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27 pages, 1879 KiB  
Article
Syndemic Synergy of HPV, HIV, and HSV-2 for Oncogenic HPV Replication in Female Sex Workers
by Jonathan Muwonga Tukisadila, Ralph-Sydney Mboumba Bouassa, Serge Tonen-Wolyec, Hugues Loemba, Jeremie Muwonga and Laurent Belec
Trop. Med. Infect. Dis. 2025, 10(6), 157; https://doi.org/10.3390/tropicalmed10060157 - 7 Jun 2025
Viewed by 1498
Abstract
Background: Female sex workers (FSWs) in sub-Saharan Africa bear a disproportionate burden of sexually transmitted infections, including HIV, high-risk HPV (HR-HPV), and herpes simplex virus type 2 (HSV-2). This study evaluated possible association between HR-HPV, HIV, and HSV-2 among FSWs in the Democratic [...] Read more.
Background: Female sex workers (FSWs) in sub-Saharan Africa bear a disproportionate burden of sexually transmitted infections, including HIV, high-risk HPV (HR-HPV), and herpes simplex virus type 2 (HSV-2). This study evaluated possible association between HR-HPV, HIV, and HSV-2 among FSWs in the Democratic Republic of the Congo. Methods: A cross-sectional study was conducted among 432 FSWs (mean age, 28.1 years) recruited via respondent-driven sampling. Genital self-sampling using the V-Veil UP2™ device was performed, followed by HPV genotyping and quantification by multiplex PCR, and HSV-2 DNA detection by PCR. Results: Among 415 participants, HR-HPV prevalence was 36.9%, with HPV-52 (14.9%), HPV-58 (10.1%), and HPV-16 (6.5%) as leading genotypes. Overall, 89% of HR-HPV-positive women harbored genotypes covered by Gardasil-9®. Co-infection with HIV and HSV-2 significantly increased HPV prevalence, genotype diversity, and viral load. Notably, HSV-2 positivity was the sole independent predictor of elevated replication of HR-HPV (p < 0.001), vaccine HR-HPV (p < 0.001), and non-vaccine HR-HPV (p < 0.021). Conclusions: FSWs exhibit a high burden of HR-HPV, shaped by co-infections with HIV and HSV-2. HSV-2 independently drives HR-HPV replication, highlighting its role in HPV persistence and cervical cancer risk. Integrated HSV-2 detection and Gardasil-9® vaccination should be prioritized in cervical cancer elimination strategies targeting high-risk populations in sub-Saharan Africa. Full article
(This article belongs to the Special Issue HIV Testing, Prevention and Care Interventions, 2nd Edition)
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15 pages, 1369 KiB  
Article
Successful Retrieval of Human Papillomavirus DNA in Veil-Based Collected Female Genital Secretions After Long-Term Storage in Universal Transport Medium
by Jonathan Muwonga Tukisadila, Juval Avala Ntsigouaye, Serge Tonen-Wolyec, Ralph-Sydney Mboumba Bouassa, Jeremie Muwonga and Laurent Belec
Diagnostics 2025, 15(9), 1079; https://doi.org/10.3390/diagnostics15091079 - 24 Apr 2025
Viewed by 814
Abstract
Background/Objectives: The surveillance of viral strain evolution is needed during prophylactic HPV vaccination programs against cervical cancer and necessitates safely archiving and storing cervical samples while maintaining the long-term stability of HPV DNA to carry out molecular diagnosis. The present proof-of-concept study [...] Read more.
Background/Objectives: The surveillance of viral strain evolution is needed during prophylactic HPV vaccination programs against cervical cancer and necessitates safely archiving and storing cervical samples while maintaining the long-term stability of HPV DNA to carry out molecular diagnosis. The present proof-of-concept study aimed to assess DNA stability for HPV molecular detection from veils resuspended in a universal transport medium (UTM) and conserved at different temperatures after long-term storage. Methods: The detection and quantification of HPV DNA were evaluated in female genital secretions self-collected using veils and conserved in Cyt-All® UTM at −30 °C, +4 °C, and +25 °C after long-term 27-month storage. Results: A slight degradation of the ubiquitous single-copy cellular DNA TOP3 gene was assessed using multiplex real-time PCR (BMRT Human Papillomavirus Genotyping Real Time PCR Kit, Bioperfectus Technologies Co., Ltd., Taizhou, Jiangsu, China) at positive temperatures (+4 °C and +25 °C) but not at a frozen temperature (−30 °C) after 27 months of storage. Nevertheless, HPV DNA preservation was sufficient at the three storage temperatures to detect and quantify HPV DNA, with a similar rate of HPV detection, a similar level of cumulative HPV viral loads, high sensitivity and specificity, and perfect concordance in HPV genotype detection after the long period of 27 months of storage. Finally, the conservation of genital samples for a prolonged period in the Cyt-All® medium, even at room temperature, allows for the detection and quantification of any HPV and HR-HPV with high accuracy. Conclusions: The combination of veil-based self-sampling of female genital secretions and their elution and conservation in UTM may be used in the field to carry out longitudinal molecular epidemiology surveys of circulating HPV. Full article
(This article belongs to the Special Issue Dermatology and Venereology: Diagnosis and Management)
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16 pages, 17976 KiB  
Technical Note
Advanced Detection of Invasive Neophytes in Agricultural Landscapes: A Multisensory and Multiscale Remote Sensing Approach
by Florian Thürkow, Christopher Günter Lorenz, Marion Pause and Jens Birger
Remote Sens. 2024, 16(3), 500; https://doi.org/10.3390/rs16030500 - 28 Jan 2024
Cited by 6 | Viewed by 2090
Abstract
The sustainable provision of ecological products and services, both natural and man-made, faces a substantial threat emanating from invasive plant species (IPS), which inflict considerable economic and ecological harm on a global scale. They are widely recognized as one of the primary drivers [...] Read more.
The sustainable provision of ecological products and services, both natural and man-made, faces a substantial threat emanating from invasive plant species (IPS), which inflict considerable economic and ecological harm on a global scale. They are widely recognized as one of the primary drivers of global biodiversity decline and have become the focal point of an increasing number of studies. The integration of remote sensing (RS) and geographic information systems (GIS) plays a pivotal role in their detection and classification across a diverse range of research endeavors, emphasizing the critical significance of accounting for the phenological stages of the targeted species when endeavoring to accurately delineate their distribution and occurrences. This study is centered on this fundamental premise, as it endeavors to amass terrestrial data encompassing the phenological stages and spectral attributes of the specified IPS, with the overarching objective of ascertaining the most opportune time frames for their detection. Moreover, it involves the development and validation of a detection and classification algorithm, harnessing a diverse array of RS datasets, including satellite and unmanned aerial vehicle (UAV) imagery spanning the spectrum from RGB to multispectral and near-infrared (NIR). Taken together, our investigation underscores the advantages of employing an array of RS datasets in conjunction with the phenological stages, offering an economically efficient and adaptable solution for the detection and monitoring of invasive plant species. Such insights hold the potential to inform both present and future policymaking pertaining to the management of invasive species in agricultural and natural ecosystems. Full article
(This article belongs to the Special Issue Remote Sensing for Management of Invasive Species)
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14 pages, 1231 KiB  
Protocol
Procedure for Handling and Storage of Onchocerca volvulus Microfilariae Obtained from Skin Snips for Downstream Genetic Work
by Shannon M. Hedtke, Anusha Kode, Tony O. Ukety, Jöel L. Mande, Germain M. Abhafule, Anuarite A. Raciu, Claude B. Uvon, Stephen R. Jada, An Hotterbeekx, Joseph Nelson Siewe Fodjo, Makedonka Mitreva, Wilson Sebit, Robert Colebunders, Warwick N. Grant and Annette C. Kuesel
Trop. Med. Infect. Dis. 2023, 8(9), 445; https://doi.org/10.3390/tropicalmed8090445 - 12 Sep 2023
Cited by 3 | Viewed by 2724
Abstract
WHO and endemic countries target elimination of transmission of Onchocerca volvulus, the parasite causing onchocerciasis. Population genetic analysis of O. volvulus may provide data to improve the evidence base for decisions on when, where, and for how long to deploy which interventions [...] Read more.
WHO and endemic countries target elimination of transmission of Onchocerca volvulus, the parasite causing onchocerciasis. Population genetic analysis of O. volvulus may provide data to improve the evidence base for decisions on when, where, and for how long to deploy which interventions and post-intervention surveillance to achieve elimination. Development of necessary methods and tools requires parasites suitable for genetic analysis. Based on our experience with microfilariae obtained from different collaborators, we developed a microfilariae transfer procedure for large-scale studies in the Democratic Republic of Congo (DRC) comparing safety and efficacy of ivermectin, the mainstay of current onchocerciasis elimination strategies, and moxidectin, a new drug. This procedure is designed to increase the percentage of microfilariae in skin snips suitable for genetic analysis, improve assignment to metadata, and minimize time and materials needed by the researchers collecting the microfilariae. Among 664 microfilariae from South Sudan, 35.7% and 39.5% failed the mitochondrial and nuclear qPCR assay. Among the 576 microfilariae from DRC, 16.0% and 16.7% failed these assays, respectively. This difference may not only be related to the microfilariae transfer procedure but also to other factors, notably the ethanol concentration in the tubes in which microfilariae were stored (64% vs. ≥75%). Full article
(This article belongs to the Section Neglected and Emerging Tropical Diseases)
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20 pages, 1592 KiB  
Article
Assessing Onchocerca volvulus Intensity of Infection and Genetic Diversity Using Mitochondrial Genome Sequencing of Single Microfilariae Obtained before and after Ivermectin Treatment
by Shannon M. Hedtke, Young-Jun Choi, Anusha Kode, Gowtam C. Chalasani, Neha Sirwani, Stephen R. Jada, An Hotterbeekx, Michel Mandro, Joseph N. Siewe Fodjo, Glory Ngongeh Amambo, Raphael A. Abong, Samuel Wanji, Annette C. Kuesel, Robert Colebunders, Makedonka Mitreva and Warwick N. Grant
Pathogens 2023, 12(7), 971; https://doi.org/10.3390/pathogens12070971 - 24 Jul 2023
Cited by 7 | Viewed by 2907
Abstract
Onchocerciasis is a neglected tropical disease targeted for elimination using ivermectin mass administration. Ivermectin kills the microfilariae and temporarily arrests microfilariae production by the macrofilariae. We genotyped 436 microfilariae from 10 people each in Ituri, Democratic Republic of the Congo (DRC), and Maridi [...] Read more.
Onchocerciasis is a neglected tropical disease targeted for elimination using ivermectin mass administration. Ivermectin kills the microfilariae and temporarily arrests microfilariae production by the macrofilariae. We genotyped 436 microfilariae from 10 people each in Ituri, Democratic Republic of the Congo (DRC), and Maridi County, South Sudan, collected before and 4–5 months after ivermectin treatment. Population genetic analyses identified 52 and 103 mitochondrial DNA haplotypes among the microfilariae from DRC and South Sudan, respectively, with few haplotypes shared between people. The percentage of genotype-based correct assignment to person within DRC was ~88% and within South Sudan ~64%. Rarefaction and extrapolation analysis showed that the genetic diversity in DRC, and even more so in South Sudan, was captured incompletely. The results indicate that the per-person adult worm burden is likely higher in South Sudan than DRC. Analyses of haplotype data from a subsample (n = 4) did not discriminate genetically between pre- and post-treatment microfilariae, confirming that post-treatment microfilariae are not the result of new infections. With appropriate sampling, mitochondrial haplotype analysis could help monitor changes in the number of macrofilariae in a population as a result of treatment, identify cases of potential treatment failure, and detect new infections as an indicator of continuing transmission. Full article
(This article belongs to the Section Parasitic Pathogens)
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16 pages, 813 KiB  
Article
Moderating Effect of Business Environmental Dynamism in the Innovativeness—Company Performance Relationship of Congolese Manufacturing Companies
by Remo Metalor Ruba, Germinah E. Chiloane-Tsoka and Thea Van der Westhuizen
Economies 2023, 11(7), 191; https://doi.org/10.3390/economies11070191 - 14 Jul 2023
Cited by 6 | Viewed by 3388
Abstract
Research has shown that innovativeness is a key factor in business performance. However, the link between innovativeness and organisational performance and the role of environmental dynamism are still being debated. This study thus sought to analyse the moderating effect of the dynamism of [...] Read more.
Research has shown that innovativeness is a key factor in business performance. However, the link between innovativeness and organisational performance and the role of environmental dynamism are still being debated. This study thus sought to analyse the moderating effect of the dynamism of the business environment in the relationship between innovativeness and performance of manufacturing companies. In order to do this, a questionnaire was distributed to 344 owners and managers of manufacturing companies operating in the north-eastern Democratic Republic of Congo. One hundred and seventy-eight of these questionnaires were returned and used to test the study’s hypotheses. The study used an ordinary least squares (OLS) regression under the hierarchical regression analysis approach. The results confirm the positive and significant effect of innovativeness on company performance. On the other hand, results indicate that business environmental dynamism has a direct positive and significant effect on company performance. However, the dynamism of the business environment negatively influences the relationship between innovativeness and company performance. Based on these results, recommendations and further research perspectives are suggested. Full article
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10 pages, 1112 KiB  
Article
Determinants of Survival of HIV Patients Receiving Dolutegravir: A Prospective Cohort Study in Conflict-Affected Bunia, Democratic Republic of Congo
by Roger T. Buju, Pierre Z. Akilimali, Nguyen-Toan Tran, Erick N. Kamangu, Gauthier K. Mesia, Jean Marie N. Kayembe and Hippolyte N. Situakibanza
Int. J. Environ. Res. Public Health 2022, 19(16), 10220; https://doi.org/10.3390/ijerph191610220 - 17 Aug 2022
Cited by 6 | Viewed by 2225
Abstract
This study aims to determine the factors influencing HIV-related mortality in settings experiencing continuous armed conflict atrocities. In such settings, people living with HIV (PLHIV), and the partners of those affected may encounter specific difficulties regarding adherence to antiretroviral therapy (ART), and retention [...] Read more.
This study aims to determine the factors influencing HIV-related mortality in settings experiencing continuous armed conflict atrocities. In such settings, people living with HIV (PLHIV), and the partners of those affected may encounter specific difficulties regarding adherence to antiretroviral therapy (ART), and retention in HIV prevention, treatment, and care programs. Between July 2019 and July 2021, we conducted an observational prospective cohort study of 468 PLHIV patients treated with Dolutegravir at all the ART facilities in Bunia. The probability of death being the primary outcome, as a function of time of inclusion in the cohort, was determined using Kaplan–Meier plots. We used the log-rank test to compare survival curves and Cox proportional hazard modeling to determine mortality predictors from the baseline to 31 July 2021 (endpoint). The total number of person-months (p-m) was 3435, with a death rate of 6.70 per 1000 p-m. Compared with the 35-year-old reference group, older patients had a higher mortality risk. ART-naïve participants at the time of enrollment had a higher mortality risk than those already using ART. Patients with a high baseline viral load (≥1000 copies/mL) had a higher mortality risk compared with the reference group (adjusted hazard ratio = 6.04; 95% CI: 1.78–20.43). One-fourth of deaths in the cohort were direct victims of armed conflict, with an estimated excess death of 35.6%. Improving baseline viral load monitoring, starting ART early in individuals with high baseline viral loads, the proper tailoring of ART regimens and optimizing long-term ART, and care to manage non-AIDS-related chronic complications are recommended actions to reduce mortality. Not least, fostering women’s inclusion, justice, peace, and security in conflict zones is critical in preventing premature deaths in the general population as well as among PLHIV. Full article
(This article belongs to the Special Issue New Challenges and Crucial Topics for 2030 Public Health)
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2 pages, 180 KiB  
Correction
Correction: Dusabimana et al. Surveillance for Onchocerciasis-Associated Epilepsy and Ov16 IgG4 Testing of Children 6–10 Years Old Should Be Used to Identify Areas Where Onchocerciasis Elimination Programs Need Strengthening. Pathogens 2022, 11, 281
by Alfred Dusabimana, Joseph Nelson Siewe Fodjo, Michel Mandro Ndahura, Bruno P. Mmbando, Stephen Raimon Jada, Annelies Boven, Eric De Smet, Tony Ukety, Alfred K. Njamnshi, Anne Laudisoit, Steven Abrams and Robert Colebunders
Pathogens 2022, 11(7), 746; https://doi.org/10.3390/pathogens11070746 - 30 Jun 2022
Viewed by 1232
Abstract
There was an error in the original publication [...] Full article
9 pages, 1237 KiB  
Article
Incidence and Predictors of Loss to Follow Up among Patients Living with HIV under Dolutegravir in Bunia, Democratic Republic of Congo: A Prospective Cohort Study
by Roger T. Buju, Pierre Z. Akilimali, Erick N. Kamangu, Gauthier K. Mesia, Jean Marie N. Kayembe and Hippolyte N. Situakibanza
Int. J. Environ. Res. Public Health 2022, 19(8), 4631; https://doi.org/10.3390/ijerph19084631 - 12 Apr 2022
Cited by 6 | Viewed by 2714
Abstract
This study aimed to examine the incidence and predictors of loss to follow up (LTFU) in the context of ongoing atrocities caused by armed conflict, where HIV treatment programs and HIV-infected patients may face unique challenges in terms of ART adherence and retention [...] Read more.
This study aimed to examine the incidence and predictors of loss to follow up (LTFU) in the context of ongoing atrocities caused by armed conflict, where HIV treatment programs and HIV-infected patients may face unique challenges in terms of ART adherence and retention in care. We conducted an observational prospective cohort study of 468 patients living with HIV (PLWHIV) under dolutegravir (DTG) in all health facilities in Bunia between July 2019 and July 2021. Kaplan–Meier plots were used to determine the probability of LTFU as a function of time as inclusive of the cohort. The main outcome variable was LTFU, defined as not taking an ART refill for a period of 3 months or longer from the last attendance for refill, and not yet classified as ‘dead’ or ‘transferred-out.’ The log-rank test was used to compare survival curves based on predictors. Cox proportional hazard modeling was used to measure predictors of LTFU from the baseline until 31 July 2021 (the endpoint). A total of 3435.22 person-months (p-m) were involved in follow up, with an overall incidence rate of 33.48 LTFU per 1000 p-m. Patients who had less experience with ART at enrolment and the ethnically Sudanese, had a higher hazard of being LTFU compared to their reference groups. This study reports a high LTFU rate in this conflict setting. An ART program in such a setting should pay more attention to naive patients and other particularly vulnerable patients such as Sudanese during the pre-ART phase. The study implies the implementation of innovative strategies to address this high risk of being LTFU, reducing either the cost or the distance to the health facility. Full article
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16 pages, 1671 KiB  
Article
Surveillance for Onchocerciasis-Associated Epilepsy and OV16 IgG4 Testing of Children 6–10 Years Old Should Be Used to Identify Areas Where Onchocerciasis Elimination Programs Need Strengthening
by Alfred Dusabimana, Joseph Nelson Siewe Fodjo, Michel Mandro Ndahura, Bruno P. Mmbando, Stephen Raimon Jada, Annelies Boven, Eric De Smet, Tony Ukety, Alfred K. Njamnshi, Anne Laudisoit, Steven Abrams and Robert Colebunders
Pathogens 2022, 11(3), 281; https://doi.org/10.3390/pathogens11030281 - 23 Feb 2022
Cited by 7 | Viewed by 3066 | Correction
Abstract
To eliminate onchocerciasis-associated morbidity, it is important to identify areas where there is still high ongoing Onchocerca volvulus transmission. Between 2015 and 2021, door-to-door surveys were conducted in onchocerciasis-endemic villages in Cameroon, the Democratic Republic of Congo (DRC), Nigeria, South Sudan, and Tanzania [...] Read more.
To eliminate onchocerciasis-associated morbidity, it is important to identify areas where there is still high ongoing Onchocerca volvulus transmission. Between 2015 and 2021, door-to-door surveys were conducted in onchocerciasis-endemic villages in Cameroon, the Democratic Republic of Congo (DRC), Nigeria, South Sudan, and Tanzania to determine epilepsy prevalence and incidence, type of epilepsy and ivermectin therapeutic coverage. Moreover, children aged between six and 10 years were tested for anti-Onchocerca antibodies using the Ov16 IgG4 rapid diagnostic test (RDT). A mixed-effect binary logistic regression analysis was used to assess significantly associated variables of Ov16 antibody seroprevalence. A high prevalence and incidence of epilepsy was found to be associated with a high Ov16 antibody seroprevalence among 6–10-year-old children, except in the Logo health zone, DRC. The low Ov16 antibody seroprevalence among young children in the Logo health zone, despite a high prevalence of epilepsy, may be explained by a recent decrease in O. volvulus transmission because of a decline in the Simulium vector population as a result of deforestation. In the Central African Republic, a new focus of O. volvulus transmission was detected based on the high Ov16 IgG4 seropositivity among children and the detecting of nodding syndrome cases, a phenotypic form of onchocerciasis-associated epilepsy (OAE). In conclusion, Ov16 IgG4 RDT testing of 6–10-year-old children is a cheap and rapid method to determine the level of ongoing O. volvulus transmission and to assess, together with surveillance for OAE, the performance of onchocerciasis elimination programs. Full article
(This article belongs to the Special Issue Onchocerciasis and River Epilepsy in 2022)
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13 pages, 1132 KiB  
Article
Predictors of Viral Non-Suppression among Patients Living with HIV under Dolutegravir in Bunia, Democratic Republic of Congo: A Prospective Cohort Study
by Roger T. Buju, Pierre Z. Akilimali, Erick N. Kamangu, Gauthier K. Mesia, Jean Marie N. Kayembe and Hippolyte N. Situakibanza
Int. J. Environ. Res. Public Health 2022, 19(3), 1085; https://doi.org/10.3390/ijerph19031085 - 19 Jan 2022
Cited by 10 | Viewed by 3036
Abstract
The Democratic Republic of the Congo adopted the integrase inhibitor dolutegravir (DTG) as part of its preferred first-line HIV treatment regimen in 2019. This study aimed to identify predictors of viral non-suppression among HIV-infected patients under a DTG-based regimen in the context of [...] Read more.
The Democratic Republic of the Congo adopted the integrase inhibitor dolutegravir (DTG) as part of its preferred first-line HIV treatment regimen in 2019. This study aimed to identify predictors of viral non-suppression among HIV-infected patients under a DTG-based regimen in the context of ongoing armed conflict since 2017 in the city of Bunia in the DRC. We conducted a cohort study of 468 patients living with HIV under DTG in all health facilities in Bunia. We calculated the proportion of participants with an HIV RNA of below 50 copies per milliliter. About three in four patients (72.8%) in this cohort had a viral load (VL) of <50 copies/mL after 6–12 months. After controlling for the effect of other covariates, the likelihood of having non-suppression remained significantly lower among the 25–34 age group and self-reported naïve patients with a baseline VL of ≥50 copies/mL. The likelihood of having non-suppression remained significantly higher among those who were at advanced stages of the disease, those with abnormal serum creatinine, those with high baseline HIV viremia over 1000 copies/mL, and the Sudanese ethnic group compared to the reference groups. This study suggests that we should better evaluate adherence, especially among adolescents and economically vulnerable populations, such as the Sudanese ethnic group in the city of Bunia. This suggests that an awareness of the potential effects of DTG and tenofovir is important for providers who take care of HIV-positive patients using antiretroviral therapy (ART), especially those with abnormal serum creatinine levels before starting treatment. Full article
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10 pages, 999 KiB  
Article
No Evidence for the Involvement of Leiomodin-1 Antibodies in the Pathogenesis of Onchocerciasis-Associated Epilepsy
by An Hotterbeekx, Melissa Krizia Vieri, Melanie Ramberger, Ashraf Jozefzoon-Aghai, Michel Mandro, Floribert Tepage, Alfred Dusabimana, Samir Kumar-Singh, Maarten J. Titulaer and Robert Colebunders
Pathogens 2021, 10(7), 845; https://doi.org/10.3390/pathogens10070845 - 5 Jul 2021
Cited by 23 | Viewed by 3011
Abstract
Nodding syndrome has been suggested to be triggered by neurotoxic leiomodin-1 auto-antibodies cross-reacting with Onchocerca volvulus. Here, we screened serum and CSF samples of persons with nodding syndrome and other forms of onchocerciasis-associated epilepsy (OAE) and African and European controls for leiomodin-1 [...] Read more.
Nodding syndrome has been suggested to be triggered by neurotoxic leiomodin-1 auto-antibodies cross-reacting with Onchocerca volvulus. Here, we screened serum and CSF samples of persons with nodding syndrome and other forms of onchocerciasis-associated epilepsy (OAE) and African and European controls for leiomodin-1 antibodies by a cell-based assay (CBA) and Western blot (WB). These samples were also investigated for the presence of auto-antibodies cross-reacting with rat brain tissue by immunohistochemistry (IHC). Additionally, IHC was used to detect the leiomodin-1 protein in post-mortem brain samples of persons with OAE who died. Leiomodin-1 antibodies were detected by CBA in 6/52 (12%) and by WB in 23/54 (43%) persons with OAE compared to in 14/61 (23%) (p = 0.113) and 23/54 (43%) (p = 0.479) of controls without epilepsy. Multivariable exact logistic regression did not show an association between O. volvulus infection or epilepsy status and the presence of leiomodin-1. Leiomodin-1 antibodies were not detected in 12 CSF samples from persons with OAE or in 16 CSF samples from persons with acute-onset neurological conditions, as well as not being detected in serum from European controls. Moreover, the leiomodin-1 protein was only detected in capillary walls in post-mortem brain tissues and not in brain cells. IHC on rat brain slides with serum samples from persons with OAE or controls from persons with or without O. volvulus infection revealed no specific staining pattern. In conclusion, our data do not support OAE to be an autoimmune disorder caused by leiomodin-1 antibodies. Full article
(This article belongs to the Special Issue Advances in Human Pathogens Infections)
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10 pages, 1031 KiB  
Article
No Evidence Known Viruses Play a Role in the Pathogenesis of Onchocerciasis-Associated Epilepsy. An Explorative Metagenomic Case-Control Study
by Michael Roach, Adrian Cantu, Melissa Krizia Vieri, Matthew Cotten, Paul Kellam, My Phan, Lia van der Hoek, Michel Mandro, Floribert Tepage, Germain Mambandu, Gisele Musinya, Anne Laudisoit, Robert Colebunders, Robert Edwards and John L. Mokili
Pathogens 2021, 10(7), 787; https://doi.org/10.3390/pathogens10070787 - 22 Jun 2021
Cited by 7 | Viewed by 5234
Abstract
Despite the increasing epidemiological evidence that the Onchocerca volvulus parasite is strongly associated with epilepsy in children, hence the name onchocerciasis-associated epilepsy (OAE), the pathophysiological mechanism of OAE remains to be elucidated. In June 2014, children with unprovoked convulsive epilepsy and healthy controls [...] Read more.
Despite the increasing epidemiological evidence that the Onchocerca volvulus parasite is strongly associated with epilepsy in children, hence the name onchocerciasis-associated epilepsy (OAE), the pathophysiological mechanism of OAE remains to be elucidated. In June 2014, children with unprovoked convulsive epilepsy and healthy controls were enrolled in a case control study in Titule, Bas-Uélé Province in the Democratic Republic of the Congo (DRC) to identify risk factors for epilepsy. Using a subset of samples collected from individuals enrolled in this study (16 persons with OAE and 9 controls) plasma, buffy coat, and cerebrospinal fluid (CSF) were subjected to random-primed next-generation sequencing. The resulting sequences were analyzed using sensitive computational methods to identify viral DNA and RNA sequences. Anneloviridae, Flaviviridae, Hepadnaviridae (Hepatitis B virus), Herpesviridae, Papillomaviridae, Polyomaviridae (Human polyomavirus), and Virgaviridae were identified in cases and in controls. Not unexpectedly, a variety of bacteriophages were also detected in all cases and controls. However, none of the identified viral sequences were found enriched in OAE cases, which was our criteria for agents that might play a role in the etiology or pathogenesis of OAE. Full article
(This article belongs to the Special Issue Advances in Human Pathogens Infections)
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8 pages, 531 KiB  
Article
Serotonin Levels in the Serum of Persons with Onchocerciasis-Associated Epilepsy: A Case-Control Study
by Melissa Krizia Vieri, An Hotterbeekx, Michel Mandro, Joseph Nelson Siewe Fodjo, Alfred Dusabimana, Francoise Nyisi, Deby Mukendi, Joe Gwatsvaira, Samir Kumar-Singh and Robert Colebunders
Pathogens 2021, 10(6), 720; https://doi.org/10.3390/pathogens10060720 - 8 Jun 2021
Cited by 4 | Viewed by 2584
Abstract
Onchocerciasis-associated epilepsy (OAE) is a devastating childhood disorder occurring in areas with high Onchocerca volvulus transmission. Despite epidemiological evidence showing the association between O. volvulus and epilepsy, the underlying mechanism remains unknown. Since high levels of serotonin are known to induce seizures, we [...] Read more.
Onchocerciasis-associated epilepsy (OAE) is a devastating childhood disorder occurring in areas with high Onchocerca volvulus transmission. Despite epidemiological evidence showing the association between O. volvulus and epilepsy, the underlying mechanism remains unknown. Since high levels of serotonin are known to induce seizures, we investigated serotonin levels in persons with OAE and controls selected from the Democratic Republic of Congo. Serum serotonin levels were determined by ELISA in 19 persons with OAE, 32 persons with epilepsy without O. volvulus infection, 18 with O. volvulus infection but without epilepsy, and 35 with neither O. volvulus infection nor epilepsy. O. volvulus infection was diagnosed by skin snip testing and/or OV16 antibody detection. Serum serotonin levels were significantly decreased in persons with OAE compared to persons with O. volvulus infection and no epilepsy. In conclusion, an increased serotonin level is unable to explain the pathogenesis of OAE. Other hypotheses to identify the causal mechanism of OAE will need to be investigated. Full article
(This article belongs to the Special Issue Onchocerciasis and River Epilepsy)
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10 pages, 663 KiB  
Article
Potential Parasitic Causes of Epilepsy in an Onchocerciasis Endemic Area in the Ituri Province, Democratic Republic of Congo
by Melissa Krizia Vieri, Michel Mandro, Chiara Simona Cardellino, Pierantonio Orza, Niccolò Ronzoni, Joseph Nelson Siewe Fodjo, An Hotterbeekx and Robert Colebunders
Pathogens 2021, 10(3), 359; https://doi.org/10.3390/pathogens10030359 - 18 Mar 2021
Cited by 3 | Viewed by 2598
Abstract
A high burden of epilepsy is observed in Africa where parasitological infections are endemic. In 2016, in an Onchocerciasis endemic area in the Logo health zone, in Ituri province in the Democratic Republic of Congo, a door-to-door study showed an epilepsy prevalence of [...] Read more.
A high burden of epilepsy is observed in Africa where parasitological infections are endemic. In 2016, in an Onchocerciasis endemic area in the Logo health zone, in Ituri province in the Democratic Republic of Congo, a door-to-door study showed an epilepsy prevalence of 4.6%, and 50.6% of persons with epilepsy were infected with Onchocerca volvulus. In the current study, the serum of 195 people infected with O. volvulus persons with epilepsy were tested to determine the proportion of co-infections with Taenia solium, Toxocara canis and Strongyloides. These proportions were, respectively, 8.2, 18.5 and 12.8%. Persons with a T. solium co-infection were older than those without co-infection (p = 0.021). In six (37.5%) of the T. solium co-infected persons, the first seizures appeared after the age of 30 years compared to three (2.1%) persons without a co-infection (p < 0.0001). Our study suggests that an O. volvulus infection is the main parasitic cause of epilepsy in the Ituri province, but in some persons, mainly in those with late onset epilepsy and with focal seizures, the epilepsy may be caused by neurocysticercosis. As the population in the area rears pigs, activities to limit T. solium transmission should be implemented. Full article
(This article belongs to the Special Issue Onchocerciasis and River Epilepsy)
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