During 2023, 10 cases of locally acquired mosquito-transmitted (autochthonous) malaria were reported to CDC from four U.S. states after a 20-year period with no autochthonous cases. These cases highlight that although the United States eliminated malaria transmission in the early 1950s, the country remains susceptible to malaria reintroduction. This report provides operational guidance to local, state, tribal, territorial, and Federalpublic health responders on public health investigation and response to a suspected autochthonous malaria case in the United States. The guidance in this report updates the 2006 guidance (CDC. Locally acquired mosquito-transmitted malaria: a guide for investigations in the United States. Atlanta, GA: US Department of Health and Human Services, CDC; 2006) and is based on CDC subject-matter expertise, outbreak response experience from 2023, and targeted literature review. Investigations of suspected autochthonous malaria cases often raise public concern and can require substantial public health resources. Public health investigations of these cases should include epidemiologic, entomologic, and laboratory components and frequently require coordination among local, state, and Federal jurisdictions. This report provides an outline ofthe essential actions for such investigations conducted by describing the components ofthe investigation andproviding resources and tools to assist public health personnel at the local, state, and Federal level.

A 65-year-old resident of Westchester County, New York was diagnosed with Plasmodium falciparum infection on 2 October 2023. The case had no recent history of international travel to a malaria-endemic area. An extensive epidemiological investigation was initiated to identify the most likely source of the infection and assess the risk of continuing local transmission. Interviews with the case identified multiple potential exposure routes including domestic travel within the United States, hospitalizations overlapping that of individuals diagnosed with travel-associated malaria, residential proximity to imported malaria cases, and outdoor activity overlapping the potential dusk/dawn biting activity of Anopheles mosquitoes. The epidemiologic investigation included syndromic surveillance, healthcare facility investigations, and genetic analysis of specimens collected from the case patient and other malarious patients with epidemiologic links. Results of the genetic analysis and epidemiologic investigation implicated blood-borne transmission in a healthcare setting from a concurrently hospitalized traveler with confirmed malaria. The mechanism remains unknown, although it was likely due to a lapse in infection control. No mosquito-transmitted cases were identified in New York. No additional induced cases from a blood-borne/healthcare-associated exposure were identified. The identification and prompt investigation of potentially locally acquired malaria infections can aid in preventing additional cases by identifying the source and enacting appropriate control measures if necessary.

Importance:In 2023, the US reported 10 locally acquired mosquito-transmitted malaria cases of 4 genetic lineages in 4 states, the first such outbreaks detected in 20 years and the largest in 35 years. Objective:To present the investigations, interventions, and challenges in the public health response to the malaria outbreaks and provide recommendations for future outbreaks. Design, Setting, and Participants:This qualitative study was an interdisciplinary public health response to the locally acquired malaria outbreaks in May to December 2023 and included case investigations, enhanced case finding, polymerase chain reaction analysis of captured Anopheles spp mosquitoes for Plasmodium spp parasites, and novel targeted amplicon sequencing of Plasmodium spp in patient blood samples. Public health interventions included incident command activation, clinician outreach, community awareness, and vector control. Patient data were acquired through public health surveillance as part of National Notifiable Disease Surveillance. Exposure:Plasmodium vivax-infected and Plasmodium falciparum-infected Anopheles spp mosquitoes. Main Outcomes and Measures:Confirmed malaria infection via blood film microscopy and polymerase chain reaction, presence of Plasmodium spp in Anopheles spp mosquitoes, and genetic markers associated with an endemic region of origin and parasite strain relatedness via targeted amplicon sequencing. Results:The study included 10 patients (mean [SD] age of 39.5 [15.0] years; 7 male [70%]) from Florida, Texas, Maryland, and Arkansas with locally acquired mosquito-transmitted malaria and 783 Anopheles spp mosquitoes across 4 states. No patient had a recent history of international travel or blood-borne exposures. Outbreak cases had epidemiologic links within but not across state lines. P vivax was detected in 3 Anopheles crucians in Florida. Sequencing data showed that all Florida P vivax cases shared the same Plasmodium strain. The Texas and Arkansas P vivax cases were genetically distinct from each other and from Florida's cases. All 9 P vivax strains had genetic signatures that were consistent with Central and South American origin. Maryland's P falciparum parasites were consistent with African origin. The outbreaks were contained. Conclusions and Relevance:In this qualitative study of locally transmitted malaria, outbreaks remained contained to individual counties, with Florida's P vivax cases linked to a single strain distinct from those in other states. Sustained Plasmodium spp transmission is unlikely in the US, though increases in global travel and migration, population, temperatures, and persistence of Anopheles spp vectors may increase risk for locally acquired malaria. Clinicians should prescribe chemoprophylaxis for patients traveling to endemic regions, ensure timely diagnosis and treatment, and facilitate public health reporting. Researching US Anopheles spp ecology and control methods while accelerating efforts to reduce malaria globally could mitigate future risk.

Most monitoring and evaluation tools for measuring malaria burden, intervention coverage, and impact of interventions use periodic nationally representative cross-sectional household surveys. These provide advantages in terms of selecting a large, unbiased, population-based sample; however, they are infrequently conducted, are resource-intensive, and do not provide longitudinal data with sufficient granularity. Given the heterogeneity of malaria transmission within most endemic countries, systems with the capacity to provide more granular and frequent data would be more actionable by national malaria control programs and local implementing partners. There is increasing interest in using routine health facility data, usually from outpatient department visits, for monitoring malaria burden. Data from pregnant women attending antenatal care (ANC) could minimize bias related to fever care-seeking among outpa-tient department visits and provide more granular parasite prevalence data. Most pregnant women attend ANC at least once and are thus highly representative of the overall pregnant population. A growing body of evidence suggests that malaria parasitemia in pregnant women is correlated with parasitemia in children aged , 5 years in moderate to high transmission areas, allowing for monitoring parasitemia in real time. Additional data are needed to assess whether preg-nant women are sufficiently representative of the overall population to yield valid malaria prevalence and intervention cov-erage estimates. Although use of routinely collected ANC data faces many of the same challenges experienced by other routinely collected health facility data, the opportunity to improve parasite prevalence monitoring and the associated health benefits to mothers and infants of early detection of parasitemia make these efforts valuable.

BACKGROUND:The Malaria Frontline Project (MFP) supported the National Malaria Elimination Program for effective program implementation in the high malaria-burden states of Kano and Zamfara adapting the National Stop Transmission of Polio (NSTOP) program elimination strategies.PROJECT IMPLEMENTATION:The MFP was implemented in 34 LGAs in the two states (20 out of 44 in Kano and all 14 in Zamfara). MFP developed training materials and job aids tailored to expected service delivery for primary and district health facilities and strengthened supportive supervision. Pre- and post-implementation assessments of intervention impacts were conducted in both states.RESULTS:A total of 158 (Kano:83; Zamfara:75) and 180 (Kano:100; Zamfara:80) healthcare workers (HCWs), were interviewed for pre-and post-implementation assessments, respectively. The proportions of HCWs with correct knowledge on diagnostic criteria were Kano: 97.5% to 92.0% and Zamfara: 94.7% to 98.8%; and knowledge of recommended first line treatment of uncomplicated malaria were Kano: 68.7% to 76.0% and Zamfara: 69.3% to 65.0%. The proportion of HCWs who adhered to national guidelines for malaria diagnosis and treatment increased in both states (Kano: 36.1% to 73.0%; Zamfara: 39.2% to 67.5%) and HCW knowledge to confirm malaria diagnosis slightly decreased in Kano State but increased in Zamfara State (Kano: 97.5% to 92.0%; Zamfara: 94.8% to 98.8%). HCWs knowledge of correct IPTp drug increased in both states (Kano: 81.9% to 94.0%; Zamfara: 85.3% to 97.5%).CONCLUSION:MFP was successfully implemented using tailored training materials, job aids, supportive supervision, and data use. The project strategy can likely be adapted to improve the effectiveness of malaria program implementation in other Nigerian states, and other malaria endemic countries.

The SARS-CoV-2 Delta variant, first identified in Octo-ber 2020, quickly became the dominant variant world-wide. We used publicly available data to explore the relationship between illness and death (peak case rates, death rates, case-fatality rates) and selected predictors (percentage vaccinated, percentage of the population >65 years, population density, testing vol-ume, index of mitigation policies) in 45 high-income countries during the Delta wave using rank-order correlation and ordinal regression. During the Delta-dominant period, most countries reported higher peak case rates (57%) and lower peak case-fatality rates (98%). Higher vaccination coverage was protective against peak case rates (odds ratio 0.95, 95% CI 0.91-0.99) and against peak death rates (odds ratio 0.96, 95% CI 0.91-0.99). Vaccination coverage was vital to preventing infection and death from COVID-19 during the Delta wave. As new variants emerge, pub-lic health authorities should encourage the uptake of COVID-19 vaccination and boosters.

The U.S. Centers for Disease Control and Prevention in collaboration with the National Malaria Elimination Program and the African Field Epidemiology Network established the Malaria Frontline Project to provide innovative approaches to improve the malaria program implementation in Kano and Zamfara States, Nigeria. Innovative approaches such as malaria bulletin, malaria monitoring wall chart, conduct of ward level data validation meetings and malaria dashboard have helped improve the use of data for decision making at all levels. Innovative approaches deployed during the project implementation facilitated data analysis and a better understanding of malaria program performance and data utilization for decision making at all levels. These innovative approaches may improve malaria control program performance in Nigeria and other resource limited countries.

INTRODUCTION:Infant and neonatal mortality estimates are typically derived from retrospective birth histories collected through surveys in countries with unreliable civil registration and vital statistics systems. Yet such data are subject to biases, including under-reporting of deaths and age misreporting, which impact mortality estimates. Prospective population-based cohort studies are an underutilized data source for mortality estimation that may offer strengths that avoid biases.METHODS:We conducted a secondary analysis of data from the Child Health Epidemiology Reference Group, including 11 population-based pregnancy or birth cohort studies, to evaluate the appropriateness of vital event data for mortality estimation. Analyses were descriptive, summarizing study designs, populations, protocols, and internal checks to assess their impact on data quality. We calculated infant and neonatal morality rates and compared patterns with Demographic and Health Survey (DHS) data.RESULTS:Studies yielded 71,760 pregnant women and 85,095 live births. Specific field protocols, especially pregnancy enrollment, limited exclusion criteria, and frequent follow-up visits after delivery, led to higher birth outcome ascertainment and fewer missing deaths. Most studies had low follow-up loss in pregnancy and the first month with little evidence of date heaping. Among studies in Asia and Latin America, neonatal mortality rates (NMR) were similar to DHS, while several studies in Sub-Saharan Africa had lower NMRs than DHS. Infant mortality varied by study and region between sources.CONCLUSIONS:Prospective, population-based cohort studies following rigorous protocols can yield high-quality vital event data to improve characterization of detailed mortality patterns of infants in low- and middle-income countries, especially in the early neonatal period where mortality risk is highest and changes rapidly.

Malaria and malnutrition remain primary causes of morbidity and mortality among children younger than 5 years in Africa. Studies investigating the association between malnutrition and subsequent malaria outcomes are inconsistent. We studied the effects of malnutrition on incidence and prevalence of malaria parasitemia in data from a cohort studied in the 1990s. Data came from the Asembo Bay cohort study, which collected malaria and health information on children from 1992 to 1996 in western Kenya. Infants were enrolled at birth and followed up until loss to follow-up, death, end of study, or 5 years old. Anthropometric measures and blood specimens were obtained monthly. Nutritional exposures included categorized Z-scores for height-for-age, weight-for-age, and weight-for-height. Febrile parasitemia and afebrile parasitemia were assessed with thick and thin blood films. Multiply imputed and weighted multinomial generalized estimating equation models estimated odds ratios (OR) for the association between exposures and outcomes. The sample included 1,182 children aged 0-30 months who contributed 18,028 follow-up visits. There was no significant association between malnutrition and either incident febrile parasitemia or prevalent febrile parasitemia. Prevalence ORs for afebrile parasitemia increased from 1.07 (95% CI: 0.89, 1.29) to 1.35 (1.03, 1.76) as stunting severity increased from mild to severe, and from 1.16 (1.02, 1.33) to 1.35 (1.09, 1.66) as underweight increased from mild to moderate. Stunting and underweight did not show a significant association with subsequent febrile parasitemia infections, but they did show a modest association with subsequent afebrile parasitemia. Consideration should be given to testing malnourished children for malaria, even if they present without fever.

The COVID-19 pandemic, caused by SARS-CoV-2, have surpassed 5 million cases globally. Current models suggest that low- and middle-income countries (LMICs) will have a similar incidence but substantially lower mortality rate than high-income countries. However, malaria and neglected tropical diseases (NTDs) are prevalent in LMICs, and coinfections are likely. Both malaria and parasitic NTDs can alter immunologic responses to other infectious agents. Malaria can induce a cytokine storm and pro-coagulant state similar to that seen in severe COVID-19. Consequently, coinfections with malaria parasites and SARS-CoV-2 could result in substantially worse outcomes than mono-infections with either pathogen, and could shift the age pattern of severe COVID-19 to younger age-groups. Enhancing surveillance platforms could provide signals that indicate whether malaria, NTDs, and COVID-19 are syndemics (synergistic epidemics). Based on the prevalence of malaria and NTDs in specific localities, efforts to characterize COVID-19 in LMICs could be expanded by adding testing for malaria and NTDs. Such additional testing would allow the determination of the rates of coinfection and comparison of severity of outcomes by infection status, greatly improving the understanding of the epidemiology of COVID-19 in LMICs and potentially helping to mitigate its impact.

Background: Impact evaluations allow countries to assess public health gains achieved through malaria investments. This study uses routine health management information system (HMIS) data from Zanzibar to describe changes in confirmed malaria incidence and impact of case management and vector control interventions during 2000-2015. Methods: HMIS data from 129 (82%) public outpatient facilities were analyzed using interrupted time series models to estimate the impact of artemisinin-based combination therapy (ACT), indoor residual spray, and long-lasting insecticidal nets. Evaluation periods were defined as pre-intervention (January 2000 to August 2003), ACT-only (September 2003 to December 2005) and ACT plus vector control (2006-2015). Findings: After accounting for climate, seasonality, diagnostic testing rates, and outpatient attendance, average monthly incidence of confirmed malaria showed no trend over the pre-intervention period 2000-2003 (incidence rate ratio (IRR) 0.998, 95% CI 0.995-1.000). During the ACT-only period (2003-2005), the averagemonthly malaria incidence rate declined compared to the pre-intervention period, showing an overall declining trend during the ACT-only period (IRR 0.984, 95% CI 0.978-0.990). There was no intercept change at the start of the ACT-only period (IRR 1.081, 95% CI 0.968-1.208), but a drop in intercept was identified at the start of the ACT plus vector control period (IRR 0.683, 95% CI 0.597-0.780). During the ACT plus vector control period (2006-2015), the rate of decline in averagemonthly malaria incidence slowed compared to the ACT-only period, but the incidence rate continued to show an overall slight declining trend during 2006-2015 (IRR 0.993, 95% CI 0.992-0.994). Interpretation: This study presents a rigorous approach to the use of HMIS data in evaluating the impact of malaria control interventions. Evidence is presented for a rapid decline in malaria incidence during the period of ACT roll out compared to pre-intervention, with a rapid drop in malaria incidence following introduction of vector control and a slower declining incidence trend thereafter. (C) 2019 Published by Elsevier Ltd.

Lingering post-treatment parasite antigen in blood complicates malaria diagnosis through antigen detection. Characterization of antigen clearance dynamics is important for interpretation of positive antigen detection tests. We used a bead-based serological assay to measure lactate dehydrogenase (LDH), aldolase (Aldo), and histidine-rich protein 2 (HRP2) levels in 196 children with Plasmodium falciparum malaria treated with effective antimalarials and followed for 28 to 42 days as part of therapeutic efficacy studies in Angola. Compared to pre-treatment levels, antigen concentrations two days after treatment declined by 99.7% for LDH, 96.3% for Aldo, and 54.6% for HRP2. After Day 2, assuming a first-order kinetics clearance model, half-lives of the antigens were 1.8 days (95% CI: 1.5–2.3) for LDH, 3.2 days (95% CI: 3.0–3.4) for Aldo, and 4.8 days (95% CI: 4.7–4.9) for HRP2. LDH and Aldo show substantially different clearance rates than HRP2, and their presence is largely indicative of active infection.

As funding for malaria control increased considerably over the past 10 years resulting in the expanded coverage of malaria control interventions, so did the need to measure the impact of these investments on malaria morbidity and mortality. Members of the Roll Back Malaria (RBM) Partnership undertook impact evaluations of malaria control programs at a time when there was little guidance in terms of the process for conducting an impact evaluation of a national-level malaria control program. The President's Malaria Initiative (PMI), as a member of the RBM Partnership, has provided financial and technical support for impact evaluations in 13 countries to date. On the basis of these experiences, PMI and its partners have developed a streamlined process for conducting the evaluations with a set of lessons learned and recommendations. Chief among these are: to ensure country ownership and involvement in the evaluations; to engage stakeholders throughout the process; to coordinate evaluations among interested partners to avoid duplication of efforts; to tailor the evaluation to the particular country context; to develop a standard methodology for the evaluations and a streamlined process for completion within a reasonable time; and to develop tailored dissemination products on the evaluation for a broad range of stakeholders. These key lessons learned and resulting recommendations will guide future impact evaluations of malaria control programs and other health programs.

As malaria control interventions are scaled-up, rational approaches are needed for monitoring impact over time. One proposed approach includes monitoring the prevalence of malaria infection among pregnant women and children at the time of routine preventive health facility (HF) visits. This pilot explored the feasibility and utility of tracking the prevalence of malaria infection in pregnant women attending their first antenatal care (ANC) visit and infants presenting at 9–12 months of age for measles vaccination.

Despite considerable reductions in malaria achieved by scaling-up long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS), maintaining sustained community protection remains operationally challenging. Increasing insecticide resistance also threatens to jeopardize the future of both strategies. Non-pyrethroid insecticide­treated wall lining (ITWL) may represent an alternate or complementary control method and a potential tool to manage insecticide resistance. To date no study has demonstrated whether ITWL can reduce malaria transmission nor provide additional protection beyond the current best practice of universal coverage (UC) of LLINs and prompt case management.

BACKGROUND:The ongoing west Africa Ebola-virus-disease epidemic has disrupted the entire health-care system in affected countries. Because of the overlap of symptoms of Ebola virus disease and malaria, the care delivery of malaria is particularly sensitive to the indirect effects of the current Ebola-virus-disease epidemic. We therefore characterise malaria case management in the context of the Ebola-virus-disease epidemic and document the effect of the Ebola-virus-disease epidemic on malaria case management. METHODS:We did a cross-sectional survey of public health facilities in Guinea in December, 2014. We selected the four prefectures most affected by Ebola virus disease and selected four randomly from prefectures without any reported cases of the disease. 60 health facilities were sampled in Ebola-affected and 60 in Ebola-unaffected prefectures. Study teams abstracted malaria case management indicators from registers for January to November for 2013 and 2014 and interviewed health-care workers. Nationwide weekly surveillance data for suspect malaria cases reported between 2011 and 2014 were analysed independently. Data for malaria indicators in 2014 were compared with previous years. FINDINGS:We noted substantial reductions in all-cause outpatient visits (by 23 103 [11%] of 214 899), cases of fever (by 20249 [15%] of 131 330), and patients treated with oral (by 22 655 [24%] of 94 785) and injectable (by 5219 [30%] of 17 684) antimalarial drugs in surveyed health facilities. In Ebola-affected prefectures, 73 of 98 interviewed community health workers were operational (74%, 95% CI 65-83) and 35 of 73 were actively treating malaria cases (48%, 36-60) compared with 106 of 112 (95%, 89-98) and 102 of 106 (96%, 91-99), respectively, in Ebola-unaffected prefectures. Nationwide, the Ebola-virus-disease epidemic was estimated to have resulted in 74 000 (71 000-77 000) fewer malaria cases seen at health facilities in 2014. INTERPRETATION:The reduction in the delivery of malaria care because of the Ebola-virus-disease epidemic threatens malaria control in Guinea. Untreated and inappropriately treated malaria cases lead to excess malaria mortality and more fever cases in the community, impeding the Ebola-virus-disease response. FUNDING:Global Fund to Fight AIDS, Tuberculosis and Malaria, and President's Malaria Initiative.

Background. Seasonal increases in malaria continue in hot spots in Zanzibar. Mass screening and treatment (MSAT) may help reduce the reservoir of infection; however, it is unclear whether rapid diagnostic tests (RDTs) detect a sufficient proportion of low-density infections to influence subsequent transmission.Methods. Two rounds of MSAT using Plasmodium falciparum-specific RDT were conducted in 5 hot spots (population, 12 000) in Zanzibar in 2012. In parallel, blood samples were collected on filter paper for polymerase chain reaction (PCR) analyses. Data on confirmed malarial parasite infections from health facilities in intervention and hot spot control areas were monitored as proxy for malaria transmission.Results. Approximately 64% of the population (7859) were screened at least once. P. falciparum prevalence, as measured by RDT, was 0.2% (95% confidence interval [CI], .1%-. 3%) in both rounds, compared with PCR measured prevalences (for all species) of 2.5% (95% CI, 2.1%-2.9%) and 3.8% (95% CI, 3.2%-4.4%) in rounds 1 and 2, respectively. Two fifths (40%) of infections detected by PCR included non-falciparum species. Treatment of RDT-positive individuals (4% of the PCR-detected parasite carriers) did not reduce subsequent malaria incidence, compared with control areas.Conclusions. Highly sensitive point-of-care diagnostic tools for detection of all human malaria species are needed to make MSAT an effective strategy in settings where malaria elimination programs are in the pre-elimination phase.