The authors have declared that no competing interests exist.
Conceived and designed the experiments: CL CDM. Senior authors: CL CDM. Analyzed the data: CL QL. Wrote the paper: QL CL AS CF DF CDM.
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.
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.
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.
Management of multidrug-resistant tuberculosis (MDR-TB) requires extensive monitoring of patients using bacteriologic testing. This is necessary to evaluate interim response to treatment; determine if patient isolation, regimen change, or adjunct therapy is required; and to classify patient treatment outcomes. In order to optimize the ability to detect non-response to treatment, recent changes to World Health Organization (WHO) Guidelines for the Programmatic Management of Drug-Resistant TB increased the frequency of sputum culture monitoring from quarterly to monthly after sputum culture conversion
One important consideration of implementing the recommendation is the increased cost required to assure monthly culture, in addition to smear. This will require substantial additional investment in laboratory infrastructure since current capacity of conventional laboratory is insufficient in many low-resource settings. In 2010, eight of the 22 high-burden countries (HBCs) that account for 80% of global TB cases did not meet the target of one microscopy center per 100,000 people. Among the 36 countries with the highest burden of TB and MDR-TB in the world, 20 had less than the recommended capacity of one laboratory to perform culture examination per 5 million people
The purpose of this study is to provide cost estimates for the different MDR-TB monitoring strategies recommended by WHO. We conducted a systematic literature review of the published cost estimates for three strategies to monitor bacteriologic response of patients on MDR-TB treatment: 1) smear only; 2) culture only; 3) combined smear and culture. Our objectives are to (1) provide a comprehensive list of published cost estimates for the three testing strategies, (2) assess the quality and limitation of the published cost estimates, (3) project the cost of combined testing when data are available, and (4) compare costs across monitoring schedules and methods when data are available.
We searched the literature published in peer-reviewed journals from 1995 to 2012 in both English and Chinese through 10 databases: Pubmed, Embase, Web of Knowledge, Health Economic Evaluation and Database (HEED), Econlit, National Health Service Economic Evaluation Database (NHSEED), Cost-Effectiveness Analysis Registry (CEA), Research Papers in Economics (RePEc), European Network of Health Economic Evaluation Database (EURONHEED), China National Knowledge Infrastructure (CNKI), Google Scholar and WHO. We also searched grey literature from System for Information on Grey Literature in Europe (OpenSIGLE), Healthcare Management Information Consortium (HMIC) database, National Technical Information Service (NTIS), and Biological Abstracts (BIOSIS).
We refined the search strategy in consultation with experts from Harvard Countway Library of Medicine and used a combination of three parts of keywords (e.g. “costs/economics/expenditure/price”, “Tuberculosis,” and “smear/culture/diagnosis/laboratory”) when searching through databases. The detailed key words used in the search can be found in
We constructed a matrix to assess the quality of collected cost estimates. In order for the cost estimates to be useful and comparable, we sought at least the following information from each study: (1) the year of cost data being collected; (2) the level of estimates (national or regional), (3) the specific diagnostic methods and materials used; (4) the sources of data; and (5) the components included in cost estimation. We treated each category as binary and assigned values “0” or “1”. For instance, if a study reported the year of data being collected, “Data collection year” takes value of 1, 0 otherwise. In tables and figures, we used publication year as a proxy if the studies did not report information data collection year. If the estimate is national, “National estimate” takes value 1, 0 otherwise. If test methods (such as light-emitting diode [LED], Ziehl-Neelsen [ZN], etc) were reported in the paper, “Specification of test methods” takes value of 1, 0 otherwise. If cost data were directly collected from health facilities, “direct data sources” takes value of 1. If cost data were obtained from published price list, “direct data sources” takes value of 0. If the cost components included in estimating the unit cost of tests was reported by the paper, “specification of cost items” takes value of 1, 0 otherwise. We then summed the scores across the five categories for each estimate with 0 representing the weakest quality and 5 the best. When information was available, we also listed cost components in
Country | Author (publication year) | Testing type |
Data collection year | Level of estimates | Data sources | Included items in cost estimation |
|
||||||
Canada | Menzies. et al. (2006) |
S; C: solid & liquid media, liquid media only; SC: smear & liquid media only | 2005–2006 | National | Interim Federal Health Fee Schedule | Labor, equipment, supplies, and overhead |
Estonia | Floyd et al. (2012) |
S; C | 2001–2002 | National | Sources of data included expenditure records, interviews with staff and patients, project records and databases, clinical records, the social insurance system | Not specified |
Finland | Rajalahti et al. (2004) |
SC | 2000 | Local(Pirkanmaa and Varsinais-Suomi) | Pirkanmaa Hospital District | Not specified |
Italy | Migliori et al. (1999) |
S; C | 1995 | National | Nationwide, 41 TB-reporting units self-selected into participating in the study | Buildings, diagnostic facilities, salaries, overhead, and direct examination costs |
UK | Dinnes et al. (2007) |
C: standard culture, rapid culture, culture and first-line sensitivity on solid media | Not available | National | Price list from the Public Health Laboratory Mycobacterium Reference Unit | Not specified |
USA | Heymann et al. (1997) |
C: combined radiometric broth and solid medium; SC: smear and conventional/radiometric culture | Not available | National | National Jewish Center for Immunology and Respiratory Medicine in Denver and Massachusetts state public health laboratory | Not specified |
Wurtz et al. (1998) |
SC | 1993 | Local(Chicago) | A public hospital ‘s 1993 Medicare Schedule C charges and a state university hospital located in close proximity to the study hospital | Not specified | |
GA for TB Drug Development (2001) |
C | 2000 | National | Medical Resource Based Relative Value Scale Reimbursement Schedule | Not specified | |
|
||||||
Brazil | Dowdy et al. (2008) |
C: LJ, MGIT | 2006–2008 | Local(Rio de Janeiro) | 29 municipal health clinics and hospitals randomly selected | Culture tubes and media, decontamination reagents, cryovials for pellet storage, lab supplies and equipment and personnel; fixed costs: transportation, and automated MGIT 960 reader |
Scherer et al. (2009) |
S: ZN; C: LJ; SC: ZN+LJ | 2003–2004 | Local(Porto Alegre City) | Public Reference Laboratory, Centro de Desenvolvimento Científico e Tecnológico and Fundação Estadual de Produção e Pesquisa em Saúde | Laboratory running costs and patient costs (including costs for travel, food and income loss) | |
China | Chen et al. (2011) |
S; C | Not available | National | Cited from the websites on health expenditure | Not specified |
Thailand | Kamolratanakul et al. (2002) |
S; C | 1996–1997 | National | Four referral centers were randomly selected from four geographical regions (Eastern, Southern, Northern and Northeastern) | Overhead costs and materials costs |
Sohn et al. (2008) |
S: ZN, FM | 2007–2008 | National | National Tuberculosis Reference Laboratory | Capital assets(e.g., building space, equipment, staff), laboratory consumables and chemicals, and recurrent costs | |
Peru | Suárez et al. (2002) |
S: ZN; C: LJ | 1997–1999 | National | MDR-TB unit in Lima | Not specified |
Russia | Floyd et al. (2012) |
S; C | 2001–2002 | Local(Tomsk Oblast) | Sources of data included expenditure records, interviews with staff and patients, project records and databases, clinical records | Not specified |
WHO Policy Brief (2005) |
S; C | 2003 | Local(Vladimir Oblast) | Clinical diagnostic laboratory of general health care; level II clinical diagnostic laboratory within primary health care services | Not specified | |
Balabanova et al. (2009) |
C: MGIT, LJ | 2006–2008 | Local(Samara Oblast) | Central TB laboratory of Samara Region | Decontamination(including specimen transportation costs), prep LJ, overhead, building, equipment, staff, medical supplies | |
South Africa | Sinanovic et al. (2003) |
S; C | 1998–1999 | Local(Guguletu and Nyanga) | Cape Town City Council, the South African Institute for Medical Research, the TB Care Association, local equipment suppliers, car dealers, staff interviews and patient survey. | Not specified |
Albert (2004) |
S: ZN; C: BACTEC 460TB | 2003 | Local(Cape Town) | National Health Laboratory Service(NHLS), Cape Town | Not specified | |
Hausler et al. (2006) |
S; C | Not available | Local(Cape Town) | Three public primary health care facilities | Not specified | |
Chihota et al. (2010) |
C: LJ, MGIT, MGIT+LJ | 2006–2007 | Local(Johannesburg) | National Health Laboratory Services regional TB laboratory in Johannesburg | Capital costs (buildings, furniture, medical equipment, non-medical equipment), recurrent costs (staff costs, medical supplies, non-medical supplies, overhead) | |
Whitelaw et al. (2011) |
S: LED, ZN | 2009 | Local(Cape Town) | Two primary care clinics in Cape Town and NHLS | Direct examination costs, capital costs (laboratory space and equipment), overhead costs (staff costs and time, and space and infrastructure utilized to each test) | |
Vassall et al. (2011) |
S: LED; C: MGIT | Not available | National | Urban or periurban primary care health centers in South Africa | Building, overhead, staff, equipment and consumables, quality control and maintenance, and calibration inputs | |
|
||||||
India | Muniyandi et al. (2006) |
S | 2002 | Local(Tamil Nadu) | All the government health facilities, including subcenters situated in a TB unit of a rural district of Tamil Nadu | Staff salary, costs incurred for reagents, drugs, maintenance, stationery and fuel etc. |
Vassall et al. (2011) |
S: LED; C: LJ | Not available | National | Urban or periurban primary care health centers in India | Building, overhead, staff, equipment and consumables, quality control and maintenance, and calibration inputs | |
Zambia | Mueller et al. (2008) |
C: HLJ, CLJ, MMGIT, AMGIT | 2006 | National | Zambia National TB Reference Laboratory | Overhead costs, running costs(rent of the building, utilities, vehicle running, staff management), culture-specific costs(equipment, consumables, staff costs) |
Low income countries | ||||||
Kenya | Kivihya-Ndugga et al. (2003) |
S: FM, ZN | 2000–2001 | Local(Nairobi) | Nairobi City Council Chest Clinic | Labour costs, investment costs and running costs |
Uganda | Okello et al. (2003) |
S | 1995–1999 | Local(Kiboga) | Kiboga district hospital and two Masindi district hospitals | Not specified |
Vassall et al. (2011) |
S: LED; C: LJ, MGIT | Not available | National | A central hospital in Uganda | Building, overhead, staff, equipment and consumables, quality control and maintenance, and calibration inputs |
S: smear test alone, C: culture test alone, SC: combined smear and culture test; ZN: Ziehl-Neelsen, FM: fluorescence microscopy, LED:
For studies with detailed information on diagnostic tests, we listed their specific type; otherwise, it’s not available.
When smear and culture costs were reported separately in the same study and the cost for combined tests was not available, we imputed the unit cost of the combined tests by adding the unit costs of the two testing strategies. The imputed value may serve as an upper bound estimate for the combined test. Total costs for combined tests may be lower than the imputed value due to a single set of procedures being performed for both tests (e.g., for sputum collection, transport, and processing). All cost estimates were converted into 2010 constant USD using an exchange rate and GDP deflator from International Monetary Fund
When papers provided unit cost estimates for both the culture and smear tests, we calculated the cost ratio of culture to smear. For studies with the values of the cost components, we first classified the components into two categories, traded and non-traded goods, based on the definition from the WHO guideline for cost-effectiveness analysis. Traded goods (e.g. equipment, supplies and pharmaceuticals) are available on the international market and available to all countries at an international market price. Personnel, utilities, buildings and domestic transport are treated as non-traded goods
26 studies published between 1995 and 2012 reported cost estimates in 16 countries (
The quality of reported data varied considerably among 26 studies. Five of them did not report which year the cost data were collected, 12 of them reported national estimates, 14 of them specified the methods used for test, 20 of them obtained data directly from health facilities, and 13 of them provided the cost components that were used to estimate of unit costs (
Author | 1) Data collection year | 2) National estimate | 3) Specification of test type | 4) Direct data source | 5) Specification of cost items | Sum |
Mueller et al. |
1 | 1 | 1 | 1 | 1 | 5 |
Sohn et al. |
1 | 1 | 1 | 1 | 1 | 5 |
Dowdy et al. |
1 | 0 | 1 | 1 | 1 | 4 |
Kamolratanakul et al. |
1 | 1 | 0 | 1 | 1 | 4 |
Balabanova et al. |
1 | 0 | 1 | 1 | 1 | 4 |
Menzies. et al. |
1 | 1 | 1 | 0 | 1 | 4 |
Suárez et al. |
1 | 1 | 1 | 1 | 0 | 4 |
Vassall et al. (South Africa) |
0 | 1 | 1 | 1 | 1 | 4 |
Vassall et al. (India) |
0 | 1 | 1 | 1 | 1 | 4 |
Vassall et al. (Uganda) |
0 | 1 | 1 | 1 | 1 | 4 |
Whitelaw et al. |
1 | 0 | 1 | 1 | 1 | 4 |
Scherer et al. |
1 | 0 | 1 | 1 | 1 | 4 |
Chihota et al. |
1 | 0 | 1 | 1 | 1 | 4 |
Kivihya-Ndugga et al. |
1 | 0 | 1 | 1 | 1 | 4 |
Migliori et al. |
1 | 1 | 0 | 1 | 1 | 4 |
Albert |
1 | 0 | 1 | 1 | 0 | 3 |
Heymann et al. |
0 | 1 | 1 | 1 | 0 | 3 |
Muniyandi et al. |
1 | 0 | 0 | 1 | 1 | 3 |
Dinnes et al. |
0 | 1 | 1 | 0 | 0 | 2 |
WHO Policy Brief |
1 | 0 | 0 | 1 | 0 | 2 |
GA for TB Drug Development |
1 | 1 | 0 | 0 | 0 | 2 |
Rajalahti et al. |
1 | 0 | 0 | 1 | 0 | 2 |
Wurtz et al. |
1 | 0 | 0 | 1 | 0 | 2 |
Okello et al. |
1 | 0 | 0 | 1 | 0 | 2 |
Floyd et al. (Estonia) |
1 | 1 | 0 | 0 | 0 | 2 |
Hausler et al. |
0 | 0 | 0 | 1 | 0 | 1 |
Chen et al. |
0 | 1 | 0 | 0 | 0 | 1 |
Sinanovic et al. |
1 | 0 | 0 | 0 | 0 | 1 |
Floyd et al. (Tomsk Oblast) |
1 | 0 | 0 | 0 | 0 | 1 |
Estimated costs of smear microscopy, presented in
(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
The estimated unit cost for mycobacterial culture is between $1.63 in Vladimir Oblast, Russia (2003)
(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
Limited data were available for the cost of combined testing. Results have only been reported in four countries and the values ranged from $26.73 in Canada (2005–2006)
(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.
The distribution of cost estimates for sputum smear is right-skewed, with a median of $1.67 (
(1) In each boxplot, dots represent outliers which are beyond the interval of (Q1–1.5*IQR, Q3+1.5*IQR): Q1 is the 25th percentile, Q3 is the 75th 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), 75th percentile, median (50%), 25th 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 75th percentile. $1.67 is the value of median. $1.21 is the value at the 25th 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.
12 studies reported cost estimates for both smear and culture tests performed separately. The ratio of estimated costs for culture to smear varies from 1.35 to 11.98 (
Author | Site | Time period | Ratio of culture to smear | Methods on smear/culture |
Scherer et al. |
Brazil | 2003–2004 | 1.35 | ZN (S) |
Sinanovic et al. |
South Africa | 1998–1999 | 2 |
Not available |
Migliori et al. |
Italy | 1995 | 2.02 | Not available |
Menzies et al. |
Canada | 2005–2006 | 2.22 | Liquid media (C) |
Albert |
South Africa | 2003 | 2.3 | ZN (S); BACTEC 460TB (C), (−) |
Hausler et al. |
South Africa | [2005] | 2.32 | Not available |
WHO Policy Brief |
Russia | 2003 | 2.58 | Not available |
Floyd |
Estonia | 2001–2002 | 2.75 | Not available |
Kamolratanakul et al. |
Thailand | 1996–1997 | 3.6 |
Not available |
Menzies et al. |
Canada | 2005–2006 | 3.89 | Solid+liquid media (C) |
Albert |
South Africa | 2003 | 4.38 |
ZN (S); BACTEC 460TB (C), (+) |
Suárez et al. |
Peru | 1997–1999 | 4.93 | ZN (S); LJ (C) |
Floyd |
Tomsk Oblast | 2001–2002 | 5.2 | Not available |
Chen et al. |
China | [2011] | 5.61 | Not available |
Vassall et al. |
Uganda | [2011] | 9.47 | LED (S); LJ (C) |
Vassall et al. |
India | [2011] | 9.67 | LED (S); LJ (C) |
Vassall et al. |
Uganda | [2011] | 11.61 | LED (S); MGIT (C) |
Vassall et al. |
South Africa | [2011] | 11.98 | LED (S); MGIT (C) |
S: smear test alone; C: culture test alone; ZN: Ziehl-Neelsen; (+): positive result; (−): negative result; TB: tuberculosis; LJ: Löwenstein-Jensen; LED: light-emitting diode; MGIT: Mycobacteria Growth Indicator Tube.
The original unit cost for culture is the average cost between negative and positive tests;
The original unit cost for culture includes the cost for sensitivity testing;
The original unit cost for positive culture includes the cost for MDR-TB identification.
Eight studies broke down estimated costs by traded inputs (i.e. supplies and equipment) and non-traded inputs (such as labor). A large variation is observed in the percentage of costs attributed to traded inputs (
Author | Site (year of study) | Test type | Tradable cost components | Non-tradable cost components | Tradable cost (%) | I$2010 |
Smear | ||||||
Kamolratanakul et al. |
Thailand (1996–1997) | Not available | Material costs: 2.04 baht | Overhead cost: 212.19 baht | 0.95% | 19.24 |
Sohn et al. |
Thailand (2007–2008) | ZN | Equipment: $0.08; reagents and chemicals: $0.04; consumables: $0.22 | Overhead: $1.06; building space: $0.01; staff: $0.69 | 16.19% | 2.06 |
FM | Equipment: $0.08; reagents and chemicals: $0.25; consumables: $0.40 | Overhead: $0.15; building space: $0.01; staff: $0.14 | 70.87% | 1.34 | ||
Whitelaw et al. |
South Africa (2009) | ZN | Equipment: $0.02; reagents and chemicals: $0.33; consumables: $0.40 | Overhead: $0.21; building space: $0.01; staff: $0.19 | 64.66% | 2.44 |
LED | Equipment: $0.08; reagents and chemicals: $0.04; consumables: $0.22 | Overhead: $0.81; building space: $0.01; staff: $0.47 | 20.86% | 2.21 | ||
Culture | ||||||
Kamolratanakul et al. |
Thailand (1996–1997) | Culture and sensitivity testing | Material cost: 557.90baht | Overhead cost: 212.19baht | 72.45% | 23.68 |
Muller et al. |
Zambia (2006) | HLJ | Consumables: $5.52; equipment: $4.6; consumables, equipment and furniture(included in the overheads ): $2.04 | Staff: $1.44; overheads(excluding consumables, equipment and furniture): $15.68 | 41.53% | 35.51 |
CLJ | Consumables: $4.62; equipment: $4.12; consumables, equipment and furniture(included in the overheads ): $2.05 | Staff: $1.31; overheads(excluding consumables, equipment and furniture): $15.69 | 38.83% | 34.49 | ||
MMGIT | Consumables: $7.14; equipment: $4.05; consumables, equipment and furniture(included in the overheads ): $2.19 | Staff: $1.73; overheads(excluding consumables, equipment and furniture): $16.35 | 42.53% | 37.88 | ||
AMGIT | Consumables: $7.13; equipment: $5.48; consumables, equipment and furniture(included in the overheads ): $2.18 | Staff: $1.24; overheads(excluding consumables, equipment and furniture): $16.24 | 45.83% | 38.84 | ||
Chihota et al. |
South Africa (2006–2007) | MGIT | Furniture: $0.35; medical equipment: $2.03; non-medical equipment: $0.09; medical supplies: $5.02; non-medical supplies: $0.21 | Buildings: $0.52; staff costs, culture: $6.53; staff costs, non culture: $1.73; overheads: $0.15 | 46.3% | 21.48 |
LJ | Furniture: $0.45; medical equipment: $0.45; non-medical equipment: $0.09; medical supplies: $2.29; non-medical supplies: $0.22 | Buildings: $0.52; staff costs, culture: $6.44; staff costs, non culture: $1.82; overheads: $0.08 | 28.32% | 16.98 | ||
MGIT+LJ | Furniture: $0.45; medical equipment: $2.05; non-medical equipment: $0.09; medical supplies: $6.28; non-medical supplies: $0.23 | Buildings: $0.52; staff costs, culture: $7.60; staff costs, non culture: $1.93; overheads: $0.15 | 47.15% | 24.86 | ||
Dowdy et al. |
Brazil (2006–2008) | Solid Media (8 patients per week per negative culture) | Culture tubes and media: $0.59; decontamination reagents: $0.83; lab supplies (e.g., pipette tips, centrifuge tubes): $0.53; lab supplies (e.g., mini-pipettes, vortex machine): $1.17; lab equipment (e.g., incubator, freezer): $0.59 | Transportation: $9.61; laboratory personnel: $4.21 | 21.16% | 19.08 |
Solid Media (8 patients per week per positive culture) | Culture tubes and media: $0.59; decontamination reagents: $0.83; lab supplies (e.g., pipette tips, centrifuge tubes): $0.53; lab supplies (e.g., mini-pipettes, vortex machine): $1.17; lab equipment (e.g., incubator, freezer): $0.59; Confirmation/speciation: $7.90 | Transportation: $9.61; laboratory personnel: $ $4.21 | 45.65% | 27.95 | ||
MGIT (8 patient per week per negative culture) | Culture tubes and media: $3.00; decontamination reagents: $0.83; cryovials for pellet storage: $0.81; lab supplies (e.g., pipette tips, centrifuge tubes): $0.53; automated MGIT 960 reader: $4.62; lab supplies (e.g., mini-pipettes, vortex machine): $1.00; lab equipment (e.g., incubator, freezer): $0.39 | Transportation: $8.57; laboratory personnel: $3.75 | 47.57% | 25.82 | ||
MGIT (8 patient per week per positive culture) | Culture tubes and media: $3.00; decontamination reagents: $0.83; cryovials for pellet storage: $0.81; lab supplies (e.g., pipette tips, centrifuge tubes): $0.53; automated MGIT 960 reader: $4.62; lab supplies (e.g., mini-pipettes, vortex machine): $1.00; lab equipment (e.g., incubator, freezer): $0.39; confirmation/speciation: $9.18 | Transportation: $8.57; laboratory personnel: $3.75 | 62.3% | 35.69 | ||
Balabanova et al. |
Russia (2006–2008) | MGIT FIND-BD | Decontamination: $2.76; equipment: $1.45; medical supplies: $4.58 | Overhead: $1.94; building: 0.42; staff: $0.51 | 75.39% | 15.32 |
LJ | Decontamination: $2.76; prep LJ: $0.10; equipment: $0.24; medical supplies: $0.05 | Overhead: $4.95; building: $1.07; staff: $1.34 | 29.97% | 18.41 | ||
Combined smear and culture | ||||||
Menzies et al. |
Canada (2005–2006) | AFB smear & culture on liquid media only | Supplies: C$10.07 | Labour costs: C$21.83 | 31.57% | 23.88 |
Notes: For studies with detailed information of cost for the included test components, we separated them into two parts: tradable costs and non-tradable costs. All the costs are the original data from selected studies without any conversion and standardization. If the detailed information for overheads is not available, we treated the overheads as non-tradable cost item.
The existing unit cost estimates for smear, culture, and combined smear and culture tests are very limited, especially in low or lower-middle income countries. Nevertheless, a wide range of published unit cost estimates was observed. For smear alone, the estimated unit cost is between $0.26 and $10.5. For culture alone, the estimated unit cost is between $1.63 and $62.01. For combined smear and culture testing, the estimated unit cost is between $2.27 and $48.23. Adjustment for purchasing power parity does not fully explain the wide range of unit cost estimates we observed.
The wide variability of unit costs is partly due to using different materials and methods in testing, or conducting the study in different years or regions, partly due to non-standardized practice in unit cost defining, data collecting, and reporting. For example, for those with cost components available, the reported components vary greatly across studies, from only including material and overhead cost to covering the costs of building, equipment, and even the spending of patients. Cost data were obtained from different sources, including citing figures from a price list, collecting data from a single health facility in a specific area of a country, and aggregating data from all regions in a country. Non-standardized cost estimates make it very difficult for cross-setting comparison and making meaningful inference.
The quality of the estimates is a concern. About one fifth of the selected studies did not even report the year in which cost data were collected. Half of the selected studies did not specify test methods (Migliori, or Kamolratanakul, or Qunfei, for example) used in reported smear or culture tests. Almost half of the studies did not report what components were included in cost estimation. Since we know these factors have a significant bearing on cost estimates, the lack of standardization–and low quality overall–in cost data collecting and reporting present major challenges for improving our knowledge of unit costs of various MDR-TB monitoring strategies.
The calculated unit cost ratio for culture tests to smear tests from existing studies is greater than the 1.6, a number which was previously generated from cost data collected from a government laboratory in South Africa
The new recommended strategy of monthly–rather than minimum of quarterly–culture test after culture conversion, would cost more. If smear and culture were done quarterly, only 6 combined tests would be required (in addition to 14 monthly smears). According to the current recommendations of monthly smear and culture, 20 combined tests would be required. Smear and culture both have limited ability to predict poor treatment response
Even within the same monitoring method, certain methodological differences may result in cost differences, but also in sensitivity and timing. For example, culture performed in liquid medium, using the MGIT system is known to increase the detection of viable mycobacteria over culture performed in solid LJ or Ogawa medium, while decreasing from 8 weeks to 6 weeks the time required to confirm a culture as negative. Although there was additional cost associated with MGIT in at least 3 studies that compared cost of culture in liquid and solid medium (
Lastly, three studies (
This study is the first systematic review of cost estimates for tests commonly used to monitor MDR-TB treatment. We reviewed the relevant literature in Chinese. China has the highest prevalence of TB after India and the availability of Chinese cost data provides critical information for scaling up the monitoring tests for this large at-risk population. Using existing cost data, we also projected the unit cost of combined tests which could serve as useful reference to policy makers.
We propose a framework for evaluating the quality of unit cost data for TB monitoring tests. The five categories included in the quality score are crucial for determining the generalizability and validity of the cost data. They, may not, however, cover all important aspects. For instance, we only distinguished between the availability and absence of cost components, but did not consider the comprehensiveness of cost components. We assigned each category with the same weight and this may oversimplify the evaluation.
The paucity and low quality of unit cost estimates for TB monitoring in developing countries impose technical challenges in predicting the resource needed for strengthening microbiologic monitoring. As new molecular tests are being rapidly introduced globally to diagnose patients with presumptive TB and drug-resistant TB in one step, evaluation of the costs associated with the change in diagnostic practices – which was not the object of this paper - will be necessary. High quality cost data is especially important for the regions with high incidence of tuberculosis and MDR-TB, where scarce resources must be allocated efficiently. We strongly advocate that more data are collected from these regions, and that cost data collection, estimation, and reporting should follow the protocols proposed by the WHO
Databases and search terms of the search strategy.
(DOCX)
Cost for smear/culture in different regions in China (2010 USD).
(DOCX)