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Pharmacophore Enhanced Shape Alignment (PheSA) compares the similarities of compounds based on their pharmacophoric and geometrical characteristics. Ligand efficiency is a notion used to maximize the potency and effectiveness of medication candidates by taking into account their molecular weight and binding affinity. This study mainly focused on Cycloguanil analogues to evaluate the association between PheSA scores and ligand efficiency in the identification of effective antimalarials. Information on 36 PfDHFR inhibitors, their structures and biological activity was retrieved from the ChEMBL database. Based on shape and pharmacophore similarity, the PheSA algorithm was used to compare the 3D structures of the inhibitors. Based on a de novo synthesis method, 257 new compounds with greater PheSA similarity scores that have a striking resemblance to cycloguanil were created. The PheSA score and ligand efficiency have a moderately positive link (correlation coefficient of 0.675) according to the analysis. However, the virtual screening of cycloguanil analogues based on PheSA similarity scores offers a useful initial evaluation of structural similarity, directing further experimental studies to find interesting substances for the creation of effective antimalarial drug.

The World Health Organization recommends parasite-based diagnosis of malaria before the administration of artemisininbased combination therapy (ACT). Trained community medicine distributors (CMDs) constitute a credible option in healthcare delivery in resource-limited and hard-to-reach settings. This study evaluated the performance of mRDT, microscopy and PCR in the diagnosis of malaria among febrile under-5 children in rural South-western Nigeria. One thousand and forty-three (1,043) febrile children aged 3 – 59 months were enrolled on this study as part of a larger one. The CMDs collected finger prick blood samples and performed mRDT, prepared thick blood smears for malaria microscopy and blood spots on filter paper for PCR assays. Malaria was detected in 78.7%, 69.2% and 55% by mRDT, PCR and microscopy, respectively. The sensitivity of mRDT was 88.2% versus 92.5% while specificity was 42.2% versus 38.2% against PCR and microscopy, respectively. The PPV, NPV and diagnostic accuracy were 88.2% versus 64.8, 61.7% versus 80.6% and 74.0% versus 68.1% respectively. Levels of agreement with PCR and microscopy were fair (κ-value = 0.336 versus 0.322). PCR detected 97.8% P. falciparum, 4.4% P. malariae and 2.5% P. ovale. Trained community medicine distributors can effectively performed malaria rapid diagnostic tests to guide appropriate home management of malaria in resource-limited settings. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the comparative efficacy of amodiaquine (AMQ) alone and the combination of AMQ and chlorpheniramine (CP) in the treatment of acute uncomplicated malaria in children. Subjects: Of the 110 children enrolled in the study, 103 with acute uncomplicated malaria, aged 6 months to 12 years, were evaluated using the 14-day modification of the WHO field test. The patients were randomized to 2 groups. Group 1 received supervised treatment with AMQ alone (10 mg AMQ base/kg daily for 3 days), while group 2 received supervised treatment with AMQ (same dose as group 1) plus CP (AMQCP) for 7 days. Results: Both treatment regimens were well tolerated and no patient was withdrawn as a result of recurrent vomiting or drug-related adverse events. There was no significant difference in mean fever and parasite clearance times. The cure rates at day 7 were 90.2 versus 100% (ρ = 0.027) for AMQ versus AMQCP, while the day 14 cure rates were 85.9 versus 98.1% for AMQ versus AMQCP, respectively (ρ = 0.016). Conclusion: The combination of AMQ plus CP proved significantly more effective than AMQ alone in the treatment of acute uncomplicated falciparum malaria, most probably due to the enhancement of the antimalarial effect of AMQ by CP. The combination of AMQCP could be a better alternative to AMQ alone as a companion drug in artemisinin-based combination therapies. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background Increasing resistance to sulfadoxine-pyrimethamine is leading to a decline in its effectiveness. We aimed to assess the safety profile of chlorproguanil-dapsone (CD), and to compare the safety and efficacy of this drug with that of sulfadoxine-pyrimethamine (SP) as treatment for uncomplicated falciparum malaria.Methods We undertook a double-blind, randomised trial in 1850 consecutively recruited children with uncomplicated falciparum malaria, pooling data from five African countries. Analyses were based on all randomised patients with available data.Findings CD was significantly more efficacious than SP (odds ratio 3·1 [95% CI 2·0–4·8]); 1313 patients (96%) given CD and 306 (89%) given SP achieved acceptable clinical and parasitological response by day 14. Adverse events were reported in 46% and 50% of patients randomised to CD and SP, respectively (treatment difference –4·4%, [95% CI -10·1 to 1·3]). Haemoglobin in the CD group was significantly lower than in the SP group at day 7, a difference of -4 g/L (95% CI -6 to -2). Mean day 14 haemoglobin (measured only for the small number of patients whose day 7 data caused concern) was 94 g/L (92–96) and 97 g/L (92–102) after CD and SP, respectively. Glucose-6-phosphate dehydrogenase deficient patients on CD had greater odds than those on SP of having a fall of 20 g/dL or more in haemoglobin when baseline temperature was high. Methaemoglobinaemia was seen in the CD group (n=320, mean 0·4% [95% CI 0·4–0·4]) before treatment, 4·2% (95% CI 3·8–4·6) (n=301) at day 3, and 0·6% (0·6–0·7) (n=300) at day 7).Interpretation CD had greater efficacy than SP in Africa and was well tolerated. Haematological adverse effects were more common with CD than with SP and were reversible. CD is a useful alternative where SP is failing due to resistance. [Copyright &y& Elsevier]

The clinical characteristics and the kinetics of the disposition of the hepatomegaly associated with acute, uncomplicated Plasmodium falciparum malaria were investigated in 162 children in an endemic area of Nigeria. Hepatomegaly was significantly more common in the younger than in the older children. Complete resolution occurred in 48% following antimalarial chemotherapy. In the children in whom hepatomegaly did not resolve, a reduction in liver size of < 17% by the time parasitaemia was cleared (usually on day 3) was associated with non-resolution of hepatomegaly by days 7 or 14 of follow-up. An increase in liver size to at least 125% of the baseline value by day 4 or 5 was associated with a lack of therapeutic response, providing the child involved was aged < 5 years. In the children who had complete clearance of parasitaemia and resolution of hepatomegaly, there was no significant relationship between the parasitaemia-derived conventional indices of therapeutic response [i.e. time to clearance of 50% (PC50) or 90% (PC90) of the parasitaemia, and the parasite-clearance time (PCT)] and the corresponding parameters derived from measurement of liver size [i.e. time for resolution of 50% (HR50) or 90% (HR90) of the hepatomegaly and the hepatomegaly-resolution time (HRT)] in the same patients. However, as the HR50:PC50, HR90:PC90 and HRT:PCT ratios were similar (range = 1.6-2.1), the liver parameters may have therapeutic application. In the children with drug-sensitive P. falciparum infections and in whom hepatomegaly completely resolved, the area produced by plotting liver size against time (i.e. the area under the curve of hepatomegaly v. time, or AUC[sub hp]) increased in proportion to the liver size below the costal margin (P=0.02, from analysis of variance), but there was no significant difference in the half-lives of hepatomegaly (t½[sub hp]) or in the ratios of liver size to AUC[sub hp], indicating that the kinetics of the resolution of hepatomegaly were linear in the range examined. Comparison of the kinetic indices of hepatomegaly and parasitaemia showed that, although the half-lives of parasitaemia and hepatomegaly and the corresponding clearance values were similar, there was no correlation between these parameters among those in whom hepatomegaly completely resolved and parasitaemia completely cleared. These results indicate that routine clinical measurement of the liver size in children with hepatomegaly during acute, uncomplicated, P. falciparum malaria may have some use in evaluating and monitoring the therapeutic responses of infections. The resolution of hepatomegaly, a reflection of pathological changes, lags behind clearance of parasitaemia in children with P. falciparum malaria, and supports the use of the liver 'rate' as a malariometric index for assessing the intensity of transmission in endemic areas. [ABSTRACT FROM AUTHOR]

Background: Adverse drug reaction (ADR) is a global and frequently occurring medical emergency with increased cases of mortality annually. ADRs can occur with the use of all drugs including artemisinin-based combination therapy (ACTs) which are currently the treatment of choice for acute uncomplicated malaria globally. Numerous doses of ACTs are administered daily in malaria endemic areas., Aims: This study determined the incidence, pattern of presentation and factors associated with ADRs to two ACTs- artemisinin piperaquine (AP) and artemether-lumefantrine (AL) among children with confirmed acute uncomplicated malaria in Ibadan, Nigeria., Methods: Children aged 2-10 years enrolled into a larger study evaluating the safety and efficacy of artemisinin /piperaquine (AP) and artemether /lumefantrine (AL) using the WHO 28-day protocol were studied. Monitoring for ADR was based on history from the parent and /or child (for occurrences of treatment emergent signs and symptoms), physical examinations and abnormalities in laboratory investigations- full blood count, blood chemistry and liver function tests. Causality assessment for the ADR was by the Naranjo algorithm scale., Result: 108 of 114 (94.7%) children completed the study. Over half [61(56.5%] were males. The mean age of enrollees was 65.1±30.0 months. Day 28 adequate clinical and parasitological response (ACPR) for AP was 96.1% and 90.4% for AL. Observed ADRs were cough, diarrhea, loss of appetite, abdominal pain, rash, irritability, insomnia and headache. The prevalence was similar in the two treatment groups (AL=14%, AP= 11%; ρ=1.000). The incidence of ADR to both ACTs was 12/1000 patients per day. All ADRs were mild and resolved spontaneously. No notable associated factor to ADR was detected in this study., Conclusion: Artemether-lumefantrine and Artemisinin piperaquine were found to be safe in the study population., Competing Interests: The Authors declare that no competing interest exists, (Copyright © 2023 by West African Journal of Medicine.)

Malaria remains a global public health challenge. The disease has a great impact in sub-Saharan Africa among children under five years of age and pregnant women. Malaria control programs targeting the parasite and mosquitoes vectors with combinational therapy and insecticide-treated bednets are becoming obsolete due to the phenomenon of resistance, which is a challenge for reducing morbidity and mortality. Malaria vaccines would be effective alternative to the problem of parasite and insecticide resistance, but focal reports of polymorphisms in malaria candidate antigens have made it difficult to design an effective malaria vaccine. Therefore, studies geared towards elucidating the polymorphic pattern and how genes targeted for vaccine design evolve are imperative. We have carried out molecular and genetic analysis of two genes encoding vaccine candidates-the Plasmodium falciparum cell traversal ookinetes and sporozoites ( Pfceltos ) and P. falciparum reticulocyte binding protein 5 ( Pfrh5 ) in parasite isolates from malaria-infected children in Ibadan, Nigeria to evaluate their genetic diversity, relatedness and pattern of molecular evolution. Pfceltos and Pfrh5 genes were amplified from P. falciparum positive samples. Amplified fragments were purified and sequenced using the chain termination method. Post-sequence edit of fragments and application of various population genetic analyses was done. We observed a higher number of segregating sites and haplotypes in the Pfceltos than in Pfrh5 gene, the former also presenting higher haplotype (0.942) and nucleotide diversity ( θ  = 0.01219 and π  = 0.01148). In contrast, a lower haplotype (0.426) and nucleotide diversity ( θ  = 0.00125; π  = 0.00095) was observed in the Pfrh5 gene. Neutrality tests do not show deviation from neutral expectations for Pfceltos , with the circulation of multiple low frequency haplotypes (Tajima's D = -0.21637; Fu and Li's D = -0.08164; Fu and Li's F = -0.14051). Strong linkage disequilibrium was observed between variable sites, in each of the genes studied. We postulate that the high diversity and circulation of multiple haplotypes has the potential of making a Pfceltos -subunit vaccine ineffective, while the low genetic diversity of Pfrh5 gene substantiates its evolutionary conservation and potential as a malaria vaccine candidate., Competing Interests: The authors declare there are no competing interests., (©2023 Oboh et al.)

Background: Acute respiratory failure, a major cause of death in COVID-19, is managed with high-flow oxygen therapy via invasive mechanical ventilation. In resource-limited settings like Nigeria, the shortage of ventilators and oxygen supply makes this option challenging. Evidence-based non-invasive alternatives to mechanical ventilation such as the use of continuous positive airway pressure (CPAP) devices exist, but there have been concerns that non-invasive ventilation may expose healthcare workers to infection from aerosolized dispersion of SARS-CoV-2. We propose to evaluate the feasibility, adaptability and acceptability of a CPAP/O 2 helmet solution for non-invasive ventilation among patients with COVID-19 and health workers in eight COVID-19 treatment and isolation centers in Nigeria., Methods: The study will occur in 4 stages: (1) convene a Steering Committee of key stakeholders and recruit implementation sites; (2) use the integrated Promoting Action on Research Implementation in Health Services (i-PARiHS) framework to guide a needs assessment of treatment centers' capacity to use high-flow oxygen therapy to treat COVID-19 patients and utilize the findings to develop an implementation strategy for the use of a CPAP/O 2 helmet solution; (3) build infrastructure to support training and data monitoring processes and to develop implementation protocols to evaluate the adaptability of the strategy for the use of the CPAP/O 2 helmet; and (4) train health workers, distribute a CPAP/O 2 helmet solution for non-invasive ventilation, pilot test the implementation strategy, and assess feasibility of its use and acceptability that includes monitoring altered risk of SARS-CoV-2 infection among healthcare workers., Discussion: The CPAP/O 2 helmet solution for non-invasive ventilation in Nigeria can serve as a scalable model for resource-poor countries, and beyond the COVID-19 pandemic, has the potential to be deployed for the treatment of pneumonia and other respiratory diseases., Trial Registration: NCT04929691. Registered June 18, 2021-retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04929691., (© 2021. The Author(s).)

Background: Malaria in pregnancy has significant adverse consequences for the mother, foetus and baby. Presumptive diagnosis continues despite recommendation for parasite-based diagnosis. We performed Paracheck-Pf TM , an HRP-II based malaria Rapid diagnostic test (Paracheck-Pf RDT) and microscopy among pregnant women in a prospective, cross sectional study, at the University College Hospital in Ibadan, Nigeria., Methods: The study was conducted between 2009-2011. Consecutive pregnant women presumptively diagnosed as having malaria >18 years were enrolled after obtaining written informed consent. Demographic information, symptoms and clinical measurements were obtained. Capillary blood was obtained by finger prick for thick blood smear and RDT evaluation. Summary statistics included mean (standard deviation) for quantitative variables and percentages for categorical variables. Chi-square, analysis of variance (ANOVA), the odds ratio (OR) and 95% confidence intervals (CI) were computed with p-value less than 0.05 considered statistically significant., Results: Of the 746 pregnant women aged 30.9 ± 4.6 years enrolled, 243 (32.7%) were primigravida. The mean gestational age was 23.3 ± 9.2 weeks with about 81% in the second and third trimester. The prevalence of malaria parasitaemia by microscopy and Paracheck-Pf TM were 22.8% and 24.5% respectively. The geometric mean parasite density was 2,091/µL (range 40-156,975/µL). HIV positivity rate was 8.1 % and 16.1% of patients were anaemic (PCV <30%). Women with axillary temperature >37.4°C were significantly more likely to have malaria parasitaemia [p<0.0001] by microscopy. Sensitivity and specificity of Paracheck overall were 69.9% and 88.2% respectively while those at of parasite densities ≥200/µL were 84.8% and 88.7% respectively. Positive and negative predictive values were 66.9% and over 90% respectively., Conclusion: RDTs are a reasonable alternative in view of the need for parasite-based diagnosis of malaria., (© Association of Resident Doctors, UCH, Ibadan.)

Introduction: Histidine Rich Protein 2 based (HRP2-based) malaria rapid diagnostic tests (mRDTs) have been shown to perform as well as routine light microscopy, however, they are limited by some factors including persistence of HRP2 antigenemia. In this paper we report the evaluation of an HRP2-based mRDT in a prospective study that enrolled children and followed them up for 28 days., Methods: Children aged below five years, with acute episode of fever/pyrexia, were enrolled. The enrolled participants had expert malaria microscopy and RDT done at enrolment (Day 0), and on days 1, 2, 3, 7, 14, 21, and 28. The malaria RDT test was considered positive when the antigen and control lines were visible in their respective windows, negative when only the control band was visible and invalid when the control band was not visible. Faint test lines were considered positive. The RDT results were compared to those of expert microscopy., Results: Two hundred and twenty-six children aged 29.2 ± 15.5 months were enrolled. The proportion of children positive by expert malaria microscopy and RDT was 100% and 95.6% respectively. During the 28 day follow up of the children the proportions positive by microscopy and RDT on days 3, 7, 14, and 28 were 1% and 94.6%, 0% and 93.5%, 0% and 91%, and 16.5% and 80.6% respectively. Gender and age dependent analysis of proportion of positive children were similar. Proportion of children with persistence of HRP2 antigen appeared to be lower in those with parasite density below 200/µL, however, this observation requires further evaluation in larger studies., Conclusion: the study revealed a high proportion of persistence of HRP2 antigen in the children 28 days after effective antimalarial therapy. Histidine rich protein 2 based malaria rapid diagnostic tests are not recommended for monitoring of antimalarial therapies., (© Association of Resident Doctors, UCH, Ibadan.)