Does ignoring transmission dynamics lead to underestimation of the impact of interventions against mosquito-borne disease?

New vector-control technologies to fight mosquito-borne diseases are urgently needed, the adoption of which depends on efficacy estimates from large-scale cluster-randomised trials (CRTs). The release of Wolbachia-infected mosquitoes is one promising strategy to curb dengue virus (DENV) transmission, and a recent CRT reported impressive reductions in dengue incidence following the release of these mosquitoes. Such trials can be affected by multiple sources of bias, however. We used mathematical models of DENV transmission during a CRT of Wolbachia-infected mosquitoes to explore three such biases: human movement, mosquito movement and coupled transmission dynamics between trial arms. We show that failure to account for each of these biases would lead to underestimated efficacy, and that the majority of this underestimation is due to a heretofore unrecognised bias caused by transmission coupling. Taken together, our findings suggest that Wolbachia-infected mosquitoes could be even more promising than the recent CRT suggested. By emphasising the importance of accounting for transmission coupling between arms, which requires a mathematical model, we highlight the key role that models can play in interpreting and extrapolating the results from trials of vector control interventions.

Expected endpoints from future chikungunya vaccine trial sites informed by serological data and modeling.

In recent decades, there has been an increased interest in developing a vaccine for chikungunya. However, due to its unpredictable transmission, planning for a chikungunya vaccine trial is challenging. To inform decision making on the selection of sites for a vaccine efficacy trial, we developed a new framework for projecting the expected number of endpoint events at a given site. In this framework, we first accounted for population immunity using serological data collated from a systematic review and used it to estimate parameters related to the timing and size of past outbreaks, as predicted by an SIR transmission model. Then, we used that model to project the infection attack rate of a hypothetical future outbreak, in the event that one were to occur at the time of a future trial. This informed projections of how many endpoint events could be expected if a trial were to take place at that site. Our results suggest that some sites may have sufficient transmission potential and susceptibility to support future vaccine trials, in the event that an outbreak were to occur at those sites. In general, we conclude that sites that have experienced outbreaks within the past 10 years may be poorer targets for chikungunya vaccine efficacy trials in the near future. Our framework also generates projections of the numbers of endpoint events by age, which could inform study participant recruitment efforts.

Lying in wait: the resurgence of dengue virus after the Zika epidemic in Brazil.

After the Zika virus (ZIKV) epidemic in the Americas in 2016, both Zika and dengue incidence declined to record lows in many countries in 2017-2018, but in 2019 dengue resurged in Brazil, causing ~2.1 million cases. In this study we use epidemiological, climatological and genomic data to investigate dengue dynamics in recent years in Brazil. First, we estimate dengue virus force of infection (FOI) and model mosquito-borne transmission suitability since the early 2000s. Our estimates reveal that DENV transmission was low in 2017-2018, despite conditions being suitable for viral spread. Our study also shows a marked decline in dengue susceptibility between 2002 and 2019, which could explain the synchronous decline of dengue in the country, partially as a result of protective immunity from prior ZIKV and/or DENV infections. Furthermore, we performed phylogeographic analyses using 69 newly sequenced genomes of dengue virus serotype 1 and 2 from Brazil, and found that the outbreaks in 2018-2019 were caused by local DENV lineages that persisted for 5-10 years, circulating cryptically before and after the Zika epidemic. We hypothesize that DENV lineages may circulate at low transmission levels for many years, until local conditions are suitable for higher transmission, when they cause major outbreaks.

Estimating the health impact of vaccination against ten pathogens in 98 low-income and middle-income countries from 2000 to 2030: a modelling study.

BACKGROUND: The past two decades have seen expansion of childhood vaccination programmes in low-income and middle-income countries (LMICs). We quantify the health impact of these programmes by estimating the deaths and disability-adjusted life-years (DALYs) averted by vaccination against ten pathogens in 98 LMICs between 2000 and 2030. METHODS: 16 independent research groups provided model-based disease burden estimates under a range of vaccination coverage scenarios for ten pathogens: hepatitis B virus, Haemophilus influenzae type B, human papillomavirus, Japanese encephalitis, measles, Neisseria meningitidis serogroup A, Streptococcus pneumoniae, rotavirus, rubella, and yellow fever. Using standardised demographic data and vaccine coverage, the impact of vaccination programmes was determined by comparing model estimates from a no-vaccination counterfactual scenario with those from a reported and projected vaccination scenario. We present deaths and DALYs averted between 2000 and 2030 by calendar year and by annual birth cohort. FINDINGS: We estimate that vaccination of the ten selected pathogens will have averted 69 million (95% credible interval 52-88) deaths between 2000 and 2030, of which 37 million (30-48) were averted between 2000 and 2019. From 2000 to 2019, this represents a 45% (36-58) reduction in deaths compared with the counterfactual scenario of no vaccination. Most of this impact is concentrated in a reduction in mortality among children younger than 5 years (57% reduction [52-66]), most notably from measles. Over the lifetime of birth cohorts born between 2000 and 2030, we predict that 120 million (93-150) deaths will be averted by vaccination, of which 58 million (39-76) are due to measles vaccination and 38 million (25-52) are due to hepatitis B vaccination. We estimate that increases in vaccine coverage and introductions of additional vaccines will result in a 72% (59-81) reduction in lifetime mortality in the 2019 birth cohort. INTERPRETATION: Increases in vaccine coverage and the introduction of new vaccines into LMICs have had a major impact in reducing mortality. These public health gains are predicted to increase in coming decades if progress in increasing coverage is sustained. FUNDING: Gavi, the Vaccine Alliance and the Bill & Melinda Gates Foundation.

Predictive value of the sFlt-1 and PlGF in women at risk for preeclampsia in the south of Vietnam.

BACKGROUND: It has been suggested that soluble fms-like tyrosine kinase receptor-1 (sFlt-1) and placental growth factor (PlGF) play potential roles in preeclampsia diagnosis. Nevertheless, studies on the use of sFlt-1, PlGF, and sFlt-1/PlGF ratio in predicting preeclampsia have found contradictory results. Thus, more studies in different populations are needed. OBJECTIVES: This study aims to (i) examine the associations between sFlt-1, PlGF, or sFlt-1/PlGF ratio at gestational ages of 24-28 weeks and subsequent preeclampsia, and (ii) estimate predictive values of these markers in southern Vietnamese women. METHODS: We used a nested case-control design from a cohort of 490 pregnant women who were at risk of preeclampsia. The total sample size for statistical analysis consisted of 30 cases and 67controls. Levels of sFlt-1 and PlGF were quantified by using a fully automated electrochemiluminescence immunoassay platform (Elecsys®/Cobas®). RESULTS: The median of sFlt-1 concentration was not statistically different between case and control groups. The median PlGF concentration was lower (349.7 pg/ml versus 534.6 pg/ml, P < .001) and the median sFlt-1/PlGF ratio was higher in the preeclampsia group (4.3 versus 1.9, P < .001). After adjusting for maternal age, gestational age, nullipara, and body mass index, the odds of preeclampsia in women with an sFlt-1/PlGF ratio in the fourth quartile were 10 times greater than in women with an sFlt-1/PlGF ratio in the other quartiles (95% confidence interval, 3.2-31.4; P < .001). CONCLUSIONS: This study contributes to the literature that sFlt-1/PlGF ratio measured at gestational weeks 24-28 in southern Vietnamese women can separate preeclamptic from normotensive cases.

Women's communication self-efficacy and expectations of primary male partners' cooperation in sexually transmitted infection treatment in Ho Chi Minh City, Vietnam: a cross-sectional study.

BACKGROUND: Effective control of sexually transmitted infections (STIs) depends on affected patients notifying their sexual partners, and partners following through with screening and treatment. Our study assessed high-risk-STI women's confidence in STI-diagnosis-related communications with their primary male partners in Ho Chi Minh City, Vietnam, and determined associated characteristics of the women and their partners. METHODS: We employed convenience and snowball sampling in a clinic-based setting to recruit 126 women from August to October 2013. All data were obtained from women's self-report. RESULTS: The proportions of participants who were "slightly confident" or "very confident" that they could disclose their STI positivity to partners, ask partners to have an STI examination or treatment, and give partners bacterial-STI medications were 70.3%, 62.1%, and 69.0%, respectively. The proportions who perceived that their partners would be "very likely" to have an STI examination and to take STI medications were 16.2% and 38.8%, respectively. Significantly lower self-efficacy was observed in women who had a lower education level, who had ever traded sex, or whose primary partners were not husbands or fiancés. CONCLUSIONS: Our results suggest potential for piloting STI-partner-targeted interventions. To be effective, these programs should improve women's self-efficacy and primary partners' cooperation with screening and treatment.

Self-reported oral health, oral hygiene, and oral HPV infection in at-risk women in Ho Chi Minh City, Vietnam.

OBJECTIVES: This study aimed to examine the relationships among self-reported oral health, oral hygiene practices, and oral human papillomavirus (HPV) infection in women at risk for sexually transmitted infections (STIs) in Ho Chi Minh City, Vietnam. STUDY DESIGN: Convenience and referral sampling methods were used in a clinic-based setting to recruit 126 women aged 18-45 years between August and October 2013. Behavioral factors were self-reported. Oral-rinse samples were tested for HPV DNA of 2 low-risk and 13 high-risk genotypes. RESULTS: A higher unadjusted prevalence of oral HPV infection was associated with poorer self-rated overall oral health (P = .001), reported oral lesions or problems in the past year (P = .001), and reported a tooth loss not because of injury (P = .001). Higher unadjusted prevalence of oral HPV infection was also associated with two measures of oral hygiene: lower frequencies of toothbrushing per day (P = .047) and gargling without toothbrushing (P = .037). After adjusting for other factors in multivariable logistic regression models, poorer self-rated overall oral health remained statistically associated with oral HPV infection (P = .042); yet the frequency of tooth-brushing per day did not (P = .704). CONCLUSION: Results corroborate the association between self-reported poor oral health and oral HPV infection. The effect of oral hygiene on oral HPV infection remains inconclusive.