Validity, reliability, and measurement invariance of an adapted short version of the HIV stigma scale among perinatally HIV infected adolescents at the Kenyan coast

Background: There is a dearth of instruments that have been developed and validated for use with children living with HIV under the age of 17 years in the Kenyan context. We examined the psychometric properties and measurement invariance of a short version of the Berger HIV stigma scale administered to perinatally HIV-infected adolescents in a rural setting on the Kenyan coast. Methods: A cross-sectional study was conducted among 201 perinatally HIV-infected adolescents aged 12-17 years between November 2017 and October 2018. A short version of the Berger HIV stigma scale (HSS-40) containing twelve items (HSS-12) covering the four dimensions of stigma was evaluated. The psychometric assessment included exploratory factor analysis, confirmatory factor analysis (CFA), and multi-group CFA. Additionally, scale reliability was evaluated as internal consistency by calculating Cronbach\u27s alpha. Results: Evaluation of the reliability and construct validity of the HSS-12 indicated insufficient reliability on three of the four subscales. Consequently, Exploratory Factor Analysis (EFA) was conducted to identify problematic items and determine ways to enhance the scale\u27s reliability. Based on the EFA results, two items were dropped. The Swahili version of this new 10-item HIV stigma scale (HSS-10) demonstrated excellent internal consistency with a Cronbach alpha of 0.86 (95% confidence interval (CI) 0.84-0.89). Confirmatory Factor Analysis indicated that a unidimensional model best fitted the data. The HSS-10 presented a good fit (overall Comparative Fit Index = 0.976, Tucker Lewis Index = 0.969, Root Mean Square Error of Approximation = 0.040, Standardised Root Mean Residual = 0.045). Additionally, multi-group CFA indicated measurement invariance across gender and age groups at the strict invariance level as ΔCFI was ≤ 0.01. Conclusion: Our findings indicate that the HSS-10 has good psychometric properties and is appropriate for evaluating HIV stigma among perinatally HIV-infected adolescents on the Kenyan coast. Further, study results support the unidimensional model and measurement invariance across gender and age groups of the HSS-10 measure

FCRL5 Delineates Functionally Impaired Memory B Cells Associated with Plasmodium falciparum Exposure.

Exposure to Plasmodium falciparum is associated with circulating "atypical" memory B cells (atMBCs), which appear similar to dysfunctional B cells found in HIV-infected individuals. Functional analysis of atMBCs has been limited, with one report suggesting these cells are not dysfunctional but produce protective antibodies. To better understand the function of malaria-associated atMBCs, we performed global transcriptome analysis of these cells, obtained from individuals living in an area of high malaria endemicity in Uganda. Comparison of gene expression data suggested down-modulation of B cell receptor signaling and apoptosis in atMBCs compared to classical MBCs. Additionally, in contrast to previous reports, we found upregulation of Fc receptor-like 5 (FCRL5), but not FCRL4, on atMBCs. Atypical MBCs were poor spontaneous producers of antibody ex vivo, and higher surface expression of FCRL5 defined a distinct subset of atMBCs compromised in its ability to produce antibody upon stimulation. Moreover, higher levels of P. falciparum exposure were associated with increased frequencies of FCRL5+ atMBCs. Together, our findings suggest that FCLR5+ identifies a functionally distinct, and perhaps dysfunctional, subset of MBCs in individuals exposed to P. falciparum

Avidity of anti-malarial antibodies inversely related to transmission intensity at three sites in Uganda.

BACKGROUND: People living in malaria endemic areas acquire protection from severe malaria quickly, but protection from clinical disease and control of parasitaemia is acquired only after many years of repeated infections. Antibodies play a central role in protection from clinical disease; however, protective antibodies are slow to develop. This study sought to investigate the influence of Plasmodium falciparum exposure on the acquisition of high-avidity antibodies to P. falciparum antigens, which may be associated with protection. METHODS: Cross-sectional surveys were performed in children and adults at three sites in Uganda with varied P. falciparum transmission intensity (entomological inoculation rates; 3.8, 26.6, and 125 infectious bites per person per year). Sandwich ELISA was used to measure antibody responses to two P. falciparum merozoite surface antigens: merozoite surface protein 1-19 (MSP1-19) and apical membrane antigen 1 (AMA1). In individuals with detectable antibody levels, guanidine hydrochloride (GuHCl) was added to measure the relative avidity of antibody responses by ELISA. RESULTS: Within a site, there were no significant differences in median antibody levels between the three age groups. Between sites, median antibody levels were generally higher in the higher transmission sites, with differences more apparent for AMA-1 and in ≥5 year group. Similarly, median avidity index (proportion of high avidity antibodies) showed no significant increase with increasing age but was significantly lower at sites of higher transmission amongst participants ≥5 years of age. Using 5 M GuHCl, the median avidity indices in the ≥5 year group at the highest and lowest transmission sites were 19.9 and 26.8, respectively (p = 0.0002) for MSP1-19 and 12.2 and 17.2 (p = 0.0007) for AMA1. CONCLUSION: Avidity to two different P. falciparum antigens was lower in areas of high transmission intensity compared to areas with lower transmission. Appreciation of the mechanisms behind these findings as well as their clinical consequences will require additional investigation, ideally utilizing longitudinal data and investigation of a broader array of responses

B cell sub-types following acute malaria and associations with clinical immunity.

BACKGROUND: Repeated exposure to Plasmodium falciparum is associated with perturbations in B cell sub-set homeostasis, including expansion atypical memory B cells. However, B cell perturbations immediately following acute malaria infection have been poorly characterized, especially with regard to their relationship with immunity to malaria. METHODS: To better understand the kinetics of B cell sub-sets following malaria, the proportions of six B cell sub-sets were assessed at five time points following acute malaria in four to 5 years old children living in a high transmission region of Uganda. B cell sub-set kinetics were compared with measures of clinical immunity to malaria-lower parasite density at the time of malaria diagnosis and recent asymptomatic parasitaemia. RESULTS: Atypical memory B cell and transitional B cell proportions increased following malaria. In contrast, plasmablast proportions were highest at the time of malaria diagnosis and rapidly declined following treatment. Increased proportions of atypical memory B cells were associated with greater immunity to malaria, whereas increased proportions of transitional B cells were associated with evidence of less immunity to malaria. CONCLUSIONS: These findings highlight the dynamic changes in multiple B cell sub-sets following acute, uncomplicated malaria, and how these sub-sets are associated with developing immunity to malaria

Quantification of anti-parasite and anti-disease immunity to malaria as a function of age and exposure.

Fundamental gaps remain in our understanding of how immunity to malaria develops. We used detailed clinical and entomological data from parallel cohort studies conducted across the malaria transmission spectrum in Uganda to quantify the development of immunity against symptomatic P. falciparum as a function of age and transmission intensity. We focus on: anti-parasite immunity (i.e. ability to control parasite densities) and anti-disease immunity (i.e. ability to tolerate higher parasite densities without fever). Our findings suggest a strong effect of age on both types of immunity, not explained by cumulative-exposure. They also show an independent effect of exposure, where children living in moderate/high transmission settings develop immunity faster as transmission increases. Surprisingly, children in the lowest transmission setting appear to develop immunity more efficiently than those living in moderate transmission settings. Anti-parasite and anti-disease immunity develop in parallel, reducing the probability of experiencing symptomatic malaria upon each subsequent P. falciparum infection

A year of genomic surveillance reveals how the SARS-CoV-2 pandemic unfolded in Africa

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The global financial crisis and developing countries

When the global financial crisis broke out in earnest in September 2008, it quickly became clear that developing countries would also be affected, but that the impacts would vary markedly. The Overseas Development Institute (ODI) coordinated a multi-country study over January-March 2009 involving developing country teams in 10 countries. This showed that, while the transmission mechanisms were similar in each (trade, private capital flows, remittances, aid), the effects varied by country, and much was not yet visible. As such, further country-specific monitoring was required. Most findings suggested that, as a result of time lags, the worst effects were yet to come. This synthesis of the effects of the global financial crisis on developing countries updates the description of the economic and social situation during the course of the crisis in 11 countries

The evolving SARS-CoV-2 epidemic in Africa: insights from rapidly expanding genomic surveillance

Investment in SARS-CoV-2 sequencing in Africa over the past year has led to a major increase in the number of sequences generated, now exceeding 100,000 genomes, used to track the pandemic on the continent. Our results show an increase in the number of African countries able to sequence domestically, and highlight that local sequencing enables faster turnaround time and more regular routine surveillance. Despite limitations of low testing proportions, findings from this genomic surveillance study underscore the heterogeneous nature of the pandemic and shed light on the distinct dispersal dynamics of Variants of Concern, particularly Alpha, Beta, Delta, and Omicron, on the continent. Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve, while the continent faces many emerging and re-emerging infectious disease threats. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century