Population genetic analysis of Plasmodium falciparum cell-traversal protein for ookinetes and sporozoite among malaria patients from southern Nigeria

Plasmodium falciparum immune escape mechanisms affect antigens being prioritized for vaccine design. As a result of the multiple surface antigens the parasite exhibits at different life cycle stages, designing a vaccine that would efficiently boost the immune system in clearing infections has been challenging. The P. falciparum cell-traversal protein for ookinetes and sporozoite (Pfceltos) is instrumental for ookinete traversal of the mosquito midgut and sporozoites invasion of the human liver cells. Pfceltos elicits both humoral and cellular immune response but has been reported with multiple single nucleotide polymorphisms in global isolates. A cross-sectional survey, conducted in southern Nigeria, between January-March 2021 recruited 283 individuals. Of this, 166 demonstrated P. falciparum infections (86 from Cross River and 80 from Edo), 48 (55.8%) while only 36 (45%) were amplified for Pfceltos gene from both sites respectively. Fifty amplified samples were sequenced and analysed for their diversity, polymorphisms and population structure of the gene. The number of segregating sites in Edo State was higher (34) than that of Cross River State. Though nucleotide diversity was higher for Edo compared to Cross River State (θw = 0.02505; π = 0.03993 versus θw = 0.00930; π = 0.01033 respectively), the reverse was the case for haplotype diversity (0.757 versus 0.890 for Edo and Cross River respectively). Of the twelve haplotypes observed from both states, only two (KASLPVEK and NAFLSFEK) were shared, with haplotype prevalence higher in Edo (16% and 36%) than Cross River (8% and 4%). The Tajima's D test was positive for both states, with Fst value showing a strong genetic differentiation (Fst = 0.25599), indicating the occurrence of balancing selection favoring haplotype circulation at a low frequency. The shared haplotypes, low Hst and Fst values presents a challenge to predict the extent of gene flow. High LD values present a grim public health consequence should a Pfceltos-conjugated vaccine be considered for prophylaxis in Nigeria

Allelic diversity of MSP1 and MSP2 repeat loci correlate with levels of malaria endemicity in Senegal and Nigerian populations.

BACKGROUND: Characterizing the genetic diversity of malaria parasite populations in different endemic settings (from low to high) could be helpful in determining the effectiveness of malaria interventions. This study compared Plasmodium falciparum parasite population diversity from two sites with low (pre-elimination) and high transmission in Senegal and Nigeria, respectively. METHODS: Parasite genomic DNA was extracted from 187 dried blood spot collected from confirmed uncomplicated P. falciparum malaria infected patients in Senegal (94) and Nigeria (93). Allelic polymorphism at merozoite surface protein 1 (msp1) and merozoite surface protein- 2 (msp2) genes were assessed by nested PCR. RESULTS: The most frequent msp1 and msp2 allelic families are the K1 and IC3D7 allelotypes in both Senegal and Nigeria. Multiplicity of infection (MOI) of greater that 1 and thus complex infections was common in both study sites in Senegal (Thies:1.51/2.53; Kedougou:2.2/2.0 for msp1/2) than in Nigeria (Gbagada: 1.39/1.96; Oredo: 1.35/1.75]). The heterozygosity of msp1 gene was higher in P. falciparum isolates from Senegal (Thies: 0.62; Kedougou: 0.53) than isolates from Nigeria (Gbagada: 0.55; Oredo: 0.50). In Senegal, K1 alleles was associated with heavy than with moderate parasite density. Meanwhile, equal proportions of K1 were observed in both heavy and moderate infection types in Nigeria. The IC3D7 subtype allele of the msp2 family was the most frequent in heavily parasitaemic individuals from both countries than in the moderately infected participants. CONCLUSION: The unexpectedly low genetic diversity of infections high endemic Nigerian setting compared to the low endemic settings in Senegal is suggestive of possible epidemic outbreak in Nigeria

Origin of imported SARS-CoV-2 strains in The Gambia identified from whole genome sequences.

The SARS-CoV-2 disease, first detected in Wuhan, China, in December 2019 has become a global pandemic and is causing an unprecedented burden on health care systems and the economy globally. While the travel history of index cases may suggest the origin of infection, phylogenetic analysis of isolated strains from these cases and contacts will increase the understanding and link between local transmission and other global populations. The objective of this analysis was to provide genomic data on the first six cases of SARS-CoV-2 in The Gambia and to determine the source of infection. This ultimately provide baseline data for subsequent local transmission and contribute genomic diversity information towards local and global data. Our analysis has shown that the SARS-CoV-2 virus identified in The Gambia are of European and Asian origin and sequenced data matched patients' travel history. In addition, we were able to show that two COVID-19 positive cases travelling in the same flight had different strains of SARS-CoV-2. Although whole genome sequencing (WGS) data is still limited in sub-Saharan Africa, this approach has proven to be a highly sensitive, specific and confirmatory tool for SARS-CoV-2 detection

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation

Genetic Diversity and Phylogenetic Relatedness of Plasmodium ovale curtisi and Plasmodium ovale wallikeri in sub-Saharan Africa

P. ovale was until recently thought to be a single unique species. However, the deployment of more sensitive tools has led to increased diagnostic sensitivity, including new evidence supporting the presence of two sympatric species: P. ovale curtisi (Poc) and P. ovale wallikeri (Pow). The increased reports and evolution of P. ovale subspecies are concerning for sub-Saharan Africa where the greatest burden of malaria is borne. Employing published sequence data, we set out to decipher the genetic diversity and phylogenetic relatedness of P. ovale curtisi and P. ovale wallikeri using the tryptophan-rich protein and small subunit ribosomal RNA genes from Gabon, Senegal, Ethiopia and Kenya. Higher number of segregating sites were recorded in Poc isolates from Gabon than from Ethiopia, with a similar trend in the number of haplotypes. With regards to Pow, the number of segregating sites and haplotypes from Ethiopia were higher than from those in Gabon. Poc from Kenya, had higher segregating sites (20), and haplotypes (4) than isolates from Senegal (8 and 3 respectively), while nucleotide from Senegal were more diverse (θw = 0.02159; π = 0.02159) than those from Kenya (θw = 0.01452; π = 0.01583). Phylogenetic tree construction reveal two large clades with Poc from Gabon and Ethiopia, and distinct Gabonese and Ethiopian clades on opposite ends. A similar observation was recorded for the phylogeny of Poc isolates from Kenya and Senegal. With such results, there is a high potential that ovale malaria control measures deployed in one country may be effective in the other since parasite from both countries show some degree of relatedness. How this translates to malaria control efforts throughout the continent would be next step deserving more studies

Severity of Schistosoma haematobium co-infection with malaria in school-children is potentially modulated by host CD14 gene variants

Abstract Objective Schistosomiasis remains a chronic disease of global importance, especially in many rural areas of the world where co-infection with Plasmodium falciparum is common. It is critical to decipher the role of single or co-infected disease scenarios on immune system regulation in such individuals and how such co-infections can either ameliorate or complicate immune response and the consequent disease outcome. First, 10 ml of urine samples, collected between 10:00 am and 2:00 pm, was filtered for diagnosis of schistosomiasis, while egg count, indicative of disease severity, was determined by microscopy. Furthermore, genomic DNA samples extracted from dried blood spots collected on filter paper from one hundred and forty-four Schistosoma haematobium-infected school-children was tested for P. falciparum parasite positivity by an allele-specific nested-PCR analysis of merozoite surface protein (msp)-1 and -2 genes and a real-time PCR assay. In addition, among P. falciparum parasite-positive individuals, we carried out a Taqman SNP genotyping assay to extrapolate the effect of host CD14 (-159 C/T; rs2569190) genetic variants on schistosome egg count. Results Of the 144 individuals recruited, P. falciparum parasite positivity with msp-1 gene were 34%, 43% and 55% for MAD20, RO33 and K1 alleles respectively. Of the co-infected individuals, CD14 genetic variants ranged from 18.8% vs 21.5%, 33.3% vs 44.4%, 9.7% vs 11.8% for single versus schistosome co-infection for the wild type (CC), heterozygous (CT) and mutant (TT) variants respectively. Though the mean egg count for co-infected individuals with CD14 wild type (33.7 eggs per 10 ml of urine) and heterozygote variants (37.5 eggs per 10 ml of urine) were lower than that of schistosome infection alone (52.48 and 48.08 eggs/10 ml of urine respectively), it lacked statistical significance (p-value 0.12 and 0.29), possibly reflecting the benefit of the CD14 activation in schistosome plus malaria co-infection and not schistosome infection alone. In addition, the lower mean egg count in co-infected individuals reveal the benefit of downstream Th1 immune response mitigated by CD14 innate activation that is absent in schistosome infection alone

Palynofacies analysis of sediments from the Cote d\u27Ivoire-Ghana Transform Margin: Preliminary correlation with some regional events in the Equatorial Atlantic

Analyses of the palynofacies and sporomorph thermal alteration indices (TAI) of sediments from Ocean Drilling Program (ODP) Sites 959 to 962 in the Cote d\u27Ivoire-Ghana Transform Margin, West Africa were undertaken to (1) determine the source and depositional conditions of the organic matter in the sediments, (2) refine a paleobathymetric curve derived from other data for Site 959, which drilled the most continuous sedimentary sequence from Pleistocene to Albian and (3) interpret the paleothermal history of the area. Twelve types of dispersed organic matter were identified: amorphous organic matter (AOM), marine palynomorphs, algae, resins, black debris, yellow-brown fragments, black-brown fragments, cuticles, plant tissue, wood, sporomorphs and fungi. The relative abundances of these organic matter components at each site were analyzed using cluster analysis, resulting in the identification of seven palynofacies assemblages at Site 959, five each at sites 960 and 961, and four at Site 962. Amorphous organic matter (which is chiefly marine derived), black debris and wood have played the most significant role in defining palynofacies assemblages. The palynofacies assemblages show some correlation with lithologic units, sediment sources and depositional environments. Previous palynofacies studies in passive margins have demonstrated that changes in the ratio of AOM to terrestrial organic matter are related primarily to proximal-distal positions of depositional environments relative to the shoreline. However, this assumption does not always hold true for a transform margin where tectonic factors play an important role in the organic matter distribution, at least in the early stages of evolution. Lithofacies, CCD paleodepths for the North Atlantic, trace fossil association, benthic foraminifera and palynofacies data were the criteria used for reconstructing a paleobathymetric curve for Site 959. A cyclicity in the organic matter distribution of the Upper Miocene to Lower Pliocene pelagic sediments could be related to fluctuations in productivity of biosiliceous and calcareous organisms, and sedimentation rates. A drastic increase in the amount of AOM and a decrease in black debris and wood in the carbonate and elastic rocks (Lithologic Unit IV) overlying the tectonized Albian sediments (Lithologic Unit V) at Sites 959 and 960 coincide with the presence of an unconformity. Qualitative color analysis of palynomorphs was undertaken for all sites, although the main focus was on Site 959 where detailed organic geochemical data were available. At Site 959, TAI values indicate an immature stage of organic maturation (\u3c21 down to the black claystones of Lithologic Unit III at about 918.47 mbsf. Below this, samples show an increase with depth to a moderately mature stage (\u3e2 except for the claystone samples between 1012.52 and 1036.5 mbsf, and one limestone sample at 1043.4 mbsf), reaching peak levels of 2.58 to 3.0 in the tectonized Albian sediments below the unconformity. These TAI values show a positive correlation with the T(max) values derived from Rock-Eval pyrolysis data. The highest values recorded in the basal tectonized units at all the sites (Sites 960 962 have mean values between 2.25 and 3.13) may be related to high heat flow during the intracontinental to syntransform basin stage in the region

Development of a Passive Transform Margin: Côte d\u27Ivoire-Ghana Transform Margin - ODP Leg 159 Preliminary Results

The Côte d’Ivoire–Ghana transform margin is bounded to the south by a prominent marginal ridge. ODP Leg 159 shipboard analyses on sediments from four sites document three distinct transform margin sedimentary and tectonic stages of evolution: (1) an intracontinental stage of transform faulting recorded in deformed lacustrine to marine siliciclastic sequences; (2) a marginal ridge uplift stage, recorded by shallow water limestones, appears coeval with the passing of a hot, oceanic spreading center just south of the sediment wedge; and (3) cool ing subsidence of the transform margin recorded in bathyal to abyssal sediments emphasizes a passive margin stage. These results are consistent with previously published models of evolution