A call to action: securing an uninterrupted supply of Africa's medical products and technologies post COVID-19.

The COVID-19 pandemic unveiled the vulnerability of many African healthcare systems, amplifying inadequacies and constraints in the supply chain for medical products and technologies on the continent. Disruptions in the global supply chain due to the pandemic resulted in the continent's population of over one billion people grappling with shortages in the supply of essential medicines. The shortages and their consequences set back achievement of Sustainable Development Goals and progress towards universal health coverage. A virtual meeting of global experts in medical products and supply chain identified as urgent the need for Africa to build capacity for a self-reliant public health system. Discussants challenged the governments of African countries to turn the continent from its current import driven economy to a continent of indigenous research and development, local production, and an exporter of its medical products and innovations.

A descriptive study of healthcare-providers' experiences with the use and quality of oxytocin for the prevention of post-partum hemorrhage in Nigeria: A nation-wide survey.

BACKGROUND: Oxytocin is recommended as an affordable and effective drug in the prevention of postpartum hemorrhage-one of the leading causes of maternal morbidity and mortality in low- and middle-income countries, however, there are concerns about its proper use and quality. This study builds on earlier work conducted in a South-Western state in Nigeria. OBJECTIVE: The study assessed the knowledge around oxytocin, usage, storage practices and perceived quality of oxytocin used by healthcare providers that directly administer oxytocin for the prevention of postpartum hemorrhage across Nigeria. METHODS: This was a descriptive cross-sectional study that surveyed a representative sample of 6,299 healthcare providers who offer obstetrics and gynecological services and recruited from 1,894 healthcare facilities in Public and Private sectors in 12 states across Nigeria. Data were collected using an electronic questionnaire, analyzed using SPSS, and presented in frequencies and percentages. RESULTS: Only forty-six percent of respondents (52.8% in private; 40.0% in public sector) had proper knowledge that oxytocin storage is in the refrigerator. Proper knowledge also varied by professional cadre, doctors (71.2%); nurses (46.6%); Community Health Workers (28.4%) and by years of experience, less than 10 years (51.4%); more than 10 years (40.8%). Only 34% of the respondents (41% in private and 27.5% in public sector) reported good practices that oxytocin is stored in the refrigerator in their facilities. Most healthcare providers used oxytocin for prevention of PPH (77.9%). Oxytocin was also used for augmentation (66.7%) and induction of labor (52.6%). Half of respondents used above the WHO-recommended oxytocin dose of 10IU for prevention of PPH. Twenty-three percent of respondents reported experiencing oxytocin failure in PPH prevention of whom, 54.3% changed to another uterotonic and 37.1% doubled the dose of oxytocin for their patients. CONCLUSION: Our study findings should be used to establish clinical guidelines and trainings for healthcare providers to improve their knowledge and storage practices and use to safeguard the quality of these lifesaving medicines.

Clinical experiences with the use of oxytocin injection by healthcare providers in a southwestern state of Nigeria: A cross-sectional study.

BACKGROUND: Postpartum hemorrhage (PPH) is a leading cause of maternal mortality in Nigeria and in most low- and middle-income countries. The World Health Organization (WHO) strongly recommends oxytocin as effective, affordable, and the safest drug of first choice in the prevention and treatment of PPH in the third stage of labor. However, there are concerns about its quality. Very high prevalence of poor-quality oxytocin, especially in Africa and Asia, has been reported in literature. Excessive and inappropriate use of oxytocin is also common in low-resource settings. OBJECTIVE: To assess clinical experiences with quality of oxytocin used by healthcare providers in Lagos State, Nigeria. METHODS: This was a descriptive cross-sectional study conducted in 2017, with 705 respondents (doctors and nurses) who use oxytocin for obstetrics and gynecological services recruited from 195 health facilities (public and registered private) across Lagos State. Data collection was quantitative, using a pretested self-administered questionnaire. Data analysis was performed with IBM SPSS version 21. Statistical significance was set at 5 percent (p<0.05). Ethical approval was obtained from Lagos University Teaching Hospital Health Research Ethics Committee. RESULTS: Only 52 percent of the respondents knew oxytocin should be stored at 2°C to 8°C. About 80 percent of respondents used oxytocin for augmentation of labor, 68 percent for induction of labor, 51 percent for stimulation of labor, and 78 percent for management of PPH. Forty-one percent used 20IU and as much as 10% used 30IU to 60IU for management of PPH. About 13 percent of respondents reported believing they had used an ineffective brand of oxytocin in their practice. Just over a third (36%) had an available means of documenting or reporting perceived ineffectiveness of drugs in their facility; of these, only about 12 percent had pharmacovigilance forms in their facilities to report the ineffectiveness. CONCLUSION: The inappropriate and inconsistent use of oxytocin, especially overdosing, likely led to the high perception of medicine effectiveness among respondents. This is coupled with lack of suspicion of medicine ineffectiveness by clinicians as a possible root cause of poor treatment response or disease progression. Poor knowledge of oxytocin storage and consequent poor storage practices could have contributed to the ineffectiveness reported by some respondents. It is necessary to establish a unified protocol for oxytocin use that is strictly complied with. Continuous training of healthcare providers in medicine safety monitoring is advocated.

Identification and quantification of 19 pharmaceutical active compounds and metabolites in hospital wastewater in Cameroon using LC/QQQ and LC/Q-TOF.

Human pharmaceutical residues are a serious environmental concern. They have been reported to have eco, geno, and human toxic effects, and thus their importance as micropollutants cannot be ignored. These have been studied extensively in Europe and North America. However, African countries are still lagging behind in research on these micropollutants. In this study, the wastewaters of the University Teaching Hospital of Yaoundé (UTHY) were screened for the presence of active pharmaceutical ingredients and their metabolites. The screening was carried out using two methods: high-performance liquid chromatography coupled to a triple quadrupole analyzer (LC/QQQ) and high-performance coupled to a mass spectrometer with a time of flight analyzer (LC/Q-TOF). A total of 19 active pharmaceutical ingredients and metabolites were identified and quantified. The compounds identified include paracetamol (211.93 µg/L), ibuprofen (141 µg/L), tramadol (76 µg/L), O-demethyltramadol (141 µg/L), erythromycinanhydrate (7 µg/L), ciprofloxacin (24 µg/L), clarinthromycine (0.088 µg/L), azitromycine (0.39 µg/L), sulfamethoxazole 0.16 µg/L), trimetoprime (0.27 µg/L), caffeine (5.8 µg/L), carnamaeepine (0.94 µg/L), atenolol (0.43 µg/L), propranolol (0.3 µg/L), cimetidine (34 µg/L), hydroxy omeprazole (5 µg/L), diphenhydramine (0.38 µg/L), metformine (154 µg/L), and sucralose (13.07 µg/L).

Quality medicines in maternal health: results of oxytocin, misoprostol, magnesium sulfate and calcium gluconate quality audits.

BACKGROUND: The high level of maternal mortality and morbidity as a result of complications due to childbirth is unacceptable. The impact of quality medicines in the management of these complications cannot be overemphasized. Most of those medicines are sensitive to environmental conditions and must be handled properly. In this study, the quality of oxytocin injection, misoprostol tablets, magnesium sulfate, and calcium gluconate injections was assessed across the six geopolitical zones of Nigeria. METHOD: Simple, stratified random sampling of health facilities in each of the political zones of Nigeria. Analysis for identification and content of active pharmaceutical ingredient was performed using high-performance liquid chromatography procedures of 159 samples of oxytocin injection and 166 samples of misoprostol tablets. Titrimetric methods were used to analyze 164 samples of magnesium sulfate and 148 samples of calcium gluconate injection. Other tests included sterility, pH measurement, and fill volume. RESULTS: Samples of these commodities were procured mainly from wholesale and retail pharmacies, where these were readily available, while the federal medical centers reported low availability. Approximately, 74.2% of oxytocin injection samples failed the assay test, with the northeast and southeast zones registering the highest failure rates. Misoprostol tablets recorded a percentage failure of 33.7%. Magnesium sulfate and Calcium gluconate injection samples recorded a failure rate of 6.8% and 2.4%, respectively. CONCLUSION: The prevalence of particularly of oxytocin and misoprostol commodities was of substandard quality. Strengthening the supply chain of these important medicines is paramount to ensuring their effectiveness in reducing maternal deaths in Nigeria.

Cost benefit of investment on quality in pharmaceutical manufacturing: WHO GMP pre- and post-certification of a Nigerian pharmaceutical manufacturer.

BACKGROUND: Pharmaceutical companies in Africa need to invest in both facilities and quality management systems to achieve good manufacturing practice (GMP) compliance. Compliance to international GMP standards is important to the attainment of World Health Organization (WHO) prequalification. However, most of the local pharmaceutical manufacturing companies may be deterred from investing in quality because of many reasons, ranging from financial constraints to technical capacity. This paper primarily evaluates benefits against the cost of investing in GMP, using a Nigerian pharmaceutical company, Chi Pharmaceuticals Limited, as a case study. This paper also discusses how to drive more local manufacturers to invest in quality to attain GMP compliance; and proffers practical recommendations for local manufacturers who would want to invest in quality to meet ethical and regulatory obligations. METHOD: The cost benefit of improving the quality of Chi Pharmaceuticals Limited's facilities and system to attain WHO GMP certification for the production of zinc sulfate 20-mg dispersible tablets was calculated by dividing the annual benefits derived from quality improvement interventions by the annual costs of implementing quality improvement interventions, referred to as a benefit-cost ratio (BCR). RESULT: Cost benefit of obtaining WHO GMP certification for the production of zinc sulfate 20-mg dispersible tablets was 5.3 (95% confidence interval of 5.0-5.5). CONCLUSION: Investment in quality improvement intervention is cost-beneficial for local manufacturing companies. Governments and regulators in African countries should support pharmaceutical companies striving to invest in quality. Collaboration of local manufacturing companies with global companies will further improve quality. Local pharmaceutical companies should be encouraged to key into development opportunities available for pharmaceutical companies in Africa.

Polycyclic Aromatic Hydrocarbons: Part I. Exposure.

Polycyclic aromatic hydrocarbons (PAH) comprise the largest class of cancer-causing chemicals and are ranked ninth among chemical compounds threatening to humans. Although interest in PAH has been mainly due to their carcinogenic property, many of these compounds are genotoxic, mutagenic, teratogenic, and carcinogenic. They tend to bioaccumulate in the soft tissues of living organisms. Interestingly, many are not directly carcinogenic, but act like synergists. PAH carcinogenicity is related to their ability to bind DNA thereby causing a series of disruptive effects that can result in tumor initiation. Thus, any structural attribute or modification of a PAH molecule that enhances DNA cross linking can cause carcinogenicity. In part I, we review exposure to these dangerous chemicals across a spectrum of use in the community and industry.

Application of Nanofiber-packed SPE for Determination of Urinary 1-Hydroxypyrene Level Using HPLC.

It is always desirable to achieve maximum sample clean-up, extraction, and pre-concentration with the minimum possible organic solvent. The miniaturization of sample preparation devices was successfully demonstrated by packing 10 mg of 11 electrospun polymer nanofibers into pipette tip micro column and mini disc cartridges for efficient pre-concentration of 1-hydroxypyrene in urine samples. 1-hydroxypyrene is an extensively studied biomarker of the largest class of chemical carcinogens. Excretory 1-hydroxypyrene was monitored with HPLC/fluorescence detector. Important parameters influencing the percentage recovery such as fiber diameter, fiber packing amount, eluent, fiber packing format, eluent volume, surface area, porosity, and breakthrough parameters were thoroughly studied and optimized. Under optimized condition, there was a near perfect linearity of response in the range of 1-1000 µg/L with a coefficient of determination (r (2)) between 0.9992 and 0.9999 and precision (% RSD) ≤7.64% (n = 6) for all the analysis (10, 25, and 50 µg/L). The Limit of detection (LOD) was between 0.022 and 0.15 µg/L. When compared to the batch studies, both disc packed nanofiber sorbents and pipette tip packed sorbents exhibited evident dominance based on their efficiencies. The experimental results showed comparable absolute recoveries for the mini disc packed fibers (84% for Nylon 6) and micro columns (80% for Nylon 6), although the disc displayed slightly higher recoveries possibly due to the exposure of the analyte to a larger reacting surface. The results also showed highly comparative extraction efficiencies between the nanofibers and conventional C-18 SPE sorbent. Nevertheless, miniaturized SPE devices simplified sample preparation, reducing back pressure, time of the analysis with acceptable reliability, selectivity, detection levels, and environmental friendliness, hence promoting green chemistry.

1-hydroxypyrene levels in blood samples of rats after exposure to generator fumes.

Polynuclear Aromatic Hydrocarbons (PAHs) are a major component of fuel generator fumes. Carcinogenicity of these compounds has long been established. In this study, 37 Swiss albino rats were exposed to generator fumes at varied distances for 8 hours per day for a period of 42 days and the level of 1-hydroxypyrene in their blood was evaluated. This study also tried to correlate the level of blood 1-hyroxypyrene with the distance from the source of pollution. Plasma was collected by centrifuging the whole blood sample followed by complete hydrolysis of the conjugated 1-hydroxypyrene glucuronide to yield the analyte of interest, 1-hydroxypyrene, which was achieved using beta glucuronidase. High performance liquid chromatography (HPLC) with UV detector was used to determine the 1-hydroxypyrene concentrations in the blood samples. The mobile phase was water:methanol (12:88 v/v) isocratic run at the flow rate of 1.2 mL/min with CI8 stationary phase at 250 nm. After 42 days of exposure, blood concentration level of 1-hydroxypyrene ranged from 34 µg/mL to 26.29 µg/mL depending on the distance from source of exposure. The control group had no 1-hydroxypyrene in their blood. After the period of exposure, percentage of death correlated with the distance from the source of exposure. Percentage of death ranged from 56% to zero depending on the proximity to source of pollution.

Urinary 1-hydroxypyrene as a biomarker to carcinogenic polycyclic aromatic hydrocarbon exposure.

In order to capture the extent of exposure to polycyclic aromatic hydrocarbons (PAHs), various biomarkers have been employed. The biomarkers employed for PAHs include PAHs genetoxic end points in lymphocytes, urinary metabolites, PAH-DNA adducts, and PAH-Protein adducts. Of these, excretory 1-hydroxypyene, a metabolite of pyrene, has been used extensively as a biological monitoring indicator of exposure to PAHs. This study attempts to assess the level of this biomarker in the body fluid of 68 exposed subjects using high performance liquid chromatography HPLC. The subjects screened included auto mechanics, drivers, and fuel attendants. 1-hydroxypyrene was extracted from the urine of the subjects using solid phase extraction method. The HPLC analysis was done in isocratic mode using water:methanol (12:88 v/v) mobile phase. The stationary phase was XBridge C18 (150 × 4.6 mm) 5 µm column. The wavelength was 250 nm at a flow rate of 1.2 mL/min. The oven temperature was 30 ºC and the injection volume was 20 µL. The run time was 3 minutes. The level of urinary 1-hydroxypyrene detected varied for the different categories of occupation studied. About 27% of sampled fuel attendants and 22% of auto mechanics had detectable 1-hydroxypyrene in their urine samples. There was no detectable 1-hydroxypyene in the urine samples of commercial drivers or in the urine samples of students used as controls. The results of this study showed that fuel attendants and auto mechanics have significant exposures to PAHs. So far, there is no established benchmark for level of PAHs in urine, but our findings indicate the possibility of future cancer cases in this population as a result of their occupational exposure. The study was not able to link the level of 1-hydroxypyene with the smoking habits of the subjects.

GC/MS analysis of polynuclear aromatic hydrocarbons in sediment samples from the Niger Delta region.

Thirteen sediment samples from different locations in the Niger Delta region of Nigeria were analyzed for the presence of 16 polynuclear aromatic hydrocarbons (PAHs) via gas chromatography/mass spectrometry. The specific target compounds for this study included naphthalene, acenaphthylene, acenaphthene, flourene, phenanthrene, anthracene, flouranthene, pyrene, benz[a]anthracene, chrysene, benzo[b]fluoranthene, benzo[k]flouranthene, benzo[a]pyrene, benzo[ghi]perylene, dibenz[a,h]anthracene, and indeno[1,2,3-cd]pyrene. Four isotopically labeled polynuclear aromatic hydrocarbons (acanaphthene-d10, phenanthrene-d10, chrysene-d12 and perylene-d12) were used for internal standardization. All 16 PAHs were found in most of the thirteen samples with concentration ranging from 0.1 microg/kg to 28 microg/kg. It was also found that the 5 and 6-ring PAHs were present in higher concentrations than all the other compounds, indicating their high resistance to microbial degradation.

Determination of polynuclear aromatic hydrocarbons in marine samples of Siokolo Fishing Settlement.

Analysis for the presence of 16 priority polynuclear aromatic hydrocarbons (PAHs) was carried out in fish, sediment and water samples of a fishing settlement in the Niger Delta region of Nigeria which is supposed to be extensively polluted by seepages from oil discharge terminals. The determination and quantification of PAHs in water, fish and sediment samples were done by GC-MS with the aid of isotopically labeled internal standards. The 16 priority PAHs, namely naphthalene, acenaphthylene, acenaphthene, flourene, phenanthrene, anthracene, flouranthene, pyrene, benz[a]anthracene, chrysene, benzo[b]flouranthene, benzo[k]flouranthene, benzo[a]pyrene, benzo[ghi]perylene, dibenz[a,h]anthracene and indeno[1,2,3-cd]pyrene, were found to be present in significant amount in all three samples.