Testing Pooled Sputum with Xpert MTB/RIF for Diagnosis of Pulmonary Tuberculosis To Increase Affordability in Low-Income Countries

Abstract

Tuberculosis (TB) is a global public health problem, with the highest burden occurring in low-income countries. In these countries, the use of more sensitive diagnostics, such as Xpert MTB/RIF (Xpert), is still limited by costs. A cost-saving strategy to diagnose other diseases is to pool samples from various individuals and test them with single tests. The samples in positive pool samples are then retested individually to identify the patients with the disease. We assessed a pooled testing strategy to optimize the affordability of Xpert for the diagnosis of TB. Adults with presumptive TB attending hospitals or identified by canvassing of households in Abuja, Nigeria, were asked to provide sputum for individual and pooled (4 per T uberculosis (TB) is a significant global public health problem (1). Despite the availability of curative treatment, TB sits behind only human immunodeficiency virus (HIV) as the major cause of mortality associated with infectious disease worldwide (1). In 2013 there were an estimated 9 million new cases and 1.5 million deaths from TB, most of which occurred in low-and middle-income countries (LMICs) (1). The highest rates of TB per capita and the highest proportion of cases with HIV coinfection occur in sub-Saharan Africa (1).In most low-income countries, direct sputum smear microscopy is the mainstay of TB diagnostics (2), as this test is inexpensive and highly specific, but it has a low to moderate sensitivity (2). The sensitivity of direct sputum smear microscopy is lower in patients with paucibacillary disease associated with HIV coinfection and in children, due to lower bacillary loads (3), and it cannot provide information on drug susceptibility (4). Conversely, sputum culture, in particular, automated liquid culture, is the most sensitive and specific diagnostic tool available for TB and facilitates drug susceptibility testing (2). However, culture requires a laboratory infrastructure, including biosafety equipment, not widely available in low-resource settings, and results typically take 2 to 6 weeks and, therefore, are rarely helpful for initial treatment decisions (2, 4).The Xpert MTB/RIF (Xpert) assay (Cepheid Inc., Sunnyvale, CA, USA) is a self-contained, fully automated, real-time PCR assay that facilitates rapid semiquantitative detection of Mycobacterium tuberculosis and rifampin (RIF) resistance with minimal laboratory requirements compared to those needed for culture and other manually operated nucleic acid amplification tests (NAATs) (4). Xpert is highly specific (99%) and substantially more sensitive than smear microscopy (4). The assay's turnaround time is less than 2 h, greatly shortening the time to TB diagnosis in locations where the machine is available, and it detects markers of RIF resistance (4). For low-income countries, the single-use cartridges cost $9.98 (FIND, 2013). However, despite this concessionary pricing, the cost involved to purchase and run the tests is still a limiting factor for widespread sustainable adoption of Xpert by TB control programs i...

Can the High Sensitivity of Xpert MTB/RIF Ultra Be Harnessed to Save Cartridge Costs? Results from a Pooled Sputum Evaluation in Cambodia

“…However, the few studies which have been published on this approach show its promise. A study evaluating the pooled Xpert testing strategy in Nigeria showed that it would have identified 96% of individual specimens containing TB bacteria and could have reduced Xpert costs and usage by 30% [19]. Another evaluation in South Africa showed that Xpert identified 100% of pools containing AFB smear-positive specimens, but just 76% of pools with AFB smear-negative, culture-positive specimens [20].…”

Teste rápido molecular GeneXpert MTB/RIF para diagnóstico da tuberculose

“…Dentre outros pontos citados como desfavoráveis, podem ser observados: o custo, que impossibilita, por muitas vezes, a repetição dos testes 37,57,58,59 ; a detecção de falso-positivos e falsonegativos durante o estudo 49 ; o número de erros e resultados inválidos; as amostras com volume insuficiente (menos de 1 mL); e as amostras que apresentam vestígios de sangue pesados ou resíduos de alimentos e têm que ser examinadas por baciloscopia 46 .…”

Sample pooling methods for efficient pathogen screening: Practical implications

“…These costs can quickly become prohibitively expensive in resource-poor settings (e.g. pathogen surveillance in developing countries [1,2], in non-human systems, such as wildlife disease surveillance [3]), or when reagents become scarce due to a rapid spike in testing demand (e.g. during the SARS-CoV-2 pandemic [4]).…”