Frequency In Africa Research Articles

African coups in the COVID-19 era: A current history

What explains the explosion of coup activity in Africa over the last few years? To answer this question, this article presents narrative summaries—a current history—of all eleven coups attempts in Africa between August 2020 and November 2022. We then discuss the most relevant causal explanations for the observed increase in coup frequency in Africa in this period. Though we find relatively little evidence of direct coup diffusion or democratic backsliding as coup triggers, our findings suggest that coup-struck African countries over the last few years are disproportionately poor, have a recent history of coups, and face ongoing dilemmas of democratic consolidation. Ongoing Islamist insurgencies may have helped precipitate recent coups in West Africa but not elsewhere.

Theoretical origin of genetically homologous Plasmodium vivax malarial recurrences.

Malaria caused by Plasmodium vivax is being diagnosed with increasing frequency in Africa. Some southern countries where it has been detected are Angola, Botswana, Mozambique, Namibia, Zambia and Zimbabwe. Knowing the parasite origin of P. vivax infection recurrences (which can be reinfections, recrudescences or relapses) is important epidemiologically for malaria elimination in Africa. Although hypnozoites will no doubt be a source, we should try to determine how frequently the origin of non-reinfection recurrences of P. vivax malaria involving closely related parasites may be non-circulating merozoites rather than hypnozoites.

Fibromatosis Colli: A Review of 4 Cases

Fibromatosis colli is a rare congenital pseudotumor of the sternocleidomastoid muscle, mainly found in the pediatric population. We propose to present four cases diagnosed in the ENT-Neck and head surgery department of the university medical center Mohammed VI in Marrakech, moreover we will recap the management strategy of this entity but also its evolution. We received in the pediatric emergency three infants of 1, 3 and 6 months old and one child of 7 years old, with as a main symptom a painful congenital torticollis. The ultrasound added to our clinical inspection allowed us fairly easily to diagnose the patients. No drug or surgical treatment was prescribed in the infant cases, though surgical treatment was inevitable in the 7 years old patient’s case. During the follow-up, carried out each month, we observed a gradual regression of swelling and torticollis. The prevalence of FC is estimated at 0.3-2% of births. The diagnosis is made at the age of 3 to 4 weeks of life by a thorough inspection of a torticollis associated with a later cervical mass in the framework of a difficult delivery (use of forceps or suction cup). Ultrasonography allows us to diagnose this entity due to the typical aspect of a fusiform thickening of the Sternocleidomastoid muscle. Surgical and medical treatment is rarely useful, and only symptomatic treatment is indicated. The spontaneous evolution of Fibromatosis colli is, even in the absence of treatment, the regression spontaneously in 4 to 6 months. Fibromatosis colli is a relatively rare entity, its frequency in Africa remains to be established, but it is clear that an early diagnosis is key to a speedy recovery.

Genetic disease risks can be misestimated across global populations

BackgroundAccurate assessment of health disparities requires unbiased knowledge of genetic risks in different populations. Unfortunately, most genome-wide association studies use genotyping arrays and European samples. Here, we integrate whole genome sequence data from global populations, results from thousands of genome-wide association studies (GWAS), and extensive computer simulations to identify how genetic disease risks can be misestimated.ResultsIn contrast to null expectations, we find that risk allele frequencies at known disease loci are significantly different for African populations compared to other continents. Strikingly, ancestral risk alleles are found at 9.51% higher frequency in Africa, and derived risk alleles are found at 5.40% lower frequency in Africa. By simulating GWAS with different study populations, we find that non-African cohorts yield disease associations that have biased allele frequencies and that African cohorts yield disease associations that are relatively free of bias. We also find empirical evidence that genotyping arrays and SNP ascertainment bias contribute to continental differences in risk allele frequencies. Because of these causes, polygenic risk scores can be grossly misestimated for individuals of African descent. Importantly, continental differences in risk allele frequencies are only moderately reduced if GWAS use whole genome sequences and hundreds of thousands of cases and controls. Finally, comparisons between uncorrected and corrected genetic risk scores reveal the benefits of considering whether risk alleles are ancestral or derived.ConclusionsOur results imply that caution must be taken when extrapolating GWAS results from one population to predict disease risks in another population.

Functional Analysis Reveals Geographical Variation in Inhibitory Immune Responses Against a Polymorphic Malaria Antigen.

Plasmodium falciparum reticulocyte-binding protein homologue 2b (PfRh2b) is an invasion ligand that is a potential blood-stage vaccine candidate antigen; however, a naturally occurring deletion within an immunogenic domain is present at high frequencies in Africa and has been associated with alternative invasion pathway usage. Standardized tools that provide antigenic specificity in in vitro assays are needed to functionally assess the neutralizing potential of humoral responses against malaria vaccine candidate antigens. Transgenic parasite lines were generated to express the PfRh2b deletion. Total immunoglobulin G (IgG) from individuals residing in malaria-endemic regions in Tanzania, Senegal, and Mali were used in growth inhibition assays with transgenic parasite lines. While the PfRh2b deletion transgenic line showed no change in invasion pathway utilization compared to the wild-type in the absence of specific antibodies, it outgrew wild-type controls in competitive growth experiments. Inhibition differences with total IgG were observed in the different endemic sites, ranging from allele-specific inhibition to allele-independent inhibitory immune responses. The PfRh2b deletion may allow the parasite to escape neutralizing antibody responses in some regions. This difference in geographical inhibition was revealed using transgenic methodologies, which provide valuable tools for functionally assessing neutralizing antibodies against vaccine-candidate antigens in regions with varying malaria endemicity.

Hyperbilirubinemia in atazanavir treated HIV-infected patients: the impact of the UGT1A1*28 allele.

Combination antiretroviral treatment (cART) has significantly improved the life expectancy of people living with HIV. The life-long nature of cART increases the risk of side effects, which in some cases may have been caused by specific genetic characteristics. Patients treated with atazanavir (ATV) boosted with ritonavir (rit), which is a protease inhibitor used for the treatment of HIV, present with elevated bilirubin levels, at high proportions. ATV/rit-related hyperbilirubinemia has been previously associated with genetic characteristics in uridine diphosphate glucuronosyltransferase (UGT) enzyme. The prevalence of the UGT1A1*28 variant, which is the most frequent polymorphism in the UGT1A1 superfamily, has been found to range between 9% and ~60% with the highest frequency in Africa. Pharmacokinetics for additional HIV drugs, such as the integrase inhibitors Raltegravir and Elvitegravir, has been also shown to be influenced by UGT1A1 polymorphisms. Pharmacogenetics/pharmacogenomics testing can be useful to identify a patient’s susceptibility to drug toxicity and therefore to facilitate selection of the optimal long-term suppressive regimen.

The historical spread of Arabian Pastoralists to the eastern African Sahel evidenced by the lactase persistence -13,915*G allele and mitochondrial DNA.

Thanks to the ability to digest lactose, Arabian nomads had become less dependent upon their sedentary neighbors and some of these populations spread to Africa. When and by which route they migrated to their current locations have previously been addressed only by historical and archaeological data. To address the question of Arab expansion into Africa, we collected samples from several Arabic populations, especially the Baggara in Chad and Sudan. We analyzed mutations associated with lactase persistence and reconstructed the surrounding haplotypes defined by SNP polymorphisms. We also sequenced their mitochondrial DNA to investigate relative proportions of sub-Saharan and Eurasian origins. We estimated the expansion age of the -13,915*G mutation in four different Arabian datasets. The oldest age was identified in Yemen (1,356-1,799 ya) and the youngest in a Sudanese group of Rashaayda Arabs (219-312 ya). We also found a negative correlation between the frequency of the -13,915*G allele and the frequency of sub-Saharan mtDNA haplotypes. Even if the age of the most recent common ancestor of -13,915*G is ∼4 ka as shown in a previous study, our results suggest that its spread to Africa was more recent, which is consistent with the migrations of Arabic tribes. Because the incidence of sub-Saharan mtDNA haplotypes is negatively correlated with the occurrence of -13,915*G, we suggest that the decrease of its frequency in Africa has been caused by progressive admixture of the Arabian nomads with sub-Saharan populations.

Genomic epidemiology of artemisinin resistant malaria.

The current epidemic of artemisinin resistant Plasmodium falciparum in Southeast Asia is the result of a soft selective sweep involving at least 20 independent kelch13 mutations. In a large global survey, we find that kelch13 mutations which cause resistance in Southeast Asia are present at low frequency in Africa. We show that African kelch13 mutations have originated locally, and that kelch13 shows a normal variation pattern relative to other genes in Africa, whereas in Southeast Asia there is a great excess of non-synonymous mutations, many of which cause radical amino-acid changes. Thus, kelch13 is not currently undergoing strong selection in Africa, despite a deep reservoir of variations that could potentially allow resistance to emerge rapidly. The practical implications are that public health surveillance for artemisinin resistance should not rely on kelch13 data alone, and interventions to prevent resistance must account for local evolutionary conditions, shown by genomic epidemiology to differ greatly between geographical regions.

Selection on a variant associated with improved viral clearance drives local, adaptive pseudogenization of interferon lambda 4 (IFNL4).

Interferon lambda 4 gene (IFNL4) encodes IFN-λ4, a new member of the IFN-λ family with antiviral activity. In humans IFNL4 open reading frame is truncated by a polymorphic frame-shift insertion that eliminates IFN-λ4 and turns IFNL4 into a polymorphic pseudogene. Functional IFN-λ4 has antiviral activity but the elimination of IFN-λ4 through pseudogenization is strongly associated with improved clearance of hepatitis C virus (HCV) infection. We show that functional IFN-λ4 is conserved and evolutionarily constrained in mammals and thus functionally relevant. However, the pseudogene has reached moderately high frequency in Africa, America, and Europe, and near fixation in East Asia. In fact, the pseudogenizing variant is among the 0.8% most differentiated SNPs between Africa and East Asia genome-wide. Its raise in frequency is associated with additional evidence of positive selection, which is strongest in East Asia, where this variant falls in the 0.5% tail of SNPs with strongest signatures of recent positive selection genome-wide. Using a new Approximate Bayesian Computation (ABC) approach we infer that the pseudogenizing allele appeared just before the out-of-Africa migration and was immediately targeted by moderate positive selection; selection subsequently strengthened in European and Asian populations resulting in the high frequency observed today. This provides evidence for a changing adaptive process that, by favoring IFN-λ4 inactivation, has shaped present-day phenotypic diversity and susceptibility to disease.

Reduced prevalence of placental malaria in primiparae with blood group O.

BackgroundBlood group O protects African children against severe malaria and has reached high prevalence in malarious regions. However, its role in malaria in pregnancy is ambiguous. In 839 delivering Ghanaian women, associations of ABO blood groups with Plasmodium falciparum infection were examined.MethodsPlasmodium falciparum infection was diagnosed in placental blood samples by microscopy and PCR assays. Present or past infection was defined as the detection of parasitaemia or haemozoin by microscopy, or a positive PCR result. Blood groups were inferred from genotyping rs8176719 (indicating the O allele) and rs8176746/rs8176747 (distinguishing the B allele from the A allele).ResultsThe majority of women had blood group O (55.4%); present or past P. falciparum infection was seen in 62.3% of all women. Among multiparae, the blood groups had no influence on P. falciparum infection. In contrast, primiparae with blood group O had significantly less present or past infection than women with non-O blood groups (61.5 vs 76.2%, P = 0.007). In multivariate analysis, the odds of present or past placental P. falciparum infection were reduced by 45% in blood group O primiparae (aOR, 0.55 [95% CI, 0.33–0.94]).ConclusionsThe present study shows a clear protective effect of blood group O against malaria in primiparae. This accords with findings in severe malaria and in vitro results. The data underline the relevance of host genetic protection among primiparae, i.e. the high-risk group for malaria in pregnancy, and contribute to the understanding of high O allele frequencies in Africa.

The apolipoprotein L1 (APOL1) gene and nondiabetic nephropathy in African Americans.

Mapping by admixture linkage disequilibrium (LD) detected strong association between nonmuscle myosin heavy chain 9 gene (MYH9) variants on chromosome 22 and nondiabetic nephropathy in African Americans. MYH9-related variants were posited to be the probable, but not necessarily the definitive, causal variants as a result of impressive statistical evidence of association, renal expression, and a role in autosomal dominant MYH9 disorders characterized by progressive glomerulosclerosis (Epstein and Fechtner syndromes). Dense mapping within MYH9 revealed striking LD patterns and racial variation in risk allele frequencies, suggesting population genetic factors such as selection may be operative in this region. Genovese and colleagues examined large chromosomal regions adjacent to MYH9 using genome-wide association methods and non-HapMap single nucleotide polymorphisms identified in Yoruba from the 1000 Genomes project. Statistically stronger associations were detected between two independent sequence variants in the Apolipoprotein L1 gene (APOL1) and nondiabetic nephropathy in African Americans, with odds ratios of 10.5 in idiopathic FSGS and 7.3 in hypertension-attributed ESRD. These kidney disease risk variants likely rose to high frequency in Africa because they confer resistance to trypanosomal infection and protect from African sleeping sickness. Risk variants in MYH9 and APOL1 are in strong LD, and the genetic risk that was previously attributed to MYH9 may reside, in part or in whole, in APOL1, although more complex models of risk cannot be excluded. This association likely explains racial disparities in nondiabetic nephropathy as a result of the high prevalence of risk alleles in individuals of African ancestry.

The Distribution and Most Recent Common Ancestor of the 17q21 Inversion in Humans

The polymorphic inversion on 17q21, sometimes called the microtubular associated protein tau (MAPT) inversion, is an approximately 900 kb inversion found primarily in Europeans and Southwest Asians. We have identified 21 SNPs that act as markers of the inverted, i.e., H2, haplotype. The inversion is found at the highest frequencies in Southwest Asia and Southern Europe (frequencies of approximately 30%); elsewhere in Europe, frequencies vary from < 5%, in Finns, to 28%, in Orcadians. The H2 inversion haplotype also occurs at low frequencies in Africa, Central Asia, East Asia, and the Americas, though the East Asian and Amerindian alleles may be due to recent gene flow from Europe. Molecular evolution analyses indicate that the H2 haplotype originally arose in Africa or Southwest Asia. Though the H2 inversion has many fixed differences across the approximately 900 kb, short tandem repeat polymorphism data indicate a very recent date for the most recent common ancestor, with dates ranging from 13,600 to 108,400 years, depending on assumptions and estimation methods. This estimate range is much more recent than the 3 million year age estimated by Stefansson et al. in 2005.

Stepwise acquisition of pyrimethamine resistance in the malaria parasite.

The spread of high-level pyrimethamine resistance in Africa threatens to curtail the therapeutic lifetime of antifolate antimalarials. We studied the possible evolutionary pathways in the evolution of pyrimethamine resistance using an approach in which all possible mutational intermediates were created by site-directed mutagenesis and assayed for their level of drug resistance. The coding sequence for dihydrofolate reductase (DHFR) from the malaria parasite Plasmodium falciparum was mutagenized, and tests were carried out in Escherichia coli under conditions in which the endogenous bacterial enzyme was selectively inhibited. We studied 4 key amino acid replacements implicated in pyrimethamine resistance: N51I, C59R, S108N, and I164L. Using empirical estimates of the mutational spectrum in P. falciparum and probabilities of fixation based on the relative levels of resistance, we found that the predicted favored pathways of drug resistance are consistent with those reported in previous kinetic studies, as well as DHFR polymorphisms observed in natural populations. We found that 3 pathways account for nearly 90% of the simulated realizations of the evolution of pyrimethamine resistance. The most frequent pathway (S108N and then C59R, N51I, and I164L) accounts for more than half of the simulated realizations. Our results also suggest an explanation for why I164L is detected in Southeast Asia and South America, but not at significant frequencies in Africa.

Surgical Outcomes of Abdominoperineal Resection for Low Rectal Cancer in a Nigerian Tertiary Institution

Dr. Alatise and colleagues have presented their experience of performing abdominoperineal resection (APR) in a tertiary referral center in Nigeria [1]. They are to be praised for the extraordinary effort they demonstrate in an area where limited resources prevent optimum treatment of a disease that is increasing in frequency in Africa. These limited resources include minimal access to computerized tomography and other advanced imaging techniques, as well as reduced ability to include chemotherapy and radiation therapy into their treatment algorithm for distal rectal cancer.

Platelet glycoprotein I(b)alpha and integrin alpha2 beta1 polymorphisms: gene frequencies and linkage disequilibrium in a population diversity panel.

Genetic variants in the GP1BA and ITGA2 genes have been proposed as potential modifiers for arterial vascular disease and bleeding disorders. Since ancestry may play an important role in the prevalence of these variants, we sought to determine their allele frequency and linkage disequilibrium in a collection of 1064 DNA samples from 51 ethnic groups. We studied haplotypes of ITGA2 defined by single nucleotide substitutions at positions -52, 807, and 1648, and GP1BA variants defined by sequence changes in positions -5 (Kozak), 1018 (T145M, HPA-2) and 1285 (VNTR A, B, C and D). Frequency of haplotypes of ITGA2 showed considerable variation across the different groups, with a higher prevalence of the haplotype -52C or T/807C/1648A observed in African compared with caucasian and Asian populations. The haplotypes 52C/807T/1648A and -52T/807T/1648A were not observed in caucasians or South Americans. While relative frequencies of the GP1BA Kozak alleles were comparable across groups, the methionine allele (HPA-2b) showed a higher frequency in Africa (0.26) than in the other groups. We also observed a high prevalence of the VNTR B allele in the African and Israeli populations. Haplotype analysis revealed incomplete linkage disequilibrium between the HPA-2 and VNTR alleles. Incorporation of GP1BA variants into the set of SNPs already genotyped by the HapMap project disrupted the pre-existing haplotype block. These data provide a valuable resource for optimal selection of variants best tailored for association studies of vascular disease or bleeding disorders when examining individuals of different ancestral origins.

Sickle Cell Trait and Competitive Athletics: Is There a Risk?

The gene for sickle hemoglobin has a nearly global distribution, occurring with great frequency in Africa (and from there to the Western Hemisphere), southern Europe, the Mideast, and parts of the Indian subcontinent. In the homozygous state, homozygosity for sickle cell genes (sickle cell anemia) produces great concentrations of sickle hemoglobin [HbS] within the RBCs, usually &amp;gt;90%. Such large concentrations of HbS are associated with spontaneous sickling under physiologic conditions in vivo that result in severe hemolytic anemia and vasooclusive complications that compromise and threaten health, and even survival. In contrast, the heterozygous state, designated sickle cell trait, is associated with only 30% to 40% HbS in the RBCs, most of the remainder being normal adult hemoglobin (HbA). These relatively small concentrations of HbS are not associated with in vivo sickling.

Endocardial fibroelastosis with embolism.

The clinical and pathological features of an unusual type of infantile endocardial fibroelastosis with intra-cardiac thrombus formation and peripheral emboli are described as encountered in a Scottish boy aged 10 months. The rarity of this condition in Europe and America is contrasted with its frequency in Africa.

Dose, Time and Volume Parameters in Irradiation Therapy of Kaposi's Sarcoma

In a recent review on the treatment of Kaposi's sarcoma (Cohen, Palmer and Nickson, 1962), it appeared that there was relatively little information published on its radiosensitivity, and that reported methods of management varied widely and were often contradictory. It has, however, become possible, since the disease is of extraordinary frequency in Africa, to present the following analysis of a comparatively large irradiated series from which appropriate data can be extracted. The pathological and clinical features of this African series are described in detail by a number of investigators (U.I.C.C. Symposium on Kaposi's Sarcoma, 1962, in press); the present report deals with the radiosensitivity of the individual lesions and the tolerance limits of the associated normal tissues. Between 1949 and 1960, 58 cases of typical Kaposi's sarcoma were referred to the Radiation Therapy Department of the Johannesburg Hospital for therapy. Of these, 16 were lost to follow-up yielding no information on the length of...