Browsing by Author "Quaye, L."
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Item A SYBR Green 1-based in vitro test of susceptibility of Ghanaian Plasmodium falciparum clinical isolates to a panel of anti-malarial drugs(2013-12-17) Quashie, N.B.; Duah, N.O.; Abuaku, B.; Quaye, L.; Ayanful-Torgby, R.; Akwoviah, G.A.; Kweku, M.; Johnson, J.D.; Lucchi, N.W.; Udhayakumar, V.; Duplessis, C.; Kronmann, K.C.; Koram, K.A.Abstract Background Based on report of declining efficacy of chloroquine, Ghana shifted to the use of artemisinin-based combination therapy (ACT) in 2005 as the first-line anti-malarial drug. Since then, there has not been any major evaluation of the efficacy of anti-malarial drugs in Ghana in vitro. The sensitivity of Ghanaian Plasmodium falciparum isolates to anti-malarial drugs was, therefore, assessed and the data compared with that obtained prior to the change in the malaria treatment policy. Methods A SYBR Green 1 fluorescent-based in vitro drug sensitivity assay was used to assess the susceptibility of clinical isolates of P. falciparum to a panel of 12 anti-malarial drugs in three distinct eco-epidemiological zones in Ghana. The isolates were obtained from children visiting health facilities in sentinel sites located in Hohoe, Navrongo and Cape Coast municipalities. The concentration of anti-malarial drug inhibiting parasite growth by 50% (IC50) for each drug was estimated using the online program, ICEstimator. Results Pooled results from all the sentinel sites indicated geometric mean IC50 values of 1.60, 3.80, 4.00, 4.56, 5.20, 6.11, 10.12, 28.32, 31.56, 93.60, 107.20, and 8952.50 nM for atovaquone, artesunate, dihydroartemisin, artemether, lumefantrine, amodiaquine, mefloquine, piperaquine, chloroquine, tafenoquine, quinine, and doxycycline, respectively. With reference to the literature threshold value indicative of resistance, the parasites showed resistance to all the test drugs except the artemisinin derivatives, atovaquone and to a lesser extent, lumefantrine. There was nearly a two-fold decrease in the IC50 value determined for chloroquine in this study compared to that determined in 2004 (57.56 nM). This observation is important, since it suggests a significant improvement in the efficacy of chloroquine, probably as a direct consequence of reduced drug pressure after cessation of its use. Compared to that measured prior to the change in treatment policy, significant elevation of artesunate IC50 value was observed. The results also suggest the existence of possible cross-resistance among some of the test drugs. Conclusion Ghanaian P. falciparum isolates, to some extent, have become susceptible to chloroquine in vitro, however the increasing trend in artesunate IC50 value observed should be of concern. Continuous monitoring of ACT in Ghana is recommended.Item Association of single nucleotide polymorphisms with dyslipidemia in antiretroviral exposed HIV patients in a Ghanaian population: A case-control study(Plos One, 2020-01-20) Amos-Abanyie, E.K.; Obirikorang, C.; Acheampong, E.; Quaye, L.; Yorke, J.; Akyaw, P.A.; Anto, E.O.; Bani, S.B.; Asamoah, E.A.; Batu, E.N.Dyslipidemia is a potential complication of long-term usage of antiretroviral therapy (ART) and also known to be associated with genetic factors. The host genetic variants associated with dyslipidemia in HIV patients on ART in Ghana have not been fully explored. The study constituted a total of 289 HIV-infected patients on stable ART for at least a year. Fasting blood was collected into EDTA tube for lipids measurement. Lipid profiles were used to define dyslipidemia based on the NCEP-ATP III criteria. HIV-infected subjects were categorized into two groups; those with dyslipidemia (cases) (n = 90; 31.1%) and without dyslipidemia (controls)(n = 199; 68.9%). Four candidate single nucleotide polymorphism (SNP) genes (ABCA1-rs2066714, LDLR-rs6511720, APOA5-rs662799 and DSCAML1- rs10892151) were determined. Genotyping was performed on isolated genomic DNA of study participants using PCR followed by a multiplex ligation detection reaction (LDR). The percentage of the population who had the rare homozygote alleles for rs6511720 (T/T), rs2066714 (G/G), rs10892151 (T/T) and rs662799 (G/G) among case subjects were 5.5%, 14.4%, 6.6% and 10.0% whiles 2.0% 9.1%, 6.5% and 4.0% were observed among control subjects. There were statistically significant differences in the genotypic prevalence of APOA5 (p = 0.0357) and LDLR polymorphisms (p = 0.0387) between case and control subjects. Compared to the AA genotype of the APOA5 polymorphisms, individuals with the rare homozygote genotype [aOR = 2.38, 95%CI(1.06–6.54), p = 0.004] were significantly associated with an increased likelihood of developing dyslipidemia after controlling for age, gender, treatment duration, CD4 counts and BMI. Moreover, individuals with the rare homozygous genotype of ABCA1 (G/G) [aOR = 10.7(1.3–88.7), p = 0.0280] and LDLR (rs6511720) G>T [aOR = 61.2(7.6–493.4), p<0.0001) were more likely to have high levels of total cholesterol levels. Our data accentuate the presence of SNPs in four candidate genes and their association with dyslipidemia among HIV patients exposed to ART in the Ghanaian population, especially variants in APOA5-rs662799 and LDLR rs6511720 respectively. These findings provide baseline information that necessitates a pre-symptomatic strategy for monitoring dyslipidemia in ART-treated HIV patients. There is a need for longitudinal studies to validate a comprehensive number of SNPs and their associations with dyslipidemia.Item Efficacy of Amodiaquine/Artesunate combination therapy for uncomplicated malaria in children under five years in Ghana(Ghana Medical Journal 42(2): 55-60, 2008) Koram, K.A.; Quaye, L.; Abuaku, B.K.Background: In 2005, following several years of declining efficacy of chloroquine, the Ministry of Health recommended the use of Amodiaquine/Artesunate combination therapy for the treatment of uncomplicated malaria. A system of continuous monitoring of therapeutic responses has been established in 10 district hospitals across the country. The data gathered will enable National Malaria Control Programme (NMCP) to respond to changes in the efficacy of the new treatment in a timely manner. Objectives: To determine the 28 day therapeutic efficacy of Amodiaquine/Artesunate (AQ/AS) combination treatment in children with uncomplicated malaria in Ghana. Methods: Children aged 6 ¡V 59 months attending clinic with signs/symptoms of uncomplicated malaria at 9 district hospitals (3 in each of the 3 ecoepidemiological zones of the country) were eligible for enrolment. Enrolled children were followed up after treatment for a total of 28 days to record the clinical and parasitological resolution of their malaria episode as well as any adverse drug reactions. Results: Treatment resulted in rapid and complete cure in almost all the children; 99.3% 14 days after treatment and 93.0%, 28 days after treatment. The majority of treatment failures on D28 were seen in the 3 sites located in the forest zones (Sunyani, Bekwai and Begoro). There was no case of Early Treatment Failure at both D14 and D28 assessments. Adverse events (AE¡¦s) were minimal, less than 4%, with the most common complaint being vomiting. Conclusion: AQ/AS combination for uncomplicated malaria is efficacious and safe in children less than 5 years.Item Molecular epidemiology of bovine tuberculosis in Northern Ghana identifies several uncharacterized bovine spoligotypes and suggests possible zoonotic transmission(PLOS NEGLECTED TROPICAL DISEASES, 2022) Acquah, S.E.K.; Asare, P.; Danso, E.K; Tetteh, P.; Tetteh, A.Y.; Boateng, D.; Osei-Wusu, S.; Afum, T.; Ayamdooh, Y.I.; Akugre, E.A.; Samad, O.A.; Quaye, L.; Obiri-Danso, K.; Kock, R.; Asante-Poku, A.; Yeboah-Manu, D.Objective We conducted an abattoir-based cross-sectional study in the five administrative regions of Northern Ghana to determine the distribution of bovine tuberculosis (BTB) among slaughtered carcasses and identify the possibility of zoonotic transmission. Methods Direct smear microscopy was done on 438 tuberculosis-like lesions from selected cattle organs and cultured on Lowenstein-Jensen media. Acid-fast bacilli (AFB) isolates were confirmed as members of the Mycobacterium tuberculosis complex (MTBC) by PCR amplification of IS6110 and rpoß. Characterization and assignment into MTBC lineage and sublineage were done by spoligotyping, with the aid of the SITVIT2, miruvntrplus and mbovis. org databases. Spoligotype data was compared to that of clinical M. bovis isolates from the same regions to identify similarities. Results A total of 319/438 (72.8%) lesion homogenates were smear positive out of which, 84.6% (270/319) had microscopic grade of at least 1+ for AFB. Two hundred and sixty-five samples (265/438; 60.5%) were culture positive, of which 212 (80.0%) were MTBC. Approximately 16.7% (34/203) of the isolates with correctly defined spoligotypes were negative for IS6110 PCR but were confirmed by rpoß. Spoligotyping characterized 203 isolates as M. bovis (198, 97.5%), M. caprae (3, 1.5%), M. tuberculosis (Mtbss) lineage (L) 4 Cameroon sub-lineage, (1, 0.5%), and M. africanum (Maf) L6 (1, 0.5%). A total of 53 unique spoligotype patterns were identified across the five administrative regions (33 and 28 were identified as orphan respectively by the SITVIT2 and mbovis.org databases), with the most dominant spoligotype being SIT1037/ SB0944 (77/203, 37.93%). Analysis of the bovine and human M. bovis isolates showed 75% (3/4) human M. bovis isolates sharing the same spoligotype pattern with the bovine isolates. Conclusion Our study identified that approximately 29% of M. bovis strains causing BTB in Northern Ghana are caused by uncharacterized spoligotypes. Our findings suggest possible zoonotic transmission and highlight the need for BTB disease control in Northern Ghana.Item A SYBR Green 1-based in vitro test of susceptibility of Ghanaian Plasmodium falciparum clinical isolates to a panel of anti-malarial drugs(Malaria Journal, 2013-12) Quashie, N.B.; Duah, N.O.; Abuaku, B.; Quaye, L.; Ayanful-Torgby, R.; Akwoviah, G.A.; Kweku, M.; Johnson, J.D.; Lucchi, N.W.; Udhayakumar, V.; Duplessis, C.; Kronmann, K.C.; Koram, K.A.Background: Based on report of declining efficacy of chloroquine, Ghana shifted to the use of artemisinin-based combination therapy (ACT) in 2005 as the first-line anti-malarial drug. Since then, there has not been any major evaluation of the efficacy of anti-malarial drugs in Ghana in vitro. The sensitivity of Ghanaian Plasmodium falciparum isolates to anti-malarial drugs was, therefore, assessed and the data compared with that obtained prior to the change in the malaria treatment policy. Methods. A SYBR Green 1 fluorescent-based in vitro drug sensitivity assay was used to assess the susceptibility of clinical isolates of P. falciparum to a panel of 12 anti-malarial drugs in three distinct eco-epidemiological zones in Ghana. The isolates were obtained from children visiting health facilities in sentinel sites located in Hohoe, Navrongo and Cape Coast municipalities. The concentration of anti-malarial drug inhibiting parasite growth by 50% (IC§ssub§50§esub§) for each drug was estimated using the online program, ICEstimator. Results: Pooled results from all the sentinel sites indicated geometric mean IC§ssub§50§esub§ values of 1.60, 3.80, 4.00, 4.56, 5.20, 6.11, 10.12, 28.32, 31.56, 93.60, 107.20, and 8952.50 nM for atovaquone, artesunate, dihydroartemisin, artemether, lumefantrine, amodiaquine, mefloquine, piperaquine, chloroquine, tafenoquine, quinine, and doxycycline, respectively. With reference to the literature threshold value indicative of resistance, the parasites showed resistance to all the test drugs except the artemisinin derivatives, atovaquone and to a lesser extent, lumefantrine. There was nearly a two-fold decrease in the IC§ssub§ 50§esub§ value determined for chloroquine in this study compared to that determined in 2004 (57.56 nM). This observation is important, since it suggests a significant improvement in the efficacy of chloroquine, probably as a direct consequence of reduced drug pressure after cessation of its use. Compared to that measured prior to the change in treatment policy, significant elevation of artesunate IC§ssub§50§esub§ value was observed. The results also suggest the existence of possible cross-resistance among some of the test drugs. Conclusion: Ghanaian P. falciparum isolates, to some extent, have become susceptible to chloroquine in vitro, however the increasing trend in artesunate IC§ssub§50§esub§ value observed should be of concern. Continuous monitoring of ACT in Ghana is recommended. © 2013 Quashie et al.; licensee BioMed Central Ltd.Item Therapeutic efficacy of artemether-lumefantrine combination in the treatment of uncomplicated malaria among children under 5 years in 3 ecological zones in Ghana(2012-10-15) Abuaku, B.; Duah, N.; Quaye, L.; Quashie, N.; Koram, K.Item Therapeutic efficacy of artemether-lumefantrine combination in the treatment of uncomplicated malaria among children under five years of age in three ecological zones in Ghana(2012-11-22) Abuaku, B.; Duah, N.; Quaye, L.; Quashie, N.; Koram, K.Abstract Background In 2008, artemether - lumefantrine (AL) and dihydroartemisinin - piperaquine (DHAP) were added to artesunate - amodiaquine (AS-AQ) as first-line drugs for uncomplicated malaria in Ghana. The introduction of new drugs calls for continuous monitoring of these drugs to provide timely information on trends of their efficacy and safety to enhance timely evidence-based decision making by the National Malaria Control Programme. In this regard, the therapeutic efficacy of AL was monitored from September 2010 to April 2011 in four sentinel sites representing the three main ecological zones of the country. Methods The study was a one-arm prospective evaluation of clinical and parasitological responses to directly observed treatment for uncomplicated malaria among children aged 6 months to 59 months using the 2009 WHO protocol for surveillance of anti-malarial drug efficacy. Children recruited into the study received weight-based 20/120 mg AL at 0, 8, 24, 36, 48, and 60 hrs. Parasitaemia levels were assessed on days 2, 3, 7, 14, 21, 28, and at any time a study child was brought to the clinic with fever. Results A total of 175 children were enrolled into the study: 56 in the savanna zone, 78 in the forest zone and 41 in the coastal zone. Per-protocol analysis showed that the overall PCR-corrected cure rates on day 14 and day 28 were 96.5% (95% CI: 92.1, 98.6) and 95.4% (95% CI: 90.3, 98.0), respectively, with statistically significant differences between the ecological zones. The 90.4% day-28 cure rate observed in the savannah zone (95% CI: 78.2, 96.4) was significantly the lowest compared with 100% (95% CI: 93.2, 99.9) in the forest zone and 93.8% (95% CI: 77.8, 98.9) in the coastal zone (P = 0.017). Fever and parasite clearance were slower among children enrolled in the savannah zone. Gametocytaemia after day-3 post-treatment was rare in all the zones. Conclusions The study has shown that AL remains efficacious in Ghana with significant ecologic zonal differences. The savannah zone may be a potential zone for any emergence of resistant alleles as a result of the slower parasite clearance observed in the zone.Item Therapeutic efficacy of artemether-lumefantrine combination in the treatment of uncomplicated malaria among children under five years of age in three ecological zones in Ghana.(2012) Abuaku, B.; Duah, N.; Quaye, L.; Quashie, N.; Koram, K.A.Background: In 2008, artemether - lumefantrine (AL) and dihydroartemisinin - piperaquine (DHAP) were added to artesunate - amodiaquine (AS-AQ) as first-line drugs for uncomplicated malaria in Ghana. The introduction of new drugs calls for continuous monitoring of these drugs to provide timely information on trends of their efficacy and safety to enhance timely evidence-based decision making by the National Malaria Control Programme. In this regard, the therapeutic efficacy of AL was monitored from September 2010 to April 2011 in four sentinel sites representing the three main ecological zones of the country. Methods. The study was a one-arm prospective evaluation of clinical and parasitological responses to directly observed treatment for uncomplicated malaria among children aged 6months to 59months using the 2009 WHO protocol for surveillance of anti-malarial drug efficacy. Children recruited into the study received weight-based 20/120mg AL at 0, 8, 24, 36, 48, and 60hrs. Parasitaemia levels were assessed on days 2, 3, 7, 14, 21, 28, and at any time a study child was brought to the clinic with fever. Results: A total of 175 children were enrolled into the study: 56 in the savanna zone, 78 in the forest zone and 41 in the coastal zone. Per-protocol analysis showed that the overall PCR-corrected cure rates on day 14 and day 28 were 96.5% (95% CI: 92.1, 98.6) and 95.4% (95% CI: 90.3, 98.0), respectively, with statistically significant differences between the ecological zones. The 90.4%day-28 cure rate observed in the savannah zone (95% CI: 78.2, 96.4) was significantly the lowest compared with 100% (95% CI: 93.2, 99.9) in the forest zone and 93.8% (95% CI: 77.8, 98.9) in the coastal zone (P=0.017). Fever and parasite clearance were slower among children enrolled in the savannah zone. Gametocytaemia after day-3 post-treatment was rare in all the zones. Conclusions: The study has shown that AL remains efficacious in Ghana with significant ecologic zonal differences. The savannah zone may be a potential zone for any emergence of resistant alleles as a result of the slower parasite clearance observed in the zone. © 2012 Abuaku et al.; licensee BioMed Central Ltd.Item Therapeutic efficacy of artesunate– amodiaquine and artemether–lumefantrine combinations for uncomplicated malaria in 10 sentinel sites across Ghana: 2015–2017(Malaria Journal, 2019-06-19) Abuaku, B.; Duah‑Quashie, N.O.; Quaye, L.; Matrevi, S.A.; Quashie, N.; Gyasi, A.; Owusu‑Antwi, F.; Malm, K.; Koram, kBackground: Routine surveillance on the therapeutic efficacy of artemisinin-based combination therapy (ACT) has been ongoing in Ghana since 2005. The sixth round of surveillance was conducted between 2015 and 2017 to determine the therapeutic efficacy of artesunate–amodiaquine (AS–AQ) and artemether–lumefantrine (AL) in 10 sentinel sites across the country. Methods: The study was a one-arm, prospective, evaluation of the clinical, parasitological, and haematological responses to directly observed treatment with AS–AQ and AL among children 6 months to 9 years old with uncomplicated falciparum malaria. The WHO 2009 protocol on surveillance of anti-malaria drug efficacy was used for the study with primary outcomes as prevalence of day 3 parasitaemia and clinical and parasitological cure rates on day 28. Secondary outcomes assessed included patterns of fever and parasite clearance as well as changes in haemoglobin concentration. Results: Day 3 parasitaemia was absent in all sites following treatment with AS–AQ whilst only one person (0.2%) was parasitaemic on day 3 following treatment with AL. Day 28 PCR-corrected cure rates following treatment with AS–AQ ranged between 96.7% (95% CI 88.5–99.6) and 100%, yielding a national rate of 99.2% (95% CI 97.7–99.7). Day 28 PCR-corrected cure rates following treatment with AL ranged between 91.3% (95% CI 79.2–97.6) and 100%, yielding a national rate of 96% (95% CI 93.5–97.6). Prevalence of fever declined by 88.4 and 80.4% after first day of treatment with AS–AQ and AL, respectively, whilst prevalence of parasitaemia on day 2 was 2.1% for AS–AQ and 1.5% for AL. Gametocytaemia was maintained at low levels (< 5%) during the 3 days of treatment. Post-treatment mean haemoglobin concentration was significantly higher than pre-treatment concentration following treatment with either AS–AQ or AL. Conclusions: The therapeutic efficacy of AS–AQ and AL is over 90% in sentinel sites across Ghana. The two antimalarial drugs therefore remain efficacious in the treatment of uncomplicated malaria in the country and continue to achieve rapid fever and parasite clearance as well as low gametocyte carriage rates and improved post-treatment mean haemoglobin concentration.