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1.
PLoS Negl Trop Dis ; 16(5): e0010340, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35503786

RESUMO

BACKGROUND: Annual mass drug administrations (MDA) of ivermectin will strongly reduce Onchocerca volvulus microfilariae (mf) in the skin and in the onchocerciasis patients' eyes. Ivermectin treatment will also affect the expression of immunity in patients, such that activated immune defenses may help control and contribute to clearance of mf of O. volvulus. Longitudinal surveys are a prerequisite to determining the impact of ivermectin on the status of anti-parasite immunity, notably in risk zones where parasite transmission and active O. volvulus infections persist. METHODOLOGY/PRINCIPAL FINDINGS: Onchocerciasis patients were treated annually with ivermectin and their Onchocerca volvulus antigen (OvAg) specific IgG and cellular responses were investigated before and at 30 years post initial ivermectin treatment (30yPT). Repeated annual ivermectin treatments eliminated persisting O. volvulus microfilariae (mf) from the skin of patients and abrogated patent infections. The OvAg-specific IgG1 and IgG4 responses were diminished at 30yPT to the levels observed in endemic controls. Prior to starting ivermectin treatment, OvAg-induced cellular productions of IL-10, IFN-γ, CCL13, CCL17 and CCL18 were low in patients, and at 30yPT, cellular cytokine and chemokine responses increased to the levels observed in endemic controls. In contrast, mitogen(PHA)- induced IL-10, IFN-γ, CCL17 and CCL18 cellular production was diminished. This divergent response profile thus revealed increased parasite antigen-specific but reduced polyclonal cellular responsiveness in patients. The transmission of O. volvulus continued at the patients' location in the Mô river basin in central Togo 2018 and 2019 when 0.58% and 0.45%, respectively, of Simulium damnosum s.l. vector blackflies carried O. volvulus infections. CONCLUSIONS/SIGNIFICANCE: Repeated annual ivermectin treatment of onchocerciasis patients durably inhibited their patent O. volvulus infections despite ongoing low-level parasite transmission in the study area. Repeated MDA with ivermectin affects the expression of immunity in patients. O. volvulus parasite-specific antibody levels diminished to levels seen in infection-free endemic controls. With low antibody levels, antibody-dependent cellular cytotoxic responses against tissue-dwelling O. volvulus larvae will weaken. O. volvulus antigen inducible cytokine and chemokine production increased in treated mf-negative patients, while their innate responsiveness to mitogen declined. Such lower innate responsiveness in elderly patients could contribute to reduced adaptive immune responses to parasite infections and vaccines. On the other hand, increased specific cellular chemokine responses in mf-negative onchocerciasis patients could reflect effector cell activation against tissue invasive larval stages of O. volvulus. The annual Simulium damnosum s.l. biting rate observed in the Mô river basin was similar to levels prior to initiation of MDA with ivermectin, and the positive rtPCR results reported here confirm ongoing O. volvulus transmission.


Assuntos
Volvo Intestinal , Onchocerca volvulus , Oncocercose , Parasitos , Simuliidae , Idoso , Animais , Citocinas , Humanos , Imunoglobulina G , Interleucina-10 , Ivermectina/uso terapêutico , Microfilárias , Mitógenos/uso terapêutico , Onchocerca , Simuliidae/parasitologia , Togo/epidemiologia
2.
Front Cell Infect Microbiol ; 12: 869039, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35444961

RESUMO

Human onchocerciasis is a devastating neglected tropical disease caused by infection of the filarial nematode Onchocerca volvulus. The infection can cause irreversible visual impairment or blindness and stigmatizing dermatitis. More than 32 million people were estimated to be infected with O. volvulus in Africa, and 385,000 suffered from blindness. Even though the implementation of mass drug administration (MDA) with ivermectin has reduced the global prevalence of onchocerciasis, O. volvulus infection remains challenging to control because MDA with ivermectin cannot be implemented in endemic areas co-endemic with loiasis due to the risk of severe adverse events. There is also emerging drug resistance to ivermectin that further complicates the elimination of onchocerciasis. Thus, the development of a vaccine that would induce protective immunity and reduce infection burden is essential. Efforts to develop prophylactic and/or therapeutic vaccines for onchocerciasis have been explored since the late 1980s by many researchers and entities, and here we summarize the recent advances made in the development of vaccines against the infection of O. volvulus and onchocerciasis.


Assuntos
Volvo Intestinal , Oncocercose , Vacinas , Animais , Cegueira/induzido quimicamente , Cegueira/tratamento farmacológico , Bovinos , Humanos , Volvo Intestinal/induzido quimicamente , Ivermectina/farmacologia , Ivermectina/uso terapêutico , Onchocerca , Oncocercose/tratamento farmacológico , Oncocercose/prevenção & controle , Oncocercose/veterinária
3.
PLoS Negl Trop Dis ; 16(4): e0010320, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35446859

RESUMO

BACKGROUND AND OBJECTIVES: This study reports knowledge of residents of Alabameta community, Osun State, Nigeria on the bioecology and socio-economic burden of black flies and onchocerciasis. METHODS: Using structured questionnaires and Focus Group Discussion (FGD), a total of 150 community respondents participated in the study. RESULTS: The knowledge of the residents on the existence of black flies in the community was significant (p<0.05) as all the 150 respondents confirmed the presence of black flies with the local name 'Amukuru' i.e causing itching. However, their lack of knowledge of the flies breeding site (104) (69%), prevention (134) (89%), cause (132) (88%), and treatment (133) (89%) of onchocerciasis was profound. Majority 147(98%) of the respondents reported that flies bite more in the wet season as against dry season 3(2%) and have a higher affinity (124) (82%) for biting the leg than any other part of the body. A larger percentage (89%) of the respondents are unaware of any medication for the treatment of onchocerciasis while 11% are aware. There had been no sensitization on onchocerciasis according to 89% of the respondents. CONCLUSION: Due to lack of resident's knowledge on black flies bioecology which may continuously expose them to the bite of the flies and ultimately infection, it is paramount that the Osun State government and the NTD implementing partner map out new public health education strategies during routine Mass Administration of Medicines with Ivermectin with a view to preventing onchocerciasis infection as well as man-vector contact.


Assuntos
Oncocercose , Simuliidae , Animais , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Ivermectina/uso terapêutico , Nigéria/epidemiologia , Oncocercose/tratamento farmacológico , Oncocercose/epidemiologia , Oncocercose/prevenção & controle
4.
PLoS Negl Trop Dis ; 16(4): e0010341, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35468134

RESUMO

Hyperreactive onchocerciasis (HO) is characterized by a severe skin inflammation with elevated Th17-Th2 combined responses. We previously demonstrated the anthelminthic activity of Aframomum melegueta (AM), Xylopia aethiopica (XA) and Khaya senegalensis (KS) used by traditional healers to treat helminthiasis in the endemic area of Togo. However, their effect on severe onchocerciasis is poorly investigated. The present study aimed to investigate the anti-Th17 and anti-Th2 effects of hydro-ethanolic extracts of AM, XA and KS during HO. Onchocerca volvulus-infected individuals were recruited in the Central region of Togo in 2018. Isolated peripheral blood mononuclear cells (PBMCs) from both generalized onchocerciasis (GEO) and HO forms were activated with anti-CD3 and anti-CD28 monoclonal antibodies in the presence or absence of the hydro-ethanolic extracts of AM, XA and KS as well as their delipidated, deproteinized and deglycosylated fractions. After 72 hours, cytokines were assayed from cell culture supernatants. Then, flow cytometry was used to investigate the effects of the extracts on cell activation, proliferation, intracellular cytokines and T cells transcription factors. The production of both Th17 and Th2 cytokines IL-17A and IL-5 were significantly inhibited upon T-cell receptor (TCR) activation in the presence of the hydro-ethanolic extracts of AM, XA and KS in HO individuals' PBMCs in vitro. AM and XA inhibited CD4+RORC2+IL-17A+ and CD4+GATA3+IL-4+ cell populations induction. This inhibition was not Th1 nor Treg-dependent since both IFN-γ and IL-10 were also inhibited by the extracts. AM and XA did not interfere with T cell activation and proliferation for their inhibitory pathways. Lipid and protein compounds from AM and XA were associated with the inhibition of IL-17A. This study showed that in addition to their anthelminthic effects, hydro-ethanolic extracts of Aframomum melegueta, Xylopia aethiopica and Khaya senegalensis could downregulate both Th17 and Th2 responses and prevent the severe skin disorder observed.


Assuntos
Meliaceae , Oncocercose , Xylopia , Zingiberaceae , Citocinas/metabolismo , Humanos , Interleucina-17/metabolismo , Leucócitos Mononucleares , Extratos Vegetais/farmacologia , Células Th1 , Células Th17
5.
Infect Dis Poverty ; 11(1): 47, 2022 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-35484570

RESUMO

BACKGROUND: The current mainstay for control/elimination of onchocerciasis and soil-transmitted helminthiasis (STH) relies on ivermectin- and mebendazole/albendazole-based preventive chemotherapies. However, children under five years of age have been excluded in both research activities and control programs, because they were believed to have insignificant infection rates. There is therefore a need for up-to-date knowledge on the prevalence and intensity of STH and onchocerciasis infections in this age group. This study aimed at assessing the rates and intensities of onchocerciasis and STH infections in children under five years of age who are excluded from ivermectin- or mebendazole/albendazole-based preventive chemotherapies. METHODS: A series of cross-sectional surveys was conducted in four Health Districts in the Centre and Littoral Regions of Cameroon between 2018 and 2019. All subjects aged 2 to 4 years, were screened for prevalence (or infection rate) and intensity [number of eggs per gram of stool (epg) or number of microfilariae per skin snip (mf/ss)] of STH and onchocerciasis infections respectively using the Kato-Katz and skin snip methodologies. Chi-square and the non-parametric tests (Mann Whitney and Kruskal Wallis) were used to compare infection rates and intensities of infections between Health Districts and genders, respectively. RESULTS: A total of 421 children were enrolled in this study. The overall prevalence of onchocerciasis was 6.6% [95% confidence interval (CI): 4.3‒9.9], ranging from 3.6% (in the Ntui Health District) to 12.2% (in the Bafia Health District). The intensity of infection ranged from 0.5 to 46 microfilariae per skin snip [median: 5; interquartile range (IQR): 2.25‒8.5]. The overall prevalence of STH was 9.6% (95% CI: 6.5‒13.9), with a high infection rate (29.6%) in the Akonolinga Health District. Two STH species (Ascaris lumbricoides and Trichuris trichiura) were found among infected individuals. The median intensities of STH infections were 1,992 epg (IQR: 210‒28,704) and 96 epg (IQR: 48‒168) for A. lumbricoides and T. trichiura, respectively. CONCLUSIONS: This study reveals that children < 5 years of age are highly infected with STH and onchocerciasis, and could contribute to the spread of these diseases, perpetuating a vicious circle of transmission and hampering elimination efforts. These findings reveal the urgent need to provide (or scale) treatments (likely pediatric formulations) to these preschool-aged children, especially in areas of high transmission, to accelerate efforts to reach WHO 2030 target.


Assuntos
Helmintíase , Oncocercose , Albendazol/uso terapêutico , Animais , Criança , Pré-Escolar , Estudos Transversais , Feminino , Helmintíase/tratamento farmacológico , Helmintíase/epidemiologia , Helmintíase/prevenção & controle , Humanos , Ivermectina/uso terapêutico , Masculino , Mebendazol/uso terapêutico , Oncocercose/tratamento farmacológico , Oncocercose/epidemiologia , Oncocercose/prevenção & controle , Solo
6.
PLoS Negl Trop Dis ; 16(4): e0010079, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35476631

RESUMO

BACKGROUND: Our study in CDTI-naïve areas in Nord Kivu and Ituri (Democratic Republic of the Congo, DRC), Lofa County (Liberia) and Nkwanta district (Ghana) showed that a single 8 mg moxidectin dose reduced skin microfilariae density (microfilariae/mg skin, SmfD) better and for longer than a single 150µg/kg ivermectin dose. We now analysed efficacy by study area and pre-treatment SmfD (intensity of infection, IoI). METHODOLOGY/PRINCIPAL FINDINGS: Four and three IoI categories were defined for across-study and by-study area analyses, respectively. We used a general linear model to analyse SmfD 1, 6, 12 and 18 months post-treatment, a logistic model to determine the odds of undetectable SmfD from month 1 to month 6 (UD1-6), month 12 (UD1-12) and month 18 (UD1-18), and descriptive statistics to quantitate inter-interindividual response differences. Twelve months post-treatment, treatment differences (difference in adjusted geometric mean SmfD after moxidectin and ivermectin in percentage of the adjusted geometric mean SmfD after ivermectin treatment) were 92.9%, 90.1%, 86.8% and 84.5% in Nord Kivu, Ituri, Lofa and Nkwanta, and 74.1%, 84.2%, 90.0% and 95.4% for participants with SmfD 10-20, ≥20-<50, ≥50-<80, ≥80, respectively. Ivermectin's efficacy was lower in Ituri and Nkwanta than Nord Kivu and Lofa (p≤0.002) and moxidectin's efficacy lower in Nkwanta than Nord Kivu, Ituri and Lofa (p<0.006). Odds ratios for UD1-6, UD1-12 or UD1-18 after moxidectin versus ivermectin treatment exceeded 7.0. Suboptimal response (SmfD 12 months post-treatment >40% of pre-treatment SmfD) occurred in 0%, 0.3%, 1.6% and 3.9% of moxidectin and 12.1%, 23.7%, 10.8% and 28.0% of ivermectin treated participants in Nord Kivu, Ituri, Lofa and Nkwanta, respectively. CONCLUSIONS/SIGNIFICANCE: The benefit of moxidectin vs ivermectin treatment increased with pre-treatment IoI. The possibility that parasite populations in different areas have different drug susceptibility without prior ivermectin selection pressure needs to be considered and further investigated. CLINICAL TRIAL REGISTRATION: Registered on 14 November 2008 in Clinicaltrials.gov (ID: NCT00790998).


Assuntos
Volvo Intestinal , Oncocercose , Animais , República Democrática do Congo/epidemiologia , Gana , Humanos , Ivermectina/farmacologia , Ivermectina/uso terapêutico , Libéria , Macrolídeos , Microfilárias , Oncocercose/tratamento farmacológico
7.
PLoS One ; 17(3): e0264750, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35245320

RESUMO

Ecological control of blackflies (Simulium damnosum) can be an alternative or additional tool to enhance onchocerciasis elimination efforts. However, limited research is conducted on the ecology of blackflies in Ethiopia. In this study, we determined the habitat preference of blackfly larvae and their relationship with aquatic macroinvertebrate predators in the Omo Gibe river basin of southwest Ethiopia. Environmental and biological data were collected from 150 sampling sites during both dry and wet seasons in 2019. Generalized Linear Models (GLMs) were used to identify factors affecting the occurrence and abundance of S. damnosum larvae. Canonical Correspondence Analysis (CCA) was used to investigate the relationship between environmental and biological variables and the abundance of S. damnosum larvae. The findings of this study indicated the abundance of S. damnosum larvae increased with increasing turbidity, alkalinity and altitude, but decreased with increasing concentrations of five-day Biological Oxygen Demand (BOD5), orthophosphate and magnesium ion. Both the presence and abundance of S. damnosum larvae decreased with the increasing abundance of stonefly larvae (Perlidae). Simulium damnosum larvae were found less likely in the presence of mayfly larvae (Baetidae) and were less abundant where Chironomidae are abundant. In conclusion, the findings of this study showed that the habitat preference of S. damnosum larvae is determined by environmental factors and that the presence and abundance of the larvae are affected by macroinvertebrate predators. It is essential to establish buffer zones as a part of watershed management to retain pollutants and prevent them from entering directly into water courses to improve water quality and the assemblages of macroinvertebrate predators and enhance biocontrol of blackflies.


Assuntos
Ephemeroptera , Oncocercose , Simuliidae , Animais , Ecossistema , Etiópia , Insetos , Larva , Oncocercose/epidemiologia , Rios
8.
PLoS Negl Trop Dis ; 16(3): e0010219, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35271567

RESUMO

BACKGROUND: To accelerate the progress towards onchocerciasis elimination, a macrofilaricidal drug that kills the adult parasite is urgently needed. Emodepside has shown macrofilaricidal activity against a variety of nematodes and is currently under clinical development for the treatment of onchocerciasis. The aims of this study were i) to characterize the population pharmacokinetic properties of emodepside, ii) to link its exposure to adverse events in healthy volunteers, and iii) to propose an optimized dosing regimen for a planned phase II study in onchocerciasis patients. METHODOLOGY / PRINCIPAL FINDINGS: Plasma concentration-time profiles and adverse event data were obtained from 142 subjects enrolled in three phase I studies, including a single-dose, and a multiple-dose, dose-escalation study as well as a relative bioavailability study. Nonlinear mixed-effects modeling was used to evaluate the population pharmacokinetic properties of emodepside. Logistic regression modeling was used to link exposure to drug-related treatment-emergent adverse events (TEAEs). Emodepside pharmacokinetics were well described by a transit-absorption model, followed by a 3-compartment disposition model. Body weight was included as an allometric function and both food and formulation had a significant impact on absorption rate and relative bioavailability. All drug-related TEAEs were transient, and mild or moderate in severity. An increase in peak plasma concentration was associated with an increase in the odds of experiencing a drug-related TEAE of interest. CONCLUSIONS/SIGNIFICANCE: Pharmacokinetic modeling and simulation was used to derive an optimized, body weight-based dosing regimen, which allows for achievement of extended emodepside exposures above target concentrations while maintaining acceptable tolerability margins.


Assuntos
Depsipeptídeos , Oncocercose , Adulto , Peso Corporal , Depsipeptídeos/efeitos adversos , Desenvolvimento de Medicamentos , Humanos , Oncocercose/tratamento farmacológico
9.
PLoS Negl Trop Dis ; 16(3): e0010005, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35333880

RESUMO

BACKGROUND: Onchocerciasis ("river blindness"), is a neglected tropical disease caused by the filarial nematode Onchocerca volvulus and transmitted to humans through repeated bites by infective blackflies of the genus Simulium. Moxidectin was approved by the United States Food and Drug Administration in 2018 for the treatment of onchocerciasis in people at least 12 years of age. The pharmacokinetics of orally administered moxidectin in 18- to 60-year-old men and women infected with Onchocerca volvulus were investigated in a single-center, ivermectin-controlled, double-blind, randomized, single-ascending-dose, ascending severity of infection study in Ghana. METHODOLOGY/PRINCIPAL FINDINGS: Participants were randomized to either a single dose of 2, 4 or 8 mg moxidectin or ivermectin. Pharmacokinetic samples were collected prior to dosing and at intervals up to 12 months post-dose from 33 and 34 individuals treated with 2 and 4 mg moxidectin, respectively and up to 18 months post-dose from 31 individuals treated with 8 mg moxidectin. Moxidectin plasma concentrations were determined using high-performance liquid chromatography with fluorescence detection. Moxidectin plasma AUC0-∞ (2 mg: 26.7-31.7 days*ng/mL, 4 mg: 39.1-60.0 days*ng/mL, 8 mg: 99.5-129.0 days*ng/mL) and Cmax (2mg, 16.2 to17.3 ng/mL, 4 mg: 33.4 to 35.0 ng/mL, 8 mg: 55.7 to 74.4 ng/mL) were dose-proportional and independent of severity of infection. Maximum plasma concentrations were achieved 4 hours after drug administration. The mean terminal half-lives of moxidectin were 20.6, 17.7, and 23.3 days at the 2, 4 and 8 mg dose levels, respectively. CONCLUSION/SIGNIFICANCE: We found no relationship between severity of infection (mild, moderate or severe) and exposure parameters (AUC0-∞ and Cmax), T1/2 and Tmax for moxidectin. Tmax, volume of distribution (V/F) and oral clearance (CL/F) are similar to those in healthy volunteers from Europe. From a pharmacokinetic perspective, moxidectin is an attractive long-acting therapeutic option for the treatment of human onchocerciasis.


Assuntos
Onchocerca volvulus , Oncocercose , Simuliidae , Administração Oral , Adolescente , Adulto , Animais , Feminino , Humanos , Ivermectina/uso terapêutico , Macrolídeos/uso terapêutico , Masculino , Pessoa de Meia-Idade , Oncocercose/tratamento farmacológico , Adulto Jovem
10.
Int Health ; 14(Supplement_1): i17-i23, 2022 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-35169850

RESUMO

BACKGROUND: Onchocerciasis is targeted for elimination of transmission by 2030 in at least 21 countries. To achieve this, recent and accurate data on the extent and intensity of onchocerciasis transmission are required. This will include mapping areas previously unassessed, or remapping of areas that were last visited as part surveys aiming to prevent blindness, not assess transmission in totality. There is near universal acceptance of the need to carry out these mapping reassessments, to achieve equitable and lasting elimination of onchocerciasis transmission. However, there is no consensus on how to conduct onchocerciasis elimination mapping (OEM), and little published data to inform policymakers and programme managers, including on cost. METHODS: Here, we summarise the methods and cost implications of conducting pilot OEM surveys in Ghana and Nigeria in 2018. We have included a breakdown of costs incurred overall, per person and per implementation unit in each country, as well as detailed analysis of the cost categories and the main cost drivers. RESULTS: The procurement and logistics of diagnostics accounted for more than one-third of the total cost, a significant cost driver. CONCLUSIONS: This information will be valuable to policymakers and donors as they seek to prioritise onchocerciasis elimination and plan to complete OEM.


Assuntos
Oncocercose , Custos e Análise de Custo , Erradicação de Doenças/métodos , Estudos de Viabilidade , Humanos , Ivermectina/uso terapêutico , Oncocercose/prevenção & controle
11.
PLoS Negl Trop Dis ; 16(2): e0010182, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35139077

RESUMO

INTRODUCTION: Onchocerciasis, a neglected tropical disease of public health importance, causes chronic morbidity and severe disability that may impact on health-related quality of life (HRQoL) of the infected people. This study assessed the HRQoL and associated factors among onchocerciasis patients in southeast Nigeria. METHODS: This was a community-based cross-sectional comparative study. Using a multistage sampling technique, 340 onchocerciasis patients were selected and matched for age and gender with the healthy population in the same neighbourhood. The respondents were interviewed using the short-form-36 (SF-36) questionnaire to determine their HRQoL. WHO Disability Assessment Schedule 2.0 tool (WHODAS 2.0) was used to assess disability in persons with onchocerciasis. Means were compared with independent student t-test while Chi-square test was used to compare proportions. Also, correlation analysis and logistic regression were used in the analyses. RESULTS: A significantly lower proportion of people living with onchocerciasis had a good quality of life when compared with the healthy subjects (69.4% vs 93.5%, p<0.001). Also, an inverse relationship was seen between disability and quality of life in the onchocerciasis group (r = -0.647, p<0.001). Predictors of poor quality of life among respondents with onchocerciasis were: respondents aged ≥48 years (AOR = 2.5, 95% CI: 1.4-5.0), those with some disability associated with onchocerciasis (AOR = 3.33, 95%CI: 1.4-5.0) and respondents who perceived themselves as a burden to people (AOR = 10, 95%CI: 2.5-20). CONCLUSION: Onchocerciasis impacted negatively on HRQoL of persons with onchocerciasis when compared with the healthy population. The quality of life of persons affected with onchocerciasis reduces with increasing disability. There is the need to increase community awareness on onchocerciasis to ensure early diagnosis and prompt treatment as this will reduce disability among those affected with the disease thus enhancing their HRQoL.


Assuntos
Pessoas com Deficiência/estatística & dados numéricos , Oncocercose/psicologia , Qualidade de Vida , Adulto , Atitude , Estudos de Casos e Controles , Efeitos Psicossociais da Doença , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nigéria/epidemiologia , Oncocercose/epidemiologia , Inquéritos e Questionários
12.
PLoS One ; 17(2): e0263625, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35143567

RESUMO

Community-directed treatment with ivermectin (CDTi) is the primary strategy employed to control and eliminate human onchocerciasis in Ethiopia. After long-term mass distribution for onchocerciasis, ivermectin is expected to have additional benefits beyond the envisioned targets by reducing the burden of other co-endemic parasitic infections as to STHs. To date, studies focused on the collateral impact of CDTi on STH in Ethiopia are scanty. Two community-based cross-sectional surveys (baseline in 1997 and post-CDTi in 2017) were conducted to evaluate the impact of long-term CDTi employed to control and eliminate onchocerciasis on the burden of STH infections in Yeki district of southwest Ethiopia. Stool samples were collected and examined using Ritchie`s concentration and Kato-Katz techniques in the baseline and current study, respectively. Overall, 188(38.3%, 95% Confidence interval (CI) 34.1-42.7%) individuals were positive at least for any of the STH species from 491 study participants in the post-CDTi. The prevalence of A. lumbricoides, hookworms, and T. trichiura was 11.2% (95% CI 8.7-14.3%), 16.3% (95% CI 13.3-19.8%), and 29.9% (95% CI 26.1-34.1%), respectively. Individuals aged 5-9 years had a significantly higher prevalence of A. lumbricoides (Adjusted odds ratio (AOR) 6.5, 95% CI 1.7-25.4), T. trichuria (AOR 8, 95% CI 2.6-25.1), and any STH infection (AOR 5, 95% CI 1.7-14.7) than those of ≥ 51 years. Also, significantly higher prevalences of T. trichuria infection were observed in individuals aged 10-14 years (AOR 4.1, 95% CI 1.7-9.9), 15-20 years (AOR 3.1, 95% CI 1.2-8.1), 21-30 years (AOR 2.4, 95% CI 1.1-5.5), and 31-40 years (AOR 3.2, 95% CI 1.3-7.5) compared with those of ≥ 51 years. The prevalence of A. lumbricoides was significantly higher in males (AOR 0.5, 95% CI 0.3-0.9). Of the 491 study participants, only data from 400 individuals who had not been involved in a mass drug administration (MDA) with other STH anthelmintics were considered in the comparative analysis. Before CDTi, the prevalence of A. lumbricoides, T. trichiura, hookworm, and any STH infection was 47.1% (95% CI 41.6-52.7%), 3.3% (95% CI 1.8-5.9%), 37.9% (95% CI 32.7-43.5%), and 58.8% (95% CI 53.2-64.1%), respectively. Long-term CDTi considerably reduced the prevalences of A. lumbricoides and hookworm by 76.2% and 56.9%, respectively (p < 0.001). Nonetheless, CDTi did not affect the prevalence of T. trichiura infection and, in contrast, it was significantly higher in the current study (P < 0.001). Overall post-CDTi prevalence of any STH infection was considerably lower than reported in the baseline (p < 0.001). It is evidenced that long-term CDTi for onchocerciasis control and elimination had additional benefits by reducing the prevalence of STH infections specifically of A. lumbricoides and hookworm, but had no impact on infections with T. trichuria. Our finding of additional health benefits of large-scale ivermectin administration taking it will aid to increase positive engagement and sustain participation of communities during MDA campaigns, and strengthen governmental and non-governmental organizations (NGOs) support for the undergoing national onchocerciasis elimination program.


Assuntos
Helmintíase/epidemiologia , Helmintos/classificação , Ivermectina/administração & dosagem , Oncocercose/prevenção & controle , Solo/parasitologia , Adolescente , Adulto , Fatores Etários , Animais , Criança , Estudos Transversais , Etiópia/epidemiologia , Fezes/parasitologia , Feminino , Helmintíase/classificação , Helmintos/efeitos dos fármacos , Helmintos/isolamento & purificação , Humanos , Ivermectina/farmacologia , Masculino , Administração Massiva de Medicamentos , Pessoa de Meia-Idade , Prevalência , Caracteres Sexuais , Adulto Jovem
13.
PLoS Negl Trop Dis ; 16(2): e0010189, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35139080

RESUMO

The elimination of onchocerciasis through community-based Mass Drug Administration (MDA) of ivermectin (Mectizan) is hampered by co-endemicity of Loa loa, as individuals who are highly co-infected with Loa loa parasites can suffer serious and occasionally fatal neurological reactions from the drug. The test-and-not-treat strategy of testing all individuals participating in MDA has some operational constraints including the cost and limited availability of LoaScope diagnostic tools. As a result, a Loa loa Antibody (Ab) Rapid Test was developed to offer a complementary way of determining the prevalence of loiasis. We develop a joint geostatistical modelling framework for the analysis of Ab and Loascope data to delineate whether an area is safe for MDA. Our results support the use of a two-stage strategy, in which Ab testing is used to identify areas that, with acceptably high probability, are safe or unsafe for MDA, followed by Loascope testing in areas whose safety status is uncertain. This work therefore contributes to the global effort towards the elimination of onchocerciasis as a public health problem by potentially reducing the time and cost required to establish whether an area is safe for MDA.


Assuntos
Antiparasitários/uso terapêutico , Coinfecção/tratamento farmacológico , Ivermectina/uso terapêutico , Loa/efeitos dos fármacos , Loíase/tratamento farmacológico , Oncocercose/tratamento farmacológico , Animais , Anticorpos Anti-Helmínticos/sangue , Antiparasitários/efeitos adversos , Coinfecção/epidemiologia , Coinfecção/parasitologia , Feminino , Humanos , Ivermectina/efeitos adversos , Loa/genética , Loa/fisiologia , Loíase/epidemiologia , Loíase/parasitologia , Masculino , Administração Massiva de Medicamentos/efeitos adversos , Modelos Estatísticos , Onchocerca/efeitos dos fármacos , Onchocerca/genética , Onchocerca/fisiologia , Oncocercose/epidemiologia , Oncocercose/parasitologia
14.
Epilepsy Behav ; 128: 108568, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35101841

RESUMO

BACKGROUND: Throughout Africa, epilepsy is a highly stigmatized condition. It is often considered to be contagious. This study aimed to assess community knowledge, attitude, and practices toward epilepsy in four villages namely Mdindo, Msogezi, Mzelezi, and Sali within Mahenge division, in Morogoro region, Tanzania. These villages are located in an onchocerciasis-endemic area with a high prevalence of epilepsy. METHODS: A qualitative cross-sectional study was conducted between June and July 2019 within the framework of a multi-disciplinary research project investigating the association between onchocerciasis and epilepsy. Focus group discussions (FGDs) and in-depth interviews (IDIs) were held with persons with epilepsy (PWE) and their caretakers, community resource persons, and program coordinators of the neglected tropical diseases program. RESULTS: The main symptoms of epilepsy were well described by all participants in all villages. PWE and caretakers in all villages considered epilepsy to be a major health problem and some participants ranked it second in importance after malaria. The reported perceived causes of epilepsy included febrile seizures during childhood (locally known as degedege), heredity, evil spirits, and inhaling flatus or touching secretions from PWE, especially during seizures. Knowledge about the association between epilepsy and onchocerciasis was low. People with epilepsy are disregarded, stigmatized, and marginalized from various opportunities such as conjugal rights, schooling, leadership roles, and property inheritance. Traditional healers are often the first contact when seeking care after a person develops epilepsy. CONCLUSION: Epilepsy is a major health burden and public health concern in the Mahenge area. The negative attitudes toward PWE and misconceptions about the causes of epilepsy contribute to delays in seeking care at health facilities. Findings from this study will be used to optimize the comprehensive community-based epilepsy treatment program that was recently initiated in the area.


Assuntos
Epilepsia , Conhecimentos, Atitudes e Prática em Saúde , Estudos Transversais , Doenças Endêmicas , Epilepsia/epidemiologia , Epilepsia/psicologia , Epilepsia/terapia , Humanos , Oncocercose/epidemiologia , Prevalência , Pesquisa Qualitativa , Estigma Social , Tanzânia/epidemiologia
15.
Epilepsy Behav ; 127: 108537, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35026562

RESUMO

OBJECTIVE: To assess the community's perception of epilepsy and its treatment in onchocerciasis-endemic villages of Maridi County, Western Equatoria State, South Sudan. The study was conducted prior to the setting up of a community-based intervention to manage the important disease burden caused by onchocerciasis-associated epilepsy in these villages. METHOD: Five focus group discussions (FGD) were conducted with community leaders and with persons with epilepsy (PWE) and their families between November and December 2019. RESULTS: Villages close to the Maridi dam were considered to be most affected by epilepsy. Misconceptions about the cause and treatment of epilepsy were identified. Most people believed that epilepsy is caused by bad spirits and is contagious, transmitted through saliva, air, and contact with PWE. Very few participants were aware of the link between onchocerciasis and epilepsy. Persons with epilepsy are restricted in their day-to-day activities and children with epilepsy are often denied going to school. Persons with epilepsy are stigmatized and seen as unfit for marriage. Most participants considered both traditional and medical treatment as ineffective. Uninterrupted anti-seizure treatment continuously was unaffordable for most families with one or more PWE. CONCLUSION: There is a need to establish a comprehensive epilepsy treatment program which addresses misconceptions about epilepsy and reduces epilepsy-related stigma. Explaining the link between onchocerciasis and epilepsy could lead to a reduction in epilepsy-related stigma.


Assuntos
Epilepsia , Oncocercose , Criança , Epilepsia/complicações , Epilepsia/epidemiologia , Epilepsia/terapia , Humanos , Oncocercose/complicações , Oncocercose/epidemiologia , Percepção , Convulsões/complicações , Sudão do Sul/epidemiologia
16.
Parasitol Res ; 121(4): 1199-1206, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35006317

RESUMO

The filarial nematode Onchocerca volvulus causes onchocerciasis (river blindness), a neglected tropical disease affecting 21 million people, mostly in Sub-Saharan Africa. Targeting the endosymbiont Wolbachia with antibiotics leads to permanent sterilization and killing of adult worms. The gold standard to assess Wolbachia depletion is the histological examination of adult worms in nodules beginning at 6 months post-treatment. However, nodules can only be used once, limiting the time points to monitor Wolbachia depletion. A diagnostic to longitudinally monitor Wolbachia depletion from microfilariae (MF) at more frequent intervals < 6 months post-treatment would accelerate clinical trials of antiwolbachials. We developed a TaqMan qPCR amplifying the single-copy gene wOvftsZ to quantify Wolbachia from as few as one MF that had migrated from skin biopsies and compared quantification using circular and linearized plasmids or synthetic dsDNA (gBlock®). qPCR for MF from the rodent nematode Litomosoides sigmodontis was used to support the reproducibility and validate the principle. The qPCR using as few as 2 MF from O. volvulus and L. sigmodontis reproducibly quantified Wolbachia. Use of a linearized plasmid standard or synthesized dsDNA resulted in numbers of Wolbachia/MF congruent with biologically plausible estimates in O. volvulus and L. sigmodontis MF. The qPCR assay yielded a median of 48.8 (range 1.5-280.5) Wolbachia/O. volvulus MF. The qPCR is a sensitive tool for quantifying Wolbachia in a few MF from skin biopsies and allows for establishing the qPCR as a surrogate parameter for monitoring Wolbachia depletion in adult worms of new antiwolbachial candidates.


Assuntos
Filarioidea , Volvo Intestinal , Onchocerca volvulus , Oncocercose , Wolbachia , Animais , Humanos , Microfilárias , Onchocerca , Onchocerca volvulus/genética , Oncocercose/tratamento farmacológico , Reprodutibilidade dos Testes , Wolbachia/genética
17.
Neuroepidemiology ; 56(2): 127-137, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35045422

RESUMO

INTRODUCTION: In resource-limited countries, epilepsy prevalence is underestimated and little is known about its risk factors. OBJECTIVES: This study aimed to determine the prevalence and risk factors for epilepsy in six health districts (HDs) in Mali. METHODS: A community-based cross-sectional and nested case-control study was conducted in 180 villages with the highest number of suspicious epilepsy cases (SECs) in the six study HDs. The SECs were observed as part of a Phase 1 screening conducted by community health workers. For the nested case-control study, one case was matched with at least one control based on residence and age. A case of epilepsy was a person diagnosed with convulsive epilepsy after clinical assessment by a neurologist. A control was a person diagnosed as normal after neurological assessment by a neurologist. Data were collected on sociodemographic characteristics, familial and medical history of epilepsy, consanguinity, place of delivery, preterm birth, length/type of delivery, and history of meningitis and cerebral malaria. A univariate and multivariate binomial logistic regression model was used to analyse factors associated with epilepsy. RESULTS: A total of 1,506 cases of epilepsy and 2,199 controls were enrolled in six HDs. The mean prevalence of epilepsy was 2‰, with the highest in Kenieba (3‰), a previously meso-endemic-onchocerciasis HD, and the lowest in Kadiolo (1.5‰), a hypo-endemic-onchocerciasis HD. Age (adjusted odds ratio [aOR] = 1.02 [95% confidence intervals [CI] 1.02-1.03]), history of cerebral malaria (aOR = 11.41 [95% CI 8.86-14.85]), history of meningitis (aOR = 1.95 [95% CI 1.16-3.29]), living in the HD of Tominian (aOR = 1.69 [95% CI 1.29-2.22]), delayed delivery (aOR = 3.21 [95% CI 2.07-5.07]), and dystocia (aOR = 3.37 [95% CI 2.03-5.73]) were all significantly associated with epilepsy. CONCLUSION: The prevalence of epilepsy (3‰) in a previously meso-endemic-onchocerciasis HD was much lower than the prevalence (13.35‰) documented in onchocerciasis endemic areas in 2,000. This decrease epilepsy prevalence in the previously meso-endemic region was induced by onchocerciasis, and the reduction was due to an effective community direct treatment with ivermectin programme. Cerebral malaria and obstetrical complications were the main risk factors for epilepsy and interventions improving malaria prevention/treatment and optimizing prenatal and obstetrical care need to be implemented to reduce incidence.


Assuntos
Epilepsia , Malária Cerebral , Oncocercose , Nascimento Prematuro , Estudos de Casos e Controles , Estudos Transversais , Epilepsia/diagnóstico , Feminino , Humanos , Recém-Nascido , Malária Cerebral/complicações , Mali/epidemiologia , Oncocercose/complicações , Oncocercose/tratamento farmacológico , Oncocercose/epidemiologia , Gravidez , Prevalência , Fatores de Risco
18.
Int J Infect Dis ; 116: 302-305, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35074518

RESUMO

Efforts are being directed toward the elimination of onchocerciasis transmission in endemic areas with community-directed treatment with ivermectin (CDTI) in Africa, which greatly reduces onchocerciasis-associated disease. However, onchocerciasis remains a major public health problem in areas of South Sudan, the Democratic Republic of the Congo, Cameroon, and the Central African Republic. Strengthening onchocerciasis elimination efforts in areas with a high prevalence of disease burden is crucial to decrease transmission, morbidity, and mortality. We argue that clinical trials are needed to investigate the safety and efficacy of ivermectin treatment of Onchocerca volvulus-infected pregnant women and children younger than 5 years. Crucially, 6-monthly administration of ivermectin in school-age children at risk of onchocerciasis-associated epilepsy could be achieved by supplementing annual CDTI with an extra round of ivermectin treatment during Child Health Days in schools and/or other distribution sites every year. These strategies would help achieve the elimination of onchocerciasis and its associated disease burden.


Assuntos
Onchocerca volvulus , Oncocercose , Animais , Camarões/epidemiologia , Criança , Feminino , Humanos , Ivermectina/uso terapêutico , Oncocercose/complicações , Oncocercose/tratamento farmacológico , Oncocercose/epidemiologia , Gravidez , Prevalência
19.
PLoS Negl Trop Dis ; 16(1): e0010108, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35020729

RESUMO

BACKGROUND: In onchocerciasis endemic areas in Africa, heterogenous biting rates by blackfly vectors on humans are assumed to partially explain age- and sex-dependent infection patterns with Onchocerca volvulus. To underpin these assumptions and further improve predictions made by onchocerciasis transmission models, demographic patterns in antibody responses to salivary antigens of Simulium damnosum s.l. are evaluated as a measure of blackfly exposure. METHODOLOGY/PRINCIPAL FINDINGS: Recently developed IgG and IgM anti-saliva immunoassays for S. damnosum s.l. were applied to blood samples collected from residents in four onchocerciasis endemic villages in Ghana. Demographic patterns in antibody levels according to village, sex and age were explored by fitting generalized linear models. Antibody levels varied between villages but showed consistent patterns with age and sex. Both IgG and IgM responses declined with increasing age. IgG responses were generally lower in males than in females and exhibited a steeper decline in adult males than in adult females. No sex-specific difference was observed in IgM responses. CONCLUSIONS/SIGNIFICANCE: The decline in age-specific antibody patterns suggested development of immunotolerance or desensitization to blackfly saliva antigen in response to persistent exposure. The variation between sexes, and between adults and youngsters may reflect differences in behaviour influencing cumulative exposure. These measures of antibody acquisition and decay could be incorporated into onchocerciasis transmission models towards informing onchocerciasis control, elimination, and surveillance.


Assuntos
Anticorpos/sangue , Mordeduras e Picadas de Insetos/epidemiologia , Saliva/imunologia , Simuliidae/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Criança , Pré-Escolar , Feminino , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Insetos Vetores/imunologia , Insetos Vetores/parasitologia , Masculino , Pessoa de Meia-Idade , Onchocerca volvulus/crescimento & desenvolvimento , Oncocercose/epidemiologia , Oncocercose/transmissão , Simuliidae/parasitologia , Adulto Jovem
20.
Trans R Soc Trop Med Hyg ; 116(3): 201-212, 2022 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-34323283

RESUMO

Ivermectin is a broad-spectrum antiparasitic agent that interferes with glutamate-gated chloride channels found in invertebrates but not in vertebrate species. Mass drug administration (MDA) with ivermectin-based regimes has been a mainstay of elimination efforts targeting onchocerciasis and lymphatic filariasis for more than 3 decades. More recently, interest in the use of ivermectin to control other neglected tropical diseases (NTDs) such as soil-transmitted helminths and scabies has grown. Interest has been further stimulated by the fact that ivermectin displays endectocidal efficacy against various Anopheles species capable of transmitting malaria. Therefore there is growing interest in using ivermectin MDA as a tool that might aid in the control of both malaria and several NTDs. In this review we outline the evidence base to date on these emerging indications for ivermectin MDA with reference to clinical and public health data and discuss the rationale for evaluating the range of impacts of a malaria ivermectin MDA on other NTDs.


Assuntos
Malária , Oncocercose , Escabiose , Animais , Antiparasitários/farmacologia , Antiparasitários/uso terapêutico , Humanos , Ivermectina/farmacologia , Ivermectina/uso terapêutico , Malária/tratamento farmacológico , Doenças Negligenciadas/tratamento farmacológico , Oncocercose/tratamento farmacológico , Escabiose/tratamento farmacológico
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