Investigating the Presence of Falsified and Poor-Quality Fixed-Dose Combination Artemether-Lumefantrine Pharmaceutical Dosage Forms in Kumasi, Ghana.

Artemether-lumefantrine (AL) is a highly effective and commonly used Artemisinin-based Combination Therapy (ACT) for treating uncomplicated malaria caused by Plasmodium falciparum, including drug-resistant strains. However, ineffective regulatory systems in resource-limited settings can lead to the infiltration of poor-quality and counterfeit antimalarial medicines into the pharmaceutical supply chain, causing treatment failures, prolonged illness, and disease progression. The objective of the study was to assess the quality of selected brands of fixed-dose combination (FDC) AL tablets and suspensions marketed in Kumasi, Ghana. A total of fourteen brands of FDC AL medicines, comprising eight tablets and six suspensions were purchased from various retail pharmacy outlets in Kumasi, Ghana. All samples were subjected to thorough visual inspection as a quick means of checking quality through meticulous observation of the packaging or dosage form. The quality parameters of the tablets were determined using uniformity of weight, hardness, friability, and disintegration tests. Suspensions were assessed based on pH and compared with the British Pharmacopeia (BP) standard. The samples were then analyzed for drug content (assay) using reverse-phase high-performance liquid chromatography (RP-HPLC). All the tablet samples conformed to BP specification limits for uniformity of weight (deviation of less than ± 5%), hardness (4.0-10 kg/mm2), friability (<1%), and disintegration time (<15 minutes). The active pharmaceutical ingredients' quantitative assay demonstrated that all the tablets met the BP specifications (90-110%). The results of the pH studies showed that out of the six brands of suspension investigated, five (83.3%) were compliant with the official specification for pH, while one (16.7%) failed the requirement. Unlike the tablet brands, drug content analysis of the six suspensions showed that two (33.3%) were substandard. The artemether and lumefantrine contents in these failed suspensions were variable (artemether: 81.31%-116.76%; lumefantrine: 80.35%-99.71%). The study results indicate that most of the tested products met the required quality standards, demonstrating satisfactory drug content and other quality specifications. The presence of substandard drugs underscores the necessity for robust pharmacovigilance and surveillance systems to eliminate counterfeit and substandard drugs from the Ghanaian market.

Development of the RP-HPLC Method for Simultaneous Determination and Quantification of Artemether and Lumefantrine in Fixed-Dose Combination Pharmaceutical Dosage Forms.

Developing countries face enormous challenges with substandard and falsified antimalarial drugs. One specific issue is the lack of a simple, cost-effective, and robust HPLC method to simultaneously determine and quantify the active pharmaceutical ingredients (APIs) in fixed-dose artemether-lumefantrine pharmaceutical dosage forms. The current study developed a novel, simple, sensitive, precise, accurate, and cost-effective RP-HPLC method for the simultaneous determination and quantification of artemether and lumefantrine in pharmaceutical dosage forms. The HPLC analysis was carried out on an Agilent 1260 Infinity Series HPLC system equipped with an ODS Intersil-C8 (150 × 4.6 mm) 5.0 µm column, by isocratic elution. The mobile phase composition consisted of acetonitrile and 0.05% orthophosphoric acid buffer of pH 3.5 in the ratio of 70 : 30 v/v. The analysis was performed at a 1 mL/min flow rate and a column temperature of 25°C. The total run time was 6 minutes. The detection was done with a variable wavelength detector (VWD) at an isosbestic point wavelength (λ) of 210 nm. The developed method was validated according to the ICH guidelines concerning system suitability, specificity, linearity, accuracy, precision, and robustness. The system suitability of the developed method revealed satisfactory theoretical plates and symmetry factors. The method proved to be specific, with no interference of mobile phase or excipients. The calibration plot exhibited linearity over the concentration range of 275-1925 µg/mL with R2 = 0.9992 for artemether and a range of 150-1050 µg/mL with R2 = 0.9985 for lumefantrine. The accuracy of the method, determined by the recovery study, was 99.79-100.16% for artemether and 99.04-99.50% for lumefantrine. The % RSD values for intraday precision were 0.175 and 0.203, while interday precision values were 0.340 and 0.554 for artemether and lumefantrine, respectively. The method demonstrated robustness when subjected to slight modifications in the flow rate, column temperature, and mobile phase composition. The developed analytical method proved satisfactory as per ICH guidelines and hence can be used for the determination and quantification of artemether and lumefantrine in bulk drug and pharmaceutical dosage forms.

Self-medication among pregnant women in Ghana: A systematic review and meta-analysis.

Background: Despite the associated health risks of self-medication during pregnancy, recent evidence suggests that the phenomena persist in most countries. However, self-medication during pregnancy in Ghana is poorly understood due to the lack of a comprehensive review study. Objectives: We sought to review existing literature on the prevalence of self-medication, drugs used in self-medication, diseases associated with self-medication, and why pregnant women in Ghana self-medicate. Methods: A comprehensive search was conducted in PubMed, Science Direct, African Journal Online (AJOL), Google Scholar, and the websites of Ghanaian universities to identify studies that were published until February 2022. We performed this review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). A random-effects meta-analysis was done in StatsDirect statistical software and OpenMeta [Analyst] to estimate the prevalence of self-medication during pregnancy and was reported in a forest plot. Simple charts and tables were used to summarize evidence on drugs used in self-medication, diseases associated with self-medication, and reasons for self-medication. Results: Six (6) studies met our inclusion criteria and the pooled prevalence of self-medication during pregnancy was 65.4% (95% CI = 58.2%-72.6%; I 2 = 88.32%; p < 0.001). Common drugs used for self-medication included analgesics (48.1%) and herbal drugs (45.9%). Headache and lower abdominal pain were the most common conditions for which pregnant women self-medicated. The main reasons for self-medication were the perceived unserious nature of diseases, previous experience with drugs, and easy access to over-the-counter drugs. Conclusions: Self-medication among pregnant women in Ghana is substantially high. Measures need to be implemented to reduce the high prevalence of self-medication during pregnancy to achieve sustainable development goals on maternal health in Ghana. A limitation of this study was the small number of included studies, which calls for more studies on self-medication during pregnancy in Ghana.

Bacterial Contaminants and Antibiogram of Ghana Paper Currency Notes in Circulation and Their Associated Health Risks in Asante-Mampong, Ghana.

Transmission of pathogens through currency notes has become very relevant in today's world due to COVID-19 pandemic. This study profiled microbial flora and their antibiotic activities from Ghana paper currency (GH¢) notes in circulation in Mampong Municipal of Ashanti Region, Ghana. The study employed a cross-sectional design to assess bacterial contaminants and their antibiotic activities from January to May 2019. A total of 70 GH¢ notes consisting of 15 each of GH¢1, GH¢2, and GH¢5; 10 each of GH¢10 and GH¢20; and 5 of GH¢50 were randomly sampled from persons at different shops, canteens, and commercial drivers. The surfaces of each GH¢ note were gently swabbed, and tenfold serial dilutions made were inoculated on plate count agar (PCA), MacConkey agar, mannitol salt agar, and deoxycholate citrate agar. The study used appropriate laboratory and biochemical tests for bacterial identification. SPSS-IBM version 16.0 was used to analyze the data. Of the 70 GH¢ notes studied, 97.1% were contaminated with one or more bacterial isolates. Mean counts on PCA ranged between 3.2 cfu/ml × 105 and 4.7 cfu/ml × 105 on GH¢ notes. Of 124 bacteria isolated, 34 (27.4%), 30 (24.2%), 22 (17.7%), 17 (13.7%), 13 (10.5%), and 8 (6.5%) were from GH¢1, GH¢2, GH¢10, GH¢5, GH¢20, and GH¢50, respectively (p < 0.05). Bacterial isolates were Escherichia coli (28.23%), Staphylococcus aureus (16.94%), coagulase-negative Staphylococcus (16.13%), Klebsiella species (11.29%), Salmonella species (9.68%), Shigella species (8.87%), Pseudomonas aeruginosa (5.65%), and Proteus species (3.23%). GH¢ notes had 25.81%, 20.16%, 19.35%, 17.74%, and 16.94% from meat shops, commercial drivers, canteens, grocery shops, and vegetable shops, respectively. All bacteria were 100% resistant to erythromycin, 87.5% to tetracycline, chloramphenicol, and cotrimoxazole, 75% to vancomycin, while 87.50% sensitive to amikacin. The GH¢ notes were heavily colonized with potential pathogens, which are resistant to most commonly used antibiotics and could pose a health threat to users during commercial transactions.

Microbial Contamination, an Increasing Threat to the Consumption of Fresh Fruits and Vegetables in Today's World.

Microbes are found all over the globe with some few exceptions, including sterilized surfaces. They include normal flora that is nonpathogenic, which contribute to the larger percentage, and pathogenic species which are few. Hence, the activities of humans cannot be completely separated from microbes. Thus, many pathogenic microbes have found their way into fresh fruits and vegetables which are a great source of a healthy diet for humans. The growing demand for fresh fruits and vegetables has necessitated larger production. The larger production of vegetables within the shortest possible time to meet the growing demand has placed them at a higher risk of contamination with the pathogenic microbes, making the safety of consumers uncertain. Study of sources of contamination and type of pathogenic etiological agents isolated from fresh fruits and vegetables includes Bacillus cereus, Campylobacter jejuni, Clostridium botulinum, E. coli O157: H7, Listeria monocytogenes, Salmonella spp., Shigella, Staphylococcus, and Vibrio cholera. Several measures have proven to be effective in controlling contamination of microbes and they include the establishment of surveillance systems to monitor the production chain and thoroughly washing vegetables with vinegar water. Saltwater and other washing techniques are effective but caution should be taken to make sure one does not use one cycle of water for washing all vegetables. The consumption of fresh fruits and vegetables is still encouraged by this review but significant measures must be taken to check the safety of these products before consumption.

Three monthly doses of 60 mg/kg praziquantel for Schistosoma haematobium infection is a safe and effective treatment regimen.

BACKGROUND: Praziquantel (PZQ) is the standard treatment for Schistosomiasis in sub-Saharan Africa. However, there is evidence suggesting praziquantel treatment failure in Schistosome infections with associated potential renal impairment. The objective of this study was to determine the effect of three monthly doses of 60 mg/kg/day PZQ on schistosome egg count, liver and renal function during the treatment of urinary schistosomiasis in Ghana. METHODS: A nested case-control study was designed from a cohort screened for schistosomiasis; 28 schistosomiasis positive cases by microscopy matched with 53 healthy controls by age and gender. The study population was urban dwellers from the Asokwa sub-metropolitan area, Kumasi in Ghana. Participants were within the age range of 6 to 30 years. We assessed Schistosoma haematobium egg counts in urine and its associated impact on liver and renal function at baseline, treatment and post-treatment phases using serum. RESULTS: Of the 28 cases and 53 controls, 78.6% and 81.1% were males respectively. Globulin levels before treatment was higher in cases [36.7 (32.8, 40.1) vrs 30.5 (22.4, 33.8), p = 0.005] at pre-treatment but not at post-treatment [35.8 (31.2, 39.1) vrs 37.4 (29.7, 43.0), p = 0.767]. Estimated cure rate was 42.9, 46.4 and 96.4% after first, second and third dose respectively. Schistosome egg counts dropped significantly (p = 0.001) from before second dose to post-treatment. Similarly, levels of alanine aminotransferase (p = 0.001), aspartate aminotransferase (p = 0.028) and gamma glutamyl transferase (p = 0.001) significantly declined towards post-treatment. Estimated glomerular filtration rate significantly improved from before second dose to post-treatment using both the Chronic Kidney Disease Epidemiology Program (p = 0.001) and 4-variable Modification of Diet in Renal Disease (p = 0.002) equations. CONCLUSION: Treatment of urinary Schistosoma hematobium infections with a repeated high monthly dose of 60 mg/kg of praziquantel for 3 months is safe and effective.

Cytotoxic T Cell-Derived Granzyme B Is Increased in Severe Plasmodium Falciparum Malaria.

In Plasmodium falciparum malaria, CD8+ T cells play a double-edged role. Liver-stage specific CD8+ T cells can confer protection, as has been shown in several vaccine studies. Blood-stage specific CD8+ T cells, on the other hand, contribute to the development of cerebral malaria in murine models of malaria. The role of CD8+ T cells in humans during the blood-stage of P. falciparum remains unclear. As part of a cross-sectional malaria study in Ghana, granzyme B levels and CD8+ T cells phenotypes were compared in the peripheral blood of children with complicated malaria, uncomplicated malaria, afebrile but asymptomatically infected children and non-infected children. Granzyme B levels in the plasma were significantly higher in children with febrile malaria than in afebrile children. CD8+ T cells were the main T cell subset expressing granzyme B. The proportion of granzyme B+ CD8+ T cells was significantly higher in children with complicated malaria than in uncomplicated malaria, whereas the activation marker CD38 on CD8+ T cells showed similar expression levels. This suggests a pathogenic role of cytotoxic CD8+ T cells in the development of malaria complications in humans.

Author Correction: Differential expression pattern of co-inhibitory molecules on CD4+ T cells in uncomplicated versus complicated malaria.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.

Differential expression pattern of co-inhibitory molecules on CD4+ T cells in uncomplicated versus complicated malaria.

The immune response of malaria patients is a main factor influencing the clinical severity of malaria. A tight regulation of the CD4+ T cell response or the induction of tolerance have been proposed to contribute to protection from severe or clinical disease. We therefore compared the CD4+ T cell phenotypes of Ghanaian children with complicated malaria, uncomplicated malaria, asymptomatic Plasmodium falciparum (Pf) infection or no infection. Using flow cytometric analysis and automated multivariate clustering, we characterized the expression of the co-inhibitory molecules CTLA-4, PD-1, Tim-3, and LAG-3 and other molecules implicated in regulatory function on CD4+ T cells. Children with complicated malaria had higher frequencies of CTLA-4+ or PD-1+ CD4+ T cells than children with uncomplicated malaria. Conversely, children with uncomplicated malaria showed a higher proportion of CD4+ T cells expressing CD39 and Granzyme B, compared to children with complicated malaria. In contrast, asymptomatically infected children expressed only low levels of co-inhibitory molecules. Thus, different CD4+ T cell phenotypes are associated with complicated versus uncomplicated malaria, suggesting a two-sided role of CD4+ T cells in malaria pathogenesis and protection. Deciphering the signals that shape the CD4+ T cell phenotype in malaria will be important for new treatment and immunization strategies.

Review of Organism Density and Bacteriologic Conversion of Sputum among Tuberculosis Patients.

OBJECTIVE: This study sought to describe the trend of sputum organism density and the rate of bacteriological conversion among smear positive TB patients assessing care at the Komfo Anokye Teaching Hospital (KATH), Kumasi, Ghana. METHODS: We conducted a retrospective patient folder review from January 2013 to March 2016 at the KATH, a tertiary hospital in Ghana. The data was entered into Microsoft Access database and exported into STATA for analysis. We applied basic descriptive statistics to study variables. Sputum conversion rate (SCR) was estimated using the number of negative tests recorded over a period (numerator) and the number of patients reported in the same period (denominator) and expressed as a percentage. RESULTS: A total of 278 patient records with sputum smear positive at onset were studied. Before treatment sputum density detected in smear microscopy was as follows: 1 acid-fast bacillus (+) (n = 114), scanty (n = 19), ++ (n = 67), and +++ (n = 78). We recorded sputum conversion rate of 80.90%, 94.56%, and 98.31% in the intensive, continuation, and completion phases, respectively. CONCLUSION: This study has shown an increasing trend in sputum conversion of smear positive pulmonary tuberculosis and an increasing trend in loss to follow-ups among tuberculosis patients on treatment.

Health care workers indicate ill preparedness for Ebola Virus Disease outbreak in Ashanti Region of Ghana.

BACKGROUND: The recent Ebola Virus Disease (EVD) epidemic that hit some countries in West Africa underscores the need to train front line high-risk health workers on disease prevention skills. Although Ghana did not record (and is yet to) any case, and several health workers have received numerous training schemes, there is no record of any study that assessed preparedness of healthcare workers (HCWS) regarding EVD and any emergency prone disease in Ghana. We therefore conducted a hospital based cross sectional study involving 101 HCWs from two facilities in Kumasi, Ghana to assess the level of preparedness of HCWs to respond to any possible EVD. METHODS: We administered a face-to-face questionnaire using an adapted WHO (2015) and CDC (2014) Checklist for Ebola Preparedness and assessed overall knowledge gaps, and preparedness of the Ghanaian HCWs in selected health facilities of the Ashanti Region of Ghana from October to December 2015. RESULTS: A total 92 (91.09%) HCWs indicated they were not adequately trained to handle an EVD suspected case. Only 25.74% (n = 26) considered their facilities sufficiently equipped to handle and manage EVD patients. When asked which disinfectant to use after attending to and caring for a suspected patient with EVD, only 8.91% (n = 9) could correctly identify the right disinfectant (χ2 = 28.52, p = 0.001). CONCLUSION: Our study demonstrates poor knowledge and ill preparedness and unwillingness of many HCWs to attend to EVD. Beyond knowledge acquisition, there is the need for more training from time to time to fully prepare HCWs to handle any possible EVD case.

Bacterial etiology of sexually transmitted infections at a STI clinic in Ghana; use of multiplex real time PCR.

BACKGROUND: Most sexually transmitted infection (STI) management efforts focus on the syndromic approach to diagnose and treat patients. However, most women with STIs have been shown to be entirely asymptomatic, or if symptoms exist, are often missed when either clinical or conventional bacteriologic diagnostic tools are employed. METHODS: We assessed the performance of a multiplex real time PCR assay to describe other potential pathogens that could be missed by conventional bacteriological techniques in 200 women attending a routine STI clinic in Kumasi, Ghana. RESULTS: Although a total 78.00% of the women were asymptomatic, 77.1% of them tested positive for at least one bacterial STI pathogen. Mycoplasma genitalium was the most commonly detectable pathogen present in 67.5% of all women. Of those testing positive, 25.0% had single infections, while 38.0% and 19.5% had double and triple infections respectively. Altogether, 86.54% and 90.91% of the symptomatic and asymptomatic women respectively tested positive for at least one pathogen (p<0.05). There were no significant associations (p<0.05) between the clinical manifestations of the symptomatic women and the pathogens detected in their samples. CONCLUSIONS: Our study confirmed the importance of complementing the syndromic approach to STI management with pathogen detection and most importantly recognise that STIs in women are asymptomatic and regular empirical testing even for both symptomatic and asymptomatic patients is critical for complete clinical treatment. FUNDING: EOD (Ellis Owusu-Dabo Research working group, KCCR).

Genotypic characterisation of human papillomavirus infections among persons living with HIV infection; a case-control study in Kumasi, Ghana.

OBJECTIVES: The objective of this study is to describe the burden of human papillomavirus (HPV) infection among women living with HIV and non-infected women in Ghana. METHODS: A case-control study was conducted involving 107 women living with HIV aged between 18 and 59 years (cases) and 100 non-HIV-infected apparently healthy women (controls) who were recruited from the Kumasi South Hospital, from July to December, 2014. Cervicovaginal swabs were taken from study participants to characterise 28 high- and low-risk HPV genotypes using a multiplex real-time PCR. RESULTS: The overall mean age for the participants was 40.10 ± 9.76 years. The prevalence of high-risk (hr)-HPV genotypes was significantly higher among the cases than the controls (77.4% vs. 41.6%, P < 0.0001). Overall, HPV 58 and 54 were the most predominant high-risk (18.8%) and low-risk (15.0%) genotypes detected. The two most common hr-HPV genotype isolates were 58 (18.8%) and 35 (15.9%) with 58 being the most prevalent among age group 35-44 years compared with hr-HPV 16, 18, 35 and 45, found predominantly among 18-34 age group. CONCLUSIONS: Significant variations exist in HPV genotypes among HIV-infected and uninfected women.

Variations in levels of IL-6 and TNF-α in type 2 diabetes mellitus between rural and urban Ashanti Region of Ghana.

BACKGROUND: A surge in pro-inflammatory markers, Il-6 and TNF-α, has been associated with type 2 diabetes mellitus (T2DM). However, there is no data on the dynamics of these markers in T2DM Ghanaian populations. The aim of this study was to determine variations in the levels of IL-6 and TNF-α in T2DM patients. This study also examined the associations of IL-6 and TNF-α with anthropometric measurement and the effect of co-morbidity with hypertension using rural and urban dwellers in the Ashanti region, Ghana. METHODS: A nested case-control design using participants aged 25-70 years consisting of 77 T2DM ± hypertension patients and 112 controls were selected from a larger study on Research on Obesity and Diabetes among African Migrants (RODAM). Anthropometric measurements, blood pressure and body fat percentage were measured. Fasting blood samples were analyzed for glucose, IL-6 and TNF-α levels. RESULTS: The median level of IL-6 was significantly higher (p < 0.0001) among rural dwellers compared to urban dwellers. Inversely, urban dwellers had significantly higher (p = 0.0424) median level of TNF-α compared to rural cases. No significant differences were observed in IL-6 (p = 0.3571) and TNF-α (p = 0.2581) among T2DM patients compared with T2DM ± hypertension patients. A weak negative correlation was found between IL-6 and BMI in urban T2DM. DISCUSSION: The average level of IL-6 was higher in rural T2DM participants compared with those in urban setting. However, higher levels of TNF-α was observed among the study participants with T2DM in urban settings compared to those of rural. In this study, we observed that co-morbidity of hypertension had no significant effect on the levels of IL-6 and TNF-α. We are of the opinion that higher physical activity levels among rural particpants and high obesity levels in urabn participants explain the observation but needs more numbers to validate. CONCLUSION: This study revealed that IL-6 levels were higher among rural dwellers than urban while TNF-α levels were higher in urban dwellers than rural in patients with T2DM. There was no association of body fat percentage and body mass index with IL-6 and TNF-α levels. Co-morbidity of hypertension with T2DM had no effect on IL-6 and TNF-α levels.

Effectiveness of artemisinin-based combination therapy used in the context of home management of malaria: a report from three study sites in sub-Saharan Africa.

BACKGROUND: The use of artemisinin-based combination therapy (ACT) at the community level has been advocated as a means to increase access to effective antimalarial medicines by high risk groups living in underserved areas, mainly in sub-Saharan Africa. This strategy has been shown to be feasible and acceptable to the community. However, the parasitological effectiveness of ACT when dispensed by community medicine distributors (CMDs) within the context of home management of malaria (HMM) and used unsupervised by caregivers at home has not been evaluated. METHODS: In a sub-set of villages participating in a large-scale study on feasibility and acceptability of ACT use in areas of high malaria transmission in Ghana, Nigeria and Uganda, thick blood smears and blood spotted filter paper were prepared from finger prick blood samples collected from febrile children between six and 59 months of age reporting to trained CMDs for microscopy and PCR analysis. Presumptive antimalarial treatment with ACT (artesunate-amodiaquine in Ghana, artemether-lumefantrine in Nigeria and Uganda) was then initiated. Repeat finger prick blood samples were obtained 28 days later for children who were parasitaemic at baseline. For children who were parasitaemic at follow-up, PCR analyses were undertaken to distinguish recrudescence from re-infection. The extent to which ACTs had been correctly administered was assessed through separate household interviews with caregivers having had a child with fever in the previous two weeks. RESULTS: Over a period of 12 months, a total of 1,740 children presenting with fever were enrolled across the study sites. Patent parasitaemia at baseline was present in 1,189 children (68.3%) and varied from 60.1% in Uganda to 71.1% in Ghana. A total of 606 children (51% of infected children) reported for a repeat test 28 days after treatment. The crude parasitological failure rate varied from 3.7% in Uganda (C.I. 1.2%-6.2%) to 41.8% in Nigeria (C.I. 35%-49%). The PCR adjusted parasitological cure rate was greater than 90% in all sites, varying from 90.9% in Nigeria (C.I. 86%-95%) to 97.2% in Uganda (C.I. 95%-99%). Reported adherence to correct treatment in terms of dose and duration varied from 81% in Uganda (C.I. 67%-95%) to 97% in Ghana (C.I. 95%-99%) with an average of 94% (C.I. 91%-97%). CONCLUSION: While follow-up rates were low, this study provides encouraging data on parasitological outcomes of children treated with ACT in the context of HMM and adds to the evidence base for HMM as a public health strategy as well as for scaling-up implementation of HMM with ACTs.