Mf Prevalence Research Articles

The Epidemiological, Entomological and Socio-Economic Evaluation of Ivermectin Treatment in Imo River Basin, Nigeria

To assess the effectiveness of annual mass ivermectin treatment over 20 years in achieving elimination of onchocerciasis, we conducted a cross-sectional study between May 2021 and March 2022. A total of 540 individuals aged 5 years and above from rural farming communities selected were skin-snipped for dermal microfilariae (mf) by standard technique. Prospection of Simulium black flies was done at Lolo and Ibii Rivers. Structured questionnaires were used for the level of awareness, attitude and perceptions (KAP): onchocerciasis, vectors, treatment, drug compliance, benefits and socio-economy. Results revealed an overall mf prevalence of 12.8% and black fly infection rate (0.7%), infectivity and transmission potentials of (0.0%) indicative of non-transmission. These values contrasted with earlier reports in the range of 22%-68% for mf and 20.2%-48.2% infective rates suggesting the efficacy of mass ivermectin treatment in halting onchocerciasis. Participants had a high level of awareness about drug distribution. Benefits, dislikes and challenges of ivermectin were reported. We concluded that annual mass ivermectin treatment creditably reduced the microfilarial load and treatment in the study communities.

Persistent transmission of onchocerciasis in Kwanware-Ottou focus in Wenchi health district, Ghana

BackgroundThis study examined onchocerciasis transmission in Kwanware and Ottou in the Wenchi Health District of Ghana, where persistent onchocercal microfilariae (mf) levels have been reported since 2012.MethodsThis study was conducted from 2019 to 2021 and involved the following: (i) reviewing past records of ivermectin mass drug administration (MDA); (ii) conducting a treatment coverage evaluation survey (CES); (iii) conducting key informant interviews; (iv) prospecting blackfly breeding sites; (v) collecting and dissecting blackflies; and (vi) conducting parasitological and serological surveys.Results(i) The review indicated ongoing MDA treatment for the past 27 years, with a reported coverage of over 65% in the last 17 yearly rounds; (ii) estimated treatment coverage by the CES in 2019 was 71.3%, with most of those not taking medicine stating that they were not offered; (iii) however, the key informant interviews revealed insufficiencies in reaching a significant number of people for treatment due to remote settlement, mobility, transport logistical issues, failure to register some people for treatment, leading to a false impression of good coverage, and a short distribution time; (iv) the most productive breeding was found within 5 km of Kwanware-Ottou; and (v) blackfly daily biting rates were highest in Kwanware and Ottou, with 199 and 160 bites per day, respectively. Infection in blackflies was found only in Kwanware and Ottou, with infectivity rates of 5.9‰ (per 1000) and 6.7‰, respectively. (vi) The mf prevalence in Ottou and Kwanware, respectively, was 40.0% and 30.0% among adults aged ≥ 20 years, and the anti-(Onchocerca volvulus) Ov16 IgG4 antibodies seroprevalence rates were 8.3% and 13.3% among children aged 5–9 years. These values were reduced to undetectable levels at a radius of 10 km from Ottou.ConclusionsThis study confirms that active onchocerciasis transmission centres on Kwanware/Ottou and is confined to a 10 km radius despite 27 yearly treatment rounds. The main contributing factors are suboptimal coverage and high biting rates. Identifying and targeting such a focus with a combination of interventions will be cost-effective in accelerating onchocerciasis elimination in Ghana.

The Landscape of Cutaneous T-Cell Lymphoma (CTCL) in the Middle East and North Africa (MENA) and the Establishment of the MENA CTCL Working Group

The high cancer burden in the Middle East and North Africa (MENA region) is coupled with an increasing cancer incidence. While the MENA region constitutes 6% of the world’s population, it remains underrepresented in clinical trials. Cutaneous T-cell lymphomas (CTCLs) represent a heterogeneous group of rare extranodal non-Hodgkin lymphomas with variable clinical presentation. In the MENA region, where darker skin colors are more common than in the West, CTCL generally presents at a younger age and with distinct clinical features that necessitate special expertise and management across disciplines: rare forms of CTCL are more common (hypo- and hyperpigmented MF) and a higher prevalence of pediatric MF is noticed. The multidisciplinary approach to cancer management is growing worldwide and is necessary for the comprehensive management of CTCL. The MENA CTCL group was established with the aim of creating a collaborative environment for the diagnosis and treatment of CTCL in the region. Its first meeting was held in May 2023. The group plans to increase the global representation of the MENA region and establish CTCL registries and patient advocacy groups in the region.

Molecular xenomonitoring as an indicator of microfilaraemia prevalence for lymphatic filariasis in Samoa in 2019

BackgroundLymphatic filariasis (LF) is a globally significant, vector-borne, neglected tropical disease that can result in severe morbidity and disability. As the World Health Organization (WHO) Global Programme to Eliminate Lymphatic Filariasis makes progress towards LF elimination, there is greater need to develop sensitive strategies for post-intervention surveillance. Molecular xenomonitoring (MX), the detection of pathogen DNA in vectors, may provide a sensitive complement to traditional human-based surveillance techniques, including detection of circulating filarial antigen and microfilaraemia (Mf). This study aims to explore the relationship between human Mf prevalence and the prevalence of polymerase chain reaction (PCR)-positive mosquitoes using MX.MethodsThis study compared Mf and MX results from a 2019 community-based survey conducted in 35 primary sampling units (PSUs) in Samoa. This study also investigated concordance between presence and absence of PCR-positive mosquitoes and Mf-positive participants at the PSU level, and calculated sensitivity and negative predictive values for each indicator using presence of any Mf-positive infection in humans or PCR-positive mosquitoes as a reference. Correlation between prevalence of filarial DNA in mosquitoes and Mf in humans was estimated at the PSU and household/trap level using mixed-effect Bayesian multilevel regression analysis.ResultsMf-positive individuals were identified in less than half of PSUs in which PCR-positive mosquito pools were present (13 of 28 PSUs). Prevalence of PCR-positive mosquitoes (each species separately) was positively correlated with Mf prevalence in humans at the PSU level. Analysed at the species level, only Aedes polynesiensis demonstrated strong evidence of positive correlation (r) with human Mf prevalence at both PSU (r: 0.5, 95% CrI 0.1–0.8) and trap/household levels (r: 0.6, 95% CrI 0.2–0.9).ConclusionsFindings from this study demonstrate that MX can be a sensitive surveillance method for identifying residual infection in low Mf prevalence settings. MX identified more locations with signals of transmission than Mf-testing. Strong correlation between estimated PCR-positive mosquitoes in the primary vector species and Mf in humans at small spatial scales demonstrates the utility of MX as an indicator for LF prevalence in Samoa and similar settings. Further investigation is needed to develop MX guidelines to strengthen the ability of MX to inform operational decisions.Graphical abstract

Impact of ivermectin and vector control on onchocerciasis transmission in Togo: Assessing the empirical evidence on trends in infection and entomological indicators.

The World Health Organization's 2021-2030 Road Map for Neglected Tropical Diseases boosted global commitment towards the elimination of onchocerciasis, but the timeline to elimination will vary strongly between countries in Africa. To assess progress towards elimination in the Republic of Togo, we reviewed the history of control and time trends in infection. We collated all available programmatic, entomological, and epidemiological data since the initiation of the Onchocerciasis Control Programme (OCP) in Togo through different data sources. We then visualised data trends over time, to assess the impact of interventions on infection and transmission levels. Vector control was initiated by OCP from 1977 (northern and central parts of Togo) or 1988 (southern regions) up to 2002 (most areas) or 2007 ("special intervention zones" [SIZ], parts of Northern and Central Togo). Between 1988 and 1991, Togo initiated ivermectin mass drug administration (MDA) in eligible communities. The impact of vector control was high in most river basins, resulting in low annual biting rates and annual transmission potential declining to very low levels; the impact was lower in river basins designated as SIZ. Repeated, longitudinal ivermectin mass treatments have overall strongly reduced onchocerciasis transmission in Togo. Epidemiological surveys performed between 2014 and 2017 showed that the prevalence of skin microfilariae (mf) and anti-OV16 IgG4 antibodies had declined to low levels in several districts of the Centrale, Plateaux, and Maritime region. Yet, relatively high mf prevalences (between 5.0% and 32.7%) were still found in other districts during the same period, particularly along the Kéran, Mô and Ôti river basins (SIZ areas). Trends in infection prevalence and intensity show that onchocerciasis levels have dropped greatly over time in most areas. This demonstrates the large impact of long-term and wide-scale interventions, and suggest that several districts of Togo are approaching elimination.

Modelling the cost of engage & treat and test & treat strategies towards the elimination of lymphatic filariasis in Ghana.

Despite several years of LF-MDA implementation, Ghana still has some districts with mf prevalence >1%, partly due to poor treatment coverage levels resulting from non-participation in MDA. To address the challenges, we implemented an Engage & Treat (E&T) and Test & Treat (T&T) strategies for individuals who miss or refuse MDA respectively, in a hotspot district, enabling us to reach many of those who seldom, or never, take part in MDA. This financial cost study was undertaken to analyse data on the LF-MDA, E&T and T&T implementation in 2021 and the financial cost to inform the rollout of the E&T and T&T as mop-up strategies in future LF-MDAs. This costing study analysed cost data from the 2021 LF-MDA implementation activities carried out by the Neglected Tropical Diseases (NTD) programme of the Ghana Health Service and the SENTINEL study, carried out in Ahanta West district for the two interventions (i.e., E&T and T&T). The 2021 Ghana Population and Housing Census data was used to estimate the LF-MDA-eligible population. The financial cost per person treated was estimated and these costs were applied to the projected population to obtain the financial cost for subsequent years. Implementing MDA mop-up strategies either through the E&T or T&T to improve coverage comes at an additional cost to the elimination goals. For example, in 2024 the projected cost per person treated by the routine LF-MDA is estimated at US$0.83. The cost using the integrated LF-MDA and the E&T, T&T led by the NTD programme or T&T integrated into the health system was estimated at US$1.62, US$2.88, and US$2.33, respectively, for the same year. Despite the increased cost, the proposed combined LF-MDA and mop-up strategies will have a higher estimated population treated for 2024 (i.e., 1,392,211) compared to the routine LF-MDA approach (i.e., 988,470) for the same year. Combining LF-MDA with E&T/T&T mop-up strategies, despite their high costs, may provide NTD Programmes with the options of improving treatment coverage and reaching the LF elimination target sooner, given that the routine LF-MDA alone approach has been implemented for many years with some districts yet to reach the elimination targets.

How Does the Proportion of Never Treatment Influence the Success of Mass Drug Administration Programs for the Elimination of Lymphatic Filariasis?

Mass drug administration (MDA) is the cornerstone for the elimination of lymphatic filariasis (LF). The proportion of the population that is never treated (NT) is a crucial determinant of whether this goal is achieved within reasonable time frames. Using 2 individual-based stochastic LF transmission models, we assess the maximum permissible level of NT for which the 1% microfilaremia (mf) prevalence threshold can be achieved (with 90% probability) within 10 years under different scenarios of annual MDA coverage, drug combination and transmission setting. For Anopheles-transmission settings, we find that treating 80% of the eligible population annually with ivermectin + albendazole (IA) can achieve the 1% mf prevalence threshold within 10 years of annual treatment when baseline mf prevalence is 10%, as long as NT <10%. Higher proportions of NT are acceptable when more efficacious treatment regimens are used. For Culex-transmission settings with a low (5%) baseline mf prevalence and diethylcarbamazine + albendazole (DA) or ivermectin + diethylcarbamazine + albendazole (IDA) treatment, elimination can be reached if treatment coverage among eligibles is 80% or higher. For 10% baseline mf prevalence, the target can be achieved when the annual coverage is 80% and NT ≤15%. Higher infection prevalence or levels of NT would make achieving the target more difficult. The proportion of people never treated in MDA programmes for LF can strongly influence the achievement of elimination and the impact of NT is greater in high transmission areas. This study provides a starting point for further development of criteria for the evaluation of NT.

Predictive Value of Microfilariae-Based Stop-MDA Thresholds After Triple Drug Therapy With IDA Against Lymphatic Filariasis in Treatment-Naive Indian Settings.

Mass drug administration (MDA) of antifilarial drugs is the main strategy for the elimination of lymphatic filariasis (LF). Recent clinical trials indicated that the triple-drug therapy with ivermectin, diethylcarbamazine, and albendazole (IDA) is much more effective against LF than the widely used two-drug combinations (albendazole plus either ivermectin or diethylcarbamazine). For IDA-based MDA, the stop-MDA decision is made based on microfilariae (mf) prevalence in adults. In this study, we assess how the probability of eventually reaching elimination of transmission depends on the critical threshold used in transmission assessment surveys (TAS-es) to define whether transmission was successfully suppressed and triple-drug MDA can be stopped. This analysis focuses on treatment-naive Indian settings. We do this for a range of epidemiological and programmatic contexts, using the established LYMFASIM model for transmission and control of LF. Based on our simulations, a single TAS, one year after the last MDA round, provides limited predictive value of having achieved suppressed transmission, while a higher MDA coverage increases elimination probability, thus leading to a higher predictive value. Every additional TAS, conditional on previous TAS-es being passed with the same threshold, further improves the predictive value for low values of stop-MDA thresholds. An mf prevalence threshold of 0.5% corresponding to TAS-3 results in ≥95% predictive value even when the MDA coverage is relatively low.

Heterogeneity in elimination efforts could increase the risk of resurgence of lymphatic filariasis in Madagascar

BackgroundProgress in lymphatic filariasis (LF) elimination is spatially heterogeneous in many endemic countries, which may lead to resurgence in areas that have achieved elimination. Understanding the drivers and consequences of such heterogeneity could help inform strategies to reach global LF elimination goals by 2030. This study assesses whether differences in age-specific compliance with mass drug administration (MDA) could explain LF prevalence patterns in southeastern Madagascar and explores how spatial heterogeneity in prevalence and age-specific MDA compliance may affect the risk of LF resurgence after transmission interruption. MethodologyWe used LYMFASIM model with parameters in line with the context of southeastern Madagascar and explored a wide range of scenarios with different MDA compliance for adults and children (40–100%) to estimate the proportion of elimination, non-elimination and resurgence events associated with each scenario. Finally, we evaluated the risk of resurgence associated with different levels of migration (2–6%) from surrounding districts combined with varying levels of LF microfilaria (mf) prevalence (0–24%) during that same study period. ResultsDifferences in MDA compliance between adults and children better explained the observed heterogeneity in LF prevalence for these age groups than differences in exposure alone. The risk of resurgence associated with differences in MDA compliance scenarios ranged from 0 to 19% and was highest when compliance was high for children (e.g. 90%) and low for adults (e.g. 50%). The risk of resurgence associated with migration was generally higher, exceeding 60% risk for all the migration levels explored (2–6% per year) when mf prevalence in the source districts was between 9% and 20%. ConclusionGaps in the implementation of LF elimination programme can increase the risk of resurgence and undermine elimination efforts. In Madagascar, districts that have not attained elimination pose a significant risk for those that have achieved it. More research is needed to help guide LF elimination programme on the optimal strategies for surveillance and control that maximize the chances to sustain elimination and avoid resurgence.

Surveillance and Selective Treatment of Brugia malayi Filariasis Eleven Years after Stopping Mass Drug Administration in Belitung District, Indonesia.

Brugia malayi is the major cause of lymphatic filariasis (LF) in Indonesia. Zoophilic B. malayi was endemic in Belitung district, and mass drug administration (MDA) with diethylcarbamazine (DEC) and albendazole ceased after five annual rounds in 2010. The district passed three transmission assessment surveys (TAS) between 2011 and 2016. As part of the post-TAS3 surveillance of the national LF elimination program, we collected night blood samples for microfilaria (Mf) detection from 1,911 subjects more than 5 years of age in seven villages. A B. malayi Mf prevalence ranging from 1.7% to 5.9% was detected in five villages. Only 2 (5%) of the total 40 Mf-positive subjects were adolescents aged 18 and 19 years old, and 38 (95%) Mf-positive subjects were 21 years and older. Microfilarial densities in infected individuals were mostly low, with 60% of the subjects having Mf densities between 16 and 160 Mf/mL. Triple-drug treatment with ivermectin, DEC, and albendazole (IDA) was given to 36 eligible Mf-positive subjects. Adverse events were mostly mild, and treatment was well tolerated. One year later, 35 of the treated Mf-positive subjects were reexamined, and 33 (94%) had cleared all Mf, while the anti-Bm14 antibody prevalence remained almost unchanged. Results indicate that in B. malayi-endemic areas, post-TAS3 surveillance for Mf in the community may be needed to detect a potential parasite reservoir in adults. Selective treatment with IDA is highly effective in clearing B. malayi Mf and should be used to increase the prospects for LF elimination if MDA is reintroduced.

Five years of post-validation surveillance of lymphatic filariasis in Thailand

BackgroundThe World Health Organization (WHO) validated Thailand in 2017 as having eliminated lymphatic filariasis (LF) as a public health problem with recommendations for continued surveillance. This article describes measures and progress made in Thailand with post-validation surveillance (PVS) of LF from 2018 until 2022.MethodsThe implementation unit (IU) is a sub-village in 11 former LF endemic provinces. Human blood surveys are targeted in 10% of IUs each year. In Wuchereria bancrofti areas, filaria antigen test strips (FTS) are used, and in Brugia malayi areas, antibody test kits (Filaria DIAG RAPID) are used. Positive cases are confirmed by thick blood film (TBF) and polymerase chain reaction (PCR). Vector surveys for mosquito species identification and dissection for microfilaria (Mf)/filarial larvae are done in 1% of IUs where human blood surveys are conducted. Human blood surveys using FTS are conducted among migrants in five provinces. Surveillance of cats is done in areas that previously recorded > 1.0% Mf rate among cats. Morbidity management and disability prevention (MMDP) are done every 2 years in LF-endemic areas where chronic disease patients reside.ResultsFrom 2018 to 2022, in a total of 357 IUs in 11 provinces, human blood surveys were conducted in 145 IUs (41%) with an average population coverage of 81%. A total of 22,468 FTS and 27,741 FilariaDIAG RAPID were performed. 27 cases were detected: 3 cases of W. bancrofti in Kanchanaburi province and 24 cases of B. malayi in Narathiwat province. 4 cases of W. bancrofti were detected in two provinces through routine public health surveillance. Vector surveys in 47 IUs detected B. malayi Mf filarial larvae only in Narathiwat province. Chronic LF patients reduced from 114 in 2017 to 76 in 2022. Surveys among 7633 unregistered migrants yielded 12 cases of W. bancrofti. Mf rate among cats in Narathiwat province declined from 1.9% in 2018 to 0.7% in 2022. MMDP assessments revealed gaps in healthcare provider’s management of chronic cases due to staff turnover.ConclusionsIn 2022, after 5 years of PVS, Thailand re-surveyed 41% of its previously endemic IUs and demonstrated ongoing transmission in only one province of Narathiwat, where Mf prevalence is below the WHO provisional transmission threshold of 1%. This study highlights the importance of continued disease surveillance measures and vigilance among health care providers in LF receptive areas.Graphical

Mini-TAS as a confirmatory mapping tool for remapping areas with uncertain filarial endemicity to exclude/ include for mass drug administration: A report from field validation in India.

India has targeted elimination of lymphatic filariasis (LF) through mass drug administration (MDA) by 2027. Mapping of LF endemic areas is a priority for implementation of MDA. Current national LF remapping tool for unsurveyed/uncertain districts, have many limitations. The WHO has recommended a sensitive and rapid remapping protocol (Mini-TAS), that needs validation in Indian setting. Hence, in the present study a comparative assessment of these two protocols (national protocol vs Mini-TAS) was undertaken in two non-MDA districts of Odisha, with unknown filarial endemicity but reporting chronic cases. Purposive sampling was done in five top sites based on filarial case count as per the national protocol. Random 30 cluster survey was done by conducting school based Mini-TAS, Microfilariae (Mf) survey among adults (>10 years) in villages/wards with schools and Molecular Xenomonitoring (MX) of infection in vectors. Costing by activity and items of the surveys was acomplished using itemized cost menu. In Kalahandi, one of the five purposive sampling sites showed Mf prevalence above threshold (> 1%). But except Mini-TAS neither MX nor house-hold Mf survey among adults could detect the infection above the threshold. While in Balangir, Mf prevalence in all purposive sampling sites,Mini-TAS, Mf prevalence among adult and MX were above the respective thresholds confirming endemicity of LF in the district. The per sample cost of purposive sampling for Mf was the lowest INR 41, followed by adult Mf sampling INR 93. Mini-TAS and MX were expensive with INR 659 and 812 respectively. The study demonstrates that though all the sampling methods could detect filarial infection above the threshold in high-risk areas, Mini-TAS could only detect infection in low-risk areas. Therefore, in the national programme Mini-TAS can be used as a decision-making tool to determine whether to exclude/ include a district having uncertain endemicity for MDA.

Radiographical and Anatomical Assessment of Mandibular Mental Foramen Variations for a Sample of Yemeni Patients Undergoing Dental Implant Placement

Aim: To assess the prevalence, diameter and location of mental foramen MF, and Accessory mental foramen AMF, by cone-beam computed tomography (CBCT) for a Sample of Yemeni Patients. Methodology: The study was an analytical retrospective cross-sectional study conducted on 420 CBCT images of mandibles referred from general practitioners, surgery departments and surgeons for implant demands. The data collection took from April 2018 to July 2018. The sample size was divided according to gender, age, side, and dental condition. The images were analyzed and the measurements were done using the tools given in the software (Ez3D plus with Ez3D-I software). Results: MF was found in all patients (51.4% males and 48.6% females). The means of the MF diameter, MF-H, MF-V, MF-M1, MF-M2, AMF-HMD and AMF-VMD were 2.60 mm, 3.74 mm, 3.08 mm, 7.61 mm, 10.99 mm, 1.88 mm and 1.63 mm, respectively. Most of the cases were located under the apex of the 2nd premolar was found in only 4 (1%) of all cases. Conclusion: The most prevalent location of the MF was under the long axis of the 2nd premolar. The round shape of the MF was more prevalent than the oval shape.

Evaluating the impact of alternative intervention strategies in accelerating onchocerciasis elimination in an area of persistent transmission in the West Region of Cameroon.

Alternative strategies are recommended to accelerate onchocerciasis elimination in problematic areas including areas where annual ivermectin (IVM) distributions are unable to interrupt transmission. The aim of this study was to accelerate progress towards elimination in the Massangam health district, West Region of Cameroon where impact evaluations demonstrated ongoing transmission of onchocerciasis infection and high microfilaria (mf) prevalence despite more than 20 years of annual IVM distribution. Parasitological, entomological, and breeding site surveys were conducted in 2015 delineating a focus of high transmission and identified three communities with high mf prevalence. Individuals in these communities were screened for mf yearly for a period of two years and those positive treated each year with doxycycline 100mg daily for five weeks. In addition, surrounding communities were given biannual IVM. Temephos-based applications were performed once a week for 10 consecutive weeks on Simulium damnosum s.l. breeding sites. Parasitological and entomological assessments were conducted after two years of implementation and findings compared with 2015 baseline. Alternative strategies accelerated progress towards elimination through a significant mf reduction (χ2: 40.1; p<0.001) from 35.7% (95%CI: 29.0-42.8) to 12.3% (95%CI, 9.0-16.4). Reductions were furthermore recorded over a longer period, with a reduction of prevalence of 29.0% under AIS in 2017-2019 compared to 14.6% with IVM in 2011-2015; and by 23.2% following the two years of alternative strategies compared to 20.3% reduction over 15 years of treatment with IVM (1996-2011). Entomological assessment demonstrates that transmission is still ongoing despite the reduction in mf which is expected in an environment with complex breeding sites and open transmission zones, i.e., where migration of flies or humans to and from neighbouring areas is common. This study provides evidence that alternative strategies are feasible and effective and should be considered in areas where transmission is sustained throughout long term uninterrupted MDA with IVM. However, there is need to consider wider transmission zones, and further explore optimal timing of larviciding with treatment to impact transmission.

Comparing antigenaemia- and microfilaraemia as criteria for stopping decisions in lymphatic filariasis elimination programmes in Africa.

Mass drug administration (MDA) is the main strategy towards lymphatic filariasis (LF) elimination. Progress is monitored by assessing microfilaraemia (Mf) or circulating filarial antigenaemia (CFA) prevalence, the latter being more practical for field surveys. The current criterion for stopping MDA requires <2% CFA prevalence in 6- to 7-year olds, but this criterion is not evidence-based. We used mathematical modelling to investigate the validity of different thresholds regarding testing method and age group for African MDA programmes using ivermectin plus albendazole. We verified that our model captures observed patterns in Mf and CFA prevalence during annual MDA, assuming that CFA tests are positive if at least one adult worm is present. We then assessed how well elimination can be predicted from CFA prevalence in 6-7-year-old children or from Mf or CFA prevalence in the 5+ or 15+ population, and determined safe (>95% positive predictive value) thresholds for stopping MDA. The model captured trends in Mf and CFA prevalences reasonably well. Elimination cannot be predicted with sufficient certainty from CFA prevalence in 6-7-year olds. Resurgence may still occur if all children are antigen-negative, irrespective of the number tested. Mf-based criteria also show unfavourable results (PPV <95% or unpractically low threshold). CFA prevalences in the 5+ or 15+ population are the best predictors, and post-MDA threshold values for stopping MDA can be as high as 10% for 15+. These thresholds are robust for various alternative assumptions regarding baseline endemicity, biological parameters and sampling strategies. For African areas with moderate to high pre-treatment Mf prevalence that have had 6 or more rounds of annual ivermectin/albendazole MDA with adequate coverage, we recommend to adopt a CFA threshold prevalence of 10% in adults (15+) for stopping MDA. This could be combined with Mf testing of CFA positives to ensure absence of a significant Mf reservoir for transmission.

The filarial and the antibiotics: Single or combination therapy using antibiotics for filariasis.

Filarial infections caused by nematodes are one of the major neglected tropical diseases with public health concern. Although there is significant decrease in microfilariae (mf) prevalence following mass drug administration (IVM/DEC/ALB administration), this is transient, in that there is reported microfilaria repopulation 6-12 months after treatment. Wolbachia bacteria have been recommended as a novel target presenting antibiotic-based treatment for filarial disease. Potency of antibiotics against filarial diseases is undoubtful, however, the duration for treatment remains a hurdle yet to be overcome in filarial disease treatment.

Persistence of onchocerciasis in villages in Enugu and Ogun states in Nigeria following many rounds of mass distribution of ivermectin

BackgroundOnchocerciasis is endemic in most local government areas (LGAs) in Enugu and Ogun states. Most meso- and hyper-endemic LGAs have received many rounds of ivermectin mass drug administration (MDA). This study aimed to determine the current prevalence of onchocerciasis in villages in Enugu and Ogun states that were formerly highly endemic and to assess progress toward elimination of the infection in areas believed to be at high risk for persistence.MethodsCross-sectional community surveys were conducted 8 to 12 months after the last round of MDA in 16 villages (6 in Enugu state and 10 in Ogun state) in individuals aged ≥ 18 years. Study participants were examined for the presence of palpable subcutaneous nodules. Skin snips from the posterior iliac crests were used to assess microfiladermia (Mf) prevalence and density.Results643 subjects were palpated for nodules and 627 individuals (225 in Enugu state; 402 in Ogun state) provided skin snips. Nodule prevalence in the study villages ranged from 42 to 66.7% in Enugu state and from 0 to 25.0% in Ogun state. Mf prevalence in the Enugu and Ogun study villages ranged from 32 to 51.1% and 0 to 28.6%, respectively. Geometric mean skin Mf density in surveyed Enugu state villages ranged between 1 and 3.1 Mf/mg; these values were < 1 Mf/mg in all but one community in Ogun state villages.ConclusionResults from this study show that onchocerciasis persists in adults in many villages in Enugu and Ogun states despite many prior rounds of ivermectin MDA. Prevalence was higher in villages surveyed in Enugu than in Ogun. Low Mf densities suggest the MDA program is working well to reduce disease, but more time will be required to reach the elimination goal.

Impact of Annual versus Semiannual Mass Drug Administration with Ivermectin and Albendazole on Helminth Infections in Southeastern Liberia.

ABSTRACT.We compared the impact of three rounds of annual and five rounds of semiannual mass drug administration (MDA) with albendazole plus ivermectin on helminthic infections in Liberia. Repeated annual cross-sectional community surveys were conducted between 2013 and 2019 in individuals of 5 years and older. Primary outcome was the change of infection prevalence estimates from baseline to month 36 (12 months after the last treatment). After three rounds of annual MDA, Wuchereria bancrofti circulating filarial antigen (CFA) and microfilaria (Mf) prevalence estimates decreased from 19.7% to 4.3% and from 8.6% to 0%, respectively; after semiannual MDA, CFA and Mf prevalences decreased from 37.8% to 16.8% and 17.9% to 1%, respectively. Mixed effects logistic regression models indicated that the odds of having Mf decreased by 97% (P < 0.001) at month 36 (similar odds for annual and semiannual MDA zones). A parallel analysis showed that the odds of CFA were reduced by 83% and 69% at 36 months in the annual and semiannual treatment zones, respectively (P < 0.001). Onchocerca volvulus Mf prevalence decreased slightly after multiple MDA rounds in both treatment zones. Reductions in hookworm and Trichuris trichiura prevalences and intensities were slightly greater in the annual treatment zone. Ascaris lumbricoides prevalence rates were relatively unchanged, although infection intensities decreased sharply throughout. Results show that annual and semiannual MDA were equally effective for reducing LF and soil-transmitted helminth infection parameters over a 3-year period, and reductions recorded at month 36 were sustained by routine annual MDA through month 72.

Evaluating the diagnostic test accuracy of molecular xenomonitoring methods for characterising the community burden of Onchocerciasis.

BackgroundMolecular xenomonitoring (MX), the detection of parasite nucleic acid in the vector population, is recommended for onchocerciasis surveillance in elimination settings. However, the sensitivity of MX for detecting onchocerciasis-positive communities has not previously been evaluated. MX may have additional applications for control programmes but its utility is restricted by a limited understanding of the relationship between MX results and human prevalence.MethodsWe conducted a systematic review of studies reporting the prevalence of Onchocerca volvulus DNA in wild-caught Simulium spp. flies (MX rate) and corresponding prevalence of microfilaria (mf) in humans. We evaluated the sensitivity of MX for detecting onchocerciasis-positive communities and describe the characteristics of studies with reduced sensitivity. We conducted a linear regression to evaluate the relationship between mf prevalence and MX rate.ResultsWe identified 15 relevant studies, with 13 studies comprising 34 study communities included in the quantitative analyses. Most communities were at advanced stages towards elimination and had no or extremely low human prevalence. MX detected positive flies in every study area with >1% mf prevalence, with the exception of one study conducted in the Venezuelan Amazonian focus. We identified a significant relationship between the two measurements, with mf prevalence accounting for half of the variation in MX rate (R2 0.50, p<0.001).ConclusionMX is sensitive to communities with ongoing onchocerciasis transmission. It has potential to predict human mf prevalence, but further data is required to understand this relationship, particularly from MX surveys conducted earlier in control programmes before transmission has been interrupted.

The burden of skin disease and eye disease due to onchocerciasis in countries formerly under the African Programme for Onchocerciasis Control mandate for 1990, 2020, and 2030.

Onchocerciasis ("river blindness") can cause severe morbidity, including vision loss and various skin manifestations, and is targeted for elimination using ivermectin mass drug administration (MDA). We calculated the number of people with Onchocerca volvulus infection and onchocercal skin and eye disease as well as disability-adjusted life years (DALYs) lost from 1990 through to 2030 in areas formerly covered by the African Programme for Onchocerciasis Control. Per MDA implementation unit, we collated data on the pre-control distribution of microfilariae (mf) prevalence and the history of control. Next, we predicted trends in infection and morbidity over time using the ONCHOSIM simulation model. DALY estimates were calculated using disability weights from the Global Burden of Disease Study. In 1990, prior to MDA implementation, the total population at risk was 79.8 million with 26.0 million (32.5%) mf-positive individuals, of whom 17.5 million (21.9%) had some form of onchocercal skin or eye disease (2.5 million DALYs lost). By 2030, the total population was predicted to increase to 236.1 million, while the number of mf-positive cases (about 6.8 million, 2.9%), people with skin or eye morbidity (4.2 million, 1.8%), and DALYs lost (0.7 million) were predicted to decline. MDA has had a remarkable impact on the onchocerciasis burden in countries previously under the APOC mandate. In the few countries where we predict continued transmission between now and 2030, intensified MDA could be combined with local vector control efforts, or the introduction of new drugs for mopping up residual cases of infection and morbidity.