Coordinated In Vitro Release of Granulysin, Perforin and IFN-γ in TB and HIV/TB Co-Infection Associated with Clinical Outcomes before and after Anti-TB Treatment.

Granule-associated killing molecules released from cytotoxic T lymphocytes participate as a crucial step in immunity against tuberculosis (TB), but the role of coordinated production remains controversial. Coordinated release of effector molecules in vitro after stimulating peripheral blood mononuclear cells (PBMCs) of active TB or HIV/TB coinfection patients with PPD, purified protein derivative of tuberculin and avirulent , H37Ra, an attenuated strain were investigated in association with clinical outcomes. Perforin, granzyme-B, granulysin and IFN-γ were measured using ELISA.

Cytokine Expression in Dengue Fever and Dengue Hemorrhagic Fever Patients with Bleeding and Severe Hepatitis.

Dengue is the most common mosquito-borne flaviviral infection in the world today. Several factors contribute and act synergistically to cause severe infection. One of these is dysregulated host immunological mediators that cause transient pathophysiology during infection.

Ethical issues of informed consent in malaria research proposals submitted to a research ethics committee in Thailand: a retrospective document review.

Background: The informed-consent process should be one of meaningful information exchange between researchers and study participants. One of the responsibilities of research ethics committees is to oversee appropriate informed consent. The committee must consider various matters before deciding whether the process is appropriate, including the adequacy and completeness of the written information provided to study participants, and the process of obtaining informed consent.

Molecular and immunological analyses of confirmed Plasmodium vivax relapse episodes.

Background: Relapse infections resulting from the activation hypnozoites produced by Plasmodium vivax and Plasmodium ovale represent an important obstacle to the successful control of these species. A single licensed drug, primaquine is available to eliminate these liver dormant forms. To date, investigations of vivax relapse infections have been few in number.

Development of Rapid Enzyme-Linked Immunosorbent Assays for Detection of Antibodies to Burkholderia pseudomallei.

Burkholderia pseudomallei, the causative agent of melioidosis, is an environmental bacillus found in northeast Thailand. The mortality rate of melioidosis is ∼40%. An indirect hemagglutination assay (IHA) is used as a reference serodiagnostic test; however, it has low specificity in areas where the background seropositivity of healthy people is high.

Genetic diversity among Plasmodium vivax isolates along the Thai-Myanmar border of Thailand.

Background: Knowledge of the population genetics and transmission dynamics of Plasmodium vivax is crucial in predicting the emergence of drug resistance, relapse pattern and novel parasite phenotypes, all of which are relevant to the control of vivax infections. The aim of this study was to analyse changes in the genetic diversity of P. vivax genes from field isolates collected at different times along the Thai-Myanmar border.

Ethical considerations in malaria research proposal review: empirical evidence from 114 proposals submitted to an Ethics Committee in Thailand.

Background: Malaria research is typically conducted in developing countries in areas of endemic disease. This raises specific ethical issues, including those related to local cultural concepts of health and disease, the educational background of study subjects, and principles of justice at the community and country level. Research Ethics Committees (RECs) are responsible for regulating the ethical conduct of research, but questions have been raised whether RECs facilitate or impede research, and about the quality of REC review itself.

Genome-Wide Association Study of HIV-Related Lipoatrophy in Thai Patients: Association of a DLGAP1 Polymorphism with Fat Loss.

HIV-related lipoatrophy (LA) is a major adverse drug effect among HIV patients receiving the antiretroviral drug stavudine (d4T) in Southeast Asia. Although the development of LA could be observed in almost all HIV patients administered d4T for extended periods, there is considerable variation in the duration required to develop LA within this patient population. This study aimed to identify host genetic polymorphisms affecting the rate of LA onset in Thai HIV patients.

Is your ethics committee efficient? Using "IRB Metrics" as a self-assessment tool for continuous improvement at the Faculty of Tropical Medicine, Mahidol University, Thailand.

Tensions between researchers and ethics committees have been reported in several institutions. Some reports suggest researchers lack confidence in the quality of institutional review board (IRB) reviews, and that emphasis on strict procedural compliance and ethical issues raised by the IRB might unintentionally lead to delays in correspondence between researchers and ethics committees, and/or even encourage prevarication/equivocation, if researchers perceive committee concerns and criticisms unjust. This study systematically analyzed the efficiency of different IRB functions, and the relationship between efficiency and perceived quality of the decision-making process.

Low monocyte to neutrophil ratio in peripheral blood associated with disease complication in primary Plasmodium falciparum infection.

Immunity to malaria can be acquired but only after repeat exposures to polymorphic Plasmodium. However, the development of clinical outcomes during P. falciparum infection is not clearly understood.

Ethical issues in research involving minority populations: the process and outcomes of protocol review by the Ethics Committee of the Faculty of Tropical Medicine, Mahidol University, Thailand.

Background: Recruiting minorities into research studies requires special attention, particularly when studies involve "extra-vulnerable" participants with multiple vulnerabilities, e.g., pregnant women, the fetuses/neonates of ethnic minorities, children in refugee camps, or cross-border migrants.

Potential function of granulysin, other related effector molecules and lymphocyte subsets in patients with TB and HIV/TB coinfection.

Background: Host effector mechanism against Mycobacterium tuberculosis (Mtb) infection is dependent on innate immune response by macrophages and neutrophils and the alterations in balanced adaptive immunity. Coordinated release of cytolytic effector molecules from NK cells and effector T cells and the subsequent granule-associated killing of infected cells have been documented; however, their role in clinical tuberculosis (TB) is still controversy.

Objective: To investigate whether circulating granulysin and other effector molecules are associated with the number of NK cells, iNKT cells, Vγ9(+)Vδ2(+) T cells, CD4(+) T cells and CD8(+) T cells, and such association influences the clinical outcome of the disease in patients with pulmonary TB and HIV/TB coinfection.

Drug resistance and IS6110-RFLP patterns of Mycobacterium tuberculosis in patients with recurrent tuberculosis in northern Thailand.

The emergence of drug resistant Mycobacterium tuberculosis has become a global threat to tuberculosis (TB) prevention and control efforts. This study aimed to determine the drug resistance profiles and DNA fingerprints of M. tuberculosis strains isolated from patients with relapsed or retreatment pulmonary TB in Chiang Rai province in northern Thailand.

Influence of ABCB-1 C3435T polymorphisms on plasma nevirapine and efavirenz levels and their effects on virologic and immunological outcomes in HIV/TB co-infected Thai adults under anti-retroviral therapy.

ATP-binding cassette, sub-family B (encoded by ABCB-1 or MDR-1) has an important role in cellular export of antiretroviral agents. A previous study showed that ABCB-1 C3435T polymorphism affects plasma efavirenz and nelfinavir concentrations and rate of CD4+ T cell recovery after starting antiretroviral treatment (ART). The present study examined the influence of ABCB-1 polymorphisms on plasma nevirapine and efavirenz levels when co-administered with rifampicin in 124 HIV/TB patients who received nevirapine- (400 mg/day) (n = 59) and efavirenz- (600 mg/day) (n = 65) based ART.

Association between circulating full-length osteopontin and IFN-gamma with disease status of tuberculosis and response to successful treatment.

The T helper type 1 (Th1) immune response plays an important role in protective immunity, pathophysiology and development of tuberculosis (TB). To investigate whether osteopontin (OPN) and other Th1 response-related molecules are associated withTB disease status, including co-infection with HIV, and response to anti-TB treatment, circulating levels of full-length OPN (F-OPN), thrombin-cleaved N-terminal fragment of OPN (N-half OPN), IFN-gamma, IP-10, IL-18, IL-12/ IL-23 (p40), IL-10, IL-15 and C-reactive protein (CRP) were measured before and after anti-TB treatment. Patients with newly active pulmonary TB had significantly higher plasma levels of F-OPN, IFN-gamma and CRP than healthy controls (HC).

Decreased plasma granulysin and increased interferon-gamma concentrations in patients with newly diagnosed and relapsed tuberculosis.

Granulysin and interferon-gamma (IFN-γ) have broad antimicrobial activity which controls Mycobacterium tuberculosis (M. tuberculosis) infection. Circulating granulysin and IFN-γ concentrations were measured and correlated with clinical disease in Thai patients with newly diagnosed, relapsed and chronic tuberculosis (TB).

Detection of Salmonella invA gene in shrimp enrichment culture by polymerase chain reaction.

Contamination of seafood with salmonellae is a major public health concern. Detection of Salmonella by standard culture methods is time consuming. In this study, an enrichment culture step prior to polymerase chain reaction (PCR) was applied to detect 284 bp fragment of Salmonella invA in comparison with the conventional culture method in 100 shrimp samples collected from four different shrimp farms and fresh food markets around Bangkok.

Haplotypes of IL12B promoter polymorphisms condition susceptibility to severe malaria and functional changes in cytokine levels in Thai adults.

Polymorphic variability in immune response genes, such as IL12B, encoding the IL-12p40 subunit is associated with susceptibility to severe malaria in African populations. Since the role of genetic variation in conditioning severe malaria in Thai adults is largely unexplored, the functional association between IL12B polymorphisms [i.e.

Effects of CYP2B6 G516T polymorphisms on plasma efavirenz and nevirapine levels when co-administered with rifampicin in HIV/TB co-infected Thai adults.

Background: Cytochrome P450 2B6 (CYP2B6) metabolizes efavirenz and nevirapine, the major core antiretroviral drugs for HIV in Thailand. Rifampicin, a critical component of tuberculosis (TB) therapy is a potent inducer of CYP enzyme activity. Polymorphisms of CYP2B6 and CYP3A4 are associated with altered activity of hepatic enzyme in the liver and pharmacokinetics resulting in treatment efficacy.

IL4 gene polymorphism and previous malaria experiences manipulate anti-Plasmodium falciparum antibody isotype profiles in complicated and uncomplicated malaria.

Background: The IL4-590 gene polymorphism has been shown to be associated with elevated levels of anti-Plasmodium falciparum IgG antibodies and parasite intensity in the malaria protected Fulani of West Africa. This study aimed to investigate the possible impact of IL4-590C/T polymorphism on anti-P. falciparum IgG subclasses and IgE antibodies levels and the alteration of malaria severity in complicated and uncomplicated malaria patients with or without previous malaria experiences.

Sequence variation of PfEMP1-DBLalpha in association with rosette formation in Plasmodium falciparum isolates causing severe and uncomplicated malaria.

Background: Rosetting and cytoadherence of Plasmodium falciparum-infected red blood cells have been associated with severity of malaria. ICAM-1 and CD36 are the main host cell receptors, while PfEMP1-DBLalpha is a major parasite ligand, which can contribute to rosette formation. This study is aimed at demonstrating whether the highly polymorphic PfEMP1-DBLalpha sequences occurring among Thai isolates causing severe and uncomplicated malaria are associated with their ability to form rosettes and reflected the clinical outcome of the patients.

Polymorphism patterns in Duffy-binding protein among Thai Plasmodium vivax isolates.

Background: The Duffy-binding protein II of Plasmodium vivax (PvDBPII) has been considered as an attractive target for vaccine-mediated immunity despite a possible highly polymorphic nature. Among seven PvDBP domains, domain II has been shown to exhibit a high rate of nonsynonymous polymorphism, which has been suggested to be a potential immune (antibody binding) evasion mechanism. This study aimed to determine the extent of genetic polymorphisms and positive natural selection at domain II of the PvDBP gene among a sampling of Thai P.

Expression of toll-like receptors on antigen-presenting cells in patients with falciparum malaria.

The continuous release of blood-stage malaria parasites and their products can activate components of the innate immune system and induce the production of proinflammatory cytokines. Toll-like receptors (TLRs) have emerged as pattern-recognition receptors, residing on/in innate immune cells whose function is recognizing specific conserved components on different microbes. The aim of this study was to determine the expression of TLR2, TLR4 and TLR9 on antigen-presenting cells (APCs) in patients with mild and severe forms of falciparum malaria.

Multiple mutations in katG and inhA identified in Thai isoniazid-resistant Mycobacterium tuberculosis isolates.

A total of 29 Thai multi-drug-resistant/isoniazid-resistant Mycobacterium tuberculosis isolates were analyzed for mutations in katG from codons 254 to 549, inhA promoter and inhA open reading frame by DNA sequencing and single strand conformation polymorphism. Twenty-five multi-drug resistant isolates exhibited single point mutations (17 isolates at Ser315Thr plus Arg463Leu, 1 at Thr308Pro plus Arg463Leu, 7 at either Ser315Thr or Arg463Leu) while the other 4 isoniazid-resistant isolates had single point mutation only at Arg463Leu. Seven of 25 multi-drug-resistant isolates [4 at C(-15)T, 1 at T(-8)C; 1 at C(-15)T plus Ser94Ala and 1 at Ile21Val] and 2 of 4 isoniazid-resistant isolates [1 at C(-15)T, 1 at C (-15)T plus Ile21Thr] had mutations in inhA promoter and open reading frame, while the other 20 isolates had no mutation at any position.

IgG antibody profile to c-terminal region of Plasmodium vivax merozoite surface protein-1 in Thai individuals exposed to malaria.

Naturally acquired immune response to C-terminal region of Plasmodium vivax merozoite surface protein1 (PvMSP1) in 200 individuals with recent clinical episodes of malaria from malaria endemic areas along Thai-Myanmar border in the west and Thai-Cambodia border in the east of Thailand was evaluated by enzyme-linked immunosorbent assay (ELISA). The anti-PvMSP1-IgG antibody was observed in 110 individuals (55%). Among IgG responders, IgG1 coexpressed with IgG3 were the predominant subclasses.