Fever and microbiology

Question 1

What 3 bacteria are the most common causes of bacterial meningitis?

Morphology

Answer 1

1. hemophilus influenza - small, non-motile Gm neg coccobacillus
2. neisseria meningitidis - Gm neg diplococcus
3. strep. pneumoniae - Gm +ve lanceolate diplococcus, may also occur singly or in short chains

Question 2

What are the common bacterial species causing meningitis in prems and newborns?

Morphology?

Answer 2

1. Group B strep - gram +ve cocci in chain
2. E. coli - gm neg bacillus
3. Listeria monocytogenes - small Gm +ve rods sometimes arranged in short chains, may be mistaken for streptococcus

Question 3

Describe the organism?

Likely identification?

How many serotypes?

Which cause epidemic disease? Which season most common?

Which serotypes cause endemic disease?

What percent carries the bacteria in throat?

Answer 3

• Gram negative diplococci
• Likely N. meningitidis
• Typically grows well on blood agar
• 13 serotypes: infections caused by ABCWXY
  
  • A caused most outbreaks, usually in hot, dry season. C also, now W135 and X.
  • B causes endemic disease. Also C.
• Vaccines
  
  • A conjugate, C conjugate, Tetravalent ACYW

Question 4

What organism?

Morphology, culture media

Who should get vaccine?

Answer 4

• small motile Gram negative coccobaccilus
• Six serotypes, most common B (HiB)
• pharyngeal carriage
• in young kids higher fatality rate than N. meningitidis
• 2 HiB vaccines available: 2, 4, 6 months and booster at 12-15 mo
• also benefit: elderly, immunosuppressed, sickle cell, HIV

Question 5

Describe morphology.

likely bug.

Answer 5

• E. coli
• gm neg rod, grows on common media inc blood agar
• lactose fermenting, beta hemolytic on blood agar
• CBC increased neuts + left shift
• meningitis in newborns

Question 6

What is this?

Describe

Answer 6

• Rickettsia prowazecki, etiologic agent of epidemic typhus, transmitted in feces of lice
• Intracellular cocco-bacilli -ve gram, +ve giemsa stains Filterable
• Highly fastidious in vitro
• First identified by da Rocha Lima in 1916 ( R. prowazekii) (and named after his friend who had died of typhus).
• Obligate intracellularorganisms.
• Proliferation results in lysis of host cell

Question 7

Outline the Rickettsial Diseases

(5 groups, 8 diseases)

Answer 7

Question 8

What is this?

Vector for which diseases?

Lifecycle?

Answer 8

• pediculus humanus var. corporis (body lice)
• hard to distinguish from head lice (ped. humanus var capitis), which can also be a vector- see below
• adults of both have 6 legs
• Vector for:
  
  • ​epidemic (louse borne) typhus: Rickettsia prowazekii
  • Trench fever: Bartonella quintana
    
    • ​both spread by inhalation of louse feces or feces being rubbed into abrasion (not by bite)
  • relapsing fever: R. recurrentis
    
    • ​louse must be crushed & spirochete enters via mucosa, cut or abrasion

Question 9

How would you describe this rash?

What disease is it associated with?

Epidemiology?

Pathophysiology?

Incubation period?

Clinical features and mortality?

Answer 9

• truncal macular/petechial rash
• epidemic louse borne typhus ddx murine typhus, scrub typhus etc
• multisystem vasculitis with small and large vessel infarction
• epidemiology patchy, tends to appear in times of conflict and war
  
  • rodents reservoir (N. america flying squirrel), humans may also harbour it after apparent cure and it can manifest again in times of stress
• Clinical
  
  • incubation period 5-23 days (ave 12)
  • abrupt onset
  • high sustained fever resolved by crisis after 7-14 days
  • headache, meningoencephalitis
  • myocarditis
  • mortality approx 20%

Question 10

What is this?

In what diseases is it found?

Clinical features?

Mortality?

Answer 10

• Eschar of Tick Typhus (aka epidemic typhus) found in Tick borne rickettsiae eg. R. africae (African Spotted Fever) or R. conorri (Mediterranean Spotted Fever) or most other spotted fevers (eg RMSF -R. ricketsii)
• also found in scrub typhus but not usually in epidemic typhus (lice) or murine typhus (fleas)
• incubation period 2-14 days
• eschar (scalp, groin, under breasts etc) may precede systemic symptoms
• similar syndrome to Louse Borne Typhus
• lymphadenopathy, sometimes painful
• generalized rash may be absent (R. africae)
• mortality highest in Rocky Mountain Spotted Fever (~7%), less common (~2%) in Med Tick Bite fever (R. Conorri), Rare in African TBF (R. africaei)

Question 11

What do this diagram and pictures represent?

From what must they be distinguished and how?

How many legs do they have?

What diseases do they transmit?

Answer 11

• Life cycle of Ixodidae (hard ticks)
  
  • distinguish from Argasidae or soft ticks by presence of scutum or shield behind the head (soft ticks picture below)
  • Adults and nymphs have 8 legs (larvae have 6 but moult to 8 on becoming nymphs)
  • Ixodidae are vectors for
    
    • Spotted Fevers or Tick Typhus such as
      
      • Rocky Mountain Spotted Fever (R. rickettsi)
      • African Tick Fever (R. africae)
      • Mediterranean Tick Fever (R. conorii)
    • Arboviruses
      
      • Colorado Tick Fever (coltivirus)
      • Crimean Congo Hemorrhagic Fever (Nairovirus of bunyaviridae family)
    • Q fever - Coxiella burnetti
    • tularemia - Francisella tularensis (also deer flies)
    • Lyme disease - Borrellia burgdorfi
    • Tick paralysis
  • Argasidae are vectors for only Tick borne relapsing fever - Borrellia duttoni in sub Saharan Africa

Question 12

What does this diagram represent?

Describe it.

What is the geographic distribution of this group of diseases?

Answer 12

• The life cycle of tick borne or spotted-fever-group rickettsiae
• they are maintained in nature by transovarial and trans-stadial transmission in ticks and horizontal transmission to uninfected ticks that feed on rickettsemic rodents and other animals
• Geographic distribution widespread: South, Central and N. America, southern Europe, Mid-East, Africa, esp east cost, parts of Eurasia, Asia, Australia

Question 13

Lady presents with this rash + another blackened spot in her scalp, recent travel to South Africa on safari and fever, headache, dry cough.

What’s the dx?

Outline how to make it and how to treat it.

Answer 13

• Consider African tick typhus in tourists with fever from Africa
• Sx non-specific
• Headache often prominent
• Rash often absent
• Careful search for eschars eg hairline, groing, breast, buttocks
• Lymph nodes
• Tick bites often not noticed
• nb serology
• immunohistology/PCR of skin biopsy
• Presumptive treatment with doxycycline

Question 14

• What are these? (l⇒r)
• To what class & subclass do they belong?
• How many legs do they have?
• What is the characteristic feature of a female?

Answer 14

• Ixodidae or Hard ticks
  
  • from left to right male, female, fed female
• class Arachnida subclass acarina containing mites and ticks, from latin acari for mite
• they have eight legs, except larvae, which have 6
• must be distinguished from soft ticks (Argasidae) be the presence of a scutum or shield behind the head of the female hard tick, may be hard to see when engorged as on picture on right. see picture below

Question 15

What is this?

What microbe does it carry & what disease?

Outline lifecycle.

Geography: where does this disease occur?

Answer 15

• Leptotrombidium akamushi - Chigger Mite
• Vector of Orienta tsutsugamushi
  
  • Order:Rickettsiales
    
    • Family:Rickettsiaceae
      
      • Genus:Orientia
        
        • Species:O. tsutsugamushi
• obligate intracellular pathogen causing Scrub typhus throughout SE Asia
• Life cycle: only the 6-legged larvae are blood feeding, feeding on zoonotic rodent reservoir and opportunistically on humans. The 8 legged adults live freely in soil and there is transovarian transmission of O. tsutsugumashi .

Question 16

What is this?

What microbe does it carry and what disease does it cause?

What are the clinical features?

Answer 16

• incubation 4-10 days
• Eschar and poss multiple chigger bites
• rash delayed (day 6-7)
• complications unusual
  
  • hepatic dysfunction: jaundice, high AST/ALT, alk phos, or mixed
  • pulmonary involvement
  • chf
  • hypotension
  • renal dysfx
  • thrombocytopenia
  • Sepsis syndrome
• Mortality <2%
• worse outcome in pregnancy

Question 17

What is this?

What is the differential diagnosis?

Answer 17

• Eschar
• commoner in Scrub Typhus where it tends to be on the groin, abdomen or trunk
• some in Spotted Fever Group, e.g. RMSF, African or Mediterrannean Tick Fever
• rickettsial infections
• cutaneous anthrax
• tularemia
• necrotic arachnidism (brown recluse spider bite)
• rat bite fever (Spirillum minus)
• staph or strep ecthyma
• Bartonella henselae

Question 18

What are these?

What species?

Distinguishing characteristics.

What diseases?

Answer 18

• Fleas
  
  • Ctenocephalides “comb head” felis & canis - dog and cat fleas
    
    • 2 combs: genal and pronotal
  • Xenopsylla cheopsis “strange flea” - Oriental rat flea
    
    • no combs, meral rod on 2nd thoracic segment
    • primary vector for plague caused by Yersinia pestis in Asia, Africa, South America, acquired from meal of infected blood adn transmitted to other rodents or humans
    • also a primary vector for R. typhi, causing murine typhus
  • Pulex irritans “irritating flea” - human flea
    
    • can be vector for R. typhi, was vector for plague in Europe

Question 19

Differential dx for scrub typhus in endemic settings for:

Hepatic dysfx

Arthritis

Myocarditis

Encephalitis

Answer 19

• Hepatic dysfx
  
  • leptospirosis, dengue, Q fever, hep A/B/E
• Arthritis (sometimes delayed)
  
  • chikungunya
• myocarditis
  
  • leptospirosis
• encephalitis
  
  • arbovirus - JE, dengue etc

Question 20

• For Murine Typhus
• What does the name mean?
• What were the key findings of this 2017 Review with respect to:
  
  • presenting sx in adults?
  • lab findings?
  • frequency of complications?
  • seasonal distribution of cases?
  • children?

Answer 20

• Murine - associated with rodents
• infectious organism R. typhi
• classic triad of fever, headache & rash in only 1/3
• additional frequent symptoms: chills, malaise, myalgia, anorexia
• tetrad of lab abnormalities: elevated lft’s, ldh, esr, hypoalbuminemia
• complications: hepatitis, myocarditis, encephalitis, renal dysfx. in 1/4
• low mortality
• seasonal: disease of dry warm months
• children different: abd pain, diarrhea, sore throat, more anemia, less hypoalbuminema, hematuria, proteinuria, fewer complications

Question 21

Answer 21

• HIV
• Murine typhus
• Scrub typhus
• Syphilis
• Tick Typhus
• Other

Question 22

What diagnostic tests are best wrt rickettsial diseases?

Answer 22

• MIFA (micro-immunofluorescent assays)
  
  • Still considered gold standard
  • need rising titre in acute illness esp in endemic setting
  • prolonged persistence of IgM
  • cross reactivity with Spotted Fever Group, rarely with other illnesses
• Immunohistochemical tests
  
  • advantages: High PPV, but need path sample
• C&S
  
  • often not available, slow, labour, time, concerns re biosafety
• Molecular diagnostics
  
  • pcr increasingly useful
• Serology
  
  • numerous cross reactions
  • Weil-Felix very poor sens and specificity
• Presumptive Diagnosis
  
  • ​compatible clinical illness
  • strong: eschar, rash
  • rapid defervescence with anti-rickettsial Abiotics

Question 23

Outline treatment for Typhus

Answer 23

• doxycycline 200 mg stat dose in epidemic situations
• Mediterranean Spotted Fever: 200 mg x 2 effective
• Otherwise at least 5 days for severe cases and Rocky Mountain Spotted Fever
• Chloramphenicol an alternative
• cipro may not be as good in vivo as MIC’s sugges
• Single dose Azithromycin
• Rifampicin where TetR
• Cochrane Review says no diff btw tetracycline, doxycycline, telithromycin or azithromycin
• Rifampicin may be superior to tetracycline where Scrub typhus responds poorly

Question 24

What are the conclusion take home messages from Beeching re rickettsial diseases?

Answer 24

• consider rickettsial etiology in patients in or coming from endemic country and presenting with fever and
  
  • lymphadenopathy/hepatosplenomegaly
  • rash (discrete Maculopapular)
  • delayed onset pneumonitis, myocarditis, tinnitus, deafness, retinitis, encephalitis
  • late onset arthritis and erythema nodosum
  • pancytopenia/bicytopenia
• Rash may involve palms
• look for eschar (clue lymphadenopathy)
• careful interpretation of serology if pt from endemic area.
• Serodiagnosis may be improved by molecular techniques
• therapeutic trial of doxycyline justified in resource poor settings
• anibiotic resistance and issue with scrub typhus
• prospective trials needed for fluroquinolones, azithromycine etc.

Question 25

What is Brill-Zinnzer disease?

Answer 25

• delayed relapse of epidemic typhus, caused by Rickettsia prowazekii
• after a patient contracts epidemic typhus from the fecal matter of an infected louse (Pediculus humanus), rickettsia can remain latent and reactivate months or years later
• symptoms similar to or even identical to the original attack of typhus, including a maculopapular rash.
• this reactivation event can be transmitted to other individuals through fecal matter of the louse vector, and form the focus for a new epidemic of typhus.

Question 26

What diseases are caused by spirochetes?

Answer 26

• syphillis
• non-venereal trepanomates (yaws)
• leptospirosis
• Lyme
• rat bite fever
• relapsing fevers

Question 27

• What infection might you get doing this?
• Describe the epidemiology.

Answer 27

• Leptospirosis
• rodents and other small animals most important animal reservoirs, infected in infancy and remain chronically infected, excreting spirochetes in urine
• larger mammals may become sick or chronically infected
• orgs live in soil or water for weeks
• incidence increases after flooding
• Risk factors
  
  • Occupational (30-50%); farmers, abattoirs workers, vets, sewer workers, rice field workers, military personnel
  • Recreational; fresh water swimming, fishing, canoeing,
  • Household exposure; pet dogs, domesticated livestock, rodent infestation

Question 28

• Describe pathophysiology of leptospirosis

Answer 28

• infection acquired by leptospira penetrating skin via minor cuts or mucous membranes. ?intact skin controversial
• Leptospiraemia affects any organ, usually liver and kidney
  
  • ​Kidneys: Migrates to interstitium, tubules-tubulo-interstitial nephritis
  • Liver: Centrilobular necrosis. Proliferation in Kupffer cells. Jaundice (icterus) and hepatocellular dysfunction
  • Skeletal muscle: necrosis
  • With severe disease disseminated vasculitis
  • Eye: Recurrent uveitis
  • Multiplies in blood and tissue.

Question 29

• This might be a presenting feature of what spirochetal disease?
• Outline Clinical Features.

Answer 29

• leptospirosis
• variable, many asymptomatic seroconvertors to mild non-specific febrile illness
• incubation period 10 days (2-26)
• sudden onset fever, rigors, myalgia, headache, nausea, vomiting, diarrhea, cough
• o/e conjunctival suffusion, muscle tenderness, rarely lymphadenopathy, chest signs and rash
• ?meningeal signs
• biphasic? as immune response appears pt may deteriorate and develop:
  
  • aseptic meningitis or
  • Weil’s disease: jaundice, thrombocytopenia, renal failure
  • Pulmonary syndrome, pulmonary hemorrhage (xray below)
  • myocarditis leading to cardiac fever

Question 30

What is this?

Describe the organism?

Diagnostic Techniques?

Answer 30

• slender, spiral anaerobic rods
• dx usually by serology
  
  • ​IgM RDT available
  • Elisa IgM
  • Microscopic Agglutination Test (MAT)
    
    • x-reactivity with spirochetes and legionella
• though can be seen microscopically in blood or urine, rarely used
• blood or urine cultures
• PCR

Question 31

These might be clinical and post-mortem findings of a severe form of a spirochetal disease called …?

Describe the clinical syndrome.

Answer 31

Question 32

Outline the treatment for leptospirosis.

Mild vs severe disease?

prophylaxis?

Any complications of tx and how dealt with?

Answer 32

• Mild leptospirosis: doxycycline, amoxicillin
  
  • in endemic area, if unable to differentiate from rickettsial illness, doxycycline makes sense
• Severe leptospirosis: parenteral penicillin/cephalosporins or erythromycin
• short term prophylaxis for high risk circumstances: doxycycline weekly
• Jarisch-Herxheimer reaction:?steroids, evidence inconclusive, concern about increased infections

Question 33

What is the most widespread zoonosis on earth?

Answer 33

• leptospirosis
• it is found everywhere except the polar regions

Question 34

• What organism is this?
• What disease does it cause?
• Outline bacteriology.
• What tick is vector?

Answer 34

• Borrelia spp., at least 4 cause Lyme Disease
  
  • B. burgdorferi (North America, Europe, Asia)
  • B. lonestari (recently described in US)
  • B. afzelli, B. garinii, B. valaisaiani (Europe, Asia)
• microaerophilic, fastidious organism, hard to stain and culture
• Ixodes tick (below, note scutum)
• In Africa or Asia might be Borrellia spp. where it is reported to be the most common bacterial infection. Transmitted by soft tick (Ornithodoros). Nb cases in Western US, BC and Mexico also.

Question 35

What is this?

What diseases does it carry?

Outline life cycle.

Answer 35

• Ixodes scapularis
• Lyme disease
• Babesiosis
• Ehrlichiosis
• See life cycle below. Key points are that
  
  • nymphs bite humans and transmit Borellia spp. responsible for Lyme disease
  • Adults bite large animals
  • Borellia is transmitted transstadially and transovally

Question 36

What is this?

What disease(s) does it cause?

Describe the organism

Answer 36

• Borrellia sp. possibly Borrellia recurrentis or B. africae
• or A family of diseases caused by different species of Borrelia.
• 2 Kinds generally:
  
  • ​Epidemic Relapsing Fever, or Louse-Borne Relapsing Fever caused by Borrellia recurrentis and transmitted mainly by Pediculosis humanis var corporis
  • Endemic or Tick-Borne Relapsing Fever caused by other species of Borrellia and transmitted by Soft Ticks.
• large spirochetes measuring 10-30 x 0.2-0.5 µm visible in Giemsa
• Borrelia genome consists of combination of linear and circular plasmids
  *

Question 37

What is the Weil-Felix test?

Answer 37

• an agglutination test based on antigenic cross-reactivity between Rickettsia sp and serotypes of Proteus.
  
  • non-specific
  • poor sensitivity and specificity
• supplanted by IFA, other serologic methods and PCR for dx of epidemic or louse-borne typhua
• not to be confused ith Widal test, which is used for salmonella infections

Question 38

How is epidemic typhus transmitted?

Answer 38

• epidemic or louse borne typhus is transmitted when Rickettsia prowazecki - infected species of human body lice (Pediculosis humanus) shits on human and this is rubbed in through wound or conjunctivae. (Not transmitted by bite of louse.)

Question 39

What is Brill-Zinsser disease?

Answer 39

• recurrent louse-borne typhus occurring from latent infection with Rickettsia prowazeki becoming re-activated
• may occur months or years after original infection

Question 40

Why don’t people with epidemic typhus often have lice on their bodies or clothes?

Answer 40

• because once Rickettsiae multiply sufficiently in the louse they rupture the louse intestine, and the louse dies in 8-12 days
• the infection incubates for about 12 days before becoming symptomatic

Question 41

What are the presenting symptoms and clinical course of epidemic typhus?

aka?

Answer 41

• also known as louse-borne typhus
• incubation period about 12 days
• presents with high fever, myalgia, headache & prostration. Conjunctiva suffused, delirium
• rash about day 4, central, and macular, lesions may later become petechial or purpuric
• Complications: pneumonia +/- meningoencephalitis, myocarditis
• untreated, high mortality

Question 42

Outline treatment for rickettsial diseases.

Answer 42

• doxycycline 200 mg stat dose in epidemic situations of Epidemic or Louse-Borne Typhus
• in Meditteranean Spotted Fever (Rickettsia conorii) 200 mg x 2 effective
• Otherwise
  
  • doxycycline at least 5 days for severe cases an in RMSF (Rocky Mountain Spotted Fever)
  • chloramphenicol 500 mg q 6 hrs x 7 days an alternative
  • Rifampicin in areas where TetR (eg. northern Thailand)
  • prospective trials needed for fluroquinolones, azithromycin etc.

Question 43

Compare Mediterranean and African Spotted Fevers wrt:

organism

frequency in tourists

fever

rash

eschar

regional nodes

mortality

Answer 43

• Med vs African Spotted Fevers
• org: R. conorii vs R. africae
• affects tourists: rare vs common
• fever: in both
• rash: common vs less common
• eschar: single vis multiple
• regional nodes: yes to both but more common in ASF
• Mortality 2% vs rare

Question 44

Contrast epidemic and murine typhus.

Answer 44

• murine typhus is similar in presentation but less severe than epidemic typhus, which itself is usually less severe than tick borne typhus which is less severe than scrub typhus
• i.e. in terms of severity: scrub typhus>tick-borne typhus>epidemic typhus>murine typhus
• caused by R. typhi rather than R. prowazecki and transmitted by fleas (Xenopsylla cheopis, the Oriental rat flea) rather than lice (Pediculosis humanus)
• typically no eschar in murine typhus

Question 45

What are the usual vectors for African Tick Borne Typhus?

What is the usual clinical course?

What is the usual organism?

What is/are the main reservoir(s) for this organism?

Answer 45

• species of hard ticks: Amblyomma, dermacentor
• unlike Ixodes, these remain a short time on the host, so less likely to be detected
• fever and eschar in >90% of cases, followed by rash, headache, regional lymphadenitis and arthralgia ( in that order)
• R. africae has displaced R. conorii
• dogs, rondents, wild animals eg. hippo are main vectors

Question 46

How does murine typhus differ from endemic typhus in terms of:

severity?

vector?

organism?

reservoir?

relationships among vector, organism and reservoir?

Answer 46

• less severe syndrome
• also easier on the vector, which is the oriental rat flee. R. typhi does not kill the flea, so they can pass the disease onto rats and other reservoir mammals (e.g opossums, racoons and skunks). This helps to maintain a large reservoir of rats, which can in turn infect more fleas
• bit of rat can rarely transmit R. typhi

Question 47

• Which organism(s) causes louse borne relapsing fever (LBRF)?
• What is the vector for LBRF?
• Which organisms cause Tick Borne Relapsing Fever?
• What are the mortality rates for untreated LBRF?
• For TBRF?

Answer 47

• Borrelia recurrentis causes LBRF
• the vector is Pediculosis humanus
• many species of Borrelia cause TBRF
• Untreated LBRF ~70%
• Untreated TBRF ~10%

Question 48

• What is this?
• for what disease is it the vector?
• Describe it’s bite. When, how long, painful?
• How is the organism transmitted?
• What is/are the organism(s)?

Answer 48

• Ornithodoros moubata
• Tick Borne Relapsing Fever
• Bite is painful, relatively brief, occurs at night
• transmitted through feces smeared into skin, conjunctiva
• Various species of Borellia esp B. duttoni and B. crocidurae in Africa

Question 49

• Louse-borne relapsing fever (LBRF):
• Describe epidemiology.
• Where does it occur?
• What animal is the reservoir?
• What is the vector?
• What is the infecting organism?
• How is the disease spread?

Answer 49

• tends to occur in epidemics in situations of overcrowding
• although called “epidemic” it is also endemic in highland regions of Ethiopia and Burundi as well as other highland areas of Africa, India and the Andes.
• Humans are the reservoir host.
• Vector is pediculosis capitis
• organism is Borrelia recurrentis
• louse provokes itching and is crushed with scratching, releasing Borrellia via abrasions and mucous membranes

Question 50

Describe the pathophysiology of Relapsing Fever.

Answer 50

• Borrelia multiply by simple fission, taken up by Reticuloendothelial system, esp Liver and spleen
• Intrahepatic cholestasis
• Neurotropic (TBRF >>> LBRF)
• Bleeding dyscrasias (hemorrhage/micro-thrombosis (LBRF > TBRF)
• Thrombocytopaenia
• myocardial and pulmonary injury common
• relapses result from antigenic variation

Question 51

Describe the clinical features of Relapsing Fever

Answer 51

• incubation usually 4-8 days (range 2-15)
• typically sudden onset high fever, headache, confusion, meningism, myalgia, arthralgia, nause, vomiting, sometimes dysphagia
• dyspnea, cough may be severe, sputum may contain Borrelia
• Hepatomegaly
• jaundice 50% with LBRF, <10% TBRF
• splenomegaly, increased risk of rupture
• petechiae, rashes, epistaxis, conjunctival injection, hemorrhages more common in LBRF
• complications: pneumonia, nephritis, parotitis, arthritis, cranial and per neuropathies, meningoencephalitis, meningitis, acute ophthalmitis, iritis
• myocarditis ⇒ sudden, fatal arrhythmias
• most complications more common and more severe in LBRF with case fatality rate > 70% in epidemics
• mortality rate <10 % in TBRF

Question 52

Describe the clinical features of Relapsing Fever

Answer 52

• incubation period 4-8 days (range 2-15)
• Abrupt onset (“crisis phase”)
• High fever
• Headache
• Delirium
• Cough
• Jaundice esp in LBRF
• Hepatosplenomegaly
• Conjunctival suffusion and rash (macular or petechial) - these & bleeding more common in LBRF
• dyspnea, cough, sputum may be +ve Borrelia
• Untreated LBRF case fatality 70%, TBRF only 10%
• Complications include:
  
  • ​pneumonia
  • nephritis
  • parotitis
  • arthritis
  • cranial and peripheral neuropathy
  • meningitis & meningoencephalitis
  • opthalmitis, iritis
  • myocarditis

Question 53

What is the differential diagnosis for Relapsing fever?

Answer 53

• malaria
• typhus
• typhoid
• meningococcal septicemia/meningitis
• dengue
• hepatitis
• leptospirosis
• yellow fever
• other VHF

Question 54

Compare Tick Borne with Louse Borne Relapsing Fever in terms of:

1. spirochetemia
2. length of paroxysms
3. number of relapses
4. vomiting
5. other symptoms
6. neurologic complications
7. other complications
8. mortality

Answer 54

Question 55

Diagnosis of Relapsing Fever:

how is it usually confirmed?

Answer 55

• microsopy: Borrelia large spirochetes measuring 10-30 x 0.2-0.5 µm
• visible in Giemsa or Field stain or dark-field or immune fluorescent microscopy
• Spirochaete density 10x higher in B recurrentis vs B duttonii
• may be surprise finding in pt with suspected malaria and dual infections may occur in which Borrelia may be overlooked
• may be concentrated in Buffy Coat after centrifugation
• infected blood or CSF innoculated in mice or rats yields borreliae in blood after 2-3 days
• Serology unreliable
• PCR increasing role
• Lab findings: non-haemolytic anemia; polymorphonuclear leukocytosis; thrombocytopenia; transaminitis; lymphocytic CSF in patients with meningeal sxs
• GlpQ serology: useful for differentiating between non-Lyme and Lyme Borrelia species; if patient already on treatment

Question 56

Outline the treatment for Relapsing Fever.

Answer 56

• doxycycline single dose effective in most LBRF and TBRF
• however, usual practice is to give 5-10 day course to minimize relapse
• ceftriaxone recommended for meningitis or encephalitis
• Jarisch Herxheimer rxn in 80-90% of pts treated for LBRF and 50% of TBRF, esp if treated with bactericidal Abx (pen, ceftriaxone)
• managed with fluid support, ?Mestazinol - partial opioid antaganist? one study showed monoclonal FAb directed against TNF reduces severity, but only experimental
• Main thing is fluids and don’t give up

Question 57

What control measures could be considered for LBRF epidemic?

Answer 57

• De-louse (Don’t scratch, don’t crush)
• DDT, Permethrin or Malathion powder to skin and clothing
• Heat sterilize clothing ideally but impossible in refugee camps
• Improve routine hygiene facilities
• Mass pre-exposure prophylaxis not recommended but consider single doses during de-lousing
• Tick-borne: cut grass, residual spraying
• No vaccine

Question 58

Summary re Relapsing Fever

Answer 58

• Relapsing fever is a common and underdiagnosed cause of fever in many areas of Africa
• Diagnosis may be difficult especially in tickborne
• Louse-borne may carry a high mortality in outbreaks
• The Jarisch-Herxheimer reaction can be difficult to manage

Question 59

What is the differential diagnosis for Weil’s disease?

(presenting with fever, headaches, jaundice, resp distress and purpura)

Answer 59

• Dengue
• Hantavirus
• Viral hepatitis
• Malaria
• Meningitis
• EBV and CMV
• HIV
• Rickettsial disease
• Typhoid fever

Question 60

Describe the life-cycle/ecological niche of leptospirosis.

reservoir

transmission

Answer 60

• the most widespread zoonosis, found everywhere except polar regions
• 2 main pathogenic species L. interrogans and L. bireflexa although 250 serovars potentially pathogenic
• motile spirochetes infect rats and mice, and other mammals. rats relatively assymptomatic carriers, other mammals, inc dogs become sick
• survive weeks in water and in soil
• most commonly enter body via breaks in skin or mucous membranes, occ via inhalation, bite of infected animal, sexual contact

Question 61

What are the non-venereal treponematoses?

How are they related to syphilis?

Answer 61

• morphologically and serologically identical to Treponema pallidum subsp. pallidum
• only minor antigenic differences
• all show +ve syphilis serology
• differ only in clinical presentation
• transmission usually through direct contact
• can be latent infection for many years

Question 62

Compare Yaws, Bejel and Pinta wrt species, environment/geography and mode of transmission.

Answer 62

Question 63

Briefly describe history of Yaws.

Answer 63

• post WWWII large tropical areas Yaws endemic
• massive treatment programme with Benzathine Penicillin from 1952-1964 reduced incidence from 150 million to 2.5 million - 95% reduction
• since then widespread elimination programme stopped, resurgence of Yaws since 90’s leading to new global strategy launched in 2012 aimed at trying to eliminate Yaws by 2020
• India now free of Yaws

Question 64

What org causes Yaws?

Who does it affect?

What kind of conditions? Climate? Sociology?

Answer 64

• Treponema pallidum subsp. pertenue
• contagious non-venereal infection
• primarily affecting children <15 yrs (peak 6-10), M=F
• Warm tropical humid rural areas (Africa, Asia, South America, Oceania)
• associated with overcrowding and poor sanitation

Question 65

• Pathophysiology:
  
  • What are the 4 stages of Yaws

Answer 65

• Primary
  
  • incubation 3 wks (9-90 days)
  • Mother Yaw initial lesion at inocularion site
  • often at site of prior skin injury or insect bite
• Secondary
  
  • Widespread dissemination of treponemes
  • multiple skin lesions last for >6 months
  • “Crab Yaws” diff. walking due to lesions on palms & soles, hyperkeratoses
• Latent
  
  • Usually assymptomatic
  • skin lesions can relapse for up to 5 yrs
  • most remain non-infectious and in latent phase for lifetime
• Tertiary
  
  • after 5-10 yrs 10% untreated progress to tertialy with bone, joint, soft tissue deformities

Question 66

What are these lesions?

In what stage of the disease do they usually occur?

Describe the usual features of this stage of the disease.

Answer 66

• Mother Yaw and Daughter Yaws
• seen Primary Stage of Yaws
• incubation period 3 wk (9-90 days)
• Initial lesion at inoculation site often appears at site of prior skin injury or inoculations site
• during incubation ⇒ subq lympatic and hematogenous spread to produce daughter Yaws
• lesion enlarges to papilloma then resolves after 3-6 months

Question 67

What do these lesions represent?

Briefly outline this stage of the disease?

Answer 67

• Secondary Stage of Yaws
• widespread lymphatic and hematological dissemination of treponemes
  
  • multiple skin lesions, near primary site or elsewhere
  • lesions last > 6 months
  • macules, papules, nodules and hyperkeratotic lesions.
• may develop ‘Crab Yaws’ - referring to diff walking due to lesions on palms, soles, hyperkeratoses
• lesions can ulcerate or heal spontaneously

Question 68

Describe the Latent Stage of Yaws

Answer 68

• usually assymptomatic
• skin lesions can relapsue for up to 5 yrs
• most remain non-infectious
• most remain in latent phase for lifetime

Question 69

What do these pictures represent?

Answer 69

• Tertiary yaws with gummatous periostitis leading to monodactylitis on left, sabre tibia on right
• other bone, joint, soft tissue deformities occur
• rare to see cardio-neural involvement
• chronic periostitis of tibia lead to sabre shins
• monodactylitis, juxta-articular nodules
• rhinopharyngitis mutilans (nasal cartilage destroyed)

Question 70

What is the differential diagnosis for Yaws?

Answer 70

• impetigo
• leishmaniasis
• leprosy
• molluscum contagiosum
• sickle cell anemia
• tuberculosis
• tungiasis
• scabies
• tropical ulcer
• plantar warts
• psoriasis
• venereal syphilis
• Bejel
• osteomyelitis

Question 71

What is this?

What organism causes the disease?

Where is it found?

How common is it?

Answer 71

• Primary lesion of Bejel or Endemic syphilis
• caused by T. pallidum subsp endemicum
• worldwide distribution, now only dry, arid regions Central, Southern Africa, Middle East, Turkey
• Increasing in Sahara, Mali, Burkina Faso
• Freq unknown, seropositivity 22% in Burkina Faso, 12% Niger

Question 72

What are these?

How is it spread?

Who is primarily affected? Age groups?

Answer 72

• mucous patches of Bejel or endemic syphilis
• these are the most common initial lesions
• spread by direct contact via skin or mucous membranes
• 75% of cases children 2-15 yrs
• adults affected when in close proximity to kids
• F>M
• mothers more affected via breast feeding
• Whole families can be affected

Question 73

What is this?

What are the stages of this disease?

How long is the incubation period for the primary stage?

What is the natural history of primary lesions?

Answer 73

• angular stomatitis of Bejel, a primary lesion
• Primary, Secondary, Latent, Tertiary
• Incubation period 9-90 days
• skin lesions resemble chancres of venereal syphilis, small/white ulcers, usually painless
• oral lesions easily missed
• primary lesions heal in 1-6 wks (often undiagnosed)

Question 74

Describe secondary Bejel

Answer 74

• macerated, eroded patches on lips, tongue, tonsils
• condyloma lata can appear in anogenital area
• non-tender generalized lymphadenopathy common
• painful osteoperiostitis of long bones occurs
• angular stomatitis

Question 75

What is this?

Answer 75

• destructive gummas of skin, bone, cartilage in tertiary Bejel leading to “Saddle nose”
• palate perforation also possible
• skin depigmentation after healing
• ocular manifestations may include uveitis, optic atrophy, chorioretinitis
• (neuro and cardiac involvement uncommon)

Question 76

What is the differential diagnosis for the early skin lesions of non and venereal treponematoses?

Answer 76

• eczema
• mycoses
• psoriasis
• leprosy
• herpes
• Later Stages:
  
  • ​malignancy
  • mycosis fungoides
  • lupus vulgaris
  • SLE

Question 77

What is the differential diagnosis for nasopharyngeal lesions and collapse?

Answer 77

• tertiary venereal syphilis
• tb
• leprosy
• mucocutaneous leishmaniasis
• Wegener’s granulomatosis

Question 78

What is this?

How is it different from Bejel and Yaws?

Organism?

Who is affected?

Where?

How common?

Course?

Answer 78

• Pinta, caused by T. pallidum supsp. carateum
• pigmentary changes and depigmentation major characteristic
• more benign course
• tends to affect Young Adults, peak age 15-30
• M=F
• geography different: this tends to be Central and South America, Cuba
• now relatively rare, only ?a few hundred cases reported per year, much more common in 80’s

Question 79

Describe the course of Pinta

Answer 79

• Primary
  
  • incubation 2-3 wksSave
  • skin lesions macule/papule/plaque on exposed areas
  • enlarges and becomes pigmented and hyperkeratotic
• Secondary
  
  • 3-9 months after infection” disseminated lesions or pintids.
• Latent
  
  • assymptomatic
• Tertiary
  
  • disfiguring pigmentary lesions: hypochromic/achromic/hyperpigmented/atrophic
  • lesions appear red, white, blue, violet and brown

Question 80

What is the differential diagnosis for Pinta?

Answer 80

• leprosy
• syphilis
• yaws
• discoid lupus
• eczema
• tinea versicolor
• vitiligo

Question 81

What are the non-venereal treponematoses?

How are they diagnosed?

Answer 81

• yaws, bejel, pinta
• serodiagnosis for syphilis can be used, all +ve
• non-treponemal test
  
  • RPR/VDRL
• confirmatory treponemal tests: TPHA, FTA, EIA (IgG/IgM)
• dark field microsopy of early lesions
• epidermal histology shows treponemes

Question 82

• What are the non-venereal treponematoses?
• How are they treated?

Answer 82

• Benzathine penicillin drug of choice
  
  • Adults: 2.4 MU IM one doses
  • Ped: 50,000 U/kg once, not to exceed 2.4 MU
• Usually non-infectious after 24-48 hrs
• If unavailable Pen V x 7-10 days or
• tetracycline or erythromycin x 15 days
• Azithomycin non-inferior (Lancet 2012)
• Probable effectiveness of single lower dose as used for trachoma

Question 83

Overview of Treponemal Diseases:

name them

org

geography

primary lesion

secondary lesions

tertiary lesions

Congenital infections

Answer 83

Question 84

Summarize non-venereal treponemal diseases?

Names

Age group affected

Stages

Transmission

diagnosis

Treatment

Answer 84

Question 85

How is Brucella transmitted to man?

Answer 85

• inhalation via aerosols
• ingestion of dairy products
• inoculation/hypersentivity
• human breast milk
• sexual transmission
• blood transfusiom

Question 86

What is this?

What disease does it cause?

What are the main species and what animals do they infect?

Answer 86

• Gm -ve coccobacillus, Brucella
• causes Undulant Fever
• It is a zoonosis, occasionally infecting man
  
  • B. melitensus infects goats & cattle: aggressive, acute infection in man
  • B. abortus infects cattle causes chronic infection in man
  • B. suis, pigs, causes abscesses in mans

Question 87

What is the best way to diagnose leptospirosis?

Answer 87

• If there is a history of exposure to fresh water (including swimming pools) in the past month then the presence of fever, myalgia, and redness and oedema of the conjunctiva (especially of the palpebral conjunctiva) makes the diagnosis very probable.

Routine blood tests are non-specific. The WBC may be normal, decreased or increased. Platelets are usually decreased but not alarmingly so. Liver function and/or kidney function may be altered, but again the results are non-specific.

Urine contains leptospires during the first week but results of culture take some weeks to read and are of low sensitivity.

Urinary antigen tests and rapid dipstick tests are attractive but do not cover all the possible strains.

The MAT test is difficult to perform and usually requires paired sera 1–2 weeks apart so that the diagnosis is only made during convalescence or when the disease is progressing unfavourably. The MAT test involves antigens representing 20 serogroups of leptospirosis and will detect agglutination with serum or urine antibody providing the matching serovar is present. It is positive in many cases from the 5th day onwards.

Polymerase chain reaction (PCR), including real-time PCR assays, are excellent but are not available everywhere.

Doxycycline is a cheap and reliable treatment when given in time. Doxycycline can also be used as a chemoprophylaxis in a dose of 200 mg once a week.

Frequently, in an endemic area, the clinician is unable to differentiate quickly between leptospirosis and a rickettsial infection and vice versa. In such a situation oral doxycycline 100 mg daily is a sensible option.

Question 88

Leptospirosis: describe the range of clinical presentation.

What is differential dx for non-specific febrile phase?

Answer 88

• majority asymptomatic seroconversion
• incubation period about 10 days
• general: sudden onset fever rigors, headache, n, v, diarrhea; conjunctival suffusion & muscle tenderness
• more rarely hepatosplenomegaly, lymphadenopathy, chest signs & rash
• as immune response appears may develop one of 4 specific sx

1. aseptic meningitis - up to 50-80%
2. Weil’s disease: jaundice, thrombocytopenia, renal failure, liver fx usually rel well preserved
3. pulmonary syndrome: severe pul hemorrhage and rds
4. cardiac syndrome: myocarditis

• diff dx: malaria, typhoid, influenza, rickettsial infection (esp scrub typhus), arbovirus inf (inc dengue)

Question 89

• What disease is compatible with this fever pattern?
• What clinical syndromes may be associated with this disease?

Answer 89

• Undulant fever or Brucellosis
• undulating pattern with a periodicity of 10-14 days.

1. asymptomatic
2. acute<1 month
3. subacute/relapsing 1-6 months
4. chronic > 6 months
5. hypersensitivity

• prefer the term “active brucellosis with or without localisation”
• also consider focal symptoms, which may be easily missed because of chronicity, non-specificity:
  
  • Fever
  • GI disturbance
  • MSK: myalgia, arthralgia, backache, lethargy
  • headache
  • respiratory
  • GU - orchitis
  • psychiatric - primarily depression, not psychosis
  • hepato/splenomegaly in a minority

Question 90

• The unpasteurized milk of these animals provides one zoonotic source for which disease?
• What other animals and which species of bacteria participate in this zoonosis?

Answer 90

• Brucella melitensis - goats & camels - aggressive, acute disease
• B. abortus - cattle - chronic
• B. suis - pigs - abscesses
• B. canis - dogs - rare in man
• (recently B. pinnipedialis (seals) and B. cetis (whales))

Question 91

What 3 muskuloskeletal syndromes are associated with brucellosis?

Answer 91

• note: very easy to miss without high index of suspicion because of chronicity

1. Non-specific
   
   • fever, lethargy, sweats, anorexia
   • difficutly walking
   • pain “all over” or localized
2. Monoarthritis esp in children
3. Spinal disease:
   
   • men
   • >50
   • chronic

Question 92

• Which is the commonest zoonotic infection worldwide?
• Which is the most widespread zoonosis in the world?
• What is the most common helminthic infection in the world?

Answer 92

• Brucellosis, is the commonest zoonosis, about 500,000 cases annually.
• Leptospirosis is the most widespread zoonosis, occurring everywhere except polar regions.
• Ascariasis is the most common helminthic infection in the world with over 1 billion people infected.

Question 93

• What is the recommended treatment for brucellosis?

Answer 93

• based on a systematic review 2008 BMJ
• Should be treated with 2 drugs one from:
  
  • doxycycline
  • cotrimoxazole
  • rifampicin
    
    • with either
      
      • streptomycin or
      • gentamycin for the first 2 weeks
• uncomplicated acute disease should be treated for a total of 6 weeks
• Chronic or complicated (endocarditis, neurologic disease or bone disease) should be treated for total of 3 months

Question 94

What are Prof. Beechings take home messages regarding Brucella?

Answer 94

• In endemic area, think Brucella.
• take history!
• In ALL spinal TB consider Brucella and vice versa.
• Full micro work-up before treatment - consult with lab
• Over-treat to prevent relapse, use 2 drugs (one of which aminoglycoside) - in brackets my addition
• Prolonged f/u
• Coordinated human and veterinary public health approach

Question 95

Using Brucellosis as an example, discuss one health paradigm.

Answer 95

• can’t control human disease without controlling animal disease
• Brucellosis is one of several diseases where combined approach advocated (also HAT)
• Human disease is controlled by animal disease control (animal hygeine + vaccine) plus pasteurization
• Control by animal vaccination only cost-effective if both animal and human cost savings are included
• So Need
  
  • Animal control
    
    • test and slaughter (compensate farmers)
    • hygeine
    • vaccination
  • People
    
    • vaccination (in development)
    • health education
    • lab safety
    • effective animal control

Question 96

Diagnosis of brucellosis is made clinically.

How is it confirmed?

what is prozone effect?

Answer 96

• Culture if possible, from blood, bone marrow or other tissue or fluid.
  
  • But not sensitive
  • Lab needs alerting as brucella culture aerosolizes, safety issue for lab
• Serology - Tube Agglutination Titre or ELISA
• Prozone effect: high Ab titres lead to cross-linking of Ab’s and blocking of agglutination with Ag. Need to dilute for agglutination to occur.

Question 97

What is an intermediate host?

Answer 97

• an organism that supports the immature or non-reproductive forms of a parasite.
• eg malaria, trypanosomiasis

Question 98

• A 30-year old woman presents to hospital in Nepal with a 2-week history of fever, malaise, abdominal pain and cough. Chest X-ray is normal and blood film shows no malaria parasites.
• What is the likely diagnosis?
• Which is the best investigation to confirm the diagnosis?

Answer 98

• typhoid
• blood culture

Question 99

• You are a medical officer at a district general hospital in Northeast Thailand. A 40-year-old rice farmer is brought in to hospital by his family. He is unconscious. His extremities are warm and clammy. His airway is patent and he is breathing. His axillary temperature is 40 degrees C and his systolic blood pressure is 60 mmHg; there is no recordable diastolic blood pressure. The family tell you that the only treatment he is on is metformin for diabetes. You immediately start aggressive fluid resuscitation and a sliding scale of insulin. The patient is now stable. You are considering what antibiotics to start.

Which antibiotic must be included in the empirical antibiotic regimen you are constructing?

Answer 99

• Ceftazidime or carbopenem
• This is a clinical description of melioidosis, in an individual with relevant risk factors (diabetic Thai rice famer). Ceftazidime (or carbopenems) would give adequate cover for B. pseudomallei, whereas the other options, including ceftriaxone, would not.

Question 100

• Pseudomonas susceptible to co-amoxiclav (AMC), but resistant to gentamicin (CN) and colistin (CT).
• What might this mean?
• What would you treat it with if you are right?

Answer 100

• This antibiogram is so unusual for Pseudomonas that it has been used successfully as a screen for B. pseudomallei.
• Ceftazidime or meropenem x at least 10 days
• follow by cotrimoxazole orally x 12-20 wks to prevent relapse (otherwise relaps rate is 5-25%)

Question 101

What is melioidosis?

Answer 101

Melioidosis is caused by gram-negative bipolar, safety pin-shaped bacillus, B. pseudomallei. Familiarity with different presentations of this infection is essential for early diagnosis as delayed diagnosis contributes to increased mortality and morbidity. Melioidosis is associated with a range of mortality from 10% [3] to 39% [4]. For those with septic shock, it can rise up to 86% [5]. Globally, it is seen in tropical climates, especially in Southeast Asia (Malaysia, Thailand and Singapore), China, Taiwan and northern Australia [6, 7]. It has been reported anecdotally from all developing countries, although it frequently goes unrecognized. From India, cases are reported frequently from all regions, suggesting that it is becoming an endemic disease, but a large number of cases are not diagnosed [8]. This perceived low prevalence is due to the lack of awareness among physicians, microbiologists and poor laboratory facilities. It is usual for laboratories in non-endemic locations to misidentify the bacterium as commensal. Although there has been expansion of the disease in tropical countries due to global warming and population movement, many cases are unmasked by improved clinical surveillance and better diagnostic methodology [9].

Melioidosis is transmitted by inhalation of contaminated dust or water droplets, percutaneous inoculation and ingestion of contaminated water. Our patient most probably acquired the infection by ingesting contaminated water. It is a seasonal disease more common in wet season and epidemics occur during tropical monsoonal storms, cyclones, hurricanes and typhoons [10]. There may be a shift from inoculation to inhalation as the predominant route of spread during epidemics [11]. It is a disease of adults with <5% cases belonging to paediatric age group [12].

Risk factors for melioidosis are diabetes mellitus, chronic renal failure, alcohol abuse, thalassaemia, chronic lung or liver disease, malignancy and immunosuppression. Diabetes mellitus is found in up to 60.9% of affected patients [1]. Latent infection is common, with one study reporting a 4% reactivation rate into active illness [13]. This can occur many years after exposure—at one point in time, this was referred to as the Vietnamese time bomb due to its reactivation in returned serviceman from Vietnam [14]. Melioidosis is divided into subclinical, acute and chronic disease. Acute cases are those where symptoms were present for <2 months. The spectrum of clinical presentations ranges from to asymptomatic or minor localized abscess or nodule to severe, fulminant disease (such as shock, multiorgan abscesses and death). Exposure to bacilli most commonly results in subclinical disease. Clinical disease presents most commonly in acute form and only 9% presents as chronic illness [12]. The most common presentation of melioidosis is pneumonia, occurring in more than half the cases [15]. Acute melioidosis commonly presents as pneumonia and may progress to septic shock with mortality in up to 90% of cases [13]. Infiltrates can occur in lungs which coalesce and cavitate and may cause multiple metastatic abscesses. Initially, our patient had chest infiltrates that were non-specific. Chronic disease closely mimics tuberculosis or malignancy [6]. However, melioidosis can present in a wide variety of patterns, ranging from genitourinary symptoms to encephalomyelitis [13].

Treatment has two phases: the intravenous intensive phase for acute disease, followed by eradication phase [16]. Intravenous ceftazidime (2 g, 6 hourly) and meropenem (1 g, 8 hourly) are agents of choice in the intensive phase. Cotrimoxazole is used in the maintenance phase. Treatment duration depends on local versus severe systemic infection. In local or mild disease, intensive phase is of 2–4 weeks followed by 3 months of maintenance therapy. In severe infection including neurological disease, initial intensive therapy is prolonged for 6–8 weeks. It is followed by an eradication phase with oral cotrimoxazole for the next 6 months [17]. Meropenem in double dose is preferred in neurological melioidosis [13].

Question 102

What are risk factors for melioidosis?

Answer 102

• Risk factors
• Travel history is key. Longest reported incubation period is 62 years.
• Major (by proportion)
  
  • Exposure to soil and surface water in endemic area
  • Diabetes mellitus (risk x12)
• Minor
  
  • Thalassaemia major
  • Immune suppression (corticosteroid use) Cancer
  • Renal failure and kidney stones

Question 103

What is this?

Describe the bacterium.

Answer 103

• anthrax bacillus
  
  • large
  • encapsulated Gm +ve
  • non-motile
  • spore forming bacillus (picture of spores attached below)
  • note growth in chains
  • tacky, granular, bee’s eye growth in colonies
  • non-hemolytic

Question 104

What are these?

Describe the pathophysiology of anthrax and the clinical correlates.

Answer 104

• anthrax spores
• spores inoculated into portal of entry
  
  • skin, gut, lungs
• ingested by macrophages
  
  • migrate to regional lymph nodes
• spores germinate to vegetative bacilli
  
  • bacillary capsule coded by virulence plasmid pX02 resists phagocytosis
• bacilli release toxin coded by pX01 with 3 components
  
  • Protective antigen (PA) binds cell receptor ⇒ entry
  • Edema factor (EF) + PA produce edema toxin
  • Lethal factor (LF) + PA produce lethal toxin
  • Toxins lead to cell death
• Clinically produces widespread edema and necrosis

Question 105

What are the 4 types of clinical presentation of anthrax?

Answer 105

1. cutaneous (95%)
   
   • wool sorters disease
2. GI (rare, ?underreported)
3. Inhalational
4. (meningeal)

Question 106

What is this?

What are the characteristic features of the lesion?

What are the main pointers to diagnosis?

How long is the incubation period?

Answer 106

• cutaneous anthrax (hide handler’s disease)
• 95% of naturally occurring cases
• subQ inoculation of spores
• hands, forearm, head, neck, back
• incubation < 1 to 7 days
• Small painless papule ulcer with marginal vesicles (24-28 hrs)
• Eschar with local edema (2-6 d)
• Untreated mortality 5-20%
• Edema, no pain, no pus, exposure (occ) history

Question 107

What is the differential dx for this kind of lesion?

Answer 107

• Cellulitis (Strep/Staph)
• Tick Typhus
• Leishmania
• Pseudomonas
• Herpes viral skin infection
• Ulceroglandular tularemia
• Spider bite
• Plague
• zoonotic pox (orf from sheep or cowpox)

Question 108

Discuss GI anthrax.

How common?

Answer 108

• rare (<5% reported cases)
  
  • prob underdx
  • 1 case US 2001
• Oropharyngeal
  
  • adenopathy, edema, ulceration etc
• Intestinal
  
  • fever,syncope, malais
  • abd pain, n, v
  • ascites, acute abd, shock
• High mortality
• may need surgery

Question 109

Discuss inhalational anthrax

Answer 109

• Wool sorter’s disease
• some knowledge from Sverdlosk accident
• much from US terror attacks
• incubation 1-5 days
• hemorrhagic adenopathy, mediastinitis
• pleural effusions
• bacteremia
• meningitis common accompaniment

Question 110

Outline treatmen and prophylaxis of anthrax

Answer 110

• cipro 400 mg iv bid
• cipro 500 mg po bid
  
  • (doxy 100 mg bid/ benz pen)
• PEP prophylaxis for 30-60 days
  
  • because sporulated forms may remain in lungs for 2 months
  • cipro 500 mg bid (+/- vaccination)
  • doxy 100 mg bid
• Vaccine used by US/UK troops

Question 111

What percent of antibiotics given in the USA is given to animals.

UK?

worldwide

Answer 111

80% in US

45% in UK

50% worldwide

Question 112

What are 4 WHO 2017 recommendations wrt to address problem of antimicrobial resistance?

Answer 112

• Four recommendations
  1. Reduce use of medically important antimicrobials
  2. Stop use of antimicrobials for growth promotion
  3. Stop use of antimicrobials when no clinical illness present
  4. Control and restrict the use of antimicrobials in animals that are considered critically important to human health

Question 113

What are the 3 commonest causes of bacterial meningitis?

Include physical description

Neonates?

Answer 113

• Commonest
  
  • H. influenza - small, non motile Gm neg coccobacillus (may look Gm pos unless gm stain carefully performed)
  • N. meningitidis - Gm neg diploccocus
    
    • ​ind clusters or epidemics
  • S. pneumoniae - Gm pos lanceolate diplococcus, may occur singly or short chains
• Neonates
  
  • ​Grp. B Strep - Gm pos coccus
  • E. coli - Gm neg rods
    
    • ​individual cases or clusters
  • L. monocytogenes - small Gm pos rods

Question 114

N. meningitidis

Appearance?

Carriage rate?

How many serogroups?

Which are common pathogens?

Which serotype causes most disease?

Which causes endemic meningitis in Africa?

What vaccines available?

Answer 114

• Gm neg diplococcus
• 10-20% carriage rate, higher in epidemic situations
• 13 meningococcal serogroups
• infections mainly by A, B, C, W, X, Y
  
  • A causes 80% of outbreaks
  • B causes endemic meningitis in Africa

Question 115

What is this?

Describe

How many serotypes?

Which most pathogenic?

Pharyngeal carriage and role of vaccine?

What age groups.

Answer 115

• H. influenza
• small, motile, Gm neg coccobacillus
  
  • may look gm pos on poorly done stain
• 6 serotypes
• B causes most disease
• Pharyngeal carriage important, vaccine success may be due to reduced carriage rate
• Most disease under 5; rare above this
• in young children fatality rate gen higher than N. meningitidis

Question 116

Who should receive HiB vaccine?

Dosing in kids?

Answer 116

• all kids under 5
  
  • 2, 4, 6 months, booster at 12-15 mo
• also at risk inc. splenectomized, sickle cell, leukemia, HIV

Question 117

What is this?

Describe org

Answer 117

• E. coli
• Gm neg bacillus
• grows well on common media
• lactose fermenting and beta hemolytic on blood agar

Question 118

What is this?

Describe organism

What kind of disease?

Answer 118

• Strep pneumoniae
• lanceolate, Gm pos diplococcus, sometimes growing singly or in short chains
• Alpha hemolytic
• normal inhabitant of resp tract
• causes pneumonia, sinusitis, otitis medi, meningitis; also osteomyelitis, septic arthritis, endocarditis, peritonitis, cellulitis, brain abscess
• meningitis mostly in very young and very old

Question 119

What is this?

Describe

What disease in whom?

Answer 119

• Listeria monocytogenes
• small Gm pos rods, sometimes in short chains, in direct smears may look coccoid and be taken for streptococci
• Hemolyic on blood agar not sufficient to dx from other Listeria
• sepsis and meningitis/encephalitis in neonates
• also preg women and adults with weakened immune systems

Question 120

What is this?

Describe

What disease in whom?

Answer 120

• Pseudomonas aeruginosa
• Gm neg rod shaped bacillus
• almost all strains motile by means of single polar flagellum
• increasingly important cause of nosocomial infection in pts with compromised host defenses, elderly, hospitalized > 1 wk, sev burns, HIV
• UTI, respiratory, dermatitis, soft tissue infections, bacteremia, bone and joint, GI, meningitis

Question 121

What is this?

Describe.

Answer 121

• Cryptococcus neoformans
• pleomorphic, uninucleate thin walled yeast 2-20 µm diameter
• usually spherical to elliptical surrounded by thick mucinous capsule
• single “tear drop” budding frequently seen
• Stains: because only pathogenic fungus with capsular material, easily demonstrated with variety of stains inc mucicarmine, PAS or alcian blue. Also stains with Gm stain and easily dx from bacteria

Question 122

List common pathogens by Gm stain and microscopic morphology

Answer 122

Question 123

List the common Gram pos pathogens and the infections they cause

Answer 123

Question 124

List the common Gram neg bacteria and the infections they cause.

Answer 124

Question 125

CSF Gm Stain

Describe org

Dx

Answer 125

Question 126

CSF Gm Stain

Neonate

Describe org

Dx

Answer 126

Question 127

CSF Gm Stain

Describe org

Dx

Answer 127

Question 128

CSF Gm Stain

Describe org

Dx

Answer 128

Question 129

CSF Gm Stain

Describe org

Dx

Answer 129

Question 130

CSF ZN Stain

Describe org

Dx

Answer 130

Question 131

CSF cultured on blood agar

What are the likely organisms?

What further tests to confirm?

Answer 131

Question 132

Culture on MacConkey med from CSF for neonate.

What does this medium tell us?

What are likely organisms in this setting?

Answer 132

Question 133

Chocolate (heated blood) agar on culture from CSF.

What are likely organisms.

What test next to distinguish.

Answer 133

• f.u tests
  
  • H. flu wil be oxidase neg
  • N. meningitidis will be oxidase +ve
  • Can also do sugar metabolism test:
    
    • N. meningitidis uses Glucose and Maltose but not Lactose or Sucrose

Question 134

In Chocolate Agar, culture produces pale colony of Gram neg coccus, what further tests can be done to confirm the identity of this organism?

Results below.

What is the organism?

Answer 134

• N. meningitidis (and H. flu) are both Oxidase Positive and turn blue with oxidase reagant, so the distinction between them relies on morph differences on gm stain.
• also metabolizes glucose and maltose, but not lactose or sucrose.

Question 135

What is the definition of Fever or Pyrexia of Unknown Origin?

(Fletcher et al Medicine 2017 45:3 177-182)

Answer 135

• Fever >38.3 ⁰C on 3 occasions
• >3 wk duration
• Exclusion of immunocompromised pts:
  
  • neutropenia (WBC < 1 x10⁹/L &/or ANC < 0.5 x 10⁹/L) during at least 1 wk within 3 months preceding the fever
  • known HIV
  • known hypogammaglobulinemia (IgG < 50% normal)
  • use of equiv of >10 mg pred during at least 2 wk in prev 3 months
• Diagnosis uncertain after thorough history-taking, physical exam and following obligatory investigations: ESR or CRP, Hgb, Plt count, WBC, diff, lytes, cr, TP, protein electrophoresis, alk phos, serum transaminases, LDH, CK, ANA, RF, U/A, blood cultures x 3, urine culture, cxr, abd us, TST or IGRA, HIV test

Question 136

What are the common causes of classical PUO?

Answer 136

• Infections
  
  • Bacterial
    
    • infective endocarditis
    • abd abscess
    • diverticulitis
    • renal abscess
    • lung abscess
    • prostatitis
    • sinusitis
    • infected vascular catheter
    • septic arthritis or osteomyelitis
    • spondylodiscitis & epidural abscess
    • infected joint/vascular prosthesis
    • dental infection
    • brucellosis
    • Q fever
    • rickettsiosis
    • tuberculosis
    • enteric fevers
  • Viral
    
    • cmv
    • coxsackie virus
    • EBV
    • Hep A, B, C, or E
    • HIV
    • parvovirus
  • Fungal
    
    • endemic mycosis
    • aspergillosis
    • candidiasis
    • cryptococcosis
    • histoplasmosis
  • Parasitic
    
    • malaria
    • leishmaniasis
• Non-Infectious Inflammatory Disorders
  
  • Systemic rheumatic diseases
    
    • AS, Behcet’s disease, cryoglobulinemia, dermatomyositosis, Felty’s syndrome, gout/pseudogout, mixed CT disease, polymyositis, reactive arthritis, RA, SLE, Sjögren’s sydnrome
  • Vasculitis
    
    • Eosinophilic granulomatosis with polyangitis (Churg-Strauss syndrome), giant cell vasculitis/PMR, granulomatosis with polyangiitis (Wegener’s granulomatosis), polyarteritis nodosa, Takayusu’s arteritis
  • Autoinflammatory disorders
    
    • Adult onset Still’s disease, Familial Mediterranean Fever
  • Granulomatous disease
    
    • Sarcoid
• Neoplasia
  
  • Hematological
    
    • lymphoma, leukemia, multiple myeloma, myelodysplastic syndrome, myelofibrosis
  • Solid tumours
    
    • breast ca, colon ca, hepatocellular ca, lung ca, pancreatic ca, renal cell ca
  • Misc.
    
    • Adrenal insufficiency, amyloidosis, atrial myxoma, autoimmune hemolytic anemia, autoimmune hepatitis, Castleman’s disease, drug fever, factitious fever, Inflammatory Bowel Disease, hemaophagocytic syndrome, pheochromocytoma, pulmonary embolus/thrombosis

Question 137

What is Q fever?

Answer 137

• Q fever, also called query fever, is a bacterial infection caused by the bacteria Coxiella burnetii. The bacteria are most commonly found in cattle, sheep, and goats around the world. Humans typically get Q fever when they breathe in dust that was contaminated by infected animals

Question 138

What is Whipple disease?

Answer 138

• Whipple disease is a systemic disease most likely caused by a gram-positive bacterium, Tropheryma whippelii. [1, 2] Although the first descriptions of the disorder described a malabsorption syndrome with small intestine involvement, the disease also affects the joints, central nervous system, and cardiovascular system.
• (not for TM course)

Question 139

What is Ehrilichiosis?

Answer 139

• Ehrlichiosis is the general name used to describe several bacterial diseases that affect animals and humans. Human ehrlichiosisis a disease caused by at least three different ehrlichial species in the United States: Ehrlichia chaffeensis, Ehrlichia ewingii, and a third Ehrlichia species provisionally called Ehrlichia muris-like (EML). Ehrlichiae are transmitted to humans by the bite of an infected tick. The lone star tick (Amblyomma americanum) is the primary vector of both Ehrlichia chaffeensis and Ehrlichia ewingii in the United States. Typical symptoms include: fever, headache, fatigue, and muscle aches. Usually, these symptoms occur within 1-2 weeks following a tick bite. Ehrlichios is diagnosed based on symptoms, clinical presentation, and later confirmed with specialized laboratory tests. The first line treatment for adults and children of all ages is doxycycline.

Question 140

What is tularemia?

Answer 140

• Tularemia is a disease of animals and humans caused by the bacterium Francisella tularensis. Rabbits, hares, and rodents are especially susceptible and often die in large numbers during outbreaks. Humans can become infected through several routes, including:

Tick and deer fly bites

Skin contact with infected animals

Ingestion of contaminated water

Inhalation of contaminated aerosols or agricultural dusts

Laboratory exposure

In addition, humans could be exposed as a result of bioterrorism.

Symptoms vary depending on the route of infection. Although tularemia can be life-threatening, most infections can be treated successfully with antibiotics.

Steps to prevent tularemia include:

Use of insect repellent

Wearing gloves when handling sick or dead animals

Avoiding mowing over dead animals

In the United States, naturally occurring infections have been reported from all states except Hawaii.

Question 141

Dimorphic fungi.

What do they do?

What are they?

(Mold in the Cold, Yeast in the Heat (Beast)

Body Heat Probably (Changes) Shape)

Answer 141

• Blastomyces dermatitidis, Histoplasma capsulatum, Paracoccidioides brasiliensis, (Coccidioides immitis) is in parentheses because it changes to a spherule of endospores, not yeast, in the heat), Sporothrix schenckii.

This phrase says “Probably” because there is always an exception (in this case fungi like Candida albicans) which change in the opposite direction: to mold in the heat!

Question 142

What is the minimum infectious dose for typhoid?

What is incubation period?

Clinical course?

physical signs?

Answer 142

• 10⁵ orgs. Innocula up to 10⁹ wil just shorten the incubation period
• average 14 days (1-3+ wks)
• onset gradual, rigors unusual
• grad rising fever in first week, evening rise
• then high for a week and falling by lysis in 3rd or 4th week
• present with malaise, gen aches and pains, anorexia, abd pain or discomfort, headache, diarrhea or constipation, non-productive cough
• Complications start about day 15.
• early looks well, after 2 weeks may look very toxic, mentally stuporose and gravely dehydrated
• high fever, apathy, signs of bronchitis and meningism
• Truncal Rose spots from day 7 - blanching with spots
• relative bradycardia
• The organisms penetrate the small intestine and are carried via the lymphatic duct to the general circulation. They lodge in lymph nodes, especially in Peyer’s patches, and in the macrophages of the liver and spleen where they multiply. They then spill out from these sites causing a second bacteraemia.

As a result there is a pan-organ systemic infection with a predilection for the gall bladder, bone, brain and spleen.

This second bacteraemia coincides with the start of clinical disease.

The incubation period is generally in the region of 1–3 weeks depending on the magnitude of the infecting load and the resistance of the patient.

Overt disease is common in younger people viz. the 2–10 years of age bracket.

Question 143

Complications of Typhoid?

Answer 143

• Perforation
• Hemorrhage: rptd small bleeds, poss massive hemorrhage in 3rd week
• Severe toxemia: delirium, obtundation, stupor, coma, shock
• Hemolytic anemia: typhoid depressed G6PD in normal as well as def pts
• Typhoid lobar pneumonia
• meningitis
• renal disease: failure or acute nephrotic syndrome
• Typhoid abscess anywhere: spleen, liver, brain, breast, skeletal
• septic arthritis, osteomyelitis, Zenkers muscle degeneration, polymositis
• other: parotitis, acute cholecystitis, dvt, psych, Guillain Barré

Question 144

Confirm dx of typhoid? How.

Treatment?

Answer 144

• blood culture, esp in 1st and 2nd week, need large volume
• bone marrow culture
• aspirate rose spots
• csf
• abscess pus
• stool but pt may be chronic carrier
• Serology
  
  • Widal test lacks spec and sens
• Treatment: depends on local sensitivity
  
  • generally iv ceftriaxone, cefotaxime, cefixime best (IV route preferred at first)
  • alternatives inc fluroquinolones, amoxil, coterimoxazole (beware nephrotoxicity)
  • steroids very iffy

Question 146

What are the organisms causing enteric fever?

Answer 146

• Typhoid: Salmonella enterica serovar Typhi and
• serovars Paratyphi A, B, C
• Gm neg bacilli of the Enterobacteriacae
• All carry O (somatic) and H (flagellar) antigens. This is the basis for the Widal test (see below). However the Vi antigen is peculiar to S. typhi and S. paratyphi C.

Question 147

What are the clinically significant interactions between typhoid fever and other infections or diseases?

Answer 147

• Sickle cell and G6PD more likely to have hemolysis
• Chronic fecal carriers may have
  
  • chronic cholecystitis with or without gallstones
  • path abnormalities in urinary tract including S. hematobium
  • S. mansoni may be assiseiated with relapsing non-typhoid Salmonella septicemia

Question 148

What three filaria are responsible for most disease causing infections?

What disease?

Where?

Answer 148

• Filiariasis
  
  • Wuchereria bancrofti
    
    • ​90% of ~120 million cases
    • “all over the tropics: Africa, India, SE Asia, Pacific Islands, Caribbean & South America”
  • Brugia malayi
    
    • ​restricted to southeast Asia, with closely related Brugia timori in southeastern Indonesia
• Onchocerciasis - River Blindness
  
  • Onchocerca volvulus

Question 149

Wuchereria Bancrofti and Brugia malayi: Describe the Life Cycles.

Answer 149

• Definitive Host: Human
• Intermediate Host: Mosquito

1. Mosquito takes a blood meal, L3 larvae enter skin.
2. Adults in lymphatica
3. Adults produce sheathed microfilariae that migrate into lymph and blood channels
4. Mosquito takes a blood meal ingests microfilariae
5. Microfilariae shed sheaths, penetrate mosquito’s midgut and migrate to thoracic muscles
6. L1 larvae (sausage larvae)
7. L3 larvae
8. Migrate to head and mosquito’s proboscis

Question 150

What are these?

For what disease? And which parasite?

Periodicity?

Where?

Answer 150

• Vectors for Wucheria bancrofti, filiariasis
• Anopheles gambiae (bottom left) in sub-Saharan Africa
  
  • nocturnally periodic
• Culex (generally quinquefasciatus) (bottom right) in Americas, Asia, east Africa
• Mansonia uniformis (top right) in Papua New Guinea
• Aedes species (top left)
  
  • diurnally subperiodic in Pacific and Asia
  • nocturnally subperiodic in Thailand

Question 151

What is this?

What are the distinguishing features?

Answer 151

• Wucheria bancrofti microfilarial stage
• sheathed larvae
• nuclei stain purple and are sharply defined
• nuclei do not extend all the way to the tip of the tail
• sheath is stained a paler colour

Question 152

What is this?

What are the disginguishing features?

What are the usual vectors?

Which and how much disease?

Answer 152

• Brugia malayi microfilaria
• sheathed
• usually ‘kinked’ picture on left
• tail tapered with significant gap between terminal nuclei and two discrete sub-terminal nuclei (right)
• Mansonia (open swamp)
• Aedes
• filiariasis, about 13 million people, 10% of worlds total

Question 153

What are these?

Answer 153

• W. bancrofti (left)
  
  • ​sheath does not stain
  • nuclei stain deep blue
  • (can’t see here but nuclei don’t go all the way to the end of the tail)
• B. malayi
  
  • ​deep purple staining nuclei
  • pink staining sheath
  • (can’t see here but two distinct terminal nuclei separate from the rest, go all the way to the end of the tail)

Question 154

Filiariasis disease spectrum

Describe briefly

Answer 154

• vast majority assymptomatic but almost all have sub clinical lymphatic damage
• 40% have renal involvement with proteinuria and haematuria

1. Asymptomatic Infection (Lymphatic Dilatation)
2. Acute Lymphadenitis and Filarial Fevers
3. Elephantiasis
4. Tropical Pulmonary Eosinophilia (TPE)

Question 155

Describe the implications of periodicity

Answer 155

• Filarial worms have evolved to have diurnal cycle coincident with biting habits of their regional vector
• nocturnally periodic:
  
  • W. bancrofti Sub-Saharan Africa vector is usually malaria mosquito Anopheles gambiae, which generally bites at night, so midnight is preferred time for blood collection
• In the Pacific and Asia, the Vector is a diurnally supperiodic form of Aedes. Microfilaria are present all the time but are at peak blood levels between 10 am and 2 pm
• in Thailand it is a nocturnally subperiodic form

Question 156

What is this?

Sensitivity?

Specificity?

When can it be used?

Answer 156

• rapid Ag detection test for W. bancrofti using polyclonal and Mab’s
• Sensitivity 96%
• no cross-reactions with other human infective filariae
• finger prick blood, any time of day without regard to periodicity of parasitie

Question 157

What is this?

Distinguishing characteristics?

Periodicity?

Vector?

Answer 157

• Loa Loa
• microfilaria 250-300 µm long
• sheathed, column of irregularly spaced nuclei extends to tip of tail, which is often bent to one side
• species has diurnal periodicity so blood levels highest between 10 am and 2 am
• vector is day biting fly Chrysops

Question 158

What is this?

Vector for which parasite?

What is it’s geographic territory?

Why significant?

Answer 158

• Chrysops fly, vector for Loa Loa
• fly breeds under rainforest canopy and in mud at side of streams, more common in rainy season
• rubber plantations bring humans into contact vor work, so more exposure in adults than kids
• West Africa affecting Nigeria, Cameroon, Zaire, Angola, Gabon, Chad, South Sudan and Central African Republic
• Overlaps with distribution of Filiarisis and Onchocerciasis and complicates community treatment plans. Loa Loa is relatively assymptomatic, but treatment with Ivermectin may precipitate encephalitic crisis through killing Loa Loa microfilaria.

Question 159

Describe the Loa Loa Lifecycle.

Answer 159

• Definitive Host: Human
• Intermediate Host/Vector: Chrysops Fly (Deer Fly)
• 3 larval stages, microfilariae

1. Chrysopos takes a blood meal, L3 Larve enter bite wound
2. Adults in subcutaneous tissue
3. Adults produce sheathed microfilariae that are found in spinal fluid, urine, sputum, peripheral blood and lungs
4. Fly takes a blood meal, injesting microfilariae
5. Microfilariae shed sheaths, penetrate fly’s midgut, migrate to thoracic muscles
6. L1 (sausage) Larvae
7. L3 Larvae
8. Migrate to head and fly’s proboscis

Question 160

What is this?

Disginguishing characteristics.

Lifecycle (briefly).

Answer 160

• Mansonella perstans
• a nematode of minor medical importance
• does not cause many symptoms but worm can swim about the pericardium and peritoneum and produce some swelling
• unsheathed
• 190-200 µm long
• tail blunt and nuclei extend to tip of tail
• smaller than other species of microfilaria
• Lifecycle
  
  • similar to W. bancrofti, B. malayi except vector/intermediate host is midge (genus Culicoides)

Question 161

What is this?

How distinguished?

Answer 161

• coinfection in endemic area with
  
  • W. bancrofti and
  • M. perstans
• coinfections usually involve Mansonella and another genus
• size difference easily seen, sheath visible on larger W. bancrofti

Question 162

Outline the epidemiology of Brucellosis.

i.e. How is it spread to man?

Answer 162

• by ingesting unpasteurized milk products
• eating raw liver or meat of infected animals
• inhalation: farms or labs
• contact with parturient animals
• contact of skin or conjunctiva with soiled surfaces
• other: human breast milk
  
  • sexual transmission
  • blood broducts, bone marrow transplanatation

Question 163

What is the 2015 WHO Global Action Plan on Antimicrobial Resistance?

Answer 163

• The goal of the draft global action plan is to ensure, for as long as possible, continuity of successful treatment and prevention of infectious diseases with effective and safe medicines that are quality-assured, used in a responsible way, and accessible to all who need them.
• To achieve this goal, the global action plan sets out five strategic objectives:
  
  1. to improve awareness and understanding of antimicrobial resistance;
  2. to strengthen knowledge through surveillance and research;
  3. to reduce the incidence of infection;
  4. to optimize the use of antimicrobial agents; and
  5. develop the economic case for sustainable investment that takes account of the needs of all countries, and increase investment in new medicines, diagnostic tools, vaccines and other interventions.

Question 164

What is the differential diagnosis of pyogenic meningitis?

Answer 164

• Malaria (cerebral or otherwise)
• typhoid
• pneumonia
• urinary tract infection
• otitis media/sinusitis
• severe pediatric gastroenteritis
• brucellosis
• rickettsial disease
• subarachnoid hemorrhage
• cerebral abscess or other SOL including tuberculoma
• causes of lymphocyti CSF (TB, cryptococcus, viral meningitis etc)
• encephalitis
• poisoning (alcohol, drugs, etc.) and other causes of coma
• drug-induced extrapyramidal signs (phenothiazines, antiemetics)

Question 165

• What conditions should be considered with the following CSF patterns
  
  • pyogenic
  • lymphocytic with normal glucose
  • lymphocytic with low glucose
  • eosinophilic
  • amebic

Answer 165

• pyogenic
  
  • bacterial
• lymphocytic with normal glucose
  
  • most viruses (polio, enteroviruses, coxsackie, arboviruses)
  • rickettsiae
  • HIV
  • early TB
  • misc (eg endocarditis, neoplastic)
• lymphocytic with low glucose
  
  • partially treated bacterial meningitis
  • cerebral abscess
  • TB
  • some viral (eg mumps)
  • fungal (eg cryptococcus, aspergillus)
  • brucellosis
  • syphilis
  • leptospirosis
  • trypanosomiasis
• Eosinophilic
  
  • angiostrongylus cantonensis (rat lung worm)
  • taenia solium (cysticercosis)
  • paragonomiasis
• amebic (rare)
  
  • naegleria or balamuthia mandrillaris

Question 166

What CSF findings suggestive of Bacterial meningitis may be helpful in case of negative Gram stain?

Answer 166

Question 167

• What are the complications of bacterial meningitis

Answer 167

• cranial nerve palsy
• hemiplegia
• deafness
• subdural empyema
• abscess
• late hydrocephalus

Question 168

What are the drawbacks of polysaccharide meningococcal vaccines?

Answer 168

• Polysaccharide vaccines do not provoke T-cell immunity and therefore their effect does not provoke the formation of either memory B or memory T cells. The consequent lack of an anamnestic response means that a second or subsequent exposure to that same meningococcal polysaccharide antigen fails to induce the production of an appropriate antibody.

Thus polysaccharide vaccines

* lose their effect fairly rapidly,
* need to be repeated every 3 years, and
* fail to induce a satisfactory response in the young (0–5 years).
* Furthermore every subsequent vaccination starts from scratch and this is technically not a booster\*.
* Repeated vaccination with polysaccharide meningococcal A/C vaccine may well give reduced functional antibody responses to the serogroup C portion of the vaccine despite increased responses to the serogroup A.

These vaccines should always be transported via a cold chain with the temperature kept below 5 °C.

* The term ‘booster’ implies stimulation of dormant immunogenicity by a repeat immunization. Repeat polysaccharide vaccines are therefore not boosters.

* less effective in malnourished, malaria, HIV
* aborts epidemics but not nasal carriage

Question 169

What is the most common cause of pyogenic meningitis?

Answer 169

• S. pneumoniae is the commonest cause of pyogenic meningitis worldwide at any age, including those in the 0–14 year age group. It is certainly the most common cause of bacterial meningitis in adults, and the second most common cause of all types of meningitis in children older than age 2 years (after viral causes).

H. influenzae seldom affects children over 5 years of age.

Some pathogens are more common in some places rather than in others. For example – in Vietnam – Streptococcus suis is the most common cause of pyogenic meningitis in adults.

Staphylococcal meningitis (S. aureus or coagulase negative staphylococci) is usually the result of haematogenous spread from elsewhere or develops as a complication of a surgical procedure.

• Listeria can affect older people as well as neonates.

Question 170

• What is the most prevalent meningococcal serotype in Africa?
• South America?
• The US?
• Which serotype has more recently been associated with epidemics in Africa and on the Hajj.
• In Europe and Canada?

Answer 170

• Serotype A causes the majority of cases of meningococcal meningitis in Africa and, indeed, worldwide.
• Some serotypes are more prevalent in certain areas, e.g. serotype C in South America, serogroup Y in the US.
• W135 has become an important cause of meningitis in recent times with outbreaks reported in Burkina Faso, in the African meningitis belt and isolated cases in South Africa. It was responsible for a large outbreak in pilgrims returning from the Hajj in 2000 when it was transported back to many countries including the UK. The authorities in Saudi Arabia now insist on immunization, within 3 years, with conjugate vaccine against this strain in all those going to do the Hajj or Umrah pilgrimages.

Note that of the 13 types of Meningococcus described (all Gram negative cocci) only 6 are pathogenic viz. serotypes A, B, C, Y, W135 and X. Vaccines are now available against all these except serotype X.

• In Europe and Canada serotype B has become most dominant since the introduction of quadrivalent ACWY vaccine.

Question 171

• What are the 3 organisms and serotypes responsible for most pyogenic bacteria after the neonatal period?
• What other organisms cause pneumonia in particular groups of adults?

Answer 171

• Streptococcus pneumoniae • many serogroups (numbers)
• Neisseria meningitidis
  
  • serogroups A, B, C, Y, W135
    
    • A, W135 in Africa, A much reduced in areas where Men A vaccine introduced
    • B in Europe & Canada after introduction of quad vaccine (A, C, W, Y)
    • Y in US
• Haemophilus influenzae type b • many children <5y
• S. suis in Thailand, Vietnam
• Staph and Listeria in elderly, immunocompromised

Question 172

Dinstinguish endemic from epidemic meningococcal disease.

What is the “alert threshold”?

Answer 172

• see below
• alert threshold is >15 cases per 100,000, i.e. 2 or more cases in a camp of 10,000 people
• other features suggesting an epidemic are shift from <5 to teenagers or older esp in high risk situation
  
  • eg refugee camp in meningitis belt in dry season
• if more than 3 yrs since last epidemic then alert threshold reduced to >10/100,000

Question 173

How do you manage a meningococcal outbreak?

Answer 173

• early recognition is key
• group vaccinations of appropriate vaccine according to serotype
• mass chemoprophylaxis if org sulfa-sensitive or if decision to use fluoroquinolone

Question 174

Outline management of pyogenic meningitis.

Answer 174

• blood cultures and csf early to identify organism
• antibiotics ASAP, initially broad spectrum and take account of local sensitivities
• ceftriaxone has supplanted most others, but chloramphenicol and tifomycin (long-acting chloramphenicol) may still be only options in some resource poor settings.
• in areas of high antibiotic resistance to pneumococcus such as Thailand or Vietnam, vancomycin should be added pending culture and sensitivity.
• Steroids
  
  • although evidence of reduced disability in some settings in high-income settings, studies do not show same benefit of routine use for pyogenic meningitis in resource-poor settings.
• studies with glycerol have shown no benefit

Question 175

• Outline considerations specific to management of meningococcal disease
• Choice of antibiotic
• duration of treatment
• treatment of contacts

Answer 175

• although responsive to benzyl-penicillin and chloramphenicol, ceftriaxone now widely available and drug of choice
• uncomplicated meningococcal meningitis has mortality of <10% and rarely needs more than 5-7 days treatment
• meningococcal septicemia +/- meningitis has mortality >40%, needs max intensive care
  
  • up to 10% have immune complex disease inc uveitis, pericarditis, polyarthritis, usually in second week, can be treated with nsaids or steroids
• Contact treatment
  
  • cipro (or rifampicin or ceftriaxone) single dose can be given to contacts
  • ‘ring’ vaccination of contacts may be more appropriate in epidemic situation

Question 176

• Outline considerations specific to management of pneumococcal disease
• Choice of antibiotic
• duration of treatment
• treatment of contacts

Answer 176

• choice of antibiotic depends on local resistance patterns
• high rates of penicillin resistance, in some settings chloramphenicol resistance
  
  • eg PNG, Thailand, Vietnam (nb also p. suis)
• High dose ceftriaxone eg. 2 gm im or iv bid
• add vancomycin or give Meropenem if available in cases of P&C resistance
• treat minimum 10 days, possibly 14+ days
• up to 40% of survivors will have neuro deficits

Question 177

What is Tropical Pulmonary Eosinophilia?

What are the demographics of the typical person presenting with TPE?

What are other chronic manifestations of the underlying infection?

Answer 177

• TPE is an asthma-like condition due to an exaggerated immunological response to the common filarial parasites Wuchereria bancrofti or Brugia malayi. Sometimes the acronym TFPE is often used with the ‘F’ standing for ‘filaria’.

TFPE shows a marked eosinophilia. However a similar high eosinophil count is found in TPE from other causes e.g. when associated with worms migrating through the lungs such as Ascaris,hookworm and Strongyloides.

Although TPE starts as an acute lung condition, it may ultimately progress to a chronic restrictive lung disease with a decrease in pulmonary diffusion capacity. Chronic TPE develops most often in people under 40 years of age. It occurs in less than 0.5% in those >40 years of age.

The condition usually presents with persistent coughing, wheezing (especially at night) and systemic signs such as mild fever and weight loss. It is due to an allergic hyper-responsiveness to dead and dying microfilariae in the lungs.

TPE should be suspected in immigrants with these symptoms even if they have left endemic countries many years ago. Misdiagnoses of acute-onset asthma or even of a recrudescence of latent TB have been made in these patients.

If the patient fails to respond favourably to a 3-week course of diethylcarbamazine (DEC) then a second course should be given together with three weeks of albendazole. Alternatively doxycycline may be used for several weeks, followed by ivermectin. TPE is commonly seen in West Africa and India.

• In true TFPE, apart from a peripheral blood eosinophilia of >3000cells/μl, a massive rise in IgE is typical. The usual person who presents with TFPE is a young adult male from India. TFPE is one manifestation of ‘occult filariasis’.

Other organs affected by occult filariasis are the kidneys (glomerulonephritis), the heart (fibrosis), the large joints (especially the knee) and the breast (granulomata).

Question 178

What is Löffler’s Syndrome?

What causes it? Name the 4 species.

How is it different from Tropical Pulmonary Eosinophilia?

Answer 178

• Loeffler’s syndrome was originally described in 1932 by Wilhelm Loeffler as an acute eosinophilic pneumonia due to a reaction to a variety of parasites that normally migrate through the lungs e.g. Ascaris lumbricoides, Strongyloides stercoralis and hookworms such as Ancylostoma duodenale and Necator americanus (See Chapter 24, Section B, Q2). Although TFPE broadly fits into this definition the history is almost always that of chronic lung dysfunction rather than that of an acute transient pneumonia. Using this definition Loeffler’s syndrome affects only a very small proportion of those living in filarial endemic areas.
• Note: many nowadays include any lung disease in which eosinophils accumulate in the lungs due to a parasitic infection under the heading of Loeffler’s syndrome.

Question 179

What is leptospirosis?

Presentation?

Incubation period.

Risk?

Geography

Answer 179

• Leptospirosis is a biphasic disease that begins suddenly with fever accompanied by chills, intense headache, severe myalgia (muscle ache), abdominal pain, conjunctival suffusion (red eye), and occasionally a skin rash.
• The symptoms appear after an incubation period of 7–12 days.
• leptospira species
• contact with water
• Widespread, temperate and tropical, more common tropical

Question 180

• What is normal CSF like wrt:
  
  1. opening pressure
  2. glucose
  3. cell count
  4. protein
  5. ph?

Answer 180

1. CSF pressure varies from 10 cm H2O in children to 20 cm H2O in adults
2. Glucose concentration is only two-thirds that of plasma and is further reduced in bacterial infections.
3. CSF is free from white blood cells apart from a few lymphocytes.
4. The protein content should be <10 mg/ml.
5. The pH of the CSF is slightly acidic compared to that of plasma and remains surprisingly constant despite wide pH variations in body fluids.

Question 181

• When is an LP contraindicated?

Answer 181

• The GCS is based on best motor responses, best verbal responses and eye opening. The maximum for each is 6, 5 and 4 respectively, viz. a total of 15. Unrousable coma occurs with a score <9 and is a contraindication to LP. Although it is useful in diagnosing and differentiating the different types of meningitis, an LP should not be performed within 2 h of a convulsive seizure.

Considerable clinical acumen is often needed in deciding when and when not to do a lumbar puncture. Many patients with raised CSF pressure will either have equivocal, marginal or actually no papilloedema. In many places a CT scan may not be available.

Question 182

• What will you most likely see on a WBC for:
  
  1. Deep Sepis
  2. Schistosomiasis
  3. TB
  4. Brucellosis

Answer 182

1. A moderate to high neutrophilia and chronic fever, worst in the evening, is found in deep sepsis, e.g. subphrenic abscess, hepatic abscess.
2. The invasive stage of schistosomiasis is often, but by no means always, accompanied by a marked eosinophilia not a neutrophilia.
3. TB and
4. brucellosis frequently show a neutropenia.

Question 183

How would you approach fever in an HIV +ve patient in sub-Saharan Africa.

Answer 183

• Always beware of TB in such patients. Pulmonary examination may be negative but many co-infected patients have extrapulmonary TB. In HIV, fever only accompanies an acute attack or HIV seroconversion, where symptoms resemble infectious mononucleosis (IM) and IM-like syndromes, e.g. cytomegalovirus and toxoplasmosis. Opportunistic infections, e.g. thrush, P. jirovecii, nontyphoid salmonellosis, Kaposi changes and intractable candidiasis will occur once the CD4 count drops below 200 x 106/L.

Question 184

What are the Jones Criteria for the diagnosis of Rheumatic Fever?

Answer 184

• Evidence of preceding Strep pyogenes infection + two major or one major and 2 minor manifestations
• Major manifestations
  
  • carditis
  • polyarthritis
  • chorea
  • erythema marginatum
  • subcutaneous nodules
• Minor manifestations
  
  • arthralgias
  • fever
  • elevated ESR or CRP
  • EKG evidence of prolonged PR interval

Question 185

• What are these?

Answer 185

• Pastia’s Lines
• Pastia’s sign, Pastia lines, or Thompson’s sign is a clinical sign in which pink or red lines formed of confluent petechiae are found in skin creases, particularly the crease in the antecubital fossa, the soft inside depression on the inside of the arm; the folding crease divides this fossa where the forearm meets the (upper) arm (the biceps, triceps, humerus section of the upper extremity); the inside of the elbow (the inside flexor depression (fossa) of the elbow. It occurs in patients with scarlet fever prior to the appearance of the rash and persists as pigmented lines after desquamation.

Question 186

Treatment of Rheumatic Fever

Answer 186

• salicylates first-line agents - ie. ASA
  
  • 80-100 mg/kg/day to target plasma concentrations 200-300 mg/L
  • after 2 wks reduce to 60-70 mg/day for 3-6 wks.
  • do not shorten analgesic and anti-pyretic
• treat heart failure with bed rest and corticosteroids
• diuretics, dig, captopril for more severe
• Chorea usually self limiting
  
  • treat haloperidol
  • steroids ? IVIG, plasmapheresis
• secondary prophylaxis with antibiotics long term, 5 yrs with mild carditis, 10 yr or lifelong with chronic carditis

Question 187

What are these?

Describe the course of this disease.

Answer 187

• Koplik’s spots—small white lesions on the buccal mucosa, might be visible during the prodrome
• incubation period 7-21 days
• rash usually starts 4 days after onset fever, lasts 3-5 days
• Fever, cough, coryza, and conjunctivitis
• Malnourished children: pigmented rash that desquamates during recovery. In uncomplicated measles, clinical recovery begins soon after appearance of the rash
• Complications in up to 40% of patients due to immune suppression. Risk of complication in very young and malnourished

Question 188

List complications of measles

Answer 188

Question 189

What is NOMA?

Answer 189

• Noma is a “gangrenous affection of the mouth, especially attacking children in whom the constitution is altered by bad hygiene and serious illness especially from eruptive fevers, beginning as an ulcer of the mucous membrane with edema of the face extending from within out, rapidly destroying the soft tissues and the bone and almost always quickly fatal”. The term noma originates from the greek word “nomein” which means to devour or to graze.
• terrible complication of measles in malnourished kids

Question 190

What kind of virus is the measles virus?

Answer 190

• Family:Paramyxoviridae
• Genus:Morbillivirus
• Species:Measles morbillivirus
• Measles virus (MeV) is a single-stranded, negative-sense, enveloped (non-segmented) RNA virus of the genus Morbillivirus within the family Paramyxoviridae.

Question 191

Louse-borne epidemic typhus

microbe

disease, cfr

treatment

vector & life cycle

Answer 191

• Rickettsia prowazeki
• Disease
  
  • headaches, prostration, chills, coughing and severe muscular pain

CFR 40% without treatment

• treatment with tetracycline and chloramphenicol antibiotics
• Transmission by the vector

Louse ingests Rickettsia ⇒ invade midgut epithelium and multiply ⇒ rupture into gut lumen ⇒ high numbers in gut faeces

infection occurs through the conjuctiva or by inhalation of louse faeces faeces may remain infective for >70 days

• Epidemiology

Mainly occurs in colder regions of Africa and S/C. America

Humans only reservoir (sylvatic cycle in Americas?)

Can occur in epidemics (Burundi 1997- 100,000 cases)

asymptomatic carriers- recrudescences (Brill-Zinsser disease) leading to epidemic

Question 192

Trench fever

microbe

disease

treatment

transmission/vector

Answer 192

• Bartonella quintana
• milder than typhus; ‘rare’, but in immunocompromised hosts

5-day relapsing fever, severe persistent pain in legs

• treatment with doxycycline, erythromycin, or azithromycin
• Transmission

bacteria remain in the gut lumen and do not kill the louse

infection via faeces

• Epidemiology

cosmopolitan distribution

associated with socially disadvantaged

Re-emerging disease? – found in homeless in France, US, Japan and Russia

Question 193

Epidemic relapsing fever

microbe

disease

epidemiology

Answer 193

• Borrelia recurrentis
• Disease

Restricted/ rare, though seen immuno-compromised hosts

Neurological involvement common – mild neck stiffness, headache

Severe disease with 2-5 % CFR even after antibiotic treatment

• Transmission

Louse ingests spirochaetes in host blood

All spirochaetes leave the louse’s gut into haemocoele and multiply greatly

The louse survives

Human infection occurs after the louse is killed - e.g. crushed by human, releasing

spirochaetes that infect via mucosa, cuts, etc (not in faeces, not by bloodfeeding)

• Epidemiology

formerly cosmopolitan

Today, restricted to Ethiopia with outbreaks traced back to here (e.g. South Sudan)

Question 194

How to respond to an outbreak of plague?

microbe?

vector?

methods?

Answer 194

• Yersinia pestis
• Xenopsyalla cheopsis (oriental rat flea) or Pulex irritans var hominis (human flea)
• Insecticidal control of fleas must precede or at least be coincident with rodent control
• Xenopsylla control
  
  • residual insecticide spraying of domestic rat runs and burrows
  • during outbreaks, treat all dwellings < 200m of affected one
  • a range of insecticides available, but resistance is common
  • for wild rodent fleas, insecticide in bait boxes (e.g. bamboo tubes)
  • Volatile insecticides inside freight containers on ships
• Rodent control
  
  • • domestic
  • – rodenticides (e.g. warfarin, many others) – rodent chemosterilization (long term)
  • • wild
  • Hydrogen cyanide (HCN) or methyl bromide gas

Question 195

• You are deployed to a displaced persons camp on the borders of Country A and Country B.
• Conditions are very crowded and access to sanitation facilities and clean water very limited. Many of the people presenting at the health facility are infested with lice.How would you determine whether these are body lice or head lice?Why does it matter and what are the disease risks?
• What could you do to reduce louse infestations?

Answer 195

• These two species are morphologically identical – only distinguish this based on where they are found (on head or in clothes)
• Only the body louse transmits disease. They transmit -Louse-borne epidemic typhus, Trench fever and Epidemic relapsing fever. All can be treated with antibiotics
• Frequently change/wash clothes. Insecticide powder

Question 196

Madagascar has the highest burden of plague. Since 2014, there have been least 273 cases of plague and 71 deaths. The majority of cases were of bubonic plague pneumonic plague has also been reported

• What measures would you use to control an outbreak of plague in rural Madagascar (or similar country)?
• What are the challenges to these approaches?

Answer 196

1. Quarantine cases of pneumonic plague
2. Diagnose and treat with antibiotics
3. Kill the fleas (this must be done before you tackle the rodents). Use insecticides (but pyrethroid resistance now common) and apply to rodent burrows and rat runs. During outbreaks, treat all dwellings < 200m of affected one
4. Use rodenticides

• Antibiotic resistance, insecticide resistance

Question 197

What antibiotics affect the following targets in a bacterium?

• Cell Wall
• DNA/RNA synthesis
• folate synthesis
• cell membrane
• protein synthesis

Answer 197

• Cell Wall
  
  • Beta lactam
  • vancomycin
• DNA/RNA synthesis
  
  • fluroquinolones
  • rifamycins
• folate synthesis
  
  • trimethoprim
  • sulfonamides
• cell membrane
  
  • Daptomycin
• protein synthesis
  
  • linezolid
  • tetracyclines
  • macrolides
  • aminoglycosides

Question 198

Antimicrobial Resistance

How many deaths per year now?

Predictions for 2050

Answer 198

• currently about 700,000 (low estimate)
• predicted 10 million, would dwarf most other causes (cancer currently 8.3 million)

Question 199

How does resistance develop?

(processes)

Answer 199

• accumulation of inherently-resistant bacteria
• mutant selection, sometimes during therapy
• spread of resistance genes among bacteria
• spread of resistant strains amoung humans
• Darwinian evolution
  
  • the level of antibiotics in an environment selects for those organisms resistant to the antibiotic

Question 200

What are 3 mechanisms for transfer of resistant genes between bacteria (Horizontal Gene Transfer)?

Answer 200

1. transformation: transfer of DNA from a dead bacterium to recipient
2. conjugation: transfer of a plasmid or conjugative transposon from a donor bacterium to recipient
3. transduction: transfer of a gene from a bacterium infected with a virus via delivery system

Question 201

What are the commonest causes of bacterial bloodstream infections in Africa?

What is the commonest cause of septicemia in high HIV prevalence areas of Africa.

Answer 201

• Commonest
  
  • TB
  • Strep pneumonia
  • Non-typhoidal salmonella
  • Then
    
    • ​E. coli
    • Klebsiella sp
    • Other Enterobacteriaceae
    • S. aureus
    • other strep/enterococcus
    • Fungus
• In High HIV prevalence areas?
  
  • non-typhoid salmonella, e.g. Salmonella typhimurium

Question 202

Which pathogens might also cause non-malaria febrile illnesses that are not detectable by blood culture?

Answer 202

• •TB
• •Brucellosis
• •Leptospirosis
• •Rickettsia
• •Viruses
• •Vhf
• •Influenza
• •Arbovirus
• •Fungi
• •Histoplasma
• •Penicillium marneffei

Question 203

• What are the implications of inadequate diagnostics and surveillance systems for non-malarial causes of febrile illness?

Answer 203

• lack of surveillance or of accurate diagnostic tools means we don’t know what the non-malaria causes of febrile illness are
• nor drug susceptibility patterns
• necessitates increasing use of broad spectrum antibiotics, which drives continuing resistance …

Question 204

Consider the WHO algorithm for pts with HIV suspected of having TB in light of available knowledge about epidemiology of MBBSI in HIV pts in Africa.

Answer 204

• in high burding settings, MTBBSI is leading cause of death in hospitalized PLWHIV
• presentation v different to ‘classic’ TB
• Dx difficult but earlier treatment important to reduce mortality
• Urine Based rapid diagnostics huge breakthrough
• Use clinical judgement about empirical therapy and factor risk of dying into that decision
• prognosis is poor, but possibly slightly better with good supportive care and empirical treatment

Question 205

What is the most common OI globally in HIV patients and the leading cause of death in HIV-infected patients?

Answer 205

• TB
• the major killer of adult inpatients in South Africa
• “disseminated” in 90% of post mortem cases
• in public hospital in Cape Town, microbiologically-confirmed TB found in 1/3 of all HIV-positive acute adult medical admissions

Question 206

What are the clinical features of HIV/TB coinfection?

How sensitive is constellation of Cough, Fever, Sweats or Weight (CFSW) for people living with HIV?

Answer 206

• Altered clinical presentations of TB
  
  • increase in smear neg pulmonary disease
  • increase in extra-pulmonary/disseminated forms
  • sputum smear microscopy less sensitive during HIV infection
  • typical and atypical CXR features depending on severity of immunosuppression
• Sensitivity about 79% and specificity 50%
• Sensitivity depends on prevalence of TB varying from 98% with 5% prev to 90% with 20% prevalence

Question 207

• What signs & Sx might be seen in HIV associated TB ir MTBBSI?
• Blood results in MTBBSI?

Answer 207

• Signs & Sx
  
  • Cough, Fever, Sweats, Weight Loss
  • Wasting
  • inability to walk unaided
  • Pallor
  • doughy, tender abdomen
  • lymphadenopathy
  • fever, but rigors less common
  • raised RR (but remember PCP)
• Blood results
  
  • Low CD4
  • anemia - good predictor: Hepcidin sequesters Fe extracellularly, hepatocytes, RBC Fe to macrophages, decreased GI absorption
  • low platelets
  • hyponatremia
  • low albumin
  • lactic acidosis
  • low monocyte count
  • most patters of LFT derangement
  • Renal dysfx

Question 208

What radiological findings aremore common in HIV-Associated TB?

Answer 208

• CXR: miliary pattern, mediastinal nodes
• US spleen: microabscesses
• US abdomen: lymphadenopathy
• (Cavitation on CXR not typical finding)

Question 209

What diagnostics are helpful to make dx of TB in HIV?

Why not do Xpert or LAM on blood?

Answer 209

• Blood cultures NOT helpful: too slow, expensive, often not available
• Urinary LAM or Gene Expert better than sputum
• Gene Xpert on concentrated Urine or sputum
• Blood LAM or Gene Xpert has low yield, is not sensitive

Question 210

Treatment of Myco TB Blood Stream Infection in HIV?

Answer 210

• same as for TB

Question 211

What bacteria are responsible for the plague?

Describe the bacterium

Answer 211

• Yersinia pestis: cause of plague
• Y. pseudotruberculosis/Y. enterocolitica
  
  • enteropathogenic strains
• Gm -ve (1-3µm) bipolar staining bacillus belonging to Enterobaceriaceaa

Question 212

Yersinia pestis

• describe the transmission
• reservoirs, vectors

Answer 212

• zoonotic infection “rodent disease affecting humans”
• transmitted by flea bites on skin (Xenopsylla cheopsis) or ingestion of infected animal materia (guinea pigs in Peru, camels in Asia)
• most important reservoirs Rattus rattus (black), R. norvegicus
• other urban and sylvatic rodents
  
  • marmots, chipmunks, squirrels
• rodents tolerate plague, develop long term bacteremia allowing fleas to transmit
• Man is accidental host in cycle
• only pneumonic plague is transmitted man to man

Question 213

Describe the life cycle and pathogenesis of plague

Answer 213

• flea ingest blood from bacteremic reservoir, blood ‘clots’ in foregut, blocking flea’s swallowing
• regurgitates organisms into skin and blood stream while feeding again
• bacteri migrat by cutaneous lymphatics to regional lymph nodes
• bacilli phagocytosed, resist destruction and divide. Lysis of neutrophils release bacteria
• Lymph nodes necrotic with large # bacilli and neutrophils

Question 214

Plague, clinical course.

Incubation?

Name 4 different presentations

Answer 214

• incubation 2-7 days
• malaise
• high fever
• pain or tenderness over lymph nodes, enlarge to be called buboes
• bacteremia initially intermittent then constant
• DIC
• shock, convulsions
• “black death” diffuse, hemorrhagic changes in skin and cyanose from necrotizing pneumonia give rise to dark skin at extremities
• Presentations:
  
  1. bubonic plague
  2. septicemic plague
  3. pneumonic
  4. meningitis

Question 215

Bubonic Plague

Describe presentation

What is a bubo?

Mortality?

Answer 215

• most common presentation (80-95%)
• fever and painful nodes
• invubation 2-8 days after bite
• bacteria divide in regional lymph nodes
• sudden onset fever, chills, weakness, headache at same time or just after developing bubo
• Bubo
  
  • intense pain over lymph nodes, usually groin, axillae, neck
  • warm, edema, smooth or irregular non-fluctuant masses
  • tender
• death btw 2-4 days
• skin lesions unusual <25% can be pustules, vesicles, papules, eschar
• purpua may become necrotic leading to distal gangrene
• 5% hematogenous spread to lungs - pneumonic plague
• Mortality 50-90% if untreated

Question 217

Septicemic plague

describe course

mortality

Answer 217

• 20-25% of cases
• no bubo, massive growth of bacilli
• without tx 100% mortality
• with tx 15-20% mortality
• death rapid

Question 218

Pneumonic plague

course, morrtality

Answer 218

• spread by aerosol inhalation
• 5% hematogenous
• high mortality, very contagious
• only human-human form
• incubation 1-2 days, death can be within 24 hrs
• fever, lymphadenopathy, cough, chest pain, hemoptysis
• 100% mortality without tx, 50% with

Question 219

Plague meningitis

Answer 219

• more uncommon, usually week or so after inadequately treated bubonic plague
• usually associated with axillary nodes
• v. unusual to present without previous lymphadenitis
• clinical: fever, headach, meningism
• csf: pleocytosis, pmn’s, bacteria gm stain

Question 220

Diagnosis plague

Clinical

Microbiological

Answer 220

• consider in endemic area, e.g. Madagascar, Western US
• neutrophilia, leukemoid rxn, esp kids
• DIC, hepatorenal failure
• microbiological:
  
  • aspirate bubo and gem stain for cocco bacilli - Safety pine apppearance
  • Wayson’s stain - fuschin + methylene blue
  • innoculate on MacConkey agar
  • serologica testing

Question 221

What is this?

describe?

Answer 221

• plague bacteria
• gm -ve coccobaccilli
• safety pin appearance

Question 222

Treatment Plague

What works?

What doesn’t?

Answer 222

• supportive
  
  • iv fluids, oxygen, I & d bubo prn
  • Antibiotics: 50% mortality without, 5% with

1. Streptomycin
2. Gent + tetracycline as effective
3. doxycycline x 7 days
4. if meningitis add chloramphenicol
5. cipro/tetracycline/co-trimoxazole

• Penicillin completely ineffective

Question 223

Plague: Vaccination and Prophylaxis

Is there a vaccine?

Answer 223

• yes but not licenced, unpleasant reactions
• prophylaxis with cotrimoxazole, tetracycline recommended by WHO x 7 days for exposure
• CDC added cipro for biological threat

Question 224

Typhoid: what are the bugs?

Answer 224

1. S. typhoi - typhoid fever
2. S. paratyphi - paratyphoid fever
3. Non-typhoidal salmonella
   
   • S. typhiumriu
   • S. enteridis

• 1 & 2 are host specific, invasive orgs with rel high mortality
• 3 are generalists and cause enteric/diarrheal disease with rel low mortality

Question 225

Typhoid: Clinical Features

incubation

course: 4 stages of disease progression

Answer 225

• incubation 7-14 days
• wk 1:
  
  • slowly rising step-wise fever
  • headache, abd pain, vomiting, cough, malaise
• wk 2
  
  • high grade fever ~40⁰ C
  • obvious abd sx
  • diarrhea or constipation
  • hepatomegaly, splenomegaly
  • Rose spots (30%)
• wk 3
  
  • complications 10-15%: intestinal bleeding & perf, pneumonia etc
• wk 4
  
  • advanced illness: apathetic expression (“typhoid facies”), agitated delirium

Question 226

Typhoid dx:

• waht tests available
• what do routine tests show

Answer 226

• blood culture, culture rose spots
• blood culture may be neg due to low numbers of orgs
• RDT
• Widal test: agglutinating ab against O lipopolysaccharide ag, H flagellar ag, Vi capsular ag
• WBC normal, plts normal
• liver fx mildly elevated

Question 227

Typhoid: Differential diagnosis

Answer 227

• Fever without focus
  
  • malaria
  • rickettsia
  • dengue
  • leptospirosis
  • brusellosis
  • trypanosomiasis
• Fever with focus
  
  • rti
  • tb
  • cns infection
  • deep abscess/amebic liver abscess
  • infectious hepatitis
• Non-infective
  
  • lymphoproliferative/CT diseases

Question 228

Typhoid: management

Plan of care: general

antibiotic choice

probs with resistance

anything else for comlications

Answer 228

• 70-90% as OP
  
  • general supportive
  • oral rehydration
  • antibiotics
• inpatient care
  
  • oral or iv rehydration
  • abx
  • +/- icu
  • +/- pressure area care
  • +/- surgery
  • +/- blood transfusion
  • +/- steroids
• Antibiotics
  
  • Fluroquinolones very effective in susceptible infections, probs with resistance
  • ceftriaxone, cefixime slow response to treatment but little resistance
  • azithromycin excellent intracellular penetration, resistance rates unclear
  • nb emergence of ESBL resistance in Pakistan, India etc
• nb steroids improve survival in severe and complicated disease

Question 230

Typhoid complications

Answer 230

• gi bleed
• perforation
• encephalopathy, shock
• hepatititis
• cholecystitis
• myocarditis
• psychiatric
• bone and joint
• meningitis
• pneumonia
• anemia
• DIC
• Relapse: chronic carriage (>1yr)
• ca gallbladder

Question 231

Typhoid: treatment of chronic carriers

How

Answer 231

• prolonged course of Abx
• guided by sensitivity
• if gallstones, consider cholecystectomy

Question 232

Sepsis:

• What is it?
• Global burden?
  
  • cases
  • deaths
    *

Answer 232

• Life threatening organ dysfunction due to a dysregulated host response to infection
  
  • final common pathway for mortality due to many infectious diseases
• 31.5 million sepsis cases/yr
• 5.3 million deaths

Question 233

Spirochetes

What are the spirochetal illnesses

Answer 233

• syphilis
• non-venereal treponematoses
• leptospirosis
• Lyme: Borrellia burgdorffi
• Rat Bite Fever, Asian Form Sodoku: Spirillum minus (North American form is Streptobacillus moniliformis)
• Relapsing Fevers: Borrelia recurrans, B. duttoni and others

Question 234

Microbiology: Spirochetes

Microscopic appearance?

Diagnostic tools.

Answer 234

• Leptospira interrogans
• Slender spiral anaerobic rods
• can be seen microscopically
• unclear virulence factors
• Serology most useful method of diagnosis
  
  • ​MAT (micro agglut test)
  • x reacts with spirochetes and legionella
  • Elisa IGM, PCR may be an option
• Culture specimens but slow
  
  • blood, csf, urine

Question 235

Leptospirosis: Ecology

Answer 235

• The most common and widespread zoonosis in the world
• Leptospira interrogans has 250 serovars
• natural host mammals of all kinds, widespread in rats
• animals can develop clinical disease, 10% mortality in dogs
• animas shed organism in urine for weeks/months after infection
• can stay viable for months

Question 236

Leptospirosis: Risk Factors

What are they?

Answer 236

• exposure to water or infected animals
• occupational: 30-50%: farmers, abbatoir workers, vets, sewer workers, rice farmers, military personnel
• recreational: fresh water exposure, swimmers, canoists, fishing
• Household exposure: dogs, domest. livestock, rodent exposure
• Epidemic after floods eg phillipines

Question 237

Leptospirosis: pathophysiology

Answer 237

• after entry multiplies in blood and tissues, affects any organ esp liver and kidneys
• Kidneys: intertitium, tubulo-interstitial nephritis
• Liver: centrilobular necrosis. Proliferation in Kupffer cells, jaundice and hepatocellular dysfx
• skeletal muscle: necrosis with severe disseminated vasculitis
• Eye: recurren uveitis

Question 238

Leptospirosis: Clinical

Answer 238

• 15-40% assymptomatic, maybe more, poss flu-like illness, incubation 7-12 days (2-20)
• 90% mild anicteric, usually self limiting
• Biphasic:
  
  • leptospiremic and leptospiuric
  • brief period of 1-3 days between 2, some improvement, temp settles, pt improves
  • then fever recurs, antibodies detected and org isolated from urine
  • Meninges, liver, eyes, kidney
• Anicteric vs Icteric
  
  • Anicteric: aseptic meningitis in 50%, cranial nerve palsies, encephalitis, mild delirium
  • meningitis usually 1-2 days, may last 1-2 wk
  • abd pain with diarrhea or constipation, hepatosplenomegaly, n,v, anorexia
  • Uvietis 2-10%
  • subconjunctival hemorrhage most common ocular complication
  • renal, pulmonary sx, adenopathy, rashes, muscular pain
  • Death extremely rare in anicteric
• Icteric: Weil syndrome
  
  • jaundice, renal dysfx, hepatic necrois, pulomnary dysfx and hemorrhagic diathesis (<5%)
  • Jaundice may persist for weekes, may lead to renal failure, hemorrhagic diathesis, multi organ failure, ARDS, hemolysis, hemoptyisis
  • also splenomegaly, myocarditis, chf, myocarditis and pericarditis
  • Mortality rate 5-10 % worse with age up to 50%

Question 239

Leptospirosis: Diff dx

Answer 239

• dengue, lassa, hantavirus and other VHF
• viral hepatitis
• malaria
• meningitis
• EBV, CMV
• HIV
• rickettsial disease
• typhoid fever

Question 240

Leptospira treatment

Mild

Severe

Answer 240

• mild doxy, amoxil
• severe: parenteral penicillin, cephalosporins or erythromycin
• doxy prohylaxis weekly for short term exposure
• steroids? -inclonclusive
• Jarisch-Herxheimer rxn may develop

Question 241

Leptospira: Prevention

Answer 241

• good sanitation, prevent livestock urine from entering water
• control leptospira in pets and lifestock
• disinfect contaminated work areas
• worker education
• pretective equipment
• case finding in suspected outbreaks
• identify infected areas and avoid exposure where possible
• following floods in areas where known exposure consider administering weekly doxycycline: prophylactic abx

Question 242

What is Lyme disease?

Answer 242

• multisystem inflammatory disease caused by sprirochetes Borrelia burgdorfi (NA, Europe, Asia)
• caused by 4 other species in Europe and Asia
  
  • B. lonestari - NA
  • B. afzelli, B. garinii, B. valaisaiani

Question 243

Clinical Presentation Lyme

What are the 4 phases?

Answer 243

1. early localized
2. early disseminated
3. late chronic
4. post-Lyme

Question 244

Lyme Disease: describe 4 phases

Answer 244

1. Early localized
   
   • Erythema migrans (EM)
   • 90%, usually within 1 month of bite, only 3O% recall bite
   • Constitutional: viral syndrome, local.general lymphadenopathy, arthralgia, myalgia, headache, neck stiffness, lethargy fever, malaise
2. Early disseminated disease
   
   • days to months after infection
   • Carditis: 8% of untreated Lyme
   • any degree of heart block and any form of myopericarditis
   • majority resolves before tx
3. Neurologic manifestations
   
   • approx 10%
   • lymphocytic meningitis (resolves spontaneously)
   • cranial nerve palsies, esp VII, can be bilateral
   • radiculoneuritis
   • Cutaneous manifestation: Borrelial lymphocytoma, usually resolves with treatment
4. Post Lyme Syndromes (chronic Lyme)
   
   • fibromyalgia common
   • headache
   • CFS

Question 245

Lyme diagnosis and tx

Answer 245

• serology to confirm dx, not a screen
• tx: early localized:
  
  • amoxil, doxy, cefuroxime
• late disease doxy

Question 246

What is Lassa Fever?

Where?

Ecology?

Disease?

Answer 246

• arenavirus, ss RNA
• zoonotic, multimammate rate excretes virus in urine for extended period
• transmission: ingestion/direct contact/?inhalation of aerosol
• 100-300,00 infections each year
• high inpatient mortality and nosocomial transmission with h to h spread
• seasonal in Sierra Leone and Nigeria
• highest incidence in dry season (nov-apr)

Question 247

Lassa Case Definitions

Answer 247

• suspected case:
  
  • illness with gradual onset of malaise, fever, headache, sore throat, cough, nausea, vomiting, diarrhea, myalgia, chest pain, hearing loss
  • hx of contact with rodent excreta or a case of Lassa fever
• confirmed case:
  
  • suspected case that is lab confirmed
  • +ve IgM ab, PCR or virus isolation, or epidemiologically linked to confirmed case

Question 248

Lassa Clinical Stages

How many?

Incubation period?

What are the sx for each and when?

Chronic complications?

Answer 248

• incubation 6-21 days
• Stage 1 (d1-3)
  
  • gen weakness and malaise
  • high fever, >39 constant with peaks of 40-41
• Stage 2 (d4-7)
  
  • sore throat (white exud patches) v common
  • headache, back, chest, side or abd pain
  • conjunctivitis
  • n&v, d
  • prod cough
  • proteinuria
  • low bp (sytolic <100 mmHg)
  • anemia
• Stage 3 (d7+)
  
  • edema face and neck
  • convulsions
  • mucosal bleeding (mouth, eyes, nose)
  • internal bleeding
  • encephalopathy with confusion or disorientation
• Stage 4 (d14+)
  
  • coma
  • death
• Complications
  
  • sn hearing loss in 30%, no relation to severity
  • during convalescence transient alopecia and ataxia
  • more severe in pregnancy (80% fetal loss in 3rd trimester)

Question 249

Lassa Dx

Early Lab features

markers of poor px

Tx

Answer 249

• ​early lab: lymphopenia, thrombocytopenia
• fatal lassa associated with Age, acute kidney injury, AST>150 and high VL
• Def dx
  
  1. rev transcriptase pcr assay
  2. ab ELISA
  3. ag det tests
  4. virus isolation by cell culture
• tx Ribavirin + support, antipyretic
• early dx critical as tx >7 d asstd higher mortality
• nb recent jan-mar outbreak in Nigeria