[Life prognosis of persons with dementia: Observation of persons registered for long-term care insurance in a community in Japan].

Objectives　This study aimed to observe the life prognosis of persons with dementia during the first five years after registering for long-term care insurance, and to determine the factors affecting their prognosis.Methods　A total of 556 persons, aged 65 years or older newly registered for long-term care insurance in a city in Japan, were observed. The life prognosis of the registered persons was determined using standardized mortality ratio (SMR) with the general population as a standard, and relevant factors were observed in terms of dependence indices of dementia and disability.Results　The mean age of persons newly registered for long-term care insurance was 81.6 years and 63% of them were females. Mortality during the first 4.5 years after registration was 16.7% p.a., with males and those of older age having higher rates. The SMR was 1.80 for all individuals, with males and those of younger age having a higher SMR. The SMR increased with the severity of the disability (higher classes on the disability dependence index) at the time of the registration, while no significant trend was seen in SMR with the dementia dependence index. Multivariate analysis revealed that mortality was dependent on sex (male>female), age (older>younger), disability dependence indices (higher classes>lower classes), and current place of residence (home>facility), while there were no significant trends found in mortality with degree of severity on the dementia dependence indices. The adjusted odds ratios of dying from respective factors were as follow: from sex (male/female, with male as a standard) 0.35 (95% confidence interval 0.24-0.51), from age group (65-74 years/75-84/85+, stepwise with 65-74 years as a standard) 1.84 (1.39-2.47), from disability dependence index (normal/I/Ⅱa/Ⅱb..., stepwise with "normal" as standard) 1.38 (1.21-1.58), and from place of residence (home/facility, with home as a standard) 0.64 (0.42-0.99). When limited to only the elderly with dementia dependence indices of Ⅱa-Ⅳ, the analysis showed similar results.Conclusion　Elderly persons registered for long-term care insurance had higher mortality rates than the general population that was dependent on the disability dependence index, but not on the dementia dependent index. Further studies are therefore necessary to elucidate the factors relevant to the study's finding.

[RISK OF TUBERCULOSIS INFECTION AND DISEASE AMONG JAPANESE FEMALE NURSES AND MALE DOCTORS IN RECENT YEARS].

[Objectives and Materials] Based on the tuber- culosis (TB) surveillance database, the incidence rates of TB infection and active disease among healthcare workers were observed for female nurses and male doctors in 2010 in comparison with those of the general population. [Results] The relative risk (RR) of active TB among female nurses aged 20-69 years was 4.86 (95% confidence interval: 4.31-5.45) for 2010, which has increased from 2.30 observed in 1987-1997. The RR was highest for nurses aged 20-29 years at 8.84 and declined with age until 3.60 for those aged 50-59 years that was still significantly higher than 1. For male doctors the RR was significantly higher than 1 only for those aged 39 years or younger. The rates of those who were -indicated for treatment of latent TB infection (LTBI) were clearly higher among healthcare workers; for female nurses the RR was 32.7 (95% CI: 30.5-35.0), ranging from the highest level of 62.8 among those aged 20-29 years down to 11.6 for those aged 60-69 years. For male doctors also, the RR was high at 9.7 (7.9- 11.7) for 20-69 years, ranging from 14.5 for those aged 20- 29 years down to 5.3 for those aged 60-69 years. [Discussion] TB cases of nurses and doctors were more likely to be detected by the active case finding measures such as periodic screening and contact investigations than cases in the general population, which indicates the current effort of addressing the occupational exposure in the healthcare set- tings. The high level of risk of TB disease as Iwell as LTBI among healthcare professions and its possibly increasing trend as. seen in female nurses warrants further strengthening of monitoring of the problem and overall countermeasures in their workplaces.

Study on changes in cognitive function of elderly individuals certified for long-term care insurance.

Objectives　To elucidate the changes in cognitive function in elderly individuals as observed in the results of a long-term care certification survey.Methods　The data were obtained from the long-term care insurance of 121 subjects who applied for benefit renewal between 2010 and 2011, in a city in Japan. The subjects were grouped into one of three groups (improved, maintained, or worsened) according to the change in status of overall cognitive function. Analyses were completed with this grouping as the main dependent variable and with sex, age, degree of independence at the initial insurance application in 2006, and levels of seven categories of cognitive function as independent variables.Results　There was a statistically significant association between age and deterioration of various cognitive functions. Sex had no significant effect on the rate of deterioration. The initial degree of independence was positively associated with the cognitive function change. Multivariate analysis (logistic regression analysis) incorporating age, sex, and initial degree of dependence as independent variables revealed that sex does not significantly influence the prognosis of cognitive function. Changes in the score of each of the seven cognitive functions were analyzed with ANOVA, with categories of functions and individuals as sources of variance. Both function category and individuals were significantly associated with deterioration. Among the seven categories of functions, "understanding daily activities" had the greatest deterioration, while "calling him/herself by his/her own name" had the least.Conclusion　Cognitive function, as observed in the long-term care certification survey, is more likely to deteriorate in elderly individuals and in those who were at higher levels of dependency index at the time of initial certification, and this effect is observed equally in men and women. Our results suggest that, in providing long-term care for elderly people, it may be useful to call the clients by their names and ask them to name themselves, as well as to try to improve their understanding regarding the daily activities by articulating the components of each activity.

[NINETY YEARS OF THE JAPANESE SOCIETY FOR TUBERCULOSIS--Back to the Future for Research and Control of Tuberculosis].

The 90 years since the foundation of the Japanese Society for Tuberculosis in 1923 can be divided into three periods by three turning points, i.e., epidemiological transitions: 1911-1950 (the first period), 1953-1980 (the second period) and 1980-present (the third period). The progress of the Society is overviewed for each of these periods, and the several specific areas of research and control efforts are discussed. The first period might be viewed as a preparatory phase during which various tremendous efforts were made in basic, clinical, and epidemiological research that would bear fruit during the second period. Following this period, modern technologies were introduced into the national tuberculosis control program accompanied by related basic research, including the development and evolution of the theory of TB pathogenesis, X-ray diagnosis, and clinical trials of chemotherapy, of which the Society has been very proud. The problems of activities in the second period were carried over into the third period, together with the epidemiological challenge of the slowing of epidemiological improvement. For this period, the bibliometric technique was applied in the trial of objectively analyzing the trends of research, activities in publication. In addition, the USA's efforts to maintain awareness of TB, after the unexpected upsurge of TB during 1980s-90s due to its neglect in the past, were cited as lessons Japan should now learn.

[Considerations on uses of newly developed anti-tuberculosis drugs for multi-drug resistant tuberculosis].

We, group of tuberculosis experts, made discussions over how to improve the quality of treatment of multidrug resistant tuberculosis using a newly developed anti-tuberculosis drug, and at the same time, how to prevent the disadvantages of the treated patients and also that of persons who would be infected with newly produced drug-resistant bacilli, by preventing the emergence of resistance to the new drug. A series of proposals are made.

Challenges to the global control of tuberculosis.

Diagnosis and treatment of tuberculosis (TB) will likely navigate a historical turning point in the 2010s with a new management paradigm emerging. However, global control of TB remains a formidable challenge for the decades to come. The estimated case detection rate of TB globally was 66%, and there were 310 000 estimated multidrug-resistant TB (MDR-TB) cases among the 6.2 million TB patients notified in 2011. Although new tools are being introduced for the diagnosis of MDR-TB, there are operational and cost issues related to their use that require urgent attention, so that the poor and vulnerable can benefit. World Health Organization (WHO) estimated that globally, 3.7% of new cases and 20% of previously treated cases have MDR-TB. However, the scale-up of programmatic management of drug-resistant TB is slow, with only 60 000 MDR-TB cases notified to WHO in 2011. The overall proportion of treatment success of MDR-TB notified globally in 2009 was 48%, far below the global target of 75% success rate. Although new tools and drugs have the potential to significantly improve both case detection and treatment outcome, adequate health systems and human resources are needed for rapid uptake and proper implementation to have the impact required to eliminate TB. Hence, the global TB community should broaden its scope, seek intersectoral collaboration and advocate for cost reduction of new tools, while ensuring that the basics of TB control are implemented to reduce the TB burden through the current 'prevention through case management' paradigm.

[Impact of introducing rifampicin for the treatment of tuberculosis during the 1970's in Japan].

SETTING: The average duration of tuberculosis chemotherapy in Japan increased year by year throughout the 1960's and reached 49 months by 1973. It then began decreasing slowly in the 1970's and more rapidly after the 1980's. PURPOSE: To clarify the significant factors contributing to the prefectural variation of changes in the average duration of chemotherapy that occurred from 1973 to 1979. METHOD: Multiple regression analysis was conducted with the slopes of the average duration of chemotherapy of tuberculosis in prefectures throughout Japan from 1973 through 1979 as the dependent variable and with parameters related to treatment and patient characteristics of the prefectures as independent variables. RESULTS: The variables, including uses of rifampicin, proportion of bacteriologically confirmed patients among newly registered cases, and average duration of chemotherapy as of 1973, contributed significantly to the slope of change in chemotherapy duration of the prefectures; the duration decreased faster in prefectures where there were more bacteriologically confirmed patients, and where the duration had been shorter at the beginning of the study period. DISCUSSION: Short-course chemotherapy had not been established in the study period, but confidence in the potency of antibacterial activity of the new drug seems to have facilitated the departure from unnecessarily long treatment. The recognition of the importance of bacteriology in the clinical practice of tuberculosis worked in the same way against dependence on X-ray findings causing long-term treatment. Also, the prefectures that had been less affected by the long-term treatment could depart faster from it.

[Contact investigation using QuantiFERON-TB Gold test to evaluate TB exposure in 61 subjects in a hospital setting--(2) Change in QuantiFERON response during one year after exposure].

UNLABELLED: OBJECTIVES & SUBJECTS: The change in IGRA (interferon-gamma release assay, with QuantiFERON-TB Gold, QFT) responses was followed up for one year in a group of contacts of healthcare workers who had been exposed to tuberculosis (TB) infection for a relatively short period in a hospital. The observation was made of a total of 59 close contacts of the index case, where 16 showed positive QFT-conversion and 7 showed the intermediate response ranging 0.1 to 0.35 IU/mL. Three of the conversion cases developed active TB. RESULTS: 67% of the QFT conversions occurred within 2 months of exposure and the others between 2 to 9 months. Those having converted later than 2 months after the exposure showed generally weaker QFT responses than the earlier converters. In response to the treatment to converters (either to latent TB infection or to active TB), 80% of the cases reversed to negative or intermediate. The geometric means of the response values for ESAT-6 and CFP-10 also showed significant decline over the treatment time. DISCUSSIONS: The time profile of responses in the intermediate responders revealed an obviously distinct pattern from that of the negative responders with the values remaining uniformly at very low level throughout, which suggests that this group includes somehow exceptional responders either with or without infection.

Downregulation of katG expression is associated with isoniazid resistance in Mycobacterium tuberculosis.

Isoniazid (INH) is a key agent in the treatment of tuberculosis. In Mycobacterium tuberculosis, INH is converted to its active form by KatG, a catalase-peroxidase, and attacks InhA, which is essential for the synthesis of mycolic acids. We sequenced furA-katG and fabG1-inhA in 108 INH-resistant (INH(r) ) and 51 INH-susceptible (INH(s) ) isolates, and found three mutations in the furA-katG intergenic region (Int(g-7a) , Int(a-10c) and Int(g-12a) ) in four of 108 INH(r) isolates (4%), and the furA(c41t) mutation with an amino acid substitution in 18 INH(r) isolates (17%). These mutations were not found in any of 51 INH(s) isolates tested. We reconstructed these mutations in isogenic strains to determine whether they conferred INH resistance. We found that the Int(g-7a) , Int(a-10c) and Int(g-12a) single mutations in the furA-katG intergenic region decreased katG expression and conferred INH resistance. In contrast, the furA(c41t) mutation was not sufficient to confer INH resistance. These results suggested that downregulation of katG is a mechanism of INH resistance in M. tuberculosis and that mutations in the furA-katG intergenic region play a role in this resistance mechanism.

Comprehensive multicenter evaluation of a new line probe assay kit for identification of Mycobacterium species and detection of drug-resistant Mycobacterium tuberculosis.

We evaluated a new line probe assay (LiPA) kit to identify Mycobacterium species and to detect mutations related to drug resistance in Mycobacterium tuberculosis. A total of 554 clinical isolates of Mycobacterium tuberculosis (n = 316), Mycobacterium avium (n = 71), Mycobacterium intracellulare (n = 51), Mycobacterium kansasii (n = 54), and other Mycobacterium species (n = 62) were tested with the LiPA kit in six hospitals. The LiPA kit was also used to directly test 163 sputum specimens. The results of LiPA identification of Mycobacterium species in clinical isolates were almost identical to those of conventional methods. Compared with standard drug susceptibility testing results for the clinical isolates, LiPA showed a sensitivity and specificity of 98.9% and 97.3%, respectively, for detecting rifampin (RIF)-resistant clinical isolates; 90.6% and 100%, respectively, for isoniazid (INH) resistance; 89.7% and 96.0%, respectively, for pyrazinamide (PZA) resistance; and 93.0% and 100%, respectively, for levofloxacin (LVX) resistance. The LiPA kit could detect target species directly in sputum specimens, with a sensitivity of 85.6%. Its sensitivity and specificity for detecting RIF-, PZA-, and LVX-resistant isolates in the sputum specimens were both 100%, and those for detecting INH-resistant isolates were 75.0% and 92.9%, respectively. The kit was able to identify mycobacterial bacilli at the species level, as well as drug-resistant phenotypes, with a high sensitivity and specificity.

[Relationship between BCG immunization coverage and the immunization delivery system in the Tama area of Tokyo].

PURPOSE: The BCG immunization has long been performed in Japan. Although the BCG immunization service is the responsibility of the municipality, the manner in which the BCG immunization is delivered differs from municipality to municipality. The purpose of this study was to clarify how the different manner of the BCG immunization delivery systems influenced the BCG immunization coverage. METHODS: The study of BCG immunization coverage was conducted in the Tama area located in the western suburbs of Tokyo in 2004. The birth data and the immunization history by the age of 3 years were collected in the three-year-old health check-up from a total of 2,341 children residing in the Tama area. Based on the age at immunization for each child, the BCG immunization coverage was calculated according to the types of the BCG immunization delivery system. The immunization types were defined as follows; the BCG immunization given on the occasion of the mass health check-up (Group 1); the exclusive mass BCG immunization in a monthly service (Group 2); the exclusive mass BCG immunization in a bimonthly service (Group 3); the exclusive mass BCG immunization in services of fewer than every two months (Group 4); and the immunization given on an individual basis by a general practitioner (Group 5). A univariate analysis was performed to examine the relationship between the BCG immunization coverage by the age of 6 months and the difference among the BCG immunization delivery systems, followed by a multivariate regression analysis to adjust for the factors related to the demography, health care services and the socio-economic status of the municipalities. RESULTS: Unadjusted odds ratios and adjusted odds ratios for BCG unimmunized children under the age of 6 months by the BCG immunization delivery manner groups were OR 1 reference, adj. OR 1 reference in Group 1; OR 1.42 CI 0.87-2.29, adj. OR 4.01 CI 2.24-7.11 in Group 2; OR 4.96 CI 3.66-6.82, adj. OR 15.59 CI 10.10-24.49 in Group 3;OR 18.60 CI 13.77-25.49, adj. OR 48.17 CI 29.62-79.75 in Group 4; and OR 4.24 CI 2.86-6.31, adj. OR 15.61 CI 9.05-27.26 in Group 5. The univariate analysis and multivariate regression analysis revealed an influence of the BCG immunization delivery manner on the BCG immunization coverage. CONCLUSION: The choice of BCG immunization delivery manner is very important to raise the BCG immunization coverage. The BCG immunization given on the occasion of the mass health check-up and the high-frequent immunization service are thought to improve the BCG immunization coverage.

[Current status of multidrug-resistant tuberculosis in Japan: a literature review and meta-analysis].

A literature review and meta-analysis of the incidence, clinical characteristics, and treatment outcomes associated with multidrug-resistant (MDR) tuberculosis (TB) in Japan was performed. An estimated 110-120 new cases of MDR-TB occur every year, constituting 0.7-0.8% of all cases starting TB chemotherapy in Japan. The frequency of MDR is higher in previously treated TB patients than in primary treatment patients; it is also higher among younger patients. Treatment outcomes are poor; the cure rate as conventionally defined is 50-60%. These primary characteristics of MDR-TB in Japan are similar to those reported abroad, although it appears that the Japanese MDR strains are more resistant, such as having a high frequency of extremely drug-resistant (XDR) strains, and a higher frequency of resistance to fluoroquinolones. However, we should remember that variations among institutions and the different methodologies used in reported studies are too numerous to allow any rigorous conclusions to be drawn. This will be a major challenge to the promotion of clinical studies and the control of MDR-TB in Japan.

[Contact investigation using QuantiFERON-TB Gold test to evaluate TB exposure in 61 subjects in a hospital setting--(1) Outline of the outbreak and its clinical picture].

The index case was a patient who was admitted to a general hospital and treated with pulsed corticosteroid therapy; her breathing was assisted by a respirator. Soon she developed tuberculosis (TB) and died. Immediately after her death, QuantiFERON-TB Gold (QFT) test was conducted in healthcare workers who were in close contact with the index case. From the results of the test, all the healthworkers except 1 were TB negative. However, the QFT test repeated in the healthworkers after 8 weeks was positive in 18.6%. Subsequently, 5 healthworkers, including a doctor, nurses, and radiology technicians, developed TB. Bacterial isolates from 3 of them showed restriction fragment length polymorphism (RFLP) patterns similar to that of the index case. These 3 secondary TB cases included one healthworker who was in contact with the index case for less than 5 min, another whose QFT was negative (or "doubtful" according to the Japanese criterion of the QFT), and a third who was TB positive for QFT test but declined treatment for latent TB infection (LTBI). No other healthworkers or hospitalized patients developed TB. These healthcare workers with TB were further assessed using the QFT test at 6, 9, and 12 months after initial exposure, which showed an additional 4 positive reactors and 4 "doubtful" reactors who were indicated for LTBI treatment. Among these subjects, 7 were those who showed TB positive results 6 months after initial contact. Discussions were made on TB prevention in hospital settings including contact investigations the staff with special reference to application of the QFT test.

Computerized surveillance system of tuberculosis in Japan: its evolution, achievement and challenges.

The nationwide computerized tuberculosis (TB) surveillance system was revised in 2007. It was developed to be user-friendly and to allow the evaluation of current TB problems and control issues in Japan. All public health centers in Japan (518 as of April 2007) have system terminals connected to a central computer, and the data entered at these terminals are sent to the online central computer excluding personal identification data. All the figures and tables in this paper were created using the annual report database which are compiled from this system. The revision in 2007 added many new functions to the system, such as a function for automatically sending data upon transfer. The monitoring information for assisting case management of TB patients by the DOTS was also enhanced. The algorithm for classifying treatment outcomes automatically based on data entered regarding cancellations from registration, bacteriological results and drug usage each month was revised. The proportion of "Failed" and "Defaulted" combined was 4.6% among new sputum smear positive pulmonary TB patients newly registered in 2009, while "Died" accounted for as high as 19.3%, due largely to a high percentage of the elderly. A new system for contact examination management is provided as a subsystem. Feedback of data analyses has been strengthened by various methods. This TB surveillance system is indispensable for implementing the evidence-based TB control program in Japan. An important role of the Research Institute of Tuberculosis is to support the planning and execution of TB control with provision of useful epidemiological information from the system.

Performance of a Whole-Blood Interferon-Gamma Release Assay with Mycobacterium RD1-Specific Antigens among HIV-Infected Persons.

OBJECTIVE: To evaluate the usefulness of one of IGRAs, QuantiFERON-TB Gold (QFT-G), in human immunodeficiency virus- (HIV-) infected patients with various CD4(+) T cell counts. METHODS: The QFT-G assay was performed using QFT-G kits among 107 HIV-infected patients including 9 cases with active tuberculosis (TB). RESULTS: In HIV-infected patients with CD4(+) > 50/microL, QFT-G positive rate for active TB patients was 5/6 (sensitivity = 83%), and that for those without active disease was 1/69 (specificity = 99%). The frequency of indeterminate QFT-G test was significantly higher in those with CD4(+) less than 50/microL (P < .0001). At the same time there was a proportional relationship between CD4(+) and interferon-gamma response to mitogen (positive control) in QFT-G test (P = .0001). Conclusions. Our data suggested that QFT-G had high sensitivity and specificity in HIV-infected populations with CD4(+) greater than 50/microL. However, QFT-G did not perform well in HIV-positive patients with CD4(+) less than 50/microL.

[Comparison of conventional tuberculin skin test and QFT-2G, a new method for diagnosis of tuberculosis infection, with the use of the contact score].

BACKGROUND: QuantiFERON TB-Gold (QFT) has recently been developed as a new method for diagnosing tuberculosis (TB) infection. To evaluate the usefulness of QFT, we analyzed the relationship between QFT and the closeness of contact with a source of infection, in comparison with that of the tuberculin skin test (TST). METHODS: Male (n=322) and female (n=340) subjects (4-75 years old) who had contact with an index case received QFT and TST. The diagnostic criterion for TB infection with TST was defined as a test with an erythema diameter of > or = 30 mm. The closeness of contact with an index case was quantified in the "contact score," based on the information obtained with a questionnaire. RESULTS: There was a significant positive correlation between the contact score and QFT-positive rate, while there was no such relationship for TST positivity. The odds ratios for positive QFT rate for the subjects in the 3rd and 4th quartile groups of contact score (taking the QFT-positive rate in the lowest score quartile as unity) were 3.40 (95% confidence interval: 1.07-10.76, p<0.05) and 7.62 (95% confidence interval: 2.60-22.37, p<0.01), respectively. These odds ratios were also significantly greater than unity after adjustment for age, sex, history of BCG vaccination and history of health care-related jobs. There was a wide difference in the QFT-positive rates between the 2nd and 3rd quartiles of contact score (3.5% vs. 11.9%). The borderline value of the contact score between these two quartiles corresponded to 200, which could be a cutoff value for defining a high-risk contact. CONCLUSION: The QFT-positive rates correlated well with closeness of contact, while TST showed a poor correlation. Thus, QFT is considered more useful than TST for diagnosing tuberculosis infection.

[Clinical guidelines for tuberculosis of Japan compared with those of other countries].

The Standards of Tuberculosis Treatment of Japan issued by the government and some related announcements by the Japanese Society of Tuberculosis are compared with the Recommendations of American Thoracic Society, CDC, and Infectious Diseases Society of America, and the Treatment Guidelines of WHO. International Standards of Tuberculosis Care by Tuberculosis Coalition for Technical Assistance is also referenced as appropriate. Although they are different in many ways in minor points, they share the basic principle of using the regimen of the initial phase with four drugs followed by the maintenance with two or three drugs including rifampicin and isoniazid for new cases. They also stress the importance of support of patients for treatment completion, but the ways to realize it are delicately different among them.

Identification of katG mutations associated with high-level isoniazid resistance in Mycobacterium tuberculosis.

Isoniazid (INH) is an effective first-line antituberculosis drug. KatG, a catalase-peroxidase, converts INH to an active form in Mycobacterium tuberculosis, and katG mutations are major causes of INH resistance. In the present study, we sequenced katG of 108 INH-resistant M. tuberculosis clinical isolates. Consequently, 9 novel KatG mutants with a single-amino-acid substitution were found. All of these mutants had significantly lower INH oxidase activities than the wild type, and each mutant showed various levels of activity. Isolates having mutations with relatively low activities showed high-level INH resistance. On the basis of our results and known mutations associated with INH resistance, we developed a new hybridization-based line probe assay for rapid detection of INH-resistant M. tuberculosis isolates.

Defining the research agenda to reduce the joint burden of disease from diabetes mellitus and tuberculosis.

The steadily growing epidemic of diabetes mellitus poses a threat for global tuberculosis (TB) control. Previous studies have identified an important association between diabetes mellitus and TB. However, these studies have limitations: very few were carried out in low-income countries, with none in Africa, raising uncertainty about the strength of the diabetes mellitus-TB association in these settings, and many critical questions remain unanswered. An expert meeting was held in November 2009 to discuss where there was sufficient evidence to make firm recommendations about joint management of both diseases, to address research gaps and to develop a research agenda. Ten key research questions were identified, of which 4 were selected as high priority: (i) whether, when and how to screen for TB in patients with diabetes mellitus and vice versa; (ii) the impact of diabetes mellitus and non-diabetes mellitus hyperglycaemia on TB treatment outcomes and deaths, and the development of strategies to improve outcomes; (iii) implementation and evaluation of the tuberculosis 'DOTS' model for diabetes mellitus management; and (iv) the development and evaluation of better point-of-care diagnostic and monitoring tests, including measurements of blood glucose and glycated haemoglobin A(1c) (HbA(1c)) for patients with diabetes mellitus. Implementation of this research agenda will benefit the control of both diseases.