ABSTRACT
In resource-scarce settings, melioidosis is associated with up to 80% mortality. Studies of melioidosis in Cambodia report primarily on pediatric populations with localized infection; however, literature describing Cambodian adults with severe melioidosis is lacking. We present a case series of 35 adults with sequence-confirmed Burkholderia pseudomallei bacteremia presenting to a provincial referral hospital in rural Cambodia. More than 90% of the patients had diabetes, an important risk factor for developing melioidosis. Inappropriate antimicrobial therapy was significantly associated with lower odds of survival. Improved diagnostic testing and greater access to first-line antibiotics for acute melioidosis treatment present potential targets for intervention to reduce mortality associated with this disease in resource-limited settings.
Subject(s)
Anti-Bacterial Agents , Bacteremia , Burkholderia pseudomallei , Melioidosis , Humans , Melioidosis/drug therapy , Melioidosis/mortality , Melioidosis/epidemiology , Melioidosis/microbiology , Burkholderia pseudomallei/isolation & purification , Burkholderia pseudomallei/drug effects , Cambodia/epidemiology , Risk Factors , Male , Female , Retrospective Studies , Adult , Bacteremia/mortality , Bacteremia/drug therapy , Bacteremia/microbiology , Middle Aged , Anti-Bacterial Agents/therapeutic use , Aged , Young AdultABSTRACT
Introduction: Aedes spp. are the most prolific mosquito vectors in the world. Found on every continent, they can effectively transmit various arboviruses, including the dengue virus which continues to cause outbreaks worldwide and is spreading into previously non-endemic areas. The lack of widely available dengue vaccines accentuates the importance of targeted vector control strategies to reduce the dengue burden. High-throughput tools to estimate human-mosquito contact and evaluate vector control interventions are lacking. We propose a novel serological tool that allows rapid screening of human cohorts for exposure to potentially infectious mosquitoes. Methods: We tested 563 serum samples from a longitudinal pediatric cohort study previously conducted in Cambodia. Children enrolled in the study were dengue-naive at baseline and were followed biannually for dengue incidence for two years. We used Western blotting and enzyme-linked immunosorbent assays to identify immunogenic Aedes aegypti salivary proteins and measure total anti-Ae. aegypti IgG. Results: We found a correlation (rs=0.86) between IgG responses against AeD7L1 and AeD7L2 recombinant proteins and those to whole salivary gland homogenate. We observed seasonal fluctuations of AeD7L1+2 IgG responses and no cross-reactivity with Culex quinquefasciatus and Anopheles dirus mosquitoes. The baseline median AeD7L1+2 IgG responses for young children were higher in those who developed asymptomatic versus symptomatic dengue. Discussion: The IgG response against AeD7L1+2 recombinant proteins is a highly sensitive and Aedes specific marker of human exposure to Aedes bites that can facilitate standardization of future serosurveys and epidemiological studies by its ability to provide a robust estimation of human-mosquito contact in a high-throughput fashion.
Subject(s)
Aedes , Dengue , Insect Proteins , Mosquito Vectors , Salivary Proteins and Peptides , Humans , Aedes/immunology , Aedes/virology , Animals , Salivary Proteins and Peptides/immunology , Child , Mosquito Vectors/immunology , Mosquito Vectors/virology , Dengue/immunology , Dengue/transmission , Insect Proteins/immunology , Female , Child, Preschool , Immunoglobulin G/immunology , Immunoglobulin G/blood , Male , Cambodia , Longitudinal Studies , Dengue Virus/immunology , Adolescent , Insect Bites and Stings/immunologyABSTRACT
Introduction: Aedes spp. are the most prolific mosquito vectors in the world. Found on every continent, they can effectively transmit various arboviruses, including the dengue virus which continues to cause outbreaks worldwide and is spreading into previously non-endemic areas. The lack of widely available dengue vaccines accentuates the importance of targeted vector control strategies to reduce the dengue burden. High-throughput sensitive tools to estimate human-mosquito contact and evaluate vector control interventions are lacking. We propose a novel serological tool that allows rapid screening of large human cohorts for exposure to potentially infectious mosquitoes and effective targeting of vector control. Methods: We tested 563 serum samples from a longitudinal pediatric cohort study previously conducted in Cambodia. Children enrolled in the study were dengue-naïve at baseline and were followed biannually for dengue incidence for two years. We used Western blotting and enzyme-linked immunosorbent assays to identify the most immunogenic Aedes aegypti salivary proteins and measure total anti- Ae. Aegypti IgG. Results: We found a strong correlation (r s =0.86) between the combined IgG responses against AeD7L1 and AeD7L2 recombinant proteins and those to whole salivary gland homogenate. We observed seasonal fluctuations of AeD7L1+2 IgG responses, corresponding to Aedes spp. abundance in the region, and no cross-reactivity with Culex quinquefasciatus and Anopheles dirus mosquitoes. The baseline median AeD7L1+2 IgG responses for young children were higher in those who developed asymptomatic dengue versus those who developed symptomatic dengue. Conclusion: The IgG response against AeD7L1+2 recombinant proteins is a highly sensitive and Aedes specific marker of human exposure to Aedes bites that can facilitate standardization of future serosurveys and epidemiological studies by its ability to provide a robust estimation of human-mosquito contact in a high-throughput fashion.