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1.
PLoS Pathog ; 16(12): e1009068, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-33382858

RESUMEN

Originating from African forests, Zika virus (ZIKV) has now emerged worldwide in urbanized areas, mainly transmitted by Aedes aegypti mosquitoes. Although Aedes albopictus can transmit ZIKV experimentally and was suspected to be a ZIKV vector in Central Africa, the potential of this species to sustain virus transmission was yet to be uncovered until the end of 2019, when several autochthonous transmissions of the virus vectored by Ae. albopictus occurred in France. Aside from these few locally acquired ZIKV infections, most territories colonized by Ae. albopictus have been spared so far. The risk level of ZIKV emergence in these areas remains however an open question. To assess Ae. albopictus' vector potential for ZIKV and identify key virus outbreak predictors, we built a complete framework using the complementary combination of (i) dose-dependent experimental Ae. albopictus exposure to ZIKV followed by time-dependent assessment of infection and systemic infection rates, (ii) modeling of intra-human ZIKV viremia dynamics, and (iii) in silico epidemiological simulations using an Agent-Based Model. The highest risk of transmission occurred during the pre-symptomatic stage of the disease, at the peak of viremia. At this dose, mosquito infection probability was estimated to be 20%, and 21 days were required to reach the median systemic infection rates. Mosquito population origin, either temperate or tropical, had no impact on infection rates or intra-host virus dynamic. Despite these unfavorable characteristics for transmission, Ae. albopictus was still able to trigger and yield large outbreaks in a simulated environment in the presence of sufficiently high mosquito biting rates. Our results reveal a low but existing epidemic potential of Ae. albopictus for ZIKV, that might explain the absence of large scale ZIKV epidemics so far in territories occupied only by Ae. albopictus. They nevertheless support active surveillance and eradication programs in these territories to maintain the risk of emergence to a low level.


Asunto(s)
Mosquitos Vectores/metabolismo , Mosquitos Vectores/virología , Infección por el Virus Zika/transmisión , Aedes/metabolismo , Aedes/virología , Animales , Brotes de Enfermedades , Vectores de Enfermedades , Epidemias , Humanos , Modelos Teóricos , Saliva/virología , Carga Viral , Viremia/transmisión , Virus Zika/patogenicidad , Infección por el Virus Zika/epidemiología , Infección por el Virus Zika/virología
2.
PLoS One ; 15(8): e0234098, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32817616

RESUMEN

In French Guiana, the malaria, a parasitic infection transmitted by Anopheline mosquitoes, remains a disease of public health importance. To prevent malaria transmission, the main effective way remains Anopheles control. For an effective control, accurate Anopheles species identification is indispensable to distinguish malaria vectors from non-vectors. Although, morphological and molecular methods are largely used, an innovative tool, based on protein pattern comparisons, the Matrix Assisted Laser Desorption / Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF MS) profiling, emerged this last decade for arthropod identification. However, the limited mosquito fauna diversity of reference MS spectra remains one of the main drawback for its large usage. The aim of the present study was then to create and to share reference MS spectra for the identification of French Guiana Anopheline species. A total of eight distinct Anopheles species, among which four are malaria vectors, were collected in 6 areas. To improve Anopheles identification, two body parts, legs and thoraxes, were independently submitted to MS for the creation of respective reference MS spectra database (DB). This study underlined that double checking by MS enhanced the Anopheles identification confidence and rate of reliable classification. The sharing of this reference MS spectra DB should make easier Anopheles species monitoring in endemic malaria area to help malaria vector control or elimination programs.


Asunto(s)
Anopheles/clasificación , Mosquitos Vectores/clasificación , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción/métodos , Animales , Anopheles/química , Guyana Francesa , Malaria/clasificación , Malaria/transmisión , Especificidad de la Especie , Tórax
3.
J Antimicrob Chemother ; 75(8): 2141-2148, 2020 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-32407538

RESUMEN

BACKGROUND: Plasmodium falciparum resistance to most antimalarial compounds has emerged in Southeast Asia and spread to Africa. In this context, the development of new antimalarial drugs is urgent. OBJECTIVES: To determine the baseline in vitro activity of methylene blue (Proveblue®) on African isolates and to determine whether parasites have different phenotypes of susceptibility to methylene blue. METHODS: Ex vivo susceptibility to methylene blue was measured for 609 P. falciparum isolates of patients hospitalized in France for malaria imported from Africa. A Bayesian statistical analysis was designed to describe the distribution of median effective concentration (EC50) estimates. RESULTS: The EC50 ranged from 0.16 to 87.2 nM with a geometric mean of 7.17 nM (95% CI = 6.21-8.13). The 609 EC50 values were categorized into four components: A (mean = 2.5 nM; 95% CI = 2.28-2.72), B (mean = 7.44 nM; 95% CI = 7.07-7.81), C (mean = 16.29 nM; 95% CI = 15.40-17.18) and D (mean = 38.49 nM; 95% CI = 34.14-42.84). The threshold value for in vitro reduced susceptibility to methylene blue was estimated at 35 nM using the geometric mean of EC50 plus 2 SDs of the 609 isolates. This cut-off also corresponds to the lower limit of the 95% CI of the methylene blue EC50 of component D. Thirty-five isolates (5.7%) displayed EC50 values above this threshold. CONCLUSIONS: Methylene blue exerts a promising efficacy against P. falciparum and is a potential partner for triple combinations.

4.
PLoS Negl Trop Dis ; 13(9): e0007747, 2019 09.
Artículo en Inglés | MEDLINE | ID: mdl-31539394

RESUMEN

BACKGROUND: Zika virus (ZIKV) and Dengue virus (DENV) are often co-endemic. The high protein-sequence homology of flaviviruses renders IgG induced by and directed against them highly cross-reactive against their antigen(s), as observed on a large set of sera, leading to poorly reliable sero-diagnosis. METHODS: We selected Domain III of the ZIKV Envelope (ZEDIII) sequence, which is virus specific. This recombinant domain was expressed and purified for the specific detection of ZEDIII-induced IgG by ELISA from ZIKV-RT-PCR-positive, ZIKV-IgM-positive, flavivirus-positive but ZIKV-negative, or flavivirus-negative sera. We also assessed the reactivity of ZEDIII-specific human antibodies against EDIII of DENV serotype 4 (D4EDIII) as a specific control. Sera from ZEDIII-immunized mice were also tested. RESULTS: Cross-reactivity of IgG from 5,600 sera against total inactivated DENV or ZIKV was high (71.0% [69.1; 72.2]), whereas the specificity and sensitivity calculated using a representative cohort (242 sera) reached 90% [84.0; 95.8] and 92% [84.5; 99.5], respectively, using a ZEDIII-based ELISA. Moreover, purified human IgG against D2EDIII or D4EDIII did not bind to ZEDIII and we observed no D4EDIII reactivity with ZIKV-induced mouse polyclonal IgGs. CONCLUSIONS: We developed a ZEDIII-based ELISA that can discriminate between past or current DENV and ZIKV infections, allowing the detection of a serological scar from other flaviviruses. This could be used to confirm exposure of pregnant women or to follow the spread of an endemic disease.


Asunto(s)
Ensayo de Inmunoadsorción Enzimática/métodos , Infección por el Virus Zika/diagnóstico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Animales , Anticuerpos Antivirales/sangre , Niño , Preescolar , Dengue/diagnóstico , Dengue/inmunología , Virus del Dengue/inmunología , Femenino , Humanos , Inmunoglobulina G , Lactante , Masculino , Ratones , Persona de Mediana Edad , Sensibilidad y Especificidad , Virus Zika/inmunología , Infección por el Virus Zika/inmunología , Infección por el Virus Zika/virología
5.
Acta Trop ; 196: 126-134, 2019 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-31108084

RESUMEN

The emergence of resistance to artemisinin-based combination therapies (ACT) was described in Southeast Asia. In this context, the identification of molecular markers of ACT resistance partner drugs is urgently needed for monitoring the emergence and spread of resistance. Polymorphisms in transporter genes, especially of the ATP-binding cassette (ABC) superfamily, have been involved in anti-malarial drug resistance. In this study, the association between the mutations in the P. falciparum multidrug resistance 1 gene (pfmdr1, N86Y, Y184 F, S1034C, N1042D and D1246Y) or repetitive amino acid motifs in pfmdr5 and the ex vivo susceptibility to anti-malarial drugs was evaluated. Susceptibility to chloroquine, quinine, monodesethylamodiaquine, lumefantrine, piperaquine, pyronaridine, mefloquine and dihydroartemisinin was assessed in 67 Senegalese isolates. The shorter DNNN motif ranged from to 2 to 11 copy repeats, and the longer DHHNDHNNDNNN motif ranged from 0 to 2 in pfmdr5. The present study showed the association between repetitive amino acid motifs (DNNN-DHHNDDHNNDNNN) in pfmdr5 and in vitro susceptibility to 4-aminoquinoline-based antimalarial drugs. The parasites with 8 and more copy repeats of DNNN in pfmdr5 were significantly more susceptible to piperaquine. There was a significant association between parasites whose DHHNDHNNDNNN motif was absent and replaced by DHHNDNNN, DHHNDHNNDHNNDNNN or DHHNDHNNDHNNDHNNDNNN and increased susceptibility to chloroquine, monodesethylamodiaquine and pyronaridine. A significant association between both the wild-type allele N86 in pfmdr1 and the N86-184 F haplotype and reduced susceptibility to lumefantrine was confirmed. Further studies with a large number of samples are required to validate the association between these pfmdr5 alleles and the modulation of 4-aminoquinoline-based antimalarial drug susceptibility.


Asunto(s)
Antimaláricos/farmacología , Resistencia a Medicamentos/genética , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/genética , Plasmodium falciparum/efectos de los fármacos , Polimorfismo Genético , Proteínas Protozoarias/metabolismo , Transportadoras de Casetes de Unión a ATP/metabolismo , Haplotipos , Humanos , Malaria Falciparum/parasitología , Proteínas de Transporte de Membrana/genética , Plasmodium falciparum/genética , Proteínas Protozoarias/genética
6.
Emerg Infect Dis ; 25(6): 1153-1160, 2019 06.
Artículo en Inglés | MEDLINE | ID: mdl-31107211

RESUMEN

Reliable serologic tests are needed for diagnosis and surveillance of Zika virus infection. We evaluated the Euroimmun and Dia.Pro serologic tests for detection of Zika virus IgM and IgG by using a panel of 199 samples from a region endemic for flaviviruses. Kinetics of Zika virus antibodies were monitored from 300 sequential specimens sampled over a period of 10 months after infection. We observed suboptimal performance; sensitivity for Zika virus IgM was low, especially in the Euroimmun assay (49%), whereas IgM could be detected for months with the Dia.pro assay. The specificity of the Zika virus IgG assays was also low, especially that of Dia.Pro (62%); findings were strongly influenced by the epidemiologic context. These results highlight the complexity of serologic diagnosis of Zika virus infection in regions endemic for flaviviruses. Accurate analysis of the performance of assays is required to adapt and interpret algorithms.


Asunto(s)
Juego de Reactivos para Diagnóstico , Pruebas Serológicas , Infección por el Virus Zika/diagnóstico , Infección por el Virus Zika/virología , Virus Zika/clasificación , Adolescente , Adulto , Anciano , Anticuerpos Antivirales/inmunología , Niño , Preescolar , Reacciones Cruzadas , Femenino , Humanos , Inmunoglobulina G/inmunología , Inmunoglobulina M/inmunología , Lactante , Masculino , Persona de Mediana Edad , Juego de Reactivos para Diagnóstico/normas , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Pruebas Serológicas/métodos , Pruebas Serológicas/normas , Factores de Tiempo , Adulto Joven , Virus Zika/inmunología , Infección por el Virus Zika/inmunología
7.
Malar J ; 18(1): 91, 2019 Mar 22.
Artículo en Inglés | MEDLINE | ID: mdl-30902054

RESUMEN

BACKGROUND: In April 2017, Suriname's Ministry of Health alerted French Guiana's Regional Health Agency (RHA) about an increase of imported malaria cases among people coming from an illegal gold mining site called Sophie, in French Guiana, a French overseas territory located in the Amazonian forest. METHODS: Due to safety issues and the remoteness of Sophie, the RHA requested the collaboration of the French Armed Forces for the epidemiological investigation. A medical unit, and six soldiers to ensure the security of the mission, were transported by helicopter. RESULTS: During the investigation, two malaria episodes were diagnosed among 46 persons. Twenty-six of them were from Sophie, where PCR-Plasmodium prevalence was estimated at 60% (15/26). This result was concordant with previous studies revealing high malaria endemicity in the gold miner population. The increase of imported cases in Suriname may have resulted from decreased access to under-the-counter anti-malarials and increased migration of gold miners to Suriname following a decline of the profitability of gold mining in a context of increased repression against illegal mining by the French army. CONCLUSION: This investigation of a suspicious malaria epidemic confirms the importance of malaria among illegal gold miners. Their mobility along the Guiana Shield and their health-seeking behaviour are likely to spread malaria in populations for which significant efforts are undertaken to fight against this disease. Fighting malaria in this population remains more relevant than ever. A pilot study (Malakit project) is currently in progress to evaluate the efficacy of kits for self-diagnosis and self-treatment.


Asunto(s)
Enfermedades Transmisibles Importadas/epidemiología , Epidemias , Malaria/epidemiología , Mineros/estadística & datos numéricos , Vigilancia de la Población/métodos , Adulto , Enfermedades Transmisibles Importadas/parasitología , Femenino , Guyana Francesa/epidemiología , Oro , Humanos , Malaria/parasitología , Masculino , Persona de Mediana Edad , Proyectos Piloto
8.
Euro Surveill ; 24(8)2019 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-30808441

RESUMEN

On 16 September 2016, the World Health Organization confirmed a Rift Valley fever (RVF) outbreak in Niger. Epidemiological surveillance was reinforced among the French Armed Forces deployed in Niger and bordering countries: Chad, Mali and Burkina Faso. On 26 October, a probable case of RVF was reported in a service member sampled in Mali 3 weeks earlier. At the time the result was reported, the patient was on vacation on Martinique. An epidemiological investigation was conducted to confirm this case and identify other cases. Finally, the case was not confirmed, but three suspected cases of RVF were confirmed using serological and molecular testing. RVF viral RNA was detectable in whole blood for 57 and 67 days after onset of symptoms for two cases, although it was absent from plasma and serum. At the time of diagnosis, these cases had already returned from Mali to Europe. The infectivity of other arboviruses in whole blood has already been highlighted. That RVF virus has been detected in whole blood that long after the onset of symptoms (67 days) raises the question of its potential prolonged infectivity. Because of exposure to tropical infectious diseases during deployment, military populations could import emerging pathogens to Europe.


Asunto(s)
Fiebre/etiología , Fiebre del Valle del Rift/diagnóstico , Virus de la Fiebre del Valle del Rift/aislamiento & purificación , Adulto , Animales , Anticuerpos Antivirales/sangre , Estudios Transversales , Culex/virología , Brotes de Enfermedades , Europa (Continente)/epidemiología , Humanos , Inmunoglobulina G/sangre , Inmunoglobulina M/sangre , Masculino , Malí/epidemiología , Personal Militar , ARN Viral/sangre , ARN Viral/genética , ARN Viral/aislamiento & purificación , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Fiebre del Valle del Rift/sangre , Fiebre del Valle del Rift/epidemiología , Fiebre del Valle del Rift/transmisión , Virus de la Fiebre del Valle del Rift/genética , Vigilancia de Guardia , Estudios Seroepidemiológicos , Zoonosis
9.
Pest Manag Sci ; 75(4): 923-934, 2019 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-30178568

RESUMEN

BACKGROUND: To prevent the risk of mosquito-borne disease outbreaks, larval source management remains the most sustainable and effective mosquito control strategy. The present study aimed to determine the influence of environmental characteristics of mosquito larval habitats in an urban area of Marseille, France. Fourteen sites containing water were monitored every 2 weeks from May to October 2015 for mosquito species occurrence and larval density, and environmental parameters were measured at each visit. Rapid and accurate species identification of mosquito larvae was performed using an innovative MALDI-TOF MS method. RESULTS: A total of 6753 larvae (L1-L4) and pupae were collected, of which 35.8% (n = 2418) were speciated using MALDI-TOF MS. Correct identifications were obtained for 2259 specimens (93.4%). A total of five mosquito species were found, including Aedes (Ae.) albopictus, Culex (Cx.) p. pipiens, Cx. hortensis, Cx. impudicus, and Culiseta (Cs.) longiareolata. Larvae of the Culex genus were predominant in both density and distribution. Small, shaded pools of shallow water favored Ae. albopictus colonization, whereas the wide distribution of Cx. p. pipiens demonstrated that this species was weakly influenced by environmental changes. CONCLUSIONS: The present work confirms that MALDI-TOF MS is a useful tool for mosquito speciation and suggests that understanding the environmental factors associated with the occurrence and density of mosquito species at the larval stage in Marseille may aid in the future implementation of mosquito control programs. © 2018 Society of Chemical Industry.


Asunto(s)
Distribución Animal , Culicidae/fisiología , Ecosistema , Control de Mosquitos/métodos , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción/métodos , Animales , Ciudades , Culicidae/crecimiento & desarrollo , Francia , Larva/crecimiento & desarrollo , Larva/fisiología , Densidad de Población , Pupa/crecimiento & desarrollo , Pupa/fisiología , Especificidad de la Especie
10.
J Clin Virol ; 109: 57-62, 2018 12.
Artículo en Inglés | MEDLINE | ID: mdl-30523784

RESUMEN

BACKGROUND: Although the complications of Zika virus infection have been well described, the clinical pattern has not been reported in enough detail to differentiate this infection from those with other arboviroses, and no longitudinal study has yet been published on the persistence of symptoms and quality of life. OBJECTIVES: were to describe bio-clinical pattern and quality of life during ZIKV infection, and their evolution. STUDY DESIGN: We present a 1-year clinical follow-up of 49 people infected with Zika virus in French Guiana, for whom the diagnosis was confirmed by RT-PCR in serum or urine. RESULTS: Fever was inconsistent (95% confidence interval (CI), 39-67). Exanthema (CI, 84-100) was maculopapular, with pruritus and conjunctivitis, variable over time and disappeared 12 days after the onset of symptoms (CI, 10-14). Joint pain (CI, 39-67) occurred mainly in the hands, wrists, knees and ankles and lasted for 10 days (CI, 7-13). Asthenia (CI, 61-85) scored low (3/10) but lasted for 19 days (CI, 16-22). The last two symptoms strongly limited patients' activities in the acute stage of the disease (RAPID-3 score, CI, 5-8). None of the patients had neurological complications, but 41% (CI, 27-55) had areflexia during the first month. CONCLUSIONS: We found no real chronic evolution or decreased quality of life, function or ability to work from the first month after symptom onset.


Asunto(s)
Calidad de Vida , Infección por el Virus Zika/patología , Estudios de Seguimiento , Guyana Francesa , Humanos , Estudios Prospectivos , ARN Viral/sangre , ARN Viral/orina , Virus Zika , Infección por el Virus Zika/diagnóstico , Infección por el Virus Zika/fisiopatología
11.
Open Forum Infect Dis ; 5(11): ofy261, 2018 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-30397624

RESUMEN

Zika virus (ZIKV) has recently emerged in numerous tropical countries worldwide. In this study, we estimated ZIKV incubation period distribution using time-to-event models adapted to interval-censored data based on declared date of travels from 123 symptomatic travelers returning from areas with active ZIKV transmission. The median time and 95th percentile of ZIKV incubation period was estimated to 6.8 days (95% confidence interval [CI], 5.8-7.7 days) and 15.4 days (95% CI, 12.7-19.7 days), respectively. Determining the incubation period for ZIKV is beneficial to improve protection guidelines.

13.
Travel Med Infect Dis ; 24: 31-36, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29482012

RESUMEN

BACKGROUND: New world cutaneous leishmaniasis (NWCL) can be found in French Guiana as well as in several other parts of Central and South America. Leishmania guyanensis accounts for nearly 90% of cases in French Guiana and is treated with pentamidine isethionate, given by either intramuscular or intravenous injection. The military population is particularly exposed due to repeated missions in the rainforest. The purpose of the present study was to identify the factors associated with pentamidine isethionate treatment failure in a series of service members with L. guyanensis NWCL acquired in French Guiana. METHOD: All the French service members reported as having acquired leishmaniasis in French Guiana from December 2013 to June 2016 were included. RESULTS: Seventy-three patients infected with L. guyanensis were included in the final analysis. Patients treated with IV pentamidine isethionate had better response rates than those treated with IM pentamidine isethionate (p = 0.002, adjusted odds ratio (AOR) = 0.15, 95% CI [0.04-0.50]). The rate of treatment success was 85.3% (95% CI [68.9-95.0]) for IV pentamidine isethionate and 51.3% (95% CI [34.8-67.6]) for IM pentamidine isethionate. CONCLUSIONS: The use of intramuscular pentamidine isethionate in the treatment of Leishmania guyanensis cutaneous leishmaniasis is associated with more treatment failures than intravenous pentamidine isethionate.


Asunto(s)
Antiprotozoarios/administración & dosificación , Antiprotozoarios/efectos adversos , Inyecciones Intramusculares/efectos adversos , Leishmaniasis Cutánea/tratamiento farmacológico , Pentamidina/administración & dosificación , Pentamidina/efectos adversos , Insuficiencia del Tratamiento , Administración Intravenosa/efectos adversos , Adulto , Femenino , Guyana Francesa/epidemiología , Humanos , Leishmania guyanensis/efectos de los fármacos , Leishmaniasis Cutánea/epidemiología , Masculino , Personal Militar , Oportunidad Relativa , Pentamidina/uso terapéutico , Factores de Riesgo , América del Sur/epidemiología , Resultado del Tratamiento , Adulto Joven
14.
Artículo en Inglés | MEDLINE | ID: mdl-29406281

RESUMEN

A Q fever epidemic occurred in 2013 in a small military residential area in Cayenne, French Guiana. A retrospective cohort study was conducted to identify Q fever risk factors. Confirmed acute Q fever case was defined as positive serology (IgM ≥ 50 and phase II IgG ≥ 200) and/or positive qPCR on serum or blood. In addition, wild mammals were captured at the study site and tested by serology and real-time PCR performed on blood, vaginal swabs and ticks. The attack rate was 20 percent (11/54). All the cases were symptomatic with fever >38.5 °C and community-acquired pneumonia for four cases. Log binomial multivariate models identified two independent risk factors associated with Q fever: to clean the house (RRa = 7.5 CI95% [1.03-55.3]) and to carry a three-toed sloth in arms (RRa = 2.6 CI95% [1.1-5.8]). Eighteen marsupial individuals were captured, all PCRs were negative but 17% (3/18) had a positive serology. Another study conducted after the epidemic found only one (1/4) three-tooth sloth (Bradypus tridactylus) with feces highly infectious for C. burnetii MST17. The same strain C. burnetii genotype 17 has been laboratory- confirmed in this mammal and in human cases. These results support the implication of three-toed-sloth in this epidemic. Human contamination mainly occurs through inhalation of infectious aerosols as suggested by high relative risk associated with house cleaning activities and pulmonary forms of the disease, and through direct contact with three- toed-sloth. Positive serological results among marsupials confirm wildlife exposure and suggest a more complex sylvatic transmission cycle among wild mammals.


Asunto(s)
Coxiella burnetii , Fiebre Q/epidemiología , Perezosos/microbiología , Adolescente , Adulto , Animales , Animales Salvajes/microbiología , Niño , Preescolar , Coxiella burnetii/genética , Reservorios de Enfermedades/microbiología , Epidemias , Femenino , Guyana Francesa/epidemiología , Humanos , Lactante , Masculino , Persona de Mediana Edad , Fiebre Q/etiología , Fiebre Q/transmisión , Reacción en Cadena en Tiempo Real de la Polimerasa , Estudios Retrospectivos , Factores de Riesgo , Adulto Joven , Zoonosis/epidemiología , Zoonosis/microbiología
15.
Emerg Infect Dis ; 23(11)2017 11.
Artículo en Inglés | MEDLINE | ID: mdl-28930015

RESUMEN

We collected venous and capillary serum samples from 21 Zika virus‒infected patients on multiple days after symptom onset and found RNA load was higher and median duration of virus detection significantly longer in capillary than in venous blood. These findings raise questions about the role of the capillary compartment in virus transmission dynamics.


Asunto(s)
Capilares/virología , Venas/virología , Carga Viral , Infección por el Virus Zika/virología , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , ARN Viral/sangre , Virus Zika , Infección por el Virus Zika/sangre
17.
Int J Antimicrob Agents ; 50(2): 155-158, 2017 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-28689867

RESUMEN

Resistance to most antimalarial drugs has spread from Southeast Asia to Africa. Accordingly, new therapies to use with artemisinin-based combination therapy (triple ACT) are urgently needed. Proveblue, a methylene blue preparation, was found to exhibit antimalarial activity against Plasmodium falciparum strains in vitro. Proveblue has synergistic effects when used in combination with dihydroartemisinin, and has been shown to significantly reduce or prevent cerebral malaria in mice. The objectives of the current study were to evaluate the in vitro baseline susceptibility of clinical field isolates to Proveblue, compare its activity with that of other standard antimalarial drugs and define the patterns of cross-susceptibility between Proveblue and conventional antimalarial drugs. The Proveblue IC50 of 76 P. falciparum isolates ranged from 0.5 nM to 135.1 nM, with a mean of 8.1 nM [95% confidence interval, 6.4-10.3]. Proveblue was found to be more active against P. falciparum parasites than chloroquine, quinine, monodesethylamodiaquine, mefloquine, piperaquine, doxycycline (P <0.001) and lumefantrine (P = 0.014). Proveblue was as active as pyronaridine (P = 0.927), but was less active than dihydroartemisinin and artesunate (P <0.001). The only significant cross-susceptibilities found were between Proveblue and dihydroartemisinin (r2 = 0.195, P = 0.0001), artesunate (r2 = 0.187, P = 0.0002) and piperaquine (r2 = 0.063, P = 0.029). The present study clearly demonstrates the potential of Proveblue as an effective therapeutic agent against P. falciparum. In this context, the use of Proveblue as part of the triple ACT treatment for multidrug-resistant malaria warrants further investigation.


Asunto(s)
Antimaláricos/farmacología , Inhibidores Enzimáticos/farmacología , Azul de Metileno/farmacología , Plasmodium falciparum/efectos de los fármacos , Humanos , Concentración 50 Inhibidora , Malaria Falciparum/parasitología , Pruebas de Sensibilidad Parasitaria , Plasmodium falciparum/aislamiento & purificación , Senegal
18.
Malar J ; 16(1): 148, 2017 04 13.
Artículo en Inglés | MEDLINE | ID: mdl-28407772

RESUMEN

Anti-malarial drug resistance to chloroquine and sulfadoxine-pyrimethamine has spread from Southeast Asia to Africa. Furthermore, the recent emergence of resistance to artemisinin-based combination therapy (ACT) in Southeast Asia highlights the need to identify new anti-malarial drugs. Doxycycline is recommended for malaria chemoprophylaxis for travel in endemic areas, or in combination with the use of quinine for malaria treatment when ACT is unavailable or when the treatment of severe malaria with artesunate fails. However, doxycycline is not used in young children under 8 years of age due to its contraindication due to the risk of yellow tooth discolouration and dental enamel hypoplasia. Doxycycline was developed after tetracycline and was labelled with the same side-effects as the earlier tetracyclines. However, recent studies report little or no effects of doxycycline on tooth staining or dental enamel hypoplasia in children under 8 years of age. In the United States, the Centers for Disease Control and Prevention have recommended the use of doxycycline for the treatment of acute and chronic Q fever and tick-borne rickettsial diseases in young children. It is time to rehabilitate doxycycline and to recommend it for malaria treatment in children under 8 years of age.


Asunto(s)
Antimaláricos/efectos adversos , Antimaláricos/uso terapéutico , Hipoplasia del Esmalte Dental/inducido químicamente , Doxiciclina/efectos adversos , Doxiciclina/uso terapéutico , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Malaria/tratamiento farmacológico , Quimioprevención/efectos adversos , Quimioprevención/métodos , Niño , Preescolar , Humanos , Lactante , Recién Nacido
19.
Malar J ; 16(1): 140, 2017 04 05.
Artículo en Inglés | MEDLINE | ID: mdl-28381273

RESUMEN

BACKGROUND: A malaria hotspot in the southeastern region of Mauritania, near the Malian border, may hamper malaria control strategies. The objectives were to estimate the prevalence of genetic polymorphisms associated with drug resistance in Plasmodium falciparum isolates and establish baseline data. METHODS: The study was conducted in two malaria-endemic areas in Hodh Elgharbi, situated in the Malian-Mauritanian border area. Blood samples were collected from symptomatic patients. Single nucleotide polymorphisms in Pfcrt, Pfmdr1, Pfdhfr, and Pfdhps were genotyped using PCR-restriction fragment length polymorphism, DNA sequencing and primer extension. The Pfmdr1 gene copy number was determined by real-time PCR. RESULTS: Of 280 P. falciparum-infected patients, 193 (68.9%) carried the Pfcrt 76T mutant allele. The Pfmdr1 86Y and 184F mutations were found in 61 (23.1%) of 264 isolates and 167 (67.6%) of 247 samples that were successfully genotyped, respectively. Pfmdr1 mutant alleles 1034C, 1042D and 1246Y were rarely observed. Of 102 P. falciparum isolates analysed, ten (9.8%) had more than one copy of Pfmdr1 gene. The prevalence of isolates harbouring at least triple mutant Pfdhfr 51I, 59R, 108 N/T was 42% (112/268), of which 42 (37.5%) had an additional Pfdhps 437G mutation. The Pfdhps 540E mutation was observed in four isolates (1.5%), including three associated with Pfdhfr triple mutant. Only two quintuple mutants (Pfdhfr-51I-59R-108N Pfdhps-437G-540E) were observed. CONCLUSIONS: The observed mutations in Pfdhfr, Pfdhps, Pfmdr1, and Pfcrt may jeopardize the future of seasonal malaria chemoprevention based on amodiaquine-sulfadoxine-pyrimethamine, intermittent preventive treatment for pregnant women using sulfadoxine-pyrimethamine, and treatment with artesunate-amodiaquine. Complementary studies should be carried out to document the distribution, origin and circulation of P. falciparum populations in this region and more widely in the country to assess the risk of the spread of resistance.


Asunto(s)
Antimaláricos/farmacología , Resistencia a Medicamentos , Genes Protozoarios , Malaria Falciparum/parasitología , Plasmodium falciparum/efectos de los fármacos , Plasmodium falciparum/genética , Polimorfismo de Nucleótido Simple , Enfermedades Asintomáticas , ADN Protozoario/química , ADN Protozoario/genética , Dosificación de Gen , Humanos , Malí , Mauritania , Plasmodium falciparum/aislamiento & purificación , Reacción en Cadena de la Polimerasa , Polimorfismo de Longitud del Fragmento de Restricción , Prevalencia , Análisis de Secuencia de ADN
20.
Artículo en Inglés | MEDLINE | ID: mdl-28052850

RESUMEN

Polymorphisms and the overexpression of transporter genes, especially of the ATP-binding cassette superfamily, have been involved in antimalarial drug resistance. The objective of this study was to use 77 Senegalese Plasmodium falciparum isolates to evaluate the association between the number of Asn residues in the polymorphic microsatellite region of the Plasmodium falciparum multidrug resistance 6 gene (Pfmdr6) and the ex vivo susceptibility to antimalarials. A significant association was observed between the presence of 7 or 9 Asn repeats and reduced susceptibility to quinine.


Asunto(s)
Transportadoras de Casetes de Unión a ATP/genética , Antimaláricos/farmacología , Resistencia a Medicamentos/genética , Plasmodium falciparum/genética , Polimorfismo Genético , Proteínas Protozoarias/genética , Quinina/farmacología , Amodiaquina/análogos & derivados , Amodiaquina/farmacología , Artemisininas/farmacología , Artesunato , Asparagina/metabolismo , Cloroquina/farmacología , Doxiciclina/farmacología , Etanolaminas/farmacología , Fluorenos/farmacología , Expresión Génica , Humanos , Concentración 50 Inhibidora , Lumefantrina , Malaria Falciparum/parasitología , Mefloquina/farmacología , Naftiridinas/farmacología , Plasmodium falciparum/efectos de los fármacos , Plasmodium falciparum/crecimiento & desarrollo , Plasmodium falciparum/aislamiento & purificación , Isoformas de Proteínas/genética , Quinolinas/farmacología , Secuencias Repetitivas de Aminoácido , Senegal
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