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1.
Acta Trop ; 225: 106218, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34755644

RESUMO

Community-Directed Treatment with Ivermectin (CDTI) is the strategy of choice to fight onchocerciasis in Africa. In areas where loiasis is endemic, onchocerciasis control and/or elimination is hindered by severe adverse events (SAEs) occurring after ivermectin mass treatments. This study aimed at (i) investigating the impact of two decades of CDTI on L. loa clinical and parasitological indicators in the Ndikinimeki Health District, and (ii) assessing the risk of SAEs after this long-term preventive chemotherapy. A cluster-based cross-sectional survey was conducted in the six Health Areas of the Ndikinimeki Health District. All volunteers underwent day-time calibrated thick blood smears to search for L. loa microfilariae, as well as an interview to assess the history of migration of eye worm and Calabar swelling. The overall prevalence of L. loa microfilaraemia was 2.2 % (95% CI: 1.3-3.7%), and the proportions of individuals who had already experienced eye worm and/or Calabar swelling were 1.0% and 0.5%, respectively. The mean microfilarial density was 63.55 (SD: 559.17; maximum: 9220.0) mf/mL. These findings indicate that (i) the long-term ivermectin-based preventive chemotherapy against onchocerciasis significantly reduced L. loa clinical and parasitological indicators, and (ii) the risk of developing neurologic and potentially fatal SAE after ivermectin mass treatment is zero in the Ndikinimeki Health District.


Assuntos
Loíase , Oncocercose , Animais , Camarões/epidemiologia , Estudos Transversais , Doenças Endêmicas/prevenção & controle , Humanos , Ivermectina , Loa , Loíase/tratamento farmacológico , Loíase/epidemiologia , Loíase/prevenção & controle , Oncocercose/tratamento farmacológico , Oncocercose/epidemiologia , Oncocercose/prevenção & controle , Prevalência
3.
PLoS Negl Trop Dis ; 15(8): e0009623, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34398886

RESUMO

BACKGROUND: Loa loa and Mansonella perstans-the causative agents of loiasis and mansonellosis-are vector-borne filarial parasites co-endemic in sub-Saharan Africa. Diagnosis of both infections is usually established by microscopic analysis of blood samples. It was recently established that the odds for detecting Plasmodium spp. is higher in capillary (CAP) blood than in venous (VEN) blood. In analogy to this finding this analysis evaluates potential differences in microfilaraemia of L. loa and M. perstans in samples of CAP and VEN blood. METHODS: Recruitment took place between 2015 and 2019 at the CERMEL in Lambaréné, Gabon and its surrounding villages. Persons of all ages presenting to diagnostic services of the research center around noon were invited to participate in the study. A thick smear of each 10 microliters of CAP and VEN blood was prepared and analysed by a minimum of two independent microscopists. Differences of log2-transformed CAP and VEN microfilaraemia were computed and expressed as percentages. Furthermore, odds ratios for paired data were computed to quantify the odds to detect microfilariae in CAP blood versus in VEN blood. RESULTS: A total of 713 participants were recruited among whom 52% were below 30 years of age, 27% between 30-59 years of age and 21% above 60 years of age. Male-female ratio was 0.84. Among 152 participants with microscopically-confirmed L. loa infection median (IQR) microfilaraemia was 3,650 (275-11,100) per milliliter blood in CAP blood and 2,775 (200-8,875) in VEN blood (p<0.0001), while among 102 participants with M. perstans this was 100 (0-200) and 100 (0-200), respectively (p = 0.44). Differences in linear models amount up to an average of +34.5% (95% CI: +11.0 to +63.0) higher L. loa microfilaria quantity in CAP blood versus VEN blood and for M. perstans it was on average higher by +24.8% (95% CI: +0.0 to +60.5). Concordantly, the odds for detection of microfilaraemia in CAP samples versus VEN samples was 1.24 (95% CI: 0.65-2.34) and 1.65 (95% CI: 1.0-2.68) for infections with L. loa and M. perstans, respectively. CONCLUSION: This analysis indicates that average levels of microfilaraemia of L. loa are higher in CAP blood samples than in VEN blood samples. This might have implications for treatment algorithms of onchocerciasis and loiasis, in which exact quantification of L. loa microfilaraemia is of importance. Furthermore, the odds for detection of M. perstans microfilariae was higher in CAP than in VEN blood which may pre-dispose CAP blood for detection of M. perstans infection in large epidemiological studies when sampling of large blood quantities is not feasible. No solid evidence for a higher odds of L. loa microfilariae detection in CAP blood was revealed, which might be explained by generally high levels of L. loa microfilaraemia in CAP and VEN blood above the limit of detection of 100 microfilariae/ml. Yet, it cannot be excluded that the study was underpowered to detect a moderate difference.


Assuntos
Coinfecção/patologia , Loa/isolamento & purificação , Loíase/patologia , Mansonella/isolamento & purificação , Mansonelose/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Criança , Coinfecção/epidemiologia , Coinfecção/parasitologia , Feminino , Gabão/epidemiologia , Humanos , Loíase/epidemiologia , Loíase/parasitologia , Masculino , Mansonelose/epidemiologia , Mansonelose/parasitologia , Microscopia , Pessoa de Meia-Idade , Carga Parasitária , Parasitemia , Prevalência , Testes Sorológicos , Adulto Jovem
4.
Microb Pathog ; 158: 105101, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34303811

RESUMO

A 21-year-old young boy who lived alone since one year and a half ago in Paris was referred due to severe vertigo. He is originally from Ivory Coast but lived from 2011 to 2017 in Douala city in west of Cameroon. Beside vertigo, he complained from headache, sudden abdominal pain and edema in both left and right forearms for about two years. General examination demonstrated a healthy condition with no subcutaneous nodules and swelling on any other part of the body, not splenomegaly or lymphadenopathy. Moreover, the eyes were normal with clear lens. Blood count analysis revealed a hypereosinophilia (2670*106/L, N: <500*106/L). A couple of direct and May-Grunwald-Giemsa stained smears, analyzed by microscopy revealed the semitransparent cylindrical worms with almost 300 µm length and 45 µm width identified as Loa loa. The identity of the worm was then confirmed by bidirectional sequencing of 450 bp fragment of internal transcribed spacer 1 (ITS1-rDNA). Based on Neighbor-Joining phylogenetic tree, our isolate was clustered tightly with other few Loa species from Gabon in the same clade. No hybrid was observed among processed sequences since all species groups were discriminated separately. In the current case, he was originally from Ivory Coast but absence of medical and epidemiological evidences as well as the residency of our patient for 6 years in Cameroon made us suspicious that the patient has been most likely infected by L. loa worms in this country. The patient was treated by a couple of ivermectin (200 µg/kg for 3 days) and diethylcarbamazine (3 mg/kg, 2 times per day for 4 weeks) and a favorable evolution was observed within few weeks. Regarding at least one year and a half interval between the probable Loa loa infection in Cameroon and diagnosis, Loa loa worms are competent to persist in the human host for several years. Consequently, the clinicians should be aware of this parasitosis among the travelers or immigrants coming from endemic regions in Africa.


Assuntos
Emigrantes e Imigrantes , Loíase , Parasitos , Adulto , Animais , Camarões , Variação Genética , Humanos , Loa/genética , Loíase/diagnóstico , Masculino , Paris , Filogenia , Adulto Jovem
5.
Clin Infect Dis ; 72(Suppl 3): S158-S164, 2021 06 14.
Artigo em Inglês | MEDLINE | ID: mdl-33909066

RESUMO

BACKGROUND: The diagnostic gold standard for onchocerciasis relies on identification and enumeration of (skin-dwelling) Onchocerca volvulus microfilariae (mf) using the skin snip technique (SST). In a recent study, blood-borne Loa loa mf were found by SST in individuals heavily infected with L. loa, and microscopically misidentified as O. volvulus due to their superficially similar morphology. This study investigates the relationship between L. loa microfilarial density (Loa MFD) and the probability of testing SST positive. METHODS: A total of 1053 participants from the (onchocerciasis and loiasis coendemic) East Region in Cameroon were tested for (1) Loa MFD in blood samples, (2) O. volvulus presence by SST, and (3) Immunoglobulin (Ig) G4 antibody positivity to Ov16 by rapid diagnostic test (RDT). A Classification and Regression Tree (CART) model was used to perform a supervised classification of SST status and identify a Loa MFD threshold above which it is highly likely to find L. loa mf in skin snips. RESULTS: Of 1011 Ov16-negative individuals, 28 (2.8%) tested SST positive and 150 (14.8%) were L. loa positive. The range of Loa MFD was 0-85 200 mf/mL. The CART model subdivided the sample into 2 Loa MFD classes with a discrimination threshold of 4080 (95% CI, 2180-12 240) mf/mL. The probability of being SST positive exceeded 27% when Loa MFD was >4080 mf/mL. CONCLUSIONS: The probability of finding L. loa mf by SST increases significantly with Loa MFD. Skin-snip polymerase chain reaction would be useful when monitoring onchocerciasis prevalence by SST in onchocerciasis-loiasis coendemic areas.


Assuntos
Loíase , Oncocercose , Animais , Camarões , Humanos , Ivermectina , Loa , Microfilárias , Pele
6.
Vox Sang ; 116(7): 741-754, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33491765

RESUMO

BACKGROUND AND OBJECTIVES: Filariae are parasitic worms that include the pathogens Loa loa, Onchocerca volvulus, Wuchereria bancrofti, Brugia spp. and Mansonella spp. which are endemic in parts of Africa, Asia, Asia-Pacific, South and Central America. Filariae have a wide clinical spectrum spanning asymptomatic infection to chronic debilitating disease including blindness and lymphedema. Despite successful eradication programmes, filarial infections remain an important -albeit neglected - source of morbidity. We sought to characterize the risk of transfusion transmission of microfilaria with a view to guide mitigation practices in both endemic and non-endemic countries. MATERIALS AND METHODS: A scoping review of scientific publications as well as grey literature was carried out by a group of domain experts in microbiology, transfusion medicine and infectious diseases, representing the parasite subgroup of the International Society of Blood Transfusion. RESULTS: Cases of transfusion-transmitted filariasis are rare and confined to case reports of variable quality. Transfusion-associated adverse events related to microfilariae are confined to isolated reports of transfusion reactions. Serious outcomes have not been reported. No known strategies have been implemented, specifically, to mitigate transfusion-transmitted filariasis yet routine blood donor screening for other transfusion-transmissible infections (e.g. hepatitis B, malaria) may indirectly defer donors with microfilaremia in endemic areas. CONCLUSION: Rare examples of transfusion-transmitted filariasis, without serious clinical effect, suggest that filariasis poses low transfusion risk. Dedicated mitigation strategies against filarial transfusion transmission are not recommended. Given endemicity in low-resource regions, priority should be on the control of filariasis with public health measures.


Assuntos
Filariose , Reação Transfusional , Animais , Transfusão de Sangue , Filariose/epidemiologia , Filariose/prevenção & controle , Loa , Wuchereria bancrofti
7.
Parasit Vectors ; 14(1): 19, 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33407819

RESUMO

BACKGROUND: The mass drug administration of ivermectin for onchocerciasis control has contributed to a significant drop in Loa loa microfilaria loads in humans that has, in turn, led to reduction of infection levels in Chrysops vectors. Accurate parasite detection is essential for assessing loiasis transmission as it provides a potential alternative or indirect strategy for addressing the problem of co-endemic loiasis and lymphatic filariasis through the Onchocerciasis Elimination Programme and it further reflects the true magnitude of the loiasis problem as excess human mortality has been reported to be associated with the disease. Although microscopy is the gold standard for detecting the infection, the sensitivity of this method is compromised when the intensity of infection is low. The loop-mediated isothermal amplification (LAMP) assay of parasite DNA is an alternative method for detecting infection which offers operational simplicity, rapidity and versatility of visual readout options. The aim of this study was to validate the Loa loa LAMP assay for the detection of infected Chrysops spp. under experimental and natural field conditions. METHODS: Two sets of 18 flies were fed on volunteers with either a low (< 10 mf/ml) or high (> 30,000mf/ml) microfilarial load. The fed flies were maintained under laboratory conditions for 14 days and then analysed using LAMP for the detection of L. loa infection. In addition, a total of 9270 flies were collected from the north-west, east, and south-west regions (SW 1 and 2) of Cameroon using sweep nets and subjected to microscopy (7841 flies) and LAMP (1291 flies plus 138 nulliparous flies) analyses. RESULTS: The LAMP assay successfully detected parasites in Chrysops fed on volunteers with both low and high microfilariaemic loads. Field validation and surveillance studies revealed LAMP-based infection rates ranging from 0.5 to 31.6%, with the lowest levels in SW 2 and the highest infection rates in SW 1. The LAMP assay detected significantly higher infection rates than microscopy in four of the five study sites. CONCLUSION: This study demonstrated the potential of LAMP as a simple surveillance tool. It was found to be more sensitive than microscopy for the detection of experimental and natural L. loa infections in Chrysops vectors.


Assuntos
Dípteros/parasitologia , Loa/isolamento & purificação , Técnicas de Diagnóstico Molecular/métodos , Técnicas de Amplificação de Ácido Nucleico/métodos , Animais , Camarões/epidemiologia , DNA de Helmintos , Reservatórios de Doenças , Vetores de Doenças , Humanos , Insetos Vetores/parasitologia , Loa/genética , Loíase/diagnóstico , Loíase/parasitologia , Microfilárias/isolamento & purificação , Microscopia , Oncocercose/epidemiologia , Carga Parasitária
8.
J Infect Dis ; 223(2): 287-296, 2021 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-33099649

RESUMO

Mansonella perstans, a filarial nematode, infects large populations in Africa and Latin America. Recently, a potential new species, Mansonella sp "DEUX," was reported. Carriage of endosymbiotic Wolbachia opens treatment options for Mansonella infections. Within a cross-sectional study, we assessed the prevalence of filarial infections in 834 Gabonese individuals and the presence of the endosymbiont Wolbachia. Almost half of the participants (400/834 [48%]) were infected with filarial nematodes, with Mansonella sp "DEUX" being the most frequent (295/400 [74%]), followed by Loa loa (273/400 [68%]) and Mansonella perstans (82/400 [21%]). Being adult/elderly, male, and living in rural areas was associated with a higher risk of infection. Wolbachia carriage was confirmed in M. perstans and Mansonella sp "DEUX." In silico analysis revealed that Mansonella sp "DEUX" is not detected with currently published M. perstans-specific assays. Mansonella infections are highly prevalent in Gabon and might have been underreported, likely also beyond Gabon.


Assuntos
Mansonella/classificação , Mansonella/genética , Mansonelose/epidemiologia , Mansonelose/parasitologia , Animais , Portador Sadio/parasitologia , Estudos Transversais , Gabão/epidemiologia , Humanos , Loa/genética , Masculino , Epidemiologia Molecular , Reação em Cadeia da Polimerase , População Rural
9.
Mol Biol Evol ; 38(1): 152-167, 2021 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-32750125

RESUMO

The postsynaptic density extends across the postsynaptic dendritic spine with discs large (DLG) as the most abundant scaffolding protein. DLG dynamically alters the structure of the postsynaptic density, thus controlling the function and distribution of specific receptors at the synapse. DLG contains three PDZ domains and one important interaction governing postsynaptic architecture is that between the PDZ3 domain from DLG and a protein called cysteine-rich interactor of PDZ3 (CRIPT). However, little is known regarding functional evolution of the PDZ3:CRIPT interaction. Here, we subjected PDZ3 and CRIPT to ancestral sequence reconstruction, resurrection, and biophysical experiments. We show that the PDZ3:CRIPT interaction is an ancient interaction, which was likely present in the last common ancestor of Eukaryotes, and that high affinity is maintained in most extant animal phyla. However, affinity is low in nematodes and insects, raising questions about the physiological function of the interaction in species from these animal groups. Our findings demonstrate how an apparently established protein-protein interaction involved in cellular scaffolding in bilaterians can suddenly be subject to dynamic evolution including possible loss of function.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Evolução Molecular , Família Multigênica , Domínios PDZ , Sequência de Aminoácidos , Animais , Moléculas de Adesão Celular Neuronais/química , Análise Mutacional de DNA , Humanos , Loa/genética
10.
J Infect Dis ; 223(2): 297-305, 2021 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-32561912

RESUMO

BACKGROUND: Interleukin-10 (IL-10) has been implicated as the major cytokine responsible for the modulation of parasite-specific responses in filarial infections; however, the role of other IL-10 superfamily members in filarial infection is less well studied. METHODS: Peripheral blood mononuclear cells from loiasis patients were stimulated with or without filarial antigen. Cytokine production was quantified using a Luminex platform and T-cell expression patterns were assessed by flow cytometry. RESULTS: All patients produced significant levels of IL-10, IL-13, IL-5, IL-4, and IL-9 in response to filarial antigen, indicating a common infection-driven response. When comparing microfilaria (mf)-positive and mf-negative patients, there were no significant differences in spontaneous cytokine nor in parasite-driven IL-10, IL-22, or IL-28a production. In marked contrast, mf-positive individuals had significantly increased filarial antigen-driven IL-24 and IL-19 compared to mf-negative subjects. mf-positive patients also demonstrated significantly higher frequencies of T cells producing IL-19 in comparison to mf-negative patients. T-cell expression of IL-19 and IL-24 was positively regulated by IL-10 and IL-1ß. IL-24 production was also regulated by IL-37. CONCLUSION: These data provide an important link between IL-10 and its related family members IL-19 and IL-24 in the modulation of the immune response in human filarial infections. CLINICAL TRIALS REGISTRATION: NCT00001230.


Assuntos
Imunomodulação , Interleucina-10/metabolismo , Interleucinas/metabolismo , Loa/imunologia , Loíase/etiologia , Loíase/metabolismo , Adolescente , Adulto , Animais , Criança , Citocinas/biossíntese , Suscetibilidade a Doenças , Feminino , Interações Hospedeiro-Parasita , Humanos , Masculino , Pessoa de Meia-Idade , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Células Th2/imunologia , Células Th2/metabolismo , Adulto Jovem
11.
Clin Infect Dis ; 72(5): 789-796, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-32055862

RESUMO

BACKGROUND: We have previously demonstrated that eosinophil-associated processes underlie some of the differences in clinical presentation among patients with Loa loa infection prior to therapy and that some posttreatment adverse events appear to be dependent on eosinophil activation. METHODS: We first conducted a retrospective review of 204 patients (70 microfilaria [MF] positive/134 negative) with Loa loa both before and following definitive therapy. We then measured filarial-specific antibodies, eosinophil- and Th2-associated cytokines, and eosinophil granule proteins in their banked serum prior to and at 1 year following definitive treatment. We also evaluated the influence of pretreatment corticosteroids and/or apheresis in altering the efficacy of treatment. RESULTS: Patients without circulating microfilariae (MF negative) not only had a higher likelihood of peripheral eosinophilia and increased antifilarial antibody levels but also had significantly increased concentrations of granulocyte-macrophage colony-stimulating factor, interleukin (IL) 5, and IL-4 compared with MF-positive patients. However, these differences had all resolved by 1 year after treatment, when all parameters approached the levels seen in uninfected individuals. Neither pretreatment with corticosteroids nor apheresis reduced the efficacy of the diethylcarbamazine used to treat these subjects. CONCLUSIONS: Our results highlight that, by 1 year following treatment, infection-associated immunologic abnormalities had resolved in nearly all patients treated for loiasis, and pretreatment corticosteroids had no influence on the resolution of the immunologic perturbations nor on the efficacy of diethylcarbamazine as a curative agent in loiasis. CLINICAL TRIALS REGISTRATION: NCT00001230.


Assuntos
Loa , Loíase , Animais , Dietilcarbamazina/uso terapêutico , Humanos , Loíase/tratamento farmacológico , Microfilárias , Estudos Retrospectivos
12.
Clin Infect Dis ; 72(12): e1047-e1055, 2021 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-33289025

RESUMO

BACKGROUND: Mass drug administration (MDA) with ivermectin is the main strategy for onchocerciasis elimination. Ivermectin is generally safe, but is associated with serious adverse events in individuals with high Loa loa microfilarial densities (MFD). Therefore, ivermectin MDA is not recommended in areas where onchocerciasis is hypo-endemic and L loa is co-endemic. To eliminate onchocerciasis in those areas, a test-and-not-treat (TaNT) strategy has been proposed. We investigated whether onchocerciasis elimination can be achieved using TaNT and the required duration. METHODS: We used the individual-based model ONCHOSIM to predict the impact of TaNT on onchocerciasis microfilarial (mf) prevalence. We simulated precontrol mf prevalence levels from 2% to 40%. The impact of TaNT was simulated under varying levels of participation, systematic nonparticipation, and exclusion from ivermectin resulting from high L loa MFD. For each scenario, we assessed the time to elimination, defined as bringing onchocerciasis mf prevalence below 1.4%. RESULTS: In areas with 30% to 40% precontrol mf prevalence, the model predicted that it would take between 14 and 16 years to bring the mf prevalence below 1.4% using conventional MDA, assuming 65% participation. TaNT would increase the time to elimination by up to 1.5 years, depending on the level of systematic nonparticipation and the exclusion rate. At lower exclusion rates (≤2.5%), the delay would be less than 6 months. CONCLUSIONS: Our model predicts that onchocerciasis can be eliminated using TaNT in L loa co-endemic areas. The required treatment duration using TaNT would be only slightly longer than in areas with conventional MDA, provided that participation is good.


Assuntos
Loíase , Oncocercose , Animais , Estudos de Viabilidade , Humanos , Ivermectina/uso terapêutico , Loa , Loíase/diagnóstico , Loíase/tratamento farmacológico , Loíase/epidemiologia , Oncocercose/tratamento farmacológico , Oncocercose/epidemiologia , Oncocercose/prevenção & controle , Prevalência
15.
PLoS Negl Trop Dis ; 14(8): e0008415, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32804951

RESUMO

Basic and translational research on loiasis, a filarial nematode infection of medical importance, is impeded by a lack of suitable Loa loa infection models and techniques of obtaining and culturing life cycle stages. We describe the development of a new method for routine production of infective third-stage larvae (L3) of L. loa from the natural intermediate arthropod vector host, Chrysops silacea, following experimental infection with purified microfilariae. At 14-days post-infection of C. silacea, the fly survival rate was 43%. Survival was significantly higher in flies injected with 50 mf (55.2%) than those that received 100 mf (31.0%). However, yield per surviving fly and total yield of L3 was markedly higher in the group of flies inoculated with 100 mf (3474 vs 2462 L3 produced). The abdominal segment hosted the highest percentage recovery of L3 (47.7%) followed by head (34.5%) and thorax (17.9%). L. loa larval survival was higher than 90% after 30 days of in vitro culture. The in vitro moulting success rate to the L4 larval stage was 59.1%. After experimental infection of RAG2-/-IL-2γc-/-mice, the average L. loa juvenile adult worm recovery rate was 10.5% at 62 dpi. More than 87% of the worms were recovered from the muscles and subcutaneous tissues. Worms recovered measured an average 24.3 mm and 11.4 mm in length for females (n = 5) and males (n = 5), respectively. In conclusion, L. loa mf injected into C. silacea intrathoracically develop into infective larvae that remain viable and infective comparable to L3 obtained through natural feeding on the human host. This technique further advances the development of a full laboratory life cycle of L. loa where mf derived from experimentally-infected animals may be utilized to passage life cycle generations via intrathoracic injections of wild-caught vector hosts.


Assuntos
Dípteros/parasitologia , Vetores de Doenças , Larva/parasitologia , Loa/isolamento & purificação , Loíase/parasitologia , Animais , Modelos Animais de Doenças , Feminino , Humanos , Larva/crescimento & desenvolvimento , Estágios do Ciclo de Vida , Loa/citologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Microfilárias , Taxa de Sobrevida
16.
Lancet Infect Dis ; 20(11): 1339-1346, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32585133

RESUMO

BACKGROUND: Loiasis is a highly prevalent helminth infection found in distinct regions of sub-Saharan Africa. The disease has been considered to be of minor clinical significance, but this belief is being increasingly challenged by recent evidence. We aimed to prospectively quantify the overall burden of disease caused by loiasis in an endemic region of Gabon, using disability-adjusted life years (DALYs). METHODS: We did a cross-sectional survey during 2017 and 2018 in rural Gabon. Volunteers underwent diagnostic tests for loiasis and were given a standardised questionnaire on symptoms. Participants reporting eye worm migration or harbouring Loa loa microfilariae were defined as loiasis positive. Morbidity-based DALYs associated with loiasis were estimated for the rural population of Gabon. FINDINGS: Between Sept 1, 2017 and May 31, 2018, 1235 participants residing in 38 villages in the Gabonese departments of Tsamba-Magotsi and Ogooué et des Lacs were screened. 626 (50·8%) of 1232 eligible participants had loiasis. 520 (42·2%) of 1232 participants reported eye worm migration. 478 (93·9%) of 509 individuals with eye worm migration also reported associated pain, and 397 (78·6%) of 505 reported vision disturbances. After correcting for age and sex, loiasis was significantly associated with a variety of symptoms, including transient painful oedema (adjusted odds ratio 1·76 [95% CI 1·37-2·26]) and arthralgia (1·30 [1·01-1·69]). Application of attributable fractions of correlating symptoms resulted in 412·9 (95% CI 273·9-567·7) morbidity-based DALYs per 100 000 people in rural Gabon. INTERPRETATION: Loiasis, with the pathognomonic sign of eye worm migration, appears to not be benign, but severely impeding to affected individuals. Furthermore, loiasis is associated with substantial morbidity, comparable to that of other neglected tropical parasitic diseases. These findings call for reconsideration of L loa as a relevant pathogen in affected populations, with a need for more concerted research and control of these infections. FUNDING: Federal Ministry of Science, Research and Economy of Austria, and the European Union.


Assuntos
Efeitos Psicossociais da Doença , Loa/isolamento & purificação , Loíase/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Criança , Pré-Escolar , Estudos Transversais , Doenças Endêmicas , Feminino , Gabão/epidemiologia , Humanos , Lactente , Loíase/parasitologia , Masculino , Pessoa de Meia-Idade , Morbidade , Prevalência , Estudos Prospectivos , Anos de Vida Ajustados por Qualidade de Vida , Inquéritos e Questionários , Adulto Jovem
18.
BMC Infect Dis ; 20(1): 284, 2020 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-32299374

RESUMO

BACKGROUND: The control of lymphatic filariasis (LF) caused by Wuchereria bancrofti in the Central African Region has been hampered by the presence of Loa loa due to severe adverse events that arise in the treatment with ivermectin. The immunochromatographic test (ICT) cards used for mapping LF demonstrated cross-reactivity with L. loa and posed the problem of delineating the LF map. To verify LF endemicity in forest areas of Cameroon where mass drug administration (MDA) has not been ongoing, we used the recently developed strategy that combined serology, microscopy and molecular techniques. METHODS: This study was carried out in 124 communities in 31 health districts (HDs) where L. loa is present. At least 125 persons per site were screened. Diurnal blood samples were investigated for circulating filarial antigen (CFA) by FTS and for L. loa microfilariae (mf) using TBF. FTS positive individuals were further subjected to night blood collection for detecting W. bancrofti. qPCR was used to detect DNA of the parasites. RESULTS: Overall, 14,446 individuals took part in this study, 233 participants tested positive with FTS in 29 HDs, with positivity rates ranging from 0.0 to 8.2%. No W. bancrofti mf was found in the night blood of any individuals but L. loa mf were found in both day and night blood of participants who were FTS positive. Also, qPCR revealed that no W. bancrofti but L.loa DNA was found with dry bloodspot. Positive FTS results were strongly associated with high L. loa mf load. Similarly, a strong positive association was observed between FTS positivity and L loa prevalence. CONCLUSIONS: Using a combination of parasitological and molecular tools, we were unable to find evidence of W. bancrofti presence in the 31 HDs, but L. loa instead. Therefore, LF is not endemic and LF MDA is not required in these districts.


Assuntos
Filariose Linfática/diagnóstico , Filariose Linfática/epidemiologia , Ivermectina/uso terapêutico , Adolescente , Adulto , Animais , Antígenos de Helmintos/sangue , Camarões/epidemiologia , Reações Cruzadas , Estudos Transversais , Feminino , Florestas , Humanos , Imunoensaio , Loa/imunologia , Loa/patogenicidade , Masculino , Administração Massiva de Medicamentos , Pessoa de Meia-Idade , Prevalência , Reação em Cadeia da Polimerase em Tempo Real , Wuchereria bancrofti/imunologia , Wuchereria bancrofti/patogenicidade , Adulto Jovem
19.
Parasit Vectors ; 13(1): 51, 2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-32033624

RESUMO

BACKGROUND: Different immune mechanisms are capable of killing developmental stages of filarial nematodes and these mechanisms are also likely to vary between the primary and a challenge infection. However, the lack of a detailed analysis of cytokine, chemokine and immunoglobulin levels in human loiasis is still evident. Therefore, detailed analysis of immune responses induced by the different developmental stages of Loa loa in immune-competent BALB/c mice will aid in the characterization of distinct immune responses that are important for the immunity against loiasis. METHODS: Different developmental stages of L. loa were obtained from human peripheral blood (microfilariae, MF), the transmitting vector, Chrysops (larval stage 3, L3) and infected immune-deficient BALB/cRAG2γc-/- mice (L4, L5, adult worms). Groups of wildtype BALB/c mice were then injected with the isolated stages and after 42 days post-infection (pi), systemic cytokine, chemokine and immunoglobulin levels were determined. These were then compared to L. loa-specific responses from in vitro re-stimulated splenocytes from individual mice. All parameters were determined using Luminex technology. RESULTS: In a pilot study, BALB/c mice cleared the different life stages of L. loa within 42 days pi and systemic cytokine, chemokine and immunoglobulin levels were equal between infected and naive mice. Nevertheless, L. loa-specific re-stimulation of splenocytes from mice infected with L5, MF or adult worms led to induction of Th2, Th17 and chemokine secretion patterns. CONCLUSIONS: This study shows that although host immunity remains comparable to naive mice, clearance of L. loa life-cycle development stages can induce immune cell memory leading to cytokine, chemokine and immunoglobulins secretion patterns which might contribute to immunity and protection against reinfection.


Assuntos
Imunidade Humoral , Estágios do Ciclo de Vida/imunologia , Loa/imunologia , Loíase/imunologia , Camundongos Endogâmicos BALB C/imunologia , Animais , Antígenos de Helmintos/sangue , Citocinas/sangue , Dípteros/parasitologia , Humanos , Imunoglobulinas/sangue , Insetos Vetores/parasitologia , Larva/parasitologia , Camundongos , Camundongos Endogâmicos BALB C/parasitologia , Doenças Negligenciadas/imunologia , Células Th17/imunologia , Células Th2/imunologia
20.
BMC Infect Dis ; 20(1): 63, 2020 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-31959110

RESUMO

BACKGROUND: Imported loiasis is a rare cause of consultation at the return of stay in central Africa, which often poses difficult diagnostic and therapeutic questions to practitioners especially those who are unaccustomed to tropical medicine. These difficulties can lead to risks for the patients especially if inappropriate treatment is given. Large series of imported loiasis are scarce. METHODS: We retrospectively studied the data including outcome in patients diagnosed with imported loiasis between 1993 and 2013 in the Paris area on the basis of a parasitological diagnosis (microfilaremia > 1/ml and/or serologic tests). We compared sub-Saharan and non sub-Saharan African patients. RESULTS: Of the 177 identified cases, 167 could be analysed. Sex ratio was 1, mean age 41 years and 83% were sub-Saharan Africans. Cameroon was the main country of exposure (62%). Incubation time may be long (up to 18 months). Of the 167 cases, 57% presented with characteristic symptoms (Calabar swellings, creeping dermatitis, eyeworm) whereas 43% were diagnosed fortuitously. Microfilaremia was evidenced in 105 patients (63%), and specific antibodies in 53%. Compared to sub-Saharan Africans, other patients were presenting less frequently with eyeworm migration and microfilaremia whereas they had higher eosinophilia and positive serology. Prevalence of Calabar swellings was not significantly different between the two groups. Cure rates were 52% with ivermectin alone, and 77% with ivermectin followed by diethylcarbamazine. No severe adverse event was reported. CONCLUSIONS: Presentation of imported loiasis varies according to ethnicity. A systematic screening should be recommended in patients with potential exposure in endemic country. Treatment with ivermectin followed by diethylcarbamazine could be a valuable option.


Assuntos
Grupo com Ancestrais do Continente Africano , Doenças Transmissíveis Importadas/etnologia , Doenças Transmissíveis Importadas/epidemiologia , Loa/imunologia , Loíase/etnologia , Loíase/epidemiologia , Adolescente , Adulto , África do Norte/etnologia , Animais , Criança , Pré-Escolar , Doenças Transmissíveis Importadas/diagnóstico , Doenças Transmissíveis Importadas/tratamento farmacológico , Dietilcarbamazina/uso terapêutico , Feminino , Humanos , Lactente , Recém-Nascido , Ivermectina/uso terapêutico , Loíase/diagnóstico , Loíase/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Paris/epidemiologia , Prevalência , Estudos Retrospectivos , Resultado do Tratamento , Medicina Tropical , Adulto Jovem
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