- Malaria Vaccination-is it Possible ?
- Fever patten of the falciparum malaria
- Targets and approaches for the control of P. falci...
- Targets for Intervention
- Plasmodium falciparum- lifecycle
- Malaria life cycle
- Distribution map of occurrence of chloroquine resi...
- malaria parasite-Common Plasmodium species
- Morphology of the mosquito vector
- life cycle of vector mosquito-Anopheles
- malaria vector mosquito life cycle
- Mosquito vector in malaria- Anopheles,culex
- Prevention and control of malaria
- Management of malaria
- Diagnosis of malaria
- Some features of severe falciparum malaria
- Causes of anemia in malaria infection
- Clinical features
- Parasitology
- Epidemiology
- Malaria in sri lanka
Tuesday, March 31, 2009
CONTENTS
Tuesday, March 24, 2009
Malaria Vaccination-is it Possible ?
Human malaria is, among animal and human parasite protozoan diseases, the one for which,The most intense effort of research has been accumulated in the last decades in view of the development of vaccines. Scientific literature on this topic accounts for thousands of references every year, particularly concerning falciparum malaria. This is comprehensible because of the importance of malaria as a leading cause of morbidity and mortality in the tropical areas of the world, with an estimated 300±500 million cases each year and more than 1 million deaths, mainly among children below five years of age in Africa. A naturally acquired immunity against malaria is observed in endemic areas where people are exposedto frequent infections. This immunity develops slowly and is characterized, in a first step,by the acquisition of clinical resistance to symptoms, clinical immunity, and later by the ability to control parasitemia at a low level, antiparasite immunity, usually fully expressed only in adults. Classical experiments of British immunologists working in Africa showed in the 60s that the natural immunity was antibody-dependent, directed against the asexual blood stages of the parasite.More recently, sero-epidemiological surveys in endemic areas have shown the existence of anti-sporozoite specific antibodies as well as antibodies and CTL cells directed against antigens of the hepatic stage. Finally, naturally and artificially raised antibodies against the gametocytes and latter forms of the sexual stage have been described as able to block the development of the parasite in the mosquito. These observations indicate that immunity in malaria is stage specific and this was indeed proved in laboratory experiments with rodent and primate models. Thus, efforts in the construction of vaccines have been directed towards different target alternatives. The starting point was the impossibility of raising vaccines from parasite materials since no culture systems are available for pre-erythrocytic stages of the parasites while culture of blood stages (P. falciparum) require growth in human red cells. These constraints made malaria vaccines one of the first domains of medical sciences in which nascent genetic engineering technology was actively introduced with the aim of preparing sub-unit vaccines. In principle the ideal target would be the pre-erythrocyte stages antigens (sporozoites and hepatic forms) since an effective vaccine against these stages would block transmission. However, an inconvenience of such a vaccine is that it would need to induce sterile immunity, because a surviving sporozoite or hepatic schizont would be sufficient to produce erythrocyte invasion and multiplication of the parasite in the blood. Sterile immunity against blood stage, however,is not naturally observed in humans of endemic areas and is usually not experimentally obtained in animal models. In contrast, non sterilizing, partially active vaccines against asexual blood stages would be favorable to avoid the development of high parasitemia and presumably reduce severe malaria outcome responsible for mortality.However, it would poorly interfere at the level of sources of infection in an endemic area and, therefore, in the level of transmission. Anti sexual stage vaccines transmission blocking vaccines would abolish or reduce transmission but would not protect the vaccinated individual from infection (altruistic vaccine). In conclusion, these considerations point to the interest in developping multigene, multi-stage vaccination approach like the CDC/NIIMALVAC-1, for which preliminary assays are now in course.
Fever patten of the falciparum malaria
Plasmodium vivax. Diagrammatic representation of the relationships between development of parasites in blood and occurrence of fever in the case of Malaria tertiana (P. ovale is similar). 1, Signet ring-stage; 2, Polymorphous trophozoite; 3, Immature schizont; 4, Mature schizont before formation of merozoites
Targets for Intervention
Targets of intervention are infected humans, the vector, and the infection cycle. Approaches are numerous and their selection depends
on the given epidemiological situation, the available resources and the envisaged level of control. Treatment of infected persons may be suppressive or radical and gametocytocidal. Vector control may be directed against the aquatic stages of Anopheles, the adult mosquitoes, or both. The interruption or reduction of man-vector contact is a valuable ancillary measure. Main clinical symptom:
a) Plasmodium vivax (Malaria tertiana): fever of 40±41_C for several hours, (after 1 h of shivers) is repeated within 48 h b) P. ovale (M. tertiana): as in P. vivax infections
c) P. malariae (M. quartana): rhythmic fevers of
40±41_C (after shivers) reappear within 72 h
d) P. falciparum (Malaria tropica): Irregular high fevers of 39±41_C appear continuously after a phase of headache and general abdominal symptoms; fevers may be rhythmic (48 h) or
Even absent (Fig. 4); eventually followed by coma and death.
Incubation period:
a) P. vivax: 12±18 days, occasionally longer
b) P. ovale: 10±17 days
c) P. malariae: 18±42 days
d) P. falciparum: 8±24 days
Prepatent period:
a) P. vivax: 8±17 days, occasionally longer
b) P. ovale: 8±17 days
c) P. malariae: 13±37 days
d) P. falciparum: 5±12 days
Patent period:
a) P. vivax: up to 5 years
b) P. ovale: up to 7 years
on the given epidemiological situation, the available resources and the envisaged level of control. Treatment of infected persons may be suppressive or radical and gametocytocidal. Vector control may be directed against the aquatic stages of Anopheles, the adult mosquitoes, or both. The interruption or reduction of man-vector contact is a valuable ancillary measure. Main clinical symptom:
a) Plasmodium vivax (Malaria tertiana): fever of 40±41_C for several hours, (after 1 h of shivers) is repeated within 48 h b) P. ovale (M. tertiana): as in P. vivax infections
c) P. malariae (M. quartana): rhythmic fevers of
40±41_C (after shivers) reappear within 72 h
d) P. falciparum (Malaria tropica): Irregular high fevers of 39±41_C appear continuously after a phase of headache and general abdominal symptoms; fevers may be rhythmic (48 h) or
Even absent (Fig. 4); eventually followed by coma and death.
Incubation period:
a) P. vivax: 12±18 days, occasionally longer
b) P. ovale: 10±17 days
c) P. malariae: 18±42 days
d) P. falciparum: 8±24 days
Prepatent period:
a) P. vivax: 8±17 days, occasionally longer
b) P. ovale: 8±17 days
c) P. malariae: 13±37 days
d) P. falciparum: 5±12 days
Patent period:
a) P. vivax: up to 5 years
b) P. ovale: up to 7 years
Plasmodium falciparum- lifecycle
Life cycle stages of Plasmodium falciparum, the agent of Malaria tropica. 1 The female? Anopheles injects sporozoites which enter liver cells via the bloodstream. 2, 3 Schizonts develop numerous merozoites (3) which after rupture of the host cell leave the liver and enter erythrocytes. 4 Merozoite directly after penetration (so-called signet-ring stage) ± this stage is very small (1/5 of the red blood cell's diameter) and is the only stage found in blood cell smears of patients. 5±8 Schizonts, which are blocked within capillaries (e.g. of the brain), give rise to several merozoites (6) which invade other red blood cells and again become schizonts (5) or develop into male or female banana-shaped gamonts (7 a,b) which are taken up by another engorging mosquito (8). 9±16 the processes in the mosquito are described in Fig. 2. E, erythrocyte; H, skin surface; N, nucleus; NH, nucleus of host cell; PV,?parasitophorous vacuole; R, remnants of the erythrocyte.
Malaria life cycle
Life cycle of human malaria parasites (Plasmodium spp.) without reference to species-specific variations.1 Elongate sporozoites are injected during bite of the female mosquito (Anopheles spp.). The sporozoites are distributed by bloodstream and enter liver cells within 2 minutes after infection. 2, 3 Formation of schizonts and merozoites in liver parenchymal cells (exoerythrocytic phase). In some species this cycle may be preserved intracellularly via ``hypnozoites'' (dormozoites) for a long time (years) and cause relapses. 4±8 Erythrocytic cycle; liver merozoites enter (after typical prepatent periods,) erythrocytes, grow to ``signet-ring stages'' (5) and finally form, as schizonts (6), several merozoites (7, 8). During the digestion of hemoglobin the parasites produce pigment granules (6, 7; PG) of hemozoin. The development of such schizonts becomes synchronous and is repeated (4±8) in a 1±3 day cycle (depending on the species). 9 After an indeterminate number of such asexual generations, some merozoites enter erythrocytes and become macro- (9.1) or microgamonts (9.2). The size and shape are species specific (banana-shaped in P. falciparum). 10±11 When mosquitoes bite, they ingest erythrocytes containing such gamonts, which are released inside the gut from their enclosing erythrocytes. 12, 13 The microgamonts develop four to eight migrogametes in 10±15 min. 14 Fertilization of macrogamete. 15±19 The resultant zygote quickly elongates and becomes a motile ookinete (17) which penetrates (the not) drawn peritrophic membrane in the mosquito's gut, migrates through the cytoplasm of a gut cell and begins its transformation into an oocyst (situated between basal membrane and epithelial cells, 19). 20±22 Formation of multinucleate sporoblasts (20) which give rise to thousands of sporozoites (after 10±14 days). The latter become liberated into the hemocoel (body cavity) and migrate to salivary glands. These slender sporozoites (10±15 x 1 mm), which form a protecting surface coat, are finally injected into a new host at the next feeding act. BM, basal membrane of intestine; E, erythrocyte; IN, intestinal cell; LP, liver parenchymal cell; N, nucleus;PG,pigment; PV, parasitophorous vacuole; SG, salivary gland.
Morphology of the mosquito vector
The generally 3±6 mm long adult flies possess long slender legs. The head is globular, possessing two large compound eyes (no ocelli) and long filamentous antennae which contain sensory organs to recognize host and oviposition sites and the John ston's organ in the basic segment by which males recognize wing beats of the females. The prominent mouth part is equal in length to the head/ thorax region and formed by the labium ensheathing the stylets which have developed from the labrum (building the food channel), the two mandibles and laciniae and the unpaired hypopharynx, the latter containing the salivary channel. The length, shape and hairiness of the five-segmented maxillary palps differ according to species and sex, being reduced in males which do not feed blood, but only sugars, e.g. honeydew or nectar. In addition, males and females can usually be separated according to the antennae, which are brush-like in males, the weaker developed mouth parts of males and the external genitalia of males, jointed claspers. In both sexes only the veins of the wings are covered with scales. After emergence, male genitalia rotate by 180_, thereby making a copulation during flight easier. The elongated larvae possess a well-sclerotized head capsule, bearing pairs of heavily sclerotized mandibles and maxillae and mouth brushes, the latter helping to scrape vegetation from surfaces or sweeping food particles towards the mouth. One pair of spiracles is located on the fused segments 8/9, almost flush with the surface in Anophelinae or at the end of a sclerotized siphon in Culicinae. In all species, the last segment has a sclerotized saddle with a ventral brush which is used for swimming. On the cephalothorax of the comma-shaped pupae, a pair of respiratory trumpets is located through which the pupae breathe at the water surface. The pupae also possess paddles at the end of the abdomen. There are several criteria to distinguish Anophelinae and Culicinae (Fig. 1A±D): Anopheline eggs are boat-shaped, laid singly and remain at the water surface by air-filled floats. The larvae are surface filter feeders, siphon less and, when not disturbed, they lay parallel to the water surface. Especially adults of the genus Anopheles have at rest all parts (proboscis, head, thorax, and abdomen) in a straight line, holding an angle of 30_ to 45_ to the surface. The wing veins are covered in a Characteristic pattern by dark and pale scales. Scales are usually totally absent from the abdominal sternites. Both sexes possess long, black palps. In contrast to the Anophelines, the Culicines show the following: The larvae hang down at an angle of about 40_ to the water surface or an angle of about 40_ to the water surface or water plants (Mansonia) on which the siphon is located. In resting adults, the body is nearly parallel to the surface or directed back towards the surface. Sternites and tergites are densely covered with scales and the palps of females are not more than one-third as long as the proboscis. Within Culicines, eggs of the three genera can also be distinguished: The black Aedes eggs are laid singly, those of Culex grouped to egg rafts, those of Mansonia glued to the undersurfaces of plants.
life cycle of vector mosquito-Anopheles
Life cycle stages of three important genera of mosquitoes. A Shape of eggs which were laid on the water's edge(Aedes, Culex) or on the water itself (Anopheles). B Respiring larvae at the water surface; the four larval stages feed by filtering organic particles in the water. C Respiring pupae; pupae (described as tumblers) do not feed and remain at the\surface unless disturbed. D Sitting females; males (with brushed antennae) and females are good flyers and feed on nectar,but females of most species suck blood (vessel feeder) before depositing eggs. The latter are laid in a clutch of about 200 individuals (A). Eggs require 48±72 h to develop within the females, which thus take blood every 2±4 days and consequently provide good opportunities for the transmission of pathogens.
malaria vector mosquito life cycle
Life Cycle
Normally embryonic development is completedwithin a few hours after egg laying, and the first instar larvae hatch. Fully developed larvae of Aedes remain in the egg shell until eggs are flooded, and can thereby be stored for a long period of time (depending on temperature and humidity up to 4.5 years). Larvae are aquatic, mainly occurring in fresh water, but some species also develop in salt water. The size of the habitat can be very small, e.g. tree holes. The total duration of the four larval instars varies greatly, even within one species, especially depending on temperature and food supply. In the tropics it can be completed within one week, in temperate regions many months and even longer if a larval diapause exists.
Some species are even frost-tolerant while others live at 50_C. The larvae feed on debris or plankton (filter feeders) or predate other larvae. The development of the also aquatic pupa is also temperature- dependent, lasting between 1 day or up to three weeks. If the pupae are disturbed, they actively swim downwards with their paddles at the end of the abdomen. The longevity of the adults strongly varies according to the climatic region, on average one to two weeks in the tropics and four to five weeks in temperate regions, but up to several months for females of hibernating or aestivating species. Thereby, the whole developmental cycle (egg to egg) can last about 7 days or up to several months in diapausing species.
Distribution Mosquitoes are found almost worldwide in almost all types of ecological zones, being absent only from Antarctica and some islands.
Normally embryonic development is completedwithin a few hours after egg laying, and the first instar larvae hatch. Fully developed larvae of Aedes remain in the egg shell until eggs are flooded, and can thereby be stored for a long period of time (depending on temperature and humidity up to 4.5 years). Larvae are aquatic, mainly occurring in fresh water, but some species also develop in salt water. The size of the habitat can be very small, e.g. tree holes. The total duration of the four larval instars varies greatly, even within one species, especially depending on temperature and food supply. In the tropics it can be completed within one week, in temperate regions many months and even longer if a larval diapause exists.
Some species are even frost-tolerant while others live at 50_C. The larvae feed on debris or plankton (filter feeders) or predate other larvae. The development of the also aquatic pupa is also temperature- dependent, lasting between 1 day or up to three weeks. If the pupae are disturbed, they actively swim downwards with their paddles at the end of the abdomen. The longevity of the adults strongly varies according to the climatic region, on average one to two weeks in the tropics and four to five weeks in temperate regions, but up to several months for females of hibernating or aestivating species. Thereby, the whole developmental cycle (egg to egg) can last about 7 days or up to several months in diapausing species.
Distribution Mosquitoes are found almost worldwide in almost all types of ecological zones, being absent only from Antarctica and some islands.
Mosquito vector in malaria- Anopheles,culex
General Information
Fossil mosquitoes are about 50 million years old, which is much time to adapt to the later developing human. All human populations are affected by mosquitoes, mainly by bites but also by the transmission of diseases. About 3500 mosquitoes belong to the family Culicidae, the most important genera ?Anopheles and ?Culex, ?Mansonia and ?Aedes belonging to the subfamilies Anophelinae and Culicinae, respectively. Mosquitoes were the first insects in which a causative agent of a disease, ?Bancroftian filariasis, was observed (1877). Meanwhile they are known as vectors of many diseases, e.g. viral and bacterial diseases,
But are mostly known as vectors of malaria. Mosquitoes are holometabolous insects, larvae
And pupae live aquatically. Adults are about 5 mm long, holding their wings flat above their body. In this dipteran group, only females suck blood. The adults can be distinguished from non-blood-sucking Nematocera, e.g. chironomids, by scales on the wing veins and especially by the long, forwardly directed proboscis.
Wednesday, March 18, 2009
Prevention and control of malaria
Area visited Prophylactic regimen Alternatives
No chloroquine resistance / Chloroquine 300 mg weekly/Proguanil 200 mg daily
Limited chloroquine resistance
Significant chloroquine / Chloroquine 300 mg weekly /Doxycycline 100 mg daily Or
resist -Proguanil 200 mg daily /Mefloquine 250 mg weekly
-Mefloquine 250 mg weekly /Doxycycline 100 mg daily
or
Malarone 1 tablet daily
No chloroquine resistance / Chloroquine 300 mg weekly/Proguanil 200 mg daily
Limited chloroquine resistance
Significant chloroquine / Chloroquine 300 mg weekly /Doxycycline 100 mg daily Or
resist -Proguanil 200 mg daily /Mefloquine 250 mg weekly
-Mefloquine 250 mg weekly /Doxycycline 100 mg daily
or
Malarone 1 tablet daily
Management of malaria
Drug treatment of uncomplicated malaria in adults
Plasmodium vivax, P. ovale, P. malariae, CQ-sensitive P. falciparumChloroquine:600 mg300 mg 6 hours later300 mg 24 hours later
300 mg 24 hours later
CQ-resistant, SP-sensitive P. falciparum Fansidar (SP): 3 tablets as single doseCQ- and SP-resistant P. falciparum Quinine: 600 mg 3 times daily for 7 days plus Tetracycline: 500 mg 4 times daily for 7 days or Fansidar (SP): 3 tablets as single dose
Alternative therapies
Mefloquine: 20 mg/kg in 2 doses 8 hours apart or Malarone: 4 tablets daily for 3 days or Coartemether: 4 tablets 12-hourly for 3 days or Lapdap (chlorproguanil/dapsone)
ollowing successful treatment of P. vivax or P. ovale malaria, it is necessary to give a 2- to 3-week course of primaquine (15 mg daily) to eradicate the hepatic hypnozoites and prevent relapse. This drug can precipitate haemolysis in patients with G6PD deficiency
Plasmodium vivax, P. ovale, P. malariae, CQ-sensitive P. falciparumChloroquine:600 mg300 mg 6 hours later300 mg 24 hours later
300 mg 24 hours later
CQ-resistant, SP-sensitive P. falciparum Fansidar (SP): 3 tablets as single doseCQ- and SP-resistant P. falciparum Quinine: 600 mg 3 times daily for 7 days plus Tetracycline: 500 mg 4 times daily for 7 days or Fansidar (SP): 3 tablets as single dose
Alternative therapies
Mefloquine: 20 mg/kg in 2 doses 8 hours apart or Malarone: 4 tablets daily for 3 days or Coartemether: 4 tablets 12-hourly for 3 days or Lapdap (chlorproguanil/dapsone)
ollowing successful treatment of P. vivax or P. ovale malaria, it is necessary to give a 2- to 3-week course of primaquine (15 mg daily) to eradicate the hepatic hypnozoites and prevent relapse. This drug can precipitate haemolysis in patients with G6PD deficiency
Diagnosis of malaria
Diagnosis
Malaria should be considered in the differential diagnosis of anyone who presents with a febrile illness in, or having recently left, a malarious area. Falciparum malaria is unlikely to present more than 3 months after exposure, even if the patient has been taking prophylaxis, but vivax malaria may cause symptoms for the first time up to a year after leaving a malarious area.
Diagnosis is usually made by identifying parasites on a Giemsa-stained thick or thin blood film (thick films are more difficult to interpret, and it may be difficult to speciate the parasite, but they have a higher yield). At least three films should be examined before malaria is declared unlikely. An alternative microscopic method is quantitative buffy coat analysis (QBC), in which the centrifuged buffy coat is stained with a fluorochrome which 'lights up' malarial parasites. A number of antigen-detection methods for identifying malarial proteins and enzymes have been developed. Some of these are available in card or dipstick form, and are potentially suitable for use in resource-poor settings. Serological tests are of no diagnostic value.
Parasitaemia is common in endemic areas, and the presence of parasites does not necessarily mean that malaria is the cause of the patient's symptoms. Further investigation, including a lumbar puncture, may be needed to exclude bacterial infection.
Malaria should be considered in the differential diagnosis of anyone who presents with a febrile illness in, or having recently left, a malarious area. Falciparum malaria is unlikely to present more than 3 months after exposure, even if the patient has been taking prophylaxis, but vivax malaria may cause symptoms for the first time up to a year after leaving a malarious area.
Diagnosis is usually made by identifying parasites on a Giemsa-stained thick or thin blood film (thick films are more difficult to interpret, and it may be difficult to speciate the parasite, but they have a higher yield). At least three films should be examined before malaria is declared unlikely. An alternative microscopic method is quantitative buffy coat analysis (QBC), in which the centrifuged buffy coat is stained with a fluorochrome which 'lights up' malarial parasites. A number of antigen-detection methods for identifying malarial proteins and enzymes have been developed. Some of these are available in card or dipstick form, and are potentially suitable for use in resource-poor settings. Serological tests are of no diagnostic value.
Parasitaemia is common in endemic areas, and the presence of parasites does not necessarily mean that malaria is the cause of the patient's symptoms. Further investigation, including a lumbar puncture, may be needed to exclude bacterial infection.
Some features of severe falciparum malaria
CNS
Cerebral malaria (coma convulsion)
Renal
Haemoglobinuria (blackwater fever)
Oliguria
Uraemia (acute tubular necrosis)
Blood
Severe anaemia (haemolysis and dyserythropoiesis)
Disseminated intravascular coagulation (DIC)
Respiratory
Acute respiratory distress syndrome
Metabolic
Hypoglycaemia (particularly in children)
Metabolic acidosis
Gastrointestinal/liver
Diarrhoea
Jaundice
Splenic rupture
Other
Shock - hypotensive
Hyperpyrexia
Cerebral malaria (coma convulsion)
Renal
Haemoglobinuria (blackwater fever)
Oliguria
Uraemia (acute tubular necrosis)
Blood
Severe anaemia (haemolysis and dyserythropoiesis)
Disseminated intravascular coagulation (DIC)
Respiratory
Acute respiratory distress syndrome
Metabolic
Hypoglycaemia (particularly in children)
Metabolic acidosis
Gastrointestinal/liver
Diarrhoea
Jaundice
Splenic rupture
Other
Shock - hypotensive
Hyperpyrexia
Causes of anemia in malaria infection
Haemolysis of infected red cells
Haemolysis of non-infected red cells (blackwater fever)
Dyserythropoiesis
Splenomegaly and sequestration
Folate depletion
After repeated infections partial immunity develops, allowing the host to tolerate parasitaemia with minimal ill effects. This immunity is lost if there is no further infection for a couple of years. Certain genetic traits also confer some immunity to malaria. People who lack the Duffy antigen on the red cell membrane (a common finding in West Africa) are not susceptible to infection with P. vivax. Certain haemoglobinopathies (including sickle cell trait) also give some protection against the severe effects of malaria: this may account for the persistence of these otherwise harmful mutations in tropical countries. Iron deficiency may also have some protective effect. The spleen appears to play a role in controlling infection, and splenectomized people are at risk of overwhelming malaria. Some individuals appear to have a genetic predisposition for developing cerebral malaria following infection with P. falciparum. Pregnant women are especially susceptible to severe disease.
Haemolysis of non-infected red cells (blackwater fever)
Dyserythropoiesis
Splenomegaly and sequestration
Folate depletion
After repeated infections partial immunity develops, allowing the host to tolerate parasitaemia with minimal ill effects. This immunity is lost if there is no further infection for a couple of years. Certain genetic traits also confer some immunity to malaria. People who lack the Duffy antigen on the red cell membrane (a common finding in West Africa) are not susceptible to infection with P. vivax. Certain haemoglobinopathies (including sickle cell trait) also give some protection against the severe effects of malaria: this may account for the persistence of these otherwise harmful mutations in tropical countries. Iron deficiency may also have some protective effect. The spleen appears to play a role in controlling infection, and splenectomized people are at risk of overwhelming malaria. Some individuals appear to have a genetic predisposition for developing cerebral malaria following infection with P. falciparum. Pregnant women are especially susceptible to severe disease.
Clinical features
Typical malaria is seen in non-immune individuals. This includes children in any area, adults in hypoendemic areas, and any visitors from a non-malarious region.
the normal incubation period is 10-21 days, but can be longer. The most common symptom is fever, although malaria may present initially with general malaise, headache, vomiting, or diarrhoea. At first the fever may be continual or erratic: the classical tertian or quartan fever only appears after some days. The temperature often reaches 41°C, and is accompanied by rigors and drenching sweats.
P. vivax or P. ovale infection
The illness is relatively mild. Anaemia develops slowly, and there may be tender hepatosplenomegaly. Spontaneous recovery usually occurs within 2-6 weeks, but hypnozoites in the liver can cause relapses for many years after infection. Repeated infections often cause chronic ill health due to anaemia and hyperreactive splenomegaly.
P. malariae infection
This also causes a relatively mild illness, but tends to run a more chronic course. Parasitaemia may persist for years, with or without symptoms. In children, P. malariae infection is associated with glomerulonephritis and nephrotic syndrome.
This causes, in many cases, a self-limiting illness similar to the other types of malaria, although the paroxysms of fever are usually less marked. However it may also cause serious complications and the vast majority of malaria deaths are due to P. falciparum. Patients can deteriorate rapidly, and children in particular progress from reasonable health to coma and death within hours. A high parasitaemia (> 1% of red cells infected) is an indicator of severe disease, although patients with apparently low parasite levels may also develop complications. Cerebral malaria is marked by diminished consciousness, confusion, and convulsions, often progressing to coma and death. Untreated it is universally fatal. Blackwater fever is due to widespread intravascular haemolysis, affecting both parasitized and unparasitized red cells, giving rise to dark urine.
Parasitology
The female mosquito becomes infected after taking a blood meal containing gametocytes, the sexual form of the malarial parasite. The developmental cycle in the mosquito usually takes 7-20 days (depending on temperature), culminating in infective sporozoites migrating to the insect's salivary glands. The sporozoites are inoculated into a new human host, and those which are not destroyed by the immune response are rapidly taken up by the liver. Here they multiply inside hepatocytes as merozoites: this is pre-erythrocytic (or hepatic) sporogeny. After a few days the infected hepatocytes rupture, releasing merozoites into the blood from where they are rapidly taken up by erythrocytes. In the case of P. vivax and P. ovale, a few parasites remain dormant in the liver as hypnozoites. These may reactivate at any time subsequently, causing relapsing infection.
Inside the red cells the parasites again multiply, changing from merozoite, to trophozoite, to schizont, and finally appearing as 8-24 new merozoites. The erythrocyte ruptures, releasing the merozoites to infect further cells. Each cycle of this process, which is called erythrocytic schizogony, takes about 48 hours in P. falciparum, P. vivax and P. ovale, and about 72 hours in P. malariae. P. vivax and P. ovale mainly attack reticulocytes and young erythrocytes, while P. malariae tends to attack older cells; P. falciparum will parasitize any stage of erythrocyte.
A few merozoites develop not into trophozoites but into gametocytes. These are not released from the red cells until taken up by a feeding mosquito to complete the life cycle.
Inside the red cells the parasites again multiply, changing from merozoite, to trophozoite, to schizont, and finally appearing as 8-24 new merozoites. The erythrocyte ruptures, releasing the merozoites to infect further cells. Each cycle of this process, which is called erythrocytic schizogony, takes about 48 hours in P. falciparum, P. vivax and P. ovale, and about 72 hours in P. malariae. P. vivax and P. ovale mainly attack reticulocytes and young erythrocytes, while P. malariae tends to attack older cells; P. falciparum will parasitize any stage of erythrocyte.
A few merozoites develop not into trophozoites but into gametocytes. These are not released from the red cells until taken up by a feeding mosquito to complete the life cycle.
Epidemiology
Malaria can also be transmitted in contaminated blood transfusions. It has occasionally been seen in injecting drug users sharing needles and as a hospital-acquired infection related to contaminated equipment. Rare cases are acquired outside the tropics when mosquitoes are transported from endemic areas ('airport malaria'), or when the local mosquito population becomes infected by a returning traveller.
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