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1.
Malar J ; 23(1): 9, 2024 Jan 04.
Artículo en Inglés | MEDLINE | ID: mdl-38178227

RESUMEN

BACKGROUND: Decreased efficacy of artemisinin-based combination therapy (ACT) for Plasmodium falciparum malaria has been previously reported in patients with sickle cell disease (SCD). The main purpose of this study was to investigate the in vitro susceptibility of isolates to dihydro-artemisinin (DHA) to provide a hypothesis to explain this treatment failure. METHODS: Isolates were collected from patients attending health centres in Abidjan with uncomplicated P. falciparum malaria. The haemoglobin type has been identified and in vitro drug sensitivity tests were conducted with the ring stage assay and maturation inhibition assay. RESULTS: 134 isolates were obtained. Parasitaemia and haemoglobin levels at inclusion were lower in patients with haemoglobin HbSS and HbSC than in patients with normal HbAA. After ex vivo RSA and drug inhibition assays, the lowest rate of parasitic growth was found with isolates from HbAS red cells. Conversely, a significantly higher survival rate of parasites ranging from 15 to 34% were observed in isolates from HbSS. Isolates with in vitro reduced DHA sensitivity correlate with lower RBC count and haematocrit and higher parasitaemia at inclusion compared to those with isolates with normal DHA sensitivity. However, this decrease of in vitro sensitivity to DHA was not associated with Kelch 13-Propeller gene polymorphism. CONCLUSION: This study highlights an in vitro decreased sensitivity to DHA, for isolates collected from HbSS patients, not related to the Pfkelch13 gene mutations. These results are in line with recent studies pointing out the role of the redox context in the efficacy of the drug. Indeed, SCD red cells harbour a highly different ionic and redox context in comparison with normal red cells. This study offers new insights into the understanding of artemisinin selective pressure on the malaria parasite in the context of haemoglobinopathies in Africa.


Asunto(s)
Anemia de Células Falciformes , Antimaláricos , Artemisininas , Malaria Falciparum , Parásitos , Humanos , Animales , Antimaláricos/farmacología , Antimaláricos/uso terapéutico , Plasmodium falciparum/genética , Côte d'Ivoire , Artemisininas/farmacología , Artemisininas/uso terapéutico , Malaria Falciparum/parasitología , Hemoglobina Falciforme
2.
Matern Child Nutr ; 20(3): e13649, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38599819

RESUMEN

The main objective of this project was to compare in the field conditions two strategies of re-nutrition of children with moderate acute malnutrition (MAM) aged from 6 to 24 months, targeting the microbiota in comparison with a standard regimen. A three-arm, open-label, pragmatic randomised trial was conducted in four countries (Niger, CAR, Senegal and Madagascar). Children received for 12 weeks either fortified blended flour (FBF control) = arm 1, or FBF + azithromycin (oral suspension of 20 mg/kg/day daily given with a syringe) for the first 3 days at inclusion = arm 2 or mix FBF with inulin/fructo-oligosaccharides (6 g/day if age ≥12 months and 4 g if age <12 months) = arm 3. For each arm, children aged from 6 to 11 months received 100 g x 2 per day of flours and those aged from 12 to 24 months received 100 g × 3 per day of FBF. The primary endpoint was nutritional recovery, defined by reaching a weight-for-height z-score (WHZ) ≥ -1.5 within 12 weeks. Overall, 881 children were randomised (297, 290 and 294 in arm 1, arm 2 and arm 3, respectively). Three hundred and forty-four children were males (39%) and median/mean age were 14.6/14.4 months (SD = 4.9, IQR = 10.5-18.4). At inclusion, the three arms were comparable for all criteria, but differences were observed between countries. Overall, 44% (390/881) of the children recovered at week 12 from MAM, with no significant difference between the three arms (41.4%, 45.5% and 45.9%, in arm 1, arm 2 and arm 3, respectively, p = 0.47). This study did not support the true advantages of adding a prebiotic or antibiotic to flour. When using a threshold of WHZ ≥ -2 as an exploratory endpoint, significant differences were observed between the three arms, with higher success rates in arms with antibiotics or prebiotics compared to the control arm (66.9%, 66.0% and 55.2%, respectively, p = 0.005).


Asunto(s)
Harina , Alimentos Fortificados , Microbioma Gastrointestinal , Humanos , Microbioma Gastrointestinal/efectos de los fármacos , Microbioma Gastrointestinal/fisiología , Lactante , Femenino , Masculino , Preescolar , Azitromicina/administración & dosificación , Oligosacáridos/administración & dosificación , Inulina/administración & dosificación , Prebióticos/administración & dosificación , Antibacterianos/administración & dosificación
3.
Malar J ; 16(1): 387, 2017 09 26.
Artículo en Inglés | MEDLINE | ID: mdl-28950864

RESUMEN

BACKGROUND: The Comoros are an archipelago located in the Indian Ocean between the eastern coasts of Africa and north of Madagascar. Malaria transmission appeared late in the 19th century due to the intensification of human migration. The story of malaria transmission for the past century is depicted to provide useful lessons for the future. Currently, malaria transmission occurs differently on each island; thus, control strategies must be adapted for each particular island. Tentative malaria control in Comoros has a long history of success and failure. This study reviews the data available as a basis for recommendations for the future. RESULTS: There has been much effort to reach a pre-eradication state in Anjouan and Moheli, but only control steps have been taken in the Great Comoro. To date, the primary strategy used is mass treatment of the population using artemisinin-based combination therapy (ACT), which is similar to the strategy deployed during the 1950s in other countries. ACT appears efficient in two of the three islands; however, the sustainability of the strategy is unknown. This sustainability is compromised by (i) the huge level of uncontrolled exchange between the Comoro Islands and their neighbours, increasing the risk of introducing ACT-resistant strains, (ii) the use of large quantities of pesticides for agriculture usually associated with the resistance of mosquitoes, and (iii) the cost of the actions themselves. CONCLUSIONS: In view of the history of malaria in this area, the first recommendation is to enhance the training of health workers and the population. The second step is to establish a national strategy to assess malaria and related factors, which is currently lacking. A survey to assess the drug sensitivity of the parasites is particularly important in a context of low transmission associated with mass treatment of the population. The last point should be to secure financial support, which is not obvious in a context of pre-elimination. The Comoro Islands are thus a living laboratory to experiments with strategies for elimination, but the future is complex.


Asunto(s)
Antimaláricos/uso terapéutico , Artemisininas/uso terapéutico , Control de Enfermedades Transmisibles/métodos , Malaria/prevención & control , Comoras , Quimioterapia Combinada/estadística & datos numéricos , Humanos
4.
Antimicrob Agents Chemother ; 58(1): 602-5, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24165175

RESUMEN

Cerebral malaria (CM) is characterized by a dysregulated immune response that results in endothelial membrane destabilization and increased microparticle (MP) production. Citicoline (CTC) is a membrane stabilizer used for the treatment of neurological disorders. We evaluated the efficacy of CTC as adjunct therapy to aid recovery from experimental CM. We show that CTC reduces MP production in vitro; in combination with artesunate in vivo, confers partial protection against CM; and prolongs survival.


Asunto(s)
Antimaláricos/uso terapéutico , Citidina Difosfato Colina/uso terapéutico , Malaria Cerebral/tratamiento farmacológico , Animales , Artemisininas/uso terapéutico , Artesunato , Femenino , Humanos , Ratones
5.
Malar J ; 13: 110, 2014 Mar 21.
Artículo en Inglés | MEDLINE | ID: mdl-24649924

RESUMEN

BACKGROUND: A flow cytometric method is proposed to study in vitro drug sensitivity of Plasmodium falciparum. Standard [(3)H]-hypoxanthine incorporation assay gives only information on inhibition of maturation by drugs. This method is usable on field isolates and provides data on both inhibition of maturation and re-invasion. METHODS: The method is based on the staining of parasites with hydroethidine (HE) and thiazole orange (TO) which allow differential identification of early, trophozoite and late stage of the parasite by flow cytometry. Late stages of the parasites are obtained by incubation in culture for 24 hours. Reinvasion is followed by culturing parasitized red blood cells for 24 h more. RESULTS: Compared to the standard [(3)H]-hypoxanthine incorporation assay, it gave similar results as expressed by 50% inhibitory concentrations for chloroquine of laboratory strains and "field" isolates. The effect of quinine on the schizont-ring transition was also explored using this method. First data on the inhibition of re-invasion induced by quinine are presented for both P. falciparum-cultured strains and field isolates. DISCUSSION: This method is simple to use event for field isolate study. It is suitable to analyse effect of drugs on steps of the parasite life cycle different for the maturation one. Using this method quinine was found to have a inhibitory effect on re-invasion of red cells by Plasmodium.


Asunto(s)
Antimaláricos/farmacología , Benzotiazoles , Resistencia a Medicamentos , Citometría de Flujo/métodos , Colorantes Fluorescentes , Fenantridinas , Plasmodium falciparum/efectos de los fármacos , Quinolinas , Cloroquina/farmacología , Concentración 50 Inhibidora , Quinina/farmacología
6.
Am J Trop Med Hyg ; 109(4): 725-729, 2023 10 04.
Artículo en Inglés | MEDLINE | ID: mdl-37640288

RESUMEN

Wastewater-based surveillance is increasingly recognized as an important approach to monitoring population-level antimicrobial resistance (AMR). In this exploratory study, we examined the use of metagenomics to evaluate AMR using untreated wastewater samples routinely collected by the Niger national polio surveillance program. Forty-eight stored samples from two seasons each year over 4 years (2016-2019) in three regions were selected for inclusion in this study and processed using unbiased DNA deep sequencing. Normalized number of reads of genetic determinants for different antibiotic classes were compared over time, by season, and by location. Correlations in resistance were examined among classes. Changes in reads per million per year were demonstrated for several classes, including decreases over time in resistance determinants for phenicols (-3.3, 95% CI: -8.7 to -0.1, P = 0.029) and increases over time for aminocoumarins (3.8, 95% CI: 0.0 to 11.4, P = 0.043), fluoroquinolones (6.8, 95% CI: 0.0 to 20.5, P = 0.048), and beta-lactams (0.85, 95% CI: 0.1 to 1.7, P = 0.006). Sulfonamide resistance was higher in the post-rainy season compared with the dry season (5.2-fold change, 95% CI: 3.4 to 7.9, P < 0.001). No differences were detected when comparing other classes by season or by site for any antibiotic class. Positive correlations were identified in genetic determinants of resistance among several antibiotic classes. These results demonstrate the potential utility of leveraging existing wastewater sample collection in this setting for AMR surveillance.


Asunto(s)
Antibacterianos , Farmacorresistencia Bacteriana , Humanos , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Farmacorresistencia Bacteriana/genética , Monitoreo Epidemiológico Basado en Aguas Residuales , Aguas Residuales , Niger/epidemiología
7.
IJID Reg ; 7: 230-232, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37168517

RESUMEN

Dengue fever is the most important mosquito-borne viral disease of humans, with a significant disease burden in tropical and subtropical countries. The disease is caused by four distinct dengue virus (DENV) serotypes, DENV-1 to -4, all of which belong to the family Flaviviridae, genus Flavivirus. Approximately 3.6 billion people live in areas where they are at risk of transmission of DENVs, resulting in up to 390 million infections and 96 million symptomatic cases annually. Although the disease is highly endemic in the West Africa region, little is known about the prevalence and distribution of DENVs in Niger. We hereby report the first laboratory-confirmed case of dengue in Niger.

8.
Parasite Epidemiol Control ; 22: e00311, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37361928

RESUMEN

Background: Porcine cysticercosis is an endemic parasitic zoonosis in many developing countries. The objective of this study was to estimate the seroprevalence of porcine cysticercosis in traditional pig farms in the departments of Dabou, Aboisso and Agboville. Methods: Blood samples were taken from pigs and analyzed by ELISA (IgG) and western blot. Data on farming practices and pig characteristics were collected. Multivariate logistic regression models were constructed to identify risk factors. Results: A total of 668 pigs were sampled from 116 farms and 639 samples were analyzed. The seroprevalence of cysticercosis was estimated at 13.2%. Overweight [OR = 2.6; 95%CI (1.3-4.9)] and fat pigs [OR = 2.3; 95%CI (1.0-4.8)] were twice as likely to be seropositive for cysticercosis. This risk was increased in farms using well water for drinking [OR = 2.5; 95%CI (1.0-6.3)] as well as those reporting veterinary care of the animals (OR = 2.9; 95%CI (1.2-7.3)). Conclusions: This study demonstrated the circulation of Taenia solium in pig farms in southern Côte d'Ivoire.

9.
Heliyon ; 9(11): e20916, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37954288

RESUMEN

The emergence of the Omicron variant in November 2021, has caused panic worldwide due to the rapid evolution and the ability of the virus to escape the immune system. Since, several Omicron sublineages (BA.1 to BA.5) and their descendent recombinant lineages have been circulating worldwide. Furthermore, in December 2022, a new Omicron subvariant XBB.1.5 characterized by an unusual mutation in the spike protein evolved in the United States and rapidly spread to the other continents. Our study reports on the first cases of XBB.1.5 sublineage among indigenous Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-COV-2) positive cases detected through the influenza sentinel surveillance system in Niger. All influenza suspected cases were tested for both influenza and SARS-COV-2 using the Centre for Disease Control and prevention (CDC) Influenza SARS-COV-2 Multiplex quantitative Reverse-Transcription Polymerase Chain Reaction (qRT-PCR) Assay. SARS-COV-2 positive samples with cycle threshold ≤28 were selected for whole genome sequencing subsequently using the Oxford Nanopore Midnight protocol with rapid barcoding on a MinIon MK1B device. A total of 51 SARS-COV-2 positive samples were confirmed between December 2022 and March 2023. We successfully obtained 19 sequences with a predominance of the XBB.1/XBB.1.5 sublineages (73.7 %). In addition, a recombinant XBD sequence was also first-ever identified in early March 2023. Our findings support the need to strengthen the influenza sentinel surveillance for routine Coronavirus Disease 2019 (COVID-19) surveillance and SARS-COV-2 variants monitoring in Niger.

10.
J Travel Med ; 30(1)2023 02 18.
Artículo en Inglés | MEDLINE | ID: mdl-36222148

RESUMEN

OBJECTIVES: Neurocysticercosis (NCC) is a parasitic disease caused by the larval stage of the tapeworm Taenia solium. NCC mainly occurs in Africa, Latin America and South-East Asia and can cause a variety of clinical signs/symptoms. Although it is a rare disease in Europe, it should nonetheless be considered as a differential diagnosis. The aim of this study was to describe clinical characteristics and management of patients with NCC diagnosed and treated in Europe. METHODS: We conducted a systematic search of published and unpublished data on patients diagnosed with NCC in Europe (2000-2019) and extracted demographic, clinical and radiological information on each case, if available. RESULTS: Out of 293 identified NCC cases, 59% of patients presented initially with epileptic seizures (21% focal onset); 52% presented with headache and 54% had other neurological signs/symptoms. The majority of patients had a travel or migration history (76%), mostly from/to Latin America (38%), Africa (32%) or Asia (30%). Treatment varied largely depending on cyst location and number. The outcome was favorable in 90% of the cases. CONCLUSIONS: Management of NCC in Europe varied considerably but often had a good outcome. Travel and migration to and from areas endemic for T. solium will likely result in continued low prevalence of NCC in Europe. Therefore, training and guidance of clinicians is recommended for optimal patient management.


Asunto(s)
Neurocisticercosis , Taenia solium , Animales , Humanos , Neurocisticercosis/diagnóstico , Neurocisticercosis/tratamiento farmacológico , Neurocisticercosis/epidemiología , Estudios Retrospectivos , Europa (Continente) , Prevalencia
11.
Infect Immun ; 80(8): 2963-70, 2012 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-22753372

RESUMEN

Recent studies suggest shared pathogenic pathways during malaria and allergy. Indeed, IgE, histamine, and the parasite-derived Plasmodium falciparum histamine-releasing factor translationally controlled tumor protein (PfTCTP) can be found at high levels in serum from patients experiencing malaria, but their relationship with basophil activation remains unknown. We recruited P. falciparum-infected patients in Senegal with mild malaria (MM; n = 19) or severe malaria (SM; n = 9) symptoms and healthy controls (HC; n = 38). Levels of serum IgE, PfTCTP, and IgG antibodies against PfTCTP were determined by enzyme-linked immunosorbent assays (ELISA). Basophil reactivities to IgE-dependent and -independent stimulations were measured ex vivo using fresh blood by looking at the expression level of the basophil activation marker CD203c with flow cytometry. Unstimulated basophils from MM had significantly lower levels of CD203c expression compared to those from HC and SM. After normalization on this baseline level, basophils from SM showed an enhanced reactivity to calcimycin (A23187) and hemozoin. Although SM reached higher median levels of activation after anti-IgE stimulation, great interindividual differences did not allow the results to reach statistical significance. When primed with recombinant TCTP before anti-IgE, qualitative differences in terms of a better ability to control excessive activation could be described for SM. IgE levels were very high in malaria patients, but concentrations in MM and SM were similar and were not associated with basophil responses, which demonstrates that the presence of IgE alone cannot explain the various basophil reactivities. Indeed, PfTCTP could be detected in 32% of patients, with higher concentrations for SM. These PfTCTP-positive patients displayed significantly higher basophil reactivities to any stimulus. Moreover, the absence of anti-PfTCTP IgG was associated with higher responses in SM but not MM. Our results show an association between basophil reactivity and malaria severity and suggest a pathogenic role for plasmodial PfTCTP in the induction of this allergy-like mechanism.


Asunto(s)
Basófilos/fisiología , Malaria Falciparum/parasitología , Plasmodium falciparum/metabolismo , Proteínas Protozoarias/metabolismo , Adulto , Anticuerpos Antiprotozoarios/sangre , Femenino , Regulación de la Expresión Génica/inmunología , Humanos , Inmunoglobulina E/sangre , Inmunoglobulina G/sangre , Malaria Falciparum/sangre , Malaria Falciparum/epidemiología , Masculino , Plasmodium falciparum/genética , Plasmodium falciparum/inmunología , Proteínas Protozoarias/genética , Proteínas Protozoarias/inmunología , Senegal/epidemiología , Proteína Tumoral Controlada Traslacionalmente 1
12.
PLoS Pathog ; 6(7): e1001021, 2010 Jul 29.
Artículo en Inglés | MEDLINE | ID: mdl-20686652

RESUMEN

Cerebral malaria, a major cause of death during malaria infection, is characterised by the sequestration of infected red blood cells (IRBC) in brain microvessels. Most of the molecules implicated in the adhesion of IRBC on endothelial cells (EC) are already described; however, the structure of the IRBC/EC junction and the impact of this adhesion on the EC are poorly understood. We analysed this interaction using human brain microvascular EC monolayers co-cultured with IRBC. Our study demonstrates the transfer of material from the IRBC to the brain EC plasma membrane in a trogocytosis-like process, followed by a TNF-enhanced IRBC engulfing process. Upon IRBC/EC binding, parasite antigens are transferred to early endosomes in the EC, in a cytoskeleton-dependent process. This is associated with the opening of the intercellular junctions. The transfer of IRBC antigens can thus transform EC into a target for the immune response and contribute to the profound EC alterations, including peri-vascular oedema, associated with cerebral malaria.


Asunto(s)
Encéfalo/parasitología , Adhesión Celular , Células Endoteliales/parasitología , Uniones Intercelulares/parasitología , Microvasos/parasitología , Plasmodium falciparum/patogenicidad , Antígenos de Protozoos/metabolismo , Encéfalo/irrigación sanguínea , Encéfalo/citología , Técnicas de Cocultivo , Endosomas , Células Endoteliales/inmunología , Células Endoteliales/patología , Eritrocitos/inmunología , Eritrocitos/parasitología , Eritrocitos/patología , Humanos , Microvasos/citología
13.
Artículo en Inglés | MEDLINE | ID: mdl-36011739

RESUMEN

Climate changes in the eastern part of Sahelian regions will induce an increase in rainfalls and extreme climate events. In this area, due to the intense events and floods, malaria transmission, a climate sensitive disease, is thus slowly extending in time to the drought season and in areas close to the border of the desert. Vectors can as well modify their area of breeding. Control programs must be aware of these changes to adapt their strategies.


Asunto(s)
Cambio Climático , Malaria , Inundaciones , Humanos , Malaria/epidemiología , Estaciones del Año
14.
BMC Med Genomics ; 15(1): 120, 2022 05 23.
Artículo en Inglés | MEDLINE | ID: mdl-35606796

RESUMEN

BACKGROUND: Sickle cell disease (SCD) is a hemoglobin disorders that concern 300,000 newborns each year around the world. There are hemoglobin haplotypes that affect SCD clinic expression. METHODS: Our goal was to identify the hemoglobin's haplotypes among individuals with mild malaria independently of SCD status in Côte d'Ivoire. To determine these haplotypes, specific restriction enzyme (RE) is used after PCR amplification with each primer. According to the digestion of PCR product by RE, five hemoglobin's haplotypes are found in the world. RESULTS: In Côte d'Ivoire, no study has yet deeply described the distribution of haplotypes. Four different "classical" haplotypes of hemoglobin were detected: Benin (56.5%), Bantou (28.5%), Senegal (4%), Cameroun (1%); and 10% of atypical profiles. Heterozygous haplotype (69%) were more frequent than homozygous haplotype (31%). CONCLUSIONS: In this preliminary study, we note a high prevalence of atypical and heterozygous haplotype. Benin haplotype that is associated with severity of SCD was most predominant in our studied population.


Asunto(s)
Anemia de Células Falciformes , Malaria , Anemia de Células Falciformes/complicaciones , Anemia de Células Falciformes/epidemiología , Anemia de Células Falciformes/genética , Côte d'Ivoire , Haplotipos , Hemoglobina Falciforme/genética , Hemoglobinas , Humanos , Malaria/complicaciones , Malaria/genética
15.
Trop Med Infect Dis ; 7(8)2022 Jul 29.
Artículo en Inglés | MEDLINE | ID: mdl-36006247

RESUMEN

The effectiveness of artemisinin-based combination therapies (ACTs) depends not only on that of artemisinin but also on that of partner molecules. This study aims to evaluate the prevalence of mutations in the Pfdhfr, Pfdhps, and Pfmdr1 genes from isolates collected during a clinical study. Plasmodium genomic DNA samples extracted from symptomatic malaria patients from Dogondoutchi, Niger, were sequenced by the Sanger method to determine mutations in the Pfdhfr (codons 51, 59, 108, and 164), Pfdhps (codons 436, 437, 540, 581, and 613), and Pfmdr1 (codons 86, 184, 1034, and 1246) genes. One hundred fifty-five (155) pre-treatment samples were sequenced for the Pfdhfr, Pfdhps, and Pfmdr1 genes. A high prevalence of mutations in the Pfdhfr gene was observed at the level of the N51I (84.97%), C59R (92.62%), and S108N (97.39%) codons. The key K540E mutation in the Pfdhps gene was not observed. Only one isolate was found to harbor a mutation at codon I431V. The most common mutation on the Pfmdr1 gene was Y184F in 71.43% of the mutations found, followed by N86Y in 10.20%. The triple-mutant haplotype N51I/C59R/S108N (IRN) was detected in 97% of the samples. Single-mutant (ICS and NCN) and double-mutant (IRS, NRN, and ICN) haplotypes were prevalent at 97% and 95%, respectively. Double-mutant haplotypes of the Pfdhps (581 and 613) and Pfmdr (86 and 184) were found in 3% and 25.45% of the isolates studied, respectively. The study focused on the molecular analysis of the sequencing of the Pfdhfr, Pfdhps, and Pfmdr1 genes. Although a high prevalence of mutations in the Pfdhfr gene have been observed, there is a lack of sulfadoxine pyrimethamine resistance. There is a high prevalence of mutation in the Pfmdr184 codon associated with resistance to amodiaquine. These data will be used by Niger's National Malaria Control Program to better monitor the resistance of Plasmodium to partner molecules in artemisinin-based combination therapies.

16.
Science ; 378(6623): eadd8737, 2022 12 02.
Artículo en Inglés | MEDLINE | ID: mdl-36454863

RESUMEN

The geographic and evolutionary origins of the SARS-CoV-2 Omicron variant (BA.1), which was first detected mid-November 2021 in Southern Africa, remain unknown. We tested 13,097 COVID-19 patients sampled between mid-2021 to early 2022 from 22 African countries for BA.1 by real-time RT-PCR. By November-December 2021, BA.1 had replaced the Delta variant in all African sub-regions following a South-North gradient, with a peak Rt of 4.1. Polymerase chain reaction and near-full genome sequencing data revealed genetically diverse Omicron ancestors already existed across Africa by August 2021. Mutations, altering viral tropism, replication and immune escape, gradually accumulated in the spike gene. Omicron ancestors were therefore present in several African countries months before Omicron dominated transmission. These data also indicate that travel bans are ineffective in the face of undetected and widespread infection.

17.
Antimicrob Agents Chemother ; 55(12): 5834-41, 2011 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-21947391

RESUMEN

Plasmodium falciparum isolates with decreased susceptibility to quinine are increasingly being found in malaria patients. Mechanisms involved in this resistance are not yet understood. Several studies claim that alongside mutations in the Pfcrt and Pfmdr1 genes, the Pfnhe-1 Na(+)/H(+) exchanger polymorphism plays a role in decreasing susceptibility. However, conflicting results on the link between the Pfnhe-1 gene and quinine resistance arise from field- and culture-adapted isolates. We tested the association between Pfnhe-1, Pfcrt, and Pfmdr1 polymorphisms in field- and culture-adapted isolates from various countries with their in vitro susceptibility to quinine. Field isolates presented a higher diversity of the Pfnhe-1 microsatellite sequence than culture-adapted isolates. In culture-adapted isolates but not in field isolates, mutations in the Pfcrt and Pfmdr1 genes, as well as a higher number of DNNND repeats in the Pfnhe-1 gene, were associated with a higher 50% inhibitory concentration (IC(50)) of quinine. Furthermore, most of the culture-adapted isolates with more than one DNNND repeat in the Pfnhe-1 gene also harbored mutated Pfcrt and Pfmdr1 genes with an apparent cumulative effect on quinine susceptibility. This study supports the involvement of the Pfnhe-1 gene in the modulation of the in vitro quinine response when associated with mutated Pfcrt and Pfmdr1 genes. Culture adaptation could be responsible for selection of specific haplotypes of these three genes. Methods used for drug testing might thus influence the association between Pfnhe-1 polymorphism and quinine susceptibility. However, we do not exclude the possibility that in particular settings, Pfnhe-1 polymorphism can be used as a molecular marker for surveillance of quinine resistance.


Asunto(s)
Antimaláricos/farmacología , Resistencia a Medicamentos/genética , Plasmodium falciparum/efectos de los fármacos , Polimorfismo Genético/genética , Quinina/farmacología , Intercambiadores de Sodio-Hidrógeno/genética , Animales , Medios de Cultivo , Humanos , Concentración 50 Inhibidora , Proteínas de Transporte de Membrana/genética , Datos de Secuencia Molecular , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/genética , Pruebas de Sensibilidad Parasitaria , Plasmodium falciparum/genética , Plasmodium falciparum/crecimiento & desarrollo , Plasmodium falciparum/aislamiento & purificación , Proteínas Protozoarias/genética , Análisis de Secuencia de ADN
18.
Malar J ; 10: 346, 2011 Nov 25.
Artículo en Inglés | MEDLINE | ID: mdl-22118493

RESUMEN

BACKGROUND: Infection with Plasmodium berghei is a widely used model of murine malaria and a powerful tool for reverse genetic and pathogenesis studies. However, the efficacy of in vitro reinvasion of erythrocytes is generally low, limiting in vitro studies. METHODS: Plasmodium berghei ANKA-infected blood obtained from a susceptible infected mouse was cultured in various conditions and in vitro parasitaemia was measured every day to evaluate the rate of reinvasion. RESULTS: High quality culture media were used and reinvasion rates were improved by vigorous orbital shaking of the flask and increasing density of the medium with gelatin. DISCUSSION: Using these settings, reinvasion of normal mouse erythrocytes by the parasite was obtained in vitro over two weeks with preservation of the infectivity in vivo.


Asunto(s)
Eritrocitos/parasitología , Malaria Cerebral/parasitología , Parasitología/métodos , Plasmodium berghei/crecimiento & desarrollo , Plasmodium berghei/patogenicidad , Animales , Medios de Cultivo/química , Modelos Animales de Enfermedad , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos CBA , Parasitemia/parasitología , Plasmodium berghei/aislamiento & purificación , Virulencia
19.
Parasite ; 28: 67, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34569928

RESUMEN

BACKGROUND: Artemisinin-based treatment in malaria patients with abnormal hemoglobin may be ineffective because of their genetic particularity, which could lead to resistance. The main purpose of this study was to assess the effect of artemisinin derivatives on in vivo parasite clearance according to erythrocyte variants. In vivo response was investigated through retrospective data obtained over a 42-day artemether-lumefantrine/artesunate amodiaquine efficacy protocol conducted from 2012 to 2016. RESULTS: A total of 770 patients in Côte d'Ivoire attending the hospitals of Anonkoua-koute (Abidjan), Petit Paris (Korhogo), Libreville (Man), Dar es salam (Bouaké), Ayamé and Yamoussoukro with acute uncomplicated falciparum malaria were selected for successful hemoglobin typing. HbAS, HbSS, HbAC, and HbSC genotypes were found. Parasite clearance time was obtained for 414 patients. In the population with abnormal hemoglobin, parasite densities on admission and parasite clearance rates were significantly lower in the HbSC group compared to HbAA (p = 0.02 and p = 0.007, respectively). After PCR correction on day 42, the acute treatment rate was 100% for each group. Parasite half-life and time for initial parasitaemia to decline by 50 and 99% were longer for the HbSC group (p < 0.05). The study also investigated the prevalence of K13-propeller polymorphisms across different hemoglobin genotype groups. A total of 185 and 63 samples were sequenced in the HbAA group and patients with abnormal Hb, respectively. Only two nonsynonymous mutations D559N and V510M were found in the HbAA group. CONCLUSION: Although this study proved good efficacy of artemether-lumefantrine and artesunate amodiaquine in the treatment of uncomplicated Plasmodium falciparum malaria in patients with abnormal hemoglobin, the increased delay of parasite clearance may represent a threat to health in these patients in relation with sickle cell crisis, which could support selection of parasites resistant to artemisinin.


TITLE: Thérapies contenant des dérivés de l'artémisinine et hémoglobine anormale : faut-il adapter le traitement ? ABSTRACT: Contexte : Le traitement à base d'artémisinine chez les patients atteints de paludisme et présentant une hémoglobine anormale peut être inefficace en raison de leur particularité génétique, ce qui pourrait entraîner une résistance. L'objectif principal de cette étude était d'évaluer in vivo l'effet des dérivés de l'artémisinine sur la clairance du parasite en fonction des variantes érythrocytaires. La réponse in vivo a été étudiée à travers des données rétrospectives obtenues au cours d'un protocole d'efficacité de 42 jours artéméther-luméfantrine/artésunate-amodiaquine mené dans les années 2012 à 2016. Résultats : Un total de 770 patients en Côte d'Ivoire fréquentant les hôpitaux d'Anonkoua-koute (Abidjan), Petit Paris (Korhogo), Libreville (Man), Dar es salam (Bouaké), Ayamé et Yamoussoukro, présentant un paludisme aigu non compliqué à falciparum ont été sélectionnés pour un typage réussi de l'hémoglobine. Les génotypes HbAS, HbSS, HbAC et HbSC ont été trouvés. Le temps de clairance du parasite a été obtenu pour 414 patients. Dans la population avec une hémoglobine anormale, les densités parasitaires à l'admission et le taux de clairance parasitaire étaient significativement plus faibles dans le groupe HbSC par rapport au groupe HbAA (respectivement, p = 0,02 et p = 0,007). Le RCPA était de 100 % pour chaque groupe après correction par PCR au jour 42. La demi-vie du parasite et le temps nécessaire pour que la parasitémie initiale diminue de 50 et 99 % étaient plus longs pour le groupe HbSC (p < 0,05). L'étude a également examiné la prévalence des polymorphismes du gène K13 dans différents groupes de génotype d'hémoglobine. Un total de 185 et 63 échantillons ont été séquencés respectivement dans le groupe HbAA et chez les patients présentant une Hb anormale. Seules deux mutations non synonymes D559N et V510M ont été trouvées dans le groupe HbAA. Conclusion : Bien que cette étude ait prouvé la bonne efficacité de l'artéméther-luméfantrine et de l'artésunate amodiaquine dans le traitement du paludisme simple à Plasmodium falciparum chez les patients présentant une hémoglobine anormale, le retard accru de clairance parasitaire peut représenter une menace pour la santé de ces patients en relation avec la crise drépanocytaire, et peut favoriser la sélection de parasites résistants à l'artémisinine.


Asunto(s)
Antimaláricos , Artemisininas , Hemoglobinas Anormales , Malaria Falciparum , Antimaláricos/uso terapéutico , Arteméter/uso terapéutico , Combinación Arteméter y Lumefantrina , Artemisininas/uso terapéutico , Côte d'Ivoire/epidemiología , Combinación de Medicamentos , Etanolaminas/uso terapéutico , Hemoglobinas Anormales/uso terapéutico , Humanos , Malaria Falciparum/tratamiento farmacológico , Malaria Falciparum/epidemiología , Plasmodium falciparum/genética , Estudios Retrospectivos , Resultado del Tratamiento
20.
Microorganisms ; 9(8)2021 Aug 11.
Artículo en Inglés | MEDLINE | ID: mdl-34442791

RESUMEN

Cysticercosis is one of the main causes of secondary epilepsy in sub-Saharan Africa. To estimate the seroprevalence of cysticercosis among epileptic patients, we conducted a cross-sectional study of patients attending neurology consultation in Abidjan, Côte d'Ivoire. Methods: Patients' socio-demographic and lifestyle data were collected as well as blood samples for serological testing using ELISA and Western blot based on IgG antibodies detection. For qualitative variables comparison, Chi2 or Fisher tests were used; a Student's t-test was used to compare quantitative variables. A multivariate logistic regression model was fit to identify risks factors. Results: Among 403 epileptic patients included in the study, 55.3% were male; the median age was 16.9 years; 77% lived in Abidjan; 26.5% were workers. Most patients included in the study had tonic-clonic seizures (80%), and 11.2% had focal deficit signs. The seroprevalence of cysticercosis was 6.0%. The risk was higher in patients over 30 years old (aOR = 5.1 (1.3-20.0)) than in patients under 16. The risk was also considerably high in patients who reported epileptics in the family (aOR = 5 (1.7-14.6)). The risk was three-fold less in females than in males. Conclusions: This study highlighted the exposure of epileptic patients to Taenia solium larvae in an urban area. The risk of positive serology was increased with age, male gender, and family history of epilepsy.

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