The largest ever outbreak of Ebola virus disease has been spreading in West Africa. The authors were deployed to Liberia and Sierra Leone as short-term consultants for the World Health Organization. Our mission was to ensure clinical management and infection prevention and control priorities in frontline treatment centres. This paper describes how the disease is spread, its symptoms and progression, measures currently taken to ensure both infection control and the best possible care, and the significance of infections among health care workers. We adopted an approach which is detailed in the WHO Clinical Management of Patients with Viral Haemorrhagic Fever. Areas within the treatment centres were divided into either a “hot zone”or a “cold zone”. Patients were interviewed, and those patients who met the criteria for suspected, probable or confirmed cases were moved to hot zones. All health care workers wore personal protective equipment when entering a hot zone and washed hands with a hypochlorite solution after each patient encounter. Among the problems which we encountered was a fundamental mismatch in the numbers of patients and nurses. The nurses often had to work alone in hot zones in protective equipment which limited physical movement and blurred vision. These factors contributed to fatigue due to prolonged outbreak response and may have resulted in infections among the nursing staff. In conclusion, we present the current situation in West Africa in regard to the recent outbreak of Ebola virus disease, specifically the clinical picture based on our observation. We further propose steps to be taken to handle the patient care safely and effectively. We hope our experience will contribute to national discussions on how to respond to the Ebola virus disease.
Noroviruses (NoV) are a major cause of nonbacterial acute gastroenteritis. To efficiently control NoV infection, preventing the transmission of the virus from NoV-infected food-handlers to food may be crucial. At present, reverse-transcription real-time PCR (rRT-PCR) methods may be used as a sensitive method to detect NoV, but the method has the drawbacks of being expensive and time consuming. Other conventional immunological methods such as ELISA and immuno-chromatographic tests are more economical and easier to use than rRT-PCR, but these methods may not be highly sensitive. To overcome these problems, we have developed a novel bioluminescent enzyme immunoassay (BLEIA) system. The system is fully automated and this may enable the rapid, highly sensitive detection of NoV. To practically evaluate the BLEIA,we measured a number of fecal specimens from the patients with acute-gastroenteritis due to NoV infection or healthy adult volunteers in Japan. The performance of the BLEIA was compared with the Loop-Mediated Isothermal Amplification (LAMP) assay and rRT-PCR. The sensitivity, specificity, and correspondence rate of the BLEIA were 93.1％(135/145), 100％(87/87), and 95.7％(222/232), respectively, and those of the LAMP assay were 91.0％(132/145), 98.9％(86/87), and 94.0％(218/232), respectively. A good correlation (r＝0.72) was obtained between the virus loads measured using rRT-PCR and the cut-off index values of the BLEIA,and the sensitivity of the BLEIA was estimated to be 105-106 copies/g stool samples. No cross-reactivity toward other closely related or enteric viruses was found. The results indicated that the BLEIA may be applicable for the conventional screening for NoV detection with a large number of fecal specimens from the patients and food-handlers.
We analyzed non-serotype b encapsulated Haemophilus influenzae (non-b Hi) isolated from pediatric patients at Chiba Childrenʼs Hospital during 2000-2012. Among 3,532 clinical isolates of H. influenzae, there were 57 (1.6％) strains of non-b Hi, 152 (4.3％) of serotype b H. influenzae (Hib), and 3,323 (94.1％) of non-typeable H. influenzae (NTHi). Fifty-seven strains of non-b Hi were serotyped useing the slide agglutination test and PCR. Twenty-nine strains were identified as type e (Hie) and 28 as type f (Hif), and the results according to the slide agglutination test and PCR were completely identical. Whereas 52 of 57 strains (91.2％) were isolated from respiratory specimen, only one Hif strain (1.8％) was isolated from a sterile site. There were 47 (82.4％) β-lactamase-non-producing ampicillin (ABPC)-sensitive strains (BLNAS), 5 (8.8％) β-lactamase-producing strains (BLP), and only 1 (1.8％) β-lactamase-non-producing ABPC-resistant strain (BLNAR). Thus the frequency of non-b Hi was lower than that of Hib. The source of non-b Hi was similar to that of NTHi, which was mainly isolated from respiratory specimen. Antimicrobial resistant pattern of non-b Hi was different from that of Hib in which the frequency of BLP was relatively high, and NTHi in which that of BLNAR was high. An increase of invasive H. influenzae infections caused by NTHi, Hie, and Hif was reported in the countries where Hib vaccine had been widely used. Because it is assumed that invasive nonHib infection will be predominant in the near future in Japan, serotyping of invasive strains is crucial. Continuous monitoring of distribution of non-b Hi in the clinical isolates of H. influenzae is also important.
Recently, there has been a marked increase in the number of reports of fluoroquinolone-resistant Campylobacter jejuni and Campylobacter coli. The aim of this study was to evaluate the prevalence of antimicrobial resistance and its genetic determinants in Campylobacter species isolated from meat and human subjects in Fukuoka Prefecture, Japan. Between 2011 and 2013, 55 and 64 isolates were collected from meat (chicken meat and beef liver) and humans, respectively, in this prefecture. Antimicrobial susceptibility tests were conducted using the agar dilution method in accordance with the Clinical and Laboratory Standards Institute guidelines, using the following 11 antimicrobial agents： cephalexin, cefoxitin, nalidixic acid,ciprofloxacin, levofloxacin, tetracycline, minocycline, ampicillin, streptomycin, kanamycin and erythromycin. The susceptibility rates of the isolates to three quinolones (nalidixic acid, ciprofloxacin, levofloxacin) were 43.7%, 41.2%, 40.3%, respectively. All the isolates were multidrug resistant. Whereas 46.9%-51.6% of the human isolates were resistant to one or more of the quinolones, only 32.7%-34.5% of the meat isolates were resistant to one or more of the drugs. DNA sequencing showed that of the 50 quinolone resistant isolates 44 had position 86 isoleucine (Ile) substituted for threonine (Thr) in the GyrA protein (Thr86Ile). This amino acid substitution resulted from ACA to ATA and ACT to ATT mutations of codon 86 in C. jejuni and C. coli, respectively. Furthermore, two of the four C. jejuni isolates lacking the Thr86Ile mutation had combined Ser22Gly-Asn203Ser substitutions, while the remaining two isolates had combined Ser22Gly-Asn203Ser-Ala 206Val substitutions. These four isolates also had cmeABC sequences that differed from the quinolone sensitive C. jejuni ATCC33560T strain. In conclusion, C. jejuni and C. coli have relatively high quinolone resistance,and are resistant to other antibiotics. The new combination of amino acid substitutions in the GyrA protein could pose a potential threat to public health in Japan.
Objective：Peumocystis pneumonia (PCP) is one of the common opportunistic infections with severe respiratory failure, and is sometimes life-threatening in patients with the acquired immunodeficiency syndrome. Although treatment for PCP is established, an appropriate treatment period has not been evaluated to clarify the risk factors for immune reconstitution inflammatory syndrome (IRIS) associated with PCP. Method：We retrospectively analyzed the clinical characteristics of risk factor, which are the treatment period for PCP, and 67Ga scintigraphy (Ga-S) at the 21st day from the start of the treatment for PCP, with 21 cases of PCP and HIV infection treated during 2005-2012 at Kyushu Medical Center. Result：The rate of residual uptake by Ga-S was assessed in 17 cases (81％). Four cases were diagnosed as being PCP-IRIS, and residual uptake by Ga-S was detected in all PCP-IRIS cases. The durations of the therapy were classified into three groups：21 days, 28 days, and 35 days. All PCP-IRIS cases were treated in the period of 28 days. In contrast, in 11 cases that showed residual uptake by Ga-S, and were treated for PCP in 35 days, PCP-IRIS did not occur. Additionally, there were 4 cases in which residual uptake by Ga-S did not occur. They were treated with PCP for only 21 days, but did not show PCP-IRIS. Conclusion：In this study, we showed that Ga-S is useful to evaluate the therapeutic effect. Furthermore, we found that the occurrence of PCP-IRIS could be prevented with the early start of cART after 21 days treatment for PCP, when residual uptake by Ga-S after the first treatment for PCP was not detected. It may also be possible to start cART in the early phase after its treatment without the occurrence of PCPIRIS with the appropriate additional treatment of PCP for 14 days. These guidelines for treatment of PCP in HIV-infected adults and adolescents have been recommended for the duration of 21 days since 1984. We propose that for the prevention of PCP-IRIS, it is nessecory to reconsider recommendation for the treatment duration of 21 days, and meanwhile to evaluate the treatment effect of PCP with Ga-S, because PCP resistance to sulfa drugs, namely are trimethoprim-sulfamethoxazole, is beginning to appear.
A 44-year-old male, who was HIV seropositive, developped weight loss, high grade fever, and multiple lymphadenopathies. Bone marrow biopsy revealed a granuloma lesion, and at the same part of the specimen, Ziehl Neelsen staining showed multiple mycobacterium diffusely arranged in the histocytes. The culture did not show positive after 6 to 8 weeks. Finally we diagnosed disseminated Mycobacterium genavense using a house-keeping gene analysis including 16S rRNA sequencing of lymph punctate with fine needle aspiration and the specimen from the biopsy of the lymph node. If a specimen tests positive for Ziehl Neelsen staining smear positive, culture negative, and PCR negative for tuberculosis and Mycobacterium avium complex, we should consider M. genavense infection as one of the differential diagnoses.
We report herein on a case strongly suspected of being pulmonary toxocariasis. A 22-year-old Indonesian man referred to our hospital presented with abnormal chest shadows upon medical examination. He had no symptoms. He did not have any pets nor did he eat raw beef or chicken. Hematological examination revealed eosinophilia and elevation of IgE. Chest computed tomography revealed 3 pulmonary nodules with the halo sign. We suspected a parasite infection and performed antiparasite antibody testing. Ascaris suum was slightly positive on the screening test. As specificantibody against the larval excretory-secretory products of Toxocara canis, measured at the National Institute of Infectious Diseases, was positive (level 3 up to 8). Subsequently, the abnormal chest shadows disappeared. However, two months later, 2 pulmonary nodules with the halo sign reappeared in other places. Diagnostic therapy with albendazole was performed for 8 weeks. Mild hepatic impairment emerged during therapy, but it was within the allowed range. Thereafter,the results improved for the imaging findings, eosinophilia, serum IgE level, and specific antibody.The antibody level became negative two months after the treatment had ended. We should consider toxocariasis in the differential diagnosis of migratory nodular shadows with the halo sign on chest computed tomography,and immunoserological testing is useful for the diagnosis.
Tsutsugamushi disease (Scrub thyphus) has been reported from all over Japan except the Hokkaido area. In Okinawa, only one patient was reported in 2001, who was infected outside Okinawa Prefecture. The first case infected in Okinawa was reported at Miyakojima Island in 2008. We report herein on the second case diagnosed in 2010, and the third and fourth in 2011, and all three patients were suspected to have been infected at Ikemajima Island adjacent to the island of Miyakojima. The patients recovered without any severe complications after antibiotic therapy with tetracyclines. We should take Tsutsugamushi disease into consideration in the differential diagnosis for a patient with fever, skin rash, and/or eschar even in the Okinawa area. Implementation of appropriate information and education about the disease should be carried out for local residents and tourists.
Department of Infectious Disease Medicine, Tokyo Womenʼs Medical University An 82-year-old bedridden man with sequelae from a cerebral infarction was admitted to a welfare institution for the elderly. He developed a high fever and hematuria and was prescribed levofloxacin for the treatment of a suspected urinary tract infection. Although his condition improved, the symptoms subsequently recurred；therefore, levofloxacin was again administered. He remained febrile and was admitted to a hospital due to recalcitrant urinary tract infection. Immediately after admission, he developed ischuria and pyuria. Urine and blood cultures at admission indicated the presence of levofloxacin-resistant Oligella urethralis (O.urethralis). He recovered with ceftriaxone medication. To our knowledge, this is the first report of bacteremia associated with a urinary tract infection caused by O.urethralis in Japan.
Recovery from dengue fever is generally rapid and uneventful. However, recuperation is often prolonged and may be accompanied by noticeable depression. We present herein on a traveler to Indonesia who developed long-lasting depression after the classic symptoms of dengue fever such as fever, arthralgia,and macropapular rash had resolved. A previously healthy 42-year old Japanese woman presented to the Travel Clinic of Seirei Yokohama Hospital with complaints of 4 days of fever, joint aches, bone pain, and a macropapular rash on her torso. She had returned from Bali 5 days previously. During her 1-week stay, one day was spent in rural, mountainous areas where she was exposed to several mosquito bites. The 1st serum sample collected 4 days after the disease onset gave positive result in the rapid dengue IgM antibody test and the rapid dengue NS1 antigen immunechromatographic test. The DENV-1 genome was detected with RT-PCR. Her 13-year old son, who had accompanied her, was also diagnosed as having dengue fever and he recovered without event. The Above-mentioned symptoms resolved within one week. However, the patient suffered from prolonged depression. She also noticed loss of hair 3 months after the disease onset. Administration of a Serotonin Noradrenalin Reuptake Inhibitor and a minor tranquillizer required to allow her requied to lead a normal life. Although she gradually felt better, it took approximately 2 years until she had recovered completely without taking any antidepressant and minor tranquillizer. It is a well-known fact in endemic countries that dengue fever could have an significant impact on the patientsʼmental well-being. However, it appears that physicians in non-endemic countries are not fully aware of the prolonged depression, which can occur subsequent to the acute illness. Follow-up consultations of returing travelers who have recoverd from dengu fever should be arranged to monitor their mental and emotional states closely.