Dengue is the most prevalent arboviral disease of humans. The host and virus variables associated with dengue virus (DENV) transmission from symptomatic dengue cases (n = 208) to Aedes aegypti mosquitoes during 407 independent exposure events was defined. The 50% mosquito infectious dose for each of DENV-1-4 ranged from 6.29 to 7.52 log10 RNA copies/mL of plasma. Increasing day of illness, declining viremia, and rising antibody titers were independently associated with reduced risk of DENV transmission. High early DENV plasma viremia levels in patients were a marker of the duration of human infectiousness, and blood meals containing high concentrations of DENV were positively associated with the prevalence of infectious mosquitoes 14 d after blood feeding. Ambulatory dengue cases had lower viremia levels compared with hospitalized dengue cases but nonetheless at levels predicted to be infectious to mosquitoes. These data define serotype-specific viremia levels that vaccines or drugs must inhibit to prevent DENV transmission.engue is globally the most important mosquito-borne viral disease of humans, with a global burden of ∼100 million cases per annum (1, 2). Aedes aegypti mosquitoes are the primary mosquito vectors of dengue viruses (DENV), of which there are four virus types (DENV-1-4). Multiple factors influence the likelihood of infection and dissemination of DENV in Ae. aegypti and include the amplitude of daily temperature fluctuations (3), mean temperature (4), and the genotype of mosquito and virus (5), among others (6). The extrinsic incubation period (EIP), a critical determinant of vector competence (7,8), is widely accepted to be 7-14 d for DENV in Ae. aegypti, although a recent modeling analysis of historical DENV transmission data has suggested a wider range of 2-15 d at 30°C (9). A major caveat to many of these observations is that they stem from laboratory experiments with artificially generated virus-spiked blood meals and often in-bred colony mosquitoes.The temporal and virological variables associated with the transmission of DENV from a naturally infected human to a biting Ae. aegypti mosquito are poorly understood. Natural history studies of experimental DENV infection of small cohorts of human volunteers in the 1920s by Siler et al. (10,11), likely using DENV-4 (12), and subsequent studies by Simmons et al. (13), likely using DENV-1 (12), suggested that the window of time before the onset of clinical symptoms that DENV-1 or DENV-4 could be transmitted to Ae. aegypti mosquitoes was 6-18 h or 2 d, respectively (14). After fever onset, the duration of infectiousness was 4-5 d for DENV-1 and up to 2 d for DENV-4, with an EIP in the mosquito of 10 d or more. Consistent with this, mosquitobiting studies by Gubler et al. in the 1960s (15-18) collectively estimated that dengue cases were infectious for 4-5 d after illness onset (range, 2-12 d). The human viremia level required to infect Ae. aegypti mosquitoes is unknown, and therefore it is uncertain what percentage of symptomatic (or asymptomatic...

National Medical Research Council Singapore, Centre for Infectious Disease Epidemiology and Research, and A*STAR Biomedical Research Council.

Background Little is known about the natural history of asymptomatic SARS-CoV-2 infection or its contribution to infection transmission. Methods We conducted a prospective study at a quarantine center for COVID-19 in Ho Chi Minh City, Vietnam. We enrolled quarantined people with RT-PCR-confirmed SARS-CoV-2 infection, collecting clinical data, travel and contact history, and saliva at enrolment and daily nasopharyngeal throat swabs (NTS) for RT-PCR testing. We compared the natural history and transmission potential of asymptomatic and symptomatic individuals. Results Between March 10th and April 4th, 2020, 14,000 quarantined people were tested for SARS-CoV-2; 49 were positive. Of these, 30 participated in the study: 13(43%) never had symptoms and 17(57%) were symptomatic. 17(57%) participants acquired their infection outside Vietnam. Compared with symptomatic individuals, asymptomatic people were less likely to have detectable SARS-CoV-2 in NTS samples collected at enrolment (8/13 (62%) vs. 17/17 (100%) P=0.02). SARS-CoV-2 RNA was detected in 20/27 (74%) available saliva; 7/11 (64%) in the asymptomatic and 13/16 (81%) in the symptomatic group (P=0.56). Analysis of the probability of RT-PCR positivity showed asymptomatic participants had faster viral clearance than symptomatic participants (P<0.001 for difference over first 19 days). This difference was most pronounced during the first week of follow-up. Two of the asymptomatic individuals appeared to transmit the infection to up to four contacts. Conclusions Asymptomatic SARS-CoV-2 infection is common and can be detected by analysis of saliva or NTS. NTS viral loads fall faster in asymptomatic individuals, but they appear able to transmit the virus to others.

The interplay between bacterial antimicrobial susceptibility, phylogenetics and patient outcome is poorly understood. During a typhoid clinical treatment trial in Nepal, we observed several treatment failures and isolated highly fluoroquinolone-resistant Salmonella Typhi (S. Typhi). Seventy-eight S. Typhi isolates were genome sequenced and clinical observations, treatment failures and fever clearance times (FCTs) were stratified by lineage. Most fluoroquinolone-resistant S. Typhi belonged to a specific H58 subclade. Treatment failure with S. Typhi-H58 was significantly less frequent with ceftriaxone (3/31; 9.7%) than gatifloxacin (15/34; 44.1%)(Hazard Ratio 0.19, p=0.002). Further, for gatifloxacin-treated patients, those infected with fluoroquinolone-resistant organisms had significantly higher median FCTs (8.2 days) than those infected with susceptible (2.96) or intermediately resistant organisms (4.01)(p<0.001). H58 is the dominant S. Typhi clade internationally, but there are no data regarding disease outcome with this organism. We report an emergent new subclade of S. Typhi-H58 that is associated with fluoroquinolone treatment failure.Clinical trial registration: ISRCTN63006567.DOI: http://dx.doi.org/10.7554/eLife.14003.001