Capacity of a Multiplex IgM Antibody Capture ELISA to Differentiate Zika and Dengue Virus Infections in Areas of Concurrent Endemic Transmission

Serological cross-reactivity has proved to be a challenge to diagnose Zika virus (ZIKV) infections in dengue virus (DENV) endemic countries. Confirmatory testing of ZIKV IgM positive results by plaque reduction neutralization tests (PRNTs) provides clarification in only a minority of cases because most individuals infected with ZIKV were previously exposed to DENV. The goal of this study was to evaluate the performance of a ZIKV/DENV DUO IgM antibody capture ELISA (MAC-ELISA) for discriminating between DENV and ZIKV infections in endemic regions. Our performance evaluation included acute and convalescent specimens from patients with real-time reverse transcription polymerase chain reaction (RT-PCR)-confirmed DENV or ZIKV from the Sentinel Enhanced Dengue Surveillance System in Ponce, Puerto Rico. The ZIKV/DENV DUO MAC-ELISA specificity was 100% for DENV (N = 127) and 98.4% for ZIKV (N = 275) when specimens were tested during the optimal testing window (days post-onset of illness [DPO] 6–120). The ZIKV/DENV DUO MAC-ELISA sensitivity of RT-PCR confirmed specimens reached 100% for DENV by DPO 6 and for ZIKV by DPO 9. Our new ZIKV/DENV DUO MAC-ELISA was also able to distinguish ZIKV and DENV regardless of previous DENV exposure. We conclude this novel serologic diagnostic assay can accurately discriminate ZIKV and DENV infections. This can potentially be useful considering that the more labor-intensive and expensive PRNT assay may not be an option for confirmatory diagnosis in areas that lack PRNT capacity, but experience circulation of both DENV and ZIKV.

The estimate of the rubella elimination status in the Russian Federation in 2019

In 2002, the WHO Regional Office for Europe developed a Strategic Program for the Prevention of Measles and Congenital Rubella Infections in the European Region, which was revised in 2004. As a result of the revision, an additional target was set to eliminate endemic rubella in the region by 2010. Rubella is a disease that is well controlled by vaccination, which will determine the theoretical possibility of interrupting its global transmission. Since 2013, the Russian Federation has been implementing the National Rubella Elimination Program. Elimination criteria have been revised as the Program progresses. Currently, the main criterion for rubella elimination is the absence of endemic (local) transmission of the virus for at least 36 months, which should be confirmed by molecular genetic research methods. In addition, in the Russian Federation, an incidence rate of less than 1 case per 1 million population is also used as one of the elimination criteria. The successful implementation of the Program is supported by the fact that since 2013, against the background of a high (over 95%) coverage of preventive vaccinations, there has been a decrease in incidence rates and their stabilization at a level of less than 1 per 1 million population since 2014. Genetic monitoring of rubella virus strains circulating among the population showed the termination of endemic transmission of the virus. During the implementation of the Elimination Program, the prevailing genotypes of the virus circulating in Russia were genotypes 1E and 2B, which have a global distribution. The data obtained from the results of molecular genetic monitoring made it possible to determine that the strains isolated during the period under consideration belong to different clusters, which speaks in favour of their imported character. Considering the above factors: high vaccination coverage, low incidence and lack of endemic transmission of the virus, the WHO Committee on verification of measles and rubella elimination in 2017 awarded the Russian Federation the status of a country that has achieved rubella elimination. The continuation of the phase of elimination of infection is confirmed annually. This article presents the results of a comprehensive assessment of the rubella elimination status in the Russian Federation by specialists from the National Scientific and Methodological Center for Measles and Rubella and WHO EURO Moscow regional reference laboratory for measles and rubella based on epidemiological data and data from molecular genetic studies in 2019.

Spatial distribution of Plasmodium knowlesi cases and their vectors in Johor, Malaysia: in light of human malaria elimination

Background Plasmodium knowlesi, a simian malaria parasite infection, increases as Plasmodium falciparum and Plasmodium vivax infections decrease in Johor, Malaysia. Therefore, this study aimed to identify the distribution of vectors involved in knowlesi malaria transmission in Johor. This finding is vital in estimating hotspot areas for targeted control strategies. Methods Anopheles mosquitoes were collected from the location where P. knowlesi cases were reported. Cases of knowlesi malaria from 2011 to 2019 in Johor were analyzed. Internal transcribed spacers 2 (ITS2) and cytochrome c oxidase subunit I (COI) genes were used to identify the Leucosphyrus Group of Anopheles mosquitoes. In addition, spatial analysis was carried out on the knowlesi cases and vectors in Johor. Results One hundred and eighty-nine cases of P. knowlesi were reported in Johor over 10 years. Young adults between the ages of 20–39 years comprised 65% of the cases. Most infected individuals were involved in agriculture and army-related occupations (22% and 32%, respectively). Four hundred and eighteen Leucosphyrus Group Anopheles mosquitoes were captured during the study. Anopheles introlatus was the predominant species, followed by Anopheles latens. Spatial analysis by Kriging interpolation found that hotspot regions of P. knowlesi overlapped or were close to the areas where An. introlatus and An. latens were found. A significantly high number of vectors and P. knowlesi cases were found near the road within 0–5 km. Conclusions This study describes the distribution of P. knowlesi cases and Anopheles species in malaria-endemic transmission areas in Johor. Geospatial analysis is a valuable tool for studying the relationship between vectors and P. knowlesi cases. This study further supports that the Leucosphyrus Group of mosquitoes might be involved in transmitting knowlesi malaria cases in Johor. These findings may provide initial evidence to prioritize diseases and vector surveillance.

Spread of Gamma (P.1) sub-lineages carrying Spike mutations close to the furin cleavage site and deletions in the N-terminal domain drives ongoing transmission of SARS-CoV-2 in Amazonas, Brazil

SummaryThe Amazonas was one of the most heavily affected Brazilian states by the COVID-19 epidemic. Despite a large number of infected people, particularly during the second wave associated with the spread of the Variant of Concern (VOC) Gamma (lineage P.1), SARS-CoV-2 continues to circulate in the Amazonas. To understand how SARS-CoV-2 persisted in a human population with a high immunity barrier, we generated 1,188 SARS-CoV-2 whole-genome sequences from individuals diagnosed in the Amazonas state from 1st January to 6th July 2021, of which 38 were vaccine breakthrough infections. Our study reveals a sharp increase in the relative prevalence of Gamma plus (P.1+) variants, designated as Pango Lineages P.1.3 to P.1.6, harboring two types of additional Spike changes: deletions in the N-terminal (NTD) domain (particularly Δ144 or Δ141-144) associated with resistance to anti-NTD neutralizing antibodies or mutations at the S1/S2 junction (N679K or P681H) that probably enhance the binding affinity to the furin cleavage site, as suggested by our molecular dynamics simulations. As lineages P.1.4 (S:N679K) and P.1.6 (S:P681H) expanded (Re > 1) from March to July 2021, the lineage P.1 declined (Re < 1) and the median Ct value of SARS-CoV-2 positive cases in Amazonas significantly decreases. Still, we found no overrepresentation of P.1+ variants among breakthrough cases of fully vaccinated patients (71%) in comparison to unvaccinated individuals (93%). This evidence supports that the ongoing endemic transmission of SARS-CoV-2 in the Amazonas is driven by the spread of new local Gamma/P.1 sub-lineages that are more transmissible, although not more efficient to evade vaccine-elicited immunity than the parental VOC. Finally, as SARS-CoV-2 continues to spread in human populations with a declining density of susceptible hosts, the risk of selecting new variants with higher infectivity are expected to increase.

An Updated Review Of the Invasive Aedes Albopictus in the Americas; The Minimum Infection Rate Suggests That Is More Efficient in the Vertical Than Horizontal Transmission of Arboviruses

The aim of the work was to update the distribution range of Aedes (Stegomyia) albopictus Skuse in the Americas, review the blood feeding patterns and compare the minimum infection rate (MIR) between studies of vertical and horizontal transmission of arboviruses. The current distribution of Ae. albopictus encompasses 21 countries in the Americas. In eleven published papers on the blood feeding pattern of Ae. albopictus, DNA from 16 species of mammals and five species of avian species was found. The most common host is humans, and dogs. We found 24 published papers on the identification of arboviruses in wild populations of Ae. albopictus with the potential to infect humans and animals. Eight arboviruses have been isolated in different studies carried out in Brazil, USA, Mexico, Colombia, and Costa Rica. Fifty-eight percent (14/24) of the publications reported vertical transmission of arbovirus. Positive pools were higher in vertical (8.45%) compared to horizontal transmission (0.97%). This was supported by the MIR, which was 3 times greater in vertical (MIR=3.21) than horizontal transmission (MIR= 1.08). In conclusion, Ae. albopictus is an invasive mosquito with wide phenotypic plasticity to adapt to broad and new areas, high vectorial competence to transmit several arboviruses mainly by transovarial transmission, it can participate in the endemic transmission, and serve as a bridge vector for emerging arboviruses between sylvan, rural, and urban areas.

Multi-locus genotyping reveals established endemicity of a geographically distinct Plasmodium vivax population in Mauritania, West Africa

Background Plasmodium vivax has been recently discovered as a significant cause of malaria in Mauritania, although very rare elsewhere in West Africa. It has not been known if this is a recently introduced or locally remnant parasite population, nor whether the genetic structure reflects epidemic or endemic transmission. Methodology/Principal findings To investigate the P. vivax population genetic structure in Mauritania and compare with populations previously analysed elsewhere, multi-locus genotyping was undertaken on 100 clinical isolates, using a genome-wide panel of 38 single nucleotide polymorphisms (SNPs), plus seven SNPs in drug resistance genes. The Mauritanian P. vivax population is shown to be genetically diverse and divergent from populations elsewhere, indicated consistently by genetic distance matrix analysis, principal components analyses, and fixation indices. Only one isolate had a genotype clearly indicating recent importation, from a southeast Asian source. There was no linkage disequilibrium in the local parasite population, and only a small number of infections appeared to be closely genetically related, indicating that there is ongoing genetic recombination consistent with endemic transmission. The P. vivax diversity in a remote mining town was similar to that in the capital Nouakchott, with no indication of local substructure or of epidemic population structure. Drug resistance alleles were virtually absent in Mauritania, in contrast with P. vivax in other areas of the world. Conclusions/Significance The molecular epidemiology indicates that there is long-standing endemic transmission that will be very challenging to eliminate. The virtual absence of drug resistance alleles suggests that most infections have been untreated, and that this endemic infection has been more neglected in comparison to P. vivax elsewhere.

A model of population dynamics with complex household structure and mobility: implications for transmission and control of communicable diseases

Households are known to be high-risk locations for the transmission of communicable diseases. Numerous modelling studies have demonstrated the important role of households in sustaining both communicable diseases outbreaks and endemic transmission, and as the focus for control efforts. However, these studies typically assume that households are associated with a single dwelling and have static membership. This assumption does not appropriately reflect households in some populations, such as those in remote Australian Aboriginal and Torres Strait Islander communities, which can be distributed across more than one physical dwelling, leading to the occupancy of individual dwellings changing rapidly over time. In this study, we developed an individual-based model of an infectious disease outbreak in communities with demographic and household structure reflective of a remote Australian Aboriginal community. We used the model to compare the dynamics of unmitigated outbreaks, and outbreaks constrained by a household-focused prophylaxis intervention, in communities exhibiting fluid vs. stable dwelling occupancy. We found that fluid dwelling occupancy can lead to larger and faster outbreaks in modelled scenarios, and may interfere with the effectiveness of household-focused interventions. Our findings suggest that while short-term restrictions on movement between dwellings may be beneficial during outbreaks, in the longer-term, strategies focused on reducing household crowding may be a more effective way to reduce the risk of severe outbreaks occurring in populations with fluid dwelling occupancy.

Multi-locus genotyping reveals established endemicity of a geographically distinct Plasmodium vivax population in Mauritania, West Africa

BackgroundPlasmodium vivax has been recently discovered as a significant cause of malaria in Mauritania, although very rare elsewhere in West Africa. It has not been known if this is a recently introduced or locally remnant parasite population, nor whether the genetic structure reflects epidemic or endemic transmission.Methodology / Principal FindingsTo investigate the P. vivax population genetic structure in Mauritania and compare with populations previously analysed elsewhere, multi-locus genotyping was undertaken on 100 clinical isolates, using a genome-wide panel of 38 single nucleotide polymorphisms (SNPs), plus seven SNPs in drug resistance genes. The Mauritanian P. vivax population is shown to be genetically diverse and divergent from populations elsewhere, indicated consistently by genetic distance matrix analysis, principal components analyses, and fixation indices. Only one isolate had a genotype clearly indicating recent importation, from a southeast Asian source. There was no linkage disequilibrium in the local parasite population, and only a small number of infections appeared to be closely genetically related, indicating that there is ongoing genetic recombination consistent with endemic transmission. The P. vivax diversity in a remote mining town was similar to that in the capital Nouakchott, with no indication of local substructure or of epidemic population structure. Drug resistance alleles were virtually absent in Mauritania, in contrast with P. vivax in other areas of the world.Conclusions / SignificanceThe molecular epidemiology indicates that there is long-standing endemic transmission that will be very challenging to eliminate. The virtual absence of drug resistance alleles suggests that most infections have been untreated, and that this endemic infection has been more neglected in comparison to P. falciparum locally or to P. vivax elsewhere.Author SummaryPlasmodium vivax is a widespread cause of malaria in Mauritania, in contrast to its rarity elsewhere throughout West Africa. To investigate whether the parasite may be recently introduced or epidemic, multi-locus genotyping was performed on 100 Mauritanian P. vivax malaria cases. Analysis of a genome-wide panel of single nucleotide polymorphisms showed the P. vivax population to be genetically diverse and divergent from populations elsewhere, indicating that there has been long-standing endemic transmission. Almost all infections appear to be locally acquired, with the exception of one that was presumably imported with a genotype similar to infections seen in Southeast Asia. The Mauritanian P. vivax population shows no linkage disequilibrium, and very few infections have closely related genotypes, indicating ongoing recombination. The parasite showed no indication of local substructure or epidemic population structure. Drug resistance alleles were virtually absent, suggesting that most infections have been untreated historically. The molecular epidemiology indicates that there has been long-standing endemic transmission of this neglected parasite that requires special attention for control.

Sub-epidemic model forecasts for COVID-19 pandemic spread in the USA and European hotspots, February-May 2020

Mathematical models have been widely used to understand the dynamics of the ongoing coronavirus disease 2019 (COVID-19) pandemic as well as to predict future trends and assess intervention strategies. The asynchronicity of infection patterns during this pandemic illustrates the need for models that can capture dynamics beyond a single-peak trajectory to forecast the worldwide spread and for the spread within nations and within other sub-regions at various geographic scales. Here, we demonstrate a five-parameter sub-epidemic wave modeling framework that provides a simple characterization of unfolding trajectories of COVID-19 epidemics that are progressing across the world at different spatial scales. We calibrate the model to daily reported COVID-19 incidence data to generate six sequential weekly forecasts for five European countries and five hotspot states within the United States. The sub-epidemic approach captures the rise to an initial peak followed by a wide range of post-peak behavior, ranging from a typical decline to a steady incidence level to repeated small waves for sub-epidemic outbreaks. We show that the sub-epidemic model outperforms a three-parameter Richards model, in terms of calibration and forecasting performance, and yields excellent short- and intermediate-term forecasts that are not attainable with other single-peak transmission models of similar complexity. Overall, this approach predicts that a relaxation of social distancing measures would result in continuing sub-epidemics and ongoing endemic transmission. We illustrate how this view of the epidemic could help data scientists and policymakers better understand and predict the underlying transmission dynamics of COVID-19, as early detection of potential sub-epidemics can inform model-based decisions for tighter distancing controls.

A model of population dynamics with complex household structure and mobility: implications for transmission and control of communicable diseases

Households are known to be high-risk locations for the transmission of communicable diseases. Numerous modelling studies have demonstrated the important role of households in sustaining both communicable diseases outbreaks and endemic transmission, and as the focus for control efforts. However, these studies typically assume that households are associated with a single dwelling and have static membership. This assumption does not appropriately reflect households in some populations, such as those in remote Australian Indigenous communities, which can be distributed across more than one physical dwelling, leading to the occupancy of individual dwellings changing rapidly over time. In this study, we developed an individual-based model of an infectious disease outbreak in communities with demographic and household structure reflective of a remote Australian Indigenous community. We used the model to compare the dynamics of unmitigated outbreaks, and outbreaks constrained by a household-focused prophylaxis intervention, in communities exhibiting fluid versus stable dwelling occupancy. Our findings suggest that fluid dwelling occupancy can lead to larger and faster outbreaks, interfere with the effectiveness of household-focused interventions, and may contribute to the considerable burden of communicable diseases in communities exhibiting this type of structure.