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Polymorphisms in the human angiotensin converting enzyme gene (ACE) linked to susceptibility of COVID-19 and malaria infections in the Ghanaian population
(Infection, Genetics and Evolution, 2024) Duah-Quashie, N.O.; Opoku-Agyeman, P.; Lanza, M.; Rubio, J.M.
Genetic variations in the human angiotensin converting enzyme gene (ACE) influence ACE enzyme expression levels in humans and subsequently influence both communicable and non-communicable disease outcomes. More recently, polymorphisms in this gene have been linked to susceptibility and outcomes of infectious diseases such as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and malaria infections. This study is the first to investigate the genetic diversity of ACE and ACE2 polymorphisms in the Ghanaian population. Archived filter blood blot samples from malaria patients aged ≤9 years were used. Molecular analysis for the detection of ACE rs4646994 (I/D), ACE2 rs2106809 (C/T) and rs2285666 (G/A) alleles as well as ACE2 exons 1–4 polymorphisms was conducted on 300 samples. The D allele (54%,162/300) was the most dominant polymorphism observed in the ACE rs4646994 gene whilst the G (68%, 204/300) and T alleles (59.3%,178/300) were the most frequent ACE2 rs2285666 and rs2106809 polymorphisms observed. For the 300 samples sequenced for ACE2 exons 1–4, analyses were done on 268, 282 and 137 quality sequences for exons 1, 2 and 3–4 respectively. For exon 1, the mutation D38N (2.2%; 6/268) was the most prevalent. The S19P and E37K mu tations previously reported to influence COVID-19 infections were observed at low frequencies (0.4%, 1/268 each). No mutations were observed in exon 2. The N121K/T variants were the most seen in exons 3–4 at fre quencies of 5.1% (K121, 7/137) and 2.9% (T121, 4/137) respectively. Most of the variants observed in the exons were novel compared to those reported in other populations in the world. This is the first study to investigate the genetic diversity of ACE and ACE2 genes in Ghanaians. The observation of novel mutations in the ACE2 gene is suggesting selection pressure. The importance of the mutations for communicable and non-communicable dis eases (malaria and COVID-19) are further discussed
Alkaloidal Extracts from Avicennia africana P. Beauv. (Avicenniaceae) Leaf: An Antiplasmodial, Antioxidant, and Erythrocyte Viable
(Advances in Pharmacological and Pharmaceutical Sciences, 2024) Ahmed, M.A.; Ameyaw, E.O.; Zoiku, F.K.; et al.
Background. Te emergence of drug-resistant parasites impedes disease management and eradication eforts. Hence, a rein vigorated attempt to search for potent lead compounds in the mangroves is imperative. Aim. Tis study evaluates in vitro antiplasmodial activity, antioxidant properties, and cytotoxicity of A. africana leaf alkaloidal extracts. Methods. Te A. africana leaves were macerated with 70% ethanol to obtain a total crude extract. Dichloromethane and chloroform-isopropanol (3 :1, v/v) were used to extract the crude alkaloids and quaternary alkaloids from the total crude. Te antiplasmodial activities of the alkaloidal extracts were performed against 3D7 P. falciparum chloroquine-sensitive clone via the SYBR Green I fuorescence assay with artesunate serving as the reference drug. Te alkaloidal extracts were further evaluated for antioxidant properties via the total antioxidant capacity (TAC), the total glutathione concentration (GSH), the DPPH (2,2-diphenyl-1-picrylhydrazyl) assay, and the ferric-reducing antioxidant power (FRAP) methods. Te cytotoxic activity of the alkaloidal extracts was tested on erythrocytes using a 3-(4,5-dimethylthiazol-2-yl)-5-diphenyltetrazolium bromide-MTTassay with little modifcation. Te phytocompounds in the alkaloidal extracts were identifed via gas chromatography-mass spectrometry (GC-MS) techniques. Results. Te total crude extract showed good antiplasmodial activity (IC50 = 11.890 µg/mL). Te crude and quaternary alkaloidal extracts demonstrated promising antiplasmodial efects with IC50 values of 6.217 and 6.285 µg/mL, respectively. Te total crude and alkaloidal extracts showed good antioxidant properties with negligible cytotoxicity on erythrocytes with good selectivity indices. Te GC-MS spectral analysis of crude alkaloidal extracts gave indole and isoquinoline alkaloids and several other compounds. Dexrazoxane was found to be the main compound predicted, with an 86% peak area in the quaternary alkaloidal extract. Conclusion. Te crude and quaternary alkaloidal extracts exhibited antiplasmodial activities and ability to inhibit oxidative stress with negligible toxicity on erythrocytes. Tis may be good characteristics to avoid oxidative stress related to Plasmodium infection in the treatment of malaria.
Ethical considerations for biobanking and use of genomics data in Africa: a narrative review
(BMC Medical Ethics, 2023) Amoakoh‑Coleman, M.; Vieira, D.; Abugri, J.
Background Biobanking and genomic research requires collection and storage of human tissue from study partici‑ pants. From participants’ perspectives within the African context, this can be associated with fears and misgivings due to a myriad of factors including myths and mistrust of researchers. From the researchers angle ethical dilemmas may arise especially with consenting and sample reuse during storage. The aim of this paper was to explore these ethical considerations in the establishment and conduct of biobanking and genomic studies in Africa. Methods We conducted a narrative synthesis following a comprehensive search of nine (9) databases and grey literature. All primary research study designs were eligible for inclusion as well as both quantitative and qualitative evidence from peer reviewed journals, spanning a maximum of 20 years (2000–2020). It focused on research work conducted in Africa, even if data was stored or analysed outside the region. Results Of 2,663 title and abstracts screened, 94 full texts were retrieved and reviewed for eligibility. We included 12 studies (7 qualitative; 4 quantitative and one mixed methods). Ethical issues described in these papers related to community knowledge and understanding of biobanking and genomic research, regulation, and governance of same by research ethics committees, enrolment of participants, types of informed consents, data collection, storage, usage and sharing as well as material transfer, returning results and beneft sharing. ca. Biospecimen collection and storage is given in trust and participants expect confdentially of data and results generated. Most participants are comfortable with broad consent due to trust in researchers, though a few would like to be contacted for reconsenting in future studies, and this would depend on whether the new research is for good cause. Sharing data with external partners is welcome in some contexts but some research participants did not trust foreign researchers. Conclusion Biobanking and genomic studies are a real need in Africa. Linked to this are ethical considerations related to setting up and participation in biobanks as well as data storage, export, use and sharing. There is emerg‑ ing or pre-existing consensus around the acceptability of broad consent as a suitable model of consent, the need for Africans to take the lead in international collaborative studies, with deliberate eforts to build capacity in local storage and analysis of samples and employ processes of sample collection and use that build trust of communities and potential study participants. Research ethics committees, researchers and communities need to work together to work together to adapt and use clearly defned ethical frameworks, guidelines, and policy documents to harmonize the establishment and running of biobanking and genomic research in Africa.
Improving Access To Lymphatic Filariasis MMDP Services Through An Enhanced Evidence-Based, Cascaded Training Model For Health Worker Capacity Strengthening In Ghana: An Evaluation Study
(Frontiers in Tropical Diseases, 2023) Ahorlu, C.S.; Sedzro, K.M.; Atinbire, S.A.; et al.
Introduction: Ghana has made significant progress in reducing the transmission rate of lymphatic filariasis. However, very little progress has been made in the provision of morbidity management and disability prevention (MMDP) services, which is one of the key requirements for certification of elimination as a disease of public health importance. This study was designed to compare pre- and post-intervention to determine the feasibility and effectiveness of cascade training model for health worker capacity strengthening in Ghana, using the WHO recommended minimum intervention package to improve access to MMDP services. Methods: This study used a quasi-experimental design to assess the impact of evidence-based training of patients with lymphatic filariasis (LF) in the Upper West region of Ghana. All lymphedema patients who were available at the time of data collection participated in the study before and after the training. Results: The mean age of respondents was 54.67 years (SD ± 16.89 years) at baseline and 54.70 years (SD ± 15.80 years) at evaluation. The majority (i.e., 76.30% at baseline and 80.50% at evaluation) of the respondents were female. Most of the respondents had not completed primary school (83.82% at baseline). and 85.40% at evaluation). We found an improvement in the quality of life among LF patients, that is, the proportion of respondents who reported having a high Quality of life increased from 2.9% at baseline to 20.12% at evaluation (p < 0.001). The lymphedema management practice of “hygiene/washing and drying of affected limb” was reported by 73.17% of respondents at evaluation compared with only 32.95% of respondents at baseline (p < 0.001). The acute attack management technique of “cooling the affected limb in cool water or cold compress” was reported by 70.15% of respondents at evaluation compared with 23.70% of respondents at baseline (p < 0.001). Conclusion: The research confirmed that LF-related perceptions remained generally the same at baseline and evaluation among community members. The implementation of the LF-related morbidity management (MMDP) project has led to a significant improvement in the morbidity management practices among patients at evaluation compared with baseline. Our findings also showed that Self-care led to an improvement in patients’ quality of life. This justifies the need for investment in morbidity management interventions in endemic communities.
Endemic infectious cutaneous ulcers syndrome in the Oti Region of Ghana: Study of cutaneous leishmaniasis, yaws and Haemophilus ducreyi cutaneous ulcers
(PLOS ONE, 2023) Akuffo, R.A.; Sanchez, C.; Amanor, I.; et al.
Background A recent study detected cutaneous leishmaniasis (CL) in 31.9% of persons with skin ulcers in the Oti Region of Ghana, resulting in a need to investigate other potential causes of the unexplained skin ulcers. Methodology/Principal findings A community based cross-sectional study was conducted in the Oti region to investigate skin ulcers of undetermined aetiologies. To confirm a diagnosis of cutaneous leishmaniasis, Buruli ulcer, Haemophilus ducreyi ulcers, or yaws, DNA obtained from each patient skin ulcer sample was systematically subjected to polymerase chain reaction (PCR) for Leish mania spp., Mycobacterium ulcerans, Haemophilus ducreyi, and Treponema pallidum sub species pertenue. A total of 101 skin ulcer samples were obtained from 101 persons. Co infection of more than one organism was observed in 68.3% of the samples. Forty (39.6%) participants had a positive result for Leishmania spp., 68 (67.3%) for Treponema pallidum sub. Sp. pertenue, and 74 (73.3%) for H. ducreyi. Twenty (19.8%) of the patient ulcers were simultaneously infected with Leishmania spp., Treponema pallidum sub. Sp. pertenue, and H. ducreyi. None of the patients’ lesions yielded a positive result for Mycobacterium ulcerans. Conclusions/Significance This study detected single and mixed occurrence of the causative organisms of CL, yaws, and H. ducreyi cutaneous ulcers in CL endemic communities of the Oti Region in Ghana. These findings emphasize the importance of integrating multiple skin diseases on a com mon research platform and calls for the development of a comprehensive guideline for diag nosing and treating tropical ulcers in the study areas.
In vitro and in silico anti-malarial activity and cytotoxicity of n-hexyl 1-O-rutinoside (a glycoside) isolated from Annickia polycarpa (DC.) Setten and Maas ex I.M. Turner (Annonaceae)
(Journal of Ethnopharmacology, 2023) Kumatia, E.K.; Zoiku, F.K.; Asase, A.; Tung, N.H.
Ethnopharmacological relevance: Annickia polycarpa leaf is an effective anti-malarial agent. However, its chemical constituents have not been isolated and assayed against any pathogen. Aim of the study: To isolate and characterize anti-malarial compound(s) from the leaf of A. polycarpa. Materials and methods: Bioassay-guided fractionation was employed to isolated the compound (AL1) from the chloroform fraction (ALCF) of the basified ethanol extract of A. polycarpa leaf (ALE). AL1 was characterized by LC-MS, 1D and 2D NMR spectroscopic analysis. Anti-malarial activity was evaluated against drug resistance Dd2 and drug sensitive 3D7 Plasmodium falciparum strains using the SYBR green assay. Cytotoxicity and mechanistic studies were determined using tetrazolium-based colorimetric assay and molecular docking respectively. Results: AL1 was characterized as n-hexyl 1-O-rutinoside. The IC50 values of ALE and ALCF against 3D7 and Dd2 P. falciparum strains ranges from 3.441 (0.3389) - 4.255 (0.2246) μg/mL. The IC50s obtained for n-hexyl 1-O-ruti noside and Artesunate (standard drug) were 7.71 (0.5473) and 0.001 (0.00008) nM against the 3D7 parasite strain respectively. Also, the efficacy of n-hexyl 1-O-rutinoside increased by 24.40% against the chloroquine resistance Dd2 P. falciparum strain whiles that of Artesunate decreased by 98.96%. Furthermore, ALE, ALCF and n-hexyl 1-O-rutinoside were weakly cytotoxic to human RBCs with high selectivity indices. N-hexyl 1-O-rutino side inhibits P. falciparum chloroquine resistance transporter (PfCRT) and dihydrofolate reductase-thymidylate synthase (PfDHFR-TS) better than chloroquine and pyrimethamine respectively. But, produced similar inhibi tion of P. falciparum 2-trans-enoyl -ACP-reductase (PfERN) as triclosan. Conclusion: These results show that A. polycarpa leaf and n-hexyl 1-O-rutinoside possessed profound anti-malarial activity and are not cytotoxic. N-hexyl 1-O-rutinoside could therefore, be developed into a new anti-malarial medicine. This is the first study to report the anti-malarial activity of n-hexyl 1-O-rutinoside and its isolation from the genus Annickia.
In vitro and in silico anti-malarial activity and cytotoxicity of n-hexyl 1-O-rutinoside (a glycoside) isolated from Annickia polycarpa (DC.) Setten and Maas ex I.M. Turner (Annonaceae)
(Journal of Ethnopharmacology, 2023) Kumatia, E.K.; Zoiku, F.K.; Asase, A.; Tung, N.H.
Ethnopharmacological relevance: Annickia polycarpa leaf is an effective anti-malarial agent. However, its chemical constituents have not been isolated and assayed against any pathogen. Aim of the study: To isolate and characterize anti-malarial compound(s) from the leaf of A. polycarpa. Materials and methods: Bioassay-guided fractionation was employed to isolated the compound (AL1) from the chloroform fraction (ALCF) of the basified ethanol extract of A. polycarpa leaf (ALE). AL1 was characterized by LC-MS, 1D and 2D NMR spectroscopic analysis. Anti-malarial activity was evaluated against drug resistance Dd2 and drug sensitive 3D7 Plasmodium falciparum strains using the SYBR green assay. Cytotoxicity and mechanistic studies were determined using tetrazolium-based colorimetric assay and molecular docking respectively. Results: AL1 was characterized as n-hexyl 1-O-rutinoside. The IC50 values of ALE and ALCF against 3D7 and Dd2 P. falciparum strains ranges from 3.441 (0.3389) - 4.255 (0.2246) μg/mL. The IC50s obtained for n-hexyl 1-O-ruti noside and Artesunate (standard drug) were 7.71 (0.5473) and 0.001 (0.00008) nM against the 3D7 parasite strain respectively. Also, the efficacy of n-hexyl 1-O-rutinoside increased by 24.40% against the chloroquine resistance Dd2 P. falciparum strain whiles that of Artesunate decreased by 98.96%. Furthermore, ALE, ALCF and n-hexyl 1-O-rutinoside were weakly cytotoxic to human RBCs with high selectivity indices. N-hexyl 1-O-rutino side inhibits P. falciparum chloroquine resistance transporter (PfCRT) and dihydrofolate reductase-thymidylate synthase (PfDHFR-TS) better than chloroquine and pyrimethamine respectively. But, produced similar inhibi tion of P. falciparum 2-trans-enoyl -ACP-reductase (PfERN) as triclosan. Conclusion: These results show that A. polycarpa leaf and n-hexyl 1-O-rutinoside possessed profound anti-malarial activity and are not cytotoxic. N-hexyl 1-O-rutinoside could therefore, be developed into a new anti-malarial medicine. This is the first study to report the anti-malarial activity of n-hexyl 1-O-rutinoside and its isolation from the genus Annickia.
Gastrointestinal Parasites of the Ethiopian Rock Hyrax (Procavia capensis, Pallas, 1766) in the North East Region of Ghana
(International Journal of Zoology, 2023) Bimi, L.; Tetteh, A.K.; Oduro, D.; Anto, F.
Wildlife may serve as potential reservoirs and intermediate or accidental hosts of zoonotic pathogens due to their interactions with human beings. For the frst time in Ghana, we report extempore the gastrointestinal parasites of three Ethiopian rock hyraxes captured in September 2021. Forty adult parasites (21 nematodes and 19 tapeworms) were recovered from the gastrointestinal tracts of these three game hyraxes (Procavia capensis, Pallas, 1766) from the hills of Bimbagu (near the Gambaga Scarp) in the North East Region of Ghana. Adult worms comprising 16 tapeworms and 24 nematodes were identifed. Te intestinal faecal examination detected ova of Trichuris spp., tapeworms, and hookworms. Te results are presented alongside the results of the molecular determination of the worm identities. Since wildlife has been identifed as an important source of emerging human pathogens, including helminth parasites, there is an urgent need for sufcient literature on wildlife parasites in Ghana. As the rock hyrax is hunted for its meat, there is a potential risk of transmitting these identifed helminths and other zoonotic pathogens to humans, especially involving people who handle the carcasses as the transmission is faecal-oral. A more precarious situation may arise when the eggs of cestodes are ingested by handlers of these carcasses and could result in cysticercosis/neuro-cysticercosis when these eggs cross the blood-brain barrier in the person.
Anti-malarial activity of the alkaloid, heptaphylline, and the furanocoumarin, imperatorin, from Clausena anisata against human Plasmodium falciparum malaria parasites: ex vivo trophozoitocidal, schizonticidal and gametocytocidal approach
(Malaria Journal, 2023) Kumatia, E.K.; Zoiku, F.K.; Asase, A.; Tung, N.H.
Background The erythrocytic stage of the life cycle of the malaria parasite, Plasmodium falciparum, consists of trophozoite, schizont and gametocyte stages in humans. Various anti-malarial agents target diferent stages of the parasite to produce treatment outcomes. This study reports on the stage-specifc anti-malarial activity of hepta phylline and imperatorin against human P. falciparum in addition to their cytotoxicity and selectivity indices (SI). Methods The compounds were isolated from Clausena anisata using column chromatography and their structures elucidated using NMR spectroscopy. The anti-malarial activity was determined by measuring the trophozoitocidal, schizonticidal and gametocytocidal activities of the compounds using the SYBR green assay. Cytotoxicity was evalu ated using the tetrazolium-based colorimetric assay. Results Heptaphylline and imperatorin produced trophozoitocidal, schizonticidal and gametocytocidal activi ties with IC50s of 1.57 (0.2317)–26.92 (0.3144) µM with those of artesunate (the standard drug) being 0.00024 (0.0036)–0.0070 (0.0013) µM. In the cytotoxicity assay, the compounds produced CC50S greater than 350 µM and SI of 13.76–235.90. Also, the trophozoitocidal and schizonticidal activities of the compounds were more pronounced than their gametocytocidal activity. Imperatorin was 42.04% more trophozoitocidal than hepthaphyline. However, hepthaphyline has more schizonticidal and gametocytocidal properties than imperatorin. Conclusion Heptaphylline and imperatorin are promising anti-malarial agents, since they possess potent anti-malar ial activity with weak cytotoxicity on RBCs. However, imperatorin is a better anti-malarial prophylactic agent whereas heptaphylline is a better malaria treatment agent.
Macrophage susceptibility to infection by Ghanaian Mycobacterium tuberculosis complex lineages 4 and 5 varies with self-reported ethnicity
(Frontiers in Cellular and Infection Microbiology, 2023) Osei-Wusu, S.; Tetteh, J.K. A.; Arthur, N.
Background: The epidemiology of Mycobacterium tuberculosis complex (MTBC) lineage 5 (L5) infections in Ghana revealed a significantly increased prevalence in Ewes compared to other self-reported ethnic groups. In that context, we sought to investigate the early phase of tuberculosis (TB) infection using ex vivo infection of macrophages derived from the blood of Ewe and Akan ethnic group volunteers with MTBC L4 and L5 strains. Methods: The study participants consisted of 16 controls, among which selfreported Akan and Ewe ethnicity was equally represented, as well as 20 cured TB cases consisting of 11 Akans and 9 Ewes. Peripheral blood mononuclear cells were isolated from both healthy controls and cured TB cases. CD14+ monocytes were isolated and differentiated into monocyte-derived macrophages (MDMs) before infection with L4 or L5 endemic strains. The bacterial load was assessed after 2 hours (uptake) as well as 3 and 7 days post-infection. Results: We observed a higher capacity of MDMs from Ewes to phagocytose L4 strains (p < 0.001), translating into a higher bacillary load on day 7 (p < 0.001) compared to L5, despite the higher replication rate of L5 in Ewe MDMs (fold change: 1.4 vs. 1.2, p = 0.03) among the controls. On the contrary, within macrophages from Akans, we observed a significantly higher phagocytic uptake of L5 (p < 0.001) compared to L4, also translating into a higher load on day 7 (p = 0.04). However, the replication rate of L4 in Akan MDMs was higher than that of L5 (fold change: L4 = 1.2, L4 = 1.1, p = 0.04). Although there was no significant difference in the uptake of L4 and L5 among cured TB cases, there was a higher bacterial load of both L4 (p = 0.02) and L5 (p = 0.02) on day 7 in Ewe MDMs. Conclusion: Our results suggest that host ethnicity (driven by host genetic diversity), MTBC genetic diversity, and individual TB infection history are all acting together to modulate the outcome of macrophage infections by MTBC.
Short communication—Lessons learnt during the implementation of Unity-aligned SARS-CoV-2 seroprevalence studies in Africa
(Influenza and Other Respiratory Viruses, 2023) Farley, E.; Okeibunor, J.; Donkor, I.O.; et al.
The WHO Unity Studies initiative engaged low- and middle-income countries in the implementation of standardised SARS-CoV-2 sero-epidemiological investigation pro tocols and timely sharing of comparable results for evidence-based action. To gain a deeper understanding of the methodological challenges faced when conducting sero prevalence studies in the African region, we conducted unstructured interviews with key study teams in five countries. We discuss the challenges identified: participant recruitment and retention, sampling, sample and data management, data analysis and presentation. Potential solutions to aid future implementation include preparedness actions such as the development of new tools, robust planning and practice.
Developing home cleaning intervention through community engagement to reduce infections and antimicrobial resistance inGhanaian homes
(Nature Research, 2023) Ahorlu, C.; Tsekleves, E.; Souza, D. D.; et al.
Globally Antimicrobial Resistance (AMR) constitutes a health crisis, particularly in developing countries, where infectious disease are commonly fatal. There is clear evidence for microbial exposure and infection transmission within the home. Personal and environmental hygiene are the best ways of reducing household infections thus decreasing the need for antibiotics and consequently diminishing AMR. Despite this being an obvious step, research eforts to understand the home environment and its impact on AMR, cleaning and possible interventions on household cleaning are limited. We combined design and microbiology methods in an innovative mixed-method approach. A traditional survey design (n= 240), a design ethnography (n= 12), a co-design workshop and a pre-intervention microbiological dust sample analysis was undertaken to provide insights for codesign workshops in which new cleaning practices might be developed to minimise any AMR bacteria present in the household environments located in the Greater Accra Region of Ghana. Microbiological analysis of household dust showed that 36.6% of bacterial isolates detected were found to carry at least one resistance to the panel of antibiotics tested. Four scenarios were generated from an economic segmentation of the survey data. 50 ethnographic insights were ‘presented’ and descriptions of 12 bacteria species that showed resistance to one or more antibiotics (representing 176 bacterial isolates that showed resistance to one or more antibiotics found in the dust samples) were presented to the participants in a codesign workshop. An intervention, a new regime of cleaning practices agreed through the co-design workshop and practiced for thirty days, was made in (n= 7) households. The high prevalence of multidrug resistance observed in this study indicate the need for antibiotics surveillance program, not only in hospital settings but also in the household environment. There is, thus, an urgent need for targeting of interventions at the household level. Activating knowledge through community engagement in the research helps in increasing public perception and breaking down the scientist-public barrier
Repurposing an integrated national inﬂuenza platform for genomic surveillance of SARS-CoV-2 in Ghana: a molecular epidemiological analysis
(Elsevier Ltd, 2023) Asante, I.A.; Hsu, S. N.; Boatemaa, L.; et al.
Background Genomic surveillance of SARS-CoV-2 is crucial for monitoring the spread of COVID-19 and guiding public health decisions, but the capacity for SARS-CoV-2 testing and sequencing in Africa is low. We integrated SARS-CoV-2 surveillance into an existing inﬂuenza surveillance network with the aim of providing insights into SARS-CoV-2 transmission and genomics in Ghana. Methods In this molecular epidemiological analysis, which is part of a wider multifaceted prospective observational study, we collected national SARS-CoV-2 test data from 35 sites across 16 regions in Ghana from Sept 1, 2020, to Nov 30, 2021, via the Ghanaian integrated inﬂuenza and SARS-CoV-2 surveillance network. SARS-CoV-2-positive samples collected through this integrated national inﬂuenza surveillance network and from international travellers arriving in Accra were sequenced with Oxford Nanopore Technology sequencing and the ARTIC tiled amplicon method. The sequence lineages were typed with pangolin and the phylogenetic analysis was conducted with IQ-Tree2 and TreeTime. Findings During the study period, 5495 samples were submitted for diagnostic testing through the national inﬂuenza surveillance network (2121 [46·1%] of 4021 samples with complete demographic data were from female individuals and 2479 [53·9%] of 4021 samples were from male individuals). We also obtained 2289 samples from travellers who arrived in Accra and had a positive lateral ﬂow test, of whom 1626 (71·0%, 95% CI 69·1–72·9) were conﬁrmed to be SARS-CoV-2 positive. Co-circulation of inﬂuenza and SARS-CoV-2 in Ghana was detected, with increased cases of inﬂuenza in November, 2020, November, 2021, and January and June, 2021. In 4124 samples from individuals with inﬂuenza-like illness, SARS-CoV-2 was identiﬁed in 583 (14·1%, 95% CI 13·1–15·2) samples and inﬂuenza in 356 (8·6%, 7·8–9·5). Conversely, in 476 samples from individuals with of severe acute respiratory illness, SARS-CoV-2 was detected in 58 (12·2%, 9·5–15·5) samples and inﬂuenza in 95 (19·9%, 16·5–23·9). We detected four waves of SARS-CoV-2 infections in Ghana; each wave was driven by a different variant: B.1 and B.1.1 were the most prevalent lineages in wave 1, alpha (B.1.1.7) was responsible for wave 2, delta (B.1.617.2) and its sublineages (closely related to delta genomes from India) were responsible for wave 3, and omicron variants were responsible for wave 4. We detected omicron variants among 47 (32%) of 145 samples from travellers during the start of the omicron spread in Ghana (wave 4). Interpretation This study shows the value of repurposing existing inﬂuenza surveillance platforms to monitor SARS-CoV-2. Inﬂuenza continued to circulate in Ghana in 2020 and 2021, and remained a major cause of severe acute respiratory illness. We detected importations of SARS-CoV-2 variants into Ghana, including those that did or did not lead to onward community transmission. Investment in strengthening national inﬂuenza surveillance platforms in low-income and middle-income countries has potential for ongoing monitoring of SARS-CoV-2 and future pandemics.
Prevalence of asymptomatic malaria parasitaemia following mass testing and treatment in Pakro sub-district of Ghana
(BMC Public Health, 2019) Ndong, I.C.; Okyere, D.; Enos, J.Y.; et al.
Background: Global efforts to scale-up malaria control interventions are gaining steam. These include the use of Long-Lasting Insecticide Nets, Indoor Residual Spraying, Intermittent Preventive Treatment and Test, Treat and Track. Despite these, the drive for malaria elimination is far from being realistic in endemic communities in Africa. This is partly due to the fact that asymptomatic parasite carriage, not specifically targeted by most interventions, remains the bedrock that fuels transmission. This has led to mass testing, treatment and tracking (MTTT) as an alternative strategy to target asymptomatic individuals. We report the impact of MTTT on the prevalence of asymptomatic malaria parasitaemia over a one-year period in Ghana, hypothesizing that implementing MTTT could reduce the rate of asymptomatic parasitaemia. Methods: A population of about 5000 individuals in seven communities in the Pakro sub-district of Ghana participated in this study. A register was developed for each community following a census. MTTT engaged trained community based health volunteers who conducted house-to-house testing using RDTs every 4 months and treated positive cases with Artemisinin–based Combination Therapy. Between interventions, community-based management of malaria was implemented for symptomatic cases. Results: MTTT Coverage was 98.8% in July 2017 and 79.3% in July 2018. Of those tested, asymptomatic infection with malaria parasites reduced from 36.3% (1795/4941) in July 2017 to 32.9% (1303/3966) in July 2018 (p = 0.001). Prevalence of asymptomatic parasitaemia among children under 15 years declined from 52.6% (1043/1984) in July 2017 to 47.5% (820/1728) in July 2018 (p = 0.002). Implementing MTTT significantly reduced asymptomatic parasitaemia by 24% from July 2017 to July 2018 after adjusting for age, ITN use and axillary temperature (OR = 0.76, CI = 0.67, 0.85 p ≤ 0.001). Conclusion: This study has demonstrated that implementing MTTT is feasible and could reduce the prevalence of asymptomatic malaria parasitaemia in children under 15 years of age. Furthermore, the use of community-based health volunteers could ensure high coverage at lower cost of implementation.
Plasmodium falciparum: sensitivity to chloroquine in wiwo in three ecological zones in Ghana
(Transactions of the Royal Society of Tropical Medicine and Hygiene, 1992) Afari’, E. A.; Akanmori, B. D.; Nakano’, T.; Ofori-Adjei, D.
4690 children aged 6-15 years in 5 urban and 4 rural communities in 3 ecological zones in Ghana were screened from June 1988 to December 1990 to provide suitable candidates for the World Health Organization standard in vivo test for susceptibility of Plasmodium falciparum to chloroquine. 1880 (40.1%) had parasitaemia, mostly (83.7-98.6%) due to P. falciparum infection. Of the 626 in vivo tests performed, 570 (91.1%) showed sensitivity to chloroquine and 56 (8.9%) responses were classified as resistant to chloroquine at RI (5.1%) and RI1 (3.8%). The resistance responses were commonest (17.1-22.7%) in the coastal zone, followed by the savanna zone (8.6lO.O%), and lowest in the forest zone (3.1-6.3%). The RI1 responses occurred mainly in communities in the coastal zone. There was no RI11 resistance in any zone. The pattern of RI (early) and RI1 responses of I’. falciparum to chloroquine in this study suggested an increase in sensitivity, or a reduction in resistance, of P. falciparum to chloroquine from the coast to the forest and northern savanna zones, and from the urban to the rural communities in each zone in Ghana.
Assessment of artemisinin tolerance in Plasmodium falciparum clinical isolates in children with uncomplicated malaria in Ghana
(Malaria Journal, 2023) Ahorhorlu, S.Y.; Quashie, N.B.; Jensen, N.W.; Kudzi, W.; Nartey, E.T.; Duah‑Quashie, N.O.; Zoiku, F.; Dzudzor, B.; Wang, C.W.; Hansson, H.; Alifrangis, M.; Adjei, G.O.
Background Artemisinin-based combination therapy (ACT) is the first-line treatment for uncomplicated malaria in Ghana. Artemisinin (ART) tolerance in Plasmodium falciparum has arisen in Southeast Asia and recently, in parts of East Africa. This is ascribed to the survival of ring-stage parasites post treatment. The present study sought to assess and characterize correlates of potential ART tolerance based on post-treatment parasite clearance, ex vivo and in vitro drug sensitivity, and molecular markers of drug resistance in P. falciparum isolates from children with uncomplicated malaria in Ghana. Methods Six months to fourteen years old children presenting with acute uncomplicated malaria (n=115) were enrolled in two hospitals and a Health Centre in Ghana’s Greater Accra region and treated with artemether-lume‑ fantrine (AL) according to body weight. Pre- and post-treatment parasitaemia (day 0 and day 3) was confirmed by microscopy. The ex vivo ring-stage survival assay (RSA) was used to detect percent ring survival while the 72 h SYBR Green I assay was used to measure the 50% inhibition concentration (IC50s) of ART and its derivatives and partner drugs. Genetic markers of drug tolerance /resistance were evaluated using selective whole genome sequencing. Results Of the total of 115 participants, 85 were successfully followed up on day 3 post-treatment and 2/85 (2.4%) had parasitaemia. The IC50 values of ART, artesunate (AS), artemether (AM), dihydroartemisinin (DHA), amodiaquine (AQ), and lumefantrine (LUM) were not indicative of drug tolerance. However, 7/90 (7.8%) pre-treatment isolates had>10% ring survival rates against DHA. Of the four isolates (2 RSA positive and 2 RSA negative) with high genomic coverage, P. falciparum (Pf ) kelch 13 K188* and Pfcoronin V424I mutations were only present in the two RSA positive isolates with>10% ring survival rates. Conclusions The observed low proportion of participants with day-3 post-treatment parasitaemia is consistent with rapid ART clearance. However, the increased rates of survival observed in the ex vivo RSA against DHA, maybe a pointer of an early start of ART tolerance. Furthermore, the role of two novel mutations in PfK13 and Pfcoronin genes, harboured by the two RSA positive isolates that had high ring survival in the present study, remains to be elucidated.
Therapeutic efficacy of dihydroartemisinin-piperaquine combination for the treatment of uncomplicated malaria in Ghana
(Frontiers in Cellular and Infection Microbiology, 2023) Abuaku, B.; Boateng, P.; Peprah, N.Y.; Asamoah, A.; Duah-Quashie, N.O.; Matrevi, S.A.; Amoako, E.O.; Quashie, N.; Owusu-Antwi, F.; Malm, K.L.; Koram, K.A.
In 2020, Dihydroartemisinin-Piperaquine (DHAP) was adopted as a second-line antimalarial for treatment of uncomplicated malaria in Ghana following a review of the country’s antimalarial medicines policy. Available data obtained in 2007 had shown PCR-uncorrected therapeutic efficacy of 93.3% using a 28- day follow-up schedule. In 2020, the standard 42-day follow-up schedule for DHAP was used to estimate efficacy levels among febrile children aged 6 months to 9 years in three malaria sentinel sites representing the three main ecological zones of the country- savannah, forest, and coastal. PCR genotyping distinguished between recrudescence and re-infection using merozoite surface protein 2 (MSP2)-specific primers for FC27 and 3D7 strains. Per protocol analyses showed day 28 efficacy of 100% in all three sentinel sites with day 42 PCR-corrected efficacy ranging between 90.3% (95% CI: 80.1 – 96.4%) in the savannah zone and 100% in the forest and coastal zones, yielding a national average of 97.0% (95% CI: 93.4 – 98.8). No day 3 parasitemia was observed in all three sites. Prevalence of measured fever (axillary temperature ≥ 37.5°C) declined from 50.0 - 98.8% on day 0 to 7.1-11.5% on day 1 whilst parasitemia declined from 100% on day 0 to 1.2 - 2.3% on day 1. Mean haemoglobin levels on days 28 and 42 were significantly higher than pretreatment levels in all three sites. We conclude that DHAP is highly efficacious in the treatment of uncomplicated malaria in Ghana. This data will serve as baseline for subsequent DHAP efficacy studies in the country
Population‑based sero‑epidemiological investigation of the dynamics of SARS‑CoV‑2 infections in theGreater Accra Region ofGhana
(Scientific reports, 2022) Mensah, B.A.; Ndong, J.C.; Quashie, P.K; Guichet, E.; Abuaku, B.; et al.
The coronavirus disease 2019 (COVID-19) pandemic devastated countries worldwide, and resulted in a global shutdown. Not all infections are symptomatic and hence the extent of SARS-CoV-2 infection in the community is unknown. The paper presents the dynamics of the SARS-CoV-2 epidemic in the Greater Accra Metropolis, describing the evolution of seroprevalence through time and by age group. Three repeated independent population-based surveys at 6-week intervals were conducted in from November 2020 to July 2021. The global and by age-groups weighted seroprevalences were estimated and the risk factors for SARS-CoV-2 antibody seropositivity were assessed using logistic regression. The overall age-standardized SARS-CoV-2 antibody seroprevalence for both spike and nucleocapsid increased from 13.8% (95% CI 11.9, 16.1) in November 2020 to 39.6% (95% CI 34.8, 44.6) in July 2021. After controlling for gender, marital status, education level, and occupation, the older age group over 40 years had a higher odds of seropositivity than the younger age group (OR 3.0 [95% CI 1.1–8.5]) in the fnal survey. Pupils or students had 3.3-fold increased odds of seropositivity (OR 3.2 [95% CI 1.1–8.5]) compared to the unemployed. This study reinforces that, SARS-CoV-2 infections have been signifcantly higher than reported.
Plasmodium malariae structure and genetic diversity in sub‑Saharan Africa determined from microsatellite variants and linked SNPs in orthologues of antimalarial resistance genes
(Scientific reports, 2022) Oriero, E.C.; Demba, M.A.; Diop, M.F.; Ishengoma, D.S.; Amenga‑Etego, L.N.; Ghansah, A.; Apinjoh, T.; Issiaka, S.
Plasmodium malariae, a neglected human malaria parasite, contributes up to 10% of malaria infections in sub-Saharan Africa (sSA). Though P. malariae infection is considered clinically benign, it presents mostly as coinfections with the dominant P. falciparum. Completion of its reference genome has paved the way to further understand its biology and interactions with the human host, including responses to antimalarial interventions. We characterized 75 P. malariae isolates from seven endemic countries in sSA using highly divergent microsatellites. The P. malariae infections were highly diverse and five subpopulations from three ancestries (independent of origin of isolates) were determined. Sequences of 11 orthologous antimalarial resistance genes, identifed low frequency single nucleotide polymorphisms (SNPs), strong linkage disequilibrium between loci that may be due to antimalarial drug selection. At least three sub-populations were detectable from a subset of denoised SNP data from mostly the mitochondrial cytochrome b coding region. This evidence of diversity and selection calls for including P. malariae in malaria genomic surveillance towards improved tools and
Tuberculosis, HIV/AIDS and Malaria Health Services in sub-Saharan Africa – A Situation Analysis of the Disruptions and Impact of the COVID-19 Pandemic
(Elsevier, 2022) Chanda-Kapata, P.; Ntoumi, F.; Kapata, N.; Lungu, P.; Mucheleng’anga, L.A.; Chakaya, J.; Tembo, J.; Himwaze, C.; Ansumana, R.; Asogun, D.; Mfinanga, S.; Nyasulu, P.; Mwaba, P.; Yeboah-Manu, D.; Zumla, A.; Nachega, J.B.
Background: The unprecedented and ongoing COVID-19 pandemic has exposed weaknesses in African countries’ health systems. The impact of shifted focus on COVID-19 for the past 2 years on routine health services, especially those for the epidemics of Tuberculosis, HIV/AIDS and Malaria, have been dramatic in both quantity and quality. Methods: In this article, we reflect on the COVID-19 related disruptions on the Tuberculosis, HIV/AIDS and Malaria routine health services across Africa. Results: The COVID-19 pandemic resulted in disruptions of routine health services and diversion of already limited available resources in sub-Saharan Africa. As a result, disease programs like TB, malaria and HIV have recorded gaps in prevention and treatment with the prospects of reversing gains made towards meeting global targets. The extent of the disruption is yet to be fully quantified at country level as most data available is from modelling estimates before and during the pandemic. Conclusions: Accurate country-level data is required to convince donors and governments to invest more into revamping these health services and help prepare for managing future pandemics without disruption of routine services. Increasing government expenditure on health is a critical part of Africa’s economic policy. Strengthening health systems at various levels to overcome the negative impacts of COVID-19, and preparing for future epidemics will require strong visionary political leadership. Innovations in service delivery and technological adaptations are required as countries aim to limit disruptions to routine services.

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