Mercy Juma Flashcards
Categories of PUO
A.Classic PUO – an update of the original PUO definition
PUO is a fever >38o C for over 3 weeks despite being investigated on 2 visits at the outpatient’s or for 3 days in hospital
B. Nosocomial PUO – Fever >38o C for 3 days not present or incubating on admission
C. Immunodeficient PUO –(caused by illness eg malignancy or of treatment such as steroids – neutropenia or defective cell mediated immunity)
Fever >38oC for >3 days for outpatients or >3 days with neg blood cultures after 48 hrs
D. HIV patients – Fever >38oC for >3 wks for outpatients or >3days for inpatients
What are the 5 main catergories of causes of classic PUO
- Infection 30-50% ( abscesses, endocarditis, tuberculosis, complic UTI)
- Neoplasm 20-25% (lymphoma)
- Connective tissue disorder / vasculitis 15-20% (juvenile rheumatoid arthritis Still’s, other rheumatoid arthritis, SLE, temporal arteritis in elderly)
- Miscellaneous disorders 10-20% (FMF, pulmonary emboli, drug induced, Behcet’s syndrome)
- Undiagnosed 10-20%
Where is meliodosis found?
SE asia
Melioidosis is an infectious disease caused by a Gram-negative bacterium, Burkholderia pseudomallei, found in soil and water
Which infections are found in the mediterranean
Leishmaniasis, Ricketsial illness, brucellosis, Q fever
Which infection is commonly found in S America
dimorphic fungi
Which type of inflammtory disease is commonly seen in children <5 k. How does this compare to that in older children
kawasaki disease
Juvenile rheumatoid arthritis (Still’s disease) leading cause in older children
Cause of PUO in returning travellers Depending on the incubation period
see slide 10 on puo lecture
In which diseases are clubbing most commonly seen
- Chronic respiratory
2. Heart disease
What disease has splinter haemorrhages in nails
Endocarditis
What are subcutaneous nodules characteristic of
rheumatic fever
markers of inflammation
CRP
ESR
WBC
Ferritin
How many blood cultures would you take in first 24 hours
3
What does mycoplasma cause
Pneumonia - can have systemic manifestations
How to diagnose leishmaniasis
BM Bx
a tropical and subtropical disease caused by leishmania and transmitted by the bite of sandflies. It affects either the skin or the internal organs.
How to differentiate falciparum on a film from all of the other plasmodiums?
Two dots on the ring on the film
Use of MRI in PUO
very useful for CNS and spleen and lymph nodes
Use of radiolabelled leucoyte scans?
leucoytes accumulate in sites of accumulation so radiolabelled leucocytes will show us where there is inflammation
abscesses or malignancy
Use of PET CT
81% sens and 87% specificity (mainly for malignancy)
25yr F born Pakistan
UK 1 year
Lives alone
Travelled to Pakistan for 2 weeks and returned one week ago.
PC:
abdominal pains
fevers for over 1 month
Weight loss
HPC:
Eating well but wt down
Sweating at night; has to change the sheets
Abdo pain all the time, all over colicy, possibly worse in the RIF
Been to GP for
Think of lymphoma (due to night sweats)
What is the cause of typhoid
Salmonella typhi
What abdo features does salmonella typhi cause?
Constipation whereas normally salmonella causes diarhhoea
What abdo features does salmonella typhi cause?
Constipation and also pea-like diarrhoea whereas salmonella enteriditis causes inflammatory diarrhoea
Frequency of btypes of malaaria
- Falciparum - 70%
- Vivax - 43%
- Ovale
- Malariae - 7%
What are the complications of malaria in pregnancy
25% severe maternal anaemia,
10-20% low birth-weight,
5-10% neonatal and infant death
Indirect consequences of malaria
Impaired intellectual development, developmental abnormalities, irregular school attendance, loss of productivity
Retardation of economic development of affected countries
Why do male mosquitos not transmit malaria
Males feed on plant juices not blood
Phases of development in man
Two phases of development
- Inside the liver (tissue phase)
Pre-erythrocytic schizogony – no clinical symptoms, no pathological damage
Exo-erythrocytic schizogony – cause of relapse - Inside the RBCs (erythrocytic phase)
Erythrocytic schizogony – cause of malarial paroxsyms
Gametogony – infects mosquito
Which morphological forms of the parasite are found in the liver
Sporozoites
Pre erythrocytic schizonts
Merozoites – infect RBCs
Which morphological forms are found in the RBCs
- Trophozoites – ring form
- Schizonts
- Merozoites – released by the rupture of schizonts – infect other RBCs
- Gametocytes – micro (male) and macro (female) gametocytes
Other modes of transmission of malaria
Sporozoite- induced- malaria : injection of an emulsion of salivary glands of mosquito containing sporozoites
Trophozoite- induced- malaria : injection of blood from a malarial patient containing the asexual forms of erythrocytic schizogony e.g.
- Transfusion malaria – when persons with latent infection are used as donors
- Congenital malaria – transmission through some placental defects (a healthy placenta acts as a physiological barrier)
- Drug addicts – by using same syringe
Clinical course of Falciparum
- Asymptomatic parasitaemia (“clinical immunity”)
- Acute uncomplicated malaria
- Severe malaria
When is asymptomatc falciparum seen
Seen in older children and adults, with acquired natural immunity-living in endemic areas
There are parasites in blood but no symptoms – reservoir
Disease LOB MALARIA
SEE NOTES
Manifetations of severe and complicated malaria
- Cerebral malaria
- Severe malarial anemia
- Hypoglycemia
- Metabolic acidosis
- Acute renal failure
- Pulmonary edema
- Circulatory collapse
- Blackwater fever
Difference in clinical features of severe malaria in adults and children
See slide 20 on malaria lecture
What is pernicious malaria
Def: refers to a series of phenomena occurring during infection with P. falciparum which, if not effectively treated, threatens the life of the patient within 1 to 3 days
In children & non immune adults, can cause coma & death – Cerebral malaria.
Occurs as a result of capillary blockage.
How does cerebral malaria manifest
Falciparum associated
High fever, headache, vomiting, convulsions, delirium, respiratory failure
Hyperpyrexia: T>400C, convulsion, delirium
Children: deep coma, seizures (more common in children), hypoglycaemia
Ataxia, monoparesis, cortical blindness, aphasia/dysarthria, hearing impairment, cortical defects
What are the features of malaria acute renal failure and black water fever
Blackwater fever
Reduced perfusion (obstruction)
Acute Tubular Necrosis
Occurs in previously infected subjects
Due to severe hemolysis
Can also occur in non immune adults with severe falciparum malaria, and also as a complication of quinine therapy.
A rare but acute condition characterised by sudden & massive hemolysis of parasitised & non parasitised RBCs followed by fever and haemoglobinuria.
Often fatal due to renal failure
How to treat malarial ARF
- Dialysis
2. continue quinine
What are the clinical features of black water fever
Difficult to find the parasites in the blood following a hemolytic attack.
Urine appears dark red to brown black due to the presence of free Hb.
Clinical features – fever, rigors, aching pains in the loin, icterus, bilious vomiting, circulatory collapse, haemoglobinuria & acute renal failure
Treatment of black water fever
- Chloroquine,
- blood transfusion,
- peritoneal dialysis in ARF.
What is the cause of hypoglycemia in malaria
Parasites use up lots of glucose
metabolic consequences of malaria
- Hypoglycemia
- Lactic acidosis
- Thiamine deficiency
Two types of recurrences of malaria
- Relapse
2. Recrudescence
Which type of malaria does recrudescence occur in ?
- Falciparum
2. malariae
Cause of recrudescence reccurence
due to persistence of blood infection (some erythrocytic forms evade host immunity) even after clinical illness has subsided.
The numbers may increase later, leading to reappearance of clinical symptoms
Occur mostly up to one year or so but in P. malariae, it can occur even after decades
Which type of parasite does relapse recurrence occur in ?
Hypnozoites
- Activated from time to time to initiate pre- erythrocytic schizogony - Exoerythrocytic schizogony
Malaria protective factors
- P. vivax
Uses RBC duffy receptor not present in sickle cell anemia therefore these patients are protected from P vivax - Thalassemia and G6PD deficiency
Make parasite-exposed RBCs more susceptible to apoptosis from oxidative stress therefore malaria is unable to undergo its life cycle in these individuals - Hence a natural selection advantage for the above diseases
- HLAB53 alleles enable T cells to kill parasite-infected hepatocytes in non-Europeans.
Newborn infants and B thalassemia
High levels of HbF
Elevated CKs in malaria
TNFa (Plasma TNFα higher in fatal cases)
IL-1
How long does falciparum last in absence of treatment
1 year but reinfection possible by other strains
How long could hypnozoites last
Can have periodic relapses up to 5 years
Malariae may last up to 40 years
Diagnosis of malaria?
Thick: located parasites sitting in RBCs
- More sensitive as they allow a greater amount of blood the be examined
Thin: directly identifies the plasmodium species
- Species identification and parasitemia (% of parasitised RBCs)
>2% parasitemia is a sign of more severe disease although severe disease can occur at any %
- Patients with schizonts at higher risk of sudden deterioration - 3rd stage of the erythrocytic phase (replicative phase
Most common form seen is the trophozoite (after merozoite has differentiated in the erythrocytic phase)
Other diagnostic methods for malaria
- Antigen detection
Immunochromatographic, dipstick or
cassette format
Fast, 2-15 mins - Serology
Detection of Abs (IFA or ELISA)
Past infection related - PCR
Detection of NAs
Antimalaria Tx for causal prophylaxis
- Pyrimethamine
2. Primaquine
Antimalaria Tx for blood schizonticides (terminate atacks)
- CHoloroquine and artesmisinine
WHO recommendations for malaria treatment
WHO recommendations
Artemisinin-based combination therapies (ACTs) for the treatment of uncomplicated malaria caused by the P. falciparum parasite.
Atovaquone-proguanil is a combination of two drugs, atovaquone and proguanil, in a single tablet – for patients returning from endemic areas.
Do not use artemisinin monoterapy – resistance.
Treatment for tissue schizonticides (prevent relapse)
- Primaquine
2. Tafenooquine
Treatment for gametocytocides (block transmission)
- Primaquine
2. Tafenoquine
Treatment for sporozoitocides (ablate transmission of mosquito)
- Primaquine and progaunil
Which type of malaria is common in monkeys?
Knowlesi
Risk factors for malaria
Travel to endemic areas
Lack of chemoprophylaxis
Low host immunity
Pregnancy
<5 years old
Immunocompromised (underlying HIV)
Old age
Pathophysiology of malaria
See disease LOB in PBL notes
Incubation time of falciparum
7-10 days
Incubation time of vivax
10-17 days
Incubation time of malariae
18-40 days
- may ‘lie low’ in the blood to recrudesce after 1–52yrs.
What causes the paroxysms of fever in malaria
Release of TNF alpha and inflammatory cytokines cause fevers that correspond to the rupture of the RBC (waves of reproductive cycles)
These paroxysms of fever are specific to each type of plasmodium