The impact of mass drug administration expansion to low onchocerciasis prevalence settings in case of connected villages

Background The existence of locations with low but stable onchocerciasis prevalence is not well understood. An often suggested yet poorly investigated explanation is that the infection spills over from neighbouring locations with higher infection densities. Methodology We adapted the stochastic individual based model ONCHOSIM to enable the simulation of multiple villages, with separate blackfly (intermediate host) and human populations, which are connected through the regular movement of the villagers and/or the flies. With this model we explore the impact of the type, direction and degree of connectedness, and of the impact of localized or full-area mass drug administration (MDA) over a range of connected village settings. Principal findings In settings with annual fly biting rates (ABR) below the threshold needed for stable local transmission, persistence of onchocerciasis prevalence can well be explained by regular human traffic and/or fly movement from locations with higher ABR. Elimination of onchocerciasis will then theoretically be reached by only implementing MDA in the higher prevalence area, although lingering infection in the low prevalence location can trigger resurgence of transmission in the total region when MDA is stopped too soon. Expanding MDA implementation to the lower ABR location can therefore shorten the duration of MDA needed. For example, when prevalence spill-over is due to human traffic, and both locations have about equal populations, then the MDA duration can be shortened by up to three years. If the lower ABR location has twice as many inhabitants, the reduction can even be up to six years, but if spill-over is due to fly movement, the expected reduction is less than a year. Conclusions/Significance Although MDA implementation might not always be necessary in locations with stable low onchocerciasis prevalence, in many circumstances it is recommended to accelerate achieving elimination in the wider area.

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The effect of assortative mixing on stability of low helminth transmission levels and on the impact of mass drug administration: model explorations for onchocerciasis

10.1101/354084 ◽

2018 ◽

Author(s):

Anneke S. de Vos ◽

Wilma A. Stolk ◽

Sake J. de Vlas ◽

Luc E. Coffeng

Keyword(s):

Intermediate Host ◽

Drug Administration ◽

Mass Drug Administration ◽

Infection Intensity ◽

Risk Groups ◽

Human Populations ◽

Control Distribution ◽

Larval Infection ◽

Low Prevalence ◽

The Impact

AbstractBackgroundStable low pre-control prevalences of helminth infection are not uncommon in field settings, yet it is poorly understood how such low levels can be sustained, thereby challenging efforts to model them. Disentangling possible facilitating mechanisms is important, since these may differently affect intervention impact. Here we explore the role of assortative (i.e. non-homogenous) mixing and exposure heterogeneity in helminth transmission, using onchocerciasis as an example.Methodology/Principal FindingsWe extended the established individual-based model ONCHOSIM to allow for assortative mixing, assuming that individuals who are relatively more exposed to fly bites are more connected to each other than other individuals in the population as a result of differential exposure to a sub-population of blackflies. We used the model to investigate how transmission stability, equilibrium microfilariae (mf) prevalence and intensity, and impact of mass drug administration depend on the assumed degree of assortative mixing and exposure heterogeneity, for a typical rural population of about 400 individuals. The model clearly demonstrated that with homogeneous mixing and moderate levels of exposure heterogeneity, onchocerciasis could not be sustained below 35% mf prevalence. In contrast, assortative mixing stabilised onchocerciasis prevalence at levels as low as 8% mf prevalence. Increasing levels of assortative mixing significantly reduced the probability of interrupting transmission, given the same duration and coverage of mass drug administration.Conclusions/SignificanceAssortative mixing patterns are an important factor to explain stable low prevalence situations and are highly relevant for prospects of elimination. Their effect on the pre-control distribution of mf intensities in human populations is only detectable in settings with mf prevalences <30%, where high skin mf density in mf-positive people may be an indication of assortative mixing. Local spatial variation in larval infection intensity in the blackfly intermediate host may also be an indicator of assortative mixing.Author summaryMost mathematical models for parasitic worm infections predict that at low prevalences transmission will fade out spontaneously because of the low mating probability of male and female worms. However, sustained low prevalence situations do exist in reality. Low prevalence areas have become of particular interest now that several worm infections are being targeted for elimination and the question arises whether transmission in such areas is driven locally and should be targeted with interventions. We hypothesise that an explanation for the existence of low prevalence areas is assortative mixing, which is the preferential mixing of high-risk groups among themselves and which has been shown to play an important role in transmission of other infectious diseases. For onchocerciasis, assortative mixing would mean that transmission is sustained by a sub-group of people and a connected sub-population of the blackfly intermediate host that mix preferentially with each other. Using a mathematical model, we study how assortative mixing allows for sustained low prevalences and show that it decreases the probability of interrupting transmission by means of mass drug administration. We further identify data sources that may be used to quantify the degree of assortative mixing in field settings.

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Feasibility of onchocerciasis elimination using a “test-and-not-treat” strategy in Loa loa co-endemic areas

Clinical Infectious Diseases ◽

10.1093/cid/ciaa1829 ◽

2020 ◽

Author(s):

David J Blok ◽

Joseph Kamgno ◽

Sebastien D Pion ◽

Hugues C Nana-Djeunga ◽

Yannick Niamsi-Emalio ◽

...

Keyword(s):

Adverse Events ◽

Drug Administration ◽

Mass Drug Administration ◽

Treatment Duration ◽

Loa Loa ◽

Serious Adverse Events ◽

Endemic Areas ◽

The Individual ◽

The Impact ◽

Main Strategy

Abstract Background Mass drug administration (MDA) with ivermectin is the main strategy for onchocerciasis elimination. Ivermectin is generally safe but associated with serious adverse events in individuals with high Loa loa microfilarial densities (MFD). Therefore, ivermectin MDA is not recommended in areas where onchocerciasis is hypo-endemic and L. loa is co-endemic. To eliminate onchocerciasis in those areas, a test-and-not-treat (TaNT) strategy has been proposed. We investigated whether onchocerciasis elimination can be achieved using TaNT and the required duration. Methods We used the individual-based model ONCHOSIM to predict the impact of TaNT on onchocerciasis microfilarial (mf) prevalence. We simulated pre-control mf prevalence levels from 2-40%. The impact of TaNT was simulated under varying levels of participation, systematic non-participation and exclusion from ivermectin due to high L. loa MFD. For each scenario, we assessed the time to elimination, defined as bringing onchocerciasis mf prevalence below 1.4%. Results In areas with 30-40% pre-control mf prevalence, the model predicted that it would take between 14 and 16 years to bring the mf prevalence below 1.4% using conventional MDA, assuming 65% participation. TaNT would increase the time to elimination by up to 1.5 years, depending on the level of systematic non-participation and the exclusion rate. At lower exclusion rates (≤2.5%), the delay would be less than six months. Conclusions Our model predicts that onchocerciasis can be eliminated using TaNT in L. loa co-endemic areas. The required treatment duration using TaNT would be only slightly longer than in areas with conventional MDA, provided that participation is good.

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Can direct smear results that are routinely collected at health centre level be used for monitoring the impact of mass drug administration with praziquantel on schistosomiasis in Burundi? A preliminary assessment.

10.21203/rs.2.19785/v2 ◽

2020 ◽

Author(s):

Paul BIZIMANA ◽

Katja POLMAN ◽

Giuseppina ORTU ◽

Meryam KRIT ◽

Frédéric NSABIYUMVA ◽

...

Keyword(s):

Drug Administration ◽

Mass Drug Administration ◽

Health Centre ◽

Health Information System ◽

Routine Data ◽

Direct Smear ◽

Incidence Data ◽

Intestinal Schistosomiasis ◽

The Impact ◽

Health Centre Level

Abstract Background : Intestinal schistosomiasis is still a public health problem in Burundi. Since 2008, annual mass drug administration with praziquantel have been rolled out in 11 endemic districts. The national programme relies on school-based surveys with Kato-Katz to monitor the impact of mass drug administration. We explored whether routine data on intestinal schistosomiasis as determined by direct fecal smears at health centre level could be used. Methods : From the Burundian National Health Information System, we collected routine incidence data on intestinal schistosomiasis as determined by direct smear examination in all 45 sanitary districts between 2011 and 2015. A temporal trends analysis was performed using a mixed negative binomial regression. Sanitary districts with mass drug administration campaigns with praziquantel (n=11) were compared with those without (n=34). In addition, prevalence data on intestinal schistosomiasis based on Kato-Katz results from a school-based national mapping in 2014 were compared with the incidence data in health centres based on direct smear results, in the same 45 sanitary districts. Findings : In the 11 sanitary districts applying mass drug administration with praziquantel, the incidence rate decreased significantly for the years 2014 (β 2014 =-0.826, p=0.010) and 2015 (β 2015 =-1.294, p<0.001) and for the five-year period (β=-0.286, p<0.001), whereas in the 34 districts where mass drug administration was not delivered, there was no significant decrease over time (β=-0.087, p=0.219). In most of the 45 sanitary districts, the low prevalences based on Kato-Katz in schoolchildren were confirmed by low incidence rates based on direct smear in the health centres. Conclusions : National Health Information System surveillance data, based on routinely collected direct smear results at health centre level, may be able to monitor the impact of mass drug administration with praziquantel on intestinal schistosomiasis in Burundi. Control and elimination of intestinal schistosomiasis call for integration of adequate diagnosis and treatment into routine activities of primary health care facilities, as recommended by the World Health Organization since more than 20 years. When moving towards elimination, more sensitive tests, such as the Point-of-care Circulating Cathodic Antigen assay are desirable. Keywords : Direct smear, Health centre, Mass drug administration, Monitoring, Praziquantel, Routine data, Schistosomiasis, Burundi

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Impact of seven years of mass drug administration and recrudescence of Schistosoma haematobium infections after one year of treatment gap in Zanzibar: Repeated cross-sectional studies

PLoS Neglected Tropical Diseases ◽

10.1371/journal.pntd.0009127 ◽

2021 ◽

Vol 15 (2) ◽

pp. e0009127

Author(s):

Lydia Trippler ◽

Shaali Makame Ame ◽

Jan Hattendorf ◽

Saleh Juma ◽

Salum Abubakar ◽

...

Keyword(s):

Drug Administration ◽

Mass Drug Administration ◽

Odds Ratio ◽

Schistosoma Haematobium ◽

Treatment Gap ◽

Urogenital Schistosomiasis ◽

Cross Sectional ◽

Reagent Strips ◽

One Year ◽

Low Prevalence

Background Considerable progress towards the elimination of urogenital schistosomiasis was made by the Zanzibar Elimination of Schistosomiasis Transmission project from 2012 till 2016, when biannual praziquantel mass drug administration (MDA) alone or with additional snail control or behaviour change interventions were implemented. Annual MDA was continued in 2017 and 2018, but not in 2019, imposing a 16-month treatment gap. We monitored the Schistosoma haematobium prevalence from 2012 till 2020 and assessed recrudescence patterns with focus on 2020. Methodology Repeated cross-sectional surveys were conducted from 2011/12 till 2020 in 90 communities and 90 schools in Zanzibar. Annually, around 4,500 adults and up to 20,000 schoolchildren were surveyed. The S. haematobium prevalence was detected by urine filtration and reagent strips. In 2020, risk factors for infection were investigated using generalized estimated equation models. Principal findings In adults, the apparent S. haematobium prevalence was 3.9% in 2011 and 0.4% in 2020. In schoolchildren, the prevalence decreased from 6.6% in 2012 to 1.2% in 2019 with vicissitudes over the years. Prominent recrudescence of infection from 2.8% in 2019 to 9.1% (+225%) in 2020 was observed in 29 schools with historically moderate prevalences (≥10%). Compared with 2019, reinfection in 2020 was particularly striking in boys aged 9–16 years. Being male was a risk factor for infection in 2020 (adults: odds ratio (OR): 6.24, 95% confidence interval (95% CI): 1.96–19.60; schoolchildren: OR: 2.06, 95% CI: 1.52–2.78). Living near to a natural freshwater body significantly increased the odds of infection in adults (OR: 2.90, CI: 1.12–7.54). Conclusions/Significance After 11 rounds of MDA over 7 years and a 16-month treatment gap, the urogenital schistosomiasis prevalence considerably rebounded in hotspot areas. Future elimination efforts in Zanzibar should focus on re-intensifying MDA plus additional interventions in hotspot areas. In low-prevalence areas, the strategy might be adapted from MDA to targeted surveillance-response.

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EVALUATION OF LYMPHATIC FILARIASIS AFTER TWO ROUNDS OF MASS DRUG ADMINISTRATION IN LAU LOCAL GOVERNMENT AREA OF TARABA STATE NIGERIA

FUDMA Journal of Sciences ◽

10.33003/fjs-2020-0404-511 ◽

2021 ◽

Vol 4 (4) ◽

pp. 513-519

Author(s):

D. E. Akafyi ◽

I. S. Ndams ◽

S. A. Luka ◽

F. S. Ojeleye ◽

S. O. Elkanah ◽

...

Keyword(s):

Local Government ◽

Drug Administration ◽

Mass Drug Administration ◽

Clinical Manifestations ◽

Wuchereria Bancrofti ◽

Local Government Area ◽

Filarial Antigen ◽

Physical Examinations ◽

The Impact ◽

Card Test

This study was undertaken to evaluate the effects of Mass Drug Administration (MDA) on Wuchereria bancrofti (microfilariae) after two rounds of combined Ivermectin and Albendazole distribution. A total of 221 participants were recruited in three communities in Lau Local Government Area of Taraba State by convenience sampling method. Questionnaires and physical examinations were used to assess clinical manifestations associated with the infection. Blood samples were collected by finger prick method and stained with Giemsa stain for examination to establish the presence of W. bancrofti while immunochromatographic card test was performed to determine the presence of filarial antigen in serum. Previous data were used to determine the pre-drug prevalence of the parasite. The results showed that the drug did not significantly reduce the clinical manifestations reported among the patients. The microfilariae prevalence and microfilaria mean density after two rounds of drug administration was 19.5% and 1.49%, while the pre- MDA prevalence and microfilaria mean density was 27.8% and 2.44% respectively. There was a statistically significant decrease of microfilaria prevalence (P<0.05) after two rounds of MDA. There was no significant effect of MDA by age, sex and occupation-related microfilariae prevalence in the study area. In conclusion, the study reveals that microfilaria prevalence and load decreased after two rounds of MDA of combined Ivermectin and Albendazole distribution amongst the studied populations. Routine evaluation of the MDA is required to assess the impact of the drug for the eventual elimination of the infection.

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Optimising systemic insecticide use to improve malaria control

BMJ Global Health ◽

10.1136/bmjgh-2019-001776 ◽

2019 ◽

Vol 4 (6) ◽

pp. e001776 ◽

Cited By ~ 1

Author(s):

Hannah R Meredith ◽

Luis Furuya-Kanamori ◽

Laith Yakob

Keyword(s):

Vector Control ◽

Malaria Transmission ◽

Drug Administration ◽

Mass Drug Administration ◽

Companion Animals ◽

Malaria Vectors ◽

Systemic Insecticide ◽

Blood Concentrations ◽

Systemic Insecticides ◽

The Impact

BackgroundLong-lasting insecticidal nets and indoor residual sprays have significantly reduced the burden of malaria. However, several hurdles remain before elimination can be achieved: mosquito vectors have developed resistance to public health insecticides, including pyrethroids, and have altered their biting behaviour to avoid these indoor control tools. Systemic insecticides, drugs applied directly to blood hosts to kill mosquitoes that take a blood meal, offer a promising vector control option. To date, most studies focus on repurposing ivermectin, a drug used extensively to treat river blindness. There is concern that overdependence on a single drug will inevitably repeat past experiences with the rapid spread of pyrethroid resistance in malaria vectors. Diversifying the arsenal of systemic insecticides used for mass drug administration would improve this strategy’s sustainability.MethodsHere, a review was conducted to identify systemic insecticide candidates and consolidate their pharmacokinetic/pharmacodynamic properties. The impact of alternative integrated vector control options and different dosing regimens on malaria transmission reduction are illustrated through mathematical model simulation.ResultsThe review identified drugs from four classes commonly used in livestock and companion animals: avermectins, milbemycins, isoxazolines and spinosyns. Simulations predicted that isoxazolines and spinosyns are promising candidates for mass drug administration, as they were predicted to need less frequent application than avermectins and milbemycins to maintain mosquitocidal blood concentrations.ConclusionsThese findings will provide a guide for investigating and applying different systemic insecticides to achieve more effective and sustainable control of malaria transmission.

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Can direct smear results that are routinely collected at health centre level be used for monitoring the impact of mass drug administration with praziquantel on schistosomiasis in Burundi? A preliminary assessment

Parasites & Vectors ◽

10.1186/s13071-020-04076-4 ◽

2020 ◽

Vol 13 (1) ◽

Author(s):

Paul Bizimana ◽

Katja Polman ◽

Giuseppina Ortu ◽

Meryam Krit ◽

Frédéric Nsabiyumva ◽

...

Keyword(s):

Drug Administration ◽

Mass Drug Administration ◽

Health Centre ◽

Preliminary Assessment ◽

Direct Smear ◽

The Impact ◽

Health Centre Level

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Human population movement can impede the elimination of soil-transmitted helminth transmission in regions with heterogeneity in mass drug administration coverage and transmission potential between villages: a metapopulation analysis

Parasites & Vectors ◽

10.1186/s13071-019-3612-7 ◽

2019 ◽

Vol 12 (1) ◽

Cited By ~ 6

Author(s):

Carolin Vegvari ◽

James E. Truscott ◽

Klodeta Kura ◽

Roy M. Anderson

Keyword(s):

Drug Administration ◽

Mass Drug Administration ◽

Human Population ◽

Sub Saharan Africa ◽

Population Movement ◽

Mobility Patterns ◽

Preventive Chemotherapy ◽

Cross Sectional ◽

The Impact ◽

Human Population Movement

Abstract Background Soil-transmitted helminth (STH) infections affect predominantly socio-economically disadvantaged populations in sub-Saharan Africa, East Asia and the Americas. Previous mathematical modelling studies have evaluated optimal intervention strategies to break STH transmission in clusters of villages. These studies assumed that villages are closed independent units with no movement of people in or out of communities. Here we examine how human population movement, for example, of seasonal migrant labourers, affect the outcome of mass drug administration (MDA) programmes. Results We used a stochastic individual-based metapopulation model to analyse the impact of human population movement at varying rates on STH elimination efforts. Specifically, we looked at seasonal clumped movement events of infected individuals into a village. We showed that even if on average 75% of the entire resident population within a village are treated, an annual rate of 2–3% of the population arriving from an untreated source village can reduce the probability of STH elimination to less than 50% in high-prevalence settings. If a village is infection-free, an annual movement rate of 2–3% from an infected source village imposes a risk of re-introduction of STH of 75% or higher, unless the prevalence in the source village is less than 20%. Even a single arrival of 2–3% of the population can impose a risk of re-introducing STH of 50% or greater depending on the prevalence in the source village. The risk of re-introduction also depends on both the age group of moving individuals and STH species, since the pattern of cross-sectional age-prevalence and age-intensity profiles of infection in the human host are species-specific. Conclusions Planning for STH elimination programmes should account for human mobility patterns in defined regions. We recommend that individuals arriving from areas with ongoing STH transmission should receive preventive chemotherapy for STHs. This can most easily be implemented if migration is seasonal and overlaps with treatment rounds, e.g. seasonal migrant labour. Moreover, transmission hotspots in or near treatment clusters should be eliminated, for example, by implementing appropriate water, sanitation and hygiene (WASH) measures and targeting treatment to individuals living in hotspots.

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Modeling the Effects of Helminth Infection on the Transmission Dynamics of Mycobacterium tuberculosis under Optimal Control Strategies

Computational and Mathematical Methods in Medicine ◽

10.1155/2020/8869377 ◽

2020 ◽

Vol 2020 ◽

pp. 1-21

Author(s):

Aristide G. Lambura ◽

Gasper G. Mwanga ◽

Livingstone Luboobi ◽

Dmitry Kuznetsov

Keyword(s):

Optimal Control ◽

Equilibrium Point ◽

Drug Administration ◽

Mass Drug Administration ◽

Helminth Infection ◽

Reproduction Number ◽

Control Strategies ◽

Active Tuberculosis ◽

Control Measures ◽

The Impact

A deterministic mathematical model for the transmission and control of cointeraction of helminths and tuberculosis is presented, to examine the impact of helminth on tuberculosis and the effect of control strategies. The equilibrium point is established, and the effective reproduction number is computed. The disease-free equilibrium point is confirmed to be asymptotically stable whenever the effective reproduction number is less than the unit. The analysis of the effective reproduction number indicates that an increase in the helminth cases increases the tuberculosis cases, suggesting that the control of helminth infection has a positive impact on controlling the dynamics of tuberculosis. The possibility of bifurcation is investigated using the Center Manifold Theorem. Sensitivity analysis is performed to determine the effect of every parameter on the spread of the two diseases. The model is extended to incorporate control measures, and Pontryagin’s Maximum Principle is applied to derive the necessary conditions for optimal control. The optimal control problem is solved numerically by the iterative scheme by considering vaccination of infants for Mtb, treatment of individuals with active tuberculosis, mass drug administration with regular antihelminthic drugs, and sanitation control strategies. The results show that a combination of educational campaign, treatment of individuals with active tuberculosis, mass drug administration, and sanitation is the most effective strategy to control helminth-Mtb coinfection. Thus, to effectively control the helminth-Mtb coinfection, we suggest to public health stakeholders to apply intervention strategies that are aimed at controlling helminth infection and the combination of vaccination of infants and treatment of individuals with active tuberculosis.

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