Correction: Dengue illness impacts daily human mobility patterns in Iquitos, Peru.

[This corrects the article DOI: 10.1371/journal.pntd.0007756.].

Dengue illness impacts daily human mobility patterns in Iquitos, Peru.

BACKGROUND: Human mobility plays a central role in shaping pathogen transmission by generating spatial and/or individual variability in potential pathogen-transmitting contacts. Recent research has shown that symptomatic infection can influence human mobility and pathogen transmission dynamics. Better understanding the complex relationship between symptom severity, infectiousness, and human mobility requires quantification of movement patterns throughout infectiousness. For dengue virus (DENV), human infectiousness peaks 0-2 days after symptom onset, making it paramount to understand human movement patterns from the beginning of illness. METHODOLOGY AND PRINCIPAL FINDINGS: Through community-based febrile surveillance and RT-PCR assays, we identified a cohort of DENV+ residents of the city of Iquitos, Peru (n = 63). Using retrospective interviews, we measured the movements of these individuals when healthy and during each day of symptomatic illness. The most dramatic changes in mobility occurred during the first three days after symptom onset; individuals visited significantly fewer locations (Wilcoxon test, p = 0.017) and spent significantly more time at home (Wilcoxon test, p = 0.005), compared to when healthy. By 7-9 days after symptom onset, mobility measures had returned to healthy levels. Throughout an individual's symptomatic period, the day of illness and their subjective sense of well-being were the most significant predictors for the number of locations and houses they visited. CONCLUSIONS/SIGNIFICANCE: Our study is one of the first to collect and analyze human mobility data at a daily scale during symptomatic infection. Accounting for the observed changes in human mobility throughout illness will improve understanding of the impact of disease on DENV transmission dynamics and the interpretation of public health-based surveillance data.

A cluster of the first reported Plasmodium ovale spp. infections in Peru occuring among returning UN peace-keepers, a review of epidemiology, prevention and diagnostic challenges in nonendemic regions.

BACKGROUND: Plasmodium ovale curtisi and Plasmodium ovale wallikeri are regarded as less virulent forms of malaria with a geographic distribution including Southeast Asia, Central and West Africa, and is increasingly reported as an infection in returning travellers. A species of malaria that may have delayed or relapsing presentations similar to Plasmodium vivax, the clinical presentation of P. ovale spp. has been described to have prepatent periods of 2 weeks or slightly longer with reports of relapse following primary infection out to 8-9 months. This presentation may be obscured further in the setting of anti-malarial exposure, with report of delayed primary infection out to 4 years. Presented is a cluster of 4 imported P. ovale spp. cases in returning Peruvian military personnel assigned to United Nations peace-keeping operations in the Central African Republic. CASE PRESENTATION: From January to December 2016, Peruvian peace-keepers were deployed in support of United Nations (UN) operations in the Central African Republic (CAR). While serving abroad, Navy, Army, and Air Force members experienced 223 episodes of Plasmodium falciparum malaria following interruption of prophylaxis with mefloquine. Diagnosis was made using rapid diagnostics tests (RDTs) and/or smear with no coinfections identified. Cases of malaria were treated with locally-procured artemether-lumefantrine. Returning to Peru in January 2017, 200 peace-keepers were screened via thick and thin smear while on weekly mefloquine prophylaxis with only 1 showing nucleic acid within red blood cells consistent with Plasmodium spp. and 11 reporting syndromes of ill-defined somatic complaints. Between a period of 5 days to 11 months post return, 4 cases of P. ovale spp. were diagnosed using smear and polymerase chain reaction (PCR) following febrile complaints. All cases were subsequently treated with chloroquine and primaquine, with cure of clinical disease and documented clearance of parasitaemia. CONCLUSION: These patients represent the first imported cases in Peru of this species of malaria as well as highlight the challenges in implementing population level prophylaxis in a deployed environment, and the steps for timely diagnosis and management in a non-endemic region where risk of introduction for local transmission exists.

IgG1 and IgG4 antibodies against Aedes aegypti salivary proteins and risk for dengue infections.

Dengue virus (DENV) is an arbovirus responsible for a significant number of deaths in Latin America. This virus is transmitted through the bite of Aedes aegypti, the main mosquito vector, and Ae. albopictus. During blood uptake, the mosquito injects its saliva into the host to facilitate the feeding process. Mosquito saliva contains potent immunogens capable of inducing antibody production directly related to mosquito bite exposure intensity and disease risk. In this study, we first determined the DENV infection status by two different DENV non-structural protein 1 (NS1) based rapid tests and qRT-PCR, then measured the levels of IgG1 and IgG4 antibodies against salivary proteins of Ae. aegypti female mosquitoes in volunteers living in a dengue endemic area. Our results show that people with a positive DENV diagnosis present higher levels of IgG4 antibodies than people with a negative diagnostic test, and that these antibody levels were higher in people with secondary DENV infections. With this study, we show that detection of IgG4 antibodies against mosquito saliva may be a reliable method to evaluate the risk of dengue infection.

Aedes aegypti anti-salivary gland antibody concentration and dengue virus exposure history in healthy individuals living in an endemic area in Colombia.

INTRODUCTION: Mosquito salivary proteins are able to induce an antibody response that reflects the level of human-vector contact. IgG antibodies against dengue virus (DENV-IgG) are indicators of previous exposure. The risk of DENV transmission is not only associated to mosquito or dengue factors, but also to socioeconomic factors that may play an important role in the disease epidemiology. OBJECTIVE: To determine the effect of the presence of Aedes aegypti mosquitos in different stages in households and the history of dengue exposure on vector-human contact determined by the level of anti-salivary protein antibodies in people living in a Colombian endemic area. MATERIALS AND METHODS: A pilot study of 58 households and 55 human subjects was conducted in Norte de Santander, Colombia. A questionnaire for socioeconomic factors was administered and houses were examined for the presence of Ae. aegypti specimens in the aquatic stages. The level of DENV-IgG antibodies (DENV-IgG), in addition to IgG and IgM anti- Ae. aegypti salivary gland extract (SGE) antibodies (SGE-IgG, SGE-IgM) were evaluated by ELISA using blood collected in filter paper. RESULTS: We found a significant higher level of SGE-IgG antibodies in subjects living in houses with Ae. aegypti in aquatic stages. We also found a higher concentration of SGE-IgG antibodies in people exposed to DENV, a positive correlation between IgM-SGE and IgG-DENV and a negative correlation with IgG-SGE. CONCLUSION: Anti-salivary proteins antibodies are consistent with the presence of Ae. aegypti aquatic stages inside houses and DENV-IgG antibodies concentrations.

Effect of dengue-2 virus infection on protein expression in the salivary glands of Aedes aegypti mosquitoes.

Dengue virus (DENV) is the most important mosquito-transmitted flavivirus that is transmitted throughout the tropical and subtropical regions of the world. The primary mosquito vector of DENV in urban locations is Aedes aegypti. Key to understanding the transmission of DENV is the relationship between pathogen and vector. Accordingly, we report our preliminary characterization of the differentially expressed proteins from Ae. aegypti mosquitoes after DENV infection. We investigated the virus-vector interaction through changes in the proteome of the salivary glands of mosquitoes with disseminated DENV serotype 2 (DENV-2) infections using two-dimensional gel electrophoresis and identification by mass spectrometry. Our findings indicate that DENV-2 infection in the Ae. aegypti salivary gland alters the expression of structural, secreted, and metabolic proteins. These changes in the salivary gland proteome highlight the virally influenced environment caused by a DENV-2 infection and warrant additional investigation to determine if these differences extend to the expectorated saliva.

Use of anti-Aedes aegypti salivary extract antibody concentration to correlate risk of vector exposure and dengue transmission risk in Colombia.

Norte de Santander is a region in Colombia with a high incidence of dengue virus (DENV). In this study, we examined the serum concentration of anti-Aedes salivary gland extract (SGE) antibodies as a biomarker of DENV infection and transmission, and assessed the duration of anti-SGE antibody concentration after exposure to the vector ceased. We also determined whether SGE antibody concentration could differentiate between positive and negative DENV infected individuals and whether there are differences in exposure for each DENV serotype. We observed a significant decrease in the concentration of IgG antibodies at least 40 days after returning to an "Ae. aegypti-free" area. In addition, we found significantly higher anti-SGE IgG concentrations in DENV positive patients with some difference in exposure to mosquito bites among DENV serotypes. We conclude that the concentration of IgG antibodies against SGE is an accurate indicator of risk of dengue virus transmission and disease presence.

Phylogenetic relationships among orthobunyaviruses isolated from mosquitoes captured in Peru.

The Orthobunyavirus genus of the family Bunyaviridae is comprised of over 220 extremely diverse viral species. Members of this genus are often associated with acute febrile illness in animals and humans. As part of a longterm study of the ecology of arboviruses in the Amazon basin of Peru, we have isolated over 60 orthobunyaviruses from mosquitoes. The identification of many of these isolates by fluorescent antibody assay has been confounded by the lack of specificity of many available reagents. Therefore, we initiated genetic characterization, based on the S and M genomic segments, of selected viral isolates. Based on comparisons of the nucleotide sequences of the nucleocapsid gene, Wyeomyia, a virus in the Bunyamwera group, was the most related Orthobunyavirus species. Within the nonstructural S (NSs) open reading frame of the S segment, we found four conserved stop codons for the Peruvian isolates. Detailed comparisons of Bunyamwera, Simbu viruses, Group C viruses, and California viruses revealed all four of these NSs stop codons only appeared in Wyeomyia and the Peruvian isolates, and Guaroa conserved one of these stop codons. Such an apparent obliteration of the native NSs protein has not been described. Analysis of partial M segment amino acid sequence supports the conclusion that the viruses in this study are members of an uncharacterized orthobunyavirus group.

Experimental transmission of West Nile virus by Culex nigripalpus from Honduras.

As a result of concerns regarding the geographic spread of West Nile virus (WNV) to Central America, we evaluated the potential for Honduran Culex nigripalpus Theobald to transmit this virus. We tested individual mosquitoes captured in Olancho Province, Honduras, in September 2003. Mosquitoes were allowed to feed on 2- to 4- day-old chickens previously inoculated with a New York strain (Crow 397-99) of WNV. Infection rates in Cx. nigripalpus ranged from 81%-96% after feeding on chickens with viremias between 10(6.3) and 10(7.4) plaque-forming units per milliliter. Development of a disseminated infection was directly correlated with holding time after the infectious blood meal as 68% (19/28) of the mosquitoes tested 20 days after the infectious blood meal had a disseminated infection as compared to 38% (15/40) of the mosquitoes tested 14 days after feeding on the same viremic chickens (viremia = 10(6.97.4)). Nearly all (4/5) Cx. nigripalpus with a disseminated infection that fed on susceptible chickens transmitted virus by bite. In addition, 8 (57%) of 14 Cx. nigripalpus with a disseminated infection transmitted virus when tested by a capillary tube feeding assay. Based on its efficiency of viral transmission in this study and its role in the transmission of the closely related St. Louis encephalitis virus in the southeastern United States, Cx. nigripalpus should be considered a potentially important vector of WNV in Honduras and the rest of Central America.