Basophil; histamine; helminth; IgE; anthelmintic therapy; type 2 immune response
In this work we explore differences in blood cells and cytokine profiles in children according to atopic status and asthma (atopic or non-atopic). The study involved measurement of Th1(IFN-γ) and Th2 (IL-5 and IL-13) cytokines in Dermatophagoides pteronyssinus stimulated peripheral blood leukocytes, blood cell count, skin prick test and specific IgE against common aeroallergens. Atopic status was associated with eosinophilia and production of Th2 type cytokines. Atopic asthma was associated with eosinophilia and non-atopic asthma was associated with IFN-γ and elevated monocytes in blood. IFN-γ and monocytes might play a role in immunopathology of non-atopic asthma in Latin American children.
Non-atopic asthma; Cytokines; IFN-g; Monocytes; Atopic-asthma; IgE; Atopy
Observations that the airway microbiome is disturbed in asthma may be confounded by the widespread use of antibiotics and inhaled steroids. We have therefore examined the oropharyngeal microbiome in early onset wheezing infants from a rural area of tropical Ecuador where antibiotic usage is minimal and glucocorticoid usage is absent.
Materials and Methods
We performed pyrosequencing of amplicons of the polymorphic bacterial 16S rRNA gene from oropharyngeal samples from 24 infants with non-infectious early onset wheezing and 24 healthy controls (average age 10.2 months). We analyzed microbial community structure and differences between cases and controls by QIIME software.
We obtained 76,627 high quality sequences classified into 182 operational taxonomic units (OTUs). Firmicutes was the most common and diverse phylum (71.22% of sequences) with Streptococcus being the most common genus (49.72%). Known pathogens were found significantly more often in cases of infantile wheeze compared to controls, exemplified by Haemophilus spp. (OR = 2.12, 95% Confidence Interval (CI) 1.82–2.47; P = 5.46×10−23) and Staphylococcus spp. (OR = 124.1, 95%CI 59.0–261.2; P = 1.87×10−241). Other OTUs were less common in cases than controls, notably Veillonella spp. (OR = 0.59, 95%CI = 0.56–0.62; P = 8.06×10−86).
The airway microbiota appeared to contain many more Streptococci than found in Western Europe and the USA. Comparisons between healthy and wheezing infants revealed a significant difference in several bacterial phylotypes that were not confounded by antibiotics or use of inhaled steroids. The increased prevalence of pathogens such as Haemophilus and Staphylococcus spp. in cases may contribute to wheezing illnesses in this age group.
Rationale: IgE antibodies to the mammalian oligosaccharide galactose-α-1,3-galactose (α-gal) are common in the southeastern United States. These antibodies, which are induced by ectoparasitic ticks, can give rise to positive skin tests or serum assays with cat extract.
Objectives: To evaluate the relationship between IgE antibodies to α-gal and asthma, and compare this with the relationship between asthma and IgE antibodies to Fel d 1 and other protein allergens.
Methods: Patients being investigated for recurrent anaphylaxis, angioedema, or acute urticaria underwent spirometry, exhaled nitric oxide, questionnaires, and serum IgE antibody assays. The results were compared with control subjects and cohorts from the emergency department in Virginia (n = 130), northern Sweden (n = 963), and rural Kenya (n = 131).
Measurements and Main Results: Patients in Virginia with high-titer IgE antibodies to α-gal had normal lung function, low levels of exhaled nitric oxide, and low prevalence of asthma symptoms. Among patients in the emergency department and children in Kenya, there was no association between IgE antibodies to α-gal and asthma (odds ratios, 1.04 and 0.75, respectively). In Sweden, IgE antibodies to cat were closely correlated with IgE antibodies to Fel d 1 (r = 0.83) and to asthma (P < 0.001).
Conclusions: These results provide a model of an ectoparasite-induced specific IgE response that can increase total serum IgE without creating a risk for asthma, and further evidence that the main allergens that are causally related to asthma are those that are inhaled.
α-gal; red meat allergy; ticks; total serum IgE; ectoparasite
Purpose of review:
This article will review the findings of recent human studies of the association between helminth parasite infections and allergy and discuss their potential relevance to public health.
Different helminth parasites may have different effects on allergy that may depend on the timing of the exposure. Infections with T. trichiura in early life are associated with a reduced prevalence of allergen skin test reactivity later in life and infants of helminth-infected mothers have been reported to have a reduced prevalence of eczema. Hookworm infection has been associated with a reduced prevalence of asthma in Ethiopia. Several studies have reported that anti-Ascaris IgE is an important risk factor for asthma, but this could be explained by an enhanced ability of atopics to produce IgE. Toxocara infections may be associated with an increased risk of wheeze in some populations that may be caused by the host response to the parasite or by parasite-enhanced Th2 responses to aeroallergens.
Although helminth infections can modulate the host inflammatory response directed against the parasite, a causal association between helminths and atopic diseases remains uncertain.
Helminths; Geohelminths; Allergy; Asthma
Immune responses to oral vaccines are impaired in populations living in conditions of poverty in developing countries, and there is evidence that concurrent geohelminth infections may contribute to this effect. We vaccinated 48 children living in rural communities in Ecuador with a single oral dose of 100 mg of BCG Moreau RDJ and measured the frequencies of tuberculin-stimulated peripheral blood mononuclear cells expressing IFN-γ before and after vaccination. Vaccinated children had active ascariasis (n = 20) or had been infected but received short- (n = 13) or long-term (n = 15) repeated treatments with albendazole prior to vaccination to treat ascariasis. All children had a BCG scar from neonatal vaccination. There was no evidence of a boosting of postvaccination IFN-γ responses in any of the 3 study groups. Our data provide support for the presence of a barrier to oral vaccination among children from the rural tropics that appeared to be independent of concurrent ascariasis.
Studies conducted in transitional communities from Africa and Asia have pointed to the process of urbanisation as being responsible for the increase in asthma prevalence in developing regions. In Latin America, there are few published data available on the potential impact of urbanisation on asthma prevalence. The aim of the present study was to explore how the process of urbanisation may explain differences in asthma prevalence in transitional communities in north-eastern Ecuador.
An ecological study was conducted in 59 communities in Esmeraldas Province, Ecuador. Indicators of urbanisation were grouped into three indices representing the processes associated with urbanisation: socioeconomic, lifestyle and urban infrastructure. Categorical principal components analysis was used to generate scores for each index and a fourth index—a summary urbanisation index—was derived from the most representative variables in each of the three indices. The authors analysed the associations between community asthma prevalence and the indices, as well as with each indicator variable of every group. The overall prevalence of asthma was 10.1% (range 0–31.4% between communities). Three of the four indices presented significant associations with community asthma prevalence: socioeconomic (r=0.295, p=0.023), lifestyle (r=0.342, p=0.008) and summary urbanisation index (r=0.355, p=0.006). Variables reflecting better socioeconomic status and a more urban lifestyle were associated with greater asthma prevalence.
These data provide evidence that the prevalence of asthma increases with increasing levels of urbanisation in transitional communities, and factors associated with greater socioeconomic level and changes towards a more urban lifestyle may be particularly important.
Asthma; urbanisation; transitional communities; childhood; urban lifestyle; asthma epidemiology; asthma in primary care; bacterial infection; cytokine biology; eosinophil biology; exercise; immunodeficiency; lymphocyte biology; neutrophil biology; allergic lung disease; respiratory infection; tuberculosis; asthma guidelines; cystic fibrosis; exhaled airway markers; lung physiology; paediatric asthma; paediatric lung disease
Geohelminth infections are highly prevalent infectious diseases of childhood in many regions of the Tropics, and are associated with significant morbidity especially among pre-school and school-age children. There is growing concern that geohelminth infections, particularly exposures occurring during early life in utero through maternal infections or during infancy, may affect vaccine immunogenicity in populations among whom these infections are endemic. Further, the low prevalence of allergic disease in the rural Tropics has been attributed to the immune modulatory effects of these infections and there is concern that widespread use of anthelmintic treatment in high-risk groups may be associated with an increase in the prevalence of allergic diseases. Because the most widely used vaccines are administered during the first year of life and the antecedents of allergic disease are considered to occur in early childhood, the present study has been designed to investigate the impact of early exposures to geohelminths on the development of protective immunity to vaccines, allergic sensitization, and allergic disease.
A cohort of 2,403 neonates followed up to 8 years of age. Primary exposures are infections with geohelminth parasites during the last trimester of pregnancy and the first 2 years of life. Primary study outcomes are the development of protective immunity to common childhood vaccines (i.e. rotavirus, Haemophilus influenzae type B, Hepatitis B, tetanus toxoid, and oral poliovirus type 3) during the first 5 years of life, the development of eczema by 3 years of age, the development of allergen skin test reactivity at 5 years of age, and the development of asthma at 5 and 8 years of age. Potential immunological mechanisms by which geohelminth infections may affect the study outcomes will be investigated also.
The study will provide information on the potential effects of early exposures to geohelminths (during pregnancy and the first 2 years of life) on the development of vaccine immunity and allergy. The data will inform an ongoing debate of potential effects of geohelminths on child health and will contribute to policy decisions on new interventions designed to improve vaccine immunogenicity and protect against the development of allergic diseases.
Current Controlled Trials ISRCTN41239086.
In 2009, we reported a novel form of delayed anaphylaxis to red meat, which is related to serum IgE antibodies to the oligosaccharide galactose-alpha-1,3-galactose (alpha-gal). Most of these patients had tolerated meat for many years previously. The implication is that some exposure in adult life had stimulated the production of these IgE antibodies.
To investigate possible causes of this IgE antibody response, focusing on evidence related to tick bites, which are common in the region where these reactions occur.
Serum assays were carried out using biotinylated proteins and extracts bound to a streptavidin ImmunoCAP.
Prospective studies on IgE antibodies in three subjects following tick bites showed an increase in IgE to alpha-gal of twenty-fold or greater. Other evidence included i) a strong correlation between histories of tick bites and IgE to alpha-gal (χ2=26.8, p<0.001), ii) evidence that these IgE antibodies are common in areas where the tick Amblyomma americanum is common, and iii) a significant correlation between IgE antibodies to alpha-gal and IgE antibodies to proteins derived from A. americanum (rs=0.75, p<0.001).
The results presented here provide evidence that tick bites are a cause, or possibly the only cause, of IgE specific for alpha-gal in this area of the United States. Both the number of subjects becoming sensitized and the titer of IgE antibodies to alpha-gal are striking. Here we report the first example of a response to an ectoparasite giving rise to an important form of food allergy.
ticks; anaphylaxis; oligosaccharide; alpha-gal; IgE antibody to CCD
Allergic and other immune-mediated diseases are complex disease states determined by interplay between host genetics and environmental factors. Environmental changes such as fewer infections and reduced exposure to microbial products have been suggested to have led to insufficient regulation of Th1 and Th2 immune responses, causing an increased incidence of inflammatory diseases. The objective of the present study was to investigate the effect of poor living environmental conditions on mitogen-induced production of cytokines (Th1 and Th2) by peripheral blood leukocytes in children living in urban Brazil and investigate the role of IL-10 in modifying this effect. Our data showed that the proportion of children producing Th1 and Th2 cytokines was lower among those with poor living conditions and that this finding was stronger in children producing IL-10. These results provide a possible biologic explanation for the temporal trends of increasing risk of inflammatory diseases observed in populations living in affluent countries.
BMI, Body mass index; CpG-DNA, bacterial DNA; DC, dendritic cell; IFN, Interferon; LB, B lymphocyte; LPS, lipopolysaccharide; MΦ, macrophage; MHC, major histocompatibility complex; Neu, neutrophil; NO, nitric oxide; OR, odds ratio; PBLs, peripheral blood leukocytes; SCAALA, Social Changes Asthma and Allergy in Latin America; TGF-β, transforming growth factor β; Th1, T helper 1; Th17, T helper 17; Th2, T helper 2; TLR, toll like receptors; Treg, T regulatory; WBC, whole blood cells culture; IL-10; Th1/Th2; Environment; Sewage system; Street paving; Immune regulation
Human infections with Ascaris lumbricoides may have important effects on allergy and susceptibility to infectious diseases that start in early life. To investigate if sensitization to Ascaris occurs in utero, we measured IFN-γ and IL-4 responses in Ascaris antigen-stimulated cord blood of newborns of infected and non-infected mothers using flow cytometry. There was evidence of elevated frequencies of IFN-γ and IL-4-expressing CD4+ T cells in newborns of infected mothers compared to those of non-infected mothers. Our data provide evidence of in utero sensitization to A. lumbricoides, and raise the possibility that the immunological effects of infection start in the fetus.
Ascaris lumbricoides; in utero; sensitization; newborn
Asthma has emerged as an important public health problem of urban populations in Latin America. Epidemiological data suggest that a minority of asthma cases in Latin America may be associated with allergic sensitisation and that other mechanisms causing asthma have been overlooked. The aim of the present study was to investigate risk factors for atopic and non-atopic asthma in school-age children.
A cross-sectional study was conducted among 3960 children aged 6–16 years living in Afro-Ecuadorian rural communities in Esmeraldas province in Ecuador. Allergic diseases and risk factors were assessed by questionnaire and allergic sensitisation by allergen skin prick reactivity.
A total of 390 (10.5%) children had wheeze within the previous 12 months, of whom 14.4% had at least one positive skin test. The population-attributable fraction for recent wheeze associated with atopy was 2.4%. Heavy Trichuris trichiura infections were strongly inversely associated with atopic wheeze. Non-atopic wheeze was positively associated with maternal allergic symptoms and sedentarism (watching television (>3 h/day)) but inversely associated with age and birth order.
The present study showed a predominance of non-atopic compared with atopic wheeze among schoolchildren living in a poor rural region of tropical Latin America. Distinct risk factors were associated with the two wheeze phenotypes and may indicate different causal mechanisms. Future preventive strategies in such populations may need to be targeted at the causes of non-atopic wheeze.
Asthma; asthma epidemiology; atopy; children; Ecuador; risk factors
Helminth infections have been associated with protection against allergy and autoimmune diseases. We investigated the effects of chronic infections with Ascaris lumbricoides and Trichuris trichiura (measured twice over a 5-year period) on cytokine and antibody responses. We collected blood from 1,060 children aged 4 to 11 years living in a poor urban area of Brazil and measured Th1 (gamma interferon [IFN-γ]) and Th2 (interleukin-5 [IL-5] and IL-13) cytokines and the regulatory cytokine IL-10 in unstimulated and stimulated (with mitogen or A. lumbricoides antigens) cultures of peripheral blood leukocytes and levels of total IgE and anti-A. lumbricoides IgG4 and IgE in serum. Intestinal helminth infections were associated with an increased proportion of children producing IL-5 in response to A. lumbricoides and producing IL-10 spontaneously, especially among coinfected and chronically infected children. Helminth infections were associated with a generalized suppression of cytokine responses to mitogen. Levels of total IgE and anti-A. lumbricoides IgG4 and IgE were especially elevated in chronically infected children. In conclusion, intestinal helminth infections were associated with a typical Th2 immune response profile and with the induction of immune hyporesponsiveness that was associated with greater frequencies of the production of spontaneous IL-10.
Environmental factors are likely to have profound effects on the development of host immune responses, with serious implications for infectious diseases and inflammatory disorders such as asthma.
This study was designed to investigate the effects of environmental exposures on the cytokine profile of children.
The study involved measurement of T helper (Th) 1 (interferon-gamma), 2 [interleukin (IL)-5 and IL-13], and the regulatory cytokine IL-10 in unstimulated peripheral blood leukocytes from 1,376 children 4–11 years of age living in a poor urban area of the tropics. We also assessed the impact of environmental exposures in addition to biological characteristics recorded at the time of blood collection and earlier in childhood (0–3 years before blood collection).
The proportion of children producing IL-10 was greater among those without access to drinking water [p < 0.05, chi-square test, odds ratio (OR) = 1.67]. The proportion of children producing IL-5 and IL-10 (OR = 10.76) was significantly greater in households that had never had a sewage system (p < 0.05, trend test).
These data provide evidence for the profound effects of environmental exposures in early life as well as immune homeostasis in later childhood. Decreased hygiene (lack of access to clean drinking water and sanitation) in the first 3 years of life is associated with higher spontaneous IL-10 production up to 8 years later in life.
age; breast-feeding; cytokine profile; IL-10; SCAALA; sewage; sex; tap water
Geohelminth infections are associated with a modulation of immunity to parasite antigens and aeroallergens that may be affected by anthelmintic treatment. To investigate this, we compared cytokine responses between children that had received repeated doses of albendazole over a year or no treatment. Whole blood was cultured with Ascaris antigen and house dust mite and cockroach allergens and IL-5, IL-13, IFN-γ, and IL-10 were measured. Anthelmintic treatment was associated with enhanced production of Th2 cytokines to parasite antigen, but did not affect responses to aeroallergens. The data indicate that long-term treatment may be associated with increased antiparasite Th2 immunity.
geohelminths; Ascaris lumbricoides; allergy; atopy; aeroallergens; Th2 cytokines; immune modulation
Intestinal helminth infections may protect against allergen skin test reactivity in endemic areas and it has been suggested that IL-10 may mediate this effect. We investigated if IL-10 and populations of IL-10+ T cells may modulate atopy in children living in an endemic area for intestinal helminth parasites.
Ecuadorian school children from rural communities were assessed for allergen skin test reactivity to Periplaneta americana and Dermatophagoides pteronyssinus. Skin test positive (n=39) and skin test negative (n=41) children were bled and peripheral blood leukocytes were cultured in the presence of Ascaris lumbricoides antigen to measure IL-10 protein and the frequencies of T cell populations expressing intracellular IL-10. We investigated also if these immunological factors affected the association between specific IgE and skin test reactivity to aeroallergens.
There was no evidence of associations between levels of A. lumbricoides-induced IL-10 protein or IL-10+ T cells and allergen skin test reactivity. The association between allergen-specific IgE and skin test reactivity was not affected by levels of IL-10 protein or the frequencies of IL-10+ T cells.
Our data do not support a role for IL-10 in modulating atopy in children living in an intestinal helminth-endemic area of the tropics.
atopy; IgE; allergen skin test reactivity; Ascaris lumbricoides; intestinal helminths; IL-10; regulatory T cells
The environmental factors that determine the elevated levels of polyclonal IgE observed in populations living in the Tropics are poorly understood but may include geohelminth infections. We investigated the association between geohelminth infections and total IgE levels in school children in rural tropical Ecuador, and assessed the effect on IgE of repeated anthelmintic treatments over a period of 12 months. The study was nested within a cluster-randomized study that randomized 68 schools to receive either 400 mg of albendazole every 2 months over a year or no treatment. We studied random samples of children completing follow-up and representing four groups stratified by the presence of geohelminth infection at baseline and treatment allocation. We measured levels of total IgE and anti-A. lumbricoides IgG (used as a measure of past and current geohelminth infectious exposure) in blood samples collected at the start of the study and after 12 months.
We observed elevated levels of total IgE (compared to standard reference values) at the start of the study in this population of school children (geometric mean, 1,004 IU/mL, range 12 to 22,608 IU/mL)) and baseline IgE levels were strongly associated with parameters of geohelminth infection but not with age, nutritional and socioeconomic status. After 12 months, levels of IgE fell significantly in the treatment (by 35.1%) and no treatment (by 10.4%) groups, respectively, but the fall was significantly greater in the treatment group. Falls in IgE were independently associated with albendazole treatment, having a baseline geohelminth infection and with high baseline levels of anti-A. lumbricoides IgG. Increases in IgE at 12 months were associated with the presence of geohelminth infections and increasing levels of anti-A. lumbricoides IgG at 12 months independent of treatment allocation.
The data provide evidence that geohelminth infections are an important determinant of total IgE in school children in the rural Tropics and that periodic anthelmintic treatments over 12 months are associated with reductions in IgE. The failure of anthelmintic treatment to reduce IgE levels to that considered normal in industrialized countries may be attributed to continued exposure of children to geohelminths or to the effects of infections in early life in programming a long-lasting Th2-biassed immunity.
The number of subjects that can be recruited in immunological studies and the number of immunological parameters that can be measured has increased rapidly over the past decade and is likely to continue to expand. Large and complex immunological datasets can now be used to investigate complex scientific questions, but to make the most of the potential in such data and to get the right answers sophisticated statistical approaches are necessary. Such approaches are used in many other scientific disciplines, but immunological studies on the whole still use simple statistical techniques for data analysis.
The paper provides an overview of the range of statistical methods that can be used to answer different immunological study questions. We discuss specific aspects of immunological studies and give examples of typical scientific questions related to immunological data. We review classical bivariate and multivariate statistical techniques (factor analysis, cluster analysis, discriminant analysis) and more advanced methods aimed to explore causal relationships (path analysis/structural equation modelling) and illustrate their application to immunological data. We show the main features of each method, the type of study question they can answer, the type of data they can be applied to, the assumptions required for each method and the software that can be used.
This paper will help the immunologist to choose the correct statistical approach for a particular research question.
Onchocerciasis is a leading cause of blindness worldwide, hence elimination of the infection is an important health priority. Community-based treatment programs with ivermectin form the basis of control programs for the disease in Latin America. The long-term administration of ivermectin could eliminate Onchocerca volvulus infection from endemic areas in Latin America.
A strategy of annual to twice-annual treatments with ivermectin has been used for onchocerciasis in endemic communities in Ecuador for up to 14 years. The impact of ivermectin treatment on ocular morbidity, and O. volvulus infection and transmission was monitored in seven sentinel communities.
Over the period 1990–2003, high rates of treatment coverage of the eligible population were maintained in endemic communities (mean 85.2% per treatment round). Ivermectin reduced the prevalence of anterior segment disease of the eye to 0% in sentinel communities and had a major impact on the prevalence and transmission of infection, with possible elimination of infection in some foci.
The distribution of ivermectin in endemic communities in Ecuador might have eliminated ocular morbidity and significant progress has been made towards elimination of the infection. A strategy of more frequent treatments with ivermectin may be required in communities where the infection persists to achieve the objective of elimination of the infection from Ecuador. The elimination of the infection from an endemic country in Latin America would be a major public health achievement and could stimulate the implementation of elimination strategies in other endemic countries.
Asthma and allergic diseases are becoming increasingly frequent in children in urban centres of Latin America although the prevalence of allergic disease is still low in rural areas. Understanding better why the prevalence of asthma is greater in urban migrant populations and the role of risk factors such as life style and environmental exposures, may be key to understand what is behind this trend.
The Esmeraldas-SCAALA (Social Changes, Asthma and Allergy in Latin America) study consists of cross-sectional and nested case-control studies of school children in rural and urban areas of Esmeraldas Province in Ecuador. The cross-sectional study will investigate risk factors for atopy and allergic disease in rural and migrant urban Afro-Ecuadorian school children and the nested case-control study will examine environmental, biologic and social risk factors for asthma among asthma cases and non-asthmatic controls from the cross-sectional study. Data will be collected through standardised questionnaires, skin prick testing to relevant aeroallergen extracts, stool examinations for parasites, blood sampling (for measurement of IgE, interleukins and other immunological parameters), anthropometric measurements for assessment of nutritional status, exercise testing for assessment of exercise-induced bronchospasm and dust sampling for measurement of household endotoxin and allergen levels.
The information will be used to identify the factors associated with an increased risk of asthma and allergies in migrant and urbanizing populations, to improve the understanding of the causes of the increase in asthma prevalence and to identify potentially modifiable factors to inform the design of prevention programmes to reduce the risk of allergy in urban populations in Latin America.
We studied the transmission of rotavirus infection in households in peri-urban Ecuador in the vaccination era.
Stool samples were collected from household contacts of child rotavirus cases, diarrhea controls and healthy controls following presentation of the index child to health facilities. Rotavirus infection status of contacts was determined by RT-qPCR. We examined factors associated with transmissibility (index-case characteristics) and susceptibility (household-contact characteristics).
Amongst cases, diarrhea controls and healthy control household contacts, infection attack rates (iAR) were 55%, 8% and 2%, (n = 137, 130, 137) respectively. iARs were higher from index cases with vomiting, and amongst siblings. Disease ARs were higher when the index child was <18 months and had vomiting, with household contact <10 years and those sharing a room with the index case being more susceptible. We found no evidence of asymptomatic infections leading to disease transmission.
Transmission rates of rotavirus are high in households with an infected child, while background infections are rare. We have identified factors associated with transmission (vomiting/young age of index case) and susceptibility (young age/sharing a room/being a sibling of the index case). Vaccination may lead to indirect benefits by averting episodes or reducing symptoms in vaccinees.
To investigate the potential immunomodulatory effects of concurrent ascariasis on the cytokine response to a live oral vaccine, we measured cytokine responses to cholera toxin B subunit (CT-B) following vaccination with the live oral cholera vaccine CVD 103-HgR in Ascaris lumbricoides-infected subjects randomized in a double-blind study to receive two doses of either albendazole or placebo prior to vaccination and in a group of healthy U.S. controls. Postvaccination cytokine responses to CT-B were characterized by transient increases in the production of interleukin-2 (IL-2; P = 0.02) and gamma interferon (IFN-γ; P = 0.001) in the three study groups combined; however, postvaccination increases in IFN-γ were significant only in the albendazole-treated A. lumbricoides infection group (P = 0.008). Postvaccination levels of IL-2 were significantly greater in the albendazole-treated group compared with the placebo group (P = 0.03). No changes in levels of Th1 and Th2 cytokines in response to control ascaris antigens were observed over the same period. These findings indicate that vaccination with CVD 103-HgR is associated with a Th1 cytokine response (IL-2 and IFN-γ) to CT-B, that infection with A. lumbricoides diminishes the magnitude of this response, and that albendazole treatment prior to vaccination was able to partially reverse the deficit in IL-2. The potential modulation of the immune response to oral vaccines by geohelminth parasites has important implications for the design of vaccination campaigns in geohelminth-endemic areas.
To investigate whether helminth infections may affect the efficacy of vaccines by impairing the immune response to nonparasite vaccine antigens, we compared the antibody responses to tetanus toxoid (TT) after tetanus vaccination in 193 subjects with Onchocerca volvulus infection with 85 comparable noninfected controls. After vaccination, the proportions of subjects in each group attaining protective levels of antitetanus antibodies were similar (96.9% infected versus 97.6% noninfected). Postvaccination increases in antitetanus immunoglobulin G (IgG) and the predominant IgG isotype, IgG1, were equivalent in both groups, as were increases in specific IgG4 and IgE; however, significantly greater increases in specific IgG2 (P < 0.05) and IgG3 (P < 0.001) were observed in the noninfected group. Stratification of the O. volvulus-infected group into two groups representing light and heavy infections revealed a significantly impaired antitetanus IgG response in those with heavy infections compared to those with light infections (P < 0.01) or no infection (P < 0.05). The impact of concurrent intestinal helminth infections on the antitetanus response was also examined; an increased IgG4/IgE ratio was seen in those infected with Strongyloides stercoralis (P < 0.05) and when all helminth infections were combined as a single group (P < 0.05). These findings indicate that concurrent infection with O. volvulus does not prevent the development of a protective antitetanus response, although heavier O. volvulus infections are able to alter the magnitude of this response, and concurrent helminth infections (O. volvulus and intestinal helminths) may alter TT-specific antibody isotype responses.
Neurocysticercosis (NCC) is the most common cause of acquired epilepsy in Taenia solium endemic areas, primarily situated in low-income countries. Diagnosis is largely based upon the “Del Brutto diagnostic criteria” using the definitive/probable/no NCC diagnosis approach. Neuroimaging and specific T. solium cysticercosis antibody detection results are at the mainstay of this diagnosis, while antigen detection in serum has never been included. This study aimed at evaluating the addition of antigen detection as a major diagnostic criterion, especially in areas where neuroimaging is absent.
The B158/B60 monoclonal antibody-based enzyme-linked immunosorbent assay (ELISA) for the detection of circulating cysticercus antigen was carried out retrospectively on serum samples collected during a hospital-based study from 83 people with epilepsy (PWE) in an endemic area.
The addition of antigen results as a major criterion allowed the correct diagnosis of definitive NCC in 10 out of 17 patients as opposed to 0/17 without antigen results in the absence of neuroimaging. A sensitivity of 100% and a specificity of 84% were determined for the diagnosis of active NCC using antigen ELISA. While the use of a higher cutoff improves the specificity of the test to 96%, it decreases its sensitivity to 83%.
In areas where neuroimaging is absent, NCC diagnosis according to the existing criteria is problematic. Taking into account its limitations for diagnosis of inactive NCC, antigen detection can be of added value for diagnosing NCC in PWE by supporting diagnostic and treatment decisions. Therefore, we recommend a revision of the “Del Brutto diagnostic criteria” for use in resource poor areas and suggest the inclusion of serum antigen detection as a major criterion.
Neurocysticercosis is a parasitic infection of the central nervous system and a common cause of epilepsy in Taenia solium cysticercosis endemic countries. According to the current diagnostic criteria proposed by Del Brutto and colleagues, the diagnosis of neurocysticercosis is mainly based on neuroimaging and detection of specific antibodies. Unfortunately, especially neuroimaging is rarely available in endemic countries. The authors analyzed the value of a test that detects antigens that are excreted by living cysts in people with epilepsy. Different diagnostic scenarios and cut-off values are discussed with the respective sensitivity and specificity of the test. When using the antigen-detecting test, considerably more people with epilepsy were diagnosed correctly with neurocysticercosis. There are some concerns about possible false positive results in other cases. The test was useful for the detection of people with living cysts (active neurocysticercosis), who need further diagnostic evaluation and specific treatment. The authors recommend the addition of this test in the diagnostic criteria for neurocysticercosis.