RESUMO
Seasonal human influenza viruses continually change antigenically to escape from neutralizing antibodies. It remains unclear how genetic variation in the intrahost virus population and selection at the level of individual hosts translates to the fast-paced evolution observed at the global level because emerging intrahost antigenic variants are rarely detected. We tracked intrahost variants in the hemagglutinin and neuraminidase surface proteins using longitudinally collected samples from 52 patients infected by A/H3N2 influenza virus, mostly young children, who received oseltamivir treatment. We identified emerging putative antigenic variants and oseltamivir-resistant variants, most of which remained detectable in samples collected at subsequent days, and identified variants that emerged intrahost immediately prior to increases in global rates. In contrast to most putative antigenic variants, oseltamivir-resistant variants rapidly increased to high frequencies in the virus population. Importantly, the majority of putative antigenic variants and oseltamivir-resistant variants were first detectable four or more days after onset of symptoms or start of treatment, respectively. Our observations demonstrate that de novo variants emerge, and may be positively selected, during the course of infection. Additionally, based on the 4-7 days post-treatment delay in emergence of oseltamivir-resistant variants in six out of the eight individuals with such variants, we find that limiting sample collection for routine surveillance and diagnostic testing to early timepoints after onset of symptoms can potentially preclude detection of emerging, positively selected variants.
RESUMO
SETTING: Ho Chi Minh City (HCMC), Vietnam. OBJECTIVE: To assess the impact on case detection of a public-private mix (PPM) project linking private providers (PPs) to the National Tuberculosis Programme (NTP). METHOD: Nine-month monitoring of referral and diagnostic data recorded in new referral forms and treatment cards for PPs and upgraded NTP registers. RESULTS: A total of 1549 TB suspects were referred, of whom 1090 (70%) actually went to the NTP for sputum examination. A total of 569 cases were detected through referrals or notification, of whom 45% were new sputum smear-positive cases. The case detection of new sputum smear-positive cases in PPM districts increased by 18% (21/100,000, 95%CI 0-42) compared to the previous year, while a slight decrease occurred in control districts. In HCMC as a whole, case detection increased by 7% (7/100,000, 95%CI 2-11/100,000). Among sputum smear-positive cases detected in NTP through referrals from PPs, 58% defaulted before initiating treatment. CONCLUSIONS: The tendency towards increased case detection associated with this PPM indicates a potential for utilising PPs to improve case detection. However, the NTP and PPs should jointly address the problem of initial default before considering expansion of this PPM model.
