The emergence in 2009 of a swine-origin H1N1 influenza virus as the first pandemic of the 21st Century is a timely reminder of the international public health impact of influenza viruses, even those associated with mild disease. The widespread distribution of highly pathogenic H5N1 influenza virus in the avian population has spawned concern that it may give rise to a human influenza pandemic. The mortality rate associated with occasional human infection by H5N1 virus approximates 60%, suggesting that an H5N1 pandemic would be devastating to global health and economy. To date, the H5N1 virus has not acquired the propensity to transmit efficiently between humans. The reasons behind this are unclear, especially given the high mutation rate associated with influenza virus replication. Here we used a panel of recombinant H5 hemagglutinin (HA) variants to demonstrate the potential for H5 HA to bind human airway epithelium, the predominant target tissue for influenza virus infection and spread. While parental H5 HA exhibited limited binding to human tracheal epithelium, introduction of selected mutations converted the binding profile to that of a current human influenza strain HA. Strikingly, these amino-acid changes required multiple simultaneous mutations in the genomes of naturally occurring H5 isolates. Moreover, H5 HAs bearing intermediate sequences failed to bind airway tissues and likely represent mutations that are an evolutionary “dead end.” We conclude that, although genetic changes that adapt H5 to human airways can be demonstrated, they may not readily arise during natural virus replication. This genetic barrier limits the likelihood that current H5 viruses will originate a human pandemic.

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The host adaptation of influenza virus is partly dependent on the sialic acid (SA) isoform bound by the viral hemagglutinin (HA). Avian influenza viruses preferentially bind the α-2,3 SA and human influenza viruses the α-2,6 isoform. Each isoform is predominantly associated with different surface epithelial cell types of the human upper airway. Using recombinant HAs and human tracheal airway epithelial cells in vitro and ex vivo , we show that many avian HA subtypes do not adhere to this canonical view of SA specificity. The propensity of avian viruses to adapt to human receptors may thus be more widespread than previously supposed.

Background Quantification of adult Aedes aegypti abundance indoors has relied on estimates of relative density (e.g. number of adults per unit of sampling or time), most commonly using traps or timed collections using aspirators. The lack of estimates of the sensitivity of collections and lack of a numerical association between relative and the absolute density of adult Ae. aegypti represent a significant gap in vector surveillance. Here, we describe the use of sequential removal sampling to estimate absolute numbers of indoor resting Ae. aegypti and to calculate calibration coefficients for timed Prokopack aspirator collections in the city of Merida, Yucatan State, Mexico. The study was performed in 200 houses that were selected based on recent occurrence of Aedes -borne viral illness in residents. Removal sampling occurred in 10-minute sampling rounds performed sequentially until no Ae. aegypti adult was collected for 3 hours or over 2 consecutive 10-minute periods. Results A total of 3439 Ae. aegypti were collected. The sensitivity of detection of positive houses in the first sampling round was 82.5% for any adult Ae. aegypti , 78.5% for females, 75.5% for males and 73.3% for blood-fed females. The total number of Ae. aegypti per house was on average ~5 times higher than numbers collected for the first sampling round. There was a positive linear relationship between the relative density of Ae. aegypti collected during the first 10-min round and the absolute density for all adult metrics. Coefficients from the linear regression were used to calibrate numbers from 10-min collections into estimates of absolute indoor Ae. aegypti density for all adults, females and males. Conclusions Exhaustive removal sampling represents a promising method for quantification of absolute indoor Ae. aegypti density, leading to improved entomological estimates of mosquito distribution, a key measure in the assessments of the risk pathogen transmission, disease modeling and the evaluation of vector control interventions.

Background The combination of Wolbachia-based incompatible insect technique (IIT) and radiation-based sterile insect technique (SIT) can be used for population suppression of Aedes aegypti. Our main objective was to evaluate whether open-field mass-releases of wAlbB-infected Ae. aegypti males, as part of an Integrated Vector Management (IVM) plan led by the Mexican Ministry of Health, could suppress natural populations of Ae. aegypti in urbanized settings in south Mexico. Methodology/Principal findings We implemented a controlled before-and-after quasi-experimental study in two suburban localities of Yucatan (Mexico): San Pedro Chimay (SPC), which received IIT-SIT, and San Antonio Tahdzibichén used as control. Release of wAlbB Ae. aegypti males at SPC extended for 6 months (July-December 2019), covering the period of higher Ae. aegypti abundance. Entomological indicators included egg hatching rates and outdoor/indoor adult females collected at the release and control sites. Approximately 1,270,000 lab-produced wAlbB-infected Ae. aegypti males were released in the 50-ha treatment area (2,000 wAlbB Ae. aegypti males per hectare twice a week in two different release days, totaling 200,000 male mosquitoes per week). The efficacy of IIT-SIT in suppressing indoor female Ae. aegypti density (quantified from a generalized linear mixed model showing a statistically significant reduction in treatment versus control areas) was 90.9% a month after initiation of the suppression phase, 47.7% two months after (when number of released males was reduced in 50% to match local abundance), 61.4% four months after (when initial number of released males was re-established), 88.4% five months after and 89.4% at six months after the initiation of the suppression phase. A proportional, but lower, reduction in outdoor female Ae. aegypti was also quantified (range, 50.0–75.2% suppression). Conclusions/Significance Our study, the first open-field pilot implementation of Wolbachia IIT-SIT in Mexico and Latin-America, confirms that inundative male releases can significantly reduce natural populations of Ae. aegypti. More importantly, we present successful pilot results of the integration of Wolbachia IIT-SIT within a IVM plan implemented by Ministry of Health personnel.