University:
American Career College
Course:
NURS115 | Intermediate Medical
Academic year:

2021
Views:

92

Pages:

47
Author:

Neulri

The Global Burden of Malaria  1.5 – 2.7 million deaths annually  300 – 500 million people infected  Every about 1 or 2 minutes a child dies of malaria • At risk for malaria: 40% of the world’s population (108 countries) Africa, Latin America,India, Middle East, Southeast Asia, Central and South America, Eastern Europe, and the South Pacific 4/3/2021 2 Malaria zones are: 4/3/2021 3 Malaria is caused by a parasite of the genus Plasmodium, member of Apicomplexa – a obligatory or mandatory intracellular parasite (RBC OR reticulocyte ). Malaria is common in tropical , subtropical and temperate areas 5 species infecting humans • Plasmodium falciparum – deadliest and the most dangerous of this disease. • Plasmodium vivax –Prevalence is higher than falciparum • Plasmodium ovale – more common in western Africa • Plasmodium malariae - less common • P.knowlesi(Causes malaria in human and other primates,Rare cases) zoonotic malaria (transmitted from animal to human) 4/3/2021 4 The number of confirmed malaria cases reported in the region decreased from two million in 2000 to one million in 2013. Two countries accounted for 84% of cases in 2013: Sudan (57%) and Pakistan (27%).  Seven countries achieved >75% decrease in the incidence of microscopically confirmed cases between 2000 and 2013 (Afghanistan, Iran [Islamic Republic of], Iraq, Morocco, Oman, Saudi Arabia and the Syrian Arab Republic). 4/3/2021 5 Total and Autochthonous Malaria Cases (2008-2015) 12000 Malaria Cases 10000 8000 Total 6000 Autochthonous 4000 2000 0 2008 2009 4/3/2021 2010 2011 Year 2012 2013 2014 2015 6 Percentage of Imported Malaria Cases (2008-2015) 4/3/2021 In ten malaria-prone provinces around 14% of foci and 26% of population are affected by population movement. 7 Phases and milestones in malaria program evolution Control Afghanistan Djibouti Pakistan Sudan Somalia Yemen 4/3/2021 Preelimination Elimination Prevention of re-introduction Saudi Arabia Islamic Republic of Iran All others 8 Free World-Malaria 4/3/2021 9 Update on country(Iran) situation • Autochthonous malaria which reported in 2013 was 399, 72 falciparum and 327 vivax • In 2014,the reported autochthonous malaria was 246, including 234 vivax and 12 autochthonous falciparum cases, • In 2015 178 autochthonous cases were reported of which 26 were falciparum • In 2016 by today 51 autochthonous cases were reported of which 1is falciparum 4/3/2021 10 PATHOPHYSIOLOGY: Liver Stage. Human infection is initiated when sporozoites are injected with the saliva during mosquito feeding. The sporozoites enter the circulatory system and within 30-60 minutes will invade a liver cell. Host cell entry, as in all apicomplexa, is facilitated by the apical organelles. After invading the hepatocyte, the parasite undergoes an asexual replication. This replicative stage is often called exoerythrocytic (or pre-erythrocytic) schizogony. In P. vivax and P. ovale some of the sporozoites do not immediately undergo asexual replication, but enter a dormant phase known as the hypnozoite. This hypnozoite can reactivate and undergo schizogony at a later time resulting in a relapse. 4/3/2021 11 Blood Stage. Merozoites released from the infected liver cells invade erythrocytes. The merozoites recognize specific proteins on the surface of the erythrocyte and actively invade the cell in a manner similar to other apicomplexan parasites. After entering the erythrocyte the parasite undergoes a trophic period followed by an asexual replication. The young trophozoite is often called a ring form due to its morphology in Geimsa-stained blood smears. As the parasite increases in size this 'ring' morphology disappears and it is called a trophozoite. During the trophic period the parasite ingests the host cell cytoplasm and breaks down the hemoglobin into amino acids. A by-product of the hemoglobin digestion is the malaria pigment, or hemozoin. These golden-brown to black granules have been long recognized as a distinctive feature of blood-stage parasites. 4/3/2021 12 Nuclear division marks the end of the trophozoite stage and the beginning of the schizont stage. Erythrocytic schizogongy consists of 3-5 rounds (depending on species) of nuclear replication followed by a budding process. Late stage schizonts in which the individual merozoites become discernable are called segmenters. The host erythrocyte ruptures and releases the merozoites. These merozoites invade new erythrocytes and initiate another round of schizogony. The blood-stage parasites within a host usually undergo a synchronous schizogony. 4/3/2021 13 Sexual Stage. As an alternative to schizogony some of the parasites will undergo a sexual cycle and terminally differentiate into either micro- or macrogametocytes. Gametocytes do not cause pathology in the human host and will disappear from the circulation if not taken up by a mosquito. Gametogenesis, or the formation of micro- and macrogametes, is induced when the gametocytes are ingested by a mosquito. After ingestion by the mosquito, the microgametocyte undergoes three rounds of nuclear replication. The macrogametocytes mature into macrogametes. 4/3/2021 14 The highly mobile microgametes will seek out and fuse with a macrogamete. Within 12-24 hours the resulting zygote develops into an ookinete. The ookinete is a motile invasive stage which will transverse both the peritrophic matrix and the midgut epithelium of the mosquito. 4/3/2021 15 Sporogony. After reaching the extracellular space between the epithelial cells and the basal lamina, the ookinete develops into an oocyst. The oocysts undergo an asexual replication, called sporogony, which culminates in the production of several thousand sporozoites. This generally takes 10-28 days depending on species and temperature. Upon maturation the oocyst ruptures and releases the sporozoites which cross the basal lamina into the hemocoel (body cavity) of the mosquito.These insects are commen in Iran A .stephensi A.sacharovi A. superpictus A .fluviatilis A. culicifacies A.d'thali A.maculipenis 4/3/2021 16 The life cycle of all species that infect humans is basically the same. In fe ctio n S p o ro zo ite s Click on the diagram to explore different areas of the life cycle L ive r M e ro zo ite s A se xu a l cycle Tra n sm issio n to m o sq u ito G a m e to cyte s 4/3/2021 17 Female anopheles mosquito lays her eggs in stagnant water where they hatch. There are about 30 – 40 anopheles species that can transmit malaria. Mosquitoes take 5-14 days to go through their life cycle (depending on temperature)and can then live for up to one month •transmitted by female anophele mosquitoes 4/3/2021 The female anopheles mosquito inserts her proboscis into the skin to take a blood meal. She releases saliva which prevents the blood from clotting and so allows a free flow of blood. The saliva contains the malaria parasite which then enters the bloodstream of the victim. The mosquito is the (Biologic)vector 18 Malaria Life Cycle Life Cycle Sporogony(an exogenous sexual phase)in female An.as final host Oocyst Sporozoites Mosquito Salivary Gland Zygote Exoerythrocytic (hepatic) cycle Gametocytes Schizogony endogenous asexual phase , exo-erythrocytic phase, erythrocytic 4/3/2021 phase in vertebrate as intermediate host Hypnozoites (for P. vivax and P. ovale) Erythrocytic Cycle 19 Malaria Transmission Cycle Pre-erythrocytic Asymptomatic Sporozoites Merozoites Erythrocytic Clinical symptoms Sporozoites 4/3/2021 Male and female gametocytes 20 Disease Severity and Duration Malariae(the longest,most stable) falciparum (the most dangereous , deadliest mild moderate to severe severe 20,000 9,000 6,000 50,000-500,000 Maximum Parasitemia (mm3) 50,000 30,000 20,000 2,500,000 Symptom Duration (untreated) 3-8weeks 2-3 weeks 3-24 weeks 2-3 weeks Maximum Infection Duration (untreated) 5-8 years 12-20 months 20-50 years 6-17 months ++ + ++ ++++ vivax ovale moderate to severe Average Parasitemia (mm3) Initial Paraoxysm Severity Anemia Multi system functional in 4/3/2021 Complications renal each organ Cerebral...‫و‬ 21 Exoerythrocytic schizogony and prepatent and incubation periods P. falciparu m P. vivax P. ovale P. malariae Prepatent period (days) 6-9 8-12 10-14 15-18 Incubatio n period (days) 7-14 12-17 16-18 18-40 Merozoite maturatio n (days) 5-7 6-8 9 12-16 Merozoite s produced 40,000 10,000 15,000 2000 4/3/2021 22 Components of the Malaria Life Cycle Sporogonic cycle Infective Period Mosquito bites uninfected person Mosquito bites gametocytemic person Mosquito Vector Parasites visible Prepatent Period Human Host Symptom onset Recovery Incubation Period Pre-patent period – interval between date of infection and detection of parasites in peripheral blood Incubation period – time between infection and first 4/3/2021 appearance of clinical symptoms Clinical Illness 23 Some characteristics of infection with four species of human Plasmodia Preerythroctic stage (days) Pre-patent period (days) Incubation period (days) Erythrocytic cycle (hours) P.v. P.o. P.m. P.f. 6-8 9 14-16 5.5-7 11-13 10-14 15-16 9-10 15 (12-17) 17 (16-18) 28 (18-40) 12 (9-14) or up to 6- or longer or longer 12 months 48 (about) 50 72 48 24 Some characteristics of infection with four species of human Plasmodia P.v. Paraitemia per μl Average P.o. P.m. Attack to old and young RBC 20,000 9,000 6,000 50,000 30,000 20,000 Primary attack* Mildsevere Mild Mild Febrile paroxysms (hours) 8-12 8-12 8-10 Maximum P.f. 20,00050,000 2,000,000 Severe in nonimmunes 16-36 or longer 25 Other features of simple, uncomplicated malaria include: o o o o o Vomiting Diarrhoea – more commonly seen in young children and, when vomiting also occurs, may be misdiagnosed as viral gastroenteritis Convulsions – commonly seen in young children. Malaria is the leading cause of convulsions with fever in African children. Pallor – resulting mainly from the lysis of red blood cells. Malaria also reduces the synthesis of red blood cells in the bone marrow. Jaundice – mainly due to haemolysis. Malaria is a multisystem disease. Other common clinical features are: o Anorexia o Cough o Headache o Malaise o Muscle aches o Splenomegaly o Tender hepatomegaly These clinical features occur in “mild” malaria. However, the infection requires urgent diagnosis and management to prevent progression to severe disease. 4/3/2021 26 Malaria Ecology and Burden Clinical Manifestations Hypoglycemia Anemia Acute febrile illness Severe illness Respiratory distress Cerebral malaria Death Infected Mosquito Anemia Chronic effects Infected Human Neurologic/ cognitive Developmental Fetus Impaired growth and development Low birth weight Pregnancy 4/3/2021 Maternal r.F.Tabata Acute illness Anemia Malnutrition Infant mortality Impaired 27 productivity The periodicity of malaria fever Erythrocytic schizogony is the time taken for trophozoites to mature into merozoites before release when the cell ruptures. It is shortest in P. falciparum (36 hours), intermediate in P. vivax and P. ovale (48 hours) and longest in P. malariae (76 hours). Typical paroxysms thus occur every • 2nd day or more frequently in P. falciparum (“sub-tertian” malaria) • 3rd day in P. vivax and P. ovale (“tertian” malaria) Days 1 and 3 for P.v., P.o., (and P.f.) - tertian • 4th day in P. malariae infections, (“quartan” malaria) Days 1 and 4 for P.m. - quartian 4/3/2021 Note how the frequency of spikes of fever differ according to the Plasmodium species. In practice, spikes of fever in P. falciparum, occur irregularly - probably because of the presence of parasites at various stages of development. 28 Malaria Paroxysm • paroxysms associated with synchrony of merozoite release • between paroxysms temperature is normal and patient feels well • falciparum may not exhibit classic paroxysms (continuous fever) 4/3/2021 Tertian malaria inP.v,p.o(benign),P.f (Malignant)quartan malaria 29 in P.m(benign) Red Cell Preference Falciparum can invade cells of all ages(Red blood cell) Vivax can invade Reticulocytes and Younger RBC Ovale can invade Reticulocytes Malariae can invade Older RBC 4/3/2021 30 Relapses the result of Liver Stage,Dormant(Hypnozoites) Vivax , Ovale :Yes Recrudescence the result of Blood Stage Falciparum , Malariae :YES recrudescences and relapses can occur over months or years later 4/3/2021 31 Immunity • Influenced by – – – – – – Genetics Age Health condition Pregnancy status Intensity of transmission in region Length of exposure • Maintenance of exposures • Nutritional state, genetics 4/3/2021 32 Immunity Premunition • Acquired – Transferred from mother to child • 3-6 months protection • Then children have increased susceptibility – Increased susceptibility during early childhood • Hyper- and holoendemic areas – By age 5 attacks usually < frequent and severe – Can have > parasite densities with fewer symptoms • Meso- or hypoendemic areas – Less transmission and repeated attacks – May acquire partial immunity and be at higher risk for symptomatic disease as adults 4/3/2021 33 Geographic Distributions People who are constantly exposed to malaria gradually Naturally-acquired immunity also : Sickle Cell disease Hemoglobinopathy: Hemoglobins C and E,S,A2, F(Foetal haemoglobin (HbF): High levels of HbF occur in neonates, and in some people with inherited haemoglobin variants, protect against severe forms of P. falciparum malaria. Hereditary Ovalocytosis Thalassemias:Thalessemia – α and β G6PD (glucose-6-phosphate dehydrogenas deficiency ) these genetic disorders confer protection or Immune against death from falciparum(especially) or vivax These people can get Naturally-acquired immunity to Malaria 4/3/2021 34 Immunity Duffy blood group: P. vivax requires the Duffy blood receptor to enter red blood cells. Therefore, people who do not carry the Duffy blood group are resistant to this malaria species. This explains the rarity of P. vivax in Africa, as most Africans are Duffy blood group negative. • Acquired – No complete immunity • Can be parasitemic without clinical disease – Need long period of exposure for induction – May need continued exposure for maintenance – Immunity can be unstable • Can wane as one spends time outside endemic area • Can change with movement to area with different endemicity • Decreases during pregnancy, risk improves with increasing gravidity 4/3/2021 35 Clinical Features in simple Malaria as mentioned in previous slides : First symptoms of malaria are nonspecific Lack of a sense of well-being Headache Fatigue Abdominal discomfort Muscle aches , Headache-,Chest ,Abdominal pain -Arthralgia Myalgia -Diarrhea followed by Fever similar to the symptoms of a minor viral illness(Flu like)and as viral gastroenteritis 4/3/2021 36 Malarial Paroxysm • Can get prodrome 2-3 days before – Malaise, fever,fatigue, muscle pains, nausea, anorexia – Can mistake for influenza or gastrointestinal infection – Slight fever may worsen just prior to paroxysm • Paroxysm Respectively – 1,Cold stage - rigors – 2,Hot stage – Max temp can reach 40-41o C, splenomegaly easily palpable – 3,Sweating stage – Lasts 8-12 hours, start between midnight and midday 4/3/2021 37 Severe and complicated malaria Acute Renal Failure Acute Pulmonary Edema (Acute Respiratory Distress Syndrome) Hypoglycemia Spontaneous Bleeding Convulsions Aspiration pneumonia Bacterial Sepsis 4/3/2021 38 Malaria in pregnancy More than 45 million women (30 million in Africa) become pregnant in malaria endemic areas each year. Common adverse effects of malaria in pregnancy include: • Maternal anaemia • Stillbirths • Premature delivery and intrauterine growth retardation result in the delivery of low birth weight infants 4/3/2021 The WHO now recommends intermittent preventive treatment (IPT): the administration of antimalarial drugs (e.g. sulphadoxine-pyrimethamine) during antenatal care whether or not women show symptoms. IPT has been shown to substantially reduce the risk of maternal anaemia in the mother and low birth weight in the newborn. Previously, chemoprophylaxis (e.g. with chloroquine) was recommended for all women living in malaria endemic areas. Source: http://phil.cdc.gov/phil/quicksearch.asp 39 Cerebral malaria - clinical • • • • • The most well-known severe manifestation of malaria Defined as: – unarousable coma persisting for more than one hour – with asexual forms of P. falciparum in the peripheral blood in end stage of disease but in the first stage we see ring and gametocyte forms in patients – other common causes of encephalopathy excluded* Occurs most commonly in young children although non-immune adults are also at risk Cerebral malaria can rapidly progress to death, even with appropriate treatment. Case fatality is between 20-30%. A 4 year old boy who was deeply In survivors, resolution of coma usually occurs within 1-2 days in children and within comatose and had persistent 2-4 days in adults but may be complicated by deviation of the eyes neurological sequelae in ~5% adults and and confusion The illness may start with drowsiness and then progress to coma. The >10% of children. loss of consciousness is often preceded by repeated convulsions. Retinal haemorrhages may be seen on fundoscopy. 4/3/2021 * None of the clinical features are pathognomonic, malaria parasitaemia is common in people living in endemic areas and coma may complicate many illnesses. Therefore, a clinical diagnosis of cerebraade only after other common causes o40 f coma (e.g. meningitis) have been excluded. pathophysiology,Prostration The exact pathogenesis of cerebral malaria is not well understood. It is believed to result from sequestration of parasitised red cells in the small blood vessels in the brain. The consequences of this include: • reduced cerebral blood flow • cerebral hypoxia • release of cytokines which in turn induce the release of nitrous oxide, a known A young girl with cerebral malaria. Note the depressor of consciousness abnormal, decerebrate posturing Sequestration of parasitised red cells in different tissues probably underlies most severe manifestations of malaria A 3 year old boy with impaired consciousness, grimacing and marked extensor posturing of the arms 4/3/2021 41 Severe malaria anaemia Defined as a haematocrit of <15% or haemoglobin concentration <5 g/dl. Occurs commonly in young children and pregnant women. Anaemia in malaria results from a combination of factors: • Destruction of parasitised red blood cells • Destruction of unparasitised red cells by complement-mediated lysis • Bone marrow suppression by cytokines produced by malaria parasites • Haemolysis induced by medications in individuals with glucose-6-phosphate dehydrogenase deficiency Many patients require urgent transfusion. The condition may be rapidly fatal when blood transfusion is delayed. 4/3/2021 Marked pallor in an African child with severe anaemia due to P. falciparum infection 42 Hypoglycaemia • Blood sugar <2.5 mmol/L • Increases the risk of mortality and sequelae in children with cerebral malaria; may present with convulsions or a deterioration in level of consciousness. • Results from a combination of factors: – reduced glycogen stores because of reduced food intake – increased metabolism due to fever and repeated convulsions – glucose consumption by malaria parasites – cytokine or quinine-stimulated hyperinsulinaemia 4/3/2021 43 Metabolic acidosis, Acidaemia • Lactic acidosis is a major contributor and probably results from tissue anoxia and anaerobic glycolysis • Presents with deep, rapid respirations (as in diabetic ketoacidosis) 4/3/2021 44 Acute renal failure • occurs almost exclusively in adults and older children in areas of unstable malaria • affected patients are usually oliguric (urinary output <400 ml/day) or anuric (<50 ml/day) • serum creatinine levels are elevated 4/3/2021 45 Acute pulmonary oedema This is a grave and usually fatal manifestation of severe falciparum malaria and 4/3/2021 occurs mainly in adults. Hyperparasitaemia, renal failure and pregnancy are recognised predisposing factors and the condition is commonly associated with hypoglycaemia and metabolic acidosis. Acute pulmonary oedema, developing shortly after delivery in a woman with severe P. falciparum malaria 46 Circulatory collapse, shock, “algid malaria” Features of circulatory collapse (cold/clammy skin, hypotension, peripheral cyanosis, weak/thready pulses) may be seen in patients with severe P. falciparum malaria. “Algid malaria” is characterised by hypotension, vomiting, diarrhoea, rapid respiration and oliguria. This condition is associated with a poor prognosis. 4/3/2021 47 Haemoglobinuria or “Blackwater Fever” This results from massive intravascular haemolysis. The condition presents with severe pale, jaundice and passage of dark urine due to haemoglobinuria. It may be associated with acute renal failure due to ancomplete drug use as Quinine and autoimmune ( A 3 year old boy with severe anaemia (Hb 3.3 g/dl) and dark urine (shown in the container) 4/3/2021 Typical, dark urine of haemoglobinuria on day 0 which has cleared by day 3 These two symptoms are very important in the diagnosis of severe malaria: Hyperparasitaemia,persistent 48 fever Bac