Current status of food-borne parasitic zoonoses in Japan.

Epidemiological data on food-borne parasitic zoonoses in Japan is obscure because of the lack of legislated registration system for the incidence of such diseases. Attempts were made to draw rough estimates of the current status of food-borne parasitic diseases in Japan by gathering the annual incidence of each disease by literal survey and personal communications. In addition, parasitic diseases referred to and diagnosed in the Department of Parasitology, Miyazaki Medical College during 1999 were analyzed for the causative agents and the route of infection.

Clinical features and parasite-specific IgM/IgG antibodies of paragonimiasis patients recently found in Japan.

Clinical features of a total of 30 paragonimiasis westermani patients referred to and diagnosed in our laboratory in 1999 were analyzed retrospectively. Most patients were middle-aged (average: 48 years, range: 13-72 years) with the male/female ratio of 19/11. Over 70% of the patients had respiratory symptom and over 80% had peripheral blood eosinophilia and high serum IgE level. All but two cases had radiologic abnormalities on the chest X-ray. Only in 3 cases were Paragonimus eggs detected in the sputum smear. We classified the patients into two groups depending on the chest X-ray findings: patients having pleurisy alone and those having nodular/cavitating lesions in the lung parenchyma. We measured parasite specific IgM/IgG antibodies in all patients sera by microplate ELISA. The mean parasite-specific IgM/IgG antibody ratio was significantly higher in the parenchymatous lesion group than in the pleurisy group. While IgM antibody titer had a strong positive correlation with the degree of eosinophilia in peripheral blood, IgG antibody titer had an inverse correlation. Although the degree of eosinophilia in peripheral blood was higher in the pleurisy group than in the parenchymatous lesion group, total IgE level in serum was comparable between the two groups. The present results indicate that pleurisy with eosinophilia and dominant IgM antibody are the characteristic features of the early stage of paragonimiasis, whereas parenchymatous lesions in lungs with low grade eosinophilia and dominant IgG antibody are of the late stage. These results suggest that detection of IgM antibody should always be considered for the immunodiagnosis for paragonimiasis-suspected patients with pleurisy.

Re-emergence of paragonimiasis in Kyushu, Japan.

During 1986-1998 we found 104 paragonimiasis cases, which were referred to our laboratory for immunodiagnosis or identification of parasite eggs in sputum or bronchoscopic aspirate smears, or in histopathological sections. A majority of patients were middle-aged males. Except for 2 cases of chronic occult infection in an unexpected site, 102 cases were assumed as having active infection. Abnormal findings in chest radiograms were noted over 80% of the patients, though about 20% of them were asymptomatic. Parasite egg detection rates in sputum or bronchoscopic aspirate smears were about 50%. About 80% of patients have eosinophilia and/or elevated serum IgE level. Paragonimiasis is a re-emerging public health issue in Kyushu, Japan.

Granulocyte-macrophage colony-stimulating factor production by T lymphocytes in Plasmodium berghei-infected mice.

The production of granulocyte-macrophage colony-stimulating factor (GM-CSF) by lymphocytes was examined in murine malaria. When spleen cells or lymph node cells from P. berghei-infected mice were cultured in vitro with malaria antigen, the GM-CSF production correlated with the incubation time up to 72 hours. When lymphocytes obtained at various days after infection were cultured with the antigen, GM-CSF became detectable as early as 2 days after infection, reached a peak at day 9 and then rapidly decreased. Production of GM-CSF was antigen-specific, and related to the dose of antigen. Treatment of lymphocytes with anti-Thy-1.2 antibody and complement resulted in almost complete loss of GM-CSF-producing activity, while treatment with either anti-CD4 or anti-CD8 antibody and complement resulted in partial loss of GM-CSF-producing activity, indicating that both CD4+ and CD8+ T cells are involved in GM-CSF production in malaria. GM-CSF exhibits glycoprotein nature, and has an apparent molecular weight of 36,000. The molecular properties of this T-cell derived GM-CSF were compared with those of known lymphokine GM-CSF.

An outbreak of ascariasis with marked eosinophilia in the southern part of Kyushu District, Japan, caused by infection with swine ascaris.

Ascariasis has been a representative soil-transmitted intestinal parasitic disease in warm climates. In Japan, this disease was a major and serious public health problem only a few decades ago. However, the incidence of the disease nowadays is reportedly less than 0.01%. Recently in 1994 through 1995, we experienced a total of 14 cases who were suspected as having ascariasis. They were characterized by peripheral blood eosinophilia (30-70%), high serum titers against Ascaris antigen, and most notably, they were absolutely negative for Ascaris eggs in repeated fecal examinations. Specific antibody titers against Ascaris antigen correlated well with the degree of eosinophilia. All patients were living in narrow areas of Kyushu, Japan, where a lot of porcine farms were located. Most of the patients were asymptomatic and pointed out to have eosinophilia during follow-up studies of chronic diseases or in regular check-up. Only one patient had a clear sign of Löffler's syndrome and another had subcutaneous eosinophilic granuloma. However, laboratory examinations revealed moderate liver dysfunction in 7 patients and pulmonary infiltrations in 5 patients. Based on circumstantial and serological evidence, these patients were diagnosed as having been infected with Ascaris lumbricoides suum, a swine Ascaris.

Current status of gnathostomiasis dorolesi in Miyazaki Prefecture, Japan.

Gnathostomiasis is an important food-borne parasitic zoonosis caused mainly by ingesting uncooked or undercooked flesh of freshwater fishes. Although four distinct species of the genus Gnathostoma were identified as the causative agents for human gnathostomiasis, human infections with G. doloresi have been found only in Japan, concentrated in Miyazaki Prefecture. So far we have found 25 cases in Miyazaki Prefecture. Although most of these patients were of cutaneous gnathostomiasis, two patients presented to the hospital with unusual clinical manifestations; one case was a pulmonary gnathostomiasis diagnosed by immunoserological methods, and the other was an ileus caused by migration of the late 3rd stage larva in the colonic tissue, which was found by post-operative histopathological examination. Although cutaneous lesions such as creeping eruption or mobile erythema are the common clinical features of gnathostomiasis, caution should be paid to the presence of such unusual cases.

Depressed specific and nonspecific immune responses in secondary Brugia pahangi infection in jirds.

The immune responsiveness to specific antigens or mitogens was examined in jirds after primary and secondary infections with Brugia pahangi. When spleen cells were obtained from secondarily infected jirds, their proliferative responses to mitogens such as Con A or LPS, or to specific antigens prepared from infective larvae or adult worms were significantly lower than those of spleen cells obtained from primarily infected jirds. The proliferative responses of the peripheral blood mononuclear cells obtained from animals undergoing primary and secondary infections also showed a similar tendency. The depressed proliferative responses of the secondary infected spleen cells to Con A or LPS was partially restored by removing adherent/phagocytic cells from the original cell populations. After deletion of the adherent cells, however, antigen-specific proliferative responses were not altered and remained at low level. These results suggest that at least two different mechanisms of depression, namely adherent cell-mediated antigen-nonspecific suppression and unresponsiveness of lymphocytes to filarial antigens, are induced in jirds in the secondary infection.

Appearance of adherent cells suppressive to erythropoiesis during an early stage of Plasmodium berghei infection in mice.

We examined the effect of adherent cells from bone marrow or spleen of mice infected with Plasmodium berghei on dyserythropoiesis. Significant reduction in number of erythroid progenitors (erythroid colony-forming units: CFU-E and erythroid burst-forming units: BFU-E) was observed in bone marrow as early as 1 day after P. berghei infection. When adherent cells were removed from bone marrow or spleen cells of infected mice, the number of CFU-E and BFU-E was clearly increased. Furthermore, addition of adherent cells from infected mice to nonadherent cells from normal mice inhibited erythroid colony formation significantly in a dose-dependent manner. These results suggest that the adherent cells obtained from bone marrow or spleen of mice in the early stage of P. berghei-infection have a suppressive effect on erythropoiesis.

Recent trends of paragonimiasis westermani in Miyazaki Prefecture, Japan.

Miyazaki Prefecture has long been known as one of the endemic areas of paragonimiasis westermani. The prevalence of this disease peaked around 1956 and then drastically decreased. A few sporadic cases are still occasionally found in Miyazaki Prefecture; however, the number of new cases has gradually increased during the last 5 years. One important point to be noted is the change of clinical manifestations in the patients. A classically known form of paragonimiasis westermani is characterized by persisting cough, bloody sputum, and nodular or ring shadows in the lung field by chest x-ray. However, the patients recently found in Miyazaki Prefecture rarely showed such typical symptoms. Only four of 13 cases were found to have pulmonary infiltration and nine cases showed massive pleural effusion without pulmonary infiltration. Such atypical cases may be caused by low intensity of infection or, alternatively, be due to the earlier diagnosis.

Historical review and current status of gnathostomiasis in Asia.

The genus Gnathostoma contains at least twelve distinctive species. Among these, 6 species, namely G. spinigerum, G. hispidum, G. doloresi, G. vietnamicum, G. malaysiae and G. nipponicum, are found in wild animals in Asia. Related to human gnathostomiasis, G. spinigerum has long been believed as the only causative species. Until the early 1980s, all gnathostomiasis cases found in major endemic areas in Asia, such as Thailand, China and Japan, were caused by infection with G. spinigerum. In the early 1980s in Japan, new gnathostomiasis cases appeared in urban areas and these cases were shown to be caused by G. hispidum, of which larvae were found in loaches imported from Taiwan, Korea, or mainland China. Recently infections with G. nipponicum caused by eating locally obtained loaches raw, were found in 2 humans in Mie Prefecture, and 14 cases of infection with G. doloresi, probably caused by eating raw slices of freshwater fishes, were found in Miyazaki Prefecture. So far four Gnathostoma species are responsible for zoonotic infections in humans. Since G. hispidum and G. doloresi, like G. spinigerum, are widely distributed in Asia, care should be taken with the identification of species causing gnathostomiasis.