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The World Health Organization framework for tracking SARS-CoV-2 variants has been updated to reflect the continued evolution of the virus; this framework could be adapted for other emerging respiratory diseases with epidemic and pandemic potential.

The African BioGenome Project (AfricaBP) Open Institute for Genomics and Bioinformatics aims to overcome barriers to capacity building through its distributed African regional workshops and prioritizes the exchange of grassroots knowledge and innovation in biodiversity genomics and bioinformatics. In 2023, we implemented 28 workshops on biodiversity genomics and bioinformatics, covering 11 African countries across the 5 African geographical regions. These regional workshops trained 408 African scientists in hands-on molecular biology, genomics and bioinformatics techniques as well as the ethical, legal and social issues associated with acquiring genetic resources. Here, we discuss the implementation of transformative strategies, such as expanding the regional workshop model of AfricaBP to involve multiple countries, institutions and partners, including the proposed creation of an African digital database with sequence information relating to both biodiversity and agriculture. This will ultimately help create a critical mass of skilled genomics and bioinformatics scientists across Africa.

The African continent is poised to have a pivotal role in the global population landscape, with the United Nations projecting a population of 2.5 billion (more than 25% of the global population) by 2050. Amid this demographic shift, Africa faces a unique healthcare challenge—navigating a complex landscape of infectious and non-communicable diseases. This necessitates a departure from the conventional ‘one-size-fits-all’ medical model toward precision approaches that are efficient and sustainable. Genomic capacity is a pillar of precision health; however, access to up-to-date genetic testing in African countries is limited, compounded by a startling lack of representation of data from populations of African descent in gene discovery studies. In this Review, we delve into the challenges impeding the development of genomic capacity in Africa, such as the lack of electronic clinical and epidemiological records, infrastructural challenges, high supply chain costs and the ‘dependency trap’ that jeopardizes long-term sustainability. We emphasize the need for strategies hinged on true partnerships, robust infrastructure, workforce development and well-crafted policies. Finally, we outline recent progress and existing initiatives that should be considered as role models for future capacity-building initiatives.

Phytochemical investigation of the aerial roots of Ficus sur, a Cameroonian medicinal plant, resulted in a previously undescribed cerebroside, suroside (1), in addition to its aglycon congener suramide (2). Moreover, six known natural products including alpinumisoflavone (3), wighteone metabolite (4), oleanolic acid (5), β-sitosterol (6), β-sitosterol-3-O-β-D-glucopyranoside (7),and epi-ѱ-taraxastanolone (8)were identified. The structures of the previously undescribed compounds were determined by analysis of 1D and 2D-NMR (One and two dimensional nuclear magnetic resonance), mass spectrometry, chemical conversion, and by comparison of these data with those from the literature. Wighteone metabolite (4)exhibited a weak cytotoxic activity against the human HepG2 hepatocellular carcinoma cells with an IC50value of 51.9 µM.

Graphical abstract:

The proposed Pandemic Agreement must ensure that COVID-19 vaccine nationalism is never repeated; 290 scientists call for action.

The coronavirus disease 2019 (COVID-19) pandemic has demonstrated a clear need for high-throughput, multiplexed and sensitive assays for detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and other respiratory viruses and their emerging variants. Here, we present a cost-effective virus and variant detection platform, called microfluidic Combinatorial Arrayed Reactions for Multiplexed Evaluation of Nucleic acids (mCARMEN), which combines CRISPR-based diagnostics and microfluidics with a streamlined workflow for clinical use. We developed the mCARMEN respiratory virus panel to test for up to 21 viruses, including SARS-CoV-2, other coronaviruses and both influenza strains, and demonstrated its diagnostic-grade performance on 525 patient specimens in an academic setting and 166 specimens in a clinical setting. We further developed an mCARMEN panel to enable the identification of 6 SARS-CoV-2 variant lineages, including Delta and Omicron, and evaluated it on 2,088 patient specimens with near-perfect concordance to sequencing-based variant classification. Lastly, we implemented a combined Cas13 and Cas12 approach that enables quantitative measurement of SARS-CoV-2 and influenza A viral copies in samples. The mCARMEN platform enables high-throughput surveillance of multiple viruses and variants simultaneously, enabling rapid detection of SARS-CoV-2 variants.

Supplemental Digital Content is available in the text

Supplemental Digital Content is available in the text.

Developing and deploying new diagnostic tests are difficult, but the need to do so in response to a rapidly emerging pandemic such as COVID-19 is crucially important. During a pandemic, laboratories play a key role in helping healthcare providers and public health authorities detect active infection, a task most commonly achieved using nucleic acid-based assays. While the landscape of diagnostics is rapidly evolving, PCR remains the gold-standard of nucleic acid-based diagnostic assays, in part due to its reliability, flexibility and wide deployment. To address a critical local shortage of testing capacity persisting during the COVID-19 outbreak, our hospital set up a molecular-based laboratory developed test (LDT) to accurately and safely diagnose SARS-CoV-2. We describe here the process of developing an emergency-use LDT, in the hope that our experience will be useful to other laboratories in future outbreaks and will help to lower barriers to establishing fast and accurate diagnostic testing in crisis conditions.

BackgroundTo date, the choice of optimal anesthetic management during endovascular therapy (EVT) of acute ischemic stroke patients remains subject to debate. We aimed to compare functional outcomes and complication rates of EVT according to the first-line anesthetic management in two comprehensive stroke centers: local anesthesia (LA) versus general anesthesia (GA).MethodsRetrospective analysis of prospectively collected databases, identifying all consecutive EVT for strokes in the anterior circulation performed between January 1, 2018 and December 31, 2018 in two EVT-capable stroke centers. One center performed EVT under LA in the first intention, while the other center systematically used GA. Using propensity score analysis, the two groups underwent 1:1 matching, then procedural metrics, complications, and clinical outcomes were compared. Good outcome was defined as 90 days modified Rankin Scale (mRS) ≤2, and successful recanalization as modified Thrombolysis In Cerebral Ischemia (mTICI) 2b-3.ResultsDuring the study period, 219 patients were treated in the LA center and 142 in the GA center. Using the propensity score, 97 patients from each center were matched 1:1 according to the baseline characteristics. Local anesthesia was associated with a significantly lower proportion of good outcome (36.1% vs 52.0%, OR 0.53, 95% CI 0.33 to 0.87; p=0.039), lower rate of successful recanalization (70.1% vs 95.8%, OR 0.13, 95% CI 0.04 to 0.39; p<0.001), and more procedural complications (14.4% vs 3.0%, OR 3.44, 95% CI 1.09 to 14.28; p=0.018). There were no significant differences in 90-day mortality or symptomatic hemorrhagic transformation rates.ConclusionsIn this study, systematic use of GA for stroke EVT was associated with better clinical outcomes, higher recanalization rates, and fewer procedural complications compared with patients treated under LA as the primary anesthetic approach.

This paper focuses on the use of morphological, mineral and geochemical characterization of soil profiles to assess rocks weathering trends and intensity as tools for mineral prospection in Mei¨ganga. To that effect, seven soil profiles developed on micaschist, orthogneiss, granite and quartzite vein were analysed. Macroscopic description of these soil profiles exhibited shallow weathered soils with thickness not exceeding 4 m. Minerals recorded in their weathering products were: quartz, 60.3–93.9%; kaolinite, 0.8–22.3%; phlogopite, 0.2–15.3%; goethite, 1.9–13.0%; hematite, 0.5–8.5%; halloysite, 0.2–4.6%; and smectite, 0.5–4.3%. Geochemically, SiO2contents globally decreased upward, while Al2O3, Fe2O3and TiO2contents increased. Alkaline and alkaline earths contents were almost completely leached. The total reserve in bases and Parker's weathering index (TRB, 416–11 mg kg−1; WIP, 56–4%) decreased upward, except in the soil profile associated with the quartzite veins (TRB, 2–100 mg kg−1; WIP, 0–29%). The chemical index of alterations were 5–92% with the index of lateritization 8–39% and the silica exportation ratio was greatly above 1 (Ki2–9). Trace elements in soil profiles were, in order of decreasing contents, S, Ba, Sr, Zr, Cr, V, Zn, Rb, Ni, Y, Sb, Cu, Pb, Li, Co, Ga, Nb, Th, Sc, Cs, Hf, Sn, U, Mo and W. Scandium, V, Cr, Sb, Cs and Pb were enriched, while S, Rb and Sr were depleted, and Ba, Zr, Zn, Ni, Y, Cu, Li, Co, Ga, Nb, Th, Hf, Sn, U, Mo and W showed complex behaviour. The most abundant rare earth elements (REEs) were, in order of decreasing contents, Ce (29–273 ppm), La (26–91 ppm), Nd (14–83 ppm) and Pr (4–22 ppm). Almost all the REEs were enriched in soil profiles with respect to parent material, and strongly fractionated, with fractionation intensity increasing from light to heavy REEs. The most significant useful elements identified were: refractory metals (Zr, Cr, V, Nb, Hf, Mo and W), semi-precious metal (Cu), non-precious unreactive metal (Sb) and actinide group element (U). Statistical analysis indicated that, in soil profiles, Nb, Mo, U, W and Hf had strong affinity with Al2O3; Mo, Cr, V, Zr, Hf and Sb had strong affinity with with Fe2O3; U, Hf and Sb had strong affinity with with P2O3; and Nb, Zr, V and Cr had strong affinity with with TiO2. Fe2O3, Al2O3and TiO2are respectively the greatest markers for Mo; Nb, Mo, W, Nb and U; and Nb, V and Cr prospection in soil profiles. The Clarke of concentrations of useful elements were: Sb, 60.00; Mo, 0.83–4.17; W, 1.60; Cr, 0.08–1.56; Nb, 0.60–1.55; U, 1.11–1.48; Hf, 1.33; V, 0.36–1.27; and Zr, 0.96. Exploitability concentrations for Cr and U in soil profiles varied respectively from 1.20 to 23.85% and from 0.15 to 0.20%.

ABSTRACTHepatitis B virus (HBV) immune escape and Pol/RT mutations account for HBV immunoprophylactic, therapeutic, and diagnostic failure globally. Little is known about circulating HBV immune escape and Pol/RT mutants in Nigeria. This study focused on narrowing the knowledge gap of the pattern and prevalence of the HBV mutants across clinical cohorts of infected patients in southwestern Nigeria. Ninety-five enrollees were purposively recruited across clinical cohorts of HBV-infected patients with HBsAg or anti-HBc positive serological outcome and occult HBV infection. Total DNA was extracted from patients’ sera. HBV S and Pol gene-specific nested PCR amplification was carried out. The amplicons were further sequenced for serotypic, genotypic, phylogenetic, and mutational analysis. HBV S and Pol genes were amplified in 60 (63.2%) and 19 (20%) of HBV isolates, respectively. All the sixty HBV S gene and 14 of 19 Pol gene sequences were exploitable. The ayw4 serotype was predominant (95%) while ayw1 serotype was identified in 5% of isolates. Genotype E predominates in 95% of sequences, while genotype A, sub-genotype A3 was observed in 5%. Prevalence of HBV IEMs in the “a” determinant region was 29%. Commonest HBV IEM was S113T followed by G145A and D144E. The Pol/RT mutations rtV214A and rtI163V among others were identified in this study. This study provided data on the occurrence of existing and new HBV IEMs and Pol gene mutations in Nigeria.

Recent reports on finding Wolbachia-strain infections in field mosquito species in some West African countries and the potential for developing these as disease vector biocontrol tools have prompted a search for Wolbachiain mosquitoes within the study area. Using a completely randomised design, mosquito traps were set at different locations in a rural and an urbanised community. One hundred and eighty (180) mosquitoes were trapped and pooled on the basis of genus, sex and site of collection, because there have been no earlier reports of Wolbachiaisolated from Nigeria. Twenty pools, made up of not more than ten mosquitoes per pool, were homogenised and analysed for Wolbachia-specific DNA. Mosquitoes were trapped within Ede (urbanised community) and Akoda (rural community). Genomic DNA was extracted from trapped mosquito samples and used as a template in a PCR reaction. The Wolbachiasp. specific 16S rRNA gene was amplified, sequence analysis of PCR products was performed and a chromatogram of the sequence was subjected to Basic Local Alignment Search Tool analysis to identify the Wolbachia sp. This sequence was subsequently submitted to GenBank with accession number MK127541. The first evidence of the presence of the endosymbiont, Wolbachia in field-caught mosquitoes is hereby documented. The homology of this strain of Wolbachia bears similarities to those reported recently from other parts of West Africa and forms a single clade with a Wolbachiasp. from Mali, with a strong bootstrap support of 99%. This finding of a Wolbachiastrain in mosquitoes at Ede could form the basis for more searches for diverse strains of Wolbachiain Nigeria.

The 2013–2016 West African epidemic caused by the Ebola virus was of unprecedented magnitude, duration and impact. Here we reconstruct the dispersal, proliferation and decline of Ebola virus throughout the region by analysing 1,610 Ebola virus genomes, which represent over 5% of the known cases. We test the association of geography, climate and demography with viral movement among administrative regions, inferring a classic ‘gravity’ model, with intense dispersal between larger and closer populations. Despite attenuation of international dispersal after border closures, cross-border transmission had already sown the seeds for an international epidemic, rendering these measures ineffective at curbing the epidemic. We address why the epidemic did not spread into neighbouring countries, showing that these countries were susceptible to substantial outbreaks but at lower risk of introductions. Finally, we reveal that this large epidemic was a heterogeneous and spatially dissociated collection of transmission clusters of varying size, duration and connectivity. These insights will help to inform interventions in future epidemics.

A large genomic surveillance effort in South Africa produced 1,365 high-quality whole genomes of SARS-CoV-2; this has identified 16 new lineages of the virus that had not been identified in other countries.

Lassa fever is a deadly viral haemorrhagic fever caused by Lassa Virus (LASV). Rodents, especially, Mystomys natalensis, are the known reservoirs of LASV and humans are the defined hosts. Monkeys share many illnesses with humans and experimental LASV infections in monkeys are fatal but natural LASV infection of monkeys has not been reported. Serum samples obtained between August 2015 and December 2017 from 62 monkeys belonging to six species in Southern Nigeria were tested for LASV as part of an ongoing surveillance of monkeys in the region for zoonotic pathogens. Commercially available Recombinant LASV (ReLASV) Pan-Lassa enzyme-linked immunosorbent assay (ELISA) test kits (Zalgen Labs, Germantown, MD, USA) were used to detect antibodies (IgG and IgM) and antigen specific for LASV nucleoprotein in the sera. Lassa-fever-specific IgG and IgM, and antigen specific for LASV nucleoprotein were detected in 5/62, 0/62, and 1/62 samples, respectively. The presence of LASV-specific antibodies in the sera suggests natural exposure to the virus, while the presence of LASV antigen may mean that monkeys are carriers of the virus. There is a need to broaden Lassa fever surveillance to include nonhuman primates (NHPs) for their probable role in the epidemiology of the disease.

At present, African scientists can only participate minimally in the genomics revolution that is transforming the understanding, surveillance and clinical treatment of infectious diseases. We discuss new initiatives to equip African scientists with knowledge of cutting-edge genomics tools, and build a sustainable critical mass of well-trained African infectious diseases genomics scientists.

A new dimeric naphtho-γ-pyrone, 2-hydroxydihydronigerone (1), along with five compounds, nigerone (2), pyrophen (3), kojic acid (4), 4-(hydroxymethyl)-5-hydroxy-2H-pyran-2-one (5), and p-hydroxyphenylacetic acid (6), was isolated from an endophytic fungus Aspergillus nigerAKRN associated with the roots of Entandrophragma congoënse. The structure of the new compound has been elucidated using spectroscopic data including 1D and 2D NMR as well as the high-resolution mass spectrometry. Compounds 1–5showed weak antimicrobial activity on five selected Gram-negative bacteria, namely Enterobacter aerogenes(CM64), Enterobacter cloacae(BM67), Klebsiella pneumonia(K2), and Escherichia coli(ATCC8739 and ATCC10536).

Emergence of malaria parasites resistant to artemisinin necessitates the need for development of new antimalarial therapies. Ciprofloxacin (CFX) a second generation quinolone antibiotic possesses some antimalarial activities. We investigated the in vivo antimalarial activities of CFX in combination with amodiaquine in mice infected with chloroquine-resistant Plasmodium berghei ANKA. Animals were treated orally with 80 or 160 mg kg−1 body weight of CFX alone given twice daily or in combination with amodiaquine (AQ) 10 mg kg−1 body weight. Parasitological activity and survival of the animals were assessed over 21 days. Peak parasitaemia in the untreated control group was 72·51%. Treatment with AQ alone resulted in clearance of parasitaemia by day 4 while treatment with CFX 80 and 160 mg kg−1 alone suppressed parasitaemia by 13·94–54·64% and 35·6–92·7%, respectively. However, the combination of CFX with AQ significantly enhanced response of infection in the animals to treatment (P < 0·05) resulting in complete resolution of parasitaemia throughout follow up period with CFX 160 mg kg−1, delayed recrudescence time with CFX 80 mg kg−1 and significant increase in survival rate of the animals. The results demonstrate beneficial interaction between AQ and CFX which may provide a clinically relevant antimalarial/antibiotic therapeutic option in the management of malaria. [ABSTRACT FROM AUTHOR]

Eight new triterpenoids, prototiamins A–G (1–6, 9) and seco-tiaminic acid A (10), were isolated along with four known compounds from the bark of Entandrophragma congoënse. Their structures were elucidated by means of HRMS and different NMR techniques and chemical transformations. Assignments of relative and absolute configurations for the new compounds were achieved using NOESY experiments and by chemical modification including the advanced Mosher’s method. Additionally, the structure and relative configuration of compound 3were confirmed by single-crystal X-ray diffraction analysis. Compounds 1, 3, and 5displayed significant in vitro antiplasmodial activity against the erythrocytic stages of chloroquine-sensitive Plasmodium falciparumstrain NF54. Prototiamin C (3) was the most potent of the compounds isolated, with an IC50value of 0.44 μM. All compounds tested showed low cytotoxicity for the L6 rat skeletal myoblast cell line.

A new prenylated acridone alkaloid, medicacridone (1), and a new ferulate xanthone, medicaxanthone (5), together with 11 known compounds were isolated from the methanol extract of the bark of the Cameroonian medicinal plant Citrus medica. The structures of all compounds were determined by comprehensive analyses of their 1D and 2D NMR, mass spectral (EI and ESI) data, chemical reactions, and comparison with previously known analogues. The agar diffusion test delivered low to missing antimicrobial activities, corresponding with MICs > 1 mg mL–1, while compounds 1–6and atalantoflavone (9) displayed weak cytotoxic activity against the human Caucasian prostate adenocarcinoma cell line PC-3, with IC50values ranging from 60.5 to 80.0 μm versusdoxorubicine with IC50=0.9 μm.

We have developed a robust RNA sequencing method for generating complete de novoassemblies with intra-host variant calls of Lassa and Ebola virus genomes in clinical and biological samples. Our method uses targeted RNase H-based digestion to remove contaminating poly(rA) carrier and ribosomal RNA. This depletion step improves both the quality of data and quantity of informative reads in unbiased total RNA sequencing libraries. We have also developed a hybrid-selection protocol to further enrich the viral content of sequencing libraries. These protocols have enabled rapid deep sequencing of both Lassa and Ebola virus and are broadly applicable to other viral genomics studies.

Le but de notre étude était d'évaluer la pertinence du scanner cérébral en urgence chez les patients hospitalisés, en analysant sa performance par indication et en identifiant des facteurs prédictifs indépendants de résultats anormaux au scanner.

Two new steroids, 22E, 24R-stigmast-22-ene-3,6,11-trione (1) and 22E, 24R-3-acetylstigmasta- 5,22-diene-7,11-dione (2), and one new ceramide, (2S,3S,4R,5R) N-(1,3,4,5-tetrahydroxyundecan- 2-yl)tetradecanamide (7), together with eleven known compounds were isolated from the CH2Cl2extract of the stem bark of Odyendyea gabonensis. The structures of all compounds were determined by comprehensive analyses of their 1D and 2D NMR, mass spectral (EI and ESI) data, chemical reactions, and comparison with previously known analogs. Pure compounds were tested for their activity against the bacteria Bacillus subtilis, Staphylococcus aureus and Escherichia coli, the fungi Mucor miehei and Candida albicans, and the plant pathogen oomycetes Aphanomyces cochlioides, Pythium ultimum and Rhizoctonia solani using the paper disk agar diffusion assay. For active compounds, MICs were determined by the broth microdilution assay. Cytotoxic activity against the human lung adenocarcinoma cell line A 549 was evaluated by the MTT assay. All compounds delivered low to missing antimicrobial activities in the agar diffusion assay and MICs > 1 μg mL-1. The alkaloids 10 and 11 displayed cytotoxic activity against the human lung adenocarcinoma cell line A549 with IC502.5 and 4:5 μm respectively.

The methanol extract of dried fruits of Odyendyea gabonensis afforded one new quassinoid [(--)-odyendanol (1)], one new canthin-6-one alkaloid [9-hydroxy-5-methoxycanthin-6-one (4)], and two new steroids [22E, 24R-stigmasta-5,22- diene-3,7-dione (7) and 22E,24R-stigmast-22-ene-3,7-dione (8)] along with fourteen known compounds. The structures of all compounds were established by analyzing the spectroscopic data. The 13C-NMR values of (--)-odyendene (2) and (--)-odyendane (3), as well as the single-crystal X-ray structure of 5-methoxycanthin-6-one (6) are also reported. The oxidative burst inhibitory activity of pure compounds 1-12 was determined by the chemoluminescence assay, and cytotoxic activities of compounds 2-6 against the human prostate cancer cell PC-3 line were evaluated. Compounds 1-6 exhibited a clear suppressive effect on the phagocytosis response upon activation with serumopsonized zymosan in the range of IC50 = 0.9- 2.0 µM versus ibuprofen with IC50 = 12.1 µM, while all canthin-6-one alkaloids (4-6) displayed moderate cytotoxic activity against the human prostate cancer cell PC-3 line, with IC50 values ranging from 13.5-15.4µM versus doxorubicine with IC50 = 1.5 µM. [ABSTRACT FROM AUTHOR]

Two new O-prenylated acridone alkaloids, balsacridone A (1) and B (2), together with eighteen known compounds were isolated from the methanol extract from the stems of Balsamocitrus paniculata, a Cameroonian medicinal plant. The structures of all compounds were determined by comprehensive analyses of their 1D and 2D NMR, mass spectral (EI and ESI) data, and chemical reactions. N-methyl-6-methoxybenzoxazolinone (16) was isolated for the first time from a natural source while compounds 13, 14, and 15 for the first time from this genus. Pure compounds were tested for their activity against bacteria, fungi, and plant pathogen oomycetes, using the paper disk agar diffusion assay. The agar diffusion test delivered low to missing antimicrobial activities, corresponding to MICs > 1 mg/mL. However, compounds 1-15 exhibited a strong suppressive effect on phagocytosis response upon activation with serum opsonized zymosan in the range of IC50 = 0.5-7.2 μM, and the acridone alkaloids (1-5), Ntrans- p-coumaroyltyramine (13), and N-trans-pcoumaroyloctopamine (14) displayed weak cytotoxic activity against the human Caucasian prostate adenocarcinoma cell line PC-3, with IC50 values ranging from 69.8 to 99.0 μM. [ABSTRACT FROM AUTHOR]

A descriptive cross sectional survey using an interviewer-administered questionnaire was carried out among 700 caregivers whose children had fever during the previous two weeks. The aim was to determine the community effectiveness of malaria treatment using arthemeter-lumefantrine (AL) among under-5-year-olds in a rural community in southwestern Nigeria. A total of 353 (50.9%) children received AL. About half of these children (49%) were said to have been treated within 24 hours of onset of symptoms; 44% took the drug for the stipulated period of time; 42% received the correct dosage; and only 4% received all the treatment steps. With a drug efficacy of 100%, AL achieved a community effectiveness of 4%. The greatest effort in the home management of malaria strategy should be in reducing delay in treatment and improving dosage and duration of treatment.

Two new phenylethanoids, basalethanoid A (1) and B (2), and one new ceramide, basalamide A (3), together with eleven known compounds (4 - 14) were isolated from theMeOH extract of the stem barks of Basalmocitrus cameroonensis. The structures of all compounds were determined by comprehensive analyses of their 1D and 2D NMR, mass spectral (EI and ESI) data, chemical reactions, and comparison with previously known analogs. Compounds 1, 2, 5, and 7 - 10 demonstrated a strong inhibition on reactive oxygen species (ROS) production in the oxidative burst activity of whole blood on activation with serum opsonized zymosan in the range of IC50= 0.06 - 12.30 µg mL-1.

ABSTRACTWe assessed Plasmodium falciparum mdr1(Pfmdr1) gene polymorphisms and copy numbers as well as P. falciparumCa2+ATPase (PfATPase6) gene polymorphisms in 90 Nigerian children presenting with uncomplicated falciparum malaria and enrolled in a study of the efficacy of artemether-lumefantrine (AL). The nested PCR-restriction fragment length polymorphism and the quantitative real-time PCR methodologies were used to determine the alleles of the Pfmdr1and PfATPase6genes and the Pfmdr1copy number variation, respectively, in patients samples collected prior to treatment and at the reoccurrence of parasites during a 42-day follow-up. The Pfmdr1haplotype 86N-184F-1246Dwas significantly associated (P< 0.00001) with treatment failures and was selected for among posttreatment samples obtained from patients with newly acquired or recrudescing infections (P< 0.00001; χ2= 36.5) and in gametocytes (log rank statistic = 5; P= 0.0253) after treatment with AL. All pre- and posttreatment samples as well as gametocytes harbored a single copy of the Pfmdr1gene and the wild-type allele (L89) at codon 89 of the PfATPase6gene. These findings suggest that polymorphisms in the Pfmdr1gene are under AL selection pressure. Pfmdr1polymorphisms may result in reduction in the therapeutic efficacy of this newly adopted combination treatment for uncomplicated falciparum malaria in Saharan countries of Africa.

ABSTRACTThe activities of amodiaquine, artesunate, and artesunate-amodiaquine against asexual- and sexual-stage parasites were evaluated in 360 Nigerian children with uncomplicated Plasmodium falciparummalaria randomized to the standard dose regimens of the three drugs/combination. Clinical recovery from illness occurred in all children. There were no significant differences in fever clearance times. Patients treated with artesunate or artesunate-amodiaquine had significantly shorter parasite clearance times (1.4 ± 0.5 days or 1.4 ± 0.6 days versus 3.2 ± 2.3 days, P= 0.0001) and lower gametocyte carriage rates (3.3 or 1.7% versus 11.7%, P= 0.001) than those treated with amodiaquine alone. Gametocytemia was detected in 62 patients (11.7% before treatment and 5.6% after treatment). The pretreatment gametocyte sex ratio, which was female biased, increased significantly during the course of treatment with amodiaquine but not with artesunate and artesunate-amodiaquine. These results suggest that artesunate and artesunate-amodiaquine reduce gametocyte carriage and may reduce transmissibility in P. falciparummalaria by accelerating asexual clearance and influencing gametocyte sex ratio.

Abstract: Chloroquine (CQ) resistance in Plasmodium falciparum is associated with polymorphisms in loci on pfcrt and pfmdr1 genes. In this study, we determined the association and linkage disequilibrium between in vivo CQ resistance and P. falciparum polymorphisms in pfcrt gene at codon 76 and pfmdr1 gene at codon 86 in isolates obtained from 111 children with acute uncomplicated falciparum malaria in Nigeria. Patients were treated with standard dosage of CQ and followed up for 28 days. Filter paper samples were collected at enrollment and during follow-up for parasites genotypes and identification of pfcrt and pfmdr1 mutations. Association and linkage disequilibrium between mutant pfcrtT76 and pfmdr1Y86 alleles in pretreatment isolates of P. falciparum was determined. Fifty-five out of the 111 patients (49.5%) failed treatment. Single mutant pfcrtT76 or pfmdr1Y86 alleles were found in 55 out of 111 P. falciparum isolates screened at enrollment. Of these 55 isolates, the mutant pfcrtT76 and pfmdr1Y86 alleles were found in 84%. Both mutant pfcrtT76 (p=0.0196) and pfmdr1Y86 (p=0.000042) alleles were associated with in vivo CQ resistance. In addition, the mutant pfcrtT76 (p=0.047) and pfmdr1Y86 (p=0.006) alleles were significantly selected by CQ in patients who failed treatment. Association analysis between paired single alleles at pfcrt and pfmdr1 loci showed a significant association (p=0.0349 and χ 2=4.45) between the pfcrt T76 allele on chromosome 7 and the pfmdr1Y86 allele on chromosome 5 and that these two mutant alleles were in linkage disequilibrium (p=0.000, D′=0.64, and r 2=0.28). Considering the high level of CQ resistance and drug use in the study area, the observed linkage disequilibrium between the mutant pfcrtT76 and pfmdr1Y86 alleles is maintained epistatically through directional CQ selective pressure.

Plasmodium falciparum malaria during high and low transmission seasons was evaluated in 1031 children treated with different antimalarial drug in a hyperendemic area of southwestern Nigeria. Seventy-three (10.5%) of 693 and forty (11.8%) of 338 children were gametocyte carriers in the high transmission seasons (HTS) and low transmission seasons (LTS), respectively. In a multiple regression model, two factors were found to be independent risk factors for the presence of gametocytemia at enrolment in the HTS: duration of illness >3 d, and asexual parasite densities less than 10000/μl. Similarly male gender, duration of illness >4 d and parasite density less than 5000/μl were found independent risk factors for presence of gametocytemia during LTS. The presenting parasitemia, parasite clearance times, intensity of gametocytemia and proportion carrying gametocytes post treatment differ significantly in the 333 (32.3%) of these children that were treated with chloroquine in the two seasons. These findings may be important in our understanding of P. falciparum transmission sustenance, response to chloroquine therapy and contribution of chloroquine to gametocyte carriage as seasonal changes occur.

The risk factors associated with gametocytaemia at presentation and after treatment with different antimalarial drug regimens were evaluated in 767 children enrolled prospectively in 5 antimalarial drug trials between July 1996 and December 2002 in a hyperendemic area of southwestern Nigeria. The children were assigned to one of 6 treatment groups: chloroquine (CQ) only; pyrimethamine-sulfadoxine (PS) only; amodiaquine (AQ) only; CQ combined with chlorpheniramine (CQCP); or PS combined with CQ (CQPS) or AQ (AQPS). At enrolment, 115 (15%) of 767 children were gametocyte carriers. During follow-up, 15·6% of all patients (i.e. 120 patients) developed patent gametocytaemia, which in 85% (102 patients) had developed by day 7 following treatment. In a multiple regression model, 4 factors were found to be independent risk factors for the presence of gametocytaemia at enrolment: male gender (adjusted odds ratio [AOR]=0·55, 95% confidence interval [CI] 0·36–0·83, P=0·005), absence of fever (AOR=1·61, 95% CI 1·05–2·5, P=0·03), duration of illness >3 days (AOR=1·57, 95% CI 1·0–2·4, P=0·047), and asexual parasite densities less than 5000/μl (AOR=0·42, 95% CI 0·24–0·73, P=0·002). The presence of patent gametocytaemia at enrolment (AOR=0·04, 95% CI 0·02–0·07, P&lt;0·001) and recrudescence of asexual parasites within 14 days were associated with the presence of gametocytaemia 7 or 14 days after enrolment (AOR=0·5, 95% CI 0·3–0·8, P=0·007). Delay in the time taken to clear the initial parasitaemia (>2 days) was associated with increased risk of subsequent gametocyte carriage. These findings may have implications for malaria control efforts in sub-Saharan Africa where control of the disease depends almost entirely on chemotherapy.

Previous research has established that the duration of stressed word stem vowels is shorter in polysyllabic words than in monosyllabic words for normal speakers and for speakers with aphasia and apraxia of speech (AOS). However, the results are inconsistent across studies with regard to the magnitude and pattern of the duration reduction for apraxic speakers. We hypothesized that this inconsistency may be explained based on different relative measures of duration reduction. A speech sample was obtained from 10 aphasic speakers with AOS, 10 aphasic speakers without AOS, and 10 normal controls. As predicted, the use of two different relative measures resulted in different vowel reduction patterns, both of which were consistent with previous reports. The results further indicate that the production of polysyllabic words is particularly taxing in AOS and is associated with a substantial reduction of speaking rate compared to other aphasic and normal speakers.

The cardiac effects of halofantrine (HF) and chloroquine plus chlorpheniramine (CQ-CP), a histamine H1antagonist which reverses chloroquine insensitivity in Plasmodium falciparum in vitroand in vivo, were assessed in 41 children with acute symptomatic uncomplicated P. falciparummalaria by electrocardiographic and clinical monitoring over a period of 14 days. In addition, the cardiac effects of chloroquine (CQ) alone and CQ-CP were compared in 10 age- and sex-matched children. HF produced a significantly higher proportion of abnormally prolonged P-R interval (8 abnormally prolonged out of 132 total P-R events) than CQ-CP (1 of 133 P-R events) (P= 0·03), but a similar proportion of prolonged Q-Tc interval to that of CQ-CP (46 of 149 versus 29 of 134 events, P= 0·07). Compared with pre-treatment Q-Tc, HF significantly prolonged this interval from 6 to 96 h post treatment with a maximum effect at 24 h after commencing HF treatment. CQ-CP by contrast produced significant changes in Q-Tc values from 6 to only 48 h with a maximum effect at 48 h. HF-induced Q-Tc prolongations were significantly higher than those of CQ-CP only at 24 h. The cardiac effects of CQ-CP were similar to those of CQ alone. Despite the electrocardiogram abnormalities, rhythm disturbance was rare and there was no clinical symptom in any of the treatment groups. Compared with HF, CQ-CP produced cardiac effects that were less severe and in fewer children with acute falciparum malaria. The addition of CP to CQ does not significantly amplify the cardiac effects of CQ in children with acute uncomplicated falciparum malaria.

BackgroundConvulsions associated with fever (CAWF), are a frequent medical emergency in children. In the tropics, endemic malaria and bacterial infections are established causes. However, knowledge of the contributions of endemic viral haemorrhagic fevers, particularly Lassa fever(LF) which has multiple lineages of the virus, remains unknown It was hypothesised that LF, may be an unrecognised contributor to CAWF in areas of high disease burden.ObjectiveDetermine the prevalence of LF in children with fever, compare seizure characteristics, clinical features and outcomes. MethodA prospective case-control study of emergency admissions presenting with fever of 380 C. A positive Lassa virus Reverse-transcription Polymerase Chain Reaction (LV-RT-PCR) defined a diagnosis of LF.ResultsThree hundred and seventy three febrile children and adolescents were recruited,108 cases (CAWF) compared with 265 controls (fever without convulsions). The prevalence of LF [95% CI] was 3.5% [1.9, 5.7] The prevalence of malaria parasitaemia was significantly higher in CAWF compared with controls (OR [95% CI]=(6.38[2.86, 14.22], p=0.0001 ). There was no significant difference between the prevalence of LF in cases with non-febrile convulsions and their controls ( 2/40 versus 8/94 ) ( Fisher’s exact p=0.759 ). Bleeding was significantly associated with LF in CAWF compared with controls ( Fisher’s exact p=0.008 ).ConclusionLF is an important cause of fever. In this study LF was not significantly associated with CAWF but was a cause of fever presenting with seizures The absence of clear clinical differentiators from other aetiologies of fever without a focus inform the need for a high index of suspicion where the disease is endemic.

L’alopécie de traction (AT) semble « épidémique » en Afrique noire où elle concerne environ 33% des femmes adultes, représentant la 2° cause d’alopécie dans cette région. En dehors des mentions anecdotiques de l’utilisation du minoxidil topique, il n’a été rapporté, à ce jour, à notre connaissance, de traitement médical connu dans cette forme d’alopécie si fréquente. Notre objectif était d’évaluer l’efficacité et la tolérance du gel rubéfiant dans l’AT.

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