Mf Density Research Articles

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.

Identification of biomarker candidates for filarial parasite infections by analysis of extracellular vesicles

BackgroundImproved diagnostic tools are needed for detecting active filarial infections in humans. Tests are available that detect adult W. bancrofti circulating filarial antigen, but there are no sensitive and specific biomarker tests for brugian filariasis or loiasis. Here we explored whether extracellular vesicles released by filarial parasites contain diagnostic biomarker candidates.MethodsVesicles were isolated using VN96-affinity purification from supernatants of short-term in vitro cultured B. malayi microfilariae (Mf) and analyzed by mass spectrometry (Bruker timsTOF). Parasite-specific proteins were identified by bioinformatic analysis and a protein was called present if supported by ≥ 2 spectra. After validation with cultures parasites, this approach was then used to analyze vesicles isolated from plasma of animals infected with B. malayi and from humans with heavy Loa loa infections.ResultsVesicles from Mf cultures contained more than 300 B. malayi proteins with high consistency across biological replicates. These included the known Mf excretory antigen BmR1 (AF225296). Over 150 B. malayi proteins were detected in vesicles isolated from plasma samples from two infected animals. Vesicles isolated from plasma from 10 persons with high L. loa Mf densities contained consistently 21 proteins, 9 of them were supported by at least 5 unique peptides and 7 with spectral counts above 10. The protein EN70_10600 (an orthologue of the B. malayi antigen BmR1, GenBank AF225296) was detected in all 10 samples with a total count of 91 spectra and a paralogue (EN70_10598) was detected in 6 samples with a total of 44 spectra.DiscussionExtracellular vesicles released by filarial parasites in vitro and in vivo contain parasite proteins which can be reliably detected by mass spectrometry. This research provides the foundation to develop antigen detection assays to improve diagnosis of active filarial infections in humans.

Efficient enrichment of iodine by supported ionic liquid with three effective adsorption sites: Heteroatoms, fused aromatic rings and ionic bond

With the continuous development of nuclear energy, radioactive iodine in nuclear waste would be hazardous to human health and environment. Therefore, it is of great significance to develop an efficient adsorbent for iodine capture. In this study, a novel ionic liquid ([N4444]4PTC) was prepared which combines three effective adsorption sites of heteroatom, fused aromatic ring and ionic bond for iodine capture. To make full use of the iodine capture capacity of [N4444]4PTC, [N4444]4PTC@MF composite was fabricated by using MF as a carrier which is cheap and readily available. The hydrogen bond between MF and PTC4– increases the surface charge density of MF, and endows [N4444]4PTC with high porosity. Thus, the iodine adsorption capacity (5.81 g g−1) and adsorption rate of [N4444]4PTC@MF was significantly improved. This synergistic effect-based iodine capture system was demonstrated to convert iodine molecules into polyiodide anions via charge-transfer (CT) mechanism at electron-rich sites. The formed anionic specie was effectively stabilized by the abundant quaternary ammonium cations in the system, making it easier to take place the adsorption process and increase the stability of the captured iodine. The adsorption–desorption test showed that the composite material exhibits excellent recycling performance and was suitable for multiple use in practical applications.

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.

Safety and efficacy of mass drug administration with a single-dose triple-drug regimen of albendazole + diethylcarbamazine + ivermectin for lymphatic filariasis in Papua New Guinea: An open-label, cluster-randomised trial.

BackgroundPapua New Guinea (PNG) has a high burden of lymphatic filariasis (LF) caused by Wuchereria bancrofti, with an estimated 4.2 million people at risk of infection. A single co-administered dose of ivermectin, diethylcarbamazine and albendazole (IDA) has been shown to have superior efficacy in sustained clearance of microfilariae compared to diethylcarbamazine and albendazole (DA) in small clinical trials. A community-based cluster-randomised trial of DA versus IDA was conducted to compare the safety and efficacy of IDA and DA for LF in a moderately endemic, treatment-naive area in PNG.MethodologyAll consenting, eligible residents of 24 villages in Bogia district, Madang Province, PNG were enrolled, screened for W. bancrofti antigenemia and microfilaria (Mf) and randomised to receive IDA (N = 2382) or DA (N = 2181) according to their village of residence. Adverse events (AE) were assessed by active follow-up for 2 days and passive follow-up for an additional 5 days. Antigen-positive participants were re-tested one year after MDA to assess treatment efficacy.Principal findingsOf the 4,563 participants enrolled, 96% were assessed for AEs within 2 days after treatment. The overall frequency of AEs were similar after either DA (18%) or IDA (20%) treatment. For those individuals with AEs, 87% were mild (Grade 1), 13% were moderate (Grade 2) and there were no Grade 3, Grade 4, or serious AEs (SAEs). The frequency of AEs was greater in Mf-positive than Mf-negative individuals receiving IDA (39% vs 20% p<0.001) and in Mf-positive participants treated with IDA (39%), compared to those treated with DA (24%, p = 0.023). One year after treatment, 64% (645/1013) of participants who were antigen-positive at baseline were re-screened and 74% of these participants (475/645) remained antigen positive. Clearance of Mf was achieved in 96% (52/54) of infected individuals in the IDA arm versus 84% (56/67) of infected individuals in the DA arm (relative risk (RR) 1.15; 95% CI, 1.02 to 1.30; p = 0.019). Participants receiving DA treatment had a 4-fold higher likelihood of failing to clear Mf (RR 4.67 (95% CI: 1.05 to 20.67; p = 0.043). In the DA arm, a significant predictor of failure to clear was baseline Mf density (RR 1.54; 95% CI, 1.09 to 2.88; p = 0.007).ConclusionIDA was well tolerated and more effective than DA for clearing Mf. Widespread use of this regimen could accelerate LF elimination in PNG.Trial registrationRegistration number NCT02899936; https://clinicaltrials.gov/ct2/show/NCT02899936.

Cryogenic preservation of Dirofilaria immitis microfilariae, reactivation and completion of the life-cycle in the mosquito and vertebrate hosts

BackgroundThe cryopreservation of filarial nematodes has been studied for nearly 70 years. Largely, these studies examined the effectiveness of cryopreservation methods by using the post-thaw survival of microfilariae (mf) and the development to third-stage larvae (L3s) following inoculation into a competent insect vector. Only one study reported complete reestablishment of a filarial nematode (Brugia malayi) life-cycle in a competent vertebrate host from cryopreserved stock. Expanding on this previous research, a cryopreservation method was developed to cryopreserve the mf of the dog heartworm, Dirofilaria immitis.MethodsA combination of cryoprotectants, dimethyl sulfoxide (DMSO) and polyvinyl pyrolidone (PVP) at 6% and 4 mM, respectively, provided acceptable post-thaw survival of mf that developed into L3s in Aedes aegypti. L3s developed from cryopreserved and freshly collected mf in mosquitoes were inoculated into ferrets and dogs and were assessed after a sufficient duration post-inoculation for development into adult heartworms.ResultsFewer adult heartworms derived from cryopreserved stocks of mf were recovered from ferrets compared to adult heartworms derived from freshly collected mf, and the former were smaller by weight and length. The onset of patency (circulating mf) occurred at similar post-inoculation time points and at similar mf densities in dogs infected with L3s sourced from cryopreserved stocks or freshly collected mf. Adults derived from cryopreserved mf have survived and produced viable mf for more than 3 years in dogs. Approximately 60% of inoculated L3s were recovered as adults from dogs at 2 and 3.5 years post-inoculation.ConclusionsThe results from these direct comparisons demonstrate that cryopreserved mf can develop into L3s in vector mosquitoes and that these L3s are infective to both dogs and ferrets, where they undergo normal development into adult worms. These worms are able to mate and produce viable mf and complete the heartworm lifecycle in dog.Graphical

Triple-Drug Treatment Is Effective for Lymphatic Filariasis Microfilaria Clearance in Samoa.

Following the first triple-drug mass drug administration (MDA) for lymphatic filariasis in Samoa in 2018, unexpected persistence of microfilaria (Mf) positivity in 18 (15%) of 121 antigen-positive persons was observed in a nationwide household survey 1–2 months later. Of the 18 Mf positive persons, 14 reported taking the MDA, raising concerns about MDA efficacy. In 2019, 5–6 months after the 2018 survey, a monitored treatment study was done to evaluate directly observed weight-based treatment in these Mf positive individuals. Mf presence and density were assessed before and 7 days after treatment, using 1 mL membrane filtered venous blood, and 60 uL thick blood films on slides prepared from venous or fingerprick blood. All 14 participants were still Mf positive on filters from venous blood pre-treatment samples, but two were negative by slide made from the same samples. Mf were cleared completely by day 7 in 12 of 13 participants followed up, and by day 30 in the remaining participant. Filtered blood using EDTA samples (to reduce clumping of Mf) is preferred over slides alone for improving the likelihood of detecting Mf and estimating their density. The triple-drug MDA strategy was effective at clearing Mf when given and taken at the correct dose.

Progress towards onchocerciasis elimination in Côte d'Ivoire: A geospatial modelling study.

BackgroundCôte d’Ivoire has had 45 years of intervention for onchocerciasis by vector control (from 1975 to 1991), ivermectin mass drug administration (MDA) (from 1992 to 1994) and community directed treatment with ivermectin (CDTi) from 1995 to the present. We modeled onchocerciasis endemicity during two time periods that correspond to the scale up of vector control and ivermectin distribution, respectively. This analysis illustrates progress towards elimination during these periods, and it has identified potential hotspots areas that are at risk for ongoing transmission.Methods and findingsThe analysis used Ministry of Health skin snip microfilaria (MF) prevalence and intensity data collected between 1975 and 2016. Socio-demographic and environmental factors were incorporated into a predictive, machine learning algorithm to create continuous maps of onchocerciasis endemicity. Overall predicted mean MF prevalence decreased from 51.8% circa 1991 to 3.9% circa 2016. The model predicted infection foci with higher prevalence in the southern region of the country. Predicted mean community MF load (CMFL) decreased from 10.1MF/snip circa 1991 to 0.1MF/snip circa 2016. Again, the model predicts foci with higher Mf densities in the southern region. For assessing model performance, the root mean squared error and R2 values were 1.14 and 0.62 respectively for a model trained with data collected prior to 1991, and 1.28 and 0.57 for the model trained with infection survey data collected later, after the introduction of ivermectin. Finally, our models show that proximity to permanent inland bodies of water and altitude were the most informative variables that correlated with onchocerciasis endemicity.Conclusion/SignificanceThis study further documents the significant reduction of onchocerciasis infection following widespread use of ivermectin for onchocerciasis control in Côte d’Ivoire. Maps produced predict areas at risk for ongoing infection and transmission. Onchocerciasis might be eliminated in Côte d’Ivoire in the future with a combination of sustained CDTi with high coverage, active surveillance, and close monitoring for persistent infection in previously hyper-endemic areas.

Risk of Recrudescence of Lymphatic Filariasis after Post-MDA Surveillance in Brugia malayi Endemic Belitung District, Indonesia

Belitung district in Bangka-Belitung Province, Indonesia with a population of 0.27 million is endemic for Brugia malayi and 5 rounds of mass drug administration (MDA) were completed by 2010. Based on the results of 3 transmission assessment surveys (TAS), the district is declared as achieving elimination of lymphatic filariasis (LF) in 2017. The findings of an independent survey conducted by the National Institute of Health Research and Development (NIHRD) in the same year showed microfilaria (Mf) prevalence of 1.3% in this district. In 2019, NIHRD conducted microfilaria survey in 2 villages in Belitung district. Screening of 311 and 360 individuals in Lasar and Suak Gual villages showed Mf prevalence of 5.1% and 2.2% with mean Mf density of 120 and 354 mf/ml in the respective villages. Mf prevalence was significantly higher among farmers and fishermen compared to others and the gender specific difference was not significant. The results of a questionnaire based interview showed that 62.4% of the respondents reported to have participated in MDA in Lasar while it was 57.7% in Suak Gual village. About 42% of the Mf positive cases did not participate in MDA. Environmental surveys identified many swampy areas supporting the breeding of Mansonia vector species. Persistence of infection is evident and in the event of successful TAS3 it is necessary to monitor the situation and plan for focal MDA. Appropriate surveillance strategies including xenomonitoring in post-MDA situations need to be developed to prevent resurgence of infection. Possible role of animal reservoirs is discussed.

Heterogeneous response of Wuchereria bancrofti-infected persons to diethylcarbamazine (DEC) and its implications for the Global Programme to Eliminate Lymphatic Filariasis (GPELF).

DEC or ivermectin (IVM) in combination with albendazole (ALB) has been the recommended strategy of the Global Programme to Eliminate Lymphatic Filariasis (GPELF) since 2000. Despite effective population coverage (> 65%) with several rounds of MDA with DEC or combination of DEC plus ALB, microfilariae persist in few individuals and they continue to be the source of infection for transmitting LF. We report an individual's variability in response to DEC by defining the response as complete absence of microfilaria (mf) (post-treatment mf count = 0) and non-response as presence of mf (post-treatment mf count ≥ 1). We analyzed follow-up data on individual's response to treatment from two randomized clinical trials in which 46 microfilaremic individuals were treated with single-dose DEC (6 mg/kg body weight). They were classified into low, medium, and high mf density categories based on their pre-treatment mf counts. Of the 46 individuals, 65.2% have not responded throughout the 12-month post-treatment period. Application of a logistic regression model with fixed (age, gender, mf density, post-treatment time, and their interactions) and random (individual's response over time) effects indicated that treatment response is independent of age, gender, and time. The overall treatment response increases in low and decreases in high mf density categories. Furthermore, the estimates for the random coefficients model showed that there is a greater variability in response between individuals over post-treatment time. The results substantiate that individual variation in response to DEC exists which indicate the importance of studying the parasite as well as host genetic factors associated with DEC action.

Ivermectin Treatment Response in Onchocerca Volvulus Infected Persons with Epilepsy: A Three-Country Short Cohort Study.

Despite a long history of community-directed treatment with ivermectin (CDTI), a high ongoing Onchocerca volvulus transmission is observed in certain onchocerciasis-endemic regions in Africa with a high prevalence of epilepsy. We investigated factors associated with higher microfilarial (mf) density after ivermectin treatment. Skin snips were obtained from O. volvulus-infected persons with epilepsy before, and 3 to 5 months after ivermectin treatment. Participants were enrolled from 4 study sites: Maridi (South Sudan); Logo and Aketi (Democratic Republic of Congo); and Mahenge (Tanzania). Of the 329 participants, 105 (31.9%) had a post-treatment mf density >20% of the pre-treatment value. The percentage reduction in the geometric mean mf density ranged from 69.0% (5 months after treatment) to 89.4% (3 months after treatment). A higher pre-treatment mf density was associated with increased probability of a positive skin snip after ivermectin treatment (p = 0.016). For participants with persistent microfiladermia during follow-up, a higher number of previous CDTI rounds increased the odds of having a post-treatment mf density >20% of the pre-treatment value (p = 0.006). In conclusion, the high onchocerciasis transmission in the study sites may be due to initially high infection intensity in some individuals. Whether the decreasing effect of ivermectin with increasing years of CDTI results from sub-optimal response mechanisms warrants further research.

Persons with onchocerciasis-associated epilepsy and nodding seizures have a more severe form of epilepsy with more cognitive impairment and higher levels of Onchocerca volvulus infection.

Following previous reports of very high epilepsy prevalence in the onchocerciasis-endemic villages in Maridi County, South Sudan, a study was conducted to investigate the association between the level of Onchocerca volvulus infection, epilepsy, and related outcomes. In December 2018, persons with epilepsy (PWE) were recruited from villages where an epilepsy prevalence of 4.4% (range: 3.5-11.9%) was documented. We enrolled 318 participants from whom two skin snips were taken for microscopic detection of O. volvulus microfilariae (mf). Seizure history was obtained for all PWE and their degree of disability assessed using the modified Rankin scale. Almost all (84.9%) PWE had detectable mf in their skin snips. Onchocerciasis-infected PWE experienced nodding seizures more often than uninfected PWE (p=0.034). Moreover, persons with nodding seizures had more frequent seizures (p<0.001) and higher disability scores (p<0.001), and were more often cognitively impaired and younger at the time of their first epileptic seizure (nine years vs 12 years, p<0.001) compared to PWE without nodding seizures. Based on multivariate models, nodding seizures were associated with higher mf densities (aOR: 1.022; 95%CI: 1.005-1.041). Epilepsy onset at a younger age was associated with a worse outcome. Higher frequency of seizures, longer duration of epilepsy and younger age were associated with increased disability. Regular antiepileptic drug use was associated with better cognitive and disability outcomes. PWE with nodding seizures have a more severe form of onchocerciasis-associated epilepsy, with earlier seizure onset and higher levels of O. volvulus infection. Younger PWE were prone to worse epilepsy outcomes, which would be prevented with regular antiepileptic treatment.

The insufficiency of circulating miRNA and DNA as diagnostic tools or as biomarkers of treatment efficacy for Onchocerca volvulus

Skin snip evaluation for onchocerciasis has insufficient sensitivity when skin microfilarial (mf) densities are low, such as following ivermectin treatment. Mf density is suitable for assessing microfilaricidal efficacy but only serves as an indirect indicator of macrofilaricidal activity. We assessed circulating nucleic acids from Onchocerca volvulus as an alternative to skin snips. We screened a plasma sample set of infected individuals followed up at four, 12 and 21 months after microfilaricidal (ivermectin, n = four), macrofilaricidal (doxycycline, n = nine), or combination treatment (n = five). Two parasite-derived miRNAs, cel-miR-71-5p and bma-lin-4, and O-150 repeat DNA were assessed. Highly abundant DNA repeat families identified in the O. volvulus genome were also evaluated. miRNAs were detected in two of 72 plasma samples (2.8%) and two of 47 samples (4.3%) with microfilaridermia using RT-qPCR. O-150 DNA was detected in eight (44.4%) baseline samples by qPCR and the number of positives declined post-treatment. One doxycycline-treated individual remained O-150 positive. However, only 11 (23.4%) samples with microfilaridermia were qPCR-positive. Analysis by qPCR showed novel DNA repeat families were comparatively less abundant than the O-150 repeat. Circulating parasite-derived nucleic acids are therefore insufficient as diagnostic tools or as biomarkers of treatment efficacy for O. volvulus.

Projected Number of People With Onchocerciasis-Loiasis Coinfection in Africa, 1995 to 2025.

BackgroundOnchocerciasis elimination through mass drug administration (MDA) is hampered by coendemicity of Loa loa, as people with high L. loa microfilariae (mf) density can develop serious adverse events (SAEs) after ivermectin treatment. We assessed the geographical overlap of onchocerciasis and loiasis prevalence and estimated the number of coinfected individuals at risk of post-ivermectin SAEs in West and Central Africa from 1995 to 2025.MethodsFocusing on regions with suspected loiasis transmission in 14 countries, we overlaid precontrol maps of loiasis and onchocerciasis prevalence to calculate precontrol prevalence of coinfection by 5 km2 × 5 km2 pixel, distinguishing different categories of L. loa mf intensity. Using statistical and mathematical models, we predicted prevalence of both infections and coinfection for 2015 and 2025, accounting for the impact of MDA with ivermectin.ResultsThe number of people infected with onchocerciasis was predicted to decline from almost 19 million in 1995 to 4 million in 2025. Of these, 137 000 people were estimated to also have L. loa hypermicrofilaremia (≥20 000 L. loa mf/mL) in 1995, declining to 31 000 in 2025. In 2025, 92.8% of coinfected cases with loiasis hypermicrofilaremia are predicted to live in hypoendemic areas currently not targeted for MDA.ConclusionsLoiasis coinfection is a major concern for onchocerciasis elimination in Africa. We predict that under current strategies, at least 31 000 coinfected people still require treatment for onchocerciasis in 2025 while being at risk of SAEs, justifying continued efforts in research and development for safer drugs and control strategies.

Mapping of lymphatic filariasis in loiasis areas: A new strategy shows no evidence for Wuchereria bancrofti endemicity in Cameroon.

BackgroundMapping of lymphatic filariasis (LF) caused by Wuchereria bancrofti largely relies on the detection of circulating antigen using ICT cards. Several studies have recently shown that this test can be cross-reactive with sera of subjects heavily infected with Loa loa and thus mapping results in loiasis endemic areas may be inaccurate.Methodology/Principal findingsIn order to develop an LF mapping strategy for areas with high loiasis prevalence, we collected day blood samples from 5,001 subjects residing in 50 villages that make up 6 health districts throughout Cameroon. Antigen testing using Filarial Test Strip (FTS, a novel platform that uses the same reagents as ICT) revealed an overall positivity rate of 1.1% and L. loa microfilaria (Mf) rates of up to 46%. Among the subjects with 0 to 8,000 Mf/ml in day blood, only 0.4% were FTS positive, while 22.2% of subjects with >8,000 Mf/ml were FTS positive. A Mf density of >8,200 Mf/ml was determined as the cut point at which positive FTS results should be excluded from the analysis. No FTS positive samples were also positive for W. bancrofti antibodies as measured by two different point of care tests that use the Wb123 antigen not found in L. loa. Night blood examination of the FTS positive subjects showed a high prevalence of L. loa Mf with densities up to 12,710 Mf/ml. No W. bancrofti Mf were identified, as confirmed by qPCR. Our results show that high loads of L. loa Mf in day blood are a reliable indicator of FTS positivity, and Wb123 rapid test proved to be relatively specific.Conclusions/SignificanceOur study provides a simple day blood-based algorithm for LF mapping in loiasis areas. The results indicate that many districts that were formerly classified as endemic for LF in Cameroon are non-endemic and do not require mass drug administration for elimination of LF.

Prevalence and intensity of Loa loa infection over twenty-three years in three communities of the Mbalmayo health district (Central Cameroon)

BackgroundLoiasis is a vector-borne parasitic disease due to Loa loa and transmitted to humans by tabanids of the genus Chrysops. Loiasis has been historically considered as the second or third most common reason for medical consultation after malaria, and a recent study has reported an excess mortality associated with the infection. However, the clinical impact of this filarial disease is yet to be elucidated, and it is still considered a benign disease eliciting very little attention. As a consequence of post-treatment severe adverse events occurring in individuals harboring very high Loa microfilarial loads, ivermectin is not recommended in onchocerciasis hypo-endemic areas that are co-endemic for loiasis. Without treatment, it is likely that the transmission of the disease and the morbidity associated with the infection will increase over time. This study aimed at investigating the long-term trends in prevalence and intensity of Loa loa infection in an area where no mass anti-filarial treatment has ever been distributed.MethodsA cross-sectional survey was conducted in three communities of the Mbalmayo health district (Central Cameroon). All volunteers, males and females aged five years and above, underwent daytime calibrated thick blood smears (CTBS) to search for L. loa microfilariae (mf). A structured questionnaire was administered to assess the history of both loiasis related clinical signs and migration of enrollees.ResultsThe prevalence of loiasis was 27.3% (95% CI: 22.3–32.9) in the three surveyed communities, with a mean mf density of 1922.7 (sd: 6623.2) mf/mL. Loa loa infection rate was higher amongst females than in males (p = 0.0001) and was positively associated with age of (OR = 1.018; p = 0.007). The intensity of infection was higher among males than in females (p < 0.0001), and displayed a convex in form trends with age groups. The follow up over 23 years revealed that both the rate and intensity of infection were similar to baseline.ConclusionsThe prevalence and intensity of Loa loa infection 23 years on is stable over time, indicating that this filarial disease might be noncumulative as regarded till now.

Albendazole alone or in combination with microfilaricidal drugs for lymphatic filariasis.

Albendazole alone or in combination with microfilaricidal drugs for lymphatic filariasis.

Elimination within reach: A cross-sectional study highlighting the factors that contribute to persistent lymphatic filariasis in eight communities in rural Ghana.

BackgroundDespite the progress achieved in scaling-up mass drug administration (MDA) for lymphatic filariasis (LF) in Ghana, communities with persistent LF still exist even after 10 years of community treatment. To understand the reasons for persistence, we conducted a study to assess the status of disease elimination and understand the adherence to interventions including MDA and insecticide treated nets.Methodology and principal findingsWe conducted a parasitological and epidemiological cross-sectional study in adults from eight villages still under MDA in the Northern Region savannah and the coastal Western Region of the country. Prevalence of filarial antigen ranged 0 to 32.4% and in five villages the prevalence of night blood microfilaria (mf) was above 1%, ranging from 0 to 5.7%. Median mf density was 67 mf/ml (range: 10–3,560). LF antigen positivity was positively associated with male sex but negatively associated with participating in MDA the previous year. Male sex was also associated with a decreased probability of participating in MDA. A stochastic model (TRANSFIL) was used to assess the expected microfilaria prevalence under different MDA coverage scenarios using historical data on one community in the Western Region. In this example, the model simulations suggested that the slow decline in mf prevalence is what we would expect given high baseline prevalence and a high correlation between MDA adherence from year to year, despite high MDA coverage.ConclusionsThere is a need for an integrated quantitative and qualitative research approach to identify the variations in prevalence, associated risk factors and intervention coverage and use levels between and within regions and districts. Such knowledge will help target resources and enhance surveillance to the communities most at risk and to reach the 2020 LF elimination goals in Ghana.

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

BackgroundStable 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 microfilarial (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.

Progress on elimination of lymphatic filariasis in Sierra Leone

BackgroundA baseline survey in 2007–2008 found lymphatic filariasis (LF) to be endemic in Sierra Leone in all 14 districts and co-endemic with onchocerciasis in 12 districts. Mass drug administration (MDA) with ivermectin started in 2006 for onchocerciasis and was modified to add albendazole in 2008 to include LF treatment. In 2011, after three effective MDAs, a significant reduction in microfilaraemia (mf) prevalence and density was reported at the midterm assessment. After five MDAs, in 2013, mf prevalence and density were again measured as part of a pre-transmission assessment survey (pre-TAS) conducted per WHO guidelines.MethodsFor the pre-TAS survey, districts were paired to represent populations of one million for impact assessment. One sentinel site selected from baseline and one spot check site purposefully selected based upon local knowledge of patients with LF were surveyed per pair (two districts). At each site, 300 people over five years of age provided mid-night blood samples and mf prevalence and density were determined using thick blood film microscopy. Results are compared with baseline and midterm data.ResultsAt pre-TAS the overall mf prevalence was 0.54% (95% CI: 0.36–0.81%), compared to 0.30% (95% CI: 0.19–0.47) at midterm and 2.6% (95% CI: 2.3–3.0%) at baseline. There was a higher, but non-significant, mf prevalence among males vs females. Eight districts (four pairs) had a prevalence of mf < 1% at all sites. Two pairs (four districts) had a prevalence of mf > 1% at one of the two sites: Koinadugu 0.98% (95% CI: 0.34–2.85%) and Bombali 2.67% (95% CI: 1.41–5.00%), and Kailahun 1.56% (95% CI: 0.72–3.36%) and Kenema 0% (95% CI: 0.00–1.21%).ConclusionsCompared to baseline, there was a significant reduction of LF mf prevalence and density in the 12 districts co-endemic for LF and onchocerciasis after five annual LF MDAs. No statistically significant difference was seen in either measure compared to midterm. Eight of the 12 districts qualified for TAS. The other four districts that failed to qualify for TAS had historically high LF baseline prevalence and density and had regular cross-border movement of populations. These four districts needed to conduct two additional rounds of LF MDA before repeating the pre-TAS. The results showed that Sierra Leone continued to make progress towards the elimination of LF as a public health problem.