Burkitt’s lymphoma is a very fast growing form of non-Hodgkin’s lymphoma, a cancer in the lymphatic system.
Distinguish between the three variants of Burkitt’s lymphoma: endemic, sporadic and immunodeficiency-associated
- Burkitt’s lymphoma was first discovered in children in certain parts of Africa by surgeon Denis Parsons Burkitt, but also occurs in the United States.
- There are three types of Burkitt’s lymphoma: endemic, the sporadic and the immunodeficiency-associated. The endemic type is closely associated with the Epstein-Barr virus (EBV), the main cause of infectious mononucleosis.
- Burkitt’s lymphoma usually develops in the abdomen and spreads to other organs, including the brain. It may first be noticed as a swelling of the lymph nodes (glands) in the neck, groin, or under the arm.
- Chemotherapy and various drugs are used to treat this type of cancer.
- lymph: A colourless, watery, bodily fluid carried by the lymphatic system, that consists mainly of white blood cells.
- lymphoma: A malignant tumor that arises in the lymph nodes or in other lymphoid tissue.
- Non-Hodgkin’s lymphoma: The non-Hodgkin lymphomas are a diverse group of blood cancers that include any kind of lymphoma, except cancers originating from white blood cells called lymphocytes.
Burkitt’s lymphoma is a form of non-Hodgkin’s lymphoma, a cancer of the lymphatic system (in particular, B lymphocytes). It is named after Denis Parsons Burkitt, a surgeon who first described the disease in 1956 while working in equatorial Africa. Burkitt’s lymphoma usually develops in the abdomen and spreads to other organs, including the brain. Burkitt’s lymphoma involves B-cells and is a rapidly growing cancer. Of all cancers involving the same class of blood cell, 2% of cases are Burkitt’s lymphoma.
Currently Burkitt’s lymphoma can be divided into three main clinical variants:
- Endemic: This variant occurs in equatorial Africa. It is the most common malignancy affecting children in this area. Children affected with the disease often also have chronic malaria, which is believed to have reduced resistance to Epstein-Barr virus (EBV), allowing it to take hold. The disease characteristically involves the jaw or other facial bone, distal ileum, cecum, ovaries, kidney or the breast.
- Sporadic: This variant type, also known as “non-African” is found outside of Africa. The tumor cells have a similar appearance to that of endemic Burkitt lymphoma. Again it is believed that impaired immunity provides an opening for development of the Epstein-Barr virus. The jaw is less commonly involved, compared to the endemic variant. The ileo-cecal region is the common site of involvement.
- Immunodeficiency-associated: Immunodeficiency-associated Burkitt lymphoma is usually associated with HIV infection or occurs in the setting of post-transplant patients who are taking immunosuppressive drugs. Burkitt lymphoma can be one of the diseases associated with the initial manifestation of AIDS.
By morphology (i.e. microscopic appearance) or immunophenotype, it is almost impossible to differentiate these three clinical variants. Immunodeficiency-associated Burkitt lymphoma may demonstrate more plasmacytic appearance or more pleomorphism, but these features are not specific.
Symptoms and Treatment
Burkitt lymphoma may first be noticed as a swelling of the lymph nodes (glands) in the neck, groin, or under the arm. These swollen lymph nodes are often painless, but can grow very rapidly. In the types commonly seen in the United States, the cancer usually starts in the belly area (abdomen). The disease can also start in the ovaries, testes, brain, and spinal fluid. Symptoms include fever, night sweats, unexplained swollen lymph nodes, and unexplained weight loss.
Chemotherapy is used to treat this type of cancer. Commonly used medicines include prednisone, cyclophosphamide, doxorubicin, ifosfamide, vincristine, cytarabine, methotrexate, rituximab, and etoposide. Other treatments are immunotherapy, bone marrow transplants, stem cell transplant, surgery to remove the tumor, and radiotherapy.
Mononucleosis is an infectious disease caused by the Epstein-Barr virus (EBV) and results in flu-like symptoms.
Describe infectious mononucleosis
- Infectious mononucleosis is an infectious disease caused by the Epstein-Barr virus (EBV).
- Infectious mononucleosis (also called mono or kissing disease) is spread orally and is characterized by symptoms such as fever, sore throat, and fatigue.
- Once infected, the virus lives dormantly in B lymphocytes in a person.
- Epstein-Barr virus (EBV): Virus responsible for causing infectious mononucelosis.
- infectious mononucleosis: An infectious, widespread viral disease caused by the Epstein–Barr virus (EBV), one type of herpes virus. Most people are exposed to the virus as children, when the disease produces no noticeable or only flu-like symptoms.
Infectious mononucleosis is an infectious, widespread viral disease caused by the Epstein–Barr virus (EBV), one type of herpes virus, to which more than 90% of adults have been exposed. Occasionally, the symptoms can recur at a later period. It is sometimes colloquially known as the “kissing disease” from its oral transmission. Most people are exposed to the virus as children, when the disease produces no noticeable or only flu-like symptoms. In developing countries, people are exposed to the virus in early childhood more often than in developed countries. As a result, the disease in its observable form is more common in developed countries. It is most common among adolescents and young adults.
The disease is characterized by fever, sore throat, and fatigue, along with several other possible signs and symptoms, especially in adolescents and young adults. The infection is spread via saliva and has an incubation period of four to seven weeks. Symptoms usually persist for two to three weeks, but fatigue is often more prolonged. Infectious mononucleosis is primarily diagnosed by observation of symptoms, but suspicion can be confirmed by several diagnostic tests. The most commonly used diagnostic criterion is the presence of 50% lymphocytes with at least 10% atypical lymphocytes (large, irregular nuclei), while the person also has fever, pharyngitis, and adenopathy. Infectious mononucleosis is generally self-limiting, so only symptomatic and/or supportive treatments are used. Rest is recommended during the acute phase of the infection.
Once the acute symptoms of an initial infection disappear, they often do not return. But once infected, the patient carries the virus for the rest of his or her life. The virus typically lives dormantly in B lymphocytes. Independent infections of mononucleosis may be contracted multiple times, regardless of whether the patient is already carrying the virus dormantly.
Other Diseases and Epstein-Barr Virus
Epstein-Barr virus (EBV) is a member of the herpesvirus family and is best known as the cause of infectious mononucleosis.
Distinguish between the lytic replicative and latency cycle of the Epstein-Barr virus infection cycle and discuss the prevalence of Epstein-Barr virus infected humans
- The Epstein–Barr virus (EBV), is a very common virus and infects about 95% of all people in the United States.
- EBV can result in fever, sore throat, pharyngitis, and lymphadenopathy. Together, these symptoms are called infectious mononucleosis.
- An EBV infection can occur in two forms; a lytic replicative stage where it replicates its viral genome and produces gene products to help the virus evade the immune system and a latent stage where it remains undetected until reactivation.
- epithelial cells: cells that are part of the membranous tissue which form the covering of most internal and external surfaces of the body and its organs; internally including the lining of vessels and other small cavities, and externally being the skin.
- lytic cycle: The normal process of viral reproduction involving penetration of the cell membrane, nucleic acid synthesis, and lysis of the host cell.
- B cell: a lymphocyte, developed in the bursa of birds and the bone marrow of other animals, that produces antibodies and is responsible for the immune system.
The Epstein–Barr virus (EBV), also called human herpesvirus 4 (HHV-4), is a virus of the herpes family, and is one of the most common viruses in humans. EBV infection, which occurs by oral transfer of the saliva, results in infectious mononucleosis (glandular fever). It is also associated with particular forms of cancer, such as Hodgkin’s lymphoma, Burkitt’s lymphoma, nasopharyngeal carcinoma, and central nervous system lymphomas associated with HIV. There is evidence that infection with the virus is associated with a higher risk of certain autoimmune diseases, especially dermatomyositis, systemic lupus erythematosus, rheumatoid arthritis, Sjögren’s syndrome, and multiple sclerosis. Most people become infected with EBV and gain adaptive immunity. In the United States, about half of all five-year-old children and 90 to 95 percent of adults have evidence of previous infection. Infants become susceptible to EBV as soon as maternal antibody protection disappears. Many children become infected with EBV, and these infections usually cause no symptoms or are indistinguishable from the other mild, brief illnesses of childhood.
A mature EBV viral particle has a diameter of approximately 120 nm to 180 nm. It is composed of a double stranded, linear DNA genome enclosed by a protein capsid. The capsid is surrounded by a protein tegument, which in turn is surrounded by a lipid envelope. The EBV genome is about 192 thousand base pairs in length and contains about 85 genes. The viral envelope is embedded with glycoproteins essential to viral entry into the cell.
EBV Infection Cycle
EBV infects B cells of the immune system and epithelial cells. Once EBV enters the cell, the viral capsid dissolves and the viral genome is transported to the cell nucleus. An EBV infection can be described as being in one of two cycles; a lytic replicative cycle and a latency cycle.
The lytic cycle, or productive infection, results in the production of infectious virions. EBV can undergo lytic replication in both B cells and epithelial cells. In B cells, lytic replication normally only takes place after reactivation from latency. In epithelial cells, lytic replication often directly follows viral entry entry. For lytic replication to occur, the viral genome must be linear. The latent EBV genome is circular, so it must linearize in the process of lytic reactivation. During lytic replication, viral DNA polymerase is responsible for copying the viral genome. Unlike lytic replication for many other viruses, EBV lytic replication does not inevitably lead to lysis of the host cell because EBV virions are produced by budding from the infected cell.
Unlike lytic replication, the latent stage does not result in production of virions. Instead, the EBV genome circularizes, resides in the cell nucleus as an episome, and is copied by cellular DNA polymerase. In latency, only a portion of EBV’s genes are expressed. Latent EBV expresses its genes in one of three patterns, known as latency programs. EBV can latently persist within B cells and epithelial cells, but different latency programs are possible in the two types of cells. EBV can exhibit one of three latency programs: Latency I, Latency II, or Latency III. Each latency program leads to the production of a limited, distinct set of viral proteins and viral RNAs.
Presence and Symptoms of EBV
The EBV occurs all over the world and most people become infected with this virus at some point in their lives. When teenagers get EBV, there is a 35-50% chance that it will lead to infectious mononucleosis also known as mono. Symptoms of mono include fever, sore throat, pharyngitis, and swollen lymph glands (lymphadenopathy). Although the symptoms of infectious mononucleosis usually go away in 1-2 months, EBV remails dormant and hidden in the troat and blood cells for the rest of the person’s life.
Cytomegalovirus (CMV) is a type of herpesvirus that largely affects infants and the immunocompromised.
Describe the route of transmission and risks associated with the human cytomegalovirus (HCMV)
- Cytomegalovirus (CMV) is a viral genus of the viral family known as Herpesviridae or herpesviruses.
- CMV infections are frequently associated with the salivary glands
- HCMV is found throughout all geographic locations and socioeconomic groups, and infects between 50% and 80% of adults in the United States
- CMV is generally transmitted from infected people to others through direct contact with body fluids, such as urine, saliva, vaginal secretions, and semen.
- immunocompromised: Having an immune system that has been impaired by disease or treatment.
- Seroprevalence: Seroprevalence is the number of persons in a population who test positive for a specific disease based on serology (blood serum) specimens; often presented as a percent of the total specimens tested or as a proportion per 100,000 persons tested.
- major histocompatibility complex: MHC is a cell surface molecule that mediate interactions of immune cells with other leukocytes or body cells. MHC determines compatibility of donors for organ transplants as well as one’s susceptibility to an autoimmune disease. In humans, MHC is also called human leukocyte antigen (HLA).
Cytomegalovirus (CMV) is a viral genus of the viral family known as Herpesviridae or herpesviruses. The species that infects humans is commonly known as human CMV (HCMV) or human herpesvirus-5 (HHV-5), and is the most studied of all cytomegaloviruses. All herpesviruses can stay latent for long durations. Although they may be found throughout the body, CMV infections are frequently associated with the salivary glands in humans and other mammals. Other CMV viruses are found in several mammal species, but species isolated from animals differ from HCMV in terms of genomic structure, and have not been reported to cause human disease.
HCMV is found throughout all geographic locations and socioeconomic groups, and infects between 50% and 80% of adults in the United States (40% worldwide) as indicated by the presence of antibodies in much of the general population. Seroprevalence is age-dependent: 58.9% of individuals aged 6 and older are infected with CMV while 90.8% of individuals aged 80 and older are positive for HCMV. HCMV is also the virus most frequently transmitted to a developing fetus. HCMV infection is more widespread in developing countries and in communities with lower socioeconomic status; it represents the most significant viral cause of birth defects in industrialized countries. Major areas of risk of infection include prenatal or postnatal infants and immunocompromised individuals, such as organ transplant recipients, persons with leukemia, or those infected with human immunodeficiency virus (HIV).
CMV is generally transmitted from infected people to others through direct contact with body fluids, such as urine, saliva, vaginal secretions, and semen. Although they may be found throughout the body, HCMV infections are frequently associated with the salivary glands. HCMV infection is typically unnoticed in healthy people, but can be life-threatening for the immunocompromised, such as HIV-infected persons, organ transplant recipients, or newborn infants.
CMV, like all herpesviruses, can stay latent for long durations of time. The initial introduction of CMV generally gives way to an extended period of infection during which there is no detectable clinical illness. Severe impairment of the body’s immune system reactivates the virus from this dormant state. CMV persists in the host because the viral genome encodes multiple proteins that interfere with major histocompatibility complex (MHC) class I presentation of viral antigens. One viral protein blocks translocation of peptides into the lumen of the endoplasmic reticulum, while two other viral proteins cause degradation of MHC class I proteins before they reach the cell surface. In AIDS patients, CMV can cause loss of vision (cotton wool spots), pneumonia, and hepatitis. Transplant patients with CMV are also susceptible to pneumonia and hepatitis.
A vaccine against (CMV) is currently under investigation. Because CMV can cause congenital infection, considerable effort has been made towards the development of a vaccine, with particular emphasis on protection for pregnant women. There are currently three licensed anti-HCMV drugs target the viral DNA polymerase, pUL54. Ganciclovir (GCV) acts as nucleoside analogue. Its antiviral activity requires phosphorylation by the HCMV protein kinase, pUL97. The second drug, Cidofovir (CDV), is a nucleotide analogue, which is already phosphorylated and thus active. Finally, Foscarnet (FOS) has a different mode of action. It directly inhibits polymerase function by blocking the pyrophosphate binding site of pUL54.
Chikungunya (CHIKV) is a mosquito-borne viral disease which causes fever and severe joint pain.
Discuss the causes and symptoms associated with chikungunya virus (CHIKV)
- The chikungunya virus is transmitted from human to human by the bites of infected female mosquitoes; the Aedes aegypti and Aedes albopictus mosquitoes.
- The disease occurs in Africa, Asia and the Indian subcontinent. In recent decades mosquito vectors of CHIKV have spread to Europe and the Americas.
- There is no cure for CHIKV. Treatment is focused on relieving the symptoms which include fever and severe joint pain, muscle pain, headache, nausea, fatigue and rash.
- dengue: An acute febrile disease of the tropics caused by a flavivirus, transmitted by mosquitoes, and characterized by high fever, rash, headache, and severe muscle and joint pain.
- Aedes: Aedes is a genus of mosquito originally found in tropical and subtropical zones, but now found on all continents excluding Antarctica.
- chikungunya: A viral fever caused by an alphavirus spread by mosquito bites.
Chikungunya Virus (CHIKV)
Chikungunya (in the Makonde language “that which bends up”) virus (CHIKV) is an insect-borne virus of the genus Alphavirus, that is transmitted to humans by virus-carrying Aedes(Ae) mosquitoes. Both Ae. aegypti and Ae. albopictus have been implicated in large outbreaks of CHIKV.
CHIKV infection causes an illness with symptoms similar to dengue fever, with an acute febrile phase of the illness lasting only two to five days, followed by a prolonged arthralgic disease that affects the joints of the extremities. The pain associated with CHIKV infection of the joints persists for weeks or months or, in some cases, years. CHIKV is indigenous to tropical Africa and Asia, where it is transmitted to humans by the bite of infected mosquitoes.
SIGNS AND SYMPTOMS
The incubation period of chikungunya disease ranges from one to 12 days, but usually two to three. Its symptoms include a high fever up to 40 °C (104 °F), a petechial or maculopapular rash of the trunk and occasionally the limbs, and arthralgia or arthritis affecting multiple joints. Other nonspecific symptoms can include headache, conjunctivitis, slight photophobia and partial loss of taste. Typically, the fever lasts for two days and then ends abruptly. However, other symptoms—namely joint pain, intense headache, insomnia and an extreme degree of prostration—last for a variable period; usually for about five to seven days. Patients have complained of joint pains for much longer time periods; some for as long as two years, depending on their age.
Common laboratory tests for chikungunya include RT-PCR, virus isolation, and serological tests.
Virus isolation provides the most definitive diagnosis, but takes one to two weeks for completion and must be carried out in biosafety level-3 laboratories. The technique involves exposing specific cell lines to samples from whole blood and identifying chikungunya virus-specific responses. RT-PCR using nested-primer pairs is used to amplify several chikungunya-specific genes from whole blood. Results can be determined in one to two days. Serological diagnosis requires a larger amount of blood than the other methods, and uses an ELISA assay to measure chikungunya-specific IgM levels. Results require two to three days.
There are no specific drugs to cure the disease. Treatment is directed primarily at relieving the symptoms, especially the joint pain. There is no commercial chikungunya vaccine.
Chikungunya occurs in Africa, Asia, and the Indian subcontinent. Human infections in Africa have been at relatively low levels for a number of years, but in 1999-2000 there was a large outbreak in the Democratic Republic of the Congo, and in 2007 there was an outbreak in Gabon. Starting in February 2005, a major outbreak occurred in islands of the Indian Ocean. A large number of imported cases in Europe were associated with this outbreak, mostly in 2006 when this epidemic was at its peak.
A large outbreak of chikungunya in India occurred in 2006 and 2007. Several other countries in South-East Asia were also affected. In 2007 transmission was reported for the first time in Europe, in a localized outbreak in north-eastern Italy.
Classic Viral Hemorrhagic Fevers
Viral hemorrhagic fevers (VHFs) are a group of illnesses that are caused by several distinct families of RNA viruses.
List the types, symptoms and routes of transmission for viral hemorrhagic fevers
- VHFs are caused by viruses of four distinct families: arenaviruses, filoviruses, bunyaviruses, and flaviviruses. They are all RNA viruses covered, or enveloped, in a fatty coating.
- Viruses associated with most VHFs naturally reside in an animal host or arthropod vector. For the most part, rodents and arthropods are the main reservoirs for viruses causing VHFs.
- Symptoms include marked fever, fatigue, dizziness, muscle aches, loss of strength, exhaustion, and excessive bleeding under the skin, in internal organs, or from body orifices like the mouth, eyes, or ears.
- hemorrhagic: of, relating to, or producing excessive loss of blood or blood escape from the circulatory system.
The viral hemorrhagic (or haemorrhagic) fevers (VHFs) are a diverse group of animal and human illnesses that may be caused by five distinct families of RNA viruses: the families Arenaviridae, Filoviridae, Bunyaviridae, Flaviviridae, and Rhabdoviridae. All types of VHF are characterized by fever and bleeding disorders and all can progress to high fever, shock and death in many cases. Some of the VHF agents cause relatively mild illnesses, such as the Scandinavian nephropathia epidemica, while others, such as the African Ebola virus, can cause severe, life-threatening disease.
Four families of RNA viruses have been recognized as causing this syndrome:
- The family Arenaviridae include the viruses responsible for Lassa fever, Lujo virus, Argentine, Bolivian, Brazilian and Venezuelan hemorrhagic fevers.
- The family Bunyaviridae include the members of the Hantavirus genus that cause hemorrhagic fever with renal syndrome (HFRS), the Crimean-Congo hemorrhagic fever (CCHF) virus from the Nairovirus genus, Garissa virus from the Orthobunyavirus and the Rift Valley fever (RVF) virus from the Phlebovirus genus.
- The family Filoviridae include Ebola virus and Marburg virus. Ebola has five viral subtypes including Zaire, Sudan, Bundibugyo, Tai Forest (formerly Ivory Coast), and Reston.
- The family Flaviviridae include dengue, yellow fever, and two viruses in the tick-borne encephalitis group that cause VHF: Omsk hemorrhagic fever virus and Kyasanur Forest disease virus.
Transmission to humans depends on the specific virus, but includes:
- By contact with the urine, feces, saliva, or blood of animal hosts such as rodents, fruit bats, subhuman primates, and duikers (antelope)
- From mosquito or tick bites
- Contact with vector-infected livestock
- Consuming infected bush meat
Signs and Symptoms
Signs and symptoms of VHFs include fever and bleeding diathesis. Manifestations of VHF often also include flushing of the face and chest, petechiae, frank bleeding, edema, hypotension, and shock. Malaise, myalgias, headache, vomiting, and diarrhea occur frequently. Definitive diagnosis is usually made at a reference laboratory with advanced biocontainment capabilities.
For most viral hemorrhagic fevers, there is no effective treatment other than supportive care. The only licensed vaccine available is for yellow fever. Control of rodent populations, insect and other arthropod populations can prevent VHFs.
Emerging Viral Hemorrhagic Fevers
As human habitation expands, new viral hemorrhagic fevers are infecting humans.
Generalize the characteristics and implications of an emergent virus
- There are several types of viruses that cause hemorrhagic fevers they are typified by high fever and bleeding.
- Emergent viruses are newly discovered viruses, often coming from other animal species. Many emergent viruses are uncovered by human activity such as deforestation.
- New sequencing technologies allow the identification of emergent viruses.
- No other rhabdovirus is known to cause the acute, rapid and deadly hemorrhagic fever seen in the three cases in the Congo.
- Rhabdovirus: Rhabdoviruses are viruses belonging to the family Rhabdoviridae,that infect a broad range of hosts throughout the animal and plant kingdoms.
An emergent virus is a virus that has adapted and emerged as a new disease/pathogenic strain, with attributes facilitating pathogenicity in a field not normally associated with that virus. This includes viruses that are the cause of a disease that has notably increased in incidence; this is often a result of a wide variety of causes from both the influence of man and nature. Most emergent viruses can be categorized as zoonotic; an animal disease that can be transmitted to humans. The virus thus has the advantage of possibly having several natural reservoirs to propagate in. As human development increases, and we move into areas not previously inhabited a reservoir of a virus can be uncovered and infections of humans ensues. This is especially worse in tropical areas of the world with high levels of biodiversity such as Africa, South America, and South Asia. Many newly discovered viruses come from these parts of the world as human habitation expands.
The viral hemorrhagic fevers (VHFs) are a diverse group of animal and human illnesses that may be caused by five distinct families of RNA viruses: the families Arenaviridae, Filoviridae, Bunyaviridae, Flaviviridae, and Rhabdoviridae. All types of VHF are characterized by fever and bleeding disorders and all can progress to high fever, shock and death in many cases. Some of the VHF agents cause relatively mild illnesses, such as the Scandinavian nephropathia epidemica, while others, such as the African Ebola virus, can cause severe, life-threatening disease.
Indeed the advent of deep sequencing technologies and other methods are identifying emergent viral hemorrhagic fevers. A recent study using deep sequencing, discovered a novel rhabdovirus (Bas-Congo virus, or BASV) associated with a 2009 outbreak of three human cases of acute hemorrhagic fever in Mangala village, Democratic Republic of Congo (DRC), Africa. The cases, presenting over a three-week period, were characterized by abrupt disease onset, high fever, bloody vomiting, and diarrhea, and, in two patients, death within three days. BASV was present in the blood of the lone survivor at a concentration of over a million copies per milliliter. The genome of BASV, assembled from over 140 million sequence reads, reveals that it is very different from any other rhabdovirus. The lone survivor and a nurse caring for him (with no symptoms), both health care workers, were found to have high levels of antibodies to BASV, indicating that they both had been infected by the virus. Although the source of the virus remains unclear, the study findings suggest that BASV may be spread by human-to-human contact and is an emerging pathogen associated with acute hemorrhagic fever in Africa.