Metabolomics in the fight against malaria

Metabolomics uses high-resolution mass spectrometry to provide a chemical fingerprint of thousands of metabolites present in cells, tissues or body fluids. Such metabolic phenotyping has been successfully used to study various biologic processes and disease states. High-resolution metabolomics can shed new light on the intricacies of host-parasite interactions in each stage of the Plasmodium life cycle and the downstream ramifications on the host’s metabolism, pathogenesis and disease. Such data can become integrated with other large datasets generated using top-down systems biology approaches and be utilised by computational biologists to develop and enhance models of malaria pathogenesis relevant for identifying new drug targets or intervention strategies. Here, we focus on the promise of metabolomics to complement systems biology approaches in the quest for novel interventions in the fight against malaria. We introduce the Malaria Host-Pathogen Interaction Center (MaHPIC), a new systems biology research coalition. A primary goal of the MaHPIC is to generate systems biology datasets relating to human and non-human primate (NHP) malaria parasites and their hosts making these openly available from an online relational database. Metabolomic data from NHP infections and clinical malaria infections from around the world will comprise a unique global resource.

Immunoregulation in human malaria: the challenge of understanding asymptomatic infection

Asymptomatic Plasmodium infection carriers represent a major threat to malaria control worldwide as they are silent natural reservoirs and do not seek medical care. There are no standard criteria for asymptomaticPlasmodium infection; therefore, its diagnosis relies on the presence of the parasite during a specific period of symptomless infection. The antiparasitic immune response can result in reducedPlasmodium sp. load with control of disease manifestations, which leads to asymptomatic infection. Both the innate and adaptive immune responses seem to play major roles in asymptomatic Plasmodiuminfection; T regulatory cell activity (through the production of interleukin-10 and transforming growth factor-β) and B-cells (with a broad antibody response) both play prominent roles. Furthermore, molecules involved in the haem detoxification pathway (such as haptoglobin and haeme oxygenase-1) and iron metabolism (ferritin and activated c-Jun N-terminal kinase) have emerged in recent years as potential biomarkers and thus are helping to unravel the immune response underlying asymptomatic Plasmodium infection. The acquisition of large data sets and the use of robust statistical tools, including network analysis, associated with well-designed malaria studies will likely help elucidate the immune mechanisms responsible for asymptomatic infection.

Malaria in gold-mining areas in Colombia

Gold-mining may play an important role in the maintenance of malaria worldwide. Gold-mining, mostly illegal, has significantly expanded in Colombia during the last decade in areas with limited health care and disease prevention. We report a descriptive study that was carried out to determine the malaria prevalence in gold-mining areas of Colombia, using data from the public health surveillance system (National Health Institute) during the period 2010-2013. Gold-mining was more prevalent in the departments of Antioquia, Córdoba, Bolívar, Chocó, Nariño, Cauca, and Valle, which contributed 89.3% (270,753 cases) of the national malaria incidence from 2010-2013 and 31.6% of malaria cases were from mining areas. Mining regions, such as El Bagre, Zaragoza, and Segovia, in Antioquia, Puerto Libertador and Montelíbano, in Córdoba, and Buenaventura, in Valle del Cauca, were the most endemic areas. The annual parasite index (API) correlated with gold production (R2 0.82, p < 0.0001); for every 100 kg of gold produced, the API increased by 0.54 cases per 1,000 inhabitants. Lack of malaria control activities, together with high migration and proliferation of mosquito breeding sites, contribute to malaria in gold-mining regions. Specific control activities must be introduced to control this significant source of malaria in Colombia.

Photodynamic antimicrobial chemotherapy (PACT) for the treatment of malaria, leishmaniasis and trypanosomiasis

A photodynamic effect occurs when photosensitiser molecules absorb light and dissipate the absorbed energy by transferring it to biological acceptors (usually oxygen), generating an excess of reactive species that are able to force cells into death pathways. Several tropical diseases present physiopathological aspects that are accessible to the application of a photosensitiser and local illumination. In addition, disease may be transmitted through infected blood donations, and many of the aetiological agents associated with tropical diseases have been shown to be susceptible to the photodynamic approach. However, there has been no systematic investigation of the application of photoantimicrobial agents in the various presentations, whether to human disease or to the disinfection of blood products or even as photo-insecticides. We aim in this review to report the advances in the photoantimicrobial approach that are beneficial to the field of anti-parasite therapy and also have the potential to facilitate the development of low-cost/high-efficiency protocols for underserved populations.

Studies in search of a suitable experimental insect model for xenodiagnosis of hosts with Chagas' disease: 3 - On the interaction of vector species and parasite strain in the reaction of bugs to infection by Trypanosoma cruzi

The reaction of nine vector species of Chagas' disease to infection by seven different Trypanosoma cruzi strains; Berenice, Y, FL, CL, S. Felipe, Colombiana and Gávea, are examined and compared. On the basis of the insects' ability to establish and maintain the infection, vector species could be divided into two distinct groups which differ in their reaction to an acute infection by T. cruzi. While the proportion of positive bugs was found to be low in Triatoma infestans and Triatoma dimidiata it was high, ranging from 96.9% to 100% in the group of wild (Rhodnius neglectus, Triatoma rubrovaria)and essentially sylvatic vectors in process of adaptation to human dwellings, maintained under control following successful insecticidal elimination of Triatoma infestans (Panstrongylus megistus, Triatoma sordida and Triatoma pseudomaculata). An intermediate position is held by Triatoma brasiliensis and Rhodnius prolixus. This latter has been found to interchange between domestic and sylvatic environments. The most important finding is the strikingly good reaction between each species of the sylvatic bugs and practically all T. cruzi strains herein studied, thus indicating that the factors responsible for the excellent reaction of P.megistus to infection by Y strain, as previously reported also come into operation in the reaction of the same vector species to acute infections by five of the remaining T.cruzi strains. Comparison or data reported by other investigators with those herein described form the basis of the discussion of Dipetalogaster maximus as regards its superiority as a xenodiagnostic agent.

Biología de Anopheles (Kerteszia) neivai H., D. & K., 1913 (Diptera: Culicidae) en la Costa Pacifica de Colombia: IV - Estructura etárea y transmisión de malaria

Con el fin de determinar la dinamica de transmisión de malaria en el poblado de Charambirá (Chocó), Colombia, se estudió la estructura etárea de Anopheles neivai (reconocido vector en la Costa Pacífica) con base en su estado gonadotrófico. Se recolectaron mosquitos intradomiciliarmente durante el crepúsculo vespertino con cebos humanos y aspiradores bucales. Los mosquitos recolectados se mantuvieron en cajas cilíndricas de cartón con papel humedecido y dispensadores alimenticios hasta su disección al día siguiente. De los 200 mosquitos disecados entre septiembre y octubre de 1986,68 (34%) presentaban huellas de menos de tres oviposturas y los restantes (66%) habían efectuado al menos tres oviposturas. La diferencia entre el primer grupo considerado como mosquitos "no infectivos" y el segundo considerado como los "potencialmente infectivos" fue altamente significativa (X² = 10,68; P = 0,001). El 1,5% de A. neivai estudiados presentaban huellas correspondientes a 10 oviposturas mostrando una marcada longevidad y múltiples alimentaciones sanguíneas. Los resultados sugieren que existe un alto riesgo de contraer malaria en Charambirá durante el crepúsculo vespertino.

Studies in search of a suitable experimental insect model for xenodiagnosis of hosts with Chagas' disease: 4 - The reflection of parasite stock in the responsiveness of different vector species to chronic infection with different Trypanosoma cruzi stocks

Previous studies (1982,1987) have emphasized the superiority of sylvatic vector species over domestic species as xenodiagnostic agents in testing hosts with acute or chronic infections by T. cruzi "Y" stock. The present study, which is unique in that it contains data on both infectivity rates produced by the same stock in 11 different vector species and also the reaction of the same vector species to seven different parasite stocks, establishes the general validity of linking efficiency of xenodiagnosis to the biotope of its agent. For example, infectivity rates produced by "São Felipe" stock varied from 82.5% to 98.3% in sylvatic vectors but decreased to 42.5% to 71.3% in domestic species. "Colombiana" stock produced in the same sylvatic vectors infectivity rates ranging from 12.5% to 45%. These shrank to 5%-22.5% in domestic bugs. The functional role of the biotope in the vector-parasite interaction has not been eluddated. But since this phenomenon has been observed to be stable and easy to reproduce, it leads us to believe that the results obtained are valid. Data presented also provide increasing evidence that the infectivity rates exhibited by bugs from xenodiagnosis in chronic hosts, are parasite stock specific. For example, infectivity rates produced by "Berenice", "Y", "FL" and "CL" varied in R. neglectus from 26.3% to 75%; in P. megistus from 56.3% to 83.8%; in T. sordida from 28.8% to 58.8% in T. pseudomaculata from 41.3% to 66.3% and in T. rubrovaria from 48.8% to 85%. Data from xenodiagnosis in the same hosts, carrying acute infections by the same parasite stocks, gave the five sylvatic vectors a positive rating of approximately 100%, thus suggesting that the heavy loads of parasites circulating in the acute hosts obscured the characteristic interspecific differences for the parasite stock. Nonetheless these latter were revealed in the same hosts with chronic infections stimulated by very low numbers of the same parasite stocks. Certain observations here described lead us to speculate as to the possibility of further results from other parasite stocks, allowing the association of the infectivity rates produced in bugs by different parasite stocks with the isoenzymic patterns revealed by these stocks.

Populations of larvae of Anopheles spp. in natural breeding sites in Western Venezuela, an area of refractory malaria

Studies have been un dertaken into on the diversity and relative abundance of larvae of Anopheles (Nyssorhynchus) spp. in 22 permanent or temporary pools in an area of 70 km² in the eastern piedmont of the Venezuela Andes, between the mountains and the plains, an area in which malaria is refractory and A. nuñeztovari is present. Twelve species were identified, the most frequent, abundant and sympatric being A. triannulatus, A. albitarsis, A. nuñeztovari, A. oswaldoi and A. strodei. The samples from the permanent pools showed greater diversity of species and greater numbers of larvae than the samples from the temporary pools. The existence of the same larval associations in pools of other localities in the eastern piedmont of the Venezuelan Andes suggests the possibility of the making an ecological map of the breeding sites of A. nuñeztovari and for these anophelines in a region extending for 430 km.

Malaria transmission model for different levels of acquired immunity and temperature-dependent parameters (vector)

OBJECTIVE: Describe the overall transmission of malaria through a compartmental model, considering the human host and mosquito vector. METHODS: A mathematical model was developed based on the following parameters: human host immunity, assuming the existence of acquired immunity and immunological memory, which boosts the protective response upon reinfection; mosquito vector, taking into account that the average period of development from egg to adult mosquito and the extrinsic incubation period of parasites (transformation of infected but non-infectious mosquitoes into infectious mosquitoes) are dependent on the ambient temperature. RESULTS: The steady state equilibrium values obtained with the model allowed the calculation of the basic reproduction ratio in terms of the model's parameters. CONCLUSIONS: The model allowed the calculation of the basic reproduction ratio, one of the most important epidemiological variables.

A mathematical model for malaria transmission relating global warming and local socioeconomic conditions

OBJECTIVE: Sensitivity analysis was applied to a mathematical model describing malaria transmission relating global warming and local socioeconomic conditions. METHODS: A previous compartment model was proposed to describe the overall transmission of malaria. This model was built up on several parameters and the prevalence of malaria in a community was characterized by the values assigned to them. To assess the control efforts, the model parameters can vary on broad intervals. RESULTS: By performing the sensitivity analysis on equilibrium points, which represent the level of malaria infection in a community, the different possible scenarios are obtained when the parameters are changed. CONCLUSIONS: Depending on malaria risk, the efforts to control its transmission can be guided by a subset of parameters used in the mathematical model.

Increase in cases of malaria in Mozambique, 2014: epidemic or new endemic pattern?

ABSTRACT OBJECTIVE To describe the increase in cases of malaria in Mozambique. METHODS Cross-sectional study conducted in 2014, in Mozambique with national weekly epidemiological bulletin data. I analyzed the number of recorded cases in the 2009-2013 period, which led to the creation of an endemic channel using the quartile and C-Sum methods. Monthly incidence rates were calculated for the first half of 2014, making it possible to determine the pattern of endemicity. Months in which the incidence rates exceeded the third quartile or line C-sum were declared as epidemic months. RESULTS The provinces of Nampula, Zambezia, Sofala, and Inhambane accounted for 52.7% of all cases in the first half of 2014. Also during this period, the provinces of Nampula, Sofala and Tete were responsible for 54.9% of the deaths from malaria. The incidence rates of malaria in children, and in all ages, have showed patterns in the epidemic zone. For all ages, the incidence rate has peaked in April (2,573 cases/100,000 inhabitants). CONCLUSIONS The results suggest the occurrence of an epidemic pattern of malaria in the first half of 2014 in Mozambique. It is strategic to have a more accurate surveillance at all levels (central, provincial and district) to target prevention and control interventions in a timely manner.

Immunoserology of malaria

This literature review discusses the most frequently used serodiagnostic methods for the determination of the humoral immune response to malarial parasites. The importance of malaria as a global public health problem is stressed in the light of the new discoveries leading to the future development of an anti-malarial vaccine suitable for use in humans. Serological techniques are expected to play an important role in the assessment of the relative efficacy of these candidate vaccines. A discussion of the different antigen preparation techniques is also presented.

Malária no município de Humaitá, estado do Amazonas: XXI. Prevalência da deficiência de glicose-6-fosfato desidrogenase (G6PD) Em amostra da população e em doentes com malaria causada pelo Plasmodium falciparum

Os autores estudaram a prevalência da deficiência de glicose-6-fosfato desidrogenase (G6PD), pelo método de BREWER et alii, em 141 indivíduos da população do município de Humaitá, Estado do Amazonas. Destes, 128 eram amazônides, 67 dos quais nunca tiveram malária, enquanto que 61 tinham tido ou estavam tendo a doença; os 13 restantes que estavam com malária não eram arnazônides. Os resultados revelaram que 7 arnazônides (4,96%), eram deficientes. Destes, 5 eram do sexo feminino e 2 do masculino. Em todos os indivíduos do sexo feminino o teste foi positivo com comportamento do tipo heterozigoto. Dos indivíduos deficientes, 4 nunca tinham tido malária; dos outros 3, 2 apresentavam a reação de hemaglutinação positiva com título 1/16 e o terceiro estava tendo malária causada pelo Plasmodium falciparum pela primeira vez. Este doente apresentou forma benigna de malária evoluindo para cura clínica e parasitológica no 3.° dia de tratamento com a clindamicina. Nenhum dos 13 doentes não arnazônides apresentava deficiência de G6PD. Dessa forma, não houve diferença na prevalência da deficiência de G6PD em arnazônides que nunca tiveram malária e em arnazônides que tinham tido ou estavam tendo a doença. Portanto, os indivíduos com deficiência de G6PD estão sujeitos a infecções por Plasmodium falciparum na mesma proporção que os não deficientes. Por outro lado, o aumento da prevalência da deficiência de G6PD, na amostra estudada, poderia estar relacionado com a pressão seletiva exercida pela malária em população submetida à homozigose.