Survival case of rhinocerebral and pulmonary mucormycosis due to Cunninghamella bertholletiae during chemotherapy for acute myeloid leukemia: a case report.

A 42-year-old man diagnosed with acute myeloid leukemia complained of progressive swelling of the right side of his face with pain 11 days after the third cycle of consolidation therapy with high-dose arabinosylcytosine-cytarabine. Head and neck magnetic resonance imaging showed a mass lesion in his right maxillary sinus with parapharyngeal involvement, which included the right masseter muscle, intraorbital involvement, and an abscess in his brain. Chest computed tomography revealed peribronchial small nodules in his right upper lobe and a necrotic tumor in his right lower lobe. Molds identified as Cunninghamella bertholletiae were isolated from the necrotic ulcer. According to these results, chemotherapy for leukemia was discontinued. High-dose liposomal amphotericin (10 mg/kg/day) was initiated. Because renal dysfunction occurred, the dosage was decreased to 6 mg/kg and combined with 150 mg/day micafungin. Debridement of necrotic tissue in the right maxillary sinus and establishment of the fenestration between the sinus and oral cavity were performed. Subsequently, brain and lung lesions were surgically removed. Rhinocerebral mucormycosis was successfully treated without relapse over 3 years by a 112-day course of intravenous anti-fungal therapy and 223-day course of terbinafine and partial surgical removal, respectively, to maintain masticatory and ocular functions. To our knowledge, there has been no other report of a long-term survival case of rhinocerebral mucormycosis due to C. bertholletiae.

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.

Rabies post-exposure prophylactic vaccination for returning travelers to Japan.

BACKGROUND: Rabies post-exposure prophylaxis (PEP) in Japan is administered using 6 subcutaneous doses (on days 0, 3, 7, 14, 30, and 90), which is not in line with international recommendations of 4 or 5 intramuscular doses. For reducing dose frequency, we evaluate the immunogenicity of PEP with a regimen of 6 subcutaneous doses. METHOD: This prospective single-center cross-sectional study was performed between September 2013 and December 2014. We included patients underwent rabies PEP by purified chick embryo-cultured rabies vaccine Kaketsuken (PCEC-K) at our clinic, and excluded patients with a history of pre-exposure prophylaxis or PEP using rabies immunoglobulin. The rabies virus-neutralizing antibody tests were performed at the first visit to our office (doses 1-4) and at the fifth and sixth doses. RESULTS: Data were available for 43 of 59 enrolled patients. Thirty-two patients did not start PEP within 48 h after exposure to animals. The seroprotection rates (≥0.5 IU/mL) were 90.7% and 75.7%, at days 30 and 90, respectively. Despite receiving a fifth dose, 85.3% of the patients exhibited decreasing antibody titers during days 30-90 (p < 0.001). CONCLUSIONS: The seroprotection rates of PCEC-K induced subcutaneously were insufficient to prevent rabies at day 30 and 90.

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.

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.

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.

Amoxicillin and Ceftriaxone as Treatment Alternatives to Penicillin for Maternal Syphilis.

There is no proven alternative to penicillin for treatment of maternal syphilis. We report 2 case-patients with maternal syphilis who were successfully treated without penicillin. We used amoxicillin and probenecid for the first case-patient and amoxicillin, probenecid, and ceftriaxone for the second case-patient.

Importation of Zika Virus from Vietnam to Japan, November 2016.

We report a case of Zika virus infection that was imported to Japan by a traveler returning from Vietnam. We detected Zika virus RNA in the patient's saliva, urine, and whole blood. In the Zika virus strain isolated from the urine, we found clearly smaller plaques than in previous strains.

Chikungunya Fever in Traveler from Angola to Japan, 2016.

Simultaneous circulation of multiple arboviruses presents diagnostic challenges. In May 2016, chikungunya fever was diagnosed in a traveler from Angola to Japan. Travel history, incubation period, and phylogenetic analysis indicated probable infection acquisition in Angola, where a yellow fever outbreak is ongoing. Thus, local transmission of chikungunya virus probably also occurs in Angola.

A case of consecutive infection with Zika virus and Chikungunya virus in Bora Bora, French Polynesia.

Chikungunya fever (CHIK) and Zika virus (ZIKV) infection have similar endemic areas and clinical manifestations. We report a case of CHIK at 1 year after a ZIKV infection in Bora Bora (French Polynesia), which we diagnosed based on IgM to the CHIK virus and neutralizing antibodies to ZIKV.

Epidemiology of extended-spectrum beta-lactamase (ESBL) producing Escherichia coli in Japan: Characteristics of community-associated versus healthcare-associated ESBL E. coli.

Data on community-associated extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli (CA-ESBLEC) infections in Japan are scarce. We compared the clinical and microbiological epidemiology of CA-ESBLEC infections with that of healthcare-associated-ESBLEC infections among 76 patients with ESBLEC infections. We identified a high prevalence (26%) of CA-ESBLEC infections in Japan; only a small proportion (15%) of patients with CA-ESBLEC infections had recent exposure to antibiotics.

A fatal case of melioidosis with pancytopenia in a traveler from Indonesia.

Melioidosis, an infectious disease with high mortality, caused by Burkholderia pseudomallei, is endemic in southeast Asia and northern Australia. In Indonesia, autochthonous cases have been rarely reported, with most cases being sporadic and occurring in travelers. Herein, we report a fatal case of neurological melioidosis in a traveler from Indonesia presenting with septic shock.

[Bacteremia Due to Bacillus subtilis: A Case Report and Clinical Evaluation of 10 Cases].

A 59-year-old male presented with fever, and was admitted for bacteremia due to gram-positive rod. All 5 sets of blood cultures obtained prior to the initiation of vancomycin tested positive for Bacillus subtilis. Based on the susceptibility test result, the antibiotics were changed to levofloxacin to complete a total of fourteen days treatment. The patient recovered without relapse over one year. Despite thorough examinations, the portal of entry of B. subtilis remained unclear. We retrospectively reviewed ten cases of bacteremia due to B. subtilis over 5 years in our hospital. The cases with positive B. subtilis blood cultures which were evaluated as contamination were excluded from the review. The most common portal of entry of B. subtilis was secondary bacteremia due to perforation or ileus (70%), followed by an unknown site (30%). B. subtilis should be considered not only as a contaminant but also as a true pathogen of bacteremia.

Japanese encephalitis vaccine-facilitated dengue virus infection-enhancement antibody in adults.

BACKGROUND: Dengue virus (DENV) and Japanese encephalitis virus (JEV) belong to the genus Flavivirus, and infection with a virus within this genus induces antibodies that are cross-reactive to other flaviviruses. Particularly in DENV infection, antibodies to DENV possess two competing activities: neutralizing activity and infection-enhancing activity. These antibody activities are considered central in modulating clinical outcomes of DENV infection. Here, we determined the neutralizing and infection-enhancing activity of DENV cross-reactive antibodies in adults before and after JE vaccination. METHODS: Participants were 77 Japanese adults who had received a single dose of inactivated Vero cell-derived JE vaccine. A total of 154 serum samples were obtained either before or approximately a month after a single dose of JE vaccination. The antibody-dependent enhancement (ADE) activity to each of four DENV serotypes and the neutralizing activities to DENV and to JEV were determined in each of the serum samples by using baby hamster kidney (BHK) cells and FcγR-expressing BHK cells. RESULTS: A total of 18 post-JE immunization samples demonstrated cross-reactivity to DENV in an anti-DENV IgG ELISA. DENV neutralizing antibodies were not detected after JE vaccination in this study. However, undiluted post-JE vaccination serum samples from 26 participants demonstrated monotypic and heterotypic ADE activity to DENV. ADE activity was also observed in 1:10-diluted samples from 35 of the JE vaccine recipients (35/77, 45 %). CONCLUSION: In summary, JE vaccination induced DENV cross-reactive antibodies, and at sub-neutralizing levels, these DENV cross-reactive antibodies possess DENV infection-enhancement activity. The results also indicate that cross-reactivity to DENV is associated with high levels of JEV neutralizing antibodies and, the DENV cross-reactivity is further facilitated by JE vaccination.

[A Case of Blackwater Fever after Treatment for Plasmodium falciparum Malaria].

Blackwater fever (BWF), which causes massive intravascular hemolysis and the passage of black-colored urine, is a poorly understood condition that is rarely seen during the course of malaria. Here, we present a case of BWF that developed after treatment for falciparum malaria complicated by hyperparasitemia in a Japanese traveler. A 29-year-old woman returning from Ghana visited our travel clinic with complaints of sudden fever and headache on the third day of illness. She had taken anti-malarial drugs for intermittent malaria prophylaxis and the treatment of malaria while in Ghana. Falciparum malaria was diagnosed based on the results of a blood smear and was confirmed using PCR. She was successfully treated with a single artesunate suppository and one dose of intravenous quinine followed by artemether-lumefantrin for 3 days. She was discharged without complications on the 11th day of illness. However, she was re-admitted for fever and headache on the 16th day of illness. The recrudescence of malaria was excluded by peripheral blood smear results. BWF was diagnosed based on the presence of fever, black-colored urine, and laboratory findings suggesting intravascular hemolysis. She was treated with supportive care, including the transfusion of 10 packs of red blood cells and the maintenance of fluid and electrolyte balance, and she gradually improved within two weeks. BWF is a rare but severe complication induced by severe falciparum malaria and/or the use of the aryl-amino alcohol group of antimalarial drugs. Thus, consideration of BWF is particularly important for a rapid and accurate diagnosis.

[Unexpected Diseases in Two Patients with False-Positive Dengue Immunoglobulin M Antibody Test Results].

In 2014, an outbreak of 162 domestic dengue fever infections occurred in Tokyo, Japan; the first outbreak of its kind in 70 years. Nineteen of these cases were confirmed in our center. Advancements in diagnostic methods have enabled an earlier diagnosis of dengue fever; however, unfamiliarity with the clinical course and characteristics of diagnostic tests for dengue fever can lead to misdiagnosis. We herein describe 2 cases of Japanese patients with false-positive dengue immunoglobulin M antibody test results, who were finally diagnosed as having dermatomyositis and acute hepatitis A infection, respectively.

The first case of adult-onset PFAPA syndrome in Japan.

A 26-year-old woman presented with fever and pharyngitis. She previously experienced four periodic febrile episodes at 30- to 40-day intervals. We suspected periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome, and prescribed predisolone, thereby her fever rapidly subsided. Her febrile episodes improved after daily cimetidine treatment. Genetic testing results of genomic DNA for periodic fever syndromes were negative, although she was heterozygous for p.Glu148Gln variation in MEFV, supporting the diagnosis of PFAPA syndrome.

Malaria.

Malaria is infectious diseases caused by Plasmodium parasite, which transmitted by Anopheles mosquitoes. Although the global burden of malaria has been decreasing in recent years, malaria remains one of the most important infectious diseases, from the point of view of its morbidity and mortality. Imported malaria is one of the major concerns at the evalua- tion of a febrile illness in a traveler returned from the endemic countries. The diagnosis and management of malaria cases requires much experience and knowledge. We review the epi- demiology, pathogenesis, clinical features, diagnosis, prevention and treatment of malaria in Japan.

Autochthonous dengue fever, Tokyo, Japan, 2014.

After 70 years with no confirmed autochthonous cases of dengue fever in Japan, 19 cases were reported during August-September 2014. Dengue virus serotype 1 was detected in 18 patients. Phylogenetic analysis of the envelope protein genome sequence from 3 patients revealed 100% identity with the strain from the first patient (2014) in Japan.

Comparison of clinical characteristics and laboratory findings of malaria, dengue, and enteric fever in returning travelers: 8-year experience at a referral center in Tokyo, Japan.

BACKGROUND: Without specific symptoms, diagnosis of febrile illness in returning travelers is challenging. Dengue, malaria, and enteric fever are common causes of fever in returning travelers and timely and appropriate treatment is important. However, differentiation is difficult without specific diagnostic tests. METHODS: A retrospective study was conducted at the National Centre for Global Health and Medicine (NCGM) from April 2005 to March 2013. Febrile travelers returning from overseas who were diagnosed with dengue, malaria, or enteric fever were included in this study. Clinical characteristics and laboratory findings were compared for each diagnosis. RESULTS: During the study period, 86 malaria, 85 dengue, and 31 enteric fever cases were identified. The mean age of the study cohort was 33.1 ± 12 years and 134 (66.3%) study participants were male. Asia was the most common area visited by returning travelers with fevers (89% of dengue, 18.6% of malaria, and 100% of enteric fever cases), followed by Africa (1.2% of dengue and 70.9% of malaria cases). Clinical characteristics and laboratory findings were significantly different among each group with each diagnosis. Decision tree models revealed that returning from Africa and CRP levels <10 mg/L were factors specific for diagnosis of malaria and dengue fever, respectively. CONCLUSION: Clinical manifestations, simple laboratory test results, and regions of travel are helpful to distinguish between dengue, malaria, and enteric fever in febrile returning travelers with non-specific symptoms.