Clinical Comparison of Retinopathy-Positive and Retinopathy-Negative Cerebral Malaria

AbstractCerebral malaria (CM) is a severe and often lethal complication of falciparum malaria. A classic malaria retinopathy is seen in some (retinopathy-positive [RP]) children but not others (retinopathy-negative [RN]), and is associated with increased parasite sequestration. It is unclear whether RN CM is a severe nonmalarial illness with incidental parasitemia or a less severe form of the same malarial illness as RP CM. Understanding the clinical differences between RP and RN CM may help shed light on the pathophysiology of malarial retinopathy. We compared clinical history, physical examination, laboratory findings, and outcomes of RP (N = 167) and RN (N = 87) children admitted to Mulago Hospital, Kampala, Uganda. Compared with RN children, RP children presented with a longer history of illness, as well as physical examination and laboratory findings indicative of more severe disease and organ damage. The hospital course of RP children was complicated by longer coma duration and a greater transfusion burden than RN children. Mortality did not differ significantly between RP and RN children (14.4% versus 8.0%, P = 0.14). Further, severity of retinal hemorrhage correlated with the majority of variables that differed between RP and RN children. The data suggest that RP and RN CM may reflect the spectrum of illness in CM, and that RN CM could be an earlier, less severe form of disease

Lack of mortality in 22 children with sickle cell anemia and severe malarial anemia

Retrospective studies suggest that there is high mortality in children with sickle cell anemia (SCA) and severe malaria. We assessed mortality in Ugandan children with severe malarial anemia (SMA, n = 232) or cerebral malaria (CM, n = 267) by sickle cell hemoglobin genotype. Admission and 2‐year follow‐up mortality did not differ among children with SMA who had homozygous form of sickle cell hemoglobin (HbSS) versus normal form of adult hemoglobin (admission, 0/22, 0%, vs. 1/208, 0.5%; follow‐up, 1/22, 4.5%; 7/207, 3.4%, respectively; all P > 0.6). The single child with CM and HbSS survived. The study findings highlight the need for large prospective studies of malaria‐related mortality in children with SCA

Autoantibody levels are associated with acute kidney injury, anemia and post-discharge morbidity and mortality in Ugandan children with severe malaria

Autoantibodies targeting host antigens contribute to autoimmune disorders, frequently occur during and after infections and have been proposed to contribute to malaria-induced anemia. We measured anti-phosphatidylserine (PS) and anti-DNA antibody levels in 382 Ugandan children prospectively recruited in a study of severe malaria (SM). High antibody levels were defined as antibody levels greater than the mean plus 3 standard deviations of community children (CC). We observed increases in median levels of anti-PS and anti-DNA antibodies in children with SM compared to CC (p < 0.0001 for both). Children with severe malarial anemia were more likely to have high anti-PS antibodies than children with cerebral malaria (16.4% vs. 7.4%), p = 0.02. Increases in anti-PS and anti-DNA antibodies were associated with decreased hemoglobin (p < 0.05). A one-unit increase in anti-DNA antibodies was associated with a 2.99 (95% CI, 1.68, 5.31) increase odds of acute kidney injury (AKI) (p < 0.0001). Elevated anti-PS and anti-DNA antibodies were associated with post-discharge mortality (p = 0.031 and p = 0.042, respectively). Children with high anti-PS antibodies were more likely to have multiple hospital readmissions compared to children with normal anti-PS antibody levels (p < 0.05). SM is associated with increased autoantibodies against PS and DNA. Autoantibodies were associated with anemia, AKI, post-discharge mortality, and hospital readmission

Improving newborn care practices through home visits: lessons from Malawi, Nepal, Bangladesh, and Uganda.

Background: Nearly all newborn deaths occur in low- or middle-income countries. Many of these deaths could be prevented through promotion and provision of newborn care practices such as thermal care, early and exclusive breastfeeding, and hygienic cord care. Home visit programmes promoting these practices were piloted in Malawi, Nepal, Bangladesh, and Uganda. Objective: This study assessed changes in selected newborn care practices over time in pilot programme areas in four countries and evaluated whether women who received home visits during pregnancy were more likely to report use of three key practices. Design: Using data from cross-sectional surveys of women with live births at baseline and endline, the Pearson chi-squared test was used to assess changes over time. Generalised linear models were used to assess the relationship between the main independent variable – home visit from a community health worker (CHW) during pregnancy (0, 1–2, 3+) – and use of selected practices while controlling for antenatal care, place of delivery, and maternal age and education. Results: There were statistically significant improvements in practices, except applying nothing to the cord in Malawi and early initiation of breastfeeding in Bangladesh. In Malawi, Nepal, and Bangladesh, women who were visited by a CHW three or more times during pregnancy were more likely to report use of selected practices. Women who delivered in a facility were also more likely to report use of selected practices in Malawi, Nepal, and Uganda; association with place of birth was not examined in Bangladesh because only women who delivered outside a facility were asked about these practices. Conclusion: Home visits can play a role in improving practices in different settings. Multiple interactions are needed, so programmes need to investigate the most appropriate and efficient ways to reach families and promote newborn care practices. Meanwhile, programmes must take advantage of increasing facility delivery rates to ensure that all babies benefit from these practices

Genome-wide diversity and structure variation among lablab [Lablab purpureus (L.) Sweet] accessions and their implication in a forage breeding program

Open Access Article; Published online: 19 Mar 2021Most orphan crops have not been fully sequenced, hence we rely on genome sequences of related species to align markers to different chromosomes. This hinders their utilisation in plant population improvement programs. Utilising the advances in the science of sequencing technologies, the population structure, relatedness, and genetic diversity among accessions can be assessed quickly for better exploitation in forage breeding programs. Using DArTseq technology, we studied the genetic and structural variation in 65 Lablab purpureus (L.) Sweet conserved gene-bank accessions using 9320 DArTseq-based SNPs and 15,719 SilicoDart markers. These markers had a low discriminating ability with mean polymorphic information content (P.I.C.) of 0.14 with DArTseq-based SNPs and 0.13 with SilicoDart markers. However, the markers had a high mean call rate of 73% with DArTseq-based SNPs and 97% with SilicoDart markers. Analysis of molecular variance revealed a high within populations variance (99.4%), indicating a high gene exchange or low genetic differentiation (PhiPT = 0.0057) among the populations. Structure analysis showed three allelic pools in variable clusters of ΔK = 3 and 6. Phylogenetic tree of lablab accessions showed three main groups with variable membership coefficients. Most pairs of accessions (40.3%) had genetic distances between 0.10 and 0.15 for SilicoDart markers, while for DArTseq-based SNPs, (46.5%) had genetic distances between 0.20 and 0.25. Phylogenetic clustering and minimum spanning analysis divided the 65 accessions into three groups, irrespective of their origin. For the first time, this study produced high-density markers with good genom coverage. The utilisation of these accessions in a forage program will base on the information from molecular-based grouping. The outcomes uncovered the presence of noteworthy measure of variety in Uganda, CIAT and ILRI accessions, thus demonstrating an opportunity for further marker-trait-association studies

Evaluating kidney function using a point-of-care creatinine test in Ugandan children with severe malaria: a prospective cohort study

Background: Acute kidney injury (AKI) disproportionately affects individuals in low-and middle-income countries (LMIC). However, LMIC-particularly countries in sub-Saharan Africa- are under-represented in global AKI research. A critical barrier in diagnosing AKI is access to reliable serum creatinine results. We evaluated the utility of a point-of-care test to measure creatinine and diagnose AKI in Ugandan children with malaria. Methods: Paired admission creatinine was assessed in 539 Ugandan children 6 months to 4 years of age hospitalized with severe malaria based on blood smear or rapid diagnostic test. Creatinine levels were measured using isotope dilution mass spectrometry (IDMS)-traceable methods. The reference creatinine was measured using the modified Jaffe method by a certified laboratory and the point-of-care testing was conducted using an i-STAT blood analyzer (i-STAT1, with and without adjustment for the partial pressure of carbon dioxide). AKI was defined and staged using the Kidney Disease: Improving Global Outcomes criteria. Results: The mean age of children was 2.1 years, and 21.6% of children were stunted. Mortality was 7.6% in-hospital. Over the entire range of measured creatinine values (<0.20mg/dL-8.4mg/dL), the correlation between the reference creatinine and adjusted and unadjusted point-of-care creatinine was high with R2 values of 0.95 and 0.93 respectively; however, the correlation was significantly lower in children with creatinine values <1mg/dL (R2 of 0.44 between the reference and adjusted and unadjusted i-STAT creatinine). The prevalence of AKI was 45.5% using the reference creatinine, and 27.1 and 32.3% using the unadjusted and adjusted point-of-care creatinine values, respectively. There was a step-wise increase in mortality across AKI stages, and all methods were strongly associated with mortality (p<0.0001 for all). AKI defined using the reference creatinine measure was the most sensitive to predict mortality with a sensitivity of 85.4% compared to 70.7 and 63.4% with the adjusted and unadjusted point-of-care creatinine values, respectively. Conclusions: Point-of-care assessment of creatinine in lean Ugandan children <4 years of age underestimated creatinine and AKI compared to the clinical reference. Additional studies are needed to evaluate other biomarkers of AKI in LMIC to ensure equitable access to AKI diagnostics globally