Seroprevalence of Toxoplasma  gondii Infection among HIVInfected Patients in Tokyo, Japan

Hiromizu Takahashi; Akiko Tsubouchi; Kenji Murai; Masashi  Yamanouchi; Mika Tanei; Rino Sakamoto; Yuki Uehara; Chia-Kwung Fan; Toshio Naito

Seroprevalence of Toxoplasma gondii Infection among HIVInfected Patients in Tokyo, Japan

Research Article | Open Access

Article DOI : https://doi.org/10.47739/2374-0094/1007

Hiromizu Takahashi¹ Akiko Tsubouchi² Kenji Murai¹ Masashi Yamanouchi¹ Mika Tanei¹ Rino Sakamoto¹ Yuki Uehara^1,3 Chia-Kwung Fan^4,5 Toshio Naito^1,3*

^1. Departmentof General Medicine, Juntendo University School of Medicine, Japan
^2. Research Support Center, Juntendo University Graduate School of Medicine, Japan
^3. Department of Infection Control Science, Juntendo University School of Medicine, Japan
^4. Department of Parasitology, Taipei Medical University College of Medicine, Taiwan
^5. Center for International Tropical Medicine, Taipei Medical University College of Medicine, Taipei, Taiwan

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Corresponding Authors

Toshio Naito, Department of General Medicine, Juntendo University School of Medicine Hongo 2-1-1, Bunkyo-ku, Tokyo 113-8421, Japan, Tel: +81-3-3813-3111; Fax: +81-3-5802-1190

Abstract

The seroprevalence of IgG antibodies against Toxoplasma gondii was assessed in 169 adult non-hemophiliac Japanese patients infected with human immunodeficiency virus. The seroprevalence of T. gondii infection was only 14.2%, which was similar to findings from the USA and lower than that reported for most other countries. The positive ratio of T. gondii IgG antibodies was significantly higher in patients aged ≥ 40 years (21.0% vs. 7.9%, p=0.01) with < 200 CD4+ cells /µL (20.5% vs. 9.4%, p=0.04). Group analysis showed that seropositivity did not differ according to sexuality. The ratios of positivity for hepatitis B surface antigen, hepatitis B surface antibody, hepatitis C antibody, serological findings for syphilis and the findings of the Treponema pallidum hemaggulation test were not associated the seroprevalence of IgG antibodies against T. gondii.

These results indicate that patients in Japan with lesions of the central nervous system and antibodies against T. gondii are highly likely to have toxoplasmosis. Infection with T. gondii should be carefully assessed in elderly Japanese patients who are infected with human immunodeficiency virus.

Citation

Takahashi H, Tsubouchi A, Murai K, Yamanouchi M, Tanei M, et al. (2014) Seroprevalence of Toxoplasma gondii Infection among HIV- Infected Patients in Tokyo, Japan. Clin Res HIV/AIDS 1(2): 1007.

Keywords

•   Acquired immune deficiency syndrome
•   Toxoplasmosis
•   Hepatitis B virus
•   Hepatitis C virus
•   Syphilis
•   Opportunistic infection

INTRODUCTION

Toxoplasma encephalitis (TE) represents an important opportunistic infection in patients infected with human immunodeficiency virus (HIV). Measuring IgG antibodies to T. gondii is crucial, because the risk of developing cerebral toxoplasmosis is high among HIV-seropositve individuals. Therefore, HIV-infected patients with Toxoplasma antibodies must start oral pharmacotherapy as toxoplasmosis prophylaxis. Nissapatorn et al. reported that almost half (44.4%) of patients who are infected with HIV or have acquired immunodeficiency syndrome (AIDS) in Malaysia are seropositive for Toxoplasma [1], and seropositive ratios are also high in other countries except the USA [2-6]. We previously reported a very low seroprevalence (5.4%) in non-symptomatic Japanese patients [7].

However, differences such as age, sexuality or number of CD4 positive cells among subgroups of patients have not been discussed. Also, relationships between these seroprevalence of Toxoplasma antibodies and seropositivity to HBV, HCV and syphilis remains unclear. Seroprevalence might differ with race, region and era and thus, these issues should also be investigated in Japan. The results of such an investigation would help to determine clinical diagnoses. In present study, we investigated the prevalence of antibodies against Toxoplasma among Japanese patients infected with HIV.

PATIENTS AND METHODS

The Department of General Medicine at Juntendo University provided care to 257 patients with documented HIV infection from 1990 to 2012 in central Tokyo. Test for IgG antibodies to T. gondii has been a routine part of the initial assessment of all HIVinfected patients since 1990. Patients who missed the test were excluded from the statistical analysis. The study group comprised only Japanese patients living in Japan who were infected with non-hemophiliac HIV.

Serological test for IgG anti-Toxoplasma antibodies was employed by using enzyme-linked immunosorbent assays (ELISA) at a commercial testing laboratory (SRL, Tokyo, Japan). Chemiluminescence enzyme immunoassays (CLEIA) were used to test for HIV antibody, hepatitis B surface antigen (HBs Ag), hepatitis B surface antibody (HBs Ab) and hepatitis C virus antibody (HCV Ab), and Treponema pallidum was assessed by hemagglutination (TPHA) assays.

Statistical comparisions were done by using the chi-square test. Values of p<0.05 were considered statistically significant.

RESULTS

Toxoplasma IgG antibody results were available from 169 (male, n = 163; female; n = 6; mean age, 33 y; range, 21 - 75 y) of the 257 patients. Table 1 shows details of the patients. Most of them had acquired HIV through a sexual route, 49.7% being men who have sex with men (MSM) and 19.5% being heterosexual. Only one patient had a history of intravenous drug use. Of the 169 patients, 43.2% had a baseline CD4+ lymphocyte count < 200/μL (mean ± SD, 274.9 ± 248/μL).

Twenty four (14.2%) of the 169 patients had serological evidence of T. gondii infection. Figure 1 shows that the prevalence was increased by advancing age, especially in those > 40 y. The probability of being seropositive to T. gondii was significantly higher for patients whose age was greater than 40 years (21.0% vs. 7.9%: p=0.01; Table 2). The numbers of CD4+ cells were statistically significant; 20.5% and 9.4% of patients had < 200 and ≥ 200 CD4+ cells/µL, respectively (p=0.04). Sexuality did not significantly differ among the groups.

Seroprevalence did not significantly differ among positive ratios of HBs Ag, HBs Ab, HCV Ab, serological outcomes of syphilis (STS) and the TPHA test (Table 3). However, the seroprevalence of T. gondii seemed higher in patients with positive STS (p=0.09).

DISCUSSION

With the emergence of individuals infected with HIV in Japan, T. gondii has become an important opportunistic pathogen, especially in the central nervous system.T. gondii can reactivate and cause cerebral toxoplasmosis, usually when the CD4+ lymphocyte count falls less than 100/µL [8-10]. The incidence of TE in patients infected with HIV depends mainly on the existence of latent anti-Toxoplasma antibodies in the population [11,12].

Therefore, to understand the seroprevalence of these antibodies in HIV-infected individuals is very important.

The local prevalence of Toxoplasma antibodies in HIV-infected patients might depend on that in healthy adults. Yamaoka and Konishi showed that the seroprevalence of IgG anti-Toxoplasma antibodies among 2,564 healthy Japanese was 9.3% in 1993 [13]. Our previous study found a similar seroprevalence (7.1%) as compared to that reported [7]. T. gondii typically infects humans who have ingested tissue cysts in undercooked meat from an infected animal, or by ingesting infectious oocysts from the environment, usually from soil contaminated with feline feces [14-16]. Lower prevalence might be related to a lower risk in exposure to T. gondii infection, reflecting the dietary habits and better sanitary conditions in Japan.

These results might also explain the lower incidence of TE in Japan. One study found that only 1.07% of Japanese patients infected with HIV had toxoplasmosis [17]. TE is often difficult to distinguish from malignant lymphoma or progressive multifocal leukoencephalopathy in patients infected with HIV. However, the present results suggest that patients in Japan with lesions of the central nervous system and antibodies to T. gondii have a high probability of having TE.

It has been indicated that up to one third of the global population is infected with T. gondii [18]. As most toxoplasma infections among humans arise due to consuming undercooked or raw meat containing tissue cysts or by exposure to oocysts through ingesting food and water contaminated with cat feces. However, the incidence of toxoplasmosis among patients with AIDS with and without cats does not significantly differ [19]. One study from the USA indicates that persons who have HIV with ages ≥ 50 years were more likely to have antibodies to T. gondii [20]. Our data confirmed a similar tendency in a Japanese population.

Our present study found the seroprevalence of anti-Toxoplasma IgG antibody was higher among patients with low CD4+ cell counts (Table 2). Mice deficient in CD4 have impaired resistance to tachyzoites and HIV infection increases susceptibility to T. gondii infection [21]. The present findings are also compatible with those of a Nigerian study [22].

The relationship between T. gondii infection and sexual contact that can result in HBV, HCV or syphilis is unclear. We did not find a statistical relationship between toxoplasmosis and the seroprevalence of HBV, HCV or syphilis.

This retrospective study did not have information regarding basic risk factors such as cat ownership, dietary habits, soil exposure and other important risk factors for disease acquisition. Moreover, the number of serum samples was insufficient due to limited resources, and thus, the statistical power is lower. The present findings should be interpreted in light of these limitations.\

Table 1: HIV-infected patients who were infected by Toxoplasma gondiiinfection.

Factor	n
Median age (range; y)	169	33 (21 - 75)
Mean CD4 (± SD; cells/µL)	169	274.9 ± 248
Mean HIV RNA (range; copies/mL)	124	3.4x $10^{4}$ (0 - 3.4x $10^{5}$ )

Table 2: Seroprevalence of anti-Toxoplasma gondii antibody according to age, sexuality and CD4+ cells.

Factor	n	Toxoplasma IgG % (n)		P	Odds ratio
Age (y)	169	< 40 7.9 (7)	≥ 40 21.0 (17)	0.01*	3.16
Sexuality	122	MSM 10.1 (9)	Hetero 18.1 (6)	0.23	0.51
CD4+ cells (/µL)	169	< 200 20.5 (15)	≥ 200 9.4 (9)	0.04*	0.40

Table 3: Association between Toxoplasma gondii and other infections.

Factor	n	Toxoplasma IgG % (n)		P	Odds ratio
		Positive	Negative
HBs Ag	147	5.3 (1)	7.0 (9)	0.84	0.73
HBs Ab	69	142.9 (3)	48.4 (30)	0.90	0.80
HCV Ab	147	5.3 (1)	3.1(4)	0.84	1.72
STS	142	43.8 (7)	123.8 (30)	0.09	2.49
TPHA	131	50.0 (7)	144.4 (52)	0.69	1.25

HBs Ab, hepatitis B surface antibody; HBs Ag, hepatitis B surface antigen;
HCV Ab, hepatitis C virus antibody; STS, serological test for syphilis;
TPHA, Treponema pallidum hemagglutination.

CONCLUSIONS

The seroprevalence of anti-Toxoplasma IgG antibody among Japanese persons infected with HIV was determined. Although the rate was relatively lower that those elsewhere, our findings indicated that 14.2% of HIV positive patients in Japan are at risk of developing life-threatening, secondary reactivation of cerebral toxoplasmosis in association with AIDS. The seroprevalence of T. gondii significantly varies among subpopulations of patients with HIV, especially age groups. Therefore, individual subgroup analyses are required. Youth should also be educated to minimize risk and prevent new Toxoplasma infections arising.

FINANCIAL SUPPORT

This study was supported by a Grant-in-Aid (S1201013) from the MEXT (Ministry of Education, Culture, Sports, Science and Technology)-Supported Program for Strategic Research Foundations at Private Universities, 2012-2017.