text: Most Common Pathogens Causing Fever: also see Table Table 2
  The leading cause of travel-related hospitalization and death.
  Commonly seen species include P. falciparum (high case fatality rate if untreated), P. vivax, P. ovale, P. malariae, P. knowlesi (simian malaria found in Southeast Asia, rarely transmissible to humans and potentially fatal).
  Among 25,000 ill returned patients reported in the GeoSentinel Surveillance System
  Sub-Saharan Africa: 49% with a febrile illness of whom 42% with malaria
  The Americas (Central & South America and the Caribbean): 25% with febrile illness of whom 8% had malaria
  Southeast Asia: 34% with a febrile illness of whom 7% had malaria
  Dengue virus: 6% of all fever and 18% of undifferentiated fever from endemic regions in returned travelers primarily from Southeast Asia and The Americas.
  Less Common Pathogens Causing Fever:
  Diarrhea/dysentery + fever: non-typhoidal Salmonella spp, Shigella spp., and Campylobacter spp. are among the most commonly isolated organisms; fever is only seen in 10% of patients with E. histolytica (amebic dysentery).
  Salmonella enterica serovar typhi or paratyphi (enteric fever): 2% of all fever and 6% of undifferentiated fever
  Uncommon pathogens in systemic illnesses: also consider leptospirosis, amoebic liver abscess, Q fever, melioidosis, viral meningitis, relapsing fever
  Approximately 30% of persons seeking medical care following travel have a fever. Subsets listed in Table Table 1
  Clinical Syndrome in Returning Travelers
  Initial assessment = same as any ill person with suspected infection.
  Calculate the Quick Sepsis-related Organ Failure Assessment (qSOFA)[3] or calculate a standard SOFA using online tools (http://clincalc.com/icumortality/sofa.aspx) to determine the risk of severe sepsis and the need for urgent empirical treatment.
  History is KEY in the returned traveler: 23% of returned travelers present with fever; patterns of fever and clinical findings are similar for many infections.
  Obtaining detailed geographic travel and exposure history (including modes of possible exposure), vaccination history and treatment history is essential.
  Consider algorithmic thinking based upon the qSOFA score and signs/symptoms accompanying the fever to guide differential diagnostic considerations.[2]
  Enteric fever (typhoid and paratyphoid)
  Less common: chikungunya, brucellosis, leptospirosis, acute HIV or STDs, tick- and louse-borne-relapsing fevers, tularemia, and non-tropical disease (infectious mononucleosis, endocarditis, lymphoma).
  Note: viral hemorrhagic fevers (VHF, all): are caused by 4 distinct families of RNA, enveloped viruses (arenaviruses, filoviruses, bunyaviruses, and flaviviruses).
  Q fever (may have a longer incubation period)
  Coronavirus including Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV2)
  Plague (extremely rare in travelers)
  Fever and rash (variable incubation periods)
  HIV, acute infection syndrome
  Schistosomiasis, acute syndrome
  South-Central Asia, especially India: malaria = typhoid/paratyphoid fever (especially if visiting family) = dengue.
  See individual modules for additional, detailed information.
  Malaria thick and thin smear if travel to a malarious area regardless of having taking chemoprophylaxis. Obtain serial smears if the initial smear is negative in at-risk travelers.
  Rapid tests (e.g., histidine-rich protein [HRP]-2 antigen detection): highly specific but not as sensitive as thick and thin smears. But, provide results in about 15 minutes. But, a positive test or negative test does NOT eliminate the need for microscopy.
  P. knowlesi usually infects monkeys and rarely humans in SE Asia; can be mistaken for P. malariae on smear; suspect if high-level parasitemia (≥2.5% of RBCs infected) and lab reports P. malariae. PCR identification is needed to confirm dx.
  Dengue: suspect patient with fever, frontal headache, myalgia with or w/o skin petechial or maculopapular eruption up to 14 days after return from the region.
  Severe infection may cause hemorrhage, seizures, and shock.
  Rickettsial infection: evaluate for eschar/tache noire [Figure] may be present from a tick bite.
  PCR detection possible at specialized laboratories performed best performed on swabs of inoculation eschar or tissue biopsies.
  Pathogen-specific serology is the most commonly used in dx but often tests available (e.g., Weil-Felix or immunofluorescence assay) cannot distinguish species due to cross-reactivity. Western blot and cross-absorption are available only in reference laboratories.
  Blood and stool cultures with best yields routinely for Salmonella. Some studies suggest bone marrow aspirate has the highest yield for S. typhi.
  Bone marrow culture is 90% sensitive and not affected by up to 5 days of antibiotics, but rarely performed in the US.
  Liver aspirate (usually not done if serology is available).
  Chikungunya: three possible diagnostic modalities. All may be positive if collected within the first week after the onset of symptoms.
  Uncomplicated Plasmodium falciparum, Plasmodium knowlesi or species unspecified
  Note chloroquine-resistant P. falciparum areas in the Middle East including Iran, Oman, Saudi Arabia and Yemen.
  Atovaquone/proguanil (Malarone, adult tab = 250 mg/100 mg): 4 adult tabs PO daily x 3 days (taken with milk or a fatty meal). DO NOT USE if this drug was used for chemoprophylaxis.
  3 tablets at hour 0 and at hour 8 on the first day, then 3 tablets twice daily (in the morning and evening) on days 2 and 3 (total of 18 tablets per treatment course)
  Doxycycline: 100 mg PO twice daily x 7 days. DO NOT use for treatment if this agent was used for chemoprophylaxis
  Tetracycline 250 mg PO four times daily x 7 days. DO NOT use for treatment if this doxycycline was used for chemoprophylaxis
  Least preferred treatment: mefloquine (generics only) 684 mg base (750 mg salt) PO as initial dose, followed by 456 mg base (500 mg salt) PO given 6-12 hours after initial dose. Total dose = 1,250 mg salt. DO NOT use for treatment if this agent was used for chemoprophylaxis
  Patients with P. vivax (or P. ovale) must be tested for GGPD deficiency since patients should undergo treatment for liver stage infection (antirelapse treatment):
  Adult dosing 30 mg base PO daily x 14 days
  Adult dosing: 300 mg orally once
  Pediatric dosing (for patients 16 years and older): 300 mg orally once
  Consult an infectious or tropical diseases specialist for the treatment of patients with G6PD deficiency or with decreased G6PD activity.
  If clinical improvement is not seen within 48-72 hours, alternative therapy should be used for retreatment.
  Alternative treatments options for chloroquine-resistant P. vivax regions: If other treatments are not available, if treatment is not being tolerated or if treatment benefits outweigh the risks:
  Primaquine phosphate is contraindicated in pregnancy and breastfeeding women and should not be used at the end of treatment for the liver stage of P. vivax or P. ovale.
  Following treatment for P. vivax or P. ovale, the pregnant patient should be maintained on chloroquine or hydroxychloroquine at chemoprophylactic doses for the remainder of the pregnancy and then women without G6PD deficiency should be receive treated with primaquine phosphate following delivery.
  If breastfeeding is planned, the chemoprophylactic regimen should be maintained throughout breastfeeding and final primaquine treatment provided at the end of breastfeeding.
  Quinine sulfate 650 mg salt PO three times daily x 7 days.
  Thereafter, the woman should be maintained on weekly mefloquine at chemoprophylactic dosing for the remainder of pregnancy as mefloquine is FDA approved for chemoprophylaxis in pregnancy.
  Women without G6PD deficiency should receive primaquine phosphate following delivery. If breastfeeding is planned, the chemoprophylactic regimen should be maintained throughout breastfeeding and final primaquine treatment provided at the end of breastfeeding.
  Doxycycline and tetracycline are not generally used in pregnant women. However, one or the other may be used in combination with quinine if other treatment options are not available or not tolerated.
  Atovaquone/proguanil (MalaroneTM) and artemether/lumefantrine (CoartemTM) are classified as pregnancy Category C agents, not usually recommended. However, if other treatment options are not available or not tolerated, agents can be considered. After delivery, women without G6PD deficiency should be treated with primaquine phosphate as previously outlined.
  See additional detailed information in the Treatment Regimen Details section below.
  Adult and Pediatric Regimen: Artesunate (now commercially available or if not in stock or unable to administer within 24 hours, call CDC's Malaria Hotline: 9 am to 5 pm Mon-Fri --- 770-488-7100 or Toll-free 855-856-4713; After hours, weekends, and holidays: 770-488-7100)
  1 dose = 2.4 mg/kg
  IV doses (3 in total) at 0, 12, and 24 hours
  NOTA BENE: If IV artesunate is not readily available: INITIALLY give ORAL antimalarials (see the above) while obtaining IV Artesunate. When IV artesunate arrives, discontinue oral antimalaria and initiate IV treatment. IF ORAL TREATMENT is NOT tolerated, consider administration by nasogastric tube or give after and antiemetic.
  PLUS reassessment and follow-on treatment below
  Reassessment and Follow-On Treatment (See Uncomplicated falciparum malaria above for oral dosing)
  Reassess parasite density at least 4 hours after the 3rd IV dose of artesunate
  Parasite density less than or equal to 1 percent AND the patient is tolerating oral medications: Give a COMPLETE follow-on ORAL regimen with one of the following:
  Artemether-lumefantrine (CoArtemTM): PREFERRED; or
  Atovoquone-proguanil (MalaroneTM); or
  Quinine sulfate PLUS doxycycline OR in children less than 8 years or pregnant women substitute doxycycline with clindamycin; or
  Mefloquine (only if NO OTHER TREATMENT OPTIONS ARE AVAILABLE)
  Parasite density greater than 1 percent: continue IV artesunate at the same dose, each day for up to 6 more days until the parasite density is 1 percent or less.
  Able to take oral medications: Give the complete follow-on regimen (See Uncomplicated falciparum malaria above for oral dosing)
  If unable to take oral medications, continue IV artesunate every day for up to 6 more days until the patient can take oral medication and then give the complete follow-on regimen
  IMPORTANT: All persons treated for severe malaria with IV artesunate should be monitored WEEKLY for up to 4 WEEKS after treatment initiation for evidence of hemolytic anemia.
  IV artesunate is well tolerated.
  While rare, delayed post-artemisinin hemolytic anemia has been noted in published case reports following treatment of severe malaria with IV artesunate.
  Persons with higher parasite density seem to have a higher likelihood of delayed hemolytic anemia after treatment.
  Weekly laboratory evaluation should include:
  Total bilirubin.
  Depending on the intensity of hemolysis and the presence of anemia signs and symptoms, a blood transfusion may be needed.
  Reporting cases of delayed post-artemisinin hemolytic anemia:
  Those receiving IV artesunate from CDC should be reported to CDC no longer than 24 hours after diagnosis.
  Those receiving commercially available Artesunate for InjectionTM should be reported to MedWatch, FDA's Safety Information and Adverse Event Reporting Program.
  Exchange transfusion: no longer considered routine recommendation as this procedure has not been proven to be beneficial in an adequately powered randomized clinical trial.
  Antibiotic resistance patterns (see above) should guide treatment or modification of empiric therapy.
  Change to other agents based on resistance pattern.
  All immunocompromised persons (organ transplant, HIV-infected, persons who received corticosteroids or immunosuppressive therapies), those with sickle cell disease, hemoglobinopathies, cirrhosis, cancer or lymphoproliferative disease: treat regardless of the severity of symptoms.
  Shigella spp: In healthy adults, most Shigella infections are self-limiting but for public health reasons, all persons with a positive stool culture should be treated to decrease shedding and person-to-person spread.
  Antibiotic resistance is widespread and increasing. High levels of multidrug resistance (ciprofloxacin, trimethoprim-sulfamethoxazole, and azithromycin) in the Asian Subcontinent and Sub-Sahran Africa)
  Levofloxacin: 500 mg orally once daily x 3 d
  Ciprofloxacin 500 mg orally twice daily x 5 d
  Azithromycin: 500 mg orally once daily x 3 days
  Cefixime: 200 mg orally twice daily for 5 days
  Trimethoprim-sulfamethoxazole 160/800 mg (one double-strength tablet) orally twice daily x 5 days
  Ampicillin: 500 mg orally every 6 hours x 5 days
  Base final treatment on culture and sensitivity results (consider adding 2-4 days of treatment for immunocompromised patients)
  Drug resistance is widespread and increasing and is higher for fluoroquinolones compared with macrolides.
  Preferred: azithromycin 500 mg orally every day x 3 days or until signs and symptoms of de
  Alternative erythromycin stearate 500 mg orally twice daily for 5 days
  Adults: 500-750 mg orally three times daily x 10 d
  Children: 35 - 50 mg/kg/day in 3 divided doses x 7-10 d
  Adults:2 grams orally x 3 d
  Adults: 500 mg orally daily x 3 d
  Children: 40 mg/kg/d orally x 3 d
  Adults: 2 grams orally daily x 1-3 d
  Children: 30 mg/kg/d orally x 1-3 d
  Mild to moderate disease: Paromomycin 25 - 35 mg/kg/d in 3 divided doses x 5-10 d
  Severe disease: Metronidazole as above
  Fulminant cases should include treatment of gram-negative organisms. In the uncommon setting of toxic megacolon, surgical intervention may be needed.
  Locale of acquisition will impact treatment choices due to local resistance patterns. Empiric recommendations are given below. Adjust based on culture results.
  Severe or complicated disease
  Infections acquired outside of Pakistan or Iraq
  Ceftriaxone: 1-2 g IV once daily for 7-14 d
  Alternate if ceftriaxone is not available: Cefotaxime: 1-2 g IV every 8 h for 7-14 d
  Infection acquired in Pakistan or Iraq due to the presence of extensively drug-resistant S Typhi
  Meropenem: 1 -2 g IV every 8 h x 7-14 d
  May substitute other carbapenems if meropenem is not available.
  Uncomplicated Disease Acquired in Eastern Europe, Middle East, South America or sub-Saharan Africa:
  Cefixime: 200 mg orally twice daily x 10-14 d
  Azithromycin: 1 g orally then 500 mg orally daily OR 1 g orally once daily x 5-7 d
  Cefixime: 20 mg/kg orally in 2 divided doses (maximum 400 mg per day) x 10-14 d
  Azithromycin: 10 - 20 mg/kg orally conce per day (maximum 1000 mg/d) x 5-7 d
  Complicated infection or for those who cannot tolerate oral medications:
  Ceftriaxone: 2 g IV once or twice daily x 10-14 d
  Cefotaxime: 150-200 mg/kg IV/d in 3-4 divided doses (maximum 8 g/d) x 10-14 d
  Acquisition location unknown or in Southeast Asia (not Pakistan or Iraq):
  Azithromycin: 10 - 20 mg/kg orally once per day (maximum 1000 mg/d) x 5-7 d
  Ciprofloxacin (justified use in severe infection): 20 mg/kg/d in 2 divided doses (maximum 800 mg/d) x 7-10 d
  Ceftriaxone: 50-100 mg/kg IV in 1 or 2 divided doses (maximum 4 g/d) x 10-14 d
  Cefotaxime: 150-200 mg/kg IV in 3-4 divided doses (maximum 8 g/d) x 10-14
  No chikungunya-specific antiviral drug treatment is available.
  If suspected, begin treatment empirically since diagnostic test results are often delayed or not performed.
  Pregnant women: if a life-threatening infection, doxycycline should be used despite being a Category D agent. Consider consultation with an infectious disease expert.
  No Dengue-specific treatments are available.
  If dengue hemorrhagic fever is suspected, consider consulting with a specialist.
  Usually is a self-limited disease requiring only supportive measures.
  A risk of Guillain Barre syndrome is present for weeks following infection although the proportionate risk is small.
  Aggressive treatment is required with parenteral antimalarial therapy, if available.
  Treatment with IV quinidine should be initiated as soon as possible after diagnosis is secured. Use IV loading dose of quinidine unless they have received more than 40 mg/kg of quinine in the preceding 48 hours or if they have received mefloquine within the preceding 12 hours.
  See Treatment of complicated/severe P. falciparum section for use of investigational artemisinin for patients with severe malaria.
  Exchange transfusion if the parasite density (i.e. parasitemia) is >10% remains less favored now than historically[17] OR if the patient has altered mental status, non-volume overload pulmonary edema, or renal complications. Since 2013, CDC does not recommend red blood cell exchange transfusion.
  Parasite density: estimated by examining a monolayer of red blood cells (RBCs) on the thin smear under oil immersion magnification. The slide should be examined where the RBCs are more or less touching (approximately 400 RBCs per field). Parasite density estimated by the percentage of infected RBCs; monitor q 12h.
  If exchange transfusion is employed, continue until the parasite density is < 1% (usually requires 8-10 units).
  Each dose should be taken with fatty food to be effective because lumefantrine is highly lipophilic.
  Use with caution for treatment in persons with low GFR (10-50 ml/min). It is unlikely to be removed by hemodialysis or peritoneal dialysis. Atovaquone has a 2-3 day half-life whereas the proguanil has a half-life of 12-21 hours.
  Cross allergy with penicillin is lower than with first-generation cephalosporins; it has been used effectively in the treatment of enteric fever.
  Remains effective prophylaxis and treatment for malaria in some areas. Pruritis is not uncommon in persons with darker skin pigmentation. Lower side effect profile than mefloquine.
  Studies were done in the 1950s comparing chloroquine and hydroxychloroquine for treatment in rheumatoid arthritis demonstrating a lower side effect profile for hydroxychloroquine. Similar trials have not been done comparing malaria prophylactic and treatment regimens for these 2 drugs in terms of side effects although efficacy is equivalent.
  Do not use for prophylaxis or treatment of P. falciparum acquired in Thailand, Laos, or Cambodia. Best administered with food; coadministration with fluoroquinolones, antiarrhythmics, and macrolides may prolong QTc.
  A higher dose (30 mg vs previously used 15 mg) may be associated with neutropenia and leukopenia in some persons. Hepatic metabolism. Assess G6PD status before administration.
  Cinchonism (tinnitus, headache, nausea, abdominal pain, visual disturbances) can be seen during treatment; occasionally see hemolytic anemia in persons with G6PD deficiency
  Treatment for severe malaria is essentially its only current use; manufacturing may cease following approval of parenteral artemisinin due to ease of administration of the new drug and better safety profile.
  Consider consultation with an infectious disease- or tropical medicine expert for any returned traveler with undifferentiated fever, especially if suspects include malaria, enteric fever, or viral hemorrhagic fever, or the patient has neurological findings.
  Ballard SB, Salinger A, MPHc, et al. Updated CDC Recommendations for Using Artemether-Lumefantrine for the Treatment of Uncomplicated Malaria in Pregnant Women in the United States. MMWR Morb Mortal Wkly Rep. 2018;67(14):424-431. [PMID:29649190]
  Comment: ABSTRACT: Malaria infection during pregnancy is associated with an increased risk for maternal and fetal complications. In the United States, treatment options for uncomplicated, chloroquine-resistant Plasmodium falciparum and P. vivax malaria in pregnant women are limited to mefloquine or quinine plus clindamycin (1). However, the limited availability of quinine and increasing resistance to mefloquine restrict these options. Strong evidence now demonstrates that artemether-lumefantrine (AL) (Coartem) is effective and safe in the treatment of malaria in pregnancy. The World Health Organization (WHO) has endorsed artemisinin-based combination therapies (ACTs), such as AL, for the treatment of uncomplicated malaria during the second and third trimesters of pregnancy and is currently considering whether to add ACTs, including AL, as an option for malaria treatment during the first trimester (2,3). This policy note reviews the evidence and updates CDC recommendations to include AL as a treatment option for uncomplicated malaria during the second and third trimesters of pregnancy and during the first trimester of pregnancy when other treatment options are unavailable. These updated recommendations reflect current evidence and are consistent with WHO treatment guidelines.
  Comment: This is an outstanding review. It provides a useful algorithm to guide the workup of the febrile returning traveler, diagnoses for consideration. Additionally, there are 3 concise tables that would be of great use to the clinician. The first addresses life-threatening conditions (viral, bacterial and protozoal) which should not be missed. The second concisely outlines the critical areas in the travel and medical history to be considered in assessing the febrile returned traveler and the diseases to consider when risks are identified. The third table has both clinical and public health implications as it concisely summarizes the serious transmissible infections.
  Comment: This is an excellent editorial that summarizes the pros and cons of the use of the qSOFA vs the standard SOFA. The ability to rapidly apply the qSOFA to guide intervention at the time of presentation to an emergency department without relying on formulae or websites should be considered in assessing this tool's usefulness. The qSOFA score ranges from 0 to 3. One point is given for each of the following: SBP < /=100 mm Hg; respiratory rate >/= 22/min, and evidence of altered mental status on Glasgow Coma Score (normal = 15, range 3-15).
  Centers for Disease Control and Prevention. Treatment of Malaria: Guidelines for Clinicians (United States). Accessed 29 April 2022; last reviewed by CDC 2 Nov 2020. Found at: https://www.cdc.gov/malaria/diagnosis_treatment/clinicians1.html
  Comment: The malaria treatment guidelines are provided online for clinicians and updated as needed by CDC. IMPORTANT: All persons treated for severe malaria with IV artesunate should be monitored weekly for up to four weeks after treatment initiation for evidence of hemolytic anemia.
  Comment: This alphavirus carried by Aedes spp mosquitos has re-emerged in recent years in Africa, southern and SE Asia and the Indian Ocean islands (and now has appeared for the first time in the Caribbean islands). The disease associated with infection is usually associated with fever, headache, myalgia, rash and arthralgia which can be acute as well as chronic. It traditionally was thought to be associated with varying morbidity but only since 2005 has mortality been noted. Because Aedes spp, particularly Ae. albopictus is common in both Europe and the U.S. and infected larvae can overwinter, this virus poses a threat in the Americas.
  Comment: This is an analysis of data collected in the GeoSentinel Surveillance system examining the risk of illnesses amongst 4779 ill travelers to common destinations in Mexico and Central America in the period 1996 to 2010. Although malaria was not commonly diagnosed at participating surveillance sites when compared with travelers to subSaharan Africa or parts of Asia, malaria was seen increasingly with more southern travel. The most frequent presenting syndromes included acute and chronic diarrhea, dermatologic diseases, febrile systemic illness, and respiratory disease. The overall risk of malaria was low; only 4 cases of malaria were acquired in Mexico (Proportionate Morbidity [PM} of 2.0 per1000 ill returned travelers) in 13 years, compared with 18 from Honduras (PM, 79.6 cases per 1000 ill returned travelers) and 14 from Guatemala (PM, 34.4 cases per 1000 ill returned travelers) during the same period. Plasmodium vivax malaria was the most frequent malaria diagnosis.
  Comment: This is an analysis of 2004-2008 Salmonella spp isolates submitted to the CDC's FoodNet foodborne disease active surveillance network in which travel-acquired infections were compared with non-travel associated infections. Among 23,712 reported cases with known travel status, 11% had traveled internationally in the 7 days before illness. Travelers with Salmonella infection tended to be older (median age, 30 years) than non-travelers (median age, 24 years; p< 0.0001), but were similar with respect to gender. The most common destinations reported were Mexico (38% of travel-associated infections), India (9%), Jamaica (7%), the Dominican Republic (4%), China (3%), and the Bahamas (2%). The 2 most commonly reported serotypes, regardless of travel status, were Enteritidis (19% of cases), and Typhimurium (14%). However, serotypes associated with enteric fever (S. typhi and S. paratyphi) were found in 10% of samples from travelers but only 0.5% of samples submitted from non-travelers.
  Comment: Examines the increase in dengue worldwide as well as the reintroduction of endemic foci in the U.S. in southern Texas and in Key West and mainland Florida.
  Comment: This case series describes 62 (60% males) consecutive adult patients presenting for care after returning to France from overseas with fever (>38oC) and exanthema (widespread rash) between January 2006 and September 2007. The most common diagnoses included chikungunya (35%), dengue (26%), and African tick-bite fever (10%). The cause of the rash was not identified in 8%. Other causes accounting for 1-5% of illnesses were: infectious mononucleosis, primary HIV infection, DMV, measles, rubella, varicella, primary toxoplasmosis, and acute schistosomiasis. When comparing chikungunya with dengue virus infection those with dengue infection had significantly greater leukopenia, neutropenia, lymphopenia, thrombocytopenia, and headache. Notably, those with chikungunya had characteristic arthralgia (100%) whereas arthralgia was absent in those with dengue infection.
  Comment: This was a retrospective laboratory-based study of 960 filter paper blood spots collected from slide-positive malaria diagnosed amongst hospitalized persons by the Malaysian Ministry of Health between 2001 and 2006. Diagnostic microscopy recorded 44.6% P. vivax; 32.5% P. malariae, 22.5% P. falciparum, 0.2% P. ovale, and 0.2% mixed infections. P. knowlesi was detected in 260 of 960 (27.7%) of these samples by nested PCR; only 4 (0.4%) were confirmed as P. malariae. Additionally, 54 archived slides from 2003-2005 from outlying district hospitals and clinics with microscopically diagnosed P. malariae were further evaluated after whole blood slide extraction and nested PCR. 46 (85%) were found to be P. knowlesi; 5(15%) were confirmed as P. malariae. Four of the 46 archival cases were fatal; all had high parasitemia and significant hepato-renal dysfunction. These data suggest that P. knowlesi is not as rare as previously thought and suggest that aggressive management similar to that given for P. falciparum is warranted given the observed case fatality.
  Comment: This prospective study of 118 febrile (T ≥37.5 oC by axilla) travelers >14 years of age, 10 days before or 10 days after their return without a specific diagnosis made on their first clinic visit upon return to Spain. All had nasopharyngeal swabs, blood, stool cultures collected. Malaria was sought in all patients. Amongst the group 73 had only respiratory symptoms, 12 had gastrointestinal (GI) symptoms, 5 had both respiratory and GI symptoms, and 28 had an undifferentiated febrile illness. In the respiratory and respiratory/GI illness group 44 were found to have a viral or bacterial respiratory pathogen with 46% of travelers to Latin America infected, and 37% of travelers to both Asia and Africa. The influenza virus was isolated from 18 persons (12 influenza A and 6 influenza B). Influenza A virus was isolated from travelers returning from Asia > Africa and Latin America. Rhinovirus was isolated from 11 persons returning from all continents. Parainfluenza viruses were isolated from 6 travelers and RSV and adenovirus from 4 each.
  Comment: This is a report from the GeoSentinel Surveillance Network of 24,920 returning ill travelers evaluated in 31 international sites over a 10-year period ending in 2006. Febrile illness was the chief complaint in 6,957 persons (28%) seeking care post-travel; 26% of this group were hospitalized versus 3% of afebrile travelers. Amongst febrile persons, 35% had an undifferentiated fever, 15% had febrile diarrhea, and 14% had a febrile respiratory illness. The etiology of fever was dependent upon the region of the world that was visited and the reason for visit. Malaria was the most common specific diagnosis identified (21%) and accounted for 4 of 12 deaths among febrile travelers. The next most common cause of fever was dengue followed by enteric fever and rickettsial diseases. Vaccine-preventable infections were seen in 3% of travelers with fever (S. typhi infection [n=100], acute hepatitis A [n=41], and influenza A [n=29]. Those traveling to visit friends and relatives, so-called VFR travelers were more likely to have a vaccine-preventable febrile illness when compared to other febrile travelers (Odds Ratio 1.8, confidence interval 1.4-2.4, p< 0.001).
  Comment: This is an analysis of data collected from 30 sites participating in the CDC-sponsored GeoSentinel Surveillance Network of specialized travel or tropical medicine clinics on 6 continents regarding 17,353 ill returned travelers (persons who had crossed an international border in the 10 years prior to presenting with their illness). Significant differences were noted in proportionate traveler morbidity and mortality among the developing regions of the world. The systemic febrile illness (SFI) rate was 594 per 1000 persons with SFI and was the highest in sub-Saharan Africa (718/1000). Malaria accounted for the greatest proportionate morbidity (352/1000 with sub-Saharan Africa accounting for 2-4 times the burden as other regions (622/1000). Dengue was the second leading cause of SFI (352/1000) with the greatest burden seen in travelers returning from Asia and the Caribbean. Acute diarrheal illness was most prevalent among travelers returning from south-central Asia whereas dermatological problems were most frequent in those who had visited the Caribbean, Central or South America.
  Comment: This is a literature-based review and additional case synthesis by one world expert. There are 15 recognized tick-borne rickettsioses; 8 of the 15 have been reported in international travelers (African tick-bite fever, Mediterranean spotted fever, Indian tick typhus, Astrakhan fever, Rocky Mountain spotted fever, Queensland tick typhus, R. aeschlimannii infection and North Asian tick typhus. Off the ~400 cases of tick-borne rickettsioses reported among international travelers, most are due to either Rickettsia africae (Subsaharan Africa-African tick-bite fever) or R.conorii (North Africa/Mid-East/India--Mediterranean spotted fever). The incidence among travelers appears to be increasing for several possible reasons: increased ecotourism increased travel to previously restricted areas (such as to post-apartheid game parks in the Republic of South Africa), and increased diagnostic awareness. Provides recommendations for treatment.
  CDC. Exchange transfusion is no longer recommended. http://www.cdc.gov/malaria/new_info/2013/exchange_transfusion.html (July 2013)
  Comment: This is the report of a retrospective case review of 708 febrile returning travelers all of whom were tested for Q fever (Coxiella burnetti infection). Five (0.7%) persons were found to be infected. All patients had a fever, 4/5 had a headache, 3/5 had arthralgia and myalgia, one had a dry cough, one was jaundiced, and one complained of malaise. Chest radiographs were normal in all 5, all 5 had an enlarged liver, spleen or both. All initially had normal white blood cell counts in the setting of thrombocytopenia (13,000-98,000 cells/mL) and abnormal transaminases. Treatment was with either doxycycline or ciprofloxacin. All recovered with no complications.
  Hynes, Noreen A. "Fever in the Returned Traveler From Tropical Areas." Johns Hopkins ABX Guide, The Johns Hopkins University, 2022. Johns Hopkins Guide, www.hopkinsguides.com/hopkins/view/Johns_Hopkins_ABX_Guide/540222/3.2/Fever_in_the_returned_traveler_from_tropical_areas.
  Hynes NA. Fever in the returned traveler from tropical areas. Johns Hopkins ABX Guide. The Johns Hopkins University; 2022. https://www.hopkinsguides.com/hopkins/view/Johns_Hopkins_ABX_Guide/540222/3.2/Fever_in_the_returned_traveler_from_tropical_areas. Accessed May 27, 2022.
  Hynes, N. A. (2022). Fever in the returned traveler from tropical areas. In Johns Hopkins ABX Guide. The Johns Hopkins University. https://www.hopkinsguides.com/hopkins/view/Johns_Hopkins_ABX_Guide/540222/3.2/Fever_in_the_returned_traveler_from_tropical_areas
  Hynes NA. Fever in the Returned Traveler From Tropical Areas [Internet]. In: Johns Hopkins ABX Guide. The Johns Hopkins University; 2022. [cited 2022 May 27]. Available from: https://www.hopkinsguides.com/hopkins/view/Johns_Hopkins_ABX_Guide/540222/3.2/Fever_in_the_returned_traveler_from_tropical_areas.
  TY - ELEC T1 - Fever in the returned traveler from tropical areas ID - 540222 A1 - Hynes,Noreen,M.D., M.P.H., D.T.M.&H. Y1 - 2022/05/08/ BT - Johns Hopkins ABX Guide UR - https://www.hopkinsguides.com/hopkins/view/Johns_Hopkins_ABX_Guide/540222/3.2/Fever_in_the_returned_traveler_from_tropical_areas PB - The Johns Hopkins University DB - Johns Hopkins Guide DP - Unbound Medicine ER -