Das ABC der Tropenmedizin
Filip Moerman. 21sten März 2019 (Aachen)
The ABC of TropicalMedicine
≠ Medizin in den Tropen…
Epidemiology of Travel
Loa loa (nicht selten!)
Fever: general approach• RULE OUT the 3 major killers• Detailed travel history + clinical exam• IF NEG: start Doxycycline and perform thoroughblood 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 causes (remember Doxy!).
• Exclude IMMEDIATELY three life dangerousinfections: Malaria, Typhoid fever (vacc +/‐), Amoebic abcess of the liver. Via blood slide, Haemocult, US.
• If negative: think epidemiologically andgeographically; look at other symptoms.
• DD: katayama, trypanosomiasis, diarrhea + fever, TBC, HIV, African tick bite fever e.a. rickettsiosen (cfrSouthern Europe!), borrelioses, kala azar, dengue, virushepatitis (vacc!), brucellose, worms/loeffler, cosmopolitan diseases (EBV, CMV, Syphilis)
• Good Website for DD = www.fevertravel.ch
Malaria Burden• Disease Burden
– 300 million clinical cases per year
• 80% of cases in Africa– 1/2 million deaths per year
• > 90% of deaths in Africa
– Recent decrease due to better FLHS
– 30 million DALYs lost annually
The Malaria Challenge• Regional variation in malaria problem ‐ and response. Influenced by climate and health service performance
Significant disease
burden: poor access to
health care in the
Amazonas
MDRfalciparummalaria
Resurgence in Central Asia & Eastern Europe
Childhood dealths in
sub-Saharan
Africa
Vast burden of morbidity & economic loss
Significant epidemics in the last two years: some reflecting climate change
Why travel prophylaxis in Africa?
Malaria
• Unicellulair micro‐organism : protozoa• Eukaryote• Apical complex
• Sexual replication• Asexual replication
• Transmission: bite female Anophelesmosquito
Malaria
cyclus
Presenting Symptoms
Pitfalls
Pitfalls
82/125 = 65,6% has doctor delay
Diagnosis
• Blood slide remains Golden Standard….: malaria yes or no?
• Thin film for species identification. Non‐falciparum far less dangerous
• ICT / rapid tests – but FP & FN• PCR for P. falciparum• Serology (studies, not for diagnostic purposes)
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First group:Plasmodium malariae, ovale et vivax
• Infections rarely lethal. Attacs of fever every3rd or 4th day (tertiana P. vivax en ovale; quartana P. malariae)
• NOT common amongst tourists• Graduel splenomegaly and anaemia• Can sometimes occur YEARS after return!
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
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Second group: severe malaria
• Classic: P falciparum• Recently also P knowlesi (Asia SE) (chloroquine‐sensitive)
• Symptoms usually less than one month after return, occasionally longer
• Infection potentially lethal! Shock, kidney failure, encephalopathy (‘cerebral malaria’)
• Usually irregular fever pattern
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Criteria for severe Plasmodiumfalciparummalaria
• Clinical criteria:– Confusion, decreased conscience, coma, convulsions:
cerebral malaria– oliguria < 500ml/24hrs– ALO, circulatory collapse , jaundice, vomitting+++, diarrhea
+ dehydration• Lab‐wise:
– hyperparasitemia:> 5% RBC infected or >250000 parasites/ml
– Severe anaemia: Hct<20%; Hgb <7 g/dl– Kidney failure: creatinine >3mg/dl– hypoglycemia (<40mg/dl) or hyponatremia(<130 mmol/ml)
Treatment of severe malariaTreatment
Severe malaria (Preference) Artesunate (60 mg/vial): 2.4 mg/kg IVbolus, 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
Kinabast in wine as former malaria treatment malaria (bitter taste – Herr Schweppe 1780)
Qinghaosu (Artemisinin): The Price of Success, N. J. White et al, Science 320 (2008)
Some pertinent reflections
• Antibiotics: only in ‘algide malaria’: FQ ifsepsis by G‐ bact)
• Corticosteroids: NO, no evidence
• Exsanguinotransfusion (5% paras + ‘MOF’, or 10% without ‘MOF’). Since Artesunate: hardlyever necessary
Impregnate your mosquito net!
Malaria : prevention
the vaccin: MosquirixRand placebo Contr Trial in different Afr countries. Phase IIb & III in children aged
5‐17 months. Intermediate results and recent final results are disappointing: strongly decreased 7‐year‐efficacy after transitory improvement. Rebound
with higher‐than‐average exposure to malaria parasites.Olotu, et al. 2016
Fliegenkrankheit!
Typhoid fever
In general– Salmonella typhi (Daniel Salmon, syn. Eberth’s bacillus)– New name : Salmonella enterica sérotype typhi– Salmonella paratyphi A, B, C– Humans are the reservoir for S. typhi– ≠ Spo ed Typhus (= Ricke sia)
Clinically
• Big variability
• Incubation 7‐14 days (long!) (range 3‐60 j)
• Septicaemia ‘
• Fever that increases gradually for 5 d, than stagnating
• Dry cough
• Sick patient, headache “URTI, LRTI, flu‐like, malaria”
• Abdo pains, diarrhea, constipation (!), vomiting, becoming typhoid
Clin exam
• +/‐ Hepatosplenomegalie
• Roseola typhosa (not often)
• Relative bradycardia (Faget’s sign)
• Asymptomatic ECG changes
• Typhoid : confusion
• Spontaneous abortion
• Sometimes massive hair loss
Improvement after week 3
Diagnosis
• Non specific clinical picture, but default diagnosis• Perforation of ileum = pathognomonic but too late of course.
• Cultures : blood (!), stool, urine, bone marrow (goldstandard)
Treatment • Chloramphénicol : cheap• Quinolones : ofloxacine, ciprofloxacine excellent, minimum 10 days• Cephalosporines : ceftriaxone excellent (Asia!)• Azithromycine• Ampi, amoxy, cotrimoxazole : resistant! • Resistance especially in Asia; Nepal, India!• Laparatomy if perforation • ? Dexamethasone 3 mg/kg QDS, totale 8 doses
Prevention
Vaccination : – Typhim®– Vivotif® vaccin oral atténué (vivant)
BUT: protection 60 à 70%.... during 3 years
HYGIENE…
Geographie, Klima und Krankheit
Bartonella / Carrion’s disease.Mücken
Hautmanifestation Tödliche Anämie
Entamoeba histolytica
- transmisison via cystes
- Maladie: trophozoites
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Amoebic dysenteria• Epidemiology:adventurous travelers that stay longer in (sub)‐tropical regions
• Cause:Entamoeba histolytica
• Symptomatology:Stool not fully diarrheic + pus/mucoid +/‐ blood. Tenesmus. Hardly any fever
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Complication
LiverabcessSometimes shortly after infection,…
– Months (1/2 – 12) to years after an asymptomaticperiod: breakthrough to pericard, pleura, abdominalcavity
– SS:• intermittent fever with anorexia, loss of weight, fatigue, malaise. Painfull liver, peritoneal irritation
• septic clinical picture with pain in Right hypochondriumshortly after return
– DX: ultrasound liver and serology. Faeces examination very low sensitivity.
Liveramoebiasis : curved right hypochondr
Liverabcess :
breakthrough
pleura ‐ lung
Treatment
• Amoebicides (Tissue)
– Metronidazole (Flagyl®, Anaeromet®)– Tinidazole (Fasigyn®)– Ornidazole (Tiberal®)
FOLLOWED by Gabbroral (Paromomycine) as second amoebicide (contact).
Breakthrough liver abcess to the skin
Geographie, Klima und KrankheitBacterielle Spuren
Anthrax
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
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
eine Auswahl aus der Welt der Würmer
• Nematoda• Cestoda• Trematoda• Filaria
Trichuris female Enterobius Necator male /female
Trichurismale Trichinella Ancylostomamale /female
Löffler (Loeffler) syndrome‐ Described by Löffler in 1932
‐ Transient respiratory illness with eosinophilia and Rx infiltrates
‐ Often 10‐16 days after contamination with Ascaris eggs
‐ Symptoms due to larval lung passage or hypersensitivity reaction ?
‐ Self‐limiting 3 days ‐ 3 weeks
‐ Dry cough, slight fever, wheezing, dyspnoe
Löffler syndrome
Consolidation with surrounding ground‐glass opacity in the left lower lobe. Dilated airways are observed within the lesion.
Strongyloides stercoralis
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Schistosomiasis
Theodor Maximillian Bilharz
1825‐1862
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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
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Cestoden : Taenia saginata– Rundsvlees bevat cysticerci – Ook kamelen en rendieren– Volwassen lintworm ongewapend– Adulte worm in darmlumen van mens
– Mobiele proglottiden– R/ Niclosamide – praziquantel
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Zoetwaterkrabben Paragonimus
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Filariosen
• Lymfatische filariosen• Onchocercose• Loasis• Mansonellosis• Dirofilariosis• ( Guinea Worm)
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Lepra
Epizentrum liegt in India
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Tuberculoide lepra (paucibacillair), diff diagnose granuloma annulare
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Verdickte Nerven
‐ Hals (N. auricularis)
‐ Hand (cutane tak N. medianus)
‐ Knie (N. fibularis)
‐ Supra‐orbital (N. supraorbitalis)
‐ Ellenbogen (N. ulnaris)
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Leprosy : colder areas (back of hand) more affected than warm areas (palms)
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Mutilations through leprosy
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Lepra : Diagnose, kliniek
• Huid : type letsel, ontkleuring, infiltratie, randen• Huid :anhydrose, gevoelloos, verminderdebeharing, …
• Zenuwuitval : eerst T° > fijne tast > pijn• MICROBIOLOGY
• Complicaties: besmette ulcera, osteomyelitis, botresorptie, oogletsels, testisdestructie
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Behandelung Lepra
• Keine monotherapie• Dapsone• Rifampicine• Clofazimine (Lamprene)
Verkleuring urine : rifampicine, clofazimine
Rabies
Reeds gevreesd in vroegere eeuwen
TOLLWUT : geografie– Weltweit, 50.000 Tote jährlich– Nicht in Neu Seeland, West Maleisia, Bali, Hawaii, UK
RABIES : Klinik
• Incubatie gemiddeld 20‐90 dagen
• Extreme incubatietijden : 6 dagen tot 6 jaar
• Beten dicht bij gelaat hebben kortere incubatieduur
• Prodroma gedurende 2‐10 dagen
Furieuze rabiës• Angst – hyperactief
• Intermittente desorientatie – hallucinaties
• Destructie inhibitoire centra
• Spasmen : keel, larynx
• Hydrofobie
• Speekselvloed
Diff. Diagnose paralytische rabiës• Polio
• Guillain‐ Barré
• Difterie
• Elapidenbeet (speekselvloed door sliklast)
• Encefalopathie: metabool, hypoxisch, toxisch
• Syndroom van Reye: braken en lever‐
• Botulisme (afdalend, geen t°, droge mond, mydriasis)
RABIES : Preventie
• Geen wilde dieren aanraken
• Loslopende honden doden
• Honden (huisdieren) vaccineren
• Vaccinatie wilde dieren
• Hoog risico mensen vaccineren
Boosterinjecties
Antistoftiter
Wasbeer verorbert oraal vaccin in lokaas
Scorpions
• 1400 species
• 20 potentially lethal
• Nearly all fatal stings occur in :– Mexico– Brazil, Trinidad– Maghreb– Southern Africa– Middle East
– India
Opisthoptalmus carinatus
Parabuthus granulatus
Triangular sternal plate
Spiders : dangerous species
• Loxosceles sp.
• Latrodectus sp.
• Atrax sp.
• Phoneutria sp.
General
• 2700 snake species
• 200 potentially lethal
• Diverse biotopes
• Not in Chile, Madagaskar, New Zealand
Snake familiesFangs
• Viperidae : mobile‐front• Crotalidae : mobile‐front• Elapidae : fixed‐front• Hydrophiidae : fixed‐front• Colubridae : fixed‐back• Atractaspididae : sideways
Note : Loreal pit Pit vipers
Venom gland• Main and accessory venom glands• Fast, active emptying (muscle contraction)• Slow emptying (Duvernoy’s gland) in colubrids
Elapids : example• King cobra
Initial generalised symptoms• Fear• Dizziness • Nausea and vomiting• Malaise• Weakness
Neurological symptoms
• paresthesias• ptosis• ophtalmoplegia• diplopia and blurred vision• metallic taste• myokymia
• dysphagia• slurred speech and aphony• general paralysis• respiratory arrest
Ptosis
Hemostasis ‐ coagulation effects• Procoagulantia• Anticoagulantia
• Trombine‐like effect (eg. crotalase) • Coagulation V + X factor activation (eg. Russell’s viper)• Increase fibrinolysis (eg. lebetase; Vipera
lebetina)
• Thrombocyt‐aggregation or –inhibition• Endothelial damage
DIC
Treatment : before hospital• Diminish fear• Immobilise limb with splint• Compressive elastic bandage• Rinse eyes if relevant
• Transport to hospital
• Avoid electroshock• Avoid arterial tourniquet• Avoid cutting or bleeding• ?? Mechanical vacuum “Extractor” doubtful
Prepare (1)• Plasma‐expander• Neostigmine 1 mg: blocks acetylcholinesterase• Atropine 0,6 mg : inhibition muscarine receptors
Locate antivenin : monovalentpolyvalent
Adrenaline or ephedrine SteroidsAntihistaminicum (?)
Thank you for your attention.Danke für Ihre Aufmerksamkeit
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