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Treatments for HIV / AIDS and Malaria

TJC Global Translation & Interpreting Services since 1985

HIV

AIDS (Acquired Immuno-Deficiency Syndrome) is pandemic, affecting an estimated 33.2 million people (2007) worldwide. Areas where the proportion of infection is greatest include sub-Saharan Africa and South and East Asia. The disease can be transmitted via sexual contact or blood, and is caused by a virus; HIV (Human Immunodeficiency Virus). At the beginning of the disease, three to four weeks following infection, viral load in the blood is very high. After this, there may be a long period of clinical latency, where the individual is still infected but viral load in the blood is almost negligible. This may last for years, before AIDS develops.

 

Development of AIDS

As HIV attacks T cells, an important white blood cell needed for the immune system to function properly, infection with HIV leaves the individual open to 'opportunistic infections'. Commonly these include respiratory or pulmonary diseases such as TB and pneumocystis pneumonia. Patients with HIV also display an enormously increased incidence of certain types of tumours, normally due to coinfection with tumour viruses (oncoviruses) such as Epstein-Barr virus, Karposi's sarcoma associated herpesvirus and human papillomavirus. Karposi's sarcoma is the most common tumour found in HIV patients, and was one of the symptoms which lead to the identification of AIDS as a disease in 1981. Burkitt's lymphoma is also common.


Treatments for HIV

Antiviral therapy

Currently there is no cure for HIV. However, there are some effective antivirals which help to reduce the viral load in the blood and therefore extend the period of clinical latency, allowing patients to lead a longer, more normal life. This treatment is normally referred to as HAART (highly active anti-retroviral therapy), and functions by preventing the replication of the virus within the body. Several different drugs are taken at once in order to reduce the chance of the virus developing resistance to treatment. Drugs used include zidovudine, lamivudine and saquinavir.

 

Difficulties of developing a vaccine

There has been constant and ongoing research into the possibility of the development of an HIV vaccine. There are several obstacles to the creation of this vaccine, including the fact that the virus has a high mutation rate (it is a retrovirus and consequently contains not DNA, but RNA. There are no 'proof-reading' mechanisms for RNA replication, and therefore errors are made at a higher frequency when copying the genome). This high mutation rate means that it is difficult to develop a vaccine or cure that cannot be rapidly evaded by the virus through development of a new characteristic through mutation.

 

New possibilities in treatment for HIV

There have been many vaccine trials which so far have been unsuccessful. Due to pre-existing diversity between clades of HIV, and its high rate of mutation, it may be that a hugely complex vaccine is required. Research that has been carried out has shown that currently the most effective and most promising vaccines are those which stimulate the cellular arm of the immune system; i.e., those which activate white blood cells (CD8+ T cells) against the HIV lying dormant or replicating within T cells.

More promising has been the possibility of using therapeutic vaccines. These slow the progression of the disease and reduce the viral load. This may be useful in allowing people to take a break from their normal drug regimen (which can be up to four or five pills twice a day for people who with HIV that has developed resistance).

 

Malaria

Malaria is a disease caused by a parasite, a protazoa called Plasmodium. There are four different types of malaria, each caused by different Plasmodium strains; P. vivax, P. malariae, P. ovale and P. falciparum. Malaria caused by P. falciparum is by far the most severe. The causative protazoa is carried by a vector, the female Anopheles mosquito. The parasite survives within the saliva glands of the mosquito, and when blood feeding on a human, the mosquito releases saliva containing the parasite, which infects the human host. The parasite can survive within the liver, undergoing the next stage of its lifecycle, and then is released into the bloodstream where it infects red blood cells. The ability of the strain of Plasmodium to infect and destroy red blood cells determines the severity and duration of the disease.

Because malaria is mainly a disease of sub-Saharan
Africa, often it does not receive recognition in the Western world as one of the biggest public health problems worldwide. Every year approximately 515 million people contract the disease, and between 1 and 3 million die.

 

Treatments for Malaria

Infection with P.vivax, P. ovale and P. malariae do not normally require hospitalisation; however infection with P. falciparum is a medical emergency and does require hospitalisation. 

 

Antimalarial drugs

There are many effective antimalarial drugs. Until very recently, the cheap and effective chloroquinine was most commonly used in treatment; however lately resistance of P. falciparum has developed in sub-Saharan Africa and spread to Asia. Other drugs may be given in prophylaxis; these are particularly used for those travelling to regions with malaria, and have to be taken for 6 weeks before and after the trip. Other preventative measures include sleeping under mosquito nets (as the Anopheles mosquito feeds at night) and killing the vector mosquitoes through the use of pesticides (although at first this was effective, the mosquitoes have now developed resistance to DDP).

One of the main problems with current treatments and prophylaxis is that the drugs are developed mainly for people travelling to malarial areas; there is little available effective prophylaxis or treatment for malaria in the populations of malaria regions. Consequently there has been much research into the possibility of the development of a malaria vaccine.

 

Malaria vaccines

There has never been a successful vaccine manufactured against a human parasite. The parasite is extremely adept in evading the host (human) immune system. It also has a high mutation rate and the ability to change which proteins it uses so that vaccines targeting particular molecules or proteins are rapidly rendered ineffective.

Possibilities for vaccines are those which have many different targets, those which stimulate the immune system to destroy the parasite, those which act while the parasite is in the blood, or in the liver, and many more. There are currently multiple strategies in development in clinical trials, showing some promising results.

TJC Global is situated in
Oxford, close to the Malaria Vaccine Trials group (part of Oxford University) which is based both at the Nuffield Department of Medicine and at the Wellcome Trust Centre for Human Genetics.


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