Plasmodium. These parasites are transmitted by the bite of an infective female Anopheles species mosquito. The majority of malaria infections in the United States occur among persons who have traveled to regions with ongoing malaria transmission. However, malaria is occasionally acquired by persons who have not traveled out of the country through exposure to infected blood products, congenital transmission, laboratory exposure, or local mosquitoborne transmission. Malaria surveillance in the United States is conducted to provide information on its occurrence , guide prevention and treatment recommendations for travelers and patients, and facilitate transmission control measures if locally acquired cases are identified.Malaria in humans is caused by intraerythrocytic protozoa of the genus This report summarizes confirmed malaria cases in persons with onset of illness in 2015 and summarizes trends in previous years.Malaria cases diagnosed by blood film microscopy, polymerase chain reaction, or rapid diagnostic tests are reported to local and state health departments by health care providers or laboratory staff members. Case investigations are conducted by local and state health departments, and reports are transmitted to CDC through the National Malaria Surveillance System (NMSS), the National Notifiable Diseases Surveillance System (NNDSS), or direct CDC consultations. CDC reference laboratories provide diagnostic assistance and conduct antimalarial drug resistance marker testing on blood samples submitted by health care providers or local or state health departments. This report summarizes data from the integration of all NMSS and NNDSS cases, CDC reference laboratory reports, and CDC clinical consultations.Plasmodium falciparum, P. vivax, P. ovale, and P. malariae were identified in 67.4%, 11.7%, 4.1%, and 3.1% of cases, respectively. Less than 1% of patients were infected by two species. The infecting species was unreported or undetermined in 12.9% of cases. CDC provided diagnostic assistance for 13.1% of patients with confirmed cases and tested 15.0% of P. falciparum specimens for antimalarial resistance markers. Of the U.S. resident patients who reported purpose of travel, 68.4% were visiting friends or relatives. A lower proportion of U.S. residents with malaria reported taking any chemoprophylaxis in 2015 (26.5%) compared with 2014 (32.5%), and adherence was poor in this group. Among the U.S residents for whom information on chemoprophylaxis use and travel region were known, 95.3% of patients with malaria did not adhere to or did not take a CDC-recommended chemoprophylaxis regimen. Among women with malaria, 32 were pregnant, and none had adhered to chemoprophylaxis. A total of 23 malaria cases occurred among U.S. military personnel in 2015. Three cases of malaria were imported from the approximately 3,000 military personnel deployed to an Ebola-affected country; two of these were not P. falciparum species, and one species was unspecified. Among all reported cases in 2015, 17.1% were classified as severe illnesses and 11 persons died, compared with an average of 6.1 deaths per year during 2000–2014. In 2015, CDC received 153 P. falciparum-positive samples for surveillance of antimalarial resistance markers ; genetic polymorphisms associated with resistance to pyrimethamine were identified in 132 (86.3%), to sulfadoxine in 112 (73.7%), to chloroquine in 48 (31.4%), to mefloquine in six (4.3%), and to artemisinin in one (<1%), and no sample had resistance to atovaquone. Completion of data elements on the malaria case report form decreased from 2014 to 2015 and remains low, with 24.2% of case report forms missing at least one key element .CDC received reports of 1,517 confirmed malaria cases, including one congenital case, with an onset of symptoms in 2015 among persons who received their diagnoses in the United States. Although the number of malaria cases diagnosed in the United States has been increasing since the mid-1970s, the number of cases decreased by 208 from 2014 to 2015. Among the regions of acquisition , the only region with significantly fewer imported cases in 2015 compared with 2014 was West Africa (781 versus 969). The decrease in malaria cases from 2014 to 2015 is associated with a decrease in imported cases from West Africa. This finding might be related to altered or curtailed travel to Ebola-affected countries in in this region. Despite progress in reducing malaria worldwide, the disease remains endemic in many regions, and the use of appropriate prevention measures by travelers is still inadequate.P. falciparum, even in high transmission areas. Detailed recommendations for preventing malaria are available to the general public at the CDC website . Malaria infections can be fatal if not diagnosed and treated promptly with antimalarial medications appropriate for the patient’s age and medical history, the likely country of malaria acquisition, and previous use of antimalarial chemoprophylaxis. Health care providers should consult the CDC Guidelines for Treatment of Malaria in the United States and contact the CDC’s Malaria Hotline for case management advice when needed. Malaria treatment recommendations are available online  and from the Malaria Hotline (770-488-7788 or toll-free at 855-856-4713). Persons submitting malaria case reports  should provide complete information because incomplete reporting compromises case investigations and efforts to prevent infections and examine trends in malaria cases. Compliance with recommended malaria prevention strategies is low among U.S. travelers visiting friends and relatives. Evidence-based prevention strategies that effectively target travelers who are visiting friends and relatives need to be developed and implemented to reduce the numbers of imported malaria cases in the United States. Molecular surveillance of antimalarial drug resistance markers  has enabled CDC to track, guide treatment, and manage drug resistance in malaria parasites both domestically and internationally. More samples are needed to improve the completeness of antimalarial drug resistance marker analysis; therefore, CDC requests that blood specimens be submitted for all cases diagnosed in the United States.The best way to prevent malaria is to take chemoprophylaxis medication during travel to a country where malaria is endemic. As demonstrated by the U.S. military during the Ebola response, use of chemoprophylaxis and other protection measures is possible in stressful environments, and this can prevent malaria, especially  Plasmodium genus are transmitted through the bite of infected mosquitoes. Female Anopheles species mosquitoes transmit four Plasmodium species that commonly cause illness in humans: P. falciparum, P. vivax, P. ovale, and P. malariae. Mixed infections with multiple species are possible and occur in areas where more than one species is in circulation  estimated that 212 million cases of malaria occurred worldwide in 2015, resulting in 429,000 deaths  that can reactivate months or years after the acute infection. P. malariae parasites mature slowly in human and mosquito hosts, and although they do not typically cause severe symptoms, they can result in persistent low-density infections that can last for years or even a lifetime  and the National Notifiable Diseases Surveillance System (NNDSS) . A rapid diagnostic test (RDT) can be used to detect malaria antigens  was used to assess the linear trend in the number of cases during 1973–2015 and the number of airline flights from the United States to Africa.The chi-square test was used to calculate p values and assess differences between variables reported in 2015 compared with previous years. A p value of <0.05 was considered statistically significant. Linear regression using least-squares methods : Immigrants, ethnically and racially distinct from the major population of the country of residence , who return to their homeland  to visit friends or relatives; includes family members  who were born in the country of residence .Confirmed case: Symptomatic or asymptomatic infection that occurs in a person in the United States or one of its territories who has laboratory-confirmed (by microscopy or PCR) malaria parasitemia, regardless of whether the person had previous episodes of malaria while in other countries. A subsequent episode of malaria is counted as an additional case, regardless of the detected Plasmodium species, unless the case is indicated as a treatment failure.Suspect case: Symptomatic or asymptomatic infection that occurs in a person in the United States or one of its territories who has Plasmodium species infection detected by RDT without confirmation by microscopy or PCR, regardless of whether the person experienced previous episodes of malaria while in other countries.Adherence to chemoprophylaxis: Self-reported response to the question, “Was chemoprophylaxis taken as prescribed?”Treatment according to CDC recommendations : Treated with a CDC-recommended regimen appropriate for species, region, and severity of disease  of P. vivax and P. ovale only. Acute illness typically occurs within 45 days of exposure; therefore, likely relapses of P. vivax and P. ovale are defined as occurring >45 days after travel to an area where malaria is endemic.Severe malaria: A case of malaria with one or more of the following manifestations: neurologic symptoms, acute kidney injury, severe anemia (hemoglobin [Hb] <7g/dL), acute respiratory distress syndrome (ARDS), jaundice, or ≥5% parasitemia  detects circulating malaria-specific antigens and is approved for use by hospital and commercial laboratories. Therefore, the test should be used in a clinical laboratory by trained staff members and not by clinicians or the general public  are investigated for all P. falciparum samples. Additional species will be similarly evaluated as new laboratory methods are developed. Each sample submitted is tested for molecular markers associated with resistance to sulfadoxine, pyrimethamine, chloroquine, mefloquine, atovaquone, and artemisinin.In 2012, CDC began molecular surveillance for malaria drug resistance markers, with the goal of detecting and characterizing malaria parasites that carry genetic markers  associated with drug resistance. The surveillance data will help identify where drug-resistant foci might be present or emerging in specific parts of the world where malaria is endemic. For each sample submitted, species confirmation testing is conducted using a duplex real-time PCR capable of detecting the four human-infecting pfcrt), pyrimethamine , sulfadoxine , atovaquone , mefloquine , and artemisinin (kelch K13-propeller domain) are analyzed for SNPs by comparing each sequence to the reference genome.Samples for molecular resistance monitoring are processed for PCR amplification of parasite DNA using appropriate primers for the genes of interest and sequenced by the Sanger method using the ABI 3130 capillary sequencer  according to described methods  method as previously described  (2 = 0.742), and an average annual gain of approximately 12,000 to Africa (R2 = 0.703) .= 0.695) . This in= 0.703)  (35). In= 0.703) .Among the 1,517 confirmed cases, one was classified as congenital, 1,485 were imported from countries in which malaria is endemic, and 31 case reports had an incomplete travel history, which prevented classification. Of the 31 cases with unknown classification, 10 had laboratory reports only, which provided diagnostic test information and demographic data; 16 cases were reported through NNDSS with basic demographic data; and five were reported by local or state health departments as lost to follow-up with insufficient information to classify importation status. No case in 2015 was reported as having been acquired by local transmission in the United States.Plasmodium species, which is similar to the proportion from 2014 (88.3%). Specimens from 198 (13.1%) cases were sent to the CDC reference laboratory for diagnostic assistance in 2015, and CDC identified the species for 195 (98.5%) specimens. Among these 195 specimens, CDC determined or corrected the species for 108 (55.4%)  cases reported to CDC included information on the infecting  (55.4%) . No PlasP. falciparum ; P. vivax infections were the second most common, with 13.5% (n = 178) of cases reported in 2015  were acquired in Africa, which was significantly lower than in 2014 . P. falciparum infections accounted for 86.6% of cases from Africa, 4.8% from Asia, 70.9% from Central America and the Caribbean, and 20.8% from South America . The increase in P. falciparum infections imported from this region resulted from cases acquired from the island of Hispaniola. The number of cases from Haiti decreased from a peak of 171 cases in 2010 to five in 2014; in 2015, the number of malaria cases from Haiti was 11. During 2005–2014, the United States had an average of 4.6 cases per year imported from the Dominican Republic. In 2014, two cases were imported from the Dominican Republic, and the number increased significantly to 32 cases in 2015.Information on the infecting species and region of acquisition was included for 1,264 case reports; of these 1,078 (85.3%) were from Africa. Information on region of acquisition information was available for 984  America . The numP. vivax infections with information about region of acquisition, 91 (55.2%) were acquired from Asia, followed by 39 (23.6%) from Africa, 16 (9.7%) from Central America and the Caribbean, 17 (10.3%) from South America, and two (1.2%) from Oceania. In 2015, a total of 59 P. ovale and 44 P. malariae infections were reported with information about the region of acquisition; 56 (94.9%) and 39 (88.6%) were acquired in Africa, respectively. P. vivax cases imported from Central America and the Caribbean totaled 13 in 2014 and 16 in 2015.Of 165 imported In 2015, the region of acquisition was known for 1,428 (96.2%) of 1,485 imported cases. Among these, 1,210 (84.7%) were acquired in Africa, 123 (8.6%) from Asia, and 66 (4.6%) from Central America and the Caribbean. Less than 2% of the imported malaria cases were acquired from South America (26 cases), Oceania (two cases), or the Middle East (one case).Overall, 175 fewer cases were acquired from Africa in 2015 than in 2014 . In 2015The number of cases imported from Asia in 2015 was not significantly different from the number imported in 2014 . India had the most cases imported from this region; cases from India decreased from 100 in 2014 to 64 in 2015. Cases imported from Afghanistan totaled 11 in 2014 and 20 in 2015, and the numbers of infections imported from Pakistan totaled 25 cases in 2014 and 27 cases in 2015.P. vivax with 0.03% parasitemia. Neither case was confirmed by a public health laboratory or the CDC reference laboratory. The patients had symptoms 11 and 15 days after arrival to the area where malaria is endemic, suggesting short incubation periods. The patients were lost to follow-up, and no additional information could be obtained to confirm their travel histories.Imported cases from Central and South America and the Caribbean increased significantly from 54 (3.4%) in 2014 to 92 (6.4%) in 2015. Although the number of cases imported from Central America (17 cases in 2014 and 23 cases in 2015) and South America (29 cases in 2014 and 26 cases in 2015) remained steady, in 2015 the number of cases imported from the Caribbean increased from eight in 2014 to 43 cases in 2015. Two cases were imported from the Dominican Republic in 2014, which increased to 32 in 2015. Of these 32 cases, 25 patients provided a reason for travel, and of these, 22 traveled to the Dominican Republic for tourism; three patients reported VFR travel. Seven cases described as a cluster were imported into Puerto Rico after patients went on a school trip and took no chemoprophylaxis , Maryland (127), California (106), Texas (100), New Jersey (86), Virginia (71), Georgia (69), Massachusetts (60), Florida (58), New York State (not including New York City) (58), and Illinois (54) . ConsistAmong 1,485 imported cases, 1,318 (88.8%) reported their residency status; 951 (72.2%) were U.S. residents and 367 (27.9%) were foreign residents . The majThree fourths of malaria cases imported among foreign residents in 2015 were from Africa (274 [74.7%]), followed by Asia (63 [17.2%]) and the Americas and Caribbean (15 [4.1%]). Among foreign residents, regional differences in the numbers of imported malaria cases did not vary significantly from 2014 to 2015. From 2014 to 2015, fewer cases were imported among residents of Ghana (30 to 15 cases), India (40 to 30 cases), Nigeria (75 to 67 cases), and Ethiopia (16 to eight cases). However, more cases were reported from 2014 to 2015 among residents of Côte d’Ivoire (10 to 17 cases), Democratic Republic of the Congo (11 to 15 cases), Afghanistan (eight to 15 cases), Burkina Faso (seven to 11 cases), and Sudan (one to seven cases).In 2015, during the Ebola outbreak in West Africa, a significant decrease occurred in the proportion of U.S. residents who acquired malaria from West Africa: 710 (62.2%) in 2014 compared with 540 (56.8%) in 2015. Likewise, a twofold decrease occurred in the number of U.S. residents who acquired malaria from countries with widespread Ebola transmission (214 [18.7%] in 2014 versus 91 [9.6%] in 2015). The change from 2014 to 2015 in imported malaria cases among foreign residents from West Africa (194 [50.5%] in 2014 versus 175 [47.7%] in 2015) and among foreign residents from countries with widespread Ebola transmission (Ebola-affected countries) (51 [13.3%] in 2014 versus 41 [11.2%] in 2015) was not significant.P. falciparum species accounted for 150 (72.8%) of 206 cases imported in August 2015 and 23 (57.5%) of 40 cases in February 2015. P. vivax and P. ovale infections were combined because the illnesses have relapsing potential, and a secondary peak can occur after the main peak. In 2015, the mean number of P. vivax and P. ovale cases was 19.0 per month; the maximum (34 cases) occurred in July. The number of P. vivax and P. ovale cases was greater than the mean during June–August and in October. In 2015, no obvious secondary peak of imported cases for P. vivax and P. ovale occurred, although the numbers were small.As in previous years . A totalPlasmodium species determination, 1,068 (81.8%) had complete information on return travel and illness onset dates, allowing for calculation of the interval between dates  had symptom onset before or within 29 days of arrival to the United States. In contrast, 51 (38.9%) of P. vivax patients and 25 (59.5%) of P. ovale patients had illness onset ≥30 days after arrival in the United States, consistent with the potential for these species to relapse because of the persistence of liver hypnozoites. Ninety-nine percent of infections of any species occurred within 1 year of arrival to the United States after travel to a country where malaria is endemic.Among 1,306 imported cases with a en dates . Among aP. falciparum, four (25.0%) were P. vivax, two (12.5%) were P. ovale, and one (6.3%) was P. malariae. Four of the six patients who were infected with a species capable of relapse  received primaquine to treat liver hypnozoites. Seventeen patients had information on chemoprophylaxis use; five did not take an antimalarial medication to prevent malaria. Of the 12 patients who took chemoprophylaxis, nine took an appropriate regimen for the region of travel, and five of these reported missing doses of the regimen. One patient had a severe illness after deployment in South Korea (severe anemia associated with P. vivax illness); no uniform policy exists requiring active-duty military personnel to take chemoprophylaxis during deployment in many parts of South Korea . In 2015, a total of 16 cases of malaria among U.S. military members were acquired in Africa, of which nine were acquired in West Africa and three from Liberia during deployment for the Ebola response. Two cases were acquired from South Korea, two were from Afghanistan, and three did not have a reported country of acquisition. The numbers of cases acquired in Afghanistan were comparable in 2014 and 2015 . Sixteen (69.6%) of 23 cases among military personnel had a reported species: nine (56.3%) were P. malariae antigens, with no reactivity to all other species examined, suggesting infection with P. malariae. A second military service member was deployed to Liberia for 6 months (dates unknown) and had symptom onset in mid-February 2015; in early March 2015, PCR testing confirmed a P. ovale infection. Neither treatment medications nor adherence to chemoprophylaxis was reported. A third member of the military was deployed to Liberia (dates unknown). He took atovaquone-proguanil for chemoprophylaxis but did not adhere to the regimen. He had symptom onset in April 2015, and a malaria diagnosis was confirmed by blood film microscopy in May 2015 (species unknown). He was treated with artemether-lumefantrine and recovered. Of the three military patients who acquired malaria during deployment to Liberia, all reported taking atovaquone-proguanil for chemoprophylaxis. One patient reported not missing any dose of chemoprophylaxis for a 5-week deployment during October–November 2014; he received the malaria diagnosis (confirmed by blood film microscopy) with an unknown species in February 2015. He was treated with mefloquine and recovered. Three months after his diagnosis and treatment, a convalescent blood sample was sent to CDC for reference laboratory testing. The PCR test of the convalescent sample was negative; however, serology results indicated reactivity to Among U.S. residents, information about malaria chemoprophylaxis use was reported for 860 (90.4%) of 951 imported cases; of these patients, 632 (73.5%) indicated that no chemoprophylaxis regimen was taken during travel. Among the 228 patients who reported taking chemoprophylaxis, 49 (21.5%) did not indicate which medication was taken. Among 178 patients who reported specific drug information, 154 (86.5%) took a regimen recommended by CDC for the region of travel. Among 127 reports containing self-reported adherence information, 91 (71.7%) patients reported missing doses. Reported adherence to chemoprophylaxis in 2015 was 28.4% (36 of 127) and in 2014 was 38.1% (64 of 168). Among 154 patients who took CDC-recommended chemoprophylaxis, 53 (34.4%) took doxycycline, 49 (31.8%) took mefloquine, 45 (29.2%) took atovaquone-proguanil, six (3.9%) took two or more CDC-recommended medications, and one reported taking primaquine (0.7%); no patients took chloroquine alone. Among the 766 cases in U.S. residents with complete information on chemoprophylaxis, 36 (4.7%) patients were adherent to an appropriate regimen, 639 (83.4%) patients did not take chemoprophylaxis or took an incorrect regimen, and 91 (11.9%) patients did not adhere to an appropriate regimen. A total of 95.3% of U.S. residents with malaria did not adhere to or did not take a CDC-recommended chemoprophylaxis regimen.P. vivax and P. ovale infections, although the patient might have a relapse unless terminal prophylaxis with primaquine is taken to clear dormant hypnozoites (P. vivax accounted for 11 (8.2%) and P. ovale for 13 (9.6%) of these cases. Sufficient information was available for 22 of the 24 P. vivax or P. ovale patients to calculate the number of days between the return travel date and the date of illness onset. Symptom onset occurred >45 days after return to the United States among 12 patients and is consistent with relapsing illness rather than failure of primary prophylaxis. Ten cases occurred ≤45 days after the patients returned to the United States, suggesting an acute infection and possible primary prophylaxis failure; five of the patients reported nonadherence to the chemoprophylaxis regimen, three reported missing no doses, and two did not provide information on adherence. Of the three patients with P. vivax or P. ovale infections who adhered to chemoprophylaxis, one traveled to Sudan for business for an unknown length of time, took atovaquone-proguanil for chemoprophylaxis, and became ill 30 days after return; one traveled to Peru for a 10-day missionary trip, took doxycycline for chemoprophylaxis, and became ill 12 days after return to the United States; and one spent 14 months in Togo as a missionary, reported taking mefloquine and doxycycline for chemoprophylaxis, and became ill 24 days after return. Potential reasons for infection in these patients include early relapse from hypnozoites established at the onset of travel , inadequate dosing or malabsorption of the chemoprophylaxis medication, inaccurate reporting of adherence, or emerging parasite resistance.Primary prophylaxis can prevent acute illness in P. falciparum, 11 (8.2%) were from P. malariae, and one (0.74%) was a mixed infection. Among the patients with P. falciparum infections, 97 (98.0%) reported travel to Africa, and 48 (48.5%) had traveled to West Africa. One P. falciparum case each occurred after persons traveled to Indonesia and the Dominican Republic. Of 85 P. falciparum case reports containing information on adherence to the recommended prophylaxis regimen, 65 (76.5%) patients indicated nonadherence. Twenty cases of P. falciparum occurred among patients who reported adherence to a recommended prophylaxis regimen; nine (45.0%) patients took mefloquine, seven (35.0%) took atovaquone-proguanil, and four (20.0%) took doxycycline. All 20 patients with P. falciparum infections who adhered to chemoprophylaxis acquired their infections in Africa, with nine (45.0%) from the West African region. Specimens from patients who adhered to the chemoprophylaxis regimen and had traveled to Uganda (two specimens) and Ghana (one specimen) were provided to CDC for molecular resistance surveillance; two patients reported taking doxycycline, and one took atovaquone-proguanil. No valid genetic markers are available to assess doxycycline resistance. The patient who reported adherence to atovaquone-proguanil had an atovaquone-sensitive genotype, suggesting that this marker for antimalarial resistance was not a factor. Among the 135 patients with malaria with known species and who reported taking a CDC-recommended prophylaxis regimen, 99 (73.3%) of the infections were from P. malariae occurred after taking a recommended prophylaxis regimen. Among the five patients with information on adherence, one patient reported adhering to atovaquone-proguanil for chemoprophylaxis . Eleven cases of P. falciparum and P. ovale. Mefloquine was reported as prophylaxis; however, no adherence information was provided, and the specimen was not available for molecular resistance testing. One patient acquired a mixed-species infection after taking a recommended prophylaxis regimen. This infection was PCR-confirmed, and the patient had traveled to Nigeria for an unknown duration, and was positive for Plasmodium infections in patients who adhered to chemoprophylaxis include inadequate dosing or malabsorption of the chemoprophylaxis medication, inaccurate reporting of adherence, or emerging parasite resistance.Possible explanations for P. falciparum, eight (23.5%) recalled P. vivax, three (8.8%) recalled P. ovale, and four (11.8%) recalled P. malariae infection. Based on illness onset date, previous date of illness, and species, nine probable relapse cases were identified: eight caused by P. vivax and one caused by P. ovale. Two additional P. ovale cases were considered to be probable relapses, because the species was the same for the previous and current illnesses; however, the previous date of illness onset was missing. Among the 19 patients who recalled a P. falciparum infection in the past 12 months, 12 (63.2%) had a current infection with P. falciparum. Among the four patients who recalled a previous P. malariae infection in the past 12 months, three were infected with species other than P. malariae, and one was infected with an unspecified species.Among the 1,485 cases of malaria imported into the United States in 2015, a total of 1,095 (73.7%) patients provided information on previous history of malaria; 202 (18.5%) reported having had malaria in the past 12 months. The infecting species for the previous illness was reported for 34 (16.8%) of 202 patients with a previous history of malaria; 19 (55.9%) recalled Among nonmilitary U.S. residents, the reason for travel to a country where malaria is endemic was reported for 753 (81.1%) cases of 928 imported malaria illnesses . Of thesAmong the 367 imported cases among foreign residents, reason for travel was indicated for 270 (73.6%) cases . TraveliP. falciparum, two cases were severe, and all recovered from their illness.Age was reported for 1,513 (99.7%) of 1,517 patients with malaria in 2015, and of these, adults aged ≥18 years accounted for 1,272 (84.1%) cases. Fifty-five (3.6%) patients were aged <5 years, and 95 (6.3%) were aged ≥65 years. Of the 241 children (aged <18 years), 103 (42.7%) were U.S. residents, and 88 (85.4%) of these had traveled to Africa. Among the U.S. civilian children, 78 (75.7%) traveled to visit friends and relatives, five (4.9%) traveled for missionary reasons, four (3.9%) for tourism, and one (1.0%) for education. No reason for travel was provided for 15 (14.6%) children. Among the 103 U.S. civilian children, information on chemoprophylaxis use and adherence was reported for 98 (95.1%); 67 (68.4%) did not take medication during travel to prevent malaria. Of the 31 children who took a chemoprophylaxis regimen, 22 (71.0%) took a CDC-recommended antimalarial that was appropriate for the region of travel. Of the 14 children with information on adherence, case reports from eight (57.1%) indicated that all doses were taken. All eight cases were acquired in Africa, seven were confirmed P. falciparum malaria, and 236 (24.1%) hospitalized persons had one or more signs or symptoms of severe malaria. No significant change in these percentages occurred from 2014 to 2015; in 2014, a total of 1,046 [70.0%] patients were hospitalized of 1,498 with complete information; 766 [73.2%] with P. falciparum; 257 [24.6%] with severe malaria).In 2015, hospitalization information was reported for 1,362 (89.8%) of 1,517 confirmed cases; 981 (72.0%) persons were hospitalized for their malaria illness. A total of 714 (72.8%) of hospitalized persons had Among the 1,517 confirmed malaria cases in 2015, a total of 1,258 (82.9%) cases were uncomplicated malaria. Of these, 1,028 (81.7%) had antimalarial treatment information indicated on the case report form. The most common treatment administered for uncomplicated malaria in 2015 was atovaquone-proguanil, used to treat 609 (59.2%) of imported cases in patients with treatment information. Quinine-based treatment ranked second, with 159 (15.5%) patients treated with this regimen. Artemether-lumefantrine, the only artemisinin-based combination therapy approved by the Food and Drug Administration (FDA) for treatment of uncomplicated malaria in the United States, was administered to 119 (11.6%) patients. A total of 102 (9.9%) uncomplicated cases were treated with chloroquine, and 62 (6.0%) were treated with mefloquine. CDC Guidelines for Treatment of Malaria in the United States, herein referred to as the CDC guidelines, provides recommendations for the treatment of malaria according to species, disease severity, and region of acquisition  were treated according to CDC guidelines 109 (17.3%) of these patients received an antimalarial treatment that exceeded the recommendations. Three (6%) of 49 P. falciparum patients who were not treated in accordance with CDC recommendations were pregnant. Treatment was in accordance with CDC guidelines for 31 (93.9%) of 33 cases of uncomplicated P. malariae, and eight (25.8%) patients received an additional antimalarial medication. Of those with P. vivax and P. ovale infections, 116 (84.1%) and 39 (79.6%), respectively, were appropriately treated for their acute infection, of whom seven (6.0%) patients with P. vivax infections and three (7.7%) with P. ovale infections received an additional acute-phase antimalarial medication. Administration of primaquine to treat relapsing illness (the liver hypnozoite stage of the parasite) was reported for 58 (42.3%) of all 137 nonpregnant patients with P. vivax infections and treatment information and was administered to 46 (39.7%) of 116 nonpregnant patients with P. vivax infections who were appropriately treated for the acute-phase illness. Among the 48 nonpregnant patients with P. ovale infections, primaquine was administered to 18 (37.5%), and among the 39 nonpregnant patients with P. ovale infections appropriately treated for the acute-phase infection, primaquine was administered to 15 (38.5%). Five (55.6%) of nine mixed infections with treatment information recorded were treated according to CDC guidelines; three (60.0%) of these patients received an additional antimalarial. Malaria infections with an unknown species should be treated following recommendations for P. falciparum  had infections with an unknown Plasmodium species, and 15 (5.8%) patients had P. vivax infections. In 2015, the species distribution among severe cases was similar to the distribution in 2014.In 2015, a total of 259 (17.1%) of 1,517 cases were classified as severe cases. Eleven (4.3%) of the patients with severe malaria died. Among severe cases, 201 (77.6%) occurred in adults aged 18–64 years. However, children (aged <18 years) were significantly more likely to have severe malaria than adults . Likewise, the proportion of persons aged ≥65 years with severe malaria was significantly higher than the proportion among patients aged <65 years . In 2015, a total of 78 (21.3%) of 367 foreign residents had severe malaria, compared with 172 (18.1%) of 952 U.S. residents; foreign residents were equally as likely as U.S. residents to have a severe illness. This finding varies from 2014, when foreign residents were significantly less likely to have severe illness than U.S. residents . Among patients with severe malaria in 2015, a total of 219 (84.6%) had Among 230 (88.8% of 259 severe cases) patients with severe malaria and information on chemoprophylaxis, 52 (22.6%) reported having taken any medication for chemoprophylaxis; 16 (30.8%) of these did not provide adherence or chemoprophylaxis medication information. Of 32 patients with severe malaria with chemoprophylaxis adherence information, 25 (78.1%) did not adhere to or take a recommended regimen for malaria prevention, compared with 66.4% of persons with uncomplicated cases who did not adhere to chemoprophylaxis or take a correct regimen. Of the seven patients who adhered to a recommended chemoprophylaxis regimen, four took doxycycline, two took mefloquine, and one took atovaquone-proguanil. No specimens from these patients were tested at CDC for molecular resistance. Potential reasons for chemoprophylaxis failure in these patients with severe malaria include inadequate dosing or malabsorption of the chemoprophylaxis medication, inaccurate reporting of adherence, or emerging parasite resistance.Plasmodium species parasitemia, of which 146 (73.7%) had ≥5% parasitized red blood cells. CDC guidelines state that patients with severe malaria should be treated aggressively in an inpatient setting with intravenous quinidine gluconate or artesunate. In 2015, a total of 18 (7.0%) patients with severe malaria were not hospitalized; the hospitalization status for five patients (1.9%) was unknown. Quinidine gluconate is the only FDA-approved medication for severe malaria. Artesunate is not FDA approved but is available from CDC as an investigational new drug for patients who cannot tolerate quinidine gluconate or when it is not available  patients. Cerebral malaria was reported for 30 (11.6%) patients, acute respiratory distress syndrome for 28 (10.8%), severe anemia for 26 (10.0%), and jaundice for 12 (4.6%). Case reports from 198 patients with severe malaria contained information on the percentage of Plasmodium species can cause severe malaria, the rapid proliferation of P. falciparum parasites in nonimmune persons requires timely diagnosis and treatment to prevent progression to hyperparasitemia and severe illness. In 2015, on average, inpatients with P. falciparum infections had been hospitalized on day 4 after illness onset, regardless of disease severity (with a mean of day 4.2 for uncomplicated cases and day 4.3 for severe cases). Because the malaria case report form does not include the date of the clinical visit for patients who are not hospitalized, determining the time between illness onset and when outpatients seek medical care is not possible.Although all malaria Among the 259 patients with severe illness, 234 (90.4%) infections were acquired in Africa; 17 (6.6%) in Asia; <1% in the Caribbean (two cases), Central America (two cases), or Oceania (one case); three severe cases were acquired in an unknown region. Among the 218 patients with severe malaria who reported a reason for travel, 122 (56.0%) reported VFR as the primary reason travel, of whom 89 (73.0%) had traveled to West Africa. Twenty-seven (12.4%) patients with severe malaria traveled to the United States as immigrants or refugees, or for business; 17 (7.8%) patients traveled for missionary work. Three patients (1.4%) with severe malaria traveled for education (as a student or teacher), one was an airline or a ship crewmember, and one was a member of the U.S. military. A total of 47 patients had unknown (41 [15.8%]) or other reasons for travel (six [2.3%]).P. ovale infection with <1% parasitemia also had hyperemesis gravidarum; she was treated with parenteral medication. She initially received quinidine gluconate, which was discontinued after detection of a prolonged heart-rate corrected Q-T interval (QTc). She then received artesunate and recovered. Although systematic information was not collected on birth outcomes, clinical notes were available for five pregnant women, indicating that delivery occurred near the time of infection. Of these, two infants were healthy. One infant had congenital malaria, and one was born at 27 weeks’ gestation and treated in the neonatal intensive care unit. One pregnant woman, originally from Tanzania, experienced fever and had a low platelet count at 31 weeks’ gestation. These symptoms were interpreted as signs of hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome, and an emergency cesarean section was performed 2 days after symptom onset. The woman continued to have fever and a low platelet count, and 3 days after delivery (5 days after illness onset), she was tested for malaria and found to have a P. falciparum infection with 16% parasitemia. The woman was treated with artesunate and atovaquone-proguanil and recovered. Her infant tested negative for malaria.Among 546 women with malaria diagnosed in the United States in 2015, a total of 32 (5.9%) were pregnant, and 12 (37.5%) of these had severe malaria. Twenty-seven (84.4%) pregnant women were hospitalized, including 12 patients with severe malaria, and all recovered. One woman with a PCR-confirmed P. falciparum infections, six (18.8%) were infected with an unspecified Plasmodium species, two (6.3%) had infections with P. ovale, and one with P. vivax. Most pregnant women (21 [65.6%]) were foreign residents, and 11 (34.4%) infections were in U.S. residents. Of 25 (78.1%) women who indicated a reason for travel, 14 (56.0%) were VFR travelers, six (24.0%) were refugees or immigrants, and one each (4.0%) traveled as a missionary or for education (as a student or a teacher) or tourism. Two (8.0%) women provided other reasons.Twenty-three (71.9%) pregnant women had Antimalarial drug choices to prevent or treat malaria during pregnancy are limited. In most areas where malaria is endemic, only mefloquine is approved for chemoprophylaxis; mefloquine and quinine with clindamycin are recommended as treatment for uncomplicated malaria during pregnancy   contained polymorphisms associated with pyrimethamine resistance, and 115 (87.1%) of these had three or more pyrimethamine resistance markers. One sample was not amplified for sulfadoxine resistance analysis, and 112 (73.7%) had at least one marker associated with sulfadoxine resistance; 13 (11.6%) of these had three or more sulfadoxine resistance markers. Of 153 samples tested for chloroquine resistance markers, 105 (68.6%) did not have the resistant genotype. Amplification of the mefloquine locus was completed for 141 of 153 samples, and six (4.3%) contained the resistant genotype. Amplification of the genes associated with atovaquone resistance was possible for 135 of 153 samples, and none had the polymorphism associated with the resistance. Of 149 samples that could be amplified for artemisinin resistance, one sample had a marker associated with resistance. Because of widespread resistance to pyrimethamine and sulfadoxine, CDC does not recommend using drugs containing these components to treat malaria in the United States  . One jur. ovale) . Of the One case of congenital malaria was reported in 2015. Parasites were transmitted from mother to child during pregnancy or during labor and delivery.Case 1. A pregnant women aged 26 years immigrated to the United States in December 2014 from Pakistan. She gave birth in early June 2015 at 37 weeks gestation and experienced a fever a few days later. She received a diagnosis of a P. vivax malaria infection with 0.3% parasitemia and was treated with quinine. Blood smear microscopy was performed on a sample from the infant and was negative for malaria. Three weeks later, the infant experienced fever and received a diagnosis a P. vivax malaria infection with 2.2% parasitemia, thrombocytopenia, anemia (hemoglobin 7.9 g/dL), and splenomegaly. The infant received intravenous quinidine, clindamycin, and platelet transfusions. After 6 days of inpatient care, the infant recovered and was discharged.Eleven fatal malaria cases were reported in 2015.Case 1. A man aged 25 years spent 6 months teaching in Ghana. For 2 months he took atovaquone-proguanil for malaria chemoprophylaxis but reportedly stopped early because he thought it was unnecessary. His symptoms began on February 27, 2015, a total of 3 days after returning to the United States, and he was hospitalized on March 1, 2015; he received a diagnosis of cerebral malaria from a P. falciparum infection with 29% parasitemia. He was treated with intravenous quinidine and doxycycline, and in the early afternoon of March 2, 2015, he experienced two cardiac arrests. After the second episode, he was nonresponsive. Artesunate was obtained from CDC; the first dose was administered at 8:30 p.m. on March 2, 2015, and the parasitemia rapidly resolved. Approximately 2 hours after administration of artesunate, electroencephalography demonstrated an absence of significant brain activity. Subsequent imaging and perfusion studies demonstrated cerebral herniation and brain death. The patient was pronounced dead on March 15, 2015.Case 2. In November 2014, a woman aged 69 years traveled to India for 4 weeks, returning on December 8, 2014. On December 11, 2014, she experienced a fever and headache. On December 21, 2014, she was admitted to the hospital with a diagnosis of malaria caused by P. vivax and was treated with quinine and doxycycline. She developed acute respiratory distress syndrome and remained hospitalized for 3 weeks before returning home. She was not treated with primaquine to prevent relapses. She remained in the United States and did not travel out of the country again. On November 11, 2015, her fever returned. On November 21, she received a diagnosis of an uncomplicated P. vivax malaria infection and was hospitalized. She was treated with quinine, doxycycline, and primaquine. Her fever resolved, and she appeared to be clinically stable. The patient was discharged from the hospital on November 23 but then died on November 25. No autopsy was performed, and no additional investigation occurred.Cases 3 and 4. Two men aged 45 and 44 years who were residents of an African country where malaria is endemic had recently traveled for work to one or two other countries in Africa where malaria is endemic before traveling to the United States for a vacation. On May 1, 2015, they arrived in Chicago, Illinois, after traveling through Amsterdam, Netherlands. According to law enforcement officials and public health investigation records, the man aged 45 years was the first to feel ill, with onset of headache and body aches on May 1 while in Amsterdam. The man aged 44 years reported similar symptoms on May 2. The men were found dead in adjacent hotel rooms on May 9, 2015. The county medical examiner performed autopsies and sent tissue samples from multiple organs from both men to the CDC reference laboratory, which confirmed P. falciparum infections in both patients based on immunohistochemistry and PCR. Parasites from the men contained identical molecular resistance signatures, suggesting that the infections were acquired from the same region. The parasites contained the triple mutation in the dhfr gene and a single mutation in the dhps gene (pyrimethamine and sulfadoxine resistance markers), which are a common signature of parasites from Africa. However, microsatellite analysis revealed discrepant signatures at seven loci, and the man aged 45 years was infected with two different parasite strains. These data suggest that the men acquired the infections independently. No drug paraphernalia were found in either hotel room, nor was there evidence of a struggle or any disarray. No weapons or poisons were found. Law enforcement officials did not suspect foul play in their deaths.Case 5. A woman aged 67 years from India who had diabetes and a recent history of a myocardial infarction visited the United States. Two days after arrival in the United States, she experienced fever, and 5 days later, she sought medical attention, with a temperature of 102.2°F (39°C). A malaria antigen test was negative; the malaria smear was positive, indicating a P. vivax infection with 1.8% parasitemia, which was confirmed by the state public health laboratory. The woman had lactic acidosis and hypotension and was admitted to the hospital intensive care unit. She was treated with intravenous quinidine; electrocardiography did not reveal QTc prolongation or QRS widening. On the second day in the hospital, the woman experienced a cardiac arrest and died.Case 6. In July 2015, a man aged 64 years returned from a 3-month visit in Ghana to visit friends and relatives, and he did not take chemoprophylaxis. Symptoms began 8 days before his return to the United States. Two days after his return, he was admitted to the hospital with hypotension, renal failure, and respiratory distress caused by a severe P. falciparum infection with 20% parasitemia. Health care providers initially treated the man with intravenous quinidine and doxycycline; however, after QTc prolongation was detected, artesunate was obtained from CDC. The patient experienced a cardiac arrest but was resuscitated. He received his first and only dose of artesunate a few minutes after resuscitation. A few hours later, he experienced a second cardiac arrest and died.Case 7. In 2012, a woman aged 25 years from Ghana with a history of sickle cell disease moved to the United States. In late August 2015, she returned from visiting friends and family in Ghana, and she did not take chemoprophylaxis. Symptoms began on September 5 with a headache and fatigue. On September 7, she had yellow eyes and called her physician; however, the office was closed for Labor Day, so she sought treatment on the morning of September 8; after consultation at the primary care clinic, her health care provider called an ambulance. In the emergency department, the initial diagnosis was sickle cell crisis. Laboratory tests revealed an increased anion gap (22 mEq/L), lactic acidosis, severe hemolytic anemia (hemoglobin 4.1 g/dL and bilirubin 40 mg/dL), and the blood smear was positive for a P. falciparum infection (2% parasitemia). The spleen was not visualized with abdominal ultrasound. She was admitted and administered oral artemether-lumefantrine. Later the same day, the woman became confused and agitated and then unresponsive. She was noted to be in asystole and was resuscitated twice in the next few hours. She was treated with blood transfusions and intravenous bicarbonate, quinidine, and doxycycline. The woman became progressively more acidotic and died approximately 14 hours after arriving at the hospital.Case 8. A man aged 62 years traveled to Ghana for 1 month to visit friends and relatives. He did not take chemoprophylaxis. One day before returning to the United States, he experienced fever, sweating, myalgia, nausea, vomiting, and diarrhea. He also noticed that his eyes were turning yellow. He did not seek medical attention. Five days after returning to the United States, he attempted to return to work but was sent home because he was visibly ill. Three days later, he was found dead at his home. An autopsy revealed that he had a P. falciparum infection with parasites in multiple organs. The species was confirmed using immunohistochemical staining specific for P. falciparum.Case 9. A man aged 58 years from Egypt visited the United States after a 2-week business trip in Nigeria. On January 27, 2015, while in the United States, he experienced fever and a headache and immediately sought medical attention. Initial laboratory tests were unrevealing. Tests were repeated approximately 12 hours later and indicated acute kidney injury and metabolic acidosis. A blood smear was positive for malaria parasites at 4 a.m. on January 28, 2015, with 80% parasitemia. The man was treated with oral quinine and doxycycline. He became confused and somnolent. Because quinidine was not available, CDC provided artesunate. Before administration of the first dose of artesunate, computed tomography (CT) of the head demonstrated cerebral edema in the posterior fossa. The man received all 4 doses of artesunate and an exchange transfusion, and the parasitemia resolved. He remained unresponsive and hospitalized in the intensive care unit, receiving mechanical ventilation and dialysis until March 13, 2015, when he was pronounced dead.Case 10. A man aged 63 years traveled from the United States to Tanzania for a hunting trip and took no chemoprophylaxis. He returned to the United States on September 28, 2015, and was found unresponsive on the morning of October 5. When he arrived at the hospital, he received a diagnosis of severe cerebral malaria and lactic acidosis from a P. falciparum infection with 23.3% parasitemia. He received intravenous quinidine gluconate; however, because a sufficient amount was not available, artesunate was obtained from CDC. The man received the first of 4 doses of artesunate on the evening of October 5, and the subsequent treatment included doxycycline as recommended, resulting in the resolution of the parasitemia. The patient remained comatose throughout his hospitalization. CT of the head on October 9 demonstrated severe cerebral ischemia. A decision was made to withdraw support, and the patient died on October 12.Case 11. A woman aged 75 years visited India for 6 months during June 2014-January 2015 but did not take malaria chemoprophylaxis. She had onset of fever and abdominal pain on May 28. She sought care in the emergency department on May 30 but initially denied any foreign travel; therefore, no malaria testing was performed. She returned on June 1 as her symptoms continued and was discharged again without evaluation for malaria. On June 5, she returned with worsening symptoms including shortness of breath and confusion. At this time, she had lactic acidosis and thrombocytopenia, and a malaria blood smear was positive with a 2% parasitemia for unspecified Plasmodium species. Her initial antimalarial treatment included atovaquone-proguanil, which was changed to intravenous quinidine with doxycycline. Her shortness of breath progressed as she developed acute respiratory distress syndrome necessitating intubation and mechanical ventilation. She also developed acute kidney injury requiring dialysis. Despite resolution of her parasitemia, she continued to experience multisystem organ failure, and life support was withdrawn on June 10. She died on the same day.Although malaria cases diagnosed in the United States have generally been increasing since the 1970s, 208 fewer cases of malaria were reported in the United States in 2015 than in 2014  in 2015 is comparable to that in 2014 (66.1%); these percentages are the highest recorded for the period of 2005–2015. Use of PCR testing to identify the Plasmodium species might have contribute to this finding. Travel to the African region also could contribute to the large proportion of P. falciparum infections; UNWTO reports an overall in increase in travel rates to sub-Saharan Africa, with 35.4 million international tourist arrivals reported for 2015, an increase from 34.6 million in 2014 .Chemoprophylaxis is the most effective way for U.S. residents to prevent malaria during travel to a country where malaria is endemic; however, persons who receive a diagnosis of malaria in the United States often do not obtain or adhere to chemoprophylaxis. Barriers to adherence include lack of awareness about the disease and its potential severity  . Of the reports of confirmed cases the United States in 2015, 12.9% were missing the infecting species, 13.1% were missing residence status, and 5.9% were missing the country of acquisition. Incomplete reporting of antimalarial treatments and the infecting species could result in the patient being misclassified as having been treated according to the CDC guidelines. CDC occasionally receives incomplete records for cases only reported electronically through NNDSS; these records contain basic demographic data but not the additional malaria case information from the NMSS case report form. CDC is collaborating with state and local health departments to update the NNDSS reporting platform through the NNDSS Modernization Initiative (NMI). Electronic submission of extended malaria data elements through NMI is anticipated to begin in early 2019. States that implement the malaria NMI surveillance system will no longer be required to submit paper case report forms, which should improve the timeliness and accuracy of malaria surveillance in the United States. State and local health departments are encouraged to report cases using the NMSS case report form until malaria-specific data can be received electronically through NMI. In 2015, a total of 31 (2.0%) cases were not able to be classified, comparable with the number from 2014. All elements on the malaria case report form should be completed as this provides critical information for examining malaria trends that are used to develop recommendations for malaria chemoprophylaxis. Local and state health departments, health care providers, and other health personnel should be vigilant in reporting complete information for malaria cases, especially for essential variables including species, residence, and country of acquisition.In 2015, the reported number of cases (n = 32) imported from the Dominican Republic increased substantially. In the Caribbean region, endemic transmission of malaria ended in the mid-1960s, except on the island of Hispaniola, which includes the countries of the Dominican Republic and Haiti . From 2014 to 2015, no significant change occurred in the number of military cases reported. Approximately 70.0% of cases diagnosed among military personnel in the United States were acquired in Africa, and more than half (nine cases) of those were from West Africa. The United States responded to the Ebola emergency with the deployment of approximately 3,000 military personnel to Ebola-affected countries starting in September 2014 , 68 (35.2%) received primaquine, the only antimalarial that is active against the dormant parasite liver forms and prevents relapses . Certain guidelines and eligibility requirements must be met to enroll a patient in the investigational new drug treatment protocol. Providers who administer artesunate to patients must comply with the investigational new drug protocol and notify CDC of any adverse event after administration . CDC provides several resources for health care providers; care providers seeking assistance with diagnosis (including telediagnosis) or treatment of patients with suspected or confirmed malaria should call CDC’s Malaria Hotline at 770-488-7788 or toll-free 855-856-4713 during regular business hours or CDC’s Emergency Operations Center at 770-488-7100 during evenings, weekends, and holidays , or go to CDC’s website at https://www.cdc.gov/malaria/diagnosis_treatment/index.html.Patients with severe malaria were significantly more likely to have been inappropriately treated compared with those patients with uncomplicated malaria , and 37.0% of all pregnant women received treatment contrary to the CDC guidelines for treatment. Health care providers should be familiar with prevention, recognition, and treatment of malaria and are encouraged to consult appropriate sources for malaria prevention and treatment recommendations . Health Plasmodium parasites into receptive areas , which is available and updated on the CDC Travelers’ Health website at https://www.cdc.gov/Features/TravelersHealth.html. (Even though malaria is not endemic in the United States, malaria causes illness and deaths in this country. Imported cases of malaria can reintroduce th.html. .


Salmonella Typhi and invasive non-Typhoidal Salmonella (iNTS) frequently affect children living in rural sub-Saharan Africa but data about incidence and serotype distribution are rare.Bloodstream infections (BSI) caused by Salmonella BSI and severe malaria in a Health and Demographic Surveillance System in a rural area with seasonal malaria transmission in Nanoro, Burkina Faso.The present study assessed the population-based incidence of Children between 2 months—15 years old with severe febrile illness were enrolled during a one-year surveillance period (May 2013—May 2014). Thick blood films and blood cultures were sampled and processed upon admission. Population-based incidences were corrected for non-referral, health seeking behavior, non-inclusion and blood culture sensitivity. Adjusted incidence rates were expressed per 100,000 person-years of observations (PYO).Salmonella Typhi and severe malaria per 100,000 PYO were 4,138 : 3,740–4,572), 224 (95% CI: 138–340) and 2,866  respectively. Among those aged 5–15 years, corresponding incidence rates were 25 (95% CI: 8–60), 273 (95% CI: 203–355) and 135 (95% CI: 87–195) respectively. Most iNTS occurred during the peak of the rainy season and in parallel with the increase of Plasmodium falciparum malaria; for Salmonella Typhi no clear seasonal pattern was observed. Salmonella Typhi and iNTS accounted for 13.3% and 55.8% of all 118 BSI episodes; 71.6% of iNTS (48/67) isolates were Salmonella enterica serovar Typhimurium and 25.4% (17/67) Salmonella enterica serovar Enteritidis; there was no apparent geographical clustering.Among children < 5 years old, incidence rates for iNTS, Salmonella Typhi and iNTS, the latter with a seasonal and Plasmodium falciparum-related pattern. It urges prioritization of the development and implementation of Salmonella Typhi as well as iNTS vaccines in this setting.The present findings from rural West-Africa confirm high incidences of  Salmonella infections  cause a huge burden of disease, especially in resource-limited settings. Unlike Salmonella Typhi which occurs in previously healthy individuals, invasive non-Typhoidal Salmonella (iNTS) infection appears to be predominantly associated with host-related factors including malnutrition and malaria in children, and HIV in children as well as adults [Invasive s adults . The ests adults . For iNTs adults . An estis adults . Howevers adults .Salmonella Typhi BSI among febrile and severely ill children. Additionally we assessed the population-based incidence of severe malaria among enrolled children.The Clinical Research Unit of Nanoro (CRUN), Burkina Faso has established a Health and Demographic Surveillance System (HDSS) since 2009, allowing the measurement of incidences of health-related events . We cond2. The HDSS catchment area comprises 36% of the Nanoro Health district, encompassing 24 villages with a population of about 60,000 inhabitants of whom 20% are children less than five years of age [Plasmodium falciparum) is hyper-endemic from July—October corresponding to the rainy season [Haemophilus influenzae type b since January 2006 and the 13-valent Pneumococcal Conjugate Vaccine (PCV-13) since October 2013; typhoid vaccination is not routinely done. Malaria control programs in place during the study period included the distribution of bed nets among families.Burkina Faso is a low income country in western Africa with a population of 18 million, ranking 183/188 on the Human Development Index of 2015 . The Nany season . The HIVy season . The natThe Nanoro HDSS encompasses 7 Healthcare Centers (HC) with to one district referral hospital “Centre Médical avec Antenne Chirurgicale (CMA)”. Typically HCs provide first line care. All HCs have an observation ward (3–6 beds) where patients can be observed for a maximum of one day. Patients in critical condition or with warning signs are referred to CMA.Enrollment was performed at 2 sites: the Pediatric ward (36 beds) of CMA and the Healthcare Center of Nazoanga. HC Nazoanga is the largest HC in the HDSS and located at 14 km distance of CMA. Due to its function as a reference hospital, patients enrolled at CMA include patients living inside and outside the HDSS catchment area.th 2013 and May 12th 2014 were screened for eligibility.All children between 2 months and 15 years of age (representing the most vulnerable patient group) presenting at either site between May 13Patients were eligible for inclusion if they had (i) fever (axillary temperature ≥ 37.5°C or reported history of fever in the past 48 hours) or temperature ≤ 35.5°C (ii) or suspicion of severe localized bacterial infection such as pneumonia, arthritis, osteomyelitis and/or soft tissue infection, peritonitis, meningitis, or complicated urinary tract infection. Clinical examination was performed by trained nurses trough a detailed case report form and under the supervision of the study principal investigator  and a qualified pediatrician. Basic demographic data including age, gender and geographic origin as well as medical history, reported prior antibiotic (48 h) or antimalarial (2 weeks) treatment and presumptive diagnosis upon admission were recorded. Discharge and in-hospital mortality were recorded.The clinical laboratory of CRUN is situated on the same compound as CMA. Laboratory practices have been standardized using Standard Operational Procedures (SOPs) and a quality management system according to Good Clinical Laboratory Practices principles is implemented.Upon inclusion venous blood was sampled for malaria microscopy, full blood count ) and blood cultures ) as previously described . MalariaSamples from CMA were transported to CRUN within 15 minutes after collection. For HC Nazoanga, samples were stored and transported to CRUN by car  at the end of each day and transport time was recorded. The quality indicators are reported in Data on rainfall were collected from “Zone d’Appui Technique” in Nanoro, which records rainfall data (mm of precipitation) on a monthly basis.Bacillus spp., Corynebacterium spp. and Propionibacterium spp. were considered contaminants. Malaria was defined as the presence of asexual P. falciparum parasites by microscopy. Severe malaria was defined as confirmed malaria in presence of at least one of the World Health Organization criteria for severe malaria [i.e. severe anemia—(hemoglobin concentration < 5 g/dl), hyperparasitemia (≥ 4%), coma or impaired consciousness, respiratory distress, icterus, hemoglobinuria or seizures). In children < 5 years old, severe acute malnutrition was defined as a mid-upper arm circumference less than 115 millimeters [Bloodstream Infection (BSI) was defined as growth of pathogens from blood culture. Non-pathogenic bacteria or skin flora including coagulase-negative staphylococci,  malaria  . After conformity check, statistical analysis was done with Stata 12 . To assess differences in proportions, the Chi-square or two-tailed Fisher’s exact test were used. Mean and median values were compared using the Student’s t-test and the Wilcoxon Mann–Whitney non-parametric test respectively. A p-value < 0.05 was considered significant.For the duration of the study compliance to good clinical (laboratory) practices was monitored by the Clinical Trials Unit of the Institute of Tropical Medicine, Antwerp (ITM). Trial Management Group Meetings were organized once a month. Data quality was monitored and bi-monthly status reports were provided by the principal investigator. Clinical and laboratory data were entered twice into an Epi-InfoTMPopulation-based incidence rates were calculated for patients residing in the HDSS area. Only the first isolate per patient was considered, except if subsequent sampling had been done more than two weeks after the first sampling. For calculation of the crude incidence rates, the total and age-specific numbers of cases were used as the numerator and the respective person-year of observations (PYO) as the denominator; 95% confidence intervals (CI) were calculated using the Wilson score method. Incidence rates were calculated per 100,000 PYO and expressed for (i) children aged 2 months– 5 years (further referred to as “< 5 years old group”) and (ii) children aged 5–15 years (further referred to as “5–15 years old group”).Crude incidences were converted to adjusted incidences by correcting for the following factors: (i) non-referral from Healthcare Centers to CMA, (ii) seeking healthcare elsewhere than in CMA or Health Centers, (iii) non-enrollment of eligible patients, (iv) sensitivity of blood cultures combined with estimated loss of sensitivity due to under-filling of the bottles. For correction of the incidence of severe malaria, only correction factors (ii) and (iii) were considered.(i) Correction for non-referral to CMA: Only patients with acute warning signs are referred to CMA hospital whereas those with a milder clinical presentation are treated at the HC level. Based on statistics from the District Health Office complemented with surveillance data from HC, Nazoanga the referral proportion of children with febrile illness was estimated at 25% .(ii) Correction for seeking healthcare elsewhere than in Healthcare Centers and CMA: A Healthcare Utilization Survey (HUS) was carried out among a sample of households in the HDSS area in order to map the healthcare utilization of children in case of fever. HUS methods were based on those previously published by the Typhoid Fever surveillance in Africa Program consortium (TSAP) . A total(iii) Correction for non-enrollment of eligible children comprised not giving consent, leaving CMA or HC Nazoanga before sampling as well as patients who were not sampled because of lack of blood culture bottles.(iv) Correction for sensitivity of blood culture and inadequate filling: Under-filling and over-filling of blood cultures was defined as filling below or above the recommended volume of 1–3 ml. To estimate the impact of under-filling, the volume lost by under-filling was calculated by subtracting the actual median volume of the under-filled bottles from the minimum volume required (= 1.0 ml). Next, this difference was multiplied by the proportion of under-filled bottles. Finally the correction for sensitivity of blood culture was applied. The age groups of < 5 years old and 5–15 years old were considered separately.A detailed description of the methodology and results of the HUS and a brief literature review about the sensitivity of blood cultures can be found in th 2013), the institutional review board of the ITM, Antwerp  and the ethics committee of the University Hospital of Antwerp . Written informed consent was obtained from parents/guardians prior to inclusion, in presence of an independent witness in case of illiteracy.The study was conducted according to the principles expressed in the Declaration of Helsinki  and the In total 1,339 children were enrolled, representing 91.6% of 1,461 eligible children. Salmonella Typhi and iNTS accounting for 13.6% and 56.8% of BSI episodes and representing 16 and 67 isolates respectively.Blood culture confirmed BSI was found in 8.8% of patients ; there wPlasmodium falciparum malaria. Among the patients for whom both RDT and microscopy were performed, 11.7% (76/648) had a positive RDT but a negative result for microscopy, which is indicative of a recent malaria infection.Overall, 58.0%  of children had microscopically confirmed malaria, of whom 32.4%  had severe malaria. All malaria cases were microscopically confirmed as Salmonella Typhi (n = 3), Streptococcus pneumoniae (n = 5) and Staphylococcus aureus (n = 2).A total of 2.8% (22/777) of patients with malaria also had a BSI. Conversely, 18.6% (22/118) of patients with BSI had malaria. The pathogens found in those patients were iNTS (n = 12) Children with reported use of antibiotics prior to sampling had a higher proportion of growth compared to those without antibiotics (13.9% (35/252) versus 7.8%  respectively p = 0.001). There was no apparent difference between pathogens recovered in both groups.Salmonella Typhi BSI died.In-hospital mortality rates were 10.2% (12/118), 6.0% (4/67) and 7.1% (18/252) for BSI, iNTS and severe malaria respectively; none of the children with Crude and adjusted incidence rates were calculated based on a one year time frame: from May 2013 to May 2014. Only patients living inside the HDSS area were considered. (i) Non-referral: Data from the District Health Officer showed that a median of 25% of patients with fever are referred from HCs to CMA. The surveillance data showed that a large proportion (>80%) of patients with confirmed BSI were not referred from HC Nazoanga to CMA, and supported the correction factor based on District Health Office data of 1/0.25 = 4.0. This correction factor was only applied to patients who were referred from other HCs than Nazoanga. For example, in the age group < 5 years, there were a total of 38 children with iNTS BSI; 12 of them were referred to CMA from Healthcare Centers other than HC Nazoanga, the remaining 26 were admitted to CMA without referral or were enrolled at HC Nazoanga. In this case, application of the correction factor resulted in a total of 74 BSI episodes: The correction factor of 4 was applied to the 12 cases of iNTS referred from other HC than Nazoanga (4 x 12 = 48), plus 26 enrolled at HC Nazoanga or directly at CMA. Among the age group 5–15 years, there were no patients with an iNTS BSI so for this age group this correction factor was not applied.(ii) Seeking healthcare elsewhere than in CMA or Health Centers: A total of 164 households were visited during the HUS, representing 1,615 participants including 695 children < 15 years old. Among children a total of 789 episodes of febrile illness were reported over a total observation period of 6,957 months. After extrapolating this data to represent a 12-months period for each participant, a total of 920 episodes of febrile illness in children were recorded over 8,340 months; In 460 (50%) of episodes healthcare was sought elsewhere than in Health Centers or CMA. A corresponding correction factor of 1/0.5 = x 2.0 was applied.(iii) Non-enrollment of eligible children. The proportion of children eligible but not enrolled was 9.7% , the cor(iv) Sensitivity of the blood cultures and inadequate filling. The volume lost by under-filling was 0.4 ml for both age groups (the minimum volume required (1 ml) minus the actual median volume of under-filled bottles (= 0.6 ml)). This volume was subsequently multiplied by the proportion of under-filled bottles in each age group. For age group < 5 years this was 39.8% and for age group 5–15 years this was 24.9%, resulting in a loss of 0.16 ml and 0.10 ml respectively. Corresponding correction factors were 1/ (1–0.16) = x 1.2 and 1/ (1–0.10) = x 1.1 respectively. Combined with the correction factor for the 50% estimated overall sensitivity of blood cultures, the final correction factors were 1.2 x 2 = x 2.4 and 1.1 x 2 = x 2.2 for age groups < 5 years and 5–15 years respectively.Salmonella Typhi BSI was similar to that observed in the < 5 years old group . Of note, nearly three-quarter (73.8% (45/61)) of iNTS isolates of the < 5 years old group were recovered in children between 2 months and 3 years of age. There was no association with severe acute malnutrition. Reported data are made available in Salmonella Typhi and iNTS. The number of iNTS sharply increased sharply in September and lasted for a period of six months. The increase coincided with the peak of the rainy season and the seasonal increase of Plasmodium falciparum malaria. There were no apparent clusters (in time and location) for iNTS [Salmonella Typhi isolates were recovered from patients from Nazoanga village over a three-month period, which may be suggestive of a common source outbreak.for iNTS . In our Salmonella BSI among febrile and severely ill children in a rural area with seasonal malaria transmission.The present study in rural Burkina Faso assessed the population-based incidence of Salmonella Typhi and iNTS accounted for 13.3% and 55.8% of all 118 BSI episodes; 71.6% of iNTS (48/67) isolates were Salmonella Typhimurium and 25.4% (17/67) Salmonella Enteritidis; there was no apparent geographical clustering. The adjusted incidence of iNTS in the < 5 years old group was 4,138 per 100,000 PYO and exceeded the incidence of severe malaria . Incidences of Salmonella Typhi BSI were 224 and 273 per 1000,000 PYO for the < 5 years old group and 5–15 years old group respectively. Most iNTS occurred at the peak of the rainy season and during a three-month period thereafter. There was no clear-cut seasonal pattern for Salmonella Typhi.Salmonella Typhi cases among the 5–15 years and <5 years old groups respectively were relatively low, resulting in corresponding incidence rates with wide confidence intervals. The proportion of iNTS and Salmonella Typhi grown from blood cultures in the present study were however in line with those of a similar study conducted at the same site one year previously [Limitations to this study included the relatively short duration of the study. The study period of 12 months was chosen to adjust for seasonal variation. Additionally, the absolute numbers of iNTS and eviously .Despite training and supervision subjectivity in clinical assessment (and consequent differences in blood culture sampling) cannot be excluded. Other limitations of the present study are related to refusal rates, sub-optimal volumes taken for blood culture and the organization of the HUS. The overall refusal rate among eligible children was 9.4%, of which the majority occurred over a short period at the beginning of the study. The adjusted incidence rates were corrected for refusals. The common practice of sampling sub-optimal volumes for blood culture was related to sampling in small children  and for Salmonella Typhi [Only few studies have provided population-based incidence rates for BSI caused by la Typhi –21 or iNla Typhi –23 and tSalmonella Typhi were two-to-three fold higher in the present study compared to those observed in Pemba, an island of the Zanzibar archipelago [2) [Salmonella Typhi infection in both sites compared to the present one, which may be related to the higher population density at the semi-urban sites .Incidence rates of hipelago . Differehipelago , 20. In lago [2) . Marks elago [2)  recentlyIn the present study incidence rates of iNTS among the < 5 years old group were nearly twice as high compared to observed incidences rates from rural Kenya and Ghana , 22. ThiP. falciparum malaria during the study period as a factor explaining this low incidence [By contrast, another study site in rural Kenya (Kilifi) reported an incidence of only 33/100,000 PYO among the < 5 years old group; the authors mentioned a declining incidence of ncidence , 24. Thencidence . The Typncidence  reportedncidence , 26.Most correction factors used for incidence calculation in this study have been previously described. Unlike previous studies, the current study additionally corrected for non-referral of patients from healthcare centers to the reference hospital. Non-referral was estimated by statistics obtained by the district health office, but could not be validated. As a result, this correction factor may have caused either an over- or underestimation of the true incidence. The correction factor was applied to a limited number of cases and we therefore believe has had a low impact on the incidence calculations.Salmonella Typhi from blood culture was 40.3% compared to 86.7% from bone marrow punction among HIV infected adults in Malawi.The HUS formed an integral part of the current study and was organized in the same way as previously reported by the TSAP consortium. The HUS was corrected for seasonality by covering a full year for each sampled household. We would however like to caution that health-seeking behavior may slightly differ over age group and gender. The present study did not correct for these factor because of concern to decrease reliability as numbers of cases in some groups would be small. Surprisingly, many other authors do not correct for blood culture nor filling rate, a factor of high impact to sensitivity. This finding is further supported by Gorden et al.  who demoSalmonella Typhimurium and Salmonella Enteritidis were the most prevalent serotypes at proportions of 71.6% and 25.4% respectively. These proportions are in line with the results of a meta-analysis of community acquired BSI in children in Africa which showed that serotypes Typhimurium and Enteritidis accounted for respectively two-thirds (65.2%) and one third (33.1%) of 706 Salmonella isolates [isolates .P. falciparum malaria is moreover thought to predispose to iNTS in several ways: (i) iron released by lysis of P. falciparum-infected red blood cells is an essential substrate for bacteria; (ii) the accumulation of the hemozoin inside monocytes alters cell differentiation to antigen presenting cells; (iii) production of interleukin-12 during malaria infection may increase susceptibility to iNTS; (iv) sequestration of P. falciparum parasites in the microcirculation of the intestinal mucosa during sever malaria renders it more susceptible to bacteria that colonize the gut [Salmonella Typhi at the start of the rainy season was linked to Nazoanga village and, may have represented clustered cases from a common source outbreak.We saw an increase of iNTS at the peak of the rainy season, extending into the dry season . Annual  the gut –36. The In the present study, combined malaria (uncomplicated and severe) and BSI was observed in 2.8% of children with malaria. The overall percentage of BSI among children with malaria was lower than the 5.6% to 6.5% proportion aggregated in two metadata studies on BSI in Africa , 37. TheSalmonella Typhi and iNTS as major public health issues in children from West Africa. As for Salmonella Typhi, the present incidence confirms that West Africa may be considered among the high-incidence regions  [i.e. 10–100 cases/100,000/year), as opposed to high incidence regions in South-Central and South-East Asia [The present findings depict 00/year) . This coast Asia . This swast Asia .Salmonella  in development include live-attenuated, protein-based vaccines with a novel self-adjuvanting antigen-delivery strategy  technology) vaccines [Given their association with multidrug resistance and case fatality , 40, 41,vaccines . An addiSalmonella Typhi and Salmonella non-Typhi infection was higher than that of severe malaria in children across different ages in rural Burkina Faso. Even though malaria has been declining worldwide, it is clear that the incidence of bloodstream infection and invasive salmonellosis in sub-Saharan Africa has been underestimated before. This is probably due to the lack of appropriate diagnostic methods to obtain accurate bacteriological diagnosis, in particular in low resource settings where malaria is most prevalent. Significant efforts are still necessary towards better preventive, diagnostic and therapeutic tools to improve the clinical care and community control of this neglected disease. Prioritization of the implementation of Salmonella Typhi as well as iNTS vaccines is needed.The present results confirm iNTS as the predominant BSI pathogen in children in rural Africa . It showS1 Appendix(DOCX)Click here for additional data file.S2 Appendix(DOCX)Click here for additional data file.S1 DatabaseTab one: database/ Tab 2: code.(XLSX)Click here for additional data file.


Malaria is a preventable and curable disease. Mazowe district had been experiencing a lower malaria transmission rate in comparison to other districts in the Mashonaland Central province but it experienced a huge outbreak in the 2013-2014 rainy seasons with a case fatality rate (CFR) of 0.21%. This CFR was the highest in the province and it was twice as much as the national CFR (0.12%) for the same period. We evaluated severe malaria case management in Mazowe district to determine if practice is as per standard treatment guidelines.A descriptive cross sectional study was conducted in Mazowe district using the Logical Framework approach. District Health Executives (DHE) members, nurses and severe malaria case notes were purposively and conveniently selected into the study. Key informant Interviews and review of case notes were carried out. All data were analysed using Epi Info 3.5.1.to calculate means and frequencies. Permission to conduct the study was obtained from the Mashonaland Central Provincial Medical Directorate (PMD) Institutional Ethical Review Board (IRB).The median age in years of the cases was 16  and up to 58.1% of the cases were female. Inputs including staff, medicines and medical and laboratory equipment for severe case management were inadequate in the district. Only 60% of severe cases were diagnosed using blood slides and up to 95.6% of cases presented with one or more of the clinical signs of severe malaria. All severe cases were treated using correct anti-malarial and analgesic doses. Patient monitoring was not done as per prerequisite intervals and up to 5% of cases died. The health workers had above average knowledge on severe malaria.Severe malaria case management inputs were inadequate in the district. For many cases, the district did not follow complicated malaria treatment guidelines for diagnosis, treatment and monitoring. Untrained staff needs training in Severe Malaria Case Management and monitoring of commodity stocks needs to be strengthened. Malaria is a fatal disease that is both preventable and curable. It is caused by parasites that are transmitted to people through the bites of infected mosquitoes . In the A descriptive cross sectional study was conducted using the Logical Framework approach. A review of severe malaria case notes was done in order to assess whether the cases were treated according to the recommended protocol. The study was carried out in Mazowe district at the three referral hospitals namely, Concession District Hospital (CDH), Mvurwi Hospital and Howard Mission Hospital which were selected purposively. Key Informant Interviews were carried out with District health staff  and hospital nurses. These were purposively and conveniently selected. Purposive sampling was used because the knowledge we required in some instances required specific individuals who alone had that kind of knowledge. Such individuals were pharmacy staff and DHE members. Convenient sampling was used in the case of nurses who do case management in the wards. We recruited those who were available in the wards during the period of the study. A total of 94 severe case notes from the period April 2014 to May 2015 were randomly selected into the study from the 3 hospitals. These were captured onto a data abstraction form and then entered into an Epi Info database. Key informant interviews were conducted with the health staff using a questionnaire. All data were analysed using Epi Info 3.5.1. to calculate means and frequencies. Permission to conduct the study was obtained from the Mashonaland Central Provincial Medical Directorate (PMD) Institutional Ethical Review Board (IRB).Demographics: A total of 40 health workers of median age 35 years and median period on current post 7.5 years were recruited into the study from 2 rural hospitals, 1 district hospital and 1 mission hospital. Most of the participant health workers were female (70 %) and 70 % were nurses. For all the severe cases sampled from the case notes, 15% were aged less than five years and 3.2% were over at least 65 years of age. The median age was however 16 years and up to 58.1% were female. Only 14% of these cases had been referred.Case management Inputs: Across the three hospitals in the district, only environmental health staff were as per staff establishment. Only Howard mission hospital met the recommended staff compliment for doctors while the other three hospitals only met the staff compliment requirements for environmental health. Except at Howard hospital were minimum stock levels could not be calculated, coartem was at least 3.5 times the minimum stock level at the time of data collection. The district hospital did not have any quinine in stock. 5% dextrose was on average 47.0% in short fall for Concession and Mvurwi hospitals. Only the district hospital surpassed the minimum stock requirements for glucometers and glucose test strips Diagnoses of Complicated Cases: Across all age groups and hospitals, an average of 97.5 % was diagnosed by RDT while an average of 54.6% was diagnosed by microscopy. The greatest proportion of cases tested by Microscopy came from Concession (80.6%), followed by Mvurwi (7.4%) and then Howard (6.0%). By microscopy, 85.9% of the cases tested positive for multi-parasitemia and among the under 5s, only 75.0% were hyper parasitemic. By rapid diagnostic test, 93.5 % tested antigen positive. Up to 95.6% of these cases were diagnosed as complicated malaria, 1.1% was uncomplicated malaria and 3.3% were not specified.Treatment and Monitoring of Complicated Cases : IV Quinine was administered to 78.7% of all the cases of which the loading and maintenance doses were as per guidelines. Oral quinine was administered to 80.9% of all the cases and 94.7% of these had doses as per guidelines. Paracetamol was correctly used among all the 81.9% who got it prescribed as pain killer of choice. Doxycycline and Clindamycin were used as antibiotics of choice among 35.1% and 14.9% of all the cases respectively and in each case, correct doses were administered Treatment Outcomes: At the end of admission the well and discharged were mostly among those aged 64 years and above and those aged 5 to 64 years (3 of 3) and those aged 5 to 64 years (91.0%). However, 4 of the 5 who died were aged 5 to 64 years. About 94% of severe malaria cases who were admitted within one day of falling sick got well and discharged and none of them died. 88% of severe malaria cases who were admitted after one day of complaining got well and discharged but 8.9% of them died Health Worker Knowledge on Signs and Complications of Severe Malaria: Fever, pallor and rigors were most mentioned as signs of severe malaria while on the other end convulsions and prostration were the least stated signs by the participants. All the participants recognized anaemia as a complication of severe malaria while renal failure was least recognized as a severe malaria complication among 75% of participants. Pregnant women and children under 5 years of age were most recognized as high risk groups among the health workers. At 96.9 % of respondents IV Quinine was most recognized as medicine for treating severe malaria while ASAQ, at 25% of participants was least stated as medicine for treating severe malaria The anti-malarial drug Quinine was relatively below minimum stock status throughout the district except at Mvurwi hospital where it was 133% above minimum stock requirements. Correct loading and maintenance doses of IV Quinine adjusted to age and body weight were administered to all patients to whom it was prescribed. Admitted cases were mostly monitored for Temperature, BP, and Fluid intake and output. Patient monitoring for all necessary parameters was however not done as recommended for patients in admission. About 90.4% of the patients got well and were discharged. Those who died presented at least one day after commencement of complaints. The health workers were able to state correctly most of the signs and complications of severe malaria as well as some of its high risk groups and its treatment. At the point of the study, the stock status for severe malaria medicines was not uniformly distributed among the hospitals in the district. A key thing to note is that the pharmacy at Concession Hospital  also stocks for the district. When medicines have run out at the district hospital, it means either that they have been distributed to the respective health centres in the district or they have literally just run out of stock. The district hospital alone had artesunate and Artesunate-Amodiquine (ASAQ) in stock as it hadn't been distributed to the other hospitals in the district.This was because the staff at those hospitals had not yet been trained in administration of these medicines. The dispensary assistant at Howard Mission Hospital had not been oriented in calculation of minimum stock requirements so it was difficult to measure the availability of medicines at this mission hospital. Since most malaria cases were non-complicated and the district had been experiencing an outbreak, the stock status for coartem was well above minimum stock requirements by at least 350% across the 3 hospitals, Concession, Mvurwi and Rossa. Zurovac D et.al, 2014, found that avoidance of stock-outs causes major improvement to implementation of case management at hospital level [Most tests were done at the hospitals using RDTs 97.5%) but only 54.6% by Microscopy. Concession hospital was able to do blood slides for all its cases and was also able to do serial MPS tests for 81.8% of all those who had severe malaria and were admitted. Concession hospital being both a referral and district hospital tends to secure more of the laboratory reagents for its broader clientele before distributing them to the other hospitals. Mvurwi and Howard hospitals only carried out tests for 83.8% and 44.4% respectively of all severe malaria cases evaluated. Rossa hospital does not admit patients except prior to referrals out. Only those with a 2+ and above MPS result are technically considered hyperparasitemic. All those who have hyperparasitemia are considered to be severe cases according to the case management guidelines and these were 60.0% of all clients. The rest (40.0%) of the severe cases were not hyperparasitemic and were diagnosed symptomatically and by RDT confirmation. RDTs seem to be a reliable diagnostic method even under emergencies. Similarly, in Malawi Steinhardt L et.al, 2014, the improvement of diagnosis was found to be linked to the cost effective RDTs [% but onlRegular 4 hourly intervals are meant to be used to monitor different Temperature, Pulse, Blood Pressure, Respiratory rate and Blood sugar. The nursing staff at the clinics either did not do meticulous recording on the patient monitoring charts or were not monitoring patients 100% of the time they should have. The parameter most monitored was temperature with 69.4% of patients monitored 50%-99% of the recommended intervals. A patient is meant to remain in care until their condition stabilizes. The purpose of monitoring a patient during admission is to ensure tracking of the recuperation process and to be able to promptly respond to abnormalities as they emerge in the progression of sickness. Inconsistent monitoring may lead to inappropriate patient care that can lead to the worsening of patient condition or even fatality. Of the 5 patients who died, none of them had had a 100% monitoring. Poor adherence to patient treatment and management guidelines was noted to be associated with poor outcomes by Chanda-Kapata P et al (2011) . The fatStudy Limitations: We used convenience sampling and we could not reach the calculated sample size as our study participants were attending to patients in the wards. This might have caused under representation of the target population.Inputs including Staff, Medicines and Medical Equipment for Complicated Case Management were inadequate in the district. Only 60% of severe cases were diagnosed using the gold standard blood slides and only 95.6% of cases presented with one or more of the clinical signs of severe malaria. All severe cases were treated using correct anti-malarial and analgesic doses. Patient monitoring was not done per prerequisite intervals. Up to 91% of cases recovered and got discharged and 5 % died. Most health workers knew at least one high risk group for severe malaria, clinical signs of and treatment of severe malaria. We therefore recommended training and mentorship of clinicians in severe malaria case management according to new guidelines and strengthening of pharmacovigilance for rigorous commodity stock level management.Mortality from untreated severe malaria  approaches 100%. With prompt, effective antimalarial treatment and supportive care, the rate falls to 10-20% overall. Within the broad definition of severe malaria some syndromes are associated with lower mortality rates (e.g. severe anaemia) and others with higher mortality rates (e.g. acidosis). The risk for death increases in the presence of multiple complications.In addition to inputs  for Complicated Case Management, patient monitoring is very key to good prognosis.The authors declare no competing interests.