Risk Factors For Epilepsy in Rural Lao PDR: A Case-Control Study
Risk Factors For Epilepsy in Rural Lao PDR: A Case-Control Study
Risk Factors For Epilepsy in Rural Lao PDR: A Case-Control Study
1
Institut de la Francophonie pour la Médecine Tropicale, Vientiane, Lao PDR;
2
Institut d’Épidémiologie Neurologique et de Nneurologie Tropicale (EA 3174), Limoges,
France; 3Department of Public Health and Epidemiology, Swiss Tropical Institute, Basel,
Switzerland; 4Faculty of Medical Sciences, National University of Laos, Vientiane, Lao PDR;
5
Department of Parasitology, Asahikawa Medical College, Asahikawa, Japan
Abstract. The objective of this study was to assess the major etiologic categories of epilepsy in
a rural district of the Lao PDR. Thirty-one newly identified patients with confirmed active epi-
lepsy were compared with 124 controls, matched for gender, age and village residence. Risk
factors for epilepsy were investigated with particular focus on cysticercosis serology. A history
of head trauma (OR=4.7, p=0.05), family history of epilepsy (OR=12.8, p=0.03), and the use of
human feces to fertilize domestic vegetable gardens (OR=4.9, p=0.04) were significantly asso-
ciated with epilepsy. The study did not confirm any direct relation between epilepsy and cys-
ticercosis serology. The cysticercosis seroprevalence was nil in the epilepsy group. This is the
first study in the Lao PDR on epilepsy risk factors representing important data for the sub-
region. Parasitic, environmental, and behavioral factors of this traditional population deserve
further studies to explain the missing link between epilepsy and cysticercosis.
2005; Tran et al, 2006; Somers et al, 2006). available for cases and controls. Each sub-
We performed a case-control study in ject provided a stool sample, which was pre-
rural Lao PDR to assess the main determinants served in sodium-acetyl-formalin solution and
of epilepsy, with a special focus on cysticer- examined using a standard concentration
cosis serology. technique (Yang and Scholten, 1997). Venous
blood (5 ml) was drawn from all subjects, and
MATERIALS AND METHODS the serum was stored at 4ºC for 6 hours, then
frozen at -20ºC. Frozen sera were flown in dry
Study area ice to Asahikawa Medical School, Japan.
The study was carried out in eight villages In Japan, ELISA and Immunoblot were
of the Hinheub District, Vientiane Province, Lao independently carried out by a similar proce-
PDR. The district is located 120 km north of dure, except that the antigens used were
Vientiane capital town. Rice farming, garden- isoelectrically purified glycoproteins (GPs)
ing, fishing and breeding, notably pig rearing, (Rotofor, BioRad, USA) extracted from T.
are the main subsistence activities of these solium glycoproteins (Ito et al, 1998).
communities.
Statistical analysis
Definition and identification of cases and con-
Data was entered in Epidata freeware,
trols
version 3.02 (www.epidata.dk, Odense Den-
A two-step community screening was mark) and analyzed with STATA, version 8.2
used to identify and ascertain the frequency (Stata Cooperation, College Station, TX, USA).
of epilepsy cases (Preux et al, 2000; Tran et Proportions, means and their standard devia-
al, 2006); terms and classification according tions (SD) were calculated to compare cases
to recommendation of the Commission on Epi- and controls. Odd ratios and the 95% confi-
demiology and Prognosis of the International dence intervals were calculated for the risk
League Against Epilepsy (ILAE, 1993). A total factors using the matched analysis procedure.
of 33 new patients with active epilepsy (last The significance threshold was set at 0.05.
seizure within 5 years) were confirmed among
Ethical clearance was obtained from the
4,310 interviewed villagers, of whom 31 con-
Ministry of Health, Lao PDR. Informed con-
sented to participate in the study. For each
sent was obtained from each of the subjects
case, four controls were matched for gender,
prior to enrollment in the study.
age (± 5 years) and village residence.
Procedures in cases and controls RESULTS
Cases and controls were interviewed re-
garding risk factors for epilepsy. The question- Study population
naire addressed family history of epilepsy, A total of 31 newly diagnosed cases of
perinatal events (from the caretaker of the active epilepsy, and 124 controls were enrolled.
children), history of head trauma, and risk fac- There were no significant differences between
tors for cysticercosis and taeniasis, including cases and controls in gender (p=1.00) or age
the presence of pigs in the household, the use (p=0.82). The male/female ratio was 1.2/1 for
of latrines, the consumption of pork meat, and both groups. The mean ages of cases and con-
the use of human feces as fertilizer. trols were 22.2 years (SD=12.5 years) and 22.7
Each subject underwent a general and years (SD=11.8 years), respectively. All controls
neurological clinical examination. Brain CT had their residency in the village of the corre-
scans and other imaging procedures were not sponding matched case.
Table 1
Potential risk factors for epilepsy in Lao PDR, 2004.
Risk factors Cases (n=31) Controls (n=124) OR 95% CI p
(%) (%)
from 1.5 to 17.0 fold, is relating to the gravity valence rates have been found, at around
of trauma (Annegers et al, 1998). Patients in 30% for people with epilepsy and 5% in the
our study were young adults; most of them general population (Preux et al, 1996; Wandra
developed the disease during childhood. Ru- et al, 2000,2003; Rajshekhar et al, 2003;
ral, mountainous environment and houses on Garcia et al, 2003; Ito et al, 2005; Krecek et
piles explain the high risk for trauma in these al, 2004; Ngowi et al, 2004; Del Brutto et al,
children. 2005). A similar result was also found in the
A positive family history of epilepsy is general population from a mountainous region
another classical risk factor for epilepsy. It in- in Vietnam (Dorny et al, 2004). Our sample
creased the risk of developing epilepsy by 3 size was based on these prevalences. In re-
fold in a case-control study of childhood epi- ality we found a result of 4.8% positive in the
lepsy in Iran (Asadi-Pooya, 2005). Consan- controls.
guinity, socially accepted by the Lao tradition Unexpectedly, no positive results were
beyond the second degree of kinship, may found in the group of epileptic cases. The con-
also play a role in epilepsy, as previously clusion is that the seroprevalence of cysticer-
shown in sub-Saharan Africa (Preux and cosis in the population with epilepsy in Lao
Druet-Cabanac, 2005). A history of peri-natal PDR may not be as high as that found in those
distress could not be traced accurately in our African or South American studies. It was not
series because only children over 5 years were sufficient to state the importance of cysticer-
included in the study. However, this factor may cosis as the etiology of epilepsy in Lao PDR
not be excluded since 80% to 90% of deliver- due to the sample size.
ies in rural Lao PDR take place at home in The risk factors for cysticercosis infection
unsafe conditions, resulting in high infant and include exposure to human feces with Taenia
mother mortality rates (70/1,000 and 405/ eggs, either directly or via food products
100,000, respectively) (National Statistic Cen- (Willingham et al, 2003). In the present study,
ter Lao PDR, 2005). a significant correlation was found between
In severa l tropical developing countries, epilepsy and using human feces as fertilizer
neurocysticercosis is the leading cause of in the vegetable garden. This practice is a po-
epilepsy (ILAE, 1994). Cysticercosis and hu- tential risk factor since most people in this re-
man taeniasis have been previously reported gion favor raw vegetables.
in Lao PDR as well as in neighboring Vietnam In Lao PDR, a recent questionnaire inves-
and Cambodia (Dorny et al, 2004), but their tigation found that pork meat, especially pork
relationship to epilepsy have never been as- fat, was traditionally believed to be related to
sessed. seizures, and therefore largely avoided once
Neuroimaging, the gold standard for the the disease commenced, not only by the pa-
diagnosis of cerebral cysticercosis was not tients but also by the family members, in some
available in our setting. The study could not de- cases (unpublished personal data). This fact
finitively assess the rate of cerebral cysticerco- may explain why our patients with epilepsy had
sis in our series of patients, however, we at- significantly lower pork consumption than the
tempted to assess the relationship between controls (OR=0.1, p<0.01). This dietary
epilepsy and cysticercosis using seropreva- change, not found in other countries, may in-
lence rates as an indirect marker. In this con- terrupt the parasite life cycle and cause a
text, the study demonstrated a negative result. negative serological result after several years.
In Africa, South America, India and In- Other studies of patients with new onset epi-
donesia, much higher cysticercosis seropre- lepsy may reveal this paradox.
All the above data are consistent with a population-based study of seizures after trau-
low or negligible T. solium transmission rate matic brain injuries. N Engl J Med 1998; 338:
in Lao PDR. Similar findings have been docu- 20-4.
mented in the neighboring Vietnam where Arruda WO. Etiology of epilepsie. A prospective
human taeniasis and cysticercosis have de- study of 210 cases. Arq Neuropsiquiatr 1991;
creased remarkably within the last decade 49: 251-4.
(Willingham et al, 2003), with very low persis- Asadi-Pooya AA. Epilepsy and consanguinity in
tent rates in coastal and mountain areas, and Shiraz, Iran. Eur J Paediatr Neurol 2005; 9:
a quasi complete elimination in urban areas 383-6.
(Somers et al, 2006). Chadwick D. Seizures and epilepsy after traumatic
brain injury. Lancet 2000; 355: 334-6.
In conclusion, in a series of patients with
active epilepsy from a rural, deprived area of Chen CC, Chen TF, Hwang YC, et al. Population-
Lao PDR, the prevalence of taeniasis and the based survey on prevalence of adult patients
with epilepsy in Taiwan (Keelung community-
seroprevalence of cysticercosis were found
based integrated screening no. 12). Epilepsy
surprisingly low. Traditional practices, such as
Res 2006; 26. (Epub ahead of print).
avoiding pork consumption, may have pro-
Chen YD, Xu LQ, Zhou XN. Distribution and disease
tected people with epilepsy from intestinal tae-
burden of cysticercosis in China. Southeast
niasis. On the other hand, roaming pigs and
Asian J Trop Med Public Health 2004; 35: 231-
the use of human feces as fertilizer may have
9.
favored the acquisition of cysticercosis. The
Commission on Epidemiology and Prognosis of the
latter, however, appeared to play little etiologic
International League Against Epilepsy. Guide-
role, if any. Finally, these low prevalences of lines for epidemiologic studies on epilepsy.
epilepsy, taeniasis, and cysticercosis, appear Epilepsia 1993; 34: 592-6.
as a paradox in a setting were poverty, poor
Commission on Tropical Diseases of the Interna-
hygiene, human-animal promiscuity, and an tional League Against Epilepsy. Relationship
overall high burden of parasitic diseases would between epilepsy and tropical diseases.
all be expected to act as risk factors. To ex- Epilepsia 1994; 35: 89-93.
plain this paradox, further studies are needed De Bittencourt PR, Adamolekum B, Bharucha N, et
to address other potential determinants, such al. Epilepsy in tropics: Epidemiology, socio-
as environmental, parasitic, or genetic factors. economic risk factors and etiology. Epilepsia
1996; 37: 1121-7.
ACKNOWLEDGEMENTS Del Brutto OH, Santibanez R, Idrovo L, et al. Epi-
We gratefully thank the authorities of the lepsy and neurocysticercosis in Atahualpa: A
provincial health department (Vientiane Prov- door-to-door survey in rural coastal Ecuador.
ince). This study received a grant from the Epilepsia 2005; 46: 583-7.
French Ministry of Foreign Affairs (CORUS Dorny P, Somers R, Cam-Thach D, Viet-Khong N,
project number 02-811-052), and was sup- Vercruysse J. Cysticercosis in Cambodia, Lao
ported by the IFMT project of the Agence PDR and Vietnam. Southeast Asian J Trop
Med Public Health 2004; 35: 223-6.
Universitaire de la Francophonie (AUF).
Erhart A, Dorny P, De NV, et al. Taenia solium cys-
ticercosis in a village in northern Viet Nam:
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