Parvovirus B19 Myocarditis: Looking Beyond the Heart.

Human parvovirus B19 represents the most common etiology of myocarditis in the pediatric population. Although it usually causes a benign exanthematic viral infection, parvovirus B19 may also present as disseminated disease with tropism for the myocardium, causing heart failure with high mortality. We present the case of a 2-year-old patient with fulminating acute myocarditis in whom the histological, immunophenotypic, and microbiological findings in necropsy showed multiorgan involvement caused by parvovirus B19. The autopsy revealed changes due to infection with parvovirus B19 as well as hypoxic-ischemic and secondary autoimmune changes. Medullary aplasia was observed, transmural lymphocyte myocarditis, lymphocytosis in the dermis with endothelial cells positive for parvovirus B19 in immunohistochemistry, cholestatic hepatitis due to ischemia and autoimmune hepatitis, lymphadenitis, and signs of hemophagocytosis. We also found hypoxic-ischemic encephalopathy.

Severe Symptomatic Primary Human Cytomegalovirus Infection despite Effective Innate and Adaptive Immune Responses.

Primary human cytomegalovirus (HCMV) infection usually goes unnoticed, causing mild or no symptoms in immunocompetent individuals. However, some rare severe clinical cases have been reported without investigation of host immune responses or viral virulence. In the present study, we investigate for the first time phenotypic and functional features, together with gene expression profiles in immunocompetent adults experiencing a severe primary HCMV infection. Twenty primary HCMV-infected patients (PHIP) were enrolled, as well as 26 HCMV-seronegative and 39 HCMV-seropositive healthy controls. PHIP had extensive lymphocytosis marked by massive expansion of natural killer (NK) and T cell compartments. Interestingly, PHIP mounted efficient innate and adaptive immune responses with a deep HCMV imprint, revealed mainly by the expansion of NKG2C+ NK cells, CD16+ Vδ2(-) γδ T cells, and conventional HCMV-specific CD8+ T cells. The main effector lymphocytes were activated and displayed an early immune phenotype that developed toward a more mature differentiated status. We suggest that both massive lymphocytosis and excessive lymphocyte activation could contribute to massive cytokine production, known to mediate tissue damage observed in PHIP. Taken together, these findings bring new insights into the comprehensive understanding of immune mechanisms involved during primary HCMV infection in immunocompetent individuals.IMPORTANCE HCMV-specific immune responses have been extensively documented in immunocompromised patients and during in utero acquisition. While it usually goes unnoticed, some rare severe clinical cases of primary HCMV infection have been reported in immunocompetent patients. However, host immune responses or HCMV virulence in these patients has not so far been investigated. In the present study, we show massive expansion of NK and T cell compartments during the symptomatic stage of acute HCMV infection. The patients mounted efficient innate and adaptive immune responses with a deep HCMV imprint. The massive lymphocytosis could be the result of nonadapted or uncontrolled immune responses limiting the effectiveness of the specific responses mounted. Both massive lymphocytosis and excessive lymphocyte activation could contribute to massive cytokine production, known to mediate tissue damage. Furthermore, we cannot exclude a delayed immune response caused by immune escape established by HCMV strains.

Syndrome of transient headache and neurological deficits with cerebrospinal fluid lymphocytosis (HaNDL): A case report with serial electroencephalography (EEG) recordings.. Is there an association with human herpes virus type 7 (HHV-7) infection?

Introduction The syndrome of transient headache and neurological deficits with cerebrospinal fluid lymphocytosis (HaNDL) is a diagnosis made by exclusion. In the literature, different etiological explanations are proposed for HaNDL, including an immune-mediated reaction after a viral infection. Case description We present a case of a 23-year-old woman with several episodes of transient headache, neurological deficits and cerebrospinal fluid lymphocytosis. All diagnostic criteria for the HaNDL syndrome were fulfilled; however, additional cerebrospinal fluid analysis showed a positive polymerase chain reaction (PCR) for human herpes virus type 7 (HHV-7). Discussion The possible role of a (prodromal) viral infection in the etiology of HaNDL is discussed. Also the role of electroencephalography (EEG) recordings is discussed. Serial EEG recordings showed generalized slowing, frontal intermittent rhythmic delta activity (FIRDA) and symmetric triphasic frontal waves with a dilation lag.

HTLV-2 APH-2 expression is correlated with proviral load but APH-2 does not promote lymphocytosis.

We recently discovered the antisense protein of human T-cell leukemia virus (HTLV) type 2 (APH-2), whose messenger RNA is encoded by the antisense strand of the HTLV-2 genome. We quantified proviral load, level of tax, and APH-2 in a series of blood samples obtained from a cohort of HTLV-2 carriers. We determined whether APH-2 promotes cell proliferation. APH-2 was detectable in most samples tested and was correlated with proviral load. APH-2 levels were not correlated with lymphocyte count in vivo, consistent with the inability of APH-2 to promote cell proliferation in vitro. APH-2 does not promote cell proliferation and does not cause lymphocytosis.

Cyclosporine-induced immune suppression alters establishment of HTLV-1 infection in a rabbit model.

Human T-lymphotropic virus type 1 (HTLV-1) infection causes adult T-cell leukemia and several lymphocyte-mediated inflammatory diseases. Persistent HTLV-1 infection is determined by a balance between host immune responses and virus spread. Immunomodulatory therapy involving HTLV-1-infected patients occurs in a variety of clinical settings. Knowledge of how these treatments influence host-virus relationships is not understood. In this study, we examined the effects of cyclosporine A (CsA)-induced immune suppression during early infection of HTLV-1. Twenty-four New Zealand white rabbits were split into 4 groups. Three groups were treated with either 10 or 20 mg/kg CsA or saline before infection. The fourth group was treated with 20 mg/kg CsA 1 week after infection. Immune suppression, plasma CsA concentration, ex vivo lymphocyte HTLV-1 p19 production, anti-HTLV-1 serologic responses, and proviral load levels were measured during infection. Our data indicated that CsA treatment before HTLV-1 infection enhanced early viral expression compared with untreated HTLV-1-infected rabbits, and altered long-term viral expression parameters. However, CsA treatment 1 week after infection diminished HTLV-1 expression throughout the 10-week study course. Collectively, these data indicate immunologic control is a key determinant of early HTLV-1 spread and have important implications for therapeutic intervention during HTLV-1-associated diseases.

Changing haematological parameters in dengue viral infections.

BACKGROUND: Dengue Fever is the most common arboviral disease in the world, and presents cyclically in tropical and subtropical regions of the world. The four serotypes of dengue virus, 1, 2, 3, and 4, form an antigenic subgroup of the flaviviruses (Group B arboviruses). Transmission to humans of any of these serotypes initiates a spectrum of host responses, from in apparent to severe and sometimes lethal infections. Complete Blood count (CBC) is an important part of the diagnostic workup of patients. Comparison of various finding in CBC including peripheral smear can help the physician in better management of the patient. MATERIAL AND METHODS: This cross sectional study was carried out on a series of suspected patients of Dengue viral infection reporting in Ittefaq Hospital (Trust). All were investigated for serological markers of acute infection. RESULTS: Out of 341 acute cases 166 (48.7%) were confirmed by IgM against Dengue virus. IgG anti-dengue was used on 200 suspected re-infected patients. Seventy-one (39.5%) were positive and 118 (59%) were negative. Among 245 confirmed dengue fever patients 43 (17.6%) were considered having dengue hemorrhagic fever on the basis of lab and clinical findings. Raised haematocrit, Leukopenia with relative Lymphocytosis and presence atypical lymphocytes along with plasmacytoid cells was consistent finding at presentation in both the patterns of disease, i.e., Dengue Haemorrhagic fever (DHF) and Dengue fever (DF). CONCLUSION: Changes in relative percentage of cells appear with improvement in the symptoms and recovery from the disease. These findings indicate that in the course of the disease, there are major shifts within cellular component of blood.

Viruses and salivary gland disease (SGD): lessons from HIV SGD.

Viral infections are often associated with salivary gland pathology. Here we review the pathogenesis of HIV-associated salivary gland disease (HIV-SGD), a hallmark of diffuse infiltrative lymphocytosis syndrome. We investigate the presence and contributions of viral diseases to the pathogenesis of salivary gland diseases, particularly HIV-SGD. We have detected BK viral shedding in the saliva of HIV-SGD patients consistent with viral infection and replication, suggesting a role for oral transmission. For further investigation of BKV pathogenesis in salivary glands, an in vitro model of BKV infection is described. Submandibular (HSG) and parotid (HSY) gland salivary cell lines were capable of permissive BKV infection, as determined by BKV gene expression and replication. Analysis of these data collectively suggests the potential for a BKV oral route of transmission and salivary gland pathogenesis within HIV-SGD.

Clinical and demographic characteristics of patients with COVID-19 infection: Statistics from a single hospital in Iran.

Coronavirus disease 2019 (COVID-19) has caused a global pandemic in early 2020. This infectious disorder has a heterogeneous course ranging from asymptomatic disorder to a critical situation needing intensive cares. In the current study, we present a report of affected patients admitted in a single hospital in Iran. Eighty-two hospitalized patients with COVID-19 were assessed. Demographic, clinical, and paraclinical parameters were gathered and statistically analyzed. The median age (IQR) of the patients was 57.32 (45.75, 70) years. At primary evaluation, fever was present in 45.12% of the affected individuals. The most common clinical symptoms were dyspnea (81.71%) and cough (65.85%). Totally, 12 (14.63%) and 14 (17.07%) of patients had low and high WBC counts, respectively. Lymphopenia was detected in 36 (43.9%) of patients, while 6 (7.32%) of patients had lymphocytosis. High levels of Il-6 were detected in 4 (4.88%) of patients. CRP levels were elevated in 69 (84.1%) of patients. The median (IQR) of hospitalization was 7 (5, 9) days. Totally, 26 patients (31%) were hospitalized in ICU. All patients were discharged with good health conditions except for one patient who died. The current study shows the heterogeneous clinical manifestations and paraclinical parameters of COVID-19 patients.

Expanded cells in monoclonal TCR-alphabeta+/CD4+/NKa+/CD8-/+dim T-LGL lymphocytosis recognize hCMV antigens.

Recent studies suggest the potential involvement of common antigenic stimuli on the ontogeny of monoclonal T-cell receptor (TCR)-alphabeta(+)/CD4(+)/NKa(+)/CD8(-/+dim) T-large granular lymphocyte (LGL) lymphocytosis. Because healthy persons show (oligo)clonal expansions of human cytomegalovirus (hCMV)-specific TCRVbeta(+)/CD4(+)/cytotoxic/memory T cells, we investigate the potential involvement of hCMV in the origin and/or expansion of monoclonal CD4(+) T-LGL. Peripheral blood samples from patients with monoclonal TCR-alphabeta(+)/CD4(+) T-LGL lymphocytosis and other T-chronic lymphoproliferative disorders were evaluated for the specific functional response against hCMV and hEBV whole lysates as well as the "MQLIPDDYSNTHSTRYVTVK" hCMV peptide, which is specifically loaded in HLA-DRB1*0701 molecules. A detailed characterization of those genes that underwent changes in T-LGL cells responding to hCMV was performed by microarray gene expression profile analysis. Patients with TCR-alphabeta(+)/CD4(+) T-LGL displayed a strong and characteristic hCMV-specific functional response, reproduced by the hCMV peptide in a subset of HLA-DRB1*0701(+) patients bearing TCRVbeta13.1(+) clonal T cells. Gene expression profile showed that the hCMV-induced response affects genes involved in inflammatory and immune responses, cell cycle progression, resistance to apoptosis, and genetic instability. This is the first study providing evidence for the involvement of hCMV in the ontogeny of CD4(+) T-LGL, emerging as a model disorder to determine the potential implications of quite a focused CD4(+)/cytotoxic immune response.

COVID-19 in children: a case series from Nigeria.

INTRODUCTION: The global spread of COVID-19 remains unabated in the past few months with a rise in the number of available literature on the novel virus. There are very few paediatric studies and are mainly from developed countries with a paucity of information on the clinical manifestation of COVID-19 disease in African children, including Nigeria. METHODS: We described the clinical presentation, laboratory findings, treatment and outcome in a group of five Nigerian children managed at a COVID-19 isolation and treatment centre in Nigeria. RESULTS: We managed a total of five children with an age range of 3 months to 8 years in the last four weeks (16th April to 15th May 2020). Three of the five children were males. All the children had close contact with family members that tested positive for COVID-19. Out of the five children, one had moderate disease, three had mild symptomatic disease, and one was asymptomatic. Two out of the five children had lymphocytosis. Out of the four children who had chest radiograph, two had features of pneumonia. CONCLUSION: COVID-19 is not uncommon in Nigerian children, and all had a confirmed family member with COVID-19. Besides, contrary to leucopaenia with lymphopaenia observed in the adult's population, we found lymphocytosis in this cohort and about 50.0% had pneumonic changes on chest radiograph.

No effects of noncytopathic bovine viral diarrhea virus type 2 on the reproductive tract of experimentally inoculated boars.

Bovine viral diarrhea virus (BVDV) infections in pigs may result in transient leukopenia, chronic gastroenteritis, septicemia, and hemorrhagic lesions. Both classical swine fever virus (CSF) and the atypical porcine pestivirus (APPV) are shed in the semen of infected boars. Because these viruses share conserved regions and present antigenic similarity, they may not be the only species belonging to the genus Pestivirus that can be shed in the semen of infected pigs. The objective of this study was to evaluate the testicular and epididymal changes, seminal parameters, and viral shedding in the reproductive tract of boars experimentally inoculated with noncytopathic BVDV-2. Six males were selected, and samples of blood, semen, and preputial swabs were collected every four days until the 52nd day after inoculation. The samples were tested for the presence of viral RNA by RT-PCR. An aliquot of whole blood was used to perform hematological analyses, which showed a significant reduction in monocyte counts and a significant increase in lymphocyte counts when comparing the pre- and postinoculation periods. The neutralizing antibody titers were determined by the virus neutralization test. None of the animals presented clinical signs or worsening of the seminal parameters that were evaluated. Moreover, BVDV-2 shedding by the reproductive route was not observed.

[Characterization of B1-cells during experimental leukomogenesis.]

BACKGROUND: Bovine leukemia causes a significant polyclonal expansion of CD5+, IgM+ B lymphocytes, known as persistent lymphocytosis (PL), in approximately 30% of infected cattle. However, it is not yet clear what happens to this subpopulation of B cells in the early period of infection of animals. PURPOSE: Quantitative characterization of IgM+ and CD5+ B cells during the immune response, which can provide important information on the mechanisms of lymphocyte priming in BLV infection. MATERIAL AND METHODS: The experiment used BLV-negative calves of black-motley breed at the age of 8 months (n = 11). Animals (n = 8) were intravenously injected with blood of a BLV-positive cow. Control calves (n = 3) were injected with saline. Studies were performed before and after infection on days 5, 7, 14, 21, 28 and 65 of the immune response. The determination of the number of B-lymphocytes in the blood was carried out by the method of immunoperoxidase staining based on monoclonal antibodies to IgM, CD5. RESULTS: As a result of the studies, it was found that the level of CD5+ B cells increases on the 14th day of the primary immune response, characterized by polyclonal proliferation of CD5+ B cells, which are the primary target for BLV. Our research data confirm that in the lymphocytes of experimentally infected cattle, surface aggregation of IgM and CD5 molecules on B-lymphocytes is absent. DISCUSSION: It is known that the wave-like nature of IgM synthesis, which was shown in previous studies, depends on a subpopulation of B1 cells. After 7 days of the immune response, IgM+ and CD5+ cells do not correlate, which shows their functional difference. The increase in CD5+ cells is probably not associated with B cells, but with T cells differentiating under the influence of the virus. CONCLUSIONS: A subset of B1 cells is the primary target of cattle leukemia virus. The 65th day of the immune response is characterized by the expansion of IgM+ B cells, a decrease in the number of CD5+ cells and a uniform distribution of receptors around the perimeter of the cells.

Clinical features and laboratory findings in children hospitalized with acute Epstein-Barr virus infection: a crosssectional study in a tertiary care hospital.

Çaglar I, Topal S, Çokboz M, Düzgöl M, Kara A, Bayram SN, Apa H, Devrim I. Clinical features and laboratory findings in children hospitalized with acute Epstein-Barr virus infection: a cross-sectional study in a tertiary care hospital. Turk J Pediatr 2019; 61: 368-373. Epstein-Barr virus (EBV) is widespread all over the world. It causes infectious mononucleosis (IM) mostly in adolescents and adults. Although IM is considered to be rare in younger children and infants, acute EBV infection may have various manifestations in this age group. We aimed to describe the clinical features and laboratory findings of children hospitalized with acute EBV infection. All children hospitalized at Dr. Behçet Uz Children`s Hospital, between January 2010 and January 2017, who tested positive by presence of EBV-specific antibodies and had the diagnosis of acute EBV infection, were included (n=66). Thirty four of the patients (51.5%) were under 6 years of age, and 23 (34.8%) children were below 3 years of age. The most common physical finding was fever (92.4%) followed by cervical lymphadenopathy and tonsillopharyngitis. Leukocytosis (65.1%) and lymphocytosis (42.4%) were the most common laboratory findings. Reactive and atypical lymphocytes were present in 77.2% of the patients. Fifty-three (80.3%) of the patients had a doctor visit before hospitalization, and the ratio of patients using antibiotics was 77.3%. Skin rash was observed in 14 (27.4%) of the patients who used antibiotic treatment and in 2 (13.3%) of the patients who did not (p > 0.05). EBV infection resulting in admission to hospital is common in younger children, even in pre-school period. Serological tests for EBV specific antibody responses and peripheral blood smear evaluation are important diagnostic tools. In addition, rapid streptococcal antigen test and throat culture should be performed in patients presenting with tonsillopharyngitis in order to exclude Group A beta-hemolytic streptococci and reduce unnecessary antibiotic consumption.

Concomitant EBV-related B-cell proliferation and juvenile myelomonocytic leukemia in a 2-year-old child.

We present a case of a 2-year-old girl, who developed concomitant EBV-related B-cell proliferation and juvenile myelomonocytic leukemia (JMML). JMML was initially not recognized because of predominant B-cell proliferation. The activating N-RAS mutation was retrospectively already detectable at this early stage. Our findings support the hypothesis that EBV may contribute to JMML pathogenesis by stimulating pre-existing malignant clones. However, such stimulation of leukemic clone does not require the direct incorporation of the virus into myeloid progenitors. Most probably a cytokine burst resulting from EBV infection allows expansion of pre-existing malignant myeloid progenitors. Further studies are required to delineate exact mechanisms of EBV-related promotion of the JMML clone.

Determination of proviral load in bovine leukemia virus-infected cattle with and without lymphocytosis.

OBJECTIVE: To determine proviral load in bovine leukemia virus (BLV)-infected cattle with and without persistent lymphocytosis to assess the potential of transmitting the virus. ANIMALS: Cattle in 6 dairy herds. PROCEDURES: Blood samples from infected cows were evaluated 3 times at 6-month intervals for determination of proviral load via PCR assay, serologic results via ELISA, and hematologic status via differential cell counts. RESULTS: Infected cattle were classified into lymphocytotic and nonlymphocytotic groups. Lymphocytotic cattle consistently had > 100,000 copies of integrated provirus/mug of DNA (ie, high proviral load) in peripheral blood leukocytes. Titers of antibodies against BLVgp51 and BLVp24 indicated a strong immune response. Nonlymphocytotic cattle comprised 2 subgroups: a group with high proviral load and strong immune response, and a group with a weaker immune response, mostly against BLVp24, and a proviral load of < 100 copies/microg of DNA (ie, low proviral load). CONCLUSIONS AND CLINICAL RELEVANCE: Results emphasized the importance of characterizing nonlymphocytotic BLV-infected cattle during eradication programs. The risk of transmitting BLV infection from nonlymphocytotic cattle may differ depending on the proviral load. Nonlymphocytotic cattle with high proviral load could be efficient transmitters (as efficient as lymphocytotic cattle), whereas nonlymphocytotic cattle with low proviral load could be inefficient transmitters under standard husbandry conditions. Because most cattle with low proviral load do not develop anti-BLVp24 antibodies, it appears that lack of an anti-BLVp24 antibody response may be a good marker of this condition.

Prolonged lymphocytosis as the first manifestation of Hodgkin-like adult T-cell leukemia/lymphoma.

Hodgkin-like ATLL is a rare variant of adult T-cell leukemia/lymphoma (ATLL), a disease caused by human T-cell lymphotropic virus type-1 (HTLV-1). At admission, a 46-year-old female presented with lymphadenomegaly, lymphocytosis, slight elevation of LDH blood level, and acid-alcohol resistant bacilli in sputum and was being treated for pulmonary tuberculosis (Tb). She had lymphocytosis in the previous 20 months. Serology for HTLV-1 was positive. Lymph node was infiltrated by medium-sized lymphocytes with scattered Hodgkin and Reed-Sternberg-like cells CD30+, CS1-4+, and CD79a+. Background cells were CD4+ and CD25+. A clinical diagnosis of favorable chronic ATLL was given. She was treated with chemotherapy but later progressed to acute ATLL and ultimately died. Hodgkin-like ATLL should be considered in the histological differential diagnosis with Hodgkin lymphoma since treatment and prognosis of these diseases are distinct. It is also important to search for HTLV-1 infection in patients with unexplained prolonged lymphocytosis.

Expression of tumor necrosis factor-alpha in IgM+ B-cells from bovine leukemia virus-infected lymphocytotic sheep.

Tumor necrosis factor (TNF)-alpha is thought to be one of the cytokines that account for bovine leukemia virus (BLV)-induced B-cell lymphoproliferative disorder, however, information on TNF-alpha expression in B-cells is limited. In this study, the expression of TNF-alpha in IgM(+) B-cells from BLV-infected sheep with or without lymphocytosis was determined. Freshly isolated IgM(+) B-cells from three sheep with lymphocytosis constitutively transcribed TNF-alpha mRNA. Although TNF-alpha mRNA expression in IgM(+) B-cells was transiently up-regulated after cell culture, TNF-alpha mRNA expression was markedly higher in lymphocytotic sheep when compared to that of non-lymphocytotic sheep or uninfected sheep. Expression of membrane-bound TNF-alpha on IgM(+) B-cells was also augmented in lymphocytotic sheep. TNF-alpha expression in lymphocytotic sheep may support the proliferation of B-cells.

Acute lymphoblast leukemia in sheep induced by inoculation of bovine leukemia virus: diagnostic electron microscopic morphological study.

Six control lambs were inoculated with Tris buffer, 7 lambs were inoculated with an early passage of bovine leukemia virus (B.L.V.) culture, and 7 lambs with a late passage B.L.V. All experimental lambs were positive with the agar gel immunodiffusion assay (AGID) within 3 months of inoculation and remained positive throughout the 8-year duration of the experiment. The earliest onset of leukemia was at 14 months and the latest was at 44 months after inoculation. Five lambs died with leukemia, two were inoculated with early passage, and three were inoculated with late passage of B.L.V. Eight years after the inoculation, the remaining nine inoculated lambs were clinically normal. The diagnostic ultrastructural morphology of the leukemic lymphoblasts in this study were characterized by hand-mirror cells, multiple nucleoli, irregular nuclear contour with deep indentions, electron-dense granules in the euchromatin, and nuclear cytoplasmic pockets, nuclear myelin figures, mitochondrial variation in size and density, disruption of rough endoplasmic reticulum, and increased ribosomal density. This study shows abundant cytoplasmic processes of hairy cell leukemia. The nuclei of the leukemia lymphoblasts showed electron-dense granules of varying sizes, which were not seen in any of the normal lymphoblasts.

Serological and molecular detection of bovine leukemia virus in cattle in Iraq.

Bovine leukemia virus (BLV) is highly endemic in many countries, including Iraq, and it impacts the beef and dairy industries. The current study sought to determine the percentage of BLV infection and persistent lymphocytosis (PL) in cattle in central Iraq. Hematological, serological, and molecular observations in cross breeds and local breeds of Iraqi cattle naturally infected with BLV were conducted in the peripheral blood mononuclear cells of 400 cattle (340 cross breed and 60 local breed) using enzyme-linked immunosorbent assay and polymerase chain reaction (PCR). On the basis of the absolute number of lymphocytes, five of the 31 positive PCR cases had PL. Among these leukemic cattle, one case exhibited overt neutrophilia. Serum samples were used to detect BLV antibodies, which were observed in 28 (7%) samples. PCR detected BLV provirus in 31 samples (7.75%). All 28 of the seropositive samples and the 3 seronegative samples were positive using PCR. Associations were observed between bovine leukosis and cattle breed, age and sex. Age-specific analysis showed that the BLV percentage increased with age in both breeds. Female cattle (29 animals; 7.34%) exhibited significantly higher infectivity than male cattle (two animals; 4.34%). In conclusion, comprehensive screening for all affected animals is needed in Iraq; programs that segregate cattle can be an effective and important method to control and/or eliminate the BLV.