Strategies supporting the prevention and control of neglected tropical diseases during and beyond the COVID-19 pandemic.

Emerging and re-emerging zoonotic diseases represent a public health challenge of international concern. They include a large group of neglected tropical diseases (NTDs), many of which are of zoonotic nature. Coronavirus disease 2019 (COVID-19), another emerging zoonotic disease, has just increased the stakes exponentially. Most NTDs are subject to the impact of some of the very same human-related activities triggering other emerging and re-emerging diseases, including COVID-19, severe acute respiratory syndrome (SARS), bird flu and swine flu. It is conceivable that COVID-19 will exacerbate the NTDs, as it will divert much needed financial and human resources. There is considerable concern that recent progress achieved with control and elimination efforts will be reverted. Future potential strategies will need to reconsider the determinants of health in NTDs in order to galvanize efforts and come up with a comprehensive, well defined programme that will set the stage for an effective multi-sectorial approach. In this Commentary, we propose areas of potential synergies between the COVID-19 pandemic control efforts, other health and non-health sector initiatives and NTD control and elimination programmes.

Identification of Entamoeba histolytica and E. dispar infection in Maceió, Alagoas State, northeast Brazil.

INTRODUCTION: A cross-sectional study was carried out to assess the prevalence of E. histolytica and E. dispar by examining stool samples obtained from 1,003 students of public schools in Maceió, Alagoas, Brazil. METHODOLOGY: All stool samples were processed using the spontaneous sedimentation technique and examined microscopically for the presence of Entamoeba species. In order to distinguish infections caused by E. histolytica, fecal samples presenting cysts of Entamoeba were subjected to specific enzyme-linked immunosorbent assay (ELISA) and polymerase chain reaction (PCR). RESULTS: The analysis of the fecal specimens by microscopy identified 6.4% (64/1,003) students positive for E. histolytica/E. dispar/E. moshkovskii cysts. The prevalence of E. histolytica detected by ELISA was 3.0% (30/1,003) and by PCR 2.8% (28/1,003), but the difference is not statistically significant (p > 0.05). The prevalence of E. dispar in schoolchildren was 5.0% (50/1,003). Mixed infections with E. histolytica and E. dispar were also detected by PCR.  Even though immunological and molecular methods have shown similar results for identification of E. histolytica, ELISA is advantageous over the PCR since it is relatively cheaper and easier to perform. CONCLUSIONS: Our study demonstrated the occurrence of E. histolytica in Maceió and highlights the need to introduce a specific diagnostic test to detect amoebiasis cases in public laboratories.

New approaches in antimalarial drug discovery and development: a review.

Malaria remains a major world health problem following the emergence and spread of Plasmodium falciparum that is resistant to the majority of antimalarial drugs. This problem has since been aggravated by a decreased sensitivity of Plasmodium vivax to chloroquine. This review discusses strategies for evaluating the antimalarial activity of new compounds in vitro and in animal models ranging from conventional tests to the latest high-throughput screening technologies. Antimalarial discovery approaches include the following: the discovery of antimalarials from natural sources, chemical modifications of existing antimalarials, the development of hybrid compounds, testing of commercially available drugs that have been approved for human use for other diseases and molecular modelling using virtual screening technology and docking. Using these approaches, thousands of new drugs with known molecular specificity and active against P. falciparum have been selected. The inhibition of haemozoin formation in vitro, an indirect test that does not require P. falciparum cultures, has been described and this test is believed to improve antimalarial drug discovery. Clinical trials conducted with new funds from international agencies and the participation of several industries committed to the eradication of malaria should accelerate the discovery of drugs that are as effective as artemisinin derivatives, thus providing new hope for the control of malaria.

Assessment of family and neighbors of an individual infected with Wuchereria bancrofti from a non-endemic area in the city of Maceió, Brazil.

The family and neighbors of a patient infected with W. bancrofti microfilariae were assessed aiming to evaluate the occurrence of cases of lymphatic filariasis in a non-endemic area in the city of Maceió, in the Brazilian state of Alagoas. The patient had previously lived in an endemic focus; however, he has been living in an area where the parasite has never been detected for the past ten years. Female ingurgitated Culex quinquefasciatus mosquitoes captured in the houses of the microfilaremic individual and of his neighbors in the non-endemic region were also examined by polymerase chain reaction (PCR) technique. The thick blood smear examination, blood membrane filtration, and rapid immunochromatography (antigen search) revealed no infected individuals in the family of the microfilaremic individual. All 334 neighbors undergoing the thick blood smear examination were negative for W. bancrofti microfilariae. In 478 ingurgitated C. quinquefasciatus mosquitoes examined by PCR, no W. bancrofti DNA was detected. The microfilaremic individual had a microfilaremia considered very low according to WHO standards (4 microfilariae/mL of blood). As the vectorial infection depends on microfilaremia, the patient's low parasite load did not determine the contamination of other individuals in the area. Our data have shown that the long-term residence of the microfilaremic individual in the non-endemic region was not sufficient to start a new transmission focus of lymphatic filariasis in Maceió.

Studies on the antimicrobial activity and brine shrimp toxicity of Zeyheria tuberculosa (Vell.) Bur. (Bignoniaceae) extracts and their main constituents.

BACKGROUND: Due to the indiscriminate use of antimicrobial drugs, the emergence of human pathogenic microorganisms resistant to major classes of antibiotics has been increased and has caused many clinical problems in the treatment of infectious diseases. Thus, the aim of this study was to evaluate for the first time the in vitro antimicrobial activity and brine shrimp lethality of extracts and isolated compounds from Zeyheria tuberculosa (Vell.) Bur., a species used in Brazilian folk medicine for treatment of cancer and skin diseases. METHODS: Using the disc diffusion method, bioautography assay and brine shrimp toxicity test (Artemia salina Leach), we studied the antimicrobial activity and lethality of extracts and isolated compounds against three microorganisms strains, including Gram-positive (Staphylococcus aureus) and Gram-negative (Pseudomonas aeruginosa) bacteria and yeasts (Candida albicans). RESULTS: In this study, the extracts inhibited S. aureus (8.0 +/- 0.0 to 14.0 +/- 0.0 mm) and C. albicans (15.3 +/- 0.68 to 25.6 +/- 0.4 mm) growth. In the brine shrimp test, only two of them showed toxic effects (LC50 29.55 to 398.05 microg/mL) and some extracts were non-toxic or showed weak lethality (LC50 705.02 to > 1000 microg/mL). From these extracts, four flavones [5,6,7,8-tetramethoxyflavone (1), 5,6,7-trimethoxyflavone (2), 4'-hydroxy-5,6,7,8-tetramethoxyflavone (3), and 4'-hydroxy-5,6,7-trimethoxyflavone (4)] were isolated through bioassay-guided fractionation and identified based on the 1D and 2D NMR spectral data. By bioautography assays, compounds 1 [S. aureus (16.0 +/- 0.0 mm) and C. albicans (20.0 +/- 0.0 mm)] and 3 [S. aureus (10.3 +/- 0.6 mm) and C. albicans (19.7 +/- 0.6 mm)] inhibited both microorganisms while 2 inhibited only S. aureus (11.7 +/- 0.6 mm). Compound 4 did not restrain the growth of any tested microorganism. CONCLUSION: Our results showed that extracts and isolated flavones from Z. tuberculosa may be particularly useful against two pathogenic microorganisms, S. aureus and C. albicans. These results may justify the popular use this species since some fractions tested had antimicrobial activity and others showed significant toxic effects on brine shrimps. However, in order to evaluate possible clinical application in therapy of infectious diseases, further studies about the safety and toxicity of isolated compounds are needed.

Constituintes químicos e avaliação preliminar in vivo da atividade antimalárica de Ouratea nitida Aubl (Ochnaceae) / Chemical constituents and in vivo preliminary evaluation of antimalarial activity of Ouratea nitida Aubl. (Ochnaceae)

O presente trabalho descreve o isolamento de triterpenos (ácido 3,4-seco-friedelan-3-óico, friedelina e b-amirina) e outros compostos (éster etílico do ácido p-hidroxibenzóico e tetracosano), bem como a avaliação preliminar in vivo da atividade antimalárica de extratos das folhas de Ouratea nitida Aubl. Análise qualitativa através de CG-EM de uma fração apolar do extrato em hexano também foi efetuada. Ésteres metílicos e etílicos dos ácidos laúrico, mirístico, palmítico, esteárico e oléico, metílicos dos ácidos pentadecanóico, heptadecanóico, araquidônico, behênico e lignocérico e o etílico do ácido linoléico foram os componentes majoritários; enquanto que o estearato de n-butila, o tetracosano e a 6,10,14-trimetil-2-pentadecanona foram os minoritários. Os compostos isolados foram identificados com base na análise dos dados espectrais (IV, EM e RMN, incluindo DEPT) e estão sendo descritos pela primeira vez nesta espécie.

This work describes the isolation of triterpenes (3,4-seco-friedelan-3-oic acid, friedelin, and b-amyrin) and other compounds (p-hydroxybenzoic acid ethyl ester and tetracosane) as well as a preliminary evaluation of in vivo antimalarial activity of the extracts from the leaves of Ouratea nitida Aubl. Qualitative analysis by GC-MS of an apolar fraction from the hexane extract was also carried out. Methyl and ethyl esters of lauric, myristic, palmitic, stearic and oleic acids, methyl ester of pentadecanoic, heptadecanoic, arachidonic, beenic and lignoceric acids, and ethyl ester of linoleic acid were found to be the main constituents while n-butyl stearate, tetracosane and 6,10,14-trimetthyl-2-pentadecanone were the minor. All isolated compounds were identified on basis of the spectral data (IR, MS and NMR, including DEPT) and are being described for the first time in this specie.

Filariose bancroftiana no Brasil / Bancroftian filariasis in Brazil

Foi feita revisäo dos estudos sobre a distribuiçäo geográfica e prevalência da filariose linfática bancroftiana no Brasil. Entre 1951 a 1958 foram realizados inquéritos hemoscópicos e entomológicos no país, sendo a transmissäo autóctone comprovada em apenas 11 Municípios: Ponta Grossa (SC), 14,5 por cento; Belém (PA), 9,8 por cento; Barra de Laguna (SC), 9,4 por cento; Recife (PE), 6,9 por cento; Castro Alves (BA), 5,9 por cento; Florianópolis (SC), 1,4 por cento; Säo Luís (MA), 0,6 por cento; Salvador (BA), 0,4 por cento; Maceió (AL), 0,3 por cento; Manaus (AM), 0,2 por cento e Porto Alegre (RS), 0,1 por cento. A distribuiçaö da parasitose era urbana e focal, principamente em cidades litorânes. As açöes de controle implementadas levaram a uma precíavel queda nas taxas de microfilarêmicos sendo consideradas, a partir de entäo, áreas endemicas para Filariose linfática no Brasil somente as cidades de Belém e Recife. Estudos recentes mostram a transmissäo ativa de parasitose, com prevalências superiores às detectadas no passado, em Maceió, cujo foco era considerado extinto, e em Recife. O conhecimento da situaçäo atual de bancroftose no Brasil é de fundamental importância para a implementaçäo de açöes de controle da endemia envolvendo o Ministério da Saúde e órgäo de saúde pública.

A comparison of two Brazilian populations of Culex quinquefasciatus (Say, 1823) from endemic and non-endemic areas to infection with Wuchereria bancrofti (Cobbold, 1877)

Culex quinquefasciatus is known to be an efficient insect host of Wuchereria bancrofti. In Brazil Cx. quinquefasciatus is widely distributed throughout the country and is often abundant in and around human habitations. In contrast, Bancroftian filariasis is limited to three foci in Brazil. Experiments were undertaken to compare the vector capacities of Cx. quinquefasciatus originating from Maceio (Alagoas), one of the endemic areas of W. bancrofti infection in Brazil, and Belo Horizonte (Minas Gerais), a non endemic area. Laboratory-reared Cx. quinquefasciatus were dissected 20 days after blood feeding on microfilaraemic patients. Survival rates and the number of infective larvae that developed did not differ in female mosquitoes of different origins. Thus both populations of Culex were susceptible to infection with W. bancrofti.

Situaçäo atual da filariose bancroftiana na cidade de Maceió, estado de Alagoas, Brasil / Present status of bancroftian filariasis in Maceió, state of Alagoas, Brazil

Determina a prevalência e a distribuiçäo da filariose linfática bancroftiana na área urbana de Maceió, estado de Alagoas, assim como identifica os insetos vetores na regiäo, com esse objetivo, foram realizados inquéritos hemoscópicos e entomológicos. Foram examinados, pelo método da gota espessa, amostras de sangue de 10.450 escolares oriundos de diferentes regioes da cidade, sendo detectado 0,66 por cento de indivíduos microfilarêmicos por Wuchereria bancrofti. A parasitose tem distribuiçäo focal com 80 por cento dos indivíduos com infecçäo patente detectados em duas regioes vizinhas, cujas prevalências atingiram 1,24 por cento e 5,25 por cento. Estudos paralelos feitos em amostras populacionais com indivíduos de diferentes faixas etárias mostraram prevalências semelhantes às detectadas entre os escolares. No entanto, o exame dos familiares de indivíduos infectados pela W. bancrofti mostrou prevalência seis vezes mais alta, sugerindo maior transmissäo no intradomicílio. A percentagem de parasitados foi maior no grupo etário mais jovem (< 20 anos). Mosquitos culex quinquefasciatus capturados nos bairros onde a parasitose foi detectada apresentavam taxas de infecçäo natural de 0,28 por cento até 4,62 por cento. Descreve a ocorrência da transmissäo natural da filariose bancroftiana na área urbana de Maceió, Alagoas. Medidas de controle da filariose foram planejadas para conter sua expansäo na regiäo analisada.