Objectives

  The International Health Regulations (2005) bound the member states of the World Health Organization (WHO) to initiate epidemiological investigations of disease outbreaks and to notify WHO within 24 hours of their detection if the event is deemed to constitute public health emergency of international concern. The Japan International Cooperation Agency started the Amhara Regional Infectious Disease Surveillance Project to strengthen the surveillance and response system in the Amhara Region of Ethiopia in 2008. The objectives of the study were to review the project activities and to share the experiences and lessons learned in 22 districts of the North and South Gondar and West Gojjam Zones from mid-2012 through 2014.

Methods

  We conducted training for district surveillance officers and focal point personnel at health centres (HCs), monitoring visits to district health offices and HCs, held review meetings on surveillance, and provided technical assistance in outbreak investigations. We evaluated the project activities in terms of the timeliness of the surveillance reports submitted by the health facilities, provision of technical assistance in outbreak investigations, and the number of training sessions held for the surveillance personnel.

Results

  The timeliness of submission of surveillance reports had improved to almost 100% at end of 2014 compared with before the review period (about 68%). From the third quarter of 2013, we conducted monitoring visits to 59 HCs every semester. We were involved in 11 outbreak investigations of measles, anthrax, pertussis, neonatal tetanus, and typhoid fever. We held a total of 25 training sessions for district surveillance officers and HC focal points.

Conclusion

  The project successfully strengthened the surveillance and response system. We recommend that the Amhara Regional Health Bureau maintain its commitment to the system in terms of human resources and funding. Training for surveillance officers and focal points should be conducted periodically.

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Bacterial flora of a biofilm formed on the submerged stems of reeds (Phragmites australis) was studied in comparison with the flora in the water surrounding the reeds and on the aerial stems of the reeds. Most of the isolates from the above three samples were Gram-negative (90%) and rod-shaped (87%) with a distinct difference in glucose metabolism: largely oxidative (aerial stem surface), less oxidative (biofilm) and not at all (water). Most of the isolates (90%) belonged to the α, β, and γ-Proteobacteria, with Sphingomonadaceae a common group. Isolates from the aerial stem were phylogenetically different from those of the biofilm and water. The biofilm and water samples consisted of a phylogenetically common and a different group. The biofilm was characterized by 1) a seasonal change in thickness with a maximum in spring and a minimum in winter, 2) the existence of plastic-degrading strains phylogenetically close to Roseateles depolymerans, and 3) strong denitrifying activity even under aerobic conditions in a thicker biofilm formed in spring.

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目的：看護師の研究活用の障壁と教育的支援によって変化可能な影響要因を明らかにする．

方法：A大学病院の看護師とA県内医療・福祉機関に所属もしくはA大学院修了の専門看護師計860名を対象に質問票調査を行った．研究活用の障壁を従属変数，看護研究への態度，臨床実践力，看護研究に関する経験を独立変数とする重回帰分析を行った．

結果：295名を分析対象とした．障壁が高かった因子は「研究活用の組織的支援」であった．重回帰分析の結果，全変数を投入したモデル1と教育的支援によって変化可能な変数を投入したモデル2では，回帰式の適合度にほぼ差がなかった．肯定的な看護研究への態度，専門性の高い看護実践，看護研究の指導経験がある看護師は障壁が少なかった．

結論：研究活用の障壁は，基本属性を除く教育的支援によって変化可能な変数で説明可能であった．影響要因として，看護研究の態度，臨床実践力，看護研究の指導経験が示された．

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We experienced two cases of hepatocellular carcinoma (HCC) occurring immediately after treatment with direct-acting antiviral agents (DAAs). Case 1 was a 75-year-old woman in whom HCC was detected immediately after completion of DAA treatment. Case 2 was a 75-year-old woman who had a hypovascular nodule in liver. The hypovascular nodule became hypervascular without enlargement of the nodule size immediately after DAA treatment completion. Although the association between DAA treatment and hepatocarcinogenesis is unknown, sufficient surveillance after achieving a sustained viral response is required, as a large number of patients at a high risk of hepatocarcinogenesis are treated with DAAs.

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直接作用型抗ウイルス薬（direct-acting antiviral：DAA）治療の時代になり，かつては治療適応でなかったC型慢性肝疾患の進展した患者や高齢者からウイルス排除が得られる時代になった．ウイルス排除後の肝癌の問題は，今後C型肝炎患者のなかで最も大きな患者群に関係する重要な課題になっている．本稿では，DAA治療の時代の持続的ウイルス学的著効（sustained virologic response：SVR）後の発癌及び癌の再発について概説し，いくつかの関連論文を紹介する．いずれの報告も観察期間が未だ十分でなく，今後のさらなる評価が必要である．また，SVR後の肝癌に関しては，リスクを層別化するバイオマーカーの開発が期待される．

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Objective Owing to advances in direct-acting antiviral (DAA) therapy, a considerable number of patients with hepatitis C virus (HCV)-positive hepatocellular carcinoma (HCC) are now able to achieve a sustained viral response (SVR) after curative treatment of HCC. However, the beneficial effect of a DAA-SVR on the survival remains unclear.

Methods A total of 205 patients with HCC who were HCV-positive with Child-Pugh A at the onset from 2008 to 2018 were categorized into 2 groups: 140 patients untreated for HCV throughout the entire course after HCC development (untreated group) and 65 patients treated for HCV with DAAs following HCC treatment who achieved an SVR (SVR group). After propensity score matching, 63 patients from each group were selected. Using these patients, the survival and maintenance of Child-Pugh A after HCC treatment were compared between the untreated group and SVR group.

Results There was a significant difference in the overall survival (p<0.001) and the rate of maintaining Child-Pugh A (p<0.001) between the groups. The 5-year survival rates were 96% (SVR group) and 60% (untreated group), and the proportions of patients with Child-Pugh A at 5 years after HCC treatment were 96% (SVR group) and 38% (untreated group).

Conclusion In patients with HCV-positive HCC, achieving a DAA-SVR after HCC treatment significantly improved the overall survival rate compared with HCV-untreated patients. The contribution of DAA-SVR during the course of HCC treatment to a longer survival is mainly due to the prevention of the progression of Child-Pugh A to B/C. Further research is needed to determine whether aggressive antiviral therapy is also effective for HCC patients with Child-Pugh B/C.

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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.

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DAA製剤の登場以降、C型肝炎に対する抗ウイルス治療は大きく進歩した。現在はインターフェロンフリー療法が治療の中心であり、ウイルス排除が100％近く期待できる時代になった。一方、治療対象に高齢者や線維化進展例が多く含まれるようになり、DAA治療後の肝発癌の増加が懸念されている。当院の経験でも年齢、線維化の程度、肝癌既往の有無、抗ウイルス効果が、治療後発癌に影響していた。DAA治療による肝発癌抑制効果は依然検証が必要な時期であり、慎重なフォローアップが必要である。

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70歳代男性．びまん性大細胞型B細胞リンパ腫の既往あり，11年間無治療で寛解維持していた．今回direct-acting antiviralsによるC型肝炎治療を行い，SVRを達成．投与終了直後にsIL-2R上昇，腹腔内リンパ節腫脹を認めた．生検でリンパ腫の再発と診断し，急速な進行を認め死亡に至った．Direct-acting antivirals治療後のリンパ腫再発を考える上で重要な症例と考える．

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　症例は35歳の女性で，2007年9月中旬頃から38℃前後の発熱，筋肉痛，関節痛を繰り返すため，同年10月上旬当院内科を受診した．血液生化学的検査で軽度の肝機能異常を認めたためCTを施行したところ，最大径約3 cm大の脾臓腫瘍を認めた．入院後，全身精査で他臓器に悪性腫瘍を指摘しえず，原発性脾臓腫瘍を疑い，同年11月腹腔鏡下脾臓摘出術を施行した．手術時間は80分，出血量は20 mlであった．脾臓摘出のための創部を最小限に収めるために，Endocatch II^TMに収納したうえで3分割後体外に摘出した．肉眼検査所見では被膜を有さない比較的境界明瞭な3×2.5 cmの結節性病変であった．病理組織学的検査において，腫瘍は赤脾髄の脾索性毛細血管の増殖からなり，その形態学的特徴と免疫組織学的検索での特徴としてCD34陽性，CD8陰性，第VIII因子関連抗原（以下，Factor VIII）陰性の増殖内皮細胞の性状であったことから，過誤腫に包括されているsplenic cord capillary hemangiomaと診断した．本症は過誤腫の中でも非常にまれと推察され，自験例が本邦1例目であり報告する．

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More than 30 drugs for antiretroviral therapy (ART), including integrase inhibitors (INIs), have been approved by the U.S. Food and Drug Administration (FDA) as of 2017. Integrase is the third essential enzyme in the cycle of human immunodeficiency virus (HIV) replication. INIs can effectively inhibit the replication of HIV and HIV is less prone to develop resistance to INIs clinically. Previous studies based on 7 phase III clinic trials indicate that INIs have satisfactory efficacy and tolerability in patients infected with HIV. The latest advances in INIs indicate that: i) dolutegravir (DTG)-based regimens are more efficacious, tolerable, and safer forms of first-, second-, and third-Line ART; ii) current studies have indicated that DTG monotherapy fails both virologically and clinically; and iii) whether the most cost-effective treatment for DTG is to replace efavirenz (EFV) as a first-line ART, to replace protease inhibitors (PIs) in second-line ART, or to replace both as a monotherapy is unclear. Given these circumstances, further study of INIs in terms of drug interactions, dose reduction, drug convenience, and drug costs is warranted.

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Laboratory-scale acidophilic nitrifying sequencing-batch reactors (ANSBRs) were constructed by seeding with sewage-activated sludge and cultivating with ammonium-containing acidic mineral medium (pH 4.0) with or without a trace amount of yeast extract. In every batch cycle, the pH varied between 2.7 and 4.0, and ammonium was completely converted to nitrate. Attempts to detect nitrifying functional genes in the fully acclimated ANSBRs by PCR with previously designed primers mostly gave negative results. 16S rRNA gene-targeted PCR and a subsequent denaturating gradient gel electrophoresis analysis revealed that a marked change occurred in the bacterial community during the overall period of operation, in which members of the candidate phylum TM7 and the class Gammaproteobacteria became predominant at the fully acclimated stage. This result was fully supported by a 16S rRNA gene clone library analysis, as the major phylogenetic groups of clones detected (>5% of the total) were TM7 (33%), Gammaproteobacteria (37%), Actinobacteria (10%), and Alphaproteobacteria (8%). Fluorescence in situ hybridization with specific probes also demonstrated the prevalence of TM7 bacteria and Gammaproteobacteria. These results suggest that previously unknown nitrifying microorganisms may play a major role in ANSBRs; however, the ecophysiological significance of the TM7 bacteria predominating in this process remains unclear.

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我が国の門脈圧亢進症の原因の大部分は肝硬変であり，肝硬変の成因としてはC型肝炎ウイルス（HCV）が最多である．C型慢性肝炎・肝硬変の治療はインターフェロン（IFN）を基軸に発展してきたが，2014年よりIFNフリーのdirect-acting antivirals（DAA）治療により高率にsustained virological response（SVR）が得られ，非代償性肝硬変を除くすべての症例が治療対象となった．IFN治療でSVRが得られた場合，肝線維化は可逆的で門脈圧亢進症も長期的には改善することが示されている．DAA治療による肝線維化，門脈圧亢進症の改善も非侵襲的診断法で示唆されているが，今後更に長期観察による検証の必要がある．DAA治療による肝予備能改善効果も報告され，欧米では非代償性肝硬変への使用も試みられている．今後，DAA後の肝発癌など病態進展例の頻度や背景を明らかにし，危険群を囲い込む方策の確立が望まれる．

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