The World Health Organization (WHO) stated in March 2016 that there was scientific consensus that the mosquito-borne Zika virus was a cause of the neurological disorder Guillain–Barré syndrome (GBS) and of microcephaly and other congenital brain abnormalities based on rapid evidence assessments. Decisions about causality require systematic assessment to guide public health actions. The objectives of this study were to update and reassess the evidence for causality through a rapid and systematic review about links between Zika virus infection and (a) congenital brain abnormalities, including microcephaly, in the foetuses and offspring of pregnant women and (b) GBS in any population, and to describe the process and outcomes of an expert assessment of the evidence about causality. The study had three linked components. First, in February 2016, we developed a causality framework that defined questions about the relationship between Zika virus infection and each of the two clinical outcomes in ten dimensions: temporality, biological plausibility, strength of association, alternative explanations, cessation, dose–response relationship, animal experiments, analogy, specificity, and consistency. Second, we did a systematic review (protocol number CRD42016036693). We searched multiple online sources up to May 30, 2016 to find studies that directly addressed either outcome and any causality dimension, used methods to expedite study selection, data extraction, and quality assessment, and summarised evidence descriptively. Third, WHO convened a multidisciplinary panel of experts who assessed the review findings and reached consensus statements to update the WHO position on causality. We found 1,091 unique items up to May 30, 2016. For congenital brain abnormalities, including microcephaly, we included 72 items; for eight of ten causality dimensions (all except dose–response relationship and specificity), we found that more than half the relevant studies supported a causal association with Zika virus infection. For GBS, we included 36 items, of which more than half the relevant studies supported a causal association in seven of ten dimensions (all except dose–response relationship, specificity, and animal experimental evidence). Articles identified nonsystematically from May 30 to July 29, 2016 strengthened the review findings. The expert panel concluded that (a) the most likely explanation of available evidence from outbreaks of Zika virus infection and clusters of microcephaly is that Zika virus infection during pregnancy is a cause of congenital brain abnormalities including microcephaly, and (b) the most likely explanation of available evidence from outbreaks of Zika virus infection and GBS is that Zika virus infection is a trigger of GBS. The expert panel recognised that Zika virus alone may not be sufficient to cause either congenital brain abnormalities or GBS but agreed that the evidence was sufficient to recommend increased public health measures. Weaknesses are the limited assessment of the role of dengue virus and other possible cofactors, the small number of comparative epidemiological studies, and the difficulty in keeping the review up to date with the pace of publication of new research. Rapid and systematic reviews with frequent updating and open dissemination are now needed both for appraisal of the evidence about Zika virus infection and for the next public health threats that will emerge. This systematic review found sufficient evidence to say that Zika virus is a cause of congenital abnormalities and is a trigger of GBS.

Dengue imposes a substantial economic and disease burden in most tropical and subtropical countries. Dengue incidence and severity have dramatically increased in Mexico during the past decades. Having objective and comparable estimates of the economic burden of dengue is essential to inform health policy, increase disease awareness, and assess the impact of dengue prevention and control technologies. We estimated the annual economic and disease burden of dengue in Mexico for the years 2010–2011. We merged multiple data sources, including a prospective cohort study; patient interviews and macro-costing from major hospitals; surveillance, budget, and health data from the Ministry of Health; WHO cost estimates; and available literature. We conducted a probabilistic sensitivity analysis using Monte Carlo simulations to derive 95% certainty levels (CL) for our estimates. Results suggest that Mexico had about 139,000 (95%CL: 128,000–253,000) symptomatic and 119 (95%CL: 75–171) fatal dengue episodes annually on average (2010–2011), compared to an average of 30,941 symptomatic and 59 fatal dengue episodes reported. The annual cost, including surveillance and vector control, was US$170 (95%CL: 151–292) million, or $1.56 (95%CL: 1.38–2.68) per capita, comparable to other countries in the region. Of this, $87 (95%CL: 87–209) million or $0.80 per capita (95%CL: 0.62–1.12) corresponds to illness. Annual disease burden averaged 65 (95%CL: 36–99) disability-adjusted life years (DALYs) per million population. Inclusion of long-term sequelae, co-morbidities, impact on tourism, and health system disruption during outbreaks would further increase estimated economic and disease burden. With this study, Mexico joins Panama, Puerto Rico, Nicaragua, and Thailand as the only countries or areas worldwide with comprehensive (illness and preventive) empirical estimates of dengue burden. Burden varies annually; during an outbreak, dengue burden may be significantly higher than that of the pre-vaccine level of rotavirus diarrhea. In sum, Mexico’s potential economic benefits from dengue control would be substantial. During the past decades, dengue fever has become the most common arthropod-borne viral disease, imposing a substantial economic and disease burden in most tropical and subtropical countries, including Mexico. Dengue incidence and severity have dramatically increased in Mexico, with transmission regularly reported in 28 of 32 states. Objective estimates of the burden of dengue are important to inform policy decisions and priorities. We merged multiple data sources to estimate (i) total episodes, (ii) costs per episode, (iii) surveillance and vector control costs, and (iv) disease burden (2010–2011). Results suggest that Mexico had about 139,000 symptomatic and 119 fatal dengue episodes per year on average. The annual cost, including surveillance and vector control, was about US$170 million, or $1.56 per capita, comparable to other countries in the Americas. Annual disease burden averaged 65 disability-adjusted life years per million population, with most of the years lost to disability corresponding to ambulatory episodes. The results show a substantial burden of dengue on the health care system and economy of Mexico. This quantification of the economic burden should help public health officials make informed decisions about current and promising new preventive and control measures to reduce dengue infections.

Dengue, the predominant arthropod-borne viral disease affecting humans, is caused by one of four distinct serotypes (DENV-1, -2, -3 or -4). A literature analysis and review was undertaken to describe the molecular epidemiological trends in dengue disease and the knowledge generated in specific molecular topics in Latin America, including the Caribbean islands, from 2000 to 2013 in the context of regional trends in order to identify gaps in molecular epidemiological knowledge and future research needs. Searches of literature published between 1 January 2000 and 30 November 2013 were conducted using specific search strategies for each electronic database that was reviewed. A total of 396 relevant citations were identified, 57 of which fulfilled the inclusion criteria. All four dengue virus serotypes were present and co-circulated in many countries over the review period (with the predominance of individual serotypes varying by country and year). The number of countries in which more than one serotype circulated steadily increased during the period under review. Molecular epidemiology data were found for Argentina, Bolivia, Brazil, the Caribbean region, Colombia, Ecuador, Mexico and Central America, Paraguay, Peru and Venezuela. Distinct lineages with different dynamics were found in each country, with co-existence, extinction and replacement of lineages occurring over the review period. Despite some gaps in the literature limiting the possibility for comparison, our review has described the molecular epidemiological trends of dengue infection. However, several gaps in molecular epidemiological information across Latin America and the Caribbean were identified that provide avenues for future research; in particular, sequence determination of the dengue virus genome is important for more precise phylogenetic classification and correlation with clinical outcome and disease severity. The wide distribution of the mosquito vector and the co-circulation of multiple dengue virus serotypes has led to increases in the incidence of dengue in the Americas, where it is a major public health concern. Identifying molecular epidemiological trends may help to identify the reasons for the re-emergence of dengue across Latin America and the Caribbean, and, in turn, enable disease control and management. We conducted this review using well defined methods to search for and identify relevant research according to predetermined inclusion criteria. The objective was to obtain a clearer understanding of changes occurring within dengue serotypes that have resulted in substantial genetic diversity and the emergence of endemic and epidemic strains in different parts of the region. There remain fundamental gaps in our understanding of the epidemiological and evolutionary dynamics of dengue and its relation with disease, and it is not possible to correlate accurately spatial or temporal trends in disease epidemiology, disease severity, or the genetic diversity of DENV. It is important to maintain comprehensive epidemiological surveillance throughout the region (including sequencing of viral strains) to detect new DENV lineages and to understand the regional patterns of DENV dissemination.

Community integration in dengue control requires assessments of knowledge, attitudes and practices (KAPs), which can vary widely according to demographic and educational factors. We aimed to describe and compare the KAPs according to level of education in municipalities in the Caribbean region of Colombia. A survey was administered from October to December 2015, including families selected through probabilistic sampling in eleven municipalities. The analysis focused on the comparative description of the responses according to level of education. The KAP prevalence ratios (PR) according to education were estimated using Poisson regression (robust), including age and sex as adjustment variables. Out of 1057 participants, 1054 (99.7%) surveys were available for analysis, including 614 (58.3%) who had a high school level of education or higher and 440 (41.7%) who had a lower level of education (not high school graduates). The high school graduates showed a higher frequency of correct answers in relation to knowledge about dengue symptoms and transmission. On the other hand, graduates showed a higher probability of practices and attitudes that favor dengue control, including not storing water in containers (PR: 2.2; 95% Confidence Interval [CI]: 1.42–3.43), attend community meetings (PR: 1.33; 95% CI: 1.07–1.65), educate family members and neighbors in prevention measures (PR: 1.35; 95% CI: 1.15–1.59). Level of education could be a key determinant of knowledge of the disease and its transmission, as well as attitudes and practices, especially those that involve the integration of community efforts for dengue control.

We evaluated biochemical alterations as predictors of dengue hemorrhagic fever (DHF). Patients with confirmed infection with dengue virus were prospectively evaluated for the first seven days of disease to determine their final clinical outcome. Serum samples taken 48–96 hours after onset of fever were used for biochemical tests. Of 199 patients, 30 developed DHF. Cases of DHF had higher levels of lactate dehydrogenase (LDH), creatine kinase (CK), and aspartate aminotransferase, and lower levels of albumin, total cholesterol, and triglycerides. Multivariate analysis showed that early alterations of CK (hazard ratio [HR] = 6.98, 95% confidence interval [CI] = 2.34–20.85, P = 0.001), LDH (HR = 3.19, 95% CI = 1.01–10.12, P < 0.05), and albumin (HR = 2.54, 95% CI = 1.09–5.92, P = 0.03) were associated with DHF. Triglyceride levels > 160 mg/dL were negatively associated with developing DHF (HR = 0.07, 95% CI = 0.01–0.59, P = 0.01). Early alterations of biochemical markers can predict DHF in patients with acute fever caused by dengue.

Humoral immune response against dengue virus (DENV) is an important component in dengue-endemic transmission. We conducted a cross-sectional nested cohort study to determine the seroprevalence and frequency of neutralizing antibodies against DENV serotypes in two endemic localities in the state of Morelos, Mexico. The cohort participants (N = 1,196) were screened to determine previous exposure to DENV. Overall seroprevalence was 76.6% (95% confidence interval [95% CI] = 73.6–79.2), and prevalence of neutralizing antibodies in the 5- to 9-year-old group was 82.5% (95% CI = 67.2–92.7), 45% (95% CI = 29.3–61.5), and 65% (95% CI = 48.3–79.4) for DENV-1, DENV-2, and DENV-3, respectively. For participants older than 10 years, the observed seroprevalence was above 60% for each serotype, except DENV-4 in the 10- to 25-year-old group (42.9%); 81% of humoral responses were multitypic. The outcomes of our study contribute to understanding the immune component of dengue transmission and provide focal information for the evaluation of vaccine candidates under development.