Fever after a stay in the Tropics

Filip Moerman. Liège le 29/11/2014Infectiologie.

CHR Citadelle LiègeInstitut de Médecine Tropical Anvers

Major increase in Intern. Travel

Epidemiology of Travel

Fièvre: prise en charge• RULE OUT the 3 major killers• Anamnèse de voyage (en détail!) + examen clinique

(hépatospléno, peau, poumons, …)• IF NEG: start Doxycycline and perform thorough

blood analysis (eosinophilia!)• Doxy treats all tick bite fevers (mainly rickettsiae),

Borrelioses, Syphilis, Q-fever, Leptospirosis,…• If Eosinophilia present: quantify (Very high =

Schistosomiasis, Filariasis, Strongyloidiasis, Trichinosis, Fasciolasis); less high (loeffler, …)

In detail: the three killers; in overview: other In detail: the three killers; in overview: other causes (remember Doxy!).causes (remember Doxy!).

•• Exclude IMMEDIATELY three life dangerous Exclude IMMEDIATELY three life dangerous infections: Malaria, Typhoid fever (vacc +/infections: Malaria, Typhoid fever (vacc +/--), ), Amoebic abcess of the liver. Via blood slide, Amoebic abcess of the liver. Via blood slide, Haemocult, USHaemocult, US..

•• If negative: think epidemiologically and geographically; If negative: think epidemiologically and geographically; look at other symptoms.look at other symptoms.

•• DD: katayama, trypanosomiasis, diarrhea + fever, TBC, DD: katayama, trypanosomiasis, diarrhea + fever, TBC, HIV, African tick bite fever e.a. rickettsiosen (cfr HIV, African tick bite fever e.a. rickettsiosen (cfr Southern Europe!), borrelioses, kala azar, dengue, Southern Europe!), borrelioses, kala azar, dengue, virushepatitis (vacc!), brucellose, worms/loeffler, virushepatitis (vacc!), brucellose, worms/loeffler, cosmopolitan diseases (EBV, CMV, Syphilis)cosmopolitan diseases (EBV, CMV, Syphilis)

•• Good Website for DD = www.fevertravel.chGood Website for DD = www.fevertravel.ch

Malaria Burden• Disease Burden

– 300-500 million clinical cases per year

• 80% of cases in Africa

– 1 million deaths per year

• > 90% of deaths in Africa

– Recent decrease due to better FLHS

– 40 million DALYs lost annually

The Malaria Challenge• Regional variation in malaria problem - and response. Influenced by climate and

health service performance

Significant Significant disease disease

burden: poor burden: poor access to access to

health care health care in the in the

AmazonasAmazonas

MDRMDRfalciparumfalciparummalariamalaria

Resurgence in Resurgence in Central Asia & Central Asia & Eastern EuropeEastern Europe

Childhood Childhood dealths in dealths in

subsub-- Saharan Saharan

AfricaAfrica

Vast burden of Vast burden of morbidity & morbidity & economic losseconomic loss

Significant epidemics in the last two years: some reflecting cliSignificant epidemics in the last two years: some reflecting climate changemate change

http://www.itg.be/itg/Uploads/MedServ/2handout2010.pdf

Malaria

• Unicellulair micro-organism : protozoa• Eukaryote• Apical complex

• Sexual replication• Asexual replication

• Transmission: bite female Anopheles mosquito

Malaria

cyclus

Presenting Symptoms

Pitfalls

Pitfalls

82/125 = 65,6% has doctor delay

Le diagnostic

• Goutte épaisse (‘Blood slide’) reste le Golden Standard….: palu oui ou non?

• Frottis mince (‘Thin film’) pour identifier le type. Non-falciparum bcp moins dangereux

• ICT / Tests rapides – mais FP et FN.• PCR pour P. falciparum• Sérologie (études, pas pour diagn)

Premier groupe: Plasmodium

malariae, ovale

et vivax

• Infections benignes, rarement lethales. Attaques de fièvre répétitives chaque 3ème (tertiana P. vivax en ovale) ou 4ème jour (quartana P. malariae)

• PAS souvent typique parmi touristes• Graduellement splénomegalie/anémie• Parfois après des années après le séjour

aux pays tropicaux.

Treatment – Non severe malariaPlasmodium identification and prophylaxis history

Treatment

No definitive identification – no prophylaxis

Malarone (atovaquone 250 mg/proguanil 100 mg) 4 tablets po daily with food for 3 days

No definitive identification - prophylaxis with Malarone

Riamet (arthemether 20 mg/lumefantrine 120 mg) - ECG! – 4 tablets at 0, 8, 24, 36, 48 en 60 hours

P. vivax, ovale or malariae

(except originating from Indonesia and Papua New Guinea)

Nivaquine (chloroquine 100 mg base) 10 base/kg (max 600 mg) loading dose, followed by 5 mg/kg (max 300 mg) at 6, 24 and 48 hoursPrimaquine 30 mg daily for 14 days (G6PD deficiency)

P. falciparum

– no prophylaxis with Malarone

Malarone (atovaquone 250 mg/proguanil 100 mg) 4 tablets po daily with food for 3 days

Adapted from P. De Munter. Pentalfa

Deuxième groupe: paludisme agressif

• Classique: P falciparum• Récent aussi P knowlesi (Asie SE) (chloroquine-

sensible)

• Symptômes en moins d’un mois après retour (bien que exceptionellement plus long)

• Infections potentiellement rapidement léthales: shock, insuffisance rénale, encéphalopathie (‘cerebral malaria’)

• Plutôt fièvre irrégulière (pas toujours haute)

Critères Plasmodium falciparum malaria sévère

• Critères cliniques:– Confusion, diminution de conscience, coma, convulsions:

malaria cérébrale– oligurie < 500ml/24hrs– OAP, collapsus circulatoire, ictère, vomissements+++,

diarrhée + déshydration• Hématologique/biochimique/parasitologique:

– hyperparasitémie:> 5% Glob R infectés ou >250000 parasites/ml

– anémie sévère: Hct<20%; Hgb <7 g/dl– Insuffisance rénale: creatinine >3mg/dl– hypoglycémie (<40mg/dl) ou hyponatrémie(<130 mmol/ml)

Traitement – malaria SévèreTreatment

Severe malaria (Preference) Artesunate (60 mg/vial): 2.4 mg/kg IV bolus, folowed by 2.4 mg/kg at 12 and 24 hours, followed by 2.4 mg daily for 6 days Doxycycline 200 mg daily or Clindamycin 5 mg/kg base QID of (if > 60 kg) 300 mg QID (prenancy or children) for 5 days as soon as possible

Severe malaria (Alternative) Quininehydrochloride (amp 250 mg/2ml or 500 mg/2 ml) 20 mg/kg over 4 hours (cardiac monitoring!), followed by 10 mg/kg over 4 hours IV TIDDoxycycline 200 mg daily or Clindamycin 5 mg base/kg or (if > 60 kg) 300 mg QID (prenancy or children) for 7 days as soon as possible + quinine sulfate (325 mg) 10/kg salt TID

Adapted from P. De Munter. Pentalfa

Qinghaosu (Artemisinin): The Price of Success, N. J. White et al, Science 320 (2008)

Questions pertinentes• Antibiotiques dans la prise en charge d’un

Paludisme (‘malaria algide’: FQ si sepsis Gram-nég)

• Corticosteroides dans la prise en charge d’un Paludisme: NON, pas d’évidence

• Exsanguinotransfusion (5% paras + ‘MOF’, ou 10% sans ‘MOF’). Artesunate: presque plus nécessaire

Pyrethrum et pyréthroides

Imprégner la moustiquaire augmente la  protection

Malaria : prevention

Waiting for the vaccin (‘RTSS’)Rand placebo Contr Trial in different Afr countries. Phase IIb & III in

children aged 5-17 months. Intermediate results demonstrate efficacy of 50% on average

2015 at the earliest (Access? Febrile convulsions?)

Fièvre Typhoide• En général

– Salmonella typhi (Daniel Salmon, syn. Eberth’s bacillus)

– Nouveau nom : Salmonella enterica

sérotype typhi– Salmonella paratyphi A, B, C– L’Homme est le réservoir pour S. typhi– ≠

Spotted Typhus (= Rickettsia)

• Fièvre Typhoide : nom donné par le Dr Pierre Louis (1827), sur base de l’examen ‘post-mortem’

Clinique

• Grande variabilité

• Incubation 7-14 jours (long!) (range 3-60 j)

• Septicemie ‘densité moyenne: 1 bacterie per ml bloed - 2/3 intracellulair’‘densité moyenne 10 bacillen per ml beenmerg’

• Fièvre qui monte progressivement pendant environ 5 j, puis plateau

• Toux seche

• Malaise, céphalées “URTI, LRTI, grippe, malaria”

• Douleurs abdo, diarrhée, constipation (!), vomissements

Ex Clin

• Légère hépatosplenomegalie

• Roseola typhosa (pas souvent)

• Bradycardie relative (signe de Faget)

• Asymptomatic ECG changes

• Typhoid : confusion – très malade x 2 sem

• Avortement spontané

• Parfois perte de cheveux massive

• Troisième semaine: amélioration

Examen Clin• Perforation of terminal ileum (late)

peritonitis

• Hémorrhagie interne

• Abces organique

Diagnostic• Image clinique peu spécifique, mais…• …diagnostic ‘par défaut’ dans la clinique tropicale

quotidienne• Perforation d’ileum terminale = pathognomonique, mais

bien sûr trop tard.• Cultures : sang, copro, urine, moelle (goldstandard)

– Volumes de 15 ml de sang (adultes): hémoculture 60-80% sensibilité

– Moelle 80-95% sensibilité– Coproculture 30% sensibilité (plus haute si plus tard dans la

maladie)

Traitement • Chloramphénicol : pas cher• Quinolones : ofloxacine, ciprofloxacine excellent, minimum 10 jours• Schémas plus courts existent (3-5 jours) : quid sélection résistance?• Céphalosporines : ceftriaxone excellent (Asie!)• Azithromycine• Ampi, amoxy, cotrimoxazole : résistance! • Résistance varie entre régions (Asie; Nepal, Inde!)• Laparatomie si perforation : résection, stomie temporaire, lavage• Drainage abces• ? Dexamethasone 3 mg/kg QDS, totale 8 doses : reduction mortalité

sévère typhoid 50 10%

Prevention

Vaccination : – Typhim®– Vivotif® vaccin oral atténué (vivant)

MAIS: protection 60 à 70%.... Pendant 3 ans

HYGIENE…

Entamoeba histolytica

- transmisison via cystes

- Maladie: trophozoites

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Dysentérie par Amoebes• Epidémio:

voyageurs avontureux ou séjour plus long dans les (sub-)trop

• Cause:Entamoeba histolytica

• Symptomatologie:Selles bien formée + pus/mucoide +/- sang. Ténesmus. Presque pas de fièvre.

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Complication

LiverabcessSometimes shortly after infection,…

– Months (1/2 – 12) to years after an asymptomatic period: breakthrough to pericard, pleura, abdominal cavity

– SS:• intermittent fever with anorexia, loss of weight, fatigue,

malaise. Painfull liver, peritoneal irritation• septic clinical picture with pain in Right

hypochondrium shortly after return– DX: ultrasound liver and serology. Faeces

examination very low sensitivity.

Liveramoebiasis : curved right hypochondr

Liverabcess :

breakthrough

pleura - lung

Traitement

• Amoebicides tissulaires

– Métronidazole (Flagyl®, Anaeromet®)– Tinidazole (Fasigyn®)– Ornidazole (Tiberal®)

SUIVI par le Gabbroral (Paromomycine) comme amoebicide de contact.

Breakthrough liver abcess to

the skin

Pathology

• Skin amoebiasis

In detail: the three killers; in overview: In detail: the three killers; in overview: other causes (remember Doxy!).other causes (remember Doxy!).

•• Exclude IMMEDIATELY three life dangerous infections: Exclude IMMEDIATELY three life dangerous infections: Malaria, Typhoid fever (vacc +/Malaria, Typhoid fever (vacc +/--), Amoebic abcess of the ), Amoebic abcess of the liver. Via blood slide, Haemocult, US.liver. Via blood slide, Haemocult, US.

•• If negative: think epidemiologically and geographically; If negative: think epidemiologically and geographically; look at other symptoms.look at other symptoms.

•• DD: katayama, trypanosomiasis, diarrhea + fever, DD: katayama, trypanosomiasis, diarrhea + fever, TBC, HIV, African tick bite fever e.a. rickettsiosen TBC, HIV, African tick bite fever e.a. rickettsiosen (cfr Southern Europe!), borrelioses, kala azar, (cfr Southern Europe!), borrelioses, kala azar, dengue, virushepatitis (vacc!), brucellose, dengue, virushepatitis (vacc!), brucellose, worms/loeffler, cosmopolitan diseases (EBV, CMV, worms/loeffler, cosmopolitan diseases (EBV, CMV, Syphilis) Syphilis) this list is not exhaustive for FECIthis list is not exhaustive for FECI

•• Good Website for DD = www.fevertravel.chGood Website for DD = www.fevertravel.ch

Syndrome de Loeffler

Trichuris

female

Enterobius

Necator

male /female

Trichuris

male

Trichinella

Ancylostoma

male /female

Régions en haute incidence d’infection Strongyloides stercoralis

50

51

Schistosomiasis

Theodor Maximillian  Bilharz

1825‐1862

52

53

Schistosomiasis : clinical picture

• Swimmer’s itch : cercariële dermatitis• Katayama syndrome : reaction on first eggs in non-immune persons (you and me)

– Fever ± 4-8 weeks after infection (!)– Abd pains - nausea– Cough – asthma-like picture– Eosinophilia (!)– Hepatosplenomegaly

Swimmer’s itch

CT‐scan lung :  Katayama

Serologie and copro/urine initially negative

Leishmaniasis

• 1900: William Boog Leishman• Several sorts of Leishmania,

all are morphologically identical

• But different clinical pictures– Visceral leishmaniasis (Kala Azar)– Cutaneous leishmaniasis – Muco-cutaneous L (South-America)

Leishmaniasis : L. donovani complex

– L. donovani – L. infantum– L. chagasi

Tuberculosis

– Disease known in old times– 1882 : Robert Koch : Bacil of Koch– Acid fast bacilli– Mycobacterium tuberculosis

complex

• M. tuberculosis hominis• M. tuberculosis bovis• M. microti• M. africanus

Sleeping disease - African Trypanosomiasis• Only in Africa: 20 NB - 20 ZB• Estimated: 300.000 cases/y• Transmission via TseTse-fly• Low vectorial capacity (rarely

import)

African Trypanosomiasis• Sometimes small epidemics• Foci depending on epidemiology of insectvector: TSE-TSE-FLY• Western-Africa: Trypanosoma gambiense• Eastern-Africa: Trypanosoma rhodesiense

Clinically: Hematolymphatic

• LNN: Glands in neck (Winterbottom)• Splenomegalie• Fever and headache• Oedemas• Rash• Anemia

Dengue - Chikungunya

First cases of autochthonous dengue fever and chikungunya fever in France: from bad

dream to reality!

Treatment and Prevention

• No specific treatment exists• Prevention

• Vaccination

Rickettsiosen – Typhus

• In general– Very small bacteria– Antibiotics work well– Frequent discovery of new subtypes– zoönoses (except for R. prowazekii)– transmission via arthropodes– entire genome R. prowazekii

known

– Ehrlichia

and Q-fever different but same treatment

24-12-2014 65

Fièvre boutonneuse (Rickettsia conori)

24-12-2014 66

Treponema pallidum: primary stage

Thank you for your attention.