Delayed acquisition of Plasmodium falciparum antigen-specific CD4+ T cell responses in HIV-exposed uninfected Malawian children receiving daily cotrimoxazole prophylaxis

BACKGROUND: Cotrimoxazole (CTX) prophylaxis, recommended in HIV-exposed uninfected (HEU) children primarily against HIV-related opportunistic infections, has been shown to have some efficacy against Plasmodium falciparum malaria. The effects of CTX prophylaxis on the acquisition of P. falciparum antigen specific CD4(+) T cells-mediated immunity in HEU children is still not fully understood. METHODS: Peripheral blood was collected from HEU and HIV-unexposed uninfected (HUU) children at 6, 12 and 18 months of age. Proportion of CD4(+) T cells subsets were determined by immunophenotyping. P. falciparum antigen-specific CD4(+) T cells responses were measured by intracellular cytokine staining assay. RESULTS: There were no differences in the proportions of naïve, effector and memory CD4(+) T cell subsets between HEU and HUU children at all ages. There was a trend showing acquisition of P. falciparum-specific IFN-γ and TNF-producing CD4(+) T cells with age in both HUU and HEU children. There was, however, lower frequency of P. falciparum-specific IFN-γ-producing CD4(+) T cells in HEU compared to HUU at 6 and 12 months, which normalized 6 months after stopping CTX prophylaxis. CONCLUSION: The results demonstrate that there is delayed acquisition of P. falciparum-specific IFN-γ-producing CD4(+) T cells in HEU children on daily cotrimoxazole prophylaxis, which is evident at 6 and 12 months of age in comparison to HUU age-matched controls. However, whether this delayed acquisition of P. falciparum-specific IFN-γ-producing CD4(+) T cells leads to higher risk to malaria disease remains unknown and warrants further investigation

Characterising B cell numbers and memory B cells in HIV infected and uninfected Malawian adults

BACKGROUND: Untreated human immunodeficiency virus (HIV) disease disrupts B cell populations causing reduced memory and reduced naïve resting B cells leading to increases in specific co-infections and impaired responses to vaccines. To what extent antiretroviral treatment reverses these changes in an African population is uncertain. METHODS: A cross-sectional study was performed. We recruited HIV-uninfected and HIV-infected Malawian adults both on and off antiretroviral therapy attending the Queen Elizabeth Central hospital in Malawi. Using flow cytometry, we enumerated B cells and characterized memory B cells and compared these measurements by the different recruitment groups. RESULTS: Overall 64 participants were recruited - 20 HIV uninfected (HIV-), 30 HIV infected ART naïve (HIV+N) and 14 HIV-infected ART treated (HIV+T). ART treatment had been taken for a median of 33 months (Range 12-60 months). Compared to HIV- the HIV+N adults had low absolute number of naïve resting B cells (111 vs. 180 cells/μl p = 0.008); reduced memory B cells (27 vs. 51 cells/μl p = 0.0008). The HIV+T adults had B-cell numbers similar to HIV- except for memory B cells that remained significantly lower (30 vs. 51 cells/μl p = 0.02). In the HIV+N group we did not find an association between CD4 count and B cell numbers. CONCLUSIONS: HIV infected Malawian adults have abnormal B-cell numbers. Individuals treated with ART show a return to normal in B-cell numbers but a persistent deficit in the memory subset is noted. This has important implications for long term susceptibility to co-infections and should be evaluated further in a larger cohort study

Facilitating factors and barriers to malaria research utilization for policy development in Malawi

BACKGROUND : Research on various determinants of health is key in providing evidence for policy development, thereby leading to successful interventions. Utilization of research is an intricate process requiring an understanding of contextual factors. The study was conducted to assess enhancing factors and barriers of research utilization for malaria policy development in Malawi. METHODS : Qualitative research approach was used through in-depth interviews with 39 key informants that included malaria researchers, policy makers, programme managers, and key stakeholders. Purposive sampling and snowballing techniques were used in identifying key informants. Interview transcripts were entered in QSR Nvivo 11 software for coding and analysis. RESULTS : Respondents identified global efforts as key in advancing knowledge translation, while local political will has been conducive for research utilization. Other factors were availability of research, availability of diverse local researchers and stakeholders supporting knowledge translation. While barriers included: lack of platforms for researcher-public engagement, politics, researchers’ lack of communication skills, lack of research collaborations, funder driven research, unknown World Health Organization policy position, and the lack of a malaria research repository. CONCLUSION : Overall, the study identified facilitating factors to malaria research utilization for policy development in Malawi. These factors need to be systematically coordinated to address the identified barriers and improve on malaria research utilization in policy development. Malaria research can be key in the implementation of evidence-based interventions to reduce the malaria burden and assist in the paradigm shift from malaria control to elimination in Malawi.University of Pretoria Institute for Sustainable Malaria Control (UP ISMC)http://www.malariajournal.comam2016School of Health Systems and Public Health (SHSPH

Critical agency and development: applying Freire and Sen to ICT4D in Zambia and Brazil

This paper draws upon critical theories and the capability approach. It argues for a conceptualization of development as a process designed to enable people to free themselves from structural disadvantage. Amartya Sen has argued that people’s “critical-agency” to question and reject unjust social norms is “pivotal” to human development and important for tackling inequalities of any kind. Freire’s critical pedagogy, and critical feminism, go further by providing disadvantaged people with the practical means to do this; to identify the structural root causes of unjust social norms and the critical-agency to challenge and change them. Two empirical case studies of ICT4D are presented, from Zambia and Brazil, which draw upon these critical approaches but use them in different ways. The paper argues that ICT4D must go beyond addressing people’s immediate practical needs for access to ICT tools and skills, to also address their strategic interest in identifying and tackling the root causes of disadvantage

The effect of daily co-trimoxazole prophylaxis on natural development of antibody-mediated immunity against P. falciparum malaria infection in HIV-exposed uninfected Malawian children.

BACKGROUND AND OBJECTIVES: Co-trimoxazole prophylaxis, currently recommended in HIV-exposed, uninfected (HEU) children as protection against opportunistic infections, also has some anti-malarial efficacy. We determined whether daily co-trimoxazole prophylaxis affects the natural development of antibody-mediated immunity to blood-stage Plasmodium falciparum malaria infection. METHODS: Using an enzyme-linked immunosorbent assay, we measured antibodies to 8 Plasmodium falciparum antigens (AMA-1, MSP-119, MSP-3, PfSE, EBA-175RII, GLURP R0, GLURP R2 and CSP) in serum samples from 33 HEU children and 31 HIV-unexposed, uninfected (HUU) children, collected at 6, 12 and 18 months of age. RESULTS: Compared to HIV-uninfected children, HEU children had significantly lower levels of specific IgG against AMA-1 at 6 months (p = 0.001), MSP-119 at 12 months (p = 0.041) and PfSE at 6 months (p = 0.038), 12 months (p = 0.0012) and 18 months (p = 0.0097). No differences in the IgG antibody responses against the rest of the antigens were observed between the two groups at all time points. The breadth of specificity of IgG response was reduced in HEU children compared to HUU children during the follow up period. CONCLUSIONS: Co-trimoxazole prophylaxis seems to reduce IgG antibody responses to P. falciparum blood stage antigens, which could be as a result of a reduction in exposure of those children under this regime. Although antibody responses were regarded as markers of exposure in this study, further studies are required to establish whether these responses are correlated in any way to clinical immunity to malaria