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June 2011, Volume 8, No. 6 (Serial No. 79), pp. 359-365 Journal of US-China Medical Science, ISSN 1548-6648, USA

DAVID

PUBLISHING

Severe Unexplained Headache and Toxoplasmosis in the Normal “Imunocompetent Patients” Sefar Mohamad Haj Department of Medicine, College of Medicine-University of Dohuk, Iraq

Abstract: Background: Toxoplasma Gondii is an obligate intracellular parasite that affects large number of world population. It can affect all mammals who serve as an intermediate host, cats are the definitive host. Toxoplasma may be transmitted via mouth-to-hand contact from improper handling of, or ingestion, of raw meat or undercooked meat containing cyst from cat feces. The acute infection in the immune-competent host usually causes self limited flu-like illness. Material and methods: A total of 687 patients suffering from unexplained severe headache, along with 200 age and sex matched patients presenting with various unrelated symptoms were enrolled in this study in the period between April 2005 toMarch 2010. All patients and controls were screened for anti-toxplasma antibody. Those individuals who had a positive antibody tests, were treated with Pyrimethamine 25 mg + Sulfadoxine 500 mg once daily (Fansidar) supplemented with 5 mg Folic acid daily for one month and their outcome were recorded. Results: Out of 687 patients with unexplained headache investigated for toxoplasmosis as a possible cause, 79 patients (11.5%), and 5% of the controls were positive. All positive cases were treated with Pyrimethamine 25 mg + Sulfadoxine 500 mg once daily (Fansidar) supplemented with 5mg Folic acid daily for one month. Which were effective in 76.7% of all patients and 87.5% of those suffering from headache of recent onset. Conclusion: The study indicate that toxoplasmosis may be a rather uncommon cause of unexplained headache in some normal immunocompetent patients and any patient complaining of headache with no obvious cause should be also investigated for toxoplasmosis. Key words: Severe unexplained headache, Toxoplasmosis, serological survey.

1. Introduction Toxoplasmosis is a zoonotic diseases caused by the ubiquitous protozoan called Toxoplasma gondii. The parasite can infects most warm- blooded animals throughout the world, including humans but the primary host is cat family, it has been estimated that up to one billion people have been exposed to the parasite worldwide. Virtually all warm blooded animals can act as intermediate hosts of T. gondii, but the parasite's life cycle is only completed in cats and several species of wild felidae, which are the definitive hosts [1]. The seroprevalance varies widely between countries. Animals are infected by eating infected meat or by ingestion of food contaminated with faeces of a cat that has itself recently been infected, or by Correspondence author: Sefar Mohamad Haj, MD, lecturer, research fields: headache and toxoplasmosis. E-mail: [email protected].

transmission from mother to foetus. Cats have been shown as a major reservoir of this infection. The parasite T gondi exist in 3 forms, Oocyst, tachyzoite and cyst. Toxoplasmosis is not passed from person-to-person, except in instances of mother to child (congenital) transmission and blood transfusion or organ transplantation. After oral infection, tachyzoite disseminate from gastro-intestinal tract and can invade virtually any cell or tissue where they proliferate and infect adjoining cells and produce necrotic focci surrounded by inflammation [2]. Most patients with acute acquired Ttoxoplasmosis have no systemic symptoms but some complain of flu-like illness, malaise, fever, fatique, muscle pain. Sore throat and headache, which occurs in about 10% of patients and is self limiting illness. The peak incidence of clinical illness is in adult aged 25-35 years [1, 3, 4]. Hoe ever clinical or pathological evidence of the diseases toxoplasmosis may occur

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Severe Unexplained Headache and Toxoplasmosis in the Normal “Imunocompetent Patients”

particularly in the immuno-compromised patients, congenitally infected foetus and child and in those in whom chorioretinitis develop during the acute acquired infection [1, 3]. Clinically either acute or chronic in immuno-compromissed patients presents with above symptoms and with non tender lymphadenopayhy, visual disturbances due to chorioretinitis, maculopapular rash, urticaria, hepatosplenomegaly, myocrditis, rarely abdominal pain due to involvement of reteroperitoneal or mesenteric nodes,and toxoplasma pneumonitis. Toxoplasmosis is usually self limiting diseases [3]. Headache which occurs in about 10% of patients and is a self limiting illness. The peak incidence of clinical illness is in adult aged 25-35 years [5]. However clinical/or pathological evidence of the diseases Toxoplasmosis may occur particularly in the immuno-compromised patients, congenitally infected fetus and child and in those in whom chorioretinitis develop during the acute acquired infection [5, 6]. Headache is a common problem in pediatric and internal medicine, affect about 5-10% of children and nearly 30% of middle aged women. Headache is also one of the most common clinical manifestation of acquired toxoplasmosis of the central nervous system in immunosuppressed subject [5]. Headache is classified by international classification of headache disorder to 3 classes, primary, secondary, cranial neuralgia and primary facial pain [7]. Duration, location, radiation & severity of headache is also very important. Cluster headache is strictly unilateral, whereas tension-type headache are usually band like and bilateral. Migraine generally begin unilaterally but may progress to involve the entire head, is moderate to severe pain lasting from 4-72 hours and is usually pulsating comes in attacks aggravated by walking and physical activity associated with nausea or vomiting, photophobia and visual aura. Pain along the distribution of temporal artery may suggest temporal

arteritis, is persistent but worse at night and accompanied marked scalp tenderness. Pain along the distribution of the trigeminal nerve is sign of trigeminal neuralgia (tic doloureux). Eye pain may suggest primary angle glaucoma, a painful red eye, mid-dilated fixed pupil, nausea and vomiting with impaired vision and the patient reporting coloured halos around eye. In meningitis is usually accompanied by fever and neck stiffness in obviously ill patient. In intracranial tumours produce headache when they are large enough to cause raised intracranial pressure, which is apparent from the history, papilloedema or neurological signs. In suarachnoid hemorrhage headache is often described as the worst ever, and is usually of sudden onset, neck stiffness may take hours to develop, in elderly patient classic symptoms and signs may be absent [3, 8]. Diagnosis of toxoplasmosis is complicated by the fact that the parasite can be present in an acute, chronic, latent or reactivated form. Diagnosis of toxoplasmosis can be achieved by isolation of the organism, molecular methods and serological testing. Serological analysis for IgM and IgG antibodies is commonly used for diagnosis. IgG antibodies appear 1-2 weeks after infection, peak in 6-8 weeks and gradually decline thereafter. Low titers generally persist for life. Detection of IgM by antibodies using enzyme-linked immunofluorescence technique, on the other hand is frequently used when attempting to diagnose acute infection. IgM antibodies are demonstrable as early as 5 days after infection and usually decrease after few weeks or months [1, 3, 9].

2. Patients and Methods In the period Between April 2005 and March 2010, total of 687 patients (aged >16 years) with unexplained severe or moderately severe headache were enrolled for the purposes of this study. Headache was considered unexplained if no cause was found despite detailed history, full clinical examination and normal relevant investigations. The

Severe Unexplained Headache and Toxoplasmosis in the Normal “Imunocompetent Patients”

examination include particular examination of their blood pressure, temperature, tenderness over the sinuses, tender spots, neck rigidity, upper teeth, eye pressure manually, ophthalmoscope, thereafter all had their Complete Blood examination, ESR, CRP, general urine examination, random blood sugar, Urea & electrolytes, X-ray of the sinuses, HlV test, Brucella agglutination tests, Widal agglutination test by standard laboratory procedures, other investigations such as CT scan of the brain was done for selected patients, collagen screen for patients who were suspected to have connective tissue diseases. Patients were selected according to special criteria. (1) Headache should be the most prominent symptom. (2) Headache should be of severe degree enough to interfering with patient normal life. (3) The headache without clear cause (unexplained headache) are selected and included in the study. (4) The age 16 years and more are only included. Patients with a definitive cause for headache as documented by above investigation were excluded from the study. All other patients with unexplained headache were sent for Toxoplasma latex agglutination study (Plasmatec Laboratory products Ltd, UK) for detection of antibodies to T.gondi. The antibodies titer was also estimated by serial dilution. The agglutination test is sensitive and inexpensive method to screen for IgG antibodies [3]. All the positive cases were confirmed by specific antitoxoplasma IgM antibodies testing using enzyme-linked immunofluorescence technique (Mini Vidas Toxo IgM, bioMerieux), Marcy-1’Etoile, France). A clear positive reaction indicates the presence of toxoplasma antibodies which reflect either a past infection or an evolving infection. In the next step we identified the level IgM. The sensitivity & specificity of latex agglutination test is 96.6% of sabin and Feldman dye test [10], which is the gold standard test.

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A patient was considered to be positive if the agglutination titer was higher than 1/16 for IgM, though in most patients the titer was much higher, a lower titer was repeated after 10 days, if they remain low they are considered to reflect past infection [11, 12]. Negative IgM antibodies virtually rule out acute infections [4]. The titer of 76.7% of positive IgM were either negative or at least 1 or 2 dilution lower after treatment (Table 1). Over the same period 200 patient with comparable age groups presenting with un related complaints were send for Toxoplasma latex agglutination test and only 10 were positive, among them 8 shows only low IgG titer and two shows low titer for both IgG & IgM indicating old infection (Table 1) All positive patients, with a high titer of IgM, were treated with Pyrimethamine 25 mg + Sulfadoxine 500 mg OD (Fansidar, Roche) supplemented with 5 mg Folic acid daily for one month. While the pregnant women, those with allery to sulfonamide and those who can’t tolerate Fansidar were treated with Spiramycin 1gm BD or Co-Trimoxazole 960 mg BD [13, 14]. All the patients were followed up weekly for 4 weeks, but 6 patients failed to attend the follow up. All cured patients were re-examined after 2 & 3 months.

3. Result In this study 687 patients (428 female & 259 male) with unexplained severe headache were enrolled and were investigated to find out the cause of their unexplained headache, their ages were between 16-55 years (Fig. 1). Apart from headache most of the patients

were

also

complaining

from

other

constitutional symptoms but by far the headache was the major & most prminanant symptom, the headache was diffuse and non-specific. On examination there was non tender cervical lymphadenopathy in 15 patients. Fatigue in 12 patients, Maculopapullar rash in

Severe Unexplained Headache and Toxoplasmosis in the Normal “Imunocompetent Patients”

362

Table 1

Titres of Toxoplasma Gondii antibodies by the latex agglutination test in 79 patients. The antibodies titer IgM < 1:20

1: 20

1:40

1:80

1:160

1:320

1:640

Total

Patients

0

7

5

12

22

18

5

79

Control

8

2

0

0

0

0

0

10

21-25

26-30

14

Number of cases

12 10 8 6 4 2 0

Fig. 1

31-35 Age group

36-40

41-045

46 and above

The distribution of headache according to age group.

2 patients. Nervous system examination was normal apart from 5 patients who had chorio-retinitis. It was documented that 79 (11.5%) patients had positive toxoplasma agglutination test (48 female and 31 male) (Fig. 2). The specific anti-toxoplasma IgM antibodies was high for headache patients group (I:20-1:640) but IgM was low or undetectable in the control group (