Incipient colonisation of Lutzomyia longipalpis in the city of Resistencia, province of Chaco, Argentina (2010-2012)

Lutzomyia longipalpis was recorded for the first time in Argentina in 2004, in the province of Formosa. In the following years, the vector spread to the south and west in the country and was recorded in the province of Chaco in 2010. From November 2010-May 2012, captures of Phlebotominae were made in the city of Resistencia and its surroundings, to monitor the spread and possible colonisation of Lu. longipalpis in the province of Chaco. In this monitoring, Lu. longipalpis was absent in urban sampling sites and its presence was restricted to Barrio de los Pescadores. This suggests that the incipient colonisation observed in 2010 was not followed by continuous installation of vector populations and expansion of their spatial distribution as in other urban centres of Argentina.

A four-year surveillance program for detection of Plasmodium falciparum chloroquine resistance in Honduras

Countries could use the monitoring of drug resistance in malaria parasites as an effective early warning system to develop the timely response mechanisms that are required to avert the further spread of malaria. Drug resistance surveillance is essential in areas where no drug resistance has been reported, especially if neighbouring countries have previously reported resistance. Here, we present the results of a four-year surveillance program based on the sequencing of the pfcrt gene of Plasmodium falciparum populations from endemic areas of Honduras. All isolates were susceptible to chloroquine, as revealed by the pfcrt “CVMNK” genotype in codons 72-76.

Mitochondrial genome sequence diversity of Indian Plasmodium falciparum isolates

We have analysed the whole mitochondrial (mt) genome sequences (each ~6 kilo nucleotide base pairs in length) of four field isolates of the malaria parasite Plasmodium falciparum collected from different locations in India. Comparative genomic analyses of mt genome sequences revealed three novel India-specific single nucleotide polymorphisms. In general, high mt genome diversity was found in Indian P. falciparum, at a level comparable to African isolates. A population phylogenetic tree placed the presently sequenced Indian P. falciparum with the global isolates, while a previously sequenced Indian isolate was an outlier. Although this preliminary study is limited to a few numbers of isolates, the data have provided fundamental evidence of the mt genome diversity and evolutionary relationships of Indian P. falciparum with that of global isolates.

Varicella zoster virus reactivation during or immediately following treatment of tegumentary leishmaniasis with antimony compounds

Antimony compounds are the cornerstone treatments for tegumentary leishmaniasis. The reactivation of herpes virus is a side effect described in few reports. We conducted an observational study to describe the incidence of herpes zoster reactivation during treatment with antimony compounds. The global incidence of herpes zoster is approximately 2.5 cases per 1,000 persons per month (or 30 cases per 1,000 persons per year). The estimated incidence of herpes zoster in patients undergoing antimony therapy is higher than previously reported.

The mazEF toxin-antitoxin system as a novel antibacterial target in Acinetobacter baumannii

Although analysis of toxin-antitoxin (TA) systems can be instructive, to date, there is no information on the prevalence and identity of TA systems based on a large panel of Acinetobacter baumannii clinical isolates. The aim of the current study was to screen for functional TA systems among clinical isolates of A. baumannii and to identify the systems’ locations. For this purpose, we screened 85 A. baumannii isolates collected from different clinical sources for the presence of the mazEF, relBE and higBA TA genes. The results revealed that the genes coding for the mazEF TA system were commonly present in all clinical isolates of A. baumannii. Reverse transcriptase-polymerase chain reaction analysis showed that transcripts were produced in the clinical isolates. Our findings showed that TA genes are prevalent, harboured by chromosomes and transcribed within A. baumannii. Hence, activation of the toxin proteins in the mazEF TA system should be investigated further as an effective antibacterial strategy against this bacterium.

Outstanding insecurities concerning the use of an Ov16-based ELISA in the Amazonia onchocerciasis focus

In a recent issue of Memórias do Instituto Oswaldo Cruz, published in Rio de Janeiro in February 2014 (109: 87-92), Adami et al. have published a survey reporting Mansonella parasite prevalence in the Amazon Region. This report makes a useful contribution to the existing knowledge of filarial parasite distribution within the Amazon area, parasite prevalence rates in relation to age and occupation and provides observations on the possible clinical impact of Mansonella ozzardi. Their publication also provides an account of what appears to be a novel ELISA that has recently been used in the Simuliidae and Onchocerciasis Laboratory of the Oswaldo Cruz Institute, Rio de Janeiro, Brazil. We are concerned that the publication of this ELISA may have created an excessively positive impression of the effectiveness of the onchocerciasis recrudescence serological surveillance tools that are presently available for use in the Amazonia onchocerciasis focus. In this letter we have, thus, sought to highlight some of the limitations of this ELISA and suggest how continuing insecurities concerning the detection of antibodies to Onchocerca volvulus within the Amazonia onchocerciasis focus might be minimised.

Knockout confirmation for Hurries: rapid genotype identification of Trypanosoma cruzi transfectants by polymerase chain reaction directly from liquid culture

Gene knockout is a widely used approach to evaluate loss-of-function phenotypes and it can be facilitated by the incorporation of a DNA cassette having a drug-selectable marker. Confirmation of the correct knockout cassette insertion is an important step in gene removal validation and has generally been performed by polymerase chain reaction (PCR) assays following a time-consuming DNA extraction step. Here, we show a rapid procedure for the identification of Trypanosoma cruzi transfectants by PCR directly from liquid culture - without prior DNA extraction. This simple approach enabled us to generate PCR amplifications from different cultures varying from 106-108 cells/mL. We also show that it is possible to combine different primer pairs in a multiplex detection reaction and even to achieve knockout confirmation with an extremely simple interpretation of a real-time PCR result. Using the “culture PCR” approach, we show for the first time that we can assess different DNA sequence combinations by PCR directly from liquid culture, saving time in several tasks for T. cruzi genotype interrogation.

Getting ready for malaria elimination: a check list of critical issues to consider

In recent years, a renewed interest in malaria elimination and eradication has emerged and seems to be rooting in the minds of the scientific community, public health specialists, funding bodies, policy makers and politicians. Malaria eradication will certainly benefit from improved and innovative tools; notwithstanding novel knowledge in fields ranging from basic science to mathematical modelling and health systems research. However, the elimination of malaria also encompasses a broad range of essential aspects that countries and other actors need to consider when thinking of embarking on such an adventure, including the implementation of innovative strategies, the ability to incorporate the most up-to-date evidence into policy, the integration of malaria into the broader health agenda, the strengthening of surveillance and health systems, capacity building, funding, advocacy and, very importantly, research. While in some cases this enthusiasm is clearly justified, some countries are still a long way from realistically advancing towards elimination. This paper attempts to provide guidance on all the necessary issues that should be considered when initiating a malaria elimination program.

Plasmodium vivax malaria elimination: should innovative ideas from the past be revisited?

In the 1950s, the strategy of adding chloroquine to food salt as a prophylaxis against malaria was considered to be a successful tool. However, with the development of Plasmodium resistance in the Brazilian Amazon, this control strategy was abandoned. More than 50 years later, asexual stage resistance can be avoided by screening for antimalarial drugs that have a selective action against gametocytes, thus old prophylactic measures can be revisited. The efficacy of the old methods should be tested as complementary tools for the elimination of malaria.

Malaria on the Guiana Shield: a review of the situation in French Guiana

In a climate of growing concern that Plasmodium falciparum may be developing a drug resistance to artemisinin derivatives in the Guiana Shield, this review details our current knowledge of malaria and control strategy in one part of the Shield, French Guiana. Local epidemiology, test-treat-track strategy, the state of parasite drug resistance and vector control measures are summarised. Current issues in terms of mobile populations and legislative limitations are also discussed.

Emerging Plasmodium vivax resistance to chloroquine in South America: an overview

The global emergence of Plasmodium vivax strains resistant to chloroquine (CQ) since the late 1980s is complicating the current international efforts for malaria control and elimination. Furthermore, CQ-resistant vivax malaria has already reached an alarming prevalence in Indonesia, East Timor and Papua New Guinea. More recently, in vivo studies have documented CQ-resistant P. vivax infections in Guyana, Peru and Brazil. Here, we summarise the available data on CQ resistance across P. vivax-endemic areas of Latin America by combining published in vivo and in vitro studies. We also review the current knowledge regarding the molecular mechanisms of CQ resistance in P. vivax and the prospects for developing and standardising reliable molecular markers of drug resistance. Finally, we discuss how the Worldwide Antimalarial Resistance Network, an international collaborative effort involving malaria experts from all continents, might contribute to the current regional efforts to map CQ-resistant vivax malaria in South America.

Slow clearance of Plasmodium vivax with chloroquine amongst children younger than six months of age in the Brazilian Amazon

Plasmodium vivax is the most widespread parasite causing malaria, being especially prevalent in the Americas and Southeast Asia. Children are one of the most affected populations, especially in highly endemic areas. However, there are few studies evaluating the therapeutic response of infants with vivax malaria. This study retrospectively evaluated the parasitaemia clearance in children diagnosed with vivax malaria during the first five days of exclusive treatment with chloroquine (CQ). Infants aged less than six months old had a significantly slower parasitaemia clearance time compared to the group of infants and children between six months and 12 years old (Kaplan-Meier survival analysis; Wilcoxon test; p = 0.004). The impaired clearance of parasitaemia in younger children with vivax malaria is shown for the first time in Latin America. It is speculated that CQ pharmacokinetics in young children with vivax malaria is distinct, but this specific population may also allow the detection of CQ-resistant parasites during follow-up, due to the lack of previous immunity.

Blood shizonticidal activities of phenazines and naphthoquinoidal compounds against Plasmodium falciparum in vitro and in mice malaria studies

Due to the recent advances of atovaquone, a naphthoquinone, through clinical trials as treatment for malarial infection, 19 quinone derivatives with previously reported structures were also evaluated for blood schizonticide activity against the malaria parasite Plasmodium falciparum. These compounds include 2-hydroxy-3-methylamino naphthoquinones (2-9), lapachol (10), nor-lapachol (11), iso-lapachol (12), phthiocol (13) and phenazines (12-20). Their cytotoxicities were also evaluated against human hepatoma and normal monkey kidney cell lines. Compounds 2 and 5 showed the highest activity against P. falciparum chloroquine-resistant blood-stage parasites (clone W2), indicated by their low inhibitory concentration for 50% (IC50) of parasite growth. The therapeutic potential of the active compounds was evaluated according to the selectivity index, which is a ratio of the cytotoxicity minimum lethal dose which eliminates 50% of cells and the in vitro IC50. Naphthoquinones 2 and 5, with activities similar to the reference antimalarial chloroquine, were also active against malaria in mice and suppressed parasitaemia by more than 60% in contrast to compound 11 which was inactive. Based on their in vitro and in vivo activities, compounds 2 and 5 are considered promising molecules for antimalarial treatment and warrant further study.

G6PD deficiency in Latin America: systematic review on prevalence and variants

Plasmodium vivax radical cure requires the use of primaquine (PQ), a drug that induces haemolysis in glucose-6-phosphate dehydrogenase deficient (G6PDd) individuals, which further hampers malaria control efforts. The aim of this work was to study the G6PDd prevalence and variants in Latin America (LA) and the Caribbean region. A systematic search of the published literature was undertaken in August 2013. Bibliographies of manuscripts were also searched and additional references were identified. Low prevalence rates of G6PDd were documented in Argentina, Bolivia, Mexico, Peru and Uruguay, but studies from Curaçao, Ecuador, Jamaica, Saint Lucia, Suriname and Trinidad, as well as some surveys carried out in areas of Brazil, Colombia and Cuba, have shown a high prevalence (> 10%) of G6PDd. The G6PD A-202A mutation was the variant most broadly distributed across LA and was identified in 81.1% of the deficient individuals surveyed. G6PDd is a frequent phenomenon in LA, although certain Amerindian populations may not be affected, suggesting that PQ could be safely used in these specific populations. Population-wide use of PQ as part of malaria elimination strategies in LA cannot be supported unless a rapid, accurate and field-deployable G6PDd diagnostic test is made available.