Respiratory viruses in rural Zambia during the second year of the COVID-19 pandemic.

Objectives: Limited data on respiratory infections are available from sub-Saharan Africa during the COVID-19 pandemic. The objective of this study was to evaluate the burden of respiratory viruses in rural Zambia from 2019-2021. Methods: Surveillance was initiated at Macha Hospital in Zambia in December 2018. Each week, patients with respiratory symptoms were enrolled from the outpatient clinic. Nasopharyngeal samples were collected and tested for respiratory pathogens. The prevalence of respiratory symptoms and viruses in 2021 was compared to results from 2019 and 2020. Results: After seeing few cases of influenza virus and respiratory syncytial virus in 2020, a return to prepandemic levels was observed in 2021. Rhinovirus/enterovirus, parainfluenza virus 1-4, and adenovirus circulated from 2019 to 2021, while human metapneumovirus and human coronaviruses (HKU1, 229E, OC43, and NL63 subtypes) were observed sporadically. SARS-CoV-2 was observed consistently in 2021 after being first identified in December 2020. The proportion of participants with co-infections in 2021 (11.6%) was significantly higher than in 2019 (6.9%) or 2020 (7.7%). Conclusion: Declines in influenza virus and respiratory syncytial virus were reversed once public health measures were lifted. Respiratory viruses contributed to a significant burden of respiratory infections in 2021. This study provides important information about respiratory viruses in this changing context and underrepresented region.

Quantifying quality: The impact of measures of school quality on children's academic achievement across diverse societies.

Recent decades have seen a rapid acceleration in global participation in formal education, due to worldwide initiatives aimed to provide school access to all children. Research in high income countries has shown that school quality indicators have a significant, positive impact on numeracy and literacy-skills required to participate in the increasingly globalized economy. Schools vary enormously in kind, resources, and teacher training around the world, however, and the validity of using diverse school quality measures in populations with diverse educational profiles remains unclear. First, we assessed whether children's numeracy and literacy performance across populations improves with age, as evidence of general school-related learning effects. Next, we examined whether several school quality measures related to classroom experience and composition, and to educational resources, were correlated with one another. Finally, we examined whether they were associated with children's (4-12-year-olds, N = 889) numeracy and literacy performance in 10 culturally and geographically diverse populations which vary in historical engagement with formal schooling. Across populations, age was a strong positive predictor of academic achievement. Measures related to classroom experience and composition were correlated with one another, as were measures of access to educational resources and classroom experience and composition. The number of teachers per class and access to writing materials were key predictors of numeracy and literacy, while the number of students per classroom, often linked to academic achievement, was not. We discuss these results in the context of maximising children's learning environments and highlight study limitations to motivate future research. RESEARCH HIGHLIGHTS: We examined the extent to which four measures of school quality were associated with one another, and whether they predicted children's academic achievement in 10 culturally and geographically diverse societies. Across populations, measures related to classroom experience and composition were correlated with one another as were measures of access to educational resources to classroom experience and composition. Age, the number of teachers per class, and access to writing materials were key predictors of academic achievement across populations. Our data have implications for designing efficacious educational initiatives to improve school quality globally.

Cellular and humoral immunity to Ebola Zaire glycoprotein and viral vector proteins following immunization with recombinant vesicular stomatitis virus-based Ebola vaccine (rVSVΔG-ZEBOV-GP).

While effective at preventing Zaire ebolavirus (ZEBOV) disease, cellular immunity to ZEBOV and vector-directed immunity elicited by the recombinant vesicular stomatitis virus expressing ZEBOV glycoprotein (rVSVΔG-ZEBOV-GP) vaccine remain poorly understood. Sera and peripheral blood mononuclear cells were collected from 32 participants enrolled in a prospective multicenter study [ClinicalTrials.gov NCT02788227] before vaccination and up to six months post-vaccination. IgM and IgG antibodies, IgG-producing memory B cells (MBCs), and T cell reactivity to ZEBOV glycoprotein (ZEBOV-GP), vesicular stomatitis virus-Indiana strain (VSV-I) matrix (M) protein, and VSV-I nucleoprotein (NP) were measured using ELISA, ELISpot, and flow cytometry, respectively. 11/32 (34.4%) participants previously received a different investigational ZEBOV vaccine prior to enrollment and 21/32 (65.6%) participants were ZEBOV vaccine naïve. Both ZEBOV vaccine naïve and experienced participants had increased ZEBOV-GP IgG optical densities (ODs) post-rVSVΔG-ZEBOV-GP vaccination while only ZEBOV vaccine naïve participants had increased ZEBOV-GP IgM ODs. Transient IgM and IgG antibody responses to VSV-I M protein and NP were observed in a minority of participants. All participants had detectable ZEBOV-GP specific IgG-producing MBCs by 6 months post-vaccination while no changes were observed in the median IgG-producing MBCs to VSV-I proteins. T cell responses to ZEBOV-GP differed between ZEBOV vaccine experienced and ZEBOV vaccine naïve participants. T cell responses to both VSV-I M protein and VSV-I NP were observed, but were of a low magnitude. The rVSVΔG-ZEBOV-GP vaccine elicits robust humoral and memory B cell responses to ZEBOV glycoprotein in both ZEBOV vaccine naïve and experienced individuals and can generate vector-directed T cell immunity. Further research is needed to understand the significance of pre-existing vector and target antigen immunity on responses to booster doses of rVSVΔG-ZEBOV-GP and other rVSV-vectored vaccines.

Uptake of public health measures and vaccine acceptance during the COVID-19 pandemic in rural Zambia.

Vaccines are effective tools to prevent COVID-19-related morbidity. However, coverage is low throughout sub-Saharan Africa. Uptake of public health measures, perceptions of COVID-19 illness and vaccines, and intention to vaccinate were evaluated in 2021-2022 in rural Zambia. Adherence to public health measures, perceptions of COVID-19 risk and severity, and vaccine acceptance increased significantly over time, particularly in December 2021, coinciding with the fourth pandemic wave and relaunch of the national vaccine campaign. Vaccine acceptance was associated with perceptions of vaccine safety and effectiveness, but not disease severity. These findings highlight the importance of strong pandemic response and public communication for increased uptake of mitigatory measures, including vaccine acceptance.

Factors associated with antiretroviral therapy use among pregnant women in rural and urban settings in Southern Province, Zambia: 2016-2019.

OBJECTIVES: To assess antiretroviral therapy (ART) coverage among pregnant women living with HIV and compare the characteristics of women who received and did not receive ART during pregnancy in Zambia. METHODS: A cross-sectional study was conducted at urban and rural health facilities in Southern Province, Zambia, from 2016 to 2019. Pregnant women living with HIV delivering at study sites were enrolled and administered a questionnaire, and the results of infant diagnostic testing for HIV at birth was documented. RESULTS: About 1184 mother/infant pairs were enrolled. ART coverage was 93.7%. Most women who did not receive ART during pregnancy reported HIV diagnosis at delivery (18.0%) or during pregnancy (57.7%). The primary reported reason for not receiving ART was not wanting to take the drugs. Women who did not receive ART during pregnancy were significantly younger, less likely to have disclosed their HIV-infection status to others, and less likely to have received antenatal care than women who received ART. ART use correlated with higher levels of education in urban but not rural sites. Overall, 1.0% of infants were infected with HIV at birth, including 0.8% of infants born to women who received ART and 4.1% of infants born to women who did not. CONCLUSIONS: Most women received ART according to guidelines, resulting in low perinatal transmission rates of HIV to infants. Efforts to increase ART coverage and prevent vertical transmission should focus on identifying incident HIV infections during pregnancy and strengthening counselling for newly diagnosed pregnant women.

Rapid Generation of Neutralizing Antibody Responses in COVID-19 Patients.

SARS-CoV-2, the virus responsible for COVID-19, is causing a devastating worldwide pandemic, and there is a pressing need to understand the development, specificity, and neutralizing potency of humoral immune responses during acute infection. We report a cross-sectional study of antibody responses to the receptor-binding domain (RBD) of the spike protein and virus neutralization activity in a cohort of 44 hospitalized COVID-19 patients. RBD-specific IgG responses are detectable in all patients 6 days after PCR confirmation. Isotype switching to IgG occurs rapidly, primarily to IgG1 and IgG3. Using a clinical SARS-CoV-2 isolate, neutralizing antibody titers are detectable in all patients by 6 days after PCR confirmation and correlate with RBD-specific binding IgG titers. The RBD-specific binding data were further validated in a clinical setting with 231 PCR-confirmed COVID-19 patient samples. These findings have implications for understanding protective immunity against SARS-CoV-2, therapeutic use of immune plasma, and development of much-needed vaccines.

Rapid generation of neutralizing antibody responses in COVID-19 patients.

SARS-CoV-2 is currently causing a devastating pandemic and there is a pressing need to understand the dynamics, specificity, and neutralizing potency of the humoral immune response during acute infection. Herein, we report the dynamics of antibody responses to the receptor-binding domain (RBD) of the spike protein and virus neutralization activity in 44 COVID-19 patients. RBD-specific IgG responses were detectable in all patients 6 days after PCR confirmation. Using a clinical isolate of SARS-CoV-2, neutralizing antibody titers were also detectable in all patients 6 days after PCR confirmation. The magnitude of RBD-specific IgG binding titers correlated strongly with viral neutralization. In a clinical setting, the initial analysis of the dynamics of RBD-specific IgG titers was corroborated in a larger cohort of PCR-confirmed patients (n=231). These findings have important implications for our understanding of protective immunity against SARS-CoV-2, the use of immune plasma as a therapy, and the development of much-needed vaccines.