subunit 1 (cox1) gene. Case 2 was a 26-year-old male who spent 2 years as an overseas cooperation volunteer for agriculture in Papua New Guinea. He did not note any symptoms at that time, though eggs were detected in feces samples at a medical check-up examination after returning. Although collection of adult worms was unsuccessful, DNA analysis of the eggs for cox1 and the ribosomal internal transcribed spacer (ITS)-1 and ITS-2 genes demonstrated that they were A. ceylanicum. Case 3 was a 47-year-old male who spent 1 month in a rural village in Lao People's Democratic Republic and began suffering from watery diarrhea from the third week. A total of nine adult worms (three males, six females) were collected by endoscopic procedures and following treatment with pyrantel pamoate. Morphological examination and molecular analyses of the cox1 gene showed that they were A. ceylanicum. Case 4 was a 27-year-old male who participated in group travel to India for 5 days. Three weeks after returning, he developed abdominal pain and diarrhea. Hookworm eggs were found in feces samples and developed into larvae in culture, which were identified as A. ceylanicum based on molecular analysis of the cox1 gene. Eosinophilia was observed in all of the cases prior to treatment. CONCLUSIONS: A. ceylanicum should be recognized as an important etiologic pathogen of hookworm diseases in travelers to countries in the Southeast Asia and West Pacific Ocean regions.

Retrospective observational study of the use of artemether-lumefantrine in the treatment of malaria in Japan.

BACKGROUND: The Research Group on Chemotherapy of Tropical Diseases, Japan, introduced artemether-lumefantrine (AL) in late 2002, mainly for treating uncomplicated Plasmodium falciparum malaria. Because AL was on the market in Japan in March 2017, the effectiveness and safety of AL were analyzed to help medical personnel use AL optimally. METHODS: Case report forms submitted by the attending physicians were analyzed. When necessary, direct contact with the attending physicians was made to obtain detailed information. RESULTS: Effectiveness analysis was performed for 62 cases and safety analysis was performed for 66 cases. In P. falciparum malaria, the overall cure rate was 91.1% (51/56), of which the cure rates for Japanese and non-Japanese patients were 82.1% (23/28) and 100% (28/28), respectively. The successfully treated cases included severe P. falciparum malaria, with parasite densities exceeding 500,000/µL. Adverse events were reported in 14 patients, including delayed hemolytic anemia which occurred in the top four highest parasitemic cases. CONCLUSIONS: AL treatment failure in P. falciparum malaria may not be rare among non-immune individuals, including Japanese. The possibility of delayed hemolytic anemia, which occurs preferentially in high parasitemic cases, should be considered following AL treatment.

Clinical characteristics and epidemiology of intestinal tapeworm infections over the last decade in Tokyo, Japan: A retrospective review.

BACKGROUND: Tapeworm (cestode) infections occur worldwide even in developed countries and globalization has further complicated the epidemiology of such infections. Nonetheless, recent epidemiological data on cestode infections are limited. Our objectives were to elucidate the clinical characteristics and epidemiology of diphyllobothriosis and taeniosis in Tokyo, Japan. METHODOLOGY/PRINCIPAL FINDINGS: We retrospectively reviewed 24 cases of human intestinal cestode infection from January 2006 to December 2015 at a tertiary referral hospital in Tokyo, Japan. The patients included were diagnosed with cestode infection based on morphological and/or molecular identification of expelled proglottids and/or eggs and treated in our hospital. Fifteen and 9 patients were diagnosed with diphyllobothriosis and taeniosis, respectively. The median patient age was 31 years (interquartile range [IQR]: 26-42 years), and 13 (54%) were male. Most of the patients (91.7%) were Japanese. All patients were successfully treated with praziquantel without recurrence. Diphyllobothriosis was caused by Diphyllobothrium nihonkaiense in all patients. Taeniosis was due to infection of Taenia saginata in 8 [88.9%] patients and T. asiatica in 1 [11.1%] patient. All patients with taeniosis were infected outside Japan, as opposed to those with diphyllobothriosis, which were domestic. The source locations of taeniosis were mostly in developing regions. The median duration of the stay of the patients with taeniosis at the respective source location was 1 month (IQR: 1-8). CONCLUSIONS/SIGNIFICANCE: The cestode infection, especially with D. nihonkaiense, has frequently occurred, even in Japanese cities, thereby implicating the probable increase in the prevalence of diphyllobothriosis among travelers, as the number of travelers is expected to increase owing to the Tokyo Olympics/Paralympics in 2020. In addition, medical practitioners should be aware of the importance of providing advice to travelers to endemic countries of taeniosis, including the potential risks of infection and preventive methods for these infections.

Cryptococcus gattii genotype VGIIa infection imported from Vancouver Island to Japan.

A 71-year-old Japanese man with travel history to the Vancouver Island, Canada was diagnosed the pulmonary and central nervous system infections caused by Cryptococcus gattii genotype VGIIa. This is the first imported case of Cryptococcus gattii genotype VGIIa infection from endemic area of North America to Japan. He was recovery with no residual neurological dysfunction by early resection of brain mass and antifungal therapy. Early surgical resection of cerebellar cryptococcoma may shorten the length of induction therapy with antifungal drugs.

A Retrospective Single-center Analysis of 16 Cases of Imported Chikungunya Fever in Japan.

Objective Chikungunya fever (CHIK) is a re-emerging arboviral disease that is transmitted through the bite of infected Aedes mosquitoes. There is limited information regarding the epidemiology and clinical information of imported CHIK in Japan. The objective of this study was to review the epidemiology and clinical information of imported CHIK patients treated at the National Center for Global Health and Medicine (NCGM). Methods We evaluated all patients (n=16) who were diagnosed with imported CHIK and treated at the NCGM between October 1, 2005 and March 31, 2016. Results The primary complaint of 7 patients who presented to the NCGM after 31 days from disease onset was persistent arthritis, and the primary complaints of 9 patients who presented within 30 days after disease onset were a fever, headache, arthralgia, and rash. Eleven patients experienced a rash during the first week of illness. The median duration of the arthralgia was 75 days, and the joint pain lasted for >2 months in 8 patients and >6 months in 3 patients. Persistent arthralgia was not significantly associated with an age of >35 years (p=0.13) or patient sex (p=0.69). All 16 patients exhibited positive results for CHIK IgM, although only 4 exhibited positive real-time polymerase chain reaction results. Conclusion Physicians should consider CHIK in patients with a fever who have returned from areas where CHIK is endemic.

A case report of Vibrio furnissii bacteremia and cellulitis in a malnourished patient without an apparent site of entry.

We herein report a case of Vibrio furnissii bacteremia with bilateral lower limb cellulitis. A 53-year-old Japanese man with a mood disorder presented to our hospital with fever and a complaint of an inability to walk. Two sets of blood cultures became positive for V. furnissii. The treatment regimen was modified to ceftazidime and doxycycline. The patient recovered without relapse. Despite thorough examinations, portal of entry of V. furnissii remained unclear. Although the bacteria was first misidentified as V. fluvialis by the phenotyping assay (API rapid ID 32E) and matrix-assisted laser-desorption/ionization time-of-flight mass spectrometry, it was later confirmed as V. furnissii by dnaJ gene sequencing.

A Case of Dengue Fever Imported from Burkina Faso to Japan in October 2016.

Dengue fever remains underreported in Africa due to a lack of awareness among healthcare providers, the presence of other febrile illnesses, and insufficient laboratory testing. We present a case of dengue fever imported from Burkina Faso to Japan, where an outbreak of dengue was reported on October 18, 2016. Phylogenetic analysis revealed that the isolate from our patient belonged to a distinct cluster of sylvatic dengue viruses, suggesting that dengue viruses have been maintained in mosquitoes and human cycles in Burkina Faso for more than 30 years.

Dengue Virus Type 2 in Travelers Returning to Japan from Sri Lanka, 2017.

In June 2017, dengue virus type 2 infection was diagnosed in 2 travelers returned to Japan from Sri Lanka, where the country's largest dengue fever outbreak is ongoing. Travelers, especially those previously affected by dengue fever, should take measures to avoid mosquito bites.

Impact of rapid identification of positive blood cultures using the Verigene system on antibiotic prescriptions: A prospective study of community-onset bacteremia in a tertiary hospital in Japan.

BACKGROUND: Rapid identification of positive blood cultures is important for initiation of optimal treatment in septic patients. Effects of automated, microarray-based rapid identification systems on antibiotic prescription against community-onset bacteremia (COB) remain unclear. METHODS: We prospectively enrolled 177 patients with 185 COB episodes (occurring within 72 h of admission) over 17 months. Bacteremia episodes due to gram-positive bacteria (GP) and gram-negative bacteria (GN) in the same patient were counted separately. For GP bacteremia, patients with ≥2 sets of positive blood cultures were included. The primary study objective was evaluating the rates of antibiotic prescription changes within 2 days of rapid identification using the Verigene system. RESULTS: Bacteremia due to GN and GP included 144/185 (77.8%) and 41/185 (22.2%) episodes, respectively. Antibiotic prescription changes occurred in 51/185 cases (27.6% [95%CI:21.3-34.6%]) after Verigene analysis and 70/185 cases (37.8% [30.8-45.2%]) after conventional identification and susceptibility testing. Prescription changes after Verigene identification were more frequent in GP (17/41[41.5%]) than in GN (34/144[23.5%]). Among bacteremia due to single pathogen targeted by Verigene test, bacterial identification agreement between the two tests was high (GP: 38/39[97.4%], GN: 116/116[100%]). The Verigene test correctly predicted targeted antimicrobial resistance. The durations between the initiation of incubation and reporting of the results for the Verigene system and conventional test was 28.3 h (IQR: 25.8-43.4 h) and 90.6 h (68.3-118.4 h), respectively. In only four of the seven episodes of COB in which two isolates were identified by conventional tests, the Verigene test correctly identified both organisms. CONCLUSION: We observed a high rate of antibiotic prescription changes after the Verigene test in a population with COB especially in GP. The Verigene test would be a useful tool in antimicrobial stewardship programs among patients with COB.

Risk factors of catheter-related bloodstream infection caused by Bacillus cereus: Case-control study in 8 teaching hospitals in Japan.

In this multicenter, matched case-control study, patients diagnosed with catheter-related bloodstream infection (CRBSI) caused by Bacillus cereus (n = 108) were matched to controls (n = 269). In the multivariable analysis, administration of an amino acid preparation and an indwelling peripheral catheter were significant variables for B cereus-related CRBSI.

Role of classic signs as diagnostic predictors for enteric fever among returned travellers: Relative bradycardia and eosinopenia.

BACKGROUND: The lack of characteristic clinical findings and accurate diagnostic tools has made the diagnosis of enteric fever difficult. We evaluated the classic signs of relative bradycardia and eosinopenia as diagnostic predictors for enteric fever among travellers who had returned from the tropics or subtropics. METHODS: This matched case-control study used data from 2006 to 2015 for culture-proven enteric fever patients as cases. Febrile patients (>38.3°C) with non-enteric fever, who had returned from the tropics or subtropics, were matched to the cases in a 1:3 ratio by age (±3 years), sex, and year of diagnosis as controls. Cunha's criteria were used for relative bradycardia. Absolute eosinopenia was defined as an eosinophilic count of 0/µL. RESULTS: Data from 160 patients (40 cases and 120 controls) were analysed. Cases predominantly returned from South Asia (70% versus 18%, p <0.001). Relative bradycardia (88% versus 51%, p <0.001) and absolute eosinopenia (63% versus 38%, p = 0.008) were more frequent in cases than controls. In multivariate logistic regression analysis, return from South Asia (aOR: 21.6; 95% CI: 7.17-64.9) and relative bradycardia (aOR: 11.7; 95% CI: 3.21-42.5) were independent predictors for a diagnosis of enteric fever. The positive likelihood ratio was 4.00 (95% CI: 2.58-6.20) for return from South Asia, 1.72 (95% CI: 1.39-2.13) for relative bradycardia, and 1.63 (95%CI: 1.17-2.27) for absolute eosinopenia. The negative predictive values of the three variables were notably high (83-92%);. however, positive predictive values were 35-57%. CONCLUSIONS: The classic signs of relative bradycardia and eosinopenia were not specific for enteric fever; however both met the criteria for being diagnostic predictors for enteric fever. Among febrile returned travellers, relative bradycardia and eosinopenia should be re-evaluated for predicting a diagnosis of enteric fever in non-endemic areas prior to obtaining blood cultures.

Detection of Zika virus in a traveller from Vietnam to Japan.

We report an imported case of Zika fever in a traveller from Vietnam. Zika virus (ZIKV) is currently widespread in Vietnam. Ongoing transmission of ZIKV has been reported in Southeast Asia, and with frequent travel between neighbouring regions, careful surveillance for imported cases is needed.