Tuberculosis (TB) continues to be a leading public health problem in the developing countries, with Sub Saharan Africa being hardest hit 
. Besides HIV/AIDS, drug-resistance is now recognized as one of the major factors underlying the failure to control TB 
. Drug resistance in M. tuberculosis
(MTB) develops by sequential selection following exposure to TB drugs 
. In most of the low income Sub-Saharan African countries, only first line drugs [isoniazid (INH) and rifampicin (RIF), Ethambutol (ETH) and Pyrazinamide (PZA)] are available for TB treatment. Thus, multi drug resistance (MDR) - defined as resistance to at least INH and RIF is currently the main concern. The prevalence of MDR-TB in Africa remains largely unknown but is estimated to be between 1–4% among new and 4–17% among re-treatment TB cases 
. The high number of TB cases per year in each of the high burden African countries 
by itself implies that even a limited prevalence of MDR-TB represents a significant pool of potentially infectious MDR-TB cases. Timely detection of these cases is crucial for patient management and control of further MDR transmission 
Indirect susceptibility testing on Lowenstein-Jensen (LJ) medium is the most common method for detection of TB drug resistance in Africa. With this method, results take 2–3 months and during this period patients are given inappropriate drug regimens with poor responses and they continue to spread MDR strains, which might be causing MDR-TB outbreaks 
. Commercial liquid culture techniques, such as the Mycobacterium Growth Indicator Tube (MGIT 960: Becton Dickinson, Sparks, Maryland) and line probe assays 
allow more rapid detection of resistance, and have been recommended by the WHO 
. However, the investment and recurrent costs is an obstacle for the broad implementation of these techniques in the resource-limited settings (RLSs) of Africa. Therefore, the need for a rapid, affordable, accurate and easy to use test for MDR-TB in RLSs remains a priority.
The Nitrate Reductase Assay (NRA) and the Microscopic Observation Drug Susceptibility (MODS) are two of the most promising rapid tests for MDR-TB proposed for RLSs. Both techniques have been reported to be low cost in-house assays that can be applied directly on smear positive sputum 
. Resistance detection with the NRA is based on visual observation of a pink to purple color in a culture tube upon addition of the so called Griess reagent, due to nitro-reductase enzymes in metabolically active mycobacterial cells converting nitrate to nitrite 
. MODS relies on microscopic observation of characteristic cord-like structures in the drug-containing wells of a tissue culture plate where resistant MTB cells are growing 
In 2009, we conducted a meta-analysis of studies of the direct NRA and MODS, and the pooled data showed high sensitivity and specificity for detection of resistance to RIF and INH 
. The direct NRA has been studied in Brazil, India and Nigeria with good results 
, but these studies had limitations. For example in the Brazil study, the direct proportion method was the reference test, while in Nigeria only 20 sputum samples were studied. The World Health Organization (WHO) in July 2010 recommended the use of NRA and MODS to screen for MDR-TB in RLSs, but the available data to support the direct NRA was admittedly limited 
. It is of priority to obtain sufficient data on these tests before full scale recommendation of their implementation in Africa.
In this study we provide more recent data and field experience with the NRA and MODS assays in the East African country of Uganda, a typical RLS. The assays were prospectively compared side by side for interpretable susceptibility results, contamination rates, sensitivity and specificity, time to results and cost per sample on a consecutive population of previously treated TB patients attending a TB clinic in Kampala. The study was approved by the Research and Ethics Committee of Makerere University College of Health Sciences Kampala, Uganda.