Clinical effectiveness and analytical quality of a national point-of-care testing network for sexually transmitted infections integrated into rural and remote primary care clinics in Australia, 2016-2022: an observational program evaluation.

Background: To address inequitable diagnostic access and improve time-to-treatment for First Nations peoples, molecular point-of-care (POC) testing for chlamydia, gonorrhoea and trichomonas was integrated into 49 primary care clinics across Australia. We conducted an observational evaluation to determine clinical effectiveness and analytical quality of POC testing delivered through this national program. Methods: We evaluated (i) implementation by measuring trends in mean monthly POC testing; ii) clinical effectiveness by comparing proportions of positive patients treated by historical control/intervention period and by test type, and calculated infectious days averted; (iii) analytical quality by calculating result concordance by test type, and proportion of unsuccessful POC tests. Findings: Between 2016 and 2022, 46,153 POC tests were performed; an increasing mean monthly testing trend was observed in the first four years (p < 0.0001). A greater proportion of chlamydia/gonorrhoea positives were treated in intervention compared with historical control periods (≤2 days: 37% vs 22% [RR 1.68; 95% CI 1.12, 2.53]; ≤7 days: 48% vs 30% [RR 1.6; 95% CI 1.10, 2.33]; ≤120 days: 79% vs 54% [RR 1.46; 95% CI 1.10, 1.95]); similarly for trichomonas positives and by test type. POC testing for chlamydia, gonorrhoea and trichomonas averted 4930, 5620 and 7075 infectious days, respectively. Results concordance was high [99.0% (chlamydia), 99.3% (gonorrhoea) and 98.9% (trichomonas)]; unsuccessful POC test proportion was 1.8% for chlamydia/gonorrhoea and 2.1% for trichomonas. Interpretation: Molecular POC testing was successfully integrated into primary care settings as part of a routinely implemented program achieving significant clinical benefits with high analytical quality. In addition to the individual health benefits of earlier treatment, fewer infective days could contribute to reduced transmissions in First Nations communities. Funding: This work was supported by an Australian National Health and Medical Research Council Partnership Grant (APP1092503), the Australian Government Department of Health, Western Australia and Queensland Departments of Health.

External Quality Assessment (EQA) for SARS-CoV-2 RNA Point-of-Care Testing in Primary Healthcare Services: Analytical Performance over Seven EQA Cycles.

In April 2020, the Aboriginal and Torres Strait Islander COVID-19 Point-of-Care (POC) Testing Program was initiated to improve access to rapid molecular-based SARS-CoV-2 detection in First Nations communities. At capacity, the program reached 105 health services across Australia. An external review estimated the program contributed to averting between 23,000 and 122,000 COVID-19 infections within 40 days of the first infection in a remote community, equating to cost savings of between AU$337 million and AU$1.8 billion. Essential to the quality management of this program, a customised External Quality Assessment (EQA) program was developed with the Royal College of Pathologists of Australasia Quality Assurance Programs (RCPAQAP). From July 2020 to May 2022, SARS-CoV-2 EQA participation ranged from 93 to 100%. Overall concordance of valid EQA results was high (98%), with improved performance following the first survey. These results are consistent with those reported by 12 Australian and 4 New Zealand laboratories for three SARS-CoV-2 RNA EQA surveys in March 2020, demonstrating that SARS-CoV-2 RNA POC testing in primary care settings can be performed to an equivalent laboratory analytical standard. More broadly, this study highlights the value of quality management practices in real-world testing environments and the benefits of ongoing EQA program participation.

We have reached single-visit testing, diagnosis, and treatment for hepatitis C infection, now what?

INTRODUCTION: Progress toward hepatitis C virus (HCV) elimination is impeded by low testing and treatment due to the current diagnostic pathway requiring multiple visits leading to loss to follow-up. Point-of-care testing technologies capable of detecting current HCV infection in one hour are a 'game-changer.' These tests enable diagnosis and treatment in a single visit, overcoming the barrier of multiple visits that frequently leads to loss to follow-up. Combining point-of-care HCV antibody and RNA tests should improve cost-effectiveness, patient/provider acceptability, and testing efficiency. However, implementing HCV point-of-care testing programs at scale requires multiple considerations. AREAS COVERED: This commentary explores the need for point-of-care HCV tests, diagnostic strategies to improve HCV testing, key considerations for implementing point-of-care HCV testing programs, and remaining challenges for point-of-care testing (including operator training, quality management, connectivity and reporting systems, regulatory approval processes, and the need for more efficient tests). EXPERT OPINION: It is exciting that single-visit testing, diagnosis, and treatment for HCV infection have been achieved. Innovations afforded through COVID-19 should facilitate the accelerated development of low-cost, rapid, and accurate tests to improve HCV testing. The next challenge will be to address barriers and facilitators for implementing point-of-care testing to deliver them at scale.

Incidence and risk factors for syphilis infection among men who have sex with men: A cohort study from an urban sexual health clinic in Jakarta, Indonesia.

Objective: Syphilis infection remains a significant health issue among marginalised populations in Indonesia, in particular among men who have sex with men (MSM), in whom there are limited studies from Indonesia exploring risk factors associated with STI acquisition.Our study aimed to identify risk factors of syphilis infection among MSM attending large sexual health clinic in Jakarta. Methods: We conducted a retrospective cohort analysis using patient records (MSM aged 18 years or older) period Jan 2018-Dec 2019. We used Cox regression to identify risk factors associated with syphilis incidence. Results: Study population were 2912 MSM tested for syphilis, 473 (16.2%) were diagnosed with syphilis on their first visit; early syphilis (415; 14%) and latent syphilis (58, 2%). Among the cohort of 2439 MSM who tested negative at baseline, 40 MSM were identified with a new positive syphilis result during 2 years follow up. Risk factors remaining significantly associated with syphilis incidence included having STI symptom at 1st visit (aHR, 2.8; 95% CI, 1.38-5.65), and HIV-infection (aHR 4.53; 95% CI 2.24 - 9.17).Syphilis incidence rate was 8.19 (95% CI 6.01-11.16) per 100 PYFU. Conclusions: Syphilis infection at baseline and incidence was high among MSM attending this large clinic in Jakarta. Integrated and accessible syphilis prevention and detection coupled with HIV services are needed, with a special focus on high-risk individuals.

Economic evaluation of point-of-care testing and treatment for sexually transmitted and genital infections in pregnancy in low- and middle-income countries: A systematic review.

BACKGROUND: Sexually transmitted and genital infections in pregnancy are associated with adverse pregnancy and birth outcomes. Point-of-care tests for these infections facilitate testing and treatment in a single antenatal clinic visit and may reduce the risk of adverse outcomes. Successful implementation and scale-up depends on understanding comparative effectiveness of such programmes and their comparative costs and cost effectiveness. This systematic review synthesises and appraises evidence from economic evaluations of point-of-care testing and treatment for sexually transmitted and genital infections among pregnant women in low- and middle-income countries. METHODS: Medline, Embase and Web of Science databases were comprehensively searched using pre-determined criteria. Additional literature was identified by searching Google Scholar and the bibliographies of all included studies. Economic evaluations were eligible if they were set in low- and middle-income countries and assessed antenatal point-of-care testing and treatment for syphilis, chlamydia, gonorrhoea, trichomoniasis, and/or bacterial vaginosis. Studies were analysed using narrative synthesis. Methodological and reporting standards were assessed using two published checklists. RESULTS: Sixteen economic evaluations were included in this review; ten based in Africa, three in Latin and South America and three were cross-continent comparisons. Fifteen studies assessed point-of-care testing and treatment for syphilis, while one evaluated chlamydia. Key drivers of cost and cost-effectiveness included disease prevalence; test, treatment, and staff costs; test sensitivity and specificity; and screening and treatment coverage. All studies met 75% or more of the criteria of the Drummond Checklist and 60% of the Consolidated Health Economics Evaluation Reporting Standards. CONCLUSIONS: Generally, point-of-care testing and treatment was cost-effective compared to no screening, syndromic management, and laboratory-based testing. Future economic evaluations should consider other common infections, and their lifetime impact on mothers and babies. Complementary affordability and equity analyses would strengthen the case for greater investment in antenatal point-of-care testing and treatment for sexually transmitted and genital infections.

Molecular point-of-care testing for chlamydia and gonorrhoea in Indigenous Australians attending remote primary health services (TTANGO): a cluster-randomised, controlled, crossover trial.

BACKGROUND: Timely diagnosis and treatment of sexually transmissible infections will prevent morbidity and onward transmission. We aimed to assess the efficacy of a point-of-care molecular test for Chlamydia trachomatis and Neisseria gonorrhoeae infections at the cluster level to improve infection management among Indigenous Australian communities with high prevalence of sexually transmissible infections. METHODS: In this cluster-randomised crossover study, we recruited primary health services in Western Australia, Far North Queensland, and South Australia that provide care to Indigenous people in regional or remote locations. The services were eligible if they did 150 or more tests for C trachomatis or N gonorrhoeae infection per year among individuals aged 16-29 years, and if C trachomatis or N gonorrhoeae positivity was 10% or higher. Services were randomly assigned (1:1) by use of a random-number generator, stratified by geographical region, to either standard care conditions with routine laboratory-based sexually transmissible infection testing for 12 months followed by 12 months of intervention with molecular point-of-care testing, or the reverse sequence. The primary outcome was the proportion of people (aged 16-29 years) found to have C trachomatis or N gonorrhoeae who had a positive result at retesting 3 weeks to 3 months after treatment, and a secondary outcome was treatment within 7 days, both in those aged 16-29 years and at the cluster level. We did these analyses using data from all participants who had a positive result at testing, by point-of-care of laboratory testing (ie, the intention-to-treat population). The trial is registered with Australian and New Zealand Clinical Trials Registry (ACTRN12613000808741). FINDINGS: Between June 1, 2013, and Feb 29, 2016, 12 health services were enrolled and randomly assigned to standard care followed by intervention (six) and the reverse sequence (six). After randomisation, one health service that was initially assigned to standard care was excluded because it no longer met the inclusion criteria. 455 individuals tested positive for C trachomatis or N gonorrhoeae infection in the intervention group, and 405 tested positive in the standard care group. In the intervention group, 12 (19%) of 63 individuals retested had a positive test result, compared with nine (13%) of 67 with positive retests in the standard care group (relative ratio [RR] 1·42, 95% CI 0·64-3·13; p=0·405), and 347 (76%) were treated within 7 days in the intervention group, compared with 191 (47%) in the standard care group (RR 1·66, 1·41-1·93; p<0·0001). INTERPRETATION: Retesting rates were too low to draw conclusions on the effect of the intervention on repeat infections. Further research will be needed to determine whether point-of-care tests have an effect on reinfection rates, and the sustainability of using this technology. However, our findings show that time to treatment of C trachomatis or N gonorrhoeae infections in primary care clinics in remote areas in Australia with a high prevalence of sexually transmissible infections could be substantially reduced by the use of molecular point-of-care tests. FUNDING: The National Health and Medical Research Council, Australia.

Molecular test for chlamydia and gonorrhoea used at point of care in remote primary healthcare settings: a diagnostic test evaluation.

OBJECTIVES: A new molecular test for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) (GeneXpert CT/NG) has been demonstrated to be as accurate as conventional nucleic acid amplification tests (NAAT), but performance has not been evaluated in routine primary care, performed at the point of care by clinicians. We aimed to examine its diagnostic performance when used by clinicians in remote community health services in Australia with high prevalences of CT and NG infection. The trial was registered with the Australian and New Zealand Clinical Trials Registry (#12613000808741) METHODS: At 12 health services, training was provided to 99 clinicians in the use of the GeneXpert CT/NG assay who tested specimens from all patients undergoing STI screening. Specimens were also sent in parallel for conventional laboratory-based NAATs and the concordance of results was evaluated. RESULTS: Clinicians conducted 2486 tests: CT concordance was 99.4% (95% CI 99.1 to 99.7) with a positive concordance of 98.6% (95% CI 95.9 to 99.7) and negative concordance of 99.5% (95% CI 99.1 to 99.8); NG concordance was 99.9% (95% CI 99.7 to 100.0) with a positive concordance of 100.0% (95% CI 97.5 to 100.0) and negative concordance of 99.9% (95% CI 99.7 to 100.0). CONCLUSIONS: In this first study reporting routine point-of-care use of GeneXpert CT/NG by primary care clinicians, we found excellent concordance with conventional NAATs. The use of the GeneXpert CT/NG at the point of care could potentially transform management and control of these infections in many endemic settings, including low/middle-income countries.

Performance and operational characteristics of point-of-care tests for the diagnosis of urogenital gonococcal infections.

BACKGROUND: In 2012, there was an estimated 78 million new cases of gonorrhoea globally. Untreated infection may lead to reproductive and neonatal morbidity and facilitate HIV transmission. Diagnosis and treatment are a priority for control and prevention, yet use of point-of-care tests (POCTs) for Neisseria gonorrhoeae (NG) is limited. OBJECTIVES: To review the performance and operational characteristics of NG POCTs for diagnosis of urogenital gonorrhoea. METHODS: We compiled and synthesised findings from two separate systematic reviews which included evaluations published until August 2015. RESULTS: Six tests were included: five were immunochromatographic tests (ICTs) or optical immunoassay (OIAs) based on antigen detection; with 5-7 steps and results in 25-40 min, and one (GeneXpert CT/NG) was a 'near-patient test' based on nucleic acid amplification technique (NAAT); with three steps, electricity required, and results in 90 min. When compared with laboratory-based NAATs as the reference tests, sensitivities of ICT and OIA-based POCTs ranged from 12.5% to 70% when cervical/vaginal swabs were tested. Specificities ranged from 89% to 99.8%. The near-patient NAAT had sensitivities of >95% and specificities of >99.8% consistently across all specimen types (urine, cervical and vaginal swabs). CONCLUSIONS: Based on a limited number of evaluations, antigen detection POCTs for NG lacked sufficient sensitivity to be used for screening. A near-patient NAAT has acceptable performance, only involved a few steps, but needs electricity, a temperature-controlled environment and has a 90 min run time. To achieve wider scale up of NG POCTs, we need strong evidence of cost-effectiveness, which should inform guidelines and ultimately increase test development, demand and reduce costs.

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.

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.

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 an interferon-gamma release assay in children with suspected tuberculosis in Papua New Guinea.

There are few data from tuberculosis (TB) endemic settings of the performance and outcome predictors of the QuantiFERON-TB Gold in Tube assay (QFT) in children with suspected TB. A prospective cross-sectional study was conducted in Papua New Guinea children with suspected TB evaluated at Port Moresby General Hospital (Port Moresby, Papua New Guinea). Two hundred sixteen children were enrolled including 106 probable TB, 87 possible TB and 23 without TB. Concordance between QFT and tuberculin skin test results was 86% (P < 0.001, κ = 0.70). QFT was significantly more likely to be positive than tuberculin skin test, overall and within the probable or possible TB categories, with no difference in prevalence of positivity between these 2 categories. The role of QFT in supporting the clinical diagnosis of TB in endemic settings, where resources are limited, remains uncertain especially as cost and technical requirements remain considerable.

Effect of malaria rapid diagnostic tests on the management of uncomplicated malaria with artemether-lumefantrine in Kenya: a cluster randomized trial.

Shortly after Kenya introduced artemether-lumefantrine (AL) for first-line treatment of uncomplicated malaria, we conducted a pre-post cluster randomized controlled trial to assess the effect of providing malaria rapid diagnostic tests (RDTs) on recommended treatment (patients with malaria prescribed AL) and overtreatment (patients without malaria prescribed AL) in outpatients >/= 5 years old. Sixty health facilities were randomized to receive either RDTs plus training, guidelines, and supervision (TGS) or TGS alone. Of 1,540 patients included in the analysis, 7% had uncomplicated malaria. The provision of RDTs coupled with TGS emphasizing AL use only after laboratory confirmation of malaria reduced recommended treatment by 63%-points (P = 0.04), because diagnostic test use did not change (-2%-points), but health workers significantly reduced presumptive treatment with AL for patients with a clinical diagnosis of malaria who did not undergo testing (-36%-points; P = 0.03). Health workers generally adhered to RDT results when prescribing AL: 88% of RDT-positive and 9% of RDT-negative patients were treated with AL, respectively. Overtreatment was low in both arms and was not significantly reduced by the provision of RDTs (-12%-points, P = 0.30). RDTs could potentially improve malaria case management, but we urgently need to develop more effective strategies for implementing guidelines before large scale implementation.

Performance of malaria rapid diagnostic tests as part of routine malaria case management in Kenya.

Data on malaria rapid diagnostic test (RDT) performance under routine program conditions are limited. We assessed the attributes of RDTs performed by study and health facility (HF) staffs as part of routine malaria case management of patients > or = 5 years of age in Kenya. Expert microscopy was used as our gold standard. A total of 1,827 patients were enrolled; 191 (11.6%) were parasitemic by expert microscopy. Sensitivity and specificity of RDTs performed by study staff were 86.6% (95% confidence interval [CI]: 79.8-93.5%) and 95.4% (95% CI: 93.9-96.9%), respectively. Among tests performed by HF staff, RDTs were 91.7% (95% CI: 80.8-100.0%) sensitive and 96.7% (95% CI: 92.8-100.0%) specific, whereas microscopy was 52.5% (95% CI: 33.2-71.9%) sensitive and 77.0% (95% CI: 67.9-86.2%) specific. Our findings suggest that RDTs perform better than microscopy under routine conditions. Further efforts are needed to maintain this high RDT performance over time.

Pre-departure and post-arrival management of P. falciparum malaria in refugees relocating from sub-Saharan Africa to the United States.

Plasmodium infection, often sub-clinical, is common in migrating sub-Saharan refugee populations. Refugees who subsequently develop clinical malaria suffer illness and exact a cost on state and local health care facilities. Untreated infection is also of public health concern because of the potential for local transmission. In response to increasing numbers of refugees originating in sub-Saharan Africa guidelines for the management of malaria in refugees migrating to the United States have been broadened and updated. The guidelines are based on available evidence-based literature and recent public health experience. These guidelines were critically reviewed, assessed, and approved by multiple National and State entities as well as outside experts. These consensus guidelines recommend that sub-Saharan African refugees relocating to the United States receive presumptive treatment of P. falciparum malaria before departure or during the domestic refugee medical screening after arrival. Presumptive therapy is not currently recommended for either non-falciparum malaria or for refugees relocating from areas outside sub-Saharan Africa.

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.

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. METHOD: Follow-back study of 2466 client visits selected from all 10 drug stores operating in the town of Ikwiriri between May 30 and August 31 2004. Of these, 521 (21.2%) were made by or on behalf of persons ill with fever or malaria. Two hundred and ninety three were eligible as residents of the surrounding nine villages and all agreed to participate in the study. Each patient was evaluated by a clinical officer and provided a blood sample for malaria on the day of the shop visit, either at the shop or at home. RESULTS: Only 50 (17.1%) visits by or on behalf of febrile patients resulted in the purchase of an antimalarial drug, while an antipyretic medication was obtained at 226 visits (77.1%). Clinicians diagnosed malaria in 63.8% of patients. Malaria parasites were identified in blood film samples from 24.2% (95% CI: 19.6, 29.5). This is double the parasite prevalence rate of 10.7% (95% CI: 8.6, 13.1) obtained from a household survey of 1004 healthy individuals selected from these villages at the same time. It is not significantly lower than the prevalence observed among 880 clients presenting with fever at health facilities in the district: 29.7% (95% CI: 23.0, 37.3). The prevalence of malaria parasitemia among children younger than 5 years whose families sought fever treatment from drug stores (42.1%; 95% CI: 31.4, 53.5) was equal to that of children presenting with fever at health facilities (42.5%; 95% CI: 25.0, 62.2). CONCLUSIONS: Currently, drug store clients do not obtain malaria-specific treatment in the majority of cases where it might be warranted. Parasitological findings indicate that drug store clients, especially children, are as likely to be infected with malaria as patients seeking care for similar illnesses at health facilities. Drug stores may be attractive partners for policy makers eager to engage the private retail sector in expanding coverage of malaria treatment.

Rapid malaria screening and targeted treatment of United States-bound Montagnard refugees from Cambodia in 2002.

In 2002, a group of Montagnard refugees living in Cambodia was accepted for resettlement in the United States. Pre-departure malaria screening and targeted treatment was conducted to prevent morbidity, and minimize the potential for local malaria transmission post-arrival. We screened 902 of 906 refugees using rapid diagnostic tests (RDTs), microscopy, and polymerase chain reaction (PCR) analysis. Twelve (1.3%) RDT results were positive and 28 (3.1%) were indeterminate. Microscopy confirmed Plasmodium species in two of the positive RDT and one of the indeterminate results. Among a random 10% sample of negative RDT results (n = 86), none were positive by microscopy. The PCR confirmed the two microscopically (and RDT) positive specimens. The PCR result was negative for all other specimens tested. Eighteen (2.0%) refugees were treated with antimalarials. The RDTs were useful in this setting, facilitating timely, sensitive diagnosis and targeted treatment. Evaluations to determine the most appropriate interventions in other refugee settings should include cost-effectiveness analyses of alternative strategies.

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.