Browsing by Author "Adjei, G.O."

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A randomized trial of artesunate-amodiaquine versus artemether-lumefantrine in Ghanaian paediatric sickle cell and non-sickle cell disease patients with acute uncomplicated malaria
(2014-09-19) Adjei, G.O.; Goka, B.Q.; Enweronu-Laryea, C.C.; Rodrigues, O.P.; Renner, L.; Sulley, A.M.; Alifrangis, M.; Khalil, I.; Kurtzhals, J.A.
Abstract Background Sickle cell disease (SCD) is a genetic disorder common in malaria endemic areas. In endemic areas, malaria is a major cause of morbidity and mortality among SCD patients. This suggests the need for prompt initiation of efficacious anti-malarial therapy in SCD patients with acute malaria. However, there is no information to date, on the efficacy or safety of artemisinin combination therapy when used for malaria treatment in SCD patients. Methods Children with SCD and acute uncomplicated malaria (n = 60) were randomized to treatment with artesunate-amodiaquine (AA), or artemether-lumefantrine (AL). A comparison group of non-SCD children (HbAA genotype; n = 59) with uncomplicated malaria were also randomized to treatment with AA or AL. Recruited children were followed up and selected investigations were done on days 1, 2, 3, 7, 14, 28, 35, and 42. Selected clinical and laboratory parameters of the SCD patients were also compared with a group of malaria-negative SCD children (n = 82) in steady state. Results The parasite densities on admission were significantly lower in the SCD group, compared with the non-SCD group (p = 0.0006). The parasite reduction ratio (PRR) was lower, clearance was slower (p < 0.0001), and time for initial parasitaemia to decline by 50 and 90% were longer for the SCD group. Adequate clinical and parasitological response (ACPR) on day 28 was 98.3% (58/59) in the SCD group and 100% (57/57) in the non-SCD group. Corresponding ACPR rates on day 42 were 96.5% (55/57) in the SCD group and 96.4% (53/55) in the non-SCD group. The fractional changes in haemoglobin, platelets and white blood cell counts between baseline (day 0) and endpoint (day 42) were 16.9, 40.6 and 92.3%, respectively, for the SCD group, and, 12.3, 48.8 and 7.5%, respectively, for the non-SCD group. There were no differences in these indices between AA- and AL-treated subjects. Conclusions The parasite clearance of SCD children with uncomplicated malaria was slower compared with non-SCD children. AA and AL showed similar clinical and parasitological effects in the SCD and non-SCD groups. The alterations in WBC and platelet counts may have implications for SCD severity. Trial registration Current controlled trials ISRCTN96891086.
Acceptability of rapid diagnostic test-based management of malaria among caregivers of under-five children in rural Ghana
(PLoS ONE, 2012) Baiden, F.; Owusu-Agyei, S.; Okyere, E.; Tivura, M.; Adjei, G.O.; Chandramohan, D.; Webster, J.
Introduction WHO now recommends test-based management of malaria (TBMM) across all age-groups. This implies artemisinin-based combination treatment (ACT) should be restricted to rapid diagnostic test (RDT)-positive cases. This is a departure from what caregivers in rural communities have been used to for many years. Methods We conducted a survey among caregivers living close to 32 health centres in six districts in rural Ghana and used logistic regression to explore factors likely to influence caregiver acceptability of RDT based case management and concern about the denial of ACT on account of negative RDT results. Focus group discussions were conducted to explain the quantitative findings and to elicit further factors. Results A total of 3047 caregivers were interviewed. Nearly all (98%) reported a preference for TBMM over presumptive treatment. Caregivers who preferred TBMM were less likely to be concerned about the denial of ACT to their test-negative children (O.R. 0.57, 95%C.I. 0.33–0.98). Compared with caregivers who had never secured national health insurance cover, caregivers who had valid (adjusted O.R. 1.30, 95% CI 1.07–1.61) or expired (adjusted O.R. 1.38, 95% CI 1.12–1.73) insurance cover were more likely to be concerned about the denial of ACT to their RDT-negative children. Major factors that promote TBMM acceptability include the perception that a blood test at health centre level represents improvement in the quality of care, leads to improvement in treatment outcomes, and offers opportunity for better communication between health workers and caregivers. Acceptability is also enhanced by engaging caregivers in the procedures of the test. Apprehensions about negative health worker attitude could however undermine acceptance. Conclusion Test (RDT)-based management of malaria in under-five children is likely to be acceptable to caregivers in rural Ghana. The quality of caregiver-health worker interaction needs to be improved if acceptability is to be sustained.
Amodiaquine-artesunate vs artemether-lumefantrine for uncomplicated malaria in Ghanaian children: a randomized efficacy and safety trial with one year follow-up
(2008-07-11) Adjei, G.O.; Kurtzhals, J.A.L.; Rodrigues, O.P.; Alifrangis, M.; Hoegberg, L.C.G.; Kitcher, E.D.; Badoe, E.V.; Lamptey, R.; Goka, B.Q.
Abstract Background Artesunate-amodiaquine (AS+AQ) and artemether-lumefantrine (AM-L) are efficacious artemisinin combination therapy (ACT) regimens that have been widely adopted in sub-Saharan Africa. However, there is little information on the efficacy of these regimens on subsequent episodes beyond 28 days, or on the safety of repeated treatments. Methods Children aged six months to 14 years with uncomplicated malaria were randomly assigned to treatment with AS+AQ (n = 116), or AM-L (n = 111). Recruited subjects were followed-up, initially for 28 days, and then monthly for up to one year. All subsequent attacks of uncomplicated malaria after 28 days were treated with the same regimen as at randomization. Investigations aimed at determining efficacy and side effects were conducted. Results Adequate clinical and parasitological response in subjects with evaluable end-points were, 97.1% (100/103) and 98.2% (107/109) on day 14, and 94.2% (97/103) and 95.3% (102/107) on day 28 in the AM-L and AS+AQ groups, respectively. Similar results were obtained after PCR correction. The incidence of malaria attacks in the year following recruitment was similar between the two treatment groups (p = 0.93). There was a high incidence of potentially AQ-resistant parasites in the study area. The incidence of adverse events, such as pruritus, fatigue and neutropaenia were similar in the two treatment groups. No patient showed signs of hearing impairment, and no abnormal neurological signs were observed during one year of follow-up. Other adverse events were mild in intensity and overlapped with known malaria symptomatology. No adverse event exacerbation was observed in any of the subjects who received multiple treatment courses with these ACT regimens during one year follow-up. Conclusion AS+AQ and AM-L were efficacious for treatment of children with uncomplicated malaria in Ghana and drug-related adverse events were rare in treated subjects during one year of follow-up. The high prevalence of potentially AQ resistant parasites raises questions about the utility of AQ as a partner drug for ACT in Ghana. The efficacy of AS+AQ in Ghana requires, therefore, continuous monitoring and evaluation. Trial registration NCT 00406146 http://www.clinicaltrials.gov
Amodiaquine-associated adverse effects after inadvertent overdose and after a standard therapeutic dose
(Ghana Medical Journal 43(3):135-8, 2009) Adjei, G.O.; Goka, B.Q.; Rodrigues, O.P.; Hoegberg, L.C.; Alifrangis, M.; Kurtzhals, J.
A case of an acute dystonic reaction in a child presumptively treated for malaria with amodiaquine, and a case of persistent asymptomatic bradycardia in another child with mild pulmonary stenosis treated with a standard dose of amodiaquine for parasitologically confirmed uncomplicated malaria, is reported. Both subjects were homozygous for the wild type allele of cytochrome P450 2C8, the main enzyme responsible for amodiaquine metabolism. In both subjects, plasma concentrations of N-desethylamodiaquine and N-bis-desethylamodiaquine, the main metabolites of amodiaquine, were normal. No other drugs were detectable in the plasma of these two subjects after further toxicological screening. These observations, which suggest altered metabolism in the subject with an acute dystonic reaction, support the assertion that amodiaquine-associated dystonia is an idiosyncratic reaction. However, the occurrence of bradycardia after a standard dose of amodiaquine, which coincided with the time of expected peak concentrations of the active metabolite of amodiaquine, suggests a direct drug effect. These less reported adverse effects are likely to increase in parallel with the increased use of amodiaquine as a partner drug for combination therapy of malaria in Ghana. Further studies aimed at elucidating the mechanisms underlying these effects are, therefore, required.
Antioxidant Status of Sickle Cell Disease Children with and without Malaria at the Korle-Bu Teaching Hospital
(University of Ghana, 2013-07) Dzigba, P.; Oppong, S.Y.; Adjei, G.O.; University of Ghana, College of Health Sciences, School of Biomedical and Allied Health Sciences, Department of Chemical Pathology
Background Sickle cell disease (SCD) is a hereditary disorder prevalent in malaria endemic areas, in which there is state of chronic vasculopathy characterized by endothelial dysfunction, and increased oxidative stress. SCD patients with malaria may experience worse outcomes because malaria infection in SCD leads to depletion of antioxidants which may complicate the disease. Few studies, however, have evaluated the antioxidant status of SCD patients with discrete clinical syndromes. There is also little information on the extent to which malaria depletes antioxidants in SCD patients. Setting The study was carried out at the Department of Child Health, Korle-Bu Teaching Hospital and the Centre for Tropical Clinical Pharmacology and Therapeutics. Aim The objective of the study was to investigate the levels of selected antioxidants in acutely ill sickle cell disease children with and without malaria. Methods Blood samples of 121 children between ages of 6 months and 13 years presenting with sickle cell and acute febrile illness were recruited. Known SCD children with confirmed malaria (n=26) or bacteremia (n=21) were enrolled. SCD children in steady state (n=21) visiting clinic for routine check- up as well as children with haemoglobin genotype, HbAA with malaria (n=26) and without malaria (n=25) attending the Korle-Bu Polyclinic were recruited. Relevant demographic data was recorded and clinical examination was undertaken. Haematological parameters as well as levels of the following antioxidants: reduced glutathione (GSH), glutathione peroxidase (GPx), superoxide dismutase (SOD) and ascorbic acid (ASC) were determined for each group. Results The mean levels of the antioxidants SOD, GSH and ASC was higher in non-SCD children, whowere malaria negative (AAM-) compared to SCD steady state children. The results for the anitoxidants were; SOD ( AAM- = 27.51, SCDSS= 25.85 ) U/ml, GSH( AAM- = 10800, SCDSS= 4465) mg/dl and ASC( AAM- = 3567, SCDSS= 2598) mg/dl. However, the reverse was found for GPx ( AAM- = 29.8, SCDSS= 259) U/, where mean activity was lower for non- sickle cell malaria negative children. Also, the mean levels of SOD, GPx and ASC in confirmed malaria positive children (SCDM+, AAM+) had lower activity than the non-malaria children (SCDSS, AAM-). Results for the antioxidant s were; SOD ( SCDSS =25.85, SCDM+=18.51 / AAM- =27.51 , AAM+= 23.99) U/ml , GPx ( SCDSS =259, SCDM+= 92.60 / AAM- =29.8, AAM+= 7.05) U/ml and ASC( SCDSS = 2598, SCDM+= 2401/ AAM- =3567, AAM+= 2514) mg/dl. However, the mean GSH ( SCDSS = 4465, SCDM+= 7941/ AAM- =10800, AAM+= 11700) mg/dl was higher for malaria positive compared to malaria negative groups.
Are currently deployed artemisinins neurotoxic?
(Toxicology Letters, 2006) Adjei, G.O.; Goka, B.Q.; Kurtzhals, J.A.L.; Gordi, T.
In vitro, animal, and human clinical studies suggest currently deployed artemisinins possess neurotoxic potential. A specific and consistent pattern of brainstem injuries that includes auditory processing centers has been reported from all laboratory animals studied. Hearing loss, ataxia, and tremor are reported from humans. Neurotoxicity appears mediated in part through artemisinin induced oxidative stress in exposed brainstems. In vitro studies suggest that artemisinin neurotoxicity does not manifest immediately upon exposure, but that once commenced it is inevitable and irreversible; extrapolation from in vitro data suggests that 14 days may possibly be required for full development, casting doubt upon some animal safety studies and human necropsy studies. Uncertainty remains over the neurotoxicity of currently deployed artemisinins, and their safety profile should be reviewed, especially in pediatric use. The development of non-neurotoxic artemisinins is possible and should be encouraged.
Artemether-lumefantrine: An oral antimalarial for uncomplicated malaria in children
(Expert Review of Anti-Infective Therapy, 2009-09) Adjei, G.O.; Goka, B.Q.; Binka, F.; Al Kurtzhals, J.
Artemether-lumefantrine (AL; Coartem®, Riamet®) is the first fixed-dose artemisinin combination therapy (ACT) regimen to be manufactured under Good Manufacturing Practice conditions, and is the most widely adopted ACT regimen used in malaria control programs. AL is approved for the treatment of uncomplicated malaria in adults, children and infants, and as treatment of uncomplicated malaria in nonimmune travelers returning from malarious areas. AL is efficacious for treating uncomplicated malaria in children and the frequency of associated adverse events is not higher than other available ACT regimens. In this review, available evidence on efficacy and safety of AL in the treatment of uncomplicated malaria, with emphasis on children where appropriate, and focusing on characteristics that are potentially important for malaria control policy decisions, are presented and discussed. © 2009 Expert Reviews Ltd.
Artesunate plus amodiaquine combination therapy - reviewing the evidence
(Drug Development Research, 2010) Adjei, G.O.; Kudzi, W.; Dodoo, A.; Kurtzhals, J.A.L.
The combination of artesunate plus amodiaquine (AS/AQ) is, next to the fixed-dose combination of artemether-lumefantrine, the most widely adopted artemisinin combination therapy (ACT) regimen being used as first-line therapy for uncomplicated malaria by National Malaria Control Programs in sub-Saharan Africa. In contrast to other ACT regimens in current use, on which reviews of the available evidence on safety and efficacy have been periodically published, no, or few summaries of the extensive data available on the safety and efficacy of this widely used ACT are available in the published literature. The available evidence on AS/AQ indicates high efficacy of this combination in children, variable tolerability in adults, and an interaction between artesunate and amodiaquine that could have implications for medium term efficacy or safety of the combination. In this article, a review of the available evidence on the efficacy and safety on AS/AQ, with a particular focus on parameters that could have operational significance for malaria control in endemic areas, is presented and discussed. Drug Dev Res 71: 33–43, 2010. © 2009 Wiley-Liss, Inc.
Artesunate plus amodiaquine combination therapy - reviewing the evidence
(Drug Development Research, 2010) Adjei, G.O.; Kudzi, W.; Dodoo, A.; Kurtzhals, J.A.L
The combination of artesunate plus amodiaquine (AS/AQ) is, next to the fixed-dose combination of artemether-lumefantrine, the most widely adopted artemisinin combination therapy (ACT) regimen being used as first-line therapy for uncomplicated malaria by National Malaria Control Programs in sub-Saharan Africa. In contrast to other ACT regimens in current use, on which reviews of the available evidence on safety and efficacy have been periodically published, no, or few summaries of the extensive data available on the safety and efficacy of this widely used ACT are available in the published literature. The available evidence on AS/AQ indicates high efficacy of this combination in children, variable tolerability in adults, and an interaction between artesunate and amodiaquine that could have implications for medium term efficacy or safety of the combination. In this article, a review of the available evidence on the efficacy and safety on AS/AQ, with a particular focus on parameters that could have operational significance for malaria control in endemic areas, is presented and discussed. Drug Dev Res 71:33–43, 2010.
Artesunate Plus Amodiaquine Combination Therapy: Reviewing the Evidence
(Drug Dev. Res. (71): 33-43, 2010) Kudzi, W.; Adjei, G.O.; Dodoo, A.; Kurtzhals, J.A.L.
Assessment of artemisinin tolerance in Plasmodium falciparum clinical isolates in children with uncomplicated malaria in Ghana
(Malaria Journal, 2023) Ahorhorlu, S.Y.; Quashie, N.B.; Jensen, N.W.; Kudzi, W.; Nartey, E.T.; Duah‑Quashie, N.O.; Zoiku, F.; Dzudzor, B.; Wang, C.W.; Hansson, H.; Alifrangis, M.; Adjei, G.O.
Background Artemisinin-based combination therapy (ACT) is the first-line treatment for uncomplicated malaria in Ghana. Artemisinin (ART) tolerance in Plasmodium falciparum has arisen in Southeast Asia and recently, in parts of East Africa. This is ascribed to the survival of ring-stage parasites post treatment. The present study sought to assess and characterize correlates of potential ART tolerance based on post-treatment parasite clearance, ex vivo and in vitro drug sensitivity, and molecular markers of drug resistance in P. falciparum isolates from children with uncomplicated malaria in Ghana. Methods Six months to fourteen years old children presenting with acute uncomplicated malaria (n=115) were enrolled in two hospitals and a Health Centre in Ghana’s Greater Accra region and treated with artemether-lume‑ fantrine (AL) according to body weight. Pre- and post-treatment parasitaemia (day 0 and day 3) was confirmed by microscopy. The ex vivo ring-stage survival assay (RSA) was used to detect percent ring survival while the 72 h SYBR Green I assay was used to measure the 50% inhibition concentration (IC50s) of ART and its derivatives and partner drugs. Genetic markers of drug tolerance /resistance were evaluated using selective whole genome sequencing. Results Of the total of 115 participants, 85 were successfully followed up on day 3 post-treatment and 2/85 (2.4%) had parasitaemia. The IC50 values of ART, artesunate (AS), artemether (AM), dihydroartemisinin (DHA), amodiaquine (AQ), and lumefantrine (LUM) were not indicative of drug tolerance. However, 7/90 (7.8%) pre-treatment isolates had>10% ring survival rates against DHA. Of the four isolates (2 RSA positive and 2 RSA negative) with high genomic coverage, P. falciparum (Pf ) kelch 13 K188* and Pfcoronin V424I mutations were only present in the two RSA positive isolates with>10% ring survival rates. Conclusions The observed low proportion of participants with day-3 post-treatment parasitaemia is consistent with rapid ART clearance. However, the increased rates of survival observed in the ex vivo RSA against DHA, maybe a pointer of an early start of ART tolerance. Furthermore, the role of two novel mutations in PfK13 and Pfcoronin genes, harboured by the two RSA positive isolates that had high ring survival in the present study, remains to be elucidated.
An assessment of the likely acceptability of vaginal microbicides for HIV prevention among women in rural Ghana
(BMC Women's Health, 2012) Abdulai, M.A.; Baiden, F.; Adjei, G.O.; Afari-Asiedu, S.; Adjei, K.; Tawiah, C.; Newton, S.
Background The findings of the CAPRISA tenofovir studies have raised expectations that soon an approved microbicide would be available. However it is in only a limited number of countries in sub-Saharan Africa that the acceptability of microbicides has been evaluated. We conducted a study to assess the acceptability of vaginal microbicides among women in rural Ghana. Methods The study employs a mixed method design, using cross-sectional survey and focus group discussions to further understand issues related to awareness and attitudes towards microbicide development, acceptability and perceived partner attitudes among pregnant women attending antenatal clinic in two health facilities in the Kintampo North municipality of Ghana. We used logistic regression to identify possible predictors of microbicide acceptability among the women surveyed. Results Although only 2% of the 504 women were aware of the development of microbicides, 95% were willing to use one when it became available. The cost of a microbicide that will be considered affordable to 50% of women was US$0.75. Although there were concerns about possible wetting effect, gel or creams were the most preferred (68% of women) formulation. Although 71% thought their partners will find microbicide acceptable, apprehensions about the feasibility of and consequences of failed discreet use were evident. 49% of women were concerned about possible negative effect of microbicide on sexual pleasure. Perceived partner acceptability (O.R. =17.7; 95%C.I. 5.03-62.5) and possibility of discreet use (O.R. =8.9 95%C.I. 2.63-30.13) were the important predictors of microbicide acceptability. Conclusion Achieving microbicide acceptability among male partners should be made a part of the promotive interventions for ensuring effective use among women in rural Ghana.
Association Between Selected Single Nucleotide Polymorphisms in Globin and Related Genes and Response to Hydroxyurea Therapy in Ghanaian Children with Sickle Cell Disease
(Pharmacogenomics and Personalized Medicine, 2022) Manu, G.P.; Segbefia, C.; N’guessan, B.B.; Coffie, S.A.; Adjei, G.O.
Background: Sickle cell disease (SCD) is a group of genetic disorders affecting the structure and function of haemoglobin. Hydroxyurea (HU) stimulates fetal haemoglobin (HbF) and reduces sickle erythrocyte-endothelial cell interaction. However, the degree of HbF response to HU varies, with HbF expression-associated single nucleotide polymorphisms (SNPs) in quantitative trait loci (QTL) been implicated. We investigated the relationship between four SNPs (rs11886868, rs6706648, rs7606173 and 158C/T Xmn1) in two QTL (B-cell lymphoma 11A (BCL11A) and Xmn1) and HbF levels in children with SCD in Accra, Ghana. Methods: A total of 110 children with SCD in steady-state, comprising 64 and 46 SCD children treated with HU (HU+) or with no history of HU therapy (HU-), respectively, were recruited. HbF levels were measured in peripheral blood by alkali denaturation and SNPs were genotyped using polymerase chain reaction and restriction fragment length polymorphism. Results: The presence of SNPs (rs11886868, rs6706648, rs7606173 and −158C/T Xmn1) was identified. Observed heterozygosity and homozygosity for the derived alleles were 45.7%, 82.6%, 21.7% and 39.1% in rs11886868, rs6706648, rs7606173 and −158C/T Xmn1 polymorphisms, respectively, for the HU+ population. Observed frequencies of the minor alleles were 0.204, 0.477, 0.171 and 0.190 for rs11886868, rs6706648, rs7606173 and −158C/T Xmn1 polymorphisms, respectively. The three BCL11A SNPs in the HU+ population showed homozygous individuals for rs11886868 (CC), rs6706648 (CC) and heterozygous or homozygous mutant individuals for rs7606173 (CG/GG) having higher HbF values. The combined effect of the SNPs was associated with variance in HbF levels in the HU+ population. The BCL11A SNP, rs6706648 was strongly associated with HbF levels and the C allele frequency, with significantly elevated HbF levels. Conclusion: An association between the various variants and combined effect of SNPs and HbF among children with SCD was found and confirms the known association between HU intake and increased HbF in SCD.
The burden and characteristics of peripheral arterial disease in patients undergoing amputation in Korle Bu Teaching Hospital, Accra, Ghana
(Ghana Medical Journal, 2017-09) Bediako-Bowan, A.A.A.; Adjei, G.O.; Clegg-Lamptey, J.N.; Naaeder, S.B.
Background: To determine the prevalence of Peripheral Arterial Disease (PAD) and associated risk factors in patients undergoing amputation at the Korle Bu Teaching Hospital (KBTH), Accra, Ghana. Objectives: A cross- sectional study of all patients undergoing lower extremity amputation at the Department of Surgery, KBTH. Materials: A coded questionnaire was used to ascertain risk factors for PAD. The Edinburgh Claudication Questionnaire was used to determine symptomatic PAD and a 5 mmHz hand held Summit® Doppler together with an Accoson ® sphygmomanometer was used to determine PAD and its severity. Method: Clinical diagnosis of symptomatic PAD was made using a symptom-based questionnaire and signs of PAD determined by measuring the ankle brachial pressure index (ABPI) by means of a handheld Doppler and sphygmomanometer. Risk factors were determined using the coded questionnaire and related to the occurrence and severity of PAD. Results: The prevalence of PAD among recruited participants was 71%. Twenty-eight per cent of participants with PAD in the index limb also showed signs of PAD in the other limb. The diagnosis of PAD was made in 71%, using ABPI, and 13%, using ECQ. Twenty-seven per cent of patient with hypertension, seventeen per cent with diabetes and all patients with hypercholesterolemia were not on any form of medication. Conclusion: There is a high prevalence of PAD among patients undergoing lower extremity amputation at the KBTH. The majority of PAD patients presented with moderate to severe PAD. Instituting measures to identify and control risk factors of PAD may reduce this high burden.
Cerebral malaria is associated with low levels of circulating endothelial progenitor cells in African children
(American Journal of Tropical Medicine and Hygiene, 2009) Gyan, B.; Goka, B.Q.; Adjei, G.O.; Tetteh, J.K.; Kusi, K.A.; Aikins, A.; Dodoo, D.; Lesser, M.L.; Sison, C.P.; Das, S.; Howard, M.E.; Milbank, E.; Fischer, K.; Rafii, S.; Jin, D.; Golightly, L.M.
Damage to the cerebral microvasculature is a feature of cerebral malaria. Circulating endothelial progenitor cells are needed for microvascular repair. Based on this knowledge, we hypothesized that the failure to mobilize sufficient circulating endothelial progenitor cells to the cerebral microvasculature is a pathophysiologic feature of cerebral malaria. To test this hypothesis, we compared peripheral blood levels of CD34 (+)/VEGFR2(+) and CD34 (+)/CD133(+) cells and plasma levels of the chemokine stromal cell-derived growth factor 1 (SDF-1) in 214 children in Accra, Ghana. Children with cerebral malaria had lower levels of CD34 (+)/VEGFR2(+) and CD34 (+)/CD133(+) cells compared with those with uncomplicated malaria, asymptomatic parasitemia, or healthy controls. SDF-1 levels were higher in children with acute malaria compared with healthy controls. Together, these results uncover a potentially novel role for endothelial progenitor cell mobilization in the pathophysiology of cerebral malaria.
Cerebral malaria is associated with low levels of circulating endothelial progenitor cells in African children
(American Journal Trop. Med. Hyg. 80(4): 541-6, 2009) Adjei, G.O.; Gyan, B.; Goka, B.Q.; Tetteh, J.K.; Kusi, K.A.; Aikins, A.; Dodoo, D.; Lesser, M.L.; Sison, C.P.; Das, S.; Howard, M.E.; Milbank, E.; Fischer, K.; Rafii, S.; Jin, D.; Golightly, L.M.
Damage to the cerebral microvasculature is a feature of cerebral malaria. Circulating endothelial progenitor cells are needed for microvascular repair. Based on this knowledge, we hypothesized that the failure to mobilize sufficient circulating endothelial progenitor cells to the cerebral microvasculature is a pathophysiologic feature of cerebral malaria. To test this hypothesis, we compared peripheral blood levels of CD34 (+)/VEGFR2(+) and CD34 (+)/CD133(+) cells and plasma levels of the chemokine stromal cell-derived growth factor 1 (SDF-1) in 214 children in Accra, Ghana. Children with cerebral malaria had lower levels of CD34 (+)/VEGFR2(+) and CD34 (+)/CD133(+) cells compared with those with uncomplicated malaria, asymptomatic parasitemia, or healthy controls. SDF-1 levels were higher in children with acute malaria compared with healthy controls. Together, these results uncover a potentially novel role for endothelial progenitor cell mobilization in the pathophysiology of cerebral malaria.
Clinical determinants of early parasitological response to ACTs in African patients with uncomplicated falciparum malaria: a literature review and meta-analysis of individual patient data.
(BMC Medicine, 2015-09) Abdulla, S.; Adam, I.; Adjei, G.O.; Borrmann, S.; Brasseur, P.; Falade, C.O.; D'Alessandro, U.; Flegg, J.A.; Martensson, A.; WWARN Artemisinin based Combination Therapy (ACT) Africa Baseline Study Group; Dorsey, G.; Guerin, P.J.; Nsanzabana, C.; Price, R.N.; Sibley, C.H.; Stepniewska, K.; Talisuna, A.O.
BACKGROUND: Artemisinin-resistant Plasmodium falciparum has emerged in the Greater Mekong sub-region and poses a major global public health threat. Slow parasite clearance is a key clinical manifestation of reduced susceptibility to artemisinin. This study was designed to establish the baseline values for clearance in patients from Sub-Saharan African countries with uncomplicated malaria treated with artemisinin-based combination therapies (ACTs). METHODS: A literature review in PubMed was conducted in March 2013 to identify all prospective clinical trials (uncontrolled trials, controlled trials and randomized controlled trials), including ACTs conducted in Sub-Saharan Africa, between 1960 and 2012. Individual patient data from these studies were shared with the WorldWide Antimalarial Resistance Network (WWARN) and pooled using an a priori statistical analytical plan. Factors affecting early parasitological response were investigated using logistic regression with study sites fitted as a random effect. The risk of bias in included studies was evaluated based on study design, methodology and missing data. RESULTS: In total, 29,493 patients from 84 clinical trials were included in the analysis, treated with artemether-lumefantrine (n = 13,664), artesunate-amodiaquine (n = 11,337) and dihydroartemisinin-piperaquine (n = 4,492). The overall parasite clearance rate was rapid. The parasite positivity rate (PPR) decreased from 59.7 % (95 % CI: 54.5-64.9) on day 1 to 6.7 % (95 % CI: 4.8-8.7) on day 2 and 0.9 % (95 % CI: 0.5-1.2) on day 3. The 95th percentile of observed day 3 PPR was 5.3 %. Independent risk factors predictive of day 3 positivity were: high baseline parasitaemia (adjusted odds ratio (AOR) = 1.16 (95 % CI: 1.08-1.25); per 2-fold increase in parasite density, P <0.001); fever (>37.5 °C) (AOR = 1.50 (95 % CI: 1.06-2.13), P = 0.022); severe anaemia (AOR = 2.04 (95 % CI: 1.21-3.44), P = 0.008); areas of low/moderate transmission setting (AOR = 2.71 (95 % CI: 1.38-5.36), P = 0.004); and treatment with the loose formulation of artesunate-amodiaquine (AOR = 2.27 (95 % CI: 1.14-4.51), P = 0.020, compared to dihydroartemisinin-piperaquine). CONCLUSIONS: The three ACTs assessed in this analysis continue to achieve rapid early parasitological clearance across the sites assessed in Sub-Saharan Africa. A threshold of 5 % day 3 parasite positivity from a minimum sample size of 50 patients provides a more sensitive benchmark in Sub-Saharan Africa compared to the current recommended threshold of 10 % to trigger further investigation of artemisinin susceptibility.
Comparison of chloroquine with quinimax in the treatment of cerebral malaria in Ghanaian children
(Ghana Medical Journal, 2003-09) Goka, B.Q.; Rodrigues, O.P.; Adjei, G.O.; Quarshie, B.; Akanmori, B.D.; Kurtzhals, J.A.L.; Neequaye, J.
Despite earlier reports of R2 and R3 resistance of Plasmodium,1 falciparum to chloroquine. it remained the drug of choice for the treatment of cerebra1 malaria in Ghana. The World Health Organization, however, recommends the use of parenteral quinine salts in such circumstances. In order to guide local treatment policies, an open randomized trial comparing the effect of enteral chloroquine and intravenous followed by oral Quinimax. a quinine preparation approved by the World Health Organization was conducted in 70 children with cerebral malaria. The primary endpoints were mortality, prevalence of residual neurologic sequalae and treatment failure (clinical and parasitological). Thirty-three patients received chloroquine and 37 received Quinimax"'. There was no significant difference in mortality rates (chlorO(IUine. 12.1 %; Quinimax 10.8%; p= 1.00) and neurologic sequelae on day 7 (chloroquine. 12.1%; Quinimax ·, 8.1%; p: O.70) . There was a significantly higher prevalence of early treatment failure in the chloroqU111e group (chloroquine, 12.1 %; Quinimax®. 0%; 1)-"-0.045). Significantly more patients on chloroquine were parasitaemia on day 3 (chloroquine, 21.8%; Qumimax ~. 2.7%; p 0.022) but times to parasite clearance. fever clearance and recovery of full consciousness were similar. We conclude that treatment failure is more likely when chloroquine is used to treat cerebral malaria th'111 when Quinimax® is used. We therefore recommend that quinine salts, or other antimalarial 110 drugs of equal efficacy be used to treat cerebral malaria in Ghanaian children instead of chloroquine.
Diabetes self-management education interventions and self-management in low resource settings; a mixed methods study
(PLOS ONE, 2023) Lamptey, R.; Amoakoh-Coleman, M.; Djobala, B.; Grobbee, D.E.; Adjei, G.O.; Klipstein-Grobusch, K.
Introduction Diabetes is largely a self-managed disease; thus, care outcomes are closely linked to self management behaviours. Structured self-management education (DSME) interventions are, however, largely unavailable in Africa. Aim We sought to characterise DSME interventions in two urban low-resource primary settings; and to explore diabetes self-management knowledge and behaviours, of persons living with diabetes (PLD). Research design and methods A convergent parallel mixed-methods study was conducted between January and February 2021 in Accra, Ghana. The sampling methods used for selecting participants were total enu meration, consecutive sampling, purposive and judgemental sampling. Multivariable regres sion models were used to study the association between diabetes self-management knowledge and behaviours. We employed inductive content analysis of informants’ experi ences and context, to complement the quantitative findings. Results In total, 425 PLD (70.1% (n = 298) females, mean age 58 years (SD 12), with a mean blood glucose of 9.4 mmol/l (SD 6.4)) participated in the quantitative study. Two managers, five professionals, two diabetes experts and 16 PLD participated in in-depth interviews. Finally, 24 PLD were involved in four focus group discussions. The median diabetes self-manage ment knowledge score was 40% ((IQR 20–60). For every one unit increase in diabetes self management knowledge, there were corresponding increases in the diet (5%;[95% CI: 2%- 9%, p<0.05]), exercise (5%; [95% CI:2%-8%, p<0.05]) and glucose monitoring (4%;[95% CI:2%-5%, p<0.05]) domains of the diabetes self-care activities scale respectively. The DSME interventions studied, were unstructured and limited by resources. Financial con straints, conflicting messages, beliefs, and stigma were the themes underpinning self-man agement behaviour. Conclusions The DSME interventions studied were under-resourced, and unstructured. Diabetes self management knowledge though limited, was associated with self-management behaviour. DSME interventions in low resource settings should be culturally tailored and should incor porate sessions on mitigating financial constraints. Future studies should focus on creating structured DSME interventions suited to resource-constrained settings.
Diagnostic capacity, and predictive values of rapid diagnostic tests for accurate diagnosis of Plasmodium falciparum in febrile children in Asante-Akim, Ghana
(Malaria Journal, 2018-12) Quakyi, I.A.; Adjei, G.O.; Sullivan, D.J.; Laar, A.; Stephens, J.K.; Owusu, R.; Winch, P.; Sakyi, K.S.; Coleman, N.; Krampa, F.D.; Essuman, E.et.al.
Background This study seeks to compare the performance of HRP2 (First Response) and pLDH/HRP2 (Combo) RDTs for falciparum malaria against microscopy and PCR in acutely ill febrile children at presentation and follow-up. Methods This is an interventional study that recruited children < 5 years who reported to health facilities with a history of fever within the past 72 h or a documented axillary temperature of 37.5 °C. Using a longitudinal approach, recruitment and follow-up of participants was done between January and May 2012. Based on results of HRP2-RDT screening, the children were grouped into one of the following three categories: (1) tested positive for malaria using RDT and received anti-malarial treatment (group 1, n = 85); (2) tested negative for malaria using RDT and were given anti-malarial treatment by the admitting physician (group 2, n = 74); or, (3) tested negative for malaria using RDT and did not receive any anti-malarial treatment (group 3, n = 101). Independent microscopy, PCR and Combo-RDT tests were done for each sample on day 0 and all follow-up days. Results Mean age of the study participants was 22 months and females accounted for nearly 50%. At the time of diagnosis, the mean body temperature was 37.9 °C (range 35–40.1 °C). Microscopic parasite density ranged between 300 and 99,500 parasites/µL. With microscopy as gold standard, the sensitivity of HRP2 and Combo-RDTs were 95.1 and 96.3%, respectively. The sensitivities, specificities and predictive values for RDTs were relatively higher in microscopy-defined malaria cases than in PCR positive-defined cases. On day 0, participants who initially tested negative for HRP2 were positive by microscopy (n = 2), Combo (n = 1) and PCR (n = 17). On days 1 and 2, five of the children in this group (initially HRP2-negative) tested positive by PCR alone. On day 28, four patients who were originally HRP2-negative tested positive for microscopy (n = 2), Combo (n = 2) and PCR (n = 4). Conclusion The HRP2/pLDH RDTs showed comparable diagnostic accuracy in children presenting with an acute febrile illness to health facilities in a hard-to-reach rural area in Ghana. Nevertheless, discordant results recorded on day 0 and follow-up visits using the recommended RDTs means improved malaria diagnostic capability in malaria-endemic regions is necessary.