Zika Transmission Research Articles

Complete NMR chemical shift assignments of odorant binding protein 22 from the yellow fever mosquito, Aedes aegypti, bound to arachidonic acid

Aedes aegypti mosquitoes are the vector for transmission of Dengue, Zika and chikungunya viruses. These mosquitos feed exclusively on human hosts for a blood meal. Previous studies have established that Dengue virus infection of the mosquito results in increased expression of the odorant binding proteins 22 and 10 within the mosquito salivary gland and silencing of these genes dramatically reduces blood-feeding behaviors. Odorant binding proteins are implicated in modulating the chemosensory perception of external stimuli that regulate behaviors such as host location, feeding and reproduction. However, the role that AeOBP22 plays in the salivary gland is unclear. Here, as a first step to a more complete understanding of the function of AeOBP22, we present the complete backbone and side chain chemical shift assignments of the protein in the complex it forms with arachidonic acid. These assignments reveal that the protein consists of seven α-helices, and that the arachidonic acid is bound tightly to the protein. Comparison with the chemical shift assignments of the apo-form of the protein reveals that binding of the fatty acid is accompanied by a large conformational change in the C-terminal helix, which appears disordered in the absence of lipid. This NMR data provides the basis for determining the structure of AeOBP22 and understanding the nature of the conformational changes that occur upon ligand binding. This information will provide a path to discover novel compounds that can interfere with AeOBP22 function and impact blood feeding by this mosquito.

Congenital Zika syndrome arising from sexual transmission of Zika virus, a case report

BackgroundSexual transmission of Zika virus is well documented and pregnant women are advised to abstain or use barrier protection if a sexual partner has risk for Zika infection. However, to date there has not been a documented case of the congenital Zika syndrome resulting from sexual transmission.Case presentationA 32 year-old woman who had not traveled to any area with local Zika transmission in years became pregnant via frozen embryo transfer. Her husband traveled to Haiti several times prior to embryo transfer and during the pregnancy. Neither partner was ever symptomatic. In her second trimester when recommendations were published by the Centers for Disease Control and Prevention (CDC) regarding prevention of sexual transmission during pregnancy she was counseled to abstain or use barrier protection with her partner. At delivery, the infant head circumference measured less than the first percentile. Placental samples were sent to the CDC and all were positive for Zika RNA by RT-PCR. Evaluation for other causes of microcephaly was negative. Consistent with the most up to date diagnostic parameters for congenital Zika, including viral infection of the placenta, the baby was diagnosed with congenital Zika syndrome.ConclusionsTransmission via sexual contact during assisted reproductive therapies (ART) and pregnancy can result in Zika fetopathy. This case supports recommendations to counsel women undergoing ART and pregnant women to use barrier protection with partners with Zika exposure regardless of their symptoms.

Implication of sexual transmission of Zika on dengue and Zika outbreaks.

Dengue and Zika viruses belong to the same Flavivirus family and usually cocirculate within the same area. Both the viruses can be transmitted by a common mosquito species Aedes aegypti. However, non-vector-borne transmission of Zika virus, such as sexual transmission and vertical transmission, has been reported in recent studies. In this study, we develop a dengue-Zika coinfection model with a particular focus on the impact of Zika sexual transmission to the transmission dynamics of both dengue and Zika. Our sensitivity analysis shows that Zika sexual transmission has a significant influence on the Zika basic reproduction number. Consequently, Zika sexual transmission can lead Zika to be endemic within an area where vector-borne transmission only cannot. Theoretically, we prove that the disease-free equilibrium for dengue only model is always globally stable if the dengue basic reproduction number is less than 1. However, our cascade analysis and numerical simulations show that increasing the sexual transmission coefficient of Zika can also result in the persistence of dengue even though the dengue basic reproduction number is less than 1, due to the cocirculation of dengue and Zika and the antibody-dependent enhancement of Zika infection for dengue infection. Our numerical analyses also show that the endemic levels of Zika increase as the Zika sexual transmission probability increases.

Knowledge of the Sexual Transmission of Zika Virus and Preventive Practices Against Zika Virus Among U.S. Travelers.

Individuals are often at increased risk of acquiring infectious disease while traveling. We sought to understand knowledge, attitudes and practices (KAP) regarding Zika virus among travelers from the United States. A total of 1043 study participants were recruited from a probability-based internet panel. Participants self-reported their knowledge of Zika infection and modes of transmission, and identified actions they had taken to prevent Zika infection and transmission including actions to prevent unintentional pregnancy since becoming aware of the Zika virus. Logistic regression was used to model the odds of taking preventive actions against Zika infection with adjustment for potential confounding factors. Knowledge of the sexual transmissibility of Zika virus significantly increased the odds of taking a preventive action against Zika infection, especially condom use or sexual abstention. Participants reported preferences for receiving information about Zika from private doctors and from the Internet. Discrepancies between where travelers seek information about Zika and how they would like to receive information regarding Zika were also found. These findings suggest that improving targeted messaging through online media may increase awareness of the sexual transmissibility of Zika as well as improve health communications with U.S. travelers. Travelers who are unaware of potential disease risks are less likely to adopt personal protective measures to protect themselves and reduce disease spread. Thus, future work should focus on improving communication and providing education to adopt effective prevention strategies while traveling.

The Effects of Zika Virus Risk Coverage on Familiarity, Knowledge and Behavior in the U.S. – A Time Series Analysis Combining Content Analysis and a Nationally Representative Survey

ABSTRACTThis study assessed the effects of the February through September 2016 American news media’s coverage of Zika Virus (ZIKV) risk on the U.S. public’s familiarity, knowledge and behavior in the form of interpersonal discussions. A content analysis (N = 2,782 pieces) revealed that the Rio Olympic Games elicited a spike in coverage of Zika. We also found that newsworthy and easy- to- depict aspects of the disease, specifically its transmission by mosquitoes and its relation to microcephaly were covered more extensively than its sexual transmission and transmissibility from an infected person who is asymptomatic. Nevertheless, survey data over the same period of time (N = 37,180 respondents) revealed that the general amount of coverage, rather than the specifics about Zika transmission and its consequences, influenced the public’s familiarity, knowledge, and behavior.

Mathematics of a model for Zika transmission dynamics.

Zika is a flavivirus transmitted to humans through either the bite of infected Aedes mosquitoes or sexual intercourse with infected individuals. In this paper, we present a mathematical model based on these two modes of transmission. Using the next-generation matrix method, a threshold parameter called basic reproduction number is determined. Sensitivity analysis of the basic reproduction number in terms of parameters involved in its formulation is discussed. A dynamically consistent nonstandard finite difference scheme is designed to replicate the properties of the continuous model. Numerical simulations of the nonstandard finite difference scheme that we have constructed show the number of infected humans due to sexual intercourse with Zika virus infectious individuals. The numerical simulations also support the theoretical analysis of the model.

Estimating under-observation and the full size of the 2016 Zika epidemic in Rio de Janeiro.

The 2015-16 Zika epidemic spread quickly from north to south in Brazil. Two striking features were the much higher incidence in young adult women due to sexual transmission, and the serious congenital malformations and miscarriages associated to Zika infection in pregnant women. In this paper we use case reporting data along with live-birth records to reconstruct the full size of the epidemic through a Bayesian probabilistic graph model representing the Zika transmission probabilities of observation (case reporting) and of birth loss (through miscarriage or abortion). We find that the probability of observing (reporting) a Zika case is different between men and women and ranges between 10 to 13%. From these estimates we reconstruct the full size of the Zika epidemic in Rio de Janeiro in 2015-16.

Modeling the Spread of Zika Virus in a Stage-Structured Population: Effect of Sexual Transmission.

The recent Zika virus outbreak has been spreading rapidly all over the world, expanding its traditionally geographical affected regions, making it a global public health hazard and endangering millions of people. One unique property of the Zika virus compared to most vector-borne diseases is the fact that the virus is transmitted both by mosquitoes and by direct sexual contact. In the present manuscript, we formulate and analyze five mathematical compartmental models of Zika transmission. We model both transmission routes (i.e., vector-borne and sexual transmission). In order to make the model more realistic, heterogeneity in the sexual transmission is modeled in several ways. We fitted the five different models to data, inferred the parameters and selected the most appropriated model, which describes the Zika outbreak in Columbia. For all the models, we estimate the reproduction numbers, namely direct (sexual) transmission, vector transmission and the basic reproduction number [Formula: see text]. The analysis revealed that the sexual transmission contribution to [Formula: see text] is highest [15.36% (95% CI 12.83-17.4)] for the model which stratifies each gender to high-risk and low-risk individuals in their sexual behavior. For this model, the estimated [Formula: see text] is 1.89 (95% CI 1.21-2.13), the direct transmission reproduction number is 0.42 (95% CI 0.29-0.64), and the vector transmission reproduction number is 1.51 (95% CI 1.23-1.87). The sensitivity analysis demonstrated that the value of [Formula: see text] depends on three controllable parameters: the biting rate, the sexual transmission rate and the average ratio of mosquito to human.

A comparison of mosquito densities, weather and infection rates of Aedes aegypti during the first epidemics of Chikungunya (2014) and Zika (2016) in areas with and without vector control in Puerto Rico

In Puerto Rico, the first records of the transmission of Chikungunya (CHIKV) and Zika (ZIKV) viruses were confirmed in May 2014 and December 2015, respectively. Transmission of CHIKV peaked in September 2014, whereas that of ZIKV peaked in August 2016. The emergence of these mosquito‐transmitted arboviruses in the context of a lack of human population immunity allowed observations of whether the outbreaks were associated with Aedes aegypti (Diptera: Culicidae) densities and weather. Mosquito density was monitored weekly in four communities using sentinel autocidal gravid ovitraps (AGO traps) during 2016 in order to provide data to be compared with the findings of a previous study carried out during the 2014 CHIKV epidemic. Findings in two communities protected against Ae. aegypti using mass AGO trapping (three traps per house in most houses) were compared with those in two nearby communities without vector control. Mosquito pools were collected to detect viral RNA of ZIKV, CHIKV and dengue virus. In areas without vector control, mosquito densities and rates of ZIKV detection in 2016 were significantly higher, similarly to those observed for CHIKV in 2014. The density of Ae. aegypti in treated sites was less than two females/trap/week, which is similar to the putative adult female threshold for CHIKV transmission. No significant differences in mosquito density or infection rates with ZIKV and CHIKV at the same sites between years were observed. Although 2016 was significantly wetter, mosquito densities were similar.

Residential Location and Psychological Distance in Americans' Risk Views and Behavioral Intentions Regarding Zika Virus.

Two 2017 experiments with a U.S. national opportunity sample tested effects of location, psychological distance (PD), and exposure to location-related information on Americans' Zika risk views and behavioral intentions. Location-distance from mosquito transmission of the virus in Florida and Texas; residence within states with 100+ Zika infections; residence within potential mosquito vector ranges-had small, inconsistent effects. Hazard proximity weakly enhanced personal risk judgments and concern about Zika transmission locally. It also increased psychological proximity, and intentions of mosquito control, avoiding travel to Zika-infected areas, and practicing safe sex. PD-particularly social and geographical distance, followed by temporal distance, with few effects for uncertainty-modestly and inconsistently decreased risk views and intentions. Exposure to location-related information from the U.S. Centers for Disease Control and Prevention website-naming states with 100+ Zika cases; maps of potential mosquito vector habitat-increased risk views and psychological closeness, but not intentions; maps had slightly stronger if inconsistent effects versus prevalence information. Structural equation modeling (SEM) of a location > PD > risk views > intention path explained modest variance in intentions. This varied in degree and kind (e.g., which location measures were significant) across behaviors, and between pre- and postinformation exposure analyses. These results suggest need for both theoretical and measurement advances regarding effects of location and PD on risk views and behavior. PD mediates location effects on risk views. Online background information, like that used here, will not enhance protective behavior without explicitly focused communication and perhaps higher objective risk.

Quiescence in Aedes aegypti: Interpopulation Differences Contribute to Population Dynamics and Vectorial Capacity.

The strategy of Aedes aegypti to prolong embryonic viability by quiescence has severe implications for geographic expansion and maintenance of mosquito populations in areas under control measures. We evaluated the effects of quiescence on biological parameters directly or indirectly associated with population dynamics and vectorial capacity in populations of this mosquito species from two Brazilian municipalities characterized as dengue, chikungunya, and Zika transmission areas. Egg viability, initial hatching time, post-embryonic development time, adult emergence rate, sexual proportion, adult size, fecundity, and fertility were analyzed using eggs stored for 10, 40, 70, 100, 130, and 160 d. Quiescence time reduced overall egg viability and post-embryonic development time in both municipalities but was more costly in Aracaju (100 d, 8 d) than in Recife (130 d, 7.5 d). Emergence rates increased in Recife when the eggs were older, but not in Aracaju. Significant deviations in sexual proportion, with male predominance, were observed in both populations. Initial hatch, fecundity, fertility, and adult size did not significantly influence egg quiescence time. These results indicate intrinsic and differential characteristics for each A. aegypti population, suggesting a differential cost of quiescence for population dynamics parameters that can indirectly affect vectorial capacity and control measures.

Serological Evidence of Dengue and West Nile Virus Human Infection in Juarez City, Mexico

Arboviruses are significant causes of human and animal diseases, globally. In the Rio Grande Valley of the United States-Mexico border region, endemic transmission of Dengue (DENV), Zika (ZIKV), and West Nile (WNV) viruses have been documented as a cause of human disease. Otherwise, very little is known about the distribution of arboviruses and their possible cause of human disease in other areas of the United States-Mexico border region. Therefore, a pilot serosurvey was conducted to determine if there was evidence of DENV and WNV infection among a human cohort in Anapra, Ciudad Juarez, Mexico. Baseline blood samples were obtained from 78 participants during May-June, 2015 and from 60 of the same participants again during November-December, 2015, and all the samples were tested for DENV and WNV indirect immunoglobulin G antibodies by an enzyme-linked immunosorbent assay and plaque reduction neutralization test (PRNT). The results showed that 14.1% (n = 11) of the 78 participants had neutralizing antibody to DENV and 5.13% (n = 4) had WNV-neutralizing antibody. Among 48 of 60 participants who were negative for DENV and WNV antibody during the baseline survey, 10.4% (n = 5) had acquired antibody to DENV (n = 4) and WNV (n = 1) by the second survey during November-December, 2015. These data support the local transmission of DENV and WNV in the Anapra, Ciudad Juarez community and therefore warrant further epidemiological studies to better understand the dynamics of transmission of these viruses in this United States-Mexico border city.

"Zika is everywhere": A qualitative exploration of knowledge, attitudes and practices towards Zika virus among women of reproductive age in Iquitos, Peru.

Zika virus was reported in the rainforest city of Iquitos, Peru in 2016. The potential associations between Zika and fetal neurological disorders were reported extensively in the media regarding neighboring Brazil, and led to great concern about the impact Zika could have on people’s health in Iquitos when it arrived. The aim of this study was to explore the knowledge, attitudes, and preventative practices related to Zika virus and its transmission among women of childbearing age in Iquitos, Peru. Six focus group discussions with 46 women of ages 20–35 from an Iquitos district with confirmed Zika cases were conducted to explore: 1) knowledge of Zika transmission, its symptoms, and treatment, 2) attitudes regarding Zika, including perceptions of risk for and severity of Zika, and 3) preventative practices, including awareness of health promotion activities. Participants were knowledgeable about Zika symptoms and knew it was transmitted by mosquitoes, and about half had heard about the association between Zika and microcephaly, but most lacked knowledge about the associated neurological disorders in adults, its sexual transmission, and ways to prevent infection. They expressed concern for pregnant women exposed to the virus and the impact on the fetus. Participants felt at risk of contracting the Zika virus, yet had not changed preventive practices, possibly in part because their perception of the severity of this disease was low. This study reveals knowledge gaps that could be addressed via health promotion messages that might improve prevention practices to help community members protect themselves from Zika virus during this outbreak.

Experimental evaluation of the impact of household aerosolized insecticides on pyrethroid resistant Aedes aegypti

The extensive reliance on insecticides to control Aedes aegypti mosquitoes and disrupt transmission of dengue, chikungunya and Zika has fueled the emergence of widespread resistance to insecticides. Mismatch between the frequency of pyrethroid resistance in mosquitoes and the occurrence of pyrethroid-based insecticide applications for vector control is often hypothesized to be due to household use of commercial insecticide products. We experimentally quantified phenotypic and genotypic responses of four Ae. aegypti strains (three field, pyrethroid resistant, and one laboratory, pyrethroid susceptible) after exposure to two commonly used household aerosol insecticide products (a space spray and a residual spray formulation) containing pyrethroid active ingredients. Experiments were performed within homes of Mérida, Mexico. After exposure to the products, all three pyrethroid resistant field Ae. aegypti strains had significantly lower mortality rates (averaging 41% and 50% for the two products, respectively) than the controls (99%). Applying insecticides as surface sprays led to a significant increase in the frequency of I1016 kdr homozygotes in surviving Ae. aegypti, suggesting strong selection pressure for this allele. Given the large-scale use of household aerosol insecticide products in areas that are endemic for Ae. aegypti–transmitted diseases, their role as a pyrethroid resistance selection source, particularly when used as space sprays, should be taken into consideration when designing resistance management plans.

Temperature drives Zika virus transmission: evidence from empirical and mathematical models.

Temperature is a strong driver of vector-borne disease transmission. Yet, for emerging arboviruses we lack fundamental knowledge on the relationship between transmission and temperature. Current models rely on the untested assumption that Zika virus responds similarly to dengue virus, potentially limiting our ability to accurately predict the spread of Zika. We conducted experiments to estimate the thermal performance of Zika virus (ZIKV) in field-derived Aedes aegypti across eight constant temperatures. We observed strong, unimodal effects of temperature on vector competence, extrinsic incubation period and mosquito survival. We used thermal responses of these traits to update an existing temperature-dependent model to infer temperature effects on ZIKV transmission. ZIKV transmission was optimized at 29°C, and had a thermal range of 22.7°C–34.7°C. Thus, as temperatures move towards the predicted thermal optimum (29°C) owing to climate change, urbanization or seasonality, Zika could expand north and into longer seasons. By contrast, areas that are near the thermal optimum were predicted to experience a decrease in overall environmental suitability. We also demonstrate that the predicted thermal minimum for Zika transmission is 5°C warmer than that of dengue, and current global estimates on the environmental suitability for Zika are greatly over-predicting its possible range.

Managing Aedes aegypti populations in the first Zika transmission zones in the continental United States

The African Zika virus swept across the Pacific, reaching the New World in 2014. In July, 2016, Miami-Dade County, Florida became the locus of the first mosquito-borne Zika transmission zones in the continental United States. Control efforts were guided by the Centers for Disease Control and Prevention, including aerial and truck sprays of adulticides and larvicides. To improve our understanding of how best to fight Zika transmission in an urban environment in the developed world, trap counts of adult Aedes (Stegomyia) aegypti (L.) mosquitoes from the treatment zones were analyzed to determine efficacy of the different insecticide treatments. Analysis revealed that application of four different ester pyrethroid and one non-ester pyrethroid had no statistically significant effect on mosquito counts. Aerial application of naled, a potent organophosphate adulticide, produced significant but short-lived drops in Ae. aegypti counts in the first two applications in the first active transmission zone (Wynwood), then lost some efficacy with subsequent application. In the other active transmission zone (Miami Beach), naled produced no measurable effect in the first three applications, and only a small, transient, and marginally significant reduction in the fourth application. Repeated application of the larvicidal bacterium Bti was accompanied by steady declines of Ae. aegypti populations in both sites. Zika transmission ceased in the first transmission zone, but expanded in the second transmission zone during this period. Specific recommendations are proposed for future treatments of urban mosquitoes.

Modelling the distribution of the vector Aedes aegypti in a central Argentine city.

Aedes aegypti (Diptera: Culicidae) is an urban mosquito involved in the transmission of numerous viruses, including dengue, chikungunya and Zika. In Argentina, Ae.aegypti is the main vector of dengue virus and has been involved in several outbreaks in regions ranging from northern to central Argentina since 2009. In order to evaluate areas of potential vector-borne disease transmission in the city of Córdoba, Argentina, the present study aimed to identify the environmental, socioeconomic and demographic factors driving the distribution of Ae.aegypti larvae through spatial analysis in the form of species distribution models (SDMs). These models elucidate relationships between known occurrences of a species and environmental data in order to identify areas with suitable habitats for that species and the consequent risk for disease transmission. The maximum entropy species distribution model was able to fit the training data well, with an average area under the receiver operating characteristic curve (AUC) of > 0.8, and produced models with fair extrapolation capacity (average test AUC: > 0.75). Human population density, distance to vegetation and water channels were the main variables predictive of the vector suitability of an area. The results of this work will be used to target surveillance and prevention measures, as well as in mosquito management.

Exploring satellite based temporal forecast modelling of Aedes aegypti oviposition from an operational perspective

Aedes aegypti, responsible for the transmission of Chikungunya, Dengue, and Zika in Latin America, represents a large public health problem for the region. For this reason, several efforts have been made to use geospatial technologies to support vector control actions developed by the public health sector.Therefore, this study establishes the base for the application of freely available remotely sensed products to assess Ae. aegypti oviposition activity from an operational perspective for the entire north region of Argentina (region with a high risk of arbovirus transmission). In particular, we improve, in several aspects from an operative vision, previous studies with a concurrent objective.This study includes Normalized Difference Vegetation Index (NDVI), Normalized Difference Water Index (NDWI), day and night Land Surface Temperature (LST) from Moderate Resolution Imaging Spectroradiometer (MODIS, and Tropical Rain Measurement Mission (TRMM)) / Global Precipitation Measurement (GPM) as remotely sensed (RS) variables in addition to integral LST variables for modelling a set of four years of weekly oviposition data (August 2011 – July 2015).From an initial set of 42 variables (the original RS and their lags), a subset of 11 variables were selected and retained based on the correlation between them and the oviposition series. Using these data as independent variables, we develop temporal forecasting models of Ae. aegypti oviposition using a linear multivariate method, including its validation. Several models for different time periods were obtained and a final model with prediction capacity (R2 = 0.7, p < 0.05) was established.With these results, an improved, complete set of satellite derived variables was established as the basis for the national operational risk system that was already being used in Argentina which could be used for health decision makers to develop oriented control actions.

Legacy and social media respectively influence risk perceptions and protective behaviors during emerging health threats: A multi-wave analysis of communications on Zika virus cases

ObjectiveBoth legacy media, such as television and newspapers, and online social media are potentially important but incompletely understood sources of information in the face of emerging public health risks. This research aimed to understand media effects on risk perceptions and behaviors concerning the Zika virus in the United States. MethodsWe analyzed a multi-wave nationally representative survey (N = 29,062) and the volume of communications in social and legacy media (i.e., legacy media data from news sources and databases, N = 2,660 and social media data from Twitter, N = 1,605,752) in the United States between April and October 2016, dates coinciding with the early cases of local transmission of Zika in the United States (i.e., 25 weeks). The present study conducted econometric analyses (i.e., Granger causality tests) to assess the associations of legacy and social media coverage with risk perceptions and protective behaviors in the total sample and specific groups separated by pregnancy status/intent, geographic region, income, education level, age, and ethnicity. ResultsThe results from the overall sample suggested that changes in the volume of information in legacy and social media (i.e., Twitter) were followed by different changes in community risk perceptions and protective behaviors. Specifically, social media coverage correlated with the level of risk perceptions, whereas the legacy media coverage correlated with the level of protective behaviors. Analyses across different subpopulations, including those of different pregnancy status/intent, geographic Zika risk, income, education level, age, and ethnicity, replicated the social media associations with risk perceptions in most cases. However, legacy media and protective behaviors were linked only in some vulnerable subpopulations (e.g., the less-educated populations). ConclusionUnderstanding how media coverage relates to Zika risk perceptions and protective behaviors will help to facilitate effective risk communications by healthcare professionals and providers, particularly when a health risk emerges.

Estimating underobservation and the full size of the 2016 Zika epidemic in Rio de Janeiro

Introduction The 2015–16 Zika epidemic in Rio de Janeiro followed a quick spread of the disease throughout Brazil from north to south. One of the striking features of this epidemic was the much higher incidence in young adult women, attributed to sexual transmission, and the serious congenital malformations and miscarriages associated to Zika infection in pregnant women. Methods In this paper we use case reporting data along with live birth records to reconstruct the full size of the Zika epidemic through a Bayesian probabilistic graph model representing Zika transmission in this context. Based on the rate of lost pregnancies estimated from the deviations of the weekly birth rate from historical means, we estimated the probabilities of observation (case reporting) of a Zika case on women of fertile age. Results We find that the probability of observing (reporting) a Zika case is different between men and women and ranges between 10 to 13%. From these estimates we reconstruct the full Zika epidemic size in Rio de Janeiro in 2015–16. Conclusion The high underreporting rate helps explain the quick spread of Zika through Brazil and later through South America. The epidemic was much bigger than reported likely due to the contribution of sexual transmission and the long infectious periods of men.