Global Infectious Diseases: Four Steps Toward a Differential Diagnosis





Symptoms and Signs


Fever




  • 1.

    Etiologies to think about



    • a.

      Malaria, visceral leishmaniasis, African trypanosomiasis, Chagas’ disease, relapsing fever, rickettsial infections, arboviral diseases (e.g., dengue fever), rabies, typhoid/paratyphoid, leptospirosis, tuberculosis, human immunodeficiency virus (HIV).



  • 2.

    Things to do routinely



    • a.

      Thick blood films to evaluate for malaria. In endemic areas, remember fever may be caused by something other than malaria in patients with (+) films. Malaria can cause acute, chronic, or relapsing fever. Malaria is highly suspicious when fevers occur every (q) 48–72 hours but may usually take 2 weeks for schizontocytes to become synchronized. Plasmodium falciparum rarely develops such a fever pattern.


    • b.

      Complete blood count with differential (CBC with differential [w/ diff])



      • i.

        Malaria will usually have normal or low white blood cell count (WBC), often with thrombocytopenia.


      • ii.

        With leukocytosis (especially with left shift), even patients with a (+) film are very likely to have a cause other than malaria.



    • c.

      Begin a fever chart: 4-hour intervals are most useful.


    • d.

      Check for rash, lymphadenopathy (LAD), splenomegaly, anemia, jaundice, polyarthritis, and so on.




Acute Fevers (<2 Weeks)




  • 1.

    Acute fever + negative malarial film



    • a.

      Polymorphonuclear leukocytosis (PNL)?



      • i.

        Yes: pyogenic infection, leptospirosis, relapsing fever, amebic hepatic abscess, collagen-vascular disease (collagenosis)


      • ii.

        No: viral infection, rickettsial infection, typhoid




        • PNL often does develop after onset of severe viral infections such as Lassa fever.



        • Typhoid may be of gradual onset with remittent fever (never quite fully defervesces).





  • 2.

    Acute fever + negative malarial film + PNL + localizing symptoms (sx)?



    • a.

      Sore throat: various pharyngitis etiologies, remember Corynebacterium diphtheriae


    • b.

      Pulmonary: various pneumonial etiologies


    • c.

      Pain, swelling in joint: pyogenic arthritis


    • d.

      Urinary tract infection (UTI) sx + flank/back pain: pyelonephritis


    • e.

      Headache, neck stiffness: meningitis


    • f.

      Bone pain: osteomyelitis


    • g.

      Bloody diarrhea: bacterial dysentery ( Shigella , Salmonella , Campylobacter , enteroinvasive Escherichia coli , Yersinia , etc.)


    • h.

      Local lymphadenopathy: local infection, plague


    • i.

      Sharply defined cutaneous inflammation: erysipelas


    • j.

      Poorly defined subcutaneous inflammation: cellulitis



  • 3.

    Acute fever + negative malarial film + leukocytosis but no localizing sx?



    • a.

      Septicemia: Staphylococcus , Streptococcus , Meningococcus , endocarditis


    • b.

      Leptospira , Borrelia spp.



      • i.

        Leptospirosis: look for jaundice, renal involvement


      • ii.

        Tick-borne relapsing fever


      • iii.

        Louse-borne relapsing fever



    • c.

      Nontyphoid Salmonella septicemia: may be paucity of gastrointestinal (GI) sx; rose spots, splenomegaly possible



  • 4.

    Acute fever + negative malarial film, but no PNL?



    • a.

      Consider virus, rickettsia, typhoid



      • i.

        Double-humped fever pattern suggests virus, especially dengue.




        • First fever represents viremia; second fever represents antibody-mediated viral destruction, perhaps with cells.



      • ii.

        Significant space-time clustering suggests nonspecific viral source.




        • With rickettsial diseases, look for adenopathy, possibly an eschar.



        • With typhoid, pay attention to abdominal sx.





  • 5.

    Acute fever + right upper quadrant (RUQ) tenderness?



    • a.

      Obtain CBC w/ diff, malarial film, liver function tests (LFTs).


    • b.

      Ultrasound (U/S) liver, gallbladder


    • c.

      Amebic sensitized particle agglutination test (SPAG); often (–) in early amebic liver abscess



      • i.

        Typically, ALA with (w/) leukocytosis, increased erythrocyte sedimentation rate (ESR).



    • d.

      ESR


    • e.

      Hepatitides panel



  • 6.

    Acute fever + hemorrhagic rash?



    • a.

      Consider viral hemorrhagic fevers (dengue, Crimean-Congo, etc.) meningococcemia.


    • b.

      Can be fatal w/in hours if meningococcemia; aspirate from spots should be examined for meningococci.


      Note that cases of acute fevers may be accompanied by nonhemorrhagic rashes. A notable exception is malaria (rarely causes a rash); a drug eruption in treated malaria patients could still occur.



  • 7.

    Acute fever + anemia?



    • a.

      Although anemia is common in developing areas (diet, sickle cell diseases (SCDz), thalassemia, glucose-6-phosphate dehydrogenase [G6PD] deficiency), consider malaria, babesiosis, and bartonellosis specifically.




Chronic Fever (>2 Weeks)




  • 1.

    Overlap



    • a.

      Borrelia infections, typhoid, and malaria may be seen as acute or chronic.



  • 2.

    Chronic fever + PNL



    • a.

      Typically sustained fever



      • i.

        Deep sepsis


      • ii.

        ALA


      • iii.

        Erythema nodosum leprosum



    • b.

      Typically relapsing fever



      • i.

        Cholangitis


      • ii.

        Relapsing fever




  • 3.

    Chronic fever + eosinophilia



    • a.

      Invasive Schistosoma mansoni , Schistosoma japonicum


    • b.

      Invasive Fasciola hepatica


    • c.

      Acute lymphangitic exacerbations of Wuchereria bancrofti , Brugia malayi


    • d.

      Gross visceral larva migrans ( Toxocara canis )



  • 4.

    Chronic fever + neutropenia



    • a.

      Malaria


    • b.

      Disseminated tuberculosis


    • c.

      Visceral leishmaniasis


    • d.

      Brucellosis



  • 5.

    Chronic fever + normal WBC



    • a.

      Localized tuberculosis


    • b.

      Brucellosis


    • c.

      Secondary syphilis


    • d.

      Trypanosomiasis


    • e.

      Toxoplasmosis


    • f.

      Subacute bacterial endocarditis (SBE)


    • g.

      Chronic meningococcal septicemia



  • 6.

    Chronic fever + variable WBC



    • a.

      Tumors


    • b.

      Drug reactions


    • c.

      Other fever of unknown origin differential diagnosis (FUO ddx)



  • 7.

    Chronic fever w/ relapsing pattern



    • a.

      Malaria


    • b.

      Visceral leishmaniasis


    • c.

      Trypanosomiasis, especially African


    • d.

      Relapsing fever ( Borrelia spp.)


    • e.

      Brucellosis


    • f.

      Filariasis


    • g.

      Cholangitis


    • h.

      Subacute bacterial endocarditis


      Note that many other diseases may have a relapsing pattern; these frequently do.



  • 8.

    Fever of unknown origin w/u for tropical and/or developing areas



    • a.

      CBC w/ diff, repeated malarial films


    • b.

      Chest x-ray (CXR)


    • c.

      Urine analysis (U/A)


    • d.

      Repeated blood culture (cx)


    • e.

      Liver biopsy (bx), to include tuberculosis cx


    • f.

      Marrow bx, to include cx and animal inoculation


    • g.

      IVP


    • h.

      Mantoux test to 1, 10, and 100 tuberculin units


    • i.

      Brucella cx and antibody titers


    • j.

      Toxoplasma dye test


    • k.

      Rickettsial and viral antibodies


    • l.

      Serum assays for systemic lupus erythematous (SLE), and antinuclear factor


    • m.

      ESR


      Note that disseminated tuberculosis is a common cause; remember it can manifest in the spine (Pott’s dz), bowel (enteritis), abdominal viscera, and as ascites and/or peritonitis.



  • 9.

    Chronic fever + normal WBC + normal ESR



    • a.

      Consider spurious fever or toxoplasmosis



  • 10.

    Chronic fever and HIV infection



    • a.

      The virus itself can cause fever, but opportunistic organisms should be ruled out (R/O’d), especially Salmonella , Pneumococcus , and tuberculosis.




Abdominal Pain




  • 1.

    Abdominal pain



    • a.

      Amebiasis


    • b.

      Anisakiasis


    • c.

      Bacterial enteritis ( Salmonella, Shigella, Yersinia ; especially right lower quadrant [RLQ]), Campylobacter (can be very intense)


    • d.

      Fascioliasis


    • e.

      Giardiasis


    • f.

      Hymenolepiasis


    • g.

      Strongyloidiasis


    • h.

      Taeniasis


    • i.

      Typhoid


    • j.

      Abscess (hepatic, splenic)


    • k.

      Pancreatitis


    • l.

      Hepatitis


    • m.

      Other non-ID causes




Diarrhea




  • 1.

    Historical considerations



    • a.

      Duration?



      • i.

        Acute <2 w, chronic >2 w.



    • b.

      Fever?



      • i.

        May be resulting from enteritis, dehydration, or extraenteric source (i.e., malaria)



    • c.

      Appearance? Blood? Mucous?



      • i.

        Blood may signify colonic ulceration, especially in developing nations where hemorrhoids are less common.



    • d.

      Frequency?



      • i.

        Mainly ask to gauge need for hydration.



    • e.

      Abdominal pain?



      • i.

        Most acute with bacterial organisms ( Campylobacter, Shigella , etc.), necrotizing toxin ( Clostridium perfringens ), or w/ electrolyte imbalances in cholera.



    • f.

      Tenesmus?



      • i.

        Suggests rectal inflammation, sometimes seen with shigellosis.



    • g.

      Vomiting?



      • i.

        May indicate systemic illness, preformed toxins, or intestinal infections. In nonimmune patients, may be a sx of malaria, especially P. falciparum .



    • h.

      Others w/ similar sx?



      • i.

        For obvious epidemiologic reasons




  • 2.

    The three essential questions: Duration? Fever? Blood?



    • a.

      Acute + Fever + Blood



      • i.

        Bacterial dysentery/enterocolitis ( Campylobacter , Salmonella , enteropathogenic E. coli , etc.)




        • Macrophages in stool may be mistaken for amoebae.



        • Shigella : suggested by sheets of PMNs in stained smears; antibiotic (abx) resistance is an increasing problem



        • Campylobacter : tends to be more painful and lasts longer than other bacteria and may be dx’d under dark-field microscopy of wet specimens (small spirillum-like organisms with characteristic movement)



        • Salmonella : increased risk if meat ingested; stool is only rarely grossly bloody as main pathology is in small bowel



        • Enterotoxigenic E. coli may be complicated by hemolytic-uremic syndrome.



        • Vomiting is common with any/all of these organisms.


          Note that in outbreaks with limited resources, it is reasonable to provide IV hydration to the very ill and oral rehydration to the mildly ill, and provide chemotherapy (tetracycline, ciprofloxacin) only selectively. Regardless of bacterial species, almost all cases are self-limiting, requiring only hydration/electrolyte management and supportive care. (See Chapter 3 for more details.)


          Note that Bacillary dysentery not uncommonly accompanies visceral leishmaniasis. Falciparum malaria has been reported to cause bloody diarrhea.




    • b.

      Acute + fever, but no blood



      • i.

        Salmonella enteritis.




        • Usually in food-borne outbreaks; food usually looks and tastes fine. In contrast to shigella, person-to-person spread rare because it is water-borne transmission.



        • Incubation period 12 to 48 hours. Onset usually w/ fever and chills, followed by vomiting and diarrhea. A zoonosis of mammals, reptiles, and birds, more than 100 spp. exist; invasive forms may mimic typhoid, especially in acquired immunodeficiency syndrome (AIDS); HIV (+) pts should get abx.



        • Consider abx for anyone w/ invasive dz: fever >48 hours, rose spots (pink macules scattered over trunk), splenomegaly.



        • Relapsing salmonellosis associated w/ Schistosoma mansoni , biliary dz



        • Sickle-cell pts should always get abx at increased risk for Salmonella osteomyelitis.



      • ii.

        Malaria, especially P. falciparum.


      • iii.

        Almost any infection in a child


      • iv.

        Mild (nonulcerating) shigellosis


      • v.

        Campylobacter infection


      • vi.

        In children especially, fever with diarrhea may be indicative of an infection elsewhere than in the gut.



    • c.

      Acute, no fever, but + blood



      • i.

        Entamoeba histolytica (or other amoeba)




        • Most common cause



      • ii.

        Balantidium coli


      • iii.

        Acute schistosomiasis ( S. mansoni , S. japonicum )




        • Check for eosinophilia: early on, fever may be present



      • iv.

        Trichuriasis




        • Most common in children w/ pica or institutionalized adults.



      • v.

        Ulcerative colitis or other inflammatory bowel disease




        • Rarer in developing nations than in Europe, United States.



      • vi.

        Pseudomembranous colitis




        • From Clostridium difficile , usually after abx course.




    • d.

      Acute, but no fever, no blood



      • i.

        Most often preformed toxins in food




        • S. aureus : usually from hands of food preparer, but occasionally from milk of cow w/ mastitis.



        • Incubation period short: 2 to 6 hours. Vomiting is soon followed by diarrhea which can be almost as severe as in cholera. Intuitively, abx are useless.



      • ii.

        Enterotoxigenic E. coli : most important cause of travelers’ diarrhea, conferring prolonged immunity to victims; most often in children and tourists/visitors (becomes part of normal flora in residents after initial infection). Widespread antibiotics (abx) resistance except to newer fluoroquinolones.


      • iii.

        Loperamide (Imodium) and other antimotility agents are often used for convenience but should never be given for bloody diarrhea or to children—even when used for properly selected pts, may delay elimination of pathogen. Some prophylaxis is afforded by taking bismuth subsalicylate two × 262 mg po, chewed, qid. Abx should not be used for prophylaxis routinely because of possible side effects and resistance induction; exceptional pts can use a regimen such as ciprofloxacin 500 mg po qd. (See Chapter 3 for more details.)


        C. perfringens : a significant inoculum is needed, but may occur with various foods, especially meats, left at ambient temperature. Heat-resistant spores can also cause sx in well-cooked foods. Type A strains produce a toxin which causes diarrhea with abdominal cramps. Type C strains are enteroinvasive and can produce full-thickness intestinal wall necrosis; these are the organisms responsible for “pig bel” in Papua New Guinea following communal pig feasts. Severe cases may present with abdominal pain and ileus rather than diarrhea, possibly leading to obstruction and/or peritonitis. A vaccine is available for type C strains.




        • Cholera



        • Consider with voluminous watery stool in the midst of a diarrheal outbreak or when diarrhea is associated w/ muscle cramps.



        • Enterotoxigenic E. coli may mimic this as well.



      • iv.

        Viral




        • Rotaviral (and others) gastroenteritis is common in children worldwide. Treatment is supportive.



      • v.

        Toxins




        • Foods which are new to visitors may occasionally cause diarrhea (i.e., capsaicin), but enterotoxigenic E. coli or S. aureus are more commonly responsible. Incubation is very short, and the illness is short-lived.




    • e.

      Persistent (after an acute attack) diarrhea



      • i.

        Disaccharidase deficiency following infectious diarrhea


      • ii.

        Giardiasis, amebiasis


      • iii.

        Tropical sprue


      • iv.

        HIV, especially with Cryptosporidium or Isospora spp.


      • v.

        Enteropathogenic E. coli , causing long-lasting damage to enterocyte brush border.


      • vi.

        Inflammatory bowel disease. Infectious diarrhea may precede onset of ulcerative colitis.


      • vii.

        Tuberculous enteritis



    • f.

      Chronic + fever



      • i.

        Tuberculous enteritis




        • May be marked wasting, acid-fast bacillus (AFB) (+) sputum



      • ii.

        Visceral leishmaniasis




        • May be caused by direct gut mucosa involvement or to variety of secondary infections



      • iii.

        Schistosomiasis ( S. japonicum , S. mansoni )




        • Fever in early stages only; look for eosinophilia



      • iv.

        Yersiniosis


      • v.

        AIDS



    • g.

      Chronic: fever + blood



      • i.

        Amebiasis


      • ii.

        Balantidiasis


      • iii.

        Schistosomiasis ( S. japonicum , S. mansoni )


      • iv.

        Trichuriasis



    • h.

      Chronic: fever–blood


      Note that fatty diarrhea is common.



      • i.

        Giardiasis




        • Diarrhea resolves spontaneously in a few months.



      • ii.

        Celiac dz.




        • Gluten enteropathy: accompanying iron deficiency is common



      • iii.

        Tropical sprue




        • An accompanying megaloblastic anemia is common (low folate and/or B12)



      • iv.

        Strongyloidiasis




        • Upper abdominal pain early on, eosinophilia suggestive. Gradually becomes a commensal infection.



      • v.

        Capillaria philippinensis




        • Clinical pictures simulate severe strongyloidiasis and will often not resolve spontaneously. May lead to fatally severe malabsorption.



        • Small bowel lymphoma



        • Often diffusely infiltrates bowel walls, making intestine rigid. Often responds to chemotherapy.



      • vi.

        Chronic pancreatitis or tropical pancreatitis


      • vii.

        Cryptosporidiosis




        • Usually self-limiting but can be fatal in immunocompromised pts.






Organomegaly




  • 1.

    Hepatomegaly



    • a.

      Amoebic liver abscess


    • b.

      Clonorchiasis


    • c.

      Echinococcosis


    • d.

      Fascioliasis


    • e.

      Histoplasmosis


    • f.

      Malaria


    • g.

      Leishmaniasis, visceral


    • h.

      Opisthorchiasis


    • i.

      Schistosomiasis


    • j.

      Toxocariasis


    • k.

      Trypanosomiasis, American


    • l.

      Typhoid



  • 2.

    Splenomegaly



    • a.

      Leishmaniasis, visceral


    • b.

      Malaria


    • c.

      Schistosomiasis


    • d.

      Trypanosomiasis, American


    • e.

      Typhoid



  • 3.

    Variable (may see hepatic tenderness instead of either or all three)



    • a.

      Typhoid


    • b.

      Brucellosis


    • c.

      Relapsing fever


    • d.

      Leptospirosis


    • e.

      Rocky Mountain spotted fever


    • f.

      Q fever (chronic)


    • g.

      Psittacosis


    • h.

      Hepatitis


    • i.

      Yellow fever


    • j.

      Malaria


    • k.

      Toxoplasmosis


    • l.

      Leishmaniasis, visceral (kala-azar)


    • m.

      Amebic abscess


    • n.

      Schistosomiasis


    • o.

      Liver flukes


    • p.

      Visceral larva migrans




Jaundice




  • 1.

    Jaundice



    • a.

      Hepatitis


    • b.

      Leptospirosis


    • c.

      Malaria ( P. falciparum )




Respiratory Complaints




  • 1.

    Cough



    • a.

      Ascariasis


    • b.

      Bacterial or chlamydial pneumonia


    • c.

      Lassa fever


    • d.

      Paragonimiasis


    • e.

      Pertussis


    • f.

      Plague


    • g.

      Psittacosis


    • h.

      Tuberculosis


    • i.

      Viral upper respiratory infection (URI), postnasal drip, etc.



  • 2.

    CXR anomalies



    • a.

      Blastomycosis


    • b.

      Coccidioidomycosis


    • c.

      Echinococcosis


    • d.

      Histoplasmosis


    • e.

      Melioidosis


    • f.

      Pneumocystosis


    • g.

      Tuberculosis



  • 3.

    Pharyngitis



    • a.

      Diphtheria


    • b.

      Mycoplasma or chlamydia


    • c.

      Streptococcus


    • d.

      Viral



  • 4.

    Pneumonia



    • a.

      AIDS


    • b.

      Anthrax


    • c.

      Ascariasis


    • d.

      Blastomycosis


    • e.

      Coccidioidomycosis


    • f.

      Histoplasmosis


    • g.

      Legionellosis


    • h.

      Paragonimiasis


    • i.

      Plague


    • j.

      Pneumococcosis


    • k.

      Psittacosis


    • l.

      Q fever


    • m.

      Scrub typhus


    • n.

      Strongyloidiasis


    • o.

      Tuberculosis




Headache, Other Central Nervous System Complaints




  • 1.

    Altered mental status



    • a.

      Acute psychosis


    • b.

      Trypanosomiasis, African (can coma)


    • c.

      Relapsing fever


    • d.

      Leptospirosis


    • e.

      Rickettsial dz (esp. Rocky Mountain spotted fever)


    • f.

      Psittacosis


    • g.

      Tuberculosis


    • h.

      Viral encephalitis (can coma)


    • i.

      Malaria ( P. falciparum —can coma)


    • j.

      African trypanosomiasis


    • k.

      Impending sudden unexplained adult death


    • l.

      Meningococcal meningitis


    • m.

      Rabies


    • n.

      Tick-borne encephalitis



  • 2.

    Neurologic lesion with localizing sign(s)



    • a.

      Angiostrongyliasis


    • b.

      Botulism


    • c.

      Cryptococcosis


    • d.

      Cysticercosis (seizures)


    • e.

      Diphtheria


    • f.

      Echinococcosis


    • g.

      Gnathostomiasis


    • h.

      Lyme disease


    • i.

      Meningococcal meningitis


    • j.

      Naegleria/Acanthamoeba infection


    • k.

      Paragonimiasis (seizures)


    • l.

      Poliomyelitis


    • m.

      Schistosomiasis (seizures w/ S. japonicum )


    • n.

      Strongyloidiasis, disseminated


    • o.

      Tetanus




Skin Lesions




  • 1.

    Analgesia



    • a.

      Leprosy



  • 2.

    Anal pruritis



    • a.

      Enterobiasis


    • b.

      Strongyloides



  • 3.

    General pruritis



    • a.

      Onchocerciasis


    • b.

      Toxocariasis


    • c.

      Any etiology of jaundice


    • d.

      Filarial disease (Loa, Oncho, Mansonella)



  • 4.

    Rash



    • a.

      Chikungunya fever


    • b.

      Childhood exanthems


    • c.

      Dengue


    • d.

      Enteroviral infections


    • e.

      Filariasis (may cause recurrent cellulitis)


    • f.

      Glanders


    • g.

      Gonococcemia


    • h.

      Leptospirosis


    • i.

      Meningococcemia


    • j.

      Melioidosis (multiple pustular or necrotic lesions)


    • k.

      Plague


    • l.

      Rat-bite fever


    • m.

      Relapsing fever


    • n.

      Rickettsial diseases


    • o.

      Syphilis (secondary): especially on palms/soles, as does rubella and measles


    • p.

      Toxoplasmosis


    • q.

      Typhoid: 10% with “rose spots”



  • 5.

    Swelling or erythema



    • a.

      Gnathostomiasis (migratory)


    • b.

      Loiasis (migratory)


    • c.

      Lyme disease


    • d.

      Pinta (?)


    • e.

      Wuchereria



  • 6.

    Ulcer, eschar, or abscess



    • a.

      Anthrax (eschar with surrounding edema)


    • b.

      Buruli ulcer (ulcer)


    • c.

      Dracunculiasis


    • d.

      Glanders


    • e.

      Leishmaniasis, cutaneous (ulcer)


    • f.

      Lymphogranuloma venereum


    • g.

      Mycobacterial ( Mycobacterium ulcerans , M. marinum ) (ulcer)


    • h.

      Mycosis (blastomycosis, coccidioidomycosis, sporotrichosis)


    • i.

      Rickettsial—eschar—(scrub typhus, rickettsialpox, boutonneuse fever, Queensland tick typhus, North Asian tick typhus, etc.)


    • j.

      Syphilis


    • k.

      Tropical ulcer


    • l.

      Trypanosomiasis, American


    • m.

      Trypanosomiasis, African


    • n.

      Tularemia


    • o.

      Yaws



  • 7.

    Nodules



    • a.

      Bartonellosis


    • b.

      Cysticercosis


    • c.

      Onchocerciasis


    • d.

      Myiasis


    • e.

      Hansen’s disease


    • f.

      Elephantiasis


    • g.

      Chromoblastomycosis


    • h.

      Leishmaniasis



  • 8.

    Hypopigmented



    • a.

      Leprosy


    • b.

      Onchocerciasis


    • c.

      Tinea versicolor


    • d.

      Vitiligo


    • e.

      Mansonella streptocerca


    • f.

      Pinta



  • 9.

    Hyperpigmented



    • a.

      Pinta


    • b.

      Onchocerciasis ( sowda )




Hematologic Abnormalities




  • 1.

    Anemia



    • a.

      Diphyllobothriasis (typically megaloblastic)


    • b.

      Histoplasmosis


    • c.

      Hookworm infection (typically microcytic)


    • d.

      Iron deficiency, nutritional origin (typically microcytic)


    • e.

      Malaria (typically microcytic)


    • f.

      Tropical sprue


    • g.

      Visceral leishmaniasis


    • h.

      Pernicious anemia (typically megaloblastic)



  • 2.

    Eosinophilia



    • a.

      Filariasis


    • b.

      Fascioliasis


    • c.

      Schistosomiasis


    • d.

      Strongyloidiasis


    • e.

      Toxocariasis


    • f.

      Trichinosis


    • g.

      Coccidioidomycosis




Lymphadenopathy




  • 1.

    Lymphadenopathy (general vs. regional)



    • a.

      Blastomycosis, South American


    • b.

      Dengue


    • c.

      Filariasis


    • d.

      Glanders


    • e.

      Histoplasmosis


    • f.

      HIV infection


    • g.

      Leishmaniasis, visceral (kala-azar)


    • h.

      Lymphogranuloma venereum


    • i.

      Onchocerciasis


    • j.

      Plague


    • k.

      Rubella (posterior auricular/cervical LAD + rash suggestive of rubella or toxoplasmosis)


    • l.

      Scrub typhus


    • m.

      Syphilis (secondary)


    • n.

      Toxoplasmosis (posterior auricular/cervical LAD + rash suggestive of rubella or toxoplasmosis)


    • o.

      Trypanosomiasis, African (occipital LAD = “Winterbottom’s sign”)


    • p.

      Trypanosomiasis, American


    • q.

      Tuberculosis


    • r.

      Tularemia


    • s.

      Sporotrichosis (chain of lymphadenitis extending proximally from lesion)


    • t.

      Cat-scratch fever (chain of lymphadenitis extending proximally from lesion)


    • u.

      Cutaneous leishmaniasis (chain of lymphadenitis extending proximally from lesion)


    • v.

      Mycobacterial (chain of lymphadenitis extending proximally from lesion)




Cardiovascular Findings




  • 1.

    Heart murmur



    • a.

      Trypanosomiasis, American


    • b.

      Enteroviral carditis


    • c.

      Rheumatic heart disease



  • 2.

    Myocarditis



    • a.

      Trypanosomiasis, American


    • b.

      Rheumatic heart disease


    • c.

      Trichinosis


    • d.

      Trypanosomiasis, African (Rhodesian)



  • 3.

    Paradoxical bradycardia



    • a.

      Typhoid


    • b.

      Psittacosis


    • c.

      Dengue


    • d.

      Yellow fever


    • e.

      Q fever


    • f.

      Scrub typhus


    • g.

      Leptospirosis (anicteric)



  • 4.

    Afebrile tachycardia



    • a.

      Myocarditis (viral, bacterial, parasitic etiologies)



      • i.

        Consider: trichinosis, toxoplasmosis, Chagas’ disease, African trypanosomiasis





Head and Neck Findings




  • 1.

    Periorbital swelling



    • a.

      Bilateral: trichinosis, Rocky Mountain spotted fever, nephrotic syndrome


    • b.

      Unilateral: Chagas’ disease (Romaña sign)



  • 2.

    Conjunctival abnormalities



    • a.

      Injection: leptospirosis, Rocky Mountain spotted fever


    • b.

      Conjunctivitis, ulcerating and/or purulent: oculoglandular tularemia (w/ regional lymphadenitis)



  • 3.

    Throat complaints



    • a.

      Tonsillitis w/ pseudomembranes/lymphadenopathy: tularemia, diphtheria




Musculoskeletal




  • 1.

    Myalgia



    • a.

      Dengue


    • b.

      Trichinosis


    • c.

      Rickettsial disease


    • d.

      Bartonellosis



  • 2.

    Bone/joint infection



    • a.

      Tuberculosis


    • b.

      Bartonellosis


    • c.

      Brucellosis


    • d.

      Other




Genitourinary




  • 1.

    Dysuria



    • a.

      Gonorrhea


    • b.

      Chlamydia


    • c.

      Candiru (males)


    • d.

      Other



  • 2.

    Pyuria



    • a.

      Tuberculosis


    • b.

      Hansen’s disease


    • c.

      Bartonellosis


    • d.

      Other



  • 3.

    Epididymo-orchitis



    • a.

      Tuberculosis


    • b.

      Hansen’s disease


    • c.

      Filariasis


    • d.

      Mumps


    • e.

      Other




Incubation/Latency Period


Less Than 2 Hours





  • Chemical exposure




Hours





  • Staphylococcal preformed toxin



1 to 3 Days





  • Scabies



  • Influenza



  • Puerperal infection



  • Bacterial pneumonia



1 to 7 Days





  • Anthrax



  • Bacillary dysentery



  • Cholera (often 3 days)



  • Tularemia



  • Scarlet fever



  • Diphtheria



  • Chancroid



  • Gonorrhea



  • Plague



  • Yellow fever



  • Relapsing fever (tick)



  • Dengue



  • Paratyphoid



  • Infectious keratoconjunctivitis



  • Meningococcal meningitis



  • Rocky Mountain spotted fever



  • Legionellosis



7 to 14 Days





  • Pertussis



  • Relapsing fever (louse)



  • Trichinosis



  • Leptospirosis



  • Viral encephalitides



  • Psittacosis



  • Poliomyelitis



  • Typhoid



  • Lymphocytic choriomeningitis



  • Malaria



  • Mononucleosis



  • Mycoplasma pneumonia



  • Measles



  • Typhus



  • Coccidiomycosis



  • Chlamydia



  • Giardiasis



  • Trachoma



More than 14 Days





  • Tetanus



  • Malaria



  • Brucellosis



  • Chickenpox



  • Lymphogranuloma venereum



  • Q fever



  • Rubella



  • Mumps



  • Syphilis



  • Amebic dysentery



  • Hepatitis



  • Rabies



  • Granuloma inguinale



  • Yaws



  • Tuberculosis



  • HIV



  • Enterobiasis



  • Lyme disease



Year(s)





  • P. malariae



  • Onchocerciasis



  • Echinococcosis



  • Hansen’s disease (6–10+ years)



Geography


Anthrax, Q fever, brucellosis, plague, botulism, tularemia are used as biological weapons: may not follow geographical boundaries.


For country-specific or new information, refer to the Centers for Disease Control and Prevention (CDC) Yellow Book, available on the Internet.


The Americas




  • 1.

    North America



    • a.

      Food/water-borne: E. coli, Salmonella spp, shigella spp, giadria, norovirus.


    • b.

      Vector-borne: plague (primary), rabies, Rocky Mountain spotted fever, tularemia (primary), encephalitis (arthropod-borne), hantavirus (rodent-borne), Lyme disease, babesiosis, scrub typhus


    • c.

      Interpersonal: plague (rare, only in pneumonic form), Q fever (rare)


    • d.

      Environmental: tularemia (rare), hantavirus (rodent-borne), Q fever (primary)



  • 2.

    The Caribbean islands



    • a.

      Food/water-borne: amebiasis, ascariasis, fascioliasis, hepatitis A (primary), trichuriasis


    • b.

      Vector-borne: dengue, filariasis, leishmaniasis (cutaneous), malaria, rabies, tularemia (primary)


    • c.

      Interpersonal: hepatitis A (rare), yaws


    • d.

      Environmental: amebiasis, hookworm, schistosomiasis, trichuriasis, tularemia (rare)



  • 3.

    Mexico



    • a.

      Food/water-borne: amebiasis, anisakiasis, ascariasis, campylobacter, cysticercosis, E. coli enteritis, echinococcosis, hepatitis A/E


    • b.

      Vector-borne: American trypanosomiasis, campylobacter, dengue, leishmaniasis (cutaneous and visceral), malaria, rabies, relapsing fever, typhus


    • c.

      Interpersonal: hepatitis B/C/D, leprosy, pinta, tuberculosis


    • d.

      Environmental: hookworm, trichuriasis



  • 4.

    Tropical South America (Bolivia, Brazil, Colombia, Ecuador, French Guiana, Guyana, Paraguay, Peru, Suriname, Venezuela)



    • a.

      Food/water-borne: cholera, brucellosis, hepatitis A/E (esp. D in Amazon basin), amebiasis (esp. Colombia), cryptosporidium, giardia, ascariasis, echinococcosis (esp. Peru), fascioliasis (rare), taeniasis, trichinosis, paragonimiasis (rare, Ecuador, Peru, Venezuela)


    • b.

      Vector-borne: Rocky Mountain spotted fever (Brazil, Colombia), tick-borne relapsing fever (sporadic), dengue, equine encephalitis (Eastern/Western/Venezuelan), yellow fever, Oropouche fever (rural Peru, Brazil), Chagas’ disease, bancroftian filariasis (foci in Brazil, Guyana, Suriname), plague (foci in NE Brazil, Ecuador, Peru, Bolivia), onchocerciasis (foci in N Brazil, Colombia, Ecuador, Venezuela), trench fever (foci in Bolivia), louse-borne typhus (foci in highlands of Colombia, Peru, Ecuador, Bolivia), bartonellosis (foci in W Andes to 3000 m), cutaneous/mucocutaneous leishmaniasis (all, mucocutaneous esp. in Brazil), visceral leishmaniasis (esp. NE Brazil)


    • c.

      Interpersonal: diphtheria (sporadic), leprosy (esp. Brazil), pertussis, meningococcus (sporadic, esp. Brazil), Q fever, measles (rare), mumps, rubella, hepatitis B (esp. Amazon basin), hepatitis C/D


    • d.

      Environmental: anthrax, leptospirosis, psittacosis, hemorrhagic fever (sporadic, Venezuela, Bolivia), rabies, cat-scratch fever (rare), rat-bite fever (rare), intestinal schistosomiasis (Brazil, Suriname, N Venezuela)



  • 5.

    Temperate South America



    • a.

      Food/water-borne: cholera, echinococcosis, hepatitis A, salmonellosis, taeniasis, typhoid


    • b.

      Vector-borne: arenavirus infection (primary), American trypanosomiasis, cutaneous leishmaniasis, rabies, typhus


    • c.

      Interpersonal: arenavirus infection (rare, healthcare settings), hepatitis B, meningococcal meningitis (esp. Chile), typhoid


    • d.

      Environmental: anthrax (animal skins, contaminated animal products)



  • 6.

    Andes Mountains



    • a.

      Food/water-borne: brucellosis, tapeworm


    • b.

      Vector-borne: bartonellosis, rabies, plague, typhus


    • c.

      Interpersonal: plague (rare, only in pneumonic form), tuberculosis


    • d.

      Environmental: brucellosis




Europe




  • 1.

    Northern Europe



    • a.

      Food/water-borne: cholera (rare dz), diphyllobothriasis (Baltic Sea), fasciolopsiasis, hepatitis A (Eastern Europe), taeniasis, trichinellosis


    • b.

      Vector-borne: Crimean-Congo hemorrhagic fever, hemorrhagic fever with renal syndrome (low risk), Lyme disease, rabies, typhus (tick-borne, Siberia, rare)


    • c.

      Interpersonal: diphtheria (various Baltic nations and former Union of Soviet Socialist Republic [USSR] states and Poland), encephalitis (tick-borne, vaccine available) poliomyelitis (various former USSR states)


    • d.

      Environmental: diphtheria (various Baltic nations and former USSR states)



  • 2.

    Southern Europe



    • a.

      Food/water-borne: brucellosis, cholera, echinococcosis, fasciolopsiasis, typhoid


    • b.

      Vector-borne: encephalitis (tick-borne, vaccine available), hemorrhagic fever with renal syndrome (rodent-borne), leishmaniasis (cutaneous and visceral), Lyme disease, rabies, sandfly fever, typhus (murine and tick-borne), West Nile fever


    • c.

      Interpersonal: hepatitis B


    • d.

      Environmental: brucellosis




Africa and the Middle East




  • 1.

    North Africa



    • a.

      Food/water-borne: ascariasis, brucellosis, cholera, dracunculiasis, E. coli enteritis, giardiasis, hepatitis A/E, hydatid disease, hymenolepiasis, taeniasis, typhoid


    • b.

      Vector-borne: boutonneuse fever, Crimean-Congo hemorrhagic fever, dengue (Nile), filariasis (Nile), leishmaniasis, malaria, plague, rabies, relapsing fever, Rift Valley fever, sandfly fever, typhus, West Nile fever


    • c.

      Interpersonal: giardiasis, poliomyelitis (rare), trachoma, tuberculosis


    • d.

      Environmental: anthrax, brucellosis, giardiasis hookworm, schistosomiasis, trachoma



  • 2.

    East, West, and Central Africa



    • a.

      Food/water-borne: ascariasis, cholera, dracunculiasis, E. coli enteritis, echinococcosis, giardiasis, hepatitis A, paragonimiasis, schistosomiasis, taeniasis, trichinosis, typhoid


    • b.

      Vector-borne: boutonneuse fever, Crimean-Congo fever, Ebola-Marburg hemorrhagic fever, filariasis, Lassa fever, leishmaniasis (cutaneous and visceral), loiasis, malaria (up to 2600 m), onchocerciasis, plague (primary), rabies, relapsing fever, Rift Valley fever, African trypanosomiasis (eastern and western variants), tungiasis, typhus (louse-, tick-, and flea-borne), yellow fever


    • c.

      Interpersonal: HIV/AIDS, hepatitis B, giardiasis, leprosy, plague (rare, only in pneumonic form), poliomyelitis, meningococcal meningitis, trachoma, tuberculosis, yaws


    • d.

      Environmental: anthrax, giardiasis, hookworm, strongyloidiasis, trichuriasis



  • 3.

    South Africa



    • a.

      Food/water-borne: amebiasis, ascariasis, hepatitis A, schistosomiasis, typhoid


    • b.

      Vector-borne: African trypanosomiasis (Botswana, Namibia), Crimean-Congo hemorrhagic fever, malaria, plague, relapsing fever, Rift Valley fever, tick-bite fever, typhus (mostly tick-borne)


    • c.

      Interpersonal: hepatitis B, plague (rare, only in pneumonic form), poliomyelitis (rare), tuberculosis


    • d.

      Environmental: anthrax, hookworm, trichuriasis



  • 4.

    Middle East



    • a.

      Food/water-borne: ascariasis, brucellosis, dracunculiasis, E. coli enteritis, giardiasis, hepatitis A, hydatid disease, hymenolepiasis, schistosomiasis, taeniasis, typhoid


    • b.

      Vector-borne: dengue fever, boutonneuse fever, Crimean-Congo hemorrhagic fever, filariasis, leishmaniasis (cutaneous and visceral), malaria, onchocerciasis (Yemen only), plague, rabies, relapsing fever, typhus (murine and tick-borne)


    • c.

      Interpersonal: diphtheria (various former USSR states), giardiasis, hepatitis B, plague (rare, only in pneumonic form), poliomyelitis, trachoma, tuberculosis


    • d.

      Environmental: anthrax, brucellosis, giardiasis, hookworm




Asia




  • 1.

    India, Bangladesh, Pakistan, and Sri Lanka



    • a.

      Food/water-borne: amebiasis, ascariasis, brucellosis, cholera, dracunculiasis, echinococcosis, E. coli enteritis, giardiasis, hepatitis A, hymenolepiasis, shigellosis, trichinosis, typhoid


    • b.

      Vector-borne: boutonneuse fever, dengue, filariasis, hemorrhagic fever (tick-borne), Japanese encephalitis, leishmaniasis (cutaneous and visceral), malaria, plague, rabies, relapsing fever, scrub typhus, typhus


    • c.

      Interpersonal: giardiasis, hepatitis B, leprosy, meningococcal meningitis, plague (rare, only in pneumonic form), poliomyelitis, trachoma, tuberculosis


    • d.

      Environmental: brucellosis, giardiasis, hookworm, strongyloidiasis, trichuriasis,



  • 2.

    Southeast Asia



    • a.

      Food/water-borne: amebiasis, angiostrongyliasis, clonorchiasis, E. coli enteritis, fasciolopsiasis, giardiasis, gnathostomiasis, hepatitis A/E, melioidosis, opisthorchiasis, paragonimiasis, schistosomiasis, shigellosis, taeniasis, trichinosis, typhoid


    • b.

      Vector-borne: dengue, filariasis, Japanese encephalitis, malaria, plague, rabies, scrub typhus


    • c.

      Interpersonal: giardiasis, hepatitis B, leprosy, plague (rare, only in pneumonic form), poliomyelitis, trachoma, tuberculosis


    • d.

      Environmental: giardiasis, hookworm, strongyloidiasis, trichuriasis



  • 3.

    China and Korea



    • a.

      Food/water-borne: ascariasis, clonorchiasis, E. coli enteritis, hepatitis A/E, leptospirosis, paragonimiasis, schistosomiasis, trichinosis


    • b.

      Vector-borne: dengue, filariasis, hemorrhagic fever with renal failure, Japanese encephalitis, leishmaniasis (cutaneous and visceral), malaria, plague, rabies, scrub typhus


    • c.

      Interpersonal: hepatitis B, leprosy, meningococcal meningitis, plague (rare, only in pneumonic form), poliomyelitis, trachoma, tuberculosis


    • d.

      Environmental: hookworm, leptospirosis, trichuriasis




Oceana




  • 1.

    Australia, New Zealand, and the Antarctic



    • a.

      Food/water-borne: rare


    • b.

      Vector-borne: encephalitis (viral), dengue (Northern Australia, occasional)


    • c.

      Interpersonal: rare


    • d.

      Environmental: rare



  • 2.

    Melanesia and Micronesia-Polynesia/Pacific Islands



    • a.

      Food/water-borne: angiostrongyliasis, ascariasis, ciguatera poisoning, hepatitis A, scombroid poisoning, trichinosis, typhoid


    • b.

      Vector-borne: dengue, filariasis, malaria, Ross River fever, typhus (mite-borne, Papua New Guinea)


    • c.

      Interpersonal: hepatitis B, leprosy, trachoma, tuberculosis, yaws


    • d.

      Environmental: hookworm, strongyloidiasis, trichuriasis




Vectors and Environmental Exposures


Sampling Strategies for Arthropod Vectors




  • 1.

    Sampling methodology



    • a.

      Presence-absence: As name suggests, provides determination if arthropod exists in environment



      • i.

        Quick to complete


      • ii.

        No quantitative information (i.e., no sense of population density)



    • b.

      Direct counts/absolute estimates



      • i.

        Generally too resource-intensive in large areas to be feasible


      • ii.

        Most accurate because provides as accurate a count of population possible



    • c.

      Relative estimate of population



      • i.

        Best balance between generalities of presence-absence and absolute estimate


      • ii.

        Results are influenced by method used




  • 2.

    Random, systematic, serial sampling



    • a.

      Random samples less useful because implies that animals have equal chance of being found throughout environment



      • i.

        Least bias introduced in this method


      • ii.

        Least reflective of animal behavior (i.e., animals prefer favorable habitats and will, generally, cluster in those habitats rather than randomly in environment)



    • b.

      Systematic samples are easiest method to obtain samples from large population



      • i.

        Pick samples via some predetermined rules (e.g., hang trap from every third tree; drag for ticks every second meter)


      • ii.

        Can introduce bias via choice of sampling sites



    • c.

      Serial samples are collected at same location



      • i.

        Trapping at the same location(s) over time


      • ii.

        Provides reasonable estimate of population changes over time (e.g., with seasonal variation)




  • 3.

    Sampling/trapping methods vary by arthropod but general methods include



    • a.

      Plastic dipper in standing water for larval stage mosquitoes


    • b.

      Light traps



      • i.

        Light trap with CO 2 or other attractant for mosquitoes


      • ii.

        Without attractant can be used for sand flies



    • c.

      Natural resting stations with white sheet on ground to collect arthropods after spraying aerosol pesticide


    • d.

      Sticky/oil paper traps



      • i.

        Used with many species of biting fly


      • ii.

        Method varies by location (indoor/outdoor) and arthropod of interest



    • e.

      Visual landing counts



      • i.

        Used with aspirator to collect insect before biting


      • ii.

        Technique may increase risk to personnel collecting arthropods



    • f.

      Tick drags



      • i.

        Done with soft, white cloth


      • ii.

        Cannot be done in wet/damp conditions



    • g.

      Direct observation



  • 4.

    Sample size considerations



    • a.

      Multiple samples (more than three) are general preferable for better accuracy of information


    • b.

      Typically balanced with resource considerations (e.g., cost, available manpower to set, collect traps, review collected arthropods)




General Protective Measures Against Vector Contact




  • 1.

    Arthropods



    • a.

      Use of protective clothing impregnated with permethrin


    • b.

      For flying insects, use of screened rooms a/o insecticide-impregnated bed netting


    • c.

      Spray rooms with pyrethroids during evening


    • d.

      Personal application of 35% nonabsorbable N,N-diethyl-metatoluamide (DEET)




Ticks and Mites



Aug 20, 2021 | Posted by in GENERAL & FAMILY MEDICINE | Comments Off on Global Infectious Diseases: Four Steps Toward a Differential Diagnosis

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