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1.
Front Cell Infect Microbiol ; 14: 1366563, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38716192

RESUMO

Background: Routine surveillance for antimalarial drug resistance is critical to sustaining the efficacy of artemisinin-based Combination Therapies (ACTs). Plasmodium falciparum kelch-13 (Pfkelch-13) and non-Pfkelch-13 artemisinin (ART) resistance-associated mutations are uncommon in Africa. We investigated polymorphisms in Plasmodium falciparum actin-binding protein (Pfcoronin) associated with in vivo reduced sensitivity to ART in Nigeria. Methods: Fifty-two P. falciparum malaria subjects who met the inclusion criteria were followed up in a 28-day therapeutic efficacy study of artemether-lumefantrine in Lagos, Nigeria. Parasite detection was done by microscopy and molecular diagnostic approaches involving PCR amplification of genes for Pf18S rRNA, varATS, telomere-associated repetitive elements-2 (TARE-2). Pfcoronin and Pfkelch-13 genes were sequenced bi-directionally while clonality of infections was determined using 12 neutral P. falciparum microsatellite loci and msp2 analyses. Antimalarial drugs (sulfadoxine-pyrimethamine, amodiaquine, chloroquine and some quinolones) resistance variants (DHFR_51, DHFR_59, DHFR_108, DHFR_164, MDR1_86, MDR1_184, DHPS_581 and DHPS_613) were genotyped by high-resolution melting (HRM) analysis. Results: A total of 7 (26.92%) cases were identified either as early treatment failure, late parasitological failure or late clinical failure. Of the four post-treatment infections identified as recrudescence by msp2 genotypes, only one was classified as recrudescence by multilocus microsatellites genotyping. Microsatellite analysis revealed no significant difference in the mean allelic diversity, He, (P = 0.19, Mann-Whitney test). Allele sizes and frequency per locus implicated one isolate. Genetic analysis of this isolate identified two new Pfcoronin SNVs (I68G and L173F) in addition to the P76S earlier reported. Linkage-Disequilibrium as a standardized association index, IAS, between multiple P. falciparum loci revealed significant LD (IAS = 0.2865, P=0.02, Monte-Carlo simulation) around the neutral microsatellite loci. The pfdhfr/pfdhps/pfmdr1 drug resistance-associated haplotypes combinations, (108T/N/51I/164L/59R/581G/86Y/184F), were observed in two samples. Conclusion: Pfcoronin mutations identified in this study, with potential to impact parasite clearance, may guide investigations on emerging ART tolerance in Nigeria, and West African endemic countries.


Assuntos
Antimaláricos , Artemisininas , Resistência a Medicamentos , Malária Falciparum , Proteínas dos Microfilamentos , Plasmodium falciparum , Adulto , Feminino , Humanos , Masculino , Antimaláricos/farmacologia , Antimaláricos/uso terapêutico , Combinação Arteméter e Lumefantrina/uso terapêutico , Artemisininas/farmacologia , Artemisininas/uso terapêutico , Combinação de Medicamentos , Resistência a Medicamentos/genética , Genótipo , Malária Falciparum/tratamento farmacológico , Malária Falciparum/parasitologia , Proteínas dos Microfilamentos/genética , Repetições de Microssatélites/genética , Mutação , Nigéria , Plasmodium falciparum/genética , Plasmodium falciparum/efeitos dos fármacos , Polimorfismo Genético , Proteínas de Protozoários/genética , Recidiva
2.
Bioresour Technol ; 399: 130587, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38490464

RESUMO

Textile industries discharge up to 280,000 tons of dye waste annually, resulting in global pollution and health risks. In Nigeria and other African countries, persistent dyes threaten aquatic life and human health. This study introduces a cost-effective, enzyme-mediated bioremediation alternative using a novel laccase from the cyanobacteriumMicrocystis flos-aquae. This purified enzyme yielded 0.55 % (w/w)with significant activity at 40 °C and pH 4.00. Kinetic studies showed the dependence of M. flos-aquae laccase on Cu2+and its inhibition by EDTA and Fe2+. The efficacy of the enzyme was demonstrated through rapid decolorization of the azo dye Cibacron Brilliant Blue over a wide temperature and pH range. As this enzyme effectively decolorizes dyes across a broad temperature and pH range, it offers a promising solution for bioremediation of textile effluents.


Assuntos
Cianobactérias , Microcystis , Humanos , Compostos Azo , Lacase/metabolismo , Biodegradação Ambiental , Cinética , Corantes , Microcystis/metabolismo , Cianobactérias/metabolismo
3.
Pathog Glob Health ; : 1-9, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38419138

RESUMO

Schistosomiasis and anemia, are one of the leading global public health problem among children between age 5 and 14 years in marginalized settings. In this study, we provide prevalence and intensity data for both conditions in three southwestern states of Nigeria, where such are lacking. Epidemiological assessment involving parasitological analysis of urine and blood samples was conducted among 1783 consenting school-aged children in Ondo, Osun, Ekiti States of Nigeria. Participants' age and sex data were obtained using field forms, and statistical analysis was performed in R software with a significance level of 95%. An overall prevalence of 26.8% and 29.5% was recorded for urinary schistosomiasis and anemia, respectively. Prevalence varied by location with (40.3% and 29.8%) in Ondo (34.4% and 37.5%) in Osun and (13.4% and 20.9%) in Ekiti for urinary schistosomiasis and anemia, respectively (p=0.00). Schistosoma infections were found among males (28.7%, p=0.05) and children between the age 9-11 years (30.0%, p=0.01). About 36% of children with anemia was also infected with schistosomiasis. Children who were positive for schistosomiasis (OR:1.51; 95% CI: 1.19, 1.93; p=0.001) and between the age category 15-16 years, (OR:1.86; 95% CI: 1.12, 3.09; p<0.05) were twice likely to become anemic. Our findings have shown that children infected with schistosomiasis are twice likely to become anemic than those without infection. It is important to complement ongoing MDA programmes targeted at schistosomiasis with nutrition intervention programs for example micronutrient supplementation for better impact and cost-effectiveness.

4.
Pan Afr Med J ; 46: 18, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38035158

RESUMO

Introduction: Ascorbic acid (AA) is a water-soluble vitamin that is well known for its antioxidant and immune-boosting properties. Owing to the wide-range application of AA in the treatment of numerous ailments and its sweet taste, it is usually abused i.e. overused. However, the effect of the abuse has rarely received attention. Therefore, this study was designed to assess the effect of oral administration of high-dose ascorbic acid on biochemical and haematological parameters as well as the effects on the kidney, liver and lungs. Methods: adult guinea pigs were divided into four (4) groups where group 1 served as the untreated control group and groups 2-4 were dosed with 29 mg, 662 mg and 1258 mg of ascorbic acid per day, respectively for 28 days. Results: the result revealed that administration of high dose ascorbic acid significantly (P<0.05) increased serum creatinine from 50.0 ± 7.09 (NC) to AA29- 73.8 ± 4.5, AA-662-89.7 ± 3.3 and AA1258- 79.9 ± 5.7mmol/L and urea levels in the treatment group AA-1258 -18.3 ± 0.5 µmol/L compared to the normal group (NC-2.15 ± 0.6 µmol/L). Disturbance in electrolyte balance was observed with a significant (P<0.05) increase in Na+ from NC- 131.3 ± 3.5 mmol/L to 135.7 ± 3.6 mmol/L in the AA-1258 treatment group, Cl- ( NC- 67.1 ± 1.6 mmol/L increased to AA29- 92.1 ± 0.83, AA662- 95.3 ± 1.3 and AA-1258- 95.6 ± 0.4 mmol/L), and Ca2+ (NC- 2.66 ± 0.03 to AA1258- 3.36 ± 0.03 mmol/L) and a significant (P<0.05) decrease in serum K+ in the AA29-5.0 ± 0.2, AA662-5.2 ± 0.3 and AA1258-5.6 ± 0.3 mmol/L treatment groups compared to the normal group 6.6 ± 0.3 mmol/L. There was also a significant (P<0.05) increase in the differential blood count in the animals with a significant (P<0.05) increase in red blood count ( NC-5.11 ± 0.13 ×106/µL to AA1258- 5.75 ± 0.11×106/µL ), haematocrit count (NC 39.90 ± 0.52% to AA-29-42.08 ± 0.24 and AA1258-46.13 ± 0.86%), white blood count (NC 10.15 ± 1.01 ×103/µL to AA1258- 15.18 ± 1.65×103/µL ), total lymphocytes (NC 3.5 ± 0.51×103/µL to AA29-5.28 ±0.43×103/µL), monocytes (NC 0.45 ± 0.07×103/µL to AA1258 0.80 ± 0.07×103/µL), eosinophils (NC 0.23 ± 0.03×103/µL to AA12580.40 ± 0.03×103/µL), basophils (NC0.68 ± 0.10×103/µL to AA12581.20 ± 0.10×103/µL) and neutrophil count (NC 4.73 ± 0.68×103/µL to AA1258 8.36 ± 0.71×103/µL). The histopathological indices indicate cellular necrosis in the AA662 and AA1258 treatment groups of the kidney and liver respectively compared to the normal control which has normal cells. Conclusion: high dose of ascorbic acid can therefore be suggested to cause damage to the cells by causing cellular necrosis as observed in the histopathology results and has effect on the blood cells as observed in the increase compared to the normal control, and the consequences are possibly triggered through inflammatory responses.


Assuntos
Antineoplásicos , Antioxidantes , Cobaias , Animais , Espécies Reativas de Oxigênio , Antioxidantes/farmacologia , Ácido Ascórbico/farmacologia , Pulmão , Necrose
5.
BMC Pediatr ; 23(1): 538, 2023 10 28.
Artigo em Inglês | MEDLINE | ID: mdl-37891551

RESUMO

BACKGROUND: This study presents the clinical pattern of presentation and survival rate of retinoblastoma, which is the most prevalent form of pediatric intraocular cancer. The aim of this study is to provide baseline information about the clinical presentation and management of retinoblastoma at ECWA Eye Hospital. Additionally, the study identifies priority areas for enhancing medical care for children diagnosed with this cancer. ECWA Eye Hospital, situated in Kano State, Nigeria, is a specialized eye center located in the North-Western region of the country. METHODS: A prospective study spanning five years was conducted at ECWA Eye Hospital to investigate clinically diagnosed cases of retinoblastoma. The study took place from January 2018 to December 2022. The patients received standardized pre-medication and chemotherapy protocols for retinoblastoma. Subsequently, a five-year follow-up was conducted to monitor the patients' progress. The collected data was analyzed, descriptive statistics were generated, and the survival rate was calculated. RESULTS: During the five-year study period, a total of 35 cases of retinoblastoma were diagnosed. The patients had an average age of 3.21 ± 1.32 years. The most common presentation patterns observed were fungating ocular mass and proptosis. Among the cases, there were 10 instances of bilateral proptosis and 25 instances of unilateral proptosis. While no patients exhibited bilateral leukocoria, eight cases of unilateral leukocoria with anterior segment seedlings were identified. The additional patterns of presentation are proptosis, leukocoria, fungating orbital mass, redness and loss of vision. The mortality rate was 80% (28 cases), while the survival rate was 20% (7 cases). Notably, all the survivors had unilateral retinoblastoma. CONCLUSION: The majority of cases observed at ECWA Eye Hospital involve advanced retinoblastoma. In low-resource settings where alternative treatment options are limited, chemotherapy is considered a viable treatment option. Early presentation of retinoblastoma in patients may lead to a higher survival rate when chemotherapy is administered.


Assuntos
Exoftalmia , Neoplasias da Retina , Retinoblastoma , Criança , Humanos , Lactente , Pré-Escolar , Retinoblastoma/tratamento farmacológico , Neoplasias da Retina/tratamento farmacológico , Estudos Prospectivos , Taxa de Sobrevida , Nigéria/epidemiologia , Enucleação Ocular , Estudos Retrospectivos
6.
Parasitol Res ; 122(12): 2751-2772, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37851179

RESUMO

Schistosomiasis is a neglected tropical disease caused by a parasitic, trematode blood fluke of the genus Schistosoma. With 20 million people infected, mostly due to Schistosoma haematobium, Nigeria has the highest burden of schistosomiasis in the world. We review the status of human schistosomiasis in Nigeria regarding its distribution, prevalence, diagnosis, prevention, orthodox and traditional treatments, as well as snail control strategies. Of the country's 36 states, the highest disease prevalence is found in Lagos State, but at a geo-political zonal level, the northwest is the most endemic. The predominantly used diagnostic techniques are based on microscopy. Other methods such as antibody-based serological assays and DNA detection methods are rarely employed. Possible biomarkers of disease have been identified in fecal and blood samples from patients. With respect to preventive chemotherapy, mass drug administration with praziquantel as well as individual studies with artemisinin or albendazole have been reported in 11 out of the 36 states with cure rates between 51.1 and 100%. Also, Nigerian medicinal plants have been traditionally used as anti-schistosomal agents or molluscicides, of which Tetrapleura tetraptera (Oshosho, aridan, Aidan fruit), Carica papaya (Gwanda, Ìbépe, Pawpaw), Borreria verticillata (Karya garma, Irawo-ile, African borreria), and Calliandra portoricensis (Tude, Oga, corpse awakener) are most common in the scientific literature. We conclude that the high endemicity of the disease in Nigeria is associated with the limited application of various diagnostic tools and preventive chemotherapy efforts as well as poor knowledge, attitudes, and practices (KAP). Nonetheless, the country could serve as a scientific base in the discovery of biomarkers, as well as novel plant-derived schistosomicides and molluscicides.


Assuntos
Plantas Medicinais , Esquistossomose Urinária , Esquistossomose , Animais , Humanos , Nigéria/epidemiologia , Esquistossomose/diagnóstico , Esquistossomose/tratamento farmacológico , Esquistossomose/epidemiologia , Schistosoma haematobium , Extratos Vegetais , Biomarcadores , Esquistossomose Urinária/parasitologia
7.
Sci Rep ; 13(1): 14596, 2023 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-37669981

RESUMO

Amebiasis is caused by the protozoan parasite Entamoeba histolytica. Treatment options other than metronidazole and its derivatives are few, and their low efficacy against asymptomatic cyst carriers, and experimental evidence of resistance in vitro justify the discovery/repurposing campaign for new drugs against amebiasis. Global metabolic responses to oxidative stress and cysteine deprivation by E. histolytica revealed glycerol metabolism may represent a rational target for drug development. In this study using 14C-labelled glucose, only 11% of the total glucose taken up by E. histolytica trophozoites is incorporated to lipids. To better understand the role of glycerol metabolism in this parasite, we focused on characterizing two important enzymes, glycerol kinase (GK) and glycerol 3-phosphate dehydrogenase (G3PDH). Recombinant GK was biochemically characterized in detail, while G3PDH was not due to failure of protein expression and purification. GK revealed novel characteristics and unprecedented kinetic properties in reverse reaction. Gene silencing revealed that GK is essential for optimum growth, whereas G3PDH is not. Gene silencing of G3PDH caused upregulated GK expression, while that of GK resulted in upregulation of antioxidant enzymes as shown by RNA-seq analysis. Although the precise molecular link between GK and the upregulation of antioxidant enzymes was not demonstrated, the observed increase in antioxidant enzyme expression upon GK gene silencing suggests a potential connection between GK and the cellular response to oxidative stress. Together, these results provide the first direct evidence of the biological importance and coordinated regulation of the glycerol metabolic pathways for proliferation and antioxidative defense in E. histolytica, justifying the exploitation of these enzymes as future drug targets.


Assuntos
Amebíase , Entamoeba histolytica , Parasitos , Humanos , Animais , Antioxidantes , Vias Biossintéticas , Glicerol , Glicerol Quinase , Proliferação de Células
8.
BMC Microbiol ; 23(1): 260, 2023 09 16.
Artigo em Inglês | MEDLINE | ID: mdl-37716961

RESUMO

BACKGROUND: Tsetse flies are cyclical vectors of African trypanosomiasis (AT). The flies have established symbiotic associations with different bacteria that influence certain aspects of their physiology. Vector competence of tsetse flies for different trypanosome species is highly variable and is suggested to be affected by bacterial endosymbionts amongst other factors. Symbiotic interactions may provide an avenue for AT control. The current study provided prevalence of three tsetse symbionts in Glossina species from Cameroon, Chad and Nigeria. RESULTS: Tsetse flies were collected and dissected from five different locations. DNA was extracted and polymerase chain reaction used to detect presence of Sodalis glossinidius, Spiroplasma species and Wolbachia endosymbionts, using species specific primers. A total of 848 tsetse samples were analysed: Glossina morsitans submorsitans (47.52%), Glossina palpalis palpalis (37.26%), Glossina fuscipes fuscipes (9.08%) and Glossina tachinoides (6.13%). Only 95 (11.20%) were infected with at least one of the three symbionts. Among infected flies, six (6.31%) had Wolbachia and Spiroplasma mixed infection. The overall symbiont prevalence was 0.88, 3.66 and 11.00% respectively, for Sodalis glossinidius, Spiroplasma species and Wolbachia endosymbionts. Prevalence varied between countries and tsetse fly species. Neither Spiroplasma species nor S. glossinidius were detected in samples from Cameroon and Nigeria respectively. CONCLUSION: The present study revealed, for the first time, presence of Spiroplasma species infections in tsetse fly populations in Chad and Nigeria. These findings provide useful information on repertoire of bacterial flora of tsetse flies and incite more investigations to understand their implication in the vector competence of tsetse flies.


Assuntos
Glossinidae , Spiroplasma , Tripanossomíase Africana , Moscas Tsé-Tsé , Wolbachia , Animais , Wolbachia/genética , Camarões , Chade , Nigéria , Spiroplasma/genética
9.
Front Cell Infect Microbiol ; 13: 1219629, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37719668

RESUMO

Introduction: Female sand flies are hematophagous, feeding on animals and in the process serve as vectors for Leishmania, the parasites that cause leishmaniasis in humans. Leishmaniasis are a group of parasitic neglected tropical diseases in 98 countries including Nigeria and kills ~60,000 people/year. In Nigeria, Sokoto State is endemic to leishmaniasis but there is a knowledge gap on the identity of the prevalent sand flies and the Leishmania species they transmit. Hence, this cross-sectional study was designed to take inventory of the species of sand flies in Sokoto using genetic methods. Methods: 1,260 (310 females) sand flies were collected from three Local Government Areas (L.G.A) of Sokoto State- Wamakko, Sokoto South and Kware. Genomic DNA was extracted from each fly and DNA amplification by polymerase chain reaction (PCR) was carried out on the DNA samples using primers targeting the arthropods mitochondrial cytochrome oxidase subunit 1 (mt-coI) gene, and nested PCR with primers targeting the gene for Leishmania internal transcribed spacer-1 (its-1) of ribosomal RNA its-1rRNA. The PCR products were sequenced. Results: Gene sequence analysis revealed five species of sand flies belonging to the old-world genera namely Phlebotomus and Sergentomyia. The identified species were P. papatasi (6.45%), S. adleri (6.45%), S. affinis (9.7%), S. distincta (9.7%), S. schwetzi (67.7%). Within the sampling period, sand flies were most abundant in the rainy months of August (104/33.5%) and September (116/37.4%) with all the five identified species occurring. Sequence analysis of its-1 gene identified Leishmania infantum in two sand flies (2/310)- P. papatasi (from Sokoto South) and S. affinis (from Wamakko). BLAST search in NCBI and phylogenetic analysis revealed that the sand fly species are related to the species reported in different parts of Africa, while the L. infantum is identical to strain reported in Brazil (KY379083.1). Discussion: Phlebotomus papatasi and four species belonging to the genus Sergentomyia are the most prevalent sand flies in Sokoto State, Nigeria and they harbor L. infantum solely. The results shed light on why visceral leishmaniasis is the most predominant form of the disease. Therefore, we recommend that adequate care for dogs must be instituted as dogs are the major animal reservoir for L. infantum.


Assuntos
Leishmania infantum , Phlebotomus , Psychodidae , Humanos , Feminino , Animais , Cães , Nigéria , Estudos Transversais , Filogenia
10.
Toxicon ; 229: 107138, 2023 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-37127124

RESUMO

African trypanosomiasis is an infectious disease caused by hemoparasites of the genus Trypanosoma and remains a major health problem in Africa - killing around 4000 people and animals worth an estimated $5 billion, annually. The absence of a vaccine and satisfactory drug against African trypanosomiasis (AT) necessitates the continued search for new chemotherapy options. Owing to the rich biochemical diversity in snake venom, it has recently become a source of therapeutic peptides that are being explored for the development of novel drug candidates for diverse ailments such as cancers and infectious diseases. To explore this, Echis ocellatus venom (EOV) was investigated for the presence of an anti-Trypanosoma factor, with the subsequent aim to isolate and identify it. Crude EOV was collected and tested in vitro on the bloodstream form (BSF) i.e. long and slender morphological form of Trypanosoma brucei and T. congolense. This initial testing was followed by a sequential anti-trypanosomal assay guided purification of EOV using ethanol precipitation, distillation, and ion exchange (IEX) chromatography to obtain the active trypanocidal component. The purified anti-Trypanosoma factor, estimated to be a 52-kDa protein on SDS-PAGE, was subjected to in-gel trypsin digestion and 2D RP HPLC-MS/MS to identify the protein. The anti-Trypanosoma factor was revealed to be a zinc-dependent metalloproteinase that contains the HEXXHXXGXXH adamalysin motif. This protein may provide a conceptual framework for the possible design of a safe and effective anti-trypanosomal peptide for the treatment of AT.


Assuntos
Trypanosoma , Tripanossomíase Africana , Viperidae , Animais , Venenos de Víboras/química , Tripanossomíase Africana/tratamento farmacológico , Espectrometria de Massas em Tandem , Viperidae/metabolismo , Metaloproteases/metabolismo
11.
Ann Med Surg (Lond) ; 85(5): 1518-1522, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37229087

RESUMO

Glaucoma is a group of diseases that damage the optic nerve in the eye, resulting in vision loss and, in severe cases, blindness. The prevalence of glaucoma and glaucoma blindness is highest in West Africans. Objective: The study presents a 5-year retrospective analysis of intraocular pressure (IOP) and complications after trabeculectomy. Materials and methods: Trabeculectomy was performed using 5 mg/ml of 5-fluorouracil. A gentle diathermy was performed to secure hemostasis. Using a blade fragment of the scleral thickness, a 4×3 mm rectangular scleral flap was dissected. The central part of the flap was dissected 1 mm into the clear cornea. Before being tailed down, the patient was given topical 0.05% dexamethasone qid, 1% atropine tid, and 0.3% ciprofloxacin qid for 4-6 weeks. Patients with pain were given pain relievers, and all patients with photophobia were given sun protection. A successful surgical outcome was defined as a postoperative IOP of 20 mmHg or less. Results: There were 161 patients over the 5-year period under review, with men constituting 70.2% of the total. Out of 275 eyes operated on, 82.9% were bilateral cases, while 17.1% were unilateral. Glaucoma was found in both children and adults aged 11-82 years. However, it was observed to predominate between the ages of 51 and 60, with males having the highest incidence. The average preoperative IOP was 24.37 mmHg, while it was 15.24 mmHg postoperatively. The complication with the highest ranking was shallow anterior chamber (24; 8.73%) due to overfiltration, followed by leaking bleb (8; 2.91%). The most common late complications were cataract (32; 11.64%) and fibrotic bleb (8; 2.91%). Bilateral cataracts developed at an average of 25 months after trabeculectomy. It was seen in patients aged 2-3 with a frequency of 9, whereas 5 years after, 77 patients had improved vision, with a postoperative visual acuity of 6/18-6/6. Conclusion: Postoperatively, the patients had satisfying surgical outcomes as a result of the decrease in preoperative IOP. Although postoperative complications occurred, they had no effect on the surgical outcomes because they were temporary and not optically threatening. In our experience, trabeculectomy is an effective and safe procedure for achieving IOP control.

12.
Res Sq ; 2023 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-37214831

RESUMO

Background Tsetse flies are cyclical vectors of African trypanosomiasis. They have established symbiotic associations with different bacteria, which influence certain aspects of their physiology. The vector competence of tsetse flies for different trypanosome species is highly variable and is suggested to be affected by various factors, amongst which are bacterial endosymbionts. Symbiotic interactions may provide an avenue for the disease control. The current study provided the prevalence of 3 tsetse symbionts in Glossina species from Cameroon, Chad and Nigeria. Results Tsetse flies were collected from five different locations and dissected. DNA was extracted and polymerase chain reaction PCR was used to detect the presence of Sodalis glossinidius , Spiroplasma sp and Wolbachia using specific primers. A total of 848 tsetse samples were analysed: Glossina morsitans submorsitans (47.52%), Glossina palpalis palpalis (37.26%), Glossina fuscipes fuscipes (9.08%) and Glossina tachinoides (6.13%). Only 95 (11.20%) were infected with at least one of the 3 symbionts. Among the infected, 6 (6.31%) were carrying mixed infection ( Wolbachia and Spiroplasma ). The overall symbiont prevalence was 0.88%, 3.66% and 11.00% respectively, for Sodalis , Spiroplasma and Wolbachia . Prevalence varied between countries and tsetse species. No Spiroplasma was detected in samples from Cameroon and no Sodalis was found in samples from Nigeria. Conclusion The present study revealed for the first time, the presence of infection by Spiroplasma in tsetse in Chad and Nigeria. These findings provide useful information to the repertoire of bacterial flora of tsetse flies and incite to more investigations to understand their implication in the vector competence of tsetse flies.

13.
Eur J Pharm Sci ; 186: 106451, 2023 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-37088149

RESUMO

African trypanosomiasis (AT) is a hemoparasitic disease caused by infection with African trypanosomes and it is prevalent in many sub-Saharan African countries, affecting both humans and domestic animals. The disease is transmitted mostly by haematophagous insects of the genus Glossina while taking blood meal, in the process spreading the parasites from an infected animal to an uninfected animal. The disease is fatal if untreated, and the available drugs are generally ineffective and resulting in toxicities. Therefore, it is still pertinent to explore novel methods and targets for drug discovery. Proteolysis-targeting chimeras (PROTACs) present a new strategy for development of therapeutic molecules that mimic cellular proteasomal-mediated protein degradation to target proteins involved in different disease types. PROTACs have been used to degrade proteins involved in various cancers, neurodegenerative diseases, and immune disorders with remarkable success. Here, we highlight the problems associated with the current treatments for AT, discuss the concept of PROTACs and associated targeted protein degradation (TPD) approaches, and provide some insights on the future potential for the use of these emerging technologies (PROTACs and TPD) for the development of new generation of anti-Trypanosoma drugs and the first "TrypPROTACs".


Assuntos
Tripanossomíase Africana , Ubiquitina-Proteína Ligases , Animais , Humanos , Proteólise , Ubiquitina-Proteína Ligases/metabolismo , Tripanossomíase Africana/tratamento farmacológico , Proteínas , Descoberta de Drogas/métodos
14.
Pathogens ; 12(3)2023 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-36986413

RESUMO

Nigeria remains the most endemic country in sub-Saharan Africa (SSA) for soil-transmitted helminthiases (STH). In line with ongoing monitoring plans, we present findings from a recent analysis of STH epidemiological data in Borgu, one of the non-endemic implementation units for STH in the northcentral region of Nigeria. An overall prevalence of 8.8% was recorded for STH infection, which corresponds to a 51.9% decline from the 18.3% reported in 2013. All the infected participants (36 out of 410) had a low intensity of infection. However, more than two-thirds (69%) of the children do not have access to latrine facilities, and 45% of them walk barefoot. Prevalence was significantly associated with community, age, and parental occupation. About 21-25% reduced odds were reported in some of the study communities, and children whose parents were traders had 20 times lower odds of infection compared to those whose parents were farmers. The ongoing preventive chemotherapy program for lymphatic filariasis in the area could be responsible for the huge reduction in prevalence and intensity estimates for STH. It is therefore important to invest in monitoring transmission dynamics in other non-endemic areas to arrest emerging threats through the provision of complementary interventions including WASH facilities and other health educational tools.

15.
Curr Trop Med Rep ; 10(2): 47-70, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36742193

RESUMO

Purpose of Review: The climate change (CC) or global warming (GW) modifies environment that favors vectors' abundance, growth, and reproduction, and consequently, the rate of development of pathogens within the vectors. This review highlights the threats of GW-induced vector-borne diseases (VBDs) in Southern Europe (SE) and the need for mitigation efforts to prevent potential global health catastrophe. Recent Findings: Reports showed astronomical surges in the incidences of CC-induced VBDs in the SE. The recently (2022) reported first cases of African swine fever in Northern Italy and West Nile fever in SE are linked to the CC-modified environmental conditions that support vectors and pathogens' growth and development, and disease transmission. Summary: VBDs endemic to the tropics are increasingly becoming a major health challenge in the SE, a temperate region, due to the favorable environmental conditions caused by CC/GW that support vectors and pathogens' biology in the previously non-endemic temperate regions.

16.
J Biomol Struct Dyn ; 41(1): 45-54, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-34812693

RESUMO

African trypanosomiasis is caused by Trypanosoma brucei subspecies and available drugs against it, are unsatisfactory due to poor pharmacokinetic properties. Trypanosomal Alternative Oxidase (TAO) is an attractive target for anti-trypanosome rational drug discovery because it is essential for parasite-specific ATP generation and absent in the mammalian host. In this study, 360 filtered ligands from the Universal Natural Product Database were virtually screened and docked on T. brucei brucei TAO (PDB-ID 3VVA). From the virtual screening, 10 ligands with binding energy from -10.6 to -9.0 kcal/mol were selected as hits and further subjected pharmacokinetic and toxicity analyses where all of them passed Lipinski's rule of five. Also, the compounds were non-mutagenic, non-tumorigenic and could cross the blood brain barrier. The two topmost hits (UNPD29179; megacerotonic acid and UNPD41551; a quinazoline derivative) interacted with `four glutamates (Glu123, Glu162, Glu213 and Glu266) close to di-iron (2 iron elements) at the catalytic site of the enzyme. Subsequently, 100 ns MD simulations of the two topmost hits were performed using GROMACS where high RMSD values of 0.75 nm (TAO-UNPD29179) and 0.52 nm (TAO- UNPD41551), low residues fluctuations and consistent values of radius of gyration were observed. Moreover, Solvent Accessible Surface Area showed a consistent value of 160 nm2 for both complexes while TAO-UNPD29179 had higher number of hydrogen bonds than the TAO-UNPD41551. Similarly, MM/PBSA calculations indicated that UNPD29179 had higher free binding energy with TAO than UNPD41551. The data suggest that megacerotonic acid and a quinazoline derivative could be potential inhibitors of TAO with improved pharmacokinetic properties.Communicated by Ramaswamy H. Sarma.


Assuntos
Trypanosoma brucei brucei , Tripanossomíase Africana , Animais , Trypanosoma brucei brucei/metabolismo , Simulação de Acoplamento Molecular , Tripanossomíase Africana/tratamento farmacológico , Simulação de Dinâmica Molecular , Mamíferos
17.
Toxics ; 10(12)2022 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-36548605

RESUMO

Microcystins are produced by multifaceted organisms called cyanobacteria, which are integral to Africa's freshwater environments. The excessive proliferation of cyanobacteria caused by rising temperature and eutrophication leads to the production and release of copious amounts of microcystins, requiring critical management and control approaches to prevent the adverse environmental and public health problems associated with these bioactive metabolites. Despite hypotheses reported to explain the phylogeography and mechanisms responsible for cyanobacterial blooms in aquatic water bodies, many aspects are scarcely understood in Africa due to the paucity of investigations and lack of uniformity of experimental methods. Due to a lack of information and large-scale studies, cyanobacteria occurrence and genetic diversity are seldom reported in African aquatic ecosystems. This review covers the diversity and geographical distribution of potential microcystin-producing and non-microcystin-producing cyanobacterial taxa in Africa. Molecular analyses using housekeeping genes (e.g., 16S rRNA, ITS, rpoC1, etc.) revealed significant sequence divergence across several cyanobacterial strains from East, North, West, and South Africa, but the lack of uniformity in molecular markers employed made continent-wise phylogenetic comparisons impossible. Planktothrix agardhii, Microcystis aeruginosa, and Cylindrospermopsis raciborskii (presently known as Raphidiopsis raciborskii) were the most commonly reported genera. Potential microcystin (MCs)-producing cyanobacteria were detected using mcy genes, and several microcystin congeners were recorded. Studying cyanobacteria species from the African continent is urgent to effectively safeguard public and environmental health because more than 80% of the continent has no data on these important microorganisms and their bioactive secondary metabolites.

18.
Comput Struct Biotechnol J ; 20: 5574-5585, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36284708

RESUMO

Human African trypanosomiasis (HAT) is a neglected tropical disease that is caused by flagellated parasites of the genus Trypanosoma. HAT imposes a significant socio-economic burden on many countries in sub-Saharan Africa and its control is hampered by several drawbacks ranging from the ineffectiveness of drugs, complex dosing regimens, drug resistance, and lack of a vaccine. Despite more than a century of research and investigations, the development of a vaccine to tackle HAT is still challenging due to the complex biology of the pathogens. Advancements in computational modeling coupled with the availability of an unprecedented amount of omics data from different organisms have allowed the design of new generation vaccines that offer better antigenicity and safety profile. One of such new generation approaches is a multi-epitope vaccine (MEV) designed from a collection of antigenic peptides. A MEV can stimulate both cellular and humoral immune responses as well as avoiding possible allergenic reactions. Herein, we take advantage of this approach to design a MEV from conserved hypothetical plasma membrane proteins of Trypanosoma brucei gambiense, the trypanosome subspecies that is responsible for the west and central African forms of HAT. The designed MEV is 402 amino acids long (41.5 kDa). It is predicted to be antigenic, non-toxic, to assume a stable 3D conformation, and to interact with a key immune receptor. In addition, immune simulation foresaw adequate immune stimulation by the putative antigen and a lasting memory. Therefore, the designed chimeric vaccine represents a potential candidate that could be used to target HAT.

19.
F1000Res ; 11: 345, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36128553

RESUMO

Background: Risk perceptions of coronavirus disease 2019 (COVID-19) are considered important as they impact community health behaviors. The aim of this study was to determine the perceived risk of infection and death due to COVID-19 and to assess the factors associated with such risk perceptions among community members in low- and middle-income countries (LMICs) in Africa, Asia, and South America. Methods: An online cross-sectional study was conducted in 10 LMICs in Africa, Asia, and South America from February to May 2021. A questionnaire was utilized to assess the perceived risk of infection and death from COVID-19 and its plausible determinants. A logistic regression model was used to identify the factors associated with such risk perceptions. Results: A total of 1,646 responses were included in the analysis of the perceived risk of becoming infected and dying from COVID-19. Our data suggested that 36.4% of participants had a high perceived risk of COVID-19 infection, while only 22.4% had a perceived risk of dying from COVID-19. Being a woman, working in healthcare-related sectors, contracting pulmonary disease, knowing people in the immediate social environment who are or have been infected with COVID-19, as well as seeing or reading about individuals infected with COVID-19 on social media or TV were all associated with a higher perceived risk of becoming infected with COVID-19. In addition, being a woman, elderly, having heart disease and pulmonary disease, knowing people in the immediate social environment who are or have been infected with COVID-19, and seeing or reading about individuals infected with COVID-19 on social media or TV had a higher perceived risk of dying from COVID-19. Conclusions: The perceived risk of infection and death due to COVID-19 are relatively low among respondents; this suggests the need to conduct health campaigns to disseminate knowledge and information on the ongoing pandemic.


Assuntos
COVID-19 , Idoso , Estudos Transversais , Países em Desenvolvimento , Feminino , Humanos , Pandemias , Pobreza
20.
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