ghanaopendata/ghanaian-research-english huggingface dataset:
Plasmodium and intestinal parasite perturbations of the infected host’s inflammatory responses: a systematic review

The Department of Parasitology conducts research into parasitic diseases of public health importance with the overall goal of reducing their transmission and the heavy disease burden that they impose on affected populations. The Department maintains focus on parasitic diseases in general. These include major diseases such as malaria, and others listed under the Neglected Tropical Diseases (NTD) control initiative such as, lymphatic filariasis, onchocerciasis, schistosomiasis, soil-transmitted helminthiasis, trypanosomiasis and leishmaniasis.

Source: UG
Plasmodium falciparum : Assessment of Selectivity of Action of Chloroquine, Alchornea cordifolia, Ficus polita, and Other Drugs by a Tetrazolium-Based Colorimetric Assay

Most research activities involve the use of molecular methods such as regular PCR (PCR), quantitative PCR (Q-PCR), genomic sequence and analysis using different software, genetic engineering, probe hybridization techniques, biological and molecular cloning, evaluation of immune markers for laboratory diagnosis of infections, serological assays involving the use of rapid tests, ELISA-based evaluations and immunofluorescent assay techniques.

Source: UG
Plasmodium Falciparum and Mosquito Vector Igg Patterns Across Suspected Malaria Cases In Ghana.

The Department of Immunology conducts research in the field of immunology of infectious and non-infectious diseases. The Department has the overall goal of contributing knowledge to better diagnosis, management, control and prevention of infectious and non-infectious diseases in Ghana and worldwide. This is consistent with the overall strategy of the Noguchi Memorial Institute for Medical Research (NMIMR) and in line with the strategy of the College of Health Sciences of the University of Ghana.

Source: UG
The Plasmodium falciparum circumsporozoite protein produced in Lactococcus lactis is a pure and stable

The Department of Immunology conducts research in the field of immunology of infectious and non-infectious diseases. The Department has the overall goal of contributing knowledge to better diagnosis, management, control and prevention of infectious and non-infectious diseases in Ghana and worldwide. This is consistent with the overall strategy of the Noguchi Memorial Institute for Medical Research (NMIMR) and in line with the strategy of the College of Health Sciences of the University of Ghana.

Source: UG
Plasmodium falciparum field isolates use complement receptor 1 (CR1) as a receptor for invasion of erythrocytes

A majority of Plasmodium falciparum strains invade erythrocytes through interactions with sialic acid (SA) on glycophorins. However, we recently reported that complement receptor 1 (CR1) is a SA-independent invasion receptor of many laboratory strains of P. falciparum. To determine the role of CR1 in erythrocyte invasion among P. falciparum field isolates, we tested eight isolates obtained from children in Kenya. All the parasites examined were capable of invading in a SA-independent manner, and invasion of neuraminidase-treated erythrocytes was nearly completely blocked by anti-CR1 and soluble CR1 (sCR1). In addition, anti-CR1 and sCR1 partially inhibited invasion of intact erythrocytes in a majority of isolates tested. Sequencing of the hypervariable region of P. falciparum AMA-1 showed considerable diversity among all the isolates. These data demonstrate that CR1 mediates SA-independent erythrocyte invasion in P. falciparum field isolates

Source: UG
Plasmodium falciparum gene encoding a protein similar to the 78-kDa rat glucose-regulated stress protein.

Genes homologous to heat shock protein 70 have been described in parasitic protozoa. It has been proposed that they may be important to the parasite as it moves from the vertebrate host at 37°C to the insect. We now describe a genomic DNA clone isolated from Plasmodium falciparum that encodes a protein similar in sequence to a mammalian heat shock-related protein, the 78-kDa glucose-regulated protein of rat and hamster. The gene is expressed during the erythrocytic stage in both asexual and sexual parasites (RNA blot analysis) and a 72-kDa protein is immunoprecipitated from erythrocytic stage parasites. Importantly, the sequence of the clone is similar to the canonical sequence at the carboxyl termini of glucose-regulated proteins of mammals that determines their localization within endoplasmic reticulum. Since the parasite sequence has only three (Asp-Glu-Leu) of the four carboxyl-terminal amino acids, its location and its function within the parasite remain to be determined.

Source: UG
Plasmodium falciparum immunodominant IgG epitopes in subclinical malaria

Incomplete non-sterile immunity to malaria is attained in endemic regions after recurrent infections by a large percentage of the adult population, who carry the malaria parasite asymptomatically. Although blood-stage Plasmodium falciparum rapidly elicits IgG responses, the target antigens of partially protective and non-protective IgG antibodies as well as the basis for the acquisition of these antibodies remain largely unknown. We performed IgG-immunomics to screen for P. falciparum antigens and to identify epitopes associated with exposure and clinical disease. Sera from malaria cases identified five prevalent antigens recognized by all analyzed patients’ IgGs. Epitope mapping of them, using adult and children sera samples from an endemic malaria region in Ghana segregated into patients with positive or negative subclinical detection of P. falciparum, revealed binding specificity for two 20-mer immunodominant antigenic regions within the START-related lipid transfer protein and the protein disulfide isomerase PDI8. These 20-mer epitopes challenged with sera samples from children under 5 years old displayed specific IgG binding in those with detectable parasitemia, even at subclinical level. These results suggest that humoral response against START and PDI8 antigens may be triggered at submicroscopic parasitemia levels in children and may eventually be used to differentially diagnose subclinical malaria in children.

Source: UG
Plasmodium falciparum infection and naturally acquired immunity to malaria antigens among Ghanaian children in northern Ghana

The Department of Immunology conducts research in the field of immunology of infectious and non-infectious diseases. The Department has the overall goal of contributing knowledge to better diagnosis, management, control and prevention of infectious and non-infectious diseases in Ghana and worldwide. This is consistent with the overall strategy of the Noguchi Memorial Institute for Medical Research (NMIMR) and in line with the strategy of the College of Health Sciences of the University of Ghana.

Source: UG
Plasmodium falciparum isolates from southern Ghana exhibit polymorphisms in the SERCA-type PfATPase6 though sensitive to artesunate in vitro

The Department of Parasitology conducts research into parasitic diseases of public health importance with the overall goal of reducing their transmission and the heavy disease burden that they impose on affected populations. The Department maintains focus on parasitic diseases in general. These include major diseases such as malaria, and others listed under the Neglected Tropical Diseases (NTD) control initiative such as, lymphatic filariasis, onchocerciasis, schistosomiasis, soil-transmitted helminthiasis, trypanosomiasis and leishmaniasis.

Source: UG
Plasmodium falciparum isolates from southern Ghana exhibit polymorphisms in the SERCA-type PfATPase6 though sensitive to artesunate in vitro

BACKGROUND: In 2005, Ghana replaced chloroquine with artemisinin-based combination therapy as the first-line treatment for uncomplicated malaria. The aim of this work was to determine for the first time, polymorphisms in the putative pfATPase6 and pftctp, pfmdr1, pfcrt genes in Ghanaian isolates, particularly at a time when there is no report on artemisinin resistance in malaria parasites from Ghana. The sensitivity of parasite isolates to anti-malaria drugs were also evaluated for a possible association with polymorphisms in these genes. METHODS: The prevalence of point mutations in the above Plasmodium falciparum genes were assessed from filter-paper blood blot samples by DNA sequencing. In vitro drug sensitivity test was carried out on some of the blood samples from volunteers visiting hospitals/clinics in southern Ghana using a modified version of the standard WHO Mark III micro-test. RESULTS: All successfully tested parasite isolates were sensitive to artesunate; while 19.4%, 29.0% and 51.6% were resistant to quinine, amodiaquine and chloroquine respectively. The geometric mean of IC50 value for artesunate was 0.73 nM (95% CI, 0.38-1.08), amodiaquine 30.69 nM (95% CI, 14.18-47.20) and chloroquine 58.73 nM (95% CI, 38.08-79.38). Twenty point mutations were observed in pfATPase6 gene, with no L263E and S769N. All mutations found were low in frequency, except D639G which was observed in about half of the isolates but was not associated with artesunate response (p = 0.42). The pftctp gene is highly conserved as no mutation was observed, while CVIET which is chloroquine-resistant genotype at codon 72-76 of the pfcrt gene was identified in about half of the isolates; this was consistent with chloroquine IC50 values (p = 0.001). Mutations were present in pfmdr1 gene but were not associated with artemisinin response (p = 1.00). CONCLUSION: The pfATPase6 gene is highly polymorphic with D639G appearing to be fixed in Ghanaian isolates. These may just be spontaneous mutations as all parasite isolates that were tested displayed satisfactory in vitro response to artesunate. However, there is no improvement in susceptibility of the parasites to chloroquine five years after its proscription.

Source: UG
Plasmodium falciparum isolates: ex vivo drug response

Objectives: While artemisinin-based combination therapies (ACTs) are effective in sub-Saharan Africa, clinical isolates that are refractory to artemisinin derivatives are emerging in East Africa and ACT partner drugs are be coming less effective in West Africa. We investigated the ex vivo responses of Plasmodium falciparum clinical isolates to frontline antimalarials and the contribution of validated molecular markers of antimalarial drug resistance. Methods: Ex vivo susceptibility was measured for 66 clinical isolates collected from uncomplicated malaria patients. IC50 was measured for dihydroartemisinin, artesunate, lumefantrine, amodiaquine and chloroquine using a SYBR Green I growth inhibition assay. We also assessed known drug resistance-mediating polymorph isms in pfcrt, pfmdr1 and pfkelch13 using Oxford Nanopore amplicon sequencing. Results: P. falciparum clinical isolates were susceptible to dihydroartemisinin and artesunate. Clinical isolates showed a wide distribution of susceptibility to lumefantrine and amodiaquine, with some parasites having IC50 values above reference cut-offs for resistance to lumefantrine (150 nM) and amodiaquine (60 nM), suggest ing decreased drug susceptibility. Ninety-seven percent of the isolates carried WT pfcrt K76 and pfmdr1 N86 al leles, reported to mediate reduced response to lumefantrine and artemether/lumefantrine. pfmdr1 N86 and 184F haplotype was carried by 62.1% of parasites. None of the clinical isolates carried validated pfkelch13 mu tations known to mediate artemisinin partial resistance. Conclusions: Clinical isolates from coastal Ghana remain susceptible to artemisinin derivatives in commonly used ACTs in Ghana. However, we observed lower susceptibility to the ACT partner drugs lumefantrine and amo diaquine, suggesting the emergence of drug-tolerance phenotypes. Consistent surveillance of drug phenotype– genotype is needed to support ACT efficacy in Ghana.

Source: UG
Plasmodium falciparum Kelch Propeller Polymorphisms in Clinical Isolates from Ghana from 2007 to 2016

The Epidemiology Department contributes to the mission of the institute through basic and applied epidemiological research on, but not limited to, malaria and other diseases of public health importance. It is also home to the Social Science Unit of the Institute, including the Health Support Centre for HIV/AIDS and other communicable and noncommunicable health problems.

Source: UG
Plasmodium falciparum malaria cases detected for prompt treatment by rapid diagnostic tests in the Ho Teaching Hospital of the Volta Region of Ghana

Background: Prompt diagnosis and effective treatment of malaria cases with efficacious drugs is an important strategy in the management and control of malaria in endemic populations. As part of a study investigating the factors modulating the development of Plasmodium falciparum gametocytes in the human host, we assessed the rate of RDT positivity of patients in different departments of the Ho Teaching Hospital and the relation with age and anaemia. Materials and methods: Eight-hundred and ten individuals attending clinic at various departments within the Ho Teaching Hospital were screened for malaria antigenaemia using RDT as a point-of-entry investigation. RDT positive individuals were immediately treated for malaria whereas RDT negative individuals were treated for other ailments. Haematological analyses were performed for 69 of these patients and the relationship between RDT results and haemoglobin levels were investigated. Results: The overall RDT positivity rate was 19.8% (160/810) of all individuals screened. There was no significant difference in the haemoglobin levels of RDT-positive and RDT-negative individuals (p value = 0.272). The highest number of attendees screened was children in the paediatric outpatient department and paediatric ward, 62% (507/810), with RDT positivity rate of 17% (91/507). We found the highest RDT positivity rate of 51% (19/37) in the male medical ward. Conclusions: This study shows that RDT is a useful tool in promoting prompt diagnosis and management of malaria and though children form a majority of hospital attendees and malaria infections, the frequency of malaria detection may be higher in adults as compared to children. © 2018

Source: UG
Plasmodium falciparum Malaria Parasites in Ghana Show Signatures of Balancing Selection at Artemisinin Resistance Predisposing Background Genes

Sub-Saharan Africa is courting the risk of artemisinin resistance (ARTr) emerging in Plasmodium falciparum malaria parasites. Current molecular surveillance efforts for ARTr have been built on the utility of P. falciparum kelch13 (pfk13) validated molecular markers. However, whether these molecular markers will serve the purpose of early detection of artemisinin-resistant parasites in Ghana is hinged on a pfk13 dependent evolution. Here, we tested the hypothesis that the background pfk13 genome may be present before the pfk13 ARTr-conferring variant(s) is selected and that signatures of balancing selection on these genomic loci may serve as an early warning signal of ARTr. We analyzed 12198 single nucleotide polymorphisms (SNPs) in Ghanaian clinical isolates in the Pf3K MalariaGEN dataset that passed a stringent filter ing regimen. We identified signatures of balancing selection in 2 genes (phosphatidylinositol 4-kinase and chloroquine resistance transporter) previously reported as background loci for ARTr. These genes showed statistically significant and high positive values for Tajima’s D, Fu and Li’s F, and Fu and Li’s D. This indicates that the biodiversity required to establish a pfk13 background genome may have been primed in clinical isolates of P. falciparum from Ghana as of 2010. Despite the absence of ARTr in Ghana to date, our finding supports the current use of pfk13 for molecular surveillance of ARTr in Ghana and highlights the potential utility of monitoring malaria parasite populations for balancing selection in ARTr precursor background genes as early warning molecular signatures for the emergence of ARTr.

Source: UG
Plasmodium falciparum msp1 and msp2 genetic diversity in parasites isolated from symptomatic and asymptomatic malaria subjects in the South of Benin

The Department of Immunology conducts research in the field of immunology of infectious and non-infectious diseases. The Department has the overall goal of contributing knowledge to better diagnosis, management, control and prevention of infectious and non-infectious diseases in Ghana and worldwide. This is consistent with the overall strategy of the Noguchi Memorial Institute for Medical Research (NMIMR) and in line with the strategy of the College of Health Sciences of the University of Ghana.

Source: UG
Plasmodium falciparum parasites expressing pregnancy-specific variant surface antigens adhere strongly to the choriocarcinoma cell line BeWo

The Department of Immunology conducts research in the field of immunology of infectious and non-infectious diseases. The Department has the overall goal of contributing knowledge to better diagnosis, management, control and prevention of infectious and non-infectious diseases in Ghana and worldwide. This is consistent with the overall strategy of the Noguchi Memorial Institute for Medical Research (NMIMR) and in line with the strategy of the College of Health Sciences of the University of Ghana.

Source: UG
Plasmodium Falciparum Pfs47 Haplotype Compatibility To Anopheles Gambiae In Kisumu, A Malaria-Endemic Region Of Kenya.

Insecticide resistance and outdoor transmission have reduced the effectiveness of existing malaria transmission prevention strategies. As a result, targeted approaches to support continuing malaria control, such as transmission-blocking vaccines, are required. Cross-sectional mass blood screening in children between 5 and 15 years was conducted in Chulaimbo, Kisumu, during the dry and wet seasons in 2018 and 2019. Plasmodium falciparum gametocyte carriers were identified by Microscopy. Subsequently, carriers were used to feed colony bred Anopheles gambiae females in serum replacement and whole blood membrane feeding experiments. The infection prevalence was 19.7% (95% Cl 0.003–0.007) with 95% of the infections being caused by P. falciparum. Of all confirmed P. falciparum infections, 16.9% were gametocytes. Thirty-seven paired experiments showed infection rates of 0.9% and 0.5% in the serum replacement and whole blood experiments, respectively, with no significant difference (P=0.738). Six Pfs47 haplotypes were identified from 24 sequenced infectious blood samples: Hap_1 (E27D and L240I), Hap_2 (S98T); Hap_3 (E27D); Hap_4 (L240I); Hap_5 (E188D); and Hap_6 without mutations. Haplotype 4 had the highest frequency of 29.2% followed by Hap_3 and Hap_6 at 20.8% each then Hap_1 with a frequency of 16.7%, whereas Hap_5 and Hap_2 had frequencies of 8.3% and 4.2% respectively. Varying frequencies of Pfs47 haplotypes observed from genetically heterogeneous parasite populations in endemic regions illuminates vector compatibility to refracting P. falciparum using the hypothesized lock and key analogy. This acts as a bottleneck that increases the frequency of P. falciparum haplotypes that escape elimination by vector immune responses. The interaction can be used as a potential target for transmission blocking through a refractory host.

Source: UG
Plasmodium falciparum Sexual Commitment Rate Variation among Clinical Isolates and Diverse Laboratory-Adapted Lines

Asexual blood-stage malaria parasites must produce sexual progeny to infect mosquitoes. It is important to understand the scope and causes of intraspecific variation in sexual commitment rates, particularly for the major human parasite P. falciparum. First, two alternative assay methods of measuring sexual commitment were compared to test a genetically modified P. falciparum line with elevated commitment rates inducible by overexpression of GDV1. The methods yielded correlated measurements with higher sensitivity and precision being achieved by one employing detection of the early gametocyte differentiation marker Pfs16. Thus, this was used to survey a diverse range of parasite lines and test each in multiple biological replicate assays in a serum free medium supplemented with Albumax. There were differences among six recent clinical isolates from Ghana in their mean rates of sexual commitment per cycle, ranging from 3.3% to 12.2%. Among 13 diverse long-term laboratory-adapted lines, mean sexual commitment rates for most ranged from 4.7% to 13.4%, a few had lower rates with means from 0.3 to 1.6%, and one with a nonfunctional ap2-g gene always showed zero commitment. Among a subset of lines tested for the effects of exogenous choline to suppress commitment, there were significant differences. As expected, there was no effect in a line that had lost the gdv1 gene and that had generally low commitment, whereas the others showed quantitatively variable but significant responses to choline, suggesting potential trait variation. The results indicated the value of performing multiple replicate assays for understanding the variation of this key reproductive trait that likely affects transmission Only sexual-stage malaria parasites are transmitted from human blood to mosquitoes. Thus, it is vital to understand variations in sexual commitment rates because these may be modifiable or susceptible to blocking. Two different methods of commitment rate measurement were first compared, demonstrating higher sensitivity and precision by the detection of an early differentiation marker, which was subsequently used to survey diverse lines. Clinical isolates from Ghana showed significant variation in mean per-cycle commitment rates and variation among biological replicates. Laboratory-adapted lines of diverse origins had a wider range with most being within the range observed for the clinical isolates, while a minority consistently had lower or zero rates. There was quantitative variation in the effects when adding choline to suppress commitment, indicating differing responsiveness of parasites to this environmental modification. Performing multiple assay replicates and comparisons of diverse isolates was important to understand this trait and its potential effects on transmission

Source: UG
Plasmodium falciparum sexual differentiation in malaria patients is associated with host factors and GDV1-dependent genes

The Department of Immunology conducts research in the field of immunology of infectious and non-infectious diseases. The Department has the overall goal of contributing knowledge to better diagnosis, management, control and prevention of infectious and non-infectious diseases in Ghana and worldwide. This is consistent with the overall strategy of the Noguchi Memorial Institute for Medical Research (NMIMR) and in line with the strategy of the College of Health Sciences of the University of Ghana.

Source: UG