A Comprehensive Analysis of the Genetic Diversity of Plasmodium falciparum Histidine-Rich Protein 2 (PfHRP2) in the Brazilian Amazon.

Early diagnosis and treatment are fundamental to the control and elimination of malaria. In many endemic areas, routine diagnosis is primarily performed microscopically, although rapid diagnostic tests (RDTs) provide a useful point-of-care tool. Most of the commercially available RDTs detect histidine-rich protein 2 (HRP2) of Plasmodium falciparum in the blood of infected individuals. Nonetheless, parasite isolates lacking the pfhrp2 gene are relatively frequent in some endemic regions, thereby hampering the diagnosis of malaria using HRP2-based RDTs. To track the efficacy of RDTs in areas of the Brazilian Amazon, we assessed pfhrp2 deletions in 132 P. falciparum samples collected from four malaria-endemic states in Brazil. Our findings show low to moderate levels of pfhrp2 deletion in different regions of the Brazilian Amazon. Overall, during the period covered by this study (2002-2020), we found that 10% of the P. falciparum isolates were characterized by a pfhrp2 deletion. Notably, however, the presence of pfhrp2-negative isolates has not been translated into a reduction in RDT efficacy, which in part may be explained by the presence of polyclonal infections. A further important finding was the discrepancy in the proportion of pfhrp2 deletions detected using two assessed protocols (conventional PCR versus nested PCR), which reinforces the need to perform a carefully planned laboratory workflow to assess gene deletion. This is the first study to perform a comprehensive analysis of PfHRP2 sequence diversity in Brazilian isolates of P. falciparum. We identified 10 PfHRP2 sequence patterns, which were found to be exclusive of each of the assessed regions. Despite the small number of PfHRP2 sequences available from South America, we found that the PfHRP2 sequences identified in Brazil and neighboring French Guiana show similar sequence patterns. Our findings highlight the importance of continuously monitoring the occurrence and spread of parasites with pfrhp2 deletions, while also taking into account the limitations of PCR-based testing methods associated with accuracy and the complexity of infections.

Prevalence of hepatitis B and D virus infection in a district of Mato Grosso, bordering Amazonas and Rondônia states.

INTRODUCTION: Brazil's western Amazon basin has the highest prevalence of hepatitis B virus (HBV) infection in the country. Coinfection with hepatitis D virus (HDV) is also endemic. To estimate the prevalence of HBV and HDV markers in a population inhabiting the northwest portion of Mato Grosso state in the western Amazon. METHODS: We performed a cross-sectional study of the seroprevalence of antibodies against HBV core antigen (anti-HBc) in the Três Fronteiras District northwest of Mato Grosso. Anti-HBc-positive subjects were tested for HBV surface antigen (HBsAg). Those positive for this marker were tested for HDV antibodies. Anti-HBc-negative participants were tested for anti-HBsAg. All tests were performed by EIA. RESULTS: A total of 623 individuals in the community were assessed; the majority (67.6%) were male, with a mean age of 30.8 ± 15.4 years. Two hundred and fourteen individuals (34.3%) were anti-HBc-positive, and 47 (7.5%) were HBsAg carriers. Only one individual was anti-HDV-positive. Among the 409 individuals without HBV infection, 18.3% were anti-HBsAg-positive. There was no association between HBV infection and known risk factors. CONCLUSIONS: The study area had intermediate-to-high endemicity for HBV infection, but a low prevalence of HDV. Our serological results suggesting low vaccination-induced protection indicate a need for reinforced immunization programs in the populations of northwest Mato Grosso.

Prevalence of hepatitis B and D virus infection in a district of Mato Grosso, bordering Amazonas and Rondônia states

Abstract INTRODUCTION: Brazil's western Amazon basin has the highest prevalence of hepatitis B virus (HBV) infection in the country. Coinfection with hepatitis D virus (HDV) is also endemic. To estimate the prevalence of HBV and HDV markers in a population inhabiting the northwest portion of Mato Grosso state in the western Amazon. METHODS: We performed a cross-sectional study of the seroprevalence of antibodies against HBV core antigen (anti-HBc) in the Três Fronteiras District northwest of Mato Grosso. Anti-HBc-positive subjects were tested for HBV surface antigen (HBsAg). Those positive for this marker were tested for HDV antibodies. Anti-HBc-negative participants were tested for anti-HBsAg. All tests were performed by EIA. RESULTS: A total of 623 individuals in the community were assessed; the majority (67.6%) were male, with a mean age of 30.8 ± 15.4 years. Two hundred and fourteen individuals (34.3%) were anti-HBc-positive, and 47 (7.5%) were HBsAg carriers. Only one individual was anti-HDV-positive. Among the 409 individuals without HBV infection, 18.3% were anti-HBsAg-positive. There was no association between HBV infection and known risk factors. CONCLUSIONS: The study area had intermediate-to-high endemicity for HBV infection, but a low prevalence of HDV. Our serological results suggesting low vaccination-induced protection indicate a need for reinforced immunization programs in the populations of northwest Mato Grosso.

In vitro antimalarial activity of tigecycline against Plasmodium falciparum culture-adapted reference strains and clinical isolates from the Brazilian Amazon.

INTRODUCTION: We evaluated the in vitro antimalarial activity of tigecycline as an alternative drug for the treatment of severe malaria. METHODS: A chloroquine-sensitive Plasmodium falciparum reference strain, a chloroquine-resistant reference strain, and three clinical isolates were tested for in vitro susceptibility to tigecycline. A histidine-rich protein in vitro assay was used to evaluate antimalarial activity. RESULTS: The geometric-mean 50% effective concentration (EC50%) of tigecycline was 535.5 nM (confidence interval (CI): 344.3-726.8). No significant correlation was found between the EC50% of tigecycline and that of any other tested antimalarial drug. CONCLUSIONS: Tigecycline may represent an alternative drug for the treatment of patients with severe malaria.

In vitro antimalarial activity of tigecycline against Plasmodium falciparum culture-adapted reference strains and clinical isolates from the Brazilian Amazon

Introduction: We evaluated the in vitro antimalarial activity of tigecycline as an alternative drug for the treatment of severe malaria. Methods: A chloroquine-sensitive Plasmodium falciparum reference strain, a chloroquine-resistant reference strain, and three clinical isolates were tested for in vitro susceptibility to tigecycline. A histidine-rich protein in vitro assay was used to evaluate antimalarial activity. Results: The geometric-mean 50% effective concentration (EC50%) of tigecycline was 535.5 nM (confidence interval (CI): 344.3-726.8). No significant correlation was found between the EC50% of tigecycline and that of any other tested antimalarial drug. Conclusions: Tigecycline may represent an alternative drug for the treatment of patients with severe malaria. .