Sunday, April 22, 2012

HIV Introduction

Acquired immunodeficiency syndrome or acquired immunodeficiency syndrome (AIDS) is an immune system disease caused by human immunodeficiency virus (HIV). The disease interferes with the immune system, making people with AIDS much more likely to get infections, including opportunistic infections and tumors that do not affect people who work with the immune system. This susceptibility worsens as the disease continues.
HIV is transmitted in many ways, such as sex (including oral sex and anal sex), transfusions of contaminated blood and needles, and the exchange between mother and baby during pregnancy, childbirth and breastfeeding. It can be spread by any contact of a mucous membrane or the bloodstream with a bodily fluid that has the virus on it, such as blood, semen, vaginal fluid, pre-ejaculate, or breast milk from an infected person.
The virus of the disease and are often referred to together as HIV / AIDS. The disease is a major health problem in many parts of the world, and is considered a pandemic, an outbreak of disease that is not only present in a large area but is spreading actively. In 2009, the World Health Organization (WHO) estimates there are 33.4 million people living with HIV / AIDS, with 2.7 million new HIV infections per year and 2.0 million deaths due to AIDS. In 2007, UNAIDS estimated: 33.2 million people worldwide were HIV positive, AIDS killed 2.1 million people in the course of the year, including 330,000 children, and 76% of these deaths occurred Sub-Saharan Africa. According to UNAIDS 2009 report, worldwide about 60 million people have been infected since the beginning of the pandemic, with about 25 million deaths and 14 million orphans in southern Africa.
Genetic research indicates that HIV originated in west-central Africa in the late nineteenth and early twentieth. AIDS was first identified by the Centers for Disease Control and Prevention (CDC) in 1981 and its cause, HIV, identified in the 1980's.
Although treatments for HIV / AIDS can slow the course of the disease, no cure or vaccine against HIV. Antiretroviral treatment reduces both deaths and new HIV infections / AIDS, but these are expensive drugs and medicines are not available in all countries. Because of the difficulty in treating HIV infection, preventing infection is a key aim in controlling the AIDS pandemic, with organizations of health promotion and safe sex needle exchange programs in attempts to reduce the spread of the virus.
Signs and symptoms
The main symptoms of AIDS.
X-ray of Pneumocystis pneumonia (PCP). There is increased white (opacity) of the lower lungs on both sides, characteristic of PCP.
The symptoms of AIDS are primarily the result of conditions not normally develop in individuals with healthy immune systems. Most of these conditions are opportunistic infections caused by bacteria, viruses, fungi and parasites that are normally controlled by the elements of the immune system that HIV damages. These infections affect nearly every organ system.
People with AIDS also have an increased risk of developing various cancers such as Kaposi's sarcoma, cervical cancer and cancers of the immune system known as lymphomas. In addition, people with AIDS often have systemic symptoms of infection like fevers, sweats (particularly at night), swollen glands, chills, weakness and weight loss. The specific opportunistic infections that AIDS patients develop depend in part on the prevalence of these infections in the geographic area in which the patient lives.
Pneumocystis pneumonia (originally known as Pneumocystis carinii pneumonia, and still abbreviated as PCP, which now stands for Pneumocystis carinii pneumonia) is relatively rare in healthy, immunocompetent, but common among HIV-infected individuals. It is caused by Pneumocystis jirovecii.
Before the advent of effective diagnosis, treatment and routine prophylaxis in Western countries, it was a common cause of immediate death. In developing countries, remains one of the first indications of AIDS in untested individuals, although it usually does not occur unless the CD4 count falls below 200 cells per microliter of blood.
Tuberculosis (TB) is unique among infections associated with HIV because it is transmissible to immunocompetent people, through the airway, and it is easily treatable once identified. Multidrug resistance is a serious problem. TB co-infected with HIV (TB / HIV) is a global health problem, according to World Health Organization, in 2007, 456,000 deaths among TB cases were HIV-positive, one third of deaths from TB and about a quarter of the estimated 2 million deaths from HIV in that year. Although its incidence has decreased due to the use of directly observed therapy and other best practices in Western countries, this is not the case in developing countries where HIV is most prevalent. In early HIV infection (CD4 count> 300 cells per microliter), TB typically presents as a pulmonary disease. In advanced HIV infection, TB often presents atypically with extrapulmonary (systemic) disease a common feature. Symptoms are usually constitutional and are not located in a particular site, often affecting bone marrow, bone, urinary and gastrointestinal tract, liver, lymph nodes, and central nervous system.
Esophagitis is an inflammation of the lining of the lower end of the esophagus (throat or swallowing tube leading to the stomach). In people with HIV, this is normally due to fungal (candidiasis) or viral (herpes simplex-1 or cytomegalovirus) infections. In rare cases, may be due to mycobacteria.
Unexplained chronic diarrhea in HIV infection is due to many possible causes, including common bacterial (Salmonella, Shigella, Campylobacter and Listeria) and parasitic infections, and uncommon opportunistic infections such as cryptosporidiosis, microsporidiosis, Mycobacterium avium complex ( MAC) and viruses, astrovirus adenovirus, rotavirus and cytomegalovirus, (the latter as a course of colitis).
In some cases, diarrhea can be a side effect of several medications used to treat HIV, or simply accompany HIV infection, especially during primary HIV infection. It can also be a side effect of antibiotics used to treat bacterial causes of diarrhea (common for Clostridium difficile). In the late stages of HIV infection, diarrhea is thought to be a reflection of changes in the way that nutrients absorbed intestinal tract, and may be an important component of HIV-related wasting.
Neurological and psychiatric
HIV infection can lead to a variety of neuropsychiatric sequelae, either by infection of the nervous system now by susceptible organisms, or as a direct consequence of the disease itself.
Toxoplasmosis is a disease caused by single-celled parasite called Toxoplasma gondii, which usually infects the brain, causing toxoplasma encephalitis, but can also infect and cause disease in the eyes and lungs. Cryptococcal meningitis is an infection of the meninges (the membranes covering the brain and spinal cord) by the fungus Cryptococcus neoformans. It can cause fever, headache, fatigue, nausea and vomiting. Patients may also develop seizures and confusion, left untreated, can be lethal.
Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease, in which the gradual destruction of the myelin sheath covering the axons of nerve cells affects the transmission of nerve impulses. It is caused by a virus called JC virus which occurs in 70% of the population in latent form, causing disease only when the immune system has been severely weakened, such as AIDS patients. It progresses rapidly, causing death within months of diagnosis.
AIDS dementia complex (ADC) is a metabolic encephalopathy induced by HIV infection and fueled by immune activation of HIV-infected macrophages and brain microglia. These cells are productively infected by HIV and secrete neurotoxins of both host and viral origin. Specific neurological disorders are manifested by cognitive, behavioral and motor abnormalities that occur after years of HIV infection and is associated with low CD4 T cell levels and high plasma viral loads.
The prevalence is 10-20% in Western countries, but only 1-2% of HIV infections in India. This difference is possibly due to the HIV subtype in India. The AIDS related mania is sometimes seen in patients with advanced HIV disease, but occurs more irritability and cognitive impairment and less euphoria than one episode of mania associated with bipolar disorder true. Unlike the latter condition can have a more chronic course. This syndrome is less frequent with the advent of multi-drug therapy.
Kaposi Sarcoma
Patients with HIV infection have substantially increased the incidence of various cancers. This is mainly due to the co-infection with oncogenic DNA viruses, especially Epstein-Barr virus (EBV), Kaposi's sarcoma associated herpes virus (KSHV) (also known as human herpesvirus 8 [HHV- 8]), and human papillomavirus (HPV).
Kaposi's sarcoma (KS) is the most common tumor in HIV infected patients. The appearance of this tumor in young homosexual men in 1981 was one of the first signs of the AIDS epidemic. Caused by a virus called gammaherpes Kaposi sarcoma-associated herpes virus (KSHV), which often appears as purplish nodules on the skin, but can affect other organs, especially the mouth, gastrointestinal tract and lungs. High grade B cell lymphomas such as Burkitt lymphoma, Burkitt-like lymphoma, diffuse large B-cell (DLBCL) and primary lymphoma of the central nervous system occur more frequently in HIV-infected patients. These particular cancers often foreshadow a poor prognosis. Epstein-Barr virus (EBV) or KSHV cause many of these lymphomas. In HIV-infected patients, lymphoma often occurs in extranodal sites such as the gastrointestinal tract. When produced in an HIV infected patient, KS and aggressive B-cell lymphomas confer an AIDS diagnosis.
The invasive cervical cancer in HIV-infected women also considered AIDS-defining, which is caused by human papillomavirus (HPV).
In addition to AIDS-defining tumors listed above, patients with HIV are at increased risk of certain tumors, particularly cancer Hodgkin's disease, anal and rectal carcinoma, hepatocellular carcinoma, head and neck and lung cancer. Some of these are the causes of viruses, such as Hodgkin's disease (EBV), cancer anal / rectal (HPV) in head and neck cancer (HPV) and hepatocellular carcinoma (hepatitis B or C). Other contributing factors include exposure to carcinogens (cigarette smoke to lung cancer), or live for years with minor immune defects.
Interestingly, the incidence of many common tumors such as breast or colon cancer does not increase in patients infected with HIV. In areas where HAART is widely used to treat AIDS, the incidence of many diseases, AIDS-related malignancies has decreased, but at the same time malignant cancers overall have become the most common cause of death in HIV-infected patients . In recent years, an increasing proportion of these deaths have been non-AIDS-defining cancers.
Other infections
AIDS patients often develop opportunistic infections that present with nonspecific symptoms, especially low-grade fever and weight loss. These include opportunistic infections by Mycobacterium avium-intracellulare and cytomegalovirus (CMV). CMV can cause colitis, as described above, and CMV retinitis can cause blindness.
Penicillium marneffei penicilliosis is by now the third most common opportunistic infection (after extrapulmonary tuberculosis and cryptococcosis) in HIV-endemic area of ​​Southeast Asia.
An infection that often goes unrecognized in patients with AIDS is parvovirus B19. Their main result is anemia, which is difficult to distinguish from the effects of antiretroviral drugs used to treat AIDS itself.
A generalized graph of the relationship between HIV copies (viral load) and CD4 counts over the average of untreated HIV infection, of course, any particular individual of the disease can vary considerably. CD4 T lymphocytes (cells / mm ³) HIV RNA copies per ml of plasma
AIDS is the ultimate clinical consequence of infection with HIV. HIV is a retrovirus that primarily infects vital organs of the human immune system such as CD4 T cells (a subset of T cells), macrophages and dendritic cells. It directly and indirectly destroys CD4 T cells.
Once the number of CD4 T cells per microliter (l) of blood falls below 200, cellular immunity is lost. Acute HIV infection usually progresses over time to clinical latent HIV infection and then to early symptomatic HIV infection and later to AIDS, which is identified either on the basis of the number of CD4 T cells remaining in blood, and / or the presence of certain infections, as noted above.
In the absence of antiretroviral therapy, the median time to progression of HIV infection to AIDS is nine to ten years, and median survival after developing AIDS is only 9.2 months. However, the rate of clinical disease progression varies widely between individuals, from two weeks to 20 years.
Many factors affect the rate of progression. Among them, factors that influence the body's ability to defend against HIV such as general immune function of the infected person. Older people have weaker immune systems and therefore have an increased risk of rapid disease progression than younger people.
Lack of access to health care and the existence of coexisting infections such as tuberculosis also may predispose people to disease progression faster. The genetic heritage of the infected person has an important role and some people are resistant to certain strains of HIV. An example of this is people with the homozygous CCR5-Δ32 variation are resistant to infection with certain strains of HIV. HIV is genetically variable and exists as different strains, which cause different rates of progression of clinical disease.
Sexual transmission
Main article: STD
Sexual transmission occurs with the contact between sexual secretions of a person with the rectal mucous membranes, genital or oral to the other. Unprotected sex are riskier for the receptive partner than for the insertive partner and the risk of transmitting HIV through unprotected anal intercourse is greater than the risk from vaginal intercourse or oral sex.
However, oral sex is not entirely safe, as HIV can be transmitted through oral sex insertive and receptive. Sexual assault greatly increases the risk of transmission of HIV that condoms are rarely employed and physical trauma to the vagina or rectum occurs frequently, facilitating the transmission of HIV.
The drug has been studied as a possible predictor of HIV transmission. Perry N. Halkitis found that methamphetamine use significantly related to unprotected sexual behavior. The study found that methamphetamine users to be at greater risk of contracting HIV.
Other sexually transmitted infections (STIs) increase the risk of HIV transmission and infection because they cause disruption of normal epithelial barrier by genital ulceration and / or microulceration, and the accumulation of clusters of cells susceptible to HIV or infected by HIV (lymphocytes and macrophages) in semen and vaginal secretions. Epidemiological studies of Africa, Europe and North America suggest that genital ulcers, such as those caused by syphilis and / or chancroid, increase the risk of becoming infected with HIV about four times. There is also a significant but smaller increase in the risk of sexually transmitted infections like gonorrhea, chlamydia and trichomoniasis, which all cause local accumulation of lymphocytes and macrophages.
HIV transmission depends on the infectiousness of the index case and susceptibility of the uninfected partner. Infectivity seems to vary during the course of the disease and is not constant among individuals. An undetectable viral load does not necessarily mean a low viral load in genital secretions or seminal fluid.
However, each 10-fold increase in the level of HIV in blood is associated with a 81% rate of increase in transmission. Women are more susceptible to HIV-1 infection due to hormonal changes, vaginal microbial ecology and physiology, and a higher prevalence of sexually transmitted diseases.
People who have been infected with a strain of HIV may become infected later in their lives by other more virulent strains.
Infection is unlikely in a single encounter. High rates of infection have been linked to a pattern of long-term accumulation sex. This allows the virus to spread rapidly to several couples who in turn infect their partners. A pattern of serial monogamy or occasional casual encounters is associated with lower infection rates.
HIV is easily transmitted through heterosexual sex in Africa, but less so elsewhere. One possibility is being investigated for schistosomiasis, which affects up to 50% of women in parts of Africa, damages the lining of the vagina.
Blood products
CDC poster of 1989, highlighting the threat of AIDS associated with drug use
This route of transmission is particularly relevant to intravenous drug users, hemophiliacs and transfusion recipients of blood and blood products. Sharing and reusing syringes contaminated with HIV infected blood represents a major risk for infection with HIV.
Sharing needles is the cause of one third of all new HIV infections in North America, China and Eastern Europe. The risk of getting HIV from a single prick with a needle that has been used by a person infected with HIV is thought to be about 1 in 150 (see table above). Post-exposure prophylaxis with anti-HIV drugs can further reduce this risk.
This route can also affect people who give and receive tattoos and piercings. Universal precautions are often not followed in both sub-Saharan Africa and much of Asia, both because of a shortage of supplies and inadequate training.
WHO estimates that approximately 2.5% of all HIV infections in sub-Saharan Africa are transmitted through unsafe healthcare injections. Because of this, the UN General Assembly has urged the nations of the world to implement precautions to prevent HIV transmission by health workers.
The risk of HIV transmission to recipients of blood transfusions is extremely low in developed countries, where they performed the selection of donors and HIV. However, according to WHO, the vast majority of the world's population lacks access to safe blood and between 5% and 10% of HIV infections in the world come from the transfusion of infected blood and blood products.
Perinatal transmission
HIV transmission from mother to child can occur in utero during the last weeks of pregnancy and childbirth. Untreated, the rate of transmission between mother and child during pregnancy, childbirth is 25%.
However, when the mother takes antiretroviral therapy and gives birth by caesarean section, the transmission rate is only 1%. The risk of infection is influenced by the mother's viral load at birth, with the highest viral load, the greater the risk. Breastfeeding also increases the risk of transmission by about 4%.
Main article: Misconceptions about HIV and AIDS
There are many misconceptions about HIV and AIDS. Three of the most common are that AIDS can be transmitted by casual contact (like shaking hands, hugging, or a casual kiss), that sex with a virgin cures AIDS and that HIV can infect only men homosexuals and drug users. Other misconceptions are that any act of anal sex among gay men can lead to HIV infection, and that open discussion of homosexuality and HIV in schools increased rates of homosexuality and AIDS.
The pathophysiology of AIDS is complex. Ultimately, HIV causes AIDS by depleting CD4 T helper lymphocytes. This weakens the immune system and allows opportunistic infections. T lymphocytes are essential for immune response and without them the body can not fight infections or kill cancer cells. The mechanism of depletion of CD4 T cells differ in acute and chronic phases.
During the acute phase, HIV-induced cell lysis and death of infected cells by cytotoxic T cells accounts for the depletion of CD4 T cells, although apoptosis may also be a factor. During the chronic phase, the consequences of generalized immune activation with gradual loss of the immune system's ability to generate new T cells appear to account for the slow decrease in the number of CD4 T
Although symptoms of immune deficiency characteristic of AIDS do not appear for years after a person is infected, the bulk of the loss of CD4 T cells occurs during the first weeks of infection, especially in the intestinal mucosa, which houses the majority of lymphocytes found in the body. The reason for the preferential loss of CD4 T cells mucosa is that a majority of mucosa cells expressing CD4 coreceptor CCR5, while a small fraction of CD4 T cells in the blood do so.
HIV finds and destroys CD4 cells expressing CCR5 during acute infection. A vigorous immune response eventually controls the infection and clinically latent phase starts. However, CD4 T cells in mucosal tissues remain depleted throughout infection, although sufficient to prevent a principle remain threatening infections.
Continuous HIV replication results in a state of generalized immune activation persisting throughout the chronic phase. Immune activation, as reflected in the increased activation status of immune cells and release of proinflammatory cytokines, the results of the activity of several gene products of HIV and the immune response to the ongoing HIV replication. Another cause is the breakdown of immunological surveillance of the mucosal barrier caused by the depletion of mucosal CD4 T cells during the acute phase of illness.
This results in systemic exposure of the immune system to microbial components of normal gut flora, which in a healthy person is kept in check by the immune system of mucous membranes. Activation and T cell proliferation resulting from immune activation provides new targets for HIV infection. However, the direct killing by HIV alone can not account for the observed decline of CD4 T cells, with only 0.01 to 0.10% of CD4 T cells in the blood are infected.
One of the main causes of loss of CD4 T cells appears to be the result of their increased susceptibility to apoptosis when the immune system remains active. Despite new T cells is continuously produced by the thymus to replace the lost, the regenerative capacity of the thymus is slowly destroyed by direct infection of its thymocytes by HIV. Finally, the minimum number of CD4 T cells needed to maintain a sufficient immune response is lost, which leads to AIDS
The affected cells
The virus entering through which ever route, acts primarily on the following cells:
• lymphoreticular system:
or CD4 + T-lymphocytes
Macrophages or
or monocytes
or B lymphocytes
• Endothelial cells certain
• Central nervous system:
Or microglia of the nervous system
or astrocytes
Oligodendrocytes or
Neurons or - indirectly by the action of cytokines and gp-120
The effect
The virus has cytopathic effects, but how it does, is not yet clear. It can lie dormant in cells for prolonged periods, however. This effect is hypothesized to be due to the CD4-gp120 interaction.
• The most prominent effect of HIV is the T-helper cell suppression and lysis. The cell is simply killed or disturbed to the point of being function-less (that do not respond to foreign antigens). The infected B cells can not produce enough antibodies either. Thus, the immune system collapses leading to the known complications of AIDS, such as infections and neoplasms (vide supra).
• Infection of the central nervous system cells cause acute aseptic meningitis, subacute encephalitis, vacuolar myelopathy and peripheral neuropathy. Later takes dementia complex, including AIDS.
• The interaction of CD4-gp120 (see above) also is permissive with other viruses such as cytomegalovirus, hepatitis, herpes simplex virus, etc. These viruses lead to cell damage i. e. cytopathy.
Molecular basis
For more information, see:
• Structure and genome of HIV
• HIV replication cycle
• HIV tropism
The diagnosis of AIDS in a person infected with HIV is based on the presence of certain signs or symptoms. From June 5, 1981, the definitions have been developed many of surveillance, such as the Bangui definition and the 1994 World Health Organization expanded the definition of AIDS cases. However, the clinical classification of patients was not an intended use for these systems because they are neither sensitive nor specific. In developing countries, classification system of World Health Organization for HIV infection and disease is used (from clinical and laboratory), and in developed countries, rating system CDC is used.
World Health Organization
Main article: System of Diseases of the WHO test for HIV infection and disease

Sleeping Sickness

Human African trypanosomiasis, sleeping sickness [1], the lethargy of Africa, [1] or trypanosomiasis of Congo [1] is a parasitic disease of humans and animals caused by protozoa of species Trypanosoma brucei and transmitted by the tsetse fly. [2] The disease is endemic in parts of Africa, covering about 37 countries and 60 million people. It is estimated that between 50,000 and 70,000 people are currently infected, the number has declined somewhat in recent years. [3] The number of reported cases was below 10,000 in 2009, the first time in 50 years. [4] It is believed that many cases go unreported. Around 48,000 people died of it in 2008 [5] Four major epidemics have occurred in recent history. A 1.896 to 1.906 mainly in Uganda and the Congo Basin, two epidemics in 1920 and 1970 in several African countries, and a recent epidemic of 2008 in Uganda. [6]

Signs and symptoms symptomsAfrican trypanosomiasis occur in two stages. The first stage is known as haemolymphatic phase and is characterized by fever, headaches, joint pains and itching. Invasion of the circulatory and lymphatic systems, by parasites is associated with severe inflammation of the lymph nodes, often to large sizes. Winterbottom sign, lymph nodes reveal along the back of the neck, may appear. If untreated, the disease overcomes host defenses and cause more extensive damage, enlargement of the symptoms include anemia, endocrine, cardiac and renal dysfunction. The second stage, called the neurological phase, begins when the parasite invades the central nervous system to pass through the blood-brain barrier. "Sleeping sickness" The term comes from the symptoms of neurological phase. Symptoms include confusion, decreased coordination, and alteration of the sleep cycle, with episodes of fatigue with manic periods leading to interrupted sleep during the day and insomnia at night [citation needed]. Untreated, the disease is invariably fatal, with progressive mental deterioration leading to coma and death. The damage caused in the neurological phase is irreversible. [6]

Tryptophol is a chemical compound that induces sleep in humans. It is produced by the parasite trypanosomes in sleeping sickness. [7]

The life cycle
Life cycle of the parasite Trypanosoma brucei. Source: CDCThe tsetse fly (genus Glossina) is a large fly, biting brown that serves as a host and vector of trypanosomes parasites. While taking the blood of a mammalian host, an infected tsetse fly injects metacyclic trypomastigotes into skin tissue. From the bite, parasites first enter the lymphatic system and then move into the bloodstream. Inside the mammalian host, trypomastigotes transform into blood, and taken to other sites throughout the body, reach other blood fluids (eg, lymph, cerebrospinal fluid), and continue to replicate by binary fission.

The complete life cycle of African trypanosomes is represented by extracellular stages. A tsetse fly becomes infected with bloodstream trypomastigotes when taking a blood meal from a mammalian host infected. In intestine of the fly, the parasites transform into procyclic trypomastigotes, multiply by binary fission, leave the midgut, and transform into epimastigotes. The epimastigotes reach the fly's salivary glands and continue multiplication by binary fission.

The life cycle of the fly is about 3 weeks.

In addition to the bite of the tsetse fly, the disease can be transmitted in the following ways:

Mother to child infection:. Sometimes the trypanosome can cross the placenta and infect the fetus [8]
Laboratories: accidental infections, for example, through handling an infected person's blood and organ transplantation, although this is rare.
Blood transfusion
Sexual contact (This may be possible) [9]
Two areas of a blood smear from a patient with African trypanosomiasis. Thin blood smears stained with Giemsa. Typical trypomastigote stages (the stages are only found in patients) with a posterior kinetoplast, a centrally located nucleus, an undulating membrane and flagellum above. The two subspecies of Trypanosoma brucei that cause sleeping sickness, T. b. gambiense and T. b. rhodesiense, are indistinguishable morphologically. Trypanosomes length range is 14 to 33 microns, Source: gold standard for diagnosis is the identification CDCThe of trypanosomes in a patient sample by microscopic examination. Patient samples that can be used for diagnosis include chancre fluid, lymph node aspirates, blood, bone marrow, and, during the stage neurological, cerebrospinal fluid. Detection of trypanosome-specific antibodies can be used for diagnosis, but sensitivity and specificity of these methods are too variable to be used only for clinical diagnosis. Furthermore, seroconversion occurs after the onset of clinical signs during a T. b. rhodesiense infection, and therefore is of limited diagnostic use [Edit].

Trypanosomes can be detected from patient samples using two different preparations. A wet preparation can be used to find the motile trypanosomes. Moreover, a fixed (dry) smears can be stained with Giemsa (or field) and examined. Often, the parasite is relatively low in abundance in the sample, so that the techniques for concentrating the parasites could be used before microscopic examination. For blood samples, such as centrifugation followed by an examination of the buffy coat; anion-exchange/centrifugation small, and the quantitative buffy coat (QBC) technique. For samples such as cerebrospinal fluid, concentration techniques include centrifugation followed by an examination of the sediments [citation needed].

Serologic tests are also available for the detection of the parasite: the micro-CATT, wb-CATT and wb-LATEX. The first uses the dried blood, while the other two test samples of whole blood. A 2002 study found the wb-CATT to be most efficient for the diagnosis, while the wb-LATEX is a better test for situations requiring greater sensitivity. [10]

PreventionSee also: Tsetse_fly Number Control_techniques
Two alternative strategies have been used in attempts to reduce trypanosomiasis. The main method focuses on the eradication of tsetse fly, altering transmission rates by reducing the number of flies. The cases of sleeping sickness are reduced by using the sterile insect technique. The second tactic is primarily medical or veterinary and tries to reduce the spread of the parasite through the surveillance, prevention, treatment and monitoring to reduce the number of people or animals that carry the disease [citation needed].

Regular monitoring active participation of the detection and treatment of new infections, and control of the tsetse fly, is the backbone of the strategy used to control sleeping sickness. Systematic screening of communities at risk is the best approach, since each case, the review is not practical in endemic regions. Systematic screening may be in the form of mobile clinics and fixed detection centers, where teams travel daily to areas of high infection rates. These are important efforts to detect because early symptoms are not evident or serious enough to justify gambiense disease patients to seek medical attention, especially in remote areas. Moreover, diagnosis of the disease is difficult and health workers can not be associated with these general symptoms of trypanosomiasis. Systematic screening allows early-stage disease to be detected and treated before the disease progresses, and eliminates the reservoir of human potential. [11] There is no single case of sexual transmission of West African sleeping sickness [12], but this is believed to be an important route of transmission.

 Treatment [edit] First line, first stageThe current standard treatment for early stage (haemolymphatic) disease is:

Pentamidine intravenously or intramuscularly (for Tb gambiense) or
Intravenous suramin (for T.b. rhodesiense)
The drug eflornithine - previously used as an alternative treatment for sleeping sickness due to their workforce management - was found to be safe and effective as first-line treatment for the disease in 2008, according to the science and Sub-Saharan Africa Development Network news updates. [1]. The researchers followed more than 1,000 adults and children in a center in the IBBA, southern Sudan, the first use of eflornithine on a large scale and is very effective in the treatment of the issue.

According to a study of treatment of Trypanosoma gambiense cause human African trypanosomiasis, the use of eflornithine (DMFO) resulted in fewer adverse events than treatment with melarsoprol. [13]

 The first line, second stageThe current standard treatment for the second stage (neurological phase) is the disease:

Intravenous melarsoprol 2.2 mg / kg daily for 12 consecutive days. [14]
Alternative first-line therapies include:

Intravenous melarsoprol 0.6 mg / kg on day 1, 1.2 mg / kg IV melarsoprol on day 2, and 1.2 mg / kg / day IV in combination with oral melarsoprol 7.5 mg / kg nifurtimox twice a day on days 3 to 10, [15] or
Intravenous eflornithine 50 mg / kg every six hours for 14 days. [16]
Combination therapy with eflornithine and nifurtimox is safer and easier than treatment with eflornithine alone, and appears to be equally or more effective. It has been recommended as first-line treatment for second stage of T. b. gambiensis disease. [17]

 resistant areas diseaseIn melarsoprol resistance or in patients who have relapsed after melarsoprol monotherapy, treatment should be:

melarsoprol and nifurtimox, or
 protocolsThe Outdated after traditional systems should no longer be used:

(Old "standard" 26-day melarsoprol treatment) Intravenous melarsoprol therapy (3 sets of 3.6 mg / kg / day intravenously for 3 days, 7 days rest between sets) (this regimen is less convenient and patients are less likely to complete treatment) [18];
(Incremental melarsoprol treatment) 10-day melarsoprol treatment with increasing doses (0.6 mg / kg iv on day 1, 1.2 mg / kg iv on day 2, and 1.8 mg / kg iv on days 3 - 10) (thought to reduce the risk of treatment-induced encephalopathy, but now known to be associated with an increased risk of relapse and an increased incidence of encephalopathy), [15] [18]
Deaths per 100,000 population due to African trypanosomiasis country in 2002. [19] The disease is found in two forms, depending on the parasite, either Trypanosoma brucei gambiense or Trypanosoma brucei rhodesiense. Humans are the main reservoir for Trypanosoma brucei gambiense, but this species is also found in pigs and other animals. Hunting wild animals and livestock are the main reservoir of infection with T. b. rhodesiense. T. b. gambiense is found in Central and West Africa, but that causes a chronic disease that can remain in a passive phase for months or years before symptoms appear. T. b. rhodesiense is the acute form of the disease, but has a much more limited geographic range. It is located in southern and eastern Africa and the symptoms of the infection appears in a few weeks and is more virulent and faster developing T. b. gambiense. According to recent estimates, years of disability-adjusted life (9 to 10 years) (DALYs) lost due to sleeping sickness are 2.0 million. [20] Recent estimates indicate that more than 60 million people living in about 250 locations are at risk of contracting the disease, and there were fewer than 10,000 cases reported in 2009, according to WHO figures, representing a huge decrease of the approximately 300,000 new cases in 1998. [21] The disease has been recorded as in 36 countries, all in sub-Saharan Africa. It is endemic in southeast Uganda and western Kenya, killing more than 48,000 Africans in 2008. [6]

Horse flies (Tabanidae) and stable flies (Muscidae), possibly playing a role in the transmission of nagana (the animal form of sleeping sickness) and the shape of the human disease. [22]

 HistoryThe condition has been present in Africa, at least since the 14th century, and probably for thousands of years before that. Because there was a lack of travel between indigenous peoples, sleeping sickness in humans had been limited to isolated areas. This changed when Arab slave traders came into the center of Africa from the east along the Congo River, which along parasites. Sleeping sickness Gambia traveled up the Congo River, then further east. In 1901 a devastating epidemic outbreak in Uganda, killing more than 250,000 people, [23], including about two thirds of the population in coastal areas affected by the lake. According to The Cambridge History of Africa "has been estimated that up to half of people who died of sleeping sickness and smallpox in the lands on both sides of the lower Congo River." [24]

In 1903, David Bruce recognized the tsetse fly in the arthropod vector vector.The causative agent and were identified in 1903 by David Bruce, and differentiation between the subspecies of the protozoan carried out in 1910. The first effective treatment, atoxyl, an arsenic-based drug developed by Paul Ehrlich and Kiyoshi Shiga, was introduced in 1910, but blindness is a serious side effect. A large number of drugs designed to treat the disease have been introduced since then, [citation needed].

Suramin was introduced in 1920 to treat the first stage of the disease. In 1922, suramin are generally combined with triparsamida (other organo-arsenic pentavalent drug) in the treatment of the second stage of the form gambiense. It was used during the epidemic of glue in West and Central Africa in millions of people and was the mainstay of therapy until the year 1969 [citation needed].

Pentamidine, a very effective drug for the first stage of the disease, has been used since 1939. During the fifties, was widely used as a prophylactic agent in West Africa, leading to a sharp decline in infection rates. At that time, it was thought that the eradication of the disease was at hand [citation needed].

Organo-arsenical melarsoprol (Arsobal) was developed in the 1940s, and is effective for patients with second stage of sleep. However, 10.3% of those injected have reactive encephalopathy (convulsions, coma, progressive, or psychotic reactions), and 10-70% of cases resulting in death, but can cause brain damage in patients who survive the encephalopathy . However, because of its effectiveness, melarsoprol is still used today. Resistance to melarsoprol is increasing, and combination therapy with nifurtimox is currently under investigation [citation needed].

Eflornithine (difluoromethylornithine or DFMO), art therapy, developed in the 1970s by Albert Sjoerdsmanot and underwent clinical trials in the 1980s. The drug was approved by the Food and Drug Administration in 1990, but Aventis, the company responsible for manufacturing, production stopped in 1999. In 2001, however, Aventis, in partnership with Doctors Without Borders and the World Health Organization, signed a long-term agreement to manufacture and donate the drug [citation needed].

ResearchThe parasite genome has been sequenced and several proteins have been identified as potential targets for drug treatment. Genome analysis also revealed the reason for the generation of a vaccine for this disease has been so difficult. T. brucei has more than 800 genes that make proteins of the parasite "mix and match" to evade immune system detection. [25]

Recent studies indicate that the parasite can not survive in the bloodstream without the scourge. This insight gives researchers a new perspective with which to attack the parasite. [26]

A new treatment based on a truncated version of apolipoprotein L-1 high density lipoprotein and a single domain antibody has recently been found to work in mice, but was not tested in humans. [27]

The cover story of August 25, 2006 Number of the journal Cell described a breakthrough in understanding how trypanosomes escape the immune system. Dr Lee Soo Hee and colleagues, working at Johns Hopkins investigated the pathway by which trypanosomes myristate, a 14-carbon fatty acid length. Myristate is a component of the variant surface glycoprotein (VSG), the molecule that forms the outer layer of the trypanosome. The outer surface layer of VSG is vital for trypanosome's ability to avoid destruction by the host immune system. Dr. Lee and his colleagues discovered trypanosomes use a novel pathway of fatty acid synthesis involving fatty acid elongases to make myristate and other fatty acids.

An international team of researchers working in the Democratic Republic of Congo, southern Sudan and Angola involving Immtech International and the University of North Carolina at Chapel Hill has completed a Phase IIb clinical trial and began a Phase III trial in year 2005 to test the efficacy of the first oral treatment for sleeping sickness, pafuramidine (DB289). [28] [29] Trypanosomiasis vaccines are being investigated.

Two independent variants APOL1 gene found in African haplotypes carrying the signature of natural selection has been shown to confer protection against acute version of sleeping sickness caused by Trypanosoma brucei rhodesiense, while at the same time increasing the risk of kidney disease when inherited from both parents. [30]

The synthetic approaches and the computer are used to develop new anti-trypanosomal analogs with greater efficacy and oral bioavailability. [31]

See alsoHuman trypanosomiasis
Initiative Drugs for Neglected Diseases
David Bruce (microbiologist)
Sleep disorders
Chagas disease (American trypanosomiasis), another tropical disease caused by human trypanosomes
Nagana (trypanosomiasis Animal)
Tsetse fly
GD Hale Carpenter joined the London School of Hygiene and Tropical Medicine, and took the DM in 1913 with a thesis on the tsetse fly (Glossina palpalis) and sleeping sickness. He has published A Naturalist on Lake Victoria, with an account of sleeping sickness and tsetse flies, 1920. T.F. Unwin Ltd, London; Biodiversity File
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