Neurocysticercosis Among Resettled Refugees From Burma

Authors


Seth O’Neal, MD, MPH, 3181 SW Sam Jackson Park Road, CSB 681, Portland, OR 97239, USA. E-mail: oneals@ohsu.edu

Abstract

Taenia solium is the most common helminthic infection of the central nervous system and a leading cause of epilepsy in developing nations. Little is known about neurocysticercosis in refugees from Southeast Asia which is endemic for T solium. We present two cases in a single household of refugees from Burma.

Cysticercosis is a disease caused by parasitic tissue infection by the larval form of the pork tapeworm, Taenia solium. Humans acquire cysticercosis by ingesting T solium eggs shed in the feces of a human infected with an adult intestinal tapeworm (taeniasis). Neurocysticercosis (NCC) occurs when T solium larvae infect the central nervous system (CNS), causing an inflammatory response or mass effect that may result in diverse clinical presentations including seizures, headaches, cognitive impairment, psychiatric disturbances, encephalitis, hydrocephalus, stroke, and death.1

Data verifying T solium endemicity is emerging from Southeast Asia, a region from which various refugee populations originate. Cysticercosis has been reported in Vietnam, Thailand, Lao PDR, Cambodia, Bali, and the Philippines.2 However, little is known about cysticercosis among populations in Burma. This information is increasingly relevant as the United Nations High Commission on Refugees pursues a policy of voluntary resettlement for refugees from Burma residing in camps in Thailand. As of 2010, over 65,000 refugees had resettled to the United States, Canada, Australia, and other countries.

Through this report, we aim to inform clinicians about the possibility of encountering T solium infection among resettled refugees from Burma. We present two clinical cases of NCC occurring in a single family along with results of the ensuing household investigation. We then discuss public health implications and areas for further research.

Case Report(s)

A 46-year-old ethnic Karen female developed severe debilitating occipital headache during transit to the United States from a refugee camp in Thailand, and within days of receiving 400 mg oral albendazole for presumptive intestinal roundworm infection. Her persistent headache was noted during post-arrival health screening but no follow-up was arranged.

Six months after arrival the intensity of headache increased, she suffered a generalized tonic-clonic seizure and was hospitalized under intensive care. Magnetic resonance imaging (MRI) revealed innumerous cystic intraparenchymal lesions with extensive surrounding inflammation (Figure 1). Serum was positive on enzyme-linked immunoelectrotransfer blot (EITB LLGP, CDC Parasitology Diagnostics Laboratory) for antibodies against T solium cyst glycoproteins and stool was negative on light microscopy for Taenia eggs or proglottids. She was treated with praziquantel and high-dose corticosteroids and was discharged on antiepileptic medication. Her treatment has been complicated by difficult to control epilepsy, multiple readmissions, and significant short-term memory deficit.

Figure 1.

Magnetic resonance images of the brain showing multiple ring-enhancing parenchymal cystic lesions with surrounding inflammation.

A public health investigation ensued in which all household members (n = 7) were screened for taeniasis using enzyme-linked immunosorbent assay (ELISA) for stool coproantigens and EITB for serum antibodies against recombinant antigen rES33. All laboratory procedures were completed at the CDC Parasitology Diagnostics Laboratory. The patient's husband had serum antibodies against rES33 but his stool was negative for tapeworm antigens. This was interpreted as evidence of cleared intestinal infection; therefore treatment for taeniasis was not given. Stool and serum screening tests for taeniasis were negative for all other household members.

Household members were also screened for symptoms suggestive of NCC. After multiple household visits, the family disclosed that the patient's 7-year-old son had a 3-year history of recurring tonic-clonic seizures not reported during post-arrival health screening. The boy was referred for evaluation, placed on antiepileptic therapy, and subsequently diagnosed with NCC. Computerized tomography (CT) revealed three parenchymal calcifications and serum EITB LLGP was negative for T solium cysticercosis. Antiparasitic treatment was not given as there was no evidence of infection with viable cysts.

Discussion

The ongoing resettlement of refugees from Burma to communities where advanced diagnostic infrastructure is widely available has highlighted the presence of T solium infection in this population. Case reports of cysticercosis among refugees from Burma are now appearing (Table 1). Clinicians should consider NCC in patients from Burma with epilepsy, chronic headache, or unexplained neurologic symptoms. Clinicians should also be aware of stigma and cultural interpretations related to epilepsy which may preclude patient disclosure of seizures.

Table 1.  Cases of cysticercosis among resettled refugees from Burma
Age / genderSymptomsNeuroimagingSerologyRemarks
  1. Cases encountered through combination keyword search in Medline and Google. Keywords included “Cysticercosis,”“Neurocysticercosis,”“Taenia,”“Burma,”“Myanmar,” and “refugee.”

  2. MRI = magnetic resonance imaging; CT = computerized tomography; ELISA = enzyme-linked immunosorbent assay; EITB LLGP = enzyme-linked immunoelectrotransfer blot; NCC = neurocysticercosis.

46 / MaleSeizure in known epileptic3MRI, single parenchymal cyst with visible scolexSerum ELISA negativeDefinitive diagnosis of NCC based on histology. Craniotomy and cyst removal for diagnosis may have been avoided as pathognomonic scolex was visible on MRI.
21 / MaleNontender subcutaneous nodulesMRI, multiple parenchymal cysts without edemaSerum EITB LLGP positiveDefinitive diagnosis of NCC based on consensus criteria.7 An example of occult asymptomatic NCC.
23 / MaleNew-onset seizure4MRI, multiple ring-enhancing parenchymal cystsNot reportedProbable diagnosis of NCC based on consensus criteria.7 Symptoms began 3 d after treatment with praziquantel for presumptive schistosome infection.
27 / MalePainless orbital swelling5CT head, normalSerum ELISA negativeDefinitive diagnosis of orbital cysticercosis based on histological examination of excised cyst. No evidence of NCC.

The primary tools for diagnosis of NCC include neuroimaging and serology assays. However, additional clinical and epidemiologic criteria are usually required to establish the diagnosis per consensus guidelines.6 Occasionally, a definitive diagnosis is possible with neuroimaging by demonstration of a visible scolex within a cyst, or with histopathologic confirmation of an excised or biopsied cyst. Head CT readily identifies most forms of NCC and can facilitate detection of small calcifications. The fine resolution possible with MRI aids in detection of smaller cysts, as well as cysts near bony structures or within the ventricles. The EITB LLGP serologic assay is highly specific (∼100%) and sensitive (∼98%) for detection of NCC involving more than one cyst.7 However, false-negative results frequently occur in NCC involving only calcified cysts, or in cases involving a single parenchymal cyst. Recently developed assays detect T solium cyst antigens or DNA in serum, cerebrospinal fluid, or urine, but these are not yet routinely available and their contribution to clinical diagnosis remains unclear. Further detail regarding diagnosis, treatment, and outcome of NCC is available in recent reviews.1,8,9

Consideration of the health of the patient's family is important when NCC is diagnosed as there may be additional infections within the household. In addition to NCC acquired in the country of origin, transmission can occur after resettlement as an adult intestinal tapeworm can live for several years. Exposure may also be maintained through travel and visiting friends and relatives. Stool examination of the index NCC case and household members can identify taeniasis and treatment may prevent additional NCC cases.10–12 Stool screening is accomplished preferentially by ELISA for Taenia sp. coproantigens or otherwise by light microscopy for eggs and proglottids. A combination of symptom screening, serology, and neuroimaging may identify additional cases of NCC.

Finally, in the case we present here as well as in the case described by Hewagama and colleagues, neurologic symptoms first appeared within days of treatment with albendazole or praziquantel for presumed intestinal helminth infection. Both medications penetrate the CNS well and are used in the treatment of NCC, typically in conjunction with corticosteroids to control resulting inflammation. The Food and Drug Administration recently updated labels for both drugs to warn clinicians of the possibility of precipitating inflammatory reactions in patients with occult asymptomatic NCC. Multiple suspected adverse reactions of this type have been reported.4,13–16 While temporality alone does not prove causation, the widespread use of presumptive treatment and the severity of potential adverse events suggests the need for further evaluation. There is currently no safe, practical, and effective method to screen at-risk populations for occult NCC prior to treatment with presumptive anthelmintics. The costs and benefits of overseas presumptive treatment of resettling refugees should be revisited with consideration of potential harm to refugees from T solium endemic areas. In addition, as T solium is coendemic with other helminthic infections frequently targeted by mass drug administration (MDA), prospective studies are needed to establish the actual incidence of neurologic adverse events following MDA in regions where NCC is known to occur.

Acknowledgments

The authors are supported in their research by the National Institutes of Health Fogarty International Center Clinical Research Scholars and Fellows Training Program at Vanderbilt University (R24 TW007988), the Research Institute for Health Sciences at Chiang Mai University, and through funding from the Centers for Disease Control and Prevention Emerging Infections Program.

Declaration of Interests

The authors state that they have no conflicts of interest.

Appendix

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The pig is the only intermediate host of importance in the transmission of cysticercosis, which is the infection with the larvae of the pork tapeworm, Taenia solium (see the Editorial by H.Garcia on pp. 73–75; the Review article by O. Del Brutto on pp. 112–17; and the Brief Communication by S. O'Neal on pp. 118–21).

Humans acquire neurocysticercosis by ingesting eggs of Taenia solium from contaminated food or, most often, directly via the fecal-oral route from a Taenia carrier. On the other hand, tapeworms are acquired by ingesting undercooked pork containing cystic larvae, after which the host may acquire neurocysticercosis by autoinfection, i.e., fecal-oral autoinfection.

Photo credit: Eric Caumes. Setting: Island of Cebu, Philippines

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