...other major trends noted in GBD 2013 include a 71% reduction in the number of cases of human African trypanosomiasis (HAT) infection. Because such cases were not included in the current estimates, ...this may have led to an underestimation of the burden of cysticercosis by the GBD 2013. ...this means that part of the disability incurred by other neurological and mental health disorders caused by NCC increases the DALYs of these diseases, making other disorders look less important. ...terms such as prevalence or cases are not always clearly defined in GBD models for individual diseases, which can create some confusion when interpreting the meaning of the results. ...we have not seen meaningful declines in diseases such as hookworm infection, trichuriasis, and schistosomiasis, while for dengue, leishmaniasis, and foodborne trematodiases, we have seen substantial increases 3. ...we need to consider adopting public health policies to address these trends and adapt our current approaches to specifically guide better disease surveillance, improved water quality and sanitation, affordable diagnostic tests, access to healthcare and medications, and further investments in new preventive and disease-control technologies.
Abstract
Background
Due to spatial heterogeneity in onchocerciasis transmission, the duration of ivermectin mass drug administration (MDA) required for eliminating onchocerciasis will vary within ...endemic areas and the occurrence of transmission “hotspots” is inevitable. The geographical scale at which stop-MDA decisions are made will be a key driver in how rapidly national programs can scale down active intervention upon achieving the epidemiological targets for elimination.
Methods
We used 2 onchocerciasis models (EPIONCHO-IBM and ONCHOSIM) to predict the likelihood of achieving elimination by 2030 in Africa, accounting for variation in preintervention endemicity levels and histories of ivermectin treatment. We explore how decision making at contrasting geographical scales (community vs larger scale “project”) changes projections on populations still requiring MDA or transitioning to post-treatment surveillance.
Results
The total population considered grows from 118 million people in 2020 to 136 million in 2030. If stop-MDA decisions are made at project level, the number of people requiring treatment declines from 69–118 million in 2020 to 59–118 million in 2030. If stop-MDA decisions are made at community level, the numbers decline from 23–81 million in 2020 to 15–63 million in 2030. The lower estimates in these prediction intervals are based on ONCHOSIM, the upper limits on EPIONCHO-IBM.
Conclusions
The geographical scale at which stop-MDA decisions are made strongly determines how rapidly national onchocerciasis programs can scale down MDA programs. Stopping in portions of project areas or transmission zones would free up human and economic resources.
A disproportionate burden of helminthiases in human populations occurs in marginalised, low-income, and resource-constrained regions of the world, with over 1 billion people in developing areas of ...sub-Saharan Africa, Asia, and the Americas infected with one or more helminth species. The morbidity caused by such infections imposes a substantial burden of disease, contributing to a vicious circle of infection, poverty, decreased productivity, and inadequate socioeconomic development. Furthermore, helminth infection accentuates the morbidity of malaria and HIV/AIDS, and impairs vaccine efficacy. Polyparasitism is the norm in these populations, and infections tend to be persistent. Hence, there is a great need to reduce morbidity caused by helminth infections. However, major deficiencies exist in diagnostics and interventions, including vector control, drugs, and vaccines. Overcoming these deficiencies is hampered by major gaps in knowledge of helminth biology and transmission dynamics, platforms from which to help develop such tools. The Disease Reference Group on Helminths Infections (DRG4), established in 2009 by the Special Programme for Research and Training in Tropical Diseases (TDR), was given the mandate to review helminthiases research and identify research priorities and gaps. In this review, we provide an overview of the forces driving the persistence of helminthiases as a public health problem despite the many control initiatives that have been put in place; identify the main obstacles that impede progress towards their control and elimination; and discuss recent advances, opportunities, and challenges for the understanding of the biology, epidemiology, and control of these infections. The helminth infections that will be discussed include: onchocerciasis, lymphatic filariasis, soil-transmitted helminthiases, schistosomiasis, food-borne trematodiases, and taeniasis/cysticercosis.
As part of a 4-year control programme beginning in 2003 and entitled
Piga Vita Kichocho, around 140 000 school-aged children on Unguja Island, Zanzibar were treated annually with a combination of ...praziquantel and albendazole. To provide information on the impact of this intervention, a subset of children, originating from 24 sentinel schools, were monitored in 2004, 2005 and 2006 using both parasitological and behavioural questionnaire methods. Overall, prevalence of urinary schistosomiasis fell by 52%, intensity by 55% and gross haematuria by 82%. There was a positive and statistically significant correlation between areas of elevated disease prevalence and areas of predicted high transmission based upon local occurrence of the permissive intermediate snail host. In areas of low transmission, urinary schistosomiasis was greatly reduced, but, by contrast, other intervention strategies are needed to complement and synergise with chemotherapy in high transmission areas. Whereas significant reductions were documented in the prevalence of both
Trichuris trichiura and hookworm, prevalence of
Ascaris lumbricoides significantly increased over the monitoring period. Through a detailed analysis of named child records, evidence of predisposition to helminth (re)infection and individual bias towards polyparasitism was detected, highlighting the often overlapping distribution of these parasites within the school-aged child.
Over the past decade malaria intervention coverage has been scaled up across Africa. However, it remains unclear what overall reduction in transmission is achievable using currently available tools.
...We developed an individual-based simulation model for Plasmodium falciparum transmission in an African context incorporating the three major vector species (Anopheles gambiae s.s., An. arabiensis, and An. funestus) with parameters obtained by fitting to parasite prevalence data from 34 transmission settings across Africa. We incorporated the effect of the switch to artemisinin-combination therapy (ACT) and increasing coverage of long-lasting insecticide treated nets (LLINs) from the year 2000 onwards. We then explored the impact on transmission of continued roll-out of LLINs, additional rounds of indoor residual spraying (IRS), mass screening and treatment (MSAT), and a future RTS,S/AS01 vaccine in six representative settings with varying transmission intensity (as summarized by the annual entomological inoculation rate, EIR: 1 setting with low, 3 with moderate, and 2 with high EIRs), vector-species combinations, and patterns of seasonality. In all settings we considered a realistic target of 80% coverage of interventions. In the low-transmission setting (EIR approximately 3 ibppy infectious bites per person per year), LLINs have the potential to reduce malaria transmission to low levels (<1% parasite prevalence in all age-groups) provided usage levels are high and sustained. In two of the moderate-transmission settings (EIR approximately 43 and 81 ibppy), additional rounds of IRS with DDT coupled with MSAT could drive parasite prevalence below a 1% threshold. However, in the third (EIR = 46) with An. arabiensis prevailing, these interventions are insufficient to reach this threshold. In both high-transmission settings (EIR approximately 586 and 675 ibppy), either unrealistically high coverage levels (>90%) or novel tools and/or substantial social improvements will be required, although considerable reductions in prevalence can be achieved with existing tools and realistic coverage levels.
Interventions using current tools can result in major reductions in P. falciparum malaria transmission and the associated disease burden in Africa. Reduction to the 1% parasite prevalence threshold is possible in low- to moderate-transmission settings when vectors are primarily endophilic (indoor-resting), provided a comprehensive and sustained intervention program is achieved through roll-out of interventions. In high-transmission settings and those in which vectors are mainly exophilic (outdoor-resting), additional new tools that target exophagic (outdoor-biting), exophilic, and partly zoophagic mosquitoes will be required.
Abstract
Background
The diagnostic gold standard for onchocerciasis relies on identification and enumeration of (skin-dwelling) Onchocerca volvulus microfilariae (mf) using the skin snip technique ...(SST). In a recent study, blood-borne Loa loa mf were found by SST in individuals heavily infected with L. loa, and microscopically misidentified as O. volvulus due to their superficially similar morphology. This study investigates the relationship between L. loa microfilarial density (Loa MFD) and the probability of testing SST positive.
Methods
A total of 1053 participants from the (onchocerciasis and loiasis coendemic) East Region in Cameroon were tested for (1) Loa MFD in blood samples, (2) O. volvulus presence by SST, and (3) Immunoglobulin (Ig) G4 antibody positivity to Ov16 by rapid diagnostic test (RDT). A Classification and Regression Tree (CART) model was used to perform a supervised classification of SST status and identify a Loa MFD threshold above which it is highly likely to find L. loa mf in skin snips.
Results
Of 1011 Ov16-negative individuals, 28 (2.8%) tested SST positive and 150 (14.8%) were L. loa positive. The range of Loa MFD was 0–85 200 mf/mL. The CART model subdivided the sample into 2 Loa MFD classes with a discrimination threshold of 4080 (95% CI, 2180–12 240) mf/mL. The probability of being SST positive exceeded 27% when Loa MFD was >4080 mf/mL.
Conclusions
The probability of finding L. loa mf by SST increases significantly with Loa MFD. Skin-snip polymerase chain reaction would be useful when monitoring onchocerciasis prevalence by SST in onchocerciasis–loiasis coendemic areas.
Highlights • Modern statistical methods offer robust ways to estimate anthelmintic drug efficacy. • Marginal models permit robust inference on population covariates of drug efficacy. • Mixed models ...allow inference on individuals and quantify inter-individual variation. • Models may be used to detect changing drug efficacy during mass drug administration.
Malaria transmission depends on vector life-history parameters and population dynamics, and particularly on the survival of adult Anopheles mosquitoes. These dynamics are sensitive to climatic and ...environmental factors, and temperature is a particularly important driver. Data currently exist on the influence of constant and fluctuating adult environmental temperature on adult Anopheles gambiae s.s. survival and on the effect of larval environmental temperature on larval survival, but none on how larval temperature affects adult life-history parameters.
Mosquito larvae and pupae were reared individually at different temperatures (23 ± 1°C, 27 ± 1°C, 31 ± 1°C, and 35 ± 1°C), 75 ± 5% relative humidity. Upon emergence into imagoes, individual adult females were either left at their larval temperature or placed at a different temperature within the range above. Survival was monitored every 24 hours and data were analysed using non-parametric and parametric methods. The Gompertz distribution fitted the survivorship data better than the gamma, Weibull, and exponential distributions overall and was adopted to describe mosquito mortality rates.
Increasing environmental temperature during the larval stages decreased larval survival (p < 0.001). Increases of 4°C (from 23°C to 27°C, 27°C to 31°C, and 31°C to 35°C), 8°C (27°C to 35°C) and 12°C (23°C to 35°C) statistically significantly increased larval mortality (p < 0.001). Higher environmental temperature during the adult stages significantly lowered adult survival overall (p < 0.001), with increases of 4°C and 8°C significantly influencing survival (p < 0.001). Increasing the larval environment temperature also significantly increased adult mortality overall (p < 0.001): a 4°C increase (23°C to 27°C) did not significantly affect adult survival (p > 0.05), but an 8°C increase did (p < 0.05). The effect of a 4°C increase in larval temperature from 27°C to 31°C depended on the adult environmental temperature. The data also suggest that differences between the temperatures of the larval and adult environments affects adult mosquito survival.
Environmental temperature affects Anopheles survival directly during the juvenile and adult stages, and indirectly, since temperature during larval development significantly influences adult survival. These results will help to parameterise more reliable mathematical models investigating the potential impact of temperature and global warming on malaria transmission.
About the Authors: Matthew R. Behrend * E-mail: behrend04@gmail.com Affiliations Neglected Tropical Diseases, Bill & Melinda Gates Foundation, Seattle, Washington, United States of America, Blue Well ...8, Seattle, Washington, United States of America ORCID logo http://orcid.org/0000-0002-5664-0520 María-Gloria Basáñez Affiliation: MRC Centre for Global Infectious Disease Analysis and London Centre for Neglected Tropical Disease Research, Department of Infectious Disease Epidemiology, Imperial College London, London, United Kingdom Jonathan I. D. Hamley Affiliation: MRC Centre for Global Infectious Disease Analysis and London Centre for Neglected Tropical Disease Research, Department of Infectious Disease Epidemiology, Imperial College London, London, United Kingdom Travis C. Porco Affiliation: Francis I. Proctor Foundation for Research in Ophthalmology, Department of Epidemiology and Biostatistics, and Department of Ophthalmology, University of California, San Francisco, United States of America Wilma A. Stolk Affiliation: Department of Public Health, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands Martin Walker Affiliations London Centre for Neglected Tropical Disease Research, Department of Pathobiology and Population Sciences, Royal Veterinary College, Hatfield, Hertfordshire, United Kingdom, London Centre for Neglected Tropical Disease Research and Department of Infectious Disease Epidemiology, Imperial College London, London, United Kingdom Sake J. de Vlas Affiliation: Department of Public Health, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands ORCID logo http://orcid.org/0000-0002-1830-5668 for the NTD Modelling Consortium Introduction The neglected tropical diseases (NTDs) thrive mainly among the poorest populations of the world.
Onchocerciasis (a filarial disease caused by infection with Onchocerca volvulus and transmitted by blackfly, Simulium, vectors) probably provides the best example of impactful modelling, with its long history of using evidence—mostly from the ONCHOSIM and EPIONCHO transmission models 7—to support decision-making within ongoing multicountry control initiatives (Table 1).
Onchocerciasis modelling and policy impact. https://doi.org/10.1371/journal.pntd.0008033.t001 From the start of the NTD Modelling Consortium in 2015, there have been several other examples of impactful modelling, which could be divided over three major scales of operations: (1) developing WHO guidelines (e.g., for triple-drug therapy, with ivermectin, diethylcarbamazine, and albendazole, against lymphatic filariasis 16, 17); (2) informing funding decisions for new intervention tools (e.g., the development of a schistosomiasis vaccine 18); and (3) guiding within-country targeting of control (e.g., local vector control for human African trypanosomiasis in the Democratic Republic of the Congo 19, 20 and Chad 21).
Relative word frequencies are represented by size of the font. https://doi.org/10.1371/journal.pntd.0008033.g002 Scoring the guidance statements Authors coded the data set individually (MRB, TCP, WAS, SJdV) and jointly (M-GB, JIDH, MW), producing five independently coded sets of data (S1 Table).
The clinical outcomes associated with Chagas disease remain poorly understood. In addition to the burden of morbidity, the burden of mortality due to Trypanosoma cruzi infection can be substantial, ...yet its quantification has eluded rigorous scrutiny. This is partly due to considerable heterogeneity between studies, which can influence the resulting estimates. There is a pressing need for accurate estimates of mortality due to Chagas disease that can be used to improve mathematical modelling, burden of disease evaluations, and cost-effectiveness studies.
A systematic literature review was conducted to select observational studies comparing mortality in populations with and without a diagnosis of Chagas disease using the PubMed, MEDLINE, EMBASE, Web of Science and LILACS databases, without restrictions on language or date of publication. The primary outcome of interest was mortality (as all-cause mortality, sudden cardiac death, heart transplant or cardiovascular deaths). Data were analysed using a random-effects model to obtain the relative risk (RR) of mortality, the attributable risk percent (ARP), and the annual mortality rates (AMR). The statistic I(2) (proportion of variance in the meta-analysis due to study heterogeneity) was calculated. Sensitivity analyses and publication bias test were also conducted.
Twenty five studies were selected for quantitative analysis, providing data on 10,638 patients, 53,346 patient-years of follow-up, and 2739 events. Pooled estimates revealed that Chagas disease patients have significantly higher AMR compared with non-Chagas disease patients (0.18 versus 0.10; RR = 1.74, 95% CI 1.49-2.03). Substantial heterogeneity was found among studies (I(2) = 67.3%). The ARP above background mortality was 42.5%. Through a sub-analysis patients were classified by clinical group (severe, moderate, asymptomatic). While RR did not differ significantly between clinical groups, important differences in AMR were found: AMR = 0.43 in Chagas vs. 0.29 in non-Chagas patients (RR = 1.40, 95% CI 1.21-1.62) in the severe group; AMR = 0.16 (Chagas) vs. 0.08 (non-Chagas) (RR = 2.10, 95% CI 1.52-2.91) in the moderate group, and AMR = 0.02 vs. 0.01 (RR = 1.42, 95% CI 1.14-1.77) in the asymptomatic group. Meta-regression showed no evidence of study-level covariates on the effect size. Publication bias was not statistically significant (Egger's test p=0.08).
The results indicate a statistically significant excess of mortality due to Chagas disease that is shared among both symptomatic and asymptomatic populations.
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