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1.
PLoS Negl Trop Dis ; 15(6): e0009448, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34106920

RESUMO

BACKGROUND: In Mali, cutaneous leishmaniasis (CL) and filariasis are co-endemic. Previous studies in animal models of infection have shown that sand fly saliva enhance infectivity of Leishmania parasites in naïve hosts while saliva-specific adaptive immune responses may protect against cutaneous and visceral leishmaniasis. In contrast, the human immune response to Phlebotomus duboscqi (Pd) saliva, the principal sand fly vector in Mali, was found to be dichotomously polarized with some individuals having a Th1-dominated response and others having a Th2-biased response. We hypothesized that co-infection with filarial parasites may be an underlying factor that modulates the immune response to Pd saliva in endemic regions. METHODOLOGY/PRINCIPAL FINDINGS: To understand which cell types may be responsible for polarizing human responses to sand fly saliva, we investigated the effect of salivary glands (SG) of Pd on human monocytes. To this end, elutriated monocytes were cultured in vitro, alone, or with SG, microfilariae antigen (MF ag) of Brugia malayi, or LPS, a positive control. The mRNA expression of genes involved in inflammatory or regulatory responses was then measured as were cytokines and chemokines associated with these responses. Monocytes of individuals who were not exposed to sand fly bites (mainly North American controls) significantly upregulated the production of IL-6 and CCL4; cytokines that enhance leishmania parasite establishment, in response to SG from Pd or other vector species. This selective inflammatory response was lost in individuals that were exposed to sand fly bites which was not changed by co-infection with filarial parasites. Furthermore, infection with filarial parasites resulted in upregulation of CCL22, a type-2 associated chemokine, both at the mRNA levels and by its observed effect on the frequency of recruited monocytes. CONCLUSIONS/SIGNIFICANCE: Together, our data suggest that SG or recombinant salivary proteins from Pd alter human monocyte function by upregulating selective inflammatory cytokines.


Assuntos
Brugia Malayi/imunologia , Proteínas de Insetos/imunologia , Monócitos/parasitologia , Phlebotomus/imunologia , Saliva/imunologia , Imunidade Adaptativa , Animais , Células Cultivadas , Quimiocina CCL22/genética , Quimiocina CCL22/metabolismo , Coinfecção , Doenças Endêmicas , Filariose/complicações , Filariose/imunologia , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/imunologia , Imunidade Celular , Leishmaniose Cutânea/complicações , Leishmaniose Cutânea/imunologia , Lipopolissacarídeos/toxicidade , Mali , Monócitos/fisiologia , RNA Mensageiro , Proteínas Recombinantes , Glândulas Salivares , Linfócitos T Auxiliares-Indutores
2.
Clin Infect Dis ; 72(9): 1585-1593, 2021 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-32206773

RESUMO

BACKGROUND: Ivermectin-based onchocerciasis elimination, reported in 2009-2012, for Bakoye and Falémé, Mali, supported policy-shifting from morbidity control to elimination of transmission (EOT). These foci are coendemic with lymphatic filariasis (LF). In 2007-2016 mass ivermectin plus albendazole administration was implemented. We report Ov16 (onchocerciasis) and Wb123 (LF) seroprevalence after 24-25 years of treatment to determine if onchocerciasis EOT and LF elimination as a public health problem (EPHP) have been achieved. METHODS: The SD Bioline Onchocerciasis/LF Ig[immunoglobulin]G4 biplex rapid diagnostic test (RDT) was used in 2186 children aged 3-10 years in 13 villages (plus 2 hamlets) in Bakoye and in 2270 children in 15 villages (plus 1 hamlet) in Falémé. In Bakoye, all-age serosurveys were conducted in 3 historically hyperendemic villages (1867 individuals aged 3 -78 years). RESULTS: In Bakoye, IgG4 seropositivity was 0.27% (95% confidence interval [CI] = .13%-.60%) for both Ov16 and Wb123 antigens. In Falémé, Ov16 and Wb123 seroprevalence was 0.04% (95% CI = .01%-.25%) and 0.09% (95% CI = .02%-.32%), respectively. Ov16-seropositive children were from historically meso/hyperendemic villages. Ov16 positivity was <2% in ≤14 year-olds, and 16% in ≥40 year-olds. Wb123 seropositivity was <2% in ≤39 year-olds, reaching 3% in ≥40 year-olds. CONCLUSIONS: Notwithstanding uncertainty in the biplex RDT sensitivity, Ov16 and Wb123 seroprevalence among children in Bakoye and Falémé is consistent with EOT (onchocerciasis) and EPHP (LF) since stopping treatment in 2016. The few Ov16-seropositive children should be skin-snip polymerase chain reaction tested and followed up.


Assuntos
Filariose Linfática , Oncocercose , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Filariose Linfática/tratamento farmacológico , Filariose Linfática/epidemiologia , Filariose Linfática/prevenção & controle , Humanos , Ivermectina/uso terapêutico , Mali/epidemiologia , Pessoa de Meia-Idade , Oncocercose/tratamento farmacológico , Oncocercose/epidemiologia , Oncocercose/prevenção & controle , Estudos Soroepidemiológicos , Adulto Jovem
3.
Infect Disord Drug Targets ; 20(2): 167-174, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-30727921

RESUMO

BACKGROUND: Lymphatic filariasis (LF) is a parasitic disease that has been targeted for elimination through the Mass Drug Administration (MDA.) Although the MDA started in the Ankobra community in Ghana in 2000, LF prevalence as reported in 2014 was relatively high (4.5%). Non-compliance to the MDA has been associated with the persistent LF prevalence in endemic regions. OBJECTIVE: This study determined the factors associated with the non-compliance to the MDA among patients living in the Ankobra community, Ghana. METHODS: A cross-sectional study using a one-stage cluster sampling method was used to collect data between June and July, 2017 in Ankobra. Questionnaires were used to collect data from health workers, the MDA drug distributors and study participants in Ankobra. Data analysis was performed using STATA 14. Logistic regression was used to measure the degree of association between the dependent (non-compliance) and independent variables. Non-compliance rate was defined as the percentage of individuals who self-reported that they did not actually swallow the drugs provided during the MDA. RESULTS: The MDA coverage and non-compliance rates were 73.5% (147/200) and 33.33% (49/147) respectively. The main reason for non-compliance was fear of drug adverse events (75.51%, 37/49). Thought of "not being susceptible to LF" was significantly associated with the non-compliance (aOR= 2.83, [CI= 1.15, 6.98]). CONCLUSION: Health education about the susceptibility of residents getting LF disease in endemic community must be intensified to improve compliance to MDA medication ingestion and thus meet the Global Elimination of Lymphatic Filariasis by 2020.


Assuntos
Suscetibilidade a Doenças/psicologia , Filariose Linfática/tratamento farmacológico , Conhecimentos, Atitudes e Prática em Saúde , Administração Massiva de Medicamentos , Cooperação do Paciente/psicologia , Percepção Social , Adulto , Albendazol/uso terapêutico , Anti-Helmínticos/uso terapêutico , Estudos Transversais , Erradicação de Doenças/métodos , Filariose Linfática/epidemiologia , Feminino , Gana/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Cooperação do Paciente/estatística & dados numéricos , Prevalência , Inquéritos e Questionários , Adulto Jovem
4.
PLoS Negl Trop Dis ; 13(1): e0007064, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30699120

RESUMO

BACKGROUND: Mali has become increasingly interested in the evaluation of transmission of both Wuchereria bancrofti and Onchocerca volvulus as prevalences of both infections move toward their respective elimination targets. The SD Bioline Onchocerciasis/LF IgG4 Rapid Test was used in 2 evaluation units (EU) to assess its performance as an integrated surveillance tool for elimination of lymphatic filariasis (LF) and onchocerciasis. METHODOLOGY/PRINCIPAL FINDINGS: A cross sectional survey with SD Bioline Onchocerciasis/LF IgG4 Rapid Test was piggy-backed onto a transmission assessment survey (TAS) (using the immunochromatographic card test (ICT) Binax Filariasis Now test for filarial adult circulating antigen (CFA) detection) for LF in Mali among 6-7 year old children in 2016 as part of the TAS in two EUs namely Kadiolo-Kolondieba in the region of Sikasso and Bafoulabe -Kita-Oussoubidiagna-Yelimane in the region of Kayes. In the EU of Kadiolo- Kolondieba, of the 1,625 children tested, the overall prevalence of W. bancrofti CFA was 0.62% (10/1,625) [CI = 0.31-1.09]; while that of IgG4 to Wb123 was 0.19% (3/1,600) [CI = 0.04-0.50]. The number of positives tested with the two tests were statistically comparable (p = 0.09). In the EU of Bafoulabe-Kita-Oussoubidiagna-Yelimane, an overall prevalence of W. bancrofti CFA was 0% (0/1,700) and that of Wb123 IgG4 antibody was 0.06% (1/1,700), with no statistically significant difference between the two rates (p = 0.99). In the EU of Kadiolo- Kolondieba, the prevalence of Ov16-specific IgG4 was 0.19% (3/1,600) [CI = 0.04-0.50]. All 3 positives were in the previously O. volvulus-hyperendemic district of Kolondieba. In the EU of Bafoulabe-Kita-Oussoubidiagna-Yelimane, an overall prevalence of Ov16-specific IgG4 was 0.18% (3/1,700) [CI = 0.04-0.47]. These 3 Ov16 IgG4 positives were from previously O.volvulus-mesoendemic district of Kita. CONCLUSIONS/SIGNIFICANCE: The SD Bioline Onchocerciasis/LF IgG4 Rapid test appears to be a good tool for integrated exposure measures of LF and onchocerciasis in co-endemic areas.


Assuntos
Anticorpos Anti-Helmínticos/imunologia , Filariose Linfática/imunologia , Imunoglobulina G/imunologia , Onchocerca volvulus/imunologia , Oncocercose/imunologia , Wuchereria bancrofti/imunologia , Animais , Anticorpos Anti-Helmínticos/sangue , Criança , Estudos Transversais , Filariose Linfática/sangue , Filariose Linfática/epidemiologia , Filariose Linfática/parasitologia , Humanos , Imunoglobulina G/sangue , Testes Imunológicos , Mali/epidemiologia , Doenças Negligenciadas/sangue , Doenças Negligenciadas/epidemiologia , Doenças Negligenciadas/imunologia , Doenças Negligenciadas/parasitologia , Oncocercose/sangue , Oncocercose/epidemiologia , Oncocercose/parasitologia , Estudos Soroepidemiológicos
5.
Parasit Vectors ; 11(1): 18, 2018 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-29310700

RESUMO

BACKGROUND: Filariasis and leishmaniasis are two neglected tropical diseases in Mali. Due to distribution and associated clinical features, both diseases are of concern to public health. The goal of this study was to determine the prevalence of co-infection with filarial (Wuchereria bancrofti and Mansonella perstans) and Leishmania major parasites in two ecologically distinct areas of Mali, the Kolokani district (villages of Tieneguebougou and Bougoudiana) in North Sudan Savanna area, and the district of Kolondieba (village of Boundioba) in the South Sudan Savanna area. METHODS: The prevalence of co-infection (filarial and Leishmania) was measured based on (i) Mansonella perstans microfilaremia count and/or filariasis immunochromatographic test (ICT) for Wuchereria bancrofti-specific circulating antigen, and (ii) the prevalence of delayed type hypersensitivity (DTH) responses to Leishmania measured by leishmanin skin test (LST). RESULTS: In this study, a total of 930 volunteers between the age of 18 and 65 were included from the two endemic areas of Kolokani and Kolondieba. In general, in both areas, filarial infection was more prevalent than Leishmania infection with an overall prevalence of 15.27% (142/930) including 8.7% (81/930) for Mansonella perstans and 8% (74/930) for Wuchereria bancrofti-specific circulating antigen. The prevalence of Leishmania major infection was 7.7% (72/930) and was significantly higher in Tieneguebougou and Bougoudiana (15.05%; 64/425) than in Boundioba (2.04%; 8/505) (χ2 = 58.66, P < 0.0001). Among the filarial infected population, nearly 10% (14/142) were also positive for Leishmania with an overall prevalence of co-infection of 1.50% (14/930) varying from 2.82% (12/425) in Tieneguebougou and Bougoudiana to 0.39% (2/505) in Boundioba (P = 0.0048). CONCLUSION: This study established the existence of co-endemicity of filarial and Leishmania infections in specific regions of Mali. Since both filarial and Leishmania infections are vector-borne with mosquitoes and sand flies as respective vectors, an integrated vector control approach should be considered in co-endemic areas. The effect of potential interaction between filarial and Leishmania parasites on the disease outcomes may be further studied.


Assuntos
Coinfecção/epidemiologia , Doenças Endêmicas , Filariose/epidemiologia , Leishmaniose/epidemiologia , Adulto , Animais , Cromatografia de Afinidade , Estudos Transversais , Feminino , Filariose/complicações , Voluntários Saudáveis , Humanos , Leishmaniose/complicações , Masculino , Mali/epidemiologia , Microscopia , Pessoa de Meia-Idade , Prevalência , Testes Cutâneos , Sudão/epidemiologia , Adulto Jovem
6.
Parasit Vectors ; 9(1): 628, 2016 12 03.
Artigo em Inglês | MEDLINE | ID: mdl-27912789

RESUMO

BACKGROUND: After seven annual rounds of mass drug administration (MDA) in six Malian villages highly endemic for Wuchereria bancrofti (overall prevalence rate of 42.7%), treatment was discontinued in 2008. Surveillance was performed over the ensuing 5 years to detect recrudescence. METHODS: Circulating filarial antigen (CFA) was measured using immunochromatographic card tests (ICT) and Og4C3 ELISA in 6-7 year-olds. Antibody to the W. bancrofti infective larval stage (L3) antigen, Wb123, was tested in the same population in 2012. Microfilaraemia was assessed in ICT-positive subjects. Anopheles gambiae complex specimens were collected monthly using human landing catch (HLC) and pyrethrum spray catch (PSC). Anopheles gambiae complex infection with W. bancrofti was determined by dissection and reverse transcriptase polymerase chain reaction (RT-PCR) of mosquito pools. RESULTS: Annual CFA prevalence rates using ICT in children increased over time from 0% (0/289) in 2009 to 2.7% (8/301) in 2011, 3.9% (11/285) in 2012 and 4.5% (14/309) in 2013 (trend χ 2 = 11.85, df =3, P = 0.0006). Wb123 antibody positivity rates in 2013 were similar to the CFA prevalence by ELISA (5/285). Although two W. bancrofti-infected Anopheles were observed by dissection among 12,951 mosquitoes collected by HLC, none had L3 larvae when tested by L3-specific RT-PCR. No positive pools were detected among the mosquitoes collected by pyrethrum spray catch. Whereas ICT in 6-7 year-olds was the major surveillance tool, ICT positivity was also assessed in older children and adults (8-65 years old). CFA prevalence decreased in this group from 4.9% (39/800) to 3.5% (28/795) and 2.8% (50/1,812) in 2009, 2011 and 2012, respectively (trend χ 2 = 7.361, df =2, P = 0.0067). Some ICT-positive individuals were microfilaraemic in 2009 [2.6% (1/39)] and 2011 [8.3% (3/36)], but none were positive in 2012 or 2013. CONCLUSION: Although ICT rates in children increased over the 5-year surveillance period, the decrease in ICT prevalence in the older group suggests a reduction in transmission intensity. This was consistent with the failure to detect infective mosquitoes or microfilaraemia. The threshold of ICT positivity in children may need to be re-assessed and other adjunct surveillance tools considered.


Assuntos
Antígenos de Helmintos/sangue , Transmissão de Doença Infecciosa , Tratamento Farmacológico/métodos , Filariose Linfática/epidemiologia , Filariose Linfática/transmissão , Filaricidas/administração & dosagem , Wuchereria bancrofti/isolamento & purificação , Animais , Anopheles/parasitologia , Anticorpos Anti-Helmínticos/sangue , Cromatografia de Afinidade , Filariose Linfática/tratamento farmacológico , Ensaio de Imunoadsorção Enzimática , Monitoramento Epidemiológico , Humanos , Mali , Prevalência , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Wuchereria bancrofti/genética , Wuchereria bancrofti/imunologia
7.
eNeurologicalSci ; 3: 17-20, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29430530

RESUMO

Introduction: Spinal muscular atrophy (SMA) and sporadic amyotrophic lateral sclerosis (SALS) are both motor neuron disorders. SMA results from the deletion of the survival motor neuron (SMN) 1 gene. High or low SMN1 copy number and the absence of SMN2 have been reported as risk factors for the development or severity of SALS. Objective: To investigate the role of SMN gene copy number in the onset and severity of SALS in Malians. Material and Methods: We determined the SMN1 and SMN2 copy number in genomic DNA samples from 391 Malian adult volunteers, 120 Yoruba from Nigeria, 120 Luyha from Kenya and 74 U.S. Caucasians using a Taqman quantitative PCR assay. We evaluated the SALS risk based on the estimated SMA protein level using the Veldink formula (SMN1 copy number + 0.2 ∗ SMN2 copy number). We also characterized the disease natural history in 15 ALS patients at the teaching hospital of Point G, Bamako, Mali. Results: We found that 131 of 391 (33.5%) had an estimated SMN protein expression of ≤ 2.2; 60 out of 391 (15.3%) had an estimated SMN protein expression < 2 and would be at risk of ALS and the disease onset was as early as 16 years old. All 15 patients were male and some were physically handicapped within 1-2 years in the disease course. Conclusion: Because of the short survival time of our patients, family histories and sample DNA for testing were not done. However, our results show that sporadic ALS is of earlier onset and shorter survival time as compared to patients elsewhere. We plan to establish a network of neurologists and researchers for early screening of ALS.

8.
Parasit Vectors ; 6(1): 247, 2013 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-23981378

RESUMO

BACKGROUND: The Global Programme to Eliminate Lymphatic Filariasis (GPELF) was launched in 2000 with the goal of stopping transmission of lymphatic filariasis (LF) through yearly mass drug administration (MDA). Although preliminary surveys of the human population in Mali suggested that Wuchereria bancrofti infection was highly endemic in the Sikasso district, baseline entomological data were required to confirm high levels of transmission prior to the selection of villages in this region for a study of the impact of MDA on transmission of LF by anopheline vectors. METHODS: W. bancrofti transmission was assessed in 2001 (pre-MDA) and 2002 (post-MDA) in the Central District of Sikasso in southern Mali by dissection of Anopheles mosquitoes caught using the human landing catch (HLC) method. The relative frequencies and molecular forms of An. gambiae complex were determined. RESULTS: The majority (86%) of the anopheline vectors captured were identified as An. gambiae complex, and these accounted for >90% of the entomological inoculation rate (EIR) during both years of the study. There was a dramatic decrease in the number of An. gambiae complex mosquitoes captured and in the An. gambiae complex infectivity rates following MDA, accounting for the observed decrease in EIR in 2002 (from 12.55 to 3.79 infective bites per person during the transmission season). An. funestus complex mosquitoes were responsible for a low level of transmission, which was similar during both years of the study (1.2 infective bites per person during the transmission season in 2001 and 1.03 in 2002). CONCLUSIONS: Based on the entomological data from this study, the district of Sikasso was confirmed as an area of high W. bancrofti transmission. This led to the selection of this area for a multi-national study on the effects of MDA on LF transmission by anopheline vectors. Comparison of vector transmission parameters prior to and immediately following the first round of MDA demonstrated a significant decrease in overall transmission. Importantly, the dramatic variability in EIR over the transmission season suggests that the efficacy of MDA can be maximized by delivering drug at the beginning of the rainy season (just prior to the peak of transmission).


Assuntos
Anopheles/parasitologia , Anti-Helmínticos/administração & dosagem , Filariose Linfática/tratamento farmacológico , Filariose Linfática/transmissão , Wuchereria bancrofti/isolamento & purificação , Animais , Anopheles/classificação , Filariose Linfática/epidemiologia , Filariose Linfática/prevenção & controle , Feminino , Humanos , Estudos Longitudinais , Masculino , Mali/epidemiologia
9.
PLoS Negl Trop Dis ; 7(5): e2221, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23675549

RESUMO

BACKGROUND: Neglected tropical diseases are co-endemic in many areas of the world, including sub Saharan Africa. Currently lymphatic filariasis (albendazole/ivermectin) and trachoma (azithromycin) are treated separately. Consequently, financial and logistical benefit can be gained from integration of preventive chemotherapy programs in such areas. METHODOLOGY/FINDINGS: 4 villages in two co-endemic districts (Kolondièba and Bougouni) of Sikasso, Mali, were randomly assigned to coadministered treatment (ivermectin/albendazole/azithromycin) or standard therapy (ivermectin/albendazole with azithromycin 1 week later). These villages had previously undergone 4 annual MDA campaigns with ivermectin/albendazole and 2 with azithromycin. One village was randomly assigned to each treatment arm in each district. There were 7515 eligible individuals in the 4 villages, 3011(40.1%) of whom participated in the study. No serious adverse events occurred, and the majority of adverse events were mild in intensity (mainly headache, abdominal pain, diarrhoea and "other signs/symptoms"). The median time to the onset of the first event, of any type, was later (8 days) in the two standard treatment villages than in the co-administration villages. Overall the number of subjects reporting any event was similar in the co-administration group compared to the standard treatment group [18.7% (281/1501) vs. 15.8% (239/1510)]. However, the event frequency was higher in the coadministration group (30.4%) than in the standard treatment group (11.0%) in Kolondièba, while the opposite was observed in Bougouni (7.1% and 20.9% respectively). Additionally, the overall frequency of adverse events in the co-administration group (18.7%) was comparable to or lower than published frequencies for ivermectin+albendazole alone. CONCLUSIONS: These data suggest that co-administration of ivermectin+albendazole and azithromycin is safe; however the small number of villages studied and the large differences between them resulted in an inability to calculate a meaningful overall estimate of the difference in adverse event rates between the regimens. Further work is therefore needed before co-administration can be definitively recommended. TRIAL REGISTRATION: ClinicalTrials.gov; NCT01586169.


Assuntos
Anti-Helmínticos/efeitos adversos , Antibacterianos/efeitos adversos , Filariose Linfática/tratamento farmacológico , Filariose Linfática/prevenção & controle , Tracoma/tratamento farmacológico , Tracoma/prevenção & controle , Adolescente , Adulto , Idoso , Albendazol/efeitos adversos , Albendazol/uso terapêutico , Anti-Helmínticos/uso terapêutico , Antibacterianos/uso terapêutico , Azitromicina/efeitos adversos , Azitromicina/uso terapêutico , Quimioprevenção/efeitos adversos , Quimioprevenção/métodos , Criança , Pré-Escolar , Coinfecção/tratamento farmacológico , Coinfecção/prevenção & controle , Quimioterapia Combinada/efeitos adversos , Quimioterapia Combinada/métodos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Feminino , Humanos , Ivermectina/efeitos adversos , Ivermectina/uso terapêutico , Masculino , Mali , Pessoa de Meia-Idade , Doenças Negligenciadas/tratamento farmacológico , Doenças Negligenciadas/prevenção & controle , Adulto Jovem
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