Hybrid Immunity Results in Enhanced and More Sustained Antibody Responses after the Second Sinovac-CoronaVac Dose in a Brazilian Cohort: DETECTCoV-19 Cohort.

We measured anti-SARS-CoV-2 antibody responses before and after CoronaVac (inactivated) vaccination in a case-control study performed in CoronaVac-immunized individuals participating in a longitudinal prospective study of adults in Manaus (DETECTCoV-19). Antibody responses were measured by standard serological immunoassays. Peak anti-S-RBD and neutralizing RBD-ACE2 blocking antibody responses after two doses of CoronaVac vaccine were similar in vaccine breakthrough cases (n = 9) and matched controls (n = 45). Individuals with hybrid immunity resulting from prior SARS-CoV-2 infection followed by vaccination (n = 22) had elevated levels of anti-N, anti-S-RBD and RBD-ACE2 blocking antibodies after the second vaccine dose compared to infection-naïve individuals (n = 48). Post-vaccination SARS-CoV-2-specific antibody responses rapidly waned in infection-naïve individuals. Antibody responses wane after vaccination, making individuals susceptible to infection by SARS-CoV-2 variants. These findings support the need for booster doses after primary vaccination. Population antibody serosurveys provide critical information toward implementing optimal timing of booster doses.

Acute Chagas disease associated with ingestion of contaminated food in Brazilian western Amazon.

OBJECTIVE: To describe clinical, epidemiological and management information on cases of acute Chagas disease (ACD) by oral transmission in the state of Amazonas in western Amazon. METHODS: Manual and electronic medical records of patients diagnosed with ACD at the Fundação de Medicina Tropical Doutor Heitor Vieira Dourado (FMT-HVD) were included. RESULTS: There were 147 cases of acute CD registered from 10 outbreaks that occurred in the state of Amazonas between 2004 and 2022. The transmission pathway was through oral route, with probable contaminated palm fruit juice (açaí and/or papatuá), and involved people from the same family, friends or neighbours. Of 147 identified cases, 87 (59%) were males; cases were aged 10 months to 82 years. The most common symptom was the febrile syndrome (123/147; 91.8%); cardiac alterations were present in 33/100 (33%), (2/147; 1.4%) had severe ACD with meningoencephalitis, and 12 (8.2%) were asymptomatic. Most cases were diagnosed through thick blood smear (132/147; 89.8%), a few (14/147; 9.5%) were diagnosed by serology and (1/147; 0.7%) by polymerase chain reaction (PCR) and blood culture. In all these outbreaks, 74.1% of the patients were analysed by PCR, and Trypanosoma cruzi TcIV was detected in all of them. No deaths were recorded. The incidence of these foci coincided with the fruit harvest period in the state of Amazonas. CONCLUSION: The occurrence of ACD outbreaks in the Amazon affected individuals of both sexes, young adults, living in rural and peri-urban areas and related to the consumption of regional foods. Early diagnosis is an important factor in surveillance. There was a low frequency of cardiac alterations. Continuous follow-up of most patients was not carried out due to difficulty in getting to specialised centres; therefore, little is known about post-treatment.

Multiple introductions and country-wide spread of DENV-2 genotype II (Cosmopolitan) in Brazil.

Dengue virus serotype 2, genotype Cosmopolitan (DENV-2-GII), is one of the most widespread DENV strains globally. In the USA, DENV-2 epidemics have been dominated by DENV-2 genotype Asian-American (DENV-2-GIII), and the first cases of DENV-2-GII were only described in 2019, in Peru, and in 2021 in Brazil. To gain new information about the circulation of DENV-2-GII in Brazil, we sequenced 237 DENV-2 confirmed cases sampled between March 2021 and March 2023 and revealed that DENV-2-GII is already present in all geographic regions of Brazil. The phylogeographic analysis inferred that DENV-2-GII was introduced at least four times in Brazil, between May 2020 and August 2022, generating multiple clades that spread throughout the country with different success. Despite multiple introductions of DENV-2-GII, analysis of the country-wide laboratory surveillance data showed that the Brazilian dengue epidemic in 2022 was dominated by DENV-1 in most states. We hypothesize that massive circulation of DENV-2-GIII in previous years in Brazil might have created a population immune barrier against symptomatic homotypic reinfections by DENV-2-GII, leading to sustained cryptic circulation in asymptomatic cases and localized outbreaks of this new genotype. In summary, our study stresses the importance of arboviral genomic surveillance to close monitoring and better understanding the potential impact of DENV-2-GII in the coming years.

Quantitative G6PD Deficiency Screening in Routine Malaria Diagnostic Units in the Brazilian Amazon (SAFEPRIM): An Operational Mixed-Methods Study.

BACKGROUND: Glucose-6-phosphate dehydrogenase (G6PD) deficiency testing is not routinely performed before primaquine treatment in most Plasmodium vivax endemic areas, despite the risk of primaquine-associated hemolysis. This is due to the operational challenges associated with pragmatic G6PD testing and as such needs to be addressed. METHODS AND FINDINGS: This mixed-methods operational study was aimed at implementing the quantitative point-of-care StandardTM G6PD (SD Biosensor, Korea) screening test in malaria treatment units (MTUs) in the municipalities of Rio Preto da Eva and Mâncio Lima, in the Brazilian Amazon, between mid-January 2020 and December 2020. In total, 1286 P. vivax cases were treated based on the Standard G6PD test: 1230 had activity equal to or greater than 4.0 U/g Hb, and 56 less than 4.0 U/g Hb. No G6PD deficient (G6PDd) genotypes were found in 96 samples from the 1230, and only 21 of the 56 G6PDd cases had confirmed G6PDd genotypes. Evaluations were conducted on the proficiency of health care professionals (HCPs) training to perform the test, the reliability of testing performed in the field, and the perceptions of HCPs and patients about the implementation. Post-training proficiency was 73.4% after a 4-hour training session. This study revealed that locations with lower malaria caseloads will need regular refresher training. The test was well accepted by both HCPs and patients. Signs and symptoms of hemolysis were not always associated with malaria treatment drugs by HCPs and patients. INTERPRETATION: Point-of-care quantitative G6PD testing can be performed at MTUs in the Brazilian Amazon to inform treatment decisions with primaquine. Limitations related to technical and cultural aspects need to be addressed further when expanding screening to larger areas.

Acute micro-outbreak of Chagas disease in the southeastern Amazon: a report of five cases.

BACKGROUND: Chagas disease is gaining importance in the Brazilian Amazon region as a differential diagnosis of febrile syndrome. The most recent microoutbreak occurred in Ipixuna, in Amazonas state. METHODS: An epidemiological survey was conducted using parasitological and serological tests, and electrocardiographic analysis. RESULTS: The patients belonged to one family and had ingested açaí acquired from Ipixuna. All patients reported fever and initially a thick blood smear test was done to identify Trypanosoma cruzi. Benznidazole treatment was administered to all patients. CONCLUSIONS: Knowledge of the epidemiological dynamics of Chagas disease allows us to improve control and management measures for this disease.

Acute micro-outbreak of Chagas disease in the southeastern Amazon: a report of five cases

ABSTRACT Background: Chagas disease is gaining importance in the Brazilian Amazon region as a differential diagnosis of febrile syndrome. The most recent microoutbreak occurred in Ipixuna, in Amazonas state. Methods: An epidemiological survey was conducted using parasitological and serological tests, and electrocardiographic analysis. Results: The patients belonged to one family and had ingested açaí acquired from Ipixuna. All patients reported fever and initially a thick blood smear test was done to identify Trypanosoma cruzi. Benznidazole treatment was administered to all patients. Conclusions: Knowledge of the epidemiological dynamics of Chagas disease allows us to improve control and management measures for this disease.

Real-life implementation of a G6PD deficiency screening qualitative test into routine vivax malaria diagnostic units in the Brazilian Amazon (SAFEPRIM study).

BACKGROUND: Glucose-6-phosphate dehydrogenase (G6PD) deficiency greatly hinders Plasmodium vivax malaria radical cure and further elimination due to 8-aminoquinolines-associated hemolysis. Although the deleterious health effects of primaquine in G6PD deficient individuals have been known for over 50 years, G6PD testing is not routinely performed before primaquine treatment in most P. vivax endemic areas. METHOD/PRINCIPAL FINDINGS: The qualitative CareStart G6PD screening test was implemented in 12 malaria treatment units (MTUs) in the municipality of Rio Preto da Eva, Western Brazilian Amazon, a malaria endemic area, between February 2019 and early January 2020. Training materials were developed and validated; evaluations were conducted on the effectiveness of training health care professionals (HCPs) to perform the test, the interpretation and reliability of routine testing performed by HCPs, and perceptions of HCPs and patients. Most HCPs were unaware of G6PD deficiency and primaquine-related adverse effects. Most of 110 HCPs trained (86/110, 78%) were able to correctly perform the G6PD test after a single 4-hour training session. The test performed by HCPs during implementation showed 100.0% (4/4) sensitivity and 68.1% (62/91) specificity in identifying G6PD deficient patients as compared to a point-of-care quantitative test (Standard G6PD). CONCLUSIONS/SIGNIFICANCE: G6PD screening using the qualitative CareStart G6PD test performed by HCPs in MTUs of an endemic area showed high sensitivity and concerning low specificity. The amount of false G6PD deficiency detected led to substantial loss of opportunities for radical cure.

Evaluation of Histidine-Rich Proteins 2 and 3 Gene Deletions in Plasmodium falciparum in Endemic Areas of the Brazilian Amazon.

Histidine-rich proteins 2 and 3 gene (pfhrp2 and pfhrp3) deletions affect the efficacy of rapid diagnostic tests (RDTs) based on the histidine-rich protein 2 (HRP2), compromising the correct identification of the Plasmodium falciparum species. Therefore, molecular surveillance is necessary for the investigation of the actual prevalence of this phenomenon and the extent of the disappearance of these genes in these areas and other South American countries, thus guiding national malaria control programs on the appropriate use of RDTs. This study aimed to evaluate the pfhrp2 and pfhrp3 gene deletion in P. falciparum in endemic areas of the Brazilian Amazon. Aliquots of DNA from the biorepository of the Laboratory of Basic Research in Malaria, Evandro Chagas Institute, with a positive diagnosis for P. falciparum infection as determined by microscopy and molecular assays, were included. Monoinfection was confirmed by nested-polymerase chain reaction assay, and DNA quality was assessed by amplification of the merozoite surface protein-2 gene (msp2). The pfhrp2 and pfhrp3 genes were amplified using primers for the region between exons 1 and 2 and for all extension of exon 2. Aliquots of DNA from 192 P. falciparum isolates were included in the study, with 68.7% (132/192) from the municipality of Cruzeiro do Sul (Acre) and 31.3% (60/192) from Manaus (Amazonas). Of this total, 82.8% (159/192) of the samples were considered of good quality. In the state of Acre, 71.7% (71/99) showed pfhrp2 gene deletion and 94.9% (94/99) showed pfhrp3 gene deletion, while in the state of Amazonas, 100.0% (60/60) of the samples showed pfhrp2 gene deletion and 98.3% (59/60) showed pfhrp3 gene deletion. Moreover, 79.8% (127/159) of isolates displayed gene deletion. Our findings confirm the presence of a parasite population with high frequencies of pfhrp2 and pfhrp3 gene deletions in the Brazilian Amazon region. This suggests reconsidering the use of HRP2-based RDTs in the Acre and Amazonas states and calls attention to the importance of molecular surveillance and mapping of pfhrp2/pfhrp3 deletions in this area and in other locations in the Amazon region to guarantee appropriate patient care, control and ultimately contribute to achieving P. falciparum malaria elimination.

Oral Transmission of Trypanosoma cruzi, Brazilian Amazon.

In the Brazilian Amazon, the suspected source of infection in an outbreak of acute Chagas disease involving 10 patients was Euterpe oleracea (açaí berry) juice. Patient blood and juice samples contained Trypanosoma cruzi TcIV, indicating oral transmission of the Chagas disease agent.

Chagas disease in the State of Amazonas: history, epidemiological evolution, risks of endemicity and future perspectives.

Chagas disease (CD) is a parasitic infection that originated in the Americas and is caused by Trypanosoma cruzi. In the last few years, the disease has spread to countries in North America, Asia and Europe due to the migration of Latin Americans. In the Brazilian Amazon, CD has an endemic transmission, especially in the Rio Negro region, where an occupational hazard was described for piaçaveiros (piassaba gatherers). In the State of Amazonas, the first chagasic infection was reported in 1977, and the first acute CD case was recorded in 1980. After initiatives to integrate acute CD diagnostics with the malaria laboratories network, reports of acute CD cases have increased. Most of these cases are associated with oral transmission by the consumption of contaminated food. Chronic cases have also been diagnosed, mostly in the indeterminate form. These cases were detected by serological surveys in cardiologic outpatient clinics and during blood donor screening. Considering that the control mechanisms adopted in Brazil's classic transmission areas are not fully applicable in the Amazon, it is important to understand the disease behavior in this region, both in the acute and chronic cases. Therefore, the pursuit of control measures for the Amazon region should be a priority given that CD represents a challenge to preserving the way of life of the Amazon's inhabitants.

Chagas disease in the State of Amazonas: history, epidemiological evolution, risks of endemicity and future perspectives

Chagas disease (CD) is a parasitic infection that originated in the Americas and is caused by Trypanosoma cruzi. In the last few years, the disease has spread to countries in North America, Asia and Europe due to the migration of Latin Americans. In the Brazilian Amazon, CD has an endemic transmission, especially in the Rio Negro region, where an occupational hazard was described for piaçaveiros (piassaba gatherers). In the State of Amazonas, the first chagasic infection was reported in 1977, and the first acute CD case was recorded in 1980. After initiatives to integrate acute CD diagnostics with the malaria laboratories network, reports of acute CD cases have increased. Most of these cases are associated with oral transmission by the consumption of contaminated food. Chronic cases have also been diagnosed, mostly in the indeterminate form. These cases were detected by serological surveys in cardiologic outpatient clinics and during blood donor screening. Considering that the control mechanisms adopted in Brazil's classic transmission areas are not fully applicable in the Amazon, it is important to understand the disease behavior in this region, both in the acute and chronic cases. Therefore, the pursuit of control measures for the Amazon region should be a priority given that CD represents a challenge to preserving the way of life of the Amazon's inhabitants.

Outbreak of acute Chagas disease associated with oral transmission in the Rio Negro region, Brazilian Amazon.

INTRODUCTION: Chagas disease is considered as emerging in the Brazilian Amazon, usually occurring in acute outbreaks. METHODS: We describe 17 cases of acute Chagas disease in Rio Negro, Amazonas. RESULTS: There were 15 males (average age, 31.3 years), all positive for Trypanosoma cruzi in fresh blood smear examination, and 14 positive by xenodiagnosis and PCR. The top clinical manifestations were fever, asthenia, abdominal pain, and palpitations. Electrocardiograms featured low-voltage QRS, anterosuperior divisional block, and right bundle branch block associated with anterosuperior divisional block. CONCLUSIONS: All patients had consumed açaí products from Monte Alegre in the rural area around Santa Izabel do Rio Negro, Brazil.

Low sensitivity of malaria rapid diagnostic tests stored at room temperature in the Brazilian Amazon Region.

INTRODUCTION: In remote areas of the Amazon Region, diagnosis of malaria by microscopy is practically impossible. This study aimed to evaluate the performance of two rapid diagnostic tests (RDTs) targeting different malaria antigens stored at room temperature in the Brazilian Amazon Region. METHODOLOGY: Performance of the OptiMal Pf/Pan test and ICT-Now Pf/Pan test was analyzed retrospectively in 1,627 and 1,602 blood samples, respectively. Tests were performed over a 15-month period. Kits were stored at room temperature in five community health centres located in the Brazilian Amazon Region. RDT results were compared with thick blood smear (TBS) results to determine sensitivity, specificity, and accuracy of the RDT. RESULTS: The sensitivities of the OptiMal Pf/Pan test were 79.7% for Plasmodium falciparum malaria diagnosis and 85.7% for non-P. falciparum infections. The results showed a crude agreement of 88.5% for P. falciparum, and 88.3% for non-P. falciparum infections (Kappa index = 0.74 and 0.75, respectively). For the ICT-Now Pf/Pan test (CI 95%), the sensitivities were 87.9% for P. falciparum malaria diagnosis and 72.5% for non-P. falciparum infection. Crude agreement between the ICT-Now Pf/Pan test and TBS was 91.4% for P. falciparum and 79.7% for non-P. falciparum infection. The Kappa index was 0.81 and 0.59 for the final diagnosis of P. falciparum and non-P. falciparum, respectively. Higher levels of parasitaemia were associated with higher crude agreement between RDT and TBS. CONCLUSIONS: The sensitivities of RDTs stored at room temperature over a 15-month period and performed in field conditions were lower than those previously reported.

[Association of methemoglobinemia and glucose-6-phosphate dehydrogenase deficiency in malaria patients treated with primaquine]. / Associação de metemoglobinemia e deficiência de glicose-6-fosfato desidrogenase em pacientes com malária tratados com primaquina.

This study had the aim of investigating occurrences of methemoglobinemia among individuals with glucose-6-phosphate dehydrogenase deficiency during treatment for malaria infection using primaquine. Patients with a diagnosis of malaria caused by Plasmodium vivax or the V+F mixture (Plasmodium vivax + Plasmodium falciparum) were selected. Group 1 consisted of 74 individuals with a clinical diagnosis of methemoglobinemia and Group 2 consisted of 161 individuals without a clinical diagnosis of methemoglobinemia. The glucose-6-phosphate dehydrogenase deficiency rates (numbers of enzymopenic individuals) in Groups 1 and 2 were 51.3% (38) and 8.7% (14) respectively. These data demonstrated a statistically significant association with methemoglobinemia only among the individuals in Group 1 (p<0.05). Investigation of the relationship between methemoglobinemia and glucose-6-phosphate dehydrogenase deficiency showed that there was a possible association such that enzymopenic individuals may develop methemoglobinemia more frequently.

Associação de metemoglobinemia e deficiência de glicose-6-fosfato desidrogenase em pacientes com malária tratados com primaquina / Association of methemoglobinemia and glucose-6-phosphate dehydrogenase deficiency in malaria patients treated with primaquine

Este estudo teve como objetivo verificar a ocorrência de metemoglobinemia em indivíduos deficientes da glicose-6-fosfato desidrogenase durante o tratamento da infecção malárica com primaquina. Foram selecionados pacientes com diagnóstico para malária por Plasmodium vivax ou mista V+F (Plasmodium vivax + Plasmodium falciparum), Grupo 1: com 74 indivíduos com diagnóstico clínico de metemoglobinemia e Grupo 2: 161 indivíduos sem diagnóstico clínico de metemoglobinemia. Quanto à deficiência da G6PD, nos Grupos 1 e 2, houveram 51,3 por cento (38) e 8,7 por cento (14) de indivíduos enzimopênicos, respectivamente, demonstrando através de tais dados, significância estatística na associação com a metemoglobinemia somente nos indivíduos do Grupo 1 (p<0,05). A comparação da relação da metemoglobinemia à deficiência da G6PD mostrou haver uma possível associação de indivíduos enzimopênicos desenvolverem metemoglobinemia com maior freqüência.

This study had the aim of investigating occurrences of methemoglobinemia among individuals with glucose-6-phosphate dehydrogenase deficiency during treatment for malaria infection using primaquine. Patients with a diagnosis of malaria caused by Plasmodium vivax or the V+F mixture (Plasmodium vivax + Plasmodium falciparum) were selected. Group 1 consisted of 74 individuals with a clinical diagnosis of methemoglobinemia and Group 2 consisted of 161 individuals without a clinical diagnosis of methemoglobinemia. The glucose-6-phosphate dehydrogenase deficiency rates (numbers of enzymopenic individuals) in Groups 1 and 2 were 51.3 percent (38) and 8.7 percent (14) respectively. These data demonstrated a statistically significant association with methemoglobinemia only among the individuals in Group 1 (p<0.05). Investigation of the relationship between methemoglobinemia and glucose-6-phosphate dehydrogenase deficiency showed that there was a possible association such that enzymopenic individuals may develop methemoglobinemia more frequently.

[Evaluation of the Optimal-IT and ICT P.f./P.v. rapid dipstick tests for diagnosing malaria within primary healthcare in the municipality of Manaus, Amazonas]. / Avaliação dos testes rápidos Optimal-IT e ICT P.f./P.v. para o diagnóstico da malária, na Atenção Básica de Saúde, no município de Manaus, Amazonas.

Malaria is routinely diagnosed using the thick blood smear test. However, this technique requires the training of microscopists and may be time-consuming. A concordance study was conducted on two dipstick tests (Optimal-IT and ICT P.f./P.v.) and the thick blood smear test, within primary healthcare in Manaus.

Avaliação dos testes rápidos Optimal-IT® e ICT P.f./P.v.® para o diagnóstico da malária, na Atenção Básica de Saúde, no município de Manaus, Amazonas / Evaluation of the Optimal-IT® and ICT Pf/Pv® rapid dipstick tests for diagnosing malaria within primary healthcare in the municipality of Manaus, Amazonas

O diagnóstico da malária é realizado rotineiramente pelo exame da gota espessa, entretanto, esta técnica requer o treinamento de microscopistas e pode consumir muito tempo. Foi realizado um estudo de concordância de dois testes rápidos (Optimal-IT® e ICT P.f./P.v.®) com a gota espessa, na atenção básica de saúde, em Manaus.

Malaria is routinely diagnosed using the thick blood smear test. However, this technique requires the training of microscopists and may be time-consuming. A concordance study was conducted on two dipstick tests (Optimal-IT® and ICT P.f./P.v.®) and the thick blood smear test, within primary healthcare in Manaus.

[Treatment of children with malaria Plasmodium falciparum with derivatives artemisinin]. / Tratamento de crianças com malária pelo Plasmodium falciparum com derivados da artemisinina.

From January 1996 to December 1998, artemisinin derivatives were prescribed to 108 children infected with Plasmodium falciparum. The therapeutic effect was evaluated. Only children with moderate or severe malaria were included. Group I (intravenous artesunate; n = 62): 50.8% with moderate malaria and 49.2% with severe malaria; 53.2% with mild parasitemia, 22.6% with moderate parasitemia and 24.2% with high parasitemia; Group II (intramuscular artemether [Paluter ]; n = 46): 67.4% with moderate malaria and 32.6% with severe malaria; 52.2% with mild parasitemia, 36.2% with moderate parasitemia and 15.2% with high parasitemia; clinical amelioration and clearance of parasitemia showed no statistical difference between the groups. All patients cleared the parasitemia at the seventh day of follow-up (D7). In order to avoid recrudescence, mefloquine or clindamycin was used.

Tratamento de crianças com malária pelo Plasmodium falciparum com derivados da artemisinina / Treatment of children with malaria Plasmodium falciparum with derivatives artemisinin

No período compreendido entre janeiro de 1996 e dezembro de 1998, administramos derivados da artemisinina em 108 crianças com malária por Plasmodium falciparum, para avaliar a resposta clínica e terapêutica. Foram incluídas apenas crianças com clínica de malária moderada ou grave. No Grupo I, incluímos 62 pacientes e administramos artesunate por via endovenosa. Clinicamente, 50,8 por cento tinham malária moderada e 49,2 por cento malária grave; a parasitemia foi baixa em 53,2 por cento, média em 22,6 por cento e alta em 24,2 por cento; no D2 a parasitemia estava negativa em 58,1 por cento. No Grupo II,incluímos 46 pacientes que receberam artemeter (Paluter®) intramuscular. Clinicamente, 67,4 por cento apresentavam malária moderada e 32,6 por cento malária grave; a parasitemia foi baixa em 52,2 por cento, média em 36,2 por cento e alta em 15,2 por cento; em D2, 56,5 por cento apresentaram negativaçäo da parasitemia. Nos dois grupos, a melhora clínica e evoluçäo da parasitemia näo mostraram diferença estatística; no D7 havia clareada a parasitemia em todos os pacientes. Para evitar recrudescência usamos mefloquina ou clindamicina