Combinations of non-invasive techniques could be the answer

Researchers found that minimally invasive nasopharyngeal aspirate (NPA) sampling — either in duplicate or in combination with stool or urine sampling — was as effective as gastric aspirate and induced sputum sampling in diagnosing tuberculosis in kids younger than five years and could potentially improve tuberculosis diagnosis in resource-limited settings.

Tuberculosis is a leading cause of infectious death across the globe, and it poses a particular risk for children, with the World Health Organization estimating that 230,000 children under the age of 15 died of the tuberculosis in 2020, Rinn Song, MD, MD(Res), MPH, MSc, of the Division of Infectious Diseases at Boston Children’s Hospital in Boston, and colleagues explained in JAMA Pediatrics. That risk is even greater for younger children, with mortality rates 9 times higher for children under the age of 5 than for those aged 5-15 years.

Furthermore, while aspiration of gastric fluid (GA) and suctioning following sputum induction (IS) are the current standard for tuberculosis diagnosis in children, both approaches are invasive and, in the case of GA, will usually require hospitalization. “Therefore, few children (estimated 30% to 40%) with tuberculosis have disease confirmed by mycobacterial culture even in ideal settings,” the authors wrote. In this study, they set out to evaluate the sensitivity of a combination of minimally invasive techniques compared with the more invasive GA and IS techniques.

In an editorial accompanying the study, Jeffrey R. Starke, MD, and Andrea T. Cruz, MD, both of the Department of Pediatrics, Baylor College of Medicine, Houston, Texas, wrote that improving diagnostic accuracy is “the holy grail of care for tuberculosis in young children,” and that the ability to detect Mycobacterium tuberculosis in children using minimally invasive techniques would be an important step forward in improving diagnosis, particularly in resource-limited settings.

“Currently, in many low-resource areas with a high burden of tuberculosis, few attempts are being made to microbiologically confirm the disease,” Starke and Cruz pointed out. “It is important that these noninvasive tests be used more widely as they may not only confirm the diagnosis, but also may provide the only clue to the presence of drug-resistant tuberculosis in children.”

In this prospective cross-sectional diagnostic study, Song and colleagues enrolled a consecutive series of 300 children under 5 years of age (median 2.0 years) from inpatient and outpatient settings in Kisumu County, Kenya, between October 2013 and August 2015. These children had symptoms of tuberculosis — unexplained cough, fever, malnutrition — and parenchymal abnormality on chest radiography or had cervical lymphadenopathy.

The reference standard was a panel of up to two samples of each of six specimen types (GA, IS, NPA, gastric string tests, urine samples, and stool samples) collected and tested for Mycobacterium tuberculosis complex with the Xpert nucleic amplification tests and mycobacterial growth indicator tube culture.

Of the children enrolled in the study, 31 had confirmed tuberculosis. 24 of whom had positive results on up to two GA samples (sensitivity 77%) and 20 had positive test results on up to two IS samples (sensitivity 64%).

The diagnostic yields of the minimally invasive specimen and assay combinations were as follows:

  • Two nasopharyngeal aspirate (NPA) samples had a sensitivity of 74%.
  • One NPA sample and one stool sample had a sensitivity of 71%.
  • One NPA sample and one urine sample had a sensitivity of 69%.

“We found that testing two NPA samples or a single NPA sample plus a stool sample had similar bacteriologic yield to testing two GA or two IS samples,” wrote the authors. “These combinations are a novel, less-invasive diagnostic approach for children in standard care settings.”

They also found that combining up to two each of GA and NPA samples had an average yield of 90%. “Combining GA and NPA had greater yield than that of the current reference standards and may be useful in certain clinical and research settings,” the authors noted.

Song and colleagues acknowledged that the children enrolled in this study “may not be representative of the wide spectrum of tuberculosis presentation in children, particularly for those with early disease without pulmonary involvement,” a potential study limitation. Other study limitations included the small number of children with confirmed tuberculosis, conducting the study at a single site, and an inability to assess additional diagnostic combinations (e.g., up to three of some sample types) in this analysis.

  1. Combining nasopharyngeal aspirate (NPA) sampling with stool or urine sampling was as effective at diagnosing tuberculosis in kids 5 years and younger as other, more invasive techniques.

  2. These results suggest that duplicate NPA sampling or NPA plus stool or urine samples may improve tuberculosis diagnosis in resource-limited settings where gastric aspirate (GA) and induced sputum (IS) sampling is more difficult.

Michael Bassett, Contributing Writer, BreakingMED™

Coauthor Okumu reported nonfinancial support from the U.S. CDC and Kenya Medical Research Institute.

Editorialist Starke reported a relationship with Otsuka Pharmaceuticals outside the submitted work.

Cat ID: 125

Topic ID: 79,125,730,125,190,310,138,192,151,195,311,925