Efficacy and safety of chloroquine and hydroxychloroquine for the treatment of COVID19 infection: An umbrella review

Introduction: Among all therapeutic approaches for COVID-19, most controversies have been raised about the efficacy and safety hydroxychloroquine (HCQ) and chloroquine. We conducted an umbrella review to assess any potential benefits of hydroxychloroquine and chloroquine in treating COVID-19.Methods: We searched the Cochrane Database of Systematic Reviews, PubMed and covid-evidence.org from December 2019 until July 2022. Time to viral clearance, need for mechanical ventilation and mortality were assessed as main efficacy outcomes. The analysis was performed using R package version 4.1.2.Result : Hydroxychloroquine had no benefit in decreasing time to viral clearance at days 7 (RR 0.81; 95% CI 0.63, 1.03) and 14 (RR 1.00; 95% CI 0.90, 1.139). Chloroquine has no statistically significant effect in decreasing the time of viral negativity at days 7 (RR 1.20; 95%CI 0.64, 2.25) and 14 (RR 1.08; 95%CI 0.85, 1.36). There is no difference in the need for mechanical ventilation among hydroxychloroquine plus azithromycin versus standard of care groups. Hydroxychloroquine marginally increased the mortality rate compared to placebo but not statistically significant (RR 1.09; P-value 0.05). Adding azithromycin to hydroxychloroquine had no statistically significant effect of decreasing mortality (RR 0.52; 95%CI 0.13, 2.07). Treatments with hydroxychloroquine increased the risk of adverse effects (RR 2.71; 95%CI 1.66, 4.43; p-value <0.0001). Adding azithromycin to hydroxychloroquine increased the adverse events (RR 1.74; 95% CI 1.27, 2.38). Conclusion: Though access to antivirals is an important challenge in developing countries, the decision to sus-pend hydroxychloroquine and chloroquine in treating COVID-19 appears right

COVID-19: Guidelines for pharmacists in South Africa

Since the outbreak of COVID-19, and its declaration as a pandemic by the World Health Organization (WHO), the reliance on pharmacists as one of the first points of contact within the healthcare system has been highlighted. This evidence-based review is aimed at providing guidance for pharmacists in community, hospital and other settings in South Africa, on the management of patients with suspected or confirmed coronavirus disease 2019, or COVID-19. The situation is rapidly evolving, and new evidence continues to emerge on a daily basis. This guidance document takes into account and includes newly available evidence and recommendations, particularly around the following aspects relating to COVID-19: • Epidemiology • The virus, its modes of transmission and incubation period • Symptom identification, including the differentiation between influenza, allergic rhinitis, sinusitis and COVID-19 • Social media myths and misinformation • Treatment guidelines and medicines that may need to be kept in stock • Treatment and prevention options, including an update on vaccine development • The case for and against the use of NSAIDs, ACE-inhibitors and angiotensin receptor blockers (ARBs) in patients with COVID-19 • Interventions and patient counselling by the pharmacist. It is critical, though, that pharmacists access the most recent and authoritative information to guide their practice. Key websites that can be relied upon are: • World Health Organization (WHO): https://www.who.int/emergencies/diseases/novelcoronavirus-2019 • National Institute for Communicable Diseases (NICD): https://www.nicd.ac.za/diseasesa-z-index/covid-19/ • National Department of Health (NDoH): http://www.health.gov.za/index.php/ outbreaks/145-corona-virus-outbreak/465-corona-virus-outbreak; https://sacoronavirus. co.za/

Management of malaria in pregnancy by Traditional Birth Attendants in Ogun State, Nigeria

Background: Malaria in pregnancy is a major public health issue in sub-Saharan Africa. Most deliveries in this region are attended by the Traditional Birth Attendants (TBAs).Objective: To assess the knowledge and practice of prevention and treatment of malaria in pregnancy amongst TBAs in Ogun State, south-west Nigeria.Methods: This descriptive, cross-sectional study used systematic random sampling to select 200 registered TBAs within the state. Pre-tested, semi-structured interviewer-based questionnaires were used to obtain relevant data.Results: The mean age of respondents was 37.7 ± 2.2 years. Most of the respondents had secondary school education (82.0%) and were females (89.0%). The majority (68.0%) had good knowledge of malaria during pregnancy; 83.0% used blood test for the diagnosis of malaria while 62.2% of these used Malaria Rapid Diagnostic Test kits. A third of the respondents (33.0%) used Artemisinin-Combination Therapy for treatment while 13.0% used Chloroquine. The majority (85.5%) of the respondents did not practice directly observed therapy in intermittent preventive treatment for malaria using Sulphadoxine-Pyrimethamine (SP). The age of the respondents was significantly associated with their level of knowledge (p = 0.019).Conclusion: The TBAs had high level of knowledge and good practice of the management of malaria in pregnancy. However, some still treated malaria with Chloroquine and were not conversant with the use of SP for the prevention of malaria. It is recommended that capacity building sessions for the TBAs be instituted to improve the quality of care they provide

The Prevalence of Multi-Drug Resistance-1 Gene of Plasmodium Falciparum Malaria in Gezira State-Central Sudan

Abstract:Malaria parasite resistance to chloroquine poses a severe and increasing health problem in tropical countries. Implementing molecular markers for monitoring the drug resistance may be essential to overcome the problem. The aim of the present study is to investigate the prevalence of multi-drug resistance of p. falciparum parasite in malaria patients. Blood samples for DNA extraction were collected from the positive malaria patients. The prevalence of mutations in P. falciparum multi-drug resistant gene-1 (pfmdr-1) was detected by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) methods. Approximately; 74.1 of study populations are adults and 25.9 are children. Regression analysis shows a decrease in malaria incidence with increasing age. The prevalence of malaria is higher in males (58.6) compared to females (41.4). There were no statistical differences between malaria incidence and the socioeconomic level within the study population. The frequency of homozygous N/86 and Y/86 alleles were 51.7 and 37.9; respectively; and the heterozygous N/Y86 allele was 10.3.In conclusion the frequency of Pfmdr-1 N/Y86 allele among P. falciparum multi-drug resistant isolates support the hypothesis that Pfmdr-1 N/Y86 allele could be used as predictive marker to monitor multi-drug susceptibility in epidemiological surveys

Use of Chloroquine in Uncomplicated Falciparum Malaria Chemotherapy: The Past; the Present and the Future

Chloroquine is a 4-aminoquinoline discovered over five decades ago for treatment of uncomplicated malaria. It was widely used as first line treatment and prophylaxis for individuals going into malaria endemic regions. It was initially highly effective against the four Plasmodium species (P. falciparum; P. malaria; P. ovale and P. vivax) infecting human. It is also effective against gametocytes except those of P. falciparum. Resistance of P. falciparum to chloroquine is widespread and led to discontinuation of chloroquine in malaria treatment by most countries. In recent times; evidences are emerging for chloroquine to probably secure its original place in treatment of acute uncomplicated falciparum malaria. This would be a welcome idea since chloroquine is readily available; relatively safer and cheaper than most currently use antimalarial drugs. Thus; researchers should intensify efforts on periodic in vitro monitoring of chloroquine efficacy; clinicians should further discourage use of chloroquine until efficacy is remarkably restored and pharmaceutical industries should look into potential chloroquine and chloroquine-resistance reversal fixed and non-fixed doses combinations

Antimalarial Prescribing Patterns in State Hospitals and Selected Parastatal Hospitals in Lagos; Nigeria

Background: Malaria is a curable and preventable disease and it is a major public health problem in Nigeria. Chloroquine was the first line drug in its treatment in Nigeria until recently where the Artemisinin based Combination Therapies (ACTs) are being promoted. Inappropriate prescribing i.e. the failure to prescribe drugs in accordance with guidelines based on scientific evidence to ensure safe; effective; and economic use; is an irrational drug use behavior. Increased benefits from chloroquine or a slowdown of progression to resistance could be achieved by improving prescribing practice; drug quality; and patient compliance. Objective: To determine the antimalarial prescribing pattern and to assess rational prescribing of chloroquine by prescribers in government hospitals and parastatals in Lagos State. Methods: The study was carried out in all the ten government General Hospitals under Lagos State Hospitals Management Board (now Lagos State Health Service Commission); one parastatal hospital and one oil company clinic; using patient prescriptions. One hundred prescriptions each for adults and children for each month for a period of one year ( January to December 2000) were systematically sampled. Where there were fewer than 100 prescriptions in a month; all the prescriptions available were sampled for analysis. Results: Average number of drugs per encounter in all the hospitals was 4.259 + 0.009. Average number of injections per encounter was 1.215 + 0.009. About 48.5of all the presriptions had at least one injection while 40.9of the prescriptions had dipyrone injection. Average drug cost per encounter was N 147.40 + 0.765. Percentage of encounters with chloroquine was 82.5followed by sulphadoxinepyrimethamine 14.2. Percentage of prescriptions with correct dose of chloroquine was 47.5Conclusions: Polypharmacy exists in all the hospitals.The average number of drugs per encounter for the majority of the hospitals was above 4 . Less than half of the prescriptions had the correct dose of chloroquine. This study can serve as a baseline for intervention on irrational prescribing

Enhanced Antimalarial Effects of Chloroquine by Aqueous Vernonia Amygdalina Leaf Extract in Mice Infected with Chloroquine Resistant and Sensitive Plasmodium berghei strains

Background: The emergence and spread of Plasmodium falciparum with resistance to chloroquine (CQ); the safest and cheapest antimalarial drug coupled with the increasing cost of alternative drugs especially in developing countries have necessitated the need to optimize antimalarial actions of plant extracts and restore chloroquine efficacy. Objective: The present study determines the ability of Vernonia amygdalina leaf extract to enhance the prophylactic and therapeutic efficacy of chloroquine against Plasmo- dium berghei malaria in mice. Methods: Chloroquine sensitive (P. bergheiS) and resistant (P.bergheiR) ANKA clones of Plasmodium berghei maintained by serial passage in mice were used to develop respective experimental rodent malaria models based on intraperitoneal injection of 106 parasitize erythrocyte suspension in PBS (pH 7.2) and subsequent development of parasitaemia. These models were then used to investigate the prophylactic enhancement of chloroquine (CQ) at 5 mg/kg via combination with selected doses (31.25; 62.5; 125mg/kbw) of Vernonia amygdalina leaf extracts using a 4-day suppression test. Effect of these combinations on the therapeutic efficacy of CQ at 30mg/kg over 3 days were evaluated. Treatment outcomes including parasite clearance (PCT) and rescrudescent time (RT) were compared with CQchlorpheniramine com-bination. The acute toxicity of the extract-CQ combinations was also determined enzymatically. Results: Prophylatically; chloroquine (5mg/kg) in combination with vernonia extracts achieved a dose-dependent (57.2 - 72.7) suppression of parasitaemia due to CQ sensitive and resistant P berghei strains in the experimental animals. Therapeutically; chloroquine (30mg/kg for 3 days) combined with vernonia to dose-dependently shorten the parasite clearance times (2.6 - 4.4 vs. 4.8 days; P 0.05 for CQ-V62.5/125 combination); prolong the recrudescent times (8.9 - 18.9 vs. 7.2 days; P 0.05) and improve day 14 cure rate (66.7 - 100 vs. 58.3) in the treated P. bergheiS infected mice compared to CQ monotherapy. Whereas CQ monotherapy failed; resolution of parasitaemia due to the CQ resistant parasite with day 14 cure rates of 25 - 100were also observed with these combinations. In therapeutic terms; the potencies of CQ-V125 combination were comparable to those of CQ-chlorpheniramine (0.25mg/kg; 12hourly; 7 days) in the infected animals. Toxicity testing indicates that these combinations elicited mild to - moderate increases in the liver enzymes measured when adminis- tered orally to mice for 7 days. Conclusion: This study indicates that Vernonia amygdalina leaf extract dose - dependently restore the efficacy of CQ against CQ resistance P. berghei malaria in mice

Biological and Haematological Safety Profile of Oral Amodiaquine and Chloroquine in Healthy Volunteers with or without Plasmodium falciparum Infection in Northeast Tanzania

Amodiaquine (AQ); an effective antimalarial drug for uncomplicated malaria; has been greatly restricted after cases of life-threatening agranulocytosis and hepatic toxicity during prophylactic use. We conducted a hospital based open-label randomised clinical trial in 40 indigenous semi-immune healthy adult male volunteers with and without malaria parasites. The objective was to collect data on biological and haematological safety; tolerability; and parasitological efficacy to serve as baseline in the evaluation of the effectiveness of AQ preventive intermittent treatment against malaria morbidity in infants. Volunteers were stratified according to parasitaemia status and randomly assigned 20 participants each arm to three days treatment with either AQ or chloroquine (CQ). The level of difference of selected haematological and hepatological values pre-and post-trial were marginal and within the normal limits. Clinical adverse effects mostly mild and transient were noticed in 33.3CQ treated-aparasitaemic; 23.8of CQ treated-parasitaemic; 28.6of AQ-treated parasitaemic and 14.3of aparasitaemic receiving AQ. Amodiaquine attained 100parasitological clearance rate versus 70in CQ-treated volunteers. The findings indicate that there was no agranulocytosis or hepatic toxicity suggesting that AQ may pose no public health risk in its wide therapeutic dosage uses. Larger studies are needed to exclude rare adverse effects

Chimio-sensibilité de plasmodium falciparum aux antipaludiques au Niger

Nous avons réalisé un test thérapeutique in vivo à la chloroquine, couplé à une étude in vitro de chimiosensibilité et à une étude des gènes de mutation associés à la résistance aux antipaludiques en Septembre et Octobre 2001 à Niamey au Niger. Au total, 244 enfants ont été inclus. Une réponse clinique adéquate du traitement par chloroquine a été observée chez 78,3% des enfants de 1-15 ans,78,9% des enfants de 1-5 ans, 77,9% des enfants de 6-10 ans et 78% des enfants de 11-15 ans. L'échec thérapeutique a été constaté dans 13,1% des cas dont 9,4% d'échec thérapeutique précoce et 3,7% d'échec thérapeutique tardif. Au vu de ces résultats, le Programme National de Lutte contre le Paludisme a décidé de maintenir la chloroquine comme traitement de première intention du paludisme simple à P. falciparum à Niamey. Concernant les tests in vitro, sur les 244 souches, 26 seulement ont pu être cultivées, par défaut du transporteur. Sur ces 26 souches, 15 étaient sensibles à la chloroquine par les tests in vitro isotopiques. Concernant la sensibilité aux autres antipaludiques, 4 étaient résistantes la pyriméthamine, 5 au cycloguanil, 3 à l'atovaquone. Les tests moléculaires ont été effectués sur les souches qui avaient pu être isolées en cultures. Nous présentons ainsi les résultats de la prévalence des mutations des gènes pfcrt, dhfr et dhps et discutons ces résultats par rapport à ceux des tests classiques

Cost implication of irrational prescribing of chloroquine in Lagos State general hospitals

Background: A major share of the hospital budget is spent on drugs. Irrational use of these drugs is a waste of financial and human resources that could have been deployed for another use within the hospital setting especially in cases where such drugs are provided free to patients. Also there is increased morbidity and progression of severity with irrational use. The objective of this study was to determine the irrational use of chloroquine and the subsequent cost implications in Lagos State general hospitals. Methodology: A retrospective study period of one year (January to December, 2000) was selected. A total of 18,781 prescription forms of "Free Eko Malaria" were sampled for children and adults from all the Lagos State general hospitals. Drug costs in each prescription form were identified. Cost effectiveness analysis of chloroquine tablet and intramuscular injection was undertaken. Results: The average cost of medicine per prescription was N 132.071 ($1.03) which should have been N 94.22 ($0.73) if prescribed rationally. The total cost of prescriptions for malaria under study was 2,480,425.00 ($19,348.09). About 68% {(N1,679,444.00) ($13,100.19)} of the total cost was lost to irrational prescribing. This is a waste of scarce resources. When the prescriptions were differentiated into the different dosage forms prescribed, the prescriptions containing intramuscular injections only had over 90% of the cost lost to irrational prescribing. Cost effectiveness analysis showed that chloroquine tablet was 17 times more cost effective than chloroquine injection (intramuscular) from a health care system perspective while it was 14 times more cost effective from a patient perspective. Conclusion: There is waste of scarce resources with irrational dispensing of drugs and these resources could have been deployed to other uses or areas within the hospitals. The tablet chloroquine was more cost effective than injection chloroquine (intramuscular). Increasing the cost of tablets, decreasing effectiveness of tablets, decreasing the cost of injections and increasing the effectiveness of injections did not change the cost effectiveness conclusion

Mini Review - Chloroquine has not Disappeared

Chloroquine (CHQ); an antimalarial; is also used as an anti-inflammatory drug for systemic lupus erythematosus and rheumatoid arthritis (RA). Hydroxychloroquine (HCQ) reduces the frequency of organ involvement and disease flares; and relieves skin and joint symptoms. CHQ reduces the immunologically-mediated inflammation of the joints. HCQ and combination therapies have a significant benefit on synovitis; pain and physical disability on RA. We advocate the investment of resistance Plasmodium prevalence determina-tions in countries beset by malaria; and to match thereafter the quantity of persons administered CHQ. Follow-up investigations are essential to diagnose and prevent visual damage

"A Study of the Pharmaceutical Quality of Chloroquine and Paracetamol Products Sold in a Major Nigerian ""Market"""

"Malaria is a major public health problem in endemic countries; and the quality of anti-malarial products is a concern in the therapeutic management of individual patient. In this study; we have evaluated the pharmaceutical quality of chloroquine and paracetamol oral products obtained from a major Nigerian drug ""market"" using a less elaborate sampling procedure. Results have shown that there are still some defects in the pharmaceutical quality of these drugs; despite the activities of the Nigeria's drug regulatory agency (National agency for Food and Drug Administration and Control; NAFDAC). 21(7/34) of the drug products were not registered by NAFDAC. The pharmaceutical properties of the products indicated that 6; 15; 9; and 9of them failed tests for disintegration; dissolution; crushing strength; and percentage of active content; respectively. 4 out of the 6 chloroquine liquid preparations evaluated had inadequate active content. These defects could have resulted from deliberate counterfeiting; poor quality control during manufacture or decomposition of the products. However; this could not be ascertained from the data available to us in this study. The implication of these findings; however; is that the newer anti-malarial drugs that have recently been introduced into the Nigerian market should be safeguarded; if their therapeutic usefulness must be sustained."

Health workers perceptions on chloroquine and sulfadoxine/sulfalene-pyrimethamine monotherapies: implications for the change to combination therapy of artemether/lumefantrine in Tanzania

Objective: To describe; from health workers (HWs) perspectives; the potential and actual barriers to the implementation of the first change of policy from chloroquine (CQ) to Sulfadoxine / Sulfalane - Pyrimewthamine (SP) in preparation for the second change of policy to Artemisinin based Combination Therapies (ACTs). Methods: A descriptive cross-sectional survey of HWs using questionnaire interviews was carried out in public and private health facilities in Songea Urban district. The interview concerned awareness and knowledge on the commonly used antimalarial drugs as given in the new policy; focusing on SP use and the associated side effects as well as perceptions on the potency and safety of SP versus CQ and the perceived alternative antimalarial drugs to non-response or reaction to SP. Results: Awareness on the new policy was very high; 91.4 of HWs were aware that SP was the new drug. Although the majority of HWs (81.9) reported using the new policy as soon as it was out; a significant percentage (76.2) reported continued use of SP (P-value 0.001). SP was perceived to have a low potency in that it was slow in fever clearance. A significant percentage (65.7) of HWs reported a history of problems with SP use namely headaches and skin reactions. Quinine (QN) was significantly frequently mentioned as the perceived alternative drug to CQ (61.1) and non-response (56.6) or reaction (54.1) to SP. Conclusion: Findings show that SP was generally not preferred by HWs; and they continued to use CQ despite the evidence that it was no longer effective indicating that. HWs tend to maintain perceptions based on their experiences with drugs currently in use. Pertinent information; education and behaviour change communication strategies related to the change from SP to ACT should focus on the fact that the previous drug is no longer effective so as to induce consistent use of the new drug

Use of pre-packaged chloroquine for the home of presumed malaria in Malagasy children

Objective: The main objective of this study was to assess the quality of home malaria management with pre-packaged chloroquine in two areas in the Moramanga district of Madagascar. The knowledge; attitude and practices of care providers in terms of home treatment options were evaluated and compared. The availability of treatment options by studying retailers and community-based service providers was also investigated. Methods: A cross-sectional investigation in two communities; in the hamlets and villages located close to carers; retailers; community-based service providers and primary health centres was carried out. Results :Carers in the two districts were equally well aware of the use of pre-packaged chloroquine. Their first response to the onset of fever was to treat children with this antimalarial drug at home. The dose administered and treatment compliance were entirely satisfactory (100) with pre-packaged chloroquine and rarely satisfactory (1.6to 4.5) with non pre-packaged chloroquine. In cases of treatment failure; the carers took patients to health centres. Chloroquine was supplied principally by private pharmacies and travelling salesmen selling unpackaged chloroquine tablets. Non pre-packaged chloroquine was the most common drug used at health centres. The frequency of positive rapid malaria tests (P=0.01) was significantly higher in children treated with non pre-packaged chloroquine (38) than in children treated with pre-packaged chloroquine (1.3). Conclusions: Home malaria management should be improved in Madagascar. Efforts should focus on communication; the training of community-based service providers; access to pre-packaged drugs and the gradual withdrawal of pre-packaged chloroquine and its replacement by pre-packaged artemisinin-based combination therapies