Uncommon Association Between Diabetic Ketoacidosis, Thyrotoxicosis, Cutaneous Abscess and Acute Pericarditis in an Immunocompetent Patient: A Single Case Report and Literature Review.

INTRODUCTION: The typical factors precipitating diabetic ketoacidosis (DKA) include infections (30%), cessation of antidiabetic medication (20%), and a new diagnosis of diabetes (25%). The etiology remains unknown in 25% of cases. Less frequent causes cited in the literature include severe thyrotoxicosis and, infrequently, pericarditis. Few publications have described the role of human T lymphotropic virus type 1 (HTLV-1) in endocrine and metabolic disorders. Based on a clinical case associated with several endocrine and metabolic disorders, we suggest a potential role for HTLV-1, an endemic virus in the Amazonian area, and review the literature concerning the role of this virus in thyroiditis, pericarditis and diabetes mellitus. CASE REPORT: A fifty-year-old Surinamese woman without any medical history was admitted for diabetic ketoacidosis. No specific anti-pancreatic autoimmunity was observed, and the C-peptide level was low, indicating atypical type-1 diabetes mellitus. DKA was associated with thyrotoxicosis in the context of thyroiditis and complicated by nonbacterial pericarditis and a Staphylococcus aureus subcutaneous abscess. The patient was infected with HTLV-1. CONCLUSION: To our knowledge, this uncommon association is described for the first time. Few studies have analyzed the implications of HTLV-1 infection in thyroiditis and diabetes mellitus. We did not find any reports describing the association of pericarditis with HTLV-1 infection. Additional studies are necessary to understand the role of HTLV-1 in endocrine and cardiac disorders.

STLV-1 co-infection is correlated with an increased SFV proviral load in the peripheral blood of SFV/STLV-1 naturally infected non-human primates.

Simian T-Leukemia Virus type 1 and Simian Foamy Virus infect non-human primates. While STLV-1, as HTLV-1, causes Adult T-cell Leukemia/lymphoma, SFV infection is asymptomatic. Both retroviruses can be transmitted from NHPs to humans through bites that allow contact between infected saliva and recipient blood. Because both viruses infect CD4+ T-cells, they might interfere with each other replication, and this might impact viral transmission. Impact of STLV-1 co-infection on SFV replication was analyzed in 18 SFV-positive/STLV-1-negative and 18 naturally SFV/STLV-1 co-infected Papio anubis. Even if 9 animals were found STLV-1-positive in saliva, STLV-1 PVL was much higher in the blood. SFV proviruses were detected in the saliva of all animals. Interestingly, SFV proviral load was much higher in the blood of STLV-1/SFV co-infected animals, compared to STLV-1-negative animals. Given that soluble Tax protein can enter uninfected cells, we tested its effect on foamy virus promoter and we show that Tax protein can transactivate the foamy LTR. This demonstrates that true STLV-1 co-infection or Tax only has an impact on SFV replication and may influence the ability of the virus to be zoonotically transmitted as well as its ability to promote hematological abnormalities.

A 61-Year-Old Caribbean Man With Thrush and Acute Respiratory Failure.

CASE PRESENTATION: A 61-year-old Caribbean man presented to the ED with dyspnea that had progressed over the previous week with associated cough and high fevers. Four days prior to admission, his primary care physician noted oral thrush and obtained a chest radiograph that revealed a right middle lobe infiltrate. He was prescribed levofloxacin and clotrimazole. Despite therapy, his symptoms progressed. He had an 11 pack-year smoking history and hypertension but had been in good health. He denied recent travel, alcohol or illicit drug use, or high-risk sexual behaviors, and his only previous medicine was amlodipine. Institutional review board approval was not obtained for this case report, as all patient data are anonymous and obtained during routine patient care activities.

A 17-Year-Old Boy With Right Face Palsy, Left Leg Weakness, and Lytic Skull-Bone Lesions.

Human T-cell lymphotropic virus (HTLV), an infection that is endemic in certain parts of Asia, Africa, and South America, has been associated with malignancy and neurological deficits. Here, we describe a pediatric patient with chronic HTLV-I infection who developed complications associated with HTLV-I (ie, adult T-cell leukemia/lymphoma and HTLV-I-associated myelopathy/tropical spastic paraparesis). To our knowledge, this presentation in a child has never been described. The patient underwent a bone marrow transplant and, at the time of this writing, was in remission. This case report highlights the fact that HTLV-related complications, previously expected to occur after decades of infection, also can occur in pediatric patients, particularly those who acquired HTLV-I perinatally.

No significant HTLV seroprevalence in German people who inject drugs.

BACKGROUND: Although human T-lymphotropic virus (HTLV) is transmitted via the same routes as human immunodeficiency virus (HIV), its worldwide seroprevalence differs drastically because HTLV is transmitted mainly via infected cells rather than free virus. The sharing of needles and other equipment places people who inject drugs (PWID) at particularly high-risk for such blood-borne diseases. METHODS: To validate the methodology used to process and analyze the dried blood spots (DBS) utilized in the study, dried serum spots (DSS) with dilutions of sera from known HTLV infected individuals were analyzed by ELISA and Western blot. DBS collected between 2011 and 2015 from 2,077 PWID in eight German cities recruited by respondent-driven sampling were tested for HTLV-specific antibodies. RESULTS: The validation demonstrated that the use of DSS allowed identification of samples with even low titers of HTLV-specific antibodies, although a confirmatory Western blot with an additional venous blood sample would often be required. Despite numerous HIV and HCV positive individuals being identified within the study population, none tested positive for HTLV. CONCLUSION: While the HIV and HCV prevalences in German PWID are comparable to those in other European countries, the very low prevalence of HTLV reflects the situation in the general population.

Development of neurologic diseases in a patient with primate T lymphotropic virus type 1 (PTLV-1).

BACKGROUND: Virus transmission from various wild and domestic animals contributes to an increased risk of emerging infectious diseases in human populations. HTLV-1 is a human retrovirus associated with acute T-cell leukemia and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). HTLV-1 originated from ancient zoonotic transmission from nonhuman primates, although cases of zoonotic infections continue to occur. Similar to HTLV-1, the simian counterpart, STLV-1, causes chronic infection and leukemia and lymphoma in naturally infected monkeys, and combined are called primate T-lymphotropic viruses (PTLV-1). However, other clinical syndromes typically seen in humans such as a chronic progressive myelopathy have not been observed in nonhuman primates. Little is known about the development of neurologic and inflammatory diseases in human populations infected with STLV-1-like viruses following nonhuman primate exposure. RESULTS: We performed detailed laboratory analyses on an HTLV-1 seropositive patient with typical HAM/TSP who was born in Liberia and now resides in the United States. Using a novel droplet digital PCR for the detection of the HTLV-1 tax gene, the proviral load in PBMC and cerebrospinal fluid cells was 12.98 and 51.68 %, respectively; however, we observed a distinct difference in fluorescence amplitude of the positive droplet population suggesting possible mutations in proviral DNA. A complete PTLV-1 proviral genome was amplified from the patient's PBMC DNA using an overlapping PCR strategy. Phylogenetic analysis of the envelope and LTR sequences showed the virus was highly related to PTLV-1 from sooty mangabey monkeys (smm) and humans exposed via nonhuman primates in West Africa. CONCLUSIONS: These results demonstrate the patient is infected with a simian variant of PTLV-1, suggesting for the first time that PTLV-1smm infection in humans may be associated with a chronic progressive neurologic disease.

Short communication: Prevalence and risk factors for human T cell lymphotropic virus infection in Southern Brazilian HIV-positive patients.

HIV/human T cell lymphotropic virus (HTLV) coinfection has a large range of prevalence in the different risk groups and geographic regions of the world. Most of the HTLV-infected people live in geographic areas where the virus is endemic, as it happens in Brazil. The aim of this study was to identify HTLV prevalence and risk factors in HIV-positive patients. A cross-sectional study was conducted with 580 HIV-positive patients (mean age of 40.6 years and 45.0% men) from a specialized HIV/AIDS diagnosis and treatment center in Southern Brazil. Sociodemographic data, HIV risk factors, and HTLV-1/2 antibodies were collected. HTLV proviral DNA was detected by polymerase chain reaction (PCR). A multivariate analysis was performed to identify risk factors for HTLV infection. HTLV antibodies were detected in 29 (5.0%) and HTLV provirus in 17 (2.9%) patients. HTLV-1 was identified in 11 (64.7%) patients and HTLV-2 in 6 (35.3%) patients. No significant differences were observed between mono and coinfected patients in clinical characteristics regarding HIV/AIDS (time since HIV diagnosis, HIV viral load, lymphocytes CD4(+) count, and use of highly active antiretroviral therapy). Blood transfusion history was significantly associated with HIV/HTLV coinfection (p=0.039). Alcohol abuse was more prevalent in HTLV-positive (47.1%) than in HIV mono-infected patients (20.4%; p=0.008). Tattooing was the only risk factor independently associated with HIV/HTLV coinfection (p=0.035). This information contributes to an understanding of the epidemiology of HIV/HTLV coinfection in Brazil.

Immunological alterations and associated diseases in mandrills (Mandrillus sphinx) naturally co-infected with SIV and STLV.

Mandrills are naturally infected with simian T-cell leukaemia virus type 1 (STLV-1) and simian immunodeficiency virus (SIV)mnd. In humans, dual infection with human immunodeficiency virus (HIV) and human T-cell lymphotropic virus type 1 (HTLV-1) may worsen their clinical outcome. We evaluated the effect of co-infection in mandrills on viral burden, changes in T-cell subsets and clinical outcome. The SIV viral load was higher in SIV-infected mandrills than in co-infected animals, whereas the STLV-1 proviral load was higher in co-infected than in mono-infected groups. Dually infected mandrills had a statistically significantly lower CD4+ T-cell count, a lower proportion of naive CD8+ T cells and a higher proportion of central memory cells. CD4(+) and CD8(+) T cells from SIV-infected animals had a lower percentage of Ki67 than those from the other groups. Co-infected monkeys had higher percentages of activated CD4(+) and CD8(+) T cells. Two co-infected mandrills with high immune activation and clonal integration of STLV provirus showed pathological manifestations (infective dermatitis and generalised scabies) rarely encountered in nonhuman primates.

Human T-cell leukemia virus (HTLV)-associated neuropathy.

Symptomatic peripheral neuropathy occurs in a small proportion of HTLV-1 infected patients. Peripheral manifestations are often masked by symptoms and signs of the tropical spastic myelopathy characteristic of the disease. Peripheral neuropathy is often characterized by alteration of small-fiber functions, with inflammatory lesions of peripheral nerves, sometimes associated with symptomatic polymyositis, which may occur in isolation in this setting.

Lung miliary micro-nodules in human T-cell leukemia virus type I carriers.

Human T-cell leukemia virus type 1 (HTLV-1) carriers are rarely subject to inflammatory disorders in multiple organs, other than the well-known complication, adult T-cell leukemia/lymphoma (ATLL). HTLV-1 associated bronchiolo-alveolar disorder (HABA) has been proposed as an immune mediated pulmonary reaction seen rarely in HTLV-1 carriers. The reported clinico-pathological patterns of HABA are diffuse panbronchiolitis (DPB) and lymphoid interstitial pneumonia (LIP). We here report three cases of HTLV-1 carriers showing miliary micro-nodules throughout both lungs. Microscopic examination in the video assisted thoracic surgery biopsies demonstrated that all cases had multiple discrete micro-nodules which consisted of marked lymphoid infiltration, granulomas, eosinophils and a few foci of necrosis inside the granuloma. No findings indicating ATLL, other neoplastic conditions, infection or interstitial pneumonia, including DPB and LIP, were present following panels of special staining and immunohistochemical examinations. Two patients improved without treatment within one month, with no evidence of recurrence after 7 years. One patient showed slow deterioration of lung reticular shadows in spite of a low dose corticosteroid therapy (prednisolone 10 mg/day). We believe these cases may be a newly recognized variant of HABA.

The Smac mimetic RMT5265.2HCL induces apoptosis in EBV and HTLV-I associated lymphoma cells by inhibiting XIAP and promoting the mitochondrial release of cytochrome C and Smac.

The inhibitors of apoptosis (IAP) are important regulators of apoptosis. However, little is known about the capacity of Smac mimetics (IAP inhibitor) to overcome virally associated-lymphoma's (VAL) resistance to apoptosis. Here, we explored the pro-apoptotic effect of a novel Smac mimetic, RMT5265.2HCL (RMT) in VAL cells. RMT improved the sensitivity to apoptosis in EBV- and to some extend in HTLV-1- but not in HHV-8-VAL. Furthermore, we identified that RMT promotes caspase 3 and 9 cleavage by inhibiting XIAP and inducing the mitochondrial efflux of Smac and cytochrome C. This investigation further support exploring the use of Smac inhibitors in VAL.

HTLV infection and strongyloidal hyperinfection syndrome.

Strongyloides stercoralis can affect humans in the form of asymptomatic infections, Strongyloidal hyperinfection syndrome and disseminated Strongyloidiasis depending on the immune response of the host. We report a case of strongyloidial hyperinfection syndrome that subsequently tested positive for HTLV infection.

Neuromyelitis optica associated with subacute human T-lymphotropic virus type 1 infection.

Although human T-lymphotropic virus type 1 (HTLV-1)-associated myelopathy, or tropical spastic paraparesis (HAM/TSP), is usually considered as a progressive myelopathy, a subacute variant has been described. It is unusual for optic neuritis (ON) to be associated with an HTLV-1 infection. Neuromyelitis optica (NMO) is characterised by severe attacks of acute transverse myelitis and ON of unknown aetiology. We report a 61-year-old Afro-Caribbean male patient with subacute HAM/TSP associated with bilateral ON that occurred 5years previously. To our knowledge this is the first report of recurrent NMO syndrome associated with HTLV-1 infection.

Nonspecific interstitial pneumonia pattern as pulmonary involvement in human T-cell lymphotropic virus type 1 carriers.

It is well established that diffuse interstitial shadows are observed in human T-cell lymphotropic virus type 1 (HTLV-1) carriers. However, the pathological pattern of nonspecific interstitial pneumonia (NSIP) has rarely been reported. Here, we describe the clinical features of four patients with histologically proven NSIP and HTLV-1 infection. The patients, one woman and three men, had a median age of 59.5 years. High-resolution computed tomography of the lungs was performed in all patients, and no apparent honeycomb formations were detected. The present study demonstrates that the NSIP pattern is a significant pathological classification of interstitial pneumonia associated with HTLV-1 carriers.

Transfusion-transmitted infectious diseases.

A spectrum of blood-borne infectious agents is transmitted through transfusion of infected blood donated by apparently healthy and asymptomatic blood donors. The diversity of infectious agents includes hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency viruses (HIV-1/2), human T-cell lymphotropic viruses (HTLV-I/II), Cytomegalovirus (CMV), Parvovirus B19, West Nile Virus (WNV), Dengue virus, trypanosomiasis, malaria, and variant CJD. Several strategies are implemented to reduce the risk of transmitting these infectious agents by donor exclusion for clinical history of risk factors, screening for the serological markers of infections, and nucleic acid testing (NAT) by viral gene amplification for direct and sensitive detection of the known infectious agents. Consequently, transfusions are safer now than ever before and we have learnt how to mitigate risks of emerging infectious diseases such as West Nile, Chikungunya, and Dengue viruses.

[Fulminant strongyloidiasis successfully treated by subcutaneous ivermectin: an autopsy case].

We report a 49-year-old man who was a human T-cell leukemia virus type 1 (HTLV-1) carrier, born in Okinawa prefecture where both strongyloidiasis and HTLV-1 are endemic. He presented with fever, headache and urinary retention. On the basis of CSF examination and MRI findings, his condition was diagnosed as myelitis. He received methylprednisolone pulse therapy. He was transferred to our hospital due to severe paralytic ileus. Strongyloides stercoralis (S. stercoralis) was found in the duodenal stained tissue of a biopsy specimen. Ivermectin applied both orally and through enema were ineffective because of severe ileus and intestinal bleeding. Nine mg (200 microg/kg) of ivermectin solution was administered subcutaneously every other day for five days (total amount 45 mg). The S. stercoralis burden in the stool decreased and paralytic ileus gradually resolved. Three weeks after the resolution of S. stercoralis infection, purulent meningitis developed and acute obstructive hydrocephalus appeared. The hydrocephalus improved by ventricular drainage. Approximately three months after drainage, he died of incidental aspiratory pneumonia. Autopsy showed neither eggs nor larvae of S. stercoralis in the organs. In this case, the fourth reported case in the world, subcutaneous ivermectin injection was dramatically effective. We should consider a diagnosis of strongyloidiasis for any patient from Okinawa prefecture who was an HTLV-1 carrier presenting with unknown origin ileus after treatment of steroid therapy.