Multi-parallel qPCR provides increased sensitivity and diagnostic breadth for gastrointestinal parasites of humans: field-based inferences on the impact of mass deworming

BACKGROUND: Although chronic morbidity in humans from soil transmitted helminth (STH) infections can be reduced by anthelmintic treatment, inconsistent diagnostic tools make it difficult to reliably measure the impact of deworming programs and often miss light helminth infections. METHODS: Cryopreserved stool samples from 796 people (aged 2-81 years) in four villages in Bungoma County, western Kenya, were assessed using multi-parallel qPCR for 8 parasites and compared to point-of-contact assessments of the same stools by the 2-stool 2-slide Kato-Katz (KK) method. All subjects were treated with albendazole and all Ascaris lumbricoides expelled post-treatment were collected. Three months later, samples from 633 of these people were re-assessed by both qPCR and KK, re-treated with albendazole and the expelled worms collected. RESULTS: Baseline prevalence by qPCR (n = 796) was 17 % for A. lumbricoides, 18 % for Necator americanus, 41 % for Giardia lamblia and 15% for Entamoeba histolytica. The prevalence was <1% for Trichuris trichiura, Ancylostoma duodenale, Strongyloides stercoralis and Cryptosporidium parvum. The sensitivity of qPCR was 98% for A. lumbricoides and N. americanus, whereas KK sensitivity was 70% and 32%, respectively. Furthermore, qPCR detected infections with T. trichiura and S. stercoralis that were missed by KK, and infections with G. lamblia and E. histolytica that cannot be detected by KK. Infection intensities measured by qPCR and by KK were correlated for A. lumbricoides (r = 0.83, p < 0.0001) and N. americanus (r = 0.55, p < 0.0001). The number of A. lumbricoides worms expelled was correlated (p < 0.0001) with both the KK (r = 0.63) and qPCR intensity measurements (r = 0.60). CONCLUSIONS: KK may be an inadequate tool for stool-based surveillance in areas where hookworm or Strongyloides are common or where intensity of helminth infection is low after repeated rounds of chemotherapy. Because deworming programs need to distinguish between populations where parasitic infection is controlled and those where further treatment is required, multi-parallel qPCR (or similar high throughput molecular diagnostics) may provide new and important diagnostic information

Observed Reductions in Schistosoma mansoni Transmission from Large-Scale Administration of Praziquantel in Uganda: A Mathematical Modelling Study

To date schistosomiasis control programmes based on chemotherapy have largely aimed at controlling morbidity in treated individuals rather than at suppressing transmission. In this study, a mathematical modelling approach was used to estimate reductions in the rate of Schistosoma mansoni reinfection following annual mass drug administration (MDA) with praziquantel in Uganda over four years (2003-2006). In doing this we aim to elucidate the benefits of MDA in reducing community transmission.Age-structured models were fitted to a longitudinal cohort followed up across successive rounds of annual treatment for four years (Baseline: 2003, TREATMENT: 2004-2006; n = 1,764). Instead of modelling contamination, infection and immunity processes separately, these functions were combined in order to estimate a composite force of infection (FOI), i.e., the rate of parasite acquisition by hosts.MDA achieved substantial and statistically significant reductions in the FOI following one round of treatment in areas of low baseline infection intensity, and following two rounds in areas with high and medium intensities. In all areas, the FOI remained suppressed following a third round of treatment.This study represents one of the first attempts to monitor reductions in the FOI within a large-scale MDA schistosomiasis morbidity control programme in sub-Saharan Africa. The results indicate that the Schistosomiasis Control Initiative, as a model for other MDA programmes, is likely exerting a significant ancillary impact on reducing transmission within the community, and may provide health benefits to those who do not receive treatment. The results obtained will have implications for evaluating the cost-effectiveness of schistosomiasis control programmes and the design of monitoring and evaluation approaches in general

The global distribution of lymphatic filariasis, 2000–18: a geospatial analysis

Background Lymphatic filariasis is a neglected tropical disease that can cause permanent disability through disruption of the lymphatic system. This disease is caused by parasitic filarial worms that are transmitted by mosquitos. Mass drug administration (MDA) of antihelmintics is recommended by WHO to eliminate lymphatic filariasis as a public health problem. This study aims to produce the first geospatial estimates of the global prevalence of lymphatic filariasis infection over time, to quantify progress towards elimination, and to identify geographical variation in distribution of infection. Methods A global dataset of georeferenced surveyed locations was used to model annual 2000–18 lymphatic filariasis prevalence for 73 current or previously endemic countries. We applied Bayesian model-based geostatistics and time series methods to generate spatially continuous estimates of global all-age 2000–18 prevalence of lymphatic filariasis infection mapped at a resolution of 5 km2 and aggregated to estimate total number of individuals infected. Findings We used 14 927 datapoints to fit the geospatial models. An estimated 199 million total individuals (95% uncertainty interval 174–234 million) worldwide were infected with lymphatic filariasis in 2000, with totals for WHO regions ranging from 3·1 million (1·6–5·7 million) in the region of the Americas to 107 million (91–134 million) in the South-East Asia region. By 2018, an estimated 51 million individuals (43–63 million) were infected. Broad declines in prevalence are observed globally, but focal areas in Africa and southeast Asia remain less likely to have attained infection prevalence thresholds proposed to achieve local elimination. Interpretation Although the prevalence of lymphatic filariasis infection has declined since 2000, MDA is still necessary across large populations in Africa and Asia. Our mapped estimates can be used to identify areas where the probability of meeting infection thresholds is low, and when coupled with large uncertainty in the predictions, indicate additional data collection or intervention might be warranted before MDA programmes cease

Potential for transmission of schistosomiasis in Kayonza district

Introduction: Schistosomiasis, also known as bilharzia or snail fever, is a tropical parasitic disease caused by a trematode platyhelminthes called Schistosoma sp. Schistosoma species are transmitted by cercariae penetrating the skin when a person is bathing, washing clothes, fishing or engaged in agricultural activities; involving contact with fresh water that has fecal or urinary contamination, and contains the parasites’ snail host. The present study aimed to survey freshwater snails in Kayonza District (Rwanda) especially Lake Muhazi and surrounding water bodies, stream and swamps to assess the potential for transmission of two species of Schistosoma: S. mansoni and S. haematobium . Methods: Six sites were selected to assess the potential for transmission of schistosomiasis. The intermediate hosts of schistosomes, namely the snails Biomphalaria , Bulinus sp. and Lymnaea sp., were collected and brought to the laboratory and investigated to see if trematode cercaria responsible for the disease were present. Results: Snails dissected were not only infected with trematode cercaria but also with annelids and flatworms (Platyhelminths). Cercaria found therein were of two types: furcocercous, probably responsible for schistosomiasis; and gymnocephalous cercaria for fasciolasis: an infection of cattle, goats and sheep. Conclusion: Biomphalaria sp were the major hosts for schistosome cercaria, and most snails collected of this species were infected. Moreover, they were found in large number from all sites. Lymnaea sp, hosts snails for Fasciola cercaria , were also found in a considerable number compared to the low number of Bulinus sp in the region. District and national authorities may wish to further investigate this infestation and identify potential interventions to disrupt the disease transmission.Introduction: La schistosomiase également connue sous le nom de bilharziose est une maladie parasitaire tropicale causée par des plathelminthes trématodes appelés schistosomes. Les Schistosomes sont transmises par des cercaires pénétrant la peau quand une personne se baigne, lave des vêtements, pêche ou pendant des activités agricoles en contact avec l’eau douce contaminée par des matières fécales ou urinaires, et contenant les mollusques hôtes intermédiaires des parasites. La présente étude visait à examiner les mollusques d’eau douce dans le district de Kayonza (Rwanda) particulièrement le lac Muhazi et les eaux environnantes: les ruisseaux et les marais; pour évaluer le potentiel de la transmission de deux espèces de schistosome: Schistosoma mansoni et Schistosoma haematobium . Méthodes: Six endroits ont été choisis pour évaluer le potentiel pour la transmission de la schistosomiase. Des mollusques hôtes intermédiaires des schistosomes, à savoir les espèces de Biomphalaria , Bulinus sp. et Lymnaea sp. ont été collectés, amenés au laboratoire et étudiés pour voir si les cercaires de trématodes responsables de la maladie étaient présentes. Résultats: Des mollusques disséqués ont été atteints par les cercaires de trématodes mais également par des annélides et des vers plats (Plathelminthes). Les Cercaires trouvées là-dedans étaient de deux types: furcocercaires, probablement responsable de la schistosomiase et cercaires gymnocéphales probablement responsables du fasciolose: une infection du bétail, des chèvres et des moutons. Conclusion: Les espèces Biomphalaria étaient les principaux hôtes des cercaires des schistosomes, les plus infectés parmi les espèces des mollusques collectés. Ces espèces de Biomphalaria ont été trouvées en grand nombre dans tous les sites. Les espèces de Lymnaea, mollusques hôtes intermédiaires pour les cercaires de Fasciola cercaria , ont été également trouvés en nombre considérable comparé à un nombre peu élevé des espèces Bulinus dans la région. Les autorités de district et ainsi que nationales devraient étudier davantage cette infestation et identifier les interventions potentielles pour interrompre sa transmission

Preventive chemotherapy to control soil-transmitted helminthiasis averted more than 500 000 DALYs in 2015

Abstract Background Preventive chemotherapy (PC), the large-scale administration of anthelminthics, is recommended by the World Health Organization (WHO) for the control of soil-transmitted helminthiasis (STH). Since 2010, donated anthelminthics for STH have boosted the implementation of PC programmes in children, achieving global coverage of more than 60% in 2015. The WHO Global Health Estimates attribute an annual loss of over 3.3 million disability-adjusted life-years (DALYs) to STH. The aim of this study is to estimate the impact of PC programmes on child morbidity. Method We used data from the WHO Global Health Estimates, national coverage data on PC and the results of an evaluation of the impact of PC in 17 countries on morbidity previously conducted by our group. Results We estimated that the implementation of PC averted in 2015 over 44% of the DALYs that would have been caused in children by STH without the control intervention. A reduction in morbidity of over 75% is expected, if the global target is reached in 2020. If the programme is subsequently maintained, morbidity from STH will be almost totally removed by 2025. Conclusions In endemic areas, preventive chemotherapy provides a significant health benefit. We consider this estimation potentially useful to evaluate the cost utility of the investment made by several endemic countries on PC to control STH

Development of a public geographical information system-based website to follow the impact of control activities of soil-transmitted helminths in endemic countries

Soil-transmitted helminth (STH) infections are among the most common neglected tropical diseases worldwide causing high morbidity and mortality rates in endemic areas. Preventive chemotherapy (PC) programmes and health education are recom-mended by the World Health Organization (WHO) to reduce the impact of STH in endemic countries. Following our role as WHO collaborating centre (WHO CC ITA-116), we have developed a WebGIS and a dataset to support PC programmes to monitor the impact of STH control. This vHealth presentation shows the potentiality of these tools in improving communication among WHO’s regional and country offices, Ministries of Health, phar-maceutical industries and other partners

In-vitro susceptibility of Plasmodium falciparum to monodesethylamodiaquine, dihydroartemisinin and quinine in an area of high chloroquine resistance in Rwanda

Plasmodium falciparum in-vitro susceptibility to chloroquine (CQ), monodesethylamodiaquine, quinine and dihydroartemisinin was investigated in Rwandan patients with a parasitaemia of at least >or=4000/microl. The study was carried out in November-December 2003. Dihydroartemisinin was the most potent (GM IC(50)=2.6nmol/l, 95% CI 2.2-3.2) among the drugs tested. Resistance to chloroquine was 45% (33/74) and that to monodesethylamodiaquine 7% (5/74). All the tested isolates were susceptible to quinine. The mean IC(50) of monodesethylamodiaquine, quinine and dihydroartemisinin was significantly higher for chloroquine-resistant than for chloroquine-sensitive strains (P<0.05). The IC(50) of each drug was significantly and positively correlated to that of the other three drugs (P<0.005), and this correlation was higher between CQ and monodesethylamodiaquine (r=0.8). In-vitro CQ resistance is linked to that of the other drugs tested. Most worrying is the positive correlation between the IC(50) of dihydroartemisinin and the other drugs, more particularly with CQ, suggesting an increased tolerance of the parasites to all drugs

A Recent Update Of Schistomiasis Mansoni Endemicity Around Lake Rweru

Background: Schistosomiasis remains a global public health challenge with an estimated 200 million cases reported each year. In Rwanda, the prevalence of schistosomiasis was recently examined by a countrywide mapping conducted by the Neglected Tropical Disease (NTD) Control Programme of the Rwandan Ministry of Health in partnership with The Access Project. Unfortunately, that study failed to consider one area of endemicity -- Lake Rweru, located in Bugesera District, Eastern Province, Rwanda. This screening aimed to evaluate Lake Rweru and its environs in order to determine next steps for disease control. Methods: The lake’s shore inhabitants, including children and adults, were invited to be screened for intestinal schistosomiasis. The stool examination was performed by Kato-Katz technique. Results: A total of 270 children and adults were parasitologically screened. Fifty seven (57) cases of schistosomiasis mansoni were confirmed (21.1%). The highest proportion of S. mansoni infection was observed at Mazane Island (30.1% of 93 island inhabitants screened). Conclusion: The present results confirm that Lake Rweru is a significant source of S. mansoni infection in the country. We recommend further future investigations in order to know the true disease prevalence. While the mass de-worming campaign against schistosomiasis in addition to soil-transmitted helminthiasis is being regularly conducted by the Ministry of Health in all endemic areas, the population surrounding Lake Rweru should receive special attention.Contexte: La schistosomiase demeure un problème important de santé publique globalement avec environ 200 millions de cas rapportés chaque année. Au Rwanda, la situation de la schistosomiase a été récemment mise à jour par une cartographie nationale conduite par le Programme de Contrôle des Maladies Tropicales Négligées (MTN) du Ministère de la Santé en collaboration avec The Access Project. Cependant, le lac Rweru situé dans le District de Bugesera, Province de l’Est, Rwanda, a été incorrectement manqué parmi les foyers les plus endémiques. L’investigation visait à confirmer le foyer afin de déterminer de prochaines étapes pour le contrôle de l’infestation à Schistosoma mansoni. Méthodes: La population habitant aux alentours du lac Rweru comprenant des enfants et des adultes a été invitée à fournir leurs échantillons de selles en vue d’être examinés pour la schistosomiase intestinale. L’examen de selles a été réalisé par la technique de Kato-Katz. Résultats: Un total de 270 individus (des enfants et des adultes) ont été examinés parasitologiquement. Cinquante-sept (57) cas de schistosomiase mansoni ont été confirmés (21.1%). On a observé la proportion la plus élevée de l’infection à S. mansoni à l’île de Mazane (30.1% de 93 habitants insulaires testés). Conclusion: Les résultats actuels confirment que le lac Rweru est une source importante de S. mansoni dans le pays. Nous recommandons des enquêtes postérieures afin de connaître la vraie prévalence de la maladie dans cette zone. Pendant que la campagne de déparasitage de masse contre la schistosomiase en plus des géo-helminthiases est régulièrement organisée par le Ministère de la Santé dans toutes les zones endémiques, la population environnant le lac Rweru devrait recevoir une attention particulière

The global progress of soil-transmitted helminthiases control in 2020 and world health organization targets for 2030

Soil-transmitted helminth (STH) infections are the most widespread of the neglected tropical diseases, primarily affecting marginalized populations in low-and middle-income countries. More than one billion people are currently infected with STHs. For the control of these infec-tions, the World Health Organization (WHO) recommends an integrated approach, which includes access to appropriate sanitation, hygiene education, and preventive chemotherapy (i.e., large-scale, periodic distribution of anthelmintic drugs). Since 2010, WHO has coordinated two large donations of benzimidazoles to endemic countries. Thus far, more than 3.3 billion benzimidazole tablets have been distributed in schools for the control of STH infec-tions, resulting in an important reduction in STH-attributable morbidity in children, while addi-tional tablets have been distributed for the control of lymphatic filariasis. This paper (i) summarizes the progress of global STH control between 2008 to 2018 (based on over 690 reports submitted by endemic countries to WHO); (ii) provides regional and country details on preventive chemotherapy coverage; and (iii) indicates the targets identified by WHO for the next decade and the tools that should be developed to attain these targets. The main message is that STH-attributable morbidity can be averted with evidence-informed program planning, implementation, and monitoring. Caution will still need to be exercised in stopping control programs to avoid any rebound of prevalence and loss of accrued morbidity gains. Over the next decade, with increased country leadership and multi-sector engagement, the goal of eliminating STH infections as a public health problem can be achieved