1.
Consultation with the specialist
“Cesmet – Traveler’s Clinic” is a medical center specializing in infectious and tropical diseases. Dr. Paolo Meo, founder since 1985 and director of the Traveler’s Clinic, is a physician specializing in infectious diseases and tropical medicine. Since 1981 spending two years in Somalia, in the refugee camps of the Ogaden war, in the middle of the African savannah, and for forty years he has always worked in many countries, especially African, gaining experience in the field of malaria diagnosis and treatment. Dr, Paolo meo is at your disposal if you need information on what to do to prevent the disease
Click here and book : (1) your consultationbefore your trip to inform you about prevention and prophylaxis for malaria; or (2) laboratory tests (smear and drop and RT-PCR molecular test for plasmodesmata causing malaria; or (3) a specialist examination of tropical medicine and malariology, if you do not feel well during or after a stay in areas at risk, whether you have returned from your trip or are still in the country destination of your trip;
Request information also by calling +39 0639030481.
2. Introduction and description
Malaria, also called paludism, from the French “paludisme,” is a parasitic infectious disease with an acute, even severe or chronic course, caused by a blood parasite called Plasmodium. These parasites are protozoa of the genus Plasmodium (Kingdom Protista, Phylum Apicomplexa, Class Sporozoea, Order Eucoccidiida). There are five main types of the malarial parasite: Pl. falciparum is the type with the highest mortality rate among infested individuals; Pl. vivax; Pl. malariae; Pl. ovalis; Pl. knowlesi , is the etiologic agent of malaria in monkeys, is widespread in Southeast Asia. It causes malaria in macaques but can also infect humans, either naturally or artificially. The reservoir of the parasite is chronically infected humans.
Malaria is transmitted exclusively through the bite of mosquitoes, female, infected Anopheles genus. This type of mosquito is not present in Italy and most of Europe. Some foci of Anopheles mosquito presence semre more restricted in some countries of the Mediterranean basin: Greece, Turkey, Egypt, Tunisia, Algeria, in Morocco small sporadic outbreaks.;
Malaria is the most widespread of all parasitic diseases. Transmitted by the Anopheles mosquito, it is present in Africa, Central and South America and Asia, some parts of Oceania.
In the human body, malaria parasites multiply in the liver and then after variable incubation infect the red blood cells.
The characteristic symptoms of the disease are: Fever, even high fever, sometimes not present; headache and sensation of brain wadding; tension of nuchal muscles; chills and sweating; sometimes nausea, vomiting and diarrhea; may be present overtly and severely, but may alternate or may be very mild.
If not treated with the appropriate drugs, (Eurartesim®, a life-saving drug to treat malaria) malaria can be dangerous to the integrity of certain organs and even to the person’s life. In fact, cerebral malaria has an ominous prognosis since the generalized microthrombosis phenomena generated by the action of the plasmodium on the stacking of red blood cells, have the ability to create widespread areas of cerebral necrosis also due to the interruption of blood supply, (severe DIC phenomena).
In many parts of the world, parasite resistance to antimalarial drugs is growing unabated. The latest surveys have shown a dangerous growth of resistance even to Artemisinin, the drug of choice for treating the parasite.
Control of the disease is done by preventive and curative methods:
– Rapid and effective pharmacological treatments of the disease with artemisinin-based therapies combined with other drugs;
– The use of mosquito nets treated with effective DEET-based insecticides.
-The use of insecticides and repellents for mosquito control. (neem-based products recommended).
3. Infectious agent and life cycle
Plasmodium is a parasitic, single-celled, protozoan of the genus Plasmodium (Kingdom Protista, Phylum Apicomplexa, Class Sporozoea, Order Eucoccidiida). There are five main types of the malarial parasite: Pl. falciparum is the type with the highest mortality rate among infested individuals; Pl. vivax; Pl. malariae; Pl. ovalis; Pl. knowlesi , which is the etiologic agent of malaria in monkeys, is widespread in Southeast Asia. It causes malaria in macaques but can also infect humans. The reservoir of the parasite is acutely or chronically infected humans.
There are five main species of Plasmodium that can infect humans:
P. falciparum: is endemic in tropical Africa, minor prevalence in Asia and Latin America. It is the plasmodium with the highest mortality rate;
P. vivax: is the most prevalent, found everywhere in tropical areas; in Africa it is present in outbreaks in the territory, in patches; however, it is endemic in Latin America and Asia; it is also present in some temperate areas and persists even in restricted areas of the Mediterranean basin, where the Anopheles mosquito is still present.
P. ovale: is present and has spread mainly in West Africa between the two tropics.
P. malariae: is ubiquitous, with low prevalence but uneven distribution over the territory.
Species diagnosis is important because P. falciparum malaria is potentially the most aggressive, injurious and if untreated fatal.
Reproduction of the vector mosquito occurs at temperatures no lower than 18°C. If the temperature drops it should not stay for prolonged periods of time. Survival of the insect is also related to temperature. Transmission of the parasite occurs through the mosquito bite. It is facilitated throughout the year in areas where the temperature is consistently above 24°C. In areas with lower temperatures, transmission tends to follow seasonal rhythms. The mosquito lives three to six weeks, rarely exceeding two months, and moves within a radius of 1 to 2 kilometers. Winds and special environmental conditions can carry mosquitoes even tens of kilometers apart.
Plasmodium vivax malaria has a longer incubation time. It can last up to several months. It presents clinically like P. falciparum malaria with irregular febrile attacks followed by profuse sweating and defervescence. There may be evidence of increased spleen volume (splenomegaly) rarely lesions or splenic rupture. After a few attacks the symptomatology wears off, but it may have a recurrent course due to the persistence of “so-called dormant” intrahepatic forms called “hypnozoites.” In these cases and with this type of malaria, so-called “benign tertian fever” may occur.
If there is co-infection of two types of Plasmodium there is symptomatology determined by the displaced growth rate of the parasite, and a double tertian form may occur, with continuous fever and symptoms occurring without periodicity. Chloroquine therapy is still effective, treating the acute malarial attack but not preventing relapse and chronicity of the disease. In African countries of the Gulf of Guinea where the population lacks “duffy erythrocyte antigen,” P. vivax is absent and is replaced by Plasmodium ovalis. The clinical picture is essentially superimposed on that of P. vivax.
Plasmodium malariae manifests with a less aggressive and milder form. Plasmodium can persist for years in erythrocytes with very low parasitemia, and in recrudescences fever occurs with spikes every ¾ days. Quartan form. In the pediatric group, Pl. malariae, but also the other types of malaria, due to repeated infections can cause renal disease at the glomerular level with membranous-proliferative inflammation, with proliferation of the glomerular endothelium and mesangium. Inflammatory-type damage is caused by the deposition of immune complexes at the level of the mesangium of the renal glomerulus. Renal damage is manifested by significant proteinuria, edema to the presence of ascites in the abdomen (nephrotic syndrome)
Renal damage is found to be permanent. The prognosis is poor and patients progress to chronic renal failure.
Life cycle:
The life cycle of the parasite occurs between two hosts: (1) Anopheles mosquito and (2) humans.
The “female mosquito” of the Anopheles type is the “vector” insect to which the transmission of the disease is due. The mosquito sucks blood from an individual and, if that individual is infected, becomes infected in turn. Once infected, the mosquito again stings another individual to feed on its blood and inoculates the sporozoite, which is the form of the plasmodium that has matured inside its intestine, into the person’s circulatory stream.
The infesting “sporozoites,” from the circulatory stream, passing into the microcirculation of the liver acinus, are sequestered by liver cells. Within an hour after inoculation, they are all found within the hepatocytes.
Within the liver cells they begin a phenomenon of maturation and multiplication, transforming into a multicellular formation, still joined together called a “schizont.”
Hepatocytes, infected by this parasitic multicellular formation, which comes to fill the entire cell, are injured and rupture, releasing into the circulatory stream, unicellular “parasitic” formations called “merozoites.” The passage occurs through the intrahepatic capillary system. It may occur that for P. vivax and P. ovalis, in addition to intrahepatocyte schizonts, there may be unicellular parasitic forms that remain in the dormant stage. These forms are called ‘hypnozoites,’ and are the cause of disease recurrence by invading the bloodstream months or even years later.[A] Recurrence:
Recurrence refers to a reignition of the disease caused by the persistence of merozoites in the liver (hypnozoites) that start a new exo-erythrocytic cycle again, 5-6 months after infection.
It is typical of P. vivax and P. ovale infections in which intrahepatic forms have not been treated.
After initial multiplication in the liver lasting an average of 7 to 8 days, called the exo-erythrocyte or schizogonic phase, the merozoite, having divided into individual cells, within the circulatory stream, enters the red blood cells, where it feeds on the ferrous heme, and begins asexual multiplication within these cells, called “erythrocytic schizogony.”
Intraerythrocytic parasitic forms, called “trophozoites,” grow and mature, feeding on iron, and in 2 to 3 days become “schizonts.” These parasitic cell formations result in the rupture of the red blood cell and divide in the circulatory stream into a multitude of “merozoites.”[B] Invasive phase:
Corresponds to the rupture of the schizont and the release of merozoites that go on to invade other erythrocytes. This event manifests with intermittent fever, shaking chills, sweating, headache, arthro-mialgia, sometimes reactivation of cold sores, prostration, pain in the hypochondria, gastroenteric syndromes (diarrhea, vomiting, abdominal pain). Febrile convulsions may occur in infants.
Merozoites, malarial parasites dispersed in the blood, colonize other red blood cells. These intracellular parasite cells still feed on ferrous heme in the blood cells and as they grow they mature into trophozoites. And so a new cycle of maturation is reactivated. This mechanism the red blood cells and intracellular maturation and multiplication, is the cause of the increase of parasites in the blood and the severe hemolytic anemias caused by the disease.[C] Late phase:
when the life cycles of the different strains present in the circulatory stream have synchronized, the” tertian fever” (typical malarial attack) appears: shaking chill followed by temperature rise that resolves after a few hours with profuse sweating and a state of vague euphoria, and is “repeated every 48 hours.” Splenomegaly usually appears after days or weeks; hepatomegaly is more common at first. Mucosal pallor, jaundice, hyperchromic (strongly colored) urine are unfavorable prognostic signs. In most untreated cases, malaria resolves spontaneously after 2 weeks; it rarely lasts more than a year (never more than 2 years).
Some parasites differentiate in the circulatory stream and take the route to the sexed stage, the gametocytes.
Gametocytes, or the sexed parasite forms, male, the microgametocyte; female the macrogametocyte; are ingested by the female mosquito during the bite, and infect the insect.
C) The multiplication of the parasite in the mosquito is known as the sporogonium cycle.
The gametocytes, through the tubules of the mosquito’s salivary glands end up in the stomach of the mosquito where fertilization of the macrogametocyte, the female, by the microgametocyte, the male, takes place. The unine between macro and micro gametocyte generates the ‘zygote’.
At this point the zygote becomes motile, elongates and invades the gut wall of the mosquito where it differentiates into ‘oocyst’;
The oocyst grows and develops in the gut wall where it divides into thousands of sporozoites. At this point the sporozoites migrate to the salivary glands of the mosquito. The insect, by biting an individual, inoculates the parasite causing the cycle to begin again.
[D] Recrudescence:
Is the relapse and thus the reoccurrence of the disease after a quiescent phase. It is caused by the persistence of intra-erythrocytic forms (in red blood cells) in the circulation. It is typical of P. falciparum infections that are inadequately treated (by quality and/or duration of treatment and by dosage) and can have a latency of a few days to a few weeks. It can also occur in P. malariae infections with a latency of even many years.
P. falciparum infection is called malignant tertian fever, P. vivax and P. ovale infection is called benign tertian fever, and P. malariae infection is called quartan fever based on the occurrence of intermittent fever. Those of “tertian” and “quartan” fever are misleading definitions, because only a very small proportion of malaria cases occur with intermittent fever, either every 48 hours (tertian, every third day) or every 72 hours (quartan, every fourth day). The tertian fever was observed in Europe in areas endemic for P. vivax (benign tertian) and in immigrants: the ships in fact made voyages of 1-2 weeks, and when they arrived in Europe, following the natural history of P. falciparum infection, from irregular intermittent the fever became tertian, if the sick person had not died in the meantime or had not been treated. Tertian fever is also observed in cases where one has been infected with a single strain of P. falciparum, an uncommon occurrence in endemic areas, where one is infected several times in sequence and the cycles of the various strains overlap with irregularly occurring febrile attacks.
Malaria does not always present with typical clinical fevers, but nuchal headache, chills, and alternating hot and cold, with a worsening malaise, are almost constant in the array of malarial symptoms. Untreated or inadequately treated P. falciparum infections can result in renal failure, pulmonary edema, endocranial hypertension with coma, and reach exitus. Death is caused by the parasitized cells stacking up in the microcirculation of various vital organs, particularly in the cerebral circulation (cerebral malaria), damaging them. In endemic areas, repeated infections, to which a person is subjected, develop a high level of antibodies, which allows resistance to infection. In most cases of infection, these individuals are asymptomatic while carrying the parasite in their cells (healthy carriers of the infection). Non-immune subjects, in endemic areas, can become ill much more easily than a subject considered immune, and can have more severe forms of disease.
A very interesting example is that of the evolution of the erythrocyte Duffy antigen, the receptor through which P. vivax merozoites penetrate the red blood cell. Erythrocytes lacking this antigen (Duffy negative) are refractory to infection by that plasmodium. In West Africa, a mutation that removes the antigen from the surface of erythrocytes but has no other clinical consequences has reached (probably over several thousand years) 100% frequency, and thus most people in West and Central Africa are not infected with this plasmodium species.
As early as the early 1950s, at the conclusion of the Five-Year Antimalarial Struggle Campaign, Italy was in fact a malaria-free country, but because some sporadic cases of Plasmodium vivax malaria continued until 1962, WHO did not formalize this finding until 1970. Since then, in view of the potential conditions for malaria reintroduction in Italy, a surveillance system has been activated.
[D] Recrudescence:
Is the relapse and thus the reoccurrence of the disease after a quiescent phase. It is caused by the persistence of intra-erythrocytic forms (in red blood cells) in the circulation. It is typical of P. falciparum infections that are inadequately treated (by quality and/or duration of treatment and by dosage) and can have a latency of a few days to a few weeks. It can also occur in P. malariae infections with a latency of even many years.
P. falciparum infection is called malignant tertian fever, P. vivax and P. ovale infection is called benign tertian fever, and P. malariae infection is called quartan fever based on the occurrence of intermittent fever. Those of “tertian” and “quartan” fever are misleading definitions, because only a very small proportion of malaria cases occur with intermittent fever, either every 48 hours (tertian, every third day) or every 72 hours (quartan, every fourth day). The tertian fever was observed in Europe in areas endemic for P. vivax (benign tertian) and in immigrants: the ships in fact made voyages of 1-2 weeks, and when they arrived in Europe, following the natural history of P. falciparum infection, from irregular intermittent the fever became tertian, if the sick person had not died in the meantime or had not been treated. Tertian fever is also observed in cases where one has been infected with a single strain of P. falciparum, an uncommon occurrence in endemic areas, where one is infected several times in sequence and the cycles of the various strains overlap with irregularly occurring febrile attacks.
Malaria does not always present with typical clinical fevers, but nuchal headache, chills, and alternating hot and cold, with a worsening malaise, are almost constant in the array of malarial symptoms. Untreated or inadequately treated P. falciparum infections can result in renal failure, pulmonary edema, endocranial hypertension with coma, and reach exitus. Death is caused by the parasitized cells stacking up in the microcirculation of various vital organs, particularly in the cerebral circulation (cerebral malaria), damaging them. In endemic areas, repeated infections, to which a person is subjected, develop a high level of antibodies, which allows resistance to infection. In most cases of infection, these individuals are asymptomatic while carrying the parasite in their cells (healthy carriers of the infection). Non-immune subjects, in endemic areas, can become ill much more easily than a subject considered immune, and can have more severe forms of disease.
A very interesting example is that of the evolution of the erythrocyte Duffy antigen, the receptor through which P. vivax merozoites penetrate the red blood cell. Erythrocytes lacking this antigen (Duffy negative) are refractory to infection by that plasmodium. In West Africa, a mutation that removes the antigen from the surface of erythrocytes but has no other clinical consequences has reached (probably over several thousand years) 100% frequency, and thus most people in West and Central Africa are not infected with this plasmodium species.
As early as the early 1950s, at the conclusion of the Five-Year Antimalarial Struggle Campaign, Italy was in fact a malaria-free country, but because some sporadic cases of Plasmodium vivax malaria continued until 1962, WHO did not formalize this finding until 1970. Since then, in view of the potential conditions for malaria reintroduction in Italy, a surveillance system has been activated.
4. Transmission, gateway and incubation
Transmission:
occurs by biting infected female mosquitoes of the genus Anopheles, which, by sucking infected blood and injecting infected blood, transfer the infection from human to human. The male mosquito does not sting. Once injected into a healthy human, the parasite begins to multiply exponentially in the liver and then, after 7 to 10 days, on average, multiplies in the red blood cells. Mosquitoes become infected by ingesting the parasite, through the infected blood meal. Once inside the insect, the parasite begins another life cycle: the reproductive phase that precedes transmission to another healthy individual.
Incubation:
differs between different types of plasmodia. The incubation period averages 7-14 days for P. falciparum infection, 8-14 for P. vivax and P. ovale, and 7-30 days for P. malariae. For some strains of P. vivax, incubation may extend for 8-10 months and longer; this period may be even longer for P. ovale.
Gateway of entry: is the skin, via mosquito bite. The mosquito injects the sporozoites directly into the blood of the microcirculation present in the dermis.
5. Geographical distribution
malaria is present in more than 100 countries around the world, but predominantly confined to the poorer tropical areas of Africa, Asia and Latin America. More than 90% of cases and the vast majority of deaths occur in tropical and equatorial Africa. Plasmodium falciparum is the main type of malaria and is the cause of deaths caused by the disease.
Although the distribution of malaria worldwide has been reduced and confined mainly to tropical areas, the number of people at risk of infection has reached about 3 billion and this number is likely to increase. Each year there are 500 million cases of malaria worldwide with about 1.3 million deaths. Ninety percent of the cases are in Sub-Saharan Africa, with a devastating impact on the economy and social development of most of the affected countries.
Following the world malaria eradication campaigns launched by the World Health Organization (WHO) in 1955, and discontinued for technical and economic reasons in the late 1960s, there has been a resurgence of malaria in the intervening years, not only in areas that had benefited from the good results of the eradication campaigns, but also in Sub-Saharan Africa, mainly due to the emergence of Plasmodium falciparum resistance to chloroquine and other antimalarial drugs. (see mapping)
Mutations in hemoglobin (S,C, beta and alpha-thalassemia), glucose-6-phostate dehydrogenase and pyruvate kinase enzymes protect against severe forms of malaria caused by P.falciparum in heterozygous carriers and, in the case of hemoglobin C, especially in homozygosity. The special properties of hemoglobin chains and the oxidative stress conditions caused by the infection itself can cause hemolysis of erythrocytes by hindering the maturation of trophozoites. Although these mutations are harmful (almost always lethal in homozygosity), due to the protection conferred against malaria they are found at high frequencies in populations living in malaria endemic (or formerly endemic) areas (Mediterranean basin, sub-Saharan Africa, Southeast Asia). Except for hemoglobin C,in these populations, however, the frequency of resistance mutations is likely to reach an equilibrium value (around 15-20%) that reflects the disadvantage due to mutation lethality and the advantage with respect to malaria. In non-malaria areas, these mutations are generally very rare or absent because their lethality is not counterbalanced by positive effects.
A very interesting example is that of the evolution of the erythrocyte Duffy antigen, the receptor through which P. vivax merozoites penetrate the red blood cell. Erythrocytes lacking this antigen (Duffy negative) are refractory to infection by that plasmodium. In West Africa, a mutation that removes the antigen from the surface of erythrocytes but has no other clinical consequences has reached (probably over several thousand years) 100% frequency, and thus most people in West and Central Africa are not infected with this plasmodium species.
As early as the early 1950s, at the conclusion of the Five-Year Antimalarial Struggle Campaign, Italy was in fact a malaria-free country, but because some sporadic cases of Plasmodium vivax malaria continued until 1962, WHO did not formalize this finding until 1970. Since then, in view of the potential conditions for malaria reintroduction in Italy, a surveillance system has been activated.
6. Symptoms
Malaria Symptoms:
Initially malaria symptoms sometimes present with flu-like characteristic between 8 and 30 days after infection.
Invasive phase:
Corresponds to the rupture of the schizont and the release of merozoites that go on to invade other erythrocytes. It manifests with intermittent fever, shaking chills, sweating, headache, arthro-mialgia, sometimes reactivation of cold sores, prostration, pain in the hypochondria, gastroenteric syndromes (diarrhea, vomiting, abdominal pain). Febrile convulsions may occur in infants.
Late phase:
When the life cycles of the various strains present have synchronized, tertian fever (typical malarial attack) appears: shaking shiver followed by a rise in temperature that resolves after a few hours with profuse sweating and a state of vague euphoria, and repeats every 48 hours. Splenomegaly usually appears after days or weeks; hepatomegaly is more common at first. Mucosal pallor, jaundice, hyperchromic (strongly colored) urine are unfavorable prognostic signs. In the majority of untreated cases, malaria resolves spontaneously after 2 weeks; it rarely lasts more than a year (never more than 2 years).
Recurrence:
Is the relapse caused by the persistence of intra-erythrocytic forms (in red blood cells) in the circulation. It is typical of P. falciparum infections that are inadequately treated (by quality and/or duration of treatment and by dosage) and can have a latency of a few days to a few weeks. It can also occur in P. malariae infections with a latency of even many years.
Relapse:
Relapse refers to a relapse caused by the persistence of merozoites in the liver (hypnozoites) that start a new exo-erythrocytic cycle again, 5-6 months after infection.
It is typical of P. vivax and P. ovale infections in which intrahepatic forms have not been treated.
P. falciparum infection is called malignant tertian fever, P. vivax and P. ovale infection is called benign tertian fever, and P. malariae infection is called quartan fever based on the occurrence of intermittent fever. Those of “tertian” and “quartan” fever are misleading definitions, because only a very small proportion of malaria cases occur with intermittent fever, either every 48 hours (tertian, every third day) or every 72 hours (quartan, every fourth day). The tertian fever was observed in Europe in areas endemic for P. vivax (benign tertian) and in immigrants: the ships in fact made voyages of 1-2 weeks, and when they arrived in Europe, following the natural history of P. falciparum infection, from irregular intermittent the fever became tertian, if the sick person had not died in the meantime or had not been treated. Tertian fever is also observed in cases where one has been infected with a single strain of P. falciparum, an uncommon occurrence in endemic areas, where one is infected several times in sequence and the cycles of the various strains overlap with irregularly occurring febrile attacks.
Malaria does not always present with typical clinical fevers, but nuchal headache, chills, and alternating hot and cold, with a worsening malaise, are almost constant in the array of malarial symptoms. Untreated or inadequately treated P. falciparum infections can result in renal failure, pulmonary edema, endocranial hypertension with coma, and reach exitus. Death is caused by the parasitized cells stacking up in the microcirculation of various vital organs, particularly in the cerebral circulation (cerebral malaria), damaging them. In endemic areas, repeated infections, to which a person is subjected, develop a high level of antibodies, which allows resistance to infection. In most cases of infection, these individuals are asymptomatic while carrying the parasite in their cells (healthy carriers of the infection). Non-immune individuals in the endemic area can become ill much more easily than an individual considered immune, and may have more severe forms of disease.
Mutations in hemoglobin (S,C, beta and alpha-thalassemias), glucose-6-phostate dehydrogenase and pyruvate kinase enzymes protect against severe forms of malaria caused by P.falciparum in heterozygous carriers and, in the case of hemoglobin C, especially in homozygosity. The special properties of hemoglobin chains and the oxidative stress conditions caused by the infection itself can cause hemolysis of erythrocytes by hindering the maturation of trophozoites. Although these mutations are harmful (almost always lethal in homozygosity), due to the protection conferred against malaria they are found at high frequencies in populations living in malaria endemic (or formerly endemic) areas (Mediterranean basin, sub-Saharan Africa, Southeast Asia). Except for hemoglobin C,in these populations, however, the frequency of resistance mutations is likely to reach an equilibrium value (around 15-20%) that reflects the disadvantage due to mutation lethality and the advantage with respect to malaria. In non-malaria areas, these mutations are generally very rare or absent because their lethality is not counterbalanced by positive effects.
7. Diagnosis and treatment
DIAGNOSIS
Diagnosis:
Currently, diagnostic practice is based on two approaches: the clinical one that identifies the symptoms of the disease, and the one aimed at isolating and recognizing the causative agent, using immunochromatographic tests or, much more commonly, with microscopic observations.
The clinical picture may present strongly atypical in persons who have undergone antimalarial chemoprophylaxis at inadequate dosages or with drugs no longer effective due to resistance phenomena, or who are partially immune after long stays in endemic areas, as well as in early childhood.
To make a diagnosis of malaria, a blood smear taken from a finger prick must be prepared. The smear is fixed with methanol before staining; the thick drop is stained without being fixed. In P. falciparum infections, parasite density should be estimated by counting the percentage of infected blood cells, not the number of parasites.
It can be done by following different types of approaches.
Microscopy
– Smear and thick drop examination, Giemsa staining
– Plasmodium nucleic acid detection, rapid UV test
– ‘Quantitative buffy coat method (QBCTM, Becton-Dickinson)’
Immunological tests
– IFI test (indirect immunofluorescence)
– Other tests are based on the capture of protein II (PfHRP-II)
Study parasite-associated enzymatic or antigenic activities.
-Determination of the antigen (histidine rich protein-2, HRP-2) associated with the malaria parasite (P. falciparum and P. vivax).
-Determination of the Plasmodium lactate dehydrogenase (pLDH) enzyme both by its enzymatic activity and by immunoassay.
Molecular biology techniques
– PCR
TREATMENT
Treatment:
Plasmodia have become highly resistant to almost all drugs that have been produced to combat them, as well as to many insecticides used to disinfest malarial areas. Resistance to chloroquine, the least expensive and most widely used antimalarial, is now common throughout southeastern Africa. In these same areas, resistance has also now become established to another drug, an alternative to chloroquine and just as inexpensive, sulfadoxine-pyrimethamine. Many countries are thus forced to use new combinations of much more expensive drugs. Rapid onset response, with drug treatment with the most recently developed drugs given in combination, as an alternative to traditional monotherapies, can significantly reduce the number of deaths. The extensive and poorly controlled use of quinoline and antifolate therapies has contributed to the increased development of resistance. In the last decade, a new group of antimalarials, several artemisinin combination compounds (ATCs), are showing excellent therapeutic results even within a week, with reduction in the presence of plasmodium and thus its ability to transmit and improvement in malaria symptoms.
On the vaccine front, research has not yet produced an effective vaccine although there are several possible candidates that scientists are working on, especially with the completion of the Plasmodium genome sequence.
However, there are a number of low-cost prevention and prophylaxis measures that are being promoted especially in African countries by the Global Partnership Roll Back Malaria coordinated by the World Health Organization, which had more than 90 international institutions coming together in an effort to halve the number of malaria patients by 2010. The use of insecticide-treated mosquito nets and intermittent preventive treatments with antimalarial drugs can significantly reduce the incidence of the disease in endemic areas, both among children and pregnant women, who are particularly vulnerable.
8. Control, transmission, and vaccination
Control and prevention:
Factors that can promote the development of an epidemic are both natural, such as a climatic variation or flood, and anthropogenic, such as a war or the development of agricultural works, dams, mines, or the inability to exert control over the mosquito, the vector of the plasmodium. Large internal migratory movements within a continent promote even more exposure of vulnerable populations to the pest. The combination of meteorological, socioeconomic, and epidemiological factors, both locally and globally, can allow prediction of the risk of epidemics, especially if due to anthropogenic factors. Therefore, the accurate study of past epidemic phenomena and the construction of a monitoring network and database to record the occurrence and prevalence of malaria in different areas become important prevention tools.
-Protection from insect stings is the first precaution to be taken to prevent malaria.
This can be implemented through a series of behavioral habits (in the evening and morning wear loose clothing that reaches to cover wrists and ankles; in certain areas adopt the use of mosquito nets that wrap the bed during the night, preferably impregnated with insecticide) or through the use of chemical remedies (repellents for skin use e.g. based on DEET, use of pyrethrum mosquito coils, use of other synthetic pyrethroids and through electric stoves) or, better still, based on natural substances.
Drug prophylaxis is an important means of avoiding the risk of contracting malaria; the parasite, inoculated by the vector insect, is killed by the drug before it can exert its nefarious effects on the unfortunate individual.
In order for the most suitable pharmacological prophylaxis to be prescribed for each individual traveler, it is recommended that he or she be referred to a center specializing in tropical diseases or at least to a physician experienced in the same. Pharmacological prophylaxis is strictly individual and may vary not only from person to person, but also depending on the country visited, the length of the traveler’s stay there, as well as the time of year in which the stay is made.
Mechanical protection:
the first defense to be activated to avoid malarial risk is to avoid mosquito bites. The female Anopheles mosquito, a vector of the malarial parasite, uses thermal and olfactory, as well as visual, stimuli to locate the host to be bitten in order to carry out its blood meal. In particular, it is attracted to concentrations of carbon dioxide. Dark colors attract the insect in question, which uses to sting at dusk and during the early hours of the night. Some perfumes or natural fragrances can attract mosquitoes and induce them to sting. – Inside homes: -the protection of windows with insecticide-treated nets and the use of insecticide-impregnated mosquito nets over beds can confer good protection; the use of air conditioning greatly decreases the risk of insect bites.
Outdoors :
use clothes that cover well, preferably shirts with long sleeves and long pants, particularly from dusk to evening; advisable to wipe repellents or insecticides on clothes to further decrease the risk of bites.
Repellents are chemicals that ward off the insect:
most repellents contain DEET (N,N-diethyl-methyl-toluomide) a very active substance in use for over 40 years. -;Other synthetic repellents are active for about 3-4 hours and should be applied periodically (about every 3 hours) during malaria-risk exposure. -Repellents should not be inhaled or ingested and are dangerous on irritated skin or eyes. They should be used with caution in children and never applied to their hands because they are easy tools for contamination of the eyes and mouth. Water can easily remove different types of repellents from the skin.
Repellent should be applied to the entire uncovered part of the body: there is evidence that mosquitoes can sting within an inch of a covered area.
The use of repellents is not recommended :
In children under one year of age;
to residents for long periods (accumulation toxicity);
to pregnant women.
Insecticides:
Are chemicals that attack the insect’s nervous system and kill it.
Synthetic insecticides based on pyrethroids (permethrin, deltamethrin and others).
Natural pyrethrum-based insecticides (obtained from the flowers Crisantenum cineraricefolium).
Pyrethrum acts as both an insecticide and a repellent.
Permethrin and deltamethrin contained in many insecticides are products that are considered non-toxic to adults and therefore can be used indoors even in the presence of young children under two years of age. For them to adopt natural substances
The use of insecticides on clothes and mosquito nets maintains their effectiveness for about 2-3 months . For adults it is not considered toxic.
Malaria and pregnant women: Women residing in endemic areas possess, in most cases, a semi-immunity; this may wane temporarily during pregnancy (with even dramatic consequences, especially in primigravidae) and wanes over time in individuals who leave endemic areas (disappears after 2 years of being away). Women’s risk of death from malaria increases in pregnancy, the risk of miscarriage and stillbirth or increases the incidence of neonatal death. Do not go to malaria areas unless absolutely necessary. WHO (World Health Organization) advises pregnant women not to vacation in areas where there is transmission of chloroquine-resistant P. falciparum.
Advice in pregnancy:
Be very diligent in using protective measures against mosquito bites;
use chloroquine and proguanil for prophylaxis;
in areas with chloroquine-resistance of P. falciparum, the chloroquine-proguanil combination should be used in the first trimester of pregnancy; mefloquine can only be used from the 4th month of pregnancy onward;
do not use Doxycycline for prophylaxis;
seek medical attention immediately if malaria is suspected and do emergency self-treatment (famaco of choice is quinine) only if a doctor cannot be found immediately. Medical attention should be sought anyway after self-treatment.
Malaria and children: Children are considered to be at risk for malaria because they can develop pernicious forms that lead to early exitus.
In endemic areas, infants are protected for the first 6 months by passive maternal immunity, given by antibodies inherited from the mother, then there is a progressive acquisition of “semi-immunity” by successive exposures to plasmodium infections. One has recurrent bouts of malaria, from the age of a few months to 5-10 years, before reaching a state of semi-immunity. Many babies suffer growth retardation and others die. If the babies survive, they maintain semi-immunity for continuous reinfection, throughout their lives, as long as they reside in the endemic area. This is considered so because during life there are equally recurrent episodes of parasitemia, of short duration and low burden, mostly asymptomatic or paucisymptomatic (with few symptoms).
do not take infants and young children to malarial areas unless absolutely necessary;
protect children from mosquito bites; mosquito nets are available for cribs and cribs: keep young children under the protection of mosquito nets during the period from sunrise to sunset;
give malaria prophylaxis to babies who are still breastfed and those who are bottle-fed since they are not protected by the prophylaxis that the mother may have done earlier;
chloroquine and proguanil can be safely administered to infants and young children. For administration, the drugs can be sugarcoated with jam, bananas and other foods;
do not give sulfadoxine-pyrimethamine or sulphalene-pyrimethamine to infants under three months of age;
do not give doxycycline for chemoprophylaxis to children under 8 years of age;
keep all antimalarial drugs out of the reach of children locked in containers that cannot be opened by the children themselves. Chloroquine is particularly toxic to children if the recommended dose is exceeded;
Seek medical attention immediately if a child develops a febrile illness. Symptoms of malaria in children may not be typical so that malaria should always be suspected. In children younger than three months of age, malaria should be suspected even in cases of nonfebrile illness;
fever in a child returning from a trip to a malarial area should be considered a symptom of malaria at least unless proven otherwise;
in the case of self-treatment, quinine can be administered without weight or age limit. Mefloquine can be used above 15 kg in weight.
OSM advises against taking infants and young children on vacation to malarial areas, particularly where there is transmission of chloroquine-resistant P. falciparum.
