medicine_tropical infectious diseases,typhoid, malaria_2014a

8/13/2019 Medicine_tropical Infectious Diseases,Typhoid, Malaria_2014a

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Lets imagine it happenedGetting Sick in the Tropics

(Tropical IDs) Part 2: Typhoid Fever& Malaria

Dr. RosarioOUTLINE:

Part 1:

Overview

A. Tropical infectious diseasesB. 10 leading causes of morbidity

Dengue

A. Dengue virusB. Transmission of dengue virus by aedes

aegypti

C. Dengue infectionsD. PathophysiologyE. Course of illnessF. Old WHO dengue classificationG. Dengue case classification and levels of

severity

H. DiagnosisI. Tourniquet testJ. Step-wise approach to management of

dengue

K. Group AL. Home care for dengueM. Admission criteriaN. Group BO. Group CP. Effects of supportive treatments for DHF

or DSS in childrenQ. Group C: emergency treatmentR. Summary of blood transfusion

treatment

S. Discharge criteriaT. PrognosisU. Prevention

Part 2:

III. Typhoid feverA. Etiologic agentsB. Enteric feverC. Complications and

consequencesD. Laboratory testsE. Antibiotic therapyF. Case courseG. Prevention

IV. MalariaA. Etiologic agentsB. Transmission cycleC. Laboratory testsD. Clinical featuresE. Major signs of severe malariaF. Other signs of severe malariaG. Drugs for susceptible

plasmodium

H. Drugs for MDRI. Drugs for severe or

complicated P. falciparum

malaria

J. PrimaquineK. Other issues

Part 3: Leptospirosis

TYPHOID FEVER

Case # 2:

25 year old, female, government employee Intermittent fever and chills for seven days, relieved

temporarily by paracetamol

Headache, myalgia, body malaise and vague abdominal pain History of diarrhea x 1 day She denies travel to remote area Unremarkable PE except for T= 38.6oC

o Fever with normal heart rate relative bradycardia: seen inpatients with typhoid fever and legionella infection) [2013B]

Case # 2: Issues

Absence of focal findingsoNon-specific signs and symptomsoClues in the clinical data: historical/ suggestive physical

findings

Possible etiologic agentoStandard diagnostic procedure

Empiric therapyoDrug of choice

Resistance patternsETIOLOGIC AGENT [Harrisons]

SALMONELLA

S. typhi or S. paratyphiserotypes A, B, C Gram-negative, non-spore forming, facultative anaerobic bacilli Growth restricted to human hosts Mode of transmission: ingestion of organisms in contaminated food or

water d/t fecal contamination by ill or asymptomatic chronic c arriers.

Pathogenesis:o Penetrates and targets small intestine; phagocytosed by

macrophages

o Spread to other organs via lymphatics and colonize RES tissues

o S/Sx result from cytokine secretion in response to bacterial productafter critical no. of organisms have replicated

S. paratyphi Acauses milder disease than S. typhi Occurrence of multidrug resistant (MDR) strains of S. typhi

o Contain plasmids encoding resistance to chloramphenicoampicillin, trimethoprim

o Abx long used to treat typhoid fever ENTERIC (TYPHOID) FEVER: MANIFESTATIONS

Systemic disease characterized by fever and abdominal pain and causedby dissemination of S. typhior S. paratyphi.

Incubation period:3-21 days (ave. 10-14 days) Most prominent sx:prolonged fever (38.8-40.5oC) if untreated Early findings: rash, hepatosplenomegaly, epistaxis, relative bradycardia

at peak of high fever

Rose spots faint salmon colored, blanching, maculopapular rashlocated primarily on the trunk and chest; evident at end of 1

st week

resolves after 2-5 days

COMPLICATIONS AND CONSEQUENCES[Harrisons]

Development of severe disease depends on host factor(immunosuppression, antacid therapy, previous exposure, vaccination)

strain virulence and inoculum, and choice of antibiotic therapy.

Intestinal hemorrhageoSevere GI bleeding

Intestinal perforation Peritonitis Kidney failure Orchitis Chronic carrier states Myocarditis Neurologic manifestations

o Encephalitis (Psychosis)o Meningitis, Guillain-Barr syndrome, neuritis, and neuropsychiatrisymptoms (described as "muttering delirium" or "coma vigil"), with

picking at bedclothes or imaginary objects. [Harrisons]

LABORATORY TESTSCase 2 Lab Results:

CBC: Hgb= 14.3 Hct= 0.47 RBC = 3.85 WBC = 6.5 N=70 L=26 E=1M=3

Platelet count= 190,000 Urinalysis (-) Typhidot: IgM (-); IgG (+)Question: What laboratory examination would be the most helpfu

test before starting any antibiotic?

A. Complete blood countB. UrinalysisC. Immunochromatographic test (Typhi Dot)D. Blood culture and sensitivity

[2013B]

Immunochromatographic Test (Typhi Dot)o Antibody test; tells previous exposure; it may not truly tell if there

is a disease

Blood culture and sensitivityo Isolates organisms; best tool



RATIONALE FOR THE DIAGNOSTIC TEST

To determine the etiologic agentoBetter careoCost efficient

In suspected cases of typhoid fevero Isolation via cultures remains the gold standardoBlood in the 1stand 2ndweekoStool in the 3rdweekoUrine culture may become (+) on the 3 rdweek

ANTIBIOTIC THERAPY FOR TYPHOID FEVERQuestion: Which of the following antibiotics would you give?

A. ChloramphenicolB. AmoxicillinC. CotrimoxazoleD. Ciprofloxacin

[2013B]

Antibiotic Therapy for Typhoid fever

Optimal Therapy Alternative effective drugs

Susceptib

ilty

Antibiotic Daily

dose

mg/

Kg

Days Antibiotic Daily

dose

mg/kg

days

Fully

susceptible Fluoroquinolone

e.g. ofloxacin,

ciprofloxacin

15 5-7

Chloramphenicol

Amoxicillin

TMP-SMX

50-75

75-100

14-21

14

14

Multi-drug

resistant

Fluoroquinolone

Or

Cefixime

15

15-20

5-7

7-14

Azithromycin

Cefixime

8-10

15-20

7

7-14

Quinolone

resistant

Azithromycin8-10 7

Cefixime 20 7-14

Three-day courses are also effective, particularly in epidemic containment The treatment for quinolone resistant typhoid fever has not been

determined. Azithromycin, the third generation cephalosporins, 10-14

day course of high-dose fluoroquinolones, is effective. Combination of

these is also being evaluated.

3 First-line Agents in Philippines:1.Chloramphenicol2.Amoxicillin/ Ampicillin3.Co-trimoxazole

[Harrisons]

Prompt administration of appropriated antibiotic therapy prevents severecomplications and results in a case fatality rate of



o Vi CPS, a parenteral vaccine consisting of purified Vi polysaccharidefrom the bacterial capsule (given in 1 dose, with a booster every 2

years)

MALARIACase # 3:

A 35 year old male who had a recent travel to Palawan 1 week after arriving in manila, sudden onset of fever, chills,

severe headache, and body malaise

Consulted 2 days later: CBC, malarial smear and urinalysis showednormal results

Given Ciprofloxacin 750 mg BID x 5 days with no lysis of fever Admitted because of subsequent development of oliguria and

ictericia

Case # 3: Issues

Disease severity/ comorbid conditions or factorso IctericiaoOliguria

Etiologic agent involvedoDrug of choiceoDrug resistance

ETIOLOGIC AGENTS

PLASMODIUM FALCIPARUM

Only species associated with severe or complicated malariaoAlmost all deaths caused by this specie [Harrisons]

Problem with therapy: Multidrug resistanceoPhilippines: increasing chloroquine and sulfadoxine-

pyrimethamine resistance

DOH surveillance rate: 35- 65%Highest in Palawan

Clue: in a smear, you should see multiple affected RBC presenting withrings [2013B]

Figure 11. Malaria blood smear showing ring forms

OTHER PLASMODIUM SPECIES

Plasmodium vivax and ovaleo Both can cause relapse

A proportion of the intrahepatic forms (hypnozoites) remaindormant for a period ranging from 3 weeks to a year or longer

before reproduction begins

Hypnozoites are the cause of relapses [Harrisons] Plasmodium malariae

o Causes nephropathy Plasmodium knowlesi

o Similar to plasmodium malaria but behaves like P.falciparuminfection

MALARIA TRANSMISSION CYCLE[Harrisons]

Malaria

Protozoan disease; transmitted by the bite of an infected femaleAnopheles mosquitoes

Principal determinants of the epidemiology of malaria: number (density)human-biting habits, longevity of anopheline mosquito vectors

Transmission of malaria is directly proportional to the density of vector

Figure 12. Plasmodium sporozoites 1st vector (Plasmodium sp.) initia

human hostliver infectionblood infection2nd vectornext human

host [2013B]

LABORATORY TESTSQuestion:Which diagnostic test would be most helpful?

A. Complete blood countB. Renal and liver function testsC. Malarial smearD. Blood C/SE. Microcapsular agglutination test

[Harrisons]

Remember: The diagnosis of malaria rests on the demonstration of asexua

forms of the parasite in stained peripheral blood smears.

LABORATORY FINDINGS

Normochromic, normocytic anemiais usual Leukocyte count: generally normal (may be raised in severe infections) Slight monocytosis, lymphopenia, eosinopenia w/ reactive lymphocytosis

and eosinophilia weeks after acute infection

ESR, plasma viscosity, C-reactive protein and other acute-phase proteinHigh

Platelet count is usually reduced to 105/LCase # 3 Lab results:

CBC: Hb=9.0, Hct=28.7, RBC=2.95 WBC=14.0 (N=81, L=17 M=2)platelet count=95,00

LFTs: ALT = 120 Iu/l, AST = 96 Iu/l, AP = 54 Iu/l, B2 =15mol/l, TB =65mol/l, Crea = 200mol/l.

MAT = positive at 1:100 Blood CS: NG after 24 hours[2013B] In most malaria cases, patients would present with elevated white blood

cells, but some may present with thrombocytopenia

Liver function test results in a patient w/ Malaria:o Slightly elevated ALTo Slightly elevated ASTo Normal alkaline phosphataseo Creatinine is elevated = 200o MAT = 1: 100

Philippine cut-off : 1:1600



CLINICAL FEATURES OF MALARIA [Harrisons]

Nonspecific first symptoms: lack of sense of well-being, headache, fatigue,abdominal discomfort, and muscle aches followed by fever

Headache present but no neck stiffness or photophobia resemblingmeningitis. Myalgia may be prominent but not usually as severe as in

dengue; and muscles are not tender as in leptospirosis or typhus.

When fever spikes, chills and rigors occur at regular intervals suggest P.vivax or P. ovale infection.

Irregular feverFalciparum malaria Few abnormal physical findings other than fever, malaise, mild anemia,

palpable spleen (some cases). Slight enlargement of liver particularly

among children. Mild jaundice is common among adults and develops inpatients with uncomplicated falciparum malaria; usually resolves over 1-3

weeks.

Malaria is not associated with rashes.MAJOR SIGNS OF SEVERE MALARIA

Unarousable coma/

cerebral malaria

Failure to localize or respond appropriately

to noxious stimuli; coma should persist for

>30 min after generalized convulsion

Severe normocytic,

normochromic

anemia

Hematocrit 50 mmol/

L (>3 mg/dl)

Hyperpyrexia Rectal Temperature >40C

DRUGS FOR SUSCEPTIBLE PLASMODIUM SP.

Question:Which of the following anti-microbials would you give?

A. Chloroquine + Sulfadoxine/PyrimethamineB. Quinine + DoxycyclineC. Artemether + LumefantrineD. Primaquine

Uncomplicated malariaoSusceptible P. Falciparum

Chloroquine can cause tinnitus [2013B]Sulfadoxine/pyrimethamine

oOther susceptible Plasmodiumsp.Chloroquine

One criteria that youhave to consider in choosing drugs is resistance ofspecies

In the Philippines, more than 60% is resistant especially in PalawanDRUGS FOR MULTI-DRUG RESISTANCE PLASMODIUM

FALCIPARUM MALARIA

Artemether-lumefantrine (Co-Artem)1.5/9 mg/kg BID with foodfor 3 days (or artesunate 4mg/kg qd)

PLUS

Mefloquine15-25 mg base/kg for 3 daysDRUGS FOR SEVERE OR COMPLICATED P. FALCIPARUM

MALARIA

Drug/s of choice: IV quinine (or quinidine) + Doxycycline oclindamycin

Alternative: Artemisinin derivativesPRIMAQUINE

For radical cure Used as gametocidal drugfor P. Falciparum malaria Used as a hypnozoiticidal drugfor P. Vivax or P. Ovale infection to

prevent relapse

[2013B]

Contraindications: Patients with G6PD deficiencyhemolysis Not used for active disease

OTHER ISSUES

1.Management of Complications2.Adverse events related to drug interventions and interactions 3.Prevention

Management of Complications[2013B]

Regarding hypoglycemia, quinine can induce insulin release which canaggravate hypoglycaemia

Pulmonary edema: unknown reason why patients develop this, soventilatory support should be given

Acidosis: give bicarbonate Renal failure: require dialysis



Prevention

Chemoprophylaxis Use mosquito nets. It is more effective if the mosquito net is treated with

insecticide

Use long sleeves and pants Use repellants and screens on doors and windows Clear hanging branches of trees along the streams Have your blood examined if you have the signs and symptoms of malaria Follow the advice of health workers on how to take anti- malaria drugs. Primary area where Malaria is endemic- PALAWAN Avoidance of exposure to mosquitoes at their peak feeding times (usually

dusk to dawn) as well as the use of insect repellents containing 1035%

DEET

QUIZ:

1. What Plasmodium species causes relapse in malaria?2. Which among the dengue serotype causes the more

severe disease?

3. What is the drug of choice for the treatment of typhoidfever in the Philippines?

Answers:(1) P. vivax & P.ovale; (2) Serotype 2; (3) Chloramphenicol

medicine_tropical infectious diseases,typhoid, malaria_2014a

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