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

Geothermal Development in Malawi -a Country Update

ABSTRACT Malawi, one of the poorest countries in Africa, has major electricity generating difficulties, due to limited conventional fossil fuel resources and an over reliance on one form of electricity generation, viz. hydroelectricity, with very low generation capacity. Due to its location within the East African Rift System (EARS), one of the hottest geothermal zones in the world, it is endowed with significant potential geothermal energy resources. In recent decades, there has been major global growth in geothermal energy utilization, both in direct utilization applications and in electricity generation. However, despite its favourable location, Malawi has been slow in harnessing its potentially significant geothermal resources. Geological investigations of the Malawi sector of the EARS indicates that the Malawi Rift is controlled by N-S rift parallel normal faults, that also control upwards migration of the geothermal waters feeding hot springs, which occur along the length of the rift. The hot springs with the most potential for electricity generation occurs mainly in the northern half of the country and are thought to be sourced from porous sedimentary reservoirs at depth, either deeply buried young Neogene rift floor deposits or older Karoo sandstones, occurring in fault-bound basins within the Precambrian framework of the country. A recent investigation to catalogue all of the hot springs in Malawi has led to the identification of 15 previously undocumented springs including the third hottest spring recorded in the investigation. This exercise has resulted in the delineation of 6 or 7 groups of springs with appropriate temperatures and geological settings that suggest a potential for electricity generation. These merit further detailed surface geological, geophysical and geochemical exploration and monitoring, which should be undertaken, prior to any decisions on drilling. Other lower temperature hot springs in the country have the potential for utilisation for various direct applications, which could bring major benefits to local communities. Icelandic International Development Agency (ICEIDA) is positive to support Malawi in coming up with proper legal frameworks in geothermal development while the World Bank, under the Energy Sector Support Programme (ESSP), is supporting in the development of Terms of Reference for pre-feasibility studies in geothermal development. Some reputable international institutions, through their fact finding missions, have also made advances to assist in the exercise. Major challenges hindering geothermal development in Malawi have been the absence of both technical and financial capacity, and the lack of government leadership in spearheading an assessment of the geothermal resources of the country. This has resulted in a spirit of individualism, coupled with an absence of collaborative cooperation between government agencies, research organisations and institutes of higher learning, which has led to a failure to share information, consequent duplication of tasks and unnecessary waste of resources. The Government of Malawi claims to have instituted a geothermal working group, consisting of all the stakeholders from government, industry, research organisations and teaching institutions which seems to be non-existent due to its non-functionality. Malawi also needs to develop its technical capacity through specialized geothermal training programmes such as the United Nations University -Geothermal Training Program (UNU-GTP) in Iceland and the Postgraduate Certificate in Geothermal Energy Technology (PGCertGeothermTech) at the University of Auckland, New Zealand. With support from UNU -GTP and Government of Kenya, eleven Malawians have undergone a three week course in surface exploration of geothermal resources and one underwent a six month training fellowship to study geothermal and geological exploration while another one underwent a six month training fellowship to study geothermal utilization

Overview of the Malawi energy situation and A PESTLE analysis for sustainable development of renewable energy

This paper presents an overview of the Malawi energy situation and the potential of renewable energy resources including solar, wind, biomass, hydro and geothermal. Despite a range of efforts by local and international stakeholders to increase access to modern energy sources in the country, 89 per cent of Malawi׳s energy is still sourced from traditional biomass mainly fuel wood. Only 8 per cent of the population in Malawi have access to electricity but installed capacity of electricity generation is lower than demand. This leads to load shedding by the electricity supplier; consequently electricity supply in Malawi is unreliable and micro and macroeconomic activities are significantly affected. Solar, non-traditional biomass (crop residues and forest residues not burnt on three stone fireplaces, and biogas), hydro, wind and geothermal are potential energy resources that could enhance Malawi׳s energy security. However, unreliable financing mechanisms for large scale energy projects; shortage of trained human resource; lack of coordination among local institutions; unclear regulation enforcement; and sometimes political governance impede sustainable delivery of energy projects. The Malawi energy policy targets and drivers are also discussed in the paper. Based on the prevailing energy situation, a PESTLE analysis is provided in this paper outlining a novel thinking for addressing the political (P), economic (E), social (S), technological (T), legal (L), and environmental (E) challenges that constrain the development of renewable energy technologies in Malawi

The influence of pneumococcal conjugate vaccine-13 on nasal colonisation in a controlled human infection model of pneumococcal carriage in Malawi: a double-blinded randomised controlled trial protocol

Streptococcus pneumoniae is the leading cause of morbidity and mortality due to community acquired pneumonia, bacterial meningitis and bacteraemia worldwide. Pneumococcal conjugate vaccines protect against invasive disease, but are expensive to manufacture, limited in serotype coverage, associated with serotype replacement, and demonstrate reduced effectiveness against mucosal colonisation. For Malawi, nasopharyngeal carriage of vaccine-type pneumococci is common in vaccinated children despite national roll-out of 13-valent pneumococcal conjugate vaccine (PCV13) since 2011. Our team has safely transferred an established experimental human pneumococcal carriage method from Liverpool School of Tropical Medicine to the Malawi-Liverpool Wellcome Trust Clinical Research Programme, Malawi. This study will determine potential immunological mechanisms for the differential effects of PCV13 on nasal carriage between healthy Malawian and UK populations. We will conduct a double-blinded randomised controlled trial to vaccinate (1:1) participants with either PCV13 or control (normal saline). After a period of one month, participants will be inoculated with S. pneumoniae serotype 6B to experimentally induce nasal carriage using the EHPC method. Subsequently, participants will be invited for a second inoculation after one year to determine longer-term vaccine-induced immunological effects. Primary endpoint: detection of inoculated pneumococci by classical culture from nasal wash recovered from the participants after pneumococcal challenge. Secondary endpoints: local and systemic innate, humoral and cellular responses to PCV-13 with and without pneumococcal nasal carriage The primary objective of this controlled human infection model study is to determine if PCV-13 vaccination is protective against pneumococcal carriage in healthy adult Malawian volunteers. This study will help us to understand the observed differences in PCV-13 efficacy between populations and inform the design of future vaccines relevant to the Malawian population

Distinct clinical and immunological profiles of patients with evidence of SARS-CoV-2 infection in sub-Saharan Africa

Although the COVID-19 pandemic has left no country untouched there has been limited research to understand clinical and immunological responses in African populations. Here we characterise patients hospitalised with suspected (PCR-negative/IgG-positive) or confirmed (PCR-positive) COVID-19, and healthy community controls (PCR-negative/IgG-negative). PCR-positive COVID-19 participants were more likely to receive dexamethasone and a beta-lactam antibiotic, and survive to hospital discharge than PCR-negative/IgG-positive and PCR-negative/IgG-negative participants. PCR-negative/IgG-positive participants exhibited a nasal and systemic cytokine signature analogous to PCR-positive COVID-19 participants, predominated by chemokines and neutrophils and distinct from PCR-negative/IgG-negative participants. PCR-negative/IgG-positive participants had increased propensity for Staphylococcus aureus and Streptococcus pneumoniae colonisation. PCR-negative/IgG-positive individuals with high COVID-19 clinical suspicion had inflammatory profiles analogous to PCR-confirmed disease and potentially represent a target population for COVID-19 treatment strategies

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

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