Tropical biomedicine最新文献

Plasmodium knowlesi is the most common zoonotic parasite associated with human malaria infection in Malaysia. Apical membrane antigen 1 (AMA1) protein in the parasite plays a critical role in parasite invasion into host cells. To date, there is no complete three-dimensional ectodomain structure of P. knowlesi AMA1 (PkAMA1) protein. The knowledge of a protein structure is important to understand the protein molecular functions. Three in silico servers with respective structure prediction methods were used in this study, i.e., SWISS-MODEL for homology modeling and Phyre2 for protein threading, which are template-based modeling, while I-TASSER for template-free ab initio modeling. Two query sequences were used in the study, i.e., native ectodomain of PkAMA1 strain H protein designated as PkAMA1-H and a modified PkAMA1 (mPkAMA1) protein sequence in adaptation for Pichia pastoris expression. The quality of each model was assessed by ProSA-web, QMEAN and SAVES v6.0 (ERRAT, Verify3D and Ramachandran plot) servers. Generated models were then superimposed with two models of Plasmodium AMA1 deposited in Protein Data Bank (PDB), i.e., PkAMA1 (4UV6.B) and Plasmodium vivax AMA1 (PvAMA1, 1W81) protein structures for similarity assessment, quantified by root-meansquare deviation (RMSD) value. SWISS-MODEL, Phyre2 and I-TASSER server generated two, one and five models, respectively. All models are of good quality according to ProSA-web assessment. Based on the average values of model quality assessment and superimposition, the models that recorded highest values for most parameters were selected as best predicted models, i.e., model 2 for both PkAMA1-H and mPkAMA1 from SWISS-MODEL as well as model 1 of PkAMA1-H and model 3 of mPkAMA1 from I-TASSER. Template-based method is useful if known template is available, but template-free method is more suitable if there is no known available template. Generated models can be used as guidance in further protein study that requires protein structural data, i.e., protein-protein interaction study.

Demarginalization through initiation of resettlement program since 1978 is an inevitable progress faced by the indigenous Orang Asli (OA) population in Peninsular Malaysia. As Malaysian huntergatherers, the Negrito has been exposed to various environmental-cultural variations. These changes may influence the pattern of soil-transmitted helminth (STH) infections, the common malady amongst OA. This study evaluated the deworming effects of single-dosage albendazole (400 mg) and STH-reinfection rate between Negritos who are still living in the inland jungle versus those living in resettlements at town peripheries (RPS). Stool samples from the consented participants were first examined using the direct faecal smear, formalin-ether sedimentation and Kato Katz techniques. Subsequently, stool collections were carried out in three time points following treatment (i.e., 21 days, 3 months and 6 months). In brief, a total number of 54 Negritos (inland: 24; RPS: 30) with a complete set of stool collection was included in this longitudinal study. This study revealed 72.2% cure rate against T. trichiura in the inland but only 15.0% in the RPS. Although the efficacy of albendazole against T. trichiura was ultimately low in the RPS, 62.6% egg reduction rate (ERR) (arithmetic mean) was noted (p = 0.001). For A. lumbricoides and hookworm, high cure rates were found in both communities (85.7-100.0%). Reinfection for T. trichiura was seen in less than 1 month with higher rate in the RPS (90.0%) as opposed to the inland (44.4%) at 21 days following treatment. This study found that the inland OA had better tolerability to single-dosage albendazole and experienced slower STH reinfection rates versus the RPS. Hence, the selection of albendazole dosage should be targeted and the use of single- dosage albendazole (biannually) would be more suitable for the inland OA. Conversely, we propose the use of 3-days albendazole regimens in the resettled RPS population.

Limited information is available on human exposure to Bartonella infection, i.e., Bartonella henselae (causative agent of cat scratch disease) and Bartonella quintana (causative agent of trench fever) in West Malaysia. This study reports a review of serological findings obtained from patients attending to a teaching hospital in Klang Valley, Malaysia. An indirect immunofluorescence assay (IFA) was used to determine IgG and IgM antibody titers against B. henselae and B. quintana. In a pilot study conducted between 2013-2015, IgG antibodies against Bartonella spp. (either B. quintana and B. henselae) were detected in 14 (36.8%) of 38 patients who were clinically suspected of rickettsial infections, while IgM antibody was detected in 4 (10.5%) patients. This has prompted us to investigate the serologic responses of patients who were clinically suspected of other febrile causes besides rickettsial infection. Of the 59 serum samples analysed in a follow-up investigation, Bartonella IgG antibodies were detected from 7 (11.9%) patients, of which 5 (27.8%) and 2 (18.2%) patients were clinically suspected of rickettsial infection (n=18) and dengue (n=11), respectively. None of the sera obtained from the leptospirosis (n=10), legionellosis (n=10) and mycoplasma infection (n=10) groups were seropositive to Bartonella spp. The review of Bartonella serological findings in this study highlights that Bartonella infection is not uncommon and should be considered as one of the causes for febrile illness in Malaysia.

Mouth rinses which function as breath fresheners, medicaments, and antiseptics can also deliver oral therapeutic agents. This study evaluated and compared the antifungal effects of synthetic and herbal mouth rinses on oral C. albicans and C. glabrata via disk diffusion, minimal inhibition concentration (MIC), minimum fungicidal concentration (MFC), time-kill assay, and growth profile tests. The four chemical mouth rinses, namely Brand O (A), Brand M (B), Brand H (C), and Brand B (D) used in the study showed positive antifungal activity in these two species. The average diameter of the inhibition zones obtained from the disk diffusion test was higher in mouth rinse B (C. albicans = 12.0 ± 0.9 mm, C. glabrata = 13.5 ± 0.8 mm) compared to those in C, A and D. Both Candida species exhibited similar MIC and MFC values, ranging from 1.63 ± 0.5 to 18.75 ± 0.0 µg/mL and 6.51 ± 2.01 to 50.00 ± 9.36 µg/mL, respectively. These synthetic mouth rinses had efficient killing activity eliminating 50% of the growing population of both Candida spp. following 15 seconds exposure time. Analyses of the growth profile curves showed that mouth rinses B and A resulted in rapid growth depletion of both Candida spp. Meanwhile, three herbal mouth rinses, namely Brand S (E), Brand C (F), and Brand P (G), were less effective against C. albicans and C. glabrata. Mouth rinses B and A contained cetylpyridinium chloride and chlorhexidine, respectively, and could be an effective alternative for controlling and preventing oral candidiasis.

The early molecular identification of strains of Plasmodium vivax that have a worse prognosis is important to stratify the risk of complications and choice of conduct made by medical teams. Thus, the aim of the present study was to associate the presence of polymorphisms in the pvmdr-1 and pvcrt-o resistance genes of P. vivax in patients with better or worse prognosis. This cross-sectional epidemiological study was conducted based on data obtained from the records of 120 patients diagnosed with malaria in the Brazilian Amazon. The T958M and F1076L mutations of the pvmdr-1 gene had a frequency of 3.3 and 4.2%, respectively, and primo-infected patients had a 17 times greater chance of being infected with protozoa with the T958M mutation compared to patients with previous episodes. Regarding pvcrt-o, the C393T and T786C polymorphisms had a frequency of 14.2 and 3.3%, respectively, and self-declared white patients had a 3.1 times greater chance of being infected with protozoa with the C393T polymorphism. In addition, patients with this pvcrt-o polymorphism had lower concentrations of C-reactive protein, indicating a better prognosis. These data present clues of genetic indicators useful for assessing the virulence of the parasite and the prognosis of patients with vivax malaria.

A series of new 2,5-disubstituted-1,3,4-oxadiazole derivatives (5a-j and 6a-j) have been designed and synthesized in four-steps. Sixteen compounds among the twenty compounds are reported for the first time. The compounds were characterized and confirmed by the FTIR, 1D- and 2D-NMR and HRMS analyses, and were tested against Mycobacterium smegmatis and Mycobacterium tuberculosis H37Ra. Compound 5d was the most active against M. smegmatis with MIC value of 25 µM, and exhibited cidal activity with MBC of 68 µM, respectively. The time-kill assay showed the good killing rate at 77% with the combination of isoniazid (INH). In addition, checkboard assay confirmed the interaction of compound 5d was categorised as additive. Docking simulation has been performed to position 5d into the pantothenate synthetase active site with binding free energy value -8.6 kcal mol-1. It also occupied the same active site as that of standard native ligand with similar interactions, which clearly indicate their potential as pantothenate synthetase inhibitor.

Blastocystis is the most prevalent eukaryotic gastrointestinal symbiont found in humans and animals worldwide. Increased human infection rates are associated with raising concerns about the involvement of the parasite in public health. Over the last decade, the number of linked epidemiology studies has been prudently grown. Microscopy has been used to detect the presence of protozoan and the advent of molecular techniques has made detection easier. However, due to its limited host specificity and zoonotic potential, animals, either livestock or wildlife animals, may serve as a potential reservoir for Blastocystis infection transmission. The approach utilised in this study aided in understanding the distribution and prevalence of Blastocystis in animals, particularly captivated and free-ranging wild animals worldwide due to increased interest. This review will help comprehend the epidemiological aspects, demographic, subtypes, and the zoonotic potential of Blastocystis in wildlife and captive animals.

Chigger mites are arthropods and are the sole vectors of scrub typhus, and rodents as well as other small mammals are the most common hosts of chigger mite larvae. Therefore, it is of great medical significance to study the ecology of chigger mites. In this study, a detailed analysis of chigger mites was conducted based on field survey data. A total of 4,941 chigger mites were collected from 86 hosts at 34 survey sites in Ruili, Yunnan Province, China. Among the 4,941 chiggers, five genera in one subfamily were identified; Schoengastiella ligula was the dominant chigger species with the highest infestation index, prevalence (Pm, 42.86%) and mean intensity (MI, 59.09%) (P<0.001). The association coefficient (V) between S. ligula and Gahrliepia radiopunctata was positively correlated (P<0.05), indicating the tendency of chiggers to select and coexist on the same host at the same time. The dominant species Leptotrombidium kunmingense, Ascoschoengastia indica, S. ligula and G. radiopunctata showed aggregation distribution patterns, indicating that the distribution of chiggers among different hosts was not uniform. Low altitudes and low latitudes appeared to be more favorable for the growth and reproduction of chigger mites (P<0.05). It is suggested to collect as many host samples as possible in future field investigations to better understand the dynamics of chigger mite populations and their primary hosts.

Data on the prevalence and associated risk factors of naturally occurring haemoplasmosis in owned cats in Malaysia is limited. Being the most pathogenic of the three known feline haemoplasma species, Mycoplasma haemofelis (Mhf) infection was analysed from 2016 to 2019 to determine the periodical prevalence and associated risk factors in Northeastern Malaysia - Kelantan. Archived patient data of 77 clinically ill cats suspected of having M. haemofelis infection were reviewed in this study. Out of the 77 suspected cases, 53 (68.8%) were clinically diagnosed with haemoplasmosis amongst which 46 (59.7%) of the subpopulation were further confirmed with polymerase chain reaction (PCR). Risk factors for M. haemofelis infection (age, breed, ectoparasitism, household condition, roaming status, and sex) were analysed. There was no significant association of breed, ectoparasitism, household condition (number of cats) and occurrence of clinical signs with feline mycoplasmosis. Young, male and roamer cats were more likely to be diagnosed of mycoplasmosis than other categories of cats in this study. There was also a significant association between cats infected with 'Candidatus Mycoplasma haemominutum' with M. haemofelis. Thus, the coinfection of these two haemoplasma species is not uncommon. This study indicates that infection by M. haemofelis in anaemic cats is a common find in client-owned cats from Northeastern Malaysia. As the natural mode of transmission of haemoplasma infection remain unestablished, information in this study may highlight the importance of this disease and contribute to effective prevention and control strategies to minimize feline infectious anaemia (FIA) caused by M. haemofelis.