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44 result(s)
Journal Article > ResearchAbstract Only

Low-dose yellow fever vaccine in adults in Africa

N Engl J Med. 20 February 2025; Volume 392 (Issue 8); 788-797.; DOI:10.1056/NEJMoa2407293
Kimathi D, Juan-Giner A, Bob NS, Orindi B, Namulwana ML,  et al.
N Engl J Med. 20 February 2025; Volume 392 (Issue 8); 788-797.; DOI:10.1056/NEJMoa2407293

BACKGROUND

Yellow fever vaccine is highly effective with a single dose, but vaccine supply is limited. The minimum dose requirements for seroconversion remain unknown.


METHODS

In this double-blind, randomized, noninferiority trial in Uganda and Kenya, we assigned adults with no history of yellow fever vaccination or infection to receive vaccination with the Institut Pasteur de Dakar 17D-204 yellow fever vaccine at a standard dose (13,803 IU) or at a fractional dose of 1000 IU, 500 IU, or 250 IU. The primary outcome was seroconversion at 28 days after vaccination with each fractional dose as compared with the standard dose, evaluated in a noninferiority analysis. Seroconversion was defined as an antibody titer at day 28 that was at least four times as high as the antibody titer before vaccination, as measured by a plaque reduction neutralization test. We conducted noninferiority analyses in the per-protocol and intention-to-treat populations. Noninferiority was shown if the lower boundary of the 95% confidence interval for the difference in the incidence of seroconversion between the fractional dose and the standard dose was higher than -10 percentage points.


RESULTS

A total of 480 participants underwent randomization (120 participants in each group). The incidence of seroconversion was 98% (95% confidence interval [CI], 94 to 100) with the standard dose. The difference in the incidence of seroconversion between the 1000-IU dose and the standard dose was 0.01 percentage points (95% CI, -5.0 to 5.1) in the intention-to-treat population and -1.9 percentage points (95% CI, -7.0 to 3.2) in the per-protocol population; the corresponding differences between the 500-IU dose and the standard dose were 0.01 percentage points (95% CI, -5.0 to 5.1) and -1.8 percentage points (95% CI, -6.7 to 3.2), and those between the 250-IU dose and the standard dose were -4.4 percentage points (95% CI, -9.4 to 0.7) and -6.7 percentage points (95% CI, -11.7 to 1.6). A total of 111 vaccine-related adverse events were reported: 103 were mild in severity, 7 were moderate, and 1 was severe. The incidence of adverse events was similar in the four groups.


CONCLUSIONS

A yellow fever vaccination dose as low as 500 IU was noninferior to the standard dose of 13,803 IU for producing seroconversion within 28 days.

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Journal Article > ResearchFull Text

Oral regimens for rifampin-resistant, fluoroquinolone-susceptible tuberculosis

N Engl J Med. 29 January 2025; Volume 392 (Issue 5); 468-482.; DOI:10.1056/NEJMoa2400327
Guglielmetti L, Khan U, Velásquez GE, Gouillou M, Abubakirov A,  et al.
N Engl J Med. 29 January 2025; Volume 392 (Issue 5); 468-482.; DOI:10.1056/NEJMoa2400327

BACKGROUND

For decades, poor treatment options and low-quality evidence plagued care for patients with rifampin-resistant tuberculosis. The advent of new drugs to treat tuberculosis and enhanced funding now permit randomized, controlled trials of shortened-duration, all-oral treatments for rifampin-resistant tuberculosis.


METHODS

We conducted a phase 3, multinational, open-label, randomized, controlled noninferiority trial to compare standard therapy for treatment of fluoroquinolone-susceptible, rifampin-resistant tuberculosis with five 9-month oral regimens that included various combinations of bedaquiline (B), delamanid (D), linezolid (L), levofloxacin (Lfx) or moxifloxacin (M), clofazimine (C), and pyrazinamide (Z). Participants were randomly assigned (with the use of Bayesian response-adaptive randomization) to receive one of five combinations or standard therapy. The primary end point was a favorable outcome at week 73, defined by two negative sputum culture results or favorable bacteriologic, clinical, and radiologic evolution. The noninferiority margin was -12 percentage points.


RESULTS

 Among the 754 participants who underwent randomization, 699 were included in the modified intention-to-treat analysis, and 562 in the per-protocol analysis. In the modified intention-to-treat analysis, 80.7% of the patients in the standard-therapy group had favorable outcomes. The risk difference between standard therapy and each of the four new regimens that were found to be noninferior in the modified intention-to-treat population was as follows: BCLLfxZ, 9.8 percentage points (95% confidence interval [CI], 0.9 to 18.7); BLMZ, 8.3 percentage points (95% CI, -0.8 to 17.4); BDLLfxZ, 4.6 percentage points (95% CI, -4.9 to 14.1); and DCMZ, 2.5 percentage points (95% CI, -7.5 to 12.5). Differences were similar in the per-protocol population, with the exception of DCMZ, which was not noninferior in that population. The proportion of participants with grade 3 or higher adverse events was similar across the regimens. Grade 3 or higher hepatotoxic events occurred in 11.7% of participants overall and in 7.1% of those receiving standard therapy.


CONCLUSIONS

Consistent results across all the analyses support the noninferior efficacy of three all-oral shortened regimens for the treatment of rifampin-resistant tuberculosis. (Funded by Unitaid and others; endTB ClinicalTrials.gov number, NCT02754765.).

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Journal Article > CommentaryFull Text

Behind-the-scenes investment for equity in global health research

N Engl J Med. 2 February 2023; Volume 388 (Issue 5); 387-390.; DOI:10.1056/NEJMp2213809
Haberer JE, Boum Y
N Engl J Med. 2 February 2023; Volume 388 (Issue 5); 387-390.; DOI:10.1056/NEJMp2213809
Journal Article > ResearchFull Text

A 24-week, all-oral regimen for rifampin-resistant tuberculosis

N Engl J Med. 22 December 2022; Volume 387 (Issue 25); 2331-2343.; DOI:10.1056/NEJMoa2117166
Nyang'wa BT, Berry C, Kazounis E, Motta I, Parpieva N,  et al.
N Engl J Med. 22 December 2022; Volume 387 (Issue 25); 2331-2343.; DOI:10.1056/NEJMoa2117166
BACKGROUND
In patients with rifampin-resistant tuberculosis, all-oral treatment regimens that are more effective, shorter, and have a more acceptable side-effect profile than current regimens are needed.

METHODS
We conducted an open-label, phase 2–3, multicenter, randomized, controlled, noninferiority trial to evaluate the efficacy and safety of three 24-week, all-oral regimens for the treatment of rifampin-resistant tuberculosis. Patients in Belarus, South Africa, and Uzbekistan who were 15 years of age or older and had rifampin-resistant pulmonary tuberculosis were enrolled. In stage 2 of the trial, a 24-week regimen of bedaquiline, pretomanid, linezolid, and moxifloxacin (BPaLM) was compared with a 9-to-20-month standard-care regimen. The primary outcome was an unfavorable status (a composite of death, treatment failure, treatment discontinuation, loss to follow-up, or recurrence of tuberculosis) at 72 weeks after randomization. The noninferiority margin was 12 percentage points.

RESULTS
Recruitment was terminated early. Of 301 patients in stage 2 of the trial, 145, 128, and 90 patients were evaluable in the intention-to-treat, modified intention-to-treat, and per-protocol populations, respectively. In the modified intention-to-treat analysis, 11% of the patients in the BPaLM group and 48% of those in the standard-care group had a primary-outcome event (risk difference, -37 percentage points; 96.6% confidence interval [CI], -53 to -22). In the per-protocol analysis, 4% of the patients in the BPaLM group and 12% of those in the standard-care group had a primary-outcome event (risk difference, -9 percentage points; 96.6% CI, -22 to 4). In the as-treated population, the incidence of adverse events of grade 3 or higher or serious adverse events was lower in the BPaLM group than in the standard-care group (19% vs. 59%).

CONCLUSIONS
In patients with rifampin-resistant pulmonary tuberculosis, a 24-week, all-oral regimen was noninferior to the accepted standard-care treatment, and it had a better safety profile. (Funded by Médecins sans Frontières; TB-PRACTECAL ClinicalTrials.gov number, NCT02589782. opens in new tab.)
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Journal Article > CommentaryFull Text

Understanding the key to outbreak control — Sudan Virus Disease in Uganda

N Engl J Med. 16 November 2022; Online ahead of print; DOI:10.1056/NEJMp2213975
Sprecher A
N Engl J Med. 16 November 2022; Online ahead of print; DOI:10.1056/NEJMp2213975
Journal Article > LetterFull Text

Detection of Marburg virus disease in Guinea

N Engl J Med. 30 June 2022; Volume 386 (Issue 26); 2528-2530.; DOI:10.1056/NEJMc2120183
Koundouno FR, Kafetzopoulou LE, Faye M, Renevey A, Soropogui B,  et al.
N Engl J Med. 30 June 2022; Volume 386 (Issue 26); 2528-2530.; DOI:10.1056/NEJMc2120183
Journal Article > LetterFull Text

Shedding of Ebola Virus in an Asymptomatic Pregnant Woman

N Engl J Med. 18 June 2015; Volume 372 (Issue 25); DOI:10.1056/NEJMc1503275
Akerlund E, Prescott JB, Tampellini L
N Engl J Med. 18 June 2015; Volume 372 (Issue 25); DOI:10.1056/NEJMc1503275
Journal Article > ResearchFull Text

Earlier versus later start of antiretroviral therapy in HIV-infected adults with tuberculosis

N Engl J Med. 20 October 2011; Volume 365 (Issue 16); DOI:10.1056/NEJMoa1013911
Blanc FX, Sok T, Laureillard D, Borand L, Rekacewicz C,  et al.
N Engl J Med. 20 October 2011; Volume 365 (Issue 16); DOI:10.1056/NEJMoa1013911
Tuberculosis remains an important cause of death among patients infected with the human immunodeficiency virus (HIV). Robust data are lacking with regard to the timing for the initiation of antiretroviral therapy (ART) in relation to the start of antituberculosis therapy.More
Journal Article > LetterSubscription Only

Amoxicillin for severe acute malnutrition in children

N Engl J Med. 14 July 2016; Volume 375 (Issue 2); 190-192.; DOI:10.1056/NEJMc1605388
Isanaka S, Adehossi E, Grais RF
N Engl J Med. 14 July 2016; Volume 375 (Issue 2); 190-192.; DOI:10.1056/NEJMc1605388
Journal Article > LetterFull Text

Single-dose oral cholera vaccine in Bangladesh

N Engl J Med. 18 August 2016; Volume 375 (Issue 7); e12.; DOI:10.1056/NEJMc1607285
Azman AS, Luquero FJ
N Engl J Med. 18 August 2016; Volume 375 (Issue 7); e12.; DOI:10.1056/NEJMc1607285