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1.
Clin Infect Dis ; 75(12): 2088-2096, 2022 12 19.
Artículo en Inglés | MEDLINE | ID: mdl-35543372

RESUMEN

BACKGROUND: Waning antibody levels post-vaccination and the emergence of variants of concern (VOCs) capable of evading protective immunity have raised the need for booster vaccinations. However, which combination of coronavirus disease 2019 (COVID-19) vaccines offers the strongest immune response against the Omicron variant is unknown. METHODS: This randomized, participant-blinded, controlled trial assessed the reactogenicity and immunogenicity of different COVID-19 vaccine booster combinations. A total of 100 BNT162b2-vaccinated individuals were enrolled and randomized 1:1 to either homologous (BNT162b2 + BNT162b2 + BNT162b2; "BBB") or heterologous messenger RNA (mRNA) (BNT162b2 + BNT162b2 + mRNA-1273; "BBM") booster vaccine. The primary end point was the level of neutralizing antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) wild-type and VOCs at day 28. RESULTS: A total of 51 participants were allocated to BBB and 49 to BBM; 50 and 48, respectively, were analyzed for safety and immunogenicity outcomes. At day 28 post-boost, mean SARS-CoV-2 spike antibody titers were lower with BBB (22 382 IU/mL; 95% confidence interval [CI], 18 210 to 27 517) vs BBM (29 751 IU/mL; 95% CI, 25 281 to 35 011; P = .034) as was the median level of neutralizing antibodies: BBB 99.0% (interquartile range [IQR], 97.9% to 99.3%) vs BBM 99.3% (IQR, 98.8% to 99.5%; P = .021). On subgroup analysis, significant higher mean spike antibody titer, median surrogate neutralizing antibody level against all VOCs, and live Omicron neutralization titer were observed only in older adults receiving BBM. Both vaccines were well tolerated. CONCLUSIONS: Heterologous mRNA-1273 booster vaccination compared with homologous BNT123b2 induced a stronger neutralizing response against the Omicron variant in older individuals. CLINICAL TRIALS REGISTRATION: NCT05142319.


Asunto(s)
Vacuna BNT162 , COVID-19 , Humanos , Anciano , SARS-CoV-2 , Formación de Anticuerpos , Vacuna nCoV-2019 mRNA-1273 , Vacunación , Anticuerpos Neutralizantes , Anticuerpos Antivirales
2.
PLoS Med ; 18(4): e1003591, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33901169

RESUMEN

Jean-Marc Chavatte and Georges Snounou discuss research involving controlled malaria infections.


Asunto(s)
Control de Enfermedades Transmisibles/estadística & datos numéricos , Malaria/parasitología , Humanos
3.
Emerg Infect Dis ; 26(4): 826-828, 2020 04.
Artículo en Inglés | MEDLINE | ID: mdl-32023203

RESUMEN

In 2018, Babesia microti infection was diagnosed for a 37-year-old man in Singapore who acquired the infection in the United States. This case highlights the recent rise of tickborne infections in the United States and the risk for their spread, because of increasing global interconnectivity, to regions where they are not endemic.


Asunto(s)
Babesia microti , Babesiosis , Adulto , Babesia microti/genética , Babesiosis/diagnóstico , Babesiosis/epidemiología , Humanos , Masculino , Singapur/epidemiología , Estados Unidos
4.
Malar J ; 17(1): 35, 2018 Jan 16.
Artículo en Inglés | MEDLINE | ID: mdl-29338726

RESUMEN

BACKGROUND: Blackwater fever is a complication of malaria infection consisting of a syndrome of febrile intra-vascular haemolysis with severe anaemia and intermittent passage of dark-red to black colour urine. Despite numerous reports and studies of this condition, its pathogenesis remains incompletely understood. CASE PRESENTATION: This report describes a case of classic blackwater fever in a returning traveller, without prior history of malaria infection nor usage of anti-malarial prophylaxis, treated with two courses of oral artemether-lumefantrine combination therapy. Unusual persistence of submicroscopic Plasmodium falciparum parasitaemia was detected by PCR for 18 days after initiation of treatment. CONCLUSION: To the authors' knowledge this is the first reported occurrence of a case of blackwater fever associated with prolonged submicroscopic parasitaemia. This unusual case challenges the current knowledge of the pathogenesis of this condition and opens questions that may have important diagnostic and treatment implications.


Asunto(s)
Combinación Arteméter y Lumefantrina/uso terapéutico , Fiebre Hemoglobinúrica/tratamiento farmacológico , Enfermedades Transmisibles Importadas/tratamiento farmacológico , Malaria Falciparum/tratamiento farmacológico , Parasitemia/tratamiento farmacológico , Plasmodium falciparum/fisiología , Antimaláricos/uso terapéutico , Fiebre Hemoglobinúrica/parasitología , Enfermedades Transmisibles Importadas/parasitología , Ghana , Humanos , Malaria Falciparum/complicaciones , Malaria Falciparum/parasitología , Masculino , Parasitemia/complicaciones , Parasitemia/parasitología , Reacción en Cadena de la Polimerasa , Singapur , Resultado del Tratamiento , Adulto Joven
5.
Parasitol Res ; 117(12): 3917-3925, 2018 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-30324256

RESUMEN

Here, we report new insights on the erythrocytic murine parasite Anthemosoma garnhami, which was first described from Ethiopia in 1969. Its classification has been debated for years, as this parasite presents some intermediate characters between the Haemosporidia and the Piroplasmida. Based on electron-microscopy, immunological, biochemical and drug sensitivity studies, it was finally assigned to the piroplasms, in the family Anthemosomatidae. In 1985, Anthemosoma sp. was reported from Namibia, and since then, no investigation has involved this parasite. We re-examined the original material, illustrate the blood stages with a set of coloured microphotographs and performed a morphometric analysis. As no type material was designated at the time of the original description, we designate syntypes. This study provides also the first molecular data on A. garnhami with the amplification and sequencing of two genes: the nuclear 18S small subunit ribosomal RNA and the mitochondrial cytochrome c oxydase subunit I. The phylogenetic analyses of both genes confirm that A. garnhami belongs to the Piroplasmida and appears on its own new branch distinct from both Babesids and Theilerids. This result supports the placement of the genus Anthemosoma in its own family but also invalidates the order Anthemosomida. Being paraphyletic with Babesia, the conundrum about the systematics of the piroplasms is discussed as well as the records, the hosts and the possible vectors of Anthemosoma spp.


Asunto(s)
Piroplasmida/clasificación , Piroplasmida/genética , Animales , Babesia/clasificación , Ciclooxigenasa 1/genética , Etiopía , Ratones , Namibia , Filogenia , ARN Ribosómico 18S/genética
8.
Malar J ; 14: 454, 2015 Nov 14.
Artículo en Inglés | MEDLINE | ID: mdl-26577930

RESUMEN

BACKGROUND: Plasmodium ovale, considered the rarest of the malaria parasites of humans, consists of two morphologically identical but genetically distinct sympatric species, Plasmodium ovale curtisi and Plasmodium ovale wallikeri. These parasites resemble morphologically to Plasmodium vivax with which they also share a tertian periodicity and the ability to cause relapses, making them easily misidentified as P. vivax. Plasmodium ovale infections are rarely reported, but given the likelihood of misidentification, their prevalence might be underestimated. METHODS: Morphological and molecular analysis of confirmed malaria cases admitted in Singapore in 2012-2014 detected nine imported P. ovale cases that had been misidentified as P. vivax. Since P. ovale had not been previously officially reported in Singapore, a retrospective analysis of available, frozen, archival blood samples was performed and returned two additional misidentified P. ovale cases in 2003 and 2006. These eleven P. ovale samples were characterized with respect to seven molecular markers (ssrRNA, Potra, Porbp2, Pog3p, dhfr-ts, cytb, cox1) used in recent studies to distinguish between the two sympatric species, and to a further three genes (tufa, clpC and asl). RESULTS: The morphological features of P. ovale and the differential diagnosis with P. vivax were reviewed and illustrated by microphotographs. The genetic dimorphism between P. ovale curtisi and P. ovale wallikeri was assessed by ten molecular markers distributed across the three genomes of the parasite (Genbank KP050361-KP050470). The data obtained for seven of these markers were compared with those published and confirmed that both P. ovale species were present. This dimorphism was also confirmed for the first time on: (1) two genes from the apicoplast genome (tufA and clpC genes); and, (2) the asl gene that was used for phylogenetic analyses of other Plasmodium species, and that was found to harbour the highest number of dimorphic loci between the two P. ovale species. CONCLUSION: Misidentified P. ovale infections are reported for the first time among imported malaria cases in Singapore. Genetic dimorphism between P. ovale curtisi and P. ovale wallikeri was confirmed using markers from the parasites' three genomes. The apparent increase of imported P. ovale since 2012 (with yearly detection of cases) is puzzling. Given decrease in the overall number of malaria cases recorded in Singapore since 2010 the 'resurgence' of this neglected species raises public health concerns.


Asunto(s)
Malaria/diagnóstico , Malaria/parasitología , Plasmodium ovale/genética , Plasmodium ovale/aislamiento & purificación , ADN Protozoario/química , ADN Protozoario/genética , Genes Protozoarios , Variación Genética , Genotipo , Humanos , Datos de Secuencia Molecular , Plasmodium ovale/citología , Estudios Retrospectivos , Análisis de Secuencia de ADN , Singapur
9.
J Zoo Wildl Med ; 45(3): 577-88, 2014 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-25314825

RESUMEN

A morphologic and molecular epidemiologic investigation was conducted on a captive African black-footed penguin (Spheniscus demersus) colony with a history of Plasmodium infections at La Palmyre Zoo (France). Each penguin received 12.5 mg of pyrimethamine twice a week as a prophylaxis every year from April to November. Although Plasmodium parasites were not detected in blood smears and tissues collected from the penguins, various blood parasites were recorded in blood smears from wild Eurasian magpies (Pica pica) and carrion crows (Corvus corone) sampled at the same time in the study area. These parasites consisted of several Plasmodium spp. (P. lenoblei, P. dorsti, P bioccai, P. relictum, P. dherteae, P. beaucournui, P. maior, P. tranieri, and P. snounoui), Parahaemoproteus spp., Trypanosoma spp., and Leucocytozoon spp. On the other hand, nested polymerase chain reaction enabled detection of Plasmodium DNA in 28/44 (64%) penguins, 15/25 (60%) magpies, and 4/9 (44%) crows. Sequencing and phylogenetic analyses indicated that the parasite DNA amplified from the penguins, magpies, and crows were similar. Magpies and crows could therefore act as a reservoir for penguin Plasmodium infections, which may be more prevalent than previously thought. Morphologic characterization of the Plasmodium spp. detected in the penguins, as well as further biological and epidemiologic studies, are needed to fully understand the transmission of Plasmodium parasites to captive penguins.


Asunto(s)
Animales de Zoológico , Cuervos/sangre , ADN Protozoario/sangre , Plasmodium/genética , Spheniscidae/sangre , Animales , Animales Salvajes , ADN Protozoario/genética , Filogenia , Plasmodium/aislamiento & purificación
10.
PLoS Negl Trop Dis ; 18(7): e0012269, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38985826

RESUMEN

BACKGROUND: Ticks, as critical vectors of a variety of pathogens, pose a significant public health challenge globally. In Southeast Asia (SEA), ticks are responsible for transmitting a diverse array of pathogens affecting humans and animals. The geographical and ecological diversity of SEA provides a unique environment that supports a wide range of tick species, which complicates the management and study of tick-borne diseases (TBDs). METHODOLOGY/PRINCIPAL FINDINGS: This article synthesizes findings from the first international symposium on ticks and TBDs in Southeast Asia, held in Phnom Penh on June 22 and 23, 2023. It highlights regional efforts to understand tick ecology and pathogen transmission. This paper proposes to present a summary of the various presentations given during the symposium following 3 main parts. The first one is devoted to the state of knowledge regarding ticks and TBDs in SEA countries, with presentations from 6 different countries, namely Cambodia, Indonesia, Laos, Malaysia, Thailand, and Vietnam. The second part focuses on the development of new research approaches on tick-borne pathogens (TBPs) and TBDs. The last part is a summary of the round table discussion held on the final day, with the aim of defining the most important challenges and recommendations for researches on TBP and TBD in the SEA region. CONCLUSIONS/SIGNIFICANCE: Key topics discussed include advancements in diagnostic tools, such as MALDI-TOF MS and proteomics, and the development of sustainable strategies for tick management and disease prevention. The symposium facilitated the exchange of knowledge and collaborative networks among experts from various disciplines, promoting a unified approach to tackling TBDs in the region. The symposium underscored the need for enhanced surveillance, diagnostics, and inter-regional cooperation to manage the threat of TBDs effectively. Recommendations include the establishment of a regional database for tick identification and the expansion of vector competence studies. These initiatives are crucial for developing targeted interventions and understanding the broader implications of climate change and urbanization on the prevalence of TBDs.


Asunto(s)
Enfermedades por Picaduras de Garrapatas , Garrapatas , Animales , Enfermedades por Picaduras de Garrapatas/epidemiología , Enfermedades por Picaduras de Garrapatas/transmisión , Humanos , Garrapatas/fisiología , Asia Sudoriental/epidemiología , Cambodia/epidemiología
11.
Transplant Direct ; 9(10): e1537, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37745946

RESUMEN

Background: Immunocompromised individuals have been excluded from landmark studies of messenger RNA vaccinations for severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2). In such patients, the response to vaccination may be blunted and may wane more quickly compared with immunocompetent patients. We studied the factors associated with decreased antibody response to SARS-CoV-2 vaccination and risk factors for subsequent breakthrough infections in liver transplant (LT) patients undergoing coronavirus disease 2019 vaccination with at least 2 doses of messenger RNA vaccine from April 28, 2021, to April 28, 2022. Methods: All LT recipients received at least 2 doses of the BNT162b2 (Pfizer BioNTech) vaccine 21 d apart. We measured the antibody response against the SARS-CoV-2 spike protein using the Roche Elecsys immunoassay to the receptor-binding domain of the SARS-CoV-2 spike protein, and the presence of neutralizing antibodies was measured by the surrogate virus neutralization test (cPass) before first and second doses of vaccination and also between 2 and 3 mo after the second dose of vaccination. Results: Ninety-three LT recipients who received 2 doses of BNT162b2 were included in the analysis. The mean time from LT was 110 ± 154 mo. After 2-dose vaccination, 38.7% of LT recipients (36/93) were vaccine nonresponders on the cPass assay compared with 20.4% (19/93) on the Roche S assay. On multivariable analysis, increased age and increased tacrolimus trough were found to be associated with poor neutralizing antibody response (P = 0.038 and 0.022, respectively). The use of antimetabolite therapy in conjunction with tacrolimus approached statistical significance (odds ratio 0.21; 95% confidence interval, 0.180-3.72; P = 0.062). Breakthrough infection occurred in 18 of 88 LT recipients (20.4%). Female gender was independently associated with breakthrough infections (P < 0.001). Conclusions: Among LT recipients, older age and higher tacrolimus trough levels were associated with poorer immune response to 2-dose SARS-CoV-2 vaccination. Further studies are needed to assess variables associated with breakthrough infections and, hence, who should be prioritized for booster vaccination.

12.
Sci Rep ; 13(1): 19331, 2023 11 07.
Artículo en Inglés | MEDLINE | ID: mdl-37935965

RESUMEN

Identification of the risk factors and the high-risk groups which are most vulnerable is critical in COVID-19 disease management at a population level. Evaluating the efficacy of vaccination against infections is necessary to determine booster vaccination strategies for better protection in high-risk groups. In this study, we recruited 158 mRNA-vaccinated individuals during the Delta wave of SARS-CoV-2 infections in Singapore and examined the antibody profiles of infected individuals. We found that, despite high exposure due to communal living conditions in proximity, 4% of individuals (6/158) had PCR-confirmed infections and 96% (152/158) remained uninfected. Time-course analysis of the antibody profile at the start and the end of quarantine period showed Delta-specific boosting of anti-spike antibody response in 57% of the uninfected individuals (86/152). In the remaining 43% of the uninfected individuals (66/152) with no Delta-specific antibody boost, we found a higher Delta-specific antibody response at the start of quarantine period, which correlated with higher Delta pseudovirus neutralizing capacity. Our findings indicate that a higher basal variant-specific antibody response in the mRNA-vaccinated individuals contributes to better protection against infections by the new emerging SARS-CoV-2 variants.


Asunto(s)
Anticuerpos Neutralizantes , COVID-19 , Humanos , SARS-CoV-2 , COVID-19/prevención & control , ARN Mensajero/genética , Vacunación , Vacunas de ARNm , Anticuerpos Antivirales
13.
Front Immunol ; 14: 1206016, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37465685

RESUMEN

Vaccine immunogenicity in transplant recipients can be impacted by the immunosuppressive (IS) regimens they receive. While BNT162b2 vaccination has been shown to induce an immune response in liver transplant recipients (LTRs), it remains unclear how different IS regimens may affect vaccine immunogenicity after a third BNT162b2 dose in LTRs, which is especially important given the emergence of the Omicron sublineages of SARS-CoV-2. A total of 95 LTRs receiving single and multiple IS regimens were recruited and offered three doses of BNT162b2 during the study period. Blood samples were collected on days 0, 90, and 180 after the first BNT162b2 dose. At each time point, levels of anti-spike antibodies, their neutralizing activity, and specific memory B and T cell responses were assessed. LTRs receiving single IS regimens showed an absence of poor immunogenicity, while LTRs receiving multiple IS regimens showed lower levels of spike-specific antibodies and immunological memory compared to vaccinated healthy controls after two doses of BNT162b2. With a third dose of BNT162b2, spike-specific humoral, memory B, and T cell responses in LTR significantly improved against the ancestral strain of SARS-CoV-2 and were comparable to those seen in healthy controls who received only two doses of BNT162b2. However, LTRs receiving multiple IS regimens still showed poor antibody responses against Omicron sublineages BA.1 and XBB. A third dose of BNT162b2 may be beneficial in boosting antibody, memory B, and T cell responses in LTRs receiving multiple IS regimens, especially against the ancestral Wuhan strain of SARS-CoV-2. However, due to the continued vulnerability of LTRs to presently circulating Omicron variants, antiviral treatments such as medications need to be considered to prevent severe COVID-19 in these individuals.


Asunto(s)
COVID-19 , Trasplante de Hígado , Humanos , Vacuna BNT162 , SARS-CoV-2 , Memoria Inmunológica , Anticuerpos , Inmunosupresores/uso terapéutico
14.
PLoS Pathog ; 6(2): e1000765, 2010 Feb 12.
Artículo en Inglés | MEDLINE | ID: mdl-20169187

RESUMEN

The origin of Plasmodium falciparum, the etiological agent of the most dangerous forms of human malaria, remains controversial. Although investigations of homologous parasites in African Apes are crucial to resolve this issue, studies have been restricted to a chimpanzee parasite related to P. falciparum, P. reichenowi, for which a single isolate was available until very recently. Using PCR amplification, we detected Plasmodium parasites in blood samples from 18 of 91 individuals of the genus Pan, including six chimpanzees (three Pan troglodytes troglodytes, three Pan t. schweinfurthii) and twelve bonobos (Pan paniscus). We obtained sequences of the parasites' mitochondrial genomes and/or from two nuclear genes from 14 samples. In addition to P. reichenowi, three other hitherto unknown lineages were found in the chimpanzees. One is related to P. vivax and two to P. falciparum that are likely to belong to distinct species. In the bonobos we found P. falciparum parasites whose mitochondrial genomes indicated that they were distinct from those present in humans, and another parasite lineage related to P. malariae. Phylogenetic analyses based on this diverse set of Plasmodium parasites in African Apes shed new light on the evolutionary history of P. falciparum. The data suggested that P. falciparum did not originate from P. reichenowi of chimpanzees (Pan troglodytes), but rather evolved in bonobos (Pan paniscus), from which it subsequently colonized humans by a host-switch. Finally, our data and that of others indicated that chimpanzees and bonobos maintain malaria parasites, to which humans are susceptible, a factor of some relevance to the renewed efforts to eradicate malaria.


Asunto(s)
Malaria Falciparum/parasitología , Malaria Falciparum/veterinaria , Pan paniscus/parasitología , Pan troglodytes/parasitología , Plasmodium falciparum/genética , Animales , Genes Protozoarios , Humanos , Filogenia , Reacción en Cadena de la Polimerasa
15.
Clin Microbiol Infect ; 28(4): 612.e1-612.e7, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-34826623

RESUMEN

OBJECTIVES: Highly effective vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been developed but variants of concerns are worrisome, especially B.1.617.2 (Delta) which has rapidly spread across the world. We aim to study if vaccination alters virological and serological kinetics in breakthrough infections. METHODS: We conducted a multicentre retrospective cohort study of patients in Singapore who had received a licensed mRNA vaccine and been admitted to hospital with B.1.617.2 SARS-CoV-2 infection. We compared clinical features, virological and serological kinetics (anti-nucleocapsid, anti-spike and surrogate virus neutralization titres) between fully vaccinated and unvaccinated individuals. RESULTS: Out of 218 individuals with B.1.617.2 infection, 84 received an mRNA vaccine of which 71 were fully vaccinated, 130 were unvaccinated and four received a non-mRNA vaccine. Despite significantly older age in the vaccine breakthrough group, only 2.8% (2/71) developed severe COVID-19 requiring oxygen supplementation compared with 53.1% (69/130) in the unvaccinated group (p < 0.001). Odds of severe COVID-19 following vaccination were significantly lower (adjusted odds ratio 0.07 95% CI 0.015-0.335, p 0.001). PCR cycle threshold values were similar between vaccinated and unvaccinated groups at diagnosis, but viral loads decreased faster in vaccinated individuals. Early, robust boosting of anti-spike protein antibodies was observed in vaccinated patients; however, these titres were significantly lower against B.1.617.2 than the wildtype vaccine strain. DISCUSSION: The mRNA vaccines are highly effective at preventing symptomatic and severe COVID-19 associated with B.1.617.2 infection. Vaccination is associated with faster decline in viral RNA load and a robust serological response. Vaccination remains a key strategy for control of the COVID-19 pandemic.


Asunto(s)
COVID-19 , SARS-CoV-2 , COVID-19/prevención & control , Vacunas contra la COVID-19 , Estudios de Cohortes , Humanos , Cinética , Pandemias , Estudios Retrospectivos , SARS-CoV-2/genética , Vacunación , Vacunas Sintéticas , Vacunas de ARNm
16.
EMBO Mol Med ; 14(3): e15227, 2022 03 07.
Artículo en Inglés | MEDLINE | ID: mdl-34994081

RESUMEN

The SARS-CoV-2 Delta (B.1.617.2) variant is capable of infecting vaccinated persons. An open question remains as to whether deficiencies in specific vaccine-elicited immune responses result in susceptibility to vaccine breakthrough infection. We investigated 55 vaccine breakthrough infection cases (mostly Delta) in Singapore, comparing them against 86 vaccinated close contacts who did not contract infection. Vaccine breakthrough cases showed lower memory B cell frequencies against SARS-CoV-2 receptor-binding domain (RBD). Compared to plasma antibodies, antibodies secreted by memory B cells retained a higher fraction of neutralizing properties against the Delta variant. Inflammatory cytokines including IL-1ß and TNF were lower in vaccine breakthrough infections than primary infection of similar disease severity, underscoring the usefulness of vaccination in preventing inflammation. This report highlights the importance of memory B cells against vaccine breakthrough and suggests that lower memory B cell levels may be a correlate of risk for Delta vaccine breakthrough infection.


Asunto(s)
COVID-19 , COVID-19/prevención & control , Vacunas contra la COVID-19 , Humanos , Células B de Memoria , SARS-CoV-2
17.
Nat Commun ; 13(1): 4615, 2022 08 08.
Artículo en Inglés | MEDLINE | ID: mdl-35941158

RESUMEN

Understanding the impact of age on vaccinations is essential for the design and delivery of vaccines against SARS-CoV-2. Here, we present findings from a comprehensive analysis of multiple compartments of the memory immune response in 312 individuals vaccinated with the BNT162b2 SARS-CoV-2 mRNA vaccine. Two vaccine doses induce high antibody and T cell responses in most individuals. However, antibody recognition of the Spike protein of the Delta and Omicron variants is less efficient than that of the ancestral Wuhan strain. Age-stratified analyses identify a group of low antibody responders where individuals ≥60 years are overrepresented. Waning of the antibody and cellular responses is observed in 30% of the vaccinees after 6 months. However, age does not influence the waning of these responses. Taken together, while individuals ≥60 years old take longer to acquire vaccine-induced immunity, they develop more sustained acquired immunity at 6 months post-vaccination. A third dose strongly boosts the low antibody responses in the older individuals against the ancestral Wuhan strain, Delta and Omicron variants.


Asunto(s)
COVID-19 , Vacunas Virales , Anciano , Anticuerpos Antivirales , Formación de Anticuerpos , Vacuna BNT162 , COVID-19/prevención & control , Vacunas contra la COVID-19 , Humanos , Persona de Mediana Edad , SARS-CoV-2 , Vacunación , Vacunas Sintéticas , Vacunas de ARNm
18.
Clin Transl Immunology ; 11(8): e1403, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36016852

RESUMEN

Objective: Despite the high vaccine efficacy of mRNA COVID-19 vaccines, there are individuals who developed excessive reactogenic and/or allergic responses after the first mRNA dose and were considered ineligible for further mRNA doses. CoronaVac, an inactivated SARS-CoV-2 vaccine, is recommended in Singapore as an alternative. Methods: Individuals, ineligible for further mRNA vaccines (BNT162b2 or mRNA-1273) because of excessive reactive responses to prime mRNA vaccination, were recruited and offered two doses of CoronaVac as booster vaccination 38-224 days post their mRNA vaccine dose. Individuals who did not develop any excessive reactive responses after the prime mRNA vaccination were also recruited and given another mRNA vaccine as booster vaccination. Blood samples were collected at days 0, 21 and 90 post first CoronaVac dose and mRNA dose, respectively, for analysis. Results: We showed that two CoronaVac booster doses induced specific immunity in these mRNA vaccine-primed individuals. Although the spike-specific antibody response was lower, their memory B cell response against the receptor-binding domain (RBD) of the spike protein was similar, compared with individuals who received two BNT162b2 injections. The spike-specific memory T cell response also increased following CoronaVac booster doses. However, specific immunity against the Omicron variant was low, similar to individuals with two BNT162b2 doses. Conclusion: Our findings showed that while mRNA vaccine-primed individuals can opt for two subsequent doses of CoronaVac, an additional dose may be necessary to achieve protection, especially against newly emerging immune escape variants such as Omicron.

19.
Sante ; 21(3): 133-42, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-22294247

RESUMEN

Chemistry still has a role in the management of malaria, alongside the mosquito netting soaked in insecticide that is used increasingly, as we continue to await the long anticipated vaccine. During its cycle, the hematozoon parasite develops through three major periods. The first, malarial infection, corresponds to the intrahepatic development of infective forms from the mosquito vector; this period is not sensitive to treatment and is often asymptomatic. The period of erythrocytic schizogony is the most urgent, and treatment activity is primordial. Finally, the phase of sexual reproduction, when gametocytes develop within the erythrocytes ensures the perpetuation of the species when these reach the blood-feeding female anopheles mosquitoes. The aim of our work was to study the effect on gametocytes of drugs known to be effective on the asexual blood forms of the protozoan and thus the potential repercussions on malaria transmission. This experimental study was conducted with an animal model whose parasite cycle and modes of transmission are close to those of human malaria: Plasmodium yoelii, maintained on Swiss mice, with the Anopheles stephensi vector (maintained in an animal facility at the National Museum of Natural History in Paris). Two drugs were tested: ferroquine (a chloroquine derivative with a ferrocene molecule at the lateral carbon chain that restores its efficacy against chloroquine-resistant strains) and artesunate (a derivative of artemisinin, from ginghao, a Chinese plant also known as artemisia annua, or sweet wormwood), a treatment of choice in the combined therapies recommended by WHO. The efficacy of these drugs, prescribed at doses subcurative for the asexual forms, were tested against gametocyte production, quantitatively by counting them in the blood and qualitatively by counting the quantity of oocysts developed on the mosquito's midgut, which are indicators of gametocyte activity. The mice that were parasite-infected and then treated served as their own controls: lots of 30 mosquitoes fed on each mouse before treatment and then 90  minutes and 5  hours after treatment. Quantitatively, the comparison of the blood parasite level and the gametocyte index shows that treated mice had a higher level of circulating gametocytes than untreated parasite infested mice, regardless of drug or dose (5 or 10  mg/kg). For artesunate at 5  mg/kg, we noted that the blood gametocyte level was almost double that of the controls. On the other hand, qualitatively, the first results obtained with optical and electronic microscopy showed morphologic alterations of the circulating gametocytes (pigment clumping and lateralisation within red blood cells) and reduced infectivity of the gametocytes for the mosquitoes that fed at 1 and 5  hours after treatment. We were able to demonstrate statistically that the infectivity of gametocytes, measured by the quantity of oocysts counted in the mosquito midgut, was reduced by 70% for those treated with ferroquine and by 85% for those from mice treated by artesunate. Complementary studies will seek to specify the populations (age) of gametocytes damaged by treatment and the importance and nature of their morphologic alterations.


Asunto(s)
Aminoquinolinas/farmacología , Antimaláricos/farmacología , Artemisininas/farmacología , Compuestos Ferrosos/farmacología , Malaria/transmisión , Plasmodium yoelii/efectos de los fármacos , Animales , Anopheles/parasitología , Artesunato , Modelos Animales de Enfermedad , Femenino , Insectos Vectores/parasitología , Malaria/parasitología , Metalocenos , Ratones , Pruebas de Sensibilidad Parasitaria , Plasmodium yoelii/crecimiento & desarrollo
20.
Parasite ; 28: 6, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33464203

RESUMEN

Dermacentor (Indocentor) auratus Supino, 1897 is a prominent ixodid vector of numerous pathogens of public health and veterinary importance. Using long-range PCR of two overlapping regions sequenced on an Illumina MiSeq machine, the complete mitochondrial genome of D. auratus is reported here. The resulting contigs were able to be assembled into a complete and circularised genome which had the general organisation of the mitochondrial genomes of the Metastriates. It had a total length of 14,766 bp and contained 37 genes, including 13 protein-coding genes, 22 transfer RNA genes, and 2 ribosomal RNA genes, as well as 2 non-coding control regions and 3 tick-boxes. The phylogenetic analysis on the whole mitogenome confirmed the position of D. auratus within the Dermacentor clade.


TITLE: Le génome mitochondrial complet de Dermacentor (Indocentor) auratus (Acari, Ixodidae). ABSTRACT: Dermacentor (Indocentor) auratus Supino, 1897 est un ixode, vecteur notable de nombreux pathogènes importants en santé publique et en médecine vétérinaire. Utilisant la PCR en fragment long sur deux régions chevauchantes combinée au séquençage sur une plate-forme Illumina MiSeq, le génome mitochondrial complet de D. auratus est présenté ici. Les contigs obtenus ont été assemblés en un génome circulaire complet conforme à l'organisation générale des génomes mitochondriaux des Métastriates. D'une longueur totale de 14766 pb, il contient 37 gènes, incluant 13 gènes codants des protéines, 22 gènes d'ARN de transfert et 2 gènes d'ARN ribosomaux, ainsi que 2 régions contrôles non-codantes et 3 motifs « tick-box ¼. L'analyse phylogénétique sur le mitogénome complet confirme la position de D. auratus au sein du clade Dermacentor.


Asunto(s)
Dermacentor , Genoma Mitocondrial , Animales , Dermacentor/genética , Genoma Mitocondrial/genética , Filogenia
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