Ebola Patient Virus Cycle Threshold and Risk of Household Transmission of Ebola Virus.

BACKGROUND: Identifying risk factors for household transmission of Ebola virus (EBOV) is important to guide preventive measures during Ebola outbreaks. METHODS: We enrolled all confirmed persons with EBOV disease who were the first case patient in a household from December 2014 to April 2015 in Freetown, Sierra Leone, and their household contacts. Index patients and contacts were interviewed, and contacts were followed up for 21 days to identify secondary cases. Epidemiologic data were linked to EBOV real-time reverse-transcription polymerase chain reaction cycle threshold (Ct) data from initial diagnostic specimens obtained from enrolled index case patients. RESULTS: Ct data were available for 106 (71%) of 150 enrolled index patients. Of the Ct results, 85 (80%) were from blood specimens from live patients and 21 (20%) from oral swab specimens from deceased patients. The median Ct values for blood and swab specimens were 21.0 and 24.0, respectively (P = .007). In multivariable analysis, a Ct value from blood specimens in the lowest quintile was an independent predictor of both increased risk of household transmission (P = .009) and higher secondary attack rate among household contacts (P = .03), after adjustment for epidemiologic factors. CONCLUSIONS: Our findings suggest the potential to use Ct values from acute EBOV diagnostic specimens for index patients as an early predictor of high-risk households and high-risk groups of contacts to help prioritize EBOV disease investigation and control efforts.

Duration of Exposure Among Close Contacts of Patients With Infectious Tuberculosis and Risk of Latent Tuberculosis Infection.

BACKGROUND: Predictors of latent tuberculosis infection (LTBI) among close contacts of persons with infectious tuberculosis (TB) are incompletely understood, particularly the number of exposure hours. METHODS: We prospectively enrolled adult patients with culture-confirmed pulmonary TB and their close contacts at 9 health departments in the United States and Canada. Patients with TB were interviewed and close contacts were interviewed and screened for TB and LTBI during contact investigations. RESULTS: LTBI was diagnosed in 1390 (46%) of 3040 contacts, including 624 (31%) of 2027 US/Canadian-born and 766 (76%) of 1013 non-US/Canadian-born contacts. In multivariable analysis, age ≥5 years, male sex, non-US/Canadian birth, smear-positive index patient, and shared bedroom with an index patient (P < .001 for each), as well as exposure to >1 index patient (P < .05), were associated with LTBI diagnosis. LTBI prevalence increased with increasing exposure duration, with an incremental prevalence increase of 8.2% per 250 exposure hours (P < .0001). For contacts with <250 exposure hours, no difference in prevalence was observed per 50 exposure hours (P = .63). CONCLUSIONS: Hours of exposure to a patient with infectious TB is an important LTBI predictor, with a possible risk threshold of 250 hours. More exposures, closer exposure proximity, and more extensive index patient disease were additional LTBI predictors.

Risk Factors for Tuberculosis and Effect of Preventive Therapy Among Close Contacts of Persons With Infectious Tuberculosis.

BACKGROUND: Close contacts of persons with pulmonary tuberculosis (TB) have high rates of TB disease. METHODS: We prospectively enrolled TB patients and their close contacts at 9 US/Canadian sites. TB patients and contacts were interviewed to identify index patient, contact, and exposure risk factors for TB. Contacts were evaluated for latent TB infection (LTBI) and TB, and the effectiveness of LTBI treatment for preventing contact TB was examined. RESULTS: Among 4490 close contacts, multivariable risk factors for TB were age ≤5 years, US/Canadian birth, human immunodeficiency virus infection, skin test induration ≥10 mm, shared bedroom with an index patient, exposure to more than 1 index patient, and index patient weight loss (P < .05 for each). Of 1406 skin test-positive contacts, TB developed in 49 (9.8%) of 446 who did not initiate treatment, 8 (1.8%) of 443 who received partial treatment, and 1 (0.2%) of 517 who completed treatment (1951, 290, and 31 cases/100 000 person-years, respectively; P < .001). TB was diagnosed in 4.2% of US/Canadian-born compared with 2.3% of foreign-born contacts (P = .002), and TB rates for US/Canadian-born and foreign-born contacts who did not initiate treatment were 3592 and 811 per 100 000 person-years, respectively (P < .001). CONCLUSIONS: Treatment for LTBI was highly effective in preventing TB among close contacts of infectious TB patients. Several index patient, contact, and exposure characteristics associated with increased risk of contact TB were identified. These findings help inform contact investigation, LTBI treatment, and other public health prevention efforts.

Tuberculosis disease and infection among household contacts of bacteriologically confirmed and non-confirmed tuberculosis patients.

OBJECTIVE: To compare the prevalence of tuberculosis infection and disease in household contacts of patients with bacteriologically confirmed tuberculosis disease and contacts of non-bacteriologically confirmed disease in western Kenya. METHODS: We enrolled newly diagnosed index patients and their household contacts from March 2014 to June 2016. All contacts were evaluated with a symptom questionnaire, tuberculin skin test (TST) and HIV test. Clinical evaluation and sputum testing were performed for those with symptoms, positive TST result or HIV infection. RESULTS: We enrolled 1155 contacts of 330 index patients with bacteriologically confirmed tuberculosis and 192 contacts of 55 index patients with non-bacteriologically confirmed tuberculosis. 3.5% of contacts of patients with bacteriologically confirmed tuberculosis were diagnosed with tuberculosis, whereas no contacts of index patients with non-bacteriologically confirmed tuberculosis were. Of those diagnosed with tuberculosis disease, 58.5% reported symptoms, 34.1% reported no symptoms but had positive TST results, and 7.3% had neither symptoms nor positive TST but were HIV-positive. Among 872 contacts with a TST result, 50.9% of contacts of index patients with bacteriologically confirmed tuberculosis and 41.0% of contacts of index patients with non-bacteriologically confirmed tuberculosis had a positive result (prevalence ratio = 1.16, 95% confidence interval 0.92-1.48). CONCLUSION: In a high-burden setting, tuberculosis disease was more prevalent among contacts of patients with bacteriologically confirmed tuberculosis than contacts of patients with non-bacteriologically confirmed disease. TST was feasible to perform and helped to detect cases that would have been missed had only symptomatic contacts been evaluated.

OBJECTIF: Comparer la prévalence de l'infection et de la maladie tuberculeuses chez les contacts familiaux des patients atteints de tuberculose confirmée bactériologiquement et les contacts de maladies non bactériologiquement confirmées dans l'ouest du Kenya. MÉTHODES: Nous avons recruté des patients indice nouvellement diagnostiqués et leurs contacts familiaux de mars 2014 à juin 2016. Tous les contacts ont été évalués à l'aide d'un questionnaire sur les symptômes, le test cutané à la tuberculine (TCT) et le test VIH. Une évaluation clinique et des tests d'expectoration ont été effectués pour les personnes présentant des symptômes, un résultat positif au TCT ou une infection par le VIH. RÉSULTATS: Nous avons recruté 1.155 contacts de 330 patients index avec une tuberculose confirmée bactériologiquement et 192 contacts de 55 patients indice avec une tuberculose non confirmée bactériologiquement. 3,5% des contacts des patients atteints de tuberculose confirmée bactériologiquement ont été diagnostiqués avec la tuberculose, alors qu'aucun contact des patients indice avec une tuberculose non bactériologiquement confirmée ne l'a été. Parmi les personnes diagnostiquées avec une tuberculose, 58,5% ont signalé des symptômes, 34,1% n'ont signalé aucun symptôme mais avaient des résultats positifs au TCT, et 7,3% n'avaient ni symptômes ni TCT positifs mais étaient VIH positifs. Parmi 872 contacts avec un résultat TCT, 50,9% des contacts des patients indice avec une tuberculose confirmée bactériologiquement et 41,0% des contacts des patients indice avec une tuberculose non bactériologiquement confirmée avaient un résultat positif (rapport de prévalence = 1,16, intervalle de confiance à 95%: 0,92-1,48 ). CONCLUSION: Dans un contexte de charge élevée, la maladie tuberculose était plus fréquente chez les contacts des patients atteints de tuberculose confirmée bactériologiquement que chez les contacts des patients atteints de la maladie non bactériologiquement confirmée. Le TCT était réalisable et a aidé à détecter les cas qui auraient été ratés si seuls les contacts symptomatiques avaient été évalués.

Predictive value of TNF-α, IFN-γ, and IL-10 for tuberculosis among recently exposed contacts in the United States and Canada.

BACKGROUND: We examined cytokine immune response profiles among contacts to tuberculosis patients to identify immunologic and epidemiologic correlates of tuberculosis. METHODS: We prospectively enrolled 1272 contacts of culture-confirmed pulmonary tuberculosis patients at 9 United States and Canadian sites. Epidemiologic characteristics were recorded. Blood was collected and stimulated with Mycobacterium tuberculosis culture filtrate protein, and tumor necrosis factor (TNF-α), interferon gamma (IFN-γ), and interleukin 10 (IL-10) concentrations were determined using immunoassays. RESULTS: Of 1272 contacts, 41 (3.2%) were diagnosed with tuberculosis before or < 30 days after blood collection (co-prevalent tuberculosis) and 19 (1.5%) during subsequent four-year follow-up (incident tuberculosis). Compared with contacts without tuberculosis, those with co-prevalent tuberculosis had higher median baseline TNF-α and IFN-γ concentrations (in pg/mL, TNF-α 129 versus 71, P < .01; IFN-γ 231 versus 27, P < .001), and those who subsequently developed incident tuberculosis had higher median baseline TNF-α concentrations (in pg/mL, 257 vs. 71, P < .05). In multivariate analysis, contact age < 15 years, US/Canadian birth, and IFN or TNF concentrations > the median were associated with co-prevalent tuberculosis (P < .01 for each); female sex (P = .03) and smoking (P < .01) were associated with incident tuberculosis. In algorithms combining young age, positive skin test results, and elevated CFPS TNF-α, IFN-γ, and IL-10 responses, the positive predictive values for co-prevalent and incident tuberculosis were 40 and 25%, respectively. CONCLUSIONS: Cytokine concentrations and epidemiologic factors at the time of contact investigation may predict co-prevalent and incident tuberculosis.

Risk and Timing of Tuberculosis Among Close Contacts of Persons with Infectious Tuberculosis.

Background: The risk and timing of tuberculosis among recently exposed close contacts of patients with infectious tuberculosis are not well established. Methods: We prospectively enrolled patients ≥15 years of age with culture-confirmed pulmonary tuberculosis and their close contacts at 9 health departments in the United States and Canada. Close contacts were screened and cross-matched with tuberculosis registries to identify those who developed tuberculosis. Results: Tuberculosis was diagnosed in 158 of 4490 contacts (4%) of 718 index patients with tuberculosis. Of tuberculosis cases among contacts, cumulative totals of 81 (51%), 119 (75%), 128 (81%), and 145 (92%) were diagnosed by 1, 3, 6, and 12 months, respectively, after the index patients' diagnosis. Tuberculosis rates among contacts were 2644, 115, 46, 69, and 25 cases per 100000 persons, respectively, in the 5 consecutive years after the index patients' diagnosis. Of the tuberculosis cases among contacts, 121 (77%) were identified by contact investigation and 37 (23%) by tuberculosis registry cross-match. Conclusions: Close contacts to infectious patients with tuberculosis had high rates of tuberculosis, with most disease diagnosed before or within 3 months after the index patient' diagnosis. Contact investigations need to be prompt to detect tuberculosis and maximize the opportunity to identify and treat latent infection, to prevent disease.

Household Transmission of Ebola Virus: Risks and Preventive Factors, Freetown, Sierra Leone, 2015.

Background: Knowing risk factors for household transmission of Ebola virus is important to guide preventive measures during Ebola outbreaks. Methods: We enrolled all confirmed persons with Ebola who were the first case in a household, December 2014-April 2015, in Freetown, Sierra Leone, and their household contacts. Cases and contacts were interviewed, contacts followed prospectively through the 21-day incubation period, and secondary cases confirmed by laboratory testing. Results: We enrolled 150 index Ebola cases and 838 contacts; 83 (9.9%) contacts developed Ebola during 21-day follow-up. In multivariable analysis, risk factors for transmission included index case death in the household, Ebola symptoms but no reported fever, age <20 years, more days with wet symptoms; and providing care to the index case (P < .01 for each). Protective factors included avoiding the index case after illness onset and a piped household drinking water source (P < .01 for each). Conclusions: To reduce Ebola transmission, communities should rapidly identify and follow-up all household contacts; isolate those with Ebola symptoms, including those without reported fever; and consider closer monitoring of contacts who provided care to cases. Households could consider efforts to minimize risk by designating one care provider for ill persons with all others avoiding the suspected case.

Risk factors for Ebola virus disease among household care providers, Sierra Leone, 2015.

BACKGROUND: Household contacts who provide care to an Ebola virus disease (EVD) case have a 3-fold higher risk of EVD compared with contacts who do not provide care. METHODS: We enrolled persons with confirmed EVD from December 2014 to April 2015 in Freetown, Sierra Leone, and their household contacts. Index cases and contacts were interviewed, and contacts were followed for 21 days to identify secondary cases. Epidemiological data were analysed to describe household care and to identify risk factors for developing EVD. RESULTS: Of 838 contacts in 147 households, 156 (17%) self-reported providing care to the index case; 56 households had no care provider, 52 a single care provider and 39 multiple care providers. The median care provider age was 29 years, 68% were female and 32% were the index case's spouse. Care providers were more likely to report physical contact, contact with body fluids or sharing clothing, bed linens or utensils with an index case, compared with non-care providers (P <0.01). EVD risk among non-care providers was greater when the number of care providers in the household increased (odds ratio: 1.61; 95% confidence interval: 1.1, 2.4). In multivariable analysis, factors associated with care provider EVD risk included no piped water access and absence of index case fever, and protective factors included age <20 years and avoiding the index case. CONCLUSIONS: Limiting the number of care providers in a household could reduce the risk of EVD transmission to both care providers and non-care providers. Strategies to protect care providers from EVD exposure are needed.

Treatment success for patients with tuberculosis receiving care in areas severely affected by Hurricane Matthew - Haiti, 2016.

BACKGROUND: On October 4, 2016, Hurricane Matthew struck southwest Haiti as a category 4 storm. The goal of this study was to evaluate the impact of the hurricane on tuberculosis (TB) services and patient outcomes in the three severely affected departments-Sud, Grand'Anse, and Nippes-of southwest Haiti. METHODS: We developed a standard questionnaire to assess a convenience sample of health facilities in the affected areas, a patient tracking form, and a line list for tracking all patients with drug-susceptible TB registered in care six months before the hurricane. We analyzed data from the national TB electronic surveillance system to determine outcomes for all patients receiving anti-TB treatment in the affected areas. We used logistic regression analysis to determine factors associated with treatment success. RESULTS: Of the 66 health facilities in the three affected departments, we assessed 31, accounting for 536 (45.7%) of 1,174 TB patients registered in care when Hurricane Matthew made landfall in Haiti. Three (9.7%) health facilities sustained moderate to severe damage, whereas 18 (58.1%) were closed for <1 week, and five (16.1%) for ≥1 week. Four weeks after the hurricane, 398 (73.1%) of the 536 patients in the assessed facilities were located. Treatment success in the affected departments one year after the hurricane was 81.4%. Receiving care outside the municipality of residence (adjusted odds ratio [aOR]: 0.46, 95% confidence interval [CI]: 0.27-0.80) and HIV positivity (aOR: 0.31, 95% CI: 0.19-0.51) or unknown HIV status (aOR: 0.49, 95% CI: 0.33-0.74) were associated with significantly lower rates of treatment success. CONCLUSIONS: Despite major challenges, a high percentage of patients receiving anti-TB treatment before the hurricane were located and successfully treated in southwest Haiti. The lessons learned and results presented here may help inform policies and guidelines in similar settings for effective TB control after a natural disaster.

Performance of GeneXpert MTB/RIF for Diagnosing Tuberculosis Among Symptomatic Household Contacts of Index Patients in South Africa.

BACKGROUND: We describe the performance of GeneXpert MTB/RIF (Xpert) for diagnosing tuberculosis (TB) among symptomatic household contacts (HHCs) of rifampicin-resistant and drug-sensitive index cases. METHODS: We conducted a cross-sectional study among HHCs of recently diagnosed (<2 weeks) smear-positive and Xpert-positive index cases in the Bojanala District, South Africa. The HHCs were screened for TB symptoms; persons with ≥1 TB symptom provided 1 sputum for smear microscopy, Xpert, and mycobacterial growth indicator tube (MGIT) culture. Diagnostic test performance of Xpert was determined using MGIT as the reference standard. RESULTS: From August 2013 to July 2015, 619 HHCs from 216 index cases were enrolled: 60.6% were female, median age was 22 years (interquartile range, 9-40), and 126 (20.4%) self-reported/tested human immunodeficiency virus positive. A total of 54.3% (336 of 619) of contacts had ≥1 TB symptom (cough, fever, night sweats, weight loss), 297 of 336 (88.4%) of which provided a sputum; 289 (97.3%) had complete testing and 271 were included in the analysis. In total, 42 (6.8%) of 619 HHCs had microbiologically confirmed TB. The MGIT identified 33 HHCs as positive for Mycobacterium tuberculosis; of these, 7 were positive on Xpert resulting in a sensitivity of 21.2% (95% confidence interval [CI], 9.0-38.9), specificity of 98.3% (95% CI, 95.6-99.5), positive predictive value of 63.6% (95% CI, 30.8-89.1), and negative predictive value of 90.0 (95% CI, 85.7-93.4). CONCLUSIONS: Among symptomatic HHCs investigated for TB, Xpert performed suboptimally compared with MGIT culture. The poor performance of Xpert for diagnosing TB suggests that a more sensitive test, such a Xpert Ultra or culture, may be needed to improve yield of contact investigation, where feasible.

Prevalence in the United States of selected candidate gene variants: Third National Health and Nutrition Examination Survey, 1991-1994.

Population-based allele frequencies and genotype prevalence are important for measuring the contribution of genetic variation to human disease susceptibility, progression, and outcomes. Population-based prevalence estimates also provide the basis for epidemiologic studies of gene-disease associations, for estimating population attributable risk, and for informing health policy and clinical and public health practice. However, such prevalence estimates for genotypes important to public health remain undetermined for the major racial and ethnic groups in the US population. DNA was collected from 7,159 participants aged 12 years or older in Phase 2 (1991-1994) of the Third National Health and Nutrition Examination Survey (NHANES III). Certain age and minority groups were oversampled in this weighted, population-based US survey. Estimates of allele frequency and genotype prevalence for 90 variants in 50 genes chosen for their potential public health significance were calculated by age, sex, and race/ethnicity among non-Hispanic whites, non-Hispanic blacks, and Mexican Americans. These nationally representative data on allele frequency and genotype prevalence provide a valuable resource for future epidemiologic studies in public health in the United States.

Evaluation of investigations conducted to detect and prevent transmission of tuberculosis.

CONTEXT: Contact investigations are routinely conducted by health departments throughout the United States for all cases of active pulmonary tuberculosis (TB) to identify secondary cases of active TB and latent TB infection and to initiate therapy as needed in these contacts. Little is known about the actual procedures followed, or the results. OBJECTIVES: To evaluate contact investigations conducted by US health departments and the outcomes of these investigations. DESIGN, SETTING, AND SUBJECTS: Review of health department records for all contacts of 349 patients with culture-positive pulmonary TB aged 15 years or older reported from 5 study areas in the United States during 1996. MAIN OUTCOME MEASURES: Number of contacts identified, fully screened, and infected per TB patient; rates of TB infection and disease among contacts of TB patients; and type and completeness of data collected during contact investigations. RESULTS: A total of 3824 contacts were identified for 349 patients with active pulmonary TB. Of the TB patients, 45 (13%) had no contacts identified. Of the contacts, 55% completed screening, 27% had an initial but no postexposure tuberculin skin test, 12% were not screened, and 6% had a history of prior TB or prior positive tuberculin skin test. Of 2095 contacts who completed screening, 68% had negative skin test results, 24% had initial positive results with no prior test result available, 7% had documented skin test conversions, and 1% had active TB at the time of investigation. Close contacts younger than 15 years (76% screened vs 65% for older age groups; P<.001) or exposed to a TB patient with a positive smear (74% screened vs 59% for those with a negative smear; P<.001) were more likely to be fully screened. Close contacts exposed to TB patients with both a positive smear and a cavitary chest radiograph were more likely to have TB infection or disease (62% vs 33% for positive smear only vs 44% for cavitary radiograph only vs 37% for neither characteristic; P<.001). A number of factors associated with TB patient infectiousness, contact susceptibility to infection, contact risk of progression to active TB, and amount of contact exposure to the TB patient were not routinely recorded in health department records. CONCLUSIONS: Improvement is needed in the complex, multistep process of contact investigations to ensure that contacts of patients with active pulmonary TB are identified and appropriately screened.

Treatment of latent tuberculosis infection in contacts of new tuberculosis cases in the United States.

BACKGROUND: Few data are available describing treatment completion rates among recently infected contacts of tuberculosis (TB) cases, a group at high risk for development of active TB. METHODS: Health department records were reviewed for all contacts of 360 culture-positive pulmonary TB cases reported from five health departments in the United States in 1996. RESULTS: Of 2,267 contacts who completed screening, 630 (28%) had newly documented positive skin tests (121 with skin test conversion). Treatment of latent TB infection was documented to have been recommended for 447 (71%). Among these, treatment was documented to be initiated for 398 (89%). Of these, 203 (51%) were documented to have completed a 6-month course of treatment, and 78 (20%) received directly observed treatment. Treatment was recommended more often for contacts < 15 years of age, skin test converters, close contacts, and contacts of smear-positive cases. Treatment completion rates were higher for skin test converters. CONCLUSIONS: In this study, fewer than one third of all persons with newly documented positive skin tests detected during contact investigations were proven to have completed treatment. Achieving high rates of completion of therapy for latent TB infection in recently infected contacts of active cases of pulmonary TB is essential to maximize public health prevention efforts aimed at eliminating TB.