Use Of Chloroquine Research Articles

Overexpression of STX11 alleviates pulmonary fibrosis by inhibiting fibroblast activation via the PI3K/AKT/mTOR pathway

Fibroblast activation plays an important role in the occurrence and development of idiopathic pulmonary fibrosis (IPF), which is a progressive, incurable, and fibrotic lung disease. However, the underlying mechanism of fibroblast activation in IPF remains elusive. Here, we showed that the expression levels of STX11 and SNAP25 were downregulated in the lung tissues from patients with IPF and mice with bleomycin (BLM)-induced lung fibrosis as well as in the activated fibroblasts. Upregulation of STX11 or SNAP25 suppressed TGF-β1-induced activation of human lung fibroblasts (HLFs) via promoting autophagy. However, they failed to suppress fibroblast actviation when autophagy was blocked with the use of chloroquine (CQ). In addition, STX11 or SNAP25 could inhibit TGF-β1-induced fibroblast proliferation and migration. In vivo, overexpression of STX11 exerted its protective role in the mice with BLM-induced lung fibrosis. STX11 and SNAP25 mutually promoted expression of each other. Co-IP assay indicated that STX11 has an interaction with SNAP25. Mechanistically, STX11-SNAP25 interaction activated fibroblast autophagy and further inhibited fibroblast activation via blocking the PI3K/AKT/mTOR pathway. Overall, the results suggested that STX11-SNAP25 interaction significantly inhibited lung fibrosis by promoting fibroblast autophagy and suppressing fibroblast activation via blocking the PI3K/ATK/mTOR signaling pathway. Therefore, STX11 serves as a promising therapeutic target in IPF.

Careers of chloroquine and hydroxychloroquine as “miraculous” anti-Covid-19 drugs

In early January 2024, a widely publicized article in the journal Biomedicine and Pharmacology estimated that approximately 17,000 COVID-19 patients in France, Italy, Spain, Turkey, and the US died as a result of hydroxychloroquine treatment. The publication of this article is a fitting closure to nearly three years of controversy about the possible use of chloroquine and hydroxychloroquine to treat COVID-19. Repurposed in early 2020 as miracle answers to the COVID-19 pandemic, they had a brief moment of worldwide celebrity, despite the doubts expressed by many experts. Hydroxychloroquine’s career ended in September 2020, when a series of clinical trials showed not only inefficacy to treat COVID-19 but also safety concerns. However, the use of chloroquine and hydroxychloroquine continued in Brazil, where the government continued to promote their use as the first therapeutic choice against COVID-19. Our study outlines the employ of these drugs in France and Brazil. Grounded in the methodology developed by social studies of science, our article reconstructs the trajectories of hydroxychloroquine in France and Brazil. It aims to elucidate the reasons for the Brazilian exception, illuminating the disastrous consequences of the exercise of a monolithic political power and of anti-democratic practices on drug regulation and proposes new reflections on a topic that has been visible in the media and widely discussed in society, but attracted much less attention in the academic sphere.

Over fifteen years of chloroquine withdrawal in Nigeria: a qualitative investigation into the execution of this policy by healthcare providers and amongst patients in a rural community.

Background Chloroquine (CQ) was once an important drug used in malaria treatment especially due to its affordability, ease of use and high anti-malarial efficacy. However, it was withdrawn from clinical practice in Nigeria in 2005 following a widespread of resistance cases reported in the public health domain. This study aims to ascertain the level of compliance with the policy on CQ withdrawal among patients, Patent and proprietary medicine vendors (PPMVs), Pharmacists and Physicians. Method A cross-sectional survey involving both online and offline data collection was carried out. A total of 582 participants were recruited and consisted of patients (N = 300), PMVs (N = 94), Physicians (N = 94), and Pharmacists (N = 94). Patients spanned across health services at primary health centers and hospitals in the Anaocha community. Result Our findings show that the patients were equally aware of what CQ is used for (χ² = 7.071, p = 0.215). However, significant disparities were observed in the knowledge, attitude, and perception of CQ resistance and its continual use among health professionals and PPMVs (χ² = 160.54 and 158.54, p = 0.000). Additionally, despite the chloroquine withdrawal policy in Nigeria, there was evident non-compliance among majorly PPMVs and other healthcare professionals. A few of patients continued to utilize CQ for malaria treatment and PPMVs were mostly likely to prescribe and stock CQ. Conclusion The study revealed that chloroquine use in Nigeria is still sustained notwithstanding the switch in the antimalarial drug policy from chloroquine to ACTs in 2005. Feasible implementation strategy through awareness program and campaign especially in the primary health centers across Nigeria and through associations such as Nigeria Association of Patent and Proprietary Medicine Dealers (NAPPMED), Pharmaceutical Society of Nigeria (PSN) and Nigeria Medical Association (NMA) is recommended.

NCOA4-mediated ferritinophagy participates in cadmium-triggered ferroptosis in spermatogonia

Cadmium (Cd) is a common pollutant with reproductive toxicity. Our previous study revealed that Cd triggered spermatogonia ferroptosis. However, the underlying mechanisms remain unclear. Nuclear receptor coactivator 4 (NCOA4) mediates ferritinophagy and specific degradation of ferritin through lysosomes, resulting in the release of ferrous ions. Excessive autophagy can lead to ferroptosis. This study investigated the role of autophagy in Cd-triggered ferroptosis using GC-1 spermatogonial (spg) cells which exposed to CdCl2 (5 μM, 10 μM, or 20 μM) for 24 without/with CQ. The cells which transfected with Ncoa4-siRNA were used to explore the role of NCOA4-mediated ferritinophagy in Cd-triggered ferroptosis. The results revealed that Cd caused mitochondrial swelling, rupture of cristae, and vacuolar-like changes. The Cd-treated cells exhibited more autophagosomes. Simultaneously, Cd increased intracellular iron, reactive oxygen species, and malondialdehyde concentrations while decreasing glutathione content and Superoxide Dismutase-2 activity. Moreover, Cd upregulated mRNA levels of ferritinophagy-associated genes (Ncoa4, Lc3b and Fth1), as well as enhanced protein expression of NCOA4, LC3B, and FTH1. While Cd decreased the mRNA and protein expression of p62/SQSTM1. These results showed that Cd caused ferritinophagy and ferroptosis. The use of chloroquine to inhibit autophagy ameliorated Cd-induced iron overload and ferroptosis. Moreover, Ncoa4 knockdown in spermatogonia significantly reduced intracellular iron concentration and alleviated Cd-triggered ferroptosis. In conclusion, our findings demonstrate that Cd activates the ferritinophagy pathway mediated by NCOA4, resulting in iron accumulation through ferritin degradation. This causes oxidative stress, ultimately initiating ferroptosis in spermatogonia. Our results may provide new perspectives and potential strategies for preventing and treating Cd-induced reproductive toxicity.

Effects of Active Compounds of Nigella sativa in COVID-19: A Narrative Review.

SARS-CoV-2 infection that led to the COVID-19 pandemic has changed human health and the economy globally. SARS CoV-2 is a type of Coronaviruses that has caused pneumonia and its complications with many deaths over the past two years. The use of hydroxychloroquine and chloroquine, accepted as generally safe for patients with autoimmune diseases or malaria, was attempted in many trials for COVID-19 treatment. Nigella sativa (NS) (black caraway, also known as black cumin, nigella or Kalonji) is an annual flowering plant of the Ranunculaceae family, chemically composed of the main constituent natural Thymoquinone (TQ) (30%- 48%) in forms of thymohydroquinone, dithymoquinone (Nigellone) is a native to wider regions, including parts of eastern Europe, west Asia, North of Africa and east of Myanmar. In this review, we explored the Randomized Controlled Trial, Controlled Trial, and Systematic review studies that support Nigella sativa Thymoquinone-targeted SARS-CoV-2 targeting. Therefore, A literature search was performed for publications published on the electronic databases (PubMed, Embase, Scopus, CNKI, and Google Scholar) for Nigella sativa, black seeds, Kalonji, coronavirus, SARS-CoV -2 and COVID-19. This review aimed to find relevant evidence of Nigella sativa preferences as a natural feasible remedy with no side effects in COVID-19. Studies reported the benefits of NS as beneficial, another appropriate remedy for patients with COVID-19. However, all studies have shown limitations, such as limiting clinical symptom outcomes due to regulations imposed by isolation policies and lack of adequate funding. Therefore, the evidence suggests that the chemical contents of NS are a safe and possible treatment for COVID-19 patients that helps to improve COVID-19 infection in patients with no side effects. Nigella sativa seeds were one of the well-documented herbal products. Three reviewed randomized controlled trials reported that NS reduced covid-19 risk and could improve immune function. It was also helpful in upper respiratory infections such as asthma and bronchitis, with one RCT showing that honey and NS significantly improved symptoms, viral clearance, and mortality of COVID-19 patients. This review concludes that NS has a positive barrier effect on people at risk of acquiring a COVID-19 infection.

Comorbidities in Privately Insured South Africans With Systemic Lupus Erythematosus.

Introduction Comorbidities in systemic lupus erythematosus (SLE) impact negatively on health-related quality of life (HRQoL) and life expectancy. We investigated the frequency and spectrum of comorbidities in privately insured South Africans with SLE. Methods The data of SLE patients based on International Classification of Diseases, Tenth Revision (ICD-10) codes and insured with Discovery Health Medical Scheme (DHMS), South Africa, aged ≥16 years at diagnosisand with ≥6 months of follow-up were reviewed. Demographics, comorbidities listed in the Charlson comorbidity index (CCI), other common comorbidities, intercurrent illnesses, and drug therapy were documented. Results Of the 520 patients coded as SLE, 207 met the inclusion criteria. Most were females (90.8%), with a median (interquartile range {IQR}) age and follow-up duration of 39 (30.3-53.0) and 6.1 (3.7-8.1) years, respectively. All patients had at least one comorbidity; the most frequent CCI comorbidities were pulmonary disease (30.9%), congestive heart failure (CHF, 15%), and renal disease (14.0%). Other common comorbidities were hypertension (53.1%) and mood and anxiety disorders (46.9%). Urinary tract infections (UTIs, 37.7%) and pneumonia (33.8%) were common intercurrent illnesses. The independent predictors of CHF were renal disease (odds ratio{OR}=855), dyslipidemia (OR=15.3), and male gender (OR=43.0); the independent predictors of hypertension were age at diagnosis (OR=1.03), type 2 diabetes (OR=4.45), and renal disease (OR=4.34); and the independent predictors of mood and anxiety disorders were female gender (OR=3.98), stroke (OR=3.18), UTI (OR=2.39), and chloroquine use (OR=1.94). Conclusion In this study of privately insured South Africans with SLE, comorbidities were common, and all patients had at least one comorbidity. Hypertension, infections, and mood and anxiety disorders were the leading comorbidities overall, and pulmonary disease was the most commonCCI comorbidity. There is an obvious need to formally study the burden of mental health disorders inSouth African SLEpatients.

Degradation of Chloroquine by Ammonia-Oxidizing Bacteria: Performance, Mechanisms, and Associated Impact on N2O Production.

Since the mass production and extensive use of chloroquine (CLQ) would lead to its inevitable discharge, wastewater treatment plants (WWTPs) might play a key role in the management of CLQ. Despite the reported functional versatility of ammonia-oxidizing bacteria (AOB) that mediate the first step for biological nitrogen removal at WWTP (i.e., partial nitrification), their potential capability to degrade CLQ remains to be discovered. Therefore, with the enriched partial nitrification sludge, a series of dedicated batch tests were performed in this study to verify the performance and mechanisms of CLQ biodegradation under the ammonium conditions of mainstream wastewater. The results showed that AOB could degrade CLQ in the presence of ammonium oxidation activity, but the capability was limited by the amount of partial nitrification sludge (∼1.1 mg/L at a mixed liquor volatile suspended solids concentration of 200 mg/L). CLQ and its biodegradation products were found to have no significant effect on the ammonium oxidation activity of AOB while the latter would promote N2O production through the AOB denitrification pathway, especially at relatively low DO levels (≤0.5 mg-O2/L). This study provided valuable insights into a more comprehensive assessment of the fate of CLQ in the context of wastewater treatment.

Effect of Hydroxychloroquine and Azithromycin Combination Use in COVID-19 Patients - An Umbrella Review.

Hydroxychloroquine and Azithromycin combination was used rampantly in management of COVID-19 patients in different countries. Present review was conducted to evaluate the efficacy of Hydroxychloroquine and Azithromycin combination compared to the control (standard care) and any adverse effect following this combination use in COVID-19 patients if any. We included all the systematic review with or without meta-analysis reporting the effect of Hydroxychloroquine (HCQ) and Azithromycin (AZM) combination use in COVID-19 patient using three databases namely PubMed, medline, CINHAL, Web of Science from July 2020 till Jan 2022. The systematic search strategy has identified 104 studies in total, after removal of duplicates only 4 systematic reviews were included in the qualitative synthesis. The various tools for assessing and reporting the data in the reviews were PRISMA, ROBINS-I, Robs2, AMSTAR, MASTER checklists. Mortality among the hydroxychloroquine with azithromycin combination group was significantly higher than among the Standard Care group. The duration of hospital stay in days was shorter in the Standard Care group in comparison with the hydroxychloroquine group or the hydroxychloroquine and azithromycin combination group. Of the 4 systematic reviews included, 3 had low risk of bias and one had unclear risk of bias using the ROBIS tool. Chloroquine or Hydroxychloroquine combination did not shorten the duration of hospital stay. Rampant use of Chloroquine or Hydroxychloroquine alone or with Azithromycin combination caused adverse effects like QT prolongation. Finally, there is no evidence to support use of either Hydroxychloroquine with or without Azithromycin, for the treatment of COVID-19.

Evidence map of chikungunya treatmentsMapa de la evidencia sobre el tratamiento del chikunguña

Based on a review of the literature, to create a map of the available evidence on the treatment methods for chikungunya. In May 2022, a literature search on chikungunya was conducted using the PubMed and Virtual Health Library platforms. To create the evidence map, studies that mentioned chikungunya fever were selected and characterized based on the type of intervention, outcome, and direction of the effect (positive, negative, potentially positive or potentially negative, inconclusive, or no effect), following the methodology recommended by the Latin American and Caribbean Center on Health Sciences Information (BIREME). Fifteen studies (systematic reviews, controlled clinical trials, and narrative reviews) with both pharmacological and non-pharmacological interventions were included. All interventions focused on symptom mitigation; no study specifically investigated ways to combat the virus itself. Only one study on pharmacological interventions reported a positive effect, involving monotherapy with hydroxychloroquine and combined therapy with methotrexate plus sulfasalazine and hydroxychloroquine for reducing and relieving pain caused by post-chikungunya arthritis. The only study to report a negative effect described the use of chloroquine for post-chikungunya arthralgia. Among non-pharmacological interventions, positive effects were noted for transcranial direct current stimulation, elastic band exercises, and the Pilates method, particularly for pain relief and improvement of joint function. Although the review did not identify any treatments that act directly on the virus after the onset of the disease, the evidence map suggests that it is possible to treat the symptoms and sequelae of chikungunya with both pharmacological and non-pharmacological therapies.

A snapshot of a representative Brazilian state of illegal mining in indigenous areas during the era of malaria elimination.

Malaria is a public health problem and the cases diagnosed in the capital of Roraima, Brazil, show potential to characterize the burden of the disease in the state. This study aimed to describe the epidemiological, clinical, and laboratory aspects of malaria cases diagnosed in Boa Vista. For this purpose, a descriptive, cross-sectional study was conducted in two health units in the city, with individuals diagnosed and who agreed to respond the questionnaire. Of the total of 206 participants, characterized as men, mixed-race, and young, 96% (198) reported participating in illegal mining activity. Among the group of miners, 66% (131) came from other states of Brazil or other countries. The mines were mainly located in the Yanomami territory in Roraima. Plasmodium vivax infection occurred in 74% (153) of participants. In the miner's group, hospitalizations for severe malaria, previous malaria attacks, and delays in treatment after the onset of symptoms were reported. Although 73% (145) of miners reported knowing how malaria was transmitted, only 54% (107) used mosquito nets or repellents. The use of Artecom and chloroquine by miners is not for the complete treatment but only to relieve symptoms for returning to gold mines, highlighting the importance of molecular surveillance to antimalarial resistance. Indigenous peoples are considered vulnerable to malaria and miners promotes the increase of malaria in Roraima Indigenous Lands. Therefore, access to diagnosis and treatment in Indigenous areas invaded by miners is imperative to confront this disease that ravages Indigenous communities and threatens public health on a large scale to achieve the goal of eliminating malaria in the state.

Cornea Verticillata – a Rare Complication of Chloroquine Toxicity. Case Report

IntroductionCornea verticillata is characterized by bilateral grayish or golden-brown linear opacities in a typical vortex shape, mainly in the lower segments of the corneal epithelium, without covering the corneal stroma. It is most often associated with taking amiodarone but can be induced by other medications. Chloroquine is commonly used in treatment and prevention of protozoal diseases. Additionally, it has applications in dermatology and rheumatology as an anti-inflammatory agent in collagenosis, rheumatoid arthritis or lupus erythematosus. Its ophthalmic side effects and their management are noteworthy and are briefly summarized in this paper.Material and MethodsWe present a case of a 62-year-old female patient who was referred to the clinic for diagnosis of corneal lesions detected incidentally during a follow-up examination 6 months after starting treatment with chloroquine for rheumatoid arthritis.ResultsThe patient was diagnosed with cornea verticillata and informed that it does not affect visual acuity and is not an indication for changes in therapy. Discontinuation of medication results in partial or, in some cases, complete resolution of changes.DiscussionIt is important to closely monitor patients taking drugs that are known to have ophthalmic side effects for the first time in new indications. We should consider eye side effects when treating systemic disease and recommend screening tests.ConclusionsA baseline ophthalmic examination should be performed on all patients before initiating use of chloroquine. Moreover, chloroquine can lead to permanent loss of visual acuity contributing to bull’s eye maculopathy, which is irreversible.

Study on clinical presentation of malaria and response to antimalarial treatment in children less than twelve years

Background: In the tropical country of India, malaria in pediatric age group is one of the most important cause of mortality and morbidity. The study aimed to identify the clinicoepidemiologic features and response to antimalarial treatment in the children. Methods: Prospective analytical study conducted for the same over the period of two years in tertiary care hospital (September 2019 to September 2021). All children under twelve years hospitalised with fever and were diagnosed to have malaria by Peripheral smear or RDT were included in the study after ethical clearance and parental consent. Total sample size was 90. Results: Incidence of the malarial disease among total admitted patients in our study period was found to be 3.5%. The highest percentage of patients with malaria belonged to age group of 13m to 5 years (40%) and least being the age group 10-12years (7.7%). In study fever was found to be the major chief complaint followed by chills and rigor. Bleeding diathesis was least common It was found out from our study that overall most common clinical finding in the study patients was anemia or pallor with an overall of 35 patients (38.8%). Almost 73.3% (66) patients had anemia out of which 14.4% (13 patients) overall where found to have severe anemia and 27.7% (25) had moderate anemia and 31.1% (28 patients) had mild anemia. 27.7% (25) cases satisfied one or more WHO criteria for severe malaria. Conclusions: The emergence of severe malaria caused by P. vivax could have significant implications in planning the malaria-control programmes for the community. The widespread use of ACT for severe malaria as per the guidelines of the WHO could result in the emergence of resistant parasite strains. It may be rational to continue the use of chloroquine for malaria due to P. vivax in chloroquine-sensitive areas. In places where both P. vivax and P. falciparum co-exist, measures need to be equally targeted to P. vivax to decrease morbidity and mortality due to severe malaria.

Retinal alterations in evaluation of rheumatoid arthritis with chloroquine treatment: a new approach.

To evaluate the effect of hydroxychloroquine on conjunctival and retinal microvascular density in rheumatoid arthritis (RA) patients. 10 healthy controls, 10 RA patients who had not been treated with hydroxychloroquine, and 10 RA patients who had been treated with chloroquine for more than 5 years were recruited. Optical coherence tomography (OCTA) was used to examine the conjunctival and superficial and deep retinal microvascular density and compared the differences in microvascular density between the three groups. The vascular density in RA group in superficial microvascular was significantly lower than that in control group(P<0.001).Compared with RA group, the chloroquine group showed statistically significantly lower microvascular (P<0.001) and deep microvascular(P=0.018) .Superficial microvascular was positively correlated with conjunctival vessel density in RA patients (r=0.868, P=0.0048). The use of chloroquine could further reduce the vascular density in the absence of statistical difference in the course of the disease. This article is protected by copyright. All rights reserved.

If there's Relation between Malaria and COVID -19

Malaria is a parasitic infection, caused by parasites of the genus Plasmodium and transmitted by Anopheles mosquitoes, that leads to an acute life-threatening disease and poses a notable global health threating . According to the World Health Organization (WHO) data of 2019, about 228 million cases of malaria and 405,000 deaths were reported worldwide.Due to the similarity of symptoms between malaria and COVID-19, especially fever, difficulty in breathing, fatigue and headache of acute onset, a malaria patient may be misdiagnosed as COVID-19 and vice versa. Moreover, complications like acute respiratory distress syndrome (ARDS), septic shock, and multi-organ failure can also happen in both malaria and COVID-19. The first step to identify a COVID-19 patient is the symptomatic screening, which consists of shortness of breath, fever, dry cough, sore throat, headache and myalgia in a high-risk patient like healthcare workers or patients with a history of contact with a confirmed COVID-19 case.Some scientists attribute the inverse relationship between COVID 19 and malaria to the wide use of hydroxychloroquine (HCQ), chloroquine (CQ) and other anti-malarial drugs in countries that are endemic for malaria. In conclusion, COVID-19 has a variable prevalence among countries which is lower than expected in malaria-endemic regions. In addition to the possible role of health infrastructure and mitigation tools adopted, Both hydroxychloroquine (HCQ) and chloroquine (CQ) may have preventive and curative effects against SARS-CoV-2 virus through different mechanisms, however, clinical trials are still investigating the use of these medications as a potential treatment and preventive measures. The lower than expected number of cases detected in Asia suggests that the young age structure may be protective of severe and thus detectable cases.

Ganaplacide plus lumefantrine solid dispersion formulation: considerations for development and rollout

Due to reliance on antimalarials for clinical case management, drug resistance is a recurrent challenge for malaria control and elimination that requires relentless discovery and development of novel medicines with new modes of action. 1 Feachem RGA Chen I Akbari O et al. Malaria eradication within a generation: ambitious, achievable, and necessary. Lancet. 2019; 394: 1056-1112 Summary Full Text Full Text PDF PubMed Scopus (167) Google Scholar Since the widespread use of chloroquine in the 1950s, resistance has compromised the efficacy of all major classes of antimalarial drugs that are widely used to treat Plasmodium falciparum. These drugs include sulfadoxine–pyrimethamine and since 2007, 2 Fairhurst RM Dondorp AM Artemisinin-resistant Plasmodium falciparum malaria. Microbiol Spectr. 2016; 4 (10.1128/microbiolspec.EI10-0013-2016.) Crossref PubMed Scopus (174) Google Scholar artemisinin-class medicines and partner drugs, which have been crucial for preventing deaths from malaria in the past two decades. 1 Feachem RGA Chen I Akbari O et al. Malaria eradication within a generation: ambitious, achievable, and necessary. Lancet. 2019; 394: 1056-1112 Summary Full Text Full Text PDF PubMed Scopus (167) Google Scholar , 3 Ishengoma DS Saidi Q Sibley CH Roper C Alifrangis M Deployment and utilization of next-generation sequencing of Plasmodium falciparum to guide anti-malarial drug policy decisions in sub-Saharan Africa: opportunities and challenges. Malar J. 2019; 18: 267 Crossref PubMed Scopus (15) Google Scholar Partial resistance to artemisinin-based combinations threatens their efficacy throughout southeast Asia, and is now emerging rapidly in sub-Saharan Africa. 4 Rosenthal PJ Has artemisinin resistance emerged in Africa?. Lancet Infect Dis. 2021; 21: 1056-1057 Summary Full Text Full Text PDF PubMed Scopus (0) Google Scholar Although complete resistance has not yet been documented, this risk would be disastrous, necessitating urgent development of new antimalarial drugs that are effective against artemisinin-resistant parasites. Ganaplacide (KAF156) plus lumefantrine solid dispersion formulation combination for uncomplicated Plasmodium falciparum malaria: an open-label, multicentre, parallel-group, randomised, controlled, phase 2 trialGanaplacide plus lumefantrine-SDF was effective and well tolerated in patients, especially adults and adolescents, with uncomplicated P falciparum malaria. Ganaplacide 400 mg plus lumefantrine-SDF 960 mg once daily for 3 days was identified as the optimal treatment regimen for adults, adolescents, and children. This combination is being evaluated further in a phase 2 trial ( NCT04546633 ). Full-Text PDF

Clinical isolates of uncomplicated falciparum malaria from high and low malaria transmission areas show distinct pfcrt and pfmdr1 polymorphisms in western Ethiopia

BackgroundPfcrt gene has been associated with chloroquine resistance and the pfmdr1 gene can alter malaria parasite susceptibility to lumefantrine, mefloquine, and chloroquine. In the absence of chloroquine (CQ) and extensive use of artemether–lumefantrine (AL) from 2004 to 2020 to treat uncomplicated falciparum malaria, pfcrt haplotype, and pfmdr1 single nucleotide polymorphisms (SNPs) were determined in two sites of West Ethiopia with a gradient of malaria transmission.Methods230 microscopically confirmed P. falciparum isolates were collected from Assosa (high transmission area) and Gida Ayana (low transmission area) sites, of which 225 of them tested positive by PCR. High-Resolution Melting Assay (HRM) was used to determine the prevalence of pfcrt haplotypes and pfmdr1 SNPs. Furthermore, the pfmdr1 gene copy number (CNV) was determined using real-time PCR. A P-value of less or equal to 0.05 was considered significant.ResultsOf the 225 samples, 95.5%, 94.4%, 86.7%, 91.1%, and 94.2% were successfully genotyped with HRM for pfcrt haplotype, pfmdr1-86, pfmdr1-184, pfmdr1-1042 and pfmdr1-1246, respectively. The mutant pfcrt haplotypes were detected among 33.5% (52/155) and 80% (48/60) of isolates collected from the Assosa and Gida Ayana sites, respectively. Plasmodium falciparum with chloroquine-resistant haplotypes was more prevalent in the Gida Ayana area compared with the Assosa area (COR = 8.4, P = 0.00). Pfmdr1-N86Y wild type and 184F mutations were found in 79.8% (166/208) and 73.4% (146/199) samples, respectively. No single mutation was observed at the pfmdr1-1042 locus; however, 89.6% (190/212) of parasites in West Ethiopia carry the wild-type D1246Y variants. Eight pfmdr1 haplotypes at codons N86Y–Y184F–D1246Y were identified with the dominant NFD 61% (122/200). There was no difference in the distribution of pfmdr1 SNPs, haplotypes, and CNV between the two study sites (P > 0.05).ConclusionPlasmodium falciparum with the pfcrt wild-type haplotype was prevalent in high malaria transmission site than in low transmission area. The NFD haplotype was the predominant haplotype of the N86Y–Y184F–D1246Y. A continuous investigation is needed to closely monitor the changes in the pfmdr1 SNPs, which are associated with the selection of parasite populations by ACT.

The use of chloroquine with or without adjuncts in the effective management of scorpion sting in the tropics: case reports.

Patients presented with pain emanating from the right big toe and medial arch, respectively. The said pain had same manifestation and intensity in both patients and followed same course but radiated higher in up to the ipsilateral flank in the first patient but was limited to the ipsilateral iliac region of the second patient. The sites showed signs of inflammation with pain being most prominent. Diagnosis of scorpion envenomation were made based on the given history. The pain was eliminated using chloroquine given intramuscularly at the site of scorpion sting. Scorpion sting can occur at any time in the tropic and lidocaine only cannot alleviate pain. Chloroquine can be used in managing scorpion sting as it also has many other benefits that can make it more preferred to the other conventional approaches used.

A survey of chloroquine use for prevention and treatment of COVID-19 in Nigeria.

Rampant chloroquine/hydroxychloroquine poisoning in Nigerian hospitals following suggestions of its possible efficacy in the treatment and prevention of the newly emerged COVID-19 disease informed this survey. The aim of this study was to assess the knowledge, attitude and perception of the Nigerian populace on the use of chloroquine in the COVID-19 pandemic. This cross-sectional study was done by administering an electronic questionnaire created using Google Docs, through social media cascade methods including the WhatsApp application software to capture data on chloroquine use between April 20 and June 20, 2020. Six hundred and twenty-eight people responded to the questionnaire (response rate 99.2%, mean age 41.05 ± 12.3) from the six geopolitical zones in Nigeria with 556 (88.5%) having tertiary level education. Only 21 (3.3%) of the respondents took chloroquine for treatment or prevention. Respondents from the North-west geopolitical zones used chloroquine 5.8 (95% CI: 1.55, 21.52, p=0.02) more times than other zones while the age group 20-29 were 8.8 times more likely to use chloroquine than any other age group (95% CI: 3.53, 21.70, p = 0.00). Female respondents were 2.3 times more likely to use chloroquine than the males (OR 2.26 95% CI: 0.90-5.68; p=0.08) and those in the income bracket of N75,000-99,000, 2.5 times more than other income groups. Young adults, North-western geopolitical zone, and female gender should be target groups for education on rational chloroquine use. The danger of chloroquine overdose should be communicated to the general population in Nigeria.

Adverse events in rheumatoid arthritis patients under antimalarial treatment—Is there cardiovascular compromise?

Introduction: The antimalarials chloroquine and hydroxychloroquine have been used for several decades in treating malaria and some autoimmune diseases—mainly rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE)—with excellent efficacy and safety. Due to the massive use of antimalarials worldwide for managing SARS-CoV-2/COVID-19 infection during the last 2 years and the consequent increase in cardiac arrhythmia, fear has risen about the safety of using antimalarials, especially for patients with increased cardiovascular risk.Objective: To describe a real-life experience about the safety of antimalarials in the setting of a single rheumatological center in Colombia.Methods: This is a cross sectional study that includes patients diagnosed with RA and treated with antimalarials between 2020 and 2021. Clinical follow-up information was gathered from the medical records, and all reported adverse events were described.Results: A total of 957 patients were included, primarily women (79.2%). The most frequent comorbidities were hypertension and osteoporosis. Chloroquine use was more frequent than hydroxychloroquine (86.4% vs. 13.6%). During the observation period, 243 (25.4%) patients presented at least one adverse event, 72 (29.6%) had retinal toxicity, 85 (35%) dermatological events, and 81 (33.3%) gastrointestinal intolerance. Other adverse events reported less frequently (15.2%) included headache, dizziness, lipothymia, and elevated transaminases. There were no reports of cardiovascular events from the period of antimalarial use to the date of data collection despite the high frequency of previous metabolic or cardiovascular disease in this cohort.Conclusion: This study reasserts the evidence of antimalarials safety profile for patients with rheumatological conditions such as RA. RA patients that were treated with antimalarials at doses recommended by the guidelines had no cardiovascular events.

Maculopathy due to prolonged use of chloroquine: functional evaluation performed by microperimetry-a case report

Maculopathy due to prolonged use of chloroquine: functional evaluation performed by microperimetry-a case report