Table 2.
Most common pathogens in patients with sickle cell disease, including those living in austere environments.
| Infection/system | Micro-organism (s) | Complications/chronic organ dysfunction | Treatment |
|---|---|---|---|
| Bacteremia/sepsis | S. pneumoniae, S. aureus, GNR (Typhi and non-typhi Salmonella, E. coli, Klebsiella sp., H. influenzae type B), Bacteroides sp. (49–51) | Septic shock with multi-organ failure (50, 52) | -S. pneumoniae, Gram-negative rods, some Bacteroides: third-generation cephalosporins (Ceftriaxone, Cefotaxime)* - S. aureus: oxacillin, nafcillin, or cefazolin (MSSA)*; Vancomycin, clindamycin (MRSA)* |
| Meningitis/central nervous system infection | S. pneumoniae, H. influenzae, and N. meningitides (11, 52); Pasteurella multocida and Capnocytophaga sp. (in the presence of dog bite), viruses (Enteroviruses, herpes simplex viruses, mosquito-borne viruses); Cryptococcus neoformans and cerebral Toxoplasma gondii (especially in the presence of HIV) | Seizures, hemorrhagic stroke, acute ischemic stroke, venous sinus thrombosis, silent cerebral infarction, intra-cranial abscess, cognitive impairment (52–54) | - Third-generation cephalosporins (Ceftriaxone, Cefotaxime)* - Capnocyphaga sp.: beta-lactam/beta-lactamase inhibitors and carbapenems (imipenem, meropenem) - Pasteurella multocida: penicillin (drug of choice) - Cryptococcus neoformans: a. Amphotericin B deoxycholate or liposomal amphotericin B + fluocytosine (induction phase), followed by fluconazole (consolidation therapy). - Toxoplasma gondii: pyrimethamine + sulfadiazine + folic acid. Allergy to sulfa: pyrimethamine + folic acid + clindamycin OR atovaquone - Herpes viruses: intravenous acyclovir |
| Upper and lower respiratory tract infection (sinusitis, epiglottitis, tracheitis, bronchitis, pneumonia) | Viruses (influenza viruses, respiratory syncytial virus, adenovirus, metapneumovirus, rhino-enterovirus, parvovirus B-19, parainfluenza viruses, cytomegalovirus, Epstein-Barr virus, and herpes simplex viruses, etc.) (55, 56); bacteria (S. pneumoniae, H. influenzae, Chlamydophila pneumoniae, Mycoplasma pneumoniae, Legionella sp., S. aureus (methicillin susceptible and resistant) (11, 57–59) | Acute chest syndrome, chronic lung disease/chronic restrictive lung disease, pulmonary hypertension | - Influenza: oseltamivir, inhaled zanamivir, baxtamivir - S. pneumoniae, H. influenza type B: third-generation cephalosporins (Ceftriaxone, Cefotaxime)*; S. aureus: oxacillin, nafcillin, or cefazolin (MSSA)*; Vancomcyin, clindamycin (MRSA)* - Cytomegalovirus: intravenous gancyclovir/oral valganciclovir; Epstein-Barr virus: intravenous ganciclovir; Herpes viruses: intravenous or oral acyclovir, valacyclovir, or famciclovir - Chlamydophila pneumoniae, Mycoplasma pneumoniae, Legionella sp.: macrolides, quinolones |
| Musculoskeletal (skin and soft tissue infection, septic arthritis, fasciitis, myositis, osteomyelitis) | Typhi and non-typhi Salmonella, Gram-negative enteric bacteria, other Gram-negative (Kingella kingae, especially in the presence of negative cultures); S. aureus (methicillin susceptible and resistant), S. pneumonia (51, 52, 60–62) | Avascular necrosis, leg ulceration (skin), osteonecrosis (63, 64) | - Third-generation cephalosporins (Ceftriaxone, Cefotaxime)* - S. aureus: oxacillin, nafcillin, or cefazolin (MSSA)*; vancomycin, clindamycin (MRSA)* - Kingella kingae: ampicillin-sulbactam or a first-, second-, or third-generation cephalosporin |
| Gastrointestinal (cholelithiasis/choledocholithiasis, cholecystitis, cholangitis, intussusception), gastroenteritis | Enteric Gram-negative pathogens including Typhi and non-typhi Salmonella, Enterococci, anaerobic bacteria (65) and Yersinia enterocolitica infections (66) | Cholangiopathy (e.g., common biliary duct obstruction, cholestasis), hepatopathy (e.g., hepatic vaso-occlusive crisis, sequestration; hepatic fibrosis secondary to iron overload), mesenteric vaso-occlusion, and bowel infarcts | - Piperacillin-tazobactam or a carbapenem (imipenem, meropenem) - Surgical consult for decompression (stent/drains placement) or open/laparoscopic cholecystectomy - For Yersinia, a third-generation cephalosporin, piperacillin, or trimethoprim-sulfamethoxazole |
| Urogenital (urinary tract infection, pyelonephritis, renal abscess, urosepsis) | Gram-negative pathogens | Papillary necrosis, hematuria, renal failure, priapism (67) | - Third-generation cephalosporin (Ceftriaxone, Cefotaxime)* |
| Malaria | Plasmodium falciparum, Plasmodium vivax, Plasmodium ovale, Plasmodium malariae, and P. knowlesi | Vaso-occlusive crisis and secondary pain crisis, splenic sequestration; acute and chronic severe anemia requiring blood transfusion and causing folate-deficiency anemia; nephrotic syndrome, shock, hypoglycemia, acidosis, thrombocytopenia, and multi-organ failure | - Severe malaria requiring intensive care unit admission: intravenous quinidine until the parasite density <1% and able to tolerate oral therapy; alternative = intravenous artesunate*2 - Oral therapy: based on the infecting species, possible drug resistance, and severity of disease = Avoid exposure to mosquitoes and avoid areas with outbreaks of mosquito-borne infections. |
| Tuberculosis (Mycobacterium tuberculosis) | Mycobacterium tuberculosis | Vaso-occlusive crisis, acute chest syndrome; chronic pulmonary dysfunction, increased hemolysis, sub-optimal reticulocytosis, and anemia; extra-pulmonary tuberculosis (meningeal, lymph nodes, bones, joints, skin, middle ear, mastoid, gastrointestinal, renal) | - Presumed or known drug-susceptible pulmonary tuberculosis (except meningeal disease): a 6-month, 4-drug regimen consisting initially of rifampin, isoniazid, pyrazinamide, and ethambutol for the first 2 months and isoniazid and rifampin for the remaining 4 months - Drug-resistant tuberculosis: an expert in drug-resistant tuberculosis should be consulted for all drug-resistant cases |
| Human immunodeficiency infection | Human Immunodeficiency Virus (HIV-1 and HIV-2); HIV-2 is mainly prevalent in Western Africa | Increased risk for stroke, splenic dysfunction, avascular necrosis, and pulmonary arterial hypertension; increased risk of sepsis and bacterial infection, mainly pneumococcal infection | Because HIV treatment options and recommendations change with time and vary with occurrence of antiretroviral drug resistance and adverse event profile, consultation with a HIV expert is recommended¥. |
| Dengue fever, dengue hemorrhagic fever/dengue shock syndrome | Arbovirus (Flaviviridae family; genus Flavivirus) | Vaso-occlusive crisis, splenic sequestration, leg ulcers requiring amputation, myocarditis, heart block, shock, plasma leakage and secondary pulmonary and brain edema, ascites, anasarca, hemorrhage, multiorgan failure | - Supportive care: high intake of fluids, soft diet, acetaminophen [avoid salicylate-containing (aspirin) and non-steroidal anti-inflammatory products (ibuprofen)] and tepid sponging for relief of fever, adequate oxygenation, vasopressors, intravenous isotonic crystalloid (0.45% sodium chloride if <6 months of age) and colloids solution (avoid overload), blood products transfusion, diuretics for fluid overload; empirical therapy for bacterial infection pending cultures results. Steroids, anti-viral therapy (chloroquine, balapiravir, celgosivir). |
| Parasitic infections | Helminths: Ascaris lumbricoides, Ancylostoma duodenale, Trichuris trichiura, Strongyloides stercoralis, Schistosomiasis (S. mansoni, S. haematobium, S. japonicum), Toxocara canis, filariasis (Onchocerca volvulus) | - Vaso-occlusive crisis, chronic iron deficiency, chronic eosinophilia - Malnutrition, growth delay, cognitive deficit - Acute intestinal obstruction with intestinal perforation and peritonitis; appendicitis, common bile duct obstruction with secondary biliary colic, cholangitis, or pancreatitis (ascariasis) - Infiltrative eosinophilic pneumonitis syndrome (Ascariasis, Ancylostomiasis, schistosomiasis, filariasis, toxocariasis) with secondary hypoxia and acute chest syndrome |
- lumbricoides, A. duodenale: albendazole, mebendazole, and pyrantel pamoate - T. trichiura: albendazole, mebendazole, and ivermectin - S. stercoralis: ivermectin (drug of choice), mebendazole - Schistosomiasis: praziquantel (drug of choice) - T. canis: albendazole, mebendazole - Filariasis: ivermectin; alternative = doxycycline (not recommended for children younger than 8 years) |
| - Urinary schistosomiasis (S. haematobium) causing hematuria and predisposition to bacterial infection - Hepatosplenomegaly, bloody diarrhea, portal hypertension, ascites, esophageal varices, and hematemesis (chronic S. mansoni and S. japonicum infections) - Visual loss/blindness (filariasis, T. canis) - Strongyloides hyperinfection syndrome (in immunocompromised patients); larvae migration to distant organs causing fever, abdominal pain, diffuse pulmonary infiltrates, septicemia, and meningitis caused by enteric Gram-negative bacilli |
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| Protozoa (other than malaria): Entamoeba histolytica, Entamoeba coli and Giardia lamblia | Chronic Giardia infection with secondary chronic intestinal malabsorption and failure to thrive - Toxic megacolon, fulminant colitis, ulcerations on colonic mucosa and secondary perforation; hepatic, pleural, lungs, and pericardium abscesses (E. histolytica) |
- Hand hygiene after defecation, before preparing or eating food, after changing a diaper or caring for someone with diarrhea and after handling an animal or its waste - Sanitary disposal of fecal material - Treatment of drinking water (boiling, chemical disinfection with iodine or chlorine, use of filters) - Sexual transmission: use of condoms and avoidance of sexual practices that may permit fecal-oral transmission (E. histolytica). - Refrain from using recreational water venues (e.g., swimming pools, water parks) until asymptomatic and completed treatment |
*
Antibiotic selection should take into consideration local epidemiology and antibiotic-resistant patterns. For developing countries, also refer to World Health Organization recommendations: https://apps.who.int/medicinedocs/en/d/Js5406e/.
*2
Available through the CDC malaria hotline investigational new drug (IND) protocol.