A novel syphilis Treponema pallidum lipoprotein peptide antigen diagnostic assay using red cell kodecytes in routine blood centre column agglutination testing platforms.

BACKGROUND AND OBJECTIVES: The detection of treponemal antibodies, which are used to make a diagnosis of syphilis, is important both for diagnostic purposes and as a mandatory blood donor test in most countries. We evaluated the feasibility of using Kode Technology to make syphilis peptide red cell kodecytes for use in column agglutination serologic platforms. MATERIALS AND METHODS: Candidate Kode Technology function-spacer-lipid (FSL) constructs were made for the Treponema pallidum lipoprotein (TmpA) of T. pallidum, using the peptide and FSL selection algorithms, and then used to make kodecytes. Developmental kodecytes were evaluated against a large range of syphilis antibody reactive and non-reactive samples in column agglutination platforms and compared against established methodologies. Overall, 150 reactive and 2072 non-reactive Syphicheck assay (a modified T. pallidum particle agglutination) blood donor samples were used to evaluate the agreement rate of the developed kodecyte assay. RESULTS: From three FSL-peptide candidate constructs, one was found to be the most suitable for diagnostics. Of 150 Syphicheck assay reactive samples, 146 were TmpA-kodecyte reactive (97.3% agreement), compared with 58.0% with the rapid plasmin reagin (RPR) assay for the same samples. Against the 2072 expected syphilis non-reactive samples the agreement rate for TmpA-kodecytes was 98.8%. CONCLUSION: TmpA-kodecytes are viable for use as cost-effective serologic reagent red cells for the detection of treponemal antibodies to diagnose syphilis with a high level of specificity in blood centres. This kodecyte methodology also potentially allows for introduction of the reverse-algorithm testing into low-volume laboratories, by utilizing existing transfusion laboratory infrastructure.

Neurosyphilis Presenting as Psychiatric Symptoms at Younger Age: A Case Report.

Neurosyphilis is a central nervous system infection caused by Treponema pallidum that imitates various neurological and mental disorders. Therefore, patients with this disease are prone to misdiagnoses. Here, we report a case of neurosyphilis with a psychotic disorder as the main manifestation. A young girl exhibited mental and behavioural abnormalities after a heartbreak, which manifested as alternating low mood, emotional irritability, and a lack of interest in social relations, followed by memory loss. The cerebrospinal fluid protein - Treponema pallidum particle agglutination test was positive, the toluidine red unheated serum test titre was 1:4, the white blood cell count was 5 × 10^6/L, the cerebrospinal fluid protein level was 0.97 g/L, and the brain CT was abnormal. After admission, the possibility of neurosyphilis was considered and the patient received intravenous penicillin G treatment. The patient's clinical symptom ms improved. This case emphasises that doctors should maintain clinical suspicion of Treponema pallidum infection in adolescent patients with mental abnormalities.

Rollet's mixed chancre in an adult woman diagnosed in the state of Amazonas, Brazil: A case report.

Rollet's Mixed Chancre is a clinical presentation of sexually transmitted infections (STI), involving the coexistence of Haemophilus ducreyi and Treponema pallidum at the same site of infection. Here, we report a case of Rollet's Mixed Chancre in a 32-year-old Brazilian woman. On physical examination she presented with a unilateral bubo measuring approximately 5 × 3 centimeters in diameter, in association with an ulcerated lesion that evolved for 10 days at the inguinal region. She was successfully treated at a health unit with antibiotics. Rollet's Mixed Chancre, though uncommon, poses diagnostic challenges. This case highlights the importance of considering rare STI manifestations. Moreover, comprehensive STI screening and adherence to treatment guidelines are essential for effective management and prevention of further transmission.

Increase in congenital syphilis in a tertiary-care centre from Madrid, Spain: Back to the classics.

Globally, an increase in sexually transmitted diseases worldwide has been reported, including acquired Treponema pallidum infection. Congenital syphilis is the mother-to-child transmission syphilis infection, experiencing an increase in cases returning to incidence rates of years ago. We report three cases of symptomatic congenital syphilis occurring in a tertiary-care hospital in Madrid (Spain). Cases were diagnosed by serology and molecular biology methods. The use of molecular techniques in specimens such as skin lesion, subplacental exudate swabs, bronchoalveolar aspirate, or cerebrospinal fluid could favour the diagnosis of this clinical entity, especially in symptomatic newborns with systemic involvement.

Novel and characteristic radiological features of neurosyphilis: a case series.

BACKGROUND: Treponema pallidum can invade the central nervous system (CNS) early in its infection, causing neurosyphilis. Neurosyphilis typically presents with meningovasculitis in the acute or subacute phase, while tabes dorsalis and dementia paralytica are classical conditions in the later stages. However, syphilis is often misdiagnosed as other conditions such as tumors or autoimmune diseases including vasculitis and encephalitis, which is why the condition is known as "The Great Mimicker." The increasing incidence of syphilis in recent years emphasizes the importance of early diagnosis and treatment; however, its multiple clinical manifestations impose diagnostic challenges for clinicians because it resembles other diseases. In this case series, we present the impressive manifestations of neurosyphilis through three unique radiological presentations. CASE PRESENTATION: Case 1 details optic nerve involvement in an HIV-positive male, where MRI and fundoscopic findings confirmed syphilitic optic neuritis. Case 2 describes a patient in her pregnancy initially suspected of acoustic neuroma on MRI, later diagnosed with syphilitic gumma affecting the inner ear canal. Case 3 is a young male with clinical features mimicking temporal arteritis, ultimately identified as skull osteomyelitis secondarily causing inflammation of the musculus temporalis and meningitis. CONCLUSIONS: These cases underscore the necessity of considering syphilis in differential diagnoses, given the diversity of its clinical presentations. Radiology plays an important role in avoiding unnecessary interventions. The increasing prevalence of recurrent syphilis imposes diagnostic challenges, emphasizing the importance of the early diagnosis and treatment of neurosyphilis by clinicians.

Treponema pallidum protein Tp0136 promotes angiogenesis to facilitate the dissemination of Treponema pallidum.

The incompletely eliminated Treponema pallidum (T. pallidum) during primary syphilis chancre infection can result in the progression of secondary, tertiary, or latent syphilis in individuals, suggesting that T. pallidum has successfully evaded the immune response and spread to distant sites. The mechanism underlying the dissemination of T. pallidum is unclear. Here, a syphilitic rabbit model dorsal-injected with recombinant Tp0136 protein or Tp0136 antibody subcutaneously was used to demonstrate the role of Tp0136 protein in promoting the dissemination of T. pallidum to the testis and angiogenesis in vivo; vascular endothelial cell line HMEC-1 was employed to display that Tp0136 protein enhances the angiogenesis. Furthermore, the three-dimensional microfluidic angiogenesis system showed that the angiogenesis would heighten vascular permeability. Then transcriptome sequencing analysis, in conjunction with cell-level validation, elucidated the critical role of the PI3K-AKT signaling pathway in the promotion of angiogenesis by Tp0136 protein, resulting in heightened permeability. These findings elucidate the strategy employed by T. pallidum in evading immune clearance.

Actinic Granuloma Complicated by Secondary Syphilis: A Case Report.

Introduction: Actinic granuloma (AG) is a rare skin eruption thought to result from a sun-induced inflammatory response attracting giant cells, which are large, multinucleated, and inflammatory, to form granulomas and degrade surrounding elastic material. Clinically, lesions begin on sun-exposed skin as pink papules and nodules that coalesce into demarcated annular plaques with a hypopigmented center. Histologically, actinic elastosis surrounds the outer annulus ring, with histiocytes and giant cells within the raised border, and the innermost central zone is filled with minimal to absent elastic fibers. Case Presentation: We present a middle-aged female with a pruritic eruption of diffuse erythematous macules and papules coalescing into plaques with mild scale involving the scalp, face, neck, torso, and upper and lower extremities, including the palms and soles, but sparing the ears, bilateral axillae, elbows, and knees. Skin biopsies revealed solar elastosis and abundant multinucleated foreign body giant cells with ingested elastic fibers. The patient's clinical presentation and histopathology were consistent with a diagnosis of AG. Furthermore, spirochete immunostaining of the specimens revealed multiple Treponema pallidum spirochetes throughout the epidermis and dermis. Secondary syphilis with primary chancre was added to the diagnosis. Treatment included oral and topical steroids followed by intravenous penicillin G. After 1 month, all lesions had resolved with post-inflammatory erythema. Conclusion: Our patient differs from the typical presentation in describing intense pruritus with her eruption. This interesting collision reminds clinicians to retain a high index of suspicion for multiple diagnoses in a single patient.

Treponematosis in critically endangered Western chimpanzees (Pan troglodytes verus) in Senegal.

Treponematoses encompass a group of chronic and debilitating bacterial diseases transmitted sexually or by direct contact and attributed to Treponema pallidum. Despite being documented since as far back as 1963, the epidemiology of treponematoses in wild primates has remained an uninvestigated territory due to the inherent challenges associated with conducting examinations and obtaining invasive biological samples from wild animals. The primary aim of this study was to investigate the presence of treponemal infections in the critically endangered Western chimpanzees in Senegal, utilizing an innovative non-invasive stool serology method. We provide compelling evidence of the existence of anti-Treponema-specific antibodies in 13 out of 29 individual chimpanzees. Our study also underscores the significant potential of stool serology as a valuable non-invasive tool for monitoring and surveilling crucial emerging diseases in wild animals. We recognize two major implications: (1) the imperative need to assess the risks of treponematosis in Western chimpanzee populations and (2) the necessity to monitor and manage this disease following a holistic One Health approach.

Risk for Donor-Derived Syphilis after Kidney Transplantation, China, 2007-2022.

To evaluate the risk of acquiring syphilis from a donated kidney, we evaluated kidney transplantation pairs from West China Hospital, Sichuan, China, during 2007-2022. Donor-derived syphilis was rare. Risk may be higher if donors have active syphilis and may be reduced if recipients receive ceftriaxone.

An Exuberant Case of Ulceronodular-Rupioid (Malignant) Syphilis in an HIV Patient: A Proposal for New Diagnostic Criteria.

We report the case of a 28-year-old male with uncontrolled human immunodeficiency virus (HIV) infection who presented with extensive ulcerated lesions with dark lamellated crusting on his face, torso, and limbs. The patient had a rapid plasma reagin (RPR) titer of 1:512, indicative of syphilis. A skin biopsy revealed granulomata surrounded by lymphocytes, histiocytes, and plasma cells, with spirochetes visible on immunohistochemical staining. The patient's rash resolved with hyperpigmented scarring after penicillin and doxycycline treatment. This severe form of secondary syphilis has been termed malignant syphilis, lues maligna, ulceronodular syphilis, or rupioid syphilis. We propose a single descriptive name for this entity, ulceronodular-rupioid syphilis. In 1969, Fisher proposed criteria for malignant syphilis based on lesion appearance, histopathologic findings, high RPR values, and rapid response to treatment. We found that the Fisher criteria were imprecise with respect to specific histopathologic findings, the quantitation of RPR values, and what constitutes rapid response to treatment. Thus, we examined an additional 74 cases from the literature and propose new diagnostic criteria based on rash appearance, histopathologic characteristics, non-treponemal and treponemal test positivity, and response to therapy. We also found that uncontrolled viremia, and not a low CD4 count, is a major risk factor for ulceronodular-rupioid syphilis in HIV patients.

Uncovering the mechanisms of host mitochondrial cardiolipin release in syphilis: Insights from human microvascular endothelial cells.

The release of host mitochondrial cardiolipin is believed to be the main factor that contributes to the production of anti-cardiolipin antibodies in syphilis. However, the precise mechanism by which mitochondria release cardiolipin in this context remains elusive. This study aimed to elucidate the mechanisms underlying mitochondrial cardiolipin release in syphilis. We conducted a cardiolipin quantitative assay and immunofluorescence analysis to detect mitochondrial cardiolipin release in human microvascular endothelial cells (HMEC-1), with and without Treponema pallidum (Tp) infection. Furthermore, we explored apoptosis, a key mechanism for mitochondrial cardiolipin release. The potential mediator molecules were then analyzed through RNA-sequence and subsequently validated using in vitro knockout techniques mediated by CRISPR-Cas9 and pathway-specific inhibitors. Our findings confirm that live-Tp is capable of initiating the release of mitochondrial cardiolipin, whereas inactivated-Tp does not exhibit this capability. Additionally, apoptosis detection further supports the notion that the release of mitochondrial cardiolipin occurs independently of apoptosis. The RNA-sequencing results indicated that microtubule-associated protein2 (MAP2), an axonogenesis and dendrite development gene, was up-regulated in HMEC-1 treated with Tp, which was further confirmed in syphilitic lesions by immunofluorescence. Notably, genetic knockout of MAP2 inhibited Tp-induced mitochondrial cardiolipin release in HMEC-1. Mechanically, Tp-infection regulated MAP2 expression via the MEK-ERK-HES1 pathway, and MEK/ERK phosphorylation inhibitors effectively block Tp-induced mitochondrial cardiolipin release. This study demonstrated that the infection of live-Tp enhanced the expression of MAP2 via the MEK-ERK-HES1 pathway, thereby contributing to our understanding of the role of anti-cardiolipin antibodies in the diagnosis of syphilis.

Syphilis susceptibility factors atlas: A wide-angled Mendelian randomization study.

OBJECTIVE: The pathogenic mechanisms of syphilis and the host defense mechanisms against syphilis remain poorly understood. Exploration of the susceptibility factors of syphilis may provide crucial clues for unraveling its underlying mechanisms. METHODS: A two-sample Mendelian Randomization framework was utilized, and the inverse-variance weighted method was used as the main analysis. All data was sourced from Genome-wide association studies datasets from 2015 to 2022 in Europe, and all participants were of European descent. Only summary-level statistics were used. Sensitivity analyses were conducted to evaluate the heterogeneity and pleiotropy of the datasets. RESULTS: Our study established 18 exposure factors (12 risk factors and 6 protective factors) for syphilis susceptibility. Twelve factors encompassing body mass index, waist circumference, darker natural skin, cooked vegetable intake, processed meat intake, diabetes mellitus, glucose regulation disorders, gout, autoimmune diseases, rheumatoid arthritis, diverticulitis, and longer menstrual cycles were found to increase susceptibility to syphilis. In contrast, 6 factors including easier skin tanning, blonde natural hair color, irritability, higher neuroticism scores, extended sleep duration, and delayed age at first sexual intercourse were connected to a reduced risk of syphilis infection (all P < 0.05). CONCLUSIONS: This study identified 18 influencing factors of syphilis susceptibility. These findings offered novel insights for further probing into the underlying pathogenic mechanisms of syphilis and underscored the importance of multifaceted prevention strategies against syphilis.

Clinical presentation of early syphilis and genomic sequences of Treponema pallidum strains in patient specimens and isolates obtained by rabbit inoculation.

BACKGROUND: The global resurgence of syphilis necessitates vaccine development. METHODS: We collected ulcer exudates and blood from 17 primary syphilis (PS) participants and skin biopsies and blood from 51 secondary syphilis (SS) participants in Guangzhou, China for Treponema pallidum subsp. pallidum (TPA) qPCR, whole genome sequencing (WGS), and isolation of TPA in rabbits. RESULTS: TPA DNA was detected in 15 of 17 ulcer exudates and 3 of 17 blood PS specimens. TPA DNA was detected in 50 of 51 SS skin biopsies and 27 of 51 blood specimens. TPA was isolated from 47 rabbits with success rates of 71% (12/17) and 69% (35/51), respectively, from ulcer exudates and SS bloods. We obtained paired genomic sequences from 24 clinical samples and corresponding rabbit isolates. Six SS14- and two Nichols-clade genome pairs contained rare discordances. Forty-one of the 51 unique TPA genomes clustered within SS14 subgroups largely from East Asia, while 10 fell into Nichols C and E subgroups. CONCLUSIONS: Our TPA detection rate was high from PS ulcer exudates and SS skin biopsies and over 50% from SS blood, with TPA isolation in over two-thirds of samples. Our results support the use of WGS from rabbit isolates to inform vaccine development.

The incidence of new cases of syphilis has skyrocketed globally in the twenty-first century. This global resurgence requires new strategies, including vaccine development. As part of an NIH funded Cooperative Research Center to develop a syphilis vaccine, we established a clinical research site in Guangzhou, China to better define the local syphilis epidemic and obtain samples from patients with primary and secondary syphilis for whole genome sequencing (WGS) of circulating Treponema pallidum strains. Inoculation of rabbits enabled us to obtain T. pallidum genomic sequences from spirochetes disseminating in blood, a compartment of immense importance for syphilis pathogenesis. Collectively, our results further clarify the molecular epidemiology of syphilis in southern China, enrich our understanding of the manifestations of early syphilis, and demonstrate that the genomic sequences of spirochetes obtained by rabbit inoculation accurately represent those of the spirochetes infecting the corresponding patients.

Condyloma lata of the umbilicus: A case report highlighting the present syphilis emergency.

Syphilis is an ancient sexually transmitted infection that plagues communities across the United States and the world. Cutaneous syphilis has a wide variety of manifestations and presentations, and is notoriously difficult to identify clinically as a result. In this report, we describe the case of a 30-year-old patient with condyloma lata on the umbilicus, an extremely rare site for the presentation of these lesions. With the recent surge in syphilis infections nationwide, including congenital infections, this case underscores the urgent necessity for heightened syphilis awareness and suspicion among clinicians.

Integração da vigilância e atenção à saúde no tratamento da sífilis gestacional: análise dos indicadores do PQAVS e do Previne Brasil na Paraíba / Integration of surveillance and health care in the management of gestational syphilis: analysis of PQAVS and Previne Brasil indicators in Paraíba / Integración de la vigilancia y la atención a la salud en el tratamiento de la sífilis gestacional: análisis de los indicadores PQAVS y Previne Brasil en Paraíba

Este artigo se baseia em um estudo feito com o objetivo de analisar indicadores sobre a testagem da sífilis na gestação no Programa de Qualificação das Ações de Vigilância em Saúde (PQAVS) e no Programa Previne Brasil no estado da Paraíba, e também de levantar aspectos do tratamento terapêutico para sífilis gestacional. Trata-se de uma pesquisa descritiva-exploratória, na qual foram sistematizados dados do indicador 11, testes por gestantes, do PQAVS e do indicador de desempenho da Atenção Primária à Saúde (APS), com base na proporção de gestantes que realizaram exames de sífilis e HIV durante o pré-natal em 2020; também foi feita a sistematização do webquestionário direcionado a profissionais da APS (médicos/enfermeiros) e autoaplicado sobre a atuação e tratamento terapêutico para sífilis gestacional. Dos 223 municípios da Paraíba, apenas 12% atingiram a meta do PQAVS e 39% a do Previne Brasil em 2020. Em relação ao webquestionário, houve a participação de 142 profissionais, dos quais 85% realizam o tratamento terapêutico preconizado pelo Ministério da Saúde para a APS. Desse modo, deve ser ressaltada a importância da ampliação da oferta de testes para sífilis, dos insumos para o tratamento adequado e da qualificação dos profissionais e da informação em saúde.

This article is based on a study to analyze indicators on syphilis testing during pregnancy in the PQAVS - Programa de Qualificação das Ações de Vigilância em Saúde (Health Surveillance Actions Qualification Programme) and in the Programa Previne Brasil (Previne Brasil Programme) in the state of Paraíba, Brazil, and also to survey aspects of the therapeutic management for gestational syphilis. It is a descriptive-exploratory research, in which data from indicator 11, tests for pregnant women, from the PQAVS and from the Primary Health Care (PHC) performance indicator, based on the proportion of pregnant women with syphilis and HIV tests during prenatal care in 2020 were systematised; in addition to this systematization, a self-administered webquestionnaire on the performance and therapeutic management for gestational syphilis by professionals (doctors/nurses) from the PHC was also systematised. Taking into account the 223 municipalities in Paraíba, only 12% reached the PQAVS goal and 39% reached the Previne Brasil goal in 2020. Regarding the webquestionnaire, 85% of the 142 professionals who answered it, carry out the therapeutic management recommended by the Ministry of Health for the PHC. Thus, it is fundamental to emphasise the importance of expanding the supply of tests for syphilis, supplies for adequate treatment, and the qualification of health professionals and information.

El presente artículo se basa en un estudio efectuado con el objetivo de analizar indicadores sobre la prueba de sífilis durante el embarazo en el PQAVS - Programa de Qualificação das Ações de Vigilância em Saúde (Programa de Calificación para Acciones de Vigilancia en Salud) y en el Programa Previne Brasil en el estado de Paraíba, Brasil, y de resaltar aspectos del tratamiento terapéutico de la sífilis gestacional. Se trata de una investigación descriptiva-exploratoria, en la que se sistematizaron datos del indicador 11, pruebas realizadas por embarazadas, del PQAVS y del indicador de desempeño de la Atención Primaria de Salud (APS), a partir de la proporción de gestantes que se sometieron a pruebas de sífilis y de HIV durante la atención prenatal en 2020; también se sistematizóel cuestionario web dirigido a profesionales de la APS (médicos/enfermeros) y autoadministrado sobre el desempeño y el tratamiento terapéutico de la sífilis gestacional. De los 223 municipios de Paraíba, apenas 12% alcanzaron la meta del PQAVS y 39% lograron la meta del Previne Brasil en 2020. En relación al cuestionario web, participaron 142 profesionales, de los cuales 85% realizan el tratamiento terapéutico recomendado por el Ministerio de Salud para la APS. Así, es fundamental la importancia de ampliar la oferta de pruebas para la sífilis, de los medicamentos para el tratamiento adecuado, la calificación de los profesionales e la información relacionada a la salud.

Treponema pallidum recombinant protein Tp0768 enhances the ability of HUVECs to promote neutrophil chemotaxis through TLR2/ER stress signaling pathway.

Neutrophils are essential cells involved in inflammation. However, the specific mechanism of neutrophil chemotaxis induced by Treponema Pallidum (T. pallidum) remains unknow. In this study, human umbilical vein endothelial cells (HUVECs) were utilized as target cells to investigate the expression levels of chemokines when stimulated with different concentrations of Tp0768(also known as TpN44.5 or TmpA, a T. pallidum infection dependent antigen). The results indicated that Tp0768 treatment enhanced neutrophil chemotaxis in HUVECs, which was closely associated with the expression levels of CXCL1(C-X-C Motif Chemokine Ligand 1), CXCL2(C-X-C Motif Chemokine Ligand 2), and CXCL8(C-X-C Motif Chemokine Ligand 8, also known as interleukin-8). At the same time, the results show that Toll Like Receptor 2 (TLR2) signaling pathway is activated and endoplasmic reticulum stress (ER stress) occurs. Furthermore, the findings revealed that the use of protein kinase RNA-like endoplasmic reticulum kinase (PERK) and Immunoglobulin-Regulated Enhancer 1 (IRE1) inhibitors reduced the expression levels of CXCL1, CXCL2, and CXCL8. Additionally, inhibiting TLR2 significantly decreased the expression levels of ER stress-related proteins (PERK and IRE1), CXCL1, CXCL2, and CXCL8. Consequently, neutrophil chemotaxis was significantly inhibited after treatment with TLR2, PERK, and IRE1 inhibitors. These findings shed light on the role of Tp0768 in enhancing neutrophil chemotaxis in endothelial cells, providing a foundation for further exploration of syphilis pathogenesis and offering a new direction for the diagnosis and treatment of T. pallidum infection.

Southern African HIV Clinicians Society Guideline for the clinical management of syphilis.

Syphilis, 'the great imitator', caused by Treponema pallidum infection, remains a complex and multifaceted disease with a rich history of clinical diversity. This guideline aims to be a comprehensive guide for healthcare workers in Southern Africa, offering practical insights into the epidemiology, pathogenesis, clinical manifestations, diagnostic testing, therapeutic principles, and public health responses to syphilis. Although the syphilis burden has declined over the years, recent data indicate a troubling resurgence, particularly among pregnant women and neonates. This guideline highlights the diagnostic challenges posed by syphilis, stemming from the absence of a single high-sensitivity and -specificity test. While treatment with penicillin remains the cornerstone of treatment, alternative regimens may be used for specific scenarios. We highlight the importance of thorough patient follow-up and management of sex partners to ensure optimal care of syphilis cases. In the context of public health, we emphasise the need for concerted efforts to combat the increasing burden of syphilis, especially within high-risk populations, including people living with HIV.

Coinfection of a yaws patient with two closely related Treponema pallidum subsp. pertenue strains: A rare event with potential evolutionary implications.

The etiological agent of yaws is the spirochete Treponema pallidum (TP) subsp. pertenue (TPE) and infects the children of Papua New Guinea, causing ulcerative skin lesions that impairs normal growth and development. Closely related strains of Treponema pallidum subsp. pertenue, JE11, and TE13 were detected in an ulcer biospecimen derived from a 5-year-old yaws patient. Cloning experiments validated the presence of two distinct but similar genotypes, namely TE13 and JE11, co-occurring within a single host. While coinfection with highly related TPE strains has only limited epidemiological and clinical relevance, this is the first documented coinfection with genetically distinct TP strains in a single patient. Similar coinfections in the past were explained by the existence of over a dozen recombinant loci present in the TP genomes as a result of inter-strain or inter-subspecies recombination events following an anticipated scenario of TP coinfection, i.e., uptake of foreign DNA and DNA recombination.