Differential rates of Mycobacterium tuberculosis transmission associate with host-pathogen sympatry.

Several human-adapted Mycobacterium tuberculosis complex (Mtbc) lineages exhibit a restricted geographical distribution globally. These lineages are hypothesized to transmit more effectively among sympatric hosts, that is, those that share the same geographical area, though this is yet to be confirmed while controlling for exposure, social networks and disease risk after exposure. Using pathogen genomic and contact tracing data from 2,279 tuberculosis cases linked to 12,749 contacts from three low-incidence cities, we show that geographically restricted Mtbc lineages were less transmissible than lineages that have a widespread global distribution. Allopatric host-pathogen exposure, in which the restricted pathogen and host are from non-overlapping areas, had a 38% decrease in the odds of infection among contacts compared with sympatric exposures. We measure tenfold lower uptake of geographically restricted lineage 6 strains compared with widespread lineage 4 strains in allopatric macrophage infections. We conclude that Mtbc strain-human long-term coexistence has resulted in differential transmissibility of Mtbc lineages and that this differs by human population.

Pfizer-BioNTech Coronavirus Disease 2019 Vaccine Effectiveness Against Severe Acute Respiratory Syndrome Coronavirus 2 Infection Among Long-term Care Facility Staff With and Without Prior Infection in New York City, January-June 2021.

BACKGROUND: Evidence is accumulating of coronavirus disease 2019 (COVID-19) vaccine effectiveness among persons with prior severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. METHODS: We evaluated the effect against incident SARS-CoV-2 infection of (1) prior infection without vaccination, (2) vaccination (2 doses of Pfizer-BioNTech COVID-19 vaccine) without prior infection, and (3) vaccination after prior infection, all compared with unvaccinated persons without prior infection. We included long-term care facility staff in New York City aged <65 years with weekly SARS-CoV-2 testing from 21 January to 5 June 2021. Test results were obtained from state-mandated laboratory reporting. Vaccination status was obtained from the Citywide Immunization Registry. Cox proportional hazards models adjusted for confounding with inverse probability of treatment weights. RESULTS: Compared with unvaccinated persons without prior infection, incident SARS-CoV-2 infection risk was lower in all groups: 54.6% (95% confidence interval, 38.0%-66.8%) lower among unvaccinated, previously infected persons; 80.0% (67.6%-87.7%) lower among fully vaccinated persons without prior infection; and 82.4% (70.8%-89.3%) lower among persons fully vaccinated after prior infection. CONCLUSIONS: Two doses of Pfizer-BioNTech COVID-19 vaccine reduced SARS-CoV-2 infection risk by ≥80% and, for those with prior infection, increased protection from prior infection alone. These findings support recommendations that all eligible persons, regardless of prior infection, be vaccinated against COVID-19.

Contact tracing reveals community transmission of COVID-19 in New York City.

Understanding SARS-CoV-2 transmission within and among communities is critical for tailoring public health policies to local context. However, analysis of community transmission is challenging due to a lack of high-resolution surveillance and testing data. Here, using contact tracing records for 644,029 cases and their contacts in New York City during the second pandemic wave, we provide a detailed characterization of the operational performance of contact tracing and reconstruct exposure and transmission networks at individual and ZIP code scales. We find considerable heterogeneity in reported close contacts and secondary infections and evidence of extensive transmission across ZIP code areas. Our analysis reveals the spatial pattern of SARS-CoV-2 spread and communities that are tightly interconnected by exposure and transmission. We find that locations with higher vaccination coverage and lower numbers of visitors to points-of-interest had reduced within- and cross-ZIP code transmission events, highlighting potential measures for curtailing SARS-CoV-2 spread in urban settings.

Towards better prediction of Mycobacterium tuberculosis lineages from MIRU-VNTR data.

The determination of lineages from strain-based molecular genotyping information is an important problem in tuberculosis. Mycobacterial interspersed repetitive unit-variable number tandem repeat (MIRU-VNTR) typing is a commonly used molecular genotyping approach that uses counts of the number of times pre-specified loci repeat in a strain. There are three main approaches for determining lineage based on MIRU-VNTR data - one based on a direct comparison to the strains in a curated database, and two others, on machine learning algorithms trained on a large collection of labeled data. All existing methods have limitations. The direct approach imposes an arbitrary threshold on how much a database strain can differ from a given one to be informative. On the other hand, the machine learning-based approaches require a substantial amount of labeled data. Notably, all three methods exhibit suboptimal classification accuracy without additional data. We explore several computational approaches to address these limitations. First, we show that eliminating the arbitrary threshold improves the performance of the direct approach. Second, we introduce RuleTB, an alternative direct method that proposes a concise set of rules for determining lineages. Lastly, we propose StackTB, a machine learning approach that requires only a fraction of the training data to outperform the accuracy of both existing machine learning methods. Our approaches demonstrate superior performance on a training dataset collected in New York City over 10 years, and the improvement in performance translates to a held-out testing set. We conclude that our methods provide opportunities for improving the determination of pathogenic lineages based on MIRU-VNTR data.

Using Reports of Latent Tuberculosis Infection Among Young Children to Identify Tuberculosis Transmission in New York City, 2006-2012.

The presence of latent tuberculosis infection (LTBI) in young children indicates recent tuberculosis (TB) transmission. We reviewed surveillance reports of children with LTBI to assess whether more follow-up is needed to prevent TB in this high-risk population. Data on all children under 5 years of age who were reported by health-care providers or laboratories to the New York City Department of Health during 2006-2012 were abstracted from the TB surveillance and case management system, and those with LTBI were identified. Potential source cases, defined as any infectious TB case diagnosed in the 2 years before a child was reported and whose residence was within 0.5 miles (0.8 km) of the child's residence, were identified. Neighborhood risk factors for TB transmission were examined. Among 3,511 reports of children under age 5 years, 1,722 (49%) had LTBI. The children were aged 2.9 years, on average, and most (64%) had been born in the United States. A potential source case was identified for 92% of the children; 27 children lived in the same building as a TB patient. Children with potential source cases were more likely to reside in neighborhoods with high TB incidence, poverty, and population density. The high proportion of children born in the United States and the young average age of the cases imply that undetected TB transmission occurred. Monitoring reports could be used to identify places where transmission occurred, and additional investigation is needed to prevent TB disease.

Epidemiology of Pediatric Multidrug-Resistant Tuberculosis in the United States, 1993-2014.

BACKGROUND: Multidrug-resistant tuberculosis (MDR-TB) is an important global public health threat, but accurate estimates of MDR-TB burden among children are lacking. METHODS: We analyzed demographic, clinical, and laboratory data for newly diagnosed pediatric (age <15 years) TB cases reported to the US National TB Surveillance System during 1993-2014. MDR-TB was defined as culture-confirmed TB disease with resistance to at least isoniazid and rifampicin. To ascertain potential underestimation of pediatric MDR-TB, we surveyed high-burden states for clinically diagnosed cases treated for MDR-TB. RESULTS: Of 20789 pediatric TB cases, 5162 (24.8%) had bacteriologically confirmed TB. Among 4826 (93.5%) with drug susceptibility testing, 82 (1.7%) had MDR-TB. Most pediatric MDR-TB cases were female (n = 51 [62%]), median age was 5 years (interquartile range, 1-12 years), one-third were Hispanic (n = 28 [34%]), and two-thirds (n = 55 [67%]) were born in the United States. Most cases had additional resistance to ≥1 other first-line drug (n = 66 [81%]) and one-third had resistance to ≥1 second-line drug (24/73 tested). Of 77 who started treatment prior to 2013, 66 (86%) completed treatment and 4 (5%) died. Among the 4 high-TB-burden states/jurisdictions surveyed, there was 42%-55% underestimation of pediatric MDR-TB cases when using only culture-confirmed case definitions. CONCLUSIONS: Only one-quarter of pediatric TB cases had culture-confirmed TB, likely resulting in underestimation of true pediatric MDR-TB burden in the United States using strictly bacteriologic criteria. Better estimates of pediatric MDR-TB burden in the United States are needed and should include clinical diagnoses based on epidemiologic criteria.

Contact Investigations Around Mycobacterium tuberculosis Patients Without Positive Respiratory Culture.

OBJECTIVE: To evaluate the yield and effectiveness of contact investigations conducted around potentially infectious tuberculosis (TB) patients with no positive respiratory culture for Mycobacterium tuberculosis in New York City (NYC). DESIGN: All TB patients without a positive respiratory culture from 2003 to 2012 were extracted from the NYC TB registry, and all patients eligible for contact investigation and their contacts were evaluated. Patients without a positive respiratory culture were defined as eligible for contact investigation if they had a respiratory nucleic acid amplification result positive for M tuberculosis, a cavitary chest radiograph, or a positive respiratory acid-fast bacilli smear. SETTING: NYC, New York. MAIN OUTCOME MEASURES: To evaluate the yield of the investigations, the number of contacts identified and the outcome of testing was quantified. Potential transmission was defined on the basis of whether active TB patients were detected among the contacts and if a contact had a TB test conversion. RESULTS: From 2003 to 2012, there were 2191 TB patients without a positive respiratory culture in NYC, 374 (17%) of which were considered eligible for contact investigation. A total of 11 096 contacts were identified around 300 (80%) eligible patients, 136 of whom had a diagnosis of TB infection; of those with TB infection who initiated preventive treatment, 66% completed treatment. Potential transmission was identified around 14 patients, with the identification of 2 additional cases of active TB and 15 contacts with TB infection test conversion. CONCLUSIONS: Conducting contact investigations around patients without a positive respiratory culture yielded evidence of possible transmission and led to the identification and treatment of new TB cases and those with TB infection. These findings suggest that these investigations should be conducted in settings where resources permit.

Increasing the efficiency and yield of a tuberculosis contact investigation through electronic data systems matching.

BACKGROUND: Electronic health data may improve the timeliness and accuracy of resource-intense contact investigations (CIs) in healthcare settings. METHODS: In September 2013, we initiated a CI around a healthcare worker (HCW) with infectious tuberculosis (TB) who worked in a maternity ward. Two sources of electronic health data were employed: hospital-based electronic medical records (EMRs), to identify patients exposed to the HCW, and an electronic immunization registry, to obtain contact information for exposed infants and their providers at two points during follow-up. RESULTS: Among 954 patients cared for in the maternity ward during the HCW's infectious period, the review of EMRs identified 285 patients (30%) who interacted with the HCW and were, thus, exposed to TB. Matching infants to the immunization registry offered new provider information for 52% and 30% of the infants in the first and second matches. Providers reported evaluation results for the majority of patients (66%). CONCLUSION: Data matching improved the efficiency and yield of this CI, thereby demonstrating the usefulness of enhancing CIs with electronic health data.

Confirming Mycobacterium tuberculosis transmission from a cadaver to an embalmer using molecular epidemiology.

Genotyping results and epidemiologic investigation were used to confirm tuberculosis transmission from a cadaver to an embalmer. This investigation highlights the utility of genotyping in identifying unsuspected epidemiologic links and unusual transmission settings. In addition, the investigation provides additional evidence for the occupational risk of tuberculosis among funeral service workers and indicates a need for education about tuberculosis risk and the importance of adhering to appropriate infection control measures among funeral service workers.

Rifapentine for the treatment of pulmonary tuberculosis.

Rifapentine is a recently approved antituberculosis drug that has not yet been widely used in clinical settings. Clinical data support intermittent use of rifapentine with isoniazid during the continuation phase of tuberculosis treatment. Patients with culture-positive, noncavitary, pulmonary tuberculosis whose sputum smear is negative for acid-fast bacilli at the end of the 2-month intensive treatment phase are eligible for rifapentine therapy. Rifapentine should not be used in human immunodeficiency virus-infected patients, given their increased risk of developing rifampin resistance with currently recommended dosages. Rifapentine is not currently recommended for children aged <12 years, pregnant or lactating women, or individuals with culture-negative or extrapulmonary tuberculosis. Rifapentine (600 mg) is administered once weekly with isoniazid (900 mg) during the continuation phase of treatment. This combination should only be given under direct observation. As with rifampin, drug-drug interactions are common, and regular patient monitoring is required. Ease of administration makes this regimen attractive both for tuberculosis-control programs and for patients.

Farm visits and undercooked hamburgers as major risk factors for sporadic Escherichia coli O157:H7 infection: data from a case-control study in 5 FoodNet sites.

In 1996, active surveillance in 5 Foodborne Diseases Active Surveillance Network (FoodNet) sites revealed up to a 9-fold difference in Escherichia coli O157:H7 (O157) infection incidence between sites. A matched case-control study of sporadic O157 cases was conducted in these sites from March 1996 through April 1997. Case subjects were patients with non-outbreak-related diarrheal illness who had O157 isolated from their stool samples. Control subjects were healthy persons matched by age and telephone number exchange. Overall, 196 case patients and 372 controls were enrolled. O157 infections were associated with farm exposure, cattle exposure, eating a pink hamburger (both at home and away from home), eating at a table-service restaurant, using immunosuppressive medication, and obtaining beef through a private slaughter arrangement. Variations in cattle exposures may explain a part of the regional variability of O157 infection incidence. O157 control measures should focus on reducing risks associated with eating undercooked hamburger, dining at table-service restaurants, and farm exposures.

Risk factors for sporadic Campylobacter infection in the United States: A case-control study in FoodNet sites.

Campylobacter is a common cause of gastroenteritis in the United States. We conducted a population-based case-control study to determine risk factors for sporadic Campylobacter infection. During a 12-month study, we enrolled 1316 patients with culture-confirmed Campylobacter infections from 7 states, collecting demographic, clinical, and exposure data using a standardized questionnaire. We interviewed 1 matched control subject for each case patient. Thirteen percent of patients had traveled abroad. In multivariate analysis of persons who had not traveled, the largest population attributable fraction (PAF) of 24% was related to consumption of chicken prepared at a restaurant. The PAF for consumption of nonpoultry meat that was prepared at a restaurant was also large (21%); smaller proportions of illness were associated with other food and nonfood exposures. Efforts to reduce contamination of poultry with Campylobacter should benefit public health. Restaurants should improve food-handling practices, ensure adequate cooking of meat and poultry, and consider purchasing poultry that has been treated to reduce Campylobacter contamination.