Development of an intervention system for linkage-to-care and follow-up for hepatitis B and C virus carriers.

BACKGROUND: Poor connections in the cascade of viral hepatitis care have been discussed around the world. In 2011 in Japan, 500,000 to 1.25 million hepatitis B and C virus carriers needed to consult with hepatologists, so linkage-to-care (LTC) needs to be promoted. Therefore, in this study, to improve LTC and care-seeking behaviors, we attempted to establish a community-based intervention system and evaluate its effectiveness by analyzing behavior modifications. METHODS: In a model city, Okazaki (population: 387,887 as of 2019), LTC was encouraged among HBV and HCV carriers by annually mailed brochures, and their care-seeking behaviors were followed up through questionnaires for 8 years (2012-2019). Their behavior modifications and demographic characteristics were analyzed anonymously in cooperation with community health workers, hepatologists, and researchers. RESULTS: Through regional HBsAg and anti-HCV screening, 333 HBV and 208 HCV carriers were identified. Before the intervention, only 34.7% (25/72) of HBV- and 34.3% (24/70) of HCV-positive individuals had consulted with hepatologists. However, in 2019, after the intervention, these proportions increased to 79.8% (91/114) and 91.2% (52/57), respectively. Access to outpatient care and treatment uptake also continuously improved. However, individuals over 70 years of age were significantly less likely to engage in care-seeking behaviors (p < 0.05), and significantly fewer HCV-positive females received treatment (p = 0.03). CONCLUSIONS: A paper-based reiterative intervention encouraging LTC and follow-up successfully improved the care-seeking behaviors of hepatitis virus-positive individuals and enabled their behavior modifications to be monitored. Further trials are required to advance the system by age- and gender-specific interventions.

Does Direct-to-Consumer Personal Genetic Testing Improve Gynecological Cancer Screening Uptake among Never-Screened Attendees? A Randomized Controlled Study.

The clinical impact of direct-to-consumer genetic testing (DTC-GT) on health behavior change has remained controversial. The aim of this study is to clarify the short-term effects of DTC-GT on gynecological cancer screening uptake among middle-aged never-screened Japanese women in a randomized controlled trial (RCT). A total of 144 women aged 45-50 who had never undergone gynecological cancer screening were randomly selected to receive health education (control group), or health education and DTC-GT (intervention group), at a 1:1 ratio. We compared the gynecological screening uptake during the follow-up period. Furthermore, to estimate the impact of learning of an elevated genetic cancer risk in the intervention group, we conducted an analysis dichotomized by genetic risk category. A total of 139 women completed the one-year follow-up survey (69 in the control group and 70 in the intervention group). The follow-up period did not differ between control and intervention groups (the median follow-up period was 276 days and 279 days, respectively, p = 0.746). There were 7 (9.7%) women in the control group and 10 (13.9%) in the intervention group who attended breast cancer screening (p = 0.606), and 9 (12.5%) women from both groups attended cervical cancer screening (p = 1.000). Likewise, there were no significant differences in cancer screening uptake in the analysis stratified by risk category within the intervention group. In conclusion, there was no significant effect of DTC-GT on gynecological cancer screening uptake in this RCT setting. Increasing cancer screening attendance may require a combination of well-established intervention strategies and DTC-GT. Clinical Trial Registration: UMIN-CTR Identifier, UMIN000031709.

[Epidemiological significance of patients with extra-pulmonary TB--a study of 10,082 patients with tuberculosis].

OBJECTIVES: To elucidate the epidemiological significance of patients with extra-pulmonary TB. SUBJECTS AND METHODS: The subjects of this retrospective study were 10,088 TB patients registered in Aichi prefecture between 1989 and 2003. Of these, 8,629 patients had pulmonary TB and 1459 had extra-pulmonary TB. All registration files were reviewed to identify the epidemiological links of patients. When linked patients with an interval of less than 10 years between registrations were found, the earlier registered case was considered the primary or index case, and the other patients were regarded as secondary cases. The index case rate (ICR) for a category of patients was defined as follows: ICR=NI/NA, where NA: number of TB patients in a category A, and NI: number of index cases in category A. RESULTS: The ICR for the 1,459 extra-pulmonary TB patients was 1.1%, which was significantly different from 7.2% for 3332 patients with sputum smear-positive pulmonary TB (p < 0.001), as well as from 2.1% for 2139 patients with sputum smear-negative and bacillus-positive pulmonary TB (p < 0.05). The ICR differences were not significant between extra-pulmonary TB patients and 3,158 patients with bacteriologically negative pulmonary TB (1.2%). Of the 16 index cases with extra-pulmonary TB, the organs in which tuberculosis was found were the pleura in 13 patients, the bone in two, and the hilar nodes in one. The relationship between the 16 index cases and 18 secondary patients were husband-wife in 7 pairs, parent-child in 7 pairs, brother or sister in 2 pairs, and grandparent-grandchild in 2 pairs. The interval of the dates of registration for the index and secondary patients was within one year in 14 pairs or 77.8%. DISCUSSION: The index cases with extra-pulmonary TB can be considered as a good control in the epidemiological study on the ability of TB transmission in patients with pulmonary tuberculosis, so that they can form clusters by chance, or false positive clusters. CONCLUSION: Our findings suggest that patients with extrapulmonary TB have no ability of TB transmission, nor do patients with bacteriologically negative pulmonary TB.

[Generation-to-generation TB transmission in Aichi, Central Japan -- an epidemiological study of 701 TB patients in 290 clusters].

OBJECTIVES: To elucidate characteristics in generation-to-generation TB transmission from smear positive pulmonary TB patients. SUBJECTS AND METHODS: The subjects of this retrospective study were 10,088 TB patients registered in Aichi prefecture between 1989 and 2003. Smear-positive pulmonary TB was found in 3,332. All registration files were reviewed to identify epidemiological links of patients. When linked patients with an interval of the dates of registration of less than 10 years were found, the first case was considered as the index case, and the other patients were regarded as secondary patients. All patients were subdivided by every 10 years of age as a generation. All patients were also grouped as young generations aged 0 to 29, middle-aged generations aged 30 to 59, and elder generations aged 60 to 99. A young generations rate (YGR) for a generation of index cases was defined as following; YGR=NY/NA, where NA: Number of whole TB secondary patients transmitted from all index cases belonging to generation A, and NY: Number of secondary patients aged 0-29 in NA. A same generation rate (SGR) for a generation of index cases was defined as following; SGR=NS/NA, where NA: Number of whole TB secondary patients transmitted from all index cases belonging to generation A, and NS: Number of secondary patients belonging to the same generation A in NA. RESULTS: A total of 290 clusters were found with 290 index cases and 411 secondary cases. Of the 290 index cases, the biggest number of patients was 58 for the forties, followed by 43 patients for the twenties and the fifties. Of the 411 secondary patients, the biggest number of patients was 91 for the twenties, followed by 58 patients for the thirties, and 158 patients or 38.4% belonged to the young generations. High YGRs were found in the young and middle-aged generations ranging from 37.5% to 75.0%, while YGRs were low in the elder generations ranging from 15.9% to 26.7%. The difference was significant between the fifties and the sixties (p<0.01). The YGRs were calculated 57.1% for the young generations, 43.5% for the middle-aged generations, and 18.9% for the elder generation. The differences were significant between the young and the middle-aged (p<0.05), as well as between the middle-aged and the elder (p<0.001). The biggest SGR was calculated 42.2% for the twenties. Low SGRs were 18.2% for the forties and 17.5% for the fifties. The differences were significant between the twenties and the forties (p<0.01), as well as between the twenties and the fifties (p<0.01). The secondary patients aged 0 to 29 were counted 158: 123 were transmitted through intra-familial infection and 35 were through extra-familial infection. The major index case generation was the middle-aged generations with 82 or 66.7% secondary patients in the case of intra-familial infection, while it was the young generations with 20 or 57.1% patients in the case of extra-familial infection. CONCLUSION: These findings suggest that the major sources of TB transmission to young people are smear-positive pulmonary TB patients aged 0 to 59.

[Clustered secondary case rate in 10,088 patients with tuberculosis].

OBJECTIVES: To elucidate characteristics in clustered secondary TB patients transmitted from culture positive pulmonary TB patients. SUBJECTS AND METHODS: The subjects of this retrospective study were 10,088 TB patients registered in Aichi Prefecture between 1989 and 2003. Pulmonary TB was found in 8,629 patients, and 1,459 had extra-pulmonary TB. Bacteriological examination revealed sputum smear-positive (SPBP) in 3,332, sputum smear-negative bacillus-culture-positive (SNBP) in 2,139, and smear-negative bacillus-culture-negative (SNBN) in 3,158. All registration files were reviewed to identify epidemiological links of patients. When linked patients with an interval of the dates of registration of less than 10 years were found, the first case was considered as the index case, and the other patients were regarded as secondary cases. A clustered secondary case rate (CSR) for a category of patients was defined as follows; CSR=NCS/NA, where NA: number of TB patients in a category A, and NCS: number of secondary cases in category A. A cluster rate for a category of bacillary pulmonary patients was defined as follows; Cluster rate= (NIC+NCS)/ NA, where NA: number of TB patients in a category A, NIC: number of index cases in category A, and NCS: number of secondary cases in category A. RESULTS: A total of 417 patients were considered as clustered secondary cases, and the CSR was 4.1% in total. The CSRs were 3.5% for the SPBP patients, 3.8% for the SNBP patients, 5.4% for the SNBN patients, and 3.4% for the extra-pulmonary patients. The CSR in SNBN patients was significantly higher than the SPBP patients (p<0.001). The significant differences in the CSRs were found between the SNBN patients and the SNBP patients (p<0.01), as well as between the SNBN patients and the extra-pulmonary patients (p< 0.01). The CSRs were 42.5% in patients aged 0-9, 30.3% in those aged 10-19, 11.2% in those aged 20-29, 7.4% in those aged 30-39, 4.6% in those aged 40-49, 3.2% in those aged 50-59, 2.4% in those aged 60-69, 1.8% in those aged 70-79, 1.3% in those aged 80-89, and 0.6% in those aged 90-99. There were significant differences in the CSRs between those aged 10-19 and those aged 20-29 (p< 0.001), between those aged 20-29 and those aged 30-39 (p<0.05), and between those aged 30-39 and those aged 40-49 (p< 0.05). The male patients showed significantly lower CSR than female patients (2.9% vs 6.3%, p<0.001). The cluster rate for the 5,471 bacillary patients was 8.8%. The cluster rates were significantly different between those patients aged 10-19 and those aged 20-29 (37.1% vs 21.1%, p<0.001), as well as between those aged 40-49 and those aged 50-59 (16.4% vs 8.5%, p<0.001). CONCLUSION: These findings suggest that the CSR is closely related with patient's age, gender, and bacillary findings, and that the CSR is significantly high in young, female, and SNBN patients.

[Tuberculosis transmission with multiple secondary patients].

OBJECTIVES: To elucidate TB transmission with multiple secondary patients (MSP) in comparison with a single secondary patient (SSP). SUBJECTS AND METHODS: The subjects of this retrospective study were 10,088 TB patients registered in Aichi Prefecture between 1989 and 2003. Pulmonary TB was found in 8,629 patients, and 1,459 had extra-pulmonary TB. Bacteriological examination revealed sputum smear-positive (SPBP) in 3,332, sputum smear-negative bacillus-positive (SNBP) in 2,139, and smear-negative bacillus-negative (SNBN) in 3,158. All registration files were reviewed to identify epidemiological links of patients. When linked patients with an interval of the dates of registration of less than 10 years were found, the first case was considered as the index case, and the other patients were regarded as secondary cases. An index case rate (ICR) for a category of patients was defined as following; ICR=NI/NA, where NA: Number of TB patients in a category A, and NI: Number of index cases in category A. An epidemic source rate (ESR) was used instead of ICR when the index case and the TB patients in a category were smear-positive. RESULTS: A total of 337 patients were considered as index cases. Sixty-nine patients had MSP, while 268 had a SSP. The ICRs for MSP were 1.74% for the SPBP patients, 0.33% for the SNBP patients, 0.06% for the SNBN patients, and 0.14 % for the exrtra-pulmonary TB patients. These ICRs for SSP were 5.43%, 1.73%, 1.14%, and 0.96%, respectively. The ESR differences with MSP were highly significant (p<0.001) between patients aged 0-59 and those aged 60-99 (3.8% vs 0.5%), between patients with cavitary lesion and those with non-cavitary lesion (2.6% vs 0.4%), and between patients with large amount of bacilli and those with small amount of bacilli (2.9% vs 0.9%). These differences were also found in those with SSP. CONCLUSION: These findings suggest that TB transmission with multiple secondary patients is closely correlated with aging, cavitary lesion, and bacillary amount, and that no characteristic changes were found between index cases with multiple secondary patients and those with a single secondary patient.

[Transmission of tuberculosis from smear-negative bacillus-positive pulmonary TB patients].

OBJECTIVES: To elucidate TB transmission from smear-negative bacillus-positive patients. SUBJECTS AND METHODS: The subjects of this retrospective study were 8,339 TB patients registered in Aichi Prefecture between 1989 and 2003. Of these patients, 7,122 had pulmonary TB and 1,217 had extra-pulmonary TB. Bacteriological examination for the pulmonary patients revealed sputum smear-positive in 2,640, sputum smear-negative bacillus-positive (SNBP) in 1,794, and smear-negative bacillus-negative (SNBN) in 2,688. All registration files were reviewed to identify epidemiological links of patients. When linked patients with an interval of the dates of registration of less than 10 years were found, the initial case was considered as the index case, and the other patients were regarded as secondary cases. An index case rate (ICR) for a category of patients was defined as follows; ICR=NI/NA, where NA: Number of TB patients in a category A, and NI: Number of index cases in category A. RESULTS: A total of 287 patients were considered as index cases, and the ICR was 3.4%. The ICRs were 2.3% for the SNBP patients, 7.5% for the smear-positive patients, 1.2% for the SNBN patients, and 1.1% for the exrtra-pulmonary tuberculosis patients. The SNBP patients had a significantly higher ICR than the SNBN patients (p<0.01), and a significantly lower ICR than the smear-positive patients (p<0.001). In the SNBP patients, the ICRs were 5.0% for those aged 40 to 49 years and 1.6% for those aged 50 to 59, and the difference was statistically significant (p<0.05). All patients were grouped into two groups; younger patients with an age of less than 50 years and elder patients with an age of 50 years or higher. The ICRs showed significant differences between the younger patients and the elder patients as follows: 4.3% vs 1.7% for the SNBP patients (p<0.01), 15.5% vs 5.0% for the smear-positive patients (p<0.001), and 1.9% vs 0.9% for the SNBN patients (p<0.05). The chest X-ray showed cavitary lesion in 453 SNBP patients. The ICRs were 8.7% for 126 cavitary younger SNBP patients, 2.6% for 311 non-cavitary younger SNBP patients, 2.4% for 327 cavitary elder SNBP patients, and 1.5% for 1,030 non-cavitary elder SNBP patients. The ICR for the cavitary younger SNBP patients was significantly higher than those for the other three subgroups (p<0.01 to p<0.001). CONCLUSION: These findings suggest that TB transmission from SNBP patients depends on the patient's age and the cavity formation, and that patients aged less than 50 years with cavitary pulmonary TB is the most important target for the epidemiological research.

[Tuberculosis among nurses in Aichi Prefecture, Japan].

OBJECTIVES: To elucidate TB transmission among nurses. SUBJECTS AND METHODS: The subjects of this retrospective study were 1,283 TB women aged 20-59 years registered in Aichi Prefecture between 1989 and 2003. All registration files were reviewed to identify their occupation and working places. RESULTS: A total of 80 nurses were found among TB registers. Their age distribution was 45 (56.2%) in 20-29 years, 15 (18.8%) in 30-39 years, 14 (17.5%) in 40-49 years, and 6 (7.5%) in 50-59 years. The proportion of nurses aged 20-29 years decreased from 74.2% in 1989-93 to 24.0 % (p < 0.001) in 1999-2003, while those aged 40-49 years increased from 2.9% to 32.0% (p < 0.01). Regarding working places, 19 (23.8%) were in 4 TB hospitals, 54 (67.4%) in other 35 hospitals, 6 (7.5%) in 6 clinics, and one (1.3%) was in a home. The proportion of nurses in TB hospitals decreased from 31.4% in 1989-1993 to 4.0% (p < 0.05) in 1999-2003. Out of 73 nurses working in hospitals, 58 (79.5%) were working in hospitals with more than 250 beds with an emergency department. TB incidence were 49.1 per 100,000 population among 73 nurses working in hospital, and 14.3 among 6 nurses working in clinic, 39.5 among total 80 nurses, and 13.2 among 1203 women other than nurses. The relative risk was 3.7 for hospital nurses, 1.1 for clinic nurses, and 3.0 for whole 80 nurses. CONCLUSION: These findings suggest that TB incidence for nurses is 3-fold higher than age-matched women other than nurses, and that hospital nurses are infected with TB more frequently than clinic nurses.

[Gender difference in index and secondary patients with and without household contact].

OBJECTIVES: To investigate gender difference in index and secondary patients with or without household contact. SUBJECTS AND METHODS: The subjects of this retrospective study were 3,174 pulmonary TB patients registered in Aichi prefecture between 1989 and 2003. All recorded files were reviewed to identify epidemiologically-related TB patient clusters. In case of epidemiologically-related patients registered within less than 10 years interval, the first registered patients was defined as the index case of the cluster. The other patients in the cluster were defined as secondary cases. Therefore, all pulmonary TB patients were classified to index, secondary, or unclustered cases. An index patient with sputum smear positive was defined as the source of transmission in the cluster. The male/female ratio was calculated separately in the sources and secondary patients with or without household contact. RESULTS: A total of 100 source patients were identified. Of these, 77 were male and 23 were female, and the male/female ratio was 3.3. The secondary patients were 153, of whom 77 were male and 76 were female, and the male/female ratio was 1.0. The difference of the male/female ratio was statistically significant (p<0.001). The male/female ratio in the source patients was 2.5 for 78 clusters with household contact and 21.0 for 22 clusters without household (p<0.05), while the ratio in the secondary patients were 0.8 and 2.2 respectively (p<0.01). Of the 111 secondary patients with household contact, the relations to the source patients were wife-husband in 32, parent-child in 55, brother or sister in 12, grandparent-grandchild in 8, and the others in 4. In the 32 wife-husband transmission, most secondary patients were female (male/female = 9/23) while in other 67 transmissions with household contact, male and female secondary cases were almost same (male/female= 39/40). The male/female ratios in these two settings were significantly different (0.4 vs 1.0, p<0.05). Of the 42 secondary patients without household contact, transmission were occurred in working places in 24, schools in 11, religion circles in 4, hospital in one, and others in 2. The male/female ratio of secondary cases was 7.0 for transmission at working places, and 0.8 for transmission at the other places (p<0.01). CONCLUSION: These findings suggest that the male/female ratio of secondary patients with household contact is significantly lower than that of those without household contact.

[Influence of aging on tuberculosis infection--an epidemiological study of 1,141 smear-positive TB patients].

OBJECTIVES: To elucidate the influences of aging on the tuberculosis infection. SUBJECTS AND METHODS: The subjects of this retrospective study were 1,141 smear positive pulmonary tuberculosis (TB) patients registered in Aichi prefecture between 1989 and 2003. All registration files were reviewed to identify epidemiological links of patients. When linked patients with an interval of the dates of registration of less than 10 years were found, the earliest case was considered as the source case, and the other patients were regarded as secondary cases. An epidemic source rate (ESR) for a category of patients (e.g., age-group, etc.) was defined as following; ESR= NS/NA X 100, where NA: Number of smear-positive pulmonary TB patients in a category A, and NS: Number of source cases in category A. RESULTS: A total of 70 source cases were identifed and the ESR was 6.1%. The ESRs for different age-groups were; 14.3 % for 10-19 years of age (NA = 14), 13.5% for 20-29 years (NA = 74), 14.6% for 30-39 years (NA = 48), 15.0% for 40-49 years (NA = 107), 6.9% for 50-59 years (NA = 145), 3.5% for 60-69 years (NA = 227), 3.8% for 70-79 years (NA = 293), 2.8% for 80-89 years (NA = 212), and 0% for 90-99 years (NA = 21). The ESR were significantly different between those aged 40 to 49 years and those aged 50 to 59 (p<0.05). The ESR was significantly different between those aged 59 years and younger and those aged 60 years or older (11.6% vs 3.3%, p<0.001). The ESR was significantly different between those patients with cavitary lesion and those with noncavitary lesion in the younger groups (14.3% vs 5.2%, p<0.01), as well as in the elder age-groups (4.8% vs 1.7%, p<0.01). The rate in the younger groups was 6.3% for those with lower smear-positivity (Gaffky 1 to 4), compared with 15.3% for those with intermediate smear-positivitiy (Gaffky 5 to 8), and 32.4% for those with higher smear-positivity (Gaffky 9 and 10) (with p<0.01, p<0.05 respectively), while the rates were 3.1%, 3.9%, and 3.4%, respectively in the older groups. CONCLUSION: These findings suggest that the infectivity is significantly lower in older groups.

[The index and secondary patients in tuberculosis transmission--a retrospective epidemiological study of 3783 patients newly registered in recent 15 years in Aichi, Japan].

OBJECTIVES: To elucidate the characteristics of the index and secondary patients in clusters containing multiple TB patients who were examined epidemiologically. SUBJECTS AND METHODS: The subjects of this retrospective study were 3783 TB patients registered in Aichi between 1989 and 2003. All recorded files were reviewed to identify multiple TB patients in the same transmission group. When multiple patients with a registration interval of less than 10 years were found in the same transmission group, the first patient was considered as the index case, and the other patients were regarded as secondary cases. RESULTS: A total of 106 index patients and 132 secondary patients were found. The index patients occupied 2.8% of the total 3783 registered patients, or 0.9 per 100,000 population. Secondary patients occupied 3.5% and 1.2 per 100,000. Of the 106 clusters, 77.4% consisted of two patients, 15.1% three patients, and 7.5% four or more patients. Smear-positive patients were found in 66.0% of the index patients, 27.3% of the secondary patients, and 30.3% of the 3783 overall patients, and the differences were highly significant between the index and secondary patients, as well as between the index and overall registered patients (p < 0.001). The proportion of the index patients to all registered patients was 6.1% for smear-positive patients, 1.8% for culture-positive patients, and 1.1% for bacilli-negative patients. The differences were highly significant between smear-positive and culture-positive patients, as well as between smear-positive and bacilli-negative patients (p < 0.001). CONCLUSION: The findings of this retrospective study suggest that 2.8% of the total registered patients, 6.1% of smear-positive patients, and 0.9 per 100,000 population was the index patients.