Global prevalence of latent toxoplasmosis in pregnant women: a systematic review and meta-analysis.

BACKGROUND: Toxoplasma gondii infection, if acquired as an acute infection during pregnancy, can have substantial adverse effects on mothers, fetuses and newborns. Latent toxoplasmosis also causes a variety of pathologies and has been linked to adverse effects on pregnancy. OBJECTIVE: Here, we present results of a comprehensive systematic review and meta-analysis of the global prevalence of latent toxoplasmosis in pregnant women. DATA SOURCE: We searched PubMed, EMBASE, Web of Science, SciELO and Scopus databases for relevant studies that were published between 1 January 1988 and 20 July 2019. STUDY ELIGIBILITY CRITERIA: All population-based, cross-sectional and longitudinal studies reporting the prevalence of latent toxoplasmosis in healthy pregnant women were considered for inclusion. PARTICIPANTS: Pregnant women who were tested for prevalence of latent toxoplasmosis. INTERVENTIONS: There were no interventions. METHOD: We used a random effects model to calculate pooled prevalence estimates with 95% confidence intervals (CIs). We grouped prevalence data according to the geographic regions defined by the World Health Organization (WHO). Multiple subgroup and meta-regression analyses were performed. RESULTS: In total, 311 studies with 320 relevant data sets representing 1 148 677 pregnant women from 91 countries were eligible for inclusion in the meta-analysis. The global prevalence of latent toxoplasmosis in pregnant women was estimated at 33.8% (95% CI, 31.8-35.9%; 345 870/1 148 677). South America had the highest pooled prevalence (56.2%; 50.5-62.8%) of latent toxoplasmosis in pregnant women, whereas the Western Pacific region had the lowest prevalence (11.8%; 8.1-16.0%). A significantly higher prevalence of latent toxoplasmosis was associated with countries with low income and low human development indices (p < 0.001). CONCLUSION: Our results indicate a high level of latent toxoplasmosis in pregnant women, especially in some low- and middle-income countries of Africa and South America, although the local prevalence varied markedly. These results suggest a need for improved prevention and control efforts to reduce the health risks to women and newborns.

A phase 1 study of the safety, reactogenicity, and immunogenicity of a Schistosoma mansoni vaccine with or without glucopyranosyl lipid A aqueous formulation (GLA-AF) in healthy adults from a non-endemic area.

BACKGROUND: Schistosomiasis caused by Schistosoma mansoni (Sm) is a chronic, debilitating and potentially deadly neglected tropical disease. The licensure of a vaccine to prevent schistosomiasis would represent a major breakthrough in public health. METHODS: The safety and immunogenicity of a candidate Sm vaccine were assessed in this phase I, double-blind, dose-escalation trial. Seventy-two healthy Sm-naïve 18-50 year olds were randomized to receive 3 doses ∼ 8 weeks apart of saline placebo, or 10 µg, 30 µg, or 100 µg of recombinant Sm-Tetraspanin-2 vaccine formulated on aluminum hydroxide adjuvant (Sm-TSP-2/Al) with or without 5 µg of glucopyranosyl lipid A aqueous formulation (GLA-AF). Clinical and serologic responses were assessed for 1 year after dose 3. RESULTS: Vaccines were safe and well-tolerated. The most common reactions were injection site tenderness and pain, and headache and fatigue. Tenderness and pain were more frequent in groups receiving vaccine with GLA-AF than placebo (p = 0.0036 and p = 0.0014, respectively). Injection site reactions among those given Sm-TSP-2/Al with GLA-AF lasted 1.22 and 1.33 days longer than those receiving Sm-TSP-2/Al without GLA-AF or placebo (p < 0.001 for both). Dose- and adjuvant-related increases in serum IgG against Sm-TSP-2 were observed. Peak IgG levels occurred 14 days after dose 3. Seroresponse frequencies were low among recipients of Sm-TSP-2/Al without GLA-AF, but higher among subjects receiving 30 µg or 100 µg of Sm-TSP-2/Al with GLA-AF. More seroresponses were observed among those given 30 µg or 100 µg of Sm-TSP-2/Al with GLA-AF compared to placebo (p = 0.023 and p < 0.001, respectively). Seroresponse frequencies were 0%, 30%, 50%, and 89%, respectively, among those given placebo, or 10 µg, 30 µg or 100 µg of Sm-TSP-2/Al with GLA-AF, suggesting a dose-response relationship for Sm-TSP-2/Al with GLA-AF (p = 0.0001). CONCLUSIONS: Sm-TSP-2/Al with or without GLA-AF was safe and well tolerated in a Sm-naïve population. A vaccine like the one under development may represent our best hope to eliminating this neglected tropical disease.

Trypanosoma cruzi screening in Texas blood donors, 2008-2012.

Chagas disease is an important emerging disease in Texas that results in cardiomyopathy in about 30% of those infected with the parasite Trypanosoma cruzi. Between the years 2008 and 2012, about 1/6500 blood donors were T. cruzi antibody-confirmed positive. We found older persons and minority populations, particularly Hispanic, at highest risk for screening positive for T. cruzi antibodies during routine blood donation. Zip code analysis determined that T. cruzi is associated with poverty. Chagas disease has a significant disease burden and is a cause of substantial economic losses in Texas.

Limited antigenic variation in the Trypanosoma cruzi candidate vaccine antigen TSA-1.

Chagas disease (American trypanosomiasis caused by Trypanosoma cruzi) is one of the most important neglected tropical diseases in the Western Hemisphere. The toxicities and limited efficacies of current antitrypanosomal drugs have prompted a search for alternative technologies such as a therapeutic vaccine comprised of T. cruzi antigens, including a recombinant antigen encoding the N-terminal 65 kDa portion of Trypomastigote surface antigen-1 (TSA-1). With at least six known genetically distinct T. cruzi lineages, variability between the different lineages poses a unique challenge for the development of broadly effective therapeutic vaccine. The variability across the major lineages in the current vaccine candidate antigen TSA-1 has not previously been addressed. To assess the variation in TSA-1, we cloned and sequenced TSA-1 from several different T. cruzi strains representing three of the most clinically relevant lineages. Analysis of the different alleles showed limited variation in TSA-1 across the different strains and fit with the current theory for the evolution of the different lineages. Additionally, minimal variation in known antigenic epitopes for the HLA-A 02 allele suggests that interlineage variation in TSA-1 would not impair the range and efficacy of a vaccine containing TSA-1.

Neglected infections of poverty in Texas and the rest of the United States: management and treatment options.

In the poorest regions of the United States, especially along the Gulf Coast and in South Texas, are a group of endemic parasitic and related infections known as the neglected infections of poverty. Such infections are characterized by their chronicity, disabling features, and disproportionate impact on the estimated 46 million people who live below the U.S. poverty line. Today more Americans live in poverty than ever before in the half-century that the Census Bureau has been recording poverty rates. In association with that poverty, a group of major neglected infections of poverty have emerged in the United States. Here we describe the major neglected infections of poverty in the United States, with a brief overview of their significant epidemiological features, their links with poverty, and our approaches to their diagnosis, management, and treatment.

Fusion of Na-ASP-2 with human immunoglobulin Fcγ abrogates histamine release from basophils sensitized with anti-Na-ASP-2 IgE.

Na-ASP-2 is a major protein secreted by infective third-stage larvae (L3) of the human hookworm Necator americanus upon host entry. It was chosen as a lead vaccine candidate for its ability to elicit protective immune responses. However, clinical development of this antigen as a recombinant vaccine was halted because it caused allergic reactions among some of human volunteers previously infected with N. americanus. To prevent IgE-mediated allergic reactions induced by Na-ASP-2 but keep its immunogenicity as a vaccine antigen, we designed and tested a genetically engineered fusion protein, Fcγ/Na-ASP-2, composed of full-length Na-ASP-2 and truncated human IgG Fcγ1 that targets the negative signalling receptor FcγRIIb expressed on pro-allergic cells. The chimeric recombinant Fcγ/Na-ASP-2 protein was expressed in Pichia pastoris and shared the similar antigenicity as native Na-ASP-2. Compared to Na-ASP-2, the chimeric fusion protein efficiently reduced the release of histamine in human basophils sensitized with anti-Na-ASP-2 IgE obtained from individuals living in a hookworm-endemic area. In dogs infected with canine hookworm, Fcγ/Na-ASP-2 resulted in significantly reduced immediate-type skin reactivity when injected intradermally compared with Na-ASP-2. Hamsters vaccinated with Fcγ/Na-ASP-2 formulated with Alhydrogel(®) produced specific IgG that recognized Na-ASP-2 and elicited similar protection level against N. americanus L3 challenge as native Na-ASP-2.

Expression, immunogenicity, histopathology, and potency of a mosquito-based malaria transmission-blocking recombinant vaccine.

Vaccines have been at the forefront of global research efforts to combat malaria, yet despite several vaccine candidates, this goal has yet to be realized. A potentially effective approach to disrupting the spread of malaria is the use of transmission-blocking vaccines (TBV), which prevent the development of malarial parasites within their mosquito vector, thereby abrogating the cascade of secondary infections in humans. Since malaria is transmitted to human hosts by the bite of an obligate insect vector, mosquito species in the genus Anopheles, targeting mosquito midgut antigens that serve as ligands for Plasmodium parasites represents a promising approach to breaking the transmission cycle. The midgut-specific anopheline alanyl aminopeptidase N (AnAPN1) is highly conserved across Anopheles vectors and is a putative ligand for Plasmodium ookinete invasion. We have developed a scalable, high-yield Escherichia coli expression and purification platform for the recombinant AnAPN1 TBV antigen and report on its marked vaccine potency and immunogenicity, its capacity for eliciting transmission-blocking antibodies, and its apparent lack of immunization-associated histopathologies in a small-animal model.

Modelling heterogeneity and the impact of chemotherapy and vaccination against human hookworm.

There is a growing emphasis on the development of vaccines against helminths (worms), and mathematical models provide a useful tool to assess the impact of new vaccines under a range of scenarios. The present study describes a stochastic individual-based model to assess the relative impact of chemotherapy and vaccination against human hookworm infection and investigates the implications of potential correlations between risk of infection and vaccine efficacy. Vaccination is simulated as a reduction in susceptibility to infection and the model includes population heterogeneities and dynamical waning of protection. To help identify appropriate measures of vaccine impact, we present a novel framework to quantify the vaccine impact on the infection-associated morbidity and introduce a measure of symmetry to study the correspondence between reduction in intensity and reduction in morbidity. Our modelling shows that, in high-transmission settings, the greatest impact of vaccination will be attained when vaccine efficacy is the greatest among individuals harbouring the heaviest worm burdens, and that the decline of morbidity primarily depends on the level of protection attained in the most at risk 8-12% of the population. We also demonstrate that if risk of infection and vaccine protection are correlated, there is not always a direct correspondence between the reduction in worm burden and in morbidity, with the precise relationship varying according to transmission setting.

Use of the air pouch model to investigate immune responses to a hookworm vaccine containing the Na-ASP-2 protein in rats.

Hookworms are gastrointestinal nematodes that affect approximately 600 million people in developing countries. Using the air pouch model, we have examined the effects of vaccination with the recombinant hookworm larval antigen Na-ASP-2 and the adjuvant Alhydrogel on the skin immune response to hookworms in Sprague Dawley rats. Following vaccination, rats were inoculated 100 Necator americanus L3 into the air pouch, and the exudates and cell infiltrates were collected from the pouch 24 h later. Larval inoculation induced leucocyte recruitment into the pouch. Exudates of rats vaccinated with Na-ASP-2 showed an increase of cytokines such as IL-4, IL-10, IFN-gamma and especially, IL-5, as well as IgG1 and IgG2 antibodies. The increased amount of antigen-presenting cells and cytokines in the pouch of vaccinated animals suggests that vaccination could potentially restrain this parasite to the inoculation site, avoiding its migration and establishment in the host. Moreover, the air pouch model could constitute an alternative to screen immune responses to L3 antigens.

Vaccines against blood-feeding nematodes of humans and livestock.

This paper summarises the progress towards vaccine development against the major blood-feeding nematodes of man and livestock, the hookworms and Haemonchus contortus, respectively. The impact of the diseases and the drivers for vaccine development are summarized as well as the anticipated impact of the host immune response on vaccine design. The performance requirements are discussed and progress towards these objectives using defined larval and adult antigens, many of these being shared between species. Specific examples include the Ancylostoma secreted proteins and homologues in Haemonchus as well as proteases used for digestion of the blood meal. This discussion shows that many of the major vaccine candidates are shared between these blood-feeding species, not only those from the blood-feeding stages but also those expressed by infective L3s in the early stages of infection. Challenges for the future include: exploiting the expanding genome information for antigen discovery, use of different recombinant protein expression systems, formulation with new adjuvants, and novel methods of field testing vaccine efficacy.

An epidemiological study of ancylostomiasis in a rural area of Kanpur district Uttar Pradesh, India.

In this epidemiological study, stool samples were collected from 256 study subjects selected from seven villages of Kanpur district, Uttar Pradesh, India. The average age of the study population was 21.6 years. The overall prevalence rate of hookworm infestation was found to be 34%. Men had significantly higher rate of infestation at all ages. Prevalence rates increased with ages as well. In addition, adult worms were collected from twelve subjects. All were identified as Ancylostoma duodenale.

Electron and light microscopy of neutrophil responses in mice vaccinated and challenged with third-stage infective hookworm (Ancylostoma caninum) larvae.

The role of neutrophils in mediating host inflammation was examined in mice vaccinated with living third-stage infective hookworm larvae (L3). Mice were vaccinated by oral immunization with 500 L3 (Ancylostoma caninum) once every 2 weeks for a total of three immunizations. The vaccinated mice were then challenged intraperitoneally with 2000 L3) 1 week after the final immunization. To stimulate peritoneal production of neutrophils, 2 ml of 2% glycogen were injected intraperitoneally at 16 h prior to the challenge infection. Neutrophils were found to comprise 85% of the peritoneal cell population. L3 from the challenge infection were collected and then examined at timed intervals by inverted light microscopy, scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Greater than a fivefold increase in the total numbers of peritoneal cells was noted in the vaccinated mice as compared to unvaccinated mice. In the peritoneal cavity of vaccinated mice, the neutrophils adhered to the L3 within 2 h, and over 55% of the L3 were surround by clusters of neutrophils to form a sausage-like sheath 4 h later. At 24-72 h after challenge, almost all of the L3 recovered from the vaccinated mice were covered with thick clusters of cells. Both SEM and TEM demonstrated extensive ultrastructural damage to the L3. In contrast, the L3 recovered from the unvaccinated mice appeared to be unaffected by neutrophils. These studies suggest that neutrophils, like macrophages, can have an important role as effector cells in L3-vaccinated mice.

Epidemiology of Necator americanus hookworm infections in Xiulongkan Village, Hainan Province, China: high prevalence and intensity among middle-aged and elderly residents.

Hookworm is highly endemic to Hainan Province, an island located in the South China Sea. To investigate the prevalence and intensity of infection in the area, the village of Xiulongkan was surveyed between April and July 1998. A cross-sectional study was conducted in which fecal samples of 80% of the village residents (631 individuals) were tested for the presence of helminth eggs. Hookworm was the predominant intestinal helminth in Xiulongkan, where it was determined that 60% of those tested were infected. Necator americanus was the predominant species of hookworm in this population. The prevalence of hookworm increased with age, and then leveled to a plateau for ages 41 yr and up. This observation was in contrast to infections with Ascaris lumbricoides, where the highest prevalences occurred among school-aged children. Women had a significantly higher prevalence of hookworm than men and this difference emerged in early adulthood. The intensity of hookworm infection also significantly increased with age, with the highest intensity infections occurring among middle-aged and elderly residents. Females were more likely to have moderate or heavy infections, whereas males were more likely to have light infections. The rates of hookworm transmission are particularly high among the middle-aged and elderly residents of Xiulongkan.

Environmental exposure to Toxocara as a possible risk factor for asthma: a clinic-based case-control study.

The zoonotic ascarid Toxocara has been suggested as a possible etiologic agent of asthma. We conducted a clinic-based case-control study to examine whether the zoonotic infection acquired by ingesting Toxocara eggs is associated with asthma in children. Blood samples were collected from children aged 2-15 years, 95 of whom had asthma and 229 of whom did not have asthma. Risk factors for asthma and Toxocara infection were assessed by a questionnaire given to each child's parent or legal guardian. Blood samples were tested for the presence of Toxocara antibodies, using an enzyme-linked immunosorbent assay. No significant association was found between Toxocara infection and asthma. Significant associations were found between asthma and risk factors and between Toxocara infection and risk factors. High prevalence of Toxocara infection was noted among Hispanic children of Puerto Rican descent.

[Studies on immunological reaction of the antiserum of recombinant secreted protein from Ancylostoma caninum].

OBJECTIVE: To analyze the immunological reaction of the antiserum of recombinant secreted protein from Ancylostoma caninum with antigens of various species hookworms at different developmental stages. METHODS: SDS-PAGE and ELIB technique were employed in the study. RESULTS AND CONCLUSION: The protein component of Ac-rAsp-1 was 45 kDa, its immune serum can recognize the antigens of Ac-L3 and Ac-rAsp-1 protein, but not react to the antigens of Ad-A, Ad-L3, Na-A, Ac-A, Nb-A and Ac-rAsp-2 protein. The protein component of Ac-rAsp-2 was 24 kDa, its immune serum can recognize the antigens of Ad-A, Ad-L3, Na-A, Ac-A, Ac-L3 and Ac-rAsp-2 protein, but not react to the antigens of Nb-A and Ac-rAsp-1 protein.

Variation between ASP-1 molecules from Ancylostoma caninum in China and the United States.

Hookworm infection continues to be a serious problem in rural areas of China. Rapid reinfection and high cost limit the effectiveness of deworming programs. Vaccination offers an attractive alternative to mass chemotherapy. However, variation in vaccine antigens from field hookworm populations could conceivably limit efficacy of a vaccine developed from laboratory strains. Reported here are initial experiments to ascertain levels of molecular variation in a promising vaccine antigen, ASP-1, from the dog hookworm Ancylostoma caninum. ASP-1 from a Chinese strain of A. caninum was isolated from a third-stage larval cDNA library and compared to ASP-1 from a U.S. strain. There was 97% and 98% similarity in the DNA and amino acid sequences, respectively. There were 42 polymorphic sites between the sequences, 30 of which were synonymous. The 12 nonsynonymous substitutions resulted in 10 changes in the deduced amino acid sequence. Five of the amino acid changes were in the N-terminal domain, whereas the C-terminal domain was more highly conserved, containing only 2 amino acid changes. The results suggest that the effect of molecular variation in antigens from geographically separated parasite populations should be considered during vaccine development.

A common muscarinic pathway for diapause recovery in the distantly related nematode species Caenorhabditis elegans and Ancylostoma caninum.

Converging TGF-beta and insulin-like neuroendocrine signaling pathways regulate whether Caenorhabditis elegans develops reproductively or arrests at the dauer larval stage. We examined whether neurotransmitters act in the dauer entry or recovery pathways. Muscarinic agonists promote recovery from dauer arrest induced by pheromone as well as by mutations in the TGF-beta pathway. Dauer recovery in these animals is inhibited by the muscarinic antagonist atropine. Muscarinic agonists do not induce dauer recovery of either daf-2 or age-1 mutant animals, which have defects in the insulin-like signaling pathway. These data suggest that a metabotropic acetylcholine signaling pathway activates an insulin-like signal during C. elegans dauer recovery. Analogous and perhaps homologous cholinergic regulation of mammalian insulin release by the autonomic nervous system has been noted. In the parasitic nematode Ancylostoma caninum, the dauer larval stage is the infective stage, and recovery to the reproductive stage normally is induced by host factors. Muscarinic agonists also induce and atropine potently inhibits in vitro recovery of A. caninum dauer arrest. We suggest that host or parasite insulin-like signals may regulate recovery of A. caninum and could be potential targets for antihelminthic drugs.