Evaluating the strategies to control SARS-CoV-2 Delta variant spread in New Caledonia, a zero-COVID country until September 2021.

Objectives: New Caledonia, a former zero-COVID country, was confronted with a SARS-CoV-2 Delta variant outbreak in September 2021. We evaluate the relative contribution of vaccination, lockdown, and timing of interventions on healthcare burden. Methods: We developed an age-stratified mathematical model of SARS-CoV-2 transmission and vaccination calibrated for New Caledonia and evaluated three alternative scenarios. Results: High virus transmission early on was estimated, with R0 equal to 6.6 (95% confidence interval [6.4-6.7]). Lockdown reduced R0 by 73% (95% confidence interval [70-76%]). Easing the lockdown increased transmission (39% reduction of the initial R0); but we did not observe an epidemic rebound. This contrasts with the rebound in hospital admissions (+116% total hospital admissions) that would have been expected in the absence of an intensified vaccination campaign (76,220 people or 34% of the eligible population were first-dose vaccinated during 1 month of lockdown). A 15-day earlier lockdown would have led to a significant reduction in the magnitude of the epidemic (-53% total hospital admissions). Conclusion: The success of the response against the Delta variant epidemic in New Caledonia was due to an effective lockdown that provided additional time for people to vaccinate. Earlier lockdown would have greatly mitigated the magnitude of the epidemic.

T-cell and serological responses to Erp, an exported Mycobacterium tuberculosis protein, in tuberculosis patients and healthy individuals.

BACKGROUND: The identification of antigens able to differentiate tuberculosis (TB) disease from TB infection would be valuable. Cellular and humoral immune responses to Erp (Exported repetitive protein)--a recently identified M. tuberculosis protein--have not yet been investigated in humans and may contribute to this aim. METHODS: We analyzed the cellular and humoral immune responses to Erp, ESAT-6, Ag85B and PPD in TB patients, in BCG+ individuals without infection, BCG+ individuals with latent TB infection (LTBI) and BCG- controls. We used lymphoproliferation, ELISpot IFN-gamma, cytokine production assays and detection of specific human antibodies against recombinant M. tuberculosis proteins. RESULTS: We included 22 TB patients, 9 BCG+ individuals without TB infection, 7 LTBI and 7 BCG- controls. Erp-specific T cell counts were higher in LTBI than in the other groups. Erp-specific T cell counts were higher in LTBI subjects than TB patients (median positive frequency of 211 SFC/106 PBMC (range 118-2000) for LTBI subjects compared to 80 SFC/106 PBMC (range 50-191), p = 0.019); responses to PPD and ESAT-6 antigens did not differ between these groups. IFN-gamma secretion after Erp stimulation differed between TB patients and LTBI subjects (p = 0.02). Moreover, LTBI subjects but not TB patients or healthy subjects produced IgG3 against Erp. CONCLUSION: The frequencies of IFN-gamma-producing specific T cells, the IFN-gamma secretion and the production of IgG3 after Erp stimulation are higher in LTBI subjects than in TB patients, whereas PPD and ESAT-6 are not.

Mutations in putative mutator genes of Mycobacterium tuberculosis strains of the W-Beijing family.

Alterations in genes involved in the repair of DNA mutations (mut genes) result in an increased mutation frequency and better adaptability of the bacterium to stressful conditions. W-Beijing genotype strains displayed unique missense alterations in three putative mut genes, including two of the mutT type (Rv3908 and mutT2) and ogt. These polymorphisms were found to be characteristic and unique to W-Beijing phylogenetic lineage. Analysis of the mut genes in 55 representative W-Beijing isolates suggests a sequential acquisition of the mutations, elucidating a plausible pathway of the molecular evolution of this clonal family. The acquisition of mut genes may explain in part the ability of the isolates of W-Beijing type to rapidly adapt to their environment.

Discontinuation of secondary prophylaxis against disseminated Mycobacterium avium complex infection and toxoplasmic encephalitis.

We retrospectively studied outcomes for patients infected with human immunodeficiency virus who received highly active antiretroviral therapy (HAART) and had stopped receiving secondary prophylaxis against toxoplasmic encephalitis (TE) or disseminated Mycobacterium avium complex (MAC) infection. Nineteen patients had a history of TE, and 26 had a history of disseminated MAC infection. The median duration of secondary prophylaxis was 27 months, and the median duration of HAART before discontinuation of secondary prophylaxis was 22 months. Median CD4(+) cell counts at the time of cessation of secondary prophylaxis against TE or disseminated MAC infection were 404 and 105 cells/mm(3), respectively. Plasma virus load was undetectable in 68% of the patients who had a history of TE and in 31% of patients who had a history of disseminated MAC infection. Patients were followed up for a median of 29 months after discontinuation of secondary prophylaxis; no relapses occurred in patients with a history of TE, and 3 relapses occurred in patients with a history of disseminated MAC infection (incidence, 4 relapses per 100 person-years).