Clinical Presentation and Outcome of Toxoplasma Encephalitis in HIV-Infected Patients from Zaria,Northern Nigeria

Abstract

Toxoplasma encephalitis (TE) is the most common cause of focal deficits in patients living with HIV/AIDS. Among 257 HIV-infected adult patients seen between January 2006 and December 2010 in a tertiary hospital in Zaria, northern Nigeria, 9 (3.5%) patients had clinical, serological, and brain imaging evidence of TE. All 9 patients had CD4 count of less than 50 cells/mm³. Of the 9 patients, 7 were antiretroviral therapy (ART)-naive, while 2 were cases of ART-induced TE-immune reconstitution inflammatory syndrome. After administering intravenous dexamethasone for cerebral decompression and specific antitoxoplasma therapy, symptoms and signs resolved in 8 patients within 4 to 14 days, but 1 patient died. Our data suggest that even in the ART era in Nigeria, TE remains a fairly common cause of morbidity among HIV-infected patients due to late HIV diagnosis and significant immunosuppression at diagnosis. Early HIV diagnosis, early initiation of highly active ART, and routine prophylaxis against TE are imperative in combating the challenge of HIV/AIDS-related TE in Nigeria.

Introduction

Toxoplasma encephalitis (TE) is the most common AIDS-related opportunistic infection of the central nervous system (CNS) and the most common cause of focal deficits in HIV-positive patients. ¹ Toxoplasmosis has been serologically detected in 38% to 58% of HIV-infected adult patients from Nigeria, ^2,3 but only a few reports of TE have been documented in the literature. ^4,5 We retrospectively reviewed the clinical presentation, serological and brain imaging findings, as well as treatment outcome in 9 adult (>13 years) patients with TE managed over a 5-year period (January 2006-December 2010) in Ahmadu Bello University Teaching Hospital (ABUTH); a 700-bed tertiary hospital in Zaria, northern Nigeria. Ethical approval for the study was granted by the ethical review board at ABUTH.

Patients

During the 5-year study period, 9 (3.5%) of 257 admitted adult HIV-infected patients had diagnostic features of TE, ⁶ including (1) a recent onset of a focal neurological abnormality that is consistent with intracranial disease or reduced consciousness, (2) an evidence from brain imaging of a lesion with mass effect or a lesion that appears on a radiograph after injection of a contrast medium, and (3) a positive serum antibody to Toxoplasma gondii or successful resolution of symptoms in response to treatment of toxoplasmosis with antitoxoplasma-specific drugs.

The demographic, clinical, and laboratory features as well as the treatment outcomes of all patients are summarized in Table 1. Two patients each were admitted with TE every year between 2006 and 2009, while only 1 case was admitted in 2010.

Table 1.

Clinical Presentation and Treatment Outcome of 9 Cases with Toxoplasma Encephalitis.

Case	Age/Sex	Presenting Complaints (Duration)	ART Status	CD4 Count (cells/mm3	Toxoplasma Serology	Brain Imaging	Start of Neurological Recovery	Outcome
1	57/M	Headache, fever, altered consciousness (GCS), irrational talk, right hemiparesis (4 weeks)	Naive	41	IgG positive	Not done	4 days	Complete recovery after 9 days of therapy
2	15/M	Headache, fever, focal seizures, vomiting, right hemiparesis, slurred speech (2 weeks)	On ART for 6 weeks; ZDV /3TC/NVP	28	IgG positive	MRI: multiple left thalamic and basal ganglia, ring enhancing lesions with mass effect	12 days	Lost to follow-up after 2 months
3	24/F	Headache, fever, focal seizures, left hemiparesis (4 weeks)	Naive	18	IgG positive	CT scan: single irregular right parietal enhancing lesion with mass effect	10 days	Full recovery after 1 year of follow-up
4	39/F	Fever, altered consciousness (GCS = 11), irrational talk, forgetfulness, aggression (10 days)	On ART ZDV /3TC/NVP for 8 weeks	32	Not done	Brain CT scan: multiple-ring-enhancing lesions in the right parietal and occipital regions and left parietal region	14 days	Transferred after 1 month of follow-up
5	41/F	Fever, focal seizures, right hemiparesis, right facial nerve palsy (7 days)	Naive	20	IgG positive	Brain CT scan: single left parietal ring-enhancing lesion with mass effect	7 days	Full recovery at 6 months of follow-up
6	49/M	Headache, fever, vomiting, focal seizures, left hemiparesis, left facial palsy (3 weeks)	Naive	15	IgG positive	Brain CT scan: multiple-ring-enhancing lesions in the right frontal and parietal regions with mass effect	4 days	Lost to follow-up after 1 month
7	50/M	Headache, fever, vomiting, focal seizures, altered consciousness (GCS = 10), left hemiparesis (10 days)	Naive	14	Not done	Brain CT scan: single right parietal lobe ring-enhancing lesion with mass effect	6 days	Full recovery after 10 days of therapy
8	43/F	Headache, fever, focal seizures, altered consciousness (GCS = 11), left hemiparesis (2 weeks)	Naive	15	IgG positive	Not done	7 days	Full recovery after 15 days
9	38/M	Headache, fever, focal seizures, irrational talk, coma (GCS = 8), right hemiparesis (10 days)	Naive	20	IgG positive	Brain MRI: multiple cerebral and cerebellar enhancing lesions with mass effect		Died after 48 hours

Abbreviations: M, male; F, female; ART, antiretroviral therapy; ZDV, zidovudine; 3TC, lamivudine; NVP, nevirapine; GCS, Glasgow Coma Scale; MRI, magnetic resonance imaging; CT, computer tomography; IgG, immunoglobulin G.

Clinical and Laboratory Data

Fever, focal seizures, hemiparesis, and headaches were the most common manifestations observed in 8 patients. Toxoplasma serology by enzyme-linked immunosorbent assay (Diagnostic Automation Inc, California) was positive for immunoglobulin G (IgG) antibodies but negative for IgM antibodies (indicating latent infection) in all 7 patients who underwent serological testing. The median CD4 count by flow cytometry (Pactec, Germany) was 20 cells/mm³ (interquartile range of 15-28 cells/mm³). In view of cost constraints, brain imaging (computer tomography scan or magnetic resonance imaging) was possible in only 7 patients, revealing single-ring-enhancing cerebral lesions in 3 patients and multiple-ring-enhancing cerebral and cerebellar lesions in 4 patients.

Treatment Received

All patients received initial 6 weeks of antitoxoplasma therapy (oral pyrimethamine 200 mg day 1, then 50-75 mg daily, oral clindamycin 600 mg 6 hourly, and oral folinic acid 10 mg daily), according to standard treatment guidelines, ¹ as well as intravenous dexamethasone for cerebral decompression. Maintenance therapy using half the doses of therapeutic drugs was initiated after 6 weeks of initial therapy. Seizures were controlled using oral anticonvulsants (carbamazepine). Antiretroviral therapy (ART) was commenced according to the national HIV treatment guidelines. ⁷

Follow-up Outcome

Eight patients demonstrated resolution of neurological deficits and improvements in conscious level 4 to 14 days after commencement of antitoxoplasma therapy. One patient (case 9) with multiple cerebral and cerebellar lesions died after 48 hours of admission, probably due to significant cerebral edema and aspiration pneumonia. Permission was not granted for postmortem. Repeat brain imaging in case 7 after 6 months of follow-up revealed marked reduction in the size of the brain lesion (Figures 1 and 2). Mild medication side effects such as nausea and vomiting were reported in 2 patients. First-line regimen was continued in the 2 patients receiving ART with evidence of an increase in CD4 counts after 1 month of follow-up (ie, after 3 months of ART).

Figure 1.

Brain computer tomography scan of case 7 at initial presentation, showing single right parietal lobe ring-enhancing lesion with mass effect.

Figure 2.

Brain magnetic resonance imaging of case 7 performed 6 months after initial presentation showing a small residual right parietal lobe ring-enhancing lesion without cerebral edema.

Discussion

Our results indicate that even in the highly active ART (HAART) era in Nigeria, toxoplasma encephalitis remains a fairly common but treatable CNS opportunistic infection caused mainly due to the reactivation of latent brain infection in ART-naive HIV-infected patients with severe immunosuppression as reflected in very low CD4 counts of less than 50 cells/mm³. Similar studies from developed countries such as France ⁸ and South Africa ⁹ reveal contrasting findings of low incidence of TE due to wider availability and use of HAART.

There has been no previous report of TE from Nigeria following ART-induced immune reconstitution inflammatory syndrome (IRIS). We believe that irregular use of prophylactic cotrimoxazole and ART-induced IRIS might have led to the unmasking of latent toxoplasma infection in the brain of the patients on ART. Although viral loads were not performed for these patients due to resource constraints, our suspicion of TE-IRIS agrees with the published case definitions of IRIS, ^10,11 evident by subsequent increases in CD4 counts in these patients without the need for change in ART. ¹⁰

The clinical, serological, and brain imaging findings of our patients are typical of TE as previously described. ¹ It is notable that in all our patients, the regimen including clindamycin was effective and tolerable. Sulfadiazine, a first-line drug for treatment of TE, ¹ is less tolerable, more expensive, and not readily available in most hospitals in Nigeria.

In conclusion, to forestall the morbidity and mortality associated with HIV/AIDS-related TE in Nigeria, our results support the need to strengthen interventions that facilitate early HIV diagnosis, early initiation of ART, and routine use of cotrimoxazole prophylaxis.