Effect of voluntary human mobility restrictions on vector-borne diseases during the COVID-19 pandemic in Japan: A descriptive epidemiological study using a national database (2016 to 2021).

The coronavirus disease 2019 (COVID-19) pandemic not only encouraged people to practice good hygiene but also caused behavioral inhibitions and resulted reduction in both endemic and imported infectious diseases. However, the changing patterns of vector-borne diseases under human mobility restrictions remain unclear. Hence, we aimed to investigate the impact of transborder and local mobility restrictions on vector-borne diseases through a descriptive epidemiological study. The analysis was conducted using data from the National Epidemiological Surveillance of Infectious Diseases system in Japan. We defined the pre-pandemic period as the period between the 1st week of 2016 to the 52nd week of 2019 and defined the pandemic period as from the 1st week of 2020 to the 52nd week of 2021, with the assumption that human mobility was limited throughout the pandemic period. This study addressed 24 diseases among notifiable vector borne diseases. Datasets were obtained from weekly reports from the National Epidemiological Surveillance of Infectious Diseases, and the incidence of each vector-borne disease was examined. Interrupted time series analysis was conducted on the epidemic curves for the two periods. Between the pre- and post-pandemic periods, the incidence of dengue fever and malaria significantly decreased, which may be related to limited human transboundary mobility (p = 0.003/0.002). The incidence of severe fever with thrombocytopenia syndrome, scrub typhus, and Japanese spotted fever did not show changes between the two periods or no association with human mobility. This study suggests that behavioral control may reduce the incidence of new mosquito-borne diseases from endemic areas but may not affect tick-borne disease epidemics within an endemic area.

Incidence of common infectious diseases in Japan during the COVID-19 pandemic.

Recent reports indicate that respiratory infectious diseases were suppressed during the novel coronavirus disease-2019 (COVID-19) pandemic. COVID-19 led to behavioral changes aimed to control droplet transmission or contact transmission. In this study, we examined the incidence of common infectious diseases in Japan during the COVID-19 pandemic. COVID-19 data were extracted from the national data based on the National Epidemiological Surveillance of Infectious Diseases (NESID). Common infectious diseases were selected from notifiable infectious diseases under the NESID. The epidemic activity of the diseases during 2015-2020 was evaluated based on the Infectious Disease Weekly Reports published by the National Institute of Infectious Diseases. Each disease was then categorized according to the route of transmission. Many Japanese people had adopted hygienic activities, such as wearing masks and hand washing, even before the COVID-19 pandemic. We examined the correlation between the time-series of disease counts of common infectious diseases and COVID-19 over time using cross-correlation analysis. The weekly number of cases of measles, rotavirus, and several infections transmitted by droplet spread, was negatively correlated with the weekly number of cases of COVID-19 for up to 20 weeks in the past. According to the difference-in-differences analysis, the activity of influenza and rubella was significantly lower starting from the second week in 2020 than that in 2015-2019. Only legionellosis was more frequent throughout the year than in 2015-2019. Lower activity was also observed in some contact transmitted, airborne-transmitted, and fecal-oral transmitted diseases. However, carbapenem-resistant Enterobacteriaceae, exanthema subitum, showed the same trend as that over the previous 5 years. In conclusion, our study shows that public health interventions for the COVID-19 pandemic may have effectively prevented the transmission of most droplet-transmitted diseases and those transmitted through other routes.

Hepatocyte growth factor levels in Legionella pneumonia: a retrospective study.

BACKGROUND: Hepatocyte growth factor (HGF) is known to be involved in the resolution of pulmonary inflammation and repair of acute lung injury. Legionella pneumonia is sometimes complicated by acute lung injury. Our study aimed to determine the role of serum HGF levels in Legionella pneumonia. METHODS: Sera from patients with Legionella pneumonia (42 cases), other bacterial pneumonia (33 cases), pulmonary tuberculosis (19 cases), and normal controls (29 cases) were collected. The serum HGF levels for each serum sample were determined by sandwich ELISA. Clinical and laboratory data were collected by reviewing the medical charts. RESULTS: Serum HGF levels were higher in patients with Legionella pneumonia than in those with other bacterial pneumonia, pulmonary tuberculosis, and controls. The HGF levels were compared with white blood cell counts, C-reactive protein, Alanine amino-transferase, and lactate dehydrogenase (LDH). The HGF levels were correlated to serum LDH levels. Moreover, serum HGF levels were significantly higher in non-survivors than in survivors. CONCLUSIONS: HGF levels increased in severer pneumonia caused by Legionella, suggesting that HGF might play a significant role in the Legionella pneumonia.

Organizing pneumonia pattern in the follow-up CT of Legionella-infected patients.

The main aim of this study was to describe the appearance of the CT pattern of organizing pneumonia in Legionella-infected patients. Serial CT scans obtained from five sporadic cases of Legionella pneumophila pneumonia were retrospectively reviewed. The mean time of follow-up was 14 days. Chest CT was analyzed with regard to frequency and appearance of CT patterns of pulmonary abnormalities. Consolidation and ground-glass opacities, with or without an air bronchogram, were the most common abnormalities detected in CT scans during follow-up patients with L. pneumophila pneumonia. Two patterns were observed: subpleural and peribronchovascular. The subpleural pattern was seen in four patients and the peribronchovascular pattern in one. Interlobular septal thickening was seen in one patient. Pleural effusion was seen in one patient. The CT pattern of organizing pneumonia, a subpleural pattern, was frequently observed after treatment of L. pneumophila pneumonia.

Mechanisms involved in the extension of pulmonary Mycobacterium avium infection from the pulmonary focus to the regional lymph nodes.

PURPOSE: This study was designed to evaluate the mechanism of Mycobacterium avium extension in lung infection. STUDY DESIGN: Retrospective study. PARTICIPANTS: A 42-year-old man with acquired immune deficiency syndrome and immune reconstitution inflammatory syndrome. The patient developed mediastinal lymphadenopathy and a peripheral lesion in the right upper lobe within 2 weeks of starting highly active antiretroviral therapy. METHODS: Pulmonary tissue and lymph nodes were dissected under thoracoscopy and evaluated pathologically and immunohistochemically. RESULTS: Pulmonary pathologic examination revealed extensive granuloma formation throughout the acini. Mycobacterial antigens were found in the macrophages in the alveoli and in the alveolar septa. Some macrophages including mycobacterial antigens were surrounded by lymphatic endothelial cells in the interstitium. In addition, a proliferative granulomatous lesion was found under the intact epithelial layer of a bronchiole. Pathological examination of the lymph nodes revealed aggregated proliferative granulomas with few mycobacteria. Genetically closely related M. avium strains were isolated from both tissues. CONCLUSIONS: This study showed the mechanism involved in the progression of pulmonary M. avium infection from the pulmonary focus to the regional lymph nodes via the lymphatic vessels.

[The pathogenesis of the bowel infection with the Mycobacterium tuberculosis].

The prevalence of primary intestinal tuberculosis is increasing with social change and medical progress. However, it remains unknown whether or not primary intestinal tuberculosis exists without the involvement of other internal organs. This review verifies hypotheses about infectious courses of intestinal tuberculosis. We also evaluate the significance of bowel infection. As a result, we found some patients with intestinal tuberculosis who do not have tuberculosis lesions in other internal or external organs, and the tubercle bacillus, which is ordinarily transmitted with airborne droplet nuclei, might cause oral transmission by several factors.

Nonspecific interstitial pneumonia pattern as pulmonary involvement in human T-cell lymphotropic virus type 1 carriers.

It is well established that diffuse interstitial shadows are observed in human T-cell lymphotropic virus type 1 (HTLV-1) carriers. However, the pathological pattern of nonspecific interstitial pneumonia (NSIP) has rarely been reported. Here, we describe the clinical features of four patients with histologically proven NSIP and HTLV-1 infection. The patients, one woman and three men, had a median age of 59.5 years. High-resolution computed tomography of the lungs was performed in all patients, and no apparent honeycomb formations were detected. The present study demonstrates that the NSIP pattern is a significant pathological classification of interstitial pneumonia associated with HTLV-1 carriers.

Legionella pneumophila infection induces programmed cell death, caspase activation, and release of high-mobility group box 1 protein in A549 alveolar epithelial cells: inhibition by methyl prednisolone.

BACKGROUND: Legionella pneumophila pneumonia often exacerbates acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Apoptosis of alveolar epithelial cells is considered to play an important role in the pathogenesis of ALI and ARDS. In this study, we investigated the precise mechanism by which A549 alveolar epithelial cells induced by L. pneumophila undergo apoptosis. We also studied the effect of methyl prednisolone on apoptosis in these cells. METHODS: Nuclear deoxyribonucleic acid (DNA) fragmentation and caspase activation in L. pneumophila-infected A549 alveolar epithelial cells were assessed using the terminal deoxyribonucleotidyl transferase-mediated triphosphate (dUTP)-biotin nick end labeling method (TUNEL method) and colorimetric caspase activity assays. The virulent L. pneumophila strain AA100jm and the avirulent dotO mutant were used and compared in this study. In addition, we investigated whether methyl prednisolone has any influence on nuclear DNA fragmentation and caspase activation in A549 alveolar epithelial cells infected with L. pneumophila. RESULTS: The virulent strain of L. pneumophila grew within A549 alveolar epithelial cells and induced subsequent cell death in a dose-dependent manner. The avirulent strain dotO mutant showed no such effect. The virulent strains of L. pneumophila induced DNA fragmentation (shown by TUNEL staining) and activation of caspases 3, 8, 9, and 1 in A549 cells, while the avirulent strain did not. High-mobility group box 1 (HMGB1) protein was released from A549 cells infected with virulent Legionella. Methyl prednisolone (53.4 muM) did not influence the intracellular growth of L. pneumophila within alveolar epithelial cells, but affected DNA fragmentation and caspase activation of infected A549 cells. CONCLUSION: Infection of A549 alveolar epithelial cells with L. pneumophila caused programmed cell death, activation of various caspases, and release of HMGB1. The dot/icm system, a major virulence factor of L. pneumophila, is involved in the effects we measured in alveolar epithelial cells. Methyl prednisolone may modulate the interaction of Legionella and these cells.

Detection of Legionella pneumophila serogroup 1 antigen in respiratory samples using an immunochromatographic membrane test.

The immunochromatographic membrane test (ICT) efficacy of Legionella antigen detection (Binax Now Legionella) was evaluated using respiratory samples, including bronchial washings (44 cases) and sputum (128 cases), from suspected Legionella pneumonia patients. The ICT results using respiratory samples agreed well with isolation of L. pneumophila SG1 and ICT using urines.

Histopathological classification of systemic Mycobacterium avium complex infections in slaughtered domestic pigs.

The aim of this study was to classify the histopathological features of pigs infected with Mycobacterium avium complex (MAC). We used slaughtered pig organs systemically infected with MAC. The results showed granulomatous lesions which were observed predominantly in the digestive organs and regional lymph nodes rather than respiratory organs. The histological picture showed a wide range of granulomatous stages from exudative to fibrotic reactions to the MAC infection. Eosinophils and giant cells were characteristically observed in the exudative reactions. The histopathological type in primary focus tended to be maintained in the respective organs. Most strains with the same genotype showed pathogenicity for guinea pigs irrespective of the type of granuloma. Although these findings suggest that different stages of a granulomatous lesion originating from the same causative agent might influence histological patterns, other possibilities such as the hereditary background of the host, or the effects of viral infections should be considered.

Assessment of serum anti-Bordetella pertussis antibody titers among medical staff members.

This study comparatively evaluated the titers of the bacterial agglutination (BA) antibody for Bordetella pertussis, anti-pertussis toxin (PT) antibody, and anti-filamentous hemagglutinin (FHA) antibody in the serum of medical staff members. The geometric means of the anti-PT and anti-FHA antibody titers were 5.83 and 17.17 EU/mL, respectively. The positive rates of the BA antibodies against Tohama and Yamaguchi strains (> or = 40x), and anti-PT and anti-FHA antibodies (>10 EU/mL) were 81.3, 72.9, 43.8, and 68.8%, respectively. A high anti-PT antibody titer (>94 EU/mL) was found in 1 staff member, but this individual had no recent respiratory symptoms. The titers of the BA antibody against the Yamaguchi strain were weakly associated with the anti-PT antibody titers, but the BA antibody titer was not useful for predicting anti-PT antibody positivity. The seroprevalence of anti-pertussis antibody among medical staff was heterogeneous, suggesting that this group could be at high risk for pertussis. Judgments made using BA antibody or anti-PA antibody results differ, and thus careful evaluation of anti-pertussis antibody titers is necessary. Prompt and accurate diagnostic tools are crucial for infection control in the hospital setting.

[Mycobacteriosis as zoonotic disease--comparative pathological study on Mycobacterium avium complex infection].

Mycobacterium avium complex (MAC) infection has been giving major impact on human health. MAC infection is also one of zoonosis transmittable from environmental reservoirs to domestic animal such as pig, and from wildlife to human. Although the relationship between pig MAC infection and human MAC infection has been suggested, it has not been clarified about difference of pathogens, differences in the pathogenesis of the disease, and differences in pathological findings between them. As one of zoonosis, hog farms suffer from the epidemic in pig population and it may causes huge economical loss. At the same time, from pig to human transmission of MAC has been worried. Therefore, the control of MAC infection among hog farms is a very important issue both for pig industries and for human public health. We have demonstrated that the specific MAC strains can spread through pig market in the main island of Okinawa. In pig MAC infection, pathogens are infected orally, and granulomatous lesions are formed in abdominal lymph nodes. Subsequently, it spreads lymphogenously or hematogenously and forms disseminated disease. Pathologically, calcified lesion was formed within several months. These findings are quite different from human MAC disease, in which the infection was caused by inhalation, and form granulomatous lesions in lungs, and rarely cause lymph node swellings. Since the pathogenesis of human MAC respiratory infection has not been well clarified, it may be very important to examine the mechanism of pig MAC infection to find out some clues to explain the mechanism of human MAC infection.

[The pathogenesis and the development mechanism of Mycobacterium avium complex infection].

Mycobacterium avium complex (MAC) causes respiratory tract infections and develops granulomatous lesions in the alveolar areas and bronchioles in humans. In contrast with the above, the intestinal tract is the primary infection site of immunocompromised hosts, such as patients with acquired immune deficiency syndrome (AIDS), or animals, such as pigs. Recent studies have revealed that hosts with hereditary dysfunction of mediators in the Th-1 cascade as well as hosts with a high titer of auto-antibodies against interferon-gamma are susceptible to MAC, and such hosts facilitate dissemination of MAC. However, their disseminated lesions are formed mainly in the lung or in soft tissues, and the mechanism of development of MAC in such host may be different from that of AIDS-related MAC infection. In this review, we specifically discuss the development mechanism of disseminated MAC disease in recently-identified several pathological conditions.

[Overview of respiratory infection caused by nontuberculous mycobacteria].

Recently, the clinical importance of nontuberculous mycobacteria (especially, Mycobacterium avium complex [MAC] respiratory infection) has been increasing. In addition, an official ATS/IDSA statement about diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases has been published in February, 2007. In this review article, essence of this official statement will be introduced. In MAC respiratory infection, (i) primarily fibrocavitary disease, (ii) nodular/bronchiectatic disease, and (iii) hypersensitivity-like disease are identified, and (i) and (ii) are clinically important. Primarily fibrocavitary disease is characterized by cavitary lesions in upper lung fields in elderly subjects, smoking patients, or patients with pneumoconiosis. Nodular/bronchiectatic disease is characterized by centrilobular nodules and diffuse bronchiectases in the right middle lobe and the left lingula in middle-aged women. In addition, disseminated MAC disease in patients with acquired immunodeficiency syndrome should be considered. Further studies concerning transmission route as well as mechanism of MAC disease should be performed.

Do infections with disseminated Mycobacterium avium complex precede sweet's syndrome? A case report and literature review.

Sweet's syndrome is reportedly associated with preceding nontuberculous mycobacterial infections (NTMIs). Here, we report on a systemic Mycobacterium intracellulare infection in a patient on corticoid therapy for Sweet's syndrome. Literature searches show that 69.1% of patients with Sweet's syndrome and NTMIs developed this syndrome later than NTMIs and 89.3% of them developed during the clinical course of a rapidly growing mycobacterial infection. The residual cases were associated with slow-growing mycobacteria (14.3%), but only three cases of Mycobacterium avium complex (MAC) infections before the onset of Sweet's syndrome have been reported, and all of them were caused by disseminated MAC disease. One of these cases developed during corticoid therapy for Sweet's syndrome, while another case had underlying diabetes mellitus. Hence, the occurrence of systemic MAC disease may be an inevitable consequence of long-term steroid use and underlying diseases. Literature searches also show that cervical lymphadenitis was a predominant symptom in NTMIs (90.5%). The present case did not have cervical lymphadenitis although the previously reported MAC cases did experience it. Therefore, lymphadenitis from NTMIs may be related to the pathogenesis of Sweet's syndrome. Hence, should a patient have systemic infection without lymphadenitis, it will be more difficult to clinically confirm that MAC disease is a predisposing factor for Sweet's syndrome.

Depression of local cell-mediated immunity and histological characteristics of disseminated AIDS-related Mycobacterium avium infection after the initiation of antiretroviral therapy.

OBJECTIVE: The aim of the present study was to examine the immunohistological characteristics of disseminated Mycobacterium avium infection after the initiation of antiretroviral therapy (ART) for acquired immunodeficiency syndrome (AIDS). METHODS: We histologically investigated five autopsied AIDS patients with systemic M. avium infection. RESULTS: The inflammatory cell composition in the affected tissues was assessed using immunohistochemistry. The celiac lymph nodes and intestinal canal were the most commonly involved organs in the AIDS cases. The most common histological feature was unstructured aggregation of histiocytes. Immunohistochemistry revealed depression of CD4(+), CD8(+) and CD57(+) cells in the gut lamina propria and mesenteric lymph nodes. CONCLUSION: These findings suggest that local cell-mediated immunity is depressed in affected tissues and that the primary histological feature is poor organization of granulomas in mycobacterial lesions, despite the administration of adequate ART.

Distribution of mycobacterial antigen based on differences of histological characteristics in pulmonary Mycobacterium avium infectious diseases--consideration of the extent of surgical resection from the pathological standpoint.

Quantitative assessment of mycobacterial antigens is very important to determine the surgical indication, as well as the area of resection for pulmonary Mycobacterium avium complex (MAC) infectious disease. However, at present, pathological assessment is only possible as a postoperative examination. We performed quantitative evaluation of mycobacterial antigens using lung tissues with MAC pulmonary infection obtained from surgical resection. The distribution of mycobacterial antigens was evaluated by immunohistochemical staining with monoclonal antibody for mycobacteria. In exudative reactions, many monocyte-lineage cells containing mycobacterial antigens were observed in alveoli, whereas the quantity of mycobacterial antigens was extremely decreased in proliferative reactions. Epithelioid cells or multinucleated giant cells contained mycobacterial antigens in necrotic granulomas. In solitary nodules with central necrosis, mycobacterial antigens were frequently observed, whereas they were rarely observed in solitary nodules without caseous necrosis. Mycobacterial antigens were not observed in the epithelial layer of bronchioles in any cases, although proliferative granulomas were notably observed in the developed lymphoid follicles in subepithelial lesions of bronchiole. Thus, exudative reactions or nodules with caseous necrosis indicate the possibility of numerous mycobacteria remaining in the pulmonary focus. Therefore, intraoperative histological assessment may help in the determination of the area of surgical resection. This is the first study to quantitatively evaluate mycobacterial antigens according to histological characteristics in MAC pulmonary disease.

Diagnosis of intestinal tuberculosis using a monoclonal antibody to Mycobacterium tuberculosis.

AIM: To investigate the utility of immunohistochemical (IHC) staining with an antibody to Mycobacterium tuberculosis (M. tuberculosis) for the diagnosis of intestinal tuberculosis (TB). METHODS: We retrospectively identified 10 patients (4 males and 6 females; mean age = 65.1 ± 13.6 years) with intestinal TB. Clinical characteristics, including age, gender, underlying disease, and symptoms were obtained. Chest radiograph and laboratory tests, including sputum Ziehl-Neelsen (ZN) staining, M. tuberculosis culture, and sputum polymerase chain reaction (PCR) for tubercle bacilli DNA, as well as Tuberculin skin test (TST) and QuantiFERON-TB gold test (QFT), were examined. Colonoscopic records recorded on the basis of Sato's classification were also reviewed, in addition to data from intestinal biopsies examined for histopathological findings, including hematoxylin and eosin staining, and ZN staining, as well as M. tuberculosis culture, and PCR for tubercle bacilli DNA. For the present study, archived formalin-fixed paraffin-embedded (FFPE) intestinal tissue samples were immunohistochemically stained using a commercially available species-specific monoclonal antibody to the 38-kDa antigen of the M. tuberculosis complex. These sections were also stained with the pan-macrophage marker CD68 antibody. RESULTS: From the clinical data, we found that no patients were immunocompromised, and that the main symptoms were diarrhea and weight loss. Three patients displayed active pulmonary TB, six patients (60%) had a positive TST, and 4 patients (40%) had a positive QFT. Colonoscopic findings revealed that all patients had type 1 findings (linear ulcers in a circumferential arrangement or linear ulcers arranged circumferentially with mucosa showing multiple nodules), all of which were located in the right hemicolon and/or terminal ileum. Seven patients (70%) had concomitant healed lesions in the ileocecal area. No acid-fast bacilli were detected with ZN staining of the intestinal tissue samples, and both M. tuberculosis culture and PCR for tubercle bacilli DNA were negative in all samples. The histopathological data revealed that tuberculous granulomas were present in 4 cases (40%). IHC staining in archived FFPE samples with anti-M. tuberculosis monoclonal antibody revealed positive findings in 4 patients (40%); the same patients in which granulomas were detected by hematoxylin and eosin staining. M. tuberculosis antigens were found to be mostly intracellular, granular in pattern, and primarily located in the CD68(+) macrophages of the granulomas. CONCLUSION: IHC staining with a monoclonal antibody to M. tuberculosis may be an efficient and simple diagnostic tool in addition to classic examination methods for the diagnosis of intestinal TB.

Acquired immune-deficiency syndrome with focal onset of Mycobacterium avium infection displaying a histological/genetic pattern of disseminated mycobacteria.

A 66-year-old man with human immunodeficiency virus (HIV) infection was admitted for treatment of Pneumocystis pneumonia. Upon admission, a tumor mass adjacent to the thoracic descending aorta was revealed on computed tomography. Histology revealed an exudative granuloma with histiocytes packed with numerous acid-fast bacilli. Mycobacterium avium was isolated from the tissue. A genetic examination of the isolates demonstrated this strain to be located in the cluster consisting of strains that cause systemic infection. The patient's baseline CD4+ cell count was 9/µL and the HIV-RNA viral load was 43,800 copies/mL. This case suggests the possibility of a localized onset of disseminated M. avium infection.