College of Health Sciences

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    Malaria transmission dynamics and insecticide resistance of malaria vectors in the Kassena-Nankana Districts of Ghana
    (KNUST, 2016-02) Asoala, Victor
    ABSTRACT Plasmodium falciparum malaria is a serious tropical disease that causes more than one million deaths each year, mostly in Africa. It is transmitted by a range of Anopheles mosquitoes. Progress in global malaria control over the past decade is largely gained through investments in vector control; especially insecticide treated mosquito nets (ITNs). ITNs have been used extensively in the Kassena Nankana districts (KND) of Ghana for over two decades. This study aimed to investigate the intensity of malaria transmission and resistance status of vector populations in KND, relate these data to historical patterns of transmission intensity and determine whether the presence of insecticide resistance has an effect on malaria transmission in KND. Anopheles gambiae s.l. was the predominant Anopheles which constituted 68.82% (95% CI 68.18 - 69.45) (N=13938). Anopheles funestus constituted 10.97% (95% CI 10.55 – 11.41) (N=2222) whilst An. pharoensis and An. rufipes constituted the rest of 20. 21% (95% CI 19.66 - 20.77), (N=4092). Molecular analysis of the An. gambiae s.l. revealed only An. gambiae s.s. as sibling species, mainly of Anopheles coluzzii (M-form). Anopheles biting started early, peaked around 10.00pm and continued to the early hours of the morning. Plasmodium falciparum sporozoite infectivity results revealed active transmission by An. gambiae s.s.as early as 8pm and serious transmission occurred towards the early hours of the morning because of combined infective biting by both An. gambiae s.s and An. funestus. There was marked temporal variations in malaria intensity estimated as the entomological inoculation rate (EIR) with the irrigated zone experiencing the highest during the year. Compared to what was reported over a decade ago, the intensity of transmission has reduced by 66.7% from 418 to 139 infective bites/man/year. Results of the study indicated high phenotypic resistance to the insecticide classes tested. High frequencies of the Knock down resistance (kdr) and vi Ace-1R alleles (responsible for pyretroid/DDT and carbamate /organophosphate resistance respectively) including the N1575Y allele (reported to enhance resistance to pyrethroids) was observed. The variations observed in biting patterns, transmission intensity and the high insecticide resistance observed in the main malaria vector has important consequences for the success of the widely used insecticide-based strategies in KND.
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    Efficacy, safety and tolerability of Dihydroartemisinin-Piperaquine for treatment of uncomplicated falciparum malaria in pregnancy in Ghana.
    (KNUST, 2016-06) Osarfo, Joseph
    Primarily, the study’s original contribution to knowledge is in providing evidence of the safety and efficacy of dihydroartemisinin-piperaquine (DHA-PPQ) use in pregnant women from a clinical trial. DHA-PPQ has potential for use as treatment for uncomplicated malaria in pregnancy. However, there is a paucity of safety data on the use of this drug combination in pregnancy and only two studies have reported its use in pregnancy so far. Additionally, the prevalence of parasite mutations underscoring reported reduced susceptibility to ACTs and SP was assessed to help rationalize drug policy. The diagnostic performance of First Response® malaria rapid diagnostic test (RDT) and perceptions associated with clinical trial participation were assessed in Ghanaian pregnant women to help fill knowledge gaps in these areas. Second and third trimester pregnant women with asymptomatic parasitaemia were randomized to receive DHA-PPQ and artesunate-amodiaquine (ASAQ) in a non- inferiority trial and followed up on days 1, 2, 3, 7, 14, 28 and 42 after start of study treatment, at delivery and 6 weeks post-partum for adverse events, haematological and parasitological outcomes and neonatal morbidity and mortality data. Mutations at the Pfcrt, Pfmdr1, Pfdhfr and Pfdhps genes were investigated using polymerase chain reaction and antigen-antibody reaction-based methods. Results of RDTs at screening were compared to peripheral blood film microscopy used as reference standard. Pregnant women’s perceptions of participating in clinical trials were obtained from in-depth interviews with women who participated in the trials and those who did not. Overall parasitological efficacy for DHA-PPQ was 91.6% (95%CI: 86.7, 95.1) by day 28 and 89.0% (95%CI: 83.6. 93.0) by day 42 in the per protocol population. Efficacy estimates in both arms were comparable. DHA-PPQ was non-inferior to ASAQ with respect to parasite clearance in both analyses populations. There were no harms associated with the use of DHA-PPQ in the second and third trimesters and it fewer adverse events than ASAQ; anorexia (12.0% vs 22.3%; p=0.007), vomiting (19.5% vs 29.4%; p=0.02), dizziness (14.5% vs 26.6%; p=0.003) and general weakness (38.5% vs 62.5%; p<0.0001). Tolerability was high as no participant left the study on account of adverse events experienced. There were no overall changes in white blood cell and differential counts. Close to 90% of parasite isolates from the infected pregnant women were wild type at the Pfcrt gene with a similar prevalence of Pfmdr1 N86 alleles. The Pfdhfr/Pfdhps quintuple mutation containing the 540E allele, known to underlie marked SP resistance, was not observed. Participation in clinical trials appeared to be motivated mainly by anticipated health benefits and trust in the research team especially if they are also health workers. Study women were comfortable with blood sampling in their homes but preferred hospital-based sampling better as it supposedly assures blood samples will be used for desired purposes. They conceptualized treatment-emergent adverse events as independent entities that should be separated from drugs. Dihydroartemisinin-piperaquine is deemed safe and as effective as ASAQ when used to treat uncomplicated malaria during pregnancy. The study results are expected to contribute to evidence that will guide a policy decision on the use of DHA-PPQ use in pregnant women. The predominance of Pfcrt K76 suggests the possibility of using chloroquine again in pregnancy but this will have to be in combination with another antimalarial. The predominance of Pfcrt K76 and Pfmdr1 N86 alleles appear to suggest early declining susceptibility to artemether-lumefantrine, an artemisininbased combination treatment currently used in pregnancy. Strengthened targeting of ACT treatment through more dedicated malaria infection testing using tools such as RDTs and monitoring are required. Researchers planning similar studies in pregnant women in the study area need to emphasize transportation to health facilities for blood sampling and potential health benefits.
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    Comparative Clinical Study of Mist Amen Fevermix and Edhec Malacure: Two Polyherbal Products used for the Treatment of uncomplicated malaria in Ghana against Artemether/Lumefantrine
    (2020-11) Turkson, Bernard Kofi; https://orcid.org/0000-0002-4990-7725
    The use of herbal medicinal products for the treatment of malaria an infectious and a life threatening disease, has increased globally. However, inadequate scientific studies, questions about the quality, safety and efficacy of such herbal products have been raised. On the other hand, the reduced sensitivity of the malaria parasites to artemisinin-based combination therapies is also of concern. There is therefore the need for new antimalarial medications including those from alternative sources such as herbal medicinal products. In this study, methods for the quality control of Mist Amen Fevermix and Edhec Malacure, two polyherbal antimalarial products used in Ghana for the management of uncomplicated malaria was undertaken. The development of the quality parameters for the test samples was based on phytochemical, physicochemical, chromatographic and spectroscopic methods. The set parameters were found to be sufficient to evaluate Mist Amen Fevermix and Edhec Malacure, and can be used as reference standards for the quality control purposes. Qualitative phytochemical screening and fingerprinting were undertaken based on standard analytical methods. The antiplasmodial activity was assessed in vitro by using field isolates of Plasmodium falciparum with SYBR® Green assays to measure parasite growth inhibition. Thermo Elemental M5 Atomic Absorption Spectrophotometer (AAS) fitted with Graphite furnace and an auto sampler was used to determine the heavy metal contents of the herbal products. The herbal samples were evaluated for microbial load by using the appropriate culture media. In vivo antiparasitic activity in mice was assessed using the Rane’s curative method using ANKA strain of Plasmodium berghei parasites. A comparative clinical study was done to assess the safety and effectiveness of the test samples at the Tafo Government Hospital, Kumasi after Committee on Human Research, Publication and Ethics approval. Male and female patients aged 15-45 years with clinically established malaria were treated with Mist Amen Fevermix and Edhec Malacure, at the specified doses of 45 mls (0.1063 g) and 30 mls (0.0521 g) three times daily after meals for three days. Basic phytochemical screening of the two products indicated the presence of the following phytochemicals: alkaloids, saponins, tannins, phytosterols and flavonoids. From the data, it was established that Mist Amen Fevermix and Edhec Malacure complied with the pharmacopoeial standards after testing for microbes. The following heavy metals were present in Mist Amen Fevermix and Edhec Malacure: Fe, Ni, K, Zn, Hg, Cu, Mn, Cr, Cd, Pb, Fe, Cu, K and Na. Ni was below detectable limit in Edhec Malacure. The phytochemical screening of the products revealed the presence of alkaloid flavonoid, tannin, steroid and saponin. The HPLC method was validated for linearity, limits of detection and quantification, precision and accuracy. The test products were found not to have been adulterated with lumefantrine, artemether and quinine. The test herbal products showed in vitro and in vivo antiplasmodial activities against Plasmodium falciparum and Plasmodium berghei parasites. Inhibitory concentration (IC50) values for Edhec Malacure was 70.89 ng/ml and that of Mist Amen Fevermix was 112.5 ng/ml. Edhec Malacure suppressed 76.17% of parasitaemia while Mist Amen Fevermix suppressed 69.03% of parasitaemia. Edhec Malacure demonstrated curative chemo suppressive potentials of 80.93% at the dose of 2.234 mgkg-1 and Mist Amen Fevermix % suppression was 69.03% at a dose of 4.56mg/kg-1. Both products demonstrated antiplasmodial activity in human red blood cells. The clinical evaluation of the test samples showed that Mist Amen Fevermix exhibited a statistically significant difference between the mean malaria parasite load recorded at the first visit and those recorded at the second visit, t(23) = 4.59, p =0 .000. Similarly, there was a significant difference between the mean parasite count recorded on the second visit and the third visit, t(6) = 1.49, p =0 .187. No difference were recorded for the third and fourth visits t(3) = 1.00, p =0 .391. Edhec Malacure also exhibited a significant difference in efficacy between the mean malaria parasite count recorded at the first visit and those recorded at the second visit, t(26) =3.77, p =0 .001. Similarly, there is a statistically significant difference between malaria parasite count at the second visits and third visits, t(16) = 1.74, p =0 .100. This shows the significant effectiveness of the products. Kidney and liver panel as well as full blood count and vital signs were within normalviii reference range at the end of the 28-day study and thus established the safety of Mist Amen Fevermix and Edhec Malacure in the treatment of uncomplicated malaria. The results support claims that Mist Amen Fevermix and Edhec Malacure may be useful antimalarial agents. This study has demonstrated the in vitro and in vivo antiplasmodial activities of Mist Amen Fevermix and Edhec Malacure, and suggests that, the products have promising antimalarial activity. The in vivo findings showed that Mist Amen Fevermix and Edhec Malacure are relatively safe for oral administration at doses tested. In addition, the study supports the use of Mist Amen Fevermix and Edhec Malacure, two polyherbal products for the treatment of uncomplicated malaria. Both products achieved a comparable clinical treatment outcome to the reference control medication artemether/lumefantrine.
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    Risk Factors and Human coronaviruses Associated with Upper Respiratory Tract Infections in Three Rural Areas of Ghana.
    (2014.) Owusu, Michael
    Acute respiratory tract infections (ARI) are the leading cause of morbidity and mortality in developing countries, especially in Africa. In spite of its importance, information on the viral aetiology and risk factors associated with ARI are limited in Ghana. Even though human coronaviruses (HCoVs) are known to be associated with respiratory disease outbreaks and severe infections in some developed countries, their epidemiological role is understudied in many African countries including Ghana. It is therefore not known whether HCoVs are pathogenic viruses associated with ARI or only exist as normal commensals of the upper respiratory tract. The aim of this study was to find the association between HCoVs and ARIs, describe the sero-molecular epidemiology of HCoVs and identify the risk factors associated with upper respiratory tract infection. An unmatched case control study was conducted in Buoyem, Forikrom and Kwamang communities of Ghana. Subjects were interviewed on various socio-demographic factors and hygienic practices using structured questionnaires. Nasal/Nasopharyngeal swabs were taken from older children and adults, and tested for Middle East respiratory syndrome coronavirus (MERS-CoV), HCoV-229E, HCoV-OC43, HCoV-NL63 and HCoV-HKU1 using Reverse Transcriptase Real-Time Polymerase Chain Reaction. A total of 1272 subjects were recruited comprising of 662 (52%) controls and 610 (48%) cases. Risk factors associated with upper respiratory tract infections were school attendance to the level of Senior High and tertiary education, and being a health worker. Out of 322 subset of cases interviewed, 212 (66%) covered their nose with handkerchiefs when they sneezed, 52 (16%) covered with their hands upon xix sneezing and 79 (25%) sneezed in the open. Self-administered drugs such as herbs (2%), analgesics (25%) and antibiotics (16%) were used to manage upper respiratory tract infections. Out of the 1,272 subjects recruited, nasal swabs were taken from 1,213. Of the 1,213, 150 (12.4%) subjects were positive for one or more viruses. Of these, single virus detections occurred in 146 subjects (12.0%) and multiple detections occurred in 4 (0.3%). Compared with control subjects, infections with HCoV-229E (OR = 5.15, 95% CI = 2.24 – 11.78), HCoV-OC43 (OR = 6.16, 95% CI = 1.77 – 21.65) and combine HCoVs (OR = 2.36, 95% CI = 1.5 = 3.72) were associated with upper respiratory tract infections. Significant median virus concentration difference was observed for only HCoV- NL63 (cases: 2.41 x 106 copies per PCR reaction; IQR = 1.96 x 104 - 2.3 x 106 vrs controls: 1876.5 copies per PCR reaction; IQR =387.2 – 8.6 x 104, P=0.003) and the clinically relevant cut-off viral concentration was determined to be 7,510 copies per PCR reaction. HCoVs were found to be seasonally dependent with high proportions identified in the harmattan season (54/215, 25.1%) compared to the wet (80/516, 15.5%) seasons. The most frequent viruses detected in the harmattan and wet seasons were HCoV-229E and HCoV-NL63 respectively. HCoV-OC43 and HCoV-HKU1 were almost distributed equally throughout the year. Sequencing of the partial spike region was successful for 53 out of 146 samples (36.3%). Of the 53, 12 (22.6%) were HCoV-OC43, 14 (26.4%) were HCoV-NL63, 24 (45.3%) were HCoV-229E and 3 (5.7%) were HCoV-HKU1. A comparison of the obtained sequences resulted in no differences to sequences already published in GenBank. xx This study has identified risk factors of URTI and also demonstrated that HCoVs could play significant role in causing upper respiratory tract infections among adults and older children in rural arrears of Ghana. This information could be useful to policy makers, public health practitioners and other stakeholders in Ghana.
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    Bioactive constituents from the Ghanaian medicinal plant Chlorophora regia and its root endophytic fungus JK10.
    ( AUGUST, 2016 ) Kyekyeku, James Oppong
    The extracts of the Ghanaian medicinal plant Chlorophora regia A. Chev (Moraceae) has been used for the treatment of various ailments in traditional medicine including burns, wounds, snake bite, wasp bite. A search through the literature, however, revealed there were no available data on the phytochemical composition of the plant. Therefore, the main objective of this study was to isolate, characterize and evaluate some biological activities of secondary metabolites from the stem bark of the plant and further investigate the endophytic community harbored in the inner tissues of the plant. Extensive phytochemical investigation of the stem bark resulted in the isolation and characterization of four new metabolites, regiafuran A–C and 6–prenylated–3,5,7,4ʹ–tetrahydroxy–2ʹ–methoxyflavonol in addition to fifteen known compounds. The isolated compounds were tested for their free radical scavenging activities. Regiafuran A–B, mulberrofuran Y, kuwanol E and 5,7,4ʹ–trihydroxy–2ʹ–methoxyflavanone demonstrated significant free radical scavenging activities with IC50 values of 1.9 μg/ml, 2.4 μg/ml, 2.2 μg/ml, 2.1 μg/ml and 1.8 μg/ml respectively. An unidentified endophytic fungus, JK10, was isolated from the root of C. regia. Twelve compounds including seven new 7–desmethyl derivatives of fusarin C and five known compounds were isolated from the endophytic fungus, JK10. The planar and relative configurations of the new compounds were elucidated by combined spectroscopic analyses of their UV, IR, HRESI–MSn, ECD and NMR data. The absolute configuration of solaniol was established for the first time by X–ray diffraction analysis of a single crystal. The antibacterial activities of the isolated compounds were evaluated. 7–desmethyl fusarin C–22/23 and 7–desmethyl fusarin C–25 exhibited remarkable activity at concentrations of 10.0 μg/mL against the soil bacterium Acinetobacter sp. BD4 comparable to the reference standard streptomycin. All the tested compounds demonstrated activity against the environmental strain of E. coli. Based on the results it could be proposed that the endophytic fungus, whose origin is from the roots, contributes a chemical–mediated defensive mechanism to the host plant against iii invading specific soil and environmental bacterial pathogens. This may confirm the existence of a unique cost–benefit endophyte–plant association. The spatial distribution of three kaurane diterpenes, xylopic acid, ent–kaur–16–en–19–oic acid and 15–oxo–ent–kaur–16–en–19–oic acid, in the fruits of Xylopia aethiopica (Dunal) A. Rich (Annonaceae) were visualized by MALDI–HRMS imaging techniques. The distribution of the compounds was predominantly in the pericarp region of the fruit with non-detectable levels in the seed.