Background: Ethiopia stands 12th among the 30 high TB burden countries with incidence rate of 165rncases per 100,000 population.Continuousand sustainable efforts should be exerted in different aspectsrnincluding in research in order to reduce the burden of TB in the country.rnObjective: The present study was conducted in northeastern Ethiopia to investigate the nutritional statusrnof TB patients, TB co-infection with parasites, the types strains of M. tuberculosis circulating in the arearnand evaluate the drug sensitivity profiles the strains.rnMethods:A cross-sectional study was conducted on 384 TB patients (286 smear positive pulmonary TBrnand 98 extra-pulmonary TB cases) who were visiting health care institution for seeking treatment.rnAnthropometric measurements were used for the assessment of the nutritional status of TB patients whilerndirect wet mount microscopy, Kato-Katz and concentration techniques were used stool examination forrnparasite co-infections. Clinical examination, ZiehlNeelsen staining, mycobacterial culture, region ofrndifference (RD) 9-based polymerase chain reaction (PCR), spoligotyping and mycobacterial interspersedrnrepetitive unit-variable-number tandem repeat (MIRU-VNTR) typing were used TB investigation. Inrnaddition, Mycobacteria Growth Indicator Tube (MGIT) test and GenoTypic MTBDRplus assay were usedrnto evaluate drug sensitivity profiles of M. tuberculosis.Data were analyzed using descriptive statistics andrnPearson chi-square.rnResults: The prevalence of undernutrition was 58.6% using body mass index while it was 73.0% usingrnmid-upper arm circumference. The overall prevalence of TB-parasitosis co-infection was 10.8%;rnintestinal helminths co-infection was 9.7% while intestinal protozoa co-infection was 1.9%. Clinically, TBrnlymphadentis accounted for 85.9% of the extra-pulmonary TB of which cervical lymphadenopathy wasrn75.3%. Culture positivity was confirmed in only 29.2% (112/384). Speciation of the isolates using RD9rnPCR revealed 77.7% of the isolates were M. tuberculosis. But no signal was detected for the remainingrn22.3% (25/112) isolates. Spoligotyping of 112 identified 92.9% (104/112) as interpretable spoligotypingrnpatterns. Twenty-one percent of the isolates were grouped under 10 clustered strains while the remainingrn79% (n=83) isolates were classified as singleton strains. On the other hand, 13.5% of the isolates wererngrouped under shared types and 86.5% were orphan. Furthermore, spoligotyping grouped 52.9%, 27.9%rnand 19.2% of the isolates in Euroamerican, Indio-oceanic and East African Indian lineages, respectively.rnDNA samples of 69 isolates were tested by 24-loci MIRU-VNTR typing and 56 had valid amplificationrnproducts while the remaining 13 isolates had either incomplete or negative results. Each of the 56rnisolates had distinct MIRU-VNTR profile and as a result, 56 different genotypes (strains) were detectedrnMIRU-VNTR typing. The results of MGIT and MTBDRplus assay showed that 15.9% and 16.8% of thernisolates developed resistance to either of the first line anti-TB drugs, respectively. The percentage ofrnmulti-drug resistance (MDR) M. tuberculosis was 8.4% (8/95) as detected by GenoTypic MTBDRplusrnassay. The agreement between MGIT and MTBDRplus assay in detecting resistance to Isoniazid (INH)rnwas substantial (k=0.77) while it was near perfect in detecting either resistance to Rifampicin (RIF)rn(k=0.93) or in detecting MDR M. tuberculosis (k=0.90).rnConclusion: Undernutrition and co-infection with parasites were common in TB patients in northeasternrnEthiopia. The strains M. tuberculosis circulating in northeastern Ethiopia were highly diverse and arnsignificant proportion of the strains have developed drug resistance. Therefore, improvement of thernnutrition and regular de-worming of the population in the area would contribute significantly tornreduction of the burden TB and improves the response to TB treatment. Additionally, public education isrnrequired on the proper use of anti-TB drugs. Furthermore, special attention should be given to MDR TBrncases so that their further transmission is contained.