Evaluation of an ensemble-based distance statistic for clustering MLST datasets using epidemiologically defined clusters of cyclosporiasis.

Outbreaks of cyclosporiasis, a food-borne illness caused by the coccidian parasite Cyclospora cayetanensis have increased in the USA in recent years, with approximately 2300 laboratory-confirmed cases reported in 2018. Genotyping tools are needed to inform epidemiological investigations, yet genotyping Cyclospora has proven challenging due to its sexual reproductive cycle which produces complex infections characterized by high genetic heterogeneity. We used targeted amplicon deep sequencing and a recently described ensemble-based distance statistic that accommodates heterogeneous (mixed) genotypes and specimens with partial genotyping data, to genotype and cluster 648 C. cayetanensis samples submitted to CDC in 2018. The performance of the ensemble was assessed by comparing ensemble-identified genetic clusters to analogous clusters identified independently based on common food exposures. Using these epidemiologic clusters as a gold standard, the ensemble facilitated genetic clustering with 93.8% sensitivity and 99.7% specificity. Hence, we anticipate that this procedure will greatly complement epidemiologic investigations of cyclosporiasis.

Ox40L-Ox40 pathway plays distinct roles in regulating Th2 responses but does not determine outcome of cutaneous leishmaniasis caused by Leishmania mexicana and Leishmania major.

Ox40 ligand (Ox40L)-Ox40 pathway has been shown to enhance Th2 responses and play a role in pathogenesis of cutaneous leishmaniasis (CL) caused by Leishmania major. Using Ox40l(-/-) BALB/c mice we analyzed the role of this pathway in determining the outcome to CL caused by L. mexicana and compared to L. major. Contrary to our expectations, Ox40l(-/-) mice were highly susceptible to both L. major (LV39) and L. mexicana (M379) and developed large non-healing lesions containing parasites comparable to Ox40l(+/+) BALB/c mice. Interestingly, upon in vitro stimulation with Leishmania antigen (LmAg), the lymph node cells from L. major infected Ox40l(-/-) mice produced significantly less IL-4 and IL-10 compared to Ox40l(+/+) mice. L. mexicana infected Ox40l(-/-) and Ox40l(+/+) mice did not show any difference in the production of IL-4 and IL-10. No difference was noted in the amount of Th1 cytokines IFN-Ò¯ and IL-12 produced by Ox40l(-/-) and Ox40l(+/+) mice infected with either parasite. These results indicate that the Ox40L-Ox40 pathway promotes Th2 bias only in L. major infection but not L. mexicana infection and this pathway is not critical for susceptibility to CL.

Cytokines and their STATs in cutaneous and visceral leishmaniasis.

Cytokines play a critical role in shaping the host immune response to Leishmania infection and directing the development of protective and non-protective immunities during infection. Cytokines exert their biological activities through the activation and translocation of transcription factors into the nucleus whether they drive the expression of specific cytokine-responsive genes. Signal transducer and activator of transcription (STATs) are transcription factors which play a critical role in mediating signaling downstream of cytokine receptors and are important for shaping the host immune response during Leishmania infection. Here we discuss the signature cytokines and their associated STATs involved in the host immune response during cutaneous and visceral leishmaniasis.

Aeromonas hydrophila wound infection following a tiger bite in Nepal.

Aeromonas hydrophila is a rare human pathogen. Reports of zoonotic infection developing after large feline bites are even rarer. We are documenting the first case of human wound infection with A. hydrophila following a tiger bite. The patient responded well following wound debridement, secondary suturing and combination antibiotic therapy.

Role of co-stimulation in Leishmaniasis.

Leishmania are obligate intracellular parasites that cause a wide spectrum of diseases ranging from cutaneous, mucocutaneous and the visceral kind. Persistence or resolution of leishmaniasis is governed by host immune response. Co-stimulation is an important secondary signal that governs the extent, strength and direction of the immune response that follows. Co-stimulation by CD40, B7 and OX40 family has been shown to influence the outcome following Leishmania infection and manipulation of these pathways has shown promise for use in immune therapy of leishmaniasis. In this review, we discuss the roles of CD40, B7 and OX40 co-stimulatory pathways in regulating immunity to Leishmania and their implications in the treatment of this disease.

Empyema caused by eikenella corrodens.

Eikenella corrodens is a fastidious, facultative anerobic, non-motile, gram-negative bacilli that is part of the normal flora of the mouth and upper respiratory tract. It is being increasingly recognized as a human pathogen and has been implicated in a variety of human infections, including, periodontitis, brain abscess, endocarditis, osteomyelitis, intra-abdominal infections, and pleuropulmonary infections. We report, for the first time, from the Himalayan Kingdom of Nepal, a case of left-sided empyema due to Eikenella corrodens, in an 83-year-old man. Eikenella corrodens was isolated as a pure growth from the pleural aspirate, proving its pathogenic potential. Surgical drainage and an appropriate antimicrobial therapy resulted in a therapeutic response. We have discussed the difficulties that can be encountered in isolating Eikenella corrodens and in choosing appropriate antibiotics for its treatment.