Comparison of repeated doses of ivermectin versus ivermectin plus albendazole for the treatment of onchocerciasis: A randomized, open-label, clinical trial

BACKGROUND: Improved treatment for onchocerciasis is needed to accelerate onchocerciasis elimination in Africa. Aiming to better exploit registered drugs, this study was undertaken to determine whether annual or semiannual treatment with ivermectin (IVM; 200 µg/kg) plus albendazole (ALB; 800 mg single dose) is superior to IVM alone. METHODS: This trial was performed in Ghana and included 272 participants with microfilariae (MF), who were randomly assigned to 4 treatment arms: (1) IVM annually at 0, 12, and 24 months; (2) IVM semiannually at 0, 6, 12, 18, and 24 months; (3) IVM+ALB annually; or (4) IVM+ALB semiannually. Microfiladermia was determined pretreatment and at 6, 18, and 36 months. The primary outcome was the proportion of fertile and viable female worms in onchocercomata excised at 36 months. RESULTS: Posttreatment nodule histology showed that 15/135 (11.1%), 22/155 (14.2%), 35/154 (22.7%), and 20/125 (16.0%) living female worms had normal embryogenesis in the IVM annual, IVM semiannual, IVM+ALB annual, and IVM+ALB semiannual groups, respectively (P = .1229). Proportions of dead worms also did not differ between the 4 groups (P = .9198). Proportions of patients without MF at 36 months (1 year after the last treatment) were 35/56 (63%) after annual IVM, 42/59 (71%) after semiannual IVM, 39/64 (61%) after annual IVM+ALB, and 43/53 (81%) after semiannual IVM+ALB. CONCLUSIONS: The combination treatment of IVM plus ALB was no better than IVM alone for sterilizing, killing adult worms, or achieving sustained MF clearance. However, semiannual treatment was superior to annual treatment for achieving sustained clearance of Onchocerca volvulus MF from the skin (P = .024). CLINICAL TRIALS REGISTRATION: ISRCTN50035143

Prenatal Diagnosis and Genetic Characterization of Toxoplasmosis in Immunocompetent and Immunocompromised Pregnant Women and the Risk of Congenital Toxoplasmosis: A Prospective Study in Ghana

Background: Toxoplasmosis, a protozoan parasitic disease caused by Toxoplasma gondii is of public health concern. Studies on trans-placental transmission of T. gondii is limited in Africa. This study aimed at assessing the seroprevalence and genetically characterize T. gondii infection among pregnant women. Methods: HIV-negative pregnant women in their first trimester and HIV-positive pregnant women attending Antenatal Clinic at a University Hospital were screened for anti-Toxoplasma antibodies (IgG and IgM) using ELISA. Multi-locus gene detection was done using nested Polymerase Chain Reaction to target the Surface Antigen Gene 3 and the Dense Granule Antigen protein 6 of T. gondii parasite, followed by sequencing to identify the prevalent T. gondii strain in Ghana.  Results: The prevalence of acute T. gondii infection (ATI) among the HIV-negative pregnant women was 1.5% (6/400), transmission rate was 50% (3/6) and prevalence of congenital toxoplasmosis (CT) was 0.75% (3/400). From HIV-positive women, the prevalence of ATI was 56% (14/25), transmission rate 57% (8/14) and prevalence of CT  32% (8/25). Older aged and unemployed HIV positive women were significantly associated with T. gondii seropositivity (p=0.021) and (p=0.016) respectively. T. gondii DNA was detected in 16.7% (12/72) samples and were clonal type GRA6 type II sequences.  Conclusion: Seroprevalence of toxoplasmosis were higher in HIV-positive pregnant women. The seropositivity to T. gondii specific antibodies in the babies did not fully translate into clinical Toxoplasmosis. The strain identified was the clonal type GRA6 type II sequence. It is important to follow newborn with CT for 10 years for clinical toxoplasmosis.&nbsp

Reductions in microfilaridermia by repeated ivermectin treatment are associated with lower Plasmodium-specific Th17 immune responses in Onchocerca volvulus-infected individuals

Background: 37 million individuals are currently infected with Onchocerca volvulus (O. volvulus), a parasitic nematode that elicits various dermal manifestations and eye damage in man. Disease control is primarily based on distributing ivermectin in mass drug administration (MDA) programmes which aim at breaking transmission by eliminating microfilariae (MF), the worm's offspring. The majority of infected individuals present generalized onchocerciasis, which is characterized by hyporesponsive immune responses and high parasite burden including MF. Recently, in areas that have been part of MDA programmes, individuals have been identified that present nodules but are amicrofilaridermic (a-MF) and our previous study showed that this group has a distinct immune profile. Expanding on those findings we determined the immune responses of O. volvulus-infected individuals to a Plasmodium-derived antigen MSP-1 (merozoite surface protein-1), which is required by the parasite to enter erythrocytes. Methods: Isolated PBMCs from O. volvulus-infected individuals (164 MF+ and 46 a-MF) and non-infected volunteers from the same region (NEN), were stimulated with MSP-1 and the resulting supernatant screened for the presence of IL-5, IL-13, IFN-γ, TNF-α, IL-6, IL-17A and IL-10. These findings were then further analyzed following regression analysis using the covariates MF, ivermectin (IVM) and region. The latter referred to the Central or Ashanti regions of Ghana, which, at the time sampling, had received 8 or 1 round of MDA respectively. Results: IL-5, IL-13 and IFN-γ responses to MSP-1 were not altered between NEN and O. volvulus-infected individuals nor were any associations revealed in the regression analysis. IL-10, IL-6 and TNF-α MSP-1 responses were, however, significantly elevated in cultures from infected individuals. Interestingly, when compared to a-MF individuals, MSP-induced IL-17A responses were significantly higher in MF+ patients. Following multivariable regression analysis these IL-10, IL-6, TNF-α and IL-17A responses were all dominantly associated with the regional covariate. Conclusions: Consequently, areas with a lowered infection pressure due to IVM MDA appear to influence bystander responses to Plasmodium-derived antigens in community members even if they have not regularly participated in the therapy

Macrofilaricidal Activity in Wuchereria bancrofti after 2 Weeks Treatment with a Combination of Rifampicin plus Doxycycline

Infection with the filarial nematode Wuchereria bancrofti can lead to lymphedema, hydrocele, and elephantiasis. Since adult worms cause pathology in lymphatic filariasis (LF), it is imperative to discover macrofilaricidal drugs for the treatment of the infection. Endosymbiotic Wolbachia in filariae have emerged as a new target for antibiotics which can lead to macrofilaricidal effects. In Ghana, a pilot study was carried out with 39 LF-infected men; 12 were treated with 200 mg doxycycline/day for 4 weeks, 16 were treated with a combination of 200 mg doxycycline/day + 10 mg/kg/day rifampicin for 2 weeks, and 11 patients received placebo. Patients were monitored for Wolbachia and microfilaria loads, antigenaemia, and filarial dance sign (FDS). Both 4-week doxycycline and the 2-week combination treatment reduced Wolbachia load significantly. At 18 months posttreatment, four-week doxycycline resulted in 100% adult worm loss, and the 2-week combination treatment resulted in a 50% adult worm loss. In conclusion, this pilot study with a combination of 2-week doxycycline and rifampicin demonstrates moderate macrofilaricidal activity against W. bancrofti

Efficacy of 5-week doxycycline treatment on adult Onchocerca volvulus.

The effects of 5-week doxycycline treatment on the depletion of Wolbachia endobacteria from Onchocerca volvulus, on the interruption of embryogenesis and on microfilariae production, and with regard to macrofilaricidal activity were studied. In 2003, in an endemic area in Ghana, 22 onchocerciasis patients received 100 mg/day doxycycline for 5 weeks. Two years after the start of the study, 20 treated and ten untreated patients were nodulectomized and skin microfilariae were counted. The onchocercomas were examined by immunohistology for the presence of Wolbachia, embryogenesis, and vitality of adult filariae. The latter two parameters were further assessed by alternating logistic regression analysis, taking into account the dependency of worms and nodules in patients. Doxycycline resulted in depletion of Wolbachia and in complete interruption of embryogenesis in all worms that were assumed to have been present during treatment. In the treated patients, only 51% of the female worms were alive, compared to 84% in the untreated patients, indicating a moderate but distinct macrofilaricidal activity of doxycycline at this dose. It is concluded that, in areas with ongoing transmission, doxycycline cannot replace regular ivermectin mass treatment because new infections would require repeated rounds of doxycycline. However, doxycycline can be used for the treatment of individuals outside transmission areas, in foci where ivermectin resistance may occur, and in countries where onchocerciasis and loiasis are co-endemic

Emotional burnout of specialists in socio-occupational professions: contemporary views on the problem

Представлено сучасні підходи до проблеми вигорання у представників соціономічних професій у контексті емоційної праці, емоційного і когнітивного дисонансу. Проаналізовано й узагальнено наукову літературу з питань вигорання, визначено три основні його компоненти: емоційне і/або фізичне виснаження, зниження продуктивності праці і надмірна деперсоналізація. На основі аналізу визначень вигорання встановлено його зв’язок з емоційною працею (регуляцією і вираженням емоційних станів). Обстоюється думка, що фахівці соціономічних професій особливо вразливі до вигорання, оскільки тривалий час перебувають у стані, коли необхідно постійно контролювати свої емоції, брати на себе відповідальність і відчувати невизначеність, працюючи з іншими людьми. Емоційну працю розглянуто як предиктор вигорання у фахівців соціономічних професій. На основі аналізу літератури, присвяченої проблемам вигорання та емоційного дисонансу, висловлено припущення, що вимоги щодо емоційної праці зумовлюють різноманітність проявів синдрому виго-рання (у тому числі виснаження, цинізму, зниження продуктивності праці та погіршення самопочуття), а знання симптомів вигорання дало б змогу фахівцям соціономічних професій запобігти виникненню та загостренню цього стану.This article deals with the modern approaches to the problem of burnout of helping professionals in the context of emotional labor, emotional and cognitive dissonance. The burnout literature is reviewed, compared, and summarized. The definition of burnout is proposed including three components: emotional and/or physical exhaustion, lowered work productivity, and excessive depersonalization. Based on an analysis of the definitions of burnout, the paper focuses on the connec-tion of burnout and emotional work (regulation of feelings and emotional expression). It is also maintained a fact that helping professionals are especially vulnerable to burnout because of the necessity to control own emotions for a long time, to take responsibilities, and to feel uncertainties they encounter while working with others. The current study discussed emotional labor as a predictor of burnout of helping professionals. On the basis of the literature on burnout and emotional dissonance, the author of this article hypothesized that emotional job demands would explain variances of burnout (i.e., exhaustion and cynicism). Knowledge of abovementioned syndromes would help socionomy professionals to avoid emergence and aggravation of emotional burnout.Представлены современные подходы к проблеме выгорания у представителей социономических профессий в контексте эмоциональной труда, эмоционального и когнитивного диссонанса. Проанализированы и обобщены научную литературу по вопросам выгорания, определены три основные его компоненты: эмоциональное и / или физическое истощение, снижение производительности труда и чрезмерная деперсонализация. На основе анализа определений выгорания установлена ​​его связь с эмоциональной трудом (регуляцией и выражением эмоциональных состояний). Отстаивается мнение, что специалисты социономических профессий особенно уязвимы к выгоранию, поскольку длительное время находятся в состоянии, когда необходимо постоянно контролировать свои эмоции, брать на себя ответственность и чувствовать неопределенность, работая с другими людьми. Эмоциональный труд рассмотрен как предиктор выгорания у специалистов социономических профессий. На основе анализа литературы, посвященной проблемам выгорания и эмоционального диссонанса, высказано предположение, что требования по эмоциональной труда обусловливают разнообразие проявлений синдрома выгорания (в том числе истощения, цинизма, снижение производительности труда и ухудшение самочувствия), а знание симптомов выгорания позволило бы специалистам социономических профессий предотвратить возникновение и обострение этого состояния

Doxycycline Leads to Sterility and Enhanced Killing of Female Onchocerca volvulus Worms in an Area With Persistent Microfilaridermia After Repeated Ivermectin Treatment: A Randomized, Placebo-Controlled, Double-Blind Trial

Background Ivermectin (IVM) has been the drug of choice for the treatment of onchocerciasis. However, there have been reports of persistent microfilaridermia in individuals from an endemic area in Ghana after many rounds of IVM, raising concerns of suboptimal response or even the emergence of drug resistance. Because it is considered risky to continue relying only on IVM to combat this phenomenon, we assessed the effect of targeting the Onchocerca volvulus Wolbachia endosymbionts with doxycycline for these individuals with suboptimal response. Methods One hundred sixty-seven patients, most of them with multiple rounds of IVM, were recruited in areas with IVM suboptimal response and treated with 100 mg/day doxycycline for 6 weeks. Three and 12 months after doxycycline treatment, patients took part in standard IVM treatment. Results At 20 months after treatment, 80% of living female worms from the placebo group were Wolbachia positive, whereas only 5.1% in the doxycycline-treated group contained bacteria. Consistent with interruption of embryogenesis, none of the nodules removed from doxycycline-treated patients contained microfilariae, and 97% of those patients were without microfilaridermia, in contrast to placebo patients who remained at pretreatment levels (P < .001). Moreover, a significantly enhanced number of dead worms were observed after doxycycline. Conclusions Targeting the Wolbachia in O. volvulus is effective in clearing microfilariae in the skin of onchocerciasis patients with persistent microfilaridermia and in enhanced killing of adult worms after repeated standard IVM treatment. Strategies can now be developed that include doxycycline to control onchocerciasis in areas where infections persist despite the frequent use of IVM

Wolbachia endobacteria depletion by doxycycline as antifilarial therapy has macrofilaricidal activity in onchocerciasis: a randomized placebo-controlled study

In a randomized, placebo-controlled trial in Ghana, 67 onchocerciasis patients received 200-mg/day doxycycline for 4–6 weeks, followed by ivermectin (IVM) after 6 months. After 6–27 months, efficacy was evaluated by onchocercoma histology, PCR and microfilariae determination. Administration of doxycycline resulted in endobacteria depletion and female worm sterilization. The 6-week treatment was macrofilaricidal, with >60% of the female worms found dead, despite the presence of new, Wolbachia-containing worms acquired after the administration of doxycycline. Doxycycline may be developed as second-line drug for onchocerciasis, to be administered in areas without transmission, in foci with IVM resistance and in areas with Loa co-infections