Simulating partial vaccine protection: BCG in badgers.

In wildlife disease management there are few diseases for which vaccination is a viable option. The human vaccine BCG has been used for the control of bovine tuberculosis in badgers since 2010 and is expected to increase. Understanding the long-term effects of repeated vaccination campaigns on disease prevalence is vital, but modelling thus far has generally assumed that a vaccine provides perfect protection to a proportion of the population, and that animals exposed to a repeated vaccination have a second independent chance of becoming protected. We held a workshop with experts in the field to obtain consensus over the main pathways for partial protection in the badger, and then simulated these using an established model. The available data supported the possibility that some individuals receive no benefit from the BCG vaccine, others may result in a delayed disease progression and in the remaining animals, vaccine protected the individual from any onward transmission. Simulating these pathways using different levels of overall efficacy demonstrated that partial protection leads to a reduced effect of vaccination, but in all of the identified scenarios it was still possible to eradicate disease in an isolated population with no disease introduction. We also identify those potential vaccination failures that require further investigation to determine which of our proposed pathways is the more likely.

Presymptomatic transmission of SARS-CoV-2 infection: a secondary analysis using published data.

OBJECTIVE: To estimate the proportion of presymptomatic transmission of SARS-CoV-2 infection that can occur, and the timing of transmission relative to symptom onset. SETTING/DESIGN: Secondary analysis of international published data. DATA SOURCES: Meta-analysis of COVID-19 incubation period and a rapid review of serial interval and generation time, which are published separately. PARTICIPANTS: Data from China, the Islamic Republic of Iran, Italy, Republic of Korea, Singapore and Vietnam from December 2019 to May 2020. METHODS: Simulations were generated of incubation period and of serial interval or generation time. From these, transmission times relative to symptom onset, and the proportion of presymptomatic transmission, were estimated. OUTCOME MEASURES: Transmission time of SARS-CoV-2 relative to symptom onset and proportion of presymptomatic transmission. RESULTS: Based on 18 serial interval/generation time estimates from 15 papers, mean transmission time relative to symptom onset ranged from -2.6 (95% CI -3.0 to -2.1) days before infector symptom onset to 1.4 (95% CI 1.0 to 1.8) days after symptom onset. The proportion of presymptomatic transmission ranged from 45.9% (95% CI 42.9% to 49.0%) to 69.1% (95% CI 66.2% to 71.9%). CONCLUSIONS: There is substantial potential for presymptomatic transmission of SARS-CoV-2 across a range of different contexts. This highlights the need for rapid case detection, contact tracing and quarantine. The transmission patterns that we report reflect the combination of biological infectiousness and transmission opportunities which vary according to context.

Relative infectiousness of asymptomatic SARS-CoV-2 infected persons compared with symptomatic individuals: a rapid scoping review.

OBJECTIVES: The aim of this study was to determine the relative infectiousness of asymptomatic SARS-CoV-2 infected persons compared with symptomatic individuals based on a scoping review of available literature. DESIGN: Rapid scoping review of peer-reviewed literature from 1 January to 5 December 2020 using the LitCovid database and the Cochrane library. SETTING: International studies on the infectiousness of individuals infected with SARS-CoV-2. PARTICIPANTS: Studies were selected for inclusion if they defined asymptomatics as a separate cohort distinct from presymptomatics and if they provided a quantitative measure of the infectiousness of asymptomatics relative to symptomatics. PRIMARY OUTCOME MEASURES: PCR result (PCR studies), the rate of infection (mathematical modelling studies) and secondary attack rate (contact tracing studies) - in each case from asymptomatic in comparison with symptomatic individuals. RESULTS: There are only a limited number of published studies that report estimates of relative infectiousness of asymptomatic compared with symptomatic individuals. 12 studies were included after the screening process. Significant differences exist in the definition of infectiousness. PCR studies in general show no difference in shedding levels between symptomatic and asymptomatic individuals; however, the number of study subjects is generally limited. Two modelling studies estimate relative infectiousness to be 0.43 and 0.57, but both of these were more reflective of the infectiousness of undocumented rather than asymptomatic cases. The results from contact tracing studies include estimates of relative infectiousness of 0, but with insufficient evidence to conclude that it is significantly different from 1. CONCLUSIONS: There is considerable heterogeneity in estimates of relative infectiousness highlighting the need for further investigation of this important parameter. It is not possible to provide any conclusive estimate of relative infectiousness, as the estimates from the reviewed studies varied between 0 and 1.

Estimation of the serial interval and proportion of pre-symptomatic transmission events of COVID- 19 in Ireland using contact tracing data.

BACKGROUND: The serial interval is the period of time between the onset of symptoms in an infector and an infectee and is an important parameter which can impact on the estimation of the reproduction number. Whilst several parameters influencing infection transmission are expected to be consistent across populations, the serial interval can vary across and within populations over time. Therefore, local estimates are preferable for use in epidemiological models developed at a regional level. We used data collected as part of the national contact tracing process in Ireland to estimate the serial interval of SARS-CoV-2 infection in the Irish population, and to estimate the proportion of transmission events that occurred prior to the onset of symptoms. RESULTS: After data cleaning, the final dataset consisted of 471 infected close contacts from 471 primary cases. The median serial interval was 4 days, mean serial interval was 4.0 (95% confidence intervals 3.7, 4.3) days, whilst the 25th and 75th percentiles were 2 and 6 days respectively. We found that intervals were lower when the primary or secondary case were in the older age cohort (greater than 64 years). Simulating from an incubation period distribution from international literature, we estimated that 67% of transmission events had greater than 50% probability of occurring prior to the onset of symptoms in the infector. CONCLUSIONS: Whilst our analysis was based on a large sample size, data were collected for the primary purpose of interrupting transmission chains. Similar to other studies estimating the serial interval, our analysis is restricted to transmission pairs where the infector is known with some degree of certainty. Such pairs may represent more intense contacts with infected individuals than might occur in the overall population. It is therefore possible that our analysis is biased towards shorter serial intervals than the overall population.

Rapid review of available evidence on the serial interval and generation time of COVID-19.

The serial interval is the time between symptom onsets in an infector-infectee pair. The generation time, also known as the generation interval, is the time between infection events in an infector-infectee pair. The serial interval and the generation time are key parameters for assessing the dynamics of a disease. A number of scientific papers reported information pertaining to the serial interval and/or generation time for COVID-19. OBJECTIVE: Conduct a review of available evidence to advise on appropriate parameter values for serial interval and generation time in national COVID-19 transmission models for Ireland and on methodological issues relating to those parameters. METHODS: We conducted a rapid review of the literature covering the period 1 January 2020 and 21 August 2020, following predefined eligibility criteria. Forty scientific papers met our inclusion criteria and were included in the review. RESULTS: The mean of the serial interval ranged from 3.03 to 7.6 days, based on 38 estimates, and the median from 1.0 to 6.0 days (based on 15 estimates). Only three estimates were provided for the mean of the generation time. These ranged from 3.95 to 5.20 days. One estimate of 5.0 days was provided for the median of the generation time. DISCUSSION: Estimates of the serial interval and the generation time are very dependent on the specific factors that apply at the time that the data are collected, including the level of social contact. Consequently, the estimates may not be entirely relevant to other environments. Therefore, local estimates should be obtained as soon as possible. Careful consideration should be given to the methodology that is used. Real-time estimations of the serial interval/generation time, allowing for variations over time, may provide more accurate estimates of reproduction numbers than using conventionally fixed serial interval/generation time distributions.

Incubation period of COVID-19: a rapid systematic review and meta-analysis of observational research.

OBJECTIVES: The aim of this study was to conduct a rapid systematic review and meta-analysis of estimates of the incubation period of COVID-19. DESIGN: Rapid systematic review and meta-analysis of observational research. SETTING: International studies on incubation period of COVID-19. PARTICIPANTS: Searches were carried out in PubMed, Google Scholar, Embase, Cochrane Library as well as the preprint servers MedRxiv and BioRxiv. Studies were selected for meta-analysis if they reported either the parameters and CIs of the distributions fit to the data, or sufficient information to facilitate calculation of those values. After initial eligibility screening, 24 studies were selected for initial review, nine of these were shortlisted for meta-analysis. Final estimates are from meta-analysis of eight studies. PRIMARY OUTCOME MEASURES: Parameters of a lognormal distribution of incubation periods. RESULTS: The incubation period distribution may be modelled with a lognormal distribution with pooled mu and sigma parameters (95% CIs) of 1.63 (95% CI 1.51 to 1.75) and 0.50 (95% CI 0.46 to 0.55), respectively. The corresponding mean (95% CIs) was 5.8 (95% CI 5.0 to 6.7) days. It should be noted that uncertainty increases towards the tail of the distribution: the pooled parameter estimates (95% CIs) resulted in a median incubation period of 5.1 (95% CI 4.5 to 5.8) days, whereas the 95th percentile was 11.7 (95% CI 9.7 to 14.2) days. CONCLUSIONS: The choice of which parameter values are adopted will depend on how the information is used, the associated risks and the perceived consequences of decisions to be taken. These recommendations will need to be revisited once further relevant information becomes available. Accordingly, we present an R Shiny app that facilitates updating these estimates as new data become available.

Inferred duration of infectious period of SARS-CoV-2: rapid scoping review and analysis of available evidence for asymptomatic and symptomatic COVID-19 cases.

OBJECTIVES: Our objective was to review the literature on the inferred duration of the infectious period of COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, and provide an overview of the variation depending on the methodological approach. DESIGN: Rapid scoping review. Literature review with fixed search terms, up to 1 April 2020. Central tendency and variation of the parameter estimates for infectious period in (A) asymptomatic and (B) symptomatic cases from (1) virological studies (repeated testing), (2) tracing studies and (3) modelling studies were gathered. Narrative review of viral dynamics. INFORMATION SOURCES: Search strategies developed and the following searched: PubMed, Google Scholar, MedRxiv and BioRxiv. Additionally, the Health Information Quality Authority (Ireland) viral load synthesis was used, which screened literature from PubMed, Embase, ScienceDirect, NHS evidence, Cochrane, medRxiv and bioRxiv, and HRB open databases. RESULTS: There was substantial variation in the estimates, and how infectious period was inferred. One study provided approximate median infectious period for asymptomatic cases of 6.5-9.5 days. Median presymptomatic infectious period across studies varied over <1-4 days. Estimated mean time from symptom onset to two negative RT-PCR tests was 13.4 days (95% CI 10.9 to 15.8) but was shorter when studies included children or less severe cases. Estimated mean duration from symptom onset to hospital discharge or death (potential maximal infectious period) was 18.1 days (95% CI 15.1 to 21.0); time to discharge was on average 4 days shorter than time to death. Viral dynamic data and model infectious parameters were often shorter than repeated diagnostic data. CONCLUSIONS: There are limitations of inferring infectiousness from repeated diagnosis, viral loads and viral replication data alone and also potential patient recall bias relevant to estimating exposure and symptom onset times. Despite this, available data provide a preliminary evidence base to inform models of central tendency for key parameters and variation for exploring parameter space and sensitivity analysis.

Matching women with binge eating disorder to group treatment based on attachment anxiety: outcomes and moderating effects.

We hypothesized that compared to therapy groups homogeneously composed of women with binge eating disorder (BED) and low attachment anxiety, groups with high attachment anxiety would have better outcomes and a greater alliance-outcome relationship. We assigned 102 women with BED to therapy groups homogeneously composed of low attachment anxiety (n =52) or high attachment anxiety participants (n=50) who received Group Psychodynamic Interpersonal Psychotherapy (GPIP). GPIP resulted in improved outcomes with large effects. Attachment anxiety condition did not moderate outcomes. However, attachment anxiety condition did moderate the alliance-outcome relationship: i.e., group alliance growth was associated with improved binge eating only in the high attachment anxiety condition. Clinicians should be attentive to and encourage the growth of group therapy alliance especially for anxiously attached individuals.

Characterization of IGF-II isoforms in binge eating disorder and its group psychological treatment.

INTRO: Binge eating disorder (BED) affects 3.5% of the population and is characterized by binge eating for at least 2 days a week for 6 months. Treatment options include cognitive behavioral therapy, interpersonal psychotherapy, and pharmacotherapy which are associated with varied success. Little is known about the biology of BED. Since there is evidence that the insulin like growth factor system is implicated in regulation of body weight, insulin sensitivity and feeding behavior, we speculated it may be involved in BED. METHODS: A cross-sectional comparison was made between three groups of women: overweight with BED, overweight without BED and normal weight without BED. Women were assigned to Group Psychodynamic Interpersonal Psychotherapy. Blood was collected before therapy, at completion and at 6 months follow up for evaluation of IGF-II using Western blot. RESULTS: 97 overweight women with BED contributed to the cross-sectional comparison. The two control groups comprised 53 overweight women without BED, and 50 age matched normal weight women without BED. Obese women had significantly lower Big IGF-II than normal weight women, p = .028; Overweight women with BED had higher Mature IGF-II than normal weight women, p<.05. Big IGF-II showed a significant decreasing slope from pre- to post- to six months post-group psychological treatment, unrelated to changes in BMI (p = .008). CONCLUSION: Levels of IGF-II isoforms differed significantly between overweight and normal weight women. Overweight women with BED display abnormal levels of circulating IGF-II isoforms. BED is characterized by elevated mature IGF-II, an isoform shown to carry significant bioactivity. This finding is not related to BMI or to changes in body weight. The results also provide preliminary evidence that BIG IGF-II is sensitive to change due to group psychological treatment. We suggest that abnormalities in IGF-II processing may be involved in the neurobiology of BED.

Predictors of treatment acceptance and of participation in a randomized controlled trial among women with anorexia nervosa.

OBJECTIVE: This study aimed to identify predictors of acceptance of intensive treatment and of participation in a randomized controlled trial (RCT) among women with anorexia nervosa (AN). METHOD: Participant data were drawn from a tertiary care intensive treatment programme including a previously published RCT. Women with AN (N = 106) were offered intensive treatment, and 69 were approached to participate in an RCT of olanzapine's efficacy as an adjunctive treatment for AN. AN subtype and pretreatment psychological variables were used to predict acceptance of intensive treatment and RCT participation. RESULTS: AN binge purge subtype and higher depression and body dissatisfaction predicted intensive treatment acceptance. No variable predicted RCT participation among treatment acceptors. DISCUSSION: Clinicians may focus on enhancing motivation or use a stepped care approach to increase intensive treatment acceptance especially among women with AN-restricting type and among all those with AN who have lower levels of distress.

Maintaining medical independence in advanced age.

Juneteenth Day celebrates June 19, 1865, when Major General Granger landed in Texas with news that the Civil War had ended and that slaves were now free (History of Juneteenth, n.d.). Similarly, this article brings you news that patients are free to make their own medical decisions. American law now guarantees the right of all patients to make their own such decisions. Thus, this article introduces the concept of medical policy statements, a new way for patients to give instructions to medical professionals.

Olanzapine in the treatment of low body weight and obsessive thinking in women with anorexia nervosa: a randomized, double-blind, placebo-controlled trial.

OBJECTIVE: Anorexia nervosa is associated with high mortality, morbidity, and treatment costs. Olanzapine, an atypical antipsychotic, is known to result in weight gain in other patient populations. The objective of this trial was to assess the efficacy of olanzapine in promoting weight gain and in reducing obsessive symptoms among adult women with anorexia nervosa. METHOD: The study was a double-blind, placebo-controlled, 10-week flexible dose trial in which patients with anorexia nervosa (N=34) were randomly assigned to either olanzapine plus day hospital treatment or placebo plus day hospital treatment. RESULTS: Compared with placebo, olanzapine resulted in a greater rate of increase in weight, earlier achievement of target body mass index, and a greater rate of decrease in obsessive symptoms. No differences in adverse effects were observed between the two treatment conditions. CONCLUSIONS: These preliminary results suggest that olanzapine may be safely used in achieving more rapid weight gain and improvement in obsessive symptoms among women with anorexia nervosa. Replication, in the form of a large multicenter trial, is recommended.

"The red zone": temporal risk for unwanted sex among college students.

The "red zone" usually refers to the first few weeks of the first semester at college, when female students are believed to be at greatest risk for experiencing unwanted sex. We tested this notion using data from a survey study of 207 first-and second-year students (121 women, 84 men) at a small, liberal arts university. Results demonstrated only one significant elevation in incidence rates of first- and second-year women's unwanted sexual experiences (sexual touching, attempted and completed anal, oral, and vaginal sex), between the end of the first month and fall break (mid-October) during the second year at school. Previous research and local information about the relevant behaviors of sorority and fraternity members is discussed in light of these findings to provide heuristic material for further empirical testing. Because risk may involve both temporal and situational factors, systematic collection and dissemination of local data are recommended.

Malaria surveillance - United States, 2005.

PROBLEM/CONDITION: Malaria in humans is caused by any of four species of intraerythrocytic protozoa of the genus Plasmodium (i.e., P. falciparum, P. vivax, P. ovale, or P. malariae). These parasites are transmitted by the bite of an infective female Anopheles sp. mosquito. The majority of malaria infections in the United States occur among persons who have traveled to or from areas with ongoing malaria transmission. In the United States, cases can occur through exposure to infected blood products, congenital transmission, or local mosquitoborne transmission. Malaria surveillance 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 2005 and summarizes trends during previous years. DESCRIPTION OF SYSTEM: Malaria cases confirmed by blood film or polymerase chain reaction (PCR) 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 (NMSS). Data from NMSS serve as the basis for this report. RESULTS: CDC received reports of 1,528 cases of malaria, including seven fatal cases, with an onset of symptoms in 2005 among persons in the United States or one of its territories. This number represents an increase of 15.4% from the 1,324 cases reported for 2004. P. falciparum, P. vivax, P. malariae, and P. ovale were identified in 48.6%, 22.1%, 3.5%, and 2.5% of cases, respectively. Twelve patients (0.8% of total) were infected by two or more species. The infecting species was unreported or undetermined in 22.6% of cases. Compared with 2004, the largest increases in cases came from the Americas (23.1%; n = 213) and Asia and the Middle East (18.6%; n = 204). On the basis of estimated volume of travel, the highest estimated case rates of malaria among travelers occurred among those returning from West Africa. Of 870 U.S. civilians who acquired malaria abroad, only 160 (18.4%) reported that they had followed a chemoprophylactic drug regimen recommended by CDC for the area to which they had traveled. Two patients became infected in the United States, both attributed to congenital transmission; both were infected with P. vivax. Seven deaths were attributed to malaria, all caused by infection with P. falciparum. INTERPRETATION: The 15.4% increase in malaria cases in 2005, compared with 2004, resulted primarily from increases in the number of cases reported from Asia and the Middle East and from the Americas. This increase might in part reflect more complete reporting and in part increased travel to malarious areas. No change was noted in proportions of cases from other areas of the world, or in species responsible for the infection. In the majority of reported cases, U.S. civilians who acquired infection abroad had not adhered to a chemoprophylaxis regimen that was appropriate for the country in which they acquired malaria. U.S. civilians who traveled to West Africa had the highest estimated relative case rate. PUBLIC HEALTH ACTIONS: Additional investigations were conducted for the seven fatal cases and two infections acquired in the United States. Persons traveling to a malarious area should take one of the recommended chemoprophylaxis regimens appropriate for the region of travel and use personal protection measures to prevent mosquito bites. Any person who has been to a malarious area and who subsequently has a fever or influenza-like symptoms should seek medical care immediately and report their travel history to the clinician; investigation should include at least one blood-film test for malaria. Malaria infections can be fatal if not diagnosed and treated promptly. Recommendations concerning malaria prevention can be obtained from CDC at http://www.cdc.gov/travel or by calling the Malaria Hotline (telephone 770-488-7788). Recommendations for malaria treatment can be obtained at http://www.cdc.gov/malaria/diagnosis_treatment/treatment.htm or by calling the Malaria Hotline.

Maintaining financial independence in advanced age.

In an attempt to personalize Nobel Prize-winning financial literature, this article seeks to show how individuals can take responsibility for their own finances. For instance, before Markowitz's work, pension funds shied away from risky investments. Then, Markowitz proved that the safest portfolios are those that are diversified over many asset classes, including risky investments. More recently, Kahneman's psychological experiments proved that during uncertainty, people tend to generalize from a small number of representatives to the larger group. He warns us to collect data before drawing conclusions. Using such insights, this article shows how persons in advanced age can develop Investment Policy Statements (IPS) that tailor their financial resources to serve their life goals. This is accomplished safely and successfully by following some guidelines, based on lessons from the financial literature. These guidelines are as follows: (a) update IPS annually, (b) diversify annually by rebalancing, (c) match new liabilities to specific assets, (d) be aware of common errors, such as loss aversion, and (e) measure success by whether one's goals have been met.

Malaria surveillance--United States, 2004.

PROBLEM/CONDITION: Malaria in humans is caused by any of four species of intraerythrocytic protozoa of the genus Plasmodium (i.e., P. falciparum, P. vivax, P. ovale, or P. malariae). These parasites are transmitted by the bite of an infective female Anopheles sp. mosquito. The majority of malaria infections in the United States occur among persons who have traveled to areas with ongoing malaria transmission. In the United States, cases can occur through exposure to infected blood products, congenital transmission, or local mosquitoborne transmission. Malaria surveillance 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 2004 and summarizes trends during previous years. DESCRIPTION OF SYSTEM: Malaria cases confirmed by blood film 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 (NMSS). Data from NMSS serve as the basis for this report. RESULTS: CDC received reports of 1,324 cases of malaria, including four fatal cases, with an onset of symptoms in 2004 among persons in the United States or one of its territories. This number represents an increase of 3.6% from the 1,278 cases reported for 2003. P. falciparum, P. vivax, P. malariae, and P. ovale were identified in 49.6%, 23.8%, 3.6%, and 2.0% of cases, respectively. Seventeen patients (1.3% of total) were infected by two or more species. The infecting species was unreported or undetermined in 262 (19.8%) cases. Compared with 2003, the number of reported malaria cases acquired in the Americas (n = 173) increased 17.7%, whereas the number of cases acquired in Asia (n = 172) and Africa (n = 809) decreased 2.8% and 3.7%, respectively. Of 775 U.S. civilians who acquired malaria abroad, only 160 (20.6%) reported that they had followed a chemoprophylactic drug regimen recommended by CDC for the area to which they had traveled. Four patients became infected in the United States; three cases were attributed to congenital transmission and one to laboratory-related mosquitoborne transmission. Four deaths were attributed to malaria, including two caused by P. falciparum, one by P. vivax, and one by a mixed infection with P. falciparum and P. malariae. INTERPRETATION: The 3.6% increase in malaria cases in 2004, compared with 2003, resulted primarily from an increase in the number of cases acquired in the Americas but was offset by a decrease in the number of cases acquired in Africa and Asia. This limited increase might reflect local changes in disease transmission, increased travel to regions in which malaria is endemic, or fluctuations in reporting to state and local health departments. These changes likely reflect expected variation in annual reporting and should not be interpreted as indicating a longer-term trend. In the majority of reported cases, U.S. civilians who acquired infection abroad had not adhered to a chemoprophylaxis regimen that was appropriate for the country in which they acquired malaria. PUBLIC HEALTH ACTIONS: Additional investigations were conducted for the four fatal cases and four infections acquired in the United States. Persons traveling to a malarious area should take one of the recommended chemoprophylaxis regimens appropriate for the region of travel and use personal protection measures to prevent mosquito bites. Any person who has been to a malarious area and who subsequently has a fever or influenza-like symptoms should seek medical care immediately and report their travel history to the clinician; investigation should include a blood-film test for malaria. Malaria infections can be fatal if not diagnosed and treated promptly. Recommendations concerning malaria prevention can be obtained from CDC at http://www.cdc.gov/travel or by calling the Malaria Hotline at telephone 770-488-7788. Recommendations concerning malaria treatment can be obtained at http://www.cdc.gov/malaria/diagnosis_treatment/treatment.htm or by calling the Malaria Hotline.

Malaria surveillance--United States, 2003.

PROBLEM/CONDITION: Malaria in humans is caused by any of four species of intraerythrocytic protozoa of the genus Plasmodium (i.e., P. falciparum, P. vivax, P. ovale, or P. malariae). These parasites are transmitted by the bite of an infective female Anopheles sp. mosquito. The majority of malaria infections in the United States occur among persons who have traveled to areas with ongoing transmission. In the United States, cases can also occur through exposure to infected blood products, by congenital transmission, or by local mosquitoborne transmission. Malaria surveillance is conducted to identify episodes of local transmission and to guide prevention recommendations for travelers. PERIOD COVERED: This report covers cases with onset of illness in 2003, and summarizes trends over previous years. DESCRIPTION OF SYSTEM: Malaria cases confirmed by blood film 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 (NMSS). Data from NMSS serve as the basis for this report. RESULTS: CDC received reports of 1,278 cases of malaria with an onset of symptoms in 2003, including seven fatal cases, among persons in the United States or one of its territories. This number represents a decrease of 4.4% from the 1,337 cases reported for 2002. P. falciparum, P. vivax, P. malariae, and P. ovale were identified in 53.3%, 22.9%, 3.6%, and 2.6% of cases, respectively. Twelve patients (0.9% of total) were infected by two or more species. The infecting species was unreported or undetermined in 212 (16.6%) cases. Compared with 2002, the number of reported malaria cases acquired in Asia (n = 177) and the Americas (n = 147) increased by 3.5% and 4.3% respectively, whereas the number of cases acquired in Africa (n = 840) decreased by 7.0%. Of 762 U.S. civilians who acquired malaria abroad, 132 (17.3%) reported that they had followed a chemoprophylactic drug regimen recommended by CDC for the area to which they had traveled. Ten patients became infected in the United States, including one probable transfusion-related, one in which epidemiologic investigations failed to identify any apparent mode of acquisition, and eight which were introduced cases as a result of local mosquitoborne transmission. Of the seven deaths attributed to malaria, five were caused by P. falciparum, and a species was not identified in the other two. INTERPRETATION: The 4.4% decrease in malaria cases in 2003, compared with 2002, resulted primarily from a decrease in cases acquired in Africa, but this decrease was offset by an increase in the number of cases acquired in the Americas and Asia. This small decrease probably represents year-to-year variation in malaria cases, but also could have resulted from local changes in disease transmission, decreased travel to malaria-endemic regions, or fluctuation in reporting to state and local health departments. In the majority of reported cases, U.S. civilians who acquired infection abroad were not on an appropriate chemoprophylaxis regimen for the country in which they acquired malaria. PUBLIC HEALTH ACTION: Additional information was obtained concerning the seven fatal cases and the 10 infections acquired in the United States. Persons traveling to a malarious area should take one of the recommended chemoprophylaxis regimens appropriate for the region of travel, and travelers should use personal protection measures to prevent mosquito bites. Any person who has been to a malarious area and who subsequently experiences a fever or influenza-like symptoms should seek medical care immediately and report their travel history to the clinician; investigation should include a blood-film test for malaria. Malaria infections can be fatal if not diagnosed and treated promptly. Recommendations concerning malaria prevention can be obtained from CDC by calling the Malaria Hotline at 770-488-7788 or by accessing CDC's Internet site at http://www.cdc.gov/travel. Recommendations concerning diagnosis of malaria and its treatment can be obtained by calling the Malaria Hotline or accessing CDC's Internet site at http://www.cdc.gov/malaria/diagnosis_treatment/treatment.htm.

Malaria-related deaths among U.S. travelers, 1963-2001.

Nearly 1500 malaria cases occur each year in the United States; approximately 60% are among U.S. travelers. Despite the availability of sophisticated medical care, malaria-related deaths continue to occur. The authors reviewed all 185 fatal cases between 1963 and 2001 that were reported to the National Malaria Surveillance System: 123 (66.5%) occurred among U.S. travelers, and of these, 114 (92.7%) were attributed to Plasmodium falciparum. Failure to take or adhere to recommended chemoprophylaxis, to promptly seek medical care for post-travel illness, and to promptly diagnose and treat suspected malaria all contributed to fatal outcomes. Health care providers need to take a travel history, obtain a blood film for suspected malaria, and use the 24-hour malaria management advice available through the Centers for Disease Control and Prevention (CDC) Malaria Hotline (770-488-7788) or the CDC Malaria Web site (http://www.cdc.gov/Malaria). Hospitals must maintain intravenous quinidine gluconate on formulary because it is the only drug available to treat severe malaria in the United States.