Lessons learned from the implementation of integrated serosurveillance of communicable diseases in the Americas.

Objective: Systematize the experience and identify challenges and lessons learned in the implementation of an initiative for integrated serosurveillance of communicable diseases using a multiplex bead assay in countries of the Americas. Methods: Documents produced in the initiative were compiled and reviewed. These included concept notes, internal working papers, regional meetings reports, and survey protocols from the three participating countries (Mexico, Paraguay, and Brazil) and two additional countries (Guyana and Guatemala) where serology for several communicable diseases was included in neglected tropical diseases surveys. Information was extracted and summarized to describe the experience and the most relevant challenges and lessons learned. Results: Implementing integrated serosurveys requires interprogrammatic and interdisciplinary work teams for the design of survey protocols to respond to key programmatic questions aligned to the needs of the countries. Valid laboratory results are critical and rely on the standardized installment and roll-out of laboratory techniques. Field teams require adequate training and supervision to properly implement survey procedures. The analysis and interpretation of serosurveys results should be antigen-specific, contextualizing the responses for each disease, and triangulated with programmatic and epidemiological data for making decisions tailored to specific population socioeconomic and ecologic contexts. Conclusions: Integrated serosurveillance as a complementary tool for functional epidemiological surveillance systems is feasible to use and key components should be considered: political engagement, technical engagement, and integrated planning. Aspects such as designing the protocol, selecting target populations and diseases, laboratory capacities, anticipating the capacities to analyze and interpret complex data, and how to use it are key.

Kelch13 mutations in Plasmodium falciparum and risk of spreading in Amazon basin countries.

BACKGROUND: The first potential focus for artemisinin resistance in South America was recently confirmed with the presence of the C580Y mutation in the Plasmodium falciparum kelch 13 gene (pfk13) in Guyana. OBJECTIVES: This study aimed to strengthen pfk13 monitoring in the Amazon basin countries, to compile the available data and to evaluate the risk of spreading of mutations. METHODS: Sanger sequencing was done on 862 samples collected between 1998 and 2019, and a global map of pfk13 genotypes available for this region was constructed. Then, the risk of spreading of mutations based on P. falciparum case importation between 2015 and 2018 within countries of the Amazon basin was evaluated. RESULTS: No additional pfk13 C580Y foci were identified. Few mutations (0.5%, 95% CI = 0.3%-0.8%) in the propeller domain were observed in the general parasite population of this region despite a high proportion of K189T mutations (49.1%, 95% CI = 46.2%-52.0%) in the non-propeller domain. Case information revealed two patterns of intense human migration: Venezuela, Guyana and the Roraima State in Brazil; and French Guiana, Suriname and the Amapá State in Brazil. CONCLUSIONS: There are few pfk13 mutant foci, but a high risk of dispersion in the Amazon basin, mainly from the Guiana Shield, proportionate to mining activities. Therefore, access to prompt diagnosis and treatment, and continuous molecular monitoring is essential in these geographical areas.

Deletions of pfhrp2 and pfhrp3 genes of Plasmodium falciparum from Honduras, Guatemala and Nicaragua.

BACKGROUND: Malaria 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. METHODS: In 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. RESULTS: In 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. CONCLUSIONS: This 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.

Impact of piperaquine resistance in Plasmodium falciparum on malaria treatment effectiveness in The Guianas: a descriptive epidemiological study.

BACKGROUND: Plasmodium falciparum is an apicomplexan parasite responsible for lethal cases of malaria. According to WHO recommendations, P falciparum cases are treated with artemisinin-based combination therapy including dihydroartemisinin-piperaquine. However, the emergence of resistant parasites against dihydroartemisinin-piperaquine was reported in southeast Asia in 2008 and, a few years later, suspected in South America. METHODS: To characterise resistance emergence, a treatment efficacy study was performed on the reported patients infected with P falciparum and treated with dihydroartemisinin-piperaquine in French Guiana (n=6, 2016-18). Contemporary isolates collected in French Guiana were genotyped for P falciparum chloroquine resistance transporter (pfCRT; n=845) and pfpm2 and pfpm3 copy number (n=231), phenotyped using the in vitro piperaquine survival assay (n=86), and analysed through genomic studies (n=50). Additional samples from five Amazonian countries and one outside the region were genotyped (n=1440). FINDINGS: In field isolates, 40 (47%) of 86 (95% CI 35·9-57·1) were resistant to piperaquine in vitro; these phenotypes were more associated with pfCRTC350R (ie, Cys350Arg) and pfpm2 and pfpm3 amplifications (Dunn test, p<0·001). Those markers were also associated with dihydroartemisinin-piperaquine treatment failure (n=3 [50%] of 6). A high prevalence of piperaquine resistance markers was observed in Suriname in 19 (83%) of 35 isolates and in Guyana in 579 (73%) of 791 isolates. The pfCRTC350R mutation emerged before pfpm2 and pfpm3 amplification in a temporal sequence different from southeast Asia, and in the absence of artemisinin partial resistance, suggesting a geographically distinctive epistatic relationship between these genetic markers. INTERPRETATION: The high prevalence of piperaquine resistance markers in parasite populations of the Guianas, and the risk of associated therapeutic failures calls for caution on dihydroartemisinin-piperaquine use in the region. Furthermore, greater attention should be given to potential differences in genotype to phenotype mapping across genetically distinct parasite populations from different continents. FUNDING: Pan American Health Organization and WHO, French Ministry for Research, European Commission, Santé publique France, Agence Nationale de la Recherche, Fundação de Amparo à Pesquisa do Estado do Amazonas, Ministry of Health of Brazil, Oswaldo Cruz Foundation, and National Institutes of Health. TRANSLATIONS: For the French and Portuguese translations of the abstract see Supplementary Materials section.

Acceptability of short message service (SMS) as a tool for malaria treatment adherence in the Brazilian Amazon: a qualitative study.

BACKGROUND: Malaria is one of the leading causes of morbidity worldwide, and patient adherence to prescribed antimalarials is essential for effective treatment. METHODS: This cross-sectional study, with in-depth telephone interviews, analyzed participants' perceptions of short message service (SMS) in adherence to treatment. RESULTS: Five thematic categories emerged: decreased forgetfulness, the novelty of the tool, easy-to-understand language, the impact of SMS messages during treatment, and suggestions for improvement and complaints. CONCLUSIONS: SMS could assist patients in adhering to prescribed antimalarials.

Local emergence in Amazonia of Plasmodium falciparum k13 C580Y mutants associated with in vitro artemisinin resistance.

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.

All recommended treatments against malaria include a drug called artemisinin or some of its derivatives. However, there are concerns that Plasmodium falciparum, the parasite that causes most cases of malaria, will eventually develop widespread resistance to the drug. A strain of P. falciparum partially resistant to artemisinin was seen in Cambodia in 2008, and it has since spread across Southeast Asia. The resistance appears to be frequently linked to a mutation known as pfk13 C580Y. Southeast Asia and Amazonia are considered to be hotspots for antimalarial drug resistance, and the pfk13 C580Y mutation was detected in the South American country of Guyana in 2010. To examine whether the mutation was still circulating in this part of the world, Mathieu et al. collected and analyzed 854 samples across Guyana between 2016 and 2017. Overall, 1.6% of the samples had the pfk13 C580Y mutation, but this number was as high as 8.8% in one region. Further analyses revealed that the mutation in Guyana had not spread from Southeast Asia, but that it had occurred in Amazonia independently. To better understand the impact of the pfk13 C580Y mutation, Mathieu et al. introduced this genetic change into non-resistant parasites from a country neighbouring Guyana. As expected, the mutation made P. falciparum highly resistant to artemisinin, but it also slowed the growth rate of the parasite. This disadvantage may explain why the mutation has not spread more rapidly through Guyana in recent years. Artemisinin and its derivatives are always associated with other antimalarial drugs to slow the development of resistance; there are concerns that reduced susceptibility to artemisinin leads to the parasites becoming resistant to the partner drugs. Further research is needed to evaluate how the pfk13 C580Y mutation affects the parasite's response to the typical combination of drugs that are given to patients.

Acceptability of short message service (SMS) as a tool for malaria treatment adherence in the Brazilian Amazon: a qualitative study

ABSTRACT Background: Malaria is one of the leading causes of morbidity worldwide, and patient adherence to prescribed antimalarials is essential for effective treatment. Methods: This cross-sectional study, with in-depth telephone interviews, analyzed participants' perceptions of short message service (SMS) in adherence to treatment. Results: Five thematic categories emerged: decreased forgetfulness, the novelty of the tool, easy-to-understand language, the impact of SMS messages during treatment, and suggestions for improvement and complaints. Conclusions: SMS could assist patients in adhering to prescribed antimalarials.

Current status of human rabies transmitted by dogs in Latin America.

Latin American countries made the political decision to eliminate human rabies transmitted by dogs by the year 2005. The purpose of the current study is to evaluate to what extent this goal has been reached. The epidemiological situation and control measures were analyzed and broken down within the countries by georeferencing. The 27 human cases reported in 2003 occurred in some 0.2% of the second-level geopolitical units (municipalities or counties) in the region, suggesting that the disease is a local problem. Several areas within the countries reported no more transmission of rabies in dogs. Nearly 1 million people potentially exposed to rabies received treatment. On average, 34,383 inhabitants per health post receive anti-rabies treatment (range: 4,300-148,043). Nearly 42 million dogs are vaccinated annually. Surveillance is considered fair according to the epidemiological criteria adopted by the study. Samples sent for rabies testing represent 0.05% of the estimated canine population (range: 0.001 to 0.2%). The countries are quite close to achieving the goal.

Defining the next generation of Plasmodium vivax diagnostic tests for control and elimination: Target product profiles.

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.

Malaria in the Americas: trends from 1959 to 2011.

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.

[Prevalence and intensity of infection by soil-transmitted helminths and prevalence of malaria among schoolchildren in El Salvador]. / Prevalencia e intensidad de la infección por geohelmintos y prevalencia de la malaria en escolares de El Salvador.

INTRODUCTION: El Salvador does not have recent data on the prevalence of infection with soil-transmitted helminths among children aged under 15 years of age. As one of the countries in the Americas that reports few malaria cases, eradication of this disease from El Salvador is considered to be feasible. OBJECTIVE: To determine the prevalence and intensity of infection by soil-transmitted helminths, as well as the prevalence of Plasmodium spp. in schoolchildren aged 8-10. MATERIALS AND METHODS: A cross-sectional study was carried out in each of the five eco-epidemiological zones of the country (coastal plain, central basin, volcanic range, coastal range and mountain zone). In all 1,325 students we studied the presence of geohelminthiasis, with 152 of them also being tested for malaria. The Kato-Katz technique was used to detect geohelminths while diagnosis of malaria was performed using the rapid diagnostic test, microscopy and polymerase chain reaction. RESULTS: The overall prevalence of geohelminthiasis was 7.9% (95%CI 6.6-9.5%). Values for the five eco-epidemiological zones were as follows: coastal plain, 14.9% (95%CI 10.9-19.7%); central plateau, 9.4% (95%CI 6.5-13.3%); volcanic range, 6.6% (95%CI 4.2-10.5%); coastal range, 5.9% (95%CI 3.8-9.4%), and mountain zone, 2.6% (95%CI 1.4-5.7%). The overall rate of high intensity infection with any of the geohelminth species was 0.3%. No schoolchildren were found infected with Plasmodium spp. by any of the three diagnostic techniques used. CONCLUSION: Prevalence of geohelminths was low and Trichuris trichiura was the predominant species. Intensity of infection with any of the species of geohelminths was light (<1%). The risk factors associated with infection by soil-transmitted helminths were defecation in the open air, being barefoot and living in coastal areas.

Prevalencia e intensidad de la infección por geohelmintos y prevalencia de la malaria en escolares de El Salvador / Prevalence and intensity of infection by soil-transmitted helminths and prevalence of malaria among schoolchildren in El Salvador

Introducción. El Salvador no cuenta con datos actualizados de prevalencia en menores de 15 años de la infección por helmintos transmitidos por contacto con el suelo. Además, al ser uno de los países en las Américas que reporta un número bajo de casos de malaria, se considera que su eliminación allí es factible. Objetivo. Determinar la prevalencia y la intensidad de la infección por geohelmintos y la prevalencia de Plasmodium spp. en escolares de 8 a 10 años de El Salvador. Materiales y métodos. Se hizo un estudio de corte transversal en las cinco zonas eco-epidemiológicas del país (planicie costera, depresión central, cadena volcánica, cadena costera y zona montañosa). La presencia de geohelmintiasis se estudió en 1.325 estudiantes y, la de malaria, en 152. Se utilizó la técnica de Kato-Katz para la detección de geohelmintos, y para el diagnóstico de la malaria, una prueba rápida, el estudio mediante microscopía y la prueba de reacción en cadena de la polimerasa. Resultados. La prevalencia total de geohelmintiasis fue de 7,9 % (IC 95% 6,6-9,5). En la planicie costera fue de 14,9 % (IC 95% 10,9-19,7); en la depresión central, de 9,4 % (IC 95% 6,5-13,3); en la cadena volcánica, de 6,6 % (IC 95% 4,2-10,5); en la cadena costera, de 5,9 % (IC 95% 3,8-9,4), y en la cadena montañosa, de 2,6 % (IC 95% 1,4-5,7). La proporción de infección de gran intensidad debida a cualquiera de las especies de geohelmintos fue de 0,3 %. No se encontraron escolares infectados con Plasmodium spp. Conclusión. La prevalencia de geohelmintos fue baja y la especie más prevalente fue Trichuris trichiura . La intensidad de la infección debida a cualquiera de las especies de geohelmintos fue leve (<1 %). Los factores de riesgo asociados a la infección por geohelmintos fueron la defecación al aire libre, no usar calzado y vivir en la planicie costera.

Introduction: El Salvador does not have recent data on the prevalence of infection with soil-transmitted helminths among children aged under 15 years of age. As one of the countries in the Americas that reports few malaria cases, eradication of this disease from El Salvador is considered to be feasible. Objective: To determine the prevalence and intensity of infection by soil-transmitted helminths, as well as the prevalence of Plasmodium spp. in schoolchildren aged 8-10. Materials and methods: A cross-sectional study was carried out in each of the five eco-epidemiological zones of the country (coastal plain, central basin, volcanic range, coastal range and mountain zone). In all 1,325 students we studied the presence of geohelminthiasis, with 152 of them also being tested for malaria. The Kato-Katz technique was used to detect geohelminths while diagnosis of malaria was performed using the rapid diagnostic test, microscopy and polymerase chain reaction. Results: The overall prevalence of geohelminthiasis was 7.9% (95%CI 6.6-9.5%). Values for the five eco-epidemiological zones were as follows: coastal plain, 14.9% (95%CI 10.9-19.7%); central plateau, 9.4% (95%CI 6.5-13.3%); volcanic range, 6.6% (95%CI 4.2-10.5%); coastal range, 5.9% (95%CI 3.8-9.4%), and mountain zone, 2.6% (95%CI 1.4-5.7%). The overall rate of high intensity infection with any of the geohelminth species was 0.3%. No schoolchildren were found infected with Plasmodium spp. by any of the three diagnostic techniques used. Conclusion: Prevalence of geohelminths was low and Trichuris trichiura was the predominant species. Intensity of infection with any of the species of geohelminths was light (<1%). The risk factors associated with infection by soil-transmitted helminths were defecation in the open air, being barefoot and living in coastal areas.

Current status of human rabies transmitted by dogs in Latin America

Latin American countries made the political decision to eliminate human rabies transmitted by dogs by the year 2005. The purpose of the current study is to evaluate to what extent this goal has been reached. The epidemiological situation and control measures were analyzed and broken down within the countries by georeferencing. The 27 human cases reported in 2003 occurred in some 0.2 percent of the second-level geopolitical units (municipalities or counties) in the region, suggesting that the disease is a local problem. Several areas within the countries reported no more transmission of rabies in dogs. Nearly 1 million people potentially exposed to rabies received treatment. On average, 34,383 inhabitants per health post receive anti-rabies treatment (range: 4,300-148,043). Nearly 42 million dogs are vaccinated annually. Surveillance is considered fair according to the epidemiological criteria adopted by the study. Samples sent for rabies testing represent 0.05 percent of the estimated canine population (range: 0.001 to 0.2 percent). The countries are quite close to achieving the goal.

Os países da América Latina tomaram a decisão política de eliminar a raiva humana transmitida por cão até 2005, e o objetivo deste estudo é analisar o cumprimento desta meta. A situação epidemiológica e as ações de controle foram analisadas de forma desagregada dentro dos países, utilizando-se georreferenciamento da informação. Os 27 casos humanos relatados em 2003 ocorreram em cerca de 0,2 por cento das unidades de segundo nível geopolítico (municípios) da região. Esse dado sugere que a doença atualmente é muito localizada. Vários países não reportam mais transmissão de raiva em cães. Cerca de 1 milhão de pessoas são potencialmente expostas ao risco da raiva e recebem atendimento médico. Existem em média 34.383 (classe: 4.300-148.043) habitantes por posto de saúde com tratamento anti-rábico. São vacinados cerca de 42 milhões de cães anualmente, 70 por cento deles no Brasil e México. A vigilância epidemiológica para a raiva foi considerada média pelos critérios estabelecidos no estudo, sendo enviada 0,05 por cento da população canina estimada de amostras para diagnostico de raiva. Foi considerado que os países estão muito próximos de alcançar a meta.