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PLoS Neglected Tropical Diseases Mar 2024Cystic Echinococcosis (CE) as a prevalent tapeworm infection of human and herbivorous animals worldwide, is caused by accidental ingestion of Echinococcus granulosus...
Cystic Echinococcosis (CE) as a prevalent tapeworm infection of human and herbivorous animals worldwide, is caused by accidental ingestion of Echinococcus granulosus eggs excreted from infected dogs. CE is endemic in the Middle East and North Africa, and is considered as an important parasitic zoonosis in Iran. It is transmitted between dogs as the primary definitive host and different livestock species as the intermediate hosts. One of the most important measures for CE control is dog deworming with praziquantel. Due to the frequent reinfection of dogs, intensive deworming campaigns are critical for breaking CE transmission. Dog reinfection rate could be used as an indicator of the intensity of local CE transmission in endemic areas. However, our knowledge on the extent of reinfection in the endemic regions is poor. The purpose of the present study was to determine E. granulosus reinfection rate after praziquantel administration in a population of owned dogs in Kerman, Iran. A cohort of 150 owned dogs was recruited, with stool samples collected before praziquantel administration as a single oral dose of 5 mg/kg. The re-samplings of the owned dogs were performed at 2, 5 and 12 months following initial praziquantel administration. Stool samples were examined microscopically using Willis flotation method. Genomic DNA was extracted, and E. granulosus sensu lato-specific primers were used to PCR-amplify a 133-bp fragment of a repeat unit of the parasite genome. Survival analysis was performed using Kaplan-Meier method to calculate cumulative survival rates, which is used here to capture reinfection dynamics, and monthly incidence of infection, capturing also the spatial distribution of disease risk. Results of survival analysis showed 8, 12 and 17% total reinfection rates in 2, 5 and 12 months following initial praziquantel administration, respectively, indicating that 92, 88 and 83% of the dogs had no detectable infection in that same time periods. The monthly incidence of reinfection in total owned dog population was estimated at 1.5% (95% CI 1.0-2.1). The results showed that the prevalence of echinococcosis in owned dogs, using copro-PCR assay was 42.6%. However, using conventional microscopy, 8% of fecal samples were positive for taeniid eggs. Our results suggest that regular treatment of the dog population with praziquantel every 60 days is ideal, however the frequency of dog dosing faces major logistics and cost challenges, threatening the sustainability of control programs. Understanding the nature and extent of dog reinfection in the endemic areas is essential for successful implementation of control programs and understanding patterns of CE transmission.
Topics: Humans; Dogs; Animals; Praziquantel; Iran; Reinfection; Farms; Echinococcosis; Echinococcus granulosus; Feces; Dog Diseases
PubMed: 38536863
DOI: 10.1371/journal.pntd.0011939 -
PLoS Neglected Tropical Diseases Mar 2024Female Genital Schistosomiasis (FGS) causes intravaginal lesions and symptoms that could be mistaken for sexually transmitted diseases or cancer. In adults, FGS lesions...
OBJECTIVE
Female Genital Schistosomiasis (FGS) causes intravaginal lesions and symptoms that could be mistaken for sexually transmitted diseases or cancer. In adults, FGS lesions [grainy sandy patches (GSP), homogenous yellow patches (HYP), abnormal blood vessels and rubbery papules] are refractory to treatment. The effect of treatment has never been explored in young women; it is unclear if gynaecological investigation will be possible in this young age group (16-23 years). We explored the predictors for accepting anti-schistosomal treatment and/or gynaecological reinvestigation in young women, and the effects of anti-schistosomal mass-treatment (praziquantel) on the clinical manifestations of FGS at an adolescent age.
METHOD
The study was conducted between 2011 and 2013 in randomly selected, rural, high schools in Ilembe, uThungulu and Ugu Districts, KwaZulu-Natal Province, East Coast of South Africa. At baseline, gynaecological investigations were conducted in female learners in grades 8 to 12, aged 16-23 years (n = 2293). Mass-treatment was offered in the low-transmission season between May and August (a few in September, n = 48), in accordance with WHO recommendations. Reinvestigation was offered after a median of 9 months (range 5-14 months). Univariate, multivariable and logistic regression analysis were used to measure the association between variables.
RESULTS
Prevalence: Of the 2293 learners who came for baseline gynaecological investigations, 1045 (46%) had FGS lesions and/or schistosomiasis, 209/1045 (20%) had GSP; 208/1045 (20%) HYP; 772/1045 (74%) had abnormal blood vessels; and 404/1045 (39%) were urine positive. Overall participation rate for mass treatment and gynaecological investigation: Only 26% (587/2293) learners participated in the mass treatment and 17% (401/2293) participated in the follow up gynaecological reinvestigations. Loss to follow-up among those with FGS: More than 70% of learners with FGS lesions at baseline were lost to follow-up for gynaecological investigations: 156/209 (75%) GSP; 154/208 (74%) HYP; 539/722 (75%) abnormal blood vessels; 238/404 (59%) urine positive. The grade 12 pupil had left school and did not participate in the reinvestigations (n = 375; 16%). Follow-up findings: Amongst those with lesions who came for both treatment and reinvestigation, 12/19 still had GSP, 8/28 had HYP, and 54/90 had abnormal blood vessels. Only 3/55 remained positive for S. haematobium ova. Factors influencing treatment and follow-up gynaecological investigation: HIV, current water contact, water contact as a toddler and urinary schistosomiasis influenced participation in mass treatment. Grainy sandy patches, abnormal blood vessels, HYP, previous pregnancy, current water contact, water contact as a toddler and father present in the family were strongly associated with coming back for follow-up gynaecological investigation. Challenges in sample size for follow-up analysis of the effect of treatment: The low mass treatment uptake and loss to follow up among those who had baseline FGS reduced the chances of a larger sample size at follow up investigation. However, multivariable analysis showed that treatment had effect on the abnormal blood vessels (adjusted odds ratio = 2.1, 95% CI 1.1-3.9 and p = 0.018).
CONCLUSION
Compliance to treatment and gynaecological reinvestigation was very low. There is need to embark on large scale awareness and advocacy in schools and communities before implementing mass-treatment and investigation studies. Despite challenges in sample size and significant loss to follow-up, limiting the ability to fully understand the treatment's effect, multivariable analysis demonstrated a significant treatment effect on abnormal blood vessels.
Topics: Adult; Pregnancy; Animals; Female; Adolescent; Humans; Praziquantel; South Africa; Schistosoma haematobium; Schistosomiasis haematobia; Genitalia, Female; Genital Diseases, Female; Water
PubMed: 38536861
DOI: 10.1371/journal.pntd.0011798 -
The American Journal of Tropical... Jun 2024Disseminated cysticercosis is defined by multiple brain lesions and involvement of other body sites. Cysticidal treatment in disseminated cysticercosis is considered...
Disseminated cysticercosis is defined by multiple brain lesions and involvement of other body sites. Cysticidal treatment in disseminated cysticercosis is considered life-threatening. We conducted a systematic review of all published cases and case series to assess the safety and efficacy of cysticidal treatment. We conducted a systematic review in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (PROSPERO CRD42022331895) to assess the safety and efficacy of cysticidal treatment. Using the search term "disseminated neurocysticercosis OR disseminated cysticercosis," databases like PubMed, Scopus, Embase, and Google Scholar were searched. Outcomes included death and secondary measures like clinical improvement and lesion reduction. We calculated the predictors of primary outcome (death) using the binary logistic regression analysis. We reviewed 222 published cases from 101 publications. Approximately 87% cases were reported from India. Of 222 cases, 134 (60%) received cysticidal treatment. Follow-up information was available from 180 patients, 11 of them died, and 169 showed clinical improvement. The death rate was 4% (5 out of 114) in patients treated with cysticidal drugs plus corticosteroids, in comparison with 13% (5 out of 38) in patients who were treated with corticosteroids alone. All patients using only praziquantel faced fatality. Death predictors identified were altered sensorium and lack of treatment with albendazole. We noted that the risk of death after cysticidal treatment is not as we expected, and a multicentric randomized controlled trial is needed to resolve this issue.
Topics: Humans; Treatment Outcome; Neurocysticercosis; Cysticercosis; Anthelmintics; Albendazole; Praziquantel; Male; Adrenal Cortex Hormones; Female; Adult
PubMed: 38531095
DOI: 10.4269/ajtmh.23-0694 -
Acta Tropica Jun 2024The drug of choice for the treatment of opisthorchiasis caused by trematodes Opisthorchis viverrini and O. felineus is praziquantel (PZQ), but there is a constant search... (Comparative Study)
Comparative Study
BACKGROUND
The drug of choice for the treatment of opisthorchiasis caused by trematodes Opisthorchis viverrini and O. felineus is praziquantel (PZQ), but there is a constant search for new anthelmintics, including those of plant origin. Positive results on the use of artemisinin derivatives against O. viverrini opisthorchiasis have been shown previously, but the effect of these compounds on O. felineus has not been studied. Therefore, here, a comparative analysis of anthelmintic properties of artemisinin derivatives (artesunate [AS], artemether [AM], and dihydroartemisinin [DHA]) was carried out in vitro in relation to PZQ. Experiments were performed on newly excysted metacercariae (NEMs) and adult flukes of O. felineus.
RESULTS
Dose- and time-dependent effects of artemisinin derivatives and of PZQ were assessed in terms of motility and mortality of both NEMs and adult flukes. The most pronounced anthelmintic action was exerted by DHA, whose half-maximal inhibitory concentrations (IC) of 1.9 (NEMs) and 2.02 µg/mL (adult flukes) were lower than those of PZQ (0.56 and 0.25 µg/mL, respectively). In contrast to PZQ, the effects of DHA and AS were similar when we compared the two developmental stages of O. felineus (NEMs and adult flukes). In addition, AM, AS, and especially DHA at doses of 100 µg/mL disrupted tegument integrity in adult flukes, which was not observed with PZQ.
CONCLUSIONS
Artemisinin derivatives (AS, AM, and DHA) have good anthelmintic efficacy against the trematode O. felineus, and the action of these substances is comparable to (and sometimes better than) the effects of PZQ.
Topics: Animals; Artemisinins; Opisthorchis; Anthelmintics; Inhibitory Concentration 50; Praziquantel; Survival Analysis; Artemether; Artesunate; Dose-Response Relationship, Drug
PubMed: 38521124
DOI: 10.1016/j.actatropica.2024.107196 -
Expert Opinion on Pharmacotherapy Mar 2024Schistosomiasis, one of the current Neglected Tropical Diseases (NTDs) affects over 230 million people globally, with nearly 700 million at risk in more than 74... (Review)
Review
INTRODUCTION
Schistosomiasis, one of the current Neglected Tropical Diseases (NTDs) affects over 230 million people globally, with nearly 700 million at risk in more than 74 countries. Praziquantel (PZQ) has served as the primary treatment for the past four decades; however, its effectiveness is limited as it solely eliminates adult worms. In regions where infections are frequent, PZQ exhibits only temporary efficacy and has restricted potential to disrupt the prolonged transmission of the disease.
AREAS COVERED
A comprehensive exploration using the PubMed database was conducted to review current pharmacotherapy approaches for schistosomiasis. This review also encompasses recent research findings related to potential novel therapeutics and the repurposing of existing drugs.
EXPERT OPINION
Current schistosoma treatment strategies, primarily relying on PZQ, face challenges like temporary effectiveness and limited impact on disease transmission. Drug repurposing, due to economic constraints, is decisive for NTDs. Despite PZQ's efficacy, its failure to prevent reinfection highlights the need for complementary strategies, especially in regions with persistent environmental foci. Integrating therapies against diverse schistosome stages boosts efficacy and impedes resistance. Uncovering novel agents is essential to address resistance concerns in tackling this neglected tropical disease. Integrated strategies present a comprehensive approach to navigate the complex challenges.
Topics: Humans; Schistosomiasis; Animals; Praziquantel; Drug Repositioning; Neglected Diseases; Schistosomicides; Drug Resistance; Schistosoma
PubMed: 38511392
DOI: 10.1080/14656566.2024.2333372 -
Parasite Immunology Mar 2024In previous studies, the inhibitory effect of chloroquine on NLRP3 inflammasome and heme production was documented. This may be employed as a double-bladed sword in...
In previous studies, the inhibitory effect of chloroquine on NLRP3 inflammasome and heme production was documented. This may be employed as a double-bladed sword in schistosomiasis (anti-inflammatory and parasiticidal). In this study, chloroquine's impact on schistosomiasis mansoni was investigated. The parasitic load (worm/egg counts and reproductive capacity index [RCI]), i-Nos/Arg-1 expression, splenomegaly, hepatic insult and NLRP3-immunohistochemical expression were assessed in infected mice after receiving early and late repeated doses of chloroquine alone or dually with praziquantel. By early treatment, the least RCI was reported in dually treated mice (41.48 ± 28.58) with a significant reduction in worm/egg counts (3.50 ± 1.29/2550 ± 479.58), compared with either drug alone. A marked reduction in the splenic index was achieved by prolonged chloroquine administration (alone: 43.15 ± 5.67, dually: 36.03 ± 5.27), with significantly less fibrosis (15 ± 3.37, 14.25 ± 2.22) than after praziquantel alone (20.5 ± 2.65). Regarding inflammation, despite the praziquantel-induced significant decrease in NLRP3 expression, the inhibitory effect was marked after dual and chloroquine administration (liver: 3.13 ± 1.21/3.45 ± 1.23, spleen: 5.7 ± 1.6/4.63 ± 2.41). i-Nos RNA peaked with early/late chloroquine administration (liver: 68.53 ± 1.8/57.78 ± 7.14, spleen: 63.22 ± 2.06/62.5 ± 3.05). High i-Nos echoed with a parasiticidal and hepatoprotective effect and may indicate macrophage-1 polarisation. On the flip side, the chloroquine-induced low Arg-1 seemed to abate immune tolerance and probably macrophage-2 polarisation. Collectively, chloroquine synergised the praziquantel-schistosomicidal effect and minimised tissue inflammation, splenomegaly and hepatic fibrosis.
Topics: Animals; Mice; Chloroquine; Down-Regulation; Drug Repositioning; Inflammation; NLR Family, Pyrin Domain-Containing 3 Protein; Parasite Load; Praziquantel; Rodent Diseases; Schistosomiasis mansoni; Splenomegaly
PubMed: 38498004
DOI: 10.1111/pim.13030 -
The Journal of Parasitology Mar 2024Schistosomiasis is a globally burdensome parasitic disease caused by flatworms (blood flukes) in the genus Schistosoma. The current standard treatment for...
Schistosomiasis is a globally burdensome parasitic disease caused by flatworms (blood flukes) in the genus Schistosoma. The current standard treatment for schistosomiasis is the drug praziquantel, but there is an urgent need to advance novel interventions such as vaccines. Several glycolytic enzymes have been evaluated as vaccine targets for schistosomiasis, and data from these studies are reviewed here. Although these parasites are canonically considered to be intracellular, proteomic analysis has revealed that many schistosome glycolytic enzymes are additionally found at the host-interactive surface. We have recently found that the intravascular stage of Schistosoma mansoni (Sm) expresses the glycolytic enzyme phosphoglycerate mutase (PGM) on the tegumental surface. Live parasites display PGM activity, and suppression of PGM gene expression by RNA interference diminishes surface enzyme activity. Recombinant SmPGM (rSmPGM) can cleave its glycolytic substrate, 3-phosphoglycerate and can both bind to plasminogen and promote its conversion to an active form (plasmin) in vitro, suggesting a moonlighting role for this enzyme in regulating thrombosis in vivo. We found that antibodies in sera from chronically infected mice recognize rSmPGM. We also tested the protective efficacy of rSmPGM as a vaccine in the murine model. Although immunization generates high titers of anti-SmPGM antibodies (against both recombinant and native SmPGM), no significant differences in worm numbers were found between vaccinated and control animals.
Topics: Animals; Mice; Schistosoma mansoni; Phosphoglycerate Mutase; Schistosomiasis mansoni; Proteomics; Schistosomiasis; Vaccines; Antigens, Helminth; Antibodies, Helminth
PubMed: 38466806
DOI: 10.1645/23-7 -
PLoS Neglected Tropical Diseases Mar 2024Schistosoma haematobium, the parasite that causes urogenital schistosomiasis, is widely prevalent in Tanzania. In addition to well-known effects on the urinary tract, S.... (Review)
Review
Schistosoma haematobium, the parasite that causes urogenital schistosomiasis, is widely prevalent in Tanzania. In addition to well-known effects on the urinary tract, S. haematobium also causes clinically- evident damage to the reproductive tract in approximately half of infected women, which is known as female genital schistosomiasis (FGS). FGS has major gynecologic and social consequences on women's reproductive health, yet little information is available regarding FGS in Tanzania. To cover that gap, we conducted the present scoping review to examine the epidemiology of FGS in Tanzania (both in the mainland and Zanzibar island) and to make recommendations for future work in this area. The available evidence from community-based and hospital-based retrospective studies indicates that FGS is a significant health problem in the country. Very few community-based studies have been reported from mainland Tanzania, and Zanzibar. Our review highlights the scarcity of efforts to address FGS in Tanzania and the need for additional community-based studies. The studies will help us understand the true burden of the disease nationwide, to assess the impact of praziquantel on FGS lesions, and to address social and mental health in relation to FGS. This review emphasizes integration of delivery of FGS related services in primary health care systems through the reproductive health clinics which covers sexually transmitted infections, HIV and cervical cancer screening. These actions are essential if this neglected gynecological disease is to be addressed in Tanzania.
Topics: Animals; Female; Humans; Tanzania; Public Health; Retrospective Studies; Early Detection of Cancer; Uterine Cervical Neoplasms; Genitalia, Female; Schistosomiasis haematobia; Schistosoma haematobium; Genital Diseases, Female
PubMed: 38466660
DOI: 10.1371/journal.pntd.0011954 -
Veterinarni Medicina Jan 2024Praziquantel (PZQ) is a drug effective against several parasitic diseases of fish caused by Platyhelminthes. The study assesses the efficacy of selected in-feed PZQ...
Praziquantel (PZQ) is a drug effective against several parasitic diseases of fish caused by Platyhelminthes. The study assesses the efficacy of selected in-feed PZQ doses in eliminating metacercariae in grass carp. The fish were infected with in laboratory conditions and subsequently treated with PZQ at daily doses of 30 (PZQ1), 50 (PZQ2), and 100 (PZQ3) mg/kg bw for seven days. The treatment trial was followed by a 23-day observation period during which the fish were parasitologically examined on days 0, 2, 8 and 23. Smaller fish were infected with a significantly higher ( < 0.05) number of metacercariae than bigger fish among three weight groups as follows: up to 7 g > 7 to 12 g > 12 g. The in-feed PZQ at doses of 30, 50 and 100 mg/kg bw for seven days was 47%, 84% and 88% effective against metacercariae , respectively. A significant decrease ( < 0.01) in moving and an increase ( < 0.01) in the immotile metacercariae in the eye's lens were recorded in all the trial groups on each sampling day. An increasing proportion of motile metacercariae in the post-treatment observation period was seen in PZQ2 and PZQ3, indicating a decreasing trend in the actual efficacy in an environment with no reinfection possibility.
PubMed: 38465001
DOI: 10.17221/97/2023-VETMED -
Clinical Therapeutics Apr 2024The bad bitter taste of some medicines is a barrier to overcoming noncompliance with medication use, especially life-saving drugs given to children and the elderly....
PURPOSE
The bad bitter taste of some medicines is a barrier to overcoming noncompliance with medication use, especially life-saving drugs given to children and the elderly. Here, we evaluated a new class of bitter blockers (thiazolidinediones, TZDs).
METHODS
In this study, 2 TZDs were tested, rosiglitazone (ROSI) and a simpler form of TZD, using a high-potency sweetener as a positive control (neohesperidin dihydrochalcone, NHDC). We tested bitter-blocking effects using the bitter drugs tenofovir alafenamide fumarate (TAF), a treatment for HIV and hepatitis B infection, and praziquantel (PRAZ), a treatment for schistosomiasis, by conducting taste testing with 2 separate taste panels: a general panel (N = 97, 20-23 years, 82.5% female, all Eastern European) and a genetically informative panel (N = 158, including 68 twin pairs, 18-82 years, 76% female, 87% European ancestry). Participants rated the bitterness intensity of the solutions on a 100-point generalized visual analog scale.
FINDINGS
Person-to-person differences in drug bitterness were striking; TAF and PRAZ were weakly or not bitter for some people but moderately to highly bitter for others. Participants in both taste panels rated the bitter drugs TAF and PRAZ as less bitter on average when mixed with NHDC than when sampled alone. ROSI partially suppressed the bitterness of TAF and PRAZ, but effectiveness differed between the 2 panels: bitterness was significantly reduced for PRAZ but not TAF in the general panel and for TAF but not PRAZ in the genetically informative panel. ROSI was a more effective blocker than the other TZD.
IMPLICATIONS
These results suggest that TZDs are partially effective bitter blockers and the suppression efficacy differs from drug to drug, from person to person, and from panel to panel, suggesting other TZDs should be designed and tested with more drugs and on diverse populations to define which ones work best with which drugs and for whom. The discovery of bitter receptor blockers can improve compliance with medication use.
Topics: Humans; Female; Male; Taste; Adult; Aged; Middle Aged; Young Adult; Adolescent; Aged, 80 and over; Thiazolidinediones; Tenofovir; Rosiglitazone; Alanine
PubMed: 38462427
DOI: 10.1016/j.clinthera.2024.02.002