About

Dr. David Alland is a Professor of Medicine, Chief of Infectious Disease, and the Director of the Center for Emerging Pathogens and the Rutgers Regional Biocontainment Laboratories at Rutgers New Jersey Medical School. He is internationally recognized for his pioneering work on the epidemiology, diagnosis, treatment, and molecular evolution of Mycobacterium tuberculosis (Mtb). His epidemiologic studies in the 1990s demonstrated that drug-resistant Mtb was being transmitted in institutions and the community, impacting national TB control efforts. He led a decade-long research effort culminating in the development of the Xpert MTB/RIF Assay, the first on-demand, point-of-care TB test, which replaced the acid-fast smear for TB diagnosis and is now used in over 130 countries, recommended by the WHO. His research continues in the development of rapid diagnostics for extended TB drug resistance, bloodstream detection of bioterrorism agents, and other pathogens. Dr. Alland's work on drug resistance mechanisms includes describing the Mtb iniBAC operon as the first genetic cause of drug tolerance in Mtb and identifying Lsr2 as a novel histone-like protein regulating iniBAC expression. His group, along with the Sassetti laboratory, discovered that phase variation in the M. tuberculosis glpK gene produces heritable, yet rapidly reversible, multi-drug tolerance, which may explain TB relapse and treatment challenges.

Research topics

• Medicine
• Biology
• Virology
• Microbiology
• Genetics
• Pharmacology
• Pathology
• Internal medicine
• Immunology
• Environmental health
• Molecular biology

Selected publications

• PET–CT benchmarked detection and 5-year progression of asymptomatic tuberculosis: a longitudinal, prospective cohort study

  The Lancet Respiratory Medicine · 2026-03-01 · 2 citations

  articleOpen access

  BACKGROUND: F]-fluorodeoxyglucose PET-CT) and compared with chest x-ray computer-aided detection (CAD). METHODS: We enrolled a prospective longitudinal cohort in Khayelitsha, Cape Town, South Africa, of asymptomatic, HIV-uninfected contacts aged 18-65 years of patients with rifampicin-resistant tuberculosis, a tuberculosis high-risk group not eligible for chemoprophylaxis. Participants underwent baseline PET-CT, chest x-ray, phlebotomy, and intensive sputum collection, and were classified into four PET-CT lung categories: consistent with tuberculosis, inactive tuberculosis, other lesions, and normal. Chest x-ray was processed by three types of CAD software (CAD4TB [version 7.0], qXR [version 3.0.0], and Lunit [version 3.1.4.111]). Follow-up included symptom-agnostic tuberculosis screening (23-38 months) and provincial register review (≤74 months), and a subgroup had repeat PET-CT (5-15 months). Tuberculosis was defined as bacteriologically confirmed or clinically diagnosed. The primary outcome measures were hazard ratio (HR) for tuberculosis diagnosis and treatment by baseline PET-CT lung abnormality category with normal as the reference group, and diagnostic performance of chest x-ray CAD software using area under the receiver operator characteristic curve (AUC). FINDINGS: 250 asymptomatic adults were enrolled between March 3, 2015, and Oct 11, 2017, irrespective of tuberculosis history or previous infection, and followed up for 1107 person-years (median 4·7 years [IQR 4·0-5·1]). 18 (7%) participants were treated for tuberculosis (16 [89%] of 18 bacteriologically confirmed). Six of 18 participants were diagnosed at baseline (four requiring induced sputum culture) and 12 of 18 after a median of 32 months (IQR 12-35). By baseline PET-CT category, tuberculosis was diagnosed and treated in 12 (41%) of 29 participants with scans consistent with tuberculosis, two (7%) of 30 with scans consistent with inactive tuberculosis, two (2%) of 83 with scans showing other lesions, and two (2%) of 108 with scans showing normal lungs. Participants with baseline PET-CT scans consistent with tuberculosis had the highest risk of 5-year tuberculosis diagnosis (HR 28·54 [95% CI 6·37-127·81] compared with those with scans showing normal lungs, p<0·0001), with no significant risk for scans consistent with inactive tuberculosis (3·55 [0·50-25·21], p=0·21) or other lung lesions (1·30 [0·18-9·23], p=0·79). 11 (69%) of the 16 participants with bacteriologically confirmed tuberculosis were asymptomatic at bacteriological confirmation, and ten (91%) of 11 had baseline PET-CT scans consistent with tuberculosis. Using baseline PET-CT classification as reference, the AUC for chest x-ray CAD software ranged from 0·86 (95% CI 0·72-0·99) to 0·89 (0·75-1·00) for bacteriologically confirmed tuberculosis. INTERPRETATION: Most adult asymptomatic contacts diagnosed with tuberculosis over 5 years had baseline radiographically evident disease, not radiographically negative incipient tuberculosis. Although PET-CT is not feasible for routine screening, it provides a highly sensitive reference benchmark for diagnostic development, with chest x-ray CAD performing comparatively well. FUNDING: South Africa Medical Research Council, US National Institutes of Health, Gates Foundation, Wellcome, UK Research and Innovation Medical Research Council, and Walter and Eliza Hall Institute of Medical Research.

  PublisherDOI

• Development of a four-gene host signature for paucibacillary TB among symptomatic individuals with sputum Xpert MTB/RIF Ultra very low and trace results

  International Journal of Infectious Diseases · 2026-05-01

  articleOpen access

  OBJECTIVES: The Xpert MTB/RIF Ultra (Ultra) assay is widely used to diagnose pulmonary tuberculosis (TB), but 'very low' or 'trace' results may reflect either paucibacillary TB or TB-negative disease, complicating clinical decision-making. We evaluated host transcriptomic signatures to identify culture-confirmed paucibacillary TB among individuals with Ultra very low or trace results. METHODS: We performed whole blood targeted transcriptional profiling of 90 symptomatic adults from Uganda, Kenya, and South Africa with Ultra very low/trace sputum results. An 81-gene customized NanoString panel representing 13 published TB signatures was analyzed using machine learning to derive a novel four-gene host signature ("TRACE4") predicting MGIT and LJ culture positivity. Validation included individuals with other respiratory diseases (n=18) and North American-TB-negative controls (n=20). Data were randomly split 75/25 into training (n=67) and test (n=23) sets. Diagnostic performance was evaluated against WHO targets. RESULTS: TRACE4 outperformed all published signatures in both training (AUC 0.89) and test sets (AUC 0.88), achieving 82% specificity at 75% sensitivity. It also exceed reclassification based on prior TB history (specificity 0.58 (95% CI: 0.45-0.69); sensitivity 0.35 (95% CI: 0.15-0.61)). TRACE4 showed 100% specificity in non-TB controls. CONCLUSION: TRACE4 shows promise for identifying paucibacillary culture-positive pulmonary TB in this diagnostically challenging group.

  PublisherDOI

• Multicountry assessment of tongue swabs for tuberculosis using a common protocol for Xpert MTB/RIF Ultra testing: a prospective diagnostic accuracy study

  The Lancet Microbe · 2026-05-01

  articleOpen access

  BACKGROUND: Despite advancements in tuberculosis diagnostics, many cases remain unconfirmed because of challenges in conventional sputum-based testing. This study aimed to evaluate the diagnostic accuracy of tongue swab sampling as a non-invasive alternative for tuberculosis diagnosis using Xpert MTB/RIF Ultra (Ultra). METHODS: We conducted a large-scale, multicountry, prospective diagnostic accuracy study of Ultra using tongue swabs in people with presumptive pulmonary tuberculosis. Participants were enrolled consecutively at primary health centres and hospitals across eight countries from June 26, 2023, to Feb 15, 2024, and the study was coordinated by three consortia. Eligible participants were individuals aged 12 years or older or 18 years or older, according to the consortium involved, with presumptive pulmonary tuberculosis or at least one risk factor for tuberculosis and a positive tuberculosis screening test at the select consortia. Standardised tongue swab collection and processing protocols were used in all countries. Sensitivity and specificity with 95% CI values were calculated against sputum liquid or solid culture (primary) and sputum Ultra (secondary) reference standards using Wilson's score method. Fisher's exact tests were used for subgroup comparisons, with p values < 0·05 considered statistically significant. FINDINGS: Among the 1844 participants included in the analysis, 389 tested positive and 1455 tested negative for pulmonary tuberculosis based on the primary sputum culture reference standard. 871 (47·2%) participants were female and 973 (52·7%) were male, with a mean age of 43 years (range 12-90). Among the 1844 participants, 399 (21·7%) were enrolled in Viet Nam, 166 (9·0%) in India, 427 (23·2%) in South Africa, 271 (14·7%) in the Philippines, 138 (7·5%) in Nigeria, 102 (5·5%) in Zambia, 175 (9·5%) in Uganda, and 166 (9·0%) in Peru. Tongue swab Ultra testing showed a sensitivity of 65·6% (95% CI 60·6-70·3) and specificity of 98·5% (95% CI 97·7-99·1) against the culture-based reference standard. Sensitivity estimates varied across collection centres and were higher in individuals without HIV than in those living with HIV (68·4% vs 50·0%; absolute difference 18·4 percentage points [95% CI 3·3-33·4]). When sputum Ultra was used as the reference standard, sensitivity was 75·4% (95% CI 69·0-78·8). Tongue swab Ultra showed higher sensitivity than sputum smear microscopy. Invalid or error result rates were variable and high at certain sites (range 0-16%). INTERPRETATION: Tongue swabs are a promising sample type for rapid diagnostic tests for tuberculosis, with moderate sensitivity and high specificity when Ultra was used as the reference standard. However, further research is needed to optimise protocols for Ultra testing and develop assays tailored to tongue swab specimens. Adoption of tongue swab-based molecular testing could expand tuberculosis diagnostics access, especially for populations unable to produce sputum, thus supporting global tuberculosis elimination goals. FUNDING: National Institute of Allergy and Infectious Diseases, United States Agency for International Development.

  PublisherDOI

• Prominence of Mycobacterium tuberculosis biomarkers among sputum culture-negative clinic attendees, independent of Ultra status

  Journal of Infection and Public Health · 2025-04-24 · 3 citations

  articleOpen access

  BACKGROUND: Highly-sensitive molecular tests like GeneXpert MTB/RIF Ultra improve detection of paucibacillary pulmonary tuberculosis (TB) but occasionally detect Mycobacterium tuberculosis (Mtb) DNA in sputum from culture-negative individuals, with unclear significance. We hypothesized that Ultra may be detecting culture-negative TB, and manifest in a higher prevalence of TB biomarkers compared to Ultra-negative/culture-negative ('sputum-negative') individuals. METHODS: From 1200 symptomatic African adults undergoing evaluation for TB, we identified 66 with discordant results (Ultra-positive, culture-negative), and matched 52 sputum-negative (Ultra-negative, culture-negative) and 30 sputum-positive (Ultra-positive, culture-positive) participants. Over 12 months, participants were assessed for Mtb biomarkers (Mtb growth in augmented or follow-up sputum cultures, Mtb mRNA in baseline sputum, and symptomatic Ultra-positive after baseline) and TB-associated host transcriptional signatures. RESULTS: At baseline, TB-associated biomarker(s) were detected in 51.5 % of sputum-discordant versus 59.6 % of sputum-negative participants (p = 0.46), with at least one Mtb biomarker in 16.7 % versus 26.9 % respectively (p = 0.26). Longitudinally, 26.5 % of untreated sputum-discordant versus 41.7 % of untreated sputum-negative participants had Mtb biomarkers (p = 0.17) despite most reporting symptom improvement. Notably, 30 % of untreated sputum-negative participants converted to Ultra-positive at month 2. One sputum-discordant and one sputum-negative participant developed culture-confirmed TB at follow-up. CONCLUSION: TB bacterial and host biomarkers were prevalent and no different between sputum-discordant and sputum-negative participants, raising concern for a considerable population of undiagnosed culture-negative TB. These findings parallel new evidence of Mtb aerosolization from sputum-negative individuals and highlight a need for more comprehensive diagnostics that detect sputum culture-negative TB with respect to infectiousness, pathology, and risk of progression.

  PublisherDOI

• SuFEx-based antitubercular compound irreversibly inhibits Pks13

  Nature · 2025-07-30 · 15 citations

  articleOpen access
  PublisherOA PDFDOI

• PERFORMANCE OF FUJILAM VERSION 1 FOR THE DIAGNOSIS OF TUBERCULOSIS IN CHILDREN UNDER 5 YEARS IN UGANDA – A BRIEF REPORT

  medRxiv · 2025-10-19

  preprintOpen access

  Background: Diagnosing tuberculosis in children remains challenging due to the paucibacillary nature of the disease, non-specific symptoms, and difficulty collecting samples. New tests are urgently needed. We evaluated the diagnostic accuracy of FujiLAM version 1 urine test in children under 5 years with presumptive tuberculosis in Uganda. Methods: This was a cross-sectional evaluation nested in the NOD-pedFEND diagnostic study. Children under 5 years with signs or symptoms of tuberculosis were recruited from three hospitals in Uganda. All participants underwent comprehensive baseline investigations, including culture and Xpert MTB/RIF Ultra on reference samples and chest X-ray. Culture and Xpert MTB/RIF Ultra results were used to define a microbiological reference standard. FujiLAM version 1 testing was performed on fresh urine at the baseline visit. Results: Seventy-nine children were included in the study. Fifteen participants (19%) were classified as having microbiologically confirmed TB, 44 (56%) as unconfirmed TB, thirteen (16%) as unlikely TB, and seven participants (9%) were unclassifiable. Only one participant (with unlikely TB) had a positive FujiLAM test. Culture and Xpert MTB/RIF Ultra on reference samples were negative in this child, indicating poor diagnostic accuracy with a sensitivity of 0% (95% CI: 0 - 21.8) of FujiLAM version 1 against the microbiological reference standard. Conclusion: The poor diagnostic accuracy of FujiLAM version 1 in children under five years of age makes it unsuitable as a diagnostic test in this age group. Further evaluation with the optimized version 2 of this test is needed.

  PublisherOA PDFDOI

• Evolution of Small Molecule Inhibitors of <i>Mycobacterium tuberculosis</i> Menaquinone Biosynthesis

  Journal of Medicinal Chemistry · 2025-03-04 · 4 citations

  articleOpen accessCorresponding

  A dire need exists for novel drugs to treat Mycobacterium tuberculosis infection. In an effort to build on our early efforts targeting the MenG enzyme within the menaquinone biosynthetic pathway, we have pursued the optimization of diaryl amide JSF-2911 to address its poor metabolic stability and modest in vitro potency. A hit evolution campaign focused on modification of the amine substructure within this hit compound, resulting in a range of analogues that have been profiled extensively. Among these derivatives, JSF-4536 and JSF-4898 demonstrated significantly improved biological profiles, notably offering submicromolar MIC values versus M. tuberculosis and promising values characterizing the mouse liver microsome stability, aqueous solubility, and mouse pharmacokinetic profile. JSF-4898 enhanced the efficacy of rifampicin in a subacute model of M. tuberculosis infection in mice. The findings suggest a rationale for the further optimization of MenG inhibitors to provide a novel therapeutic strategy to address M. tuberculosis infection.

  PublisherDOI

• Divergent transcriptional regulation of redox-homeostasis and permeability modulate rifampicin tolerance and sensitivity in Mycobacterium tuberculosis

  Nature Communications · 2025-12-14

  articleOpen accessSenior author

  Drug-tolerance in Mycobacterium tuberculosis (Mtb) may delay treatment response while drug hypersusceptibility should improve treatment. We investigate the transcriptional regulation of these states in Mtb using a Transcriptional Regulator Induced Phenotype screen combined with an extended, steady-state rifampicin exposure method. We identify three transcription factors (TFs): Rv1359, Rv2887, and Rv3833, whose induction enhances rifampicin tolerance, and four TFs, Rv1189 (sigI), Rv1846c (blaI), Rv2069 (sigC), and Rv3736, whose induction elicits hypersusceptibility. Inducing the TFs blaI and Rv2887 produces opposite phenotypes due to their divergent regulation of the cydA and icl1, genes that we find to reduce redox stress when overexpressed. Thus, Rv2887 induces icl1 expression which contributes to drug tolerance whereas blaI downregulates cydA, which contributes to drug hypersusceptibility. In contrast, divergent regulation of tgs1 and Rv3083 by the TF Rv3736 results in a convergent hypersusceptible phenotype due to the opposing effects of tgs1 and Rv3083 on Mtb permeability to rifampicin. Our findings demonstrate the complex transcriptional regulation of drug tolerance and hypersusceptibility that cannot be captured by studying the activity of individual effector genes. Induction of TFs that regulate Mtb response to drug exposure may either augment or diminish treatment efficacy. These TFs are thus potential new targets for drug development.

  PublisherOA PDFDOI

• The KasA inhibitor JSF-3285 improves the sterilizing activity of bedaquiline-pretomanid-containing regimens in a mouse model of tuberculosis

  Antimicrobial Agents and Chemotherapy · 2025-04-23 · 1 citations

  articleOpen access

  ABSTRACT JSF-3285 is a promising preclinical candidate for tuberculosis that potently targets the Mycobacterium tuberculosis β-ketoacyl-ACP synthase KasA. In mouse models of acute, sub-acute, chronic, and relapse infection, JSF-3285 offers substantial activity in combination with bedaquiline and pretomanid, which could be applicable for both drug-sensitive and drug-resistant infections.

  PublisherDOI

• Oral Swab Testing With Xpert MTB/RIF Ultra for the Diagnosis of Tuberculosis in Children Aged &amp;lt;5 Years in Uganda: An Exploratory Interim Analysis of Diagnostic Accuracy in the NOD-pedFEND Cohort

  Open Forum Infectious Diseases · 2025-03-27 · 5 citations

  articleOpen access

  Background: Obtaining respiratory samples to diagnose tuberculosis in young children is challenging. Oral swabs are alternative noninvasive specimens for microbiology. Methods: We conducted an interim prospective diagnostic accuracy evaluation of Xpert MTB/RIF Ultra (Ultra) on oral swabs for pulmonary tuberculosis in children aged <5 years in Uganda. Most children had 2 consecutive swabs collected in a single cryovial (double swabs). Reference tests consisted of Ultra and culture on 2 nasopharyngeal aspirates and 1 gastric aspirate and Ultra on 1 stool. Children were classified as having confirmed tuberculosis, unconfirmed tuberculosis, or unlikely tuberculosis per the National Institutes of Health. Diagnostic accuracy was determined against a microbiological reference standard and a composite reference standard. Results: From August 2021 to February 2024, 444 children were enrolled, of whom 399 had complete classifications: 33 had confirmed tuberculosis, 269 had unconfirmed tuberculosis, 70 had unlikely tuberculosis, and 27 were unclassifiable. The median age was 16 months and 17% had HIV. Most children (398/399) had oral swabs collected, all with conclusive Ultra results. The sensitivity of double swabs was 6.9% with a microbiological reference standard (95% CI, 1.9%-22.0%) and 1.8% with a composite reference standard (95% CI, .8%-4.1%). Specificity was at least 99%. Swabs detected tuberculosis in 4 children with negative reference test results, of whom 3 had unconfirmed tuberculosis. Conclusions: The low sensitivity of Ultra on double swabs precludes its role as a principal diagnostic approach in young children. However, detection of tuberculosis in children who were not otherwise microbiologically diagnosed suggests the utility of oral swabs as add-on samples to increase yield.

  PublisherOA PDFDOI

Recent grants

• New drugs for non-tuberculous mycobacterial (NTM) lung disease in patients with cystic fibrosis

  NIH · $67.0M · 2019–2025

• NIH Grant R21AI111647

  NIH · $437k · 2016

• NIH Grant U01AI056689

  NIH · $3.9M · 2008

• FEND for TB

  NIH · $20.0M · 2020–2026

• NIH Grant RC1AI087062

  NIH · $1.0M · 2012

Frequent coauthors

• Soumitesh Chakravorty

  114 shared

• Padmapriya P. Banada

  Rutgers New Jersey Medical School

  112 shared

• Barry N. Kreiswirth

  Hackensack Meridian Health

  110 shared

• Karen Brudney

  Vital Strategies

  101 shared

• Dial Hewlett

  Westchester County Department of Health

  101 shared

• Stephen J. Peterson

  Cornell University

  100 shared

• Celia Alfalla

  NewYork–Presbyterian Hospital

  100 shared

• Ashok Kumar Patel

  Indian Institute of Technology Delhi

  100 shared

Education

• B.A.

  Columbia College

  1980

• M.S.

  London School of Hygiene & Tropical Medicine, University of London

  1988

• M.D.

  Columbia College of Physicians and Surgeons

  1984