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.

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.

Entomological assessment in 'hotspots' of four lymphatic filariasis endemic districts, Central Nepal during post-MDA surveillance.

BACKGROUND OBJECTIVES: Annual mass drug administration (MDA) is the main strategy to interrupt the transmission of lymphatic filariasis (LF) in the community. The main aim of monitoring the MDA program, for its effectiveness and interruption of LF is the post-MDA surveillance using antigen survey in children born after MDA. The latest technique of new research suggests that xenomonitoring is an effective tool for monitoring LF intervention. The objective of this study was to assess the W. bancrofti infection/or infectivity in vector mosquitoes by xenomonitoring during post-MDA surveillance. METHODS: A descriptive cross-sectional study was conducted in the hotspots of selected four districts of Central Nepal. A gravid trap technique was used for sampling mosquitoes. Infection/or infectivity was determined via the dissection of vector mosquitoes. Anopheles, Aedes, Armigerus and Culex species were collected from hotspots of four endemic districts, two from the hilly region (Lalitpur and Dhading) and two from Terai region (Bara and Mahottari) of Central Nepal. RESULTS: A total of 4450 mosquitoes belonging to four genera, Anopheles, Culex, Armigeres, and Aedes were collected from four hotspots. The distribution of Culex quinquefasciatus was found to be the highest, 88.9% (n=3955/4450) followed by Cx. vishnui (4.5%), Armigeres sp (5.8%), An. culicifascies (0.2%), Aedes spp (0.8%). The proportion of female mosquitoes trapped is significantly higher. A total of 3344 parous Cx. quinquefasciatus mosquitoes were dissected for any larval stage of W. bancrofti. We could not find any filarial infection in dissected mosquito samples. INTERPRETATION CONCLUSION: We conclude that the gravid trap is an efficient tool for the collection of gravid Cx. quinquefasciatus mosquitoes for xenomonitoring studies of filariasis endemic regions. Vector composition indicated a maximum number of vector mosquitoes of lymphatic filariasis were trapped compared with the other three species. Distribution and density of Cx. quinquefasciatus was found highest in four hotspots of endemic districts. None of the Cx. quinquefasciatus dissected were found to be infected by larval forms of filaria. Since the low levels of infection persistence in the human population in these hot spots, vector infection and infectivity can't be ignored. Microscopic xenomonitoring at a low level of infection persistent is less likely to be efficient so molecular xenomonitoring along with a large sample should be required in each of the hot spots of the districts. Additionally, area is receptive so further vector control intervention should be required to reduce the risk of resurgence of infection.

Development of a molecular xenomonitoring protocol to assess filariasis transmission.

According to the World Health Organization, lymphatic filariasis (LF), a mosquito-borne neglected tropical disease (NTD), should be eliminated as a public health concern by the end of 2020. To this end, the goals of the Global Programme to Eliminate Lymphatic Filariasis (GPELF) include interrupting transmission through mass drug administration (MDA). After two decades, several countries have implemented MDA and are now ready to confirm whether transmission has been interrupted. The method for detecting the parasites in mosquito vectors known as xenomonitoring is a non-invasive tool for assessing the current transmission status of the filarial nematode Wuchereria bancrofti (which is responsible for 90% of cases) by their vectors. There are several methods available for detection of the worm in mosquito samples, such as dissection or polymerase chain reaction (PCR). However, most of these techniques still produce a considerable number of false-negative results. The present study describes a new duplex PCR protocol, which is an improvement on the traditional PCR methodology, enhanced by introducing the actin gene as an endogenous control gene. After adjusting the mosquito pool size, DNA extraction, and WbCx PCR duplex design, we achieved a reliable and sensitive molecular xenomonitoring protocol. This assay was able to eliminate 5% of false negative samples and detected less than one Wb larvae. This high sensitivity is particularly valuable after MDA, when prevalence declines. This new method could reduce the number of false-negative samples, which will enable us to improve our ability to generate accurate results and aid the monitoring strategies used by LF elimination programmes.

A Mathematical Model for the Transmission Dynamics of Lymphatic Filariasis with Intervention Strategies.

This manuscript considers the transmission dynamics of lymphatic filariasis with some intervention strategies in place. Unlike previously developed models, our model takes into account both the exposed and infected classes in both the human and mosquito populations, respectively. We also consider vaccinated, treated and recovered humans in the presented model. The global dynamics of the proposed model are completely determined by the basic ([Formula: see text]) and effective reproduction numbers ([Formula: see text]). We then use Lyapunov function theory to find the sufficient conditions for global stability of both the disease-free equilibrium and endemic equilibrium. The Lyapunov functions show that when the basic reproduction number is less than or equal to unity, the disease-free equilibrium is globally asymptotically stable, and when it is greater than unity then the endemic equilibrium is also globally asymptotically stable. Finally, numerical simulations are carried out to investigate the effects of the intervention strategies and key parameters to the spread of lymphatic filariasis. The numerical simulations support the analytical results and illustrate possible model behavioral scenarios.

Profiling the best-performing community medicine distributors for mass drug administration: a comprehensive, data-driven analysis of treatment for schistosomiasis, lymphatic filariasis, and soil-transmitted helminths in Uganda.

BACKGROUND: The most prevalent neglected tropical diseases are treated through blanket drug distribution that is reliant on lay community medicine distributors (CMDs). Yet, treatment rates achieved by CMDs vary widely and it is not known which CMDs treat the most people. METHODS: In Mayuge District, Uganda, we tracked 6779 individuals (aged 1+ years) in 1238 households across 31 villages. Routine, community-based mass drug administration (MDA) was implemented for schistosomiasis, lymphatic filariasis, and soil-transmitted helminths. For each CMD, the percentage of eligible individuals treated (offered and ingested medicines) with at least one drug of praziquantel, albendazole, or ivermectin was examined. CMD attributes (more than 25) were measured, ranging from altruistic tendencies to socioeconomic characteristics to MDA-specific variables. The predictors of treatment rates achieved by CMDs were selected with least absolute shrinkage and selection operators and then analyzed in ordinary least squares regression with standard errors clustered by village. The influences of participant compliance and the ordering of drugs offered also were examined for the treatment rates achieved by CMDs. RESULTS: Overall, only 44.89% (3043/6779) of eligible individuals were treated with at least one drug. Treatment rates varied amongst CMDs from 0% to 84.25%. Treatment rate increases were associated (p value< 0.05) with CMDs who displayed altruistic biases towards their friends (13.88%), had friends who helped with MDA (8.43%), were male (11.96%), worked as fishermen/fishmongers (14.93%), and used protected drinking water sources (13.43%). Only 0.24% (16/6779) of all eligible individuals were noncompliant by refusing to ingest all offered drugs. Distributing praziquantel first was strongly, positively correlated (p value < 0.0001) with treatment rates for albendazole and ivermectin. CONCLUSIONS: These findings profile CMDs who treat the most people during routine MDA. Criteria currently used to select CMDs-community-wide meetings, educational attainment, age, years as a CMD, etc.-were uninformative. Participant noncompliance and the provision of praziquantel before albendazole and ivermectin did not negatively impact treatment rates achieved by CMDs. Engaging CMD friend groups with MDA, selecting CMDs who practise good preventative health behaviours, and including CMDs with high-risk occupations for endemic infections may improve MDA treatment rates. Evidence-based guidelines are needed to improve the monitoring, selection, and replacement of CMDs during MDA.

Potential of hydrocarbon and oxygenated monoterpenes against Culex pipiens larvae: Toxicity, biochemical, pharmacophore modeling and molecular docking studies.

Culex pipiens is a main vector for Bancroftian filariasis, Rift Valley Fever and diseases caused by other viruses, leaving several peoples with disabilities. In recent years, plant derived compounds have received much attention as potential alternatives to synthetic chemicals due to their low toxicity to mammals and environmental persistence. Twenty-one monoterpenes from different chemical groups (hydrocarbons and oxygenated products) were evaluated against Culex pipiens larvae. In addition, in vivo biochemical studies including effects on acetylcholine esterase (AChE), acid and alkaline phosphatases (ACP and ALP), total adenosine triphosphatase (ATPase) and gamma-aminobutyric acid transaminase (GABA-T) were investigated. Furthermore, in silico studies including pharmacophore elucidation, ADMET analysis and molecular docking of these compounds were performed. Among all tested monoterpenes, hydrocarbons [p-cymene, (R)-(+)-limonene and (+)-α-pinene], acetates (cinnamyl acetate, citronellyl acetate, eugenyl acetate and terpinyl acetate), alcohols [(±)-ß-citronellol and terpineol], aldehydes [citral and (1R)-(-)-myrtenal] and ketone [(R)-(+)-pulegone] exhibited the highest larval toxicity with LC50 = 14.88, 27.97, 26.13, 2.62, 3.81, 2.74, 21.65, 1.64, 21.70, 21.76, 1.68 and 1.90 mg/L after 48 h of exposure, respectively. The compounds proved a significant inhibition of all tested enzymes except total ATPase. The biochemical and molecular docking studies proved that AChE and GABA-T were the main targets for the tested monoterpenes.

Are Alternative Strategies Required to Accelerate the Global Elimination of Lymphatic Filariasis? Insights From Mathematical Models.

Background: With the 2020 target year for elimination of lymphatic filariasis (LF) approaching, there is an urgent need to assess how long mass drug administration (MDA) programs with annual ivermectin + albendazole (IA) or diethylcarbamazine + albendazole (DA) would still have to be continued, and how elimination can be accelerated. We addressed this using mathematical modeling. Methods: We used 3 structurally different mathematical models for LF transmission (EPIFIL, LYMFASIM, TRANSFIL) to simulate trends in microfilariae (mf) prevalence for a range of endemic settings, both for the current annual MDA strategy and alternative strategies, assessing the required duration to bring mf prevalence below the critical threshold of 1%. Results: Three annual MDA rounds with IA or DA and good coverage (≥65%) are sufficient to reach the threshold in settings that are currently at mf prevalence <4%, but the required duration increases with increasing mf prevalence. Switching to biannual MDA or employing triple-drug therapy (ivermectin, diethylcarbamazine, and albendazole [IDA]) could reduce program duration by about one-third. Optimization of coverage reduces the time to elimination and is particularly important for settings with a history of poorly implemented MDA (low coverage, high systematic noncompliance). Conclusions: Modeling suggests that, in several settings, current annual MDA strategies will be insufficient to achieve the 2020 LF elimination targets, and programs could consider policy adjustment to accelerate, guided by recent monitoring and evaluation data. Biannual treatment and IDA hold promise in reducing program duration, provided that coverage is good, but their efficacy remains to be confirmed by more extensive field studies.

Determinants of transmission hotspots and filarial infection in households after eight rounds of mass drug administration in India.

OBJECTIVES: Lymphatic filariasis (LF) elimination through mass drug administration (MDA) of DEC and albendazole have resulted in very low levels of infection in most endemic districts in India. But small pockets with residual microfilaraemia in the community and antigeneamia in children ('hotspots') are a cause of concern. We aimed to identify the determinants of such transmission hotspots and filarial infection in households using data from 33 communities. METHODS: The filariasis vector Culex quinquefasciatus was collected from 627 randomly selected households using gravid traps. Parallel data on environmental, entomological, demographical, socio-economical and behavioural factors were analysed to identify the determinants of hotspots and household-level infection. RESULTS: Hotspots and non-hotspots did not differ significantly in terms of socio-economical and behavioural aspects, but did differ in terms of demographical and environmental factors. Logistic regression revealed that tiled and concrete houses increased the risk of an area being a hotspot by 2.0 and 2.9 times respectively. Presence of Culex breeding habitats was significantly associated with elevated risk of being a hotspot. Proximity of U-drains to a house increased the risk of filarial infection 5.8 times. CONCLUSIONS: An environment suitable to Culex breeding influences continued transmission despite eight rounds of MDA, particularly in hotspots. Proximity to U-drains increases the risk of infection in households. Implementing localised vector control measures may help interrupt low-level transmission, thereby reducing the risk of resurgence in the absence of MDA.

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

Monitoring 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.

Molecular xenomonitoring (MX) and transmission assessment survey (TAS) of lymphatic filariasis elimination in two villages, Menoufyia Governorate, Egypt.

Lymphatic filariasis (LF) is focally endemic in Egypt where the female mosquito, Culex pipiens, is responsible for its transmission. The aim of the study was to investigate the impact of implementation of the 13th round of MDA in two Egyptian villages in the Menoufyia Governorate area after failing the transmission assessment survey (TAS) in 2005 using two methods, and to decide whether it is safe to stop MDA in these, as well as in similar implementation units (IUs). To achieve this aim, both the immunochromatographic card test (ICT) and molecular xenomonitoring (MX) techniques were employed. A cross-sectional study was carried out in the villages in 2014 with two sections: Section (1): a school-based survey where all the primary school entrants (6-7) years of age were tested by ICT. Section (2): a mosquito-based survey where a total of 152 mosquito pools collected from Samalay and 167 from Kafr El-Tarainah were tested for the presence of the gDNA of Wuchereria bancrofti microfilaria by real-time PCR assays. The results revealed that all primary school children in both villages were 100% negative for antigenemia. Also, all mosquito pools were 100% negative for the microfilarial gDNA.

Mathematical analysis of a lymphatic filariasis model with quarantine and treatment.

BACKGROUND: Lymphatic filariasis is a globally neglected tropical parasitic disease which affects individuals of all ages and leads to an altered lymphatic system and abnormal enlargement of body parts. METHODS: A mathematical model of lymphatic filariaris with intervention strategies is developed and analyzed. Control of infections is analyzed within the model through medical treatment of infected-acute individuals and quarantine of infected-chronic individuals. RESULTS: We derive the effective reproduction number, [Formula: see text] and its interpretation/investigation suggests that treatment contributes to a reduction in lymphatic filariasis cases faster than quarantine. However, this reduction is greater when the two intervention approaches are applied concurrently. CONCLUSIONS: Numerical simulations are carried out to monitor the dynamics of the filariasis model sub-populations for various parameter values of the associated reproduction threshold. Lastly, sensitivity analysis on key parameters that drive the disease dynamics is performed in order to identify their relative importance on the disease transmission.

DILEMMAS OF COMMUNITY-DIRECTED MASS DRUG ADMINISTRATION FOR LYMPHATIC FILARIASIS CONTROL: A QUALITATIVE STUDY FROM URBAN AND RURAL TANZANIA.

There has in recent years been a growing interest in the social significance of global health policy and associated interventions. This paper is concerned with neglected tropical disease control, which prescribes annual mass drug administration to interrupt transmission of, among others, lymphatic filariasis. In Tanzania, this intervention is conducted through community-directed distribution, which aims to improve drug uptake by promoting community participation and local ownership in the intervention. However, the average uptake of drugs often remains too low to achieve the intended interruption of transmission. The qualitative research presented here followed the implementation of mass drug administration in Lindi and Morogoro Regions, Tanzania, in 2011 to understand the different forms of involvement in the campaign and the experiences of stakeholders of their part in community-directed distribution. Some health care workers, community leaders and drug distributors were generally positive about the intervention, emphasizing that the drugs were welcome. Other stakeholders, including the drug-receiving population, reported facing a number of dilemmas of uncertainty, authority and exclusion pertaining to their roles in the intervention. These dilemmas should be of interest to donors, policymakers and implementers. Community-directed distribution relies on social relations between the many different stakeholders. Successful and justifiable interventions for lymphatic filariasis require implementers to recognize the central role of sociality and that the voices and priorities of people count.

Insecticidal bed nets and filariasis transmission in Papua New Guinea.

BACKGROUND: Global efforts to eliminate lymphatic filariasis are based on the annual mass administration of antifilarial drugs to reduce the microfilaria reservoir available to the mosquito vector. Insecticide-treated bed nets are being widely used in areas in which filariasis and malaria are coendemic. METHODS: We studied five villages in which five annual mass administrations of antifilarial drugs, which were completed in 1998, reduced the transmission of Wuchereria bancrofti, one of the nematodes that cause lymphatic filariasis. A total of 21,899 anopheles mosquitoes were collected for 26 months before and 11 to 36 months after bed nets treated with long-lasting insecticide were distributed in 2009. We evaluated the status of filarial infection and the presence of W. bancrofti DNA in anopheline mosquitoes before and after the introduction of insecticide-treated bed nets. We then used a model of population dynamics to estimate the probabilities of transmission cessation. RESULTS: Village-specific rates of bites from anopheline mosquitoes ranged from 6.4 to 61.3 bites per person per day before the bed-net distribution and from 1.1 to 9.4 bites for 11 months after distribution (P<0.001). During the same period, the rate of detection of W. bancrofti in anopheline mosquitoes decreased from 1.8% to 0.4% (P=0.005), and the rate of detection of filarial DNA decreased from 19.4% to 14.9% (P=0.13). The annual transmission potential was 5 to 325 infective larvae inoculated per person per year before the bed-net distribution and 0 after the distribution. Among all five villages with a prevalence of microfilariae of 2 to 38%, the probability of transmission cessation increased from less than 1.0% before the bed-net distribution to a range of 4.9 to 95% in the 11 months after distribution. CONCLUSIONS: Vector control with insecticide-treated bed nets is a valuable tool for W. bancrofti elimination in areas in which anopheline mosquitoes transmit the parasite. (Funded by the U.S. Public Health Service and the National Institutes of Health.).

INVESTIGATION OF MOSQUITOES WITH EMPHASIS ON AEDES (FINLAYA) POICILIUS, PUTATIVE VECTOR OF BANCROFTIAN FILARIASIS ON PANAY ISLAND, THE PHILIPPINES.

Entomological investigations were conducted in four remaining lymphatic filariasis endemic provinces of Panay Island, The Philippines to determine mosquito species present in these areas and to identify host preference and biting activity of Aedes (Finlaya) poicilius Theobald, primary vector of nocturnal periodic Wuchereria bancrofti in The Philippines. Sampling techniques targeted nocturnally active mosquito species using a carabao-baited trap (CBT) and human-landing collection (HLC), the latter taking place from 06:00 to 12:00 pm. A total of 25,536 mosquitoes comprising 42 species and 7 genera were collected from CBT, whilst HLC acquired 6,486 mosquitoes comprising 28 species and 5 genera. Three known or potential vectors of human filarial were collected, namely, Aedes poicilius, Culex quinquefasciatus and Mansonia uniformis. The peak landing (biting) activity for Ae. poicilius was between 09:00 and 11:00 pm. Comparisons between CBT and HLC yields showed this species to be more zoophilic. Based on observed mosquito behavior and interviews with residents, vector-host contact was promoted by the local practice of staying overnight in makeshift shelters in high risk areas without adequate protection against mosquito bites. Results of this survey will augment information for integrating vector control and mass drug administration into an island-wide lymphatic filariasis elimination program.

Sibling species of the Anopheles funestus group, and their infection with malaria and lymphatic filarial parasites, in archived and newly collected specimens from northeastern Tanzania.

BACKGROUND: Studies on the East African coast have shown a recent dramatic decline in malaria vector density and change in composition of sibling species of the Anopheles gambiae complex, paralleled by a major decline in malaria incidence. In order to better understand the ongoing changes in vector-parasite dynamics in the area, and to allow for appropriate adjustment of control activities, the present study examined the composition, and malaria and lymphatic filarial infection, of sibling species of the Anopheles funestus group. Similar to the An. gambiae complex, the An. funestus group contains important vectors of both malaria and lymphatic filariasis. METHODS: Archived (from 2005-2012) and newly collected (from 2014) specimens of the An. funestus group collected indoors using CDC light traps in villages in northeastern Tanzania were analysed. They were identified to sibling species by PCR based on amplification of species-specific nucleotide sequence in the ITS2 region on rDNA genes. The specimens were furthermore examined for infection with Plasmodium falciparum and Wuchereria bancrofti by PCR. RESULTS: The identified sibling species were An. funestus s.s., Anopheles parensis, Anopheles rivulorum, and Anopheles leesoni, with the first being by far the most common (overall 94.4%). When comparing archived specimens from 2005-2007 to those from 2008-2012, a small but statistically significant decrease in proportion of An. funestus s.s. was noted, but otherwise observed temporal changes in sibling species composition were minor. No P. falciparum was detected in archived specimens, while 8.3% of the newly collected An. funestus s.s. were positive for this parasite. The overall W. bancrofti infection rate decreased from 14.8% in the 2005-2007 archived specimens to only 0.5% in the newly collected specimens, and with overall 93.3% of infections being in An. funestus s.s. CONCLUSION: The study indicated that the composition of the An. funestus group had remained rather stable during the study period, with An. funestus s.s. being the most predominant. The study also showed increasing P. falciparum infection and decreasing W. bancrofti infection in An. funestus s.s. in the study period, most likely reflecting infection levels with these parasites in the human population in the area.

Prevalence of lymphatic filariasis in a tea garden worker population of Dibrugarh (Assam), India after six rounds of mass drug administration.

BACKGROUND & OBJECTIVES: Lymphatic filariasis (LF) is endemic in the state of Assam and mass drug administration (MDA) programme for LF elimination is being implemented in the state since 2004. A study on prevalence of microfilaria (mf), disease endemicity and vector infection was carried out in a tea garden population of Dibrugarh, Assam (India) to assess the effect of ongoing MDA programme on elimination of LF. METHODS: Finger prick thick blood smears (20 mm3) were made from individuals aged ≥2 yr old during night blood survey in between 2000-0000 hrs during the period of November 2012 to February 2013. Blood smears were dehaemoglobinised, stained with Giemsa and examined under microscope for presence of mf. Indoor resting mosquitoes were collected during 0600-1000 hrs and female Culex quinquefasciatus were dissected and examined under microscope for larval forms of the parasite. RESULTS: A total of 634 blood smears were collected and screened for mf and 47 (7.41%) individuals were found microfilaraemic, with predominance of males (74.5%). Highest mf rate (20.0%) was seen in the males of 30-39 yr age group while in females, age group of 10-19 yr recorded maximum mf rate (5.48%). Entomological collection and dissection of Cx. quinquefasciatus revealed presence of larval stages of the parasite and infection and infectivity rates recorded were 13.20 and 3.70%, respectively. Chronic clinical manifestations in the form of elephantiasis and hydrocele were recorded in 33 (5.73%) subjects of the 575 examined. INTERPRETATION & CONCLUSION: Mass drug administration data showed six rounds of MDA with drug distribution coverage in between 63.42 and 95.93% in the study population. Out of 634 individuals examined 47 were found microfilaraemic giving an overall infection rate of 7.41%. Mosquito vector infection and infectivity rates were 13.20 and 3.70%, respectively. Presence of high mf rate, vector infectivity rate and clinical cases in the study population after six rounds of MDA warrants concerted efforts to be made for effective implementation and monitoring of MDA for success of LF elimination programme.

Non-endemic cases of lymphatic filariasis.

OBJECTIVE: Several cases of lymphatic filariasis (LF) have been reported in non-endemic countries due to travellers, military personnel and expatriates spending time in and returning from endemic areas, as well as immigrants coming from these regions. These cases are reviewed to assess the scale and context of non-endemic presentations and to consider the biological factors underlying their relative paucity. METHODS: Cases reported in the English, French, Spanish and Portuguese literature during the last 30 years were examined through a search of the PubMed, ProMED-mail and TropNet resources. RESULTS: The literature research revealed 11 cases of lymphatic filariasis being reported in non-endemic areas. The extent of further infections in recent migrants to non-endemic countries was also revealed through the published literature. CONCLUSIONS: The life-cycle requirements of Wuchereria and Brugia species limit the extent of transmission of LF outside of tropical regions. However, until elimination, programmes are successful in managing the disease, there remains a possibility of low rates of infection being reported in non-endemic areas, and increased international travel can only contribute to this phenomenon. Physicians need to be aware of the signs and symptoms of lymphatic filariasis, and infection should be considered in the differential diagnosis of people with a relevant travel history.

Modelling co-infection with malaria and lymphatic filariasis.

Malaria and lymphatic filariasis (LF) continue to cause a considerable public health burden globally and are co-endemic in many regions of sub-Saharan Africa. These infections are transmitted by the same mosquito species which raises important questions about optimal vector control strategies in co-endemic regions, as well as the effect of the presence of each infection on endemicity of the other; there is currently little consensus on the latter. The need for comprehensive modelling studies to address such questions is therefore significant, yet very few have been undertaken to date despite the recognised explanatory power of reliable dynamic mathematical models. Here, we develop a malaria-LF co-infection modelling framework that accounts for two key interactions between these infections, namely the increase in vector mortality as LF mosquito prevalence increases and the antagonistic Th1/Th2 immune response that occurs in co-infected hosts. We consider the crucial interplay between these interactions on the resulting endemic prevalence when introducing each infection in regions where the other is already endemic (e.g. due to regional environmental change), and the associated timescale for such changes, as well as effects on the basic reproduction number R0 of each disease. We also highlight potential perverse effects of vector controls on human infection prevalence in co-endemic regions, noting that understanding such effects is critical in designing optimal integrated control programmes. Hence, as well as highlighting where better data are required to more reliably address such questions, we provide an important framework that will form the basis of future scenario analysis tools used to plan and inform policy decisions on intervention measures in different transmission settings.