A historical and systematic overview of Ascaris vaccine development.

Ascariasis is the most prevalent helminth infection in the world and leads to significant, life-long morbidity, particularly in young children. Current efforts to control and eradicate ascariasis in endemic regions have been met with significant challenges including high-rates of re-infection and potential development of anthelminthic drug resistance. Vaccines against ascariasis are a key tool that could break the transmission cycle and lead to disease eradication globally. Evolution of the Ascaris vaccine pipeline has progressed, however no vaccine product has been brought to human clinical trials to date. Advancement in recombinant protein technology may provide the first step in generating an Ascaris vaccine as well as a pan-helminthic vaccine ready for human trials. However, several roadblocks remain and investment in new technologies will be important to develop a successful human Ascaris vaccine that is critically needed to prevent significant morbidity in Ascaris-endemic regions around the world.

Cluster of Parasite Infections by the Spatial Scan Analysis in Korea.

This study was performed to find out the clusters with high parasite infection risk to discuss the geographical pattern. Clusters were detected using SatScan software, which is a statistical spatial scan program using Kulldorff's scan statistic. Information on the parasitic infection cases in Korea 2011-2019 were collected from the Korea Centers for Disease Control and Prevention. Clusters of Ascaris lumbricoides infection were detected in Jeollabuk-do, and T. trichiura in Ulsan, Busan, and Gyeongsangnam-do. C. sinensis clusters were detected in Ulsan, Daegu, Busan, Gyeongsangnam-do, and Gyeongsangbuk-do. Clusters of intestinal trematodes were detected in Ulsan, Busan, and Gyeongsangnam-do. P. westermani cluster was found in Jeollabuk-do. E. vermicularis clusters were distributed in Gangwon-do, Jeju-do, Daegu, Daejeon, and Gwangju. This clustering information can be referred for surveillance and control on the parasitic infection outbreak in the infection-prone areas.

[Current Incidence and Contamination Sources of Ascariasis in Japan].

Ascaris lumbricoides or roundworm is one of the key soil-transmitted helminths affecting humans. A small number of infections continue to occur in Japan, suggesting plant foodstuff contamination as the source of infection. To understand the current status of ascariasis incidence and to identify potential sources of infection, we extensively surveyed the available literature and collected data from testing facilities that examined clinical samples or foodstuffs. We observed that from 2002 onwards, there was a decrease in the number of ascariasis cases reported in scientific journals. Data from a clinical testing facility indicated that the number of detected cases declined remarkably from 2009. Foodstuff testing facilities reported that 11 of 10,223 plant foodstuff specimens were contaminated with anisakid nematodes but not with Ascaris. Imported kimchi was suspected as the most probable source of ascarid nematode infection, as one Ascaris egg-positive sample was detected among 60 kimchi samples in a testing facility. Therefore, the sources of Ascaris infection are still not fully known and need to be clarified to establish preventive countermeasures to safeguard Ascaris infections that continue to occur in Japan.

The impact of seasonality on the dynamics and control of Ascaris lumbricoides infections.

Intestinal nematode infections affect a huge proportion of the world's population. Increasingly these infections, particularly amongst the poorest communities, are controlled through mass drug treatment programs. Seasonal variations of climate and behaviour in these regions can be significant, but their impact on the dynamics of infection and implications for the effectiveness of any mass drug treatment program (a pulsed reduction in worm burden in hosts) is not clearly understood. Here the effect of seasonality on the dynamics of the soil-based helminth, Ascaris lumbricoides, is investigated using a reformulated version of the Anderson-May model for macro-parasitic infections. Explicit analytical expressions are obtained for the stable oscillatory solution over the annual cycle, which provides a means of relating times of peak numbers of eggs, larvae and mature worms to seasonal variations. Numerical and analytical techniques are then used to consider the impact of seasonality on the optimal timing of drug treatment. Our results show that there is a relatively large window for the timing of optimal treatment, and the impact of repeated annual mass drug treatments can be substantially improved if they are timed to coincide with the months when the number of eggs and larvae are at their lowest - minimising reinfection. In terms of a more measurable quantity, in our example this corresponds to the months when the seasonal temperature is highest. Multiple annual treatments at (or close to) the optimal time each year are predicted to achieve local elimination in the community, whereas treatment at other times has a more limited impact. A key finding is that even for pronounced seasonality, perturbations in mean worm burden, and hence seasonal variation in observed egg output, may be small, potentially explaining why seasonal effects have been overlooked. Taken together these results suggest that seasonality of soil-transmitted helminths requires further experimental, field and mathematical study if the impact for mass drug administration programs is to be exploited.

Assessment of schistosomiasis and soil-transmitted helminths prevalence in school-aged children and opportunities for integration of control in local health services in Kwilu Province, the Democratic Republic of the Congo.

OBJECTIVE: To determine the prevalence of schistosomiasis (SCH) and soil-transmitted helminths (STH) in the Democratic Republic of Congo, and to assess the capacity of the local health centres for diagnosis and treatment. METHODS: Cross-sectional school-based survey in two health districts in the Province of Kwilu. We collected a stool and a urine sample for parasitological examination. Urine filtration and duplicate Kato-Katz thick smears were used for the diagnosis of SCH. Health centres were evaluated using a structured questionnaire. RESULTS: In total, 526 children participated in the study and the overall prevalence of Schistosoma mansoni infection was 8.9% (95% CI: 3.5-13.2) in both districts. The prevalence was higher in Mosango (11.7%; 95% CI: 8.9-14.8) than Yasa Bonga district (6.2%; 95% CI: 1.1-11.4). Urine filtration showed that Schistosoma haematobium infection was not present. The combined STH infection prevalence was 58.1% in both districts; hookworm infection was the most common STH found in 52.9% (95% CI: 29.3-62.4) of subjects, followed by Ascaris lumbricoides 9.3% (95% CI: 5.8-15.5) and Trichuris trichiura 2.1% (95% CI: 0.9-4.9). Mixed STH infections were observed as well as SCH-STH coinfection. CONCLUSION: Further mapping of both SCH and STH burden is needed, and coverage of preventive chemotherapy in school-aged children should be increased.

Worm Infections in Children.

• On the basis of research evidence, worm infections are important global child health conditions causing chronic disability that lasts from childhood into adulthood (Table 1). (2)(3) Evidence Quality: B • On the basis of research evidence, the major worm infections found in developing countries include ascariasis, trichuriasis, hookworm infection, and schistosomiasis; toxocariasis, enterobiasis, and cysticercosis are also found in poor regions of North America and Europe. (4)(9)(13) Evidence Quality: B • On the basis of expert consensus, children and adolescents are often vulnerable to acquiring large numbers of worms, ie, high-intensity infections (Fig 1)(21)(22)(23) Evidence Quality: D • On the basis of expert consensus and research evidence, moderate and heavy worm burdens cause increased morbidity because of growth and intellectual stunting in children and adolescents. Many of these effects may result from helminth-induced malnutrition. (21)(22)(23) Evidence Quality: C • On the basis of expert consensus and research evidence, worm infections are also commonly associated with eosinophilia. (48) (49) Evidence Quality: B • On the basis of research evidence as well as consensus, helminthes can cause inflammation in the lung (asthma), gastrointestinal tract (enteritis and colitis), liver (hepatitis and fibrosis), and urogenital tract. (7)(21)(22)(23)(27)(28)(40)(41)(43) Evidence Quality: B • On the basis of research evidence, microscopy techniques for diagnosis of worm infections in children often exhibit suboptimal sensitivities and specificities, necessitating new or improved diagnostic modalities such as polymerase chain reaction. (54)(55) Evidence Quality: A • On the basis of research evidence and expert consensus, mass drug administration ("preventive chemotherapy") has becomea standard practice for ministries of health in low- and middle-income countries to control intestinal helminth infections and schistosomiasis. (67)(68) Evidence Quality: B.

Soil-transmitted helminths in southern highland Rwanda: associated factors and effectiveness of school-based preventive chemotherapy.

OBJECTIVES: Preventive chemotherapy of schoolchildren against soil-transmitted helminths (STHs) is widely implemented in Rwanda. However, data on its actual efficacy are lacking. We assessed prevalence, associated factors and manifestation of STH infection among schoolchildren in southern highland Rwanda as well as cure and reinfection rates. METHODS: Six hundred and twenty-two children (rural, 301; urban, 321) were included preceding the administration of a single dose of 500 mg mebendazole. Before treatment, and after 2 and 15 weeks, STH infection was determined by Kato-Katz smears and by PCR assays for Ascaris lumbricoides. Clinical and anthropometric data, socio-economic status and factors potentially associated with STH infection were assessed. RESULTS: Soil-transmitted helminth (STH) infection was present in 38% of rural and in 13% of urban schoolchildren. Ascaris lumbricoides accounted for 96% of infections. Of these, one-third was detected by PCR exclusively. Factors associated with STH infection differed greatly between rural and urban children. Likewise, STH infection was associated with stunting and anaemia only among urban children. The cure rate after 2 weeks was 92%. Among eight non-cleared A. lumbricoides infections, seven were submicroscopic. Reinfection within 3 months occurred in 7%, but the rate was higher among rural children, and with initially present infection, particularly at comparatively high intensity. CONCLUSIONS: The rural-urban difference in factors associated with STH infection and in reinfection rates highlights the need for targeted interventions to reduce transmission. PCR assays may help in detecting low-level infections persisting after treatment. In southern Rwanda, mebendazole is highly effective against the STH infections predominated by A. lumbricoides.

Application of the Fenton process in the elimination of helminth eggs.

This study relates to a method for evaluating the degradation efficiency of Ascaris lumbricoides eggs through a Fenton reaction, using hydrogen peroxide (H2O2) at 100, 250, and 500 mg/L, ferrous sulfate (FeSO4) at 458 mg/L Fe(2+) and pH values of 3, 4.5, and 6. The experiments were conducted according to a 3(2) experimental design, with 1:1, 3:1, and 5:1 (H2O2/Fe(2+)) molar ratios. The oxidation and flocculation stages were performed at 130 rpm during 2 hours and at 25-30 rpm during 20 min, respectively. As a result of the Fenton reaction, an average of 91.2% Ascaris lumbricoides egg degradation was achieved at pH 6 using a 500 mg/L dose of H2O2 and a 3:1 (H2O2/Fe(2+)) molar ratio. Thus, this process is an alternative for eliminating parasites that are resistant to conventional disinfection processes and significantly reduces the human health hazard they represent.

Bioaccessibility and oral immunization efficacy of a chimeric protein vaccine against Ascaris suum.

Human ascariasis has been characterized as the most prevalent neglected tropical disease worldwide. There is an urgent need for search to alternative prevention and control methods for ascariasis. Here we aimed to establish a protocol of oral immunization with a previously described chimera protein capable of resist through digestion and induce mucous protection against Ascaris suum infection. Mice were oral immunized with seven doses with one day interval and challenged with A. suum ten days after the last dose. In vitro digestion showed that 64% of chimeric protein was bioaccessible for absorption after digestion. Immunized mice display 66,2% reduction of larval burden in lungs compared to control group. In conclusion we demonstrated that oral immunization with chimera protein protects the host against A. suum larval migration leading to less pronounced histopathological lesions.

In silico design of a polypeptide as a vaccine candidate against ascariasis.

Ascariasis is the most prevalent zoonotic helminthic disease worldwide, and is responsible for nutritional deficiencies, particularly hindering the physical and neurological development of children. The appearance of anthelmintic resistance in Ascaris is a risk for the target of eliminating ascariasis as a public health problem by 2030 set by the World Health Organisation. The development of a vaccine could be key to achieving this target. Here we have applied an in silico approach to design a multi-epitope polypeptide that contains T-cell and B-cell epitopes of reported novel potential vaccination targets, alongside epitopes from established vaccination candidates. An artificial toll-like receptor-4 (TLR4) adjuvant (RS09) was added to improve immunogenicity. The constructed peptide was found to be non-allergic, non-toxic, with adequate antigenic and physicochemical characteristics, such as solubility and potential expression in Escherichia coli. A tertiary structure of the polypeptide was used to predict the presence of discontinuous B-cell epitopes and to confirm the molecular binding stability with TLR2 and TLR4 molecules. Immune simulations predicted an increase in B-cell and T-cell immune response after injection. This polypeptide can now be validated experimentally and compared to other vaccine candidates to assess its possible impact in human health.

Effect of sanitation on soil-transmitted helminth infection: systematic review and meta-analysis.

BACKGROUND: In countries of high endemicity of the soil-transmitted helminth parasites Ascaris lumbricoides, Trichuris trichiura, and hookworm, preventive chemotherapy (i.e., repeated administration of anthelmintic drugs to at-risk populations) is the main strategy to control morbidity. However, rapid reinfection of humans occurs after successful deworming, and therefore effective preventive measures are required to achieve public health goals with optimal efficiency and sustainability. METHODS AND FINDINGS: We conducted a systematic review and meta-analysis to assess the effect of sanitation (i.e., access and use of facilities for the safe disposal of human urine and feces) on infection with soil-transmitted helminths. PubMed, Embase, ISI Web of Science, and the World Health Organization Library Database were searched without language restrictions and year of publication (search performed until December 31, 2010). Bibliographies of identified articles were hand-searched. All types of studies reporting data on sanitation availability (i.e., having access at own household or living in close proximity to sanitation facility), or usage, and soil-transmitted helminth infections at the individual level were considered. Reported odds ratios (ORs) of the protective effect of sanitation on soil-transmitted helminth infections were extracted from the papers or calculated from reported numbers. The quality of published studies was assessed with a panel of criteria developed by the authors. Random effects meta-analyses were used to account for observed heterogeneity. Thirty-six publications, consisting of 39 datasets, met our inclusion criteria. Availability of sanitation facilities was associated with significant protection against infection with soil-transmitted helminths (OR  =  0.46 to 0.58). Regarding the use of sanitation, ORs of 0.54 (95% confidence interval [CI] 0.28-1.02), 0.63 (95% CI 0.37-1.05), and 0.78 (95% CI 0.60-1.00) were determined for T. trichiura, hookworm, and A. lumbricoides, respectively. The overall ORs, combining sanitation availability and use, were 0.51 (95% CI 0.44-0.61) for the three soil-transmitted helminths combined, 0.54 (95% CI 0.43-0.69) for A. lumbricoides, 0.58 (95% CI 0.45-0.75) for T. trichiura, and 0.60 (95% CI 0.48-0.75) for hookworm. CONCLUSIONS: Despite a number of limitations (e.g., most studies used a cross-sectional design and were of low quality, with potential biases and considerable heterogeneity), our results reveal that sanitation is associated with a reduced risk of transmission of helminthiases to humans. Access to improved sanitation should be prioritized alongside preventive chemotherapy and health education to achieve a durable reduction of the burden of helminthiases.

Soil-transmitted helminthiasis: a critical but neglected factor influencing school participation of Aboriginal children in rural Malaysia.

Soil-transmitted helminthiasis (STH), among the most common neglected tropical diseases, is a major public health problem in Malaysia with a possible impact on the nutritional status and school participation of rural children. This study was carried out among Aboriginal schoolchildren, living in an endemic area for STH in Malaysia, to determine the possible relationship between intestinal helminthiasis and school absenteeism. We also evaluated whether successful treatment of the infection will affect school attendance among the subjects. Stool analysis revealed that more than 90% of the subjects were infected with at least 1 helminth species, with Ascaris lumbricoides and Trichuris trichiura infections being most prevalent. Infection of moderate-to-heavy worm burdens, low level of fathers' education and anaemia were identified as the significant predictors of high absenteeism among the subjects (P<0·05). Following treatment of the infected children, it was found that school absenteeism was reduced significantly (P<0·01). In conclusion, STH continues to have significant impacts on public health, particularly in rural communities with a negatively significant effect on the school participation of Aboriginal children. A school-based de-worming programme should be introduced and incorporated in the current educational assistance targeted towards the Aboriginal communities, under the auspices of the government.

Chemotherapy-based control of ascariasis and hookworm in highly endemic areas of China: field observations and a modeling analysis.

OBJECTIVE: Our objective was to systematically evaluate chemotherapy-based control of ascariasis and hookworm infection and make predictions of the effectiveness of repeated mass treatment at different levels of coverage in highly endemic areas of China. METHODS: Field surveys were carried out to acquire the ascariasis and hookworm prevalence and intensity (mean worm burden) at baseline, one month and one year later. We calculated model parameters based on the survey data, then incorporated them into a quantitative framework to predict the prevalence and intensity one year later. Sensitivity analyses were performed to assess the influence of the chemotherapy measures on prevalence and intensity, and model simulations were performed to evaluate the feasibility of achieving the proposed transmission control criteria under different chemotherapy measures. RESULTS: The predicted prevalence and intensity one year from baseline were within the 95% confidence interval of actual values. As treatment frequency or coverage increased, the prevalence and intensity decreased. Model simulations show that many rounds of treatment are needed to maintain the prevalence at a low level in highly endemic areas of China. CONCLUSION: We should select different combinations of treatment frequency, coverage and drug efficacy according to available resources and practical attainable conditions. Mathematical modeling could be used to help optimize the chemotherapeutic scheme aiming at specific parasitic species and areas, and to direct the establishment of soil-transmitted helminthiasis control criteria in China.

Trichuris and hookworm infections associated with anaemia during pregnancy.

OBJECTIVE: To assess the following associations between the second and third trimesters of pregnancy: (i) the intensity of soil-transmitted helminth (STH) infection and haemoglobin/anaemia, (ii) the effect of mebendazole treatment on the occurrence of STH infection, and (iii) the effect of mebendazole treatment on haemoglobin/anaemia. METHODS: Data originated from a trial of 1042 pregnant women recruited in their second trimester and followed to delivery. Baseline assessments included socio-demographic/health information from questionnaires, haemoglobin/anaemia from HemoCue ascertainment of fingerprick blood, and the presence and intensity of STH (Ascaris lumbricoides, hookworms and Trichuris trichiura) infections from Kato-Katz examination. All women were given iron supplements; half were randomly allocated to receive single dose 500 mg mebendazole, and half, placebo. Haemoglobin/anaemia and STH infection status were determined again in the third trimester of pregnancy. RESULTS: Complete information was available from 935 (89.7%) women. Mebendazole significantly reduced the prevalence and intensity of all three STH infections. Higher intensities of hookworm and Trichuris infections in the second trimester were associated with a higher risk of anaemia in the third trimester. Overall, women with moderate/heavy Trichuris infection were found to be at a higher risk of anaemia; the highest risk was observed among those with moderate/heavy hookworm co-infection (adjusted OR = 2.77; 95% CI: 1.26, 6.11). Mebendazole treatment did not reduce the risk of anaemia. CONCLUSION: Higher intensities of both Trichuris and hookworm infections are associated with anaemia in pregnancy. The importance of Trichuris infections during pregnancy requires renewed attention.

Intervention to prevent intestinal parasitic reinfections among Tarahumara indigenous schoolchildren in northern Mexico.

OBJECTIVE: To assess the effectiveness of a 20-week, broad intervention to prevent reinfection by Ascaris lumbricoides (AL) and Giardia lamblia (GL) among indigenous schoolchildren in northern Mexico. METHODS: A prospective, comparative, ecological study. Two isolated boarding schools, each hosting 100-120 children, 4-15 years of age, were selected based on physical infrastructure: intervention school (IS), modern; control school (CS), deprived. After initial diagnosis, children with positive stool samples received supervised treatment with oral nitazoxanide. Diagnoses were made with at least one positive microscopic result from two serial samples using the Faust technique, as reported by the independent observations of two trained, laboratory technicians. Post-treatment samples were taken, and only those with negative results were followed-up. The intervention included infrastructure improvements/maintenance and an educational preventive program for children, parents, and school personnel; no activities were undertaken in the CS. RESULTS: Baseline prevalence for AL was 37.5% at the IS versus 16.6% at the CS (P < 0.01); and for GL, 51.7% versus 37.8%, respectively. At the IS, 35.7% did not speak Spanish, compared to 6.7% in the CS (P < 0.01). Cure rates were similar in both schools for AL (~ 98%) and GL (~ 80%). Final prevalence and reinfection rates for GL were 10.4% versus 10.8%, and 17.2% versus 21% at the IS and CS, respectively. No children were infected/reinfected with AL in either school. Follow-up rates were 80%-83% at the CS and 90%-95% at the IS. CONCLUSIONS: Infection/reinfection rates were similar at the schools after 20 weeks. Supervised treatment alone every semester could effectively control AL/GL infections in this indigenous setting.

Evaluation of the WHO helminth eggs criteria using a QMRA approach for the safe reuse of wastewater and sludge in developing countries.

An analysis of the actual WHO recommendations to develop standards for the safe reuse of wastewater, excreta or sludge in agriculture using a quantitative microbial risk assessment (QMRA) is presented. The proposed values are defined using a risk-based model for Ascaris lumbricoides infection to assess the human risks associated with exposure to this pathogen from crops irrigated with polluted water, or from crops grown in biosolid-enriched soil. From the results it becomes evident that, with regard to helminth eggs, the WHO guidelines for wastewater reuse in agriculture seem more stringent than are needed in developing countries, while for the reuse of sludge they appear to be the opposite. Although more information is needed to confirm this conclusion, which was derived from a single piece of research, at the very least a more cautious approach is recommended when evaluating excreta or sludge for agricultural purposes in developing countries. Additionally, this work shows that the application of some barriers, other than wastewater and sludge treatment as suggested by WHO, can play an important role in controlling risks.

Ovicidal activity of seven Pochonia chlamydosporia fungal isolates on Ascaris suum eggs.

The ovicidal effect of the nematophagous fungus Pochonia chlamydosporia on eggs of Ascaris suum was tested under laboratory conditions. A. suum eggs were plated on 2% water-agar with seven fungal isolates (Isol. 5, Isol. 31, Isol. 1, VC1, Isol. 12, Isol. 22 and VC4) and control without fungus. After 5, 7, 10, 14, 15 and 21 days of incubation, approximately 100 eggs were removed from the plates and classified according to the following parameters: type 1, biochemical and physiological effect without morphological damage to the eggshell, type 2, lytic effect with morphological alteration of the eggshell and embryo and type 3, lytic effect with morphological alteration of eggshell and embryo showing hyphal penetration and internal egg colonization. The isolates effectively destroyed A. suum eggs and all types of effects were observed during the experiment. There was no variation in ovicidal capacity (type 3 effect) among the isolates (p>0.05) throughout the experiment. After 21 days, isolate 5 showed the highest percentages of type 3 effect (58.33%). The results indicated that P. chlamydosporia (Isol. 5, Isol. 31, Isol. 1, VC1, Isol. 12, Isol. 22 and VC4) can destroy A. suum eggs and is, therefore, a potential biological control agent of nematodes.

Vaccination with chimeric protein induces protection in murine model against ascariasis.

An estimated 400 million people are infected by parasites of the genus Ascaris and the existing control measures are inefficient. Vaccine development using B cell antigens is a promising strategy for increased protection against this parasite. The present study aimed at developing a chimeric protein capable of conferring protection against infection by Ascaris sp. For this purpose, we performed B-cell epitope predictions on previously described vaccine candidate proteins from Ascaris suum and the corresponding peptides were used to construct a chimeric protein. Female BALB / c mice were immunized subcutaneously in three doses at 10 day intervals with a vaccine formulation comprised of the chimeric protein together with monophosphoryl lipid A (MPLA). Control groups included protein alone, MPLA, or PBS. After challenge infection, animals vaccinated with chimeric protein plus MPLA showed a reduction of 73.54% of larval load in the lung compared to control group animals. Animals immunized with chimeric protein plus MPLA also display higher IgG response and a reduction in lung inflammation. Our study highlights how chimeric proteins containing more than one B cell epitope can enhance immune protection against helminthic infection and offer new approaches to the development of Ascaris vaccines.

ASCVac-1, a Multi-Peptide Chimeric Vaccine, Protects Mice Against Ascaris suum Infection.

Control of human ascariasis, the most prevalent neglected tropical disease globally affecting 450 million people, mostly relies on mass drug administration of anthelmintics. However, chemotherapy alone is not efficient due to the high re-infection rate for people who live in the endemic area. The development of a vaccine that reduces the intensity of infection and maintains lower morbidity should be the primary target for infection control. Previously, our group demonstrated that immunization with crude Ascaris antigens in mice induced an IgG-mediated protective response with significant worm reduction. Here, we aimed to develop a multipeptide chimera vaccine based on conserved B-cell epitopes predicted from 17 common helminth proteomes using a bioinformatics algorithm. More than 480 B-cell epitopes were identified that are conserved in all 17 helminths. The Ascaris-specific epitopes were selected based on their reactivity to the pooled sera of mice immunized with Ascaris crude antigens or infected three times with A. suum infective eggs. The top 35 peptides with the strongest reactivity to Ascaris immune serum were selected to construct a chimeric antigen connected in sequence based on conformation. This chimera, called ASCVac-1, was produced as a soluble recombinant protein in an Escherichia coli expression system and, formulated with MPLA, was used to immunize mice. Mice immunized with ASCVac-1/MPLA showed around 50% reduced larvae production in the lungs after being challenged with A. suum infective eggs, along with significantly reduced inflammation and lung tissue/function damage. The reduced parasite count and pathology in infected lungs were associated with strong Th2 immune responses characterized by the high titers of antigen-specific IgG and its subclasses (IgG1, IgG2a, and IgG3) in the sera and significantly increased IL-4, IL-5, IL-13 levels in lung tissues. The reduced IL-33 titers and stimulated eosinophils were also observed in lung tissues and may also contribute to the ASCVac-1-induced protection. Taken together, the preclinical trial with ASCVac-1 chimera in a mouse model demonstrated its significant vaccine efficacy associated with strong IgG-based Th2 responses, without IgE induction, thus reducing the risk of an allergic response. All results suggest that the multiepitope-based ASCVac-1 chimera is a promising vaccine candidate against Ascaris sp. infections.

Spatial co-distribution of neglected tropical diseases in the east African great lakes region: revisiting the justification for integrated control.

OBJECTIVE: To determine spatial patterns of co-endemicity of schistosomiasis mansoni and the soil-transmitted helminths (STHs) Ascaris lumbricoides, Trichuris trichiura and hookworm in the Great Lakes region of East Africa, to help plan integrated neglected tropical disease programmes in this region. METHOD: Parasitological surveys were conducted in Uganda, Tanzania, Kenya and Burundi in 28 213 children in 404 schools. Bayesian geostatistical models were used to interpolate prevalence of these infections across the study area. Interpolated prevalence maps were overlaid to determine areas of co-endemicity. RESULTS: In the Great Lakes region, prevalence was 18.1% for Schistosoma mansoni, 50.0% for hookworm, 6.8% for A. lumbricoides and 6.8% for T. trichiura. Hookworm infection was ubiquitous, whereas S. mansoni, A. lumbricoides and T. trichiura were highly focal. Most areas were endemic (prevalence >or=10%) or hyperendemic (prevalence >or=50%) for one or more STHs, whereas endemic areas for schistosomiasis mansoni were restricted to foci adjacent large perennial water bodies. CONCLUSION: Because of the ubiquity of hookworm, treatment programmes are required for STH throughout the region but efficient schistosomiasis control should only be targeted at limited high-risk areas. Therefore, integration of schistosomiasis with STH control is only indicated in limited foci in East Africa.