Oxamniquine

Praziquantel is recommended as the drug of choice for all forms of schistosomiasis. We report the first case (to our knowledge) of exudative effusive polyserositis following treatment of schistosomiasis with this drug. This involved pleura, pericardium, and peritoneum and was associated with acute respiratory failure. The latter preceded the appearance of pleural effusions. We present a brief review of the literature and attract attention to the need for close observation of patients with schistosomiasis who are treated with praziquantel.

Praziquantel, a mixture of stereoisomers of pyrazinoisoquinoline ring structures, is a broad-spectrum antihelminthic that is effective against all forms of human schistosomiasis. It is generally well tolerated with only minor side effects, such as abdominal pain, headache, dizziness, epigastric discomfort, bloody diarrhea, or mild fever.[1-3]

We report an unusual complication of praziquantel therapy in schistosomiasis. Although some of the manifestations of our patient's illness, such as fever, skin rash, and diarrhea, have been described in acute schistosomiasis, this patient had hepatosplenomegaly and periportal fibrosis that persisted after recovery from acute illness making the possibility of chronic schistosomiasis more likely.

CASE REPORT

A 21-year-old man presented to another hospital with abdominal pain and bloody stools. Stool microscopy showed Schistosoma mansoni ova but examination for other parasites was negative. He was given 1.8 g of praziquantel as a single dose. Within four hours of taking this medication, he developed a generalized papulomacular itchy rash that was accompanied by myalgia, fever, abdominal pain, diarrhea, and severe pleuritic chest pain. He presented to King Khalid University Hospital 48 h later as the symptoms grew worse.

On examination he was pyrexial (oral temperature, 38 [degrees] C), pulse rate was 100 beats per minute, and blood pressure was 100/80 mm Hg. There were no clinical signs of cardiac failure. His chest was normal but he was unable to take a deep breath due to pleuritic pain. Abdominal examination revealed hepatosplenomegaly and generalized tenderness. Bowel sounds were present and findings from rectal examination were normal.

Initial investigations showed a total white blood cell count of 19,200/cu mm with 39 percent eosinophils; hemoglobin level was 11.6 g/dl with a microcytic, hypochromic blood picture. Hemoglobin electrophoresis showed no abnormality and bone marrow examination showed only an increased number of eosinophil precursors. A chest roentgenogram at the time of hospital admission showed blunting of the right costophrenic angle consistent with a small pleural effusion (Fig 1). Arterial blood gas determinations were as follows: pH, 7.42; [PaCO.sub.2], 34 mm Hg; [PaO.sub.2], 59 mm Hg; and [HCO.sub.3], 22.3 mEq/L while breathing room air. Abdominal roentgenograms were normal. Ultrasonography of the abdomen confirmed hepatosplenomegaly with periportal fibrosis compatible with chronic schistosomiasis, but there was no evidence of intrahepatic or subdiaphragmatic abscess formation.

On the second day after hospital admission his general condition deteriorated and he became tachypneic (respirations, 40/min) at rest. A repeated chest roentgenogram showed large right-sided and small left-sided pleural effusions (Fig 2). An echocardiogram revealed a moderate-sized pericardial effusion but there was no clinical or echocardiographic evidence of cardiac tamponade. By this time, he had also developed clinically detectable ascites. As the patient was very symptomatic 1 L of fluid was aspirated from his right pleural cavity. The peritoneal and pleural fluid were both exudates containing six to eight eosinophils per high-power field of 40 to 50 cells. Fluid examination and cultures for all microorganisms, including mycobacteria, were negative. Blood cultures were sterile on several occasions; stool microscopy and cultures showed no pathogens.

Mantoux test with 10 U of purified protein derivative was negative and a pleural biopsy specimen showed no granuloma. Antinuclear factor and anti-DNA autoantibodies were not detected.

He was treated with bed rest, acetaminophen (paracetamol), and oxygen inhalation. After three days of this supportive therapy his condition started to improve. All his symptoms, including abdominal pain and fever, cleared. The pleural effusions, ascites, and pericardial effusion resolved as confirmed by follow-up chest roentgenogram and echocardiogram. His arterial blood gas determinations also returned to normal (pH, 7.49; [PaO.sub.2], 100 mm Hg; [PaCO.sub.2], 35 mm Hg; and saturation, 99 percent); his white blood cell count at the time of hospital discharge was 7200/cu mm (eosinophils, 15 percent). A rectal biopsy specimen confirmed the presence of dead Schistosoma ova.

DISCUSSION

In our opinion, this patient's stormy illness was the result of administration of praziquantel for the following reasons: (1) the reaction started within four hours of administration of praziquantel; (2) marked eosinophilia which improved spontaneously; (3) other conditions were excluded that might have caused his illness, for example, disseminated pyogenic or tuberculous infection, metastatic disease, or collagen vascular disorders; (4) rapid and complete resolution occurred without the help of any specific medication; (5) all the manifestations of his illness with the exception of polyserositis were described previously as side effects of therapy with praziquantel or other antischistosomal drugs.

Praziquantel is recommended as a drug of choice in all forms of schistosomiasis and it is generally well tolerated with only minor side effects such as abdominal pain, headache, dizziness, epigastric discomfort, bloody diarrhea, or mild fever.[1-3]

Our patient developed acute respiratory failure that preceded the appearance of any significant pleural effusion in a manner denoting ventilation-perfusion mismatch. Interestingly, similar reactions were described following administration of other antischistosomal drugs but not praziquantel.

Acute respiratory failure following oxamniquine therapy was described by Davidson et al[4] in 1986 and was associated with a miliary pattern on the chest roentgenogram that resolved spontaneously. This was attributed to the shifting of worms and ova to the lung vasculature or allergy to schistosomal antigens released after worm death. Transient abnormalities of pulmonary function were documented in 11 Egyptian patients with schistosomiasis following the administration of antimony sodium dimercaptosuccinate (stibocaptate). These abnormalities manifested with decreased lung volumes, increased hypoxemia, and venous admixture,[5] but most of the patients remained asymptomatic. However, praziquantel itself was not previously reported to cause respiratory failure.

Similarly, to our knowledge, this is the first report of effusive polyserositis attributed to praziquantel or any other antischistosomal drug. The possible explanations for the illness seen in our patient are hypersensitivity reaction to the drug or the result of the sudden release of schistosomal antigens following worm death. In our opinion, the latter is the most likely explanation, and other workers have expressed similar opinions in previous reports.[6,7] This is supported by the fact that closely related pulmonary reactions have been described with other antischistosomal drugs.[6,7] The "worm shift" theory had not been substantiated as no worms or ova were seen in our pleural biopsy specimen or in the lung biopsy specimen from the patient of Davidson et al[4] that showed a miliary pattern with respiratory failure.

We conclude that all patients, particularly those with a heavy worm load, should be warned to report immediately any untoward symptoms following therapy with praziquantel, and that acute respiratory failure and exudative effusive polyserositis should be recognized as potential side effects of such therapy.

REFERENCES

[1] Smith DH. Side effects of drugs. In: Dukes MNG, ed. Meyler's side effects of drugs. Amsterdam: Elsevier Science Publishers; 1985; 9:275-6

[2] Katz N, Rocha RS, Chaves A. Bull WHO 1979; 57:781-85

[3] Nash TE. Schistosome infections in humans. Ann Intern Med 1982; 97:740-54

[4] Davidson BL, El-Kassimi FA, Uz-Zaman A, Pillai DK. Chest 1986; 89:455-57

[5] Farid JD, Fuleiham, Habaybeh A, Abdullah A, Mousa AH, Saif M, et al. Am Rev Respir Dis 1969; 100:651-61

[6] Coutinho A, Domingues L, Neves J, da Silva LC. Praziquantel in the treatment of the hepatosplenic form of schistosomiasis. Summary of Proceedings, Biltricide Symposium on African Schistosomiasis. Nairobi, Bayer Pharmaceuticals, 1980:23

[7] Higashi GI, Farid Z. Oxamniquine fever drug-induced or immune-complex reaction. Br Med J 1979; 2:830

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