A snapshot of the prevalence of dihydropteroate synthase-431V mutation and other sulfadoxine-pyrimethamine resistance markers in Plasmodium falciparum isolates in Nigeria.

BACKGROUND: Malaria is a major public health issue with substantial risks among vulnerable populations. Currently, the World Health Organization (WHO) recommends SP-IPTp in the second and third trimesters. However, the efficacy of SP-IPTp is threatened by the emergence of sulfadoxine-pyrimethamine resistant malaria parasites due to single nucleotide polymorphisms in the Plasmodium falciparum dihydrofolate reductase and dihydropteroate synthetase genes. This study aimed to assess the current prevalence of Pfdhfr/Pfdhps mutations in P. falciparum isolates collected from individuals residing in Ile-Ife, Nigeria, and also present maps of the prevalence of Pfdhps 431V and 581G within Nigeria and surrounding countries. METHODS: Between October 2020 and April 2021, samples were collected as dried blood spots among 188 participants who showed malaria positivity with a histidine-rich-protein-based rapid diagnostic test (RDT). Nested PCR assays were used to confirm falciparum in the samples with RDT positivity, and to amplify fragments of the Pfdhfr/Pfdhps genes followed by targeted amplicon sequencing. Published data since 2007 on the prevalence of the Pfdhps genotypes in Nigeria and the neighbouring countries were used to produce maps to show the distribution of the mutant genotypes. RESULTS: Only 74 and 61 samples were successfully amplified for the Pfdhfr and Pfdhps genes, respectively. At codons resulting in N51I, C59R, and S108N, Pfdhfr carried mutant alleles of 97.3% (72/74), 97.3% (72/74) and 98.6% (73/74), respectively. The Pfdhps gene carried mutations at codons resulting in amino acid changes at 431-436-437-540-581-613; I431V [45.9%, (28/61)], A581G [31.1% (19/61)] and A613S [49.2% (30/61)]. Constructed haplotypes were mainly the triple Pfdhfr mutant 51I-59R-108N (95.9%), and the most common haplotypes observed for the Pfdhps gene were the ISGKAA (32.8%), ISGKGS (8.2%), VAGKAA (14.8%), VAGKAS (9.8%) and VAGKGS (14.8%). In the context of the previously published data, a high prevalence of 431V/581G mutations was found in the study population. It seems quite evident that the Pfdhps 431V, 581G and 613S often co-occur as Pfdhps-VAGKGS haplotype. CONCLUSION: This study showed that the prevalence of VAGKGS haplotype seems to be increasing in prevalence. If this is similar in effect to the emergence of 581G in East Africa, the efficacy of SP-IPTp in the presence of these novel Pfdhps mutants should be re-assessed.

Prevalence of Vitamin A deficiency among under-five children in South-Western Nigeria.

BACKGROUND AND AIM: Vitamin A deficiency (VAD) constitutes a major nutritional concern in developing countries. It contributes significantly to the morbidity and mortality of under-five children and can result in impaired resistance to infection as well as increased risk of death. The aim of this study was to determine the prevalence of VAD among Southwestern Nigerian children. METHODS: Apparently healthy children aged between 6 months and 5 years were recruited for the study. Their serum retinol levels were determined by high-performance liquid chromatography. RESULTS: Of the 170 children studied, nine (5.3%) had VAD, although none had severe VAD. The prevalence of VAD did not show statistically significant variation with age (P = 0.159), sex (P = 1.000), social class (P = 0.740), immunisation status (P = 0.197) or nutritional status (P = 0.090). CONCLUSION: The prevalence of VAD among Nigerian children appears to have reduced, compared with previous reports; however, further studies are required to assess the current national prevalence, so as to design programmes that can achieve further reduction in the proportion of children affected.

Alteration of the Disposition of Quinine in Healthy Volunteers After Concurrent Ciprofloxacin Administration.

This study evaluated the effects of concurrent ciprofloxacin administration on the disposition of quinine in healthy volunteers. Quinine (600-mg single dose) was administered either alone or with the 11th dose of ciprofloxacin (500 mg every 12 hours for 7 days) to 15 healthy volunteers in a crossover fashion. Blood samples collected at predetermined time intervals were analyzed for quinine and its major metabolite, 3-hydroxquinine, using a validated high-performance liquid chromatographic method. Administration of quinine plus ciprofloxacin resulted in significant increases (P < 0.05) in the total area under the concentration-time curve, maximum plasma concentration (Cmax), and terminal elimination half-life (T1/2b) of quinine compared with values with quinine dosing alone (AUC: 27.93 ± 8.04 vs. 41.62 ± 13.98 h·mg/L; Cmax: 1.37 ± 0.24 vs. 1.64 ± 0.38 mg/L; T1/2b: 16.28 ± 2.66 vs. 21.43 ± 3.22 hours), whereas the oral plasma clearance markedly decreased (23.17 ± 6.49 vs. 16.00 ± 5.27 L/h). In the presence of ciprofloxacin, there was a pronounced decrease in the ratio of AUC (metabolite)/AUC (unchanged drug) and highly significant decreases in Cmax and AUC of the metabolite (P < 0.05). Ciprofloxacin may increase the adverse effects of concomitantly administered quinine, which can have serious consequences on the patient. Thus, a downward dosage adjustment of quinine seems to be necessary when concurrently administered with ciprofloxacin.

Late presentation of chronic myeloid leukaemia patients in a low-income country: the prognostic implications and impact on treatment outcome.

BACKGROUND: In Nigeria, since 2002, Imatinib mesylate (glivec®) has been available freely to chronic myeloid leukaemia (CML) patients but only at a tertiary health care centre in the southwestern part of the country. Despite this, it is not readily accessible to many patients due to the distance and other challenges including low socioeconomic status and political problems, preventing timely access to specialist care. This study evaluated the effect of the baseline characteristics on the prognostic implication and treatment outcome of CML patients in Nigeria. METHOD: This study retrospectively evaluated the baseline characteristics, clinical presentations and treatment outcomes of 889 CML patients over 18 years (2002-2020). Of these, 576 (65%) patients had complete information with up-to-date BCR::ABL1 records. These 576 patients were categorized based on their responses to Imatinib therapy into three groups viz.; Optimal response (OR) defined as BCR::ABL1 ratio of < 0.1% or major molecular remission (≥ 3-log reduction of BCR::ABL1 mRNA or BCR::ABL1 ratio of < 0.1% on the International Scale), Suboptimal response (SR) with BCR::ABL ratio of 0.1-1%, and Treatment failure (TF) when MMR has not been achieved at 12 months. The variables were analyzed using descriptive and inferential statistics and a p-value < 0.05 was considered statistically significant. RESULTS: The result revealed a median age of 37 years at diagnosis with a male-to-female ratio of 1.5:1. The majority (96.8%) of the patients presented with one or more symptoms at diagnosis with a mean symptom duration of 12 ± 10.6 months. The mean Sokal and EUTOS scores were 1.3 ± 0.8 and 73.90 ± 49.09 respectively. About half of the patients presented with high-risk Sokal (49%) and EUTOS (47%) scores. Interestingly, both the Sokal (r = 0.733, p = 0.011) and EUTOS (r = 0.102, p = 0.003) scores correlated positively and significantly with the duration of symptoms at presentation. Based on response categorization, 40.3% had OR while 27.1% and 32.6% had SR and TF respectively. CONCLUSION: This study observed a low optimal response rate of 40.3% and treatment failure rate of 32.6% in our CML cohort while on first-line Imatinib therapy. This treatment response is strongly attributable to the long duration of symptoms of 12 months or more and high Sokal and EUTOS scores at presentation. We advocate prompt and improved access to specialist care with optimization of tyrosine kinase inhibitor therapy in Nigeria.

Effect of CYP3A5*3 genotypes on lumefantrine plasma concentrations among malaria-HIV-infected women.

Aim: We aimed to assess the effect of a functional polymorphism of CYP3A5 on lumefantrine pharmacokinetics. Patients & methods: Sixty-nine women diagnosed with malaria received standard doses of artemether-lumefantrine. Concentration-time data for lumefantrine and genotyping data were obtained for each participant. Pharmacokinetic-genotype associative relationships were assessed using linear regressions, Mann-Whitney U-test or Kruskal-Wallis statistics. Results: Average age and weight (standard deviation) of the patients were 33 (6.8) years and 59.5 (11.6) kg, respectively. CYP3A5*3 genotype associated with the log-transformed maximum concentration with the median (interquartile range) values of 8279 (6516-13,420) and 6331 (4093-8631) ng/ml (p = 0.032) among the carriers and noncarriers of CYP3A5*3, respectively. Besides, the NR1I3 c.152-1089T>C genotypes had an associative trend with the lumefantrine area under the curve (AUC0-96h) and clearance. Conclusion:CYP3A5*3 genetic variant is associated with a high maximum plasma concentration of lumefantrine. This warrants further investigations on the association between CYP3A5*3 gene variants, lumefantrine pharmacokinetics and electrophysiological effect.

Post-Marketing Surveillance of Quality of Artemether Injection Marketed in Southwest Nigeria.

Access to good-quality medicines remains a contentious issue in developing countries. This development is worrisome, particularly in a setting with a high incidence of malaria. Monitoring of antimalarial drugs in the commercial domain becomes necessary; thus, we evaluated the quality of artemether injection marketed in Southwest Nigeria. A cross-sectional survey was conducted to obtain 22 different brands of artemether injections within Southwest Nigeria. The samples were examined for their sources, lot numbers, containers for injection, oil base used for preparation, and dates of expiration. Further analysis involved visual inspection, assessment of extractable volume, identity tests, and an assay of active pharmaceutical ingredient. The pharmaceutical quality of each sample was determined according to the criteria set in the International Pharmacopoeia 2019. None of the products had any particulate matter, but there were certain irregularities in their presentation. Eighteen of the 22 products (81.7%) were packaged in plain instead of amber-colored ampoules, and 77.3% (17/22) did not indicate the oil base used as the vehicle on the label as against the pharmacopoeial standard. Sixteen products (72.7%) passed the extractable volume test, although the remaining 22.3% did not conform to the extractable volume per unit dose. Artemether was present in all the samples, although only 40.9% (9/22) met the recommended percentage content of 90-110% of artemether. The study revealed the presence of a high percentage of substandard artemether injection products marketed in Nigeria. Further surveillance is warranted to confirm the quality of artemether injection circulated in other regions within Nigeria.

Vitamin A deficiency among under-five Nigerian children with diarrhoea.

BACKGROUND: Vitamin A deficiency (VAD) and diarrhoea are still important contributors to childhood deaths in Africa, and vitamin A deficient children are at increased risk as well as severity of diarrhoea. OBJECTIVES: To determine the prevalence of VAD and identify the associated factors among children with diarrhoea. METHODS: The study was a hospital-based cross-sectional descriptive study. Consecutive children with diarrhoea were recruited, provided they met the inclusion criteria. Serum retinol levels were determined by high performance liquid chromatography (HPLC) in one hundred and seventy under-five children who presented with diarrhoea at the Wesley Guild Hospital, Ilesa, Nigeria. RESULTS: The serum retinol levels of the children ranged from 0.29 - 2.35 µmol/L with a mean ± SD of 1.07 ± 0.42 µmol/L. Twenty seven (15.9%) were vitamin A deficient with three (1.8%) of these having severe VAD. Wasting was significantly associated with a higher prevalence of VAD [p = 0.023, OR (95% CI) = 3.08 (1.21 - 7.79)]. A significantly greater proportion of the subjects who had VAD were hospitalized, compared with the non-deficient ones [p = 0.001, OR (95% CI) = 4.40 (1.82 - 10.66)]. The only subject who died was vitamin A deficient. CONCLUSION: Wasting and hospitalization are factors that may indicate the presence of VAD in a child with diarrhoea. Vitamin A supplements should therefore be given, as part of the treatment for diarrhoea, to children who have wasting, especially when they require hospitalization.

Serum vitamin D profile of Nigerian children with asthma: Association with asthma severity and control.

OBJECTIVE: Childhood asthma is a chronic inflammatory airway disorder with increasing prevalence even in Africa. Vitamin D, with anti-inflammatory and immune-modulatory properties, may have effects on the severity and level of symptoms control in childhood asthma. We aimed to assess the serum vitamin D levels in children with asthma as related to disease severity and control in a tropical region. METHODS: A hospital based comparative cross sectional study was conducted in western Nigeria. Serum vitamin D (25-OH-D) levels of all the children, assayed using high-performance liquid chromatography (HPLC), were compared to the various disease severity and levels of asthma control as well as between the asthmatic and non-asthmatic children. RESULTS: A total of 206 children (103 asthmatics and 103 non-asthmatics) were recruited with a mean (SD) age of 6.6 (3.7) years. The majority (82.5%) of the children with asthma had mild intermittent form, 63.1% had well controlled symptoms while 33.0% and 3.9% had partly controlled and uncontrolled symptoms, respectively. None of the children were deficient in vitamin D. The mean (SD) serum vitamin D levels of the children with asthma (49.2 [7.2] ng/mL) was significantly lower than those without asthma (51.2 [6.9] ng/mL, P = 0.043). Varying degrees of asthma severity and levels of symptoms control were not affected by serum vitamin D levels. CONCLUSION: Children with asthma in Nigeria had marginally but significantly lower mean serum vitamin D levels when compared with their counterparts without asthma. However, serum vitamin D level does not seem to be associated with childhood asthma severity and control in these children with normal serum vitamin D levels.