Limited O-specific polysaccharide (OSP)-specific functional antibody responses in young children with Shigella infection in Bangladesh.

Shigellosis is the second leading cause of diarrheal death in children younger than five years of age globally. At present, there is no broadly licensed vaccine against shigella infection. Previous vaccine candidates have failed at providing protection for young children in endemic settings. Improved understanding of correlates of protection against Shigella infection and severe shigellosis in young children living in endemic settings is needed. Here, we applied a functional antibody profiling approach to define Shigella-specific antibody responses in young children versus older individuals with culture-confirmed shigellosis in Bangladesh, a Shigella endemic area. We analyzed Shigella-specific antibody isotypes, FcR binding and antibody-mediated innate immune cell activation in longitudinal serum samples collected at clinical presentation and up to 1 year later. We found that higher initial Shigella O-specific polysaccharide (OSP)-specific and protein-specific IgG and FcγR binding levels correlated with less severe disease regardless of patient age, but that individuals under 5 years of age developed a less prominent class switched, FcR-binding, functional and durable antibody response against both OSP and protein Shigella antigens than older individuals. Focusing on the largest cohort, we found that functional S. flexneri 2a OSP-specific responses were significantly induced only in individuals over age 5 years, and that these responses promoted monocyte phagocytosis and activation. Our findings suggest that in a Shigella endemic region, young children with shigellosis harbor a functional antibody response that fails to maximally activate monocytes; such a response may be important in facilitating subsequent innate cell clearance of Shigella, especially via recruitment and activation of polymorphonuclear cells capable of directly killing Shigella.

Longevity of memory B cells and antibodies, as well as the polarization of effector memory helper T cells, are associated with disease severity in patients with COVID-19 in Bangladesh.

The longevity of immune responses induced by different degrees of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection provides information important to understanding protection against coronavirus disease 2019 (COVID-19). Here, we report the persistence of SARS-CoV-2 spike receptor-binding domain (RBD) specific antibodies and memory B cells recognizing this antigen in sequential samples from patients in Bangladesh with asymptomatic, mild, moderate and severe COVID-19 out to six months following infection. Since the development of long-lived memory B cells, as well as antibody production, is likely to be dependent on T helper (Th) cells, we also investigated the phenotypic changes of Th cells in COVID-19 patients over time following infection. Our results show that patients with moderate to severe COVID-19 mounted significant levels of IgG antibodies out to six months following infection, while patients with asymptomatic or mild disease had significant levels of IgG antibodies out to 3 months following infection, but these then fell more rapidly at 6 months than in patients with higher disease severity. Patients from all severity groups developed circulating memory B cells (MBCs) specific to SARS-CoV-2 spike RBD by 3 months following infection, and these persisted until the last timepoint measured at 6 months. A T helper cell response with an effector memory phenotype was observed following infection in all symptomatic patients, while patients with asymptomatic infection had no significant increases in effector Th1, Th2 and Th17 effector memory cell responses. Our results suggest that the strength and magnitude of antibody and memory B cells induced following SARS-CoV-2 infection depend on the severity of the disease. Polarization of the Th cell response, with an increase in Th effector memory cells, occurs in symptomatic patients by day 7 following infection, with increases seen in Th1, Th2, Th17 and follicular helper T cell subsets.

Recent spatial gradients and time trends in Dhaka, Bangladesh, air pollution and their human health implications.

Dhaka, the capital of Bangladesh, is among the most polluted cities in the world. This research evaluates seasonal patterns, day-of-week patterns, spatial gradients, and trends in PM2.5 (<2.5 µm in aerodynamic diameter), PM10 (<10 µm in aerodynamic diameter), and gaseous pollutants concentrations (SO2, NO2, CO, and O3) monitored in Dhaka from 2013 to 2017. It expands on past work by considering multiple monitoring sites and air pollutants. Except for ozone, the average concentrations of these pollutants showed strong seasonal variation, with maximum during winter and minimum during monsoon, with the pollution concentration of PM2.5 and PM10 being roughly five- to sixfold higher during winter versus monsoon. Our comparisons of the pollutant concentrations with Bangladesh NAAQS and U.S. NAAQS limits analysis indicate particulate matter (PM2.5 and PM10) as the air pollutants of greatest concern, as they frequently exceeded the Bangladesh NAAQS and U.S. NAAQS, especially during nonmonsoon time. In contrast, gaseous pollutants reported far fewer exceedances throughout the study period. During the study period, the highest number of exceedances of NAAQS limits in Dhaka City (Darus-Salam site) were found for PM2.5 (72% of total study days), followed by PM10 (40% of total study days), O3 (1.7% of total study days), SO2 (0.38% of total study days), and CO (0.25% of total study days). The trend analyses results showed statistically significant positive slopes over time for SO2 (5.6 ppb yr-1, 95% confidence interval [CI]: 0.7, 10.5) and CO (0.32 ppm yr-1, 95% CI: 0.01, 0.56), which suggest increase in brick kilns operation and high-sulfur diesel use. Though statistically nonsignificant annual decreasing slopes for PM2.5 (-4.6 µg/m3 yr-1, 95% CI: -12.7, 3.6) and PM10 (-2.7 µg/m3 yr-1, 95% CI: -7.9, 2.5) were observed during this study period, the PM2.5 concentration is still too high (~ 82.0 µg/m3) and can cause severe impact on human health. Implications: This study revealed key insights into air quality challenges across Dhaka, Bangladesh, indicating particulate matter (PM) as Dhaka's most serious air pollutant threat to human health. The results of these analyses indicate that there is a need for immediate further investigations, and action based on those investigations, including the conduct local epidemiological PM exposure-human health effects studies for this city, in order to determine the most public health effective interventions.