The acronym CD denotes clusters of differentiation, protein molecules on the surface of blood cells. CD4 cells are specialized white blood cells carrying this molecule that can be counted to monitor the course of HIV infection and AIDS.
Treatment with expensive antiretroviral drugs and monitoring with complex lab tests can improve the general health and quality of life of infected individuals and reduce the death rate.
There is a glaring contrast between the success of teatment of HIV and AIDS in the developed west and the desolate situation in poor countries. The situation is aggravated by widespread corruption among the officials in charge of procuring the equipment in these countries and complacent tolerance of bribery by the corporations supplying the technology.
Why count the cells?
CD4 T cell count can be a useful index to judge the stage and severity of HIV infection and the deadly disease AIDS caused by a retrovirus. CD4 cell count is important for monitoring the medical treatment of HIV infection and AIDS with highly active antiretroviral therapy, since they are the cells attacked and destroyed by the virus, depleting their population.
In HIV infection
retroviruses destroy CD4 lymphocytes and impair cell-mediated immunity, increasing the risk of certain infections and cancers. Initial infection may produce unspecific febrile illness. The risk of subsequent manifestations, related to immunodeficiency, is proportional to the level of surving CD4 lymphocytes. HIV infection can remain dormant and asymptomatic in carriers
for many years, eventually progressing to full fledged AIDS
, a lethal disease
defined by serious opportunistic infections
Lymphocytes constitute around 25% of the white blood cells and are responsible for the immune defence of the organism. Haematologists can be quite poetic when naming their blood cells. Lymphocytes which recognize and destroy abnormal or infected cells are called natural killer NK cells. B cells are created and mature in bone marrow. They produce antibodies that help the body to destroy abnormal cells and infective organisms such as bacteria, viruses, and fungi. T cells are named after the thymus, the organ to which they travel to mature after developing from stem cells in the bone marrow. They are chiefly responsible for cell-mediated immunity, as they retain a memory of a previous infection, and can therefore respond to the same infectious agent quickly upon reinfection.
The main target and victims of the HIV are a category of T cells called helper cells. These T helper lymphocytes carry CD4, a glycoprotein on their surface. CD4 is a primary receptor that is necessary for the for HIV to dock on to the CD4+ T helper cell. Other CD receptors which can be measured are CD3 and CD8.
What is the CD4+ percentage?
In healthy adults, T4 cells make up between 32% and 68% of the total number of lymphocytes. CD4 percentage determines the proportion of CD4 cells in a sample of blood. The CD4 percentage is sometimes a more reliable measurement than the CD4 count because it tends to vary less between measurements. This variance is more important in children, whose normal CD4 cell count depends on age.
The HIV retrovirus tricks the lymphocytes into allowing it to enter through the cell membrane and then uses an enzyme called reverse transcriptase to converts viral RNA into a proviral copy that becomes integrated into the DNA of the host cell. These integrated proviruses are duplicated by normal cellular genes each time the cell divides. Thus, all offsprings of the originally infected cell will contain the DNA infected with the provirus. The proviral HIV DNA makes the host cell produce hundreds of copies of the infectious virus. The concentration of virus per unit of plasma is termed viral load. This slavery eventually kills the T helper cell. Much of the immunologic dysfunction in AIDS appears to be explained by loss of the helper function of CD4 T helper lymphocytes, critical to cell-mediated immunity.
The pattern of loss
Infected CD4+ lymphocytes have a half life of about 2 days. Rates of CD4+ lymphocyte destruction correlate with the viral load. Normal CD4+ T lymphocyte counts are about 750/microL, and immunity is minimally affected if counts are more than 500/microL. In the absence of anti-HIV treatment, the T4 cell count decreases, on average, about 50 to 100 cells each year. The death of CD4+ T cells proceeds in three phases and at rates that vary from patient to patient:
Within the first weeks and months after infection, the clinical symptoms are unspecific, HIV viral load is highest, and circulating CD4+ T lymphocyte counts drop rapidly.
In the relatively asymptomatic but infectious prolonged period of many years, there is a slower decline of CD4+ T cells.
This is followed by another more rapid decline in the 1- to 2-yr period until
finally, serious clinical manifestations of AIDS with opportunistic infections and malignancies start developing under a CD4+ cell count of less than 200.
Expensive lab tests
Cytoflow Cell Counters are elaborate machines to count the CD4 lymphocyte populations using the flow cytometry technique. The laboratory investigation of CD4 cell count can be costly, since the counters as well reagents for the test are very expensive. While most patients in rich countries with their medical insurance and social security schemes have little or no difficulty to afford the diagnostic workup and treatment of HIV infection, most AIDS victims in poor countries can pay neither for the CD4-cell count, in case it is available, nor for the urgent medication with antiretroviral drugs.
CD3 and CD8 count is even more costly. Measuring viral load is useful, but an illusion for underdeveloped countries, being too expensive, as a test will cost over $100 in Europe.
Flow cytometry cell counters
Flow cytometry is a technique for examining, sorting and counting microscopic particles suspended in a stream of fluid. To count CD cells in HIV patients, the blood cells are marked with reagents containing antigens which cause the CD cells to emit fluorescent light when a beam of green laser light is directed at them. Analysis of the fluorescent and scattered light picked up by detectors provides the cell count.
CyFlow is a counter manufactured by the German Firm Partec, based in Münster, the university which pioneered the cytometry technology in the fifties. It uses an open system. The CyFlow costs around $ 22,000. A CD4 T cell count for each patient costs about $ 2. The cytometer can function with accessories and reagents of several other manufacturers.
The cytometry system FAScount is produduced by the US-based firm Becton-Dickinson (BD). The machine was reported to cost $30,000 in 2003 in Kenya, with subventioned cost of $5 per test. The technology FASCount CD4 of BD uses a closed system (black box), which can function only with reagents of BD. BD boasted a 8% increase in revenue to $5.83 billion in the fiscal year 2006.
Guava Technologies, a California based firm has developed a relatively cheaper new cytometry flow machine, EZCD4 absolute count system, which is being praised by international experts and promises a CD4 cell count for about $1. While traveling in Africa July 2006, ex President Bill Clinton announced that the Clinton Foundation HIV/AIDS Initiative has signed an agreement with Guava Technologies that can reduce the cost of CD4 testing by up to 50%. Under the agreement, Guava Technologies will offer its CD4 System at a discounted price to the members of CHAI's Procurement Consortium, a coalition of 56 developing countries around the world including 27 countries across the African continent.
The racket with counters
In 2003 the Ministry of Health in Kenya awarded a tender to Faram East African Limited, agents of Becton-Dickinson( BD), for the procurement of 27 FASCount CD4 machines, although international and local experts had warned against the purchase of BD equipment, as they considered the technology to be inferior and obsolete and the reagents too expensive. The deal would have jeopardised the lives of 3.4 million AIDS victims and the government would have had to spend huge sums of money, estimated at 3 billion Kenya Shs. over many years to maintain the obsolete BD equipment and buy expensive reagents, as this firm is fond of raising the prices of the reagents once it has secured the contract.
Flamberts Holdings Limited, a subsidiary of Partech went to court and appealed against the decision. A lengthy legal battle ensued. The Public Procurement Complaints Review and Appeals Board of Kenya declared that the tender was fatally flawed. It was revealed that Faram was associated with a top official at the directorate of the Public Health laboratories. The High Court issued an order barring the Ministry of Health from executing the tender. The Director of Medical Services of Kenya, Dr. Richard Muga, lost his job for his involvement in the affair. He insisted that he had not been sacked but redeployed to the National Population Council.
A similar embezzlement and scandal involving the same manufacturer of FASCount machines occurred in Tanzania. In Zimbabwe a CD4+ T cell count is reported to cost between Z$25000 and Z$50000 (US$100-200). I am trying to find out, with which flow cytometry counters are used.
Are CD4 cell counts a luxury in some poor countries?
I know that many experts will balk at considering this provocative question. Physicians with many years of experience in treating AIDS patients will tell you that are capable of staging the patients reliably on the basis of clinical signs. But then, experienced physicians are almost as rare as CD4 cell counters those countries, having fled from poverty or been fished away by affluent societies. Foreign exchange required to purchase the expensive technology of cytometry counters and reagents is scarce.
Experts who regularly visit health institutions in Africa claim that a large proportion of the machines are defect or provide false results, as they contain high-tech requiring trained lab technicians to operate and maintain them, who are just not there. I just received an e-mail from a doctor in an African hospital complaining that the CD4 counts form his hospital lab are again not consistent with the clinical stage of his AIDS patients.
The sensational reporting by the media and the AIDS circus of celebrities may have beneficial influence in procuring funds, but it also diverts attention and resources from other equally important fields. This leads to the absurd situation that in some university hospitals in Africa you can find cytoflow CD4 cell counters, but may not be able to get simple lab tests like a malaria smear or a differential white blood cell count for lack of trained personnel. Another sobering point is that only about 12% of AIDS patients have access to treatment for HIV and AIDS.
It is commonsense that prevention of disease is a more sensible strategy than getting over active when it is too late. The role of fighting poverty, and of education to stem the spread of AIDS is a complex issue which has been discussed exhaustively in the scholarly E2 node Is AIDS a product of Empire? by blessedangel.
Bribery is the new morality
Although physicians have, on the whole, had altruistic motivation for their service as healers since ancient cultures, a monopoly nurtures tendencies to abuse it. Malpractice and unethical conduct were punished by draconian measures under the Code of Hammurabi in Babylon. Medical ethics laid down by Hippocrates are sinking into oblivion. With the industrialization and globalization of medicine, the pharmaceutical and medical technical corporations, lured by huge profits, have jumped on to the medical bandwagon. Greed has replaced humanism as the driving force in the unholy alliance of corrupt industrial corporations and doctors whose honour is for sale.
Comparing our fellow beings in the animal kingdom with humans is often an insult to the animals. Vultures feed on the dead out of hunger and provide the ecological benefit of recycling the cadavers. Many firms involved in the medical technical and pharmaceutical HIV/AiDS business not only pollute the earth, but, although overfed, scavenge for the suffering, the sick and the dying.
HIV Medicine 2006. Hoffman, Rockstroh, Kamps. www.HIVMedicine.com
Comparison of Micromicrocapillary Cytometry Technology and Flow Cytometry for CD4+ and CD8+ T/Cell Estimation. AJ Kandathil et al. Clinical and Diagnostic Laboratory Immun;logy, Aug. 2005, p1006/1009
The People on Sunday, Nairobi. December 14, 2003
East African Standard. Online Edition. October 7-13, 2003