MALARIA : MALARIA DR SS BUX BRIEF OUTLINE : BRIEF OUTLINE INTRODUCTION
PROPHYLAXIS INTRODUCTION : INTRODUCTION Malaria is a protozoan disease transmitted by the bite of infected female anopheles mosquito.
One of the most important parasitic diseases of humans.
No-1 cause of death among parasitic diseases. DISEASE BURDEN:GLOBAL : DISEASE BURDEN:GLOBAL Slide 5: 40% of the world population
3 billion infections
1-3 million deaths………per yr.
Resurgence of malaria in many parts of the world.
Emergence of drug resistance. ETIOLOGY : ETIOLOGY Slide 7: Caused by the bite of female anohiline mosquito
Inoculation of sporozoites from the salivary gland occur during the blood meal.
Four species Plasmodia cause human infections.
P.vivax , P.falciparum ,P.ovale , P.malariae . Slide 8: 1 Plasmodium vivax – Benign Tertian, Tertian Malaria
2 P.ovale - Ovale tertian Malaria
3 P.malariae – Quartan malaria
4 P.falciparum – Falciparum malaria or Malignant Tertian malaria. LIFE CYCLE : LIFE CYCLE Asexual cycle: Man
Sexual cycle: Mosquito.
Man: Intermediate host
Mosquito: Definitive host.
Infective form: sporozoite. HUMAN CYCLE : HUMAN CYCLE PRE ERYTHOCYTIC SCHIZOGONY
EXOERYTHOCYTIC SCHIZOGONY LIFE CYCLE : LIFE CYCLE INDIVIDUAL CHARACTERISTICS : INDIVIDUAL CHARACTERISTICS PATHOGENESIS : PATHOGENESIS Host –Parasite interaction.
Effects of parasite on host.
Cytoadherance, Rosette formation, Aglutination.
Nondefomability of the RBC. RBC LYSIS N TOXIN RELEASE : RBC LYSIS N TOXIN RELEASE Rupture of RBCs at the end of erythocytic cycle
Realase of putative toxins and cytokines
Responsible for various manifestations like,fever,malaise,organ dysfunctions,reduced hemopoesis n gluconeogenesis,cytoadherance.
Higher level of mediators are responsible for pathogenesis,whereas lower levels are protective. SEQUESTRATIONS : SEQUESTRATIONS CYTOADHERENCE
PfEMP1 expressin on erythrocytic membrane.
Responsible for organ dysfunction and severe malaria. CLINICAL FEATURES : CLINICAL FEATURES UNCOMPLICATED MALARIA
COMPLICATED/SEVERE MALARIA UNCOMLICATED MALARIA : UNCOMLICATED MALARIA A poor general condition, feeling unwell and having headaches like influenza.
Diarrhea, nausea and vomiting often occur as well.
Fever and shivering. The attack begins with fever, with the temperature rising as high as 40ºC and falling again over a period of several hours CONTD…. : CONTD…. Classically described as having 3 stages.
Rarely seen in the present day practice
Except for some degree of anemia n splenomegally few signs are seen. SEVERE MALARIA : SEVERE MALARIA CONTD…. : CONTD…. CEREBRAL MALARIA : CEREBRAL MALARIA The most dreaded complication
Defined: Unarousable coma/coma lasting>30min after Conv.
Any level of sensorium to b taken seriously
Extreme agitation is poor prognostic sign Signs…. : Signs…. Diffuse symmetric encephalopathy; focal signs are unusual.
Fever, Altered sensorim
Passive resistance to neck flexon but not like meningitis.
EYE: divergent,retinal hge,opacity,papilloedema.
Musle tone, DTR, Plantar reflex-variable.
Corneal reflex preserved till late.
Pout reflex may b present;no other primitive reflex found. Signs…. : Signs…. Neurological sequelae : <3% adults
Common in children:upto 15%
Especially those with sev anemia,hypoglycemia, repeated seizures,deep coma.
Hemiplegia,cerebral palsy, cortical blindness, deafness, impaired cognition n learning-variable duration.
Epilepsy; incidence increased, life expectancy decreased. HYPOGLYCEMIA : HYPOGLYCEMIA Important common complication.
Associated with poor prognosis, particularly in children and pregnat women.
Failure of hepatic gluconeogenesis
Increased consumption by both host n parasite.
Quinine induced hyper insulinemic hypo.
Increased peripheral req. due to anaerobic glyco(PASTEUR EFFECT) ACIDOSIS : ACIDOSIS One of the imp cause of death
Manifest as acidotic breathing
Leads to refractory circulatory failure
Reduced lactate clearance
Lactate production by the parasite
2 Ketoacidosis(CHILDREN) NON CARDIOGENIC PE : NON CARDIOGENIC PE Carries hihest risk of death:80%
Common in adults
Can develop even after several days of treatment
Pathogenesis is poorly understood
May be precipitated by overzealous fluid admin.
One serious comlication that can develop in otherwise uncomlicated vivax malaria also. RENAL FAILURE : RENAL FAILURE Common among adults.
Erythrocyte seqestration leading to impairment of microcircultory flow and metabolism.
Acute tubular ncrosis
Urine flow resumes in a median of 4 days and creat level normalizes in median of 17 days. HEMATOLOGIC ABNORMALITIES : HEMATOLOGIC ABNORMALITIES ANEMIIA is one of the poor prog. Factors
Obligatory rbc destruction by the parasite
Stress induced gasrtritis-hematemesis
Other hematologic complications include:
DIC <5% LIVER DYSFUNCTION : LIVER DYSFUNCTION Jaundice in malaria may b due to several causes
Liver dysfunction also contributes to several other prob
Reduced drug clearance MALARIA IN PREGNANCY : MALARIA IN PREGNANCY Leads to fetal n maternal complications
In endemic areas –LBW, fetal n infant mortality
In nonendemic areas-fetal distress,prem labour,still birth,and maternal death.
HIV infection predisposes preg women to malaria CHRONIC COMPLICATIONS : CHRONIC COMPLICATIONS TROPICAL SPLENOMEGALLY(HMS)
QUARTAN MALARIAL NEPHROPATHY
BURKIT’S LYMPHOMA TROPICAL SPLENOMEGALLY(HMS) : TROPICAL SPLENOMEGALLY(HMS) Hyper gama-globulinemia,normocytic normochromic anemia, splenomegally
Marked titres of IgM antimalarial antibody,hepatic sinusoidal lymphocytosis,peripheral B-cell lymphocytosis.
IgM antibody against CD8+T lymho,CD5+T lympho
Increased ratio of CD4+to CD8+ lympho
Uninhibited Bcell production of IgM-cryoglobulin
Rediculoendothelial hyperplasia is a cconequence Slide 33: Manifest :Mass abdomen ,anemia, pancytopenia ,susceptbility to infection.
Antimalarial chemoprophylaxis for endemic areas and antimalarial treatment for non endemic areas
Refractory: Malignant lympho proliferative disorder. QUARTAN MALARIAL NEPHROPATHY : QUARTAN MALARIAL NEPHROPATHY Chronic n repeated infection with P. malariae leads to soluble immune comlex injury to renal glomeruli
LM:Focal segmental glomerulonephritis
EM:Subendothelial dense deposit
Coarse granular pattern(IgG3)-Selective protinuria
Fine granular pattern(IgG2)-Non-selective protinuria
Poorly responds to treatment. DIAGNOSIS : DIAGNOSIS CLINICAL FEATURES
Demonstration of parasite
Biochemistry DEMO OF PARASITE : DEMO OF PARASITE THICK SMEAR
FLOURESCENT MICROSCOPY BLOOD COLLECTION : BLOOD COLLECTION MAKING OF A SMEAR : MAKING OF A SMEAR RAPID ANTIGEN METHOD : RAPID ANTIGEN METHOD Antigen Detection
Various test kits are available to detect antigens derived from malaria parasites. Such immunologic ("immunochromatographic") tests most often use a dipstick or cassette format, and provide results in 2-15 minutes. These "Rapid Diagnostic Tests" (RDTs) offer a useful alternative to microscopy in situations where reliable microscopic diagnosis is not available. Malaria RDTs are currently used in some clinical settings .
PfHRP2 BASED-specific for PF
LDH BASED-NONSPECIFIC MICROTUBE METHOD : MICROTUBE METHOD The QBC Malaria method is the simplest and most sensitive method for diagnosing the following diseases.
Trypanosomiasis (Chagas disease, Sleeping Sickness)
Filariasis (Elephantiasis, Loa-Loa)
Relapsing Fever (Borreliosis) PRICIPLE OF QBC : PRICIPLE OF QBC SEROLOGY : SEROLOGY Serology detects antibodies against malaria parasites, using either indirect immunofluorescence (IFA) or enzyme-linked immunosorbent assay (ELISA). Serology does not detect current infection but rather measures past experience. MOLECULAR DIAGNOSIS : MOLECULAR DIAGNOSIS Parasite nucleic acids are detected using polymerase chain reaction (PCR). This technique is more accurate than microscopy. However, it is expensive, and requires a specialized laboratory (even though technical advances will likely result in field-operated PCR machines). OTHER LAB TESTS : OTHER LAB TESTS Normocytic normochromic anemia
Raised ESR, CRP, Plasma viscosity
Platelet slightly reduced
PT, PTT may b prolonged in severe infection
Blood glucose TREATMENT : TREATMENT TREATMENT…… : TREATMENT…… MANAGEMENT OF COMPLICATIONS : MANAGEMENT OF COMPLICATIONS ANEMIA: Blood transfusion
Hyperparasitemia: Exchange transfusion
Hypoglycemia: Dextrose infusion
ARDS:O2 supplementation,mech ventilation,diuretics
IV antimicrobials PREVENTION : PREVENTION CHEMOPROPHYLAXIS
IMMUNOPROPHYLAXIS CHEMOPROPHYLAXIS : CHEMOPROPHYLAXIS BEHAVIURAL PROPHYLAXIS : BEHAVIURAL PROPHYLAXIS IMMUNO PROPHYLAXIS : IMMUNO PROPHYLAXIS This degree of protection would be extremely difficult to achieve and might not be technically feasible with current vaccinology art and science. Many vaccine developers have therefore focused their efforts on creating a vaccine that limits the ability of the parasite to successfully infect large numbers of red blood cells. This would not prevent infection but would limit the severity of the disease and help prevent malaria deaths.…Vaccine Challenges Slide 62: This degree of protection would be extremely difficult to achieve and might not be technically feasible with current vaccinology art and science. Many vaccine developers have therefore focused their efforts on creating a vaccine that limits the ability of the parasite to successfully infect large numbers of red blood cells. This would not prevent infection but would limit the severity of the disease and help prevent malaria deaths.…Vaccine Challenges Slide 63: The most successful candidate developed to date is the RTS,S recombinant vaccine. The RTS,S/AS02A, one of the key vaccines produced using this technique, has been used in field trials in The Gambia. Three repeat doses were administered in the 6 months leading up to the period of highest malaria transmission. The vaccine efficacy was reported at approximately 71% (with 95% confidence intervals spanning from 46 to 85%) during the first 2 months of follow-up, but falling to 0% in the last 6 weeks in 250 male volunteers.