Millisecond infrared laser pulses depolarize and elicit action potentials on in-vitro dorsal root ganglion neurons.

This work focuses on the optical stimulation of dorsal root ganglion (DRG) neurons through infrared laser light stimulation. We show that a few millisecond laser pulse at 1875 nm induces a membrane depolarization, which was observed by the patch-clamp technique. This stimulation led to action potentials firing on a minority of neurons beyond an energy threshold. A depolarization without action potential was observed for the majority of DRG neurons, even beyond the action potential energy threshold. The use of ruthenium red, a thermal channel blocker, stops the action potential generation, but has no effects on membrane depolarization. Local temperature measurements reveal that the depolarization amplitude is sensitive to the amplitude of the temperature rise as well as to the time rate of change of temperature, but in a way which may not fully follow a photothermal capacitive mechanism, suggesting that more complex mechanisms are involved.

Epilepsy-associated levels of perceived stigma, their associations with treatment, and related factors: A cross-sectional study in urban and rural areas in Ecuador.

BACKGROUND: Epilepsy is felt to be a stigmatizing condition. Stigma has been considered one of the major factors contributing to the burden of epilepsy and to the treatment gap. Stigma has a negative effect on the management of people with epilepsy (PWE). Furthermore, lack of information and inappropriate beliefs are still the factors that most contribute to stigma and discrimination. In this study, we assessed the level of perceived stigma in urban and rural areas and we report their association with in antiepileptic drug (AED) use, effects on seeking medical care, and stigma-associated factors. METHODS: A cross-sectional study in urban and rural areas in Ecuador from January 2015 until May 2016. People with a confirmed diagnosis of epilepsy were included using three sources of information. The survey was implemented through a questionnaire to determine perceived stigma and evaluate the factors associated. The perceived stigma was measured using the revised Jacoby's stigma scale to detect differences in levels of stigmatization. Access to treatment was evaluated through self-report of AED use, and attainment of medical care and stigma-associated factors were assessed. Furthermore, a multivariate analysis adjusted for possible confounders was performed using stigma as the outcome variable. RESULTS: A total of 243 PWE were interviewed, 65.8% reported feeling stigmatized and 39.1% reported a high stigmatized level. We found a significant difference in high stigma perception in the urban area compared to the rural area. However, the lack of use of AEDs was significantly higher in the rural areas. No significant correlation was found between use of AEDs and the levels of perceived stigma. PWE who did not talk about their condition and those who did not feel well informed about their epilepsy had significantly higher perceived stigma levels. Additionally, the multivariate analysis demonstrated that area, educational level, type of seizure, talk about epilepsy, and information were associated with perceived stigma. CONCLUSION: The stigma perception was relevant in all PWE. We found a higher stigma level perception in the urban compared to rural area. Moreover, the lack of treatment was a serious problem mainly in rural areas. Even though we did not find that perceived stigma was associated with AED use, our study pointed out the influence of educational level and information related to stigmatization. Consequently, a coordinated effort to reduce stigma should include strategies focused on PWE education and information about their condition.

Epilepsy in Cambodia-treatment aspects and policy implications: a population-based representative survey.

INTRODUCTION: We tested two treatment strategies to determine: treatment (a) prognosis (seizure frequency, mortality, suicide, and complications), (b) safety and adherence of treatment, (c) self-reported satisfaction with treatment and self-reported productivity, and policy aspects (a) number of required tablets for universal treatment (NRT), (b) cost of management, (c) manpower-gap and requirements for scaling-up of epilepsy care. METHODS: We performed a random-cluster survey (N = 16510) and identified 96 cases (≥1 year of age) in 24 villages. They were screened by using a validated instrument and diagnosed by the neurologists. International guidelines were used for defining and classifying epilepsy. All were given phenobarbital or valproate (cost-free) in two manners patient's door-steps (March 2009-March 2010, primary-treatment-period, PTP) and treatment through health-centers (March 2010-June 2011, treatment-continuation-period, TCP). The emphasis was to start on a minimum dosage and regime, without any polytherapy, according to the age of the recipients. No titration was done. Seizure-frequency was monthly and self-reported. RESULTS: The number of seizures reduced from 12.6 (pre-treatment) to 1.2 (end of PTP), following which there was an increase to 3.4 (end of TCP). Between start of PTP and end of TCP, >60.0% became and remained seizure-free. During TCP, ∼26.0% went to health centers to collect their treatment. Complications reduced from 12.5% to 4.2% between start and end of PTP and increased to 17.2% between start and end of TCP. Adverse events reduced from 46.8% to 16.6% between start and end of PTP. Nearly 33 million phenobarbital 100 mg tablets are needed in Cambodia. CONCLUSIONS: Epilepsy responded sufficiently well to the conventional treatment, even when taken at a minimal dosage and a simple daily regimen, without any polytherapy. This is yet another confirmation that it is possible to substantially reduce direct burden of epilepsy through means that are currently available to us.

Neurological manifestations of filarial infections.

Filarial infections cause a huge public health burden wherever they are endemic. These filaria may locate anywhere in the human body. Their manifestations and pathogenic mechanisms, except the most common ones, are rarely investigated systematically. Their neurological manifestations, however, are being increasingly recognized particularly with onchocerciasis or Loa loa infections, Wuchereria bancrofti, or Mansonella perstans. The risk of developing these manifestations may also increase in cases that harbor multiple filariasis or coinfections, for instance as with Plasmodium. The microfilaria of Onchocerca and Loa loa are seen in cerebrospinal fluid. The pathogenesis of neurological manifestations of these infections is complex; however, pathogenic reactions may be caused by mechanical disruption, e.g., degeneration often followed by granulomas, causing fibrosis or mass effects on other tissues, vascular lesions, e.g., vascular block of cerebral vessels, or disordered inflammatory responses resulting in meningitis, encephalitis or localized inflammatory responses. The chances of having neurological manifestations may also depend upon the frequency and"heaviness"of infection over a lifetime. Hence, this type of infection should no longer be considered a disease of the commonly affected areas but one that may produce systemic effects or other manifestations, and these should be considered in populations where they are endemic.

Comprehensive evaluation of the psychosocial parameters of epilepsy: a representative population-based study in Prey Veng (Cambodia).

PURPOSE: We conducted a population-based study of epilepsy in Prey Veng (Cambodia) to explore self-esteem, fear, discrimination, knowledge-attitude-practice (KAP), social-support, stigma, coping strategies, seizure-provoking factors, and patient-derived factors associated with quality of life (QOL). METHODS: The results are based on a cohort of 96 cases and matched controls (n = 192), randomly selected from the same source population. Various questionnaires were developed and validated for internal consistency (by split-half, Spearman-Brown prophecy, Kuder-Richardson 20), content clarity and soundness. Summary, descriptive statistics, classical tests of hypothesis were conducted. Uncorrected chi-square was used. Group comparison was done to determine statistically significant factors, for each domain, by conducting logistic regression; 95% confidence interval (CI) with 5% (two-sided) statistical significance was used. KEY FINDINGS: All questionnaires had high internal consistency. Stress was relevant in 14.0% cases, concealment in 6.2%, denial in 8.3%, negative feelings in public in 3.0%. Mean self-esteem was 7.5, range 0-8, related to seizure frequency. Mean discrimination was least during social interactions. Coping strategies were positive (e.g. look for treatment). Postictal headache, anger, no nearby health facility, etc. were associated with QOL. SIGNIFICANCE: The reliability of our questionnaires was high. A positive social environment was noted with many infrequent social and personal prejudices. Not all populations should (by default) be considered as stigmatized or equipped with poor KAP. We addressed themes that have been incompletely evaluated, and our approach could therefore become a model for other projects.

[Research in tropical medicine]. / La recherche en médecine tropicale.

In France, research in tropical medicine is carried out by the Institute for Research and Development (IRD), university-affiliated institutes, and other research organizations such as INSERM, CNRS and the Pasteur Institute. Currently, this research is highly fragmented and therefore inefficient. As a result, despite significant financial means, French research in this field is not sufficiently competitive. This research activity should be coordinated by creating a "federation ", that would 1) facilitate the sharing of material and human resources, thereby improving efficiency and resulting in cost savings; 2) valorize French research in tropical medicine and its expert know-how, thus favoring the nomination of French experts in large international research programs (French experts in tropical medicine are currently under-recognized); 3) attract young researchers from France and elsewhere; and 4) adapt to the ongoing demographic and economic evolution of tropical countries. The creation of a Federation of French researchers would also make research in tropical medicine more visible. The objectives to which it leads already must include 1) a better understanding of the priorities of countries in the southern hemisphere, taking into account the social, cultural and economic contexts and ensuring the consistency of current and future projects ; 2) strengthening of research networks in close and equal partnership with researchers in the southern hemisphere, with pooling of resources (scientific, human and material) to reach the critical mass required for major projects ; 3) promoting the emergence of centers of excellence for health research in tropical countries ; and 4) contributing more effectively to training, because there can be no training without research, and no research without training This consolidation will help to empower research in tropical medicine, as in other Western countries, and will allow France to recover the place it deserves. The specific conditions of this Federation of all French stakeholders (universities, research institutes, the military, and NGOs) must be defined by a committee of elected or nominated officials.

Population-based study of epilepsy in Cambodia associated factors, measures of impact, stigma, quality of life, knowledge-attitude-practice, and treatment gap.

PURPOSE: Identify epilepsy-associated factors and calculate measures of impact, stigma, quality of life (QOL), knowledge-attitude-practice (KAP) and treatment gap in Prey Veng, Cambodia. METHODS: This first Cambodian population-based case-control study had 96 epileptologist-confirmed epilepsy cases and 192 randomly selected matched healthy controls. Standard questionnaires, which have been used in similar settings, were used for collecting data on various parameters. Univariate and multivariate regression was done to determine odds ratios. Jacoby stigma, 31-item QOL, KAP etc were determined and so were the factors associated with them using STATA software. Treatment gap was measured using direct method. KEY FINDINGS: Multivariate analyses yielded family history of epilepsy, difficult or long delivery, other problems beside seizures (mainly mental retardation, hyperthermia), and eventful pregnancy of the subject's mother as factors associated with epilepsy. There was high frequency of seizure precipitants esp. those related to sleep. Population attributable risk (%) was: family history (15.0), eventful pregnancy of subject's mother (14.5), long/difficult birth (6.5), and other problem beside seizures (20.0). Mean stigma (1.9±1.1, on a scale of 3) was mainly related to treatment efficacy. Mean QOL (5.0±1.4 on a scale of 10) was mainly related to treatment regularity. Cause or risk factor could be determined in 56% of cases. Treatment gap was 65.8%. SIGNIFICANCE: Factors in pre- and perinatal period were found to be most crucial for epilepsy risk in Cambodia which inturn provides major prevention opportunities. A global action plan for treatment, stigma reduction and improvement of QOL should be set-up in this country.

Characteristics of laser stimulation by near infrared pulses of retinal and vestibular primary neurons.

BACKGROUND AND OBJECTIVE: The optical stimulation of neurons from pulsed infrared lasers has appeared over the last years as an alternative to classical electric stimulations based on conventional electrodes. Laser stimulation could provide a better spatial selectivity allowing single-cell stimulation without prerequisite contact. In this work we present relevant physical characteristics of a non-lethal stimulation of cultured mouse vestibular and retinal ganglion neurons by single infrared laser pulses. STUDY DESIGN/MATERIALS AND METHODS: Vestibular and retinal ganglion neurons were stimulated by a 100-400 mW pulsed laser diode beam (wavelengths at 1,470, 1,535, 1,875 nm) launched into a multimode optical fiber positioned at a few hundred micrometers away from the neurons. Ionic exchange measurements at the neuron membrane were achieved by whole-cell patch-clamp recordings. Stimulation and damage thresholds, duration and repetition rate of stimulation and temperature were investigated. RESULTS: All three lasers induced safe and reproducible action potentials (APs) on both types of neurons. The radiant exposure thresholds required to elicit APs range from 15 ± 5 to 100 ± 5 J cm(-2) depending on the laser power and on the pulse duration. The damage thresholds, observed by a vital dye, were significantly greater than the stimulation thresholds. In the pulse duration range of our study (2-30 milliseconds), similar effects were observed for the three lasers. Measurements of the local temperature of the neuron area show that radiant exposures required for reliable stimulations at various pulse durations or laser powers correspond to a temperature increase from 22 °C (room temperature) to 55-60 °C. Stimulations by laser pulses at repetition rate of 1, 2, and 10 Hz during 10 minutes confirmed that the neurons were not damaged and were able to survive such temperatures. CONCLUSION: These results show that infrared laser radiations provide a possible way to safely stimulate retinal and vestibular ganglion neurons. A similar temperature threshold is required to trigger neurons independently of variable energy thresholds, suggesting that an absolute temperature is required.

First-ever, door-to-door cross-sectional representative study in Prey Veng province (Cambodia).

PURPOSE: To estimate the lifetime prevalence of epilepsy in Prey Veng province (Cambodia). METHODS: Door-to-door screening was performed using a random cluster survey whereby all people >1 year of age were screened for epilepsy by using a validated and standardized questionnaire for epilepsy in tropical countries. Suspected epilepsy patients identified by the questionnaire were revisited and examined by epileptologists. The confirmation of epilepsy was based on an in-depth clinical examination. Electroencephalograms were recorded at the community dispensary. KEY FINDINGS: Five hundred three potential epilepsy cases were identified from 16,510 screened subjects, and 96 were diagnosed to have epilepsy. An overall prevalence of 5.8 per 1,000 [95% confidence interval (CI) 4.6-7.0 per 1,000] was obtained. Generalized epilepsy (76%) was more common than partial epilepsy (12.5%). Three cases were of generalized myoclonic epilepsy (3.1%) and one case each (1.0%) were of absence and olfactory partial epilepsy. Six cases (5.2%) had more than one seizure type [one case with absence + generalized tonic-clonic (GTC), one case each with GTC + partial seizures with secondary generalization and absence + generalized myoclonic seizures and absence + simple partial seizures, and two cases with GTC + complex partial seizures]. Electroencephalography (EEG) studies revealed spike and wave discharges in 43.8%, focal spikes in 21.0%, generalized slow waves in 19.2%, and generalized slowing of background in 15.7%. SIGNIFICANCE: This is the first population-based study in Cambodia that had epilepsy as a primary objective, and compared to Western and neighboring countries it shows a lower prevalence.

Mental and neurological health research priorities setting in developing countries.

INTRODUCTION: A multi-region consultation process designed to generate locally produced regional and global research priorities on mental and neurological health in low- and middle-income countries. METHODS: Between 2003 and 2005, priority setting exercises on MNH research, using the systematic combined approach matrix (CAM) were held in the six regions of the developing world. One regional meeting per region was convened, and a global meeting was organized before and after the regional exercises. RESULTS: During regional meetings, regional agendas were created listing both research priorities and local problems in MNH. During global meetings, a global research agenda was established and four crucial areas of research priorities were identified: awareness and advocacy, enhancement of research capacity, training for service delivery, and development of evidence based policy. CONCLUSIONS: The combined matrix approach enabled the development of regional and global MNH research agendas, derived from bottom up consultations within and between low- and middle-income countries. Collaboration between regions with similar priorities was instituted. Such research agendas are designed to assist policy-makers and donors in the allocation of scarce resources, but they require regular review to reflect changing needs.

[Epilepsy in tropical areas]. / Epilepsie en zone tropicale.

Epilepsy in tropical areas, and in developing countries more generally, has certain specific characteristics (in particular its severity) which help to explain why this is still a major public health problem. The authorities often neglect this disease, even though numerous alarms have been raised by national leagues against epilepsy and by the World Health Organization, in order to bring epilepsy "out of the shadows". The prevalence is two to ten times higher and the incidence rate twice that in western countries. The mortality rate is very high, and many patients do not have access to appropriate treatment. In addition to the usual etiologies, certain causes are more common or specific to patients in poor countries, such as perinatal disorders and parasitic diseases (particularly cerebral malaria and neurocysticercosis). The impact of consanguinity is difficult to assess. Many associations against epilepsy have been created. Specific standardized guidelines have been written, validated and translated into several languages but they are under-utilized. A common language needs to be found between patients and caregivers, because of the numerous dialects spoken by ethnic groups, and the hidden meanings of the words used in this disease, where interpretations and perceptions cannot be dissociated from local culture. In most developing countries epilepsy is still considered a dangerous transmissible disease, and people with epilepsy are stigmatized. Specific training programs for healthcare personnel are needed, and efforts must be made to improve awareness among the population and the authorities. Some such programs are being supported by the pharmaceutical industry. This is particularly crucial in countries where counterfeit drugs are frequent and access to medicines is limited. Indeed, up to 80 % of people with epilepsy are treated poorly or not at all, and phenobarbitone is still the most widely used drug.

Japanese encephalitis revisited.

Japanese encephalitis (JE) is a major public health problem in Southeast Asia with around 50,000 cases and 10,000 deaths per year affecting essentially children below 10 years of age. The JE virus has shown a tendency to extend to other geographic regions. JE may cause severe encephalitis and survivors are frequently left with serious neurological lesions. In the absence of an effective antiviral treatment, prevention constitutes the best defense against this disease. Besides the implementation of vector control, immunization by vaccination is available. Vector control is expensive and difficult to implement on a large scale, leaving vaccination as the best means for mass campaigns. Recent progress in the development of live attenuated vaccines has given hope of an effective vaccine, which is both easy to use and inexpensive for large scale programs.

Symptomatic human neurocysticercosis--age, sex and exposure factors relating with disease heterogeneity.

OBJECTIVE: To evaluate the relevance of exposure and host biological factors in the heterogeneity of the clinical, radiological and inflammatory picture of neurocysticercosis (NCC). METHODS: 105 Mexican symptomatic NCC patients confirmed by imaging were studied before they received any specific treatment. The relationships studied were those between a) the patients' characteristics (gender, age and level of exposure), b) the type of clinical picture and c) the radiological and inflammatory characteristics of the disease (number, aspect, localization of the parasites, and CSF leukocyte counts). RESULTS: Seizures were the most frequent symptom and multiple subarachnoid cysticerci the most frequent localization. Symptomatology related to the developmental stage, number and localization of the parasites as well as the CSF leukocyte-counts. The total number of cysticercal lesions and of vesicular cysticerci increased with age,whereas the number of colloidal cysticerci decreased. CSF leukocyte-counts were higher in women than in men. Levels of exposure did not correlate with the clinical and radiological pictures. CONCLUSIONS: The variability found in the number, stage, localization and inflammation in the parasite lesions is strongly associated with the heterogeneity of NCC symptoms. The increased number of vesicular cysticerci and the decreased number of degenerating cysticerci with aging, as well as the prominence of inflammation in women suggest that immuno-endocrinological factors may play a role in susceptibility and pathogenesis. The data also show that with increasing age and exposure there is no increment in severity, a suggestion that there might be ways of regulating pathogenicity.

Plasma kinetics and efficacy of oral megazol treatment in Trypanosoma brucei brucei-infected sheep.

Experimentally infected sheep have been previously developed as an animal model of trypanosomosis. We used this model to test the efficacy of megazol on eleven Trypanosoma brucei brucei-infected sheep. When parasites were found in blood on day 11 post-infection, megazol was orally administered at a single dose of 40 or 80mg/kg. After a transient aparasitaemic period, all animals except two relapsed starting at day 2 post-treatment, which were considerated as cured on day 150 post-treatment and showed no relapse after a follow-up period of 270 days. In order to understand the high failure of megazol treatment to cure animals, a kinetic study was carried out. Plasma concentrations of megazol determined, by reverse-phase high-performance liquid chromatography at 8h post-treatment in these animals, were lowered, suggesting slow megazol absorption, except in cured animals. However, megazol plasma profiles in uninfected sheep after a single oral dose of megazol showed a fast megazol lowered absorption associated with a short plasma half-life of drug. Inter-individual variation of megazol pharmacokinetic properties was also observed. These findings suggested that the high failure rates of megazol treatment were related to poor drug availability after oral administration in sheep. In conclusion, megazol could cure sheep with T. b. brucei infection but oral administration was not an effective route.

Megazol combined with suramin improves a new diagnosis index of the early meningo-encephalitic phase of experimental African trypanosomiasis.

In human African trypanosomiasis (HAT), the parasites invade the central nervous system (CNS), leading to the development of meningo-encephalitis and an irreversible demyelinating process, which kills the patient unless specific treatment is undertaken. Among the experimental trypanocides, the nitroimidazole derivative megazol alone at optimal doses does not cure late-stage disease tested in mouse models, however the combination of suramin and megazol is able to cure infected mice without CNS involvement. We recently developed an experimental model of HAT with a sharp decrease in both the food intake and the body weight which may constitute an effective index of the early meningo-encephalitic phase. Using this model, we tested this hypothesis by the exclusive effectiveness of a megazol and suramin combination treatment to eliminate CNS trypanosomes. Sprague-Dawley rats were infected with Trypanosoma brucei brucei AnTat 1.1E. Food intake and body weight were measured daily from the day of infection to death. Haematocrit was measured twice a week. Treatment consisted of 20 mg suramin per kg body weight administered intraperitoneally (i.p.) alone, or three daily doses (80 mg/kg) of megazol given per os, or suramin (20 mg/kg, i.p.) followed 24 h later by three daily doses (80 mg/kg) of megazol given per os. Treatment was followed by an increase in daily body weight and food intake similar to those of the control animals, 2 weeks after treatment. The anaemia developed after infection is also cleared as shown by the haematocrit measurements. The rats treated with megazol alone died about 29 days after treatment and those treated with suramin, after about 26 days. Seven months later, no signs of relapse were seen in 10 of 12 rats treated with the therapeutic combination, indicating that this chemotherapy regimen was curative. The results support our previous finding, i.e. the decrease in body weight may constitute a diagnosis index of the early meningo-encephalitic phase.

An epidemiological study of pleuropulmonary paragonimiasis among pupils in the peri-urban zone of Kumba town, Meme Division, Cameroon.

BACKGROUND: Paragonimiasis have previously been reported in two zones of the Southwest Province of Cameroon including the Kupe mountain and Mundani foci. The aim of this study was to investigate the presence and epidemiology of paragonimiasis in the peri-urban zone of Kumba, Meme Division, located about 50 km away from the Kupe mountain focus. METHODS: Pupils of several government primary schools in 5 villages around Kumba underwent both parasitologic and clinical investigations in search of signs and symptoms of paragonimiasis. Mycobacterium tuberculosis was also searched for in the differential diagnosis. Freshwater crabs from neighbouring streams in the five villages were dissected in search of paragonimus metacercariae. RESULTS: Out of a total of 1482 pupils examined in all five villages, 309 individuals (147 males and 162 females) were recruited for this study based on the presence of one or more signs or symptoms of paragonimiasis. Eggs of Paragonimus africanus were found in stools and/or sputum of pupils from all five villages, giving an overall paragonimus prevalence of 2.56%. There was no significant difference in the disease prevalence between the villages (Chi2 = 8.36, P = 0.08). The prevalence of Paragonimus africanus eggs amongst pupils with symptoms of paragonimiasis was 12.3% (38 of 309). Males were infected more than females (17.0% versus 8.0%), but the difference was not significant (Chi2 = 5.76, P = 0.16). All the 38 paragonimus egg positive subjects presented with cough, 23 (60.53%) complained of chest pain while 16 (42.11%) had haemoptysis. Stool examinations also detected some intestinal parasites including Ascaris lumbricoides (29.45%), Trichuris trichiura (6.47%), Necator americanus (2.27%), Strongyloides stercoralis (1.62%), Enterobius vermicularis (0.65%), and Entamoeba histolytica (4.53%). No case of M. tuberculosis was noted. Out of a total of 85 dissected crabs (Sudanonautes africanus), 6.02 % were infected with paragonimus metacercariae. CONCLUSION: In addition to the two previously described paragonimiasis foci of Kupe mountain and Mundani, the identification of autochthonous cases of paragonimiasis in the peri-urban zone of Kumba town, makes the South West Province the most endemic zone of paragonimiasis in Cameroon at present.

TH2 profile in asymptomatic Taenia solium human neurocysticercosis.

Neurocysticercosis (NC), a parasitic disease caused by Taenia solium, may be either asymptomatic or have mild to severe symptoms due to several factors. In this study, the immunological factors that underlie NC pleomorphism were studied. Ten of the 132 inhabitants of a rural community in Mexico (Tepez) had a computerized tomography (CT) scan compatible with calcified NC, and all were asymptomatic. Their immunological profiles were compared with those of 122 CT scan negative (non-NC) subjects from the same village. NC was associated with a TH2 response (IgG4, IL-4, IL-5, IL-13). Subjects from Tepez had higher levels of specific antibodies (IgG1, IgG2, IgG4, IgE) and specific cell proliferation than subjects from an area with low exposure (Ensenada). This suggests that non-NC subjects from Tepez had been exposed to T. solium and resisted infection in the brain. Distinct immunological profiles in equally exposed individuals differing in outcome of infection support the hypothesis of host-related factors in resistance to and pathogenesis of NC. This is the first study reporting the immunological profile associated with the asymptomatic form of NC.

Population genetic structure of Taenia solium from Madagascar and Mexico: implications for clinical profile diversity and immunological technology.

Taenia solium is a cestode parasitic of humans and pigs that strongly impacts on public health in developing countries. Its larvae (cysticercus) lodge in the brain, causing neurocysticercosis, and in other tissues, like skeletal muscle and subcutaneous space, causing extraneuronal cysticercosis. Prevalences of these two clinical manifestations vary greatly among continents. Also, neurocysticercosis may be clinically heterogeneous, ranging from asymptomatic forms to severely incapacitating and even fatal presentation. Further, vaccine design and diagnosis technology have met with difficulties in sensitivity, specificity and reproducibility. Parasite diversity underlying clinical heterogeneity and technological difficulties is little explored. Here, T. solium genetic population structure and diversity was studied by way of random amplified polymorphic DNA in individual cysticerci collected from pigs in Madagascar and two regions in Mexico. The amplification profiles of T. solium were also compared with those of the murine cysticercus Taenia crassiceps (ORF strain). We show significant genetic differentiation between Madagascar and Mexico and between regions in Mexico, but less so between cysticerci from different localities in Mexico and none between cysticerci from different tissues from the same pig. We also found restricted genetic variability within populations and gene flow was estimated to be low between populations. Thus, genetic differentiation of T. solium suggests that different evolutionary paths have been taken and provides support for its involvement in the differential tissue distribution of cysticerci and varying degrees of severity of the disease. It may also explain difficulties in the development of vaccines and tools for immunodiagnosis.