Design, expression, and evaluation of novel multiepitope chimeric antigen of Wuchereria bancrofti for the diagnosis of lymphatic filariasis – A structure-based strategy

Abstract In South and Central America, lymphatic filariasis (LF) is caused by Wuchereria bancrofti, which is transmitted by Culex quinquefasciatus, the only vector species in this region. Of the seven countries considered endemic for LF in the Americas in the last decade, Costa Rica, Suriname and Trinidad and Tobago were removed from the World Health Organization list in 2011. The remaining countries, Brazil, Dominican Republic, Guyana and Haiti, have achieved important progress in recent years. Brazil was the first country in the Americas to stop mass drug administration (MDA) and to establish post-MDA surveillance. Dominican Republic stopped MDA in all LF-endemic foci: La Ciénaga and Southwest passed the third Transmission Assessment Survey (TAS) and the Eastern focus passed TAS-1 in 2018. Haiti passed the TAS and interrupted transmission in >80% of endemic communes, achieving effective drug coverage. Guyana implemented effective coverage in MDAs in 2017 and 2018 and in 2019 scaled up the treatment for 100% of the geographical region, introducing ivermectin in the MDA in order to achieve LF elimination by the year 2026. The Americas region is on its way to eliminating LF transmission. However, efforts should be made to improve morbidity management to prevent disability of the already affected populations.

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Semiannual Treatment of Albendazole Alone is Efficacious for Treatment of Lymphatic Filariasis: A Randomized Open-label Trial in Cote d'Ivoire

Clinical Infectious Diseases ◽

10.1093/cid/ciab194 ◽

2021 ◽

Author(s):

Allassane F Ouattara ◽

Catherine M Bjerum ◽

Méité Aboulaye ◽

Olivier Kouadio ◽

Vanga K Marius ◽

...

Keyword(s):

Lymphatic Filariasis ◽

Primary Outcome ◽

Central Africa ◽

Wuchereria Bancrofti ◽

Bancroftian Filariasis ◽

Loa Loa ◽

Open Label ◽

Treatment Groups ◽

Open Label Trial ◽

To Receive

Abstract Background Ivermectin (IVM) plus albendazole (ALB), or IA, is widely used in mass drug administration (MDA) programs that aim to eliminate lymphatic filariasis (LF) in Africa. However, IVM can cause severe adverse events in persons with heavy Loa loa infections that are common in Central Africa. ALB is safe in loiasis, but more information is needed on its efficacy for LF. This study compared the efficacy and safety of three years of semiannual treatment with ALB to annual IA in persons with bancroftian filariasis. Methods Adults with Wuchereria bancrofti microfilaremia (Mf) were randomized to receive either three annual doses of IA (N=52), six semiannual doses of ALB 400mg (N=45), or six semiannual doses of ALB 800mg (N=47). The primary outcome amicrofilaremia at 36 months. Findings IA was more effective for completely clearing Mf than ALB 400mg or ALB 800mg (79%, CI 67-91; vs. 48%, CI 32-66 and 57%, CI 41-73, respectively). Mean % reductions in Mf counts at 36 months relative to baseline tended to be greater after IA (98%, CI 88-100) than after ALB 400mg (88%, CI 78-98) and ALB 800mg (89%, CI 79-99) (P=0.07 and P=0.06, respectively). Adult worm nest numbers (assessed by ultrasound) were reduced in all treatment groups. Treatments were well tolerated. Interpretation Repeated semiannual treatment with ALB is macrofilaricidal for W. bancrofti and leads to sustained reductions in Mf counts. This is a safe and effective regimen that could be used as MDA to eliminate LF in areas ivermectin cannot be used.

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Lymphatic filariasis, infection status in Culex quinquefasciatus and Anopheles species after six rounds of mass drug administration in Masasi District, Tanzania

Infectious Diseases of Poverty ◽

10.1186/s40249-021-00808-5 ◽

2021 ◽

Vol 10 (1) ◽

Author(s):

Eliza Lupenza ◽

Dinah B. Gasarasi ◽

Omary M. Minzi

Keyword(s):

Vector Control ◽

Lymphatic Filariasis ◽

Drug Administration ◽

Mass Drug Administration ◽

Wuchereria Bancrofti ◽

Elimination Phase ◽

Anopheles Species ◽

The Status ◽

Household Environment ◽

Indoor And Outdoor

Abstract Background Lymphatic filariasis (LF) elimination program in Tanzania started in 2000 in response to the Global program for the elimination of LF by 2020. Evidence shows a persistent LF transmission despite more than a decade of mass drug administration (MDA). It is advocated that, regular monitoring should be conducted in endemic areas to evaluate the progress towards elimination and detect resurgence of the disease timely. This study was therefore designed to assess the status of Wuchereria bancrofti infection in Culex quinqefasciatus and Anopheles species after six rounds of MDA in Masasi District, South Eastern Tanzania. Methods Mosquitoes were collected between June and July 2019 using Center for Diseases Control (CDC) light traps and gravid traps for indoor and outdoor respectively. The collected mosquitoes were morphologically identified into respective species. Dissections and PCR were carried out to detect W. bancrofti infection. Questionnaire survey and checklist were used to assess vector control interventions and household environment respectively. A Poisson regression model was run to determine the effects of household environment on filarial vector density. Results Overall, 12 452 mosquitoes were collected of which 10 545 (84.7%) were filarial vectors. Of these, Anopheles gambiae complex, An. funestus group and Cx. quinquefasciatus accounted for 0.1%, 0.7% and 99.2% respectively. A total of 365 pools of Cx. quinquefasciatus (each with 20 mosquitoes) and 46 individual samples of Anopheles species were analyzed by PCR. For Cx. quinquefasciatus pools, 33 were positive for W. bancrofti, giving an infection rate of 0.5%, while the 46 samples of Anopheles species were all negative. All 1859 dissected mosquitoes analyzed by microscopy were also negative. Households with modern latrines had less mosquitoes than those with pit latrines [odds ratio (OR) = 0.407, P < 0.05]. Houses with unscreened windows had more mosquitoes as compared to those with screened windows (OR = 2.125, P < 0.05). More than 80% of the participants own bednets while 16.5% had no protection. Conclusions LF low transmission is still ongoing in Masasi District after six rounds of MDA and vector control interventions. The findings also suggest that molecular tools may be essential for xenomonitoring LF transmission during elimination phase.

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An analysis of the safety of the single dose, two drug regimens used in programmes to eliminate lymphatic filariasis

Parasitology ◽

10.1017/s0031182000007423 ◽

2000 ◽

Vol 121 (S1) ◽

pp. S147-S160 ◽

Cited By ~ 63

Author(s):

J. HORTON ◽

C. WITT ◽

E.A. OTTESEN ◽

J.K. LAZDINS ◽

D.G. ADDISS ◽

...

Keyword(s):

Lymphatic Filariasis ◽

Wuchereria Bancrofti ◽

The Philippines ◽

Data Set ◽

Direct Observations ◽

National Public Health ◽

Total Data ◽

Drug Regimens ◽

At Risk Populations ◽

Health Programmes

This review of the safety of the co-administration regimens to be used in programmes to eliminate lymphatic filariasis (albendazole+ivermectin or albendazole+diethylcarbamazine [DEC]) is based on 17 studies conducted in Sri Lanka, India, Haiti, Ghana, Tanzania, Kenya, Ecuador, the Philippines, Gabon, Papua New Guinea, and Bangladesh. The total data set comprises 90635 subject exposures and includes individuals of all ages and both genders. Results are presented for hospital-based studies, laboratory studies, active surveillance of microfilaria-positive and microfilaria-negative individuals, and passive monitoring in both community-based studies and mass treatment programmes of individuals treated with albendazole (n=1538), ivermectin (9822), DEC (576), albendazole+ivermectin (7470), albendazole+DEC (69020), or placebo (1144). The most rigorous monitoring, which includes haematological and biochemical laboratory parameters pre- and post-treatment, provides no evidence that consistent changes are induced by any treatment; the majority of abnormalities appear to be sporadic, and the addition of albendazole to either ivermectin or DEC does not increase the frequency of abnormalities. Both DEC and ivermectin show, as expected, an adverse event profile compatible with the destruction of microfilariae. The addition of albendazole to either single-drug treatment regimen does not appear to increase the frequency or intensity of events seen with these microfilaricidal drugs when used alone. Direct observations indicated that the level of adverse events, both frequency and intensity, was correlated with the level of microfilaraemia. In non microfilaraemic individuals, who form 80–90% of the ‘at risk’ populations to be treated in most national public health programmes to eliminate lymphatic filariasis (LF), the event profile with the compounds alone or in combination does not differ significantly from that of placebo. Data on the use of ivermectin+albendazole in areas either of double infection (onchocerciasis and LF), or of loiais (with or without concurrent LF) are still inadequate and further studies are needed. Additional data are also recommended for populations infected with Brugia malayi, since most data thus far derive from populations infected with Wuchereria bancrofti.

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An assessment of mosquito collection techniques for xenomonitoring of anopheline-transmitted Lymphatic Filariasis in Ghana

Parasitology ◽

10.1017/s0031182018000938 ◽

2018 ◽

Vol 145 (13) ◽

pp. 1783-1791 ◽

Cited By ~ 8

Author(s):

Millicent Opoku ◽

Corrado Minetti ◽

Worlasi D. Kartey-Attipoe ◽

Sampson Otoo ◽

Joseph Otchere ◽

...

Keyword(s):

Lymphatic Filariasis ◽

Close Contact ◽

Wuchereria Bancrofti ◽

Northern Region ◽

Trapping Efficiency ◽

Mosquito Collection ◽

Control And Prevention ◽

Specific Species ◽

High Degree ◽

Collection Methods

AbstractMonitoring vectors is relevant to ascertain transmission of lymphatic filariasis (LF). This may require the best sampling method that can capture high numbers of specific species to give indication of transmission. Gravid anophelines are good indicators for assessing transmission due to close contact with humans through blood meals. This study compared the efficiency of an Anopheles gravid trap (AGT) with other mosquito collection methods including the box and the Centres for Disease Control and Prevention gravid, light, exit and BioGent-sentinel traps, indoor resting collection (IRC) and pyrethrum spray catches across two endemic regions of Ghana. The AGT showed high trapping efficiency by collecting the highest mean number of anophelines per night in the Western (4.6) and Northern (7.3) regions compared with the outdoor collection methods. Additionally, IRC was similarly efficient in the Northern region (8.9) where vectors exhibit a high degree of endophily. AGT also showed good trapping potential for collecting Anopheles melas which is usually difficult to catch with existing methods. Screening of mosquitoes for infection showed a 0.80–3.01% Wuchereria bancrofti and 2.15–3.27% Plasmodium spp. in Anopheles gambiae. The AGT has shown to be appropriate for surveying Anopheles populations and can be useful for xenomonitoring for both LF and malaria.

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PO 8239 BASELINE ASSESSMENT OF LYMPHATIC FILARIASIS IN 18 COMMUNITIES IN WESTERN GHANA BEFORE THE IMPLEMENTATION OF TWICE-YEARLY TREATMENT

BMJ Global Health ◽

10.1136/bmjgh-2019-edc.57 ◽

2019 ◽

Vol 4 (Suppl 3) ◽

pp. A22.3-A23

Author(s):

Dziedzom De Souza ◽

Collins Stephen Ahorlu ◽

Joseph Otchere ◽

Sedzro Mensah ◽

Sudan Adu-Amankwah ◽

...

Keyword(s):

Lymphatic Filariasis ◽

Demographic Data ◽

Randomised Trial ◽

Public Health Problem ◽

Wuchereria Bancrofti ◽

Community Members ◽

Commercial Activities ◽

System Disease ◽

Drug Adverse Effects ◽

Study Participants

BackgroundLymphatic filariasis (LF) is a neglected tropical disease targeted for elimination as a public health problem by 2020, with the main strategy being treatment of entire endemic communities. Since the inception of the Global Programme for the Elimination of LF in 2000, tremendous progress has been made in many endemic countries. However, current observations point to the need for improved treatment regimen, frequency of treatment or drug delivery strategies in order to achieve the elimination goals in certain endemic areas. In this randomised trial, we evaluate the use of twice-yearly treatment with ivermectin and albendazole in 18 LF-endemic communities in Ghana, where despite 15 years of yearly treatment the disease is still above the elimination thresholds.MethodsFollowing demographic data collection, Wuchereria bancrofti antigen, microfilaria and antibody prevalence were assessed in study participants using the Alere FTS kit, nucleopore filtration and Wb123 ELISA, respectively. The study assessed the perspectives of the communities’on persistent transmission of LF in view of implementing effective treatment uptake strategies.ResultsThe baseline assessments revealed antigen prevalence of 8.2% (95% CI=6.8–9.8), with overall microfilaria prevalence of 1.2%. Infections were higher in males and in individuals who spend significant amount of time outdoors for commercial activities. Barriers related to medication, personal, health system, disease and social structure were observed to affect mass drug administration compliance. Community members perceived that they were not susceptible to infection and this together with drug adverse effects strongly affect the ingestion of the drugs.ConclusionWhile this trial is still in an early phase, the baseline assessments reveal programmatic challenges to the implementation of a twice-yearly treatment strategy for the control of LF which must be addressed to enhance implementation success.

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Assessing the Presence of Wuchereria bancrofti Infections in Vectors Using Xenomonitoring in Lymphatic Filariasis Endemic Districts in Ghana

Tropical Medicine and Infectious Disease ◽

10.3390/tropicalmed4010049 ◽

2019 ◽

Vol 4 (1) ◽

pp. 49 ◽

Cited By ~ 2

Author(s):

Sellase Pi-Bansa ◽

Joseph Osei ◽

Worlasi Kartey-Attipoe ◽

Elizabeth Elhassan ◽

David Agyemang ◽

...

Keyword(s):

Lymphatic Filariasis ◽

Sampling Methods ◽

Wuchereria Bancrofti ◽

Filarial Infection ◽

Chain Reaction ◽

Mosquito Sampling ◽

Human Landing ◽

Monitoring And Surveillance ◽

Polymerase Chain ◽

New Research

Mass drug administration (MDA) is the current mainstay to interrupt the transmission of lymphatic filariasis. To monitor whether MDA is effective and transmission of lymphatic filariasis indeed has been interrupted, rigorous surveillance is required. Assessment of transmission by programme managers is usually done via serology. New research suggests that xenomonitoring holds promise for determining the success of lymphatic filariasis interventions. The objective of this study was to assess Wuchereria bancrofti infection in mosquitoes as a post-MDA surveillance tool using xenomonitoring. The study was carried out in four districts of Ghana; Ahanta West, Mpohor, Kassena Nankana West and Bongo. A suite of mosquito sampling methods was employed, including human landing collections, pyrethrum spray catches and window exit traps. Infection of W. bancrofti in mosquitoes was determined using dissection, conventional and real-time polymerase chain reaction and loop mediated isothermal amplification assays. Aedes, Anopheles coustani, An. gambiae, An. pharoensis, Culex and Mansonia mosquitoes were sampled in each of the four study districts. The dissected mosquitoes were positive for filarial infection using molecular assays. Dissected An. melas mosquitoes from Ahanta West district were the only species found positive for filarial parasites. We conclude that whilst samples extracted with Trizol reagent did not show any positives, molecular methods should still be considered for monitoring and surveillance of lymphatic filariasis transmission.

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LYMPHATIC FILARIASIS: AN OVERVIEW

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2019.v12i12.35646 ◽

2019 ◽

pp. 1-5

Author(s):

KANAAN AL-TAMEEMI ◽

RAIAAN KABAKLI

Keyword(s):

Chronic Disease ◽

Early Diagnosis ◽

Infection Control ◽

Lymphatic Filariasis ◽

Lymphatic System ◽

Wuchereria Bancrofti ◽

Health Organizations ◽

The World ◽

And Control ◽

Sexual Disability

Lymphatic filariasis (LF) is a tropical disease caused by infection with the parasitic filarial worms: Wuchereria bancrofti, Brugia malayi, and Brugia timori. The symptoms of this chronic disease appear in adults (in men more than in women) and include damage to the lymphatic system, arms, legs, and genitals, which cause significant pain, reducing productivity, and social problems. LF is a cause of continued disability, pain, disfigurement, and sexual disability in the world, so the knowledge of the disease and the infection control is very important. In addition to the importance of prevention, that includes giving medicine and using controlling ways of mosquitoes. Moreover, the prevention of disease is important, that includes giving medicine and using controlling ways of mosquitoes. However, although the efforts of health organizations to reduce the LF infections, there are still many challenges including the early diagnosis and control of infection among people.

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