Added Value of Antigen ELISA in the Diagnosis of Neurocysticercosis in Resource Poor Settings

Background

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.

Methods

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.

Results

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%.

Conclusions

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.     

Epilepsy and Neurocysticercosis in Latin America: A Systematic Review and Meta-analysis

Background

The difference in epilepsy burden existing among populations in tropical regions has been attributed to many factors, including the distribution of infectious diseases with neurologic sequels. To define the burden of epilepsy in Latin American Countries (LAC) and to investigate the strength of association with neurocysticercosis (NCC), considered one of the leading causes of epilepsy, we performed a systematic review and meta-analysis of the literature.

Methodology

Studies published until 2012 were selected applying predefined inclusion criteria. Lifetime epilepsy (LTE) prevalence, active epilepsy (AE) prevalence, incidence, mortality, treatment gap (TG) and NCC proportion among people with epilepsy (PWE) were extracted. Median values were obtained for each estimate using random effects meta-analysis. The impact of NCC prevalence on epilepsy estimates was determined using meta-regression models. To assess the association between NCC and epilepsy, a further meta-analysis was performed on case-control studies.

Principal findings

The median LTE prevalence was 15.8/1,000 (95% CI 13.5–18.3), the median AE prevalence was 10.7/1,000 (95% CI 8.4–13.2), the median incidence was 138.2/100,000 (95% CI 83.6–206.4), the overall standardized mortality ratio was 1.4 (95% CI 0.01–6.1) and the overall estimated TG was 60.6% (95% CI 45.3–74.9). The median NCC proportion among PWE was 32.3% (95% CI 26.0–39.0). Higher TG and NCC estimates were associated with higher epilepsy prevalence. The association between NCC and epilepsy was significant (p<0.001) with a common odds ratio of 2.8 (95% CI 1.9–4.0).

Significance

A high burden of epilepsy and of NCC in LAC and a consistent association between these two diseases were pointed out. Furthermore, NCC prevalence and TG were identified as important factors influencing epilepsy prevalence to be considered in prevention and intervention strategies.     

Estimating the non-monetary burden of neurocysticercosis in Mexico

Background

Neurocysticercosis (NCC) is a major public health problem in many developing countries where health education, sanitation, and meat inspection infrastructure are insufficient. The condition occurs when humans ingest eggs of the pork tapeworm Taenia solium, which then develop into larvae in the central nervous system. Although NCC is endemic in many areas of the world and is associated with considerable socio-economic losses, the burden of NCC remains largely unknown. This study provides the first estimate of disability adjusted life years (DALYs) associated with NCC in Mexico.

Methods

DALYs lost for symptomatic cases of NCC in Mexico were estimated by incorporating morbidity and mortality due to NCC-associated epilepsy, and morbidity due to NCC-associated severe chronic headaches. Latin hypercube sampling methods were employed to sample the distributions of uncertain parameters and to estimate 95% credible regions (95% CRs).

Findings

In Mexico, 144,433 and 98,520 individuals are estimated to suffer from NCC-associated epilepsy and NCC-associated severe chronic headaches, respectively. A total of 25,341 (95% CR: 12,569–46,640) DALYs were estimated to be lost due to these clinical manifestations, with 0.25 (95% CR: 0.12–0.46) DALY lost per 1,000 person-years of which 90% was due to NCC-associated epilepsy.

Conclusion

This is the first estimate of DALYs associated with NCC in Mexico. However, this value is likely to be underestimated since only the clinical manifestations of epilepsy and severe chronic headaches were included. In addition, due to limited country specific data, some parameters used in the analysis were based on systematic reviews of the literature or primary research from other geographic locations. Even with these limitations, our estimates suggest that healthy years of life are being lost due to NCC in Mexico.     

Prevalence of Neurocysticercosis in People with Epilepsy in the Eastern Province of Zambia

Zambia is endemic for Taenia solium taeniosis and cysticercosis. In this single-centered, cross-sectional, community-based study, the role of neurocysticercosis (NCC) as a cause of epilepsy was examined. People with epilepsy (PWE, n = 56) were identified in an endemic area using a screening questionnaire followed by in-depth interviews and neurological examination. Computed tomography (CT) was performed on 49 people with active epilepsy (PWAE) and their sera (specific antibody and antigen detection, n = 56) and stools (copro-antigen detection, n = 54) were analyzed. The CT scan findings were compared to a group of 40 CT scan controls. Of the PWE, 39.3% and 23.2% were positive for cysticercal antibodies and antigens, respectively, and 14.8% for coproantigens (taeniosis). Lesions highly suggestive of NCC were detected in 24.5% and definite NCC lesions in 4.1% of CT scans of PWAE. This compares to 2.5% and 0%, respectively, in the control CT scans. Using the Del Brutto diagnostic criteria, 51.8% of the PWAE were diagnosed with probable or definitive NCC and this rose to 57.1% when the adapted criteria, as proposed by Gabriël et al. (adding the sero-antigen ELISA test as a major criterion), were used. There was no statistically significant relationship between NCC, current age, age at first seizure and gender. This study suggests that NCC is the single most important cause of epilepsy in the study area. Additional large-scale studies, combining a community based prevalence study for epilepsy with neuroimaging and serological analysis in different areas are needed to estimate the true impact of neurocysticercosis in endemic regions and efforts should be instituted to the control of T. solium.     

A systematic review of the frequency of neurocyticercosis with a focus on people with epilepsy

Background

The objective of this study is to conduct a systematic review of studies reporting the frequency of neurocysticercosis (NCC) worldwide.

Methods/Principal Findings

PubMed, Commonwealth Agricultural Bureau (CAB) abstracts and 23 international databases were systematically searched for articles published from January 1, 1990 to June 1, 2008. Articles were evaluated for inclusion by at least two researchers focusing on study design and methods. Data were extracted independently using standardized forms. A random-effects binomial model was used to estimate the proportion of NCC among people with epilepsy (PWE). Overall, 565 articles were retrieved and 290 (51%) selected for further analysis. After a second analytic phase, only 4.5% of articles, all of which used neuroimaging for the diagnosis of NCC, were reviewed. Only two studies, both from the US, estimated an incidence rate of NCC using hospital discharge data. The prevalence of NCC in a random sample of village residents was reported from one study where 9.1% of the population harboured brain lesions of NCC. The proportion of NCC among different study populations varied widely. However, the proportion of NCC in PWE was a lot more consistent. The pooled estimate for this population was 29.0% (95%CI: 22.9%–35.5%). These results were not sensitive to the inclusion or exclusion of any particular study.

Conclusion/Significance

Only one study has estimated the prevalence of NCC in a random sample of all residents. Hence, the prevalence of NCC worldwide remains unknown. However, the pooled estimate for the proportion of NCC among PWE was very robust and could be used, in conjunction with estimates of the prevalence and incidence of epilepsy, to estimate this component of the burden of NCC in endemic areas. The previously recommended guidelines for the diagnostic process and for declaring NCC an international reportable disease would improve the knowledge on the global frequency of NCC.     

Accuracy of Serological Testing for the Diagnosis of Prevalent Neurocysticercosis in Outpatients with Epilepsy,Eastern Cape Province,South Africa

Background

Few studies have estimated prevalence of neurocysticercosis (NCC) among persons with epilepsy in sub-Saharan Africa. While the limitations of serological testing in identification of NCC are well known, the characteristics of persons who are misdiagnosed based on serology have not been explored. The first objective of this pilot study was to estimate the prevalence of NCC in epilepsy outpatients from an area of South Africa endemic for cysticercosis. The second objective was to estimate the accuracy of serological testing in detecting NCC in these outpatients and characterize sources of disagreement between serology and neuroimaging.

Methodology/Principal Findings

All out-patients aged 5 or older attending the epilepsy clinic of St. Elizabeth''s Hospital in Lusikisiki, Eastern Cape Province, between July 2004 and April 2005 were invited to participate. Epidemiological data were collected by local study staff using a standardized questionnaire. Blood samples were tested by ELISA for antibody and antigen for Taenia solium. Four randomly chosen, consenting participants were transported each week to Mthatha for brain CT scan. The proportion of persons with epilepsy attending St. Elizabeth clinic with CT-confirmed NCC was 37% (95% CI: 27%–48%). Using CT as the gold standard, the sensitivity and specificity of antibody testing for identifying NCC were 54.5% (36.4%–71.9%) and 69.2% (52.4%–83.0%), respectively. Sensitivity improved to 78.6% (49.2%–95.3%) for those with active lesions. Sensitivity and specificity of antigen testing were considerably poorer. Compared to false negatives, true positives more often had active lesions. False positives were more likely to keep pigs and to have seizure onset within the past year than were true negatives.

Conclusions/Significance

The prevalence of NCC in South African outpatients with epilepsy is similar to that observed in other countries where cysticercosis is prevalent. Errors in classification of NCC using serology alone may reflect the natural history of NCC.     

Distribution and Potential Indicators of Hospitalized Cases of Neurocysticercosis and Epilepsy in Ecuador from 1996 to 2008

Background

Epilepsy is one of the most common signs of Neurocysticercosis (NCC). In this study, spatial and temporal variations in the incidence of hospitalized cases (IHC) of epilepsy and NCC in Ecuadorian municipalities were analyzed. Additionally, potential socio-economic and landscape indicators were evaluated in order to understand in part the macro-epidemiology of the Taenia solium taeniasis/cysticercosis complex.

Methodology

Data on the number of hospitalized epilepsy and NCC cases by municipality of residence were obtained from morbidity-hospital systems in Ecuador. SatScan software was used to determine whether variations in the IHC of epilepsy and NCC in space and time. In addition, several socio-economic and landscape variables at municipality level were used to study factors intervening in the macro-epidemiology of these diseases. Negative Binomial regression models through stepwise selection and Bayesian Model Averaging (BMA) were used to explain the variations in the IHC of epilepsy and NCC.

Principal findings

Different clusters were identified through space and time. Traditional endemic zones for NCC and epilepsy, recognized in other studies were confirmed in our study. However, for both disorders more recent clusters were identified. Among municipalities, an increasing tendency for IHC of epilepsy, and a decreasing tendency for the IHC of NCC were observed over time. In contrast, within municipalities a positive linear relationship between both disorders was found. An increase in the implementation of systems for eliminating excrements would help to reduce the IHC of epilepsy by 1.00% (IC_95%; 0.2%–1.8%) and by 5.12% (IC_95%; 3.63%-6.59%) for the IHC of NCC. The presence of pig production was related to IHC of NCC.

Conclusion/Significance

Both disorders were related to the lack of an efficient system for eliminating excrements. Given the appearance of recent epilepsy clusters, these locations should be studied in depth to discriminate epilepsies due to NCC from epilepsies due to other causes. Field studies are needed to evaluate the true prevalence of cysticercosis in humans and pigs in different zones of the country in order to better implement and manage prevention and/or control campaigns.     

Case-control Studies on the Relationship between Onchocerciasis and Epilepsy: Systematic Review and Meta-analysis

Objective

A systematic review and meta-analysis of all available case-control studies on the relationship between onchocerciasis and epilepsy. Because age and level of onchocerciasis endemicity in the area of residence are major determinants for infection, an additional analysis was performed, restricted to studies achieving control of these confounding factors.

Data sources

Medical databases, the “African Neurology Database, Institute of Neuroepidemiology and Tropical Neurology, Limoges,” reference lists of relevant articles, commercial search engines, up to May 2012.

Methods

We searched for studies examining infection status with Onchocerca volvulus in persons with epilepsy (PWE) and without epilepsy (PWOE) providing data suitable for the calculation of pooled odds ratios (OR_p) and/or standardized mean differences (SMD) using random-effects models.

Results

Eleven studies providing data of qualitative skin biopsies for diagnosis of onchocerciasis were identified. Combined analysis on the total sample of 876 PWE and 4712 PWOE resulted in an OR_p of 2.49 (95% confidence interval (95%CI): 1.61–3.86, p<0.001). When this analysis was restricted to those studies achieving control for age, residence and sex (367 PWE, 624 PWOE), an OR_p of 1.29 (95% CI: 0.93–1.79; p = 0.139) was found. Presence of nodules for diagnosis of onchocerciasis was analyzed in four studies (225 PWE, 189 PWOE; OR_p 1.74; 95%CI: 0.94–3.20; p<0.076), including two studies of the restricted analysis (106 PWE, 106 PWOE; OR_p 2.81; 95%CI: 1.57–5.00; p<0.001). One study examined quantitative microfilariae counts in patients without preceding microfilaricidal treatment and demonstrated significantly higher counts in PWE than in PWOE.

Interpretation

Our results strengthen the hypothesis that, in onchocerciasis foci, epilepsy and infection with O. volvulus are associated. Analysis of indicators giving information on infection intensity, namely nodule palpation and quantitative microfilaria count in untreated patients, support the hypothesis that intensity of infection with O. volvulus is involved in the etiology of epilepsy.     

Taenia solium Infection in Peru: A Collaboration between Peace Corps Volunteers and Researchers in a Community Based Study

Background

Neurocysticercosis is a leading cause of seizures and epilepsy in most of the world, and it occurs when Taenia solium larval cysts infect the central nervous system. T. solium tapeworm infection is endemic in much of Peru, but there are scarce data on the prevalence in many rural highland communities where it is likely to be hyper-endemic. Peace Corps Volunteers live and work in these communities; however, to our knowledge, they have not been used to facilitate public health research.

Materials and Methods

We utilized Peace Corps Volunteers to estimate the prevalence of T. solium tapeworm infection in seven rural communities in northern Peru. A convenience non-random sampling frame was used. Peace Corps Volunteers facilitated the collection of stool samples (N = 2,328), which were analyzed by sedimentation and microscopy. Niclosamide treatment and purgation preceded species identification, which was done by PCR-REA.

Results

Taenia sp. egg-positive stool samples were found in three of the seven communities we surveyed. The overall prevalence of Taenia sp. egg positivity was 2.1% (49/2,328) (95% CI = 1.6–2.8%) with prevalence up to 4.3% (42/977) (95% CI = 3.1–5.8%) by community. All 34 of the specimens tested by PCR-REA were T. solium. The overall prevalence of T. solium tapeworm infection was 1.5% (34/2,328) (95% CI = 1.0–2.0%). Prevalence up to 2.9% (28/977) (95% CI = 1.9–4.1%) by community was observed.

Conclusion/Significance

This study recorded high T. solium tapeworm prevalence, and identified hyper-endemic rural communities. It demonstrates that synergy between researchers and Peace Corps Volunteers can be an effective means to conducting large-scale, community-based studies in remote areas of Peru.     

Taenia solium Cysticercosis Hotspots Surrounding Tapeworm Carriers: Clustering on Human Seroprevalence but Not on Seizures

Background

Neurocysticercosis accounts for 30%–50% of all late-onset epilepsy in endemic countries. We assessed the clustering patterns of Taenia solium human cysticercosis seropositivity and seizures around tapeworm carriers in seven rural communities in Peru.

Methodology

The presence of T. solium–specific antibodies was defined as one or more positive bands in the enzyme-linked immunoelectrotransfer blot (EITB). Neurocysticercosis-related seizures cases were diagnosed clinically and had positive neuroimaging or EITB.

Principal Findings

Eleven tapeworm carriers were identified by stool microscopy. The seroprevalence of human cysticercosis was 24% (196/803). Seroprevalence was 21% >50 m from a carrier and increased to 32% at 1–50 m (p = 0.047), and from that distance seroprevalence had another significant increase to 64% at the homes of carriers (p = 0.004). Seizure prevalence was 3.0% (25/837) but there were no differences between any pair of distance ranges (p = 0.629, Wald test 2 degrees of freedom).

Conclusion/Significance

We observed a significant human cysticercosis seroprevalence gradient surrounding current tapeworm carriers, although cysticercosis-related seizures did not cluster around carriers. Due to differences in the timing of the two outcomes, seroprevalence may reflect recent T. solium exposure more accurately than seizure frequency.     

Neurocysticercosis as a Cause of Epilepsy and Seizures in Two Community-Based Studies in a Cysticercosis-Endemic Region in Peru

Background

The prevalence of epilepsy added to inadequate treatment results in chronic morbidity and considerable mortality in poor populations. Neurocysticercosis (NCC), a helminthic disease of the central nervous system, is a leading cause of seizures and epilepsy in most of the world.

Methods

Taking advantage of a cysticercosis elimination program, we performed two community-based cross-sectional studies between 2006 and 2007 in 58 rural communities (population 20,610) to assess the prevalence and characteristics of epilepsy and epileptic seizures in this endemic region. Serological and computed tomography (CT) data in individuals with epilepsy were compared to previous surveys in general population from the same region.

Principal findings

In two surveys, 17,450 individuals were evaluated. Lifetime prevalence of epilepsy was 17.25/1000, and prevalence of active epilepsy was 10.8/1000 inhabitants. The prevalence of epilepsy increased after age 25 years and dropped after age 45. Only 24% (45/188) of patients with active epilepsy were taking antiepileptic drugs, all at sub-therapeutic doses. Antibodies to cysticercosis were found in approximately 40% of individuals with epilepsy in both studies. In one survey only individuals presenting strong antibody reactions were significantly associated with having epilepsy (OR 5.74; p<0.001). In the second, the seroprevalence as well as the proportion presenting strong antibody reactions were both significantly higher in individuals with epilepsy (OR 2.2 and 4.33, respectively). Brain CT showed NCC-compatible images in 109/282 individuals with epilepsy (39%). All individuals with viable parasites on CT were seropositive.

Conclusion

The prevalence of epilepsy in this cysticercosis endemic region is high and NCC is an important contributor to it.     

A Comparative Study of Peripheral Immune Responses to Taenia solium in Individuals with Parenchymal and Subarachnoid Neurocysticercosis

Background

The ability of Taenia solium to modulate the immune system likely contributes to their longevity in the human host. We tested the hypothesis that the nature of the immune response is related to the location of parasite and clinical manifestations of infection.

Methodology

Peripheral blood mononuclear cells (PBMC) were obtained from untreated patients with neurocysticercosis (NCC), categorized as having parenchymal or subarachnoid infection by the presence of cysts exclusively within the parenchyma or in subarachnoid spaces of the brain, and from uninfected (control) individuals matched by age and gender to each patient. Using multiplex detection technology, sera from NCC patients and controls and cytokine production by PBMC after T. solium antigen (TsAg) stimulation were assayed for levels of inflammatory and regulatory cytokines. PBMC were phenotyped by flow cytometry ex vivo and following in vitro stimulation with TsAg.

Principal Findings

Sera from patients with parenchymal NCC demonstrated significantly higher Th1 (IFN-γ/IL-12) and Th2 (IL-4/IL-13) cytokine responses and trends towards higher levels of IL-1β/IL-8/IL-5 than those obtained from patients with subarachnoid NCC. Also higher in vitro antigen-driven TNF-β secretion was detected in PBMC supernatants from parenchymal than in subarachnoid NCC. In contrast, there was a significantly higher IL-10 response to TsAg stimulation in patients with subarachnoid NCC compared to parenchymal NCC. Although no differences in regulatory T cells (Tregs) frequencies were found ex vivo, there was a trend towards greater expansion of Tregs upon TsAg stimulation in subarachnoid than in parenchymal NCC when data were normalized for the corresponding controls.

Conclusions/Significance

T. solium infection of the subarachnoid space is associated with an enhanced regulatory immune response compared to infection in the parenchyma. The resulting anti-inflammatory milieu may represent a parasite strategy to maintain a permissive environment in the host or diminish inflammatory damage from the host immune response in the central nervous system.     

Ring-Screening to Control Endemic Transmission of Taenia solium

Background

Taenia solium is a major cause of preventable epilepsy in developing nations. Screening and treatment of human intestinal stage infection (taeniasis) within high-risk foci may reduce transmission and prevent epilepsy by limiting human exposure to infective eggs. We piloted a ring-strategy that involves screening and treatment for taeniasis among households located nearby pigs heavily-infected with the larval stage (cysticercosis). These pigs mark areas of increased transmission and can be identified by tongue examination.

Methodology

We selected two villages in northern Peru for a controlled prospective interventional cohort pilot study. In the intervention village (1,058 residents) we examined the tongues of all pigs every 4 months for nodules characteristic of cysticercosis. We then screened all residents living within 100-meters of any tongue-positive pig using enzyme-linked immunosorbent assay to detect Taenia antigens in stool. Residents with taeniasis were treated with niclosamide. In both the intervention and control (753 residents) we measured incidence of exposure by sampling the pig population every 4 months for serum antibodies against cysticercosis using enzyme-linked immunoelectrotransfer blot.

Principal Findings

Baseline seroincidence among pigs born during the study was 22.6 cases per 100 pigs per-month (95% confidence interval [CI] 17.0–30.0) in the intervention and 18.1 (95% CI 12.7–25.9) in the control. After one year we observed a 41% reduction in seroincidence in the intervention village compared to baseline (incidence rate ratio 0.59, 95% CI 0.41–0.87) while the seroincidence in the control village remained unchanged. At study end, the prevalence of taeniasis was nearly 4 times lower in the intervention than in the control (prevalence ratio 0.28, 95% CI 0.08–0.91).

Conclusions/Significance

Ring-screening reduced transmission of T. solium in this pilot study and may provide an effective and practical approach for regions where resources are limited. However, this strategy requires validation in larger populations over a greater period of time.     

Prevalence and Risk Factors Associated with Human Taenia Solium Infections in Mbozi District,Mbeya Region,Tanzania

Background

Taenia solium cysticercosis/taeniosis is emerging as a serious public health and economic problem in many developing countries. This study was conducted to determine prevalence and risk factors of human T. solium infections in Mbeya Region, Tanzania.

Methods and Findings

A cross-sectional survey was conducted in 13 villages of Mbozi district in 2009. Sera of 830 people (mean 37.9±11.3 years (SD); 43% females) were tested for circulating cysticerci antigen (Ag-ELISA) and antibody (Ab-ELISA). A subset of persons found seropositive by Ag-ELISA underwent computed tomography (CT) scan of the brain for evidence of neurocysticercosis. Stool samples from 820 of the same participants were tested for taeniosis by copro-antigens (copro-Ag-ELISA) and formol-ether concentration technique. Cases of T. solium taeniosis were confirmed serologically by EITB assay (rES38). A questionnaire was used for identification of risk factors. Active cysticercosis by positive Ag-ELISA was found in 139 (16.7%) persons while anti-cysticercal antibodies were detected in 376 (45.3%) persons by Ab-ELISA. Among 55 persons positive for Ag-ELISA undergoing CT scan, 30 (54.6%) were found to have structures in the brain suggestive of neurocysticercosis. Using faecal analysis, 43 (5.2%) stool samples tested positive for taeniosis by copro-Ag-ELISA while Taenia eggs were detected in 9 (1.1%) stool samples by routine coprology. Antibodies specifically against adult T. solium were detected in 34 copro-Ag-ELISA positive participants by EITB (rES38) indicating T. solium taeniosis prevalence of 4.1%. Increasing age and hand washing by dipping in contrast to using running water, were found associated with Ag-ELISA seropositivity by logistic regression. Gender (higher risk in females) and water source were risk factors associated with Ab-ELISA seropositivity. Reported symptoms of chronic severe headaches and history of epileptic seizures were found associated with positive Ag-ELISA (p≤0.05).

Conclusion

The present study indicates T. solium infection in humans is highly endemic in the southern highlands of Tanzania.     

Toxocariasis and epilepsy: systematic review and meta-analysis

Objective

Human toxocariasis is a zoonotic infection caused by the larval stages of Toxocara canis (T. canis) and less frequently Toxocara cati (T. cati). A relationship between toxocariasis and epilepsy has been hypothesized. We conducted a systematic review and a meta-analysis of available data to evaluate the strength of association between epilepsy and Toxocara spp. seropositivity and to propose some guidelines for future surveys.

Data Sources

Electronic databases, the database from the Institute of Neuroepidemiology and Tropical Neurology of the University of Limoges (http://www-ient.unilim.fr/) and the reference lists of all relevant papers and books were screened up to October 2011.

Methods

We performed a systematic review of literature on toxocariasis (the exposure) and epilepsy (the outcome). Two authors independently assessed eligibility and study quality and extracted data. A common odds ratio (OR) was estimated using a random-effects meta-analysis model of aggregated published data.

Results

Seven case-control studies met the inclusion criteria, for a total of 1867 participants (850 cases and 1017 controls). The percentage of seropositivity (presence of anti-Toxocara spp. antibodies) was higher among people with epilepsy (PWE) in all the included studies even if the association between epilepsy and Toxocara spp. seropositivity was statistically significant in only 4 studies, with crude ORs ranging 2.04–2.85. Another study bordered statistical significance, while in 2 of the included studies no significant association was found. A significant (p<0.001) common OR of 1.92 [95% confidence interval (CI) 1.50–2.44] was estimated. Similar results were found when meta-analysis was restricted to the studies considering an exclusively juvenile population and to surveys using Western Blot as confirmatory or diagnostic serological assay.

Conclusion

Our results support the existence of a positive association between Toxocara spp. seropositivity and epilepsy. Further studies, possibly including incident cases, should be performed to better investigate the relationship between toxocariasis and epilepsy.     

Genetic and Infectious Profiles Influence Cerebrospinal Fluid IgG Abnormality in Japanese Multiple Sclerosis Patients

Background

Abnormal intrathecal synthesis of IgG, reflected by cerebrospinal fluid (CSF) oligoclonal IgG bands (OBs) and increased IgG index, is much less frequently observed in Japanese multiple sclerosis (MS) cohorts compared with Western cohorts. We aimed to clarify whether genetic and common infectious backgrounds influence CSF IgG abnormality in Japanese MS patients.

Methodology

We analyzed HLA-DRB1 alleles, and IgG antibodies against Chlamydia pneumoniae, Helicobacter pylori, Epstein-Barr virus nuclear antigen (EBNA), and varicella zoster virus (VZV) in 94 patients with MS and 367 unrelated healthy controls (HCs). We defined CSF IgG abnormality as the presence of CSF OBs and/or increased IgG index (>0.658).

Principal Findings

CSF IgG abnormality was found in 59 of 94 (62.8%) MS patients. CSF IgG abnormality-positive patients had a significantly higher frequency of brain MRI lesions meeting the Barkhof criteria compared with abnormality-negative patients. Compared with HCs, CSF IgG abnormality-positive MS patients showed a significantly higher frequency of DRB1*1501, whereas CSF IgG abnormality-negative patients had a significantly higher frequency of DRB1*0405. CSF IgG abnormality-positive MS patients had a significantly higher frequency of anti-C. pneumoniae IgG antibodies compared with CSF IgG abnormality-negative MS patients, although there was no difference in the frequency of anti-C. pneumoniae IgG antibodies between HCs and total MS patients. Compared with HCs, anti-H. pylori IgG antibodies were detected significantly less frequently in the total MS patients, especially in CSF IgG abnormality-negative MS patients. The frequencies of antibodies against EBNA and VZV did not differ significantly among the groups.

Conclusions

CSF IgG abnormality is associated with Western MS-like brain MRI features. DRB1*1501 and C. pneumoniae infection confer CSF IgG abnormality, while DRB1*0405 and H. pylori infection are positively and negatively associated with CSF IgG abnormality-negative MS, respectively, suggesting that genetic and environmental factors differentially contribute to MS susceptibility according to the CSF IgG abnormality status.     

TLTF in Cerebrospinal Fluid for Detection and Staging of T. b. gambiense Infection

Background

Trypanosome-derived lymphocyte triggering factor (TLTF) is a molecule released by African trypanosomes that interacts with the host immune system, resulting in increased levels of IFN-γ production.

Methodology/Principal findings

TLTF and anti-TLTF antibodies were assessed in sera and cerebrospinal fluid (CSF) from patients infected with Trypanosoma brucei gambiense (T. b. gambiense) in an attempt to identify alternative markers for diagnosis and stage determination of human African trypanosomiasis or sleeping sickness. Seventy-four serum and sixty-one CSF samples from patients with parasitologically confirmed infection and known disease stage along with 13 sera and CSF from uninfected controls were tested. In serum the levels of anti-TLTF antibodies were unrelated to the disease stage. In contrast, levels of anti-TLTF antibodies in CSF were higher in intermediate/late stages than in early stage disease patients. Specificity of the detected antibodies was assessed by inhibition of TLTF bioactivity as represented by its ability to induce IFN-γ production. Additionally, TLTF was detected in CSF from late stage patients by Western blotting with the anti-TLTF specific monoclonal antibody MO3.

Conclusions/Significance

These findings suggest a new possibility for disease diagnosis with focus on involvement of the CNS through detection of TLTF and anti-TLTF antibodies in the CSF.     

Cognitive changes and quality of life in neurocysticercosis: a longitudinal study

Background

Few studies have focused on the cognitive morbidity of neurocysticercosis (NCC), one of the most common parasitic infections of the central nervous system. We longitudinally assessed the cognitive status and quality of life (QoL) of patients with incident symptomatic NCC cases and matched controls.

Methodology/Principal Findings

The setting of the study was the Sabogal Hospital and Cysticercosis Unit, Department of Transmissible Diseases, National Institute of Neurological Sciences, Lima, Peru. The design was a longitudinal study of new onset NCC cases and controls. Participants included a total of 14 patients with recently diagnosed NCC along with 14 healthy neighborhood controls and 7 recently diagnosed epilepsy controls. A standardized neuropsychological battery was performed at baseline and at 6 months on NCC cases and controls. A brain MRI was performed in patients with NCC at baseline and 6 months. Neuropsychological results were compared between NCC cases and controls at both time points. At baseline, patients with NCC had lower scores on attention tasks (p<0.04) compared with epilepsy controls but no significant differences compared to healthy controls. Six months after receiving anti-parasitic treatment, the NCC group significantly improved on tasks involving psychomotor speed (p<0.02). QoL at baseline suggested impaired mental function and social function in both the NCC and epilepsy group compared with healthy controls. QoL gains in social function (p = 0.006) were noted at 6 months in patients with NCC.

Conclusions/Significance

Newly diagnosed patients with NCC in this sample had mild cognitive deficits and more marked decreases in quality of life at baseline compared with controls. Improvements were found in both cognitive status and quality of life in patients with NCC after treatment.     

Exposure to Multiple Parasites Is Associated with the Prevalence of Active Convulsive Epilepsy in Sub-Saharan Africa

Background

Epilepsy is common in developing countries, and it is often associated with parasitic infections. We investigated the relationship between exposure to parasitic infections, particularly multiple infections and active convulsive epilepsy (ACE), in five sites across sub-Saharan Africa.

Methods and Findings

A case-control design that matched on age and location was used. Blood samples were collected from 986 prevalent cases and 1,313 age-matched community controls and tested for presence of antibodies to Onchocerca volvulus, Toxocara canis, Toxoplasma gondii, Plasmodium falciparum, Taenia solium and HIV. Exposure (seropositivity) to Onchocerca volvulus (OR = 1.98; 95%CI: 1.52–2.58, p<0.001), Toxocara canis (OR = 1.52; 95%CI: 1.23–1.87, p<0.001), Toxoplasma gondii (OR = 1.28; 95%CI: 1.04–1.56, p = 0.018) and higher antibody levels (top tertile) to Toxocara canis (OR = 1.70; 95%CI: 1.30–2.24, p<0.001) were associated with an increased prevalence of ACE. Exposure to multiple infections was common (73.8% of cases and 65.5% of controls had been exposed to two or more infections), and for T. gondii and O. volvulus co-infection, their combined effect on the prevalence of ACE, as determined by the relative excess risk due to interaction (RERI), was more than additive (T. gondii and O. volvulus, RERI = 1.19). The prevalence of T. solium antibodies was low (2.8% of cases and 2.2% of controls) and was not associated with ACE in the study areas.

Conclusion

This study investigates how the degree of exposure to parasites and multiple parasitic infections are associated with ACE and may explain conflicting results obtained when only seropositivity is considered. The findings from this study should be further validated.     

Clinical manifestations associated with neurocysticercosis: a systematic review

Background

The clinical manifestations of neurocysticercosis (NCC) are poorly understood. This systematic review aims to estimate the frequencies of different manifestations, complications and disabilities associated with NCC.

Methods

A systematic search of the literature published from January 1, 1990, to June 1, 2008, in 24 different electronic databases and 8 languages was conducted. Meta-analyses were conducted when appropriate.

Results

A total of 1569 documents were identified, and 21 included in the analysis. Among patients seen in neurology clinics, seizures/epilepsy were the most common manifestations (78.8%, 95%CI: 65.1%–89.7%) followed by headaches (37.9%, 95%CI: 23.3%–53.7%), focal deficits (16.0%, 95%CI: 9.7%–23.6%) and signs of increased intracranial pressure (11.7%, 95%CI: 6.0%–18.9%). All other manifestations occurred in less than 10% of symptomatic NCC patients. Only four studies reported on the mortality rate of NCC.

Conclusions

NCC is a pleomorphic disease linked to a range of manifestations. Although definitions of manifestations were very rarely provided, and varied from study to study, the proportion of NCC cases with seizures/epilepsy and the proportion of headaches were consistent across studies. These estimates are only applicable to patients who are ill enough to seek care in neurology clinics and likely over estimate the frequency of manifestations among all NCC cases.