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The UK vaccination programme has prevented thousands of deaths from infection with SARS-CoV-2, but has been accompanied by new vaccine related complications. The most serious of these is a novel disorder, described as vaccine induced immune thrombocytopenia and thrombosis (VITT). This immune mediated condition is caused by development of pathological anti-platelet factor 4 (PF4) antibodies following vaccination against covid-19, which leads to intense activation of platelets and the coagulation system. The subsequent clinical syndrome often presents with life threatening thrombosis and secondary haemorrhage, which are challenging to manage in the context of new biochemical coagulopathy.

This article summarises the most recent recommendations from the rapid covid-19 guideline produced by the National Institute for Health and Care Excellence (NICE).1

NICE recommendations are based on systematic reviews of best available evidence. This guideline was developed using an interim process and methods for guidelines developed in response to health and social care emergencies. These included convening an independent advisory expert panel, scoping, identifying, and reviewing …

https://www.bmj.com/content/bmj/375/bmj.n2195.full.pdf

Vaccine induced immune thrombocytopenia and thrombosis: summary of NICE guidance.

We aimed to determine the reporting trends and characteristics of Individual Case Safety Reports (ICSRs) from the Zimbabwean national pharmacovigilance system. ICSRs submitted to VigiBaseTM , the World Health Organisation's ICSR database between January 1993 and December 2017 were retrospectively reviewed with respect to the suspected medicine, System Organ Class (SOC), adverse drug reaction (ADR) type and seriousness, Anatomic Therapeutic Chemical (ATC) group, age, and gender. In total, 4071 ICSRs were submitted to VigiBaseTM from targeted spontaneous reporting (n = 2909; 71.5%), vaccine surveillance (n = 679; 16.7%), and passive spontaneous reporting (n = 483; 11.9%), respectively. The median age, ICSR completeness score and timeliness of reporting were 34.0 years (IQR: 14.0; 43.0), 0.90 (IQR: 0.70; 1.00), and 548.0 days (IQR: 266:1131), respectively. More than half of the ICRS were from female patients (n = 2233; 54.9%). Antiretrovirals, antibiotics, vaccines, and anti-tubercular medicines were reported in 62.9%, 27.9%, 16.7%, and 13.3% of submitted ICSRs, respectively. The most frequent ADRs involved the skin and subcutaneous systems (n = 1111; 20.5%), nervous system (n = 733; 13.5%), and gastrointestinal disorders system (n = 654; 12.1%). The number of ADRs reported for each patient was significantly related to the reported medicine's ATC category (P = .001. The number of ADRs was significantly related to the use of antiretroviral agents. In conclusion, Zimbabwe has made significant progress in establishing a functional pharmacovigilance system. However, the present system reports on a limited therapeutic spectrum of medicines and potentially underestimates the national ADR burden. Further work is required to strengthen the more sustainable spontaneous reporting system which potentially captures a variety of therapeutic classes.

An analysis of the trends, characteristics, scope, and performance of the Zimbabwean pharmacovigilance reporting scheme.

Targeted eco-pharmacovigilance as an optimized management strategy for adverse effects of pharmaceuticals in the environment.

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Background Stevens-Johnson syndrome and toxic epidermal necrolysis are both skin diseases believed to be following the pattern of a type IV hypersensitivity mechanism, which can be triggered by infectious agents or administration of a variety of drugs as part of the spectrum of severe cutaneous adverse reactions (SCARs). Fever and blisters, that peel forming painful raw areas, are early symptoms of this condition, and complications such as dehydration, sepsis, pneumonia, and multiple organ failure are typically seen during the course of the disease. Case Presentation. We present a case of a 23-year-old female patient referred to our hospital after taking carbamazepine and developing high-grade fever and ulcers that appeared initially in her mouth and face but then progressed despite treatment, extending all over her body and involving about 90% of her BSA. Conclusion The use of IVIG and plasmapheresis was a good management for our case, helping in our patient's well-being and recovery. Even if there is no stipulated guideline treatment for cases of SJS and TEN, we think that further investigations about IVIG and plasmapheresis should be investigated as a possible way to treat both conditions.

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Carbamazepine Induced Stevens-Johnson Syndrome That Developed into Toxic Epidermal Necrolysis: Review of the Literature

Vaccine safety surveillance is an essential requirement in vaccination programmes. It supports signal identification, hypothesis generation, and the identification and rectification of gaps in vaccine pharmacovigilance systems. The objectives of this study were to determine the characteristics and trends of adverse events following immunisation (AEFI) and to assess the performance of the Zimbabwe Expanded Immunisation Programme safety surveillance system. We carried out a descriptive study of passively collected vaccine-related Individual Case Safety Report (ICSR) data submitted to the World Health Organization global adverse drug reaction database (VigiBase®) from Zimbabwe during the period 1997 to 2017. We extracted AEFI/ICSR data using VigiLyze® for analysis with respect to the demographic distribution, AEFI characteristics, reporting trends over time, ICSR timeliness and case completeness. A total of 272 vaccine-related ICSRs were included in the analyses with a median completeness score of 0.90 interquartile range, IQR (0.63; 0.90). The overall annual reporting rate was 0.58 per 100,000 vaccine doses and the AEFI reporting ratio ranged between 0 and 30.2 AEFI reports per 100,000 surviving infants. The majority of ICSRs were male (55.3%; p value = 0.641) and the median age was 12 (0–168) months. The majority of ICSRs were reported in children who had received measles (n = 133; 48.9%) and OPV/DTP-Hib-HepB (n = 107; 39.3%) vaccines. Of the 387 observed AEFIs, 301 (77.8%) were systemic events and 86 (22.2%) were local reactions. Systemic events were more frequently reported with doses containing the measles antigen (n = 190; 49.1%) while local events were associated with the multiple antigen OPV/DTP-Hib-HepB (n = 62; 16.0%). The multiple antigen OPV/DTP-Hib-HepB was associated with higher rates for injection site abscess (n = 57), pyrexia (n = 27), diarrhea (n = 15), vomiting (n = 12), and seizures (n = 6). The measles antigen was associated with higher rates for rash (n = 44), ocular disorders (n = 26), pyrexia (n = 26), urticaria (n = 22), diarrhea (n = 8), and vomiting (n = 12). Most of the ICSRs were associated with measles and OPV/DTP-Hib-HepB vaccines. Zimbabwe’s vaccine safety surveillance system is still developing and is not yet fully functional. However, the current system provides a reference point for the monitoring of the ongoing AEFI reporting trends and characteristics.

/pdf/adverse-events-following-immunisation-aefi-reports-from-the-5f6lh1dl57.pdf

Adverse events following immunisation (AEFI) reports from the Zimbabwe expanded programme on immunisation (ZEPI): an analysis of spontaneous reports in Vigibase® from 1997 to 2017

Few studies describe the adverse drug event profiles in patients simultaneously receiving antiretroviral and anti-tubercular medicines in resource-limited countries. To describe and compare the adverse drug reaction profiles in patients on highly active antiretroviral therapy only (HAART), HAART and isoniazid preventive therapy (HHART), and HAART and antitubercular treatment (ATTHAART). We analysed individual case safety reports (ICSRs) for patients on antiretroviral therapy and antitubercular treatment submitted to the national pharmacovigilance centre during the targeted spontaneous reporting (TSR) programme from 1 September 2012 through 31 August 2016. All reports considered certain, probable or possible were included in the analysis. A total of 1076 ICSRs were included in the analysis. Most of the reports were from the HAART only group (n = 882; 82.0%), followed by patients on HHART (n = 132; 12.3%), and ATTHAART (n = 62; 5.7%). The ATTHAART (35.5%) and HHAART (34.1%) had a higher frequency of hepatic disorders than the HAART group (5.0%) (p < 0.0001). A higher frequency of rash was reported in the HHAART (35.6%) and HAART groups (29.4%) than the ATTHAART group (14.5%) (p = 0.011). Peripheral neuropathy occurred more frequently in the ATTHAART group (19.3%) than other groups (p = 0.001) while Stevens-Johnson syndrome (14.7%; p < 0.001), gynaecomastia (18.2%; p < 0.001), and lipodystrophy (4.5%; p = 0.012) occurred more frequently in the HAART group. The HHAART group was associated with a higher frequency of psychosis (4.5%; p = 0.002). Antiretroviral therapy was associated with a higher frequency of Stevens-Johnson syndrome, gynaecomastia, and lipodystrophy. Co-administration of antiretroviral and antitubercular medicines was associated with a higher frequency of drug-induced liver injury and peripheral neuropathy. Similarly, co-administration of isoniazid preventive therapy and antiretroviral drugs was associated with a higher risk for psychosis. There is a need to carefully manage TB/HIV co-infected patients, due to the higher risk of adverse drug reactions which may lead to poor treatment adherence and outcomes.

A Comparison of Adverse Drug Reaction Profiles in Patients on Antiretroviral and Antitubercular Treatment in Zimbabwe.

A 29-year-old Black female patient was admitted to a psychiatric ward with symptoms of major depressive disorder with psychosis. The patient was started on amitriptyline 50 mg/day and haloperidol 10 mg/day. On day 4 post-admission, the preferred first-line antidepressant, fluoxetine, became available and the patient was switched from amitriptyline to fluoxetine 20 mg/day. On the same day, the dose of haloperidol was reduced to 5 mg/day. Thirteen days post-initiation of these medications the patient became talkative, associated with emotional lability, an expansive mood, irritability and restlessness. The working diagnosis was changed to bipolar affective disorder in the manic phase. Fluoxetine was discontinued and carbamazepine 600 mg/day was added to the patient’s treatment regimen. Her manic symptoms started to resolve; however, 14 days post-initiation of carbamazepine, the patient had a fever; itchy, discharging eyes; respiratory distress; generalised symmetrical erythematosus rash; buccal ulceration; and conjunctival injection with difficulty opening her eyes. Carbamazepine was immediately discontinued and the patient received intravenous fluid resuscitation. The patient recovered considerably after 12 days of symptomatic and supportive management, and was transferred back to the psychiatric ward for the continuation of bipolar disorder management. Lithium therapy was instituted and the patient was subsequently discharged. Using the Algorithm of Drug causality for Epidermal Necrolysis (ALDEN) Stevens–Johnson Syndrome/toxic epidermal necrolysis (SJS/TEN) drug causality scoring system, carbamazepine and fluoxetine were evaluated as ‘very probable’ and ‘possible’ causes of SJS, respectively, in this patient. Fluoxetine-induced SJS was considered on account of previous case reports, however no evidence of causality was found in this patient. Consecutive administration with a potential increase in carbamazepine due to inhibition of cytochrome P450 (CYP) 3A4 metabolism by fluoxetine was also not ruled out. A diagnosis of carbamazepine-induced SJS was made and was considered an idiosyncratic adverse drug reaction.

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An Interesting Case of Carbamazepine-Induced Stevens–Johnson Syndrome

Background: Tardive dyskinesia is a debilitating, intractable, hyperkinetic movement disorder which contributes to an increase in psychiatric morbidity. Reduced function CYP2D6 alleles have been associated with tardive dyskinesia pathogenesis amongst Caucasians and Asians, with CYP2D*4 and *6 and CYP2D6*10 being implicated in these races respectively. No similar study has been successfully conducted in black Africans. Objective: To determine the relationship between tardive dyskinesia and CYP2D6*17 (the major reduced function CYP2D6 allele in Africans). Methodology: Abnormal Involuntary Movements Scale (AIMS) scoring and CYP2D6 genotyping were carried out on psychiatric patients exposed to typical antipsychotic medications in an unmatched case control study. A case of tardive dyskinesia was defined as a patient with an AIMS score ≥ 2 in two body areas OR ≥ 3 in one body area Results: A total of 18 cases and 32 controls made up the study sample.The sample’s mean age was 36.9±12.0 years with median treatment duration of 7.0 years (range: 0.25 to 38 years). Multiple logistic regression revealed no significant association between tardive dyskinesia and CYP2D6*17 (OR=0.252; 95% CI: 0.038 to 1.647; p=0.150). However, use of chlorpromazine (OR=5.754; 95% CI: 1.024 to 32.328; p=0.047) and age at treatment initiation (OR=1.146; 95% CI: 1.021 to 1.287; p=0.021) were independent predictors of tardive dyskinesia. Discussion: These findings suggest that there is no association between CYP2D6*17 and tardive dyskinesia in African psychotic patients on typical antipsychotics. However, more studies with larger sample sizes are required to provide more definitive conclusions regarding the nature of the relationship betweenCYP2D6*17 and tardive dyskinesia. Key words: Tardive dyskinesia, CYP2D*17, typical antipsychotics

/pdf/cyp2d6-17-polymorphism-and-tardive-dyskinesia-in-black-3z82ztiuzk.pdf

Josiah Tatenda Masuka

Papers

Adverse events following immunisation (AEFI) reports from the Zimbabwe expanded programme on immunisation (ZEPI): an analysis of spontaneous reports in Vigibase® from 1997 to 2017

An analysis of the trends, characteristics, scope, and performance of the Zimbabwean pharmacovigilance reporting scheme.

A Comparison of Adverse Drug Reaction Profiles in Patients on Antiretroviral and Antitubercular Treatment in Zimbabwe.

An Interesting Case of Carbamazepine-Induced Stevens–Johnson Syndrome

CYP2D6*17 polymorphism and tardive dyskinesia in black psychotic patients on typical antipsychotics