Better drug regimens for mass drug administration (MDA) could accelerate the Global Programme to Eliminate Lymphatic Filariasis (LF). This community study was designed to compare the safety and ...efficacy of MDA with IDA (ivermectin, diethylcarbamazine and albendazole) or DA (diethylcarbamazine and albendazole) in India.
This two-armed, open-labelled, block randomised, community study was conducted in LF endemic villages in Yadgir district, Karnataka, India. Consenting participants ≥5 years of age were tested for circulating filarial antigenemia (CFA) and microfilaremia (Mf) before treatment with a single oral dose of IDA or DA. Adverse events (AEs) were monitored actively for two days and passively for five more days. Persons with positive CFA or Mf tests at baseline were retested 12-months post-treatment to assess treatment efficacy. Baseline CFA and Mf-rates were 26.4% and 6.9% in IDA and 24.5% and 6.4% in DA villages respectively. 4758 and 4160 participants received IDA and DA. Most AEs were mild after both treatments; fewer than 0.1% of participants experienced AEs with severity > grade 1. No serious AEs were observed. Fever, headache and dizziness were the most common AEs. AE rates were slightly higher after IDA than DA (8.3% vs. 6.4%, P<0.01). AEs were more frequent in females and Mf-positives after either treatment, but significantly more frequent after IDA (40.5% vs 20.2%, P < 0.001). IDA was more effective for clearing Mf than DA (84% vs. 61.8%, P < 0.001). Geometric mean Mf counts per 60μl in retested Mf-positives decreased by 96.4% from 11.8 after IDA and by 90.0% from 9.5 after DA. Neither treatment was effective for clearing CFA.
IDA had an acceptable safety profile and was more effective for clearing Mf than DA. With adequate compliance and medical support to manage AEs, IDA has the potential to accelerate LF elimination in India.
Clinical Trial Registry of India (CTRI No/2016/10/007399).
Lymphatic filariasis (LF) is targeted for elimination by the year 2020. As of 2017, 67 of the 72 endemic countries have implemented annual Mass Drug Administration (MDA) for interrupting LF ...transmission. Transmission Assessment Survey (TAS) is the recommended protocol to evaluate the impact of MDA and to decide when to stop MDA in an Evaluation Unit (EU, population ≤2 million). As the human infection levels go down with repeated MDA rounds, it becomes a challenge to select the appropriate survey methods to assess transmission interruption. This study validates a standard protocol for molecular xenomonitoring of infection in vectors (MX) at an EU as a complementary tool for TAS to stop MDA and its utility for post-MDA or post-validation surveillance.
The study was conducted in Cuddalore district, Tamil Nadu, India, which was found eligible for TAS after 15 annual rounds of MDA (4 with DEC alone and 11 with DEC plus albendazole). The district was divided into two EUs as per the TAS protocol and one EU was randomly selected for the study. A two-stage cluster design vector sampling, developed and validated at a sub-district level, was implemented in 30 randomly selected clusters in the EU. Female Culex quinquefasciatus were collected placing gravid traps overnight (1800-0600 hrs) inside the premises of systematically selected households. Pools of 20-25 blood-fed, semi-gravid and gravid Cx. quinquefasciatus were subjected to real-time quantitative PCR (polymerase chain reaction) assay for detecting Wuchereria bancrofti DNA. Pool infection rate (% of pools positive for W. bancrofti DNA), and the estimated prevalence of W. bancrofti DNA in mosquitoes and its 95% confidence interval were calculated. Additionally, in these 30 clusters, microfilaria (Mf) survey among individuals >5 years old was carried out. School-based TAS was conducted using Immunochromatographic Card Test (ICT) in the EU. Prepared itemized cost-menu for different cost components of MX survey and TAS were estimated and compared.
MX survey showed that only 11 (3.1%) of the 358 pools (8850 Cx.quinquefasciatus females), collected from 30 clusters, were found positive for W. bancrofti DNA. The estimated vector infection rate was 0.13% (95% CI: 0.07-0.22%), below the provisional threshold (0.25%) for transmission interruption. Of 1578 children tested in the TAS, only four (0.25%) were positive for filarial antigenemia, and it is well below the critical cut-off (18 positives) for stopping MDA. Among 9804 persons tested in the 30 clusters, only four were found positive for Mf (0.04%; 95% CI: 0.01-0.1%). The Mf-prevalence was <1% threshold for transmission interruption in humans. The estimated costs for TAS and MX per EU were $14,104 USD and $14,259 USD respectively.
The result of MX protocol was in good agreement with that of TAS, providing evidence to recommend MX as a complementary tool to TAS to decide on stopping MDA. MX can also be a potential surveillance tool for post-MDA and post-validation phases as it could detect sites with residual infection and risk of resurgence of transmission. MX is economically feasible as its cost is slightly higher than that of TAS.
Lymphatic Filariasis (LF) affects over 120 million people in 72 countries, with sub-periodic filariasis common in the Pacific.
has three physiological races, each with a unique microfilarial ...periodicity, and each race is isolated to a specific geographical region. Sub-periodic
.
is transmitted by various
mosquito species, with
and
being the primary vectors in Samoa. The
and
groups are also important vectors in the South Pacific Islands. Anopheles species are important vectors of filariasis in rural areas of Asia and Africa. The
complex,
, and the
group are the most important vectors of
.
. These vectors exhibit indoor nocturnal biting behaviour and breed in a variety of habitats, including freshwater, saltwater, and temporary water bodies. Effective vector surveillance is central to LF control and elimination programs. However, the traditional Human Landing Collection (HLC) method, while valuable, poses ethical concerns and risks to collectors. Therefore, this review critically analyses alternative trapping tools for
and
vectors in LF-endemic regions. We looked at 14 research publications that discussed
vector trapping methods. Pyrethrum Spray Catches (PSC), one of the seven traps studied for
LF vectors, was revealed to be the second most effective strategy after HLC, successfully catching
vectors in Nigeria, Ghana, Togo, and Burkina Faso. The PSC method has several drawbacks, such as the likelihood of overlooking exophilic mosquitoes or underestimating
populations. However, exit traps offered hope for capturing exophilic mosquitoes.
populations could also be sampled using the Anopheles Gravid Trap (AGT). In contrast, the effectiveness of the Double Net Traps (DNT) and the CDC Light Trap (CDC LT) varied. Gravid mosquito traps like the OviArt Gravid Trap (AGT) were shown to be useful tools for identifying endophilic and exophilic vectors during the exploration of novel collection techniques. The Stealth trap (ST) was suggested for sampling
mosquitoes, although specimen damage may make it difficult to identify the species. Although it needs more confirmation, the Ifakara Tent Trap C design (ITT-C) showed potential for outdoor mosquito sampling in Tanzania. Furvela tent traps successfully captured a variety of
species and are appropriate for use in a variety of eco-epidemiological settings. By contrast, for
LF vectors, no specific sampling tool was identified for
, necessitating further research and development. However, traps like the Duplex cone trap, Resting Bucket Trap (RB), and Sticky Resting Bucket trap (SRB) proved effective for sampling
, offering potential alternatives to HLC. This review emphasises the value of looking into alternative trapping methods for
and
vectors in the LF-endemic region. Further research is required to determine the efficacy of novel collection techniques in various contexts, even if PSC and AGT show promise for sampling Anopheles vectors. The identified traps, along with ongoing research, provide valuable contributions to vector surveillance efforts in LF-endemic regions, enabling LF control and elimination strategies to advance.
is geographically the most widely dispersed human malaria parasite species. It has shown resilience and a great deal of adaptability. Genomic studies suggest that
originated from Asia or Africa and ...moved to the rest of the world. Although
is evolutionarily an older species than
, its biology, transmission, pathology, and control still require better elucidation.
poses problems for malaria elimination because of the ability of a single primary infection to produce multiple relapses over months and years.
malaria elimination program needs early diagnosis, and prompt and complete radical treatment, which is challenging, to simultaneously exterminate the circulating parasites and dormant hypnozoites lodged in the hepatocytes of the host liver. As prompt surveillance and effective treatments are rolled out, preventing primaquine toxicity in the patients having glucose-6-phosphate dehydrogenase (G6PD) deficiency should be a priority for the
elimination program. This review sheds light on the burden of
, changing epidemiological patterns, the hurdles in elimination efforts, and the essential tools needed not just in India but globally. These tools encompass innovative treatments for eliminating dormant parasites, coping with evolving drug resistance, and the development of potential vaccines against the parasite.
Vector mosquitoes of Japanese encephalitis (JE) breed mostly in rice fields, and human cases occur scattered over extended rural rice-growing areas. From this, one may surmise an ecological ...connection with the irrigation facilities and paddy cultivation. Furthermore, it has been hypothesized that a particular stage of paddy growth is a premonitory sign that can lead to a markedly increased population of the vector mosquitoes. The present study aimed to forecast the vector abundance by monitoring the paddy growth using remote sensing and geographical information systems. The abundance of the JE vector Culex tritaeniorhynchus peaked when the paddy crop was at its heading stage and dipped when the crop reached the maturing stage. A significant positive correlation was observed between paddy growth and adult density (r = 0.73, p < 0.008). The sigma naught values (σ0) derived from satellite images of paddy fields ranged from -18.3 (during transplantation stage) to approximately -10 (during the noncultivation period). A significant positive correlation was observed between σ0 and paddy growth stages (r = 0.87, p < 0.05) and adult vector density (r = 0.74, p = 0.04). The σ0 value observed during the vegetative and flowering stages of paddy growth ranged from -17.6 to -17.16, at which period the vector density started building up. This could be the spectral signature that denotes the "risk," following which a high vector abundance is expected during heading stage of the paddy.
The Global Programme to Eliminate Lymphatic Filariasis (GPELF) provides antifilarial medications to hundreds of millions of people annually to treat filarial infections and prevent elephantiasis. ...Recent trials have shown that a single-dose, triple-drug treatment (ivermectin with diethylcarbamazine and albendazole IDA) is superior to a two-drug combination (diethylcarbamazine plus albendazole DA) that is widely used in LF elimination programs. This study was performed to assess the safety of IDA and DA in a variety of endemic settings.
Large community studies were conducted in five countries between October 2016 and November 2017. Two studies were performed in areas with no prior mass drug administration (MDA) for filariasis (Papua New Guinea and Indonesia), and three studies were performed in areas with persistent LF despite extensive prior MDA (India, Haiti, and Fiji). Participants were treated with a single oral dose of IDA (ivermectin, 200 μg/kg; diethylcarbamazine, 6 mg/kg; plus albendazole, a fixed dose of 400 mg) or with DA alone. Treatment assignment in each study site was randomized by locality of residence. Treatment was offered to residents who were ≥5 years of age and not pregnant. Adverse events (AEs) were assessed by medical teams with active follow-up for 2 days and passive follow-up for an additional 5 days. A total of 26,836 persons were enrolled (13,535 females and 13,300 males). A total of 12,280 participants were treated with DA, and 14,556 were treated with IDA. On day 1 or 2 after treatment, 97.4% of participants were assessed for AEs. The frequency of all AEs was similar after IDA and DA treatment (12% versus 12.1%, adjusted odds ratio for IDA versus DA 1.15, 95% CI 0.87-1.52, P = 0.316); 10.9% of participants experienced mild (grade 1) AEs, 1% experienced moderate (grade 2) AEs, and 0.1% experienced severe (grade 3) AEs. Rates of serious AEs after DA and IDA treatment were 0.04% (95% CI 0.01%-0.1%) and 0.01% (95% CI 0.00%-0.04%), respectively. Severity of AEs was not significantly different after IDA or DA. Five of six serious AEs reported occurred after DA treatment. The most common AEs reported were headache, dizziness, abdominal pain, fever, nausea, and fatigue. AE frequencies varied by country and were higher in adults and in females. AEs were more common in study participants with microfilaremia (33.4% versus 11.1%, P < 0.001) and more common in microfilaremic participants after IDA than after DA (39.4% versus 25.6%, P < 0.001). However, there was no excess of severe or serious AEs after IDA in this subgroup. The main limitation of the study was that it was open-label. Also, aggregation of AE data from multiple study sites tends to obscure variability among study sites.
In this study, we observed that IDA was well tolerated in LF-endemic populations. Posttreatment AE rates and severity did not differ significantly after IDA or DA treatment. Thus, results of this study suggest that IDA should be as safe as DA for use as a MDA regimen for LF elimination in areas that currently receive DA.
Clinicaltrials.gov registration number: NCT02899936.
Lymphatic Filariasis (LF) affects over 120 million people in 72 countries, with sub-periodic filariasis common in the Pacific. Wuchereria bancrofti has three physiological races, each with a unique ...microfilarial periodicity, and each race is isolated to a specific geographical region. Sub-periodic W. bancrofti is transmitted by various Aedes mosquito species, with Aedes polynesiensis and Aedes samoanus being the primary vectors in Samoa. The Aedes scutellaris and Aedes kochi groups are also important vectors in the South Pacific Islands. Anopheles species are important vectors of filariasis in rural areas of Asia and Africa. The Anopheles gambiae complex, Anopheles funestus, and the Anopheles punctulatus group are the most important vectors of W. bancrofti. These vectors exhibit indoor nocturnal biting behaviour and breed in a variety of habitats, including freshwater, saltwater, and temporary water bodies. Effective vector surveillance is central to LF control and elimination programs. However, the traditional Human Landing Collection (HLC) method, while valuable, poses ethical concerns and risks to collectors. Therefore, this review critically analyses alternative trapping tools for Aedes and Anopheles vectors in LF-endemic regions. We looked at 14 research publications that discussed W. bancrofti vector trapping methods. Pyrethrum Spray Catches (PSC), one of the seven traps studied for Anopheles LF vectors, was revealed to be the second most effective strategy after HLC, successfully catching Anopheles vectors in Nigeria, Ghana, Togo, and Burkina Faso. The PSC method has several drawbacks, such as the likelihood of overlooking exophilic mosquitoes or underestimating Anopheles populations. However, exit traps offered hope for capturing exophilic mosquitoes. Anopheles populations could also be sampled using the Anopheles Gravid Trap (AGT). In contrast, the effectiveness of the Double Net Traps (DNT) and the CDC Light Trap (CDC LT) varied. Gravid mosquito traps like the OviArt Gravid Trap (AGT) were shown to be useful tools for identifying endophilic and exophilic vectors during the exploration of novel collection techniques. The Stealth trap (ST) was suggested for sampling Anopheles mosquitoes, although specimen damage may make it difficult to identify the species. Although it needs more confirmation, the Ifakara Tent Trap C design (ITT-C) showed potential for outdoor mosquito sampling in Tanzania. Furvela tent traps successfully captured a variety of Anopheles species and are appropriate for use in a variety of eco-epidemiological settings. By contrast, for Aedes LF vectors, no specific sampling tool was identified for Aedes niveus, necessitating further research and development. However, traps like the Duplex cone trap, Resting Bucket Trap (RB), and Sticky Resting Bucket trap (SRB) proved effective for sampling Aedes albopictus, offering potential alternatives to HLC. This review emphasises the value of looking into alternative trapping methods for Aedes and Anopheles vectors in the LF-endemic region. Further research is required to determine the efficacy of novel collection techniques in various contexts, even if PSC and AGT show promise for sampling Anopheles vectors. The identified traps, along with ongoing research, provide valuable contributions to vector surveillance efforts in LF-endemic regions, enabling LF control and elimination strategies to advance.
The Global Programme to Eliminate Lymphatic Filariasis (GPELF) depends upon Mass Drug Administration (MDA) to interrupt transmission. Therefore, delimitation of transmission risk areas is an ...important step, and hence we attempted to define a geo-environmental risk model (GERM) for determining the areas of potential transmission of lymphatic filariasis.
A range of geo-environmental variables has been selected, and customized on GIS platform to develop GERM for identifying the areas of filariasis transmission in terms of "risk" and "non-risk". The model was validated through a 'ground truth study' following standard procedure using GIS tools for sampling and Immuno-chromotographic Test (ICT) for screening the individuals.
A map for filariasis transmission was created and stratified into different spatial entities, "risk' and "non-risk", depending on Filariasis Transmission Risk Index (FTRI). The model estimation corroborated well with the ground (observed) data.
The geo-environmental risk model developed on GIS platform is useful for spatial delimitation purpose on a macro scale.
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