PAX5 functions as a tumor suppressor by RB-E2F-mediated cell cycle arrest in Kaposi sarcoma-associated herpesvirus-infected primary effusion lymphoma.

Primary effusion lymphoma (PEL) is a malignant B-cell lymphoma attributable to Kaposi sarcoma-associated herpesvirus (KSHV) infection. PEL is characterized by invasive behavior, showing recurrent effusions in body cavities. The clinical outcome and typical prognosis in patients with PEL are poor and potentially lethal. Clarification of the pathogenesis in PEL is urgently needed in order to develop novel therapies. PEL cells generally lack B-cell surface markers, and we therefore hypothesized that the B-cell transcription factor, PAX5, would be down-regulated in PEL. The expression of PAX5 is detected from the pro-B to the mature B-cell stage and is indispensable for the differentiation of B-cells. PAX5 was silenced in PEL cells via its promoter methylation. Up-regulation of PAX5 induced several genes coding for B-cell surface marker mRNA, but not protein level. PAX5 inhibited cell growth via G1 cell cycle arrest. PAX5 bound to RB and increased its protein expression. RB/E2F-regulated genes were significantly down-regulated in microarray analysis and PCR experiments. To elucidate the in vivo role of PAX5, we examined the restoration of PAX5 in a PEL mouse model. The ascites volume and organ invasions were significantly suppressed by PAX5 restoration. Reduction of PAX5 has played a crucial role in the oncogenesis of PEL, and PAX5 is a tumor suppressor in PEL. Targeting PAX5 could represent a novel therapeutic strategy for patients with PEL.

Infectious Triggers of Cytokine Storm Syndromes: Herpes Virus Family (Non-EBV).

The herpesviruses are the most common infectious agents associated with both primary and secondary cytokine storm syndromes (CSS). While Epstein-Barr Virus (EBV) is most frequently reported in association with CSS, cytomegalovirus (CMV) and many other herpesviruses (e.g., herpes simplex virus, varicella zoster virus, and human herpesviruses 6 and 8) are clearly associated with CSS in children and adults. Immunocompromised hosts, whether due to primary immunodeficiency or secondary immune compromise (e.g., solid organ or stem cell transplantation), appear to be at particularly increased risk of herpesvirus-associated CSS. In this chapter, the association of the non-EBV herpesviruses with CSS will be discussed, including predisposing factors and treatment considerations.

Emerging shadows: HHV-8-associated encephalitis unveiled in a solid organ transplant recipient.

Human herpesviruses (HHVs) cause a wide variety of central nervous system (CNS) infections including meningitis and encephalitis. While HHV-8 is not typically associated with neurological diseases, several studies have indicated a relationship, such as secondary central nervous system (CNS) metastases and a few isolated cases of HHV-8 encephalitis in acquired immunodeficiency syndrome (HIV). However, it has not been previously linked to encephalitis in solid organ transplantation (SOT). This case presents the first-ever instance of HHV-8 encephalitis in a SOT recipient. Our case highlights the association of HHV-8-related diseases, such as post-transplant Kaposi's Sarcoma (KS), with encephalitis. The patient was diagnosed with KS before developing neurological symptoms and received a prompt clinical response through intravenous foscarnet and ganciclovir treatment for 14 days. It is important to note that HHV-8 is a rare cause of encephalitis, and diagnosis requires a high index of suspicion in the appropriate clinical context, allowing for the use of antiviral therapy. This case also underscores the importance of considering the possibility of HHV-8-related diseases in SOT recipients, as they are at risk of developing such infections.

Long-term performance of show-jumping horses and relationship with severity of ataxia and complications associated with myeloencephalopathy caused by equine herpes virus-1.

BACKGROUND: Equine herpesvirus myeloencephalopathy (EHM) has severe impact on the sport horse population. OBJECTIVE: Study the influence of EHM on the likelihood of affected horses to return to their previous performance and investigate the association of clinical variables with prognosis. ANIMALS: Twenty-six horses positive for equine herpesvirus type 1 (EHV-1) were admitted to a veterinary teaching hospital (VTH) during a natural EHM outbreak at an international jumping event. METHODS: Data collected from the VTH, the International Equestrian Federation, and surveys completed by the riders and horse owners were retrospectively analyzed. RESULTS: Horses affected by EHM had 68% chance of returning to exercise, and 52.9% were able to achieve their preoutbreak performance level. Horses with an ataxia grade at admission ≥4/5 had an increased fatality rate (P < .05) and 10% chance of reaching their preoutbreak performance level. None of the horses with both vascular and urinary complications returned to their previous performance level. Finally, horses vaccinated against EHV-1 and those with urinary complications had a 71.4% and 43.7% fatality rate, respectively. CONCLUSIONS AND CLINICAL IMPORTANCE: Horses affected by EHM were able to return to their previous performance levels, but certain clinical variables were negatively associated with postoutbreak performance. Ataxia grade upon admission and the development of systemic signs of vasculitis and urinary complications were potential poor prognostic indicators in sport horses. Variables linked to fatality included prior vaccination against EHV-1, ataxia grade upon admission, and the development of urinary complications.

Medical management and positive outcome after prolonged recumbency in a case of equine herpesvirus myeloencephalopathy.

A 17-year-old mare presenting with acute fever, weakness and bladder dysfunction was diagnosed with equine herpesvirus myeloencephalopathy (EHM). The mare become transiently recumbent, underwent parenteral fluid therapy, plasma infusion, steroidal/nonsteroidal anti-inflammatory drugs (SAID/NSAIDs) and bladder catheterization. After 10 days the mare was hospitalized. Neurological evaluation revealed ataxia and proprioceptive deficits mainly in the hind limbs. The mare was able to stand but unable to rise from recumbency or walk. Secondary complications included Escherichia coli cystitis, corneal ulcers and pressure sores. A full-body support sling was used for 21 days. Medical treatment included systemic antimicrobials, NSAIDs, gradual discontinuation of SAIDs, parenteral fluid therapy and bladder lavage. The mare tested positive for Varicellovirus equidalpha 1 (EHV-1) DNA in nasal swab and blood samples on day 13 and in urine samples on days 13 and 25 after the onset of fever. Neurological signs improved over a period of 34 days and the mare was discharged with mild hind limb weakness/ataxia. Secondary complications resolved within 2 weeks. At the eight-month follow-up, marked improvement in locomotory function had been achieved.

Identification of asinine gamma herpesviruses in a donkey with interstitial pulmonary fibrosis, pleural effusion and thrombocytopenia.

A 23-year-old domestic donkey (Equus asinus) referred for severe respiratory distress due to suspected equine asthma. Ultrasound of the chest revealed bilateral irregular pulmonary consolidation and pleural effusion. Airway endoscopy and tracheal wash cytology showed severe neutrophilic inflammation and bacterial culture was positive for Streptococcus equi subsp. zooepidemicus. Despite aggressive treatment, the donkey died in 48 hours. On post-mortem examination, the lung was whitish, collapsed, and firm, with fibrotic multifocal nodular areas. Pleural effusion and pleuritis were detected. Histologically, the lung architecture was markedly replaced by interstitial fibrosis. The histological features observed were suggestive of a severe chronic fibrosing interstitial pleuropneumonia with type 2 pneumocyte hyperplasia and intralesional syncytial cells. Pulmonary fibrosis was associated with the presence of asinine gammaherpesvirus 2 and 5 infection, confirmed by PCR and sequence analysis. The macroscopic and histological pattern of fibrosis was diffuse and interstitial, and the nodular lesions were consistent with spared lung parenchyma, instead of the canonical nodular distribution of the fibrosis observed in equine multinodular pulmonary fibrosis. Asinine herpesviral pulmonary fibrosis is uncommon, but should be considered by clinicians in the list of differentials in donkeys with chronic respiratory signs.

Antibody profiling and predictive modeling discriminate between Kaposi sarcoma and asymptomatic KSHV infection.

Protein-level immunodominance patterns against Kaposi sarcoma-associated herpesvirus (KSHV), the aetiologic agent of Kaposi sarcoma (KS), have been revealed from serological probing of whole protein arrays, however, the epitopes that underlie these patterns have not been defined. We recently demonstrated the utility of phage display in high-resolution linear epitope mapping of the KSHV latency-associated nuclear antigen (LANA/ORF73). Here, a VirScan phage immunoprecipitation and sequencing approach, employing a library of 1,988 KSHV proteome-derived peptides, was used to quantify the breadth and magnitude of responses of 59 sub-Saharan African KS patients and 22 KSHV-infected asymptomatic individuals (ASY), and ultimately to support an application of machine-learning-based predictive modeling using the peptide-level responses. Comparing anti-KSHV antibody repertoire revealed that magnitude, not breadth, increased in KS. The most targeted epitopes in both KS and ASY were in the immunodominant proteins, notably, K8.129-56 and ORF65140-168, in addition to LANA. Finally, using unbiased machine-learning-based predictive models, reactivity to a subset of 25 discriminative peptides was demonstrated to successfully classify KS patients from asymptomatic individuals. Our study provides the highest resolution mapping of antigenicity across the entire KSHV proteome to date, which is vital to discern mechanisms of viral pathogenesis, to define prognostic biomarkers, and to design effective vaccine and therapeutic strategies. Future studies will investigate the diagnostic, prognostic, and therapeutic potential of the 25 discriminative peptides.

Integrative Multi-omics Analysis to Characterize Herpes Virus Infection Increases the Risk of Alzheimer's Disease.

Evidence suggests that herpes virus infection is associated with an increased risk of Alzheimer's disease (AD), and innate and adaptive immunity plays an important role in the association. Although there have been many studies, the mechanism of the association is still unclear. This study aims to reveal the underlying molecular and immune regulatory network through multi-omics data and provide support for the study of the mechanism of infection and AD in the future. Here, we found that the herpes virus infection significantly increased the risk of AD. Genes associated with the occurrence and development of AD and genetically regulated by herpes virus infection are mainly enrichment in immune-related pathways. The 22 key regulatory genes identified by machine learning are mainly immune genes. They are also significantly related to the infiltration changes of 3 immune cell in AD. Furthermore, many of these genes have previously been reported to be linked, or potentially linked, to the pathological mechanisms of both herpes virus infection and AD. In conclusion, this study contributes to the study of the mechanisms related to herpes virus infection and AD, and indicates that the regulation of innate and adaptive immunity may be an effective strategy for preventing and treating herpes virus infection and AD. Additionally, the identified key regulatory genes, whether previously studied or newly discovered, may serve as valuable targets for prevention and treatment strategies.

A variant of KSHV-associated inflammatory cytokine syndrome in elderly men of Mediterranean descent.

The spectrum of HHV-8-associated disorders includes Kaposi's sarcoma, primary effusion lymphoma, multicentric Castleman's disease, and the recently described KSHV inflammatory cytokine syndrome (KICS), a life-threatening disorder complicating HIV infection. There have been no reports in the literature concerning non-immunosuppressed individuals affected with KICS. We report here a KICS-like illness occurring in two elderly Greek men without HIV infection or other recognizable cause of immunosuppression.

Prevention of Oncogenic Gammaherpesvirinae (EBV and HHV8) Associated Disease in Solid Organ Transplant Recipients.

Long-term risk for malignancy is higher among solid organ transplant (SOT) recipients compared to the general population. Four non-hepatitis viruses have been recognized as oncogenic in SOT recipients-EBV, cause of EBV-associated lymphoproliferative diseases; human herpes virus 8 (HHV8), cause of Kaposi sarcoma, primary effusion lymphoma and multicentric Castleman disease; human papilloma virus, cause of squamous cell skin cancers, and Merkel cell polyomavirus, cause of Merkel cell carcinoma. Two of these viruses (EBV and HHV8) belong to the human herpes virus family. In this review, we will discuss key aspects regarding the clinical presentation, diagnosis, treatment, and prevention of diseases in SOT recipients associated with the two herpesviruses.

Association between human herpesvirus infection and cervical carcinoma: a systematic review and meta-analysis.

BACKGROUND: Cervical cancer (CC) is one of the most common gynecologic tumors among women around the world. Although the etiological role of human papillomavirus (HPV) in CC is well established, other factors in CC carcinogenesis remains unclear. Here, we performed a systematic review and meta-analysis to explore the association between infections of human herpesvirus (HHVs) and CC risk. METHODS: Embase and PubMed databases were utilized to search the relevant studies. The revised JBI Critical Appraisal Tool was used to assess the quality of the included studies. Prevalence and odds ratios (ORs) with 95% confidence intervals (CI) were calculated to evaluate the association between viral infection and CC or precancerous cervical lesions (PCL). RESULTS: Totally 67 eligible studies involving 7 different HHVs were included in meta-analysis. We found an increased risk of CC or PCL that was associated with the overall infection of HHVs (CC, OR = 2.74, 95% CI 2.13-3.53; PCL, OR = 1.95, 95% CI 1.58-2.41). Subgroup analysis showed a trend towards positive correlations between herpes simplex virus type 2 (HSV-2) infection and CC (OR = 3.01, 95% CI 2.24 to 4.04) or PCL (OR = 2.14, 95% CI 1.55 to 2.96), and the same is true between Epstein-Barr virus (EBV) infection and CC (OR = 4.89, 95% CI 2.18 to 10.96) or PCL (OR = 3.55, 95% CI 2.52 to 5.00). However, for HSV-1 and cytomegalovirus (HCMV), there was no association between viral infection and CC or PCL. By contrast, the roles of HHV-6, HHV-7, and Kaposi sarcoma-associated herpesvirus (KSHV) in cervical lesions were unclear due to the limited number of studies. CONCLUSIONS: This study provided evidence that HHVs infection as a whole increase the risk of CC incidence. In addition, some types of HHVs such as EBV and HSV-2 may serve as potential targets in the development of new interventions or therapeutic strategies for cervical lesions.

Mendelian randomization reveals no correlations between herpesvirus infection and idiopathic pulmonary fibrosis.

BACKGROUND: Previous studies have found that the persistence of herpesvirus significantly increases the risk of idiopathic pulmonary fibrosis (IPF), but it is unclear whether this effect is causal. We conducted a two-sample Mendelian randomization (MR) study to evaluate the causal relationship between three herpesvirus infections and IPF. METHODS: We used genome-wide association studies (GWAS) data from three independent datasets, including FinnGen cohort, Milieu Intérieur cohort, and 23andMe cohort, to screen for instrumental variables (IVs) of herpesvirus infection or herpesvirus-related immunoglobulin G (IgG) levels. Outcome dataset came from the largest meta-analysis of IPF susceptibility currently available. RESULTS: In the FinnGen cohort, genetically predicted Epstein-Barr virus (EBV) (OR = 1.105, 95%CI: 0.897-1.149, p = 0.815), cytomegalovirus (CMV) (OR = 1.073, 95%CI: 0.926-1.244, p = 0.302) and herpes simplex (HSV) infection (OR = 0.906, 95%CI: 0.753-1.097, p = 0.298) were not associated with the risk of IPF. In the Milieu Intérieur cohort, we found no correlations between herpesvirus-related IgG EBV nuclear antigen-1 (EBNA1) (OR = 0.968, 95%CI: 0.782-1.198, p = 0.764), EBV viral capsid antigen (VCA) (OR = 1.061, 95CI%: 0.811-1.387, p = 0.665), CMV (OR = 1.108, 95CI%: 0.944-1.314, p = 0.240), HSV-1 (OR = 1.154, 95%CI: 0.684-1.945, p = 0.592) and HSV-2 (OR = 0.915, 95%CI: 0.793-1.056, p = 0.225) and IPF risk. Moreover, in the 23andMe cohort, no evidence of associations between mononucleosis (OR = 1.042, 95%CI: 0.709-1.532, p = 0.832) and cold scores (OR = 0.906, 95%CI: 0.603-1.362, p = 0.635) and IPF were found. Sensitivity analysis confirmed the robustness of our results. CONCLUSIONS: This study provides preliminary evidence that EBV, CMV, and HSV herpesviruses, and herpesviruses-related IgG levels, are not causally linked to IPF. Further MR analysis will be necessary when stronger instrument variables and GWAS with larger sample sizes become available.

miRNAs: Targets to Investigate Herpesvirus Infection Associated with Neurological Disorders.

Herpesvirus is associated with various neurological disorders and a specific diagnosis is associated with a better prognosis. MicroRNAs (miRNAs) are potential diagnostic and prognostic biomarkers of neurological diseases triggered by herpetic infection. In this review, we discuss miRNAs that have been associated with neurological disorders related to the action of herpesviruses. Human miRNAs and herpesvirus-encoded miRNAs were listed and discussed. This review article will be valuable in stimulating the search for new diagnostic and prognosis alternatives and understanding the role of these miRNAs in neurological diseases triggered by herpesviruses.

Soluble biomarkers of HIV-1-related systemic immune activation are associated with high plasma levels of growth factors implicated in the pathogenesis of Kaposi sarcoma in adults.

Background: Human Herpesvirus-8 (HHV-8) is the etiologic agent of Kaposi's sarcoma (KS), a multicentric angio-proliferative cancer commonly associated with Human Immunodeficiency Virus (HIV) infection. KS pathogenesis is a multifactorial condition hinged on immune dysfunction yet the mechanisms underlying the risk of developing KS in HHV-8 seropositive adults remains unclear. Here we explored whether soluble markers of HIV-1-related systemic immune activation (SIA) and angiogenesis (VEGF and FGF acidic) are involved in the pathogenesis of KS in adults with HHV8. Methodology: Blood samples from 99 HIV-1 infected and 60 HIV-1 uninfected adults were collected in Yaoundé, Cameroon. CD3+/CD4+ T cell counts and HIV-1 plasma viral load were determined using the Pima Analyzer and the RT-PCR technique, respectively. Plasma levels of SIA biomarkers (sCD163, sCD25/IL-2Rα, and sCD40/TNFRSF5) and biomarkers of progression to KS (VEGF and FGF acidic) were measured using the Luminex assay. Seropositivity (IgG) for HHV-8 was determined using the ELISA method. Results: Overall, 20.2% (20/99) of HIV-1 infected and 20% (12/60) of HIV-1 uninfected participants were seropositive for HHV8. Levels of sCD163, sCD25/IL-2Rα, sCD40/TNFRSF5, and FGF acidic were higher in the HIV-1 and HHV8 co-infection groups compared to the HIV-1 and HHV8 uninfected groups (all P <0.05). In addition, Higher plasma levels of VEGF correlated with sCD163 (rs = 0.58, P =0.0067) and sCD40/TNFRSF5 (rs = 0.59, P = 0.0064), while FGF acidic levels correlated with sCD40/TNFRSF5 (rs = 0.51, P = 0.022) in co-infected. In HIV-1 mono-infected donors, VEGF and FGF acidic levels correlated with sCD163 (rs =0.25, P = 0.03 and rs = 0.30, P = 0.006 respectively), sCD25/IL-2Rα (rs = 0.5, P <0.0001 and rs = 0.55, P <0.0001 respectively) and sCD40/TNFRSF5 (rs = 0.7, P <0.0001 and rs = 0.59, P <0.0001 respectively) and even in patients that were virally suppressed sCD25/IL-2Rα (rs = 0.39, P = 0.012 and rs = 0.53, P = 0.0004 respectively) and sCD40/TNFRSF5 (rs = 0.81, P <0.0001 and rs = 0.44, P = 0.0045 respectively). Conclusion: Our findings suggest that although the development of KS in PLWH is multifactorial, HIV-associated SIA might be among the key drivers in coinfections with HHV8 and is independent of the patients' viremic status.

Unusual herpetic reactivation in a young female following botox injection: a case report study.

BACKGROUND: Botox injections are commonly used for cosmetic and therapeutic purposes because they temporarily paralyze muscles, reduce wrinkles, and alleviate certain medical conditions. Although generally considered safe and effective, Botox injections may cause potential complications. While herpes reactivation is more commonly associated with immunosuppressive therapies, such as chemotherapy or corticosteroid use, its association with Botox injection is poorly documented. CASE PRESENTATION: A 33-year-old woman presented with progressive painful rashes and vesicles on her forehead, scalp, and right upper eyelid, accompanied by fever and malaise following a Botox injection to treat wrinkles. A positive Tzanck smear test result confirmed the diagnosis of herpes infection. The patient was treated with antiviral medication, and her symptoms gradually regressed over several days. CONCLUSIONS: Although herpes reactivation is more commonly associated with immunosuppressive therapies, few cases of herpes zoster and herpes simplex following Botox injection have been reported. The pathogenesis of herpes reactivation following Botox injection is unclear; however, it has been hypothesized that the Botox protein is a potent antigen that may activate the cellular immune system, making it easier for the virus to reactivate. Healthcare providers should be aware of this potential complication and consider it when evaluating patients who present with painful rashes following Botox injections. In addition, individuals who want to receive Botox injections should be informed of this complication. The diagnosis of herpetic infection should be made promptly, and antiviral therapy should be initiated to minimize the risk of complications. Further research is needed to better understand the pathogenesis and risk factors for herpes following Botox injection and to develop strategies for preventing and managing this complication.

Preexisting helminth challenge exacerbates infection and reactivation of gammaherpesvirus in tissue resident macrophages.

Even though gammaherpesvirus and parasitic infections are endemic in parts of the world, there is a lack of understanding about the outcome of coinfection. In humans, coinfections usually occur sequentially, with fluctuating order and timing in different hosts. However, experimental studies in mice generally do not address the variables of order and timing of coinfections. We sought to examine the variable of coinfection order in a system of gammaherpesvirus-helminth coinfection. Our previous work demonstrated that infection with the intestinal parasite, Heligmosomoides polygyrus, induced transient reactivation from latency of murine gammaherpesvirus-68 (MHV68). In this report, we reverse the order of coinfection, infecting with H. polygyrus first, followed by MHV68, and examined the effects of preexisting parasite infection on MHV68 acute and latent infection. We found that preexisting parasite infection increased the propensity of MHV68 to reactivate from latency. However, when we examined the mechanism for reactivation, we found that preexisting parasite infection increased the ability of MHV68 to reactivate in a vitamin A dependent manner, a distinct mechanism to what we found previously with parasite-induced reactivation after latency establishment. We determined that H. polygyrus infection increased both acute and latent MHV68 infection in a population of tissue resident macrophages, called large peritoneal macrophages. We demonstrate that this population of macrophages and vitamin A are required for increased acute and latent infection during parasite coinfection.

Human herpesvirus-8 infection in Tunisian adult acute leukemia patients.

Background: Human herpesvirus 8 (HHV-8) has been linked to the development of Kaposi's sarcoma (KS)and multiple other hematologic malignant disorders. However, the role of HHV-8 in acute leukemia patients is unknown. Objectives: The objective of this study was to determine the prevalence of HHV-8 in Tunisian acute leukemia patients and in healthy blood donors. Methods: An indirect immunofluorescence test was used to detect the presence of anti-HHV8 antibodies. Nested PCR was used for the detection of HHV-8 DNAemia in samples of plasma. Results: The seroprevalence of HHV-8 was significantly higher in acute leukemia patients (21,4% ,15/70) than in healthy blood donors (7,1%, 5/70), (p= 0.02). Gender, type of disease, status of disease, prior blood transfusion, and outcome were not associated with HHV-8 seroprevalence. However, among acute leukemia patients, HHV-8 seroprevalence was statistically associated with older age > 40 years of age, (p=0.002). HHV-8 DNAemia was detected (1,4%) in only one patient of acute myeloid leukemia (AML) and none of the healthy blood donors. Conclusions: The seroprevalence of HHV-8 infection in Tunisian adult acute leukemia patients was three times as high compared to healthy blood donors, suggesting that patients with acute leukemia might be at increased risk of HHV-8 infection.

HHV-6 infections in hospitalized young children of Gabon.

PURPOSE: Fever is a common cause for hospitalization among the pediatric population. The spectrum of causative agents is diverse. Human herpesvirus 6 (HHV-6) is a ubiquitous virus that often causes hospitalization of children in western countries. Previously, we investigated the cause of fever of 600 febrile hospitalized children in Gabon, and in 91 cases the causative pathogen was not determined. In this study, we assessed HHV-6 infection as potential cause of hospitalization in this group. METHODS: Blood samples were assessed for HHV-6 using real-time quantitative PCR. Three groups were investigated: (1) group of interest: 91 hospitalized children with febrile illness without a diagnosed causing pathogen; (2) hospitalized control: 91 age-matched children hospitalized with febrile illness with a potentially disease-causing pathogen identified; both groups were recruited at the Albert Schweitzer Hospital in Lambaréné, Gabon and (3) healthy control: 91 healthy children from the same area. RESULTS: Samples from 273 children were assessed. Age range was two months to 14 years, median (IQR) age was 36 (12-71) months; 52% were female. HHV-6 was detected in 64% (58/91), 41% (37/91), and 26% (24/91) of the samples from groups 1, 2, and 3, respectively; with statistically significant odds of being infected with HHV-6 in group 1 (OR = 4.62, 95% CI [2.46, 8.90]). Only HHV-6B was detected. CONCLUSIONS: Although tropical diseases account for a large proportion of children's hospitalizations, considering common childhood diseases such as HHV-6 when diagnosing febrile illnesses in pediatric populations in tropical countries is of importance.