Search Results (11)

Onchocerciasis causes severe morbidity in sub-Saharan Africa. Abia, Anambra, Enugu, and Imo states of Nigeria were historically classified meso- or hyperendemic and eligible for ivermectin mass drug administration (MDA). After ≥25 years of annual and biannual MDA, serological and entomological assessments were conducted to determine if Onchocerca volvulus transmission was interrupted. Dried blood spots collected in October 2020 from ≥3167 children 5–9 years old in each state were screened for O. volvulus-specific Ov16 antibody by enzyme-linked immunosorbent assay. Additionally, 52,187 Simulium damnosum heads (≥8845 per state) collected over 12 months between 2021 and 2022 were tested by pooled polymerase chain reaction (PCR) for O-150 DNA. Among seven seropositive children, four were found for follow-up skin snip PCR to confirm active infection. Three were negative and the fourth was excluded as he was visiting from an endemic state. The final seroprevalence estimates of each state had 95% upper confidence limits (UCL) < 0.1%. All fly pools were negative by O-150 PCR, giving a 95% UCL infective fly prevalence < 0.05% in each state. Each state therefore met the World Health Organization epidemiological and entomological criteria for stopping MDA effective January 2023. With 18.9 million residents eligible for MDA, this marked the largest global onchocerciasis stop-treatment decision to date. Full article

The establishment of the Global Programme to Eliminate Lymphatic Filariasis (GPELF) to stop the transmission of infection has significantly reduced the incidence of lymphatic filariasis, a debilitating mosquito-borne neglected tropical disease. The primary strategies that have been employed include mass drug administration (MDA) of anthelminthics and morbidity management and disability prevention (MMDP). While some countries have been able to reach elimination status in Africa, there is still active transmission of LF in Zambia. The nematode responsible for the disease is Wuchereria bancrofti, which is transmitted by Anopheles mosquitoes. To alleviate the suffering of those infected by the disease, the Zambian Ministry of Health launched a program to eliminate LF as a public health problem in 2003. This project reviewed the efforts to achieve the elimination of LF in Zambia, past and present government policies, and the anticipated challenges. MDAs have been conducted since 2014 and coverage has been between 87% and 92%. Zambia has now moved towards pre-transmission assessment surveys (PRETAS) and transmission assessment surveys (TAS). MMDP is a major priority and planned to be conducted between 2022 and 2026. COVID-19 presented a new challenge in the control of LF, while climate change, immigration, co-infections, and funding limitations will complicate further progress. Full article

Amyloid-β (Aβ) is a peptide formed by 39–43 amino acids, heterogenous by the length of its C-terminus. Aβ constitutes a subnanomolar monomeric component of human biological fluids; however, in sporadic variants of Alzheimer’s disease (AD), it forms soluble neurotoxic oligomers and accumulates as insoluble extracellular polymeric aggregates (amyloid plaques) in the brain tissues. The plaque formation is controlled by zinc ions; therefore, abnormal interactions between the ions and Aβ seem to take part in the triggering of sporadic AD. The amyloid plaques contain various Aβ isoforms, among which the most common is Aβ with an isoaspartate in position 7 (isoD7). The spontaneous conversion of D7 to isoD7 is associated with Aβ aging. Aβ molecules with isoD7 (isoD7-Aβ) easily undergo zinc-dependent oligomerization, and upon administration to transgenic animals (mice, nematodes) used for AD modeling, act as zinc-dependent seeds of the pathological aggregation of Aβ. The formation of zinc-bound homo- and hetero-oligomers with the participation of isoD7-Aβ is based on the rigidly structured segment 11-EVHH-14, located in the Aβ metal binding domain (Aβ₁₆). Some hereditary variants of AD are associated with familial mutations within the domain. Among these, the most susceptible to zinc-dependent oligomerization is Aβ with Taiwan (D7H) mutation (D7H-Aβ). In this study, the D7H-Aβ metal binding domain (D7H-Aβ₁₆) has been used as a model to establish the molecular mechanism of zinc-induced D7H-Aβ oligomerization through turbidimetry, dynamic light scattering, isothermal titration calorimetry, mass spectrometry, and computer modelling. Additionally, the modeling data showed that a molecule of D7H-Aβ, as well as isoD7-Aβ in combination with two Aβ molecules, renders a stable zinc-induced heterotrimer. The trimers are held together by intermolecular interfaces via zinc ions, with the primary interfaces formed by 11-EVHH-14 sites of the interacting trimer subunits. In summary, the obtained results confirm the role of the 11-EVHH-14 region as a structure and function determinant for the zinc-dependent oligomerization of all known Aβ species (including various chemically modified isoforms and AD-associated mutants) and point at this region as a potent target for drugs aimed to stop amyloid plaque formation in both sporadic and hereditary variants of AD. Full article

Lymphatic filariasis (LF), also commonly known as elephantiasis, is a neglected tropical disease (NTD) caused by filarial parasites. The disease is transmitted via a bite from infected mosquitoes. The bites of these infected mosquitoes deposit filarial parasites, Wuchereria or Brugia, whose predilection site is the lymphatic system. The damage to the lymph system causes swelling in the legs, arms, and genitalia. A mapping survey conducted between 2003 and 2011 determined LF as being endemic in Zambia in 96 out of 116 districts. Elimination of LF is known to be possible by stopping the spread of the infection through large-scale preventive chemotherapy. Therefore, mass drug administration (MDA) with diethylcarbamazine citrate (DEC) (6 mg/kg) and Albendazole (400 mg) for Zambia has been conducted and implemented in all endemic districts with five effective rounds. In order to determine whether LF prevalence has been sufficiently reduced to levels less than 2% antigenemia and less than 1% microfilaremia, a pre-transmission assessment survey (pre-TAS) was conducted. Therefore, post-MDA pre-TAS was conducted between 2021 and 2022 in 80 districts to determine the LF prevalence. We conducted a cross-sectional seroprevalence study involving 600 participants in each evaluation unit (EU) or each district. The study sites (sentinel and spot-check sites) were from districts that were the implementation units (IUs) of the LF MDA. These included 80 districts from the 9 provinces. A total of 47,235 people from sentinel and spot-check locations were tested. Of these, valid tests were 47,052, of which 27,762 (59%) were females and 19,290 (41%) were males. The survey revealed in the 79/80 endemic districts a prevalence of Wb antigens of 0.14% and 0.0% prevalence of microfilariae. All the surveyed districts had an optimum prevalence of less than 2% for antigenaemia, except for Chibombo district. The majority of participants that tested positive for Wuchereria bancrofti (Wb) Antigens (Ag) were those that had 2, 3, and 4 rounds of MDA. Surprisingly, individuals that had 1 round of MDA were not found to have circulating antigens of Wb. The study showed that all the surveyed districts, except for Chibombo, passed pre-TAS. This further implies that there is a need to conduct transmission assessment surveys (TASs) in these districts. Full article

Diabetes poses major economic, social, and public health challenges in all countries worldwide. Besides cardiovascular disease and microangiopathy, diabetes is a leading cause of foot ulcers and lower limb amputations. With the continued rise of diabetes prevalence, it is expected that the future burden of diabetes complications, early mortality, and disabilities will increase. The diabetes epidemic is partly caused by the current lack of clinical imaging diagnostic tools, the timely monitoring of insulin secretion and insulin-expressing cell mass (beta (β)-cells), and the lack of patients’ adherence to treatment, because some drugs are not tolerated or invasively administrated. In addition to this, there is a lack of efficient topical treatment capable of stopping the progression of disabilities, in particular for treating foot ulcers. In this context, polymer-based nanostructures garnered significant interest due to their tunable physicochemical characteristics, rich diversity, and biocompatibility. This review article emphasizes the last advances and discusses the prospects in the use of polymeric materials as nanocarriers for β-cell imaging and non-invasive drug delivery of insulin and antidiabetic drugs in the management of blood glucose and foot ulcers. Full article

Phytate (myo-inositol hexakisphosphate or InsP6) is the main phosphorus reservoir that is present in almost all wholegrains, legumes, and oilseeds. It is a major component of the Mediterranean and Dietary Approaches to Stop Hypertension (DASH) diets. Phytate is recognized as a nutraceutical and is classified by the Food and Drug Administration (FDA) as Generally Recognized As Safe (GRAS). Phytate has been shown to be effective in treating or preventing certain diseases. Phytate has been shown to inhibit calcium salt crystallization and, therefore, to reduce vascular calcifications, calcium renal calculi and soft tissue calcifications. Moreover, the adsorption of phytate to the crystal faces can inhibit hydroxyapatite dissolution and bone resorption, thereby playing a role in the treatment/prevention of bone mass loss. Phytate has a potent antioxidation and anti-inflammatory action. It is capable of inhibiting lipid peroxidation through iron chelation, reducing iron-related free radical generation. As this has the effect of mitigating neuronal damage and loss, phytate shows promise in the treatment/prevention of neurodegenerative disease. It is reported that phytate improves lipid and carbohydrate metabolism, increases adiponectin, decreases leptin and reduces protein glycation, which is linked with macrovascular and microvascular diabetes complications. In this review, we summarize the benefits of phytate intake as seen in in vitro, animal model, epidemiological and clinical trials, and we also identify questions to answer in the future. Full article

The elimination of lymphatic filariasis (LF) is achieved through repeated mass drug administration (MDA) of anti-filarial medications, which interrupts transmission and prevents new infections. Accurate transmission assessments are critical to deciding when to stop MDA. Current methods for evaluating transmission may be insufficiently sensitive, resulting in post-MDA resurgence. We, therefore, evaluated potential diagnostic testing scenarios for post-MDA surveillance. Data were used from two surveys (a household cluster and a cohort) conducted in an area of Mandalay Region, Myanmar, with ongoing transmission following several rounds of MDA. First, age- and sex-adjusted seroprevalence were estimated for the area using the household survey. Next, three Bayesian networks were built from the combined datasets to compare antigens by immunochromatic testing (ICT) and/or Og4C3 enzyme-linked immunosorbent assay (ELISA) and antibody (Ab) detection methods (Wb123 or Bm14 Ab ELISA). The networks were checked for validity and then used to compare diagnostic testing scenarios. The adjusted prevalence from the household survey for antigen, Wb123 Ab and Bm14 Ab were 4.4% (95% CI 2.6–7.3%), 8.7% (5.96–12.5%) and 20.8% (16.0–26.6%), respectively. For the three networks, the True Skill Statistic and Area Under the Receiver Operating Characteristic Curve for antigen, Wb123 and Bm14 Ab were 0.79, 0.68 and 0.55; and 0.97, 0.92 and 0.80, respectively. In the Bayesian network analysis, a positive case was defined as testing positive to one or more infection markers. A missed result was therefore the probability of a positive case having a negative test result to an alternate marker. The probability of a positive case prior to any testing scenario was 17.4%, 16.8% and 26.6% for antigen, Wb123 Ab and Bm14 Ab, respectively. In the antigen-only testing scenario, the probability of a missed positive LF result was 5.2% for Wb123 and 15.6% for Bm14 Ab. The combination of antigen plus Bm14 Ab testing reduced the probability of missing a positive LF case as measured by Wb123 Ab to 0.88%. The combination of antigen plus Wb123 Ab was less successful and yielded an 11.5% probability of a missed positive result by Bm14 Ab testing. Across scenarios, there was a greater discordance between Bm14 and both antigen and Wb123 Ab in the 1–10 age group compared to older ages. These findings suggest that the addition of Bm14 Ab improves the sensitivity of LF testing for current or past infection. The combination of antigen plus Bm14 Ab should therefore be considered for inclusion in post-MDA surveillance to improve the sensitivity of transmission surveys and prevent the premature cessation of MDA. Full article

The control of soil-transmitted helminthiasis (STH) in Cameroon is focused on large-scale deworming through annual mass drug administration (MDA) of albendazole or mebendazole to at-risk groups, principally pre-school and school-age children. After a decade of intervention, prevalence and intensity of infection have been significantly lowered, encouraging the paradigm shift from control to elimination. However, STH eggs are extremely resistant to environmental stressors and may survive for years in soils. It therefore appeared important to assess whether the risk of transmission was still prevailing, especially in a context where transmission of soil-transmitted helminths in the human population had almost been interrupted. A retrospective and a prospective cross-sectional surveys were conducted in five Health Areas of the Mifi Health District (West Region, Cameroon) to: (i) assess the trends in infestation rates over three-years (2018–2020) using health facility registers, and (ii) investigate, in 2020, the contamination rates of the environment by dissemination stages of soil-transmitted helminths using the sucrose centrifugal flotation method. The overall soil-transmitted helminth infestation rate was 4.9% (95% CI: 4.3–5.6), significantly lower than the overall soil contamination rate (12.0%; 95% CI: 8.2–17.2). These results are supportive of the low endemicity level of STHs in the Mifi Health District, but environmental pollution by dissemination stages of the parasites outlines that the risk of transmission is still persistent. It therefore appears compulsory to account for the environment when considering policy/recommendations for transmission interruption and stopping MDA, as it is in the case with vector-borne diseases. Full article

Abrupt withdrawal from antiepileptic drugs is followed by increased occurrence of epileptic seizures, a phenomenon known as the “rebound effect”. By stopping treatment with levetiracetam (LEV 300 mg/kg/day, n = 15; vs. saline, n = 15), we investigated the rebound effect in adult male Sprague-Dawley rats. LEV was continuously administered using osmotic minipumps, 7 weeks after the intraperitoneal administration of kainic acid (15 mg/kg). The effects of LEV were determined by comparing time intervals, treatments, and interactions between these main factors. Seizures were evaluated by video-electrocorticographic recordings and power band spectrum analysis. Furthermore, we assessed endogenous neurosteroid levels by liquid chromatography-electrospray-tandem mass spectrometry. LEV significantly reduced the percentage of rats experiencing seizures, reduced the seizure duration, and altered cerebral levels of neurosteroids. In the first week of LEV discontinuation, seizures increased abruptly up to 700% (p = 0.002, Tukey’s test). The power of delta band in the seizure postictal component was related to the seizure occurrence after LEV withdrawal (r² = 0.73, p < 0.001). Notably, allopregnanolone hippocampal levels were positively related to the seizure occurrence (r² = 0.51, p = 0.02) and to the power of delta band (r² = 0.67, p = 0.004). These findings suggest a role for the seizure postictal component in the rebound effect, which involves an imbalance of hippocampal neurosteroid levels. Full article

Ghana has been implementing mass drug administration (MDA) of ivermectin and albendazole for the elimination of lymphatic filariasis (LF) since the year 2000, as part of the Global Programme to Eliminate Lymphatic Filariasis (GPELF). It was estimated that 5–6 years of treatment would be sufficient to eliminate the disease. Tremendous progress has been made over the years, and treatment has stopped in many disease endemic districts. However, despite the successful implementation of MDA, there are districts with persistent transmission. In this study we assessed the epidemiology of LF in three adjoining districts that have received at least 16 years of MDA. The assessments were undertaken one year after the last MDA. 1234 adults and 182 children below the age of 10 years were assessed. The overall prevalence of circulating filarial antigen in the study participants was 8.3% (95% CI: 6.9–9.9), with an estimated microfilaria prevalence of 1.2%. The microfilarial intensity in positive individuals ranged from 1 to 57 microfilariae/mL of blood. Higher antigen prevalence was detected in males (13.0%; 95% CI: 10.3–16.2) compared to females (5.5%; 95% CI: 4.1–7.2). The presence of infection was also highest in individuals involved in outdoor commercial activities, with the risks of infection being four- to five-fold higher among farmers, fishermen, drivers and artisans, compared to all other occupations. Using bednets or participating in MDA did not significantly influence the risk of infection. No children below the age of 10 years were found with infection. Detection of Wb123 antibodies for current infections indicated a prevalence of 14.4% (95% CI: 8.1–23.0) in antigen-positive individuals above 10 years of age. No antibodies were detected in children 10 years or below. Assessment of infection within the An. gambiae vectors of LF indicated an infection rate of 0.9% (95% CI: 0.3–2.1) and infectivity rate of 0.5% (95% CI: 0.1–1.6). These results indicate low-level transmission within the districts, and suggest that it will require targeted interventions in order to eliminate the infection. Full article

Finasteride is a 5α-reductase inhibitor widely used in present in the therapeutic approach of androgenic alopecia. Adverse effects consist in variable sign and symptoms, the most common being represented by mental troubles (reduced feeling of life pleasure or emotions, depression), physical impairments (loss of muscle tone and/or mass) and sexual complains (loss of libido and sexual potency). An increasing number of studies identify and describe even a post-finasteride syndrome (persistent adverse affects three months or more after finasteride cessation) or new adverse effects including but not limited at the skin level or oral cavity (marginal periodontium). We intend to present in this study several oral adverse effects encountered during finasteride administration, represented by mild and moderate signs which generally responded to topical procedures without to require the stop of the drug administration. New studies on large samples will further document the existing relation between the described oral adverse effects and the implied pathophysiological mechanisms. For this moment, we are taking into account as possible mechanisms- a direct action of finasteride administration, possible indirect consequences due to hormonal interferences, or coexisting factors with finasteride administration that were not detected. Full article