Prevalence of substandard and falsified artemisinin-based combination antimalarial medicines on Bioko Island, Equatorial Guinea.

INTRODUCTION: Poor-quality artemisinin-containing antimalarials (ACAs), including falsified and substandard formulations, pose serious health concerns in malaria endemic countries. They can harm patients, contribute to the rise in drug resistance and increase the public's mistrust of health systems. Systematic assessment of drug quality is needed to gain knowledge on the prevalence of the problem, to provide Ministries of Health with evidence on which local regulators can take action. METHODS: We used three sampling approaches to purchase 677 ACAs from 278 outlets on Bioko Island, Equatorial Guinea as follows: convenience survey using mystery client (n=16 outlets, 31 samples), full island-wide survey using mystery client (n=174 outlets, 368 samples) and randomised survey using an overt sampling approach (n=88 outlets, 278 samples). The stated active pharmaceutical ingredients (SAPIs) were assessed using high-performance liquid chromatography and confirmed by mass spectrometry at three independent laboratories. RESULTS: Content analysis showed 91.0% of ACAs were of acceptable quality, 1.6% were substandard and 7.4% falsified. No degraded medicines were detected. The prevalence of medicines without the SAPIs was higher for ACAs purchased in the convenience survey compared with the estimates obtained using the full island-wide survey-mystery client and randomised-overt sampling approaches. Comparable results were obtained for full island survey-mystery client and randomised overt. However, the availability of purchased artesunate monotherapies differed substantially according to the sampling approach used (convenience, 45.2%; full island-wide survey-mystery client, 32.6%; random-overt sampling approach, 21.9%). Of concern is that 37.1% (n=62) of these were falsified. CONCLUSION: Falsified ACAs were found on Bioko Island, with the prevalence ranging between 6.1% and 16.1%, depending on the sampling method used. These findings underscore the vital need for national authorities to track the scale of ineffective medicines that jeopardise treatment of life-threatening diseases and value of a representative sampling approach to obtain/measure the true prevalence of poor-quality medicines

Quality of artemisinin-based combination formulations for malaria treatment: prevalence and risk factors for poor quality medicines in public facilities and private sector drug outlets in Enugu, Nigeria.

BACKGROUND: Artemisinin-based combination therapies are recommended by the World Health Organisation (WHO) as first-line treatment for Plasmodium falciparum malaria, yet medication must be of good quality for efficacious treatment. A recent meta-analysis reported 35% (796/2,296) of antimalarial drug samples from 21 Sub-Saharan African countries, purchased from outlets predominantly using convenience sampling, failed chemical content analysis. We used three sampling strategies to purchase artemisinin-containing antimalarials (ACAs) in Enugu metropolis, Nigeria, and compared the resulting quality estimates. METHODS: ACAs were purchased using three sampling approaches--convenience, mystery clients and overt, within a defined area and sampling frame in Enugu metropolis. The active pharmaceutical ingredients were assessed using high-performance liquid chromatography and confirmed by mass spectrometry at three independent laboratories. Results were expressed as percentage of APIs stated on the packaging and used to categorise each sample as acceptable quality, substandard, degraded, or falsified. RESULTS: Content analysis of 3024 samples purchased from 421 outlets using convenience (n=200), mystery (n=1,919) and overt (n=905) approaches, showed overall 90.8% ACAs to be of acceptable quality, 6.8% substandard, 1.3% degraded and 1.2% falsified. Convenience sampling yielded a significantly higher prevalence of poor quality ACAs, but was not evident by the mystery and overt sampling strategies both of which yielded results that were comparable between each other. Artesunate (n=135; 4 falsified) and dihydroartemisinin (n=14) monotherapy tablets, not recommended by WHO, were also identified. CONCLUSION: Randomised sampling identified fewer falsified ACAs than previously reported by convenience approaches. Our findings emphasise the need for specific consideration to be given to sampling frame and sampling approach if representative information on drug quality is to be obtained

Meningococcus serogroup C clonal complex ST-10217 outbreak in Zamfara State, Northern Nigeria.

After the successful roll out of MenAfriVac, Nigeria has experienced sequential meningitis outbreaks attributed to meningococcus serogroup C (NmC). Zamfara State in North-western Nigeria recently was at the epicentre of the largest NmC outbreak in the 21st Century with 7,140 suspected meningitis cases and 553 deaths reported between December 2016 and May 2017. The overall attack rate was 155 per 100,000 population and children 5-14 years accounted for 47% (3,369/7,140) of suspected cases. The case fatality rate (CFR) among children 5-9 years was 10%, double that reported among adults ≥ 30 years (5%). NmC and pneumococcus accounted for 94% (172/184) and 5% (9/184) of the laboratory-confirmed cases, respectively. The sequenced NmC belonged to the ST-10217 clonal complex (CC). All serotyped pneumococci were PCV10 serotypes. The emergence of NmC ST-10217 CC outbreaks threatens the public health gains made by MenAfriVac, which calls for an urgent strategic action against meningitis outbreaks

Epidemiology, diagnostics and factors associated with mortality during a cholera epidemic in Nigeria, October 2020-October 2021: a retrospective analysis of national surveillance data.

OBJECTIVES: Nigeria reported an upsurge in cholera cases in October 2020, which then transitioned into a large, disseminated epidemic for most of 2021. This study aimed to describe the epidemiology, diagnostic performance of rapid diagnostic test (RDT) kits and the factors associated with mortality during the epidemic. DESIGN: A retrospective analysis of national surveillance data. SETTING: 33 of 37 states (including the Federal Capital Territory) in Nigeria. PARTICIPANTS: Persons who met cholera case definition (a person of any age with acute watery diarrhoea, with or without vomiting) between October 2020 and October 2021 within the Nigeria Centre for Disease Control surveillance data. OUTCOME MEASURES: Attack rate (AR; per 100 000 persons), case fatality rate (CFR; %) and accuracy of RDT performance compared with culture using area under the receiver operating characteristic curve (AUROC). Additionally, individual factors associated with cholera deaths and hospitalisation were presented as adjusted OR with 95% CIs. RESULTS: Overall, 93 598 cholera cases and 3298 deaths (CFR: 3.5%) were reported across 33 of 37 states in Nigeria within the study period. The proportions of cholera cases were higher in men aged 5-14 years and women aged 25-44 years. The overall AR was 46.5 per 100 000 persons. The North-West region recorded the highest AR with 102 per 100 000. Older age, male gender, residency in the North-Central region and severe dehydration significantly increased the odds of cholera deaths. The cholera RDT had excellent diagnostic accuracy (AUROC=0.91; 95% CI 0.87 to 0.96). CONCLUSIONS: Cholera remains a serious public health threat in Nigeria with a high mortality rate. Thus, we recommend making RDT kits more widely accessible for improved surveillance and prompt case management across the country

Quality of Artemisinin-Containing Antimalarials (ACAs) purchased per outlet using convenience, mystery clients and overt sampling approaches in Enugu, Nigeria; n = 3024.

<p>ACAs = artemisinin containing antimalarial; AD = artemisinin derivative (always the ACAs); PD = partner drug (always the non-ACAs); PMVs = patent medicine vendors. Substandard = genuine medicines produced by legitimate manufacturers that do not satisfy the pharma set quality specifications. Degraded = result from exposure of good quality medicines to excessive heat and humidity. Falsified = deliberately and fraudulently mislabelled with respect to identity and/or source. Include both branded and generic products and may include wrong ingredients or no active ingredients or counterfeited packaging. Significant difference between sampling approaches for each quality category are indicated as follows: between convenience and mystery clients =</p><p>^a (<i>p</i> = 0.002),</p><p>^c (<i>p</i><0.001),</p><p>^e (<i>p</i> = 0.046); between convenience and overt =</p><p>^{b, f} (<i>p</i> = 0.002),</p><p>^d (<i>p</i> = 0.006). Other comparisons were not significantly different (<i>p</i>>0.05).</p><p>Quality of Artemisinin-Containing Antimalarials (ACAs) purchased per outlet using convenience, mystery clients and overt sampling approaches in Enugu, Nigeria; n = 3024.</p

Comparative strengths and weaknesses of the three sampling approaches used.

<p>Comparative strengths and weaknesses of the three sampling approaches used.</p

Quality of Artemisinin-Containing Antimalarials (ACAs) at 98 outlets visited during both mystery clients and overt sampling in Enugu, Nigeria.

<p>Total number of brands purchased were 107</p><p>Quality of Artemisinin-Containing Antimalarials (ACAs) at 98 outlets visited during both mystery clients and overt sampling in Enugu, Nigeria.</p

Description of outlets sampled using the overt sampling approach.

<p>ACA = artemisinin-containing antimalarial; IQR = interquartile range; PMVs = patent medicine vendors.</p><p>Description of outlets sampled using the overt sampling approach.</p

Description of all samples purchased using mystery clients and overt sampling approaches in Enugu, Nigeria; N = 2865.

<p>AM = artemether; ADQ = -amodiaquine; ART = artemisinin; AS = artesunate; DHA = dihydroartemisinin; LUM = lumefantrine; MEF = mefloquine; PIP = piperaquine; PYR = pyrimethamine; SULDOX = sulfadoxine; SULFMEX = sulfamethoxypyridazine; PHCs = public health facilities; PMVs = patent medicine vendors; WHO = World Health Organisation.</p><p>^aonly pharmacies and patent medicine vendors were compared as public health facilities were not visited during the overt sampling approach.</p><p>^bno significant difference (<i>p</i> = 0.29) between the proportion of monotherapy tablets purchased using the mystery clients (5.5%) and overt (4.6%) sampling approaches.</p><p>Description of all samples purchased using mystery clients and overt sampling approaches in Enugu, Nigeria; N = 2865.</p