The seroepidemiology of dengue in a US military population based in Puerto Rico during the early phase of the Zika pandemic.

Understanding the burden and risk factors of dengue virus (DENV) infection in Puerto Rico is important for the prevention of dengue in local, traveler and military populations. Using sera from the Department of Defense Serum Repository, we estimated the prevalence and predictors of DENV seropositivity in those who had served in Puerto Rico, stratified by birth or prior residence ("birth/residence") in dengue-endemic versus non-endemic regions. We selected sera collected in early 2015 from 500 U.S. military members, a time-point also permitting detection of early cryptic Zika virus (ZIKV) circulation. 87.2% were born or resided in a DENV-endemic area before their military service in Puerto Rico. A high-throughput, flow-cytometry-based neutralization assay was employed to screen sera for ZIKV and DENV neutralizing antibodies, and confirmatory testing was done by plaque-reduction neutralization test (PRNT). We identified one Puerto Rico resident who seroconverted to ZIKV by June 2015, suggesting cryptic ZIKV circulation in Puerto Rico at least 4 months before the first reported cases. A further six PRNT-positive presumptive ZIKV infections which were resolved as DENV infections only by the use of paired sera. We noted 66.8% of the total study sample was DENV seropositive by early 2015. Logistic regression analysis indicated that birth/residence in a dengue non-endemic region (before military service in Puerto Rico) was associated with a lower odds of DENV exposure by January-June 2015 (aOR = 0.28, p = 0.001). Among those with birth/residence in a non-endemic country, we noted moderate evidence to support increase in odds of DENV exposure for each year of military service in Puerto Rico (aOR = 1.58, p = 0.06), but no association with age. In those with birth/residence in dengue-endemic regions (before military service in Puerto Rico), we noted that age (aOR = 1.04, p = 0.02), rather than duration of Puerto Rico service, was associated with dengue seropositivity, suggesting earlier lifetime DENV exposure. Our findings provide insights into the burden and predictors of DENV infection in local, traveler and military populations in Puerto Rico. Our study also highlights substantial PRNT ZIKV false-positivity when paired sera are not available, even during periods of very low ZIKV prevalence.

A systematic review and meta-analysis of the potential non-human animal reservoirs and arthropod vectors of the Mayaro virus.

Improving our understanding of Mayaro virus (MAYV) ecology is critical to guide surveillance and risk assessment. We conducted a PRISMA-adherent systematic review of the published and grey literature to identify potential arthropod vectors and non-human animal reservoirs of MAYV. We searched PubMed/MEDLINE, Embase, Web of Science, SciELO and grey-literature sources including PAHO databases and dissertation repositories. Studies were included if they assessed MAYV virological/immunological measured occurrence in field-caught, domestic, or sentinel animals or in field-caught arthropods. We conducted an animal seroprevalence meta-analysis using a random effects model. We compiled granular georeferenced maps of non-human MAYV occurrence and graded the quality of the studies using a customized framework. Overall, 57 studies were eligible out of 1523 screened, published between the years 1961 and 2020. Seventeen studies reported MAYV positivity in wild mammals, birds, or reptiles and five studies reported MAYV positivity in domestic animals. MAYV positivity was reported in 12 orders of wild-caught vertebrates, most frequently in the orders Charadriiformes and Primate. Sixteen studies detected MAYV in wild-caught mosquito genera including Haemagogus, Aedes, Culex, Psorophora, Coquillettidia, and Sabethes. Vertebrate animals or arthropods with MAYV were detected in Brazil, Panama, Peru, French Guiana, Colombia, Trinidad, Venezuela, Argentina, and Paraguay. Among non-human vertebrates, the Primate order had the highest pooled seroprevalence at 13.1% (95% CI: 4.3-25.1%). From the three most studied primate genera we found the highest seroprevalence was in Alouatta (32.2%, 95% CI: 0.0-79.2%), followed by Callithrix (17.8%, 95% CI: 8.6-28.5%), and Cebus/Sapajus (3.7%, 95% CI: 0.0-11.1%). We further found that MAYV occurs in a wide range of vectors beyond Haemagogus spp. The quality of evidence behind these findings was variable and prompts calls for standardization of reporting of arbovirus occurrence. These findings support further risk emergence prediction, guide field surveillance efforts, and prompt further in-vivo studies to better define the ecological drivers of MAYV maintenance and potential for emergence.

Military Participation in Health Security: Analysis of Joint External Evaluation Reports and National Action Plans for Health Security.

Militaries around the world play an important but at times poorly defined and underappreciated role in global health security. They are often called upon to support civilian authorities in humanitarian crises and to provide routine healthcare for civilians. Military personnel are a unique population in a health security context, as they are highly mobile and often deploy to austere settings domestically and internationally, which may increase exposure to endemic and emerging infectious diseases. Despite the role of militaries, few studies have systematically evaluated their involvement in global health security activities including the Global Health Security Agenda. We analyzed Joint External Evaluation (JEE) mission reports (n = 94) and National Action Plan for Health Security plans (n = 12), published as of July 2020, to determine the extent to which military organizations were involved in the evaluation process, military involvement in health security activities were described, and specific recommendations were provided for the country's military. For JEE reports, descriptions of military involvement were highest in 3 of the 4 core areas: Respond (76%), Prevent (39%), and Detect (32%). Similarly, National Action Plan for Health Security plans mentioned military involvement in the same 3 core areas: Respond (58%), Prevent (33%), and Detect (33%). Only 28% of JEE reports provided recommendations for the military in any of the core areas. Our results indicate that military roles and contributions are incorporated into some aspects of country-level health security activities, but that more extensive involvement may be warranted to improve national capabilities to prevent, detect, and respond to infectious disease threats.

Author Correction: Global disease outbreaks associated with the 2015-2016 El Niño Event.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

The impact of insecticide treated curtains on dengue virus transmission: A cluster randomized trial in Iquitos, Peru.

Dengue is one of the most important vector-borne diseases, resulting in an estimated hundreds of millions of infections annually throughout the tropics. Control of dengue is heavily dependent upon control of its primary mosquito vector, Aedes aegypti. Innovative interventions that are effective at targeting the adult stage of the mosquito are needed to increase the options for effective control. The use of insecticide-treated curtains (ITCs) has previously been shown to significantly reduce the abundance of Ae. aegypti in and around homes, but the impact of ITCs on dengue virus (DENV) transmission has not been rigorously quantified. A parallel arm cluster-randomized controlled trial was conducted in Iquitos, Peru to quantify the impact of ITCs on DENV seroconversion as measured through plaque-reduction neutralization tests. Seroconversion data showed that individuals living in the clusters that received ITCs were at greater risk to seroconverting to DENV, with an average seroconversion rate of 50.6 per 100 person-years (PY) (CI: 29.9-71.9), while those in the control arm had an average seroconversion rate of 37.4 per 100 PY (CI: 15.2-51.7). ITCs lost their insecticidal efficacy within 6 months of deployment, necessitating re-treatment with insecticide. Entomological indicators did not show statistically significant differences between ITC and non-ITC clusters. It's unclear how the lack of protective efficacy reported here is attributable to simple failure of the intervention to protect against Ae. aegypti bites, or the presence of a faulty intervention during much of the follow-up period. The higher risk of dengue seroconversion that was detected in the ITC clusters may have arisen due to a false sense of security that inadvertently led to less routine protective behaviors on the part of households that received the ITCs. Our study provides important lessons learned for conducting cluster randomized trials for vector control interventions against Aedes-transmitted virus infections.

A systematic review and evaluation of Zika virus forecasting and prediction research during a public health emergency of international concern.

INTRODUCTION: Epidemic forecasting and prediction tools have the potential to provide actionable information in the midst of emerging epidemics. While numerous predictive studies were published during the 2016-2017 Zika Virus (ZIKV) pandemic, it remains unknown how timely, reproducible, and actionable the information produced by these studies was. METHODS: To improve the functional use of mathematical modeling in support of future infectious disease outbreaks, we conducted a systematic review of all ZIKV prediction studies published during the recent ZIKV pandemic using the PRISMA guidelines. Using MEDLINE, EMBASE, and grey literature review, we identified studies that forecasted, predicted, or simulated ecological or epidemiological phenomena related to the Zika pandemic that were published as of March 01, 2017. Eligible studies underwent evaluation of objectives, data sources, methods, timeliness, reproducibility, accessibility, and clarity by independent reviewers. RESULTS: 2034 studies were identified, of which n = 73 met the eligibility criteria. Spatial spread, R0 (basic reproductive number), and epidemic dynamics were most commonly predicted, with few studies predicting Guillain-Barré Syndrome burden (4%), sexual transmission risk (4%), and intervention impact (4%). Most studies specifically examined populations in the Americas (52%), with few African-specific studies (4%). Case count (67%), vector (41%), and demographic data (37%) were the most common data sources. Real-time internet data and pathogen genomic information were used in 7% and 0% of studies, respectively, and social science and behavioral data were typically absent in modeling efforts. Deterministic models were favored over stochastic approaches. Forty percent of studies made model data entirely available, 29% provided all relevant model code, 43% presented uncertainty in all predictions, and 54% provided sufficient methodological detail to allow complete reproducibility. Fifty-one percent of predictions were published after the epidemic peak in the Americas. While the use of preprints improved the accessibility of ZIKV predictions by a median of 119 days sooner than journal publication dates, they were used in only 30% of studies. CONCLUSIONS: Many ZIKV predictions were published during the 2016-2017 pandemic. The accessibility, reproducibility, timeliness, and incorporation of uncertainty in these published predictions varied and indicates there is substantial room for improvement. To enhance the utility of analytical tools for outbreak response it is essential to improve the sharing of model data, code, and preprints for future outbreaks, epidemics, and pandemics.

Global Disease Outbreaks Associated with the 2015-2016 El Niño Event.

Interannual climate variability patterns associated with the El Niño-Southern Oscillation phenomenon result in climate and environmental anomaly conditions in specific regions worldwide that directly favor outbreaks and/or amplification of variety of diseases of public health concern including chikungunya, hantavirus, Rift Valley fever, cholera, plague, and Zika. We analyzed patterns of some disease outbreaks during the strong 2015-2016 El Niño event in relation to climate anomalies derived from satellite measurements. Disease outbreaks in multiple El Niño-connected regions worldwide (including Southeast Asia, Tanzania, western US, and Brazil) followed shifts in rainfall, temperature, and vegetation in which both drought and flooding occurred in excess (14-81% precipitation departures from normal). These shifts favored ecological conditions appropriate for pathogens and their vectors to emerge and propagate clusters of diseases activity in these regions. Our analysis indicates that intensity of disease activity in some ENSO-teleconnected regions were approximately 2.5-28% higher during years with El Niño events than those without. Plague in Colorado and New Mexico as well as cholera in Tanzania were significantly associated with above normal rainfall (p < 0.05); while dengue in Brazil and southeast Asia were significantly associated with above normal land surface temperature (p < 0.05). Routine and ongoing global satellite monitoring of key climate variable anomalies calibrated to specific regions could identify regions at risk for emergence and propagation of disease vectors. Such information can provide sufficient lead-time for outbreak prevention and potentially reduce the burden and spread of ecologically coupled diseases.

Cluster of vivax malaria in U.S. soldiers training near the demilitarized zone, Republic of Korea during 2015.

This report describes a cluster of 11 soldiers with vivax malaria among U.S. military personnel who trained at Dagmar North training area, near the demilitarized zone (DMZ), in the Republic of Korea (ROK) in 2015. Two cases were diagnosed in the ROK in 2015, one of whom subsequently experienced a relapse, and nine other cases were diagnosed in 2016, 8-11 months after the soldiers had returned to the U.S. Vivax malaria poses a health threat to U.S. Forces Korea operating near the DMZ in the ROK. Continuing and enhanced focus on force health protection measures in endemic zones is warranted.

Molecular and antigenic characterization of group C orthobunyaviruses isolated in Peru.

Group C orthobunyaviruses (GRCVs) are a complex of viruses in the genus Orthobunyavirus and are associated with human febrile disease in tropical and subtropical areas of South and Central America. While numerous GRCVs have been isolated from mosquitoes, animals, and humans, genetic analysis of these viruses is limited. In this study, we characterized 65 GRCV isolates from febrile patients identified through clinic-based surveillance in the northern and southern Peruvian Amazon. A 500 base pair region of the S segment and 750 base pair regions of the M and L segments were sequenced. Pairwise sequence analysis of the clinical isolates showed nucleotide identities ranging from 68% to 100% and deduced amino acid sequence identities ranging from 72% to 100%. Sequences were compared with reference strains of the following GRCVs: Caraparu virus (CARV), Murutucu virus (MURV), Oriboca virus (ORIV), Marituba virus (MTBV), Itaqui virus (ITQV), Apeu virus (APEUV), and Madrid virus (MADV). Sequence comparison of clinical isolates with the prototype strains based on the S and L segments identified two clades; clade I included isolates with high genetic association with CARV-MADV, and clade II included isolates with high genetic association with MURV, ORIV, APEUV, and MTBV. Genetic relationships based on the M segment were at time inconsistent with those based on the S and L segments. However, clade groupings based on the M segment were highly consistent with relationships based on microneutralization assays. These results advance our understanding of the genetic and serologic relationships of GRCVs circulating in the Peruvian Amazon.

Prevalence and molecular characterization of Staphylococcus aureus in commercially available meat over a one-year period in Iowa, USA.

Methicillin-resistant Staphylococcus aureus (MRSA) is a leading cause of infectious disease morbidity and mortality. Previous studies have confirmed the presence of S. aureus, including MRSA, on raw meat products. We investigated the prevalence and molecular epidemiology of S. aureus and MRSA in commercially-distributed antibiotic-free and conventional raw meat products (n = 3290) purchased in 8 Iowa retail stores weekly for a period of one year. Isolates were characterized using spa typing, and PCR was used to detect the presence of the Panton-Valentine leukocidin (PVL) and mecA genes. Quantitation of S. aureus on meat products was carried out one week per month. The prevalence of S. aureus on meat samples was 27.8% (913/3290). Compared to antibiotic-free meat samples, higher prevalence of both MRSA and methicillin-susceptible S. aureus (MSSA) were found in conventional meat samples. Among the S. aureus isolates, 18 were PVL-positive (1.9%) and 41 (4.5%) carried mecA. Phenotypic oxacillin resistance was observed for 17.1% (41/239) of the isolates tested, while 23% (55/239) were multi-drug resistant. A total of 132 spa types were detected from 913 contaminated meat samples. Overall, t002 was the most common spa type identified (137; 15.0%). The number of colony-forming units (CFU) per 10 g meat ranged from 2 to 517 (median: 8 CFU per 10 g of meat; mean: 28) with the highest bacterial load observed on turkey samples. These data reinforce the need to consider meat products as potential vehicles of S. aureus transmission from farm into human households, and the potential need for public health intervention programs pre and post-slaughter in meat processing facilities.

Genome Sequence of Bellavista Virus, a Novel Orthobunyavirus Isolated from a Pool of Mosquitoes Captured near Iquitos, Peru.

A novel orthobunyavirus, Bellavista virus, was isolated from Culex (Melanoconion) portesi mosquitoes in the Bellavista neighborhood of Iquitos, Peru, in 2009. The assembled segment L, M, and S sequences of strain PRD0552 are 6,950, 4,469, and 1,256 bases in length, respectively, comprising complete protein-coding sequences and partial terminal untranslated sequences.

Calling in sick: impacts of fever on intra-urban human mobility.

Pathogens inflict a wide variety of disease manifestations on their hosts, yet the impacts of disease on the behaviour of infected hosts are rarely studied empirically and are seldom accounted for in mathematical models of transmission dynamics. We explored the potential impacts of one of the most common disease manifestations, fever, on a key determinant of pathogen transmission, host mobility, in residents of the Amazonian city of Iquitos, Peru. We did so by comparing two groups of febrile individuals (dengue-positive and dengue-negative) with an afebrile control group. A retrospective, semi-structured interview allowed us to quantify multiple aspects of mobility during the two-week period preceding each interview. We fitted nested models of each aspect of mobility to data from interviews and compared models using likelihood ratio tests to determine whether there were statistically distinguishable differences in mobility attributable to fever or its aetiology. Compared with afebrile individuals, febrile study participants spent more time at home, visited fewer locations, and, in some cases, visited locations closer to home and spent less time at certain types of locations. These multifaceted impacts are consistent with the possibility that disease-mediated changes in host mobility generate dynamic and complex changes in host contact network structure.

Incomplete Protection against Dengue Virus Type 2 Re-infection in Peru.

BACKGROUND: Nearly half of the world's population is at risk for dengue, yet no licensed vaccine or anti-viral drug is currently available. Dengue is caused by any of four dengue virus serotypes (DENV-1 through DENV-4), and infection by a DENV serotype is assumed to provide life-long protection against re-infection by that serotype. We investigated the validity of this fundamental assumption during a large dengue epidemic caused by DENV-2 in Iquitos, Peru, in 2010-2011, 15 years after the first outbreak of DENV-2 in the region. METHODOLOGY/PRINCIPAL FINDINGS: We estimated the age-dependent prevalence of serotype-specific DENV antibodies from longitudinal cohort studies conducted between 1993 and 2010. During the 2010-2011 epidemic, active dengue cases were identified through active community- and clinic-based febrile surveillance studies, and acute inapparent DENV infections were identified through contact tracing studies. Based on the age-specific prevalence of DENV-2 neutralizing antibodies, the age distribution of DENV-2 cases was markedly older than expected. Homologous protection was estimated at 35.1% (95% confidence interval: 0%-65.2%). At the individual level, pre-existing DENV-2 antibodies were associated with an incomplete reduction in the frequency of symptoms. Among dengue cases, 43% (26/66) exhibited elevated DENV-2 neutralizing antibody titers for years prior to infection, compared with 76% (13/17) of inapparent infections (age-adjusted odds ratio: 4.2; 95% confidence interval: 1.1-17.7). CONCLUSIONS/SIGNIFICANCE: Our data indicate that protection from homologous DENV re-infection may be incomplete in some circumstances, which provides context for the limited vaccine efficacy against DENV-2 in recent trials. Further studies are warranted to confirm this phenomenon and to evaluate the potential role of incomplete homologous protection in DENV transmission dynamics.

Swine Farming Is a Risk Factor for Infection With and High Prevalence of Carriage of Multidrug-Resistant Staphylococcus aureus.

BACKGROUND: Livestock-associated Staphylococcus aureus (LA-SA) has been documented worldwide. However, much remains unknown about LA-SA colonization and infection, especially in rural environments. METHODS: We conducted a large-scale prospective study of 1342 Iowans, including individuals with livestock contact and a community-based comparison group. Nasal and throat swabs were collected to determine colonization at enrollment, and skin infection swabs over 17 months were assessed for S. aureus. Outcomes included carriage of S. aureus, methicillin-resistant S. aureus (MRSA), tetracycline-resistant S. aureus (TRSA), multidrug-resistant S. aureus (MDRSA), and LA-SA. RESULTS: Of 1342 participants, 351 (26.2%; 95% confidence interval [CI], 23.8%-28.6%) carried S. aureus. MRSA was isolated from 34 (2.5%; 95% CI, 1.8%-3.5%) and LA-SA from 131 (9.8%; 95% CI, 8.3%-11.5%) of the 1342 participants. Individuals with current swine exposure were significantly more likely to carry S. aureus (prevalence ratio [PR], 1.8; 95% CI, 1.4-2.2), TRSA (PR, 8.4; 95% CI, 5.6-12.6), MDRSA (PR, 6.1; 95% CI, 3.8-10.0), and LA-SA (PR, 5.8; 95% CI, 3.9-8.4) than those lacking exposure. Skin infections (n = 103) were reported from 67 individuals, yielding an incidence rate of 6.6 (95% CI, 4.9-8.9) per 1000 person-months. CONCLUSIONS: Current swine workers are 6 times more likely to carry MDRSA than those without current swine exposure. We observed active infections caused by LA-SA. This finding suggests that individuals with livestock contact may have a high prevalence of exposure to, and potentially infection with, antibiotic-resistant S. aureus strains, including LA-SA strains.

Molecular characterization of methicillin-resistant Staphylococcus aureus (MRSA) nasal colonization and infection isolates in a Veterans Affairs hospital.

BACKGROUND: Nasal colonization with methicillin-resistant Staphylococcus aureus (MRSA) is associated with increased infection risk, yet colonization and infection isolates are rarely compared within the same study. The objectives of this study were to compare colonization and infection isolates from a Veterans Administration hospital in Iowa, and to determine the prevalence of livestock-associated MRSA (LA-MRSA) colonization and infection in a state with high livestock density. METHODS: All patients with available MRSA isolates collected through routine nasal screening (73%; n = 397) and from infections (27%; n = 148) between December 2010 and August 2012 were included and tested for spa type and presence of PVL and mecA genes. Clinical isolates were tested for antibiotic resistance patterns. Paired colonization and infection isolates were compared for genetic and phenotypic congruity. RESULTS: The most common spa types were t002 (and other CC5-associated strains; 65%) and t008 (and other CC8-associated strains; 20%). No classic LA-MRSA spa types were identified. CC5-associated strains were less likely to be associated with infections (22%; 77/353) compared with CC8-associated strains (49%; 53/109). MRSA colonization was more common among patients with infections (71%) compared with the general screening population (7%). In most cases (82%; 28/34), paired colonization and infection isolates were genetically and phenotypically indistinguishable. CONCLUSIONS: Our data demonstrate a direct link between antecedent nasal colonization and subsequent MRSA infection. Further, our data indicate variability in colonization and infection efficiency among MRSA genotypes, which points to the need to define the molecular determinants underlying emergence of S. aureus strains in the community and nosocomial setting.

Multicountry prospective clinical evaluation of two enzyme-linked immunosorbent assays and two rapid diagnostic tests for diagnosing dengue fever.

We evaluated four dengue diagnostic devices from Alere, including the SD Bioline Dengue Duo (nonstructural [NS] 1 Ag and IgG/IgM), the Panbio Dengue Duo Cassette (IgM/IgG) rapid diagnostic tests (RDTs), and the Panbio dengue IgM and IgG capture enzyme-linked immunosorbent assays (ELISAs) in a prospective, controlled, multicenter study in Peru, Venezuela, Cambodia, and the United States, using samples from 1,021 febrile individuals. Archived, well-characterized samples from an additional 135 febrile individuals from Thailand were also used. Reference testing was performed on all samples using an algorithm involving virus isolation, in-house IgM and IgG capture ELISAs, and plaque reduction neutralization tests (PRNT) to determine the infection status of the individual. The primary endpoints were the clinical sensitivities and specificities of these devices. The SD Bioline Dengue Duo had an overall sensitivity of 87.3% (95% confidence interval [CI], 84.1 to 90.2%) and specificity of 86.8% (95% CI, 83.9 to 89.3%) during the first 14 days post-symptom onset (p.s.o.). The Panbio Dengue Duo Cassette demonstrated a sensitivity of 92.1% (87.8 to 95.2%) and specificity of 62.2% (54.5 to 69.5%) during days 4 to 14 p.s.o. The Panbio IgM capture ELISA had a sensitivity of 87.6% (82.7 to 91.4%) and specificity of 88.1% (82.2 to 92.6%) during days 4 to 14 p.s.o. Finally, the Panbio IgG capture ELISA had a sensitivity of 69.6% (62.1 to 76.4%) and a specificity of 88.4% (82.6 to 92.8%) during days 4 to 14 p.s.o. for identification of secondary dengue infections. This multicountry prospective study resulted in reliable real-world performance data that will facilitate data-driven laboratory test choices for managing patient care during dengue outbreaks.

Evaluation of dengue NS1 antigen rapid tests and ELISA kits using clinical samples.

BACKGROUND: Early diagnosis of dengue virus (DENV) infection can improve clinical outcomes by ensuring close follow-up, initiating appropriate supportive therapies and raising awareness to the potential of hemorrhage or shock. Non-structural glycoprotein-1 (NS1) has proven to be a useful biomarker for early diagnosis of dengue. A number of rapid diagnostic tests (RDTs) and enzyme-linked immunosorbent assays (ELISAs) targeting NS1 antigen (Ag) are now commercially available. Here we evaluated these tests using a well-characterized panel of clinical samples to determine their effectiveness for early diagnosis. METHODOLOGY/PRINCIPAL FINDINGS: Retrospective samples from South America were used to evaluate the following tests: (i) "Dengue NS1 Ag STRIP" and (ii) "Platelia Dengue NS1 Ag ELISA" (Bio-Rad, France), (iii) "Dengue NS1 Detect Rapid Test (1st Generation)" and (iv) "DENV Detect NS1 ELISA" (InBios International, United States), (v) "Panbio Dengue Early Rapid (1st generation)" (vi) "Panbio Dengue Early ELISA (2nd generation)" and (vii) "SD Bioline Dengue NS1 Ag Rapid Test" (Alere, United States). Overall, the sensitivity of the RDTs ranged from 71.9%-79.1% while the sensitivity of the ELISAs varied between 85.6-95.9%, using virus isolation as the reference method. Most tests had lower sensitivity for DENV-4 relative to the other three serotypes, were less sensitive in detecting secondary infections, and appeared to be most sensitive on Day 3-4 post symptom onset. The specificity of all evaluated tests ranged from 95%-100%. CONCLUSIONS: ELISAs had greater overall sensitivity than RDTs. In conjunction with other parameters, the performance data can help determine which dengue diagnostics should be used during the first few days of illness, when the patients are most likely to present to a clinic seeking care.

Long-term and seasonal dynamics of dengue in Iquitos, Peru.

INTRODUCTION: Long-term disease surveillance data provide a basis for studying drivers of pathogen transmission dynamics. Dengue is a mosquito-borne disease caused by four distinct, but related, viruses (DENV-1-4) that potentially affect over half the world's population. Dengue incidence varies seasonally and on longer time scales, presumably driven by the interaction of climate and host susceptibility. Precise understanding of dengue dynamics is constrained, however, by the relative paucity of laboratory-confirmed longitudinal data. METHODS: We studied 10 years (2000-2010) of laboratory-confirmed, clinic-based surveillance data collected in Iquitos, Peru. We characterized inter and intra-annual patterns of dengue dynamics on a weekly time scale using wavelet analysis. We explored the relationships of case counts to climatic variables with cross-correlation maps on annual and trimester bases. FINDINGS: Transmission was dominated by single serotypes, first DENV-3 (2001-2007) then DENV-4 (2008-2010). After 2003, incidence fluctuated inter-annually with outbreaks usually occurring between October and April. We detected a strong positive autocorrelation in case counts at a lag of ∼ 70 weeks, indicating a shift in the timing of peak incidence year-to-year. All climatic variables showed modest seasonality and correlated weakly with the number of reported dengue cases across a range of time lags. Cases were reduced after citywide insecticide fumigation if conducted early in the transmission season. CONCLUSIONS: Dengue case counts peaked seasonally despite limited intra-annual variation in climate conditions. Contrary to expectations for this mosquito-borne disease, no climatic variable considered exhibited a strong relationship with transmission. Vector control operations did, however, appear to have a significant impact on transmission some years. Our results indicate that a complicated interplay of factors underlie DENV transmission in contexts such as Iquitos.