Paul M. Arguin

Serologic Evidence of Lyssavirus Infections among Bats, the Philippines

Active surveillance for lyssaviruses was conducted among populations of bats in the Philippines. The presence of past or current Lyssavirus infection was determined by use of direct fluorescent antibody assays on bat brains and virus neutralization assays on bat sera. Although no bats were found to have active infection with a Lyssavirus, 22 had evidence of neutralizing antibody against the Australian bat lyssavirus (ABLV). Seropositivity was statistically associated with one species of bat, Miniopterus schreibersi. Results from the virus neutralization assays are consistent with the presence in the Philippines of a naturally occurring Lyssavirus related to ABLV.

Doxycycline for Malaria Chemoprophylaxis and Treatment: Report from the CDC Expert Meeting on Malaria Chemoprophylaxis

Doxycycline, a synthetically derived tetracycline, is a partially efficacious causal prophylactic (liver stage of Plasmodium) drug and a slow acting blood schizontocidal agent highly effective for the prevention of malaria. When used in conjunction with a fast acting schizontocidal agent, it is also highly effective for malaria treatment. Doxycycline is especially useful as a prophylaxis in areas with chloroquine and multidrug-resistant Plasmodium falciparum malaria. Although not recommended for pregnant women and children < 8 years of age, severe adverse events are rarely reported for doxycycline. This report examines the evidence behind current recommendations for the use of doxycycline for malaria and summarizes the available literature on its safety and tolerability.

Risk Factors for Nipah Virus Infection among Abattoir Workers in Singapore

During 10-19 March 1999, 11 workers in 1 of 2 Singaporean abattoirs developed Nipah-virus associated encephalitis or pneumonia, resulting in 1 fatality. A case-control study was conducted to determine occupational risk factors for infection. Case patients were abattoir A workers who had anti-Nipah IgM antibodies; control subjects were randomly selected abattoir A workers who tested negative for anti-Nipah IgM. All 13 case patients versus 26 (63%) of 41 control subjects reported contact with live pigs (P=.01). Swine importation from Malaysian states concurrently experiencing a Nipah virus outbreak was banned on 3 March 1999; on 19 March 1999, importation of Malaysian pigs was banned, and abattoirs were closed. No unusual illnesses among pigs processed during February-March were reported. Contact with live pigs appeared to be the most important risk factor for human Nipah virus infection. Direct contact with live, potentially infected pigs should be minimized to prevent transmission of this potentially fatal zoonosis to humans.

Epidemiology of 2009 Pandemic Influenza A (H1N1) Deaths in the United States, April–July 2009

During the spring of 2009, pandemic influenza A (H1N1) virus (pH1N1) was recognized and rapidly spread worldwide. To describe the geographic distribution and patient characteristics of pH1N1-associated deaths in the United States, the Centers for Disease Control and Prevention requested information from health departments on all laboratory-confirmed pH1N1 deaths reported from 17 April through 23 July 2009. Data were collected using medical charts, medical examiner reports, and death certificates. A total of 377 pH1N1-associated deaths were identified, for a mortality rate of .12 deaths per 100,000 population. Activity was geographically localized, with the highest mortality rates in Hawaii, New York, and Utah. Seventy-six percent of deaths occurred in persons aged 18-65 years, and 9% occurred in persons aged ≥ 65 years. Underlying medical conditions were reported for 78% of deaths: chronic lung disease among adults (39%) and neurologic disease among children (54%). Overall mortality associated with pH1N1 was low; however, the majority of deaths occurred in persons aged <65 years with underlying medical conditions.

Impact of globalization and animal trade on infectious disease ecology.

The articles on rabies and Marburg virus featured in this months Emerging Infectious Diseases (EID) zoonoses issue illustrate common themes. Both discuss zoonotic diseases with serious health implications for humans, and both have a common reservoir, the bat. These articles, and the excitement generated by this years recognition of World Rabies Day on September 8, also described in this issue, remind us how globalization has had an impact on the worldwide animal trade. This worldwide movement of animals has increased the potential for the translocation of zoonotic diseases, which pose serious risks to human and animal health.

Pretravel Health Preparation Among US Residents Traveling to India to VFRs: Importance of Ethnicity in Defining VFRs

BACKGROUND International travelers visiting friends and relatives (VFRs) in lower income countries experience high rates of travel-related infections. We examined demographic characteristics and pretravel preparation practices among US residents traveling to India to determine factors that may contribute to higher infection rates and that would allow for improved prevention strategies. METHODS A cross-sectional study was conducted among US residents traveling to India in departure areas for flights to India at three US international airports during August 2005. Eligible travelers were US residents going to India who were English speaking and >or=18 years. Self-administered questionnaires were used to assess knowledge of and compliance with pretravel health recommendations. RESULTS Of 1,574 eligible travelers, 1,302 (83%) participated; 60% were male and the median age was 37. Eighty-five percent were of South Asian/Indian ethnicity and 76% reported VFR as the primary reason for travel. More than 90% of VFRs had at least a college education and only 6% cited financial barriers as reasons for not obtaining travel health services. VFRs were less likely than non-VFR travelers to seek pretravel health advice, to be protected against hepatitis A or typhoid fever, and less likely to be taking appropriate antimalarial chemoprophylaxis. However, when stratified by ethnicity, travelers of South Asian ethnicity were less likely than other travelers to adhere to pretravel health recommendations, regardless of VFR status. CONCLUSIONS Similar to previous studies, VFR status was associated with pretravel health practices that leave travelers at risk for important infectious diseases. This association differed by ethnicity, which may also be an important marker of nonadherence to pretravel health recommendations. These findings have important implications for identifying at-risk travelers and properly targeting prevention messages.

Malaria Surveillance — United States, 2013

PROBLEM/CONDITION Malaria in humans is caused by intraerythrocytic protozoa of the genus Plasmodium. These parasites are transmitted by the bite of an infective female Anopheles 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 also 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 identify episodes of local transmission and to guide prevention recommendations for travelers. PERIOD COVERED This report summarizes cases in persons with onset of illness in 2013 and summarizes trends during previous years. DESCRIPTION OF SYSTEM Malaria cases diagnosed by blood film, polymerase chain reaction, or rapid diagnostic tests are mandated to be reported to local and state health departments by health care providers or laboratory staff. Case investigations are conducted by local and state health departments, and reports are transmitted to CDC through the National Malaria Surveillance System, National Notifiable Diseases Surveillance System, or direct CDC consultations. CDC conducted antimalarial drug resistance marker testing on blood samples submitted to CDC by health care providers or local/state health departments. Data from these reporting systems serve as the basis for this report. RESULTS CDC received 1,727 reported cases of malaria, including two congenital cases, with an onset of symptoms in 2013 among persons in the United States. The total number of cases represents a 2% increase from the 1,687 cases reported for 2012. Plasmodium falciparum, P. vivax, P. malariae, and P. ovale were identified in 61%, 14%, 3%, and 4% of cases, respectively. Forty (2%) patients were infected by two species. The infecting species was unreported or undetermined in 17% of cases. Polymerase chain reaction testing determined or corrected the species for 85 of the 137 (62%) samples evaluated for drug resistance marker testing. Of the 904 patients who reported purpose of travel, 635 (70%) were visiting friends or relatives (VFR). Among the 961 cases in U.S. civilians for whom information on chemoprophylaxis use and travel region was known, 42 (4%) patients reported that they had initiated and adhered to a chemoprophylaxis drug regimen recommended by CDC for the regions to which they had traveled. Thirty-six cases were reported in pregnant women, none of whom had adhered to chemoprophylaxis. Among all reported cases, approximately 270 (16%) were classified as severe illnesses in 2013. Of these, 10 persons with malaria died in 2013, the highest number since 2001. In 2013, a total of 137 blood samples submitted to CDC were tested for molecular markers associated with antimalarial drug resistance. Of the 100 P. falciparum-positive samples, 95 were tested for pyrimethamine resistance: 88 (93%) had genetic polymorphisms associated with pyrimethamine drug resistance, 74 (76%) with sulfadoxine resistance, 53 (53%) with chloroquine resistance, one (1%) with atovaquone resistance, none with mefloquine drug resistance, and none with artemisinin resistance. INTERPRETATION The overall trend of malaria cases has been increasing since 1973; the number of cases reported in 2013 is the third highest annual total since then. Despite progress in reducing the global burden of malaria, the disease remains endemic in many regions, and the use of appropriate prevention measures by travelers is still inadequate. PUBLIC HEALTH ACTIONS Completion of data elements on the malaria case report form increased slightly in 2013 compared with 2012, but still remains unacceptably low. This incomplete reporting compromises efforts to examine trends in malaria cases and prevent infections. VFRs continue to be a difficult population to reach with effective malaria prevention strategies. Evidence-based prevention strategies that effectively target VFRs need to be developed and implemented to have a substantial impact on the numbers of imported malaria cases in the United States. Fewer patients reported taking chemoprophylaxis in 2013 (32%) compared with 2012 (34%), and adherence was poor among those who did take chemoprophylaxis. Proper use of malaria chemoprophylaxis will prevent the majority of malaria illness and reduce the risk for severe disease (http://www.cdc.gov/malaria/travelers/drugs.html). Malaria infections can be fatal if not diagnosed and treated promptly with antimalarial medications appropriate for the patients age and medical history, the likely country of malaria acquisition, and previous use of antimalarial chemoprophylaxis. Recent molecular laboratory advances have enabled CDC to identify and conduct molecular surveillance of antimalarial drug resistance markers (http://www.cdc.gov/malaria/features/ars.html). These advances will allow CDC to track, guide treatment, and manage drug resistance in malaria parasites both domestically and globally. For this to be successful, specimens should be submitted for all cases diagnosed in the United States. Clinicians should consult the CDC Guidelines for Treatment of Malaria and contact the CDCs Malaria Hotline for case management advice, when needed. Malaria treatment recommendations can be obtained online (http://www.cdc.gov/malaria/diagnosis_treatment) or by calling the Malaria Hotline (770-488-7788 or toll-free at 855-856-4713).

Intravenous Artesunate for the Treatment of Severe Malaria

Objective: To review the pharmacodynamics and pharmacotherapeutic use of intravenous artesunate for the treatment of severe malaria. Data Sources: Literature was retrieved through PubMed (1999–March 2010), MEDLINE (1996–March 2010), and the Centers for Disease Control and Prevention (CDC), using the search terms artemisinin, artesunate, malaria, and severe malaria. In addition, reference citations from publications identified were reviewed. Study Selection and Data Extraction: All articles in English that were identified from the data sources were reviewed. Focus was placed on postmarketing trials examining the safety and efficacy of artesunate in comparison with other regimens. Data Synthesis: The treatment of severe malaria requires prompt, safe, and effective intravenous antimalarials. Many oral and intravenous agents are available worldwide for the treatment of malaria; however, quinidine has been the only option for parenteral therapy in the US. Furthermore, this products lack of availability as well as its adverse safety profile have created a treatment option gap. Recently, intravenous artesunate was approved by the Food and Drug Administration (FDA) for investigational drug use and distribution by the CDC. Three major studies regarding the use of intravenous artesunate are reviewed, in addition to the World Health Organizations malaria treatment guidelines. While there are no published head-to-head trials of intravenous artesunate versus intravenous quinidine for severe malaria, several international studies comparing intravenous quinine and artesunate concluded that artesunate has the highest treatment success, with lower incidence of adverse events. In addition, other literature is reviewed regarding counterfeit and other issues associated with artesunate. Conclusions: Artesunate, a new antimalarial currently available through the CDC, appears to be highly effective, better tolerated than quinidine, and not hampered by accessibility issues. If it were to be FDA approved and commercially available, it would be the preferred agent for the treatment of severe malaria in the US.

Case definition: postartemisinin delayed hemolysis.

In this issue of Blood , Jaureguiberry et al appear to have proven that the hypothesis of early destruction of pitted erythrocytes is correct and propose a method for screening patients for this syndrome. 1 Early destruction of pitted erythrocytes has been the leading hypothesis for postartesunate delayed hemolysis since it was first recognized a few years ago.

The Increase of Imported Malaria Acquired in Haiti among US Travelers in 2010

From 2004 to 2009, the number of malaria cases reported in Haiti increased nearly fivefold. The effect of the 2010 earthquake and its aftermath on malaria transmission in Haiti is not known. Imported malaria cases in the United States acquired in Haiti tripled from 2009 to 2010, likely reflecting both the increased number of travelers arriving from Haiti and the increased risk of acquiring malaria infection in Haiti. The demographics of travelers and the proportion of severe cases are similar to those statistics reported in previous years. Non-adherence to malaria chemoprophylaxis remains a nearly universal modifiable risk factor among these cases.