Wolbachia depletion blocks transmission of lymphatic filariasis by preventing chitinase-dependent parasite exsheathment.

Lymphatic filariasis is a vector-borne neglected tropical disease prioritized for global elimination. The filarial nematodes that cause the disease host a symbiotic bacterium, Wolbachia, which has been targeted using antibiotics, leading to cessation of parasite embryogenesis, waning of circulating larvae (microfilariae [mf]), and gradual cure of adult infection. One of the benefits of the anti-Wolbachia mode of action is that it avoids the rapid killing of mf, which can drive inflammatory adverse events. However, mf depleted of Wolbachia persist for several months in circulation, and thus patients treated with antibiotics are assumed to remain at risk for transmitting infections. Here, we show that Wolbachia-depleted mf rapidly lose the capacity to develop in the mosquito vector through a defect in exsheathment and inability to migrate through the gut wall. Transcriptomic and Western blotting analyses demonstrate that chitinase, an enzyme essential for mf exsheathment, is down-regulated in Wolbachia-depleted mf and correlates with their inability to exsheath and escape the mosquito midgut. Supplementation of in vitro cultures of Wolbachia-depleted mf with chitinase enzymes restores their ability to exsheath to a similar level to that observed in untreated mf. Our findings elucidate a mechanism of rapid transmission-blocking activity of filariasis after depletion of Wolbachia and adds to the broad range of biological processes of filarial nematodes that are dependent on Wolbachia symbiosis.

Subnational Projections of Lymphatic Filariasis Elimination Targets in Ethiopia to Support National Level Policy.

BACKGROUND: Lymphatic filariasis (LF) is a debilitating, poverty-promoting, neglected tropical disease (NTD) targeted for worldwide elimination as a public health problem (EPHP) by 2030. Evaluating progress towards this target for national programmes is challenging, due to differences in disease transmission and interventions at the subnational level. Mathematical models can help address these challenges by capturing spatial heterogeneities and evaluating progress towards LF elimination and how different interventions could be leveraged to achieve elimination by 2030. METHODS: Here we used a novel approach to combine historical geo-spatial disease prevalence maps of LF in Ethiopia with 3 contemporary disease transmission models to project trends in infection under different intervention scenarios at subnational level. RESULTS: Our findings show that local context, particularly the coverage of interventions, is an important determinant for the success of control and elimination programmes. Furthermore, although current strategies seem sufficient to achieve LF elimination by 2030, some areas may benefit from the implementation of alternative strategies, such as using enhanced coverage or increased frequency, to accelerate progress towards the 2030 targets. CONCLUSIONS: The combination of geospatial disease prevalence maps of LF with transmission models and intervention histories enables the projection of trends in infection at the subnational level under different control scenarios in Ethiopia. This approach, which adapts transmission models to local settings, may be useful to inform the design of optimal interventions at the subnational level in other LF endemic regions.

Reducing the Antigen Prevalence Target Threshold for Stopping and Restarting Mass Drug Administration for Lymphatic Filariasis Elimination: A Model-Based Cost-effectiveness Simulation in Tanzania, India and Haiti.

BACKGROUND: The Global Programme to Eliminate Lymphatic Filariasis (GPELF) aims to reduce and maintain infection levels through mass drug administration (MDA), but there is evidence of ongoing transmission after MDA in areas where Culex mosquitoes are the main transmission vector, suggesting that a more stringent criterion is required for MDA decision making in these settings. METHODS: We use a transmission model to investigate how a lower prevalence threshold (<1% antigenemia [Ag] prevalence compared with <2% Ag prevalence) for MDA decision making would affect the probability of local elimination, health outcomes, the number of MDA rounds, including restarts, and program costs associated with MDA and surveys across different scenarios. To determine the cost-effectiveness of switching to a lower threshold, we simulated 65% and 80% MDA coverage of the total population for different willingness to pay per disability-adjusted life-year averted for India ($446.07), Tanzania ($389.83), and Haiti ($219.84). RESULTS: Our results suggest that with a lower Ag threshold, there is a small proportion of simulations where extra rounds are required to reach the target, but this also reduces the need to restart MDA later in the program. For 80% coverage, the lower threshold is cost-effective across all baseline prevalences for India, Tanzania, and Haiti. For 65% MDA coverage, the lower threshold is not cost-effective due to additional MDA rounds, although it increases the probability of local elimination. Valuing the benefits of elimination to align with the GPELF goals, we find that a willingness to pay per capita government expenditure of approximately $1000-$4000 for 1% increase in the probability of local elimination would be required to make a lower threshold cost-effective. CONCLUSIONS: Lower Ag thresholds for stopping MDAs generally mean a higher probability of local elimination, reducing long-term costs and health impacts. However, they may also lead to an increased number of MDA rounds required to reach the lower threshold and, therefore, increased short-term costs. Collectively, our analyses highlight that lower target Ag thresholds have the potential to assist programs in achieving lymphatic filariasis goals.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

An Ensemble Framework for Projecting the Impact of Lymphatic Filariasis Interventions Across Sub-Saharan Africa at a Fine Spatial Scale.

BACKGROUND: Lymphatic filariasis (LF) is a neglected tropical disease targeted for elimination as a public health problem by 2030. Although mass treatments have led to huge reductions in LF prevalence, some countries or regions may find it difficult to achieve elimination by 2030 owing to various factors, including local differences in transmission. Subnational projections of intervention impact are a useful tool in understanding these dynamics, but correctly characterizing their uncertainty is challenging. METHODS: We developed a computationally feasible framework for providing subnational projections for LF across 44 sub-Saharan African countries using ensemble models, guided by historical control data, to allow assessment of the role of subnational heterogeneities in global goal achievement. Projected scenarios include ongoing annual treatment from 2018 to 2030, enhanced coverage, and biannual treatment. RESULTS: Our projections suggest that progress is likely to continue well. However, highly endemic locations currently deploying strategies with the lower World Health Organization recommended coverage (65%) and frequency (annual) are expected to have slow decreases in prevalence. Increasing intervention frequency or coverage can accelerate progress by up to 5 or 6 years, respectively. CONCLUSIONS: While projections based on baseline data have limitations, our methodological advancements provide assessments of potential bottlenecks for the global goals for LF arising from subnational heterogeneities. In particular, areas with high baseline prevalence may face challenges in achieving the 2030 goals, extending the "tail" of interventions. Enhancing intervention frequency and/or coverage will accelerate progress. Our approach facilitates preimplementation assessments of the impact of local interventions and is applicable to other regions and neglected tropical diseases.

Wuchereria bancrofti Lymphatic Filariasis, Barrancabermeja, Colombia, 2023.

We describe a recent case of lymphatic filariasis in Colombia caused by Wuchereria bancrofti nematodes. Our study combines clinical-epidemiologic findings with phylogenetic data. Resurgence of lymphatic filariasis may be linked to increasing urbanization trends and migration from previously endemic regions. Fieldwork can be a beneficial tool for screening and containing transmission.

A dynamic game of lymphatic filariasis prevention by voluntary use of insecticide treated nets.

Lymphatic filariasis (LF) has been targeted for elimination as a public health concern by 2030 with a goal to keep the prevalence of LF infections under the 1% threshold. While mass drug administration (MDA) is a primary strategy recommended by WHO, the use of insecticide treated nets (ITN) plays a crucial role as an alternative strategy when MDA cannot be used. In this paper, we use imitation dynamics to incorporate human behavior and voluntary use of ITN into the compartmental epidemiological model of LF transmission. We find the equilibrium states of the dynamics and the ITN usage as it depends on epidemiological parameters and the cost of ITNs. We investigate the conditions under which the voluntary use of ITNs can keep the LF prevalence under the 1% threshold. We found that when the cost of using the ITNs is about 105 smaller than the perceived cost of LF, then the voluntary use of ITNs will eliminate LF as a public health concern. Furthermore, when the ITNs are given away for free, our model predicts that over 80% of the population will use them which would eliminate LF completely in regions where Anopheles are the primary vectors.

Detection of Wuchereria bancrofti DNA in wild caught vector and non-vector mosquitoes: implications for elimination of lymphatic filariasis.

BACKGROUND: Transmission Assessment Survey (TAS) is the WHO recommended method used for decision-making to stop or continue the MDA in lymphatic filariasis (LF) elimination programme. The WHO has also recommended Molecular Xenomonitoring (MX) of LF infection in vectors as an adjunct tool in settings under post-MDA or validation period. Screening of non-vectors by MX in post-MDA / validation settings could be useful to prevent a resurgence of LF infection, as there might be low abundance of vectors, especially in some seasons. In this study, we investigated the presence of LF infection in non-vectors in an area endemic for LF and has undergone many rounds of annual MDA with two drugs (Diethylcarbamazine and Albendazole, DA) and two rounds of triple drug regimens (Ivermectin + DA). METHODS AND RESULTS: Mosquitoes were collected from selected villages of Yadgir district in Karnataka state, India, during 2019. A total of 680 female mosquitoes were collected, identified morphologically by species and separated as pools. The female mosquitoes belonging to 3 species viz., Anopheles subpictus, Culex gelidus and Culex quinquefaciatus were separated, pooled, and the DNA extracted using less expensive method and followed by LDR based real-time PCR assay for detecting Wuchereria bancrofti infection in vector as well as non-vector mosquitoes. One pool out of 6 pools of An. subpictus, 2 pools out of 6 pools of Cx. gelidus, and 4 pools out of 8 pools of Cx. quinquefaciatus were found to be positive for W. bancrofti infection by RT-PCR. The infection rate in vectors and non-vectors was found to be 1.8% (95% CI: 0.5-4.2%) and 0.9% (95% CI: 0.2-2.3%), respectively. CONCLUSIONS: Our study showed that non-vectors also harbour W. bancrofti, thus opening an opportunity of using these mosquitoes as surrogate vectors for assessing risk of transmission to humans in LF endemic and post MDA areas.

Mass Spectrometric and Glycan Microarray-Based Characterization of the Filarial Nematode Brugia malayi Glycome Reveals Anionic and Zwitterionic Glycan Antigens.

Millions of people worldwide are infected with filarial nematodes, responsible for lymphatic filariasis (LF) and other diseases causing chronic disablement. Elimination programs have resulted in a substantial reduction of the rate of infection in certain areas creating a need for improved diagnostic tools to establish robust population surveillance and avoid LF resurgence. Glycans from parasitic helminths are emerging as potential antigens for use in diagnostic assays. However, despite its crucial role in host-parasite interactions, filarial glycosylation is still largely, structurally, and functionally uncharacterized. Therefore, we investigated the glycan repertoire of the filarial nematode Brugia malayi. Glycosphingolipid and N-linked glycans were extracted from several life-stages using enzymatic release and characterized using a combination of MALDI-TOF-MS and glycan sequencing techniques. Next, glycans were purified by HPLC and printed onto microarrays to assess the host anti-glycan antibody response. Comprehensive glycomic analysis of B. malayi revealed the presence of several putative antigenic motifs such as phosphorylcholine and terminal glucuronic acid. Glycan microarray screening showed a recognition of most B. malayi glycans by immunoglobulins from rhesus macaques at different time points after infection, which permitted the characterization of the dynamics of anti-glycan immunoglobulin G and M during the establishment of brugian filariasis. A significant level of IgG binding to the parasite glycans was also detected in infected human plasma, while IgG binding to glycans decreased after anthelmintic treatment. Altogether, our work identifies B. malayi glycan antigens and reveals antibody responses from the host that could be exploited as potential markers for LF.

Diethylcarbamazine elicits Ca2+ signals through TRP-2 channels that are potentiated by emodepside in Brugia malayi muscles.

Filarial nematode infections are a major health concern in several countries. Lymphatic filariasis is caused by Wuchereria bancrofti and Brugia spp. affecting over 120 million people. Heavy infections can lead to elephantiasis, which has serious effects on individuals' lives. Although current anthelmintics are effective at killing microfilariae in the bloodstream, they have little to no effect against adult parasites found in the lymphatic system. The anthelmintic diethylcarbamazine is one of the central pillars of lymphatic filariasis control. Recent studies have reported that diethylcarbamazine can open transient receptor potential (TRP) channels in the muscles of adult female Brugia malayi, leading to contraction and paralysis. Diethylcarbamazine has synergistic effects in combination with emodepside on Brugia, inhibiting motility: emodepside is an anthelmintic that has effects on filarial nematodes and is under trial for the treatment of river blindness. Here, we have studied the effects of diethylcarbamazine on single Brugia muscle cells by measuring the change in Ca2+ fluorescence in the muscle using Ca2+-imaging techniques. Diethylcarbamazine interacts with the transient receptor potential channel, C classification (TRPC) ortholog receptor TRP-2 to promote Ca2+ entry into the Brugia muscle cells, which can activate Slopoke (SLO-1) Ca2+-activated K+ channels, the putative target of emodepside. A combination of diethylcarbamazine and emodepside leads to a bigger Ca2+ signal than when either compound is applied alone. Our study shows that diethylcarbamazine targets TRP channels to promote Ca2+ entry that is increased by emodepside activation of SLO-1 K+ channels.

Human immune response against filarial HSP70 and its role in the diagnosis of lymphatic filariasis.

A sensitive and specific diagnostic kit is crucial for the detection of human lymphatic filariasis at the early stage of infection as the existing diagnostic tools are inefficient and expensive. In the present study, we have cloned and expressed Brugia malayi HSP70 (BmHSP70) protein and characterized it as a potential antigen for diagnosis of the asymptomatic microfilariae stage of Wuchereria. bancrofti infection using ELISA, western blot, and bioinformatics tools. The antigenic efficacy of BmHSP70 was also compared with ScHSP70. The BmHSP70 and ScHSP70 peptide showed highly antigenic in nature and they showed immunogenic cross-reactivity endemic normal (EN) < chronic (CH) < microfilaraemic (MF) in IgG, IgG1, and IgG4 ELISA. IgG4-specific immunoblotting of BmHSP70 with MF sera further explicated its stage-specific antigenic cross-reactivity. These antigens (ScHSP70 and BmHSP70) showed a positive immunogenic correlation with the number of MF in blood samples. Thus, proposing BmHSP70 as a potential immunodiagnostic antigen against lymphatic filariasis. A triplet of GGMP tetrapeptide specific to the filarial HSP70 was also identified which was absent in human HSP70. In terms of sensitivity and specificity of antigens, these results suggest that recombinant BmHSP70 is a good antigen and could be used to diagnose early-stage of microfilariae infection.

Discovery of potent inhibitors targeting Glutathione S-transferase of Wuchereria bancrofti: a step toward the development of effective anti-filariasis drugs.

Lymphatic filariasis (LF) is one of the major health problems for the human kind in developing countries including India. LF is caused by three major nematodes namely Wuchereria bancrofti, Brugia malayi, and Brugia timori. The recent statistics of World Health Organization (WHO) showed that 51 million people were affected and 863 million people from 47 countries around worldwide remain threatened by LF. Among them, 90% of the filarial infection was caused by the nematode W. bancrofti. Approved drugs were available for the treatment of LF but many of them developed drug resistance and no longer effective in all stages of the infection. In the current research work, we explored the Glutathione S-transferase (GST) of W. bancrofti, the key enzyme responsible for detoxification that catalyzes the conjugation of reduced GSH (glutathione) to xenobiotic compounds. Initially, we analyzed the stability of the WbGST through 200 ns MD simulation and further structure-based virtual screening approach was applied by targeting the substrate binding site to identify the potential leads from small molecule collection. The in silico ADMET profiles for the top-ranked hits were predicted and the predicted non-toxic lead molecules showed the highest docking score in the range of - 12.72 kcal/mol to - 11.97 kcal/mol. The cross docking of the identified hits with human GST revealed the potential binding specificity of the hits toward WbGST. Through WbGST-lead complex simulation, the lead molecules were observed to be stable and also intactly bound within the binding site of WbGST. Based on the computational results, the five predicted non-toxic molecules were selected for the in vitro assay. The molecules showed significant percentage of inhibition against the filarial worm Setaria digitata which is the commonly used model organism to evaluate the filarial activity. In addition, the molecules also showed better IC50 than the standard drug ivermectin. The identified lead molecules will lay a significant insight for the development of new drugs with higher specificity and lesser toxicity to control and treat filarial infections.

Coverage of preventive measures and surveillance for neglected tropical diseases in hard-to-reach communities in Ghana.

BACKGROUND: Neglected tropical diseases (NTDs) are a major public health burden which mainly affects poor populations living in tropical environments and hard-to-reach areas. The study sought to examine coverage of preventive efforts, and case surveillance for NTDs in hard-to-reach communities in Ghana. METHODS: The study investigated treatment efforts for lymphatic filariasis (LF), and onchocerciasis and schistosomiasis/soil transmitted helminths (SCH/STH) at household level, in difficult-to-access communities in Ghana. A total of 621 households were sampled from 6 communities in the Western, Oti and Greater Accra regions. RESULTS: Over 95% of the households surveyed were covered under mass drug administration (MDA) campaigns for lymphatic filariasis (LF) and onchocerciasis. More than 80% of households had received at least two visits by community drug distributors under the MDA campaigns in the last two years preceding the study. In addition, over 90% of households in the LF and onchocerciasis endemic communities had at least one member using anthelminthic medications under the MDA campaigns in the 12 months preceding the study. However, households where no member had taken anthelminthic medications in 12 months preceding the study were over 6 times likely to have someone in the household with LF. CONCLUSIONS: This study determined that SCH/STH, LF and onchocerciasis are of serious public health concern in some communities in Ghana. There is an urgent need for holistic practical disease control plan involving both financial and community support to ensure total control of NTDs in difficult-to-access communities is achieved.

Entomological surveillance reveals transmission of malaria but not lymphatic filariasis in two communities in North-West Nigeria.

Malaria and lymphatic filariasis (LF) are two serious public health challenges in sub-Saharan Africa, and both diseases are transmitted by Anopheles mosquitoes. Successful control of both diseases requires detailed information on transmission dynamics; thus, this study investigated malaria and LF transmission indices in two (2) communities (Jidawa and Kargo) in North-West Nigeria. Anopheles mosquitoes were sampled from twenty-five (25) randomly selected houses from each of the two communities using pyrethrum spray collection (PSC). The samples were identified morphologically and molecularly characterised using polymerase chain reaction (PCR). Human biting rate (HBR), indoor resting density (IRD), sporozoite rate (SR) and entomological inoculation rate (EIR) were calculated using standard formulae. The thorax region of the collected samples were dissected and smeared; then, Plasmodium and Wuchereria bancrofti parasites were identified using microscopy. A total of 2417 Anopheles mosquitoes were collected, and all were identified morphologically as An. gambiae s.l. Further molecular identification of sibling species revealed that An. gambiae and An. arabiensis were the only sibling species present. A total of 818 Anopheles mosquitoes were screened for Plasmodium and Wuchereria bancrofti parasites. A total of 180 samples were positive for Plasmodium parasites (Jidawa = 151; Kargo = 29), and none was positive for W. bancrofti (0%). Result of entomological indices for malaria transmission showed that indoor resting density was higher in Jidawa (10 mosquitoes/room/night) while human biting rate (2.07 bites/person/night), sporozoite rate (29.3%) and entomological inoculation rate (0.61) were higher in Kargo. In total, 35.2% of the samples were blood-fed while 67.4% were parous. There is active transmission of malaria in the two communities but not LF, suggesting the effectiveness of mass drug administration for LF. Concerted efforts should be focused on malaria control as transmission of the disease persists.

Self-care practices and quality of life of filariasis patients in a gram panchayat of Paschim Burdwan district, West Bengal, India.

Background & objectives: Self-care management is one of the important components in the goal of elimination of lymphatic filariasis (LF) and Quality of Life (QoL) has become an important deliverable in the present day health care system. The objective was to assess the self-care management of the affected limb and to find out the quality of life who were suffering from lymphoedema. Methods: This was a community-based cross-sectional epidemiological study conducted during 2019-2020 in a Gourbazar gram panchayat area of Paschim Burdwan district of West Bengal, India. QoL was assessed by Lymphatic Filariasis Specific Quality of life Questionnaire (LFSQQ). Results: Total 115 LF patients were identified with a mean age of 53.9 years. About 26.1% correctly knew the management of the affected area. Out of the 33 patients having cracked skin, around 39.4% used to take care of the affected skin. Overall, median quality of life score was found to be 77.84 (65.90-89.20). Age-wise, median score gradually decreased with increase in age except in the age group of 50-60 years. Males had higher score compared to females (79.54 vs. 76.13). Activity domain score was found to be lowest followed by mobility score, while social and psychological domain score was found to be good. Interpretation & conclusion: Self-care practice is not known to the affected patients. Time has also come to integrate measures like rehabilitation, psychological intervention, social assistance in addition to self-care management to put up a holistic approach of the existing program.

Influence of social and environmental factors for Culex quinquefasciatus distribution in Northeastern Brazil: a risk index.

Culex quinquefasciatus is a vector of lymphatic filariasis. One important component in planning filariasis control activities is the mapping of vector distribution. A tool that involves socio-environmental factors and Cx. quinquefasciatus density can contribute to the identification of areas that should be prioritized in surveillance actions. This is an ecological study based on the construction and validation of a risk score of urban areas according to social and environmental variables extracted from a national database. Based on this stratification, female Cx. quinquefasciatus were captured. In total, 30,635 Cx. quinquefasciatus were captured, of which 17,161 (56%) were females. The highest vector density index of mosquitoes were captured in households located in the high-risk stratum and the indicator proved to be a tool that identified an association between social and environmental conditions and areas with the highest vector density index of females Cx. quinquefasciatus.

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

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 3 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 3 annual doses of IA (N = 52), 6 semiannual doses of ALB 400 mg (N = 45), or 6 semiannual doses of ALB 800 mg (N = 47). The primary outcome is amicrofilaremia at 36 months. RESULTS: IA was more effective for completely clearing Mf than ALB 400mg or ALB 800mg (79%, 95% confidence interval [CI]: 67-91; vs 48%, 95% CI: 32-66 and 57%, 95% CI: 41-73, respectively). Mean percentage reductions in Mf counts at 36 months relative to baseline tended to be greater after IA (98%, 95% CI: 88-100) than after ALB 400 mg (88%, 95% CI: 78-98) and ALB 800 mg (89%, 95% CI: 79-99) (P = .07 and P = .06, respectively). Adult worm nest numbers (assessed by ultrasound) were reduced in all treatment groups. Treatments were well tolerated. CONCLUSIONS: 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 where ivermectin cannot be used. CLINICAL TRIALS REGISTRATION: NCT02974049.

Quantifying Population Burden and Effectiveness of Decentralized Surveillance Strategies for Skin-Presenting Neglected Tropical Diseases, Liberia.

We evaluated programmatic approaches for skin neglected tropical disease (NTD) surveillance and completed a robust estimation of the burden of skin NTDs endemic to West Africa (Buruli ulcer, leprosy, lymphatic filariasis morbidity, and yaws). In Maryland, Liberia, exhaustive case finding by community health workers of 56,285 persons across 92 clusters identified 3,241 suspected cases. A total of 236 skin NTDs (34.0 [95% CI 29.1-38.9]/10,000 persons) were confirmed by midlevel healthcare workers trained using a tailored program. Cases showed a focal and spatially heterogeneous distribution. This community health worker‒led approach showed a higher skin NTD burden than prevailing surveillance mechanisms, but also showed high (95.1%) and equitable population coverage. Specialized training and task-shifting of diagnoses to midlevel health workers led to reliable identification of skin NTDs, but reliability of individual diagnoses varied. This multifaceted evaluation of skin NTD surveillance strategies quantifies benefits and limitations of key approaches promoted by the 2030 NTD roadmap of the World Health Organization.

Multi-drug resistant bacteria isolates from lymphatic filariasis patients in the Ahanta West District, Ghana.

BACKGROUND: Antimicrobial resistance is associated with increased morbidity in secondary infections and is a global threat owning to the ubiquitous nature of resistance genes in the environment. Recent estimate put the deaths associated with bacterial antimicrobial resistance in 2019 at 4.95 million worldwide. Lymphatic filariasis (LF), a Neglected Tropical Disease (NTD), is associated with the poor living in the tropical regions of the world. LF patients are prone to developing acute dermatolymphangioadenitis (ADLA), a condition that puts them at risk of developing secondary bacterial infections due to skin peeling. ADLA particularly worsens the prognosis of patients leading to usage of antibiotics as a therapeutic intervention. This may result in inappropriate usage of antibiotics due to self-medication and non-compliance; exacerbating antimicrobial resistance in LF patients. In this perspective, we assessed the possibilities of antimicrobial resistance in LF patients. We focused on antibiotic usage, antibiotic resistance in Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa isolates and looked at genes (mecA and Extended-spectrum beta-lactamase [blaCTX-M, blaSHV and blaTEM]) coding for resistance in multi-drug resistant (MDR) bacterial isolates. RESULTS: Of the sixty (60) participants, fifty-four (n = 54, 90%) were within 31-60 years of age, twenty (n = 20, 33.33%) were unemployed and thirty-eight (n = 38, 50.67%) had wounds aged (in months) seven (7) months and above. Amoxicillin (54%) and chloramphenicol (22%) were the most frequently used antibiotics for self-medication. Staphylococcus aureus isolates (n = 26) were mostly resistant to penicillin (n = 23, 88.46%) and least resistant to erythromycin (n = 2, 7.69%). Escherichia coli isolates (n = 5) were resistant to tetracycline (n = 5, 100%) and ampicillin (n = 5, 100%) but were sensitive to meropenem (n = 5, 100%). Pseudomonas aeruginosa isolates (n = 8) were most resistant to meropenem (n = 3, 37.50%) and to a lesser ciprofloxacin (n = 2, 25%), gentamicin (n = 2, 25%) and ceftazidime (n = 2, 25%). Multi-drug resistant methicillin resistant Staphylococcus aureus (MRSA), cephalosporin resistant Escherichia coli. and carbapenem resistant Pseudomonas aeruginosa were four (n = 4, 15.38%), two (n = 2, 40%) and two (n = 2, 25%) respectively. ESBL (blaCTX-M) and mecA genes were implicated in the resistance mechanism of Escherichia coli and MRSA, respectively. CONCLUSION: The findings show presence of MDR isolates from LF patients presenting with chronic wounds; thus, the need to prioritize resistance of MDR bacteria into treatment strategies optimizing morbidity management protocols. This could guide antibiotic selection for treating LF patients presenting with ADLA.

Efficacy and safety of triple therapy versus dual therapy for lymphatic filariasis: A systematic review and meta-analysis.

OBJECTIVE: Lymphatic filariasis is a serious public health issue. Recent studies showed that a single dosage of triple therapy (Ivermectin, Diethylcarbamazepine, and Albendazole) is more effective than dual therapy (Ivermectin plus Albendazole or Diethylcarbamazepine plus Albendazole) for clearing microfilaria from the blood. We aimed to evaluate the efficacy and safety of triple therapy versus dual therapy in patients infected with microfilaria and communities endemic to lymphatic filariasis. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, EMBASE, SCOPUS, Cochrane Central Register of Controlled Trials, and Web of Science until 24th June 2021. We included randomized control trials that compared triple with dual therapy given to patients with lymphatic filariasis or endemic communities. This study was registered with PROSPERO (CRD42021266724). RESULTS: We included eight articles after the screening process. Triple therapy caused more clearance of microfilaria in the blood (RR: 1.52; 95% CI: 1.15, 2.02; p = 0.003), while dual therapy caused more clearance of the circulating filariae antigen in the blood (RR: 0.76; 95% CI: 0.65, 0.88; p = 0.0003), both 12 months after drug administration. The triple therapy had a similar adverse effect compared with the dual therapy group. CONCLUSION: Based on the greater efficacy in the clearance of microfilaria and the safety of triple therapy, it constitutes a better strategy for the eradication programs of lymphatic filariasis in endemic regions. However, further studies are needed to confirm our results.