Diagnosis, Treatment and Prevention of Malaria

Malaria Diagnosis

Diagnosis of malaria is based on an analysis of the clinical manifestations of the disease, data from an epidemiological and geographical history and is confirmed by laboratory blood tests.

The final diagnosis of the specific form of malaria infection is based on the results of a laboratory blood test.

For laboratory diagnostics, parasitological and immunological research methods are used.

Parasitological method – hemoscopy of a thin smear and a thick drop of blood is the leading one. The diagnosis is confirmed when any erythrocyte stages of plasmodia are detected in the blood. The reliability of parasitological diagnostics depends on the level of professional training of the laboratory assistant and the qualitative implementation of the research methodology.

The probability of detecting plasmodia in a thick drop is 20 to 40 times higher than in a thin smear, however, to determine the type of pathogen, a smear should be examined. Blood should be taken regardless of the rise in temperature, because parasites circulate in the blood and in the intervals between attacks and in the absence of clinical manifestations of the disease in parasitic carriers.

With the research regimen recommended by WHO for mass screening, it is necessary to carefully review 100 fields of view in a thick drop. Examination of two thick drops for 2.5 minutes. for each more effective than the study of one thick drop for 5 minutes. When plasmodia of malaria is detected in the first fields of view, the viewing of drugs does not stop until 100 fields of view are viewed so as not to miss a possible mixed infection.

The probability of their detection depends on the concentration of parasites in the blood. The minimum concentration of parasites that can be detected by examining a thick drop is called the detection threshold. In the regimen recommended by WHO for mass examinations (viewing 100 fields of view of a thick drop or 0.2 μl of blood), the detection threshold is 5 parasites in 1 μl.

Parasitemia above the detection threshold is called patent, and below it – subpatent.

If the patient reveals indirect signs of a malarial infection (stay in the malarial zone, hypochromic anemia, the presence of pigmentophages in the blood – monocytes with clumps of malarial pigment of almost black color in the cytoplasm), a thick drop should be examined more carefully and not two, and a series of 4-6 with one injection. In addition, with a negative result in suspicious cases, it is recommended that blood sampling be performed repeatedly (4-6 times a day) for 2-3 days.

The laboratory name indicates the Latin name of the pathogen, the generic name Plasmodium is reduced to “P”, the species name is not reduced, and also the stage of development of the pathogen (required when P. falciparum is detected).

To control the effectiveness of treatment and identify possible pathogen resistance to the antimalarial drugs used, the number of plasmodia is counted.

A day after the start of treatment, the level of parasitemia should decrease by 25% or more. On the 3rd day from the start of treatment, the level of parasitemia should not exceed 25% of the initial level before treatment.

The presence of parasites in blood products on the 4th day after the start of treatment is an indicator of the resistance of the pathogen to the drug used. On the recommendation of WHO, to determine the number (degree of parasitemia), you can be guided by the viewing experience if:

  • during a 5-minute viewing of a thick drop, no more than 10 plasmodia can be detected, this roughly corresponds to 5 to 50 plasmodia in 1 μl;
  • there are few parasites, but they come across in the first fields of view – 50 – 500 in 1 μl;
  • parasites are present in almost every field of view, often several pieces – 500 – 5000 in 1 μl;
  • there are many parasites, the entire field is dotted with them – more than 5000 in 1 μl.

There is also a more accurate method of counting, based on a comparison of the number of parasites with the number of blood cells – white blood cells or red blood cells.

Detection of mature trophozoites and schizonts in the peripheral blood – morula in tropical malaria indicates a malignant course of the disease, which the laboratory should immediately inform the attending physician.

Residents of endemic areas with partial immunity have low parasitemia, which leads to the need to study a series of thick drops and repeat blood tests. Diagnosis of changes in the morphology of parasites, which may be due to the use of chemotherapeutic agents, as well as the result of violations of the preparation and staining methods, is also difficult.

Immunological methods for diagnosing malaria are based on the detection of:

  1. in the blood serum of the examined antibodies;
  2. soluble parasitic antigens.

In practice, the first have found greater application. More often than other test systems, an indirect immunofluorescence reaction (NRIF) is used. As an antigen for the diagnosis of three-day and four-day malaria, smears and blood drops with a large number of schizonts are used.

For the diagnosis of tropical malaria, the antigen is prepared from a culture of P. falciparum in vitro, since most patients do not have schizonts in the peripheral blood. Therefore, for the diagnosis of tropical malaria, the French company BioMerieux produces a special commercial kit.

Difficulties in obtaining antigen (a patient’s blood product or from an in vitro culture), as well as insufficient sensitivity, make it difficult to implement NRIF.

New methods for the diagnosis of malaria are developed on the basis of luminescent enzyme immunoassays, as well as using monoclonal antibodies.

An enzyme-linked immunosorbent assay system using soluble plasmodium malaria antigens (REMA or ELISA), like RNIF, is used mainly for epidemiological studies.

According to the recommendation of A. Ya. Lysenko (1999), these reactions in areas non-endemic for malaria can be useful in screening blood donors, in determining the effectiveness of treatment, in diagnosing fevers with a negative parasitological study, in retrospective diagnosis, etc.

Currently, it has been proven that malaria can be diagnosed, especially in cases of very low parasitemia, using polymerase chain reaction (PCR). However, this method is expensive and complicated.

Malaria Treatment

The most common medication for treating malaria today, as before, is quinine. For some time it was replaced by chloroquine, but recently quinine has gained popularity again. The reason for this was the appearance in Asia and, then, the spread across Africa and other parts of the world, Plasmodium falciparum with a mutation of resistance to chloroquine.

There are also several other substances that are used to treat and, sometimes, to prevent malaria. Many of them can be used for both purposes. Their use depends mainly on the resistance of parasites to them in the area where this or that drug is used.

Extracts of the plant Artemisia annua (Wormwood), which contain the substance artemisinin and its synthetic analogues, are highly effective, but their production is expensive. Currently (2006), the clinical effects and the possibility of producing new drugs based on artemisinin are being studied. Other work by a team of French and South African researchers has developed a group of new drugs, known as G25 and TE3, successfully tested on primates.

Although antimalarial drugs are on the market, the disease poses a threat to people who live in endemic areas where there is not adequate access to effective drugs. According to Doctors Without Borders, the average cost of treating a person infected with malaria in some African countries is between $ 0.25 and $ 2.40.

Malaria Prevention

Methods that are used to prevent the spread of the disease or to protect in areas endemic to malaria include preventative drugs, mosquito killing, and mosquito bite preventers. There is currently no vaccine against malaria, but active research is underway to create it.

Prophylactic drugs
A number of drugs used to treat malaria can also be used for prevention. Typically, these medications are taken daily, or weekly, in a lower dose than for treatment. Preventive medicines are usually used by people visiting areas at risk of contracting malaria and are almost never used by the local population due to the high cost and side effects of these medicines.

Since the beginning of the XVII century, quinine has been used for prevention. The synthesis of more effective alternative substances such as quinacrine (acrychin), chloroquine, and primaquine in the 20th century reduced the use of quinine. With the advent of the chloroquine-resistant Plasmodium falciparum strain, quinine has returned as a treatment, but not for prevention.

Modern medicines for prevention include mefloquine (Lariam®), doxycycline and atovaquone-proguanil hydrochloride (bigumal, Malaron®). The choice of drug usually depends on the resistance of parasites in the area and side effects. The preventive effect does not begin immediately, so you should start taking preventive drugs 1-2 weeks before arrival in the danger zone and 1-4 weeks after returning.

Mosquito extermination
Efforts to fight malaria by killing mosquitoes have been successful in some areas. Malaria was once prevalent in the United States and Southern Europe, but draining swamps and improving sanitation, along with monitoring and treating infected people, have made these areas unsafe. For example, in 2002, 1,059 cases of malaria were reported in the United States, including 8 deaths. On the other hand, it is not possible to eradicate malaria in many parts of the world, especially in developing countries – the problem is most common in Africa.

DDT is an effective anti-mosquito drug. It was developed during World War II as the first modern insecticide. At first it was used to fight malaria, and then it spread to agriculture. Over time, control over the number of agricultural pests, instead of killing mosquitoes, began to prevail in the use of DDT, especially in developing countries. Throughout the 1960s, evidence of the negative consequences of its misuse increased, which ultimately led to the ban on DDT in many countries in the 1970s. Until this time, its widespread use has already led to the emergence of DDT-resistant mosquito populations in many areas. But now there is the prospect of a possible return of DDT. The World Health Organization (WHO) today recommends the use of DDT against malaria in endemic areas. Along with this, it is proposed to use alternative insecticides in areas where mosquitoes are resistant to DDT in order to control the evolution of resistance.

Mosquito nets and repellents
Mosquito nets help protect people from mosquitoes and thereby significantly reduce the number of infections and transmission of malaria. Nets are not an ideal barrier, so they are often used along with an insecticide that is sprayed to kill mosquitoes before they find their way through the net. Therefore, insecticide-soaked nets are much more effective.

For personal protection, covered clothing and repellents are also effective. Repellents are divided into two categories: natural and synthetic. Common natural repellents are essential oils of some plants.

Transgenic mosquitoes
Several options for possible genetic modifications of the mosquito genome are being considered. One of the potential methods for controlling the number of mosquitoes is the method of growing infertile individuals. Significant progress has now been made towards developing a transgenic or genetically modified mosquito resistant to malaria. In 2002, two groups of researchers already announced the development of the first samples of such mosquitoes.