Extensive Inactive Neurocysticercosis: A Case Report in Mbeya, Southern Highlands of Tanzania

Introduction

Taenia solium, the pork tapeworm, can cause two different diseases in humans: taeniasis and cysticercosis. If humans eat undercooked cyst-infested pork, they may develop a tapeworm in the intestines (taeniasis). If eggs of the tapeworm are ingested, larvae (cysticerci) may settle in tissues (cysticercosis). If they settle in the central nervous system, the disease is known as neurocysticercosis (NCC).¹ The period between infection with Taenia solium and clinical manifestation, as well as the clinical presentation itself, depends on the immunological response of the host, the virulence of the parasite, and the number, size, location, and stage of the cysts.² Neurocysticercosis may present with viable, degenerating, or calcified lesions in cerebral imaging. The first two are considered active stages, and the last (calcified) is considered an inactive stage.³ The evolvement of cysts from the active to the inactive stage may occur spontaneously, which can take several years. This process can also be induced by antiparasitic medication, eg, albendazole or praziquantel.^4,5 Most patients become symptomatic when cysts degenerate, but calcified lesions can also cause persistent signs/symptoms.

Epileptic seizures, severe progressive headaches, focal neurological deficits, and mental state alterations are the most common CNS signs/symptoms.⁶ Neurocysticercosis is associated with about 30% of acquired, preventable epilepsy in Taenia solium highly endemic areas.^7,8 However, there is insufficient information on which proportion of NCC patients will develop signs/symptoms, and with multiple lesions may remain asymptomatic.^9,10 In contrast, some individuals with low cyst loads are highly symptomatic and develop permanent sequelae, especially recurrent seizures, chronic headaches, or focal neurological deficits.^9,11 The variation in the manifestation of neurocysticercosis poses a challenge in the diagnosis since multiple parameters are needed to establish the degree of diagnostic certainty. Computed tomography (CT) scan and magnetic resonance imaging (MRI) are pillars for diagnosis of NCC but should ideally be supported by serological testing as suggested by the Del Brutto criteria.¹² Both, neuroimaging and serological testing, are obstacles to diagnosis, especially in low-income settings where neuroimaging (CT scan and MRI) and serological services are often not affordable to affected people as they commonly have a low socio-economic status.¹³

It has been observed that areas with a high HIV prevalence are also highly endemic to Taenia solium infection, although the evidence of this interaction is not well supported.⁷ Some individuals with neuro/cysticercosis and HIV co-infection react poorly to serological tests and others with higher cyst load become asymptomatic, especially in advanced stages of HIV.¹⁴ Thus, it is postulated that HIV might modulate presenting features of neuro/cysticercosis depending on the levels of the host’s immunity.¹⁵

We report a case study detailing the unusual manifestations of neurocysticercosis in a person living with HIV, and contrast this with typical patients uninfected with HIV.

Case Presentation

We present a case of extensive calcified neurocysticercosis in an asymptomatic 47-year-old male living with HIV. The patient was recruited through the CYSTINET-Africa study in January 2021. In this study, people living with HIV (PLHIV) attending HIV Care and Treatment Centers (CTC) clinics in Chunya and Tossamaganga (southern highlands of Tanzania) were offered serological testing for T. solium cysticercosis. If results were positive (but also for a subset of serological negatives), patients were offered a CT scan. For every PLHIV, also an HIV-negative control (matched by age, sex, and location of residence) was recruited to compare the accuracy of the serological test and NCC disease presentation between HIV-positive and negative persons. The patient we presented was recruited through the HIV care and treatment center clinic in Chunya.

In 2012, he was diagnosed with HIV. His CD4 count at diagnosis was 31 cells per cubic millimeter of blood, and he was categorized as in WHO stage II. Immediately after diagnosis and complete medical assessment, he was started on antiretroviral therapy consisting of Azidothymidine (AZT) + Lamivudine (3TC) + Efavirenz (EFZ) on the 3^rd April 2012. In 2017, he was changed to another ARV drug combination ie, started on a new drug combination consisting of Tenofovir disoproxil fumarate (TDF) +3TC+EFZ; this was due to the changes in the national guidelines in the first-line ARV treatment. Six months after the initiation (TDF +3TC+EFZ) combination, his viral load was undetectable. On the 5^th of August 2019, his antiretroviral treatment regime was again changed into Tenofovir disoproxil fumarate (TDF) + Lamivudine (3TC) + DTG (Dolutegravir) to avoid different side effects experienced from the regime he was using. His viral load was undetectable and remained undetectable in all subsequent viral load tests in 2018, 2020, and 2021 (Table 1).

Table 1 Summarized patient's clinical, antiretroviral treatmetreatment, and neuroimaging informationn

Serological testing for T. solium was positive for cysticercosis antibodies using the LDBIO Cysticercosis IgG Western Blot test, but negative for cysticercosis antigen by the apDia Cysticercosis Antigen (Ag) ELISA test. The cerebral CT scan examination was performed at Mbeya consultant hospital on 5 November 2021. The patient was examined neurologically on the day of the CT scan, and an in-depth history was taken.

Personal History, Risk Factors, and History of the Risk Factors for the Taenia Solium Infection

This patient has been an artisanal miner (small-scale gold mining worker) since 2010, with a history of keeping pigs from 2009 to 2019. He has been married with 4 children; screening of the family members for T. solium infection was done, and the patient denied anyone in the family having neurological signs and symptoms of NCC (ie severe progressive headache and epileptic seizures). The patient reported known risk factors for T. solium infection, such as eating pork and never boiling water. He reported always using the pit latrine at his home and regular handwashing after the toilet and before eating.

Medical History of Taenia Solium Infection and Neurological Examination

The patient denied having experienced any loss of consciousnessor involuntary movements of limbs or having been diagnosed with epilepsy. Any episodes of severe progressive headache, mental state alterations, or other signs/symptoms that could be associated with NCC (or taeniasis) were also denied. The overall physical examination was normal, the patient looked healthy, not pale, not jaundiced and there were no palpable nodules (head/neck, trunk, and extremities). The examination did not reveal any focal neurological deficit.

Fundoscopic Examination

The patient’s red reflex was normal, blood vessels were normal, and macular reflex was normal. The optic nerve and disc appeared normal, vitreous body, and choroid. No floaters were detected.

Chest X-Ray Examinations

Cardiac shadow was normal in size and configuration, and both lung fields and costophrenic angles were clear. No focal pulmonary lesion was seen with the intact bony thorax. Therefore, the chest radiograph was classified as normal.

Computerized Tomographic (CT) Scan Examination of the Brain

Technique

Continuous axial cuts were obtained through the skull with intravenous contrast. Multiple calcifications typical for neurocysticercosis were seen in the cerebral parenchyma, basal ganglia, and cerebellum (Figures 1–3). Bilateral orbital calcifications and calcifications involving the skin, soft palate, oropharynx, and skull base soft tissue were noted. No midline shift was observed. The features were suggestive of diffuse inyracranial and extracranial calcifications.

Figure 1 (A) Multiple NCC-typical calcifications were found in the cerebral parenchyma. (B) Calcification is also found in the cerebellum.

Figure 2 (A) In addition to multiple NCC typical calcifications in the cerebral parenchyma, there are also two calcifications in the orbitae. (B) Calcification involving the skin, soft palate, oropharynx, and skull base soft tissue are seen.

Figure 3 (A and B) Multiple NCC typical calcifications are noted throughout the brain parenchyma including the basal ganglia.

Impression

Features were suggestive of diffuse intracranial and extracranial calcification.

Discussion

We present a case of extensive calcified neurocysticercosis in a patient living with HIV. Despite a massive lesion load, he had never experienced any typical symptoms associated with neurocysticercosis (NCC). It is well known that the manifestations of NCC vary concerning the location, size, number of cysts, virulence of the agent, and immunity of the host.¹⁶ Calcified NCC has been associated with migraine in several studies, but this patient did not complain of any kind of headache.^17,18 Little is known about how HIV co-infection modifies clinical NCC presentation. It is hypothesized that HIV co-infection might contribute to a high lesion load and/or to less severe clinical signs/symptoms due to modulation of the immune system since the presence or absence of signs/symptoms largely depends on the host’s inflammatory response. Moreover, serological tests can be affected if the patient is immune-compromised.^19,20 This is speculated to be one of the reasons for asymptomatic neurocysticercosis in some individuals with advanced HIV. Calcified lesions captured by neuroimaging in people living with HIV are hard to define due to the possibility of mass lesions secondary to other opportunistic infections like toxoplasmosis and tuberculosis. Cysticercosis serological tests are also relatively affected by the host’s immune. In a highly compromised immunity, such as with very low CD4 counts, there is a likelihood of a negative cysticercosis serological test.²⁰ These possibilities might explain the asymptomatic neurocysticercosis in this patient, irrespective of the extensive calcific lesions.

Extensive Calcific Lesions Without Any Clinical Manifestations

Although the patient has a very large number of lesions, he had never had any neurological signs or signs/symptoms. The calcified stage of T. solium cysts is an inactive form and the end stage of the degeneration process. The fully developed initial viable stages (vesicular stage) then degenerate into the colloidal and granular stages and end in the calcified (inactive) stage. Whilst most patients are symptomatic in degenerative stages, they can also be symptomatic in the viable and calcified stages. Although possible, it is uncommon for patients to develop signs/symptoms for the first time in the calcified stage if they were asymptomatic in viable and degenerative stages.²¹ Studies show that patients with only calcified lesions are often not as symptomatic as before reaching the calcified stage.²² The Infectious Disease Society of America (IDSA) and the American Society of Tropical Medicine & Hygiene (ASHTM) guidelines recommend a gradual withdrawal of seizure suppressant medication in patients with epileptic seizures six months after the establishment of calcifications or resolution of all lesions if patients do not present with epileptic seizures anymore.²³ Some patients with the inactive calcified NCC lesions may be free from any neurological signs/symptoms, but some of them are left with persistent sequelae, especially epileptic seizures, focal neurological deficits, or other manifestations of neurological deficits.²⁴

The lack of any clinical manifestations in this patient evidences the symptomatic variability of neuro/cysticercosis. Extensive lesions have been observed previously among immunosuppressed individuals, and this has led to the hypothesis that immunosuppression secondary to HIV might modify the clinical presentation of neuro/cysticercosis. Other case studies have presented differing uncommon clinical manifestations related to HIV immunosuppression including Immune Reconstitution Inflammatory Syndrome (IRIS) for those who were recently initiated with antiretroviral (ARV) drugs.²⁵ One case report described a 4-year-old Tanzanian child living with HIV and presenting with disseminated cysticercosis as well as a case of disseminated NCC in the contexts of IRIS after initiation of antiretroviral treament.²⁶ There is a paucity of reliable information on the possible association between HIV and outcomes of T. solium, including the posited relationship with neurocysticercosis. Case reports are not well suited to address this, and more robust epidemiological study designs, with sufficient sample sizes are needed.⁷

Conclusion

Neurological signs/symptoms vary considerably in patients with NCC and some patients remain asymptomatic. The more NCC lesions patients have, the more likely they are to have neurological signs/symptoms. However, some patients with few lesions are highly symptomatic, and others with many disseminated lesions may not show any neurological signs/symptoms. Whether HIV alters the presentation of NCC in terms of neurological signs/symptoms or radiological characteristics is plausible, but this still needs to be evaluated reliably.