In 1983, the countries of the Americas, with support from the Pan American Health Organization (PAHO), pledged to eliminate human rabies transmitted by dogs 1 . The goal established was initially limited to the main cities and later extended to the entire Region, setting 2005 as the target date.Since then, through the Regional Program for the Elimination of Human Rabies Transmitted by Dogs, the countries have made great efforts to reach the goal, with remarkable success 2,3,4,5 . In the last 20 years, the number of cases of human and canine rabies in the Region has dropped by nearly 90% 6 .Eliminating human and canine rabies in the member states is a technical cooperation priority and key mandate for PAHO. To help analyze the extent to which the goal was reached, PAHO conducted a study entitled Elimination of Human Rabies Transmitted by Dogs in Latin America 7 to evaluate the rabies situation in the Region, resulting in this publication and a summary published in the PAHO Epidemiological Bulletin 8 . MethodologyPAHO developed standard methods 9 and sent each participating country an interactive CD-ROM with the study methodology and a bibliography pertaining to the subject area. Countries also received a diskette with an Excel spreadsheet

Antimalarial drug resistance has historically arisen through convergent de novo mutations in Plasmodium falciparum parasite populations in Southeast Asia and South America. For the past decade in Southeast Asia, artemisinins, the core component of first-line antimalarial therapies, have experienced delayed parasite clearance associated with several pfk13 mutations, primarily C580Y. We report that mutant pfk13 has emerged independently in Guyana, with genome analysis indicating an evolutionary origin distinct from Southeast Asia. Pfk13 C580Y parasites were observed in 1.6% (14/854) of samples collected in Guyana in 2016–2017. Introducing pfk13 C580Y or R539T mutations by gene editing into local parasites conferred high levels of in vitro artemisinin resistance. In vitro growth competition assays revealed a fitness cost associated with these pfk13 variants, potentially explaining why these resistance alleles have not increased in frequency more quickly in South America. These data place local malaria control efforts at risk in the Guiana Shield.

Malaria has declined in recent years in countries of the American continents. In 2011, 12 of 21 endemic countries had already met their 2015 Millennium Development Goal. However, this declining trend has not been adequately evaluated. An analysis of the number of cases per 100,000 people (annual parasite index [API]) and the percentage of positive blood slides (slide positivity rate [SPR]) during the period of 1959–2011 in 21 endemic countries was done using the joinpoint regression methodology. During 1960–1979, API and SPR increased significantly and peaked in the 1980s. Since the 1990s, there have been significant declining trends in both API and SPR. Additionally, both Plasmodium vivax and P. falciparum species-specific incidence have declined. With the exception of two countries, such a collectively declining malaria trend was not observed in previous decades. This presents a unique opportunity for the Americas to seriously consider malaria elimination as a final goal.

BackgroundMalaria remains a public health problem in some countries of Central America. Rapid diagnostic tests (RDTs) are one of the most useful tools to assist in the diagnosis of malaria in remote areas. Since its introduction, a wide variety of RDTs have been developed for the detection of different parasite antigens. PfHRP2 is the most targeted antigen for the detection of Plasmodium falciparum infections. Genetic mutations and gene deletions are important factors influencing or affecting the performance of rapid diagnostic tests.MethodsIn order to demonstrate the presence or absence of the pfhrp2 and pfhrp3 genes and their flanking regions, a total of 128 blood samples from patients with P. falciparum infection from three Central American countries were analysed through nested or semi-nested PCR approaches.ResultsIn total, 25.8 and 91.4% of the isolates lacked the region located between exon 1 and exon 2 of pfhrp2 and pfhrp3 genes, respectively. Parasites from the three countries showed deletions of one or both genes. The highest proportion of pfhrp2 deletions was found in Nicaragua while the isolates from Guatemala revealed the lowest number of pfhrp2 deletions. Parasites collected from Honduras showed the highest proportion of phfrp3 absence (96.2%). Twenty-one percent of isolates were double negative mutants for the exon 1–2 segment of both genes, and 6.3% of isolates lacked the full-length coding region of both genes.ConclusionsThis study provides molecular evidence of the existence of P. falciparum isolates lacking the pfhrp2 and pfhrp3 genes, and their flanking regions, in Honduras, Guatemala and Nicaragua. This finding could hinder progress in the control and elimination of malaria in Central America. Continuous evaluation of RDTs and molecular surveillance would be recommended.

The global prevalence of malaria has decreased over the past fifteen years, but similar gains have not been realized against Plasmodium vivax because this species is less responsive to conventional malaria control interventions aimed principally at P. falciparum. Approximately half of all malaria cases outside of Africa are caused by P. vivax. This species places dormant forms in human liver that cause repeated clinical attacks without involving another mosquito bite. The diagnosis of acute patent P. vivax malaria relies primarily on light microscopy. Specific rapid diagnostic tests exist but typically perform relatively poorly compared to those for P. falciparum. Better diagnostic tests are needed for P. vivax. To guide their development, FIND, in collaboration with P. vivax experts, identified the specific diagnostic needs associated with this species and defined a series of three distinct target product profiles, each aimed at a particular diagnostic application: (i) point-of-care of acutely ill patients for clinical care purposes; (ii) point-of-care asymptomatic and otherwise sub-patent residents for public health purposes, e.g., mass screen and treat campaigns; and (iii) ultra-sensitive not point-of-care diagnosis for epidemiological research/surveillance purposes. This report presents and discusses the rationale for these P. vivax-specific diagnostic target product profiles. These contribute to the rational development of fit-for-purpose diagnostic tests suitable for the clinical management, control and elimination of P. vivax malaria.

Artemether-lumefantrine (AL) is the first-line treatment for uncomplicated Plasmodium falciparum infection in Colombia. To assess AL efficacy for uncomplicated falciparum malaria in Quibdo, Choco, Colombia, we conducted a 28-day therapeutic efficacy study (TES) following the WHO guidelines. From July 2018 to February 2019, febrile patients aged 5-65 years with microscopy-confirmed P. falciparum mono-infection and asexual parasite density of 250-100,000 parasites/μL were enrolled and treated with a supervised 3-day course of AL. The primary endpoint was adequate clinical and parasitological response (ACPR) on day 28. We attempted to use polymerase chain reaction (PCR) genotyping to differentiate reinfection and recrudescence, and conducted genetic testing for antimalarial resistance-associated genes. Eighty-eight patients consented and were enrolled; four were lost to follow-up or missed treatment doses. Therefore, 84 (95.5%) participants reached a valid endpoint: treatment failure or ACPR. No patient remained microscopy positive for malaria on day 3, evidence of delayed parasite clearance and artemisinin resistance. One patient had recurrent infection (12 parasites/μL) on day 28. Uncorrected ACPR rate was 98.8% (83/84) (95% CI: 93.5-100%). The recurrent infection sample did not amplify during molecular testing, giving a PCR-corrected ACPR of 100% (83/83) (95% CI: 95.7-100%). No P. falciparum kelch 13 polymorphisms associated with artemisinin resistance were identified. Our results support high AL efficacy for falciparum malaria in Choco. Because of the time required to conduct TESs in low-endemic settings, it is important to consider complementary alternatives to monitor antimalarial efficacy and resistance.

Background: The World Health Organization (WHO) recommends parasite-based diagnosis of malaria. In recent years, there has been surge in the use of various kinds of nucleic-acid amplification based tests (NAATs) for detection and identification of Plasmodium spp. to support clinical care in high-resource settings and clinical and epidemiological research worldwide. However, these tests are not without challenges, including lack (or limited use) of standards and lack of reproducibility, due in part to variation in protocols amongst laboratories. Therefore, there is a need for rigorous quality control, including a robust external quality assessment (EQA) scheme targeted towards malaria NAATs. To this effect, the WHO Global Malaria Programme worked with the UK National External Quality Assessment Scheme (UK NEQAS) Parasitology and with technical experts to launch a global NAAT EQA scheme in January 2017. Methods: Panels of NAAT EQA specimens containing five major species of human-infecting Plasmodium at various parasite concentrations and negative samples were created in lyophilized blood (LB) and dried blood spot (DBS) formats. Two distributions per year were sent, containing five LB and five DBS specimens. Samples were tested and validated by six expert referee laboratories prior to distribution. Between 37 and 45 laboratories participated in each distribution and submitted results using the online submission portal of UK NEQAS. Participants were scored based on their laboratory's stated capacity to identify Plasmodium species, and individual laboratory reports were sent which included performance comparison with anonymized peers. Results: Analysis of the first three distributions revealed that the factors that most significantly affected performance were sample format (DBS vs LB), species and parasite density, while laboratory location and the reported methodology used (type of nucleic acid extraction, amplification, or DNA vs RNA target) did not significantly affect performance. Referee laboratories performed better than non-referee laboratories. Conclusions: Globally, malaria NAAT assays now inform a range of clinical, epidemiological and research investigations. EQA schemes offer a way for laboratories to assess and improve their performance, which is critical to safeguarding the reliability of data and diagnoses especially in situations where various NAAT methodologies and protocols are in use.

Background Malaria causes more than 200 million cases of illness and 400,000 deaths each year across 90 countries. The World Health Organization (WHO) set a goal for 35 countries to eliminate malaria by 2030, with an intermediate milestone of 10 countries by 2020. In 2017, the WHO established the Elimination-2020 (E-2020) initiative to help countries achieve their malaria elimination goals and included 21 countries with the potential to eliminate malaria by 2020. Methods Across its three levels of activity (country, region and global), the WHO developed normative and implementation guidance on strategies and activities to eliminate malaria; provided technical support and subnational operational assistance; convened national malaria programme managers at three global meetings to share innovations and best practices; advised countries on strengthening their strategy to prevent re-establishment and preparing for WHO malaria certification; and contributed to maintaining momentum towards elimination through periodic evaluations, monitoring and oversight of progress in the E-2020 countries. Changes in the number of indigenous cases in E-2020 countries between 2016 and 2020 are reported, along with the number of countries that eliminated malaria and received WHO certification. Results The median number of indigenous cases in the E-2020 countries declined from 165.5 (interquartile range [IQR] 14.25–563.75) in 2016 to 78 (IQR 0–356) in 2020; 12 (57%) countries reported reductions in indigenous cases over that period, of which 7 (33%) interrupted malaria transmission and maintained a malaria-free status through 2020 and 4 (19%) were certified malaria-free by the WHO. Two countries experienced outbreaks of malaria in 2020 and 2021 attributed, in part, to the COVID-19 pandemic. Conclusions Although the E-2020 countries contributed to the achievement of the 2020 global elimination milestone, the initiative highlights the difficulties countries face to interrupt malaria transmission, even when numbers of cases are very low. The 2025 global elimination milestone is now approaching, and the lessons learned, experience gained, and updated guidance developed during the E-2020 initiative will help serve the countries seeking to eliminate malaria by 2025.