**4. Neurotoxocariasis and effect modification of HIV**

### **4.1 Introduction**

Human toxocariasis is usually contracted by exposure to contaminated soil. This disease is rarely transmitted by raw meat or giblets of paratenic animals, such as chickens, lambs, or cows. Hoffmeister et al, (2007) reported a case of isolated cerebral toxocariasis presumably caused by the consumption of the raw duck liver. Their patient, a 55-year-old woman had sudden-onset hemiparesis of the right leg, eosinophilia of 30%, and markedly elevated total serum IgE levels. Magnetic resonance imaging demonstrated multiple cerebral hyperintense lesions on T2-weighed images.

Tests for antibodies to Toxocara in serum and cerebrospinal fluid yielded highly positive results and repeated courses of albendazole and corticosteroids led to significant clinical improvement. Previously, Kim et al., (2003) reported a case of cerebral infarction which was caused by toxocariasis in adults, who had headache, abdominal pain and a right side weakness. He had only a history of ingestion of raw liver of deer. Although the seriousness of infection of *Toxocara canis* depends on the site of parasite migration, the aberrant larvae occasionally invade the CNS. Neurological problems, such as epilepsy, neuropsychological deficits, and ataxia have been observed clinically in humans and in the case of ocular larval migrans, vision loss and permanent blindness may result (Akao *et al*., 2003; Nithiuthai *et al*., 2004).

Fig. 2. Shows multiple intraparenchymal calcified NC with and without perilesional edema

Human toxocariasis is usually contracted by exposure to contaminated soil. This disease is rarely transmitted by raw meat or giblets of paratenic animals, such as chickens, lambs, or cows. Hoffmeister et al, (2007) reported a case of isolated cerebral toxocariasis presumably caused by the consumption of the raw duck liver. Their patient, a 55-year-old woman had sudden-onset hemiparesis of the right leg, eosinophilia of 30%, and markedly elevated total serum IgE levels. Magnetic resonance imaging demonstrated multiple cerebral hyperintense

Tests for antibodies to Toxocara in serum and cerebrospinal fluid yielded highly positive results and repeated courses of albendazole and corticosteroids led to significant clinical improvement. Previously, Kim et al., (2003) reported a case of cerebral infarction which was caused by toxocariasis in adults, who had headache, abdominal pain and a right side weakness. He had only a history of ingestion of raw liver of deer. Although the seriousness of infection of *Toxocara canis* depends on the site of parasite migration, the aberrant larvae occasionally invade the CNS. Neurological problems, such as epilepsy, neuropsychological deficits, and ataxia have been observed clinically in humans and in the case of ocular larval migrans, vision loss and permanent blindness may result (Akao *et al*., 2003; Nithiuthai *et al*.,

and hydrocephalus secondary to intraventricular NC.

**4.1 Introduction** 

2004).

lesions on T2-weighed images.

**4. Neurotoxocariasis and effect modification of HIV** 

Three recent case-control studies conducted in rural Bolivia, Burundi and Italy (Nicoletti et al., 2002, 2007, 2008) reported a significant association between seropositivity to *T. canis* and epilepsy. The adjusted odds ratios (OR) in these three studies were 2.70 (95%CI=1.41-5.19), 2.13 (95%CI: 1.18-3.83) and 3.90 (95%CI: 1.91-7.98), in Bolivia, Burundi and Italy, respectively. Of particular interest, in 2 of the 3 studies, the OR of epilepsy associated with seropositivity to *Toxocara* spp. was higher among persons with partial seizures (OR=4.70, 95%CI=1.47-15.1 and OR=4.69, 95%CI: 2.24-9.80, respectively). The opposite was true in Burundi where the association was stronger among persons with generalized seizures (OR=2.52; 95%:1.01-6.26). Toxocariasis has also been associated with epilepsy in a study of children in Italy (Alpino et al., 1990)*.* In this study, prevalence of antibody to *T. canis* was compared in 91 children with epilepsy younger than 18 years and 214 controls. The OR for seropositivity was estimated to 2.0 (95% CI=1.0-4.0). The association was present primarily in children less than 5 years of age. Whether exposure precedes the onset of seizures or is a result of behaviors such as geophagy in children with epilepsy is uncertain. However, there was no association between pica and seropositivity in the study by Alpino et al. (1990) and Nicoletti et al. (2002), the association between seropositivity and epilepsy was stronger for adults than for children and for those with partial seizures than for those with generalized seizures. These findings argue against exposure being a consequence of seizures rather than an antecedent. Pica had a protective effect in the most recent study of Nicoletti et al. conducted in Sicily (2008).

Recall bias is unlikely since an overestimation of the association rather than an underestimation was observed. Persons with early onset seizures (<15 years old) showed a stronger association between toxocariasis and epilepsy, which tends to support the hypothesis that young children are at higher risk of infection. The prevalence of infection with *Toxocara* spp. was 50.8% among the control group in Burundi, suggesting that the exposure to this zoonotic parasite in SSA is very high (Nicoletti et al., 2002).

We were unable to find a well-designed studies from countries where parasitic zoonoses are endemic that assessed the association between HIV infection, NC and cerebral toxocariasis. While it is possible that HIV infection may modify the association between known risk factors and parasitic zoonotic infections of the brain, to our knowledge, this has never been addressed (personal communication by Carabin H, 2010). More information about parasitic zoonoses of the brain and epilepsy can be found in our book entitled Epilepsy. Clinical manifestations. ISBN 978-953-307-1341-2

In 2004 and 2005, we conducted a pilot study at the St-Elisabeth hospital in Lusikisiki (ECP) which included 296 consecutive patients consulting the medical clinic for suspected newonset seizures or existing epilepsy cases. Each week, four (4) randomly selected, consenting patients with confirmed seizure disorder were transported to Mthatha for CT scan of the brain. The prevalence of seropositivity to antigens of *T. solium* was 8% (95%CI: 4.5%-13%). A total of 92 patients with recurrent seizures and who also completed a questionnaire were referred to Mthatha for a CT-scan. Of these, 34 (37.0%, 95%CI: 27.1%-47.7%) had a definite diagnosis of neurocysticercosis (NCC), 14 of whom had active lesions visible on CT, 39 (42%) had no CT abnormality, and 19 (21%) had other, undefined non-NCC calcifications. Our results showed that serology alone cannot be used to diagnose NCC in this population (Foyaca-Sibat et al., 2009)

HIV status was available from 50 patients with confirmed seizures or epilepsy. Among the 47 patients with antibody ELISA results available, the antibody seroprevalence of *T. solium*

Epilepsy Secondary to Parasitic Zoonoses of the Brain 329

positivity (group 3) respectively. We used this inclusion criteria due to the possibility that co-infection with the study helminths may accelerate the progression of HIV infection to

Fig. 3. Shows graphical composition of each group (Made by Prof. H Carabin from

be informed, we do so and then refer them to the HIV/AIDS clinic for their care.

group, but we were aiming at sampling 50 patients in each group.

Group 5 was sampled from the neurology/epilepsy/neurocysticercosis clinic at the NMAH. We took a random sample of clinic patients newly diagnosed with epilepsy within the previous 12 months and who tested negative for HIV at that time or anytime following the initial visit. Group 6 consisted of HIV negative patients referred to the general medicine clinic of the NMAH and who have no history of any neurological disorders. Group 6 had a negative HIV diagnostic test resulted in the past month. For Groups 5 and 6, if the patients had never been tested for HIV, we offered the test. Only those HIV seronegative was included in these groups. If tested participants do not wish to be informed about their HIV status (very common situation), we respected their choice. If they test positive and want to

The sampling strategy depended on the expected number of patients available on each

Data is analyzed to estimate the cross-sectional associations between HIV and infections with *T. solium* and *Toxocara spp.* and their potential interactions in clinically apparent neurological complications. The 6 groups, which are fixed by design, will be modeled as an interaction term between HIV status and the presence or absence of neurological disorders. Either the serological results or the presence of parasitic brain lesions on CT-scan (i.e., NC or neurological toxocariasis) are the "outcomes" in the statistical analyses since they are the random variables

advanced stages.

University of Oklahoma, USA)

**4.2 Statistical method** 

was 30.0% among HIV positive patients and 48.1% among HIV negative patients. Interestingly, among the 33 patients with antigen ELISA results, the antigen seroprevalence of *T. solium* was 16.7% among the HIV positive patients but only 9.5% among the HIV negative patients. These preliminary results suggest that HIV patients may be less able to mount a detectable antibody response to cysticercosis and might be more likely to be infected with active cysts. A total of 22 of these patients (13 HIV negative and 9 HIV positive) were referred for a CT-scan. Of these, 5 HIV negative and 7 HIV positive patients had CT evidence of NC with 2 HIV negative and 5 HIV positive patients harboring active cysts. These very preliminary and imprecise results do suggest that there may be an association between NC and HIV infection. (Foyaca-Sibat et al., 2009)

#### **4.1.1 The specific research aims of the current pilot study are**


The long-term goal of this project is to develop a multidisciplinary-based interventions to more effectively control preventable parasitic zoonotic infections that are associated with epileptic disorders and that may disproportionately affect people living with HIV/AIDS.

We did a pilot cross-sectional study comparing six groups of patients defined by HIV infection status (advanced HIV, HIV positive not in the advanced stages, and HIV negative) and the presence of clinical manifestations of selected CNS disorders (yes/no).

Advanced-stage HIV patients (groups 1 and 2) are individuals who have met the WHO definition of stage 3 HIV/AIDS in the past 12 months (WHO, 2005). Patients who have ever been diagnosed with stage 4 HIV/AIDS are excluded. Only stage 3 patients not yet on HAART at the time of the study were included. (See figure 3)

Newly (< 12 months) diagnosed HIV patients not in the advanced stage (Groups 3 and 4) are defined as persons living with HIV/AIDS (PLWH/A) under care who have CD4 counts >350 cells/mm3 and who are not HIV stages 3 or 4 as defined by the WHO (WHO 2005) when the study starts or at the time of diagnosis of a neurological disorder. We needed to invite some of these patients to participate in the study during their first visit to the HIV clinic in order to recruit a sufficient number of these early stage patients.

Groups 1-4 were sampled from the Mthatha Hospital Complex's HIV/AIDS clinic which is likely to represent the largest source of PLWH/A under care in the ECP, Nelson Mandela Academic Hospital (NMAH) is included. Patients in Groups 1 and 3 have been diagnosed with epilepsy at any time following their diagnosis of advanced HIV (group 1) or HIV

was 30.0% among HIV positive patients and 48.1% among HIV negative patients. Interestingly, among the 33 patients with antigen ELISA results, the antigen seroprevalence of *T. solium* was 16.7% among the HIV positive patients but only 9.5% among the HIV negative patients. These preliminary results suggest that HIV patients may be less able to mount a detectable antibody response to cysticercosis and might be more likely to be infected with active cysts. A total of 22 of these patients (13 HIV negative and 9 HIV positive) were referred for a CT-scan. Of these, 5 HIV negative and 7 HIV positive patients had CT evidence of NC with 2 HIV negative and 5 HIV positive patients harboring active cysts. These very preliminary and imprecise results do suggest that there may be an

1. Conduct a pilot study to compare the cross-sectional seroprevalence of toxocariasis and cysticercosis in six groups: patients in the advanced stage of HIV, those who are HIV positive but not in the advanced stages, and HIV negative patients, each group being further subdivided into those with and without selected neurological disorders. Our research hypothesis was: the prevalence of parasitic zoonoses is higher among people with advanced HIV but CNS manifestations are more common among people in the early stages for HIV as compared to HIV negative people living in the Eastern Cape

2. Conduct a pilot study to estimate the interaction between HIV and cysticercosis or toxocariasis in the occurrence of neurological complications in adolescents and adults with HIV infection. To estimate the interaction between HIV and cysticercosis and toxocariasis on the prevalence of neurological disorders and generate new, testable

The long-term goal of this project is to develop a multidisciplinary-based interventions to more effectively control preventable parasitic zoonotic infections that are associated with epileptic disorders and that may disproportionately affect people living with HIV/AIDS. We did a pilot cross-sectional study comparing six groups of patients defined by HIV infection status (advanced HIV, HIV positive not in the advanced stages, and HIV negative)

Advanced-stage HIV patients (groups 1 and 2) are individuals who have met the WHO definition of stage 3 HIV/AIDS in the past 12 months (WHO, 2005). Patients who have ever been diagnosed with stage 4 HIV/AIDS are excluded. Only stage 3 patients not yet on

Newly (< 12 months) diagnosed HIV patients not in the advanced stage (Groups 3 and 4) are defined as persons living with HIV/AIDS (PLWH/A) under care who have CD4 counts >350 cells/mm3 and who are not HIV stages 3 or 4 as defined by the WHO (WHO 2005) when the study starts or at the time of diagnosis of a neurological disorder. We needed to invite some of these patients to participate in the study during their first visit to the HIV

Groups 1-4 were sampled from the Mthatha Hospital Complex's HIV/AIDS clinic which is likely to represent the largest source of PLWH/A under care in the ECP, Nelson Mandela Academic Hospital (NMAH) is included. Patients in Groups 1 and 3 have been diagnosed with epilepsy at any time following their diagnosis of advanced HIV (group 1) or HIV

hypotheses about the biological mechanisms for such interactions.

and the presence of clinical manifestations of selected CNS disorders (yes/no).

clinic in order to recruit a sufficient number of these early stage patients.

HAART at the time of the study were included. (See figure 3)

association between NC and HIV infection. (Foyaca-Sibat et al., 2009)

**4.1.1 The specific research aims of the current pilot study are** 

Province (ECP) of South Africa*.* 

positivity (group 3) respectively. We used this inclusion criteria due to the possibility that co-infection with the study helminths may accelerate the progression of HIV infection to advanced stages.

Fig. 3. Shows graphical composition of each group (Made by Prof. H Carabin from University of Oklahoma, USA)

Group 5 was sampled from the neurology/epilepsy/neurocysticercosis clinic at the NMAH. We took a random sample of clinic patients newly diagnosed with epilepsy within the previous 12 months and who tested negative for HIV at that time or anytime following the initial visit. Group 6 consisted of HIV negative patients referred to the general medicine clinic of the NMAH and who have no history of any neurological disorders. Group 6 had a negative HIV diagnostic test resulted in the past month. For Groups 5 and 6, if the patients had never been tested for HIV, we offered the test. Only those HIV seronegative was included in these groups. If tested participants do not wish to be informed about their HIV status (very common situation), we respected their choice. If they test positive and want to be informed, we do so and then refer them to the HIV/AIDS clinic for their care.

The sampling strategy depended on the expected number of patients available on each group, but we were aiming at sampling 50 patients in each group.

#### **4.2 Statistical method**

Data is analyzed to estimate the cross-sectional associations between HIV and infections with *T. solium* and *Toxocara spp.* and their potential interactions in clinically apparent neurological complications. The 6 groups, which are fixed by design, will be modeled as an interaction term between HIV status and the presence or absence of neurological disorders. Either the serological results or the presence of parasitic brain lesions on CT-scan (i.e., NC or neurological toxocariasis) are the "outcomes" in the statistical analyses since they are the random variables

Epilepsy Secondary to Parasitic Zoonoses of the Brain 331

Informed consent is obtained for all participants. All consent forms included a section in which the objectives of the study are clearly stated. This is followed by a description of what participation in the study involves for the subject. Because we know that a certain proportion of the population is illiterate, the explanation was read to the potential participants. Subjects that know how to sign asked to do it on a form that clearly explains, in simple words of either English or isi-Xhosa (local language in Mthatha), the objectives of the study. The culturally acceptable age at which individuals can be asked for either their assent or consent to participate is discussed with our local colleagues. The consent will clearly state

Persons who consent to participate in the study were identified by name and with an alphanumeric code. Only one coding sheet linking the names to the codes is created and it has a password protected. Every effort was made to keep the subject's personal data confidential. Until the end of the study, all data were entered into a password-protected database. All consent forms and the coding sheet were maintained in a locked file cabinet. Any data sent for data analysis was anonymous and with alphanumeric codes for the

All investigators and collaborators completed the CITI training-course on the Protection of Human Research. All are sworn to the Hippocratic Oath and committed to respecting the norms of good clinical practice, as well as the requirements of the Helsinki Declaration. The research protocol was evaluated and approved by Mthatha Umtata General Hospital, University of Transkei, and Walter Sisulu University IRB and the respective Ethical

Subjects who may require sedation for the CT-scan of the brain were excluded from this part of the study. Patients who do not know their HIV status or are HIV negative (groups 5 and 6) are offered an HIV test if they have not been tested in the past month. A diagnosis of HIV can be very upsetting and may lead to psychological distress. In order to assist newly diagnosed HIV positive participants, they were referred for counseling and treatment to the

The benefits of the information gained from the study outweigh the minimal risk involved. All subjects either have already received or we offer a neurological examination and a CTscan to determine the cause of their epilepsy, other neurological symptoms or the presence of silent CNS lesions. Individuals who have either never been tested or have not been

Total = 48 participants enrolled with neurological disorders

that individuals may terminate participation at any time.

Committees (UGH:0001/99, UNITRA:0018/05, and WSU:0068/009).

recently tested for HIV it was given the opportunity to be tested.

98% Rural or semi-rural residence

High proportion calcified lesions on CT 8 excluded due to CD4 counts>200

Approx 60% HIV Positive Of those with CT completed,

A brief summary about our preliminary findings can be seen in Table 6

46% Female, Median Age=29 Mean Age=33

HIV clinic of the Mthatha Hospital Complex.

**4.4 Preliminary results** 

Table 6. Some preliminary results

subjects names.

in this design. This approach allows us to test if there is indeed such interaction and if not, to assess the independent cross-sectional association between serological results (dependent variable) and HIV status and neurological disorders (independent variables).

We used three Bayesian multivariate logistic regressions with the presence/absence of antigen to cysticercosis, antibodies to cysticercosis and antibodies to *Toxocara* as outcomes. To estimate the association between the presence of NC and neurological toxocariasis (dependent variable) and HIV status among those with or without neurological disorders (independent variables), we used the same approach except that only groups 1-5 are represented. In all instances, we also run models adjusting for potential confounding variables such as age, gender, family history of epilepsy, area of residence, etc.

We want to emphasize that these analyses are also meant to direct our thinking in generating new hypotheses on the interaction between HIV and brain infection with parasitic zoonoses on neurological disorders in the developing world. We did not identify any causal relationships with data from a pilot cross-sectional study.Because of space limitation, power calculations cannot be presented here

#### **4.3 Study design and methods**

All patients meeting the inclusion criteria based on HIV stage and epilepsy have the opportunity to be included in this study. Thus, women and minorities meeting the eligibility criteria had the possibility of being included. For the CT-scan of the brain, pregnant women were excluded due to the risk to the fetus, but invited to come back to the exam after delivery.

#### **4.3.1 Selection criteria**

Fifty patients diagnosed with epilepsy in the past 12 months and receiving care at the neurology/epilepsy/neurocysticercosis clinic of the NMAH and who tested negative to HIV at that time or any time following the initial visit were invited to participate. Fifty HIV negative patients without neurological disorders, sampled from patients regularly attending a dermatology/general medicine clinic at the WSU hospital complex, were invited to participate by their physician who was informed of their eligibility by a member of the research team. Subjects included in the study were selected at random, and there are no selection criteria based on sex/gender or racial/ethnic groups.

The study is conducted in the former Transkei in South Africa where all population living in rural areas are black. Knowledge gained from this pilot study will assist in developing more definitive, prospective studies of the interaction between infections with parasitic zoonoses and HIV infection on the occurrence and clinical presentation of epilepsyat ECP of South Africa where HIV and cysticercosis are known as endemic.

A blood 10mL sample is collected on all participating subjects for the detection of antibodies to the larval stages of *T. solium* and of *Toxocara* spp and for the detection of the antigens to the larval stages of *T. solium*. Sera will be identified by their research identification numbers and stored in the NMAH laboratory. For HIV negative participants who have not been tested for HIV in the past 12 months, part of the sera will be used to test for HIV.

Each participant is assigned a research identification number. Data retained on participants will only be identified by their research ID. Information linking participants to their research ID will is stored in secured files in the research office. All of the biological specimens and the interview assessments listed above will be collected specifically for the purposes of the proposed research project.

in this design. This approach allows us to test if there is indeed such interaction and if not, to assess the independent cross-sectional association between serological results (dependent

We used three Bayesian multivariate logistic regressions with the presence/absence of antigen to cysticercosis, antibodies to cysticercosis and antibodies to *Toxocara* as outcomes. To estimate the association between the presence of NC and neurological toxocariasis (dependent variable) and HIV status among those with or without neurological disorders (independent variables), we used the same approach except that only groups 1-5 are represented. In all instances, we also run models adjusting for potential confounding

We want to emphasize that these analyses are also meant to direct our thinking in generating new hypotheses on the interaction between HIV and brain infection with parasitic zoonoses on neurological disorders in the developing world. We did not identify any causal relationships with data from a pilot cross-sectional study.Because of space

All patients meeting the inclusion criteria based on HIV stage and epilepsy have the opportunity to be included in this study. Thus, women and minorities meeting the eligibility criteria had the possibility of being included. For the CT-scan of the brain, pregnant women were excluded due to the risk to the fetus, but invited to come back to the exam after delivery.

Fifty patients diagnosed with epilepsy in the past 12 months and receiving care at the neurology/epilepsy/neurocysticercosis clinic of the NMAH and who tested negative to HIV at that time or any time following the initial visit were invited to participate. Fifty HIV negative patients without neurological disorders, sampled from patients regularly attending a dermatology/general medicine clinic at the WSU hospital complex, were invited to participate by their physician who was informed of their eligibility by a member of the research team. Subjects included in the study were selected at random, and there are no

The study is conducted in the former Transkei in South Africa where all population living in rural areas are black. Knowledge gained from this pilot study will assist in developing more definitive, prospective studies of the interaction between infections with parasitic zoonoses and HIV infection on the occurrence and clinical presentation of epilepsyat ECP of South

A blood 10mL sample is collected on all participating subjects for the detection of antibodies to the larval stages of *T. solium* and of *Toxocara* spp and for the detection of the antigens to the larval stages of *T. solium*. Sera will be identified by their research identification numbers and stored in the NMAH laboratory. For HIV negative participants who have not been

Each participant is assigned a research identification number. Data retained on participants will only be identified by their research ID. Information linking participants to their research ID will is stored in secured files in the research office. All of the biological specimens and the interview assessments listed above will be collected specifically for the purposes of the

tested for HIV in the past 12 months, part of the sera will be used to test for HIV.

variable) and HIV status and neurological disorders (independent variables).

variables such as age, gender, family history of epilepsy, area of residence, etc.

limitation, power calculations cannot be presented here

selection criteria based on sex/gender or racial/ethnic groups.

Africa where HIV and cysticercosis are known as endemic.

**4.3 Study design and methods** 

**4.3.1 Selection criteria** 

proposed research project.

Informed consent is obtained for all participants. All consent forms included a section in which the objectives of the study are clearly stated. This is followed by a description of what participation in the study involves for the subject. Because we know that a certain proportion of the population is illiterate, the explanation was read to the potential participants. Subjects that know how to sign asked to do it on a form that clearly explains, in simple words of either English or isi-Xhosa (local language in Mthatha), the objectives of the study. The culturally acceptable age at which individuals can be asked for either their assent or consent to participate is discussed with our local colleagues. The consent will clearly state that individuals may terminate participation at any time.

Persons who consent to participate in the study were identified by name and with an alphanumeric code. Only one coding sheet linking the names to the codes is created and it has a password protected. Every effort was made to keep the subject's personal data confidential. Until the end of the study, all data were entered into a password-protected database. All consent forms and the coding sheet were maintained in a locked file cabinet. Any data sent for data analysis was anonymous and with alphanumeric codes for the subjects names.

All investigators and collaborators completed the CITI training-course on the Protection of Human Research. All are sworn to the Hippocratic Oath and committed to respecting the norms of good clinical practice, as well as the requirements of the Helsinki Declaration.

The research protocol was evaluated and approved by Mthatha Umtata General Hospital, University of Transkei, and Walter Sisulu University IRB and the respective Ethical Committees (UGH:0001/99, UNITRA:0018/05, and WSU:0068/009).

Subjects who may require sedation for the CT-scan of the brain were excluded from this part of the study. Patients who do not know their HIV status or are HIV negative (groups 5 and 6) are offered an HIV test if they have not been tested in the past month. A diagnosis of HIV can be very upsetting and may lead to psychological distress. In order to assist newly diagnosed HIV positive participants, they were referred for counseling and treatment to the HIV clinic of the Mthatha Hospital Complex.

The benefits of the information gained from the study outweigh the minimal risk involved. All subjects either have already received or we offer a neurological examination and a CTscan to determine the cause of their epilepsy, other neurological symptoms or the presence of silent CNS lesions. Individuals who have either never been tested or have not been recently tested for HIV it was given the opportunity to be tested.

#### **4.4 Preliminary results**

A brief summary about our preliminary findings can be seen in Table 6


Table 6. Some preliminary results

Epilepsy Secondary to Parasitic Zoonoses of the Brain 333

Special mention is made of Mrs Noluntu Funani. Research Coordinator at the Office of

We also acknowledge financial support from, Directorate of Research Development from Walter Sisulu University in South Africa, University of Oklahoma, and South African Medical Research Council.The founder had no role in study design, data collection and

I sincerely thank to INTECH open access publisher for supporting this chapter and to my beautiful friends Ms Dragana Manestar and Natalia Reinic for their kind attention and nice

My sweet wife Lourdes de Fátima was so patient with my late nights, and I want to thank her for her faithful support in writing this book. Words cannot express my gratitude to

Finally, I wish to declare my eternal, deepest love and gratitude to Lorna María Foyaca García, Thabo Humberto Jorge Foyaca Ibañez and Fátima Susana Adolfina Foyaca Ibañez, because without their love and unconditional support this chapter would not have been written.

Akao, N., M . Tomoda, E. Hayashi, R. Suzuki, M. Shimizu-Suganuma, K. Schichionohe and

Asuman I, Nurgul C, Ilknur E, Derya E, Seniha S, Seyfi O, Pasa G. Neurobrucellosis with

Bartolini A. Epilepsy and toxocariasis: a case-control study in Italy. Epilepsia 2008;49:594-599. Bayliascariasis. Institute for International Cooperation in Animal Biologics. Iwoa State

Boongird, P., P. Phuapradit, N. Siridej, T. Chirachariyavej, S. Chuahirun, and A. Vejjajiva. 1977. Neurological manifestations of gnathostomiasis J. Neurol. Sci. 1977;31:279-291. Carod-Artal FJ, Vargas AP, Horan TA, Nunes LG. Chagasic cardiomyopathy is

Chero JC, Saito M, Bustos JA, Blanco EM, Gonzalvez G, Garcia HH. Hymenolepis nana

Centers for Disease Control and Prevention [homepage on the Internet] c-2005 Guidelines

Clausen MR, Meyer CN, Krantz , Moseril C, Gommeg G, Kayser L, et al. *Trichinella* infection

Carod-Artal FJ, Gascon J. Chagas disease and stroke. Lancet Neurol 2010; 9: 533–542

K. Cerebellar ataxia due to *Toxocara* infection in Mongolian gerbils, *Meriones* 

transient ischemic attack, vasculopathic changes, intracerebral granulomas and basal ganglia infarction: a case report. Journal of Medical Case Reports

University College of Veterinary Medicine. Full article available at the URL:

independently associated with ischemic stroke in Chagas disease. *Stroke* 2005; 36:

infection: symptoms and response to nitazoxanide in field conditions. *Trans R Soc* 

for veterinarians: prevention of zoonotic transmission of ascarids and hookworms of dogs and cats. National Center for Infectious Diseases, Division of Parasitic Diseases [updated 2011 March 22]. Available at the URL: http://www.cdc.gov/ncidod/dpd/parasites/ascaris/prevention.htm#pet\_owners

President. South Africa Medical Research Council, who gave me a valuable help.

Lourdes for her advices, encouragement, and assistance in polishing this chapter.

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*unguiculatus*. Vet. Parasit., 113: 229-237, 2003.

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Last accessed 03/20/2011.

support.

**6. References** 

2010;4(1):340.

965–70.

## **4.5 Discussion, challenges to date, and conclusions**

Our preliminary results were presented and discussed as: "Effect modification of HIVassociated central nervous system diseases by parasitic zoonoses in the Eastern Cape Province, South Africa" at 138th APHA Meeting.in Denver, Colorado. United States of America on November 9, 2010. (Abstract #222895).

Longer-term benefits of this study included a better understanding of the interaction between HIV and parasitic zoonoses on the development of seizure disorders. If the effects of parasitic zoonoses are more severe in HIV infected patients, future studies could be conducted to assess whether the risk factors for infection are the same in HIV positive and HIV negative patients, and control interventions to reduce the burden of these preventable causes of brain infection could be tested. Given that a very large proportion of HIV patients develops some neurological disorder in the course of their infection, being able to reduce the prevalence of some causes of these disorders would benefit patients themselves and the society as a whole by a reduction of medical costs and potential increase in productivity of these patients, especially in a region in which both HIV infection and parasitic zoonoses are highly prevalent.

Poor research capacity often means that there is a misunderstanding of the goals of the research and its ability to be combined with clinical and teaching services. A national political action strikes on campuses across South Africa escalated to violence, forcing the closure of WSU campus among others on four separate occasions. Though the majority of learners expressed their discontent peacefully, a small minority responded with violence. Campus activities were paralyzed on four occasions during the first phase of our study. The majority of the population speaks Isi-Xhosa (95% in ECP). Translations of study materials from English proved difficulties as few references exist containing vocabulary for scientific purposes.

There is a lack of knowledge regarding the interactions of HIV and helminthic infections, how their effects on immunological response affect risk of co-infection, and the role of altered immune responses that result from these infections.

Our pilot study is well underway and will lead to the development of new hypotheses on the interaction between HIV and parasitic infections of the brain.
