Chinedu Ogbonnia Egwu

Background: Increased tolerance and resistance to antimalarial drugs is one of the major threats responsible for the stagnation in the fight against malaria. The role of Plasmodium falciparum strain complexity to the overall efficacy of antimalarial drugs in naturally occurring infections is not fully understood. Objective: This study investigated the impact of mixed infections of resistant and susceptible strains to antimalarials. Methods: Fifteen Gambian field isolates and two laboratory strains (Dd2 and 3D7) were used for the complexity assays. IC₅₀ and malaria drug survival assay (mDSA) were used to determine the survival and erythrocyte reinvasion rates of parasites following sub-therapeutic exposure to conventional antimalarials (CQ – 200 nM; PPQ – 200 nM, DHA – 24 nM, and LUM – 200 nM). The complexity of infection (COI) in the field isolates was confirmed by McCOIL tool, and the lab strains co-cultured at different proportions (100:0, 75:25, 50:50, 25:75, and 0:100) were exposed to CQ, DHA, and LUM. Results: Our findings show that the resistant haplotype in a mixed infection drives the drug response through a significant (p < 0.05) shift in the IC₅₀ of drugs. This shift in IC₅₀ was most distinct for chloroquine using mixed infections of 3D7/Dd2. There was high reinvasion after subtherapeutic exposure to conventional antimalarial drugs in the field isolates. Isolates with resistant haplotypes against chloroquine, even in mixtures with susceptible strains, survived more. Conclusion: Responses under drug pressure are strongly driven by the resistant haplotypes circulating alongside the wild types of Plasmodium falciparum. There is a need for continuous surveillance.

Implication des mécanismes redox dans le mode d’action des antipaludiques et la résistance à l’artémisinine: Le paludisme est une maladie à transmission vectorielle causée par Plasmodium transmis par les moustiques femelles du genre Anopheles. En dépit des nombreux efforts déployés, le paludisme reste un problème majeur de santé publique avec plus de 400 000 décès chaque année. Le développement des antipaludiques fait face à l’émergence quasi-systématique de parasites résistants. La résistance aux médicaments actuels de référence, l'artémisinine et ses dérivés, a été signalée pour la première fois au Cambodge en 2008 et s'est depuis étendue à toute l’Asie. Des premiers cas de résistance ont également été rapportés récemment en Amérique du Sud et en Afrique. Il est donc urgent de proposer de nouvelles stratégies thérapeutiques pertinentes. Notre travail s’est concentré sur l’étude, chez Plasmodium falciparum, de l’implications de mécanismes redox dans i) le mode d’action de différentes molécules antipaludiques et ii) dans le phénomène de résistance associé à l’artémisinine. Pour cela, nous avons tout d’abord développé une nouvelle méthode d’analyse de la quantification des espèces réactives de l’oxygène (ROS) intra-érythrocytaire par chromatographie liquide couplée à la spectrométrie de masse (LC-MS). Ce protocole a ainsi permis de mettre en évidence l'implication des radicaux superoxydes dans le mécanisme d'action de différentes classes d'antipaludiques telles que les artémisinines ou l’atovaquone. Dans un second temps, nous avons étudié chez Plasmodium falciparum, le rôle du processus redox dans la résistance aux artémisinines en comparant une souche sensible et une souche résistante à l’artémisinine, à l’état basal et après traitement. Différents marqueurs de la régulation redox ont été suivis et comparés tels que la production de ROS, le niveau d’oxydation des protéines et l'expression de molécules ou d’enzymes aux propriétés antioxydantes. Nous avons démontré, grâce à différentes techniques analytiques originales, que les parasites résistants aux artémisinines ont une capacité accrue à gérer la production de ROS induite par le traitement, comparativement aux parasites sensibles et que ce phénomène est notamment lié à une surexpression d'antioxydants. Ce travail apporte des éléments nouveaux concernant le mécanisme d'action d’antipaludiques majeurs et met en évidence le rôle essentiel des mécanismes redox dans la résistance de Plasmodium falciparum à l'artémisinine. Ces résultats seront à prendre en compte dans le développement de nouveaux antipaludiques afin de contourner la résistance aux artémisinines et vaincre le paludisme.

Background: HIV-related opportunistic infections like Pneumocystis jirovecii Pneumonia (PCP) remain a major contributor to child morbidity and mortality globally. PCP accounts for over 60% of AIDS in the first year of life and is responsible for a third of AIDS in children globally. Cotrimoxazole prophylaxis, which is an intervention directed towards tackling this burden, has not attained remarkable coverage despite advocacy towards scale-up. This work was therefore aimed at evaluating the efficacy of cotrimoxazole in the prevention of PCP among children exposed to and infected with HIV by carrying out a systematic review. Methods: Key scientific databases were searched for primary studies not older than 15 years old without language restrictions. Randomized Control Trials (RCTs) and Cohorts comparing the effectiveness of cotrimoxazole versus placebo in the prevention of PCP among children (p-value of 0.008). The adverse events associated with cotrimoxazole are comparable to a placebo when co-administered with ARTS (p = 0.90), which did not impact adherence. Conclusion: The benefits of cotrimoxazole prophylaxis far outweigh its risks. Therefore, scaling up the intervention is recommended as a prophylactic for wider coverage, especially in resource-limited settings.

Breast cancer incidence is on the rise regardless of several interventions available for its management. This scenario may be worse in resource-limited countries. This study, therefore, aimed to evaluate the knowledge and attitude of women towards Breast Cancer Screening (BCS) in Aminu Kano Teaching Hospital (AKTH), Kano State, a typically resource-limited state in Nigeria. This was a cross-sectional study. The study population comprised female individuals aged 18–45 years attending the Antenatal and Postnatal clinics of AKTH. An adopted questionnaire instrument was used to extract vital information on the knowledge and attitude of women towards breast cancer screening in the Antenatal and Postnatal clinics of AKTH. Our findings showed that there is much awareness about BCS, even though most participants’ knowledge about the methods and timing of the scan is low. Much enlightenment is achieved through the availability of print and electronic media on BCS. A better attitude is shown when trained personnel conduct BCS. A good number of participants who have knowledge are yet to translate their knowledge and attitudes into practice. Based on our findings, coordinated and timely awareness campaigns should be organized by local health authorities to improve knowledge and attitude towards BCS.

Background: Hypertension (HTN) is a global disease of public health concern. It is considered a major cause of morbidity and mortality worldwide. The global and regional recommendations for the management of high blood pressure are complicated, with an increasing call for several adequate measures to commence treatment, increase the dosage, or introduce a new class of medication. Evidence suggests that most people with HTN require more than one drug regime to achieve blood pressure goals, with a greater percentage of patients reporting only having access to monotherapy. This work evaluated the combined effectiveness of angiotensin receptor blockers (ARBs) and hydrochlorothiazide (HCTZ) compared to ARB monotherapy in an uncontrolled hypertensive patients. Methods: The search involved screening through databases such as Cochrane Library, PubMed, CINAHL, Embase, Medline, and the Web of Science, medical journals, and international registry on clinicals from the WHO were searched for primary studies not older than 13 years. Randomized control trials (RCTs) comparing the effectiveness of ARB/HCTZ versus ARB monotherapy in hypertensive patients were selected. Care was taken to include only studies that lasted at least four weeks. Meta-analysis was conducted on RevMan 5.3 statistical application software, following data extraction. Data quality and risk of bias assessment were also all assessed. A total of seven RCTs were considered for this study involving 4814 participants. Results: The result from the intervention arm revealed that ARB/HCTZ combination resulted in a higher rate of target blood pressure achievement when compared to ARB monotherapy relative risk (RR) = 1.53, 95% confidence interval (CI) (1.42, 1.65), with p < 0.00007. The adverse effects observed in the intervention arm were not significant. Conclusion: The ARB/HCTZ combination therapy was more effective in lowering and controlling blood pressure when compared to ARB monotherapy without significant adverse drug effects reported by the participants. Health workers should therefore recommend ARB/HCTZ combination therapy for patients with uncontrolled hypertension.

There is a myriad of diseases that plague the world ranging from infectious, cancer and other chronic diseases with varying interventions. However, the dynamism of causative agents of infectious diseases and incessant mutations accompanying other forms of chronic diseases like cancer, have worsened the treatment outcomes. These factors often lead to treatment failure via different drug resistance mechanisms. More so, the cost of developing newer drugs is huge. This underscores the need for a paradigm shift in the drug delivery approach in order to achieve desired treatment outcomes. There is intensified research in nanomedicine, which has shown promises in improving the therapeutic outcome of drugs at preclinical stages with increased efficacy and reduced toxicity. Regardless of the huge benefits of nanotechnology in drug delivery, challenges such as regulatory approval, scalability, cost implication and potential toxicity must be addressed via streamlining of regulatory hurdles and increased research funding. In conclusion, the idea of nanotechnology in drug delivery holds immense promise for optimizing therapeutic outcomes. This work presents opportunities to revolutionize treatment strategies, providing expert opinions on translating the huge amount of research in nanomedicine into clinical benefits for patients with resistant infections and cancer.

The rising burden of Diabetes mellitus (DM) globally and particularly in sub-Sahara Africa calls for alternative treatment solutions. This is because the currently available drugs for its management are limited due to undesirable adverse effects and high cost. Thus, this review explores diabetes and summarizes its treatment options, focusing mainly on medicinal plants therapy. Information on twenty-five selected medicinal plants from sub-Sahara Africa having hypoglycemic and anti-diabetic potentials was obtained via electronic search of major databases, such as Pubmed/Medline, Scopus, Google Scholar and web of science. Predominant bioactive compounds found in these plants include tannins, carpaine, terpenoids, hexadecenoic acid, luteolin, saponins, glycosides, rutin, quercetin, vindoline and kaempferol. Robust evidence indicates that these medicinal plants and their bioactive components exert their antidiabetic potentials via different mechanisms, including: regeneration of pancreatic β-cell and insulin secretion; inhibition of α-amylase, inhibition of intestinal glucose absorption and liver glucose production; antioxidative stress; limitation of glycogen degradation and gluconeogenesis; anti-inflammatory, immunoregulatory. DM imposes a tremendous burden in the region, and its prevalence is not abating; thus the rich flora of the region with known hypoglycemic and antidiabetic efficacy could be explored as a complementary therapy in its management.

The fight against malaria is a continuum as the epidemic is not abating. For proper deployment of tools in the fight against malaria, an assessment of the situation is necessary. This work assessed the level of antimalarial drug treatment failure in Ebonyi State, Nigeria. Both survey and in vitro analyses were adopted. The survey was used to obtain qualitative information from both the malaria subjects and the pharmacies where antimalarial drugs are sourced. The results from the survey were complemented by an in vitro assay of the level of active pharmaceutical ingredients (APIs) in the commonly used artemisinin combination in Nigeria; artemether/lumefantrine. Results from the survey revealed that artemisinin combination therapies (ACTs) remain the mainstay in the treatment of malaria, even though other non-artemisinin drugs are still used. It also revealed that many patients still self-medicate, although, this may not be connected to the treatment failure seen among some malaria subjects. The in vitro assay showed that ACT contains the right quantity of APIs. Further surveillance is, therefore, necessary to understand the real cause of treatment failure among malaria subjects in Nigeria.

Lassa fever (LF) is a rodent-borne disease that threatens human health in the sub-region of West Africa where the zoonotic host of Lassa virus (LASV) is predominant. Currently, treatment options for LF are limited and since no preventive vaccine is approved for its infectivity, there is a high mortality rate in endemic areas. This narrative review explores the transmission, pathogenicity of LASV, advances, and challenges of different treatment options. Our findings indicate that genetic diversity among the different strains of LASV and their ability to circumvent the immune system poses a critical challenge to the development of LASV vaccines/therapeutics. Thus, understanding the biochemistry, physiology and genetic polymorphism of LASV, mechanism of evading host immunity are essential for development of effective LASV vaccines/therapeutics to combat this lethal viral disease. The LASV nucleoprotein (NP) is a novel target for therapeutics as it functions significantly in several aspects of the viral life cycle. Consequently, LASV NP inhibitors could be employed as effective therapeutics as they will potentially inhibit LASV replication. Effective preventive control measures, vaccine development, target validation, and repurposing of existing drugs, such as ribavirin, using activity or in silico-based and computational bioinformatics, would aid in the development of novel drugs for LF management.