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

Iron for Africa-Report of an Expert Workshop.

Scientific experts from nine countries gathered to share their views and experience around iron interventions in Africa. Inappropriate eating habits, infections and parasitism are responsible for significant prevalence of iron deficiency, but reliable and country-comparable prevalence estimates are lacking: improvements in biomarkers and cut-offs values adapted to context of use are needed. Benefits of iron interventions on growth and development are indisputable and outweigh risks, which exist in populations with a high infectious burden. Indeed, pathogen growth may increase with enhanced available iron, calling for caution and preventive measures where malaria or other infections are prevalent. Most African countries programmatically fortify flour and supplement pregnant women, while iron deficiency in young children is rather addressed at individual level. Coverage and efficacy could improve through increased access for target populations, raised awareness and lower cost. More bioavailable iron forms, helping to decrease iron dose, or prebiotics, which both may lower risk of infections are attractive opportunities for Africa. Fortifying specific food products could be a relevant route, adapted to local context and needs of population groups while providing education and training. More globally, partnerships involving various stakeholders are encouraged, that could tackle all aspects of the issue

Saliva urea nitrogen dipsticks to predict acute kidney injury in Malawian trauma patients

Background: Many low-resource settings have limited access to serum creatinine tests necessary for kidney disease identification. Among Malawian patients who are hospitalized after trauma, we evaluated the use of point-of-care saliva urea nitrogen (SUN) dipsticks to predict acute kidney injury (AKI). Methods: In a nested prospective cohort study, we enrolled hospitalized acute trauma patients aged ≥6 months to evaluate AKI (defined by KDIGO criteria) and the test characteristics of SUN to predict AKI. Results: Among 335 participants (approximately three-quarters able to expectorate and 34% aged ≤18 years), 12.5% (n = 42) developed AKI. At a SUN threshold of ≥40 mg/dL, a positive dipstick test was specific (99.3%) but insensitive (14.3%) in predicting AKI, with a positive predictive value of 75% and negative predictive value of 89%. At this threshold, 2.4% of participants were dipstick-positive (SUN+), and 75% of those had AKI. Reducing the SUN threshold to ≥30 mg/dL increased participants who were SUN+ to 5.0% (n = 16) but also increased the false positive rate and missed 79% (n = 33) of AKI cases. Stratified results showed better performance among adults than children and similar results when comparing participants who could and could not expectorate. There was moderate correlation between categorized BUN values and SUN (r = 0.53) but less agreement (weighted kappa 0.27; 95% CI 0.17–0.37). Conclusions: SUN dipstick testing has good specificity and negative predictive value for ruling out AKI, but poor sensitivity. We found similar results among those who could or could not expectorate a saliva sample

Collateral-flow measurements in humans by myocardial contrast echocardiography: validation of coronary pressure-derived collateral-flow assessment

AIMS: Myocardial blood flow (MBF) is the gold standard to assess myocardial blood supply and, as recently shown, can be obtained by myocardial contrast echocardiography (MCE). The aims of this human study are (i) to test whether measurements of collateral-derived MBF by MCE are feasible during elective angioplasty and (ii) to validate the concept of pressure-derived collateral-flow assessment. METHODS AND RESULTS: Thirty patients with stable coronary artery disease underwent MCE of the collateral-receiving territory during and after angioplasty of 37 stenoses. MCE perfusion analysis was successful in 32 cases. MBF during and after angioplasty varied between 0.060-0.876 mL min(-1) g(-1) (0.304+/-0.196 mL min(-1) g(-1)) and 0.676-1.773 mL min(-1) g(-1) (1.207+/-0.327 mL min(-1) g(-1)), respectively. Collateral-perfusion index (CPI) is defined as the rate of MBF during and after angioplasty varied between 0.05 and 0.67 (0.26+/-0.15). During angioplasty, simultaneous measurements of mean aortic pressure, coronary wedge pressure, and central venous pressure determined the pressure-derived collateral-flow index (CFI(p)), which varied between 0.04 and 0.61 (0.23+/-0.14). Linear-regression analysis demonstrated an excellent agreement between CFI(p) and CPI (y=0.88 x +0.01; r(2)=0.92; P<0.0001). CONCLUSION: Collateral-derived MBF measurements by MCE during angioplasty are feasible and proved that the pressure-derived CFI exactly reflects collateral relative to normal myocardial perfusion in humans

Validity of Urine NGALds Dipstick for Acute Kidney Injury in a Malawian Trauma Cohort

Introduction: Acute kidney injury (AKI) is a major cause of mortality worldwide, particularly in low-resource settings with limited diagnostic testing. Neutrophil gelatinase-associated lipocalin (NGAL) has shown promise in predicting AKI. Nested within a larger, prospective cohort study evaluating AKI incidence in admitted trauma patients, our objective was to evaluate a novel dipstick, NGALds, for the prediction of AKI in Malawi, Africa. Methods: Participants were >6 months of age. Spearman rank correlation coefficients (R) assessed NGAL categories (negative [≤50 ng/ml], low risk [51−149 ng/ml], moderate risk [150−299 ng/ml], and high risk [≥300 ng/ml]) for the urine NGALds dipstick and laboratory-based NGAL Test. Results: We enrolled 285 participants (one-third children). Thirteen percent developed AKI. The dipstick captured 45 of 52 participants (86.5%) with moderate- or high-risk NGAL values on laboratory-based testing (R = 0.74). The dipstick had sensitivity of 44.4%, specificity of 73.5%, positive predictive value of 19.5%, and negative predictive value of 90.2% for predicting AKI. Acute kidney injury was associated with an increased risk of mortality (relative risk [RR] = 3.9, 95% confidence interval [CI] = 1.9−8.2), but mortality risk greatly increased among children who first had a positive (≥150 ng/ml) NGALds result (RR = 12.0, 95% CI = 1.8−78.4). Conclusions: The NGALds dipstick performed similarly to the NGAL Test in this low-resource setting and may be a useful tool to rule out AKI. It may be even more important in predicting high mortality risk among children

High frequency of Polio-like Enterovirus C strains with differential clustering of CVA-13 and EV-C99 subgenotypes in a cohort of Malawian children

Enteroviruses (EVs) are among the most commonly detected viruses infecting humans worldwide. Although the prevalence of EVs is widely studied, the status of EV prevalence in sub-Saharan Africa remains largely unknown. The objective of our present study was therefore to increase our knowledge on EV circulation in sub-Saharan Africa. We obtained 749 fecal samples from a cross-sectional study conducted on Malawian children aged 6 to 60 months. We tested the samples for the presence of EVs using real time PCR, and typed the positive samples based on partial viral protein 1 (VP1) sequences. A large proportion of th

Tobacco and other risk factors for esophageal squamous cell carcinoma in Lilongwe Malawi: Results from the Lilongwe esophageal cancer case: Control study

Objective Esophageal cancer is the second commonest cancer in Malawi, and 95% of all cases are esophageal squamous cell carcinoma (ESCC). Very little is known about the epidemiology of ESCC in Malawi including risk factors. The main objective of the study was to evaluate and describe risk factors of ESCC in Malawi. Methods We conducted a case-control study from 2017 to 2020 at two hospitals in Lilongwe, Malawi and consenting adults were eligible for inclusion. Endoscopy was conducted on all cases and biopsies were obtained for histological confirmation. Controls were selected from patients or their guardians in orthopedic, dental and ophthalmology wards and they were frequency matched by sex, age, and region of origin to cases. An electronic structured questionnaire was delivered by a trained interviewer. Multivariate conditional logistic regression models were used to assess the associations between subject characteristics, habits, and medical history and risk of ESCC. Results During the study period, 300 cases and 300 controls were enrolled into the study. Median age of cases and controls was 56 years and 62% of the cases were male. Among cases, 30% were ever cigarette smokers as were 22% of controls. Smoking cigarettes had an adjusted odds ratio of 2.4 (95% CI 1.4–4.2 p = 0.003). HIV+ status was present in 11% of cases and 4% controls, which resulted in an adjusted odds ratio was 4.0 (95% CI 1.8–9.0 p = 0.001). Drinking hot tea was associated with an adjusted odd ratio of 2.9 (95% CI 1.3–6.3 p = 0.007). Mold on stored grain has an adjusted odd ratio of 1.6 (95% CI 1.1–2.5 p = 0.021). Conclusion Reducing smoking cigarettes, consumption of scalding hot tea, and consumption of contaminated grain, could potentially help reduce the burden of ESCC in Malawi. Further investigation of the association between HIV status and ESCC are warranted

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

Pathophysiological Mechanisms of Severe Anaemia in Malawian Children

BACKGROUND: Severe anaemia is a major cause of morbidity and mortality in African children. The aetiology is multi-factorial, but interventions have often targeted only one or a few causal factors, with limited success. METHODS AND FINDINGS: We assessed the contribution of different pathophysiological mechanisms (red cell production failure [RCPF], haemolysis and blood loss) to severe anaemia in Malawian children in whom etiological factors have been described previously. More complex associations between etiological factors and the mechanisms were explored using structural equation modelling. In 235 children with severe anaemia (haemoglobin<3.2 mMol/L [5.0 g/dl]) studied, RCPF, haemolysis and blood loss were found in 48.1%, 21.7% and 6.9%, respectively. The RCPF figure increased to 86% when a less stringent definition of RCPF was applied. RCPF was the most common mechanism in each of the major etiological subgroups (39.7-59.7%). Multiple aetiologies were common in children with severe anaemia. In the final model, nutritional and infectious factors, including malaria, were directly or indirectly associated with RCPF, but not with haemolysis. CONCLUSION: RCPF was the most common pathway leading to severe anaemia, from a variety of etiological factors, often found in combination. Unlike haemolysis or blood loss, RCPF is a defect that is likely to persist to a significant degree unless all of its contributing aetiologies are corrected. This provides a further explanation for the limited success of the single factor interventions that have commonly been applied to the prevention or treatment of severe anaemia. Our findings underline the need for a package of measures directed against all of the local aetiologies of this often fatal paediatric syndrome

Community Participation in Habitat Management and Larviciding for the Control of Malaria Vectors in Southern Malawi

Larval source management (LSM) could reduce malaria transmission when executed alongside core vector control strategies. Involving communities in LSM could increase intervention coverage, reduce operational costs, and promote sustainability via community buy-in. We assessed the effectiveness of community-led LSM to reduce anopheline larval densities in 26 villages along the perimeter of Majete Wildlife Reserve in southern Malawi. The communities formed LSM committees which coordinated LSM activities in their villages following specialized training. Effectiveness of larviciding by LSM committees was assessed via pre- and post-spray larval sampling. The effect of community-led LSM on anopheline larval densities in intervention villages was assessed via comparisons with densities in non-LSM villages over a period of 14 months. Surveys involving 502 respondents were undertaken in intervention villages to explore community motivation and participation, and factors influencing these outcomes. Larviciding by LSM committees reduced anopheline larval densities in post-spray sampling compared with pre-spray sampling (P &lt; 0.0001). No differences were observed between anopheline larval densities during pre-spray sampling in LSM villages and those in non-LSM villages (P = 0.282). Knowledge about vector biology and control, and someone’s role in LSM motivated community participation in the vector control program. Despite reducing anopheline larval densities in LSM villages, the impact of the community-led LSM could not be detected in our study setting because of low mosquito densities after scale-up of core malaria control interventions. Still, the contributions of the intervention in increasing a community’s knowledge of malaria, its risk factors, and its control methods highlight potential benefits of the approach