Life-Threatening Signs (e.g., coma, septicemia)
Anthrax (Any temperate or tropical rural area where animal husbandry is common): Anthrax is a gram positive spore-forming aerobic rod (Bacillus anthracis) cutaneous or pulmonary infection. Cutaneous anthrax is characterized by a dark centered erythematous papule surrounded by edematous and vesicular tissue. The papule enlarges, ulcerates, forms eschar, which later sloughs. Lymphadenopathy, fever, malaise, headache, and nausea and vomiting may also occur. After the eschar sloughs, hematogenous spread and sepsis may occur, with resulting shock, collapse, and hemorrhagic meningitis. Pulmonary anthrax (a concern with respect to biological warfare) is characterized by fever, malaise, headache, respiratory congestion, and pneumonia or mediastinitis. Anthrax is treated with penicillin G or tetracycline. Mortality is high, especially in pulmonary anthrax.
Arbovirus encephalitis (Worldwide - according to specific disease): The most important (highest case- fatality rates) arbovirus or arthropod-borne encephalitides are (1) Japanese encephalitis (JE), which is found throughout Asia and the Pacific; (2) Murray Valley (MV), which is found in Australia and New Guinea; and (3) eastern equine encephalomyelitis (EEE), which is found in the Americas and Caribbean. Severe infections are usually characterized by acute onset of fever, meningeal signs (headache, stiff neck, irritability, nausea and vomiting, delirium, >vital signs), tremors, convulsions, and stupor progressing to coma. Treatment is primarily supportive.
Chagas' Disease or American trypanosomiais: See full discussion (Most of Latin America): Chagas' disease is a protozoan infection with Trypanosoma cruzi transmitted by insect bite. Patients may be asymptomatic or have a lesion at the site of the bite; and symptoms of prolonged fever, tachycardia, fatigue, weakness, splenomegaly, and lymphadenopathy. Myocarditis or meningoencephalitis may also occur. Most patients experience spontaneous remission of symptoms, followed by a lifelong low-grade parasitemia. There is not currently a satisfactory treatment for any stage of Chagas' disease. Current treatment includes nifurtimox 8-10 mg/kg/day po qid for 90-120 days or benznidazole 5 mg/kg/day po for 60 days. These long-term therapies are toxic to some patients. In the United States, nifurtimox is available only from the Centers for Disease Control and benznidazole is not available in the U.S.
Clostridium botulinum and C. perfringens (Worldwide): C. botulinum causes botulism (see above) and C. perfringens causes gas gangrene and also enteritis or food poisoning especially from poultry.
Crimean-Congo hemorrhagic fever: See hemorrhagic fevers (HFs) below or full discussion of HFs (Africa, Middle East, Eastern Europe, Russia, Western China): Incubation is 3-12 days. Crimean-Congo HF is transmitted by the bite or crushing of infected ticks, or by contact with live or dead infected mammals. The clinical picture includes sudden onset fever and myalgia, headache, dizziness, photophobia, hyperesthesias, chest and/or abdominal pain, nausea and vomiting, conjunctival injection, flushing, hypotension, axillary or other petechiae, decreased blood pressure, increased heart rate, periorbital edema, proteinuria, and significant liver abnormalities (>AST, >phosphokinase, >bilirubin), leukocytosis, and signs of disseminated intravascular coagulation. Though treatment is not definitive, more severe cases are often successfully treated with IV ribavirin as described in the full discussion of Hemorrhagic Fevers.
Dengue Fever (hemorrhagic syndrome or shock syndrome) : See full discussion (East and West Africa, Southeast and East Asia, Pacific Islands, Eastern Australia, Central and South America, Mexico, South Texas, Caribbean Islands - with distribution increasing, especially in urban areas): Dengue Fever is a flavivirus (several serotypes) infection transmitted by mosquitos. There is increasing incidence and prevalence of cocirculation of multiple serotypes. Dengue is usually a self-limited illness characterized by abrupt onset high (biphasic) fever, chills, headache, rash, signs of bleeding, changes in taste, sore throat, nausea, vomiting, diarrhea, anorexia, severe aching myalgia and arthralgia (hence "bone-break" fever), and depression. Complications include meningoencephalitis, dengue hemorrhagic fever (DHF), and dengue shock syndrom (DSS). Treatment is supportive and convalescence tends to be lengthy.
Ebola hemorrhagic fever and Marburg hemorrhagic fever: See full discussion of HFs and full discussion of Ebola and Marburg HFs (Central Africa): Incubation of Ebola and Marburg HFs ranges from 3-16 days. Both Ebola and Marburg HFs are caused by viral infections characterized by sudden onset of fever, chills, severe headache, and myalgia. On about the fifth day of illness, a maculopapular rash may appear - most prominently on the trunk (the rash may eventually desquamate); along with pharyngitis, chest pain, abdominal pain, nausea, vomiting, diarrhea, and hemorrhagic symptoms, e.g., bleeding mucosal membranes. Symptoms may increase in severity and include jaundice, pancreatic inflammation, rapid weight loss, prostration, delirium, shock, hepatic failure, massive hemorrhaging, and multi-organ failure. Case fatality rates for for Ebola HF range from 50-90% and for Marburg HF around 25%. Treatment is supportive as discussed in the full discussion of hemorrhagic fevers.
Hemorrhagic fevers (HFs): See full discussion of HFs. The major HFs include hemorrhagic fever with renal syndrome, hantavirus pulmonary syndrome, South American HFs, Lassa HF, Marburg and Ebola HFs, Kyasanur Forest HF, Omsk HF, Crimean-Congo HF, Chikungunya fever, dengue fever and HF, and Rift Valley fever (distribution is noted in the full discussion). The viral hemorrhagic syndrome (VHS) results from widespread increased permeability of microvasculature. Depending on the severity of vascular instability and decrease in platelet function, presentation may range from mild to severe illness; and hemorrhagic manifestations are not always apparent. A common course of illness begins with an abrupt onset of fever, myalgia, cutaneous flushing, and conjunctival suffusion. Within several days, the patient's condition worsens to include syncope, photophobia, headache, hyperesthesia, abdominal pain, nausea/vomiting, anorexia, and prostration. Treatment is primarily supportive, except that Lassa fever, South American HFs, and possibly Crimean-Congo HF and Rift Valley HF may be treated with a slow infusion of IV ribavirin.
Hemorrhagic fever with renal syndrome: See full discussion of HFs (Europe, Russia, East China, and Korea): Hemorrhagic fever with renal syndrome is caused by hantavirus. Incubation ranges from 9-35 days. Severity of the illness varies, mild or subclinical infections common. More severe cases are characterized by a febrile stage lasting 3-5 days with abrupt onset of fever, headache, photophobia, blurred vision, facial flushing extending to neck and shoulders, conjunctival petechiae, periorbital edema, pharyngeal injection and/or petechiae, axillary petechiae, lumbar back pain and CVA tenderness lasting 3-5 days. The illness may gradually resolve after this febrile stage or a hypotensive stage may begin as the temperature falls. The hypotensive stage is characterized by decreased blood pressure, tachycardia, and sometimes shock. Proteinuria, thrombocytopenia, leukocytosis, oliguria occur, as does renal failure in some cases. Renal function returns as the oliguric phase resolves and the polyuric phase ensues. Electrolyte imbalances and dehydration may occur in the polyuric phase. Disseminated intravascular coagulation may occur relatively early in the course of illness. Treatment is supportive as discussed in Hemorrhagic Fevers.
Malaria: See full discussion (Tropical Africa, Asia, South and Central Americas; East China, Middle East): Malaria is caused by the protozoas Plasmodium falciporum, P. vivax, P. ovale, and P. malariae and is transmitted by mosquito bite, parenteral injection, or congenitally. Malaria is usually characterized by sudden onset of high fever, sweating, chills, uncontrollable shaking, headache, and splenomegaly. Fever tends to wax and wane in 48-72 hour cycles, though cycles may be irregular, especially with infection by P. falciporum. Onset may also be insidious, with less dramatic symptoms such as fever, headache, dyspnea, abdominal pain, nausea, diarrhea, myalgias, and splenomegaly. P. falciporum may cause parasitemia resulting in a life-threatening condition characterized by hemolysis, jaundice, anemia, acute renal failure, and hemoglobinuria. Cerebral malaria, also life-threatening, is characterized by gradual onset of severe headache, drowsiness, delerium, and coma. Seizures may also occur and are most common in children. P. faciporum causes death in as many as 25% of untreated cases. Treatment depends on the organism, immune status of the patient, and severity of the attack. Oral chloroquine is a mainstay of treatment except for infection with chloroquine-resistant P. falciporum. P. falciporum presents the greatest challenge because of severity of attacks as well as the existence of multidrug (especially chloroquine)-resistant strains. Combination drug treatment is common, e.g., mefloquine combined with artesunate for multidrug-resistant strains as described in the full discussion.
Melioidosis (Southeast Asia): Melioidosis is infection by Pseudomonas pseudomallei (gram negative bacillus) with symptoms of fever, pulmonary infection that may range from bronchitis to necrotizing pneumonia. Acute septicemic melioidosis is most common among debilitated persons. Focal suppuration (nodule, lymphangitis, lymphadenopathy) results from inoculation through a break in the skin. Chronic suppurative disease may involve virtually any body system. Recrudescence may occur many years after the initial infection. Treatment is according to susceptibility. Common antibiotics used are TMP-SMX (not in Thailand), Augmentin, doxycycline, and cephalosporins.
Trypanosomiasis (African) or African sleeping sickness (Tropical Africa): Trypanosomiasis is caused by protozoal parasites, Trypanosoma brucei rhodesiene or T b gambiense, transmitted by bite of the tsetse fly. T b rhodesiene infections are more virulent than T b gambiense; and in the former, patients experience three stages of illness (trypanosomal chancre, hemolymphatic, and meningoencephalitic) as opposed to two stages in the latter (trypanosomal chancre and meningoencephalitic) with significantly milder symptoms. The painful trypanosomal chancre (3-10 cm) appears about two days after the bite and lasts 2-4 weeks. The hemolymphatic stage is characterized by high fevers lasting several days, with symptom-free periods of days to weeks. Less common manifestations of this stage are severe headache, malaise, arthralgia, lymphadenopathy, circinate rash, pruritis, and hepatosplenomegaly. Weight loss and debilitation also occur, and myocarditis may develop. The meningoencephalitic stage is characterized by progressive apathy, nighttime insomnia and daytime somnolence, anorexia, retarded speech, extrapyramidal signs (tremors, fasciculations, choreiform movements, and Parkinsonian-like appearance), and finally, coma and death. Treatment is complex and toxic, and depends on the infecting organism and stage of illness. Among the medications currently in use are suramin, melarsoprol, pentamidine, eflornithine, and corticosteroids.
Meningitis, chronic and recurrent, is common worldwide, often as a complication of communicable diseases caused by a variety of pathogens as follows: (1) Bacterial causes include incompletely treated suppurative meningitis, parameningeal infection, Lyme disease, mycobacterium tuberculosis, syphilis; and less commonly actinomycosis brucellosis, leptospirosis, nocardial infection, and Whipple's disease. (2) Fungal infections with the potential to cause meningitis include aspergillosis, blastomycosis, cryptococcus, coccidiomycosis, candidiasis, histoplasma, and sporotrichosis. (3) Protozoal causes include toxoplasmosis and trypanosomiasis. (4) Helminthic causes include angiostrongyliasis, cysticercosis, gnathostomiasis, and trichinosis. (5) Viral causes include echoviral infections, herpes, HIV, lymphocytic choriomeningitis, and mumps. Viral or aseptic meningitis is characterized by sudden onset of fever and signs and symptoms of meningeal involvement (headache, neck stiffness, irritability/malaise, and sometimes rash and nausea and vomiting (from Chin, 2000; Koroshetz & Swartz, 1998).
Meningoencephalitis is relatively common worldwide and in some cases occurs as a complication of communicable diseases. Viruses are the most common pathogen, especially enteroviruses, but also arboviruses, herpesviruses, and other pathogens in illnesses including African trypanosomiasis, amebiasis, angiostrongyliasis, candidiasis, Chagas' disease, cryptococcosis, cytomegalovirus, dengue fever, hemorrhagic fevers, herpes, listeria, toxoplasmosis, and others. Young age and immunocompromise increase the risk of meningoencephalitis.