The Correlation Between Human Biting Specialization in Aedes aegypti and Modern Disease Outbreaks in Africa

Aedes aegypti (Ae. aegypti), the vector for various arboviruses, is a major source of public health concern. Currently, there is not much known about their host-seeking behavior and their evolution from generalists to human-biting specialists. By investigating their evolutionary history, I hope to elucidate the factors that drove this subspecies to diverge from their ancestors and also connect the historical narrative with their present distribution. I hypothesize that since Ae. aegypti evolved into human-biting specialists in the Sahel region of Africa, these mosquitoes should still have a larger prevalence in this region, and correspondingly an increased disease burden regarding the viruses which the vector transmits. To investigate this relationship, I used World Health Organization data to track disease outbreaks in several countries of interest in and around the Sahel. By plotting this data on a map, I was able to analyze the burden of yellow fever and dengue on the Sahel. The results showed that there was an increased prevalence of yellow fever outbreaks in the Sahel region in West Africa, but an even distribution of dengue outbreaks throughout Africa. These findings imply that the relative presence of the host may not be the only variable influencing observed transmission patterns. The vector, as well as the diseases themselves, are sensitive to external factors such as temperature and human population density which can cause unexpected health outcomes

Biomarkers of pembrolizumab efficacy in advanced anal squamous cell carcinoma: analysis of a phase II clinical trial and a cohort of long-term responders

Background Recent trials suggest that programmed cell death 1 (PD-1)-directed immunotherapy may be beneficial for some patients with anal squamous cell carcinoma and biomarkers predictive of response are greatly needed.Methods This multicenter phase II clinical trial (NCT02919969) enrolled patients with metastatic or locally advanced incurable anal squamous cell carcinoma (n=32). Patients received pembrolizumab 200 mg every 3 weeks. The primary endpoint of the trial was objective response rate (ORR). Exploratory objectives included analysis of potential predictive biomarkers including assessment of tumor-associated immune cell populations with multichannel immunofluorescence and analysis of circulating tumor tissue modified viral-human papillomavirus DNA (TTMV-HPV DNA) using serially collected blood samples. To characterize the clinical features of long-term responders, we combined data from our prospective trial with a retrospective cohort of patients with anal cancer treated with anti-PD-1 immunotherapy (n=18).Results In the phase II study, the ORR to pembrolizumab monotherapy was 9.4% and the median progression-free survival was 2.2 months. Despite the high level of HPV positivity observed with circulating TTMV-HPV DNA testing, the majority of patients had low levels of tumor-associated CD8+PD-1+ T cells on pretreatment biopsy. Patients who benefited from pembrolizumab had decreasing TTMV-HPV DNA scores and a complete responder’s TTMV-HPV DNA became undetectable. Long-term pembrolizumab responses were observed in one patient from the trial (5.3 years) and three patients (2.5, 6, and 8 years) from the retrospective cohort. Long-term responders had HPV-positive tumors, lacked liver metastases, and achieved a radiological complete response.Conclusions Pembrolizumab has durable efficacy in a rare subset of anal cancers. However, despite persistence of HPV infection, indicated by circulating HPV DNA, most advanced anal cancers have low numbers of tumor-associated CD8+PD-1+ T cells and are resistant to pembrolizumab