麻豆传媒

An outbreak of multidrug-resistant tuberculosis (TB) developed in Kansas in November 2021, and included multiple children who were born in the U.S. and became infected in the state, CDC researchers reported.

The outbreak involved 13 people across four households in Kansas City and spanned 1 year. While a majority of the seven adults identified were born outside the U.S. in a country that had experienced a multidrug-resistant TB outbreak with the same genotype in 2007-2009, most of the six children were U.S.-born, noted Elizabeth Groenweghe, MPH, of the Unified Government Public Health Department in Kansas City, and colleagues in the .

"This outbreak is ... a cautionary tale, reminding other low TB incidence jurisdictions that sustained declines in TB incidence are not assured," they wrote. "Successful TB treatment and prevention requires ongoing identification and treatment of [latent TB infection] and a swift multifaceted public health response for each person newly diagnosed with TB."

Nine additional people in the four affected households were diagnosed with latent infections, and one child in a neighboring state with an epidemiologic connection to the Kansas outbreak was also identified in July 2022.

All of the active infection isolates were resistant to rifampin, isoniazid, pyrazinamide, and ethambutol -- all first-line treatments -- but susceptible to second-line therapeutics, Groenweghe and co-authors said.

The outbreak began when an infant was hospitalized with pulmonary and meningeal TB. DNA sequencing confirmed that the infective strain was resistant to all four of the first-line drugs. An investigation by the local health department found four latent infections and four more active infections in the same household (household A), including a severely ill adult with pulmonary cavitary disease, who had exhibited symptoms since June 2021.

In January 2022, another case emerged, this time in a young child living in a different household (household B) in the same apartment building. Members of the two families socialized together extensively, shared a car, and commuted together to the same workplace.

The child was hospitalized with pulmonary TB and lymphadenitis; isolates had the same drug resistance profile as those from household A. The child's mother, who was pregnant, was soon diagnosed with pulmonary multidrug-resistant TB. Investigators found four more people in household B with active infection, including a severely ill young adult with pulmonary cavitary lesions, who had been symptomatic since September 2021.

The investigation also identified two additional households (C and D) with connections to households A and B, although located in a different neighborhood. Household C had two latent cases and two active cases, including a teen who had spent time in both households A and B; the teen was diagnosed with pulmonary multidrug-resistant TB and extrapulmonary TB vasculitis. Household D had three adults with latent infections.

Public health officials then investigated other contacts, a school, and a workplace. Potential contacts underwent an interferon-gamma release assay blood test or tuberculin skin test 8 weeks after their most recent exposure to any of those with TB.

Investigators thought the outbreak was contained within these four households until July 2022, when a child in a neighboring state was diagnosed with multidrug-resistant TB (household E).

"Additional investigation confirmed that the young adult from household B was also known to household E and had spent time in the home of household E while infectious," Groenweghe and team wrote.

Clinicians constructed individual treatment regimens for each person. Most of the adults (median age 29 years) and an older teenager in household A received 26 weeks of bedaquiline, pretomanid, linezolid, and moxifloxacin (BPaLM). The pregnant woman was treated with bedaquiline, linezolid, moxifloxacin, and clofazimine. After her baby was born and she stopped breastfeeding, she was switched to the BPaLM regimen for 6 more months.

"The infant, young child, other children, and young teenager presented a unique treatment challenge because BPaLM has not been studied in children aged <15 years," the authors noted.

Three of these children, ages 9-13, received 26 weeks of bedaquiline, linezolid, moxifloxacin, and delamanid. Delamanid is a multidrug-resistant TB medication used in Europe. The FDA granted a compassionate use authorization for these cases.

The infant and young child received bedaquiline, cycloserine, levofloxacin, and linezolid.

Length of treatment was clinically determined and differed in each case, but by September 2023, 13 of the 14 patients had completed treatment.

"One adult who received a clinical diagnosis of extrapulmonary TB disease declined treatment despite extensive measures on the part of public health and clinicians. Local public health staff members continue to maintain careful communication and relationship with this person, should they desire treatment, or should their disease progress further and pose a health risk to the community," Groenweghe and co-authors wrote.

The nine patients diagnosed with latent TB infections were all treated with 6 months of daily moxifloxacin. All completed treatment and none developed disease or complications. Local public health officials will continue to monitor all of the patients every 6 months for at least 2 years. This includes chest x-rays, review of signs and symptoms, and a physical exam.

The CDC's National TB Molecular Surveillance Center performed whole-genome sequencing on isolates from nine of those with culture-confirmed active TB. Whole-genome single nucleotide polymorphism (SNP) analysis showed that these isolates were very similar, differing only by up to three SNPs. This finding supported the investigators' hypothesis that the outbreak was locally transmitted within the social setting of these families.

The whole-genome SNP analysis also genetically tied the isolates to outbreaks that had occurred in the Federated States of Micronesia during 2007-2009 and Guam during 2009-2016. Some of the adults in the outbreak lived in those regions during those times.

"Both sentinel events of TB disease in the infant and young child included a plausible source within the household (i.e., a non-U.S.-born adult with a lengthy illness course and infectious period)," Groenweghe and team wrote. "At least one of these adults was likely infected overseas years earlier and then experienced progression to active TB disease after moving to Kansas. Unfortunately, neither of the plausible source persons received a diagnosis for many months, leading to further transmission."

"This outbreak in an urban, at-risk community resulted in tremendous financial, staffing, and capacity strain on the local public health department, where capacity was already diminished after nearly 2 years of COVID-19 pandemic response; however, recent collaborations established during COVID-19 prevention activities led to many positive working relationships with community partners such as the schools and hospitals, which facilitated efficient coordination of the outbreak response," the authors noted.

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