Immunology Department

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    Atypical memory B cell frequency correlates with antibody breadth and function in malaria immune adults
    (Scientific Reports, 2024) Partey, F.D.; Dowuona, J.N.; Pobee, A.N.; et.al
    Clinical immunity to malaria develops slowly after repeated episodes of infection and antibodies are essential in naturally acquired immunity against malaria. However, chronic exposure to malaria has been linked to perturbation in B-cell homeostasis with the accumulation of atypical memory B cells. It is unclear how perturbations in B cell subsets influence antibody breadth, avidity, and function in individuals naturally exposed to malaria. We show that individuals living in high malaria transmission regions in Ghana have higher Plasmodium falciparum merozoite antigen-specific antibodies and an increased antibody breadth score but lower antibody avidities relative to low transmission regions. The frequency of circulating atypical memory B cells is positively associated with an individual’s antibody breadth. In vitro growth inhibition is independent of the ability to bind to free merozoites but associated with the breadth of antibody reactivity in an individual. Taken together, our data shows that repeated malaria episodes hamper the development of high avid antibodies which is compensated for by an increase in antibody breadth. Our results provide evidence to reinforce the idea that in regions with high malaria prevalence, repeated malaria infections lead to the broadening of antibody diversity and the continued presence of atypical memory B cell populations.
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    In vitro assessment of crude oil degradation by Acinetobacter junii and Alcanivorax xenomutans isolated from the coast of Ghana
    (Heliyon, 2024) Gyasi, S. F.; Adu, B.; Appiah, A. S.; et al
    This study was aimed at using in vitro microcosm experiments to assess crude oil degradation efficiency of Acinetobacter junii and Alcanivorax xenomutans isolated along Ghana’s coast. Un contaminated seawater from selected locations along the coast was used to isolate bacterial species by employing enrichment culture procedures with crude oil as the only carbon source. The isolates were identified by means of the extended direct colony transfer method of the Matrix Assisted Laser Desorption Ionization Time of Flight Mass Spectroscopy (MALDI-TOF MS), as Acinetobacter junii, and Alcanivorax xenomutans. Remediation tests showed that Acinetobacter junii yielded degradation efficiencies of 27.59 %, 41.38 % and 57.47 %. Whereas efficiencies of 21.14 %, 32.18 % and 43.68 % were recorded by Alcanivorax xenomutans representing 15, 30 and 45 days respectively. Consortia of Acinetobacter junii, and Alcanivorax xenomutans also yielded 32.18 %, 48.28 % and 62.07 % for the selected days respectively. Phylogenetic characterization using ClustalW and BLAST of sequences generated from the Oxford Nanopore Sequencing technique, showed that the Ghanaian isolates clustered with Alcanivorax xenomutans and Acinetobacter junii species respectively. An analysis of the sequenced data for the 1394-bp portion of the 16S rRNA gene of the isolates revealed >99 % sequence identity with the isolates present on the GenBank database. The isolates of closest identity were Alcanivorax xenomutans and Acinetobacter junii with accession numbers, NR_133958.1 and KJ147060.1 respectively. Acinetobacter junii and Alcani vorax xenomutans isolated from Ghana’s coast under pristine seawater conditions have therefore demonstrated their capacity to be used for the remediation of crude oil spills.
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    High Prevalence Of Impaired Glucose Metabolism Among Children And Adolescents Living With HIV In Ghana
    (HIV Medicine, 2023) Ayanful-Torgby, R.; Shabanova, V.; Essuman, A.A.; et al.
    Background: Antiretroviral therapy (ART)-associated metabolic abnormalities, including impairment of glucose metabolism, are prevalent in adults living with HIV. However, the prevalence and pathogenesis of impaired glucose The metabolism of children and adolescents living with HIV, particularly in sub-Saharan Africa, is not well characterized. We investigated the prevalence of impaired glucose metabolism among children and adolescents living with perinatally infected HIV in Ghana. Methods: In this multicenter, cross-sectional study, we recruited participants from 10 paediatric antiretroviral treatment clinics from January to June 2022 in 10 facilities in the Greater Accra and Eastern regions of Ghana. We determined impaired glucose metabolism in the study sample by assessing fasting blood sugar (FBS), insulin resistance as defined by the homeostatic model assessment for insulin resistance (HOMA-IR) index and glycated haemoglobin (HbA1c) levels. The prevalence of impaired glucose metabolism using each criterion was stratified by age and sex. The phenotypic correlates of glucose metabolism Markers were also assessed among age, sex, body mass index (BMI), and waist-to-hip ratio (WHR). Results: We analysed data from 393 children and adolescents living with HIV aged 6–18 years. A little over half (205/393 or 52.25%) of the children were female. The mean age of the participants was 11.60 years (SD = 3.50), with 122/393 (31.00%) aged 6–9 years, 207/393 (52.67%) aged 10–15 years, and 62/393 (15.78%) were aged 16–18 years. The prevalence rates of glucose impairment in the study population, 15.52% [95% confidence interval (CI): 12.26– 19.45], 22.39% (95% CI: 18.54–26.78), and 26.21% (95% CI: 22.10–30.78) using HbA1c, HOMA-IR, and FBS criteria, respectively. Impaired glucose metabolism detected by FBS and HOMA-IR was higher in the older age group, whereas the prevalence of abnormal HbA1c levels was highest among the youngest age group. Age and BMI were positively associated with FBS and HOMA-IR (p < 0.001). However, there was negative correlation of WHR and HOMA-IR (p < 0.01) and HbA1c (p = 0.01).Conclusion: The high prevalence of impaired glucose metabolism observed among the children and adolescents living with HIV in sub-Saharan Africa is of concern as this could contribute to the development of metabolic syndrome in adulthood.
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    Prevalence of Leucocytozoon infection in domestic birds in Ghana
    (PLOS Neglected Tropical Diseases, 2023) Agbemelo-Tsomafo, C.; AdjeiI, S.; Kusi, K.A.; et al.
    Leucocytozoon is a haemosporidian parasite known to cause leucocytozoonosis in domes tic and wild birds in most parts of the world. It is an important pathogen, as some species can be pathogenic, especially in domestic birds. One of the factors affecting poultry health management worldwide is parasitism. However, the study of haemosporidian parasites in Ghana is still lacking. This study sought to assess the prevalence and diversity of Leucocy tozoon parasites in domestic birds in Ghana. Blood samples were collected from domestic birds in Ghana’s Bono and Eastern regions to screen for Leucocytozoon parasites. Thin blood smears were prepared for microscopy and DNA was extracted from whole blood kept in ethylenediaminetetraacetic acid (EDTA) tubes for PCR. Due to the large number of sam ples, real-time PCR was performed to amplify the conserved rDNA gene. Two different nested PCR protocols were performed on the positive samples obtained from real-time PCR results, to amplify a partial region of the mitochondrial cytochrome b gene and the amplicons were sequenced. Sequencing revealed six new lineages of Leucocytozoon sp. recovered in 976 individual domestic birds and these sequences were deposited in the National Center for Biotechnology Information (NCBI) GenBank. An overall Leucocytozoon prevalence of 11.6% was reported in all birds sampled. The most prevalent lineage LGHA146 (GenBank accession no. OM643346) (93.8%) was found infecting 3 bird species, Gallus gallus, Meleagris gallopavo, and Anas platyrhynchos. Phylogenetic analysis revealed that the new lineages (GenBank accession nos. OM643342, OM643343, OM643344, OM643345, OM643346, and OM643347), reported in this study were closely related to Leucocytozoon schoutedeni. We suggest that further studies be conducted to evaluate the effect of these parasite species on the general well-being of poultry in Ghana.
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    Distribution of Plasmodium falciparum K13 gene polymorphisms across transmission settings in Ghana
    (BMC Infectious Diseases, 2023) Dieng, C.C.; Morrison, V.; Donu, D.; Cui, L.; Amoah, L.; Afrane, Y.; Lo, E.
    Malaria is a signifcant global health concern, with a majority of cases in Sub-Saharan African nations. Numerous anti malarial drugs have been developed to counter the rampant prevalence of Plasmodium falciparum malaria. Arte misinin-based Combination Therapy (ACT) has served as the primary treatment of uncomplicated malaria in Ghana since 2005. However, a growing concern has emerged due to the escalating reports of ACT resistance, particularly in Southeast Asia, and its encroachment into Africa. Specifcally, mutations in the Kelch propeller domain on chromo some 13 (Pfk13) have been linked to ACT resistance. Yet, our understanding of mutation prevalence in Africa remains largely uncharted. In this study, we compared Pfk13 sequences obtained from 172 P. falciparum samples across three ecological and transmission zones in Ghana. We identifed 27 non-synonymous mutations among these sequences, of which two of the mutations, C580Y (found in two samples from the central region) and Y493H (found in one sam ple from the north), had previously been validated for their association with artemisinin resistance, a phenomenon widespread in Southeast Asia. The Pfk13 gene diversity was most pronounced in the northern savannah than the cen tral forest and south coastal regions, where transmission rates are lower. The observed mutations were not signif cantly associated with geographical regions, suggesting a frequent spread of mutations across the country. The ongo ing global surveillance of artemisinin resistance remains pivotal, and our fndings provides insights into the potential spread of resistant parasites in West Africa. Furthermore, the identifcation of novel codon mutations in this study raises their potential association to ACT resistance, warranting further investigation through in vitro assays to ascertain their functional signifcance.
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    Biomarker of Anopheles exposure in Ghanaian children with hemoglobin S and C
    (Acta Tropica, 2024) Londono-Renteria, B.; Seidu, Z.; Lamptey, H.; Ofori, M.F.; Hviid, L.; Lopez-Perez, M.
    Heterozygous carriers of hemoglobin S and C (HbAS and HbAC) have a reduced risk of severe malaria but are not protected from Plasmodium falciparum infection, suggesting that the protection involves acquired immunity. During a blood meal, female Anopheles mosquitoes inject saliva that can elicit a host antibody response, which can serve as a proxy for exposure to Plasmodium infection. Previous studies have shown that the peptide gSG6-P1 of An. gambiae saliva is antigenic and highly Anopheles specific. Here, we used plasma samples from 201 Gha naian children with wild-type hemoglobin (HbAA), HbAS, and HbAC to evaluate antibody levels against gSG6-P1 as a serological biomarker of Anopheles exposure and, therefore of P. falciparum infection risk. Malaria antigen (PfCSP, GLURP, Pfs230, and HB3VAR06)-specific IgG levels, demographic data, and data regarding P. falciparum infection and malaria control practices were also analyzed. Children with active P. falciparum infection had higher antibody levels against all antigens, and those with HbAS and HbAC had significantly higher antibody levels against Pfs230. Pfs230-specific IgG correlated negatively with gSG6-P1-specific IgG in children with HbAC. Our results highlight the importance of studying the role of hemoglobinopathies in malaria transmission to improve control interventions.
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    Background malaria incidence and parasitemia during the three-dose RTS,S/AS01 vaccination series do not reduce magnitude of antibody response nor efficacy against the first case of malaria
    (BMC Infectious Diseases, 2023) Bell, G.J.; Gyaase, S.; Adu, B.; et al.
    Background RTS,S/AS01 has been recommended by WHO for widespread implementation in medium to high malaria transmission settings. Previous analyses have noted lower vaccine efficacies in higher transmission settings, possibly due to the more rapid development of naturally acquired immunity in the control group. Methods To investigate a reduced immune response to vaccination as a potential mechanism behind lower efficacy in high transmission areas, we examine initial vaccine antibody (anti-CSP IgG) response and vaccine efficacy against the first case of malaria (to exclude the effect of naturally acquired immunity) using data from three study areas (Kintampo, Ghana; Lilongwe, Malawi; Lambaréné, Gabon) from the 2009–2014 phase III trial (NCT00866619). Our key exposures are parasitemia during the vaccination series and background malaria incidence. We calculate vaccine efficacy (one minus hazard ratio) using a cox-proportional hazards model and allowing for the time-varying effect of RTS,S/AS01. Results We find that antibody responses to the primary three-dose vaccination series were higher in Ghana than in Malawi and Gabon, but that neither antibody levels nor vaccine efficacy against the first case of malaria varied by background incidence or parasitemia during the primary vaccination series. Conclusions We find that vaccine efficacy is unrelated to infections during vaccination. Contributing to a conflicting literature, our results suggest that vaccine efficacy is also unrelated to infections before vaccination, meaning that control-group immunity is likely a major reason for lower efficacy in high transmission settings, not reduced immune responses to RTS,S/AS01. This may be reassuring for implementation in high transmission settings, though further studies are needed.
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    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.; et al.
    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 self reported 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.
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    The Rapid and Spontaneous Postpartum Clearance of Plasmodium falciparum Is Related to Expulsion of the Placenta
    (The Journal of Infectious Diseases, 2023) Anabire, N.G.; Quintana, M.D.P.; Ofori, M.F,; Hviid, L.
    Parasitemia among pregnant women with protective immunity to Plasmodium falciparum malaria is often dominated by VAR2CSA-positive infected erythrocytes (IEs). VAR2CSA mediates sequestration of IEs in the placenta. We hypothesized that the previously observed spontaneous postpartum clearance of parasitemia in such women is related to the expulsion of the placenta, which removes the sequestration focus of VAR2CSA-positive IEs. We assessed parasitemias and gene transcription before and shortly after delivery in 17 Ghanaian women. The precipitous decline in parasitemia postpartum was accompanied by selective reduction in transcription of the gene encoding VAR2CSA. Our findings provide a mechanistic explanation for the earlier observation.
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    Editorial: Evolution and mechanisms of anti-malarial and insecticide resistance
    (Frontiers in Cellular and Infection Microbiology, 2023) Amoah, L.E.; Lo, E.
    Malaria, a deadly disease caused by Plasmodium spp., continues to pose a significant threat to global health. This is further exacerbated by antimalarial drug and insecticide resistances. This is unfortunate, as chemical therapy and preventive medicine remain as our main defenses. This editorial highlight ongoing strategies to mitigate malaria, including the surveillance of drug and insecticide resistance and drug discovery. Human migration is a major problem for malaria control and elimination efforts as infected people can disperse the parasites during their movement. Drug resistant malaria parasites, especially those resistant to the drug family artemisinin are also a threat to malaria control and elimination efforts. Zhao et al. examined the drug susceptibility profile of parasite isolates in Chinese travelers returning from Ghana with uncomplicated malaria. The parasite isolates were susceptible to artemisinin and the partner drugs of artemisinin based combination therapies but markedly resistance to antifolate drugs. A low prevalence of chloroquine-resistant genes was consistent with the suspension of chloroquine therapy. On the drug-innovation front, Burns et al. explored the antiparasitic activity of 22 azithromycin analogues against P. falciparum and P. knowlesi and identified 17 analogues with almost 40-fold activity relative to azithromycin. Metabolomic profiling of parasites treated with the most potent compound showed a build-up of both non-hemoglobin-derived and hemoglobin-derived peptides. These findings present new grounds for further research. Dihydroartemisinin-Piperaquine (DHAP) is a second-line antimalarial therapy for uncomplicated malaria. Abuaku et al., identified a near perfect cure rate (>90%) for DHAP, with longer prophylactic benefits over artesunate-amodiaquine and artemether lumefantrine. DHAP also improved hemoglobin levels and reduced fever in treated individuals. No evidence of DHAP resistance was reported. Vaccine research is yet another field that cannot be ignored in the fight against malaria. Healer et al., investigated the efficacy of a protein-in-adjuvant blood stage malaria vaccine, RH5.1-CyRPA-Ripr antigen combination vaccine, relative to the single immunogen RH5 using animal models and reported low performance. The study also found the DPX® platform to be the best performing formulation in potentiating P. falciparum inhibitory antibody responses to these antigens. Despite low performance of the vaccine, the authors encourage further exploration of other RH5 vaccine combinations.
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    Editorial: Evolution and mechanisms of anti-malarial and insecticide resistance
    (Frontiers in Cellular and Infection Microbiology, 2023) Amoah, L.E.; Lo, E.
    Malaria, a deadly disease caused by Plasmodium spp., continues to pose a significant threat to global health. This is further exacerbated by antimalarial drug and insecticide resistances. This is unfortunate, as chemical therapy and preventive medicine remain as our main defenses. This editorial highlight ongoing strategies to mitigate malaria, including the surveillance of drug and insecticide resistance and drug discovery. Human migration is a major problem for malaria control and elimination efforts as infected people can disperse the parasites during their movement. Drug resistant malaria parasites, especially those resistant to the drug family artemisinin are also a threat to malaria control and elimination efforts. Zhao et al. examined the drug susceptibility profile of parasite isolates in Chinese travelers returning from Ghana with uncomplicated malaria. The parasite isolates were susceptible to artemisinin and the partner drugs of artemisinin based combination therapies but markedly resistance to antifolate drugs. A low prevalence of chloroquine-resistant genes was consistent with the suspension of chloroquine therapy. On the drug-innovation front, Burns et al. explored the antiparasitic activity of 22 azithromycin analogues against P. falciparum and P. knowlesi and identified 17 analogues with almost 40-fold activity relative to azithromycin. Metabolomic profiling of parasites treated with the most potent compound showed a build-up of both non-hemoglobin-derived and hemoglobin-derived peptides. These findings present new grounds for further research. Dihydroartemisinin-Piperaquine (DHAP) is a second-line antimalarial therapy for uncomplicated malaria. Abuaku et al., identified a near perfect cure rate (>90%) for DHAP, with longer prophylactic benefits over artesunate-amodiaquine and artemether lumefantrine. DHAP also improved hemoglobin levels and reduced fever in treated individuals. No evidence of DHAP resistance was reported. Vaccine research is yet another field that cannot be ignored in the fight against malaria. Healer et al., investigated the efficacy of a protein-in-adjuvant blood stage malaria vaccine, RH5.1-CyRPA-Ripr antigen combination vaccine, relative to the single immunogen RH5 using animal models and reported low performance. The study also found the DPX® platform to be the best performing formulation in potentiating P. falciparum inhibitory antibody responses to these antigens. Despite low performance of the vaccine, the authors encourage further exploration of other RH5 vaccine combinations
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    Evaluating circulating soluble markers of endothelial dysfunction and risk factors associated with PE: A multicentre longitudinal case control study in northern Ghana
    (Heliyon, 2023) Ahenkorah, B.; Helegbe, G.; Ofosu, W.; Amoah, L.E.; et al
    Serpin E1/PAI-1, N-terminal pro-brain natriuretic peptide (NTpro-BNP) and neuropilin-1 are markers which have been associated with endothelial dysfunction. However, data on the levels of these markers in PE is limited. The limited data on the pathophysiology of PE in relation to these markers necessitated the study. This was a multicentre case-control study conducted at the Obstetrics and Gynaecology Department of the Tamale Teaching Hospital, the Bawku Presbyterian Hospital and the Bolgatanga Regional Hospital. Out of 520 consenting pregnant women, 127 pregnant women met the inclusion criteria (53 with PE and 74 controls) and were included in this study. Venous, placental, cord and peripheral blood were collected for biomarker assay, haematological parameters and placental parasite determination. Placental tissue sections were obtained for placental malaria and histopathological lesions associated with hypoperfusion. Maternal heart rate and foetal.
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    The Rapid and Spontaneous Postpartum Clearance of Plasmodium falciparum Is Related to Expulsion of the Placenta
    (The Journal of Infectious Diseases, 2023) Nsoh G. Anabire, N.G.; Ofori, M.F.; Quintana, M.D.P
    Parasitemia among pregnant women with protective immunity to Plasmodium falciparum malaria is often dominated by VAR2CSA-positive infected erythrocytes (IEs). VAR2CSA mediates sequestration of IEs in the placenta. We hypothesized that the previously observed spontaneous postpartum clearance of parasitemia in such women is related to the expulsion of the placenta, which removes the sequestration focus of VAR2CSA-positive IEs. We assessed parasitemias and gene transcription before and shortly after delivery in 17 Ghanaian women. The precipitous decline in parasitemia postpartum was accompanied by selective reduction in transcription of the gene encoding VAR2CSA. Our findings provide a mechanistic explanation for the earlier observation.
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    Plasmodium falciparum infection and naturally acquired immunity to malaria antigens among Ghanaian children in northern Ghana
    (Parasite Epidemiology and Control, 2023) Seidu, Z.; Lamptey, H.; Whittle, N.O.; et al.
    Background: The surge in malaria cases and deaths in recent years, particularly in Africa, despite the widespread implementation of malaria-control measures could be due to inefficiencies in malaria control and prevention measures in malaria-endemic communities. In this context, this study provides the malaria situation report among children in three Municipalities in Northern Ghana, where Seasonal Malaria Chemotherapy (SMC) is implemented by Ghana Health Service (GHS). Methods: A cross-sectional household survey was carried out to assess the malaria knowledge, attitudes, and practices (KAP) and malaria prevalence in 394 households in 13 rural communities in the Kumbugu, Nanton and Tolon Municipalities, Northern Region, Ghana. This was followed by screening for P. falciparum infection with anti-HRP2 RDT and PCR among children 1–17 years in the households. Plasma levels of IgG specific for crude P. falciparum antigen (3D7) and four re combinant malaria antigens (CSP, GLURP, MSP3, and Pfs230) were assessed by ELISA. The malaria and parasitaemia data were converted into frequency and subgroup proportions and disaggregated by study sites and demographic information of the participants. The ELISA data was converted to arbitrary units (AU) and similarly compared across study sites and demographic information. Results: The P. falciparum infection rate and frequency of malaria were high in the study areas with significant age-dependent and inter-community differences, which were reflected by differences in plasma levels of P. falciparum-specific IgG. Over 60% of households reported the use of bed nets and indoor insecticide sprays/coils, and 14% mentioned bush clearing around homes (14%) as malaria preventive measures. Community health centres were the preferred place for households (88%) to seek malaria treatment but over-the-counter drug stores were the major source (66%) of their antimalarials. Overall, malaria preventive and treatment practices were sub-optimal. Conclusions: P. falciparum infection and malaria are still high in the studied communities, indi cating that preventive and control measures against the disease in the region remain inadequate. Efforts to ensure high SMC compliance and to improve preventative and treatment practices thus seem cost-beneficial “low-hanging fruits” in the fight against malaria in the Northern Region of Ghana.
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    Plasmodium falciparum infection and naturally acquired immunity to malaria antigens among Ghanaian children in northern Ghana
    (Parasite Epidemiology and Control, 2023) Seidu, Z.; Lamptey, H.; Whittle, N.O.; et al.
    Background: The surge in malaria cases and deaths in recent years, particularly in Africa, despite the widespread implementation of malaria-control measures could be due to inefficiencies in malaria control and prevention measures in malaria-endemic communities. In this context, this study provides the malaria situation report among children in three Municipalities in Northern Ghana, where Seasonal Malaria Chemotherapy (SMC) is implemented by Ghana Health Service (GHS). Methods: A cross-sectional household survey was carried out to assess the malaria knowledge, attitudes, and practices (KAP) and malaria prevalence in 394 households in 13 rural communities in the Kumbugu, Nanton and Tolon Municipalities, Northern Region, Ghana. This was followed by screening for P. falciparum infection with anti-HRP2 RDT and PCR among children 1–17 years in the households. Plasma levels of IgG specific for crude P. falciparum antigen (3D7) and four re combinant malaria antigens (CSP, GLURP, MSP3, and Pfs230) were assessed by ELISA. The malaria and parasitaemia data were converted into frequency and subgroup proportions and disaggregated by study sites and demographic information of the participants. The ELISA data was converted to arbitrary units (AU) and similarly compared across study sites and demographic information. Results: The P. falciparum infection rate and frequency of malaria were high in the study areas with significant age-dependent and inter-community differences, which were reflected by dif ferences in plasma levels of P. falciparum-specific IgG. Over 60% of households reported the use of bed nets and indoor insecticide sprays/coils, and 14% mentioned bush clearing around homes (14%) as malaria preventive measures. Community health centres were the preferred place for households (88%) to seek malaria treatment but over-the-counter drug stores were the major
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    Human blood neutrophils generate ROS through FcγR-signaling to mediate protection against febrile P. falciparum malaria
    (Communications Biology, 2023) Ofori, E.A.; Garcia-Senosiain, A.; Adu, B.; et al.
    Blood phagocytes, such as neutrophils and monocytes, generate reactive oxygen species (ROS) as a part of host defense response against infections. We investigated the mechanism of Fcγ-Receptor (FcγR) mediated ROS production in these cells to understand how they contribute to anti-malarial immunity. Plasmodium falciparum merozoites opsonized with naturally occurring IgG triggered both intracellular and extracellular ROS generation in blood phagocytes, with neutrophils being the main contributors. Using specific inhibitors, we show that both FcγRIIIB and FcγRIIA acted synergistically to induce ROS production in neutrophils, and that NADPH oxidase 2 and the PI3K intracellular signal transduction pathway were involved in this process. High levels of neutrophil ROS were also associated with protection against febrile malaria in two geographically diverse malaria endemic regions from Ghana and India, stressing the importance of the cooperation between anti-malarial IgG and neutrophils in triggering ROS-mediated parasite killing as a mechanism for naturally acquired immunity against malaria
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    Spatiotemporal variation in risk of Shigella infection in childhood: a global risk mapping and prediction model using individual participant data
    (Lancet Glob Health, 2023) Badr, H.S.; Colston, J.M.; Adu, B.
    Background Diarrhoeal disease is a leading cause of childhood illness and death globally, and Shigella is a major aetiological contributor for which a vaccine might soon be available. The primary objective of this study was to model the spatiotemporal variation in paediatric Shigella infection and map its predicted prevalence across low-income and middle-income countries (LMICs). Methods Individual participant data for Shigella positivity in stool samples were sourced from multiple LMIC-based studies of children aged 59 months or younger. Covariates included household-level and participant-level factors ascertained by study investigators and environmental and hydrometeorological variables extracted from various data products at georeferenced child locations. Multivariate models were fitted and prevalence predictions obtained by syndrome and age stratum. Findings 20 studies from 23 countries (including locations in Central America and South America, sub-Saharan Africa, and south and southeast Asia) contributed 66 563 sample results. Age, symptom status, and study design contributed most to model performance followed by temperature, wind speed, relative humidity, and soil moisture. Probability of Shigella infection exceeded 20% when both precipitation and soil moisture were above average and had a 43% peak in uncomplicated diarrhoea cases at 33°C temperatures, above which it decreased. Compared with unimproved sanitation, improved sanitation decreased the odds of Shigella infection by 19% (odds ratio [OR]=0·81 [95% CI 0·76–0·86]) and open defecation decreased them by 18% (OR=0·82 [0·76–0·88]). Interpretation The distribution of Shigella is more sensitive to climatological factors, such as temperature, than previously recognised. Conditions in much of sub-Saharan Africa are particularly propitious for Shigella transmission, although hotspots also occur in South America and Central America, the Ganges–Brahmaputra Delta, and the island of New Guinea. These findings can inform prioritisation of populations for future vaccine trials and campaigns.
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    Serological evidence of vector and parasite exposure in Southern Ghana: the dynamics of malaria transmission intensity
    (Parasites & Vectors, 2015) Badu, K.; Gyan, B.; Mensah, D.; et al.
    Background: Seroepidemiology provides robust estimates for tracking malaria transmission when intensity is low and useful when there is no baseline entomological data. Serological evidence of exposure to malaria vectors and parasite contribute to our understanding of the risk of pathogen transmission, and facilitates implementation of targeted interventions. Ab to Anopheles gambiae salivary peptide (gSG6-P1) and merozoite surface protein one (MSP-119) reflect human exposure to malaria vectors and parasites. This study estimated malaria transmission dynamics using serological evidence of vector and parasite exposure in southern Ghana. Methods: Total IgG responses to both antigens in an age stratified cohort (<5, 5–14, >14) were measured from South-eastern Ghana. 295 randomly selected sera were analyzed from archived samples belonging to a cohort study that were followed at 3 consecutive survey months (n = 885); February, May and August 2009. Temporal variations in seroprevalence of both antigens as well as differences between the age-stratified cohorts were determined by χ 2 test with p < 0.05 statistically significant. Non-parametric repeated ANOVA – Friedman’s test was used to test differences in antibody levels. Seroprevalence data were fitted to reversible catalytic model to estimate sero-conversion rates. Results: Whereas parasite prevalence was generally low 2.4%, 2.7% and 2.4% with no apparent trends with season, seroprevalence to both gSG6-P1 and MSP119 were high (59%, 50.9%, 52.2%) and 57.6%, 52.3% and 43.6% in respective order from Feb. to August. Repeated measures ANOVA showed differences in median antibody levels across surveys with specific significant differences between February and May but not August by post hoc Dunn’s multiple comparison tests for gSG6-P1. For MSP119, no differences were observed in antibody levels between February and May but a significant decline was observed from May to August. Seroconversion rates for gSG6-P1 increased by 1.5 folds from February to August and 3 folds for MSP119. Conclusion: Data suggests exposure to infectious bites may be declining whereas mosquito bites remains high. Sustained malaria control efforts and surveillance are needed to drive malaria further down and to prevent catastrophic rebound. Operational factors for scaling up have been discussed
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    World Hepatitis day 2021 –screening and vaccination against Hepatitis B virus in Accra, Ghana
    (BMC Public Health, 2023) Kusi, K.A.; van der Puije, W.; Asandem, D.A.; et al.
    Background In Ghana, Hepatitis B virus (HBV) infection remains a major public health threat as in many parts of the world. Even with an effective vaccine, there are shortfalls with low vaccine coverage among adults. To create awareness and encourage vaccination, community engagement and public-private partnerships are needed in endemic settings to help fund campaigns and offer screening and vaccinations at no cost to under privileged people. Objectives An awareness and screening exercise was scheduled by University of Ghana-based Hepatitis-Malaria (HEPMAL) project team to coincide with the World Hepatitis Day (WHD) 2021. It was to engage the community in creating awareness of the menace and offer diagnostic services to ascertain prevalence levels and provide needed clinical support. Methods Participants from the University of Ghana community and its immediate environs were registered, taken through pre-counselling sessions where they were educated on hepatitis transmission and prevention before consenting. Eligible participants were screened for HBV markers (HBsAg, HBeAg, HBsAb, HBcAb,HbcAg) with a rapid test kit. All HBsAb-negative participants were recommended for initial vaccination at the event, whilst the subsequent shots were administered at the University Hospital Public Health Department. Hepatitis B surface Antigen-positive participants were counselled and referred for appropriate care. Results / Outcomes: A total of 297 people, comprising of 126 (42%) males and 171 (58%) females aged between 17 and 67 years were screened during the exercise. Amongst these, 246 (82.8%) showed no detectable protective antibodies against HBV and all of them agreed to and were given the first dose HBV vaccine. Additionally, 19 (6.4%) individuals tested positive for HBsAg and were counselled and referred to specialists from the University Hospital for further assessment and management. We found that 59 (19.9%) of our participants had previously initiated HBV vaccination and had taken at least one dose of the vaccine more than 6 months prior to this screening, 3 of whom tested positive for HBsAg. For the three-dose HBV vaccines deployed, a little over 20% (50/246) and a further 17% (33/196) did not return for the second and the third doses respectively, resulting in an overall 66% (163/246) of persons who completed all three vaccinations. Conclusions / Lessons learnt: Our medical campaign exercise established an active case prevalence rate of 6.4% and achieved a full vaccination success rate of 66% which is critical in the induction of long-term immunity in the participants. Aside these achievements, we would like to reiterate the importance of the use of different approaches including educational events and WHD activities to target groups and communities to raise awareness. Additionally, home and school vaccination programmes may be adopted to enhance vaccine uptake and adherence to the vaccination schedule. We plan to extend this screening exercise to deprived and/or rural communities where HBV incidence may be higher than in urban communities
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    Healthcare Provider Perspectives on HIV Cure Research in Ghana
    (Hindawi, 2023) Lamptey, H.; Newcomb, B.; Bonney, E.Y.; et al.
    Introduction. Antiretroviral therapy (ART) has reduced mortality and improved life expectancy among HIV patients but does not provide a cure. Patients must remain on lifelong medications and deal with drug resistance and side efects. Tis underscores the need for HIV cure research. However, participation in HIV cure research has risks without guaranteed benefts. We determined what HIV healthcare providers know about HIV cure research trials, the risks involved, and what kind of cure interventions they are likely to recommend for their patients. Methods. We conducted in-depth qualitative interviews with 39 HIV care providers consisting of 12 physicians, 8 counsellors, 14 nurses, 2 pharmacists, 2 laboratory scientists, and 1 community advocate from three hospitals. Interviews were transcribed verbatim and coded, and thematic analysis was performed independently by two investigators. Results. Participants were happy about the success of current treatments and hopeful that an HIV cure will be found in the near future, just as ART was discovered through research. Tey described cure as total eradication of the virus from the body and inability to test positive for HIV or transmit the virus. In terms of risk tolerance, respondents would recommend to their patients’ studies with mild to moderate risks like what patients on antiretroviral therapy experience. Participants were reluctant to recommend treatment interruption to patients as part of a cure study and wished trials could be performed without stopping treatment. Healthcare providers categorically rejected death or permanent disability as an acceptable risk. Te possibility of fnding a cure that will beneft the individual or future generations was strong motivations for providers to recommend cure trials to their patients, as was transparency and adequate information on proposed trials. Overall, the participants were not actively seeking knowledge on cure research and lacked information on the various cure modalities under investigation. Conclusion. While hopeful for an HIV cure, healthcare providers in Ghana expect a cure to be defnitive and pose minimal risk to their patients.