Protection of Immuno-Compromised Mice from Lethal Infection of Klebsiella pneumonia by rAAV2-BPI23-Fcγ1 Gene Transfer

In previous research, chimerical BPI23-Fcy1 gene which consisted of human bactericidal/permeability increasing protein （BPI） gene of encoding the functional N terminus （amino acid residues 1 to 199） of human BPI and Fcy1 gene of encoding the Fc segment of human immunoglobulin G1 was successfully reconstructed within a recombinant adeno-associated virus serotype 2 （rAAV2） vector as rAAV2-BPI23-Fcy1. Here, to evaluate the potentiality of applying gene therapy to gram negative bacterial （GNB） infection in high-risk patients, we investigated protection of immuno-compromised mice and immunocompetent mice from challenge with minimal lethal dose （MLD） Klebsiella pneumonia infection after rAAV2-BPI23-Fcy1 gene transferred. The results showed that the survival rate of rAAV2-BPI23-Fcy1 transferred immunocompetent mice as well as immuno-compromised mice （40.0% and 44.4%, respectively） were significant higher than that of corresponding control mice （6.7% and 4.4%, respectively）; the bacteria counting, level of endotoxin and proinflammatory cytokines in the rAAV2-BP123-Fcy1 transferred immuno-compromised mice were markedly lower than that of rAAV2-EGFP and rAAV2-Null transferred immuno- compromised mice. Our data suggest that rAAV2-BPI23-Fcy1 gene transferring offered immuno-compromised mice with resistance against GNB infection, so it is quite potential in preventing GNB infection of clinical high-risk patients. Cellular ＆ Molecular Immunology. 2008;5（6）：439-445.

A rare cause of drug-induced hepatitis in an immunocompromised patient and the role of glutathione

The Food and Drug Administration (FDA) has issued a warning on numerous herbal drugs, including many popular products at General Nutrition Centers (GNC), regarding unstudied hepatotoxicity. There have been recent reports of GNC products such as hydroxycut and herbalife, causing drug-induced hepatitis. Herbal medications are over-the-counter products and are not investigated thoroughly by the FDA. Given that the mostcommon outpatient laboratory abnormality is elevated liver transaminases, a sign of hepatocellular toxicity; it is not surprising that some of these products end up causing hepatic dysfunction, especially when taken in large volume. There are numerous herbal supplements that are hepatotoxic, however, these medications have a much more significant effect in human immunodeficiency virus (HIV)/ acquired immune deficiency syndrome patients, which is secondary to depleted glutathione. We present a rare case of drug induced hepatitis secondary to herbal medications used to treat HIV and elucidate the role of glutathione depletion in immunocompromised patients.

Isolation and Antibiotic-Resistant Pattern of Opportunistic Infectious Microbes from the Infected Sites of Oral Cancer Patients Compared to That of Healthy People Oral Microbiota

Introduction: Oral cancer is the third most prominent type of cancer in Bangladesh. During or after oral cancer treatment, immune-compromised cancer patients may be susceptible to an infection by multi-drug-resistant opportunistic microbes. This study aims to identify the prevalent microorganisms from the infected site of oral cancer patients and observe their antibiotic susceptibility pattern. Materials and Methods: Clinical samples were collected from the infected sites of oral cancer patients and healthy people. The swabs collected were placed on nutrient agar slant, then incubated for 24 hours at 37ºC. Bacteria from the slant were inoculated in several selective media (Mannitol Salt Agar Media, KF Streptococcus Agar media, Cetrimide Agar, Eosin Methylene Blue Agar). Several biochemical tests identified opportunistic microorganisms. Finally, the antibiotic susceptibility test was performed by the Kirby Bauer disc diffusion method. Results: The study found that 65.4% of microbes isolated from the patients’ oral cavities were Gram-negative bacteria, and 34.6% were Gram-positive bacteria. Among the patient group isolates (n = 55), the most prevalent organism was Pseudomonas spp. (30;54.54%). Others were Klebsiella spp. (27;49.09%), Staphylococcus spp. (24;43.63%), E. coli (14;25.45%), Streptococcus spp. (14;25.45%), Proteus spp. (12;21.8%) and Enterococcus spp. (6;10.90%). Both Gram-positive and Gram-negative microbes from the patient group have shown high resistance to the commonly used antibiotics. In the control group (n = 50), the most prevalent organism was Staphylococcus spp. (15;30%). Other organisms were Streptococcus spp. (6;12%), Klebsiella spp. (11;22%), E. coli (3;6%), Streptococcus spp. (14;25.45%), Pseudomonas spp. (8;16%). The microbes of the control group showed less resistance to the antibiotics and rather showed sensitivity to them. Conclusion: The study revealed a high prevalence of multi-drug-resistant opportunistic microbes on immune-compromised oral cancer patients compared to microbes isolated from healthy people’s oral cavity.

Association between Toll-Like Receptor 4 (Thr399Ile and Asp299Gly), Toll-Like Receptor 2 196-174 Deletion Polymorphisms with cryptosporidiosis

Toll-like receptors (TLRs) 2 and 4 specifically recognize lipopolysaccharide motifs on surfaces of microorganisms. Polymorphims in the TLR genes result in structural variations in the proteins, abnormal host-pathogen interactions and hence, altered immune response. Opportunistic parasite Cryptosporidium spp. infects immuno-compromised patients who present with heterogeneous clinical manifestations ranging from mild infection resolving in a few weeks, to severe form characterized by voluminous diarrhoea, prolonged symptoms and recurrences. The present study investigates the role of TLR2 196_174del, TLR4 Asp299Gly and Thr399Ile polymorphisms in pathogenesis of cryptosporidiosis. Stool samples were collected from 210 immuno-compromised (renal transplant recipients and patients with Human immunodeficiency virus infection) both with and without cryptosporidiosis, and 200 healthy subjects for detection of Cryptosporidium spp. Blood samples were also collected from the patients and healthy subjects for genotyping of Δ22 (TLR2 196_174del) polymorphism, A896G (TLR4 Asp299Gly) and C1196T (Thr399Ile) single nucleotide polymorphisms (SNPs) by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Cryptosporidium spp. was detected in 70 immunocompromised patients, while it was absent in all the healthy controls. No significant difference was observed in Δ22, A896G and C1196T alleles and genotypes (P > 0.05), between cases and controls. Thus, TLR2 196_174del, TLR4 Asp299Gly and Thr399Ile polymorphisms are not significantly associated with the pathogenesis or progression of cryptosporidiosis, in the Indian population included in the study.

Penicillium marneffei infection involving liver

Penicillium marneffei(P.marneffei)is a pathogenic fungus that can cause fatal infections in humans,particularly immunocompromised hosts.It is prevalent only in the Southeast Asian region.A 5-year-old boy was presented with diagnosed Acute Lymphoblastic Leukemia undergoing chemotherapy and suffering from high-grade fever for 15 days positively responded to antibiotics on the initial day,but later he became unresponsive.He was found negative for blood cultures of bacterial growth.Ultrasound of the abdomen showed a borderline enlarged liver with multiple small hypoechoic areas of variable sizes seen scattered in both lobes of the liver.Morphological and microscopic analyses of liver tissues showed multiple septate hyphae of P.marneffei.Amphotericin B was found to be effective in treating the child.Appropriate identification is essential to treat the pathogen-causing disease,especially in immuno-compromised conditions like a leukemic patient,and determine underlying mechanisms behind the pathogenesis.