MBBS Lectures

6. 5-d F, 1055-d F, 105oo
F, bed-F, bed-
ridden; reddishridden; reddish
spotsspots

8. Had remittent FHad remittent F
Now abdominalNow abdominal
distensiondistension

9. SCD withSCD with
remittent Fremittent F

11. Dx.?

12. SALMONELLASALMONELLA
((E.Fs.E.Fs. && SALMONELLOSIS)SALMONELLOSIS)
dr mohammad nurul huqdr mohammad nurul huq

13. At the end of session you will learnAt the end of session you will learn
 Enteric FeversEnteric Fevers are food-borneare food-borne seriousserious d.d.
 TyphoidTyphoid iis a multi-system septicemic illnesss a multi-system septicemic illness
 TyphoidTyphoid occurs inoccurs in human onlyhuman only
– 21 million cases21 million cases withwith 200k deaths/y200k deaths/y worldwideworldwide
 Less severe:Less severe: paratyphoidparatyphoid A, B, CA, B, C
 Non-typhoidal salmonellosisNon-typhoidal salmonellosis is usually self-limiting:is usually self-limiting:
– mainly as food poisoning outbreaksmainly as food poisoning outbreaks
 Most imp. complicationsMost imp. complications of EF:of EF: bleeding, perforationbleeding, perforation
 Vax. available against typhoid onlyVax. available against typhoid only
EF: Enteric Fevers. Vax.: vaccineEF: Enteric Fevers. Vax.: vaccine

14.  BBelongs toelongs to EnterobacteriaciaeEnterobacteriaciae;; highly adaptive.highly adaptive. 3 Ag:3 Ag:
– flagellar (H)flagellar (H)
– capsular (Vi);capsular (Vi); largely restricted to S. typhilargely restricted to S. typhi
– somatic (O)somatic (O)
 TyphoidalTyphoidal salmonellas:salmonellas: S. typhi,S. typhi, S. paratyphi A, B, CS. paratyphi A, B, C
 Non-typhoidalNon-typhoidal ....: mainly GE (salmonellosis): mainly GE (salmonellosis)
– May be invasiveMay be invasive
Salmonella:Salmonella:

15. EPIDEMIOLOGYEPIDEMIOLOGY
 Only manOnly man is the reservoir ofis the reservoir of
S. typhiS. typhi
– Most common in L&MICsMost common in L&MICs
 Reservoirs for non-typhoidal salmonellas:Reservoirs for non-typhoidal salmonellas:
– MainlyMainly:: poultry, livestock, reptiles, petspoultry, livestock, reptiles, pets
– fruits, vege., bakery, frogs, newts, salamandersfruits, vege., bakery, frogs, newts, salamanders
Major outbreaks:Major outbreaks: poultry, eggs, beef, dairypoultry, eggs, beef, dairy

17. Livestock

18. Reptiles

19. Reptiles

20. PETS
Mind salmonella!

21. Fruits
Vegetables

22. Fruits
Vegetables

23. Fruits
Vegetables

24. Fruits
Vegetables

25. Fruits
Vegetables

26. Fruits
Vegetables

27. Fruits
Vegetables

28. Fruits
Vegetables

29. Lizards

30. Lizards

31. Salamander

32. Newt

35. German cockroach:German cockroach:
salmonella, food p., D,salmonella, food p., D, Staph.Staph.
Musca domesticaMusca domestica
EF, cholera, dysentery /DEF, cholera, dysentery /D

36. ETIOLOGY:ETIOLOGY: 2500 serotypes of Salmonella2500 serotypes of Salmonella
 SS Typhi in group DTyphi in group D.. Freezing does not killFreezing does not kill
SalmonellosisSalmonellosis
 Usually non-invasive self-limitingUsually non-invasive self-limiting gut infx.gut infx. But can causeBut can cause
serious invasive d. inserious invasive d. in
 infants (<3mo), immunosuppressed, elderly,infants (<3mo), immunosuppressed, elderly, SCDSCD
 Carriage:Carriage:
– acute (3mo) : 45% in U-5 & 5% in older childrenacute (3mo) : 45% in U-5 & 5% in older children
– chronic: (1y) : 1%.chronic: (1y) : 1%. Unusual in childrenUnusual in children
ABT prolongs excretionABT prolongs excretion

37. SalmonellaSalmonella GastroenteritisGastroenteritis
– IP: 6-72hIP: 6-72h
– AP, NVD (watery/bloody stools)AP, NVD (watery/bloody stools)
– LGF in 50%LGF in 50%
– Dehydration, tender abdomen (DDDehydration, tender abdomen (DD appendicitisappendicitis))
– Resolves in 2-7dResolves in 2-7d

38. EF : PathogenesisEF : Pathogenesis
 Transmission:Transmission: contaminated food/drink,contaminated food/drink, close contact,close contact,
poor personal hygiene, transfusionpoor personal hygiene, transfusion
 InoculumInoculum:: 1k-1million. Lower in1k-1million. Lower in
– achlorhydria, gastrectomyachlorhydria, gastrectomy
– H2-blocker, PPI, antacidsH2-blocker, PPI, antacids
 Invades R.E.S: lInvades R.E.S: liver, spleen, BM. GB, lungs, brain,iver, spleen, BM. GB, lungs, brain,
kidneyskidneys.. In small gut:In small gut: multiplies in phagocytes.multiplies in phagocytes. InvadeInvade
mucosa, lymphoids, then spread to blood.mucosa, lymphoids, then spread to blood. 1y1y & 2y& 2y
bacteremiabacteremia
 Severity:Severity: dose, virulence, host defensedose, virulence, host defense

39.  IP in typhoid: 7-14 d;IP in typhoid: 7-14 d; shorter in paratyphoidshorter in paratyphoid
 Endotoxin:Endotoxin: inflam., necrosis ofinflam., necrosis of Peyer patchesPeyer patches:: ulcerationulceration
 Vi strains more virulentVi strains more virulent
 SSSS appear during bacteremia. Brunt of illness is on smallappear during bacteremia. Brunt of illness is on small
gut. Bacteria are excreted in bilegut. Bacteria are excreted in bile
 Humoral & CMI response is incompleteHumoral & CMI response is incomplete
 Multi-organ failure can occurMulti-organ failure can occur
Pathogenesis ..Pathogenesis ..

40. CFCF:: Classical typhoid: 4wClassical typhoid: 4w
Week 1Week 1
 LGF,LGF, step-ladderstep-ladder to HGF; relative bradycardiato HGF; relative bradycardia
 Initially ambulant; later on bed riddenInitially ambulant; later on bed ridden
 InitialInitial constipationconstipation ⇒⇒ pea-soup stoolspea-soup stools in 4din 4d
 Malaise, HA, AN, cough (end 1Malaise, HA, AN, cough (end 1stst
w). Vomiting uncommonw). Vomiting uncommon
Rose spots 5-7dsRose spots 5-7ds
 Leukopenia, eosinopenia, lymphocytosisLeukopenia, eosinopenia, lymphocytosis
 Blood CS is positiveBlood CS is positive
HA: headache. AN: anorexia nausea. CS: culture sensitivityHA: headache. AN: anorexia nausea. CS: culture sensitivity

42. Soft palate petechiae: Ac. Fol. Tonsillitis, Septicemias, DF, ITP,
Leukemias, Inf. mononucleosis

44. Week 2Week 2
 Very ill!Very ill! Prostration,Prostration, HGF in plateauHGF in plateau, relative bradycardia,, relative bradycardia,
delirium, AP & tendernessdelirium, AP & tenderness
 Cough, rhonchi, abdo. distension,Cough, rhonchi, abdo. distension, tender RLQ, borborygmitender RLQ, borborygmi
 Diarrhea: 6-8/dDiarrhea: 6-8/d
 HSM, raised transaminasesHSM, raised transaminases
 Blood CS may still be positiveBlood CS may still be positive
 Other CS: stool, urine,Other CS: stool, urine, BM (most sensitive)BM (most sensitive)
 Widal is positiveWidal is positive (nonspecific)(nonspecific)

45. Week 3 & 4Week 3 & 4
 F gradually falls by lysis/crisisF gradually falls by lysis/crisis
 ComplicationsComplications startstart
 Hge.Hge. && perforationperforation in distal ileumin distal ileum
 Encephalitis, metastatic abscesses, cholecystitis, osteitis,Encephalitis, metastatic abscesses, cholecystitis, osteitis,
& endocarditis occur& endocarditis occur

46. Presenting symptoms Number (%)
Fever 50 100.0
Poor appetite 42 84.0
Cough 23 46.0
Diarrhea 21 42.0
Headache 20 40.0
Vomiting 19 38.0
Abdominal pain 16 32.0
Constipation 06 12.0
Convulsion 01 2.0
Presenting SS: in 50 children with culture proven typhoid in BMCH

47. Physical signs Number (%)
Tachycardia 39 78.0
Coated tongue 36 72.0
Toxic look 25 50.0
Cecal gurgling 24 48.0
Pallor 21 42.0
Hepatomegaly 18 36.0
Splenomegaly 16 32.0
HSM 10 20.0
Abdominal
distension
02 4.0
Relative
bradycardia
2 4.0
Most frequent signs in 50 children with culture proven typhoid in BMCH

48.  CSCS:: blood, stool, urine, rose spotsblood, stool, urine, rose spots
Bone MarrowBone Marrow if others negativeif others negative
 Widal:Widal: non-specific; false-positive/-negativenon-specific; false-positive/-negative
 CBC:CBC: leucocytosis in salmonella GEleucocytosis in salmonella GE
EF:EF: anemia, eosinopenic leukopenia, low Plateletsanemia, eosinopenic leukopenia, low Platelets
Leucocytosis may occur in childrenLeucocytosis may occur in children
 Mild hepatitisMild hepatitis
Imaging:Imaging: CXR if pneumonia, bronchitisCXR if pneumonia, bronchitis
 AXR if perforationAXR if perforation
 Bone scan MRI if OsteomyelitisBone scan MRI if Osteomyelitis
INVESTIGATIONSINVESTIGATIONS

49. DD: EFDD: EF
 Shigellosis/invasive diarrheaShigellosis/invasive diarrhea
 Viral feverViral fever
 TyphusTyphus
 Ac. PyelonephritisAc. Pyelonephritis
 SepticaemiaSepticaemia
 Food PoisoningFood Poisoning
 DFDF

50. TREATMENT: EFTREATMENT: EF
 Specific RxSpecific Rx : ABT: ABT
 Supportive RxSupportive Rx : FEB, nutrition: FEB, nutrition
 Symptomatic RxSymptomatic Rx
 Rx ofRx of complications; carriage; relapsecomplications; carriage; relapse
ABT:ABT: based on CS. ~14d.based on CS. ~14d. CeftriaxoneCeftriaxone 8-10d. Drug8-10d. Drug
resistance is frequent. Ceftriaxone, cefotaxime, orresistance is frequent. Ceftriaxone, cefotaxime, or
fluoroquinolonesfluoroquinolones (not <18y)(not <18y) are effectiveare effective
 Antipyretics may precipitate hypothermia & shockAntipyretics may precipitate hypothermia & shock
 Relapse must be re-treatedRelapse must be re-treated
Defervescence may take 3-11daysDefervescence may take 3-11days

51. Carriage: High dose ampicillin/amoxicillin + probenecid
x4-6w has cured many
Cipro. is the DoC for clearing adult carriageCipro. is the DoC for clearing adult carriage
Cholecystectomy may be needed for gallstonesCholecystectomy may be needed for gallstones
CorticosteroidsCorticosteroids
 Benefits in protracted SS, delirium, stupor, coma, shockBenefits in protracted SS, delirium, stupor, coma, shock
 Should be reserved for critically illShould be reserved for critically ill
 Dexamethasone IV x 2-3dDexamethasone IV x 2-3d
RelapseRelapse 15%15%
 2-3w later; usually milder2-3w later; usually milder

52. SalmonellaSalmonella GE: RxGE: Rx
 UsuallyUsually no ABTno ABT (prolongs carriage!).(prolongs carriage!). Consider itConsider it
– age: <3mo; <12mo with F >39°Cage: <3mo; <12mo with F >39°C
– SCD, immunosuppressed, chr. GI illnessesSCD, immunosuppressed, chr. GI illnesses
– Bacteremia,Bacteremia, OM,OM, meningitismeningitis,, abscessabscess
– HIV: x4-6wHIV: x4-6w
 FEBFEB
 Invasive GE:Invasive GE: cotrim, amoxicillin, cefixime x 5dcotrim, amoxicillin, cefixime x 5d

53. Prognosis
Nontyphoidal
– excellent except young infants & elderly
– poor for meningitis or endocarditis
EF
– mortality 1%. Relapse 15%
– Early ABT is very important

54. Bad prognostic signsBad prognostic signs
 HGF falls by crisis, collapse; perforation, bleedingHGF falls by crisis, collapse; perforation, bleeding
 CNS features, presence of gall stonesCNS features, presence of gall stones
 Osteitis/OM (think of SCD)Osteitis/OM (think of SCD)
Complications: non-typhoidal
 Bacteremia, meningitis, pneumonia
 Endo-/pericarditis
 Osteomyelitis (most in SCD)
 Hepatic/splenic abscess

55. Complications: Typhoidal:Complications: Typhoidal: 33rdrd
-4-4thth
ww
 GITGIT
– Perforation (3%)Perforation (3%)
– Severe hge,Severe hge, (10%)(10%)
– Peritonitis, pancreatitisPeritonitis, pancreatitis
 CNSCNS
– meningitis, encephalitismeningitis, encephalitis
– encephalopathy (10%)encephalopathy (10%)
– Transverse myelitisTransverse myelitis
 Blood: DIC,
dyselectrolytemias
 Eye: Uveitis
 RT: Pn., Br.
 CVS: Myocarditis
 HBS: Hepatitis,
Cholecystitis
 Bones: OM, arthritis
 UT: Nephritis
These may occur even during treatmentThese may occur even during treatment

56. Perforation: worsening AP, distending silent board
like abdomen, rising pulse, falling BP, collapse
Encephalopathy: delirious, or obtunded
In pregnancy: may cause miscarriage
Vertical transmission may occur

57. OM of humerus in a 14-y boy with SCD

58. CT: a large brainCT: a large brain
abscess fromabscess from
SalmonellaSalmonella
meningitis in ameningitis in a
neonateneonate

59. Salmonella pn. in a 3-y

60. SCD with Salmonella sepsis: dactylitis with septicemia

61. TraitTrait TyphoidalTyphoidal No-typhoidalNo-typhoidal commentcomment
EtiologyEtiology S typhiS typhi
S paratyphiS paratyphi
ManyMany Non-Non-
typhoidtyphoid
moremore
commoncommon
FeverFever AlwaysAlways 50%50%
SeveritySeverity MoreMore Mild-moderateMild-moderate
ReservoirReservoir HumanHuman AnimalsAnimals
IllnessIllness EFsEFs FoodFood
poisoning,poisoning,
bacteremiasbacteremias
DD SalmonellaDD Salmonella

62. HygieneHygiene
– safe foods & drinkssafe foods & drinks
– safe food handlingsafe food handling
– hand hygiene, safe sewage disposalhand hygiene, safe sewage disposal
– no sale of reptiles for petsno sale of reptiles for pets
– foods cooked thoroughlyfoods cooked thoroughly
 Vaccine:Vaccine:
PreventionPrevention

63. TYPHOID VACCINE:TYPHOID VACCINE: PreventsPrevents onlyonly S TyphiS Typhi
 Recommended forRecommended for endemic areasendemic areas
– Children, intimate exposure to a carrierChildren, intimate exposure to a carrier
– SCD, Lab. workers, physiciansSCD, Lab. workers, physicians
 Oral:Oral: livelive (Vivotif). Age >6 y. 1 EC capsule every 2d x 4/5y(Vivotif). Age >6 y. 1 EC capsule every 2d x 4/5y
 IM:IM: Vi capsular polysaccharide (Typhim Vi, Typherix, Vaxfoid). AgeVi capsular polysaccharide (Typhim Vi, Typherix, Vaxfoid). Age
≥≥2y /2y. Efficacy: 50-80%2y /2y. Efficacy: 50-80%
Can be overcome by a large inoculumCan be overcome by a large inoculum
SE:SE: Oral vax.: Abdo. discomfort, NV, F, HA, rashOral vax.: Abdo. discomfort, NV, F, HA, rash
Injectable: Mild F, HA, local erythemaInjectable: Mild F, HA, local erythema
EC: enterocoatedEC: enterocoated

64. Peculiarities of salmonellaPeculiarities of salmonella
 Highly adaptive. Survives in high alkaline mediumHighly adaptive. Survives in high alkaline medium
 Not destroyed byNot destroyed by freezingfreezing
 Human only reservoir ofHuman only reservoir of S. typhiS. typhi
 Carriage:Carriage: non-typhoidal more in small childrennon-typhoidal more in small children
ABT prolongs carriageABT prolongs carriage
typhoidal more in adultstyphoidal more in adults
 Specially serious in SCDSpecially serious in SCD
ABT: antibiotic therapyABT: antibiotic therapy

65. MCQMCQ
 Human is the only reservoir ofHuman is the only reservoir of S TyphiS Typhi
 In non-typhoidal infx. ABT stops carriageIn non-typhoidal infx. ABT stops carriage
 Typhoid is a multisystem septicemic illnessTyphoid is a multisystem septicemic illness
 More serious in SCDMore serious in SCD
 In EF the brunt of illness is borne by the small gutIn EF the brunt of illness is borne by the small gut
 Ac. Nephritis is a recognized complicationAc. Nephritis is a recognized complication

66. MCQMCQ
 Major outbreaks of salmonellosis is c/by poultry, beef,Major outbreaks of salmonellosis is c/by poultry, beef,
eggs, dairyeggs, dairy
 Perforation & bleed are fatal complications of EFPerforation & bleed are fatal complications of EF
 Parenteral typhoid vax. is more effectiveParenteral typhoid vax. is more effective
 Widal test is a specific testWidal test is a specific test
 Complications in EF can even occur during RxComplications in EF can even occur during Rx
 Typhoid can cause transverse myelitisTyphoid can cause transverse myelitis

71. Nobel Prize inNobel Prize in
Medicine 1902Medicine 1902

72. MALARIAMALARIA

75. In this session we will learn:In this session we will learn:
 50% world popn.50% world popn. live in malarious area. It islive in malarious area. It is eradicatederadicated
from the West; but every country has imported M.from the West; but every country has imported M.
 280million cases/y.280million cases/y. AgesAges 6mo-5y6mo-5y are the worst affectedare the worst affected
 It is a life-threatening d.It is a life-threatening d. c/by MP spread byc/by MP spread by F.F. nocturnal-nocturnal-
feedingfeeding AnophelesAnopheles which is ewhich is entering new areasntering new areas
 Most dangerous isMost dangerous is P falciparumP falciparum
 2015: 91 countries2015: 91 countries had ongoing transmissionhad ongoing transmission
 7,55,0007,55,000 death/y (death/y (mostly U-5mostly U-5. 1 dies/min). 1 dies/min)
– mostly from CM. Prolonged fits without CM can killmostly from CM. Prolonged fits without CM can kill
– anemia can be fatalanemia can be fatal
M: malaria. MP: malarial parasiteM: malaria. MP: malarial parasite

76.  SS AfricaSS Africa has 90% of M. & 92% of M. deathshas 90% of M. & 92% of M. deaths (2015)(2015)
 In endemic areas it causesIn endemic areas it causes 10% U-5MR10% U-5MR
 ResistanceResistance to drugs & insecticides: situation is worseningto drugs & insecticides: situation is worsening
 SE Asia:SE Asia: 9% of malaria burden9% of malaria burden
 Pregnancy:Pregnancy: abortion, preterm, IUGR, IUDabortion, preterm, IUGR, IUD
 Non-immune people are very proneNon-immune people are very prone
 M. is preventable & curable, & efforts are dramaticallyM. is preventable & curable, & efforts are dramatically
reducing burden in many placesreducing burden in many places
 2010-15:2010-15: incidence among at risk people fell by 21%; withincidence among at risk people fell by 21%; with
MR fell by 29% in all ages, 35% in U-5 childrenMR fell by 29% in all ages, 35% in U-5 children
SS: sub-saharanSS: sub-saharan

77. Distribution of P falciparum

78. Malaria in Bangladesh:Malaria in Bangladesh: eendemicndemic
Nearly eradicatedNearly eradicated by 1970s but never disappearedby 1970s but never disappeared
 Re-emergedRe-emerged in 1990sin 1990s
 Big PH problemBig PH problem
 Grossly under-reportedGrossly under-reported
 24million in 13/64 districts at risk (>90% in 5).24million in 13/64 districts at risk (>90% in 5).
PrevalencePrevalence:: 3%.3%. 400k400k cl. cases (>57k confirmed)cl. cases (>57k confirmed)/y./y.
PF in children <4y 8.5%. InPF in children <4y 8.5%. In Khagrachari:Khagrachari: >15%>15%
>500 deaths/y>500 deaths/y

79. Because of increasingBecause of increasing
MDR, monitoring is neededMDR, monitoring is needed
to see efficacy of AMDto see efficacy of AMD
MDR: multi-drug resistantMDR: multi-drug resistant
AMD: antimalarial drugsAMD: antimalarial drugs
24million in 13/64 districts24million in 13/64 districts
at risk (>90% in 5).at risk (>90% in 5).

80. ETIOLOGYETIOLOGY
Plasmodia:Plasmodia: intra-RBC parasites. Infect many mammals,intra-RBC parasites. Infect many mammals,
birds, reptilesbirds, reptiles
 4 species infect humans4 species infect humans
– P falciparumP falciparum
– P vivaxP vivax
– P ovaleP ovale
– P malariaeP malariae

81. Commonest:Commonest: vivaxvivax && falciparumfalciparum
 VivaxVivax in Indian SC & C. Americain Indian SC & C. America
 FalciparumFalciparum inin Africa & PNGAfrica & PNG
 OvaleOvale mostly in W Africamostly in W Africa
 MalariaeMalariae uncommonuncommon but present widelybut present widely
 Recrudescence:Recrudescence: PFPF && malariaemalariae (persistent low parasitemia)(persistent low parasitemia)
 Relapse may occur inRelapse may occur in vivax,vivax, ovaleovale ((hypnozoiteshypnozoites))

82. EPIDEMIOLOGYEPIDEMIOLOGY
 By vector.By vector. Rarely:Rarely: congenital, BT, contaminated needlescongenital, BT, contaminated needles
Immunity in malaria:Immunity in malaria: partialpartial
Repeated inf. in U-5sRepeated inf. in U-5s ⇒⇒ tolerance;tolerance; but lost without furtherbut lost without further
inf. Older children/adults:inf. Older children/adults: asymptomatic parasitemiaasymptomatic parasitemia
 Genetic protection:Genetic protection:
– lacking Duffy Ag prevents vivax in W Africalacking Duffy Ag prevents vivax in W Africa
– certain Hb-pathiescertain Hb-pathies (SCD) prevents PF(SCD) prevents PF
– IDA may protectIDA may protect
 Asplenia & pregnancy: more severeAsplenia & pregnancy: more severe
Inf.: infection. IDA: iron defi. Anemia. SCD: sickle cell d.Inf.: infection. IDA: iron defi. Anemia. SCD: sickle cell d.

83. SchizogonySchizogony:: HumanHuman liver (A)liver (A) VectorVector inoculatesinoculates
sporozoites (1)sporozoites (1)⇒⇒ infect liver (2): mature to schizont (3)infect liver (2): mature to schizont (3)⇒⇒
releaserelease merozoitesmerozoites (4) to invade RBCs. In(4) to invade RBCs. In vivaxvivax && ovaleovale
hypnozoiteshypnozoites can persist to relapse w/yrs latercan persist to relapse w/yrs later
Schizogony:Schizogony: RBC (B):RBC (B): asexual division (5). trophozoitesasexual division (5). trophozoites
(Ring forms)(Ring forms) ⇒⇒ schizontsschizonts ⇒⇒ releasingreleasing merozoitesmerozoites & pyrogens& pyrogens
(6)(6)⇒⇒ CF.CF. Some form gametocytes (7)Some form gametocytes (7)
MosquitoMosquito:: (C)(C) sporogonysporogony:: male (micro-) & Fmale (micro-) & F
(macrogametocytes), are taken by vector(8)(macrogametocytes), are taken by vector(8) ⇒⇒zygote forms inzygote forms in
stomach(9)stomach(9) ⇒⇒ motile & long ookinetes (10)motile & long ookinetes (10) ⇒⇒ invade midgutinvade midgut ⇒⇒
oocysts(11)oocysts(11) ⇒⇒releaserelease sporozoitessporozoites (12)(12) ⇒⇒ salivary Gs (1)salivary Gs (1)
LC:LC: 2 hosts:2 hosts: femalefemale anopheles & humananopheles & human

85. Schizont in hepatocyteSchizont in hepatocyte
Schizont in rbcSchizont in rbc

86. PathophysiologyPathophysiology
 4 Lesions4 Lesions
– 1.1. hemolysishemolysis:: anemia, jaundiceanemia, jaundice. 2.. 2. cytokinescytokines:: inflam.:inflam.: HSMHSM
– 3.3. pyrogenspyrogens:: F.F. 4.4. microcirculatory blockmicrocirculatory block (RBCs with(RBCs with
schizonts stick to capillaries):schizonts stick to capillaries): multi-organ damage in PFmulti-organ damage in PF
Cycle time:Cycle time:
 LiverLiver schizogonyschizogony: 1-2w for all: 1-2w for all
 RBC … :RBC … : 48h in PF, vivax, ovale48h in PF, vivax, ovale (TM)(TM)
72h in malariae72h in malariae (QM)(QM)
PeriodicityPeriodicity of F depends on RBC cycle & needs all parasitesof F depends on RBC cycle & needs all parasites
developing simultaneously.developing simultaneously.
TM= tertian malaria, QT= quartan M.TM= tertian malaria, QT= quartan M. HSM: hepatosplenomegalyHSM: hepatosplenomegaly

87. TypicalTypical:: (in non-immune), children, adults in hypo-(in non-immune), children, adults in hypo-
endemic/from malaria-free areaendemic/from malaria-free area
– IP: 10-21d, or longerIP: 10-21d, or longer
– HGF:HGF: oftenoften 41°C41°C; malaise, HA, ANVD, cough, arthralgia,; malaise, HA, ANVD, cough, arthralgia,
AP, fit (children), backacheAP, fit (children), backache
– Anemia, thrombocytopeniaAnemia, thrombocytopenia common. ± Jaundicecommon. ± Jaundice
– HSMHSM is more in the non-exposed, pregnant oris more in the non-exposed, pregnant or
immunocompromisedimmunocompromised
CF:CF: onlyonly due to erythrocytic cycledue to erythrocytic cycle

88. FF is continued/irregular. Classical TM/QM after someis continued/irregular. Classical TM/QM after some
days. Typical F hasdays. Typical F has 3 stages:3 stages:
– ColdCold:: chills & rigorschills & rigors
– Hot:Hot: plateauplateau
– Sweating/wetSweating/wet:: drenching sweatsdrenching sweats
Congenital MalariaCongenital Malaria
 Rare.Rare. Perinatal. MostlyPerinatal. Mostly vivaxvivax & PF& PF (80%)(80%)
 ResemblesResembles NNSNNS: F, anorexia, irritability, lethargy: F, anorexia, irritability, lethargy
NNS: neonatal sepsisNNS: neonatal sepsis

89. P falciparum:P falciparum: usuallyusually ‘flu’-like‘flu’-like but no focus.but no focus.
Potentially fatal.Potentially fatal. AspleniaAsplenia:: lethallethal
 CNS:CNS: cerebral malaria (CM):cerebral malaria (CM):
 HypoglycemiaHypoglycemia (> in children),(> in children), m. acidosis:m. acidosis:
 Respiratory:Respiratory: ARDS:ARDS:
 Renal:Renal: black water F, oliguria, ATN, NS, ARFblack water F, oliguria, ATN, NS, ARF::
 Blood:Blood: severe anemia, jaundice, collapse, shock, DICsevere anemia, jaundice, collapse, shock, DIC::
 Splenic ruptureSplenic rupture
 GIT:GIT: diarrheadiarrhea

90. Cerebral M:Cerebral M: variable CF: Fever,variable CF: Fever, fitfit, raised ICP,, raised ICP,
confusion, stupor,confusion, stupor, comacoma, death, death
FitsFits are common in children; but ifare common in children; but if prolonged postictalprolonged postictal
state:state: suspectsuspect CMCM
Rapidly fatal:Rapidly fatal: urgent Rxurgent Rx
DD:DD: meningitis, encephalitis, epilepsy. Consider CM inmeningitis, encephalitis, epilepsy. Consider CM in allall
febrile neuropathiesfebrile neuropathies in a Malarious areain a Malarious area
 Hypoglycemia:Hypoglycemia: more with quinine. Urgent Rxmore with quinine. Urgent Rx

91.  Renal failure:Renal failure: ATN (rare in <8y), N. syn.ATN (rare in <8y), N. syn.
 ARDS & m. acidosis:ARDS & m. acidosis:
Noncaardiac pulmonary edema:Noncaardiac pulmonary edema: difficult to Rxdifficult to Rx
& may be fatal (rare in children)& may be fatal (rare in children)
 Severe anemiaSevere anemia:: hemolysis, BM depressionhemolysis, BM depression
 Vascular collapse & shock:Vascular collapse & shock: hypothermia & adrenalhypothermia & adrenal
insufficiencyinsufficiency

92. Peculiarities PFPeculiarities PF
 No persistentNo persistent exo-erythrocytic cycleexo-erythrocytic cycle
 Attacks RBCs ofAttacks RBCs of all agesall ages
 >1 parasites/RBC>1 parasites/RBC
 EccoleEccole ((Appliqué) formationformation
 FalciformFalciform gametocytesgametocytes
 MicrovasculatureMicrovasculature blockadeblockade
 More anemiaMore anemia
 Blackwater FBlackwater F

93. Ring-formRing-form PFPF. As it matures, tends to retain ring shape & trace of. As it matures, tends to retain ring shape & trace of
yellow pigment may be seen within the cytoplasmyellow pigment may be seen within the cytoplasm

94. PFPF rings have delicate cytoplasm & 1 or 2 small chromatin. RBCs are notrings have delicate cytoplasm & 1 or 2 small chromatin. RBCs are not

95. PFPF gametocyte & ring. Macrogametocytes show a single mass ofgametocyte & ring. Macrogametocytes show a single mass of
chromatin, micro- show a diffuse chromatin arrangementchromatin, micro- show a diffuse chromatin arrangement

96. PFPF gametocytes:gametocytes: "Laveran's bib“."Laveran's bib“.
(E) 2 gametocytes in a thick(E) 2 gametocytes in a thick
smear. RBC is often distorted, orsmear. RBC is often distorted, or
not visiblenot visible

97. PFPF
schizonts.schizonts.
8-248-24
merozoitesmerozoites
with darkwith dark
pigment &pigment &
clumped. (C,clumped. (C,
D) rupturedD) ruptured

98. Fused plateletsFused platelets
can resemble acan resemble a
falciparumfalciparum
gametocytegametocyte
falciparumfalciparum gametocytes:gametocytes:
RBC is often distorted, orRBC is often distorted, or
not visiblenot visible

99. Nephrosis from PF. IfNephrosis from PF. If
not promptly treated,not promptly treated,
may cause kidneymay cause kidney
failurefailure

100.  Anemia develops slowly. May haveAnemia develops slowly. May have tendertender HSMHSM
 Spont. recoverySpont. recovery in 2-6w.in 2-6w. HypnozoitesHypnozoites can relapse for yrscan relapse for yrs
 Repeated inf.:Repeated inf.: hypersplenism;hypersplenism; late splenic rupturelate splenic rupture
Vivax & OvaleVivax & Ovale relatively mildrelatively mild
VivaxVivax trophozoites: amoeboid & large chromatin dots &trophozoites: amoeboid & large chromatin dots &
have yellowish-brown pigmenthave yellowish-brown pigment

101. Vivax:Vivax: a maturea mature
schizont; mimics plateletschizont; mimics platelet
artifactartifact
44 vivaxvivax rings, next to arings, next to a
growing trophozoitegrowing trophozoite

102. Ameboid trophozoite ofAmeboid trophozoite of P vivaxP vivax
VivaxVivax: a microgametocyte: a microgametocyte

103. A matureA mature P vivaxP vivax schizontschizont
33 vivaxvivax ring stage in 1 rbc.ring stage in 1 rbc.
Rbc can enlarge x1.5 - 2.Rbc can enlarge x1.5 - 2.
Numerous Schuffner's dotsNumerous Schuffner's dots
are seenare seen

104. BF: aBF: a P vivaxP vivax microgametocytemicrogametocyte.
The gametocytesThe gametocytes
ImmatureImmature vivaxvivax schizontschizont with 8with 8
chromatin masseschromatin masses

105. Stages ofStages of vivaxvivax in a PBFin a PBF
Vivax:Vivax: round-ovalround-oval
gametocytesgametocytes with brownwith brown
pigment & may fill RBC &pigment & may fill RBC &
enlarge it x1½-2; mayenlarge it x1½-2; may
distort it. Schüffner dotsdistort it. Schüffner dots
may be seenmay be seen

106. Ovale:Ovale: trophozoites;trophozoites; sturdy cytoplasm, large chromatin, compact tosturdy cytoplasm, large chromatin, compact to
slightly amoeboid. RBCs are normal to x1¼ , round to oval, may beslightly amoeboid. RBCs are normal to x1¼ , round to oval, may be
fimbriated. Schüffner dots may be seen. (A, B) Trophozoites. (A) slightlyfimbriated. Schüffner dots may be seen. (A, B) Trophozoites. (A) slightly
amoeboid. (B) more compact & Schüffner dots. (C) Trophozoite in aamoeboid. (B) more compact & Schüffner dots. (C) Trophozoite in a
thick filmthick film

107. Ovale:Ovale: schizonts 6-schizonts 6-
14 merozoites with14 merozoites with
large nuclei, aroundlarge nuclei, around
dark-brown pigment.dark-brown pigment.
(D) Schizont in a(D) Schizont in a
thick filmthick film

108. Ovale: gametocytes round-oval & almost fill RBC. Schüffner dots
can be seen (A). RBCs in (BC) show fimbriation
2 ring-forms & a schizont. As it2 ring-forms & a schizont. As it
enlarges, ring disappears: matureenlarges, ring disappears: mature
trophozoite: schizonttrophozoite: schizont

109. Ovale:Ovale: (A, B) rings. (A) RBC(A, B) rings. (A) RBC
fimbriated. (B) Schüffner's dots.fimbriated. (B) Schüffner's dots.
(C, D) rings in thick film(C, D) rings in thick film
An immatureAn immature schizont ofschizont of PP
ovaleovale with 4 chromatins, &with 4 chromatins, &
rounded RBCsrounded RBCs

110.  But tends to cause chr. parasitemia (for years), with/-out SS;But tends to cause chr. parasitemia (for years), with/-out SS; inin
children may cause GN & NSchildren may cause GN & NS ((immune compleximmune complex))
Malariae: usually mildsually mild
Ring:Ring: sturdy cytoplasm,sturdy cytoplasm,
large nuclei. RBCs are normallarge nuclei. RBCs are normal
to x¾. (ABC) rings. (D) thickto x¾. (ABC) rings. (D) thick
BF showing ring & gametocyteBF showing ring & gametocyte

111. Malariae:Malariae: trophozoitestrophozoites have compact cytoplasm & a large chromatin. (A, B, C):have compact cytoplasm & a large chromatin. (A, B, C):
Mature trophozoites in thin BF. (A)(B) are band forms. (C) is a "basket" formMature trophozoites in thin BF. (A)(B) are band forms. (C) is a "basket" form
Malariae: "banded" trophozoite.
As it enlarges, ring disappears

112. Malariae:Malariae:
schizontsschizonts 6-126-12
merozoites withmerozoites with
large nuclei, aroundlarge nuclei, around
coarse, browncoarse, brown
pigment. May makepigment. May make
rosetterosette. (A, B, C). (A, B, C)
Schizonts in thin BFSchizonts in thin BF
Thick BF: schizontThick BF: schizont

113. GrowingGrowing trophozoites.trophozoites. As enlarges, the ring disappears, & matures to schizontAs enlarges, the ring disappears, & matures to schizont

115. Histologic Variations AmongHistologic Variations Among PlasmodiaPlasmodia
FindingsFindings P falc.P falc. vivaxvivax ovaleovale malariaemalariae
Only earlyOnly early
forms in bloodforms in blood
YesYes NoNo NoNo NoNo
Multiply inMultiply in
RBCsRBCs
OftenOften OccasionallyOccasionally RareRare RareRare
Age of RBCsAge of RBCs All agesAll ages YoungYoung YoungYoung OldOld
Schüffner dotsSchüffner dots NoNo YesYes YesYes NoNo
Other featuresOther features
Thin cytoplasm, 1Thin cytoplasm, 1
or 2 chromatinor 2 chromatin
dots, accole formsdots, accole forms
LateLate
trophozoites:trophozoites:
pleomorphicpleomorphic
cytoplasmcytoplasm
RBCsRBCs
becomebecome
oval withoval with
tuftedtufted
edgesedges
DistinctiveDistinctive
bandlikebandlike
trophozoitestrophozoites

116. Complications of malariaComplications of malaria
 CM, fitCM, fit
 Bleeding:Bleeding:
 Hemolysis:Hemolysis:
 Anemia:Anemia:
 Hypoglycemia:Hypoglycemia:
 ARF:ARF:
 Pulmonary edemaPulmonary edema
 Hyperpyrexia:Hyperpyrexia:
 Circ. collapse (algid malaria):Circ. collapse (algid malaria):
 Jaundice:Jaundice:
 Abortion, IUD in pregnancyAbortion, IUD in pregnancy
 Tropical splenomegaly syn.:Tropical splenomegaly syn.:

117.  Bleeding:Bleeding: from heavy parasitemia causing DIC orfrom heavy parasitemia causing DIC or
sometimes 2y bacterial sepsis, thromocytopeniasometimes 2y bacterial sepsis, thromocytopenia
 Hemolysis:Hemolysis: is a part of Mis a part of M,, may be from G6PDD ormay be from G6PDD or
antibody-mediatedantibody-mediated
– If excessive:If excessive: ARF:ARF: Black water FBlack water F, affecting parasitized
& unparasitized rbc: dark urine. It is rare nowIt is rare now
 Anemia:Anemia: is a part of Malariais a part of Malaria
– hemolysis, G6PDD, dyserythropoiesishemolysis, G6PDD, dyserythropoiesis
– hypersplenism, short RBC survivalhypersplenism, short RBC survival
– BM suppression, chr. Inf.BM suppression, chr. Inf.

118.  HyperpyrexiaHyperpyrexia
– Ag. load, rigorsAg. load, rigors
 Circul. collapseCircul. collapse (algid malaria):(algid malaria): micro-vascular blockmicro-vascular block
 Jaundice:Jaundice: hemolysis, hepatitishemolysis, hepatitis
 Hyperreactive splenomegaly (tropical splenomegalyHyperreactive splenomegaly (tropical splenomegaly
syn., TSS):syn., TSS): seen in older children & adults inseen in older children & adults in
hyperendemic areas. Exaggerated immunity tohyperendemic areas. Exaggerated immunity to
repeated malaria causesrepeated malaria causes
pancytopeniapancytopenia, massive SM, elevated, massive SM, elevated
IgM. MP are scanty/absentIgM. MP are scanty/absent
Responds to prolonged Rx withResponds to prolonged Rx with
prophylactic AMDprophylactic AMD

119. DXDX
 Direct:Direct: thick (thick (parasite)parasite) & thin& thin forfor spp.spp. % of parasitized RBC% of parasitized RBC
 Negative? MP is still possible, repeat 12-24hly x3dNegative? MP is still possible, repeat 12-24hly x3d
 Rapid Dx testRapid Dx test (RDT):(RDT): HRP-2/pLDH based with wholeHRP-2/pLDH based with whole
blood samples for all Spp.blood samples for all Spp. Highly sensitive & specificHighly sensitive & specific
 PCR, DNA probes, etc.PCR, DNA probes, etc. (in research only)(in research only)
In hyperendemic areas, MP on BF is not conclusive of M asIn hyperendemic areas, MP on BF is not conclusive of M as
present illness, as other infx. often are superimposed onpresent illness, as other infx. often are superimposed on
low parasitemia in children & adults having partiallow parasitemia in children & adults having partial
immunityimmunity

120. DD
 Kala azar
 EF
 FUO/PUO
 DF & viral fever
 African trypanosomiasis
 Babesiosis
Infectious Mono.
Leptospirosis
CAP
F with CNS features
 HIV
 Septicemia

121. Goal:Goal: clinical cure & radical cureclinical cure & radical cure
ChemotherapyChemotherapy is based onis based on
– the speciesthe species
– possible drug resistance andpossible drug resistance and
– the severity of diseasethe severity of disease
Rx. is based on local sensitivity (often unknown)Rx. is based on local sensitivity (often unknown)
TREATMENTTREATMENT

122. Antimalarials:
 Chloroquine
 Quinine
Quinidine
Pyrimethamine-
sulfadoxine
Primaquine
Halfantrine
Mefloquine
Proguanil
 ArtemetherArtemether
 ArtesunateArtesunate
 ArtemisinArtemisin
 Tetracycline, DoxycyclineTetracycline, Doxycycline
 ClindamycinClindamycin
 AtovaquoneAtovaquone
 Atovaquone/proguanilAtovaquone/proguanil
 LumefantrineLumefantrine

123. Artemisia annua, aka sweet wormwood, sweet annie, sweet
sagewort, annual mugwort, annual wormwood: a common type
of wormwood native to temperate Asia, but naturalized in many

124. Severe malaria:Severe malaria: >5% RBC parasitized, organ>5% RBC parasitized, organ
involvement, shock, acidosis, hypoglycemiainvolvement, shock, acidosis, hypoglycemia
 ICU care:ICU care: IVQIVQ till parasite count is <1% & able to taketill parasite count is <1% & able to take
oral Rx.: pyramethamine-sulfadoxine or tetracyclineoral Rx.: pyramethamine-sulfadoxine or tetracycline
– Exchange transfusion: parasitemia >10%; CM, 2y inf.Exchange transfusion: parasitemia >10%; CM, 2y inf.
 Sequential PBF to monitor RxSequential PBF to monitor Rx
 BT SOS. FEB is essentialBT SOS. FEB is essential
 After clinical cure ofAfter clinical cure of vivax/ovale,vivax/ovale, give 2-3w primaquinegive 2-3w primaquine
(15mg/d) to clear hypnozoites (relapse). This drug can(15mg/d) to clear hypnozoites (relapse). This drug can
cause hemolysis in G6PDDcause hemolysis in G6PDD

125. Rx of Malaria in BangladeshRx of Malaria in Bangladesh
 Emergence ofEmergence of DR to PF:DR to PF: more Rx failures & CFRmore Rx failures & CFR
 CQR (70%)CQR (70%) in PF required change in Rx for UPFMin PF required change in Rx for UPFM
 UPFM responded (>97%) to artemether-lumefantrineUPFM responded (>97%) to artemether-lumefantrine
((Coartem.Coartem. 6-doses. Costly6-doses. Costly)) or artesunate-mefloquineor artesunate-mefloquine likelike
IV quinineIV quinine
AMDR: antimalarial drug resistance. CFR: case fatality rateAMDR: antimalarial drug resistance. CFR: case fatality rate
UPFM: uncomplicated PF malariaUPFM: uncomplicated PF malaria
CQR= chloroquine resistance. PFM= p falciparum MCQR= chloroquine resistance. PFM= p falciparum M

126.  UPFM: quinine p.o.UPFM: quinine p.o. 3/d x 3d followed by a3/d x 3d followed by a 1x11x1
sulfadoxine/pyrimethaminesulfadoxine/pyrimethamine (Malacide) (90% cure):(Malacide) (90% cure):
cheap, shorter course, better compliancecheap, shorter course, better compliance
 Some Malacide resistant PF are seenSome Malacide resistant PF are seen
 Resistance to quinine is emergingResistance to quinine is emerging
 Pre-referral rectal artesunate (ARTEX-50) for severePre-referral rectal artesunate (ARTEX-50) for severe
malaria can reduce mortality 25%malaria can reduce mortality 25%
 New cost effective Rx strategies are urgently neededNew cost effective Rx strategies are urgently needed

128. Further Inpatient CareFurther Inpatient Care
 Indications for ICU:Indications for ICU:
– Suspicion of CM. Complications:Suspicion of CM. Complications:
– Pt. from nonmalarious with >2% of RBCs have MP orPt. from nonmalarious with >2% of RBCs have MP or
pt. from an endemic area with >5% of RBCs …pt. from an endemic area with >5% of RBCs …
 Proof of cure:Proof of cure: BF: clear (24-48h); especially forBF: clear (24-48h); especially for PFPF
 Exchange transfusionExchange transfusion
– valuable in a v. sick childvaluable in a v. sick child
– Erythrocytapheresis removes only RBCsErythrocytapheresis removes only RBCs
 Radical cure (not for PF)Radical cure (not for PF)
– To destroy the dormant forms in the liverTo destroy the dormant forms in the liver
– Primaquine is only drug effectivePrimaquine is only drug effective

129. Patient Education
 Chemoprophylaxis & the need to continue it for some
weeks after leaving the area
– Motivate travelers. <20% imported M in US have taken
prophylaxis; >50% have no chemoprophylaxis
 Avoid bite: mosquito nets with insecticides, coils, clothing
 Advise visitors regarding Rx of M & provide them drugs if
a hospital is n/a

130. PrognosisPrognosis
 Excellent for uncomplicatedExcellent for uncomplicated vivax,vivax, malariae,malariae, ovaleovale
 Grave forGrave for PF ifPF if not treated adequatelynot treated adequately
 CM MR: 25%, even with the best Rx. Survivors may haveCM MR: 25%, even with the best Rx. Survivors may have
hemiparesis, cerebellar ataxia, aphasia, spasticityhemiparesis, cerebellar ataxia, aphasia, spasticity
 U-5 have the worst prognosis in endemic areasU-5 have the worst prognosis in endemic areas
 Nonimmune people: malaria is equally deadly at all agesNonimmune people: malaria is equally deadly at all ages
 Repeated malaria leads to chr. anemia, growth failureRepeated malaria leads to chr. anemia, growth failure

131. CONTROL MEASURESCONTROL MEASURES
 Rx of malariaRx of malaria
 Personal protection:Personal protection: Preventing mosquito bites:Preventing mosquito bites:
 Control ofControl of AnophelesAnopheles
 Chemoprophylaxis of travelersChemoprophylaxis of travelers
 Prophylaxis in pregnancyProphylaxis in pregnancy
 SSelf-Rx of malariaelf-Rx of malaria
 Prevention of relapsePrevention of relapse
 VaccineVaccine

132. PERSONAL PROTECTIVE MEASURESPERSONAL PROTECTIVE MEASURES
 Use insecticide-impregnated mosquito netsUse insecticide-impregnated mosquito nets (permethrin(permethrin
0.2g/m2 every 6mo:0.2g/m2 every 6mo: v. beneficial)v. beneficial)
 Wear protective dress: can also be permethrinWear protective dress: can also be permethrin
impregnatedimpregnated
 Stay in well-screened roomStay in well-screened room
 Mosquito repellents (cont. DEET; Diethyl-m-toluamide)Mosquito repellents (cont. DEET; Diethyl-m-toluamide)
 Prevent mosquitoes contact dusk to dawn (AnophelesPrevent mosquitoes contact dusk to dawn (Anopheles isis
nocturnal)nocturnal)
 Bedrooms should be sprayed with an aerosol insecticideBedrooms should be sprayed with an aerosol insecticide
at duskat dusk

133. CHEMOPROPHYLAXIS FOR TRAVELERSCHEMOPROPHYLAXIS FOR TRAVELERS
Is never fully effectiveIs never fully effective
 If no CQR:If no CQR: CQ 1/w, 1w before & 4w afterCQ 1/w, 1w before & 4w after
 CQR falciparum:CQR falciparum:
– Atovaquone-proguanil:Atovaquone-proguanil: 1/d. 1d before-1w after. Not for1/d. 1d before-1w after. Not for
children <11 kg nor in pregnancychildren <11 kg nor in pregnancy
– Doxycycline:Doxycycline: 1/d. 2 d before-4w after. Strict dosing;1/d. 2 d before-4w after. Strict dosing; on a fullon a full
stomach; not in preg. or children <8ystomach; not in preg. or children <8y
– Mefloquine:Mefloquine: 1/w, 1w before & 4w after. Not for children1/w, 1w before & 4w after. Not for children
<6mo. DoC in pregnancy<6mo. DoC in pregnancy
 Primaquine:Primaquine: if others cannot be used. Exclude G6PDD ! 2d before-if others cannot be used. Exclude G6PDD ! 2d before-
7d after. Not in preg.7d after. Not in preg.
 Begin earlier to ensure blood concn.; evaluate SEBegin earlier to ensure blood concn.; evaluate SE

134. PROPHYLAXIS DURING PREGNANCYPROPHYLAXIS DURING PREGNANCY
No chemoprophylaxis is completely effectiveNo chemoprophylaxis is completely effective
 Avoid travel to endemic areasAvoid travel to endemic areas
 If no CQR:If no CQR: chloroquinechloroquine prophylaxis. No fetal harmprophylaxis. No fetal harm
 CQRCQR falciparumfalciparum area:area: mefloquinemefloquine is the DoCis the DoC
SELF-Rx OF MALARIASELF-Rx OF MALARIA
 WithWith atovaquone-proguanilatovaquone-proguanil; but; but is not a replacement for medicalis not a replacement for medical
help. One on chemoprophylaxis should not take anhelp. One on chemoprophylaxis should not take an
alternative. He is advised that any fever or flu-like illness thatalternative. He is advised that any fever or flu-like illness that
develops within 3mo of departure from an endemic areadevelops within 3mo of departure from an endemic area
requires immediate medical evaluationrequires immediate medical evaluation

135. Placenta inPFMPlacenta inPFM:: LBW, preterm, increased mortality, maternal anemiaLBW, preterm, increased mortality, maternal anemia

136. Safe & effective vaccineSafe & effective vaccine
 Not too distantNot too distant
 Hopes remain for a recombinantHopes remain for a recombinant DNA vaccineDNA vaccine
 Likely to be 10y before a vaccine for routine useLikely to be 10y before a vaccine for routine use
can be expectedcan be expected
 Current focus on attenuated sporozoiteCurrent focus on attenuated sporozoite
 Impractical.Impractical. SporozitesSporozites do not breed well indo not breed well in
culture, so mosquitos need to be bredculture, so mosquitos need to be bred
 Yeah, lets breed mosquitoes. Great idea…Yeah, lets breed mosquitoes. Great idea…

137. "Mosquito fish“ Gambusia ingests a mosquito larva. These tiny fish can
eat their own weight of mosquito larvae a day, & have been introduced

138. Points to ponder
M is serious in children, pregnancy & asplenia
Hypersplenism can occur
Convulsion can occur in all cases
Hypnozoites are responsible for long IP malaria
Quinine & MP can cause hypoglycemia
Severe malaria needs ICU

139. MCQMCQ
 PF affects mainly young RBCsPF affects mainly young RBCs
 CM is mainly due to vaso-occlusionCM is mainly due to vaso-occlusion
 MP in PBF in endemic area establ. Dx of M. feverMP in PBF in endemic area establ. Dx of M. fever
 Vivax is usually sensitive to CQVivax is usually sensitive to CQ
 IV quinine can cause hypoglycemiaIV quinine can cause hypoglycemia
 Nephrotic syn can be c/byNephrotic syn can be c/by P. malariaeP. malariae
 Vivax & ovale have hypnozoitesVivax & ovale have hypnozoites
 Persistent hepatic schizogony occurs in PFPersistent hepatic schizogony occurs in PF

140. Drug Chloroquine
Description
Effective against erythrocytic parasite & is DoC for vivax, malariae, & ovale. It is gametocidal as
well. But ineffective for hypnozoites. Very effective against sensitive strains of falciparum.
Resistance is widespread in Africa & Asia, & cannot be relied on in severe malaria. Resistance to
vivax is rare.
Can be used as prophylaxis only where resistance is not common (parts of C America, the
Caribbean, parts of the ME)
Adult
600mg of base PO; then 300 mg after 6, 24, & 48 h.
200 mg of base IV; diluted in 500 ml of IVF over 4-6 h; repeat dose q8h until patient can take PO
therapy
Pediatric
10 mg/kg stat followed by 3 doses of 5 mg/kg at 6, 24, 48 h
Never IM as may cause sudden death
5 mg/kg IV diluted in IVF over 6 h (0.8 mg/kg/h) q8h until can take PO
CI Documented hypersensitivity; psoriasis; retinal & visual field changes (4-aminoquinolones)
Interactions Reduced absorption with Mg antacids; cimetidine may increase serum levels
Pregnancy
C - Fetal risk in studies in animals but not established in humans; may use if benefits outweigh risk
to fetus
PO use after meals because it causes gastritis; possible shock & death in young children with single
PO dose of 600 mg; rapid infusions: CV toxicity, irreversible ototoxicity & retinopathy with high

141. Drug Quinine
Description
A blood schizonticidal drug & still the DOC for severe & complicated malaria. It
is gametocidal for P vivax & P malariae, but not for P falciparum. It is available
as tabs containing 260 mg & as injections containing 300 mg/mL.
Spreading resistance among P falciparum make the drug less reliable in certain
parts of Asia & Africa.
Adult
Treatment: 542 mg as base (650 mg salt) PO q8h for 7 d
10 mg/kg (as base) IV diluted in IV fluid & infused slowly q8h; not to exceed
600 mg; switch to PO therapy when patient can tolerate it to complete 7-d course
Pediatric
Treatment: 8.3 mg as base/kg PO tid for 7 d (equivalent to 10 mg as salt/kg)
Do not administer IM except as lifesaving measure in severe M while awaiting
transport to hospital with requisite facilities
15-20 mg/kg IV diluted in IV infusion fluid to 1 mg/mL; infuse over at least 4 h;
followed by 10 mg/kg/dose q8-12h if continuation beyond 48 h is needed; reduce
dose to 5 mg/kg q8h; switch to PO therapy as soon as possible
Contraindications
Documented hypersensitivity; myasthenia gravis (possible respiratory distress &
dysphagia); G-6-PD deficiency (possible severe hemolysis); tinnitus or optic
neuritis
Interactions
Al. antacids delay or decrease quinine bioavailability; cimetidine increases
quinine blood levels; rifamycins decrease quinine concentrations by increasing
hepatic clearance (effect can persist for several days after discontinuing
rifamycins); concurrent administration of acetazolamide or sodium bicarbonate
may increase toxicity by increasing quinine blood levels; quinine may enhance
action of warfarin & other PO anticoagulants by decreasing synthesis of vitamin

142. Drug Name Quinidine
Description
A stereoisomer of quinine & a blood schizonticidal drug, it is as effective as quinine
against blood schizonts but has significant cardiac toxicity. This agent is used if
quinine is not readily available. It is available as tabs of quinidine sulphate containing
200 mg. The injectable preparation is not always available.
Adult Dose
7.5 mg as base/kg/dose IV in IV fluid over 4 h q8h for 7 d (salt equivalent = 12
mg/kg)
Pediatric Dose
25-30 mg as base/kg/d PO in divided doses for 7 d
15 mg/kg diluted in IV infusion fluid over at least 4h followed by 7.5 mg/kg/dose q8-
12h; switch to PO therapy as soon as possible, & complete 7-d course
Contraindications
Documented hypersensitivity; myasthenia gravis (possible respiratory distress &
dysphagia); G-6-PD deficiency (possible severe hemolysis); AV block or bundle
branch block
Interactions
Possible delayed absorption from GIT with coadministration of antacids containing
aluminium; possible delayed excretion of digoxin, warfarin, & other anticoagulants;
significantly reduced half-life possible with concomitant phenytoin & phenobarbital
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in
humans; may use if benefits outweigh risk to fetus
Precautions
Possible hyperinsulinemia & hypoglycemia; monitor blood glucose; ensure adequate
PO intake; if administered parenterally, quinidine should be diluted in dextrose-

143. Drug Name Pyrimethamine-sulfadoxine
Description
Antifolate drugs; slow-acting blood schizonticide, effective in some cases of
CQR falciparum, especially those acquired in Africa. This drug is not
effective against P vivax malaria. Being slow acting, this combination cannot
be used in potentially severe cases. It has no activity against hypnozoites &
gametocytes. Tablets contain 25 mg of pyrimethamine & 500 mg of sulfa.
Adult Dose 3 tab PO (75 mg pyrimethamine & 1500 mg sulfadoxine) as a single dose
Pediatric Dose
<2 months: Contraindicated
>2 months: 1.5 mg/kg pyrimethamine component PO as a single dose
Contraindications
Documented hypersensitivity; infants <2 mo; nursing mothers (drug passes
the placenta, is excreted in milk, & may cause kernicterus); renal impairment;
blood dyscrasias; hepatic damage
Interactions
Concurrent use of antifolic acids, such as methotrexate, & pyrimethamine
may increase risk of BM suppression; discontinue therapy if signs of folate
deficiency develop; mild hepatotoxicity may occur with concomitant
administration of lorazepam & pyrimethamine
Pregnancy
X - Contraindicated; benefit does not outweigh risk
Precautions
Possible severe, even fatal, cutaneous reactions (1 in 5000-8000): exfoliative
dermatitis, erythema multiforme, Stevens-Johnson syndrome, or epidermal
necrolysis; reported fatalities with sulfonamide like fulminant hepatic
necrosis, agranulocytosis, & aplastic anemia; hepatitis & megaloblastic
anemia can occur, especially with overdosage; not presently used for
prophylaxis because of serious adverse effects

144. Drug Name Primaquine
Description
The only drug can destroy hypnozoites of both vivax & ovale, & so is used for the radical cure
of the relapsing malarias. It is gametocidal against all 4 plasmodia & is used to render patients
noninfectious. Primaquine has a very weak effect against erythrocytic vivax & cannot be used
to terminate an acute attack. It has no activity against erythrocytic forms of P falciparum. This
drug can be administered to patients on chemoprophylaxis after they have left the endemic
area. Not to be used until erythrocytic forms have been destroyed by another drug.
Primaquine is also an effective & fairly safe drug for chemoprophylaxis. Since it acts on the
liver forms, it need not be taken before entering a malarious area, nor for more than 3 days
after leaving it. This is an advantage for people making sudden or short trips.
Adult Dose
For radical cure of P vivax & P ovale malarias: 15 mg as base PO bid for 14 d
To render patient noninfectious: 15 mg/d PO for 5 d for P falciparum inf.
As chemoprophylaxis, 0.5 mg as base/kg daily, starting on the day of entry to a malarious area
Pediatric
Dose
For radical cure of P vivax & P ovale malarias: 0.3 mg/kg/d PO primaquine base for 14 d
To render patient noninfectious: 0.3 mg/kg/d PO primaquine base for 5 d for P falciparum inf.
Contraindic
ations
Documented hypersensitivity; G-6-PD deficiency (significant hemolysis in these patients)
Interactions Coadministration with quinacrine may increase toxicity, usually not of clinical significance
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may
use if benefits outweigh risk to fetus

145. Drug Name Halofantrine
Description
A rapid-acting drug against erythrocytic forms of malaria. Primarily used
for treatment of acute attacks of M caused by MDR falciparum. It is not
active against hypnozoites & gametocytes. Because it is a slow acting drug
& does not have a parenteral preparation available, the drug is not of use
for severe & complicated malaria.
Adult Dose
500 mg PO q6h for 3 doses; repeat after 1 wk
Administer on an empty stomach at least 1 h ac or 2 h pc
Pediatric Dose
<40 kg: 8 mg/kg PO q6h for 3 doses; not to exceed 500 mg/dose; repeat
after 1 wk
>40 kg: Administer as in adults
Administer on empty stomach at least 1 h ac or 2 h pc
Contraindications
Documented hypersensitivity; heart block; QT prolongation; electrolyte
disorders; AV conduction disorders; syncope; thiamine deficiency;
ventricular dysrhythmias
Interactions
Mefloquine may interact with halofantrine, leading to potentially fatal
prolongation of QTc interval
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not
studied in humans; may use if benefits outweigh risk to fetus

146. Drug Name Mefloquine
Description
It is useful for Rx of MDR falciparum. It is effective against blood schizonts
but has no activity against hypnozoites & gametocytes. Its long half-life makes
it suitable for use as a prophylactic drug, & it is the recommended drug in areas
where drug resistance is common (chiefly Africa & Asia). Not having a
parenteral preparation limits its usefulness for severe & complicated malaria. It
is available as tabs containing 250 mg.
Adult Dose 15-25 mg as salt/kg PO as single dose; not to exceed 1500 mg
Pediatric Dose 15-25 mg as salt/kg PO as single dose
Contraindications
Documented hypersensitivity; seizure disorders; neuropsychiatric disorders;
cardiac conduction disorders
Interactions
Mefloquine administered with beta-blockers, quinine, quinidine,
antiarrhythmics, tricyclic antidepressants, or astemizole may potentially cause
ECG abnormalities or cardiac arrest; mefloquine & chloroquine administered
concomitantly may increase risk of convulsions; concomitant administration
with halofantrine may cause potentially fatal prolongation of the QTc interval;
valproic acid administered with mefloquine can increase risk for seizures by
reducing valproic acid blood levels
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in
humans; may use if benefits outweigh risk to fetus
Precautions
Possible giddiness & disturbed balance; possibly hazardous to drive or operate
machinery; monitor psychiatric symptoms with prolonged use; stop

147. Drug Name Artemether
Description
Effective against erythrocytic forms of all 4. Used only for MDR
falciparum. No action on hepatic forms or gametocytes. Very short T1/2,
requiring follow-up Rx with mefloquine or treatment for at least 7 d.
Adult Dose
200 mg PO on day 1, followed by 100 mg qd for 5 d
3.2 mg/kg IM loading dose, followed by 1.6 mg/kg qd for 5 d, or until
patient is able to take PO therapy
Pediatric Dose
4 mg/kg/d PO divided bid
IM: Administer as in adults
Contraindications Documented hypersensitivity; heart block; low leukocyte count
Interactions Aurothioglucose mat increase the risk of blood dyscrasias
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not
studied in humans; may use if benefits outweigh risk to fetus
Precautions Possible rash & fever

148. Drug
Name
Artesunate
Descripti
on
Effective against blood forms of all 4. Special use against MDR falciparum. It has no action
against hepatic schizonts, hypnozoites, or gametocytes. This drug is available as 50-mg tabs & IV
injections containing 10 mg/mL.
It is the fastest acting drug against blood forms, & so the IV form is especially valuable in the
management of severe & complicated malaria.
Resistance is also spreading, particularly in Southeast Asia. Combinations of artesunate with
mefloquine, lumefantrine, & other drugs is effective against MDR malaria.
Adult
Dose
100 mg PO initial dose, followed by 50 mg q12h for 5 d
Alternatively, 2.4 mg/kg IV loading dose, followed by 1.2 mg/kg after 12 h, then 1.2 mg/kg qd
for 5 d, or until patient is able to take PO therapy
Pediatric
Dose
4 mg/kg PO on day 1, followed by 2 mg/kg/d for 3-5 d
Alternatively, 3.2 mg/kg IV on day 1; may be divided bid; then 1.6 mg/kg IV qd for 4 d (total 9.6
mg/kg)
CI Documented hypersensitivity; heart block; low leukocyte count
Interacti
ons
None reported
Pregnan
cy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use
if benefits outweigh risk to fetus
Precauti
ons
Possible rash & fever; possible mild GI upset with PO use

149. Drug Name Tetracycline
Description
Acts against blood schizonts of all spp. Acts slowly so used in
combination with another drug, such as quinine where resistant
falciparum is common
Adult 250-500 mg PO q6h for 7 d
Pediatric
<8 years: Do not use
>8 years: 25-40 mg/kg/d PO for 7 d
CI Hypersensitivity; severe hepatic dysfunction; children <8 y
Interactions
Low absorption with antacids containing Al, Ca, Mg, iron, or
bismuth; can decrease effects of OCP (breakthrough bleeding &
pregnancy); can increase hypoprothrombinemic effects of
anticoagulants
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to
fetus
Precautions
Photosensitivity; reduce dose in renal impairment; consider drug
level in prolonged therapy; use during tooth development (<8 y)
causes permanent discoloration; Fanconi-like syndrome may occur
with outdated tetracyclines

150. Drug Doxycycline
Description
For prophylaxis or Rx. For Rx of P falciparum malaria, it must be used as part
of combination therapy (typically with quinine)
Adult
Prophylaxis: 100 mg/d PO (start 1 d prior to travel; use qd. Continue 4 w after
leaving)
Treatment: 100 mg PO bid for 7 d with second agent
Pediatric
<8 years: Do not use
>8 years:
Prophylaxis: 2 mg/kg/d. Start 1-2 d prior to entering an endemic & continue for
4 w after leaving
Treatment: 2 mg/kg/d PO divided bid for 7 d with second agent
CI Documented hypersensitivity; severe hepatic dysfunction
Interactions As with tetracyclines
Pregnancy
D - Unsafe in pregnancy
Precautions As with tetracyclines

151. Drug Name Clindamycin
Description
An antibiotic that acts against P falciparum. It has been found to be very
effective in combination with quinine, even against M acquired in areas where
DR is common. Used in combination, it shortens duration of fever &
improves cure rates. This can be used in children because tetracyclines are CI.
It is available as capsules containing 75 mg, 150 mg, & 300 mg & as granules
that, after reconstitution with water, contain 75 mg/5 mL.
Adult Dose 20 mg as base/kg/d PO divided tid for 7 d
Pediatric Dose 5-10 mg/kg PO q12h for 3-7 d
CI
Documented hypersensitivity; regional enteritis; ulcerative colitis; hepatic
impairment; antibiotic-associated colitis
Interactions
Increases duration of neuromuscular blockade induced by tubocurarine &
pancuronium; erythromycin may antagonize effects of clindamycin;
antidiarrheals may delay absorption of clindamycin
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied
in humans; may use if benefits outweigh risk to fetus
Precautions
Adjust dose in severe hepatic dysfunction; no adjustment necessary in renal
insufficiency; associated with severe & possibly fatal colitis by allowing
overgrowth of Clostridium difficile

152. Drug Atovaquone
Description
May inhibit metabolic enzymes, which in turn inhibit growth of microorganisms. Must use
in combination with proguanil
Adult
Prophylaxis: 250 mg with 100 mg proguanil PO qd; start 1-2 d before entering endemic
area, continue qd while in endemic area, & continue for 7 d after exposure has ended (this
shortened dosing schedule following travel makes it a good option for patients who are
poorly compliant
Treatment: 500 mg PO bid for 3 d
Pediatric
Prophylaxis: Start 1-2 d before entering endemic area, continue qd while in endemic area,
& continue for 7 d after exposure has ended
Treatment:
<11 kg: Not established
11-20 kg: 62.5 mg/25 mg PO qd
21-30 kg: 125 mg/50 mg PO qd
31-40 kg: 187.5 mg/75 mg PO qd
CI Documented hypersensitivity; severe renal impairment; weight <11 kg (24 lb)
Interactions
May increase zidovudine serum levels; coadministration with rifampin or rifabutin may
decrease atovaquone levels; atovaquone may decrease levels of TMP-SMZ
Pregnancy
C - Safety for use during pregnancy has not been established.
Precautions
Caution in elderly patients & in hepatic & renal impairment; must use in combination with
proguanil; adverse effects are rare & include abdominal pain, nausea, vomiting, &

153. Drug Name Proguanil
Description
This will be marketed in combination with atovaquone in the United States
(Malarone). For pediatric patients, this combination should be used for
uncomplicated P falciparum; can also be used in combination with chloroquine.
Adult Dose
Prophylaxis: 200 mg PO in combination with weekly chloroquine
Prophylaxis with atovaquone/proguanil: 250 mg/100 mg PO qd
Treatment: 200 mg PO bid for 3 d
Pediatric
Dose
Prophylaxis:
<8 months: 1/4 tab PO; 8 months-3 years: 1/2 tab PO
4-7 years: 3/4 tab PO; 8-10 years: 1 tab PO
11-13 years: 1 1/2 tab PO; >14 years: 2 tab PO
Prophylaxis with atovaquone/proguanil:
11-20 kg: 62.5 mg/25 mg PO qd; 21-30 kg: 125 mg/50 mg PO qd
31-40 kg: 187.5 mg/75 mg PO qd; 11-20 kg: 50 mg PO bid for 3 d
21-30 kg: 100 mg PO bid for 3 d;31-40 kg: 150 mg PO bid for 3 d
CI Documented hypersensitivity
Interactions None reported
Pregnancy
Precautions Anorexia, nausea, mouth ulcers, & hematuria (rare) may occur

154. Drug Name Atovaquone/proguanil
Description
Recently approved in the United States for the treatment & prophylaxis of malaria.
Atovaquone has significant parasiticidal activity. Proguanil & atovaquone have high
failure rates when used alone but are very successful in combination. Combining them
also reduces the selection of resistant mutants.
Malarone is available for PO use only, & so can be used only for uncomplicated
malaria, where it is very effective, even against resistant strains. It is also a useful drug
for chemoprophylaxis. It is available as adult (250 mg atovaquone & 100 mg proguanil
hydrochloride per tab) & pediatric (62.5 mg atovaquone & 25 mg proguanil
hydrochloride per tab) formulations.
Adult Dose
Treatment of malaria: 4 adult Malarone tab PO as a single daily dose for 3 consecutive
d
Prophylaxis of malaria: 1 adult tab PO qd; start 2 d before traveling to a malarious area
& continue for 7 d after leaving it
Pediatric Dose
Treatment of malaria: single daily dose PO for 3 consecutive d using adult strength tab
as follows:
5-8 kg: 2 pediatric tab
9-10 kg: 3 pediatric tab
11-20 kg: 1 adult tab
21-30 kg: 2 adult tab
31-40 kg: 3 adult tab
>40 kg: Administer as in adults
Prophylaxis of malaria: start 2 d before traveling to a malarious area & continue for 7 d
after leaving it; dosage is as follows:
11-20 kg: 1 pediatric tab qd

155. Drug Name Pyrimethamine-sulfadoxine (Fansidar)
Description
Can be used for treatment of malaria. No longer considered a first-line agent
for prophylaxis because of the adverse effect profile.
Adult Dose
Prophylaxis: Not indicated
Treatment: 3 tab of 25 mg pyrimethamine & 500 mg sulfadoxine PO once
Pediatric Dose
Prophylaxis: Not indicated
Treatment:
<1 year: 0.25 tab PO once
1-3 years: 0.5 tab PO once
4-8 years: 1 tab PO once
9-14 years: 2 tab PO once
Contraindicatio
ns
Documented hypersensitivity; severe renal insufficiency; marked liver
parenchymal damage; blood dyscrasias; documented megaloblastic anemia
due to folate deficiency; age <2 mo; pregnancy at term & during nursing
period
Do not use antifolic drugs (eg, sulfonamides, trimethoprim-sulfamethoxazole

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160. HEPATITIS
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