Louise M. Causer

Malaria surveillance -- United States, 2009

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 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 (e.g., temporal, geographic, and demographic), guide prevention and treatment recommendations for travelers and patients, and facilitate transmission control measures if locally acquired cases are identified. Period Covered This report summarizes confirmed malaria cases in persons with onset of illness in 2015 and summarizes trends in previous years. Description of System 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. Results 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 (Africa, West Africa, Asia, Central America, the Caribbean, South America, Oceania, and the Middle East), the only region with significantly fewer imported cases in 2015 compared with 2014 was West Africa (781 versus 969). 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 (although certain loci were untestable for some samples); 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 (species, travel history, and resident status). Interpretation 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. Public Health Actions 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 P. falciparum, even in high transmission areas. Detailed recommendations for preventing malaria are available to the general public at the CDC website (https://www.cdc.gov/malaria/travelers/drugs.html). 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 (https://www.cdc.gov/malaria/diagnosis_treatment) and from the Malaria Hotline (770-488-7788 or toll-free at 855-856-4713). Persons submitting malaria case reports (care providers, laboratories, and state and local public health officials) 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 (https://www.cdc.gov/malaria/features/ars.html) 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.

Evaluation of Three Commercial Assays for Detection of Giardia and Cryptosporidium Organisms in Fecal Specimens

ABSTRACT There is an increasing demand for diagnostic testing for Giardia intestinalis (G. lamblia) and Cryptosporidium parvum, with a priority being placed on obtaining diagnostic results in an efficient and timely manner. Several commercial companies have developed rapid diagnostic tests that are simple to perform and can be completed in less time than traditional methods for detecting Giardia and Cryptosporidium. We compared one of these rapid tests, the ImmunoCard STAT! (Meridian Bioscience, Inc.) lateral-flow immunoassay, with the MERIFLUOR direct fluorescent-antibody (DFA) test, the ProSpecT EZ microplate assay for Giardia and the ProSpecT microplate assay for Cryptosporidium, and modified Kinyouns acid-fast stained smears for the detection of Cryptosporidium using 246 specimens. The MERIFLUOR DFA (Meridian Bioscience, Inc.) test detected the largest number of cases (32 Giardia and 37 Cryptosporidium) infections and was used to calculate the sensitivity and specificity of the other tests. For Giardia, the sensitivities of the ImmunoCard STAT! and the ProSpecT Giardia EZ microplate assay (Alexon-Trend, Inc.) were 81 and 91%, respectively. For detection of Cryptosporidium, the sensitivities of the ImmunoCard STAT!, the ProSpecT Cryptosporidium microplate assay (Alexon-Trend, Inc.), and modified Kinyouns acid-fast stained smears were 68, 70, and 78%, respectively. Test specificities were equal to or greater than 99%. Specimens with very small numbers of organisms were not detected by the ImmunoCard STAT!, the ProSpecT microplate assay or modified Kinyouns acid-fast stained smears.

Prevalence of malaria parasitemia among clients seeking treatment for fever or malaria at drug stores in rural Tanzania 2004

Objective  To determine the prevalence of malaria parasitemia and other common illnesses among drug store clients in one rural community, with a view to the potential role of specialist drug stores in expanding coverage of effective malaria treatment to households in highly endemic areas.

An outbreak of Cryptosporidium hominis infection at an Illinois recreational waterpark.

Cryptosporidium has become increasingly recognized as a pathogen responsible for outbreaks of diarrhoeal illness in both immunocompetent and immunocompromised persons. In August 2001, an Illinois hospital reported a cryptosporidiosis cluster potentially linked to a local waterpark. There were 358 case-patients identified. We conducted community-based and waterpark-based case-control studies to examine potential sources of the outbreak. We collected stool specimens from ill persons and pool water samples for microscopy and molecular analysis. Laboratory-confirmed case-patients (n=77) were more likely to have attended the waterpark [odds ratio (OR) 16.0, 95% confidence interval (CI) 3.8-66.8], had pool water in the mouth (OR 6.0, 95% CI 1.3-26.8), and swallowed pool water (OR 4.5, 95% CI 1.5-13.3) than age-matched controls. Cryptosporidium was found in stool specimens and pool water samples. The chlorine resistance of oocysts, frequent swimming exposures, high bather densities, heavy usage by diaper-aged children, and increased recognition and reporting of outbreaks are likely to have contributed to the increasing trend in number of swimming pool-associated outbreaks of cryptosporidiosis. Recommendations for disease prevention include alteration of pool design to separate toddler pool filtration systems from other pools. Implementation of education programmes could reduce the risk of faecal contamination and disease transmission.

Point-of-care tests for the diagnosis of Neisseria gonorrhoeae infection: a systematic review of operational and performance characteristics

Objectives Systematic review of the performance and operational characteristics of point-of-care (POC) tests for the diagnosis of Neisseria gonorrhoeae. Methods We searched PubMed and Embase until August 2010 using variations of the terms: ‘rapid test’, ‘Neisseria gonorrhoeae’ and ‘evaluation’. Results We identified 100 papers, 14 studies were included; nine evaluated leucocyte esterase (LE) dipsticks and three immunochromatographic strips, and two clinical audits of microscopy were identified. Of the field evaluations the gold standard was nucleic acid amplification technology in six studies and bacterial culture in the other six. In four studies, 50% or more of the patients were symptomatic. The median sensitivity of LE dipsticks was 71% (range 23–85%), median specificity was 70% (33–99%), median positive predictive value (PPV) was 19% (5–40%) and median negative predictive value (NPV) was 95% (56–99%). One LE study found a sensitivity of 23% overall, increasing to 75% in symptomatic women. LE dipsticks mostly involved three steps and took under 2 min. The median sensitivity of immunochromatographic tests (ICT) was 70% (60–94%), median specificity was 96% (89–97%), median PPV was 56% (55–97%) and median NPV was 93% (92–99%). Immunochromatic strips involved five to seven steps and took 15–30 min. Specificity of microscopy ranged from 38% to 89%. Conclusions ICT and LE tests had similar sensitivities, but sensitivity results may be overestimated as largely symptomatic patients were included in some studies. ICT had a higher specificity in women than LE tests. The findings highlight the need for improved POC tests for diagnosis of N gonorrhoeae and more standardised evaluations.

A Laboratory-Based Evaluation of Four Rapid Point-of-Care Tests for Syphilis

Background Syphilis point-of-care tests may reduce morbidity and ongoing transmission by increasing the proportion of people rapidly treated. Syphilis stage and co-infection with HIV may influence test performance. We evaluated four commercially available syphilis point-of-care devices in a head-to-head comparison using sera from laboratories in Australia. Methods Point-of-care tests were evaluated using sera stored at Sydney and Melbourne laboratories. Sensitivity and specificity were calculated by standard methods, comparing point-of-care results to treponemal immunoassay (IA) reference test results. Additional analyses by clinical syphilis stage, HIV status, and non-treponemal antibody titre were performed. Non-overlapping 95% confidence intervals (CI) were considered statistically significant differences in estimates. Results In total 1203 specimens were tested (736 IA-reactive, 467 IA-nonreactive). Point-of-care test sensitivities were: Determine 97.3%(95%CI:95.8–98.3), Onsite 92.5%(90.3–94.3), DPP 89.8%(87.3–91.9) and Bioline 87.8%(85.1–90.0). Specificities were: Determine 96.4%(94.1–97.8), Onsite 92.5%(90.3–94.3), DPP 98.3%(96.5–99.2), and Bioline 98.5%(96.8–99.3). Sensitivity of the Determine test was 100% for primary and 100% for secondary syphilis. The three other tests had reduced sensitivity among primary (80.4–90.2%) compared to secondary syphilis (94.3–98.6%). No significant differences in sensitivity were observed by HIV status. Test sensitivities were significantly higher among high-RPR titre (RPR≥8) (range: 94.6–99.5%) than RPR non-reactive infections (range: 76.3–92.9%). Conclusions The Determine test had the highest sensitivity overall. All tests were most sensitive among high-RPR titre infections. Point-of-care tests have a role in syphilis control programs however in developed countries with established laboratory infrastructures, the lower sensitivities of some tests observed in primary syphilis suggest these would need to be supplemented with additional tests among populations where syphilis incidence is high to avoid missing early syphilis cases.

Evaluation of reported malaria chemoprophylactic failure among travelers in a US university exchange program, 2002.

BACKGROUND Travelers to malarious areas are at risk of acquiring malaria; however, with chemoprophylaxis and prompt, effective therapy, serious complications of infection are generally preventable. In June 2002, we investigated a report of a cluster of malaria cases among US university staff and students who visited Ghana and were reportedly adherent to appropriate malaria chemoprophylaxis. METHODS We administered a questionnaire to all participants and collected blood specimens for malaria serological examinations from those reporting malaria infection diagnosed by blood smear in Ghana. RESULTS Of the 33 participants, 25 completed the questionnaire. Twenty-four took a Centers for Disease Control and Prevention-recommended chemoprophylactic drug; 14 (56%) of 25 reported complete adherence to therapy. Twenty (80%) of 25 subjects reported symptoms consistent with possible malaria. Six of these persons reported a microscopic diagnosis of malaria and were treated in Ghana. Serological examination for malaria was performed using blood samples obtained from 5 of these participants; the results for all were negative, suggesting that incorrect diagnoses of malaria were made. CONCLUSIONS Misdiagnosis of malaria made while a person is abroad may not only lead to erroneous reports of drug resistance, but it could also result in unnecessary administration of antimalarial treatment. Health care providers and public health authorities must critically evaluate reports of chemoprophylactic failures and disseminate accurate information to travelers.

A field evaluation of a new molecular-based point-of-care test for chlamydia and gonorrhoea in remote Aboriginal health services in Australia

UNLABELLED Background Point-of-care (POC) tests could be important public health tools in settings with treatment delays and high rates of sexually transmissible infections (STIs). Use is limited due to suboptimal performance. The performance and ease-of-use of a new molecular-based POC test for simultaneous detection of Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) was assessed, alongside two single-organism immunochromatographic tests (ICT). METHODS The evaluation occurred between May 2012 and March 2013 during community STI screens in two remote Aboriginal health services. Urine was tested with the GeneXpert(®)CT/NG and if sufficient volume, also with Diaquick CT and Gonorrhoea Card. The gold standard comparison was laboratory nucleic acid amplification testing (NAAT). Operational characteristics were also assessed. RESULTS Among 198 samples, GeneXpert CT sensitivity and specificity was 100% [95% confidence intervals (CI): 75.9-100] and 99.5% (95% CI: 96.5-100), and NG was 100% (95% CI: 96.5-100) and 100% (95% CI: 97.5-100), respectively. Among a sample subset, Diaquick CT (n=104) sensitivity and specificity was 27.3% (95% CI: 7.3-60.7) and 66.7% (95% CI: 12.5-98.2), and Gonorrhoea Card (n=29), was 66.7% (95% CI: 12.5-98.2) and 76.9% (95% CI: 56.0-90.2), respectively. GeneXpert required 1mL of urine, four steps, 1min specimen preparation and 90min to result. ICTs required 15mL of urine, eight steps, 18min preparation and 10-15min to result. CONCLUSION The accuracy and operational benefits of GeneXpert CT/NG make it very suitable in these settings where delays to treatment are encountered.

An Evaluation of a Novel Dual Treponemal/Nontreponemal Point-of-Care Test for Syphilis as a Tool to Distinguish Active From Past Treated Infection

BACKGROUND Most syphilis point-of-care (POC) tests detect treponemal antibodies, which persist after successful treatment. Subsequent POC tests are positive, despite no active infection, and can lead to unnecessary treatment. We evaluated a new POC test, incorporating a nontreponemal component, to distinguish active from past infection. METHODS Sera stored at 2 Australian laboratories were tested with DPP Screen and Confirm Assay. Treponemal and nontreponemal test lines were compared to corresponding conventional treponemal and nontreponemal reference test results: immunoassays and rapid plasma reagin (RPR), respectively, with RPR quantification by endpoint titration. POC test outcome concordance with conventional test results was assessed according to serological and clinical categories. RESULTS Among 1005 serum samples tested, DPP treponemal line sensitivity was 89.8% (95% confidence interval [CI], 87.3%-91.9%) and specificity was 99.3% (95% CI, 97.0%-99.9%). DPP nontreponemal line sensitivity was 94.2% (95% CI, 91.8%-96.0%) and specificity was 62.2% (95% CI, 57.5%-66.6%). DPP test outcome (pair of test lines) was concordant with both reference test results for 94.3% of 404 high-titer infections, 90.1% of 121 low-titer infections, 27.5% of 211 past/treated infections, and 78.1% of 242 infections classified as not syphilis. Among 211 past/treated infections, 49.8% were incorrectly identified as active infection and a further 22.8% as not syphilis. CONCLUSIONS DPP test use would result in identification of >93% of active syphilis infections, whereas just over half of past infections would be diagnosed as past or not syphilis, avoiding unnecessary treatment compared with other POC tests. This may be at the expense of missing some active infections; thus, its potential benefits will depend on the prevalence of past vs active infection in a population.

Metaanalysis of the Performance of a Combined Treponemal and Nontreponemal Rapid Diagnostic Test for Syphilis and Yaws

A combined treponemal and nontreponemal rapid diagnostic test was found to have good sensitivity and specificity for both syphilis and yaws. The performance of both the treponemal and nontreponemal test components was strongly associated with the rapid plasma reagin titer.