Recently, it has been turned out that our internal defense system is composed of two distinct components; innate/natural immune system and acquired/adaptive immune system. The former innate immunity is principally located at the surface area such as skin and mucosal compartment, while the latter acquired immunity is observed mainly in the circulating blood and lymphoid organs. The critical difference between those two systems exists in the receptors as well as their ligands. Rearranged gene-derived receptors like immunoglobulin (lg) and MHC molecule-restricted ctp-type of T-cell receptors (TCR) with high specificities and memories are used to recognize peptide antigens in the acquired immunity, whereas non-rearranged invaliant receptors such as toll-like receptors (TLR), γσTCR and CD1 molecule-restricted αβ TCR are employed to detect lipid/glycolipid or nucleic acid-related antigens in the innate immunity. Based on such new findings, the actual roles of immunity are discussed.

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There are two kinds of infectious diseases in the world; diseases being paid attention and neglected diseases. The former diseases include HIV/AIDS, tuberculosis and malaria, the latter group include many parasitic, fungal, bacterial and some of viral infections. “Neglected Infectious Diseases”, which have been renamed as Endemic Tropical Diseases by WHO, are endemic in the developing world are not newly appeared diseases, but diseases affecting humans in these decades. In fact, DALYs for several diseases in the category are big enough; more than 300 millions for soil-transmitted helminthiasis, 5 millions for lymphatic filariasis, 4-5 millions for schistosomiasis and so forth. However, those diseases were not recognized as serious health problems because of socio-economical and/or scientific reasons. Furthermore, those diseases are no fatal in the acute phases; therefore, no big attention is raised by policy makers in the world. From the view point of basic medical sciences, however, there is no enough reason for neglecting the issues of those diseases: no improved diagnostics and therapeutics have been developed in spite of the urgent necessities in endemic areas. Considering those situations, WHO has started to take action for solving the problems since beginning of the 21^st century.
Recently, many of developed countries are recognizing that the imbalanced input of human and financial resources only for 3 major infectious diseases, HIV/AIDS, tuberculosis and malaria, and then, various international schemes for supporting research on Neglected diseases. DNDi, Drugs for Neglected Diseases initiative, is one of the examples and it's scope is only focusing on drug development for Neglected diseases. African trypanosomiasis is one of Neglected diseases and causing serious health problem both for humans and domestic animals in Africa. No safe and effective medicine has been available but a drug with serious side effects is only the drug of choice even nowadays. Under the grant support from DNDi, a Japanese group is developing a new drug, ascofuranone, for African trypanosomiasis without any detectable side effects. Developing new prophylactic drugs for schistosomiasis and new diagnostic tools for lymphatic filariasis are underway under the support of grant for Neglected or Re-emerging infectious diseases in Japan.
Considering that issues of “Neglected Infectious Diseases” are urgent to be solved and also are challenging for modern medicine and medical sciences, researchers in the developed countries including Japan should make efforts to promote more active researches in this field.

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The normal host defense mechanisms against infection include (1) normal skin and mucous membranes, (2) phagocytic system, (3) humoral immunity, and (4) cellular immunity. The compromised host is an individual who has one or more defects in these defense mechanisms. Defects in each aspect of host defense increase the risk of infection caused by specific groups of microorganisms. Knowledge of these defects and potential infections in the compromised host will guide the initial (empiric) selection of antibiotics, the dosage and duration of antibiotic therapy, and decisions regarding antibiotic prophylaxis and the use of immunomodulators that are likely to augment host defenses.

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A large-scale questionnaire surveillance was conducted regarding the onset of invasive infections with 3-hemolytic group C (GCS) and group G (GGS) streptococci from clinical specimens that are normally aseptic and the backgrounds of these cases. The surveillance period of the questionnaire was 8 months from January to August 2005. Completed questionnaires were received from the clinical laboratories of 193 medical institutions. One hundred two clinical laboratories (52.8%) had isolated these β-hemolytic streptococci. Of all the isolates, GCS and GGS accounted for 25 and 216 cases, respectively, or a ratio of almost 1:10. Isolates from blood cultures accounted for half the number of all isolates, followed by isolates from atretic pus or joint fluid. The isolates gradually became more prevalent from patients in their 40s, and peaked in patients in their 70s. The most prevalent disorder, described in 184 cases, was suppurative disease followed by (in descending order), bacteremia, sepsis, arthritis purulenta and cellulitis. A small number of patients had developed with streptococcal toxic shock syndrome, empyema or meningitis. Most of the patients had an underlying disease, such as diabetes mellitus, malignancy or cerebrovascular disease (in descending order). Weconclude from the above findings that background factors in patients as well as identification of the pathogen should be made public when GCS or GGS is isolated from normally aseptic clinical specimens.

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A total of 593 β-hemolytic streptococci belonging to Lancefield group A (GAS), group C (GCS) or group G (GGS) according to agglutination tests were collected from 11 medical institutions between September 2003 and October 2005. In total, 128 strains were identified as Streptococcus dysgalactiae subsp. equisimilis (S. equisimilis ) using physiological tests. Of these strains, 5 strains were agglutinated to Lancefield group A, 17 strains to group C, and 106 strains to group G. Most of these strains were largely isolated from clinical specimens collected from young patients with respiratory infections and middle-aged patients (in their 40s); most of the strains were isolated from blood, atretic pus, or joint fluid. Genetic analysis of the emm gene encoding the M protein revealed that these strains could be classified into 27 types. Also, many emm types were found in strains isolated from normally aseptic clinical specimens. In addition, all strains tested had slo, sagA, and skcg genes, which contributed to their virulence. The susceptibility of the strains to oral penicillin and cephalosporin antibiotics was excellent, with MICs ranging from 0.016 to 0.031mg/mL. In contrast, strains carrying the macrolide resistant elements of the ermA, ermB, and mefA genes and strains showing a high resistance to levofloxacin were also confirmed in this study. These results suggest that 13-hemolytic streptococci, except for S. pyogenes and S. agalactiae, should be reconsidered as a causative pathogen in streptococcal infections.

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Viral gastroenteritis caused by Norovirus (NV) mainly appears during the winter season. In fact, outbreaks and patients with NV gastroenteritis are the major cause of community disease in the winter. Strategies to avoid gastroenteritis caused by NV are thus needed. No effective method for evaluating virus inactivation and removal exists for of NV, which cannot be cultured using cell-lines. Trials using Feline Calici Virus (FCV; a member of the calicivirus family) as a NV surrogate have been conducted by culturing FCV in CRFK cells.
By washing one's hands, about 99% of the viruses can be removed, compared with simply rinsing one's hands in running water. Washing one's hands with alcohol, chlorhexidine, quaternary ammonium, or 3 other kinds of hand soaps (containing povidone-iodine, triclosan, and isopropylmethyl phenol, respectively), was also effective for removing viruses. These results suggest that washing one's hands may be an effective method of preventing viral gastroenteritis.

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We studied cytomegalovirus (CMV) pp65 positive cells (pp65⁺ cells) in 275 peripheral blood (PB) samples obtained from 157 patients with clinical symptoms such as fever and diarrhea and in 8 biopsy specimens diagnosed as CMV disease immunohistochemically and immunocytologically using the anti-CMV pp65 antibody. We compared our results to those of the clinical inspection center using 76 samples. pp65⁺ cells was detected in 164 of 275 samples by our method, and number of pp65⁺ cells in 83 samples was less than 10. The comparison showed a strong correlation between the two results (r=0.844). Fewer than 10 pp65⁺ cells were detected in 21 samples by our method, but no pp 65⁺ cell was found in 18 of the 21 samples (85.7%) by the clinical inspection center. We concluded that we detected a small number of pp65⁺ cell because we examined a large number of cells. Many pp65⁺ cell that did not show an owl's eye configuration were observed in biopsy specimens. Data suggested that cytology and immunostaining using anti-CMV pp65 antibody are useful in the detection of pp65⁺ cells in PB and biopsy specimens.

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We studied 107 isolates of Escherichia coli O153 from sporadic diarrhea cases in Fukui, Toyama, Aichi, and Saga prefectures from 1991 to 2005 for antimicrobial susceptibility and mechanisms of fluoroquinolone resistance, based on standard disk diffusion. Of 12 drugs tested, ampicillin displayed resistance to 72.9% of isolates, streptomycin to 48.6%, tetracycline to 46.7%, sulfisoxazole to 46.7%, trimethoprim/sulfamethoxazole to 29.9%, nalidixic acid (NA) to 29.9%, and ciprofloxacin (CPFX) to 24.3%. Ten of 32 isolates resistant to 3-6 drugs and 16 of 18 isolates resistant to 7-10 drugs were resistant both to NA and CPFX.
Mutations of amino acid in quinolone resistance-determining regions of gyrA and parC genes were detected in 24 isolates resistant both to NA and CPFX, and in 1 isolate resistant to NA. The former possessed a combination of double substitution (S83L and D87L) in GyrA and a single substitution (S80I) in ParC. Some 12 of 24 isolates possessed another single substitution (E84V or E84G or A108T) in ParC. The 25 isolates were classified into 4 types as follows. 1 isolate as type 1 GyrA (S83L) and ParC (S80I); 12 isolates as type 2: GyrA (S83L and D87N) and ParC (580I); 8 isolates as type 3: GyrA (S83L and D87N) and ParC (S80I and E84G/S80R and E84V); and 4 isolate as type 4: GyrA (S83L and D87N) and ParC (S80I and A108T). In the relationship between amino acid mutations and minimal inhibitory concentrations (MIC) of fluoroquinolone, MICs of CPFX, ofloxacin, and norfloxacin showed 1μg/mL 2μg/mL and 8μg/mL in type 1; 8-32μg/mL 8-32μg/mL and16-256μg/mL in type 2;and 32-256μg/mL'32-128μg/mL and128->512μg/mL in types 3 and 4. These results suggest that most of multiple-antimicrobial-resitant E. coli O153 isolates from sporadic diarrhea cases were resistant to fluoroquinolones and possessed mutations at gyrA and parCgenes associated with fluoroquinolone resistance.

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Shigella is an etiological agent of communicable and food-borne disease worldwide, so it is important to develop typing for Shigella in epidemiological studies. We compared amplified fragment length polymorphism (AFLP), molecular epidemiological typing, to pulsed-field gel electrophoresis (PFGE) and colicin typing in typeability, reproducibility, discriminatory power, ease of interpretation, and ease of use for 51 Shigella isolates to determine AFLP applicability to Shigella. AFLP showed less reproducibility and ease of interpretation although it was superior to PFGE and colicin typing in typeability and discriminatory power. Specifying the reproducibility of these typing methods, the intrastrain similarity of AFLP was 81.9%-90.5% in each of three strains tested in triplicate trials, while PFGE showed higher similarity, ranging from 92.3%-100%. AFLP created a phylogenetic tree and classified four Shigella species taxonomically, despite its lower reproducibility. These results suggest that AFLP is inferior to PFGE as molecular typing for Shigella epidemiologically in outbreaks or sporadic cases, although AFLP can create a phylogenetic tree for taxonomical purposes.

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The sensitivity of rapid diagnostic kits to influenza B is lower than to influenza A. The cause-poor performance of the kit or the scarcity of viruses in type B specimens-has yet to be clarified. Using real-time PCR, we measured the amount of influenza viruses with nasopharyngeal aspirate fluid previously identified by virus isolation culture and passing the rapid diagnosis test by four types of kits, including the ESPLINE Influenza A & B-N (Fujirebio Corp., Japan).
We classified the results of virus isolation and rapid diagnosis tests into three groups and examined them: group 1 (12 specimens, influenza B, all negative in tests using four types of kits); group 2 (57 specimens, influenza B, all positive in tests); and group 3 (36 specimens, AH3, all positive in tests). The average amount of viruses in group 1 (6.60±0.81 log₁₀copies/mL) was significantly lower (p<0.0001) than that in group 2 (8.51±0.57 log₁₀copies/mL) or group 3 (8.72±0.63 log₁₀copies/mL). No significant difference was seen in the amount of viruses between groups 2 and 3. We concluded that the cause of low sensitivity in rapid diagnostic kits to influenza B are attributable to the scarcity of viruses in the specimen.

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A 63-year-old woman suffering from dyspnea since 1 week earlier underwent a combination therapy of oral corticosteroid and ciclosporin for rheumatic arthritis. Chest radiography showed plural effusion with gas formation in the right thorax. Empyema was diagnosed based on the specimen from pleural effusion. After a chest tube was emplaced to remove and wash out pus, antibiotics were started and empyema improved immediately. Streptococcus dysgalactiae subsp. equisimilis, but not aerobic bacilli, was detected from the pus by repeated culture. Insofar as we know this is the first case of empyema with gas formation associated with Streptococcus dysgalactiae subsp. equisimilis.

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