This is a summary of the following peer-reviewed, scientific article:
Comparative Evaluation of Immunoassays to Improve Access to Diagnosis for Chagas Disease in Colombia.
Front Chem. 2021; 9: 622286.
Published online 2021 Mar 12. doi: 10.3389/fchem.2021.622286
Trypanosoma cruzi is the etiological agent of Chagas disease (CD), considered one of the most important parasitic infections in Latin America. Between 25 and 90 million humans are at infection risk via at least one of multiple infection mechanisms. Under natural conditions, the principal transmissio...n modes are transplacental or via one of more than 140 hematophagous triatomine bugs (Reduviidae: Triatominae). Triatomines acquire the parasite from mammal reservoirs due to their obligate blood-feeding (albeit triatomines can also feed on non-reservoir vertebrates such as birds and reptiles). The disease burden for CD in the Latin America and Caribbean region, based on disability-adjusted life-years (DALYs), is at least five times greater than that of malaria, and is approximately one-fifth that of HIV/AIDS. In recent decades, CD has extended to other continents outside natural reservoir or vector distributions due to human migration, with a minimum estimated 10 million individuals infected worldwide.
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Chagas disease caused by Trypanosoma cruzi is a public health issue in Latin America. This highly diverse parasite is divided into at least seven discrete typing units (DTUs) TcI-TcVI and Tcbat. Some DTUs have been associated with geographical distribution in epidemiological scenarios and clinical m...anifestations, but these aspects remain poorly understood. Many studies have focused on studying the parasite and its vectors/hosts, using a wide variety of genetic markers and methods. Here, we performed a systematic review of the literature for the last 20 years to present an update of DTUs distribution in the Americas, collecting ecoepidemiological information. We found that the DTUs are widespread across the continent and that there is a whole gamma of genetic markers used for the identification and genotyping of the parasite. The data obtained in this descriptor could improve the molecular epidemiology studies of Chagas disease in endemic regions.
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Chagas is a complex, multidimensional phenomenon in which political, economic, environmental, biomedical, epidemiological, psychological, and sociocultural factors intersect. Nonetheless, the hegemonic conceptualisation has long envisioned Chagas as primarily a biomedical question, while ignoring or... downplaying the other dimensions, and this limited view has reinforced the disease’s long neglect. Integrating the multiple dimensions of the problem into a coherent approach adapted to field realities and needs represents an immense challenge, but the payoff is more effective and sustainable experiences, with higher social awareness, increased case detection and follow-up, improved adherence to care, and integrated participation of various actors from multiple action levels. Information, Education, and Communication (IEC) initiatives have great potential for impact in the implementation of multidimensional programs of prevention and control successfully customised to the diverse and complex contexts where Chagas disease persists.
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For the molecular diagnosis of Chagas disease by real-time PCR (polymerase chain reaction), optimization of diagnostic accuracy is desirable. The detection limit of real-time PCR assays for the diagnosis of Trypanosoma cruzi in human serum is affected by various influences including the choice of th...e nucleic acid extraction assay. In this study, three nucleic acid extraction assays were compared regarding their influence on the sensitivity of a T. cruzi-specific real-time PCR with 62 reference sera containing T. cruzi target DNA (deoxyribonucleotide acid). More than 95% of the positive sera were correctly identified after all three nucleic acid extraction strategies with a detection rate ranging from 96.8% (60/62) for the worst assay to 100% (62/62) for the best one. A matched pairs analysis for the comparison of the cycle threshold (Ct) values obtained with the 59 reference samples with positive real-time PCR results after all three nucleic acid extraction schemes indicated differences in a range of about 3 Ct steps. Summarized, all three compared nucleic acid extraction schemes were basically suitable for T. cruzi-specific PCR from serum with some minor differences. However, in the case of low quantities of circulating parasite DNA in the serum of a patient with Chagas disease, even minor effects can make a difference in the individual diagnosis.
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The sub-Saharan African region, carries 90% of the over 250 million cases of schistosomiasis occurring worldwide. In this region, after Nigeria, Tanzania is second country having the highest cases of schistosomiasis and approximately 51.5%0 of the Tanzanian population is either exposed or live in ar...eas with high risk of exposure. The country is endemic to both Schistosoma mansoni and Schistosoma haematobium, these infections are common in communities characterised with limited access to water, sanitation, hygienic practices and health services. Schistosoma mansoni infection is associated with hepatosplenic disease characterised with hepatomegaly, splenomegaly, progressive periportal fibrosis (PPF) which can lead to portal hypertension and its related sequelae, mainly ascites, liver surface irregularities, oesophageal varices and haematemesis. The main consequences of S. haematobium infection are haematuria, dysuria, nutritional deficiencies, urinary bladder lesions, hydronephrosis, urinary bladder squamous cell carcinoma and in children, growth retardation. Preventive chemotherapy using mass drug administration (MDA) of praziquantel targeting primary school aged children is the main strategy for controlling schistosomiasis in Tanzania.
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Schistosomiasis is a neglected tropical disease of global medical and veterinary importance. As efforts to eliminate schistosomiasis as a public health problem and interrupt transmission gather momentum, the potential zoonotic risk posed by livestock Schistosoma species via viable hybridisation in s...ub-Saharan Africa have been largely overlooked. We aimed to investigate the prevalence, distribution, and multi-host, multiparasite transmission cycle of Haematobium group schistosomiasis in Senegal, West Africa.
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HIV-1 infection disproportionately affects women in sub-Saharan Africa, where areas of high HIV-1 prevalence and Schistosoma haematobium endemicity largely overlap. Female genital schistosomiasis (FGS), caused most frequently by S. haematobium egg deposition in the genital tract, has been associated... with prevalent HIV-1 infection in cross-sectional studies. The presence of S. haematobium eggs in genital tissue is also associated with vascularization and the accumulation of CD4+ lymphocytes and macrophages, making the granuloma-associated environment a potential contributor to HIV-1 vulnerability. In addition to modulation of the local cervicovaginal environment, FGS has also been associated with a higher frequency of systemic CD4 T-cells expressing the chemokine receptor CCR5. Tissue-entrapped eggs are also associated with clinically visible FGS-associated manifestations in the cervicovaginal mucosa. FGS lesions may breach the intact cervicovaginal immune barrier and are hypothesized to provide an entry point for HIV-1 infection. However, the underlying mechanism for potential HIV-1 vulnerability in FGS has not been fully characterized and requires further investigation.
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After 100 years of chemotherapy with impractical and toxic drugs, an oral cure for human African trypanosomiasis (HAT) is available: Fexinidazole. In this case, we review the history of drug discovery for HAT with special emphasis on the discovery, pre-clinical development, and operational challenge...s of the clinical trials of fexinidazole. The screening of the Drugs for Neglected Diseases initiative (DNDi) HAT-library by the Swiss TPH had singled out fexinidazole, originally developed by Hoechst (now Sanofi), as the most promising of a series of over 800 nitroimidazoles and related molecules. In cell culture, fexinidazole has an IC50 of around 1 µM against Trypanosoma brucei and is more than 100-fold less toxic to mammalian cells. In the mouse model, fexinidazole cures both the first, haemolymphatic, and the second, meningoencephalitic stage of the infection, the latter at 100 mg/kg twice daily for 5 days. In patients, the clinical trials managed by DNDi and supported by Swiss TPH mainly conducted in the Democratic Republic of the Congo demonstrated that oral fexinidazole is safe and effective for use against first- and early second-stage sleeping sickness. Based on the positive opinion issued by the European Medicines Agency in 2018, the WHO has released new interim guidelines for the treatment of HAT including fexinidazole as the new therapy for first-stage and non-severe second-stage sleeping sickness caused by Trypanosoma brucei gambiense (gHAT). This greatly facilitates the diagnosis and treatment algorithm for gHAT, increasing the attainable coverage and paving the way towards the envisaged goal of zero transmission by 2030.
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This was a Phase 3, multi-center, randomized, open-label, parallel-group, active control study where 273 male and female patients with first stage Trypanosoma brucei gambiense HAT were treated at six sites: one trypanosomiasis reference center in Angola, one hospital in South Sudan, and four hospita...ls in the Democratic Republic of the Congo between August 2005 and September 2009 to support the registration of pafuramidine for treatment of first stage HAT in collaboration with the United States Food and Drug Administration. Patients were treated with either 100 mg of pafuramidine orally twice a day for 10 days or 4 mg/kg pentamidine intramuscularly once daily for 7 days to assess the efficacy and safety of pafuramidine versus pentamidine. Pregnant and lactating women as well as adolescents were included.
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Schistosomiases are acute or chronic visceral parasitic diseases due to 5 species of trematodes (schistosomes). The three main species infecting humans are Schistosoma haematobium, Schistosoma mansoni and Schistosoma japonicum. Schistosoma mekongi and Schistosoma intercalatum have a more limited dis...tribution.
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Treatment of second-stage gambiense human African trypanosomiasis relied on toxicarsenic-based derivatives for over 50 years. The availability and subsequent use of eflornithine,initially in monotherapy and more recently in combination with nifurtimox (NECT), has drasticallyimproved the pro...gnosis of treated patients. However, NECT logistic and nursing requirementsremain obstacles to its deployment and use in peripheral health structures in rural sub-SaharanAfrica. Two oral compounds, fexinidazole and SCYX-7158, are currently in clinical development.The main scope of this article is to discuss the potential impact of new oral therapies to improvediagnosis-treatment algorithms and patients’access to treatment, and to contribute to reach theobjectives of the recently launched gambiense humanAfrican trypanosomiasis elimination program
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Human African Trypanosomiasis (HAT, sleeping sickness) and Animal African Trypanosomiasis (AAT) are neglected tropical diseases generally caused by the same etiological agent, Trypanosoma brucei. Despite important advances in the reduction or disappearance of HAT cases, AAT represents a risky reserv...oir of the infections. There is a strong need to control AAT, as is claimed by the European Commission in a recent document on the reservation of antimicrobials for human use. Control of AAT is considered part of the One Health approach established by the FAO program against African Trypanosomiasis. Under the umbrella of the One Health concepts, in this work, by analyzing the pharmacological properties of the therapeutic options against Trypanosoma brucei spp., we underline the need for clearer and more defined guidelines in the employment of drugs designed for HAT and AAT. Essential requirements are addressed to meet the challenge of drug use and drug resistance development. This approach shall avoid inter-species cross-resistance phenomena and retain drugs therapeutic activity.
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Chagas disease constitutes a public health problem, and Spain is the non-endemic country with the highest burden of disease outside the Americas. It represents a model for non-endemic countries regarding health policies to control the disease. This study is aimed to generate estimates of the T.cruzi... prevalence and the number of undetected and untreated individuals with the infection in Spain and to compare them with the actual number of cases reported by official sources.
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The major neglected tropical diseases, Taenia solium taeniosis/cysticercosis and schistosomiasis caused by Schistosoma mansoni or S. haematobium are presumed to be widely distributed in Africa. Taenia solium taeniosis/ cysticercosis has been reported as an emerging disease in different regions of Af...rica [1, 2], but currently the exact distribution remains unclear. Reported prevalences of T. solium taeniosis and cysticercosis in African countries are not extensive and are further complicated by the lack of ‘gold standard’ tests for diagnosis.
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Schistosomiasis and soil-transmitted helminths (STH) infections are major public health problems. We aimed to study the 6-mo impact of mass drug administration with praziquantel and albendazole on urinary schistosomiasis and STH.We examined children (aged 2–15 y) from one hamlet, who provided urin...e and faeces samples at baseline (n=197), 1 mo (n=102) and 6 mo (n=92); 67 completed the protocol.At baseline, 47/67 (70.1%) children presented Schistosoma haematobium (75.8% in the baseline total sample) and 12/67 (17.9%) with STH (30.5% in the initial sample, p=0.010). Among the children, 47.3% had heavy Schistosoma haematobium infection. The most frequent STH was Trichuris trichiura in 9.0%. We also found Hymenolepis nana (13.2%) and Plasmodium falciparum (9.1%) infections and anaemia (82.1%). One mo after chemotherapy there was a significant (p=0.013) reduction of Schistosoma haematobium prevalence (23.5%) and a high egg reduction rate (86.9%). Considering the sample of 67 children, the mean egg concentration was 498 at baseline, 65 at 1 mo and 252 at 6 mo (p<0.05). We also observed a reduction in STH infections, 50% in Ascaris lumbricoides, 33.3% in T. trichiura and 50% in hookworms. At 6 mo, the prevalence of Schistosoma haematobium (76.1%) was similar to the baseline and the STH reduction was not significant.Longitudinal studies have reported many losses in these settings, but we were able to show that mass drug administration for control of schistosomiasis and STH present low effectiveness, that reinfections occur rapidly and that stand alone anthelmintic therapy is not a sustainable choice.
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Although estimated to cause the ninth largest disease burden among individual infectious diseases, leishmaniasis is largely ignored in discussions of tropical disease priorities [1,2]. This consignment to critical oblivion results from its complex epidemiology and ecology, the lack of simple, easily...-applied tools for case management and the paucity of current incidence data, and often results in a failure on the part of policy-makers to recognize its importance [3,4]. Based on the World Health Assembly Resolu tion 2007/60.13, the World Health Organization (WHO) convened the Expert Committee on Leishmaniasis in March 2010, which subsequently issued the first updated technical report on leishmaniasis in more than 20 years [5,6].
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Background: The last decade has seen a dramatic increase in international and domestic funding for malaria control, coupled with important declines in malaria incidence and mortality in some regions of the world. As the ongoing climate of financial uncertainty places strains on investment in global ...health, there is an increasing need to audit the origin, recipients and geographical distribution of funding for malaria control relative to populations at risk of the disease. Methods: A comprehensive review of malaria control funding from international donors, bilateral sources and national governments was undertaken to reconstruct total funding by country for each year 2006 to 2010. Regions at risk from Plasmodium falciparum and/or Plasmodium vivax transmission were identified using global risk maps for 2010 and funding was assessed relative to populations at risk. Those nations with unequal funding relative to a regional average were identified and potential explanations highlighted, such as differences in national policies, government inaction or donor neglect.
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Background: Tracking of aid resources to reproductive, maternal, newborn, and child health (RMNCH) provides timely and crucial information to hold donors accountable. For the first time, we examine flows in official development assistance (ODA) and grants from the Bill & Melinda Gates Foundation (co...llectively termed ODA+) in relation to the continuum of care for RMNCH and assess progress since 2003. Methods: We coded and analysed financial disbursements for maternal, newborn, and child health (MNCH) and for reproductive health (R*) to all recipient countries worldwide from all donors reporting to the creditor reporting system database for the years 2011–12. We also included grants from the Bill & Melinda Gates Foundation. We analysed trends for MNCH for the period 2003–12 and for R* for the period 2009–12.
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