A systematic review of reported cost for smear and culture tests during multidrug-resistant tuberculosis treatment

Abstract

Background: In 2011, World Health Organization revised its recommendation for microbiological monitoring during treatment for multidrug-resistant tuberculosis (MDR-TB) by increasing the frequency of culture examination from quarterly to monthly after culture conversion. Implementing the recommendation requires substantial additional investment in laboratory infrastructure. The objective of this review is to provide cost evidence that is needed for national TB programs to budget for optimal monitoring strategies.

Methods and findings: WE CONDUCTED THE FIRST SYSTEMATIC LITERATURE REVIEW ON UNIT COST ESTIMATES OF THREE MONITORING STRATEGIES: 1) smear only; 2) culture only; 3) combined smear and culture. 26 peer-reviewed studies were selected by searching 10 databases in English and Chinese for literature published between 1995 and 2012. Cost estimates were converted into 2010 constant USD and international dollars. We assessed the quality of the estimates using a matrix with five essential elements and provided a cost projection for the combined smear and culture tests where the data were available. The 26 studies reported the cost estimates in 16 predominantly high- or middle-income countries from 1993 to 2009. The estimated unit cost for smear, culture, and combined tests ranges from $0.26 to $10.50, $1.63 to $62.01, and $26.73 to $39.57, respectively. The ratio of culture to smear costs varies from 1.35 to 11.98. The wide range of estimates is likely attributable to using different laboratory methods in different regions and years and differing practices in collecting and reporting cost data. Most studies did not report information critical for generalizing their conclusions.

Conclusion: The paucity and low quality of unit cost estimates for TB monitoring in resource-poor settings impose technical challenges in predicting the resources needed for strengthening microbiological monitoring. To improve the validity and comparability of the cost data, we strongly advocate the data collection, estimation, and reporting follow protocols proposed by WHO.

Figure 1. Study selection procedure for peer-reviewed literature from 1995–2012.

Figure 2. Unit cost in 2010 USD for smear test alone.

(1) Cost data were sorted by WHO regions: African Region (AFR), Region of the Americas (AMR), Eastern Mediterranean Region (EMR), European Region (EUR), South-East Asia Region (SEAR) and Western Pacific Region (WPR). (2) For studies with available information on test methods, we labeled them at the end of each bar. (3) [] indicates publication year when data collection year is not available. (4) ZN: Ziehl-Neelsen; FM: fluorescence microscopy; LED: light-emitting diode. ^a$1.16 is the average laboratory costs on 1000 subjects and three specimens. ^b$1.57 is the average laboratory costs on 1000 subjects and three specimens. ^c$1.88 is the total cost $26.27 divided by 14 sputum smears. ^dSum of the overhead cost ($10.4) and the material cost ($0.1). ^eFor the examination of three sputum specimens, the cost per patient evaluated is $3.24 for FM and $3.59 for ZN. ^fThe unit cost is the average over six regional estimates. For detailed information of the six regional estimates, see Table S2.

Figure 3. Unit cost in 2010 USD for culture test alone.

(1) Cost data were sorted by WHO regions: African Region (AFR), Region of the Americas (AMR), Eastern Mediterranean Region (EMR), European Region (EUR), South-East Asia Region (SEAR) and Western Pacific Region (WPR). (2) For studies with available details on test methods, we labeled them at the end of each bar. (3) “[]” indicates publication year when data collection year is not available. (4) LJ: Löwenstein-Jensen; MGIT: Mycobacteria Growth Indicator Tube; HLJ: Homemade Löwenstein-Jensen; CLJ: Commercially Löwenstein-Jensen; MMGIT: Manually Mycobacteria Growth Indicator Tube; AMGIT: Automated Mycobacteria Growth Indicator Tube; FIND: Foundation of innovative New Diagnostics; BD: Becton Dickinson. ^a$7.08 is the average costs between negative and positive tests. ^bThe paper indicates cost for organism identification per positive culture on MGIT was $37.55 for using standard biochemical tests, $16.18 for anti-MPB64 assay and $2.38 for cording; we added each of them to the cost per MGIT ($17.37) for calculating the cost for positive culture. ^c$9.25 is the total cost of $85.07 divided by 9.2 sputum cultures. ^dSum of the cost for sputum collection ($19.12) and the cost for bacterial culture ($19.99). ^eSum of the overhead cost ($10.4) and the material cost ($27.33). ^fThe unit cost is the average over six regional estimates. For detailed information of the six regional estimates, see Table S2.

Figure 4. Unit cost in 2010 USD for combined smear and culture test.

(1) Directly obtained cost data are in red; imputed cost data are in blue. (2) Cost data were sorted by WHO regions: African Region (AFR), Region of the Americas (AMR), Eastern Mediterranean Region (EMR), European Region (EUR), South-East Asia Region (SEAR) and Western Pacific Region (WPR). (3) For studies with available details on test methods, we labeled them at the end of each bar. (4) [] indicates publication year when data collection year is not available. (5) AFB: acid-fast bacillus; LJ: Löwenstein-Jensen; MGIT: Mycobacteria Growth Indicator Tube. ^aLaboratory running cost is $14.34. Estimated costs incurred by patients are $12.47 (assuming that for taking an examination, a patient has to miss one-day work, take two-way transportation and have one meal outside). ^b$31.55 is the total cost of $94.66 divided by three combined smear and culture tests.

Figure 5. Summary of estimates of the three types of tests.

(1) In each boxplot, dots represent outliers which are beyond the interval of (Q1–1.5*IQR, Q3+1.5*IQR): Q1 is the 25^th percentile, Q3 is the 75^th percentile, IQR is the interquartile range (75%–25%). (2) The five values listed beside each boxplot represent upper adjacent value (maximum value after excluding outliers), 75^th percentile, median (50%), 25^th percentile, and lower adjacent value (minimum value after excluding outliers), respectively. For instance, in Plot 5a, for estimates of smear test alone, $3.54 (upper adjacent value) is the maximum value excluding three outliers. $2.54 is the value at the 75^th percentile. $1.67 is the value of median. $1.21 is the value at the 25^th percentile. $0.26 (lower adjacent value) is the minimum value excluding outliers. (3) For Plot 5c, the estimates of combined test include the imputed values.