Lymphatic filariasis control in Tanzania: infection, disease perceptions and drug uptake patterns in an endemic community after multiple rounds of mass drug administration.

BACKGROUND: Lymphatic filariasis (LF) control in most countries of sub-Saharan Africa is based on annual mass drug administration (MDA) with a combination of ivermectin and albendazole, in order to interrupt transmission. However, attaining and maintaining high treatment coverage has been a challenge in many LF control programmes. This study was designed to elucidate reasons for continued transmission of LF in an endemic area of Tanga, northeastern Tanzania, where control activities based on MDA had been in place for eight years by the time of this study in 2012. METHODS: A cross-sectional questionnaire survey was conducted in three sentinel villages used for monitoring the impact of MDA on LF transmission. A total of 747 individuals were interviewed, out of which 172 (23.0%), 27 (3.6%) and 49 (6.5%) had been shown to have circulating filarial antigens (CFA), microfilaraemia (MF) and LF gross lesions, respectively, prior to the interviews. RESULTS: The interviewed population had a mean age of 33.7 years and a male to female ratio of 0.8. Males, individuals aged 30 years and above, peasants/fishermen and recent immigrants to the study communities were significantly more affected (CFA, MF and/ or LF gross lesions) than the other population groups. However, drug uptake rates were not significantly different between LF affected (those with CFA, MF and/ or LF gross lesions) and non-affected individuals. Likewise, drug uptake rates were not significantly different across different demographic parameters of the study population, some of which differed significantly in the level of infection. Moreover, it was found that misconceptions on how LF can be acquired were still evident, linking its transmission to witchcraft, heredity and sexual behaviour. CONCLUSIONS: The findings indicated that misconceptions about LF and its transmission still existed despite eight years of control activities in the area. Improved communication on the rationale of MDA and an enhanced drug delivery strategy that is adapted to the local settings and targeting important demographic groups that serve as reservoir of infection will help in reaching the elimination target within a reasonable timeframe.

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.

Assessing drivers of the IgG4 antibody reactivity to recombinant antigen Bm14 in Wuchereria bancrofti endemic populations in East Africa.

A high proportion of the human population in lymphatic filariasis (LF) endemic areas is positive for filarial specific IgG4 antibodies, including many individuals without microfilariae (mf; circulating larvae in the human blood) or circulating filarial antigens (CFA; marker of adult worm infection). The antibodies are commonly regarded as markers of infection and/or exposure to filarial larvae, but a direct association between the antibodies and these indices has not been well documented. The present study assessed the role and relative effect of potential drivers of the human IgG4 antibody reactivity to the recombinant filarial antigen Bm14 in Wuchereria bancrofti endemic populations in East Africa. Sera collected during previous studies from 395 well characterized individuals with regard to age, sex, mf, CFA, household vector biting and household exposure to infective filarial larvae were tested for IgG4 antibodies to Bm14, and associations between antibody reactivity and the different variables were statistically analyzed. IgG4 reactivity to Bm14 was highly positively associated with CFA, and to a lesser extent with age. However, an expected association with household exposure to infective filarial larvae was not found. Bm14 antibody reactivity thus appeared mainly to reflect actual infection of individuals with adult filarial worms rather than ongoing exposure to transmission. The analyses moreover suggested that many of the CFA negative but Bm14 positive individuals had early or low level infections where antibodies had been induced but where CFA was not (yet?) measurable. Although the study indicated that IgG4 reactivity to Bm14 is a marker of filarial infection, assessment of this reactivity, especially in children, will still be useful for indirect monitoring of changes in transmission intensity, including break of transmission and post-elimination surveillance, in LF control.

Effect of ivermectin on the larvae of Anopheles gambiae and Culex quinquefasciatus.

BACKGROUND: Ivermectin is used extensively globally for treatment of helminthic and ectoparasitic infections in animals and humans. The effect of excreted ivermectin on non-target organisms in aquatic and terrestrial environments has been increasingly reported. Due to its low water solubility and adsorption to sediments, the ivermectin exposure-risk to aquatic organisms dwelling in different strata of water bodies varies. This study assessed the survival of larvae of Anopheles gambiae Giles and Culex quinquefasciatus Say, when exposed to low concentrations of ivermectin under laboratory conditions. METHODS: A total of 1800 laboratory reared mosquito larvae of each species were used in the bioassays. Twelve replicates were performed, each testing 6 concentrations of ivermectin (0.0, 0.001, 0.01, 0.1, 1.0 and 10.0 parts per million (ppm)) against third instar larvae of An. gambiae and Cx. quinquefasciatus. Larval mortality was recorded at 24 and 48 h post addition of ivermectin. RESULTS: Survival declined markedly with increase in ivermectin concentration in both species. While mean survival of An. gambiae at 24 h of exposure was 99.6 %, 99.2 % and 61.6 % in 0.001, 0.01 and 0.1 ppm of ivermectin, respectively, the mean survival of Cx. quinquefasciatus at the same dosage and time was 89.2 %, 47.2 % and 0.0 %. A similar pattern, but with higher mortality, was observed after 48 h of exposure. Comparison between the species revealed that Cx. quinquefasciatus larvae were significantly more affected by ivermectin than those of An. gambiae, both at 24 and 48 h. CONCLUSIONS: Low concentrations of ivermectin in the aquatic environment reduced the survival of larvae of An. gambiae and Cx. quinquefasciatus, with the effect being more marked in the latter species. It is suggested that this difference may be due to the different water strata occupied by the two species, with ivermectin adsorbed in food that sediment being more readily available to the bottom feeding Cx. quinquefasciatus than the surface feeding An. gambiae larvae.

Schistosoma haematobium and soil-transmitted Helminths in Tana Delta District of Kenya: infection and morbidity patterns in primary schoolchildren from two isolated villages.

BACKGROUND: Schistosomes and soil-transmitted helminths (STH) (hookworm, Trichuris trichiura and Ascaris lumbricoides) are widely distributed in developing countries where they infect over 230 million and 1.5 billion people, respectively. The parasites are frequently co-endemic and many individuals are co-infected with two or more of the species, but information on how the parasites interact in co-infected individuals is scarce. The present study assessed Schistosoma haematobium and STH infection and morbidity patterns among school children in a hyper-endemic focus in the Tana River delta of coastal Kenya. METHODS: Two hundred and sixty-two children aged 5-12 years from two primary schools were enrolled in the study. For each child, urine was examined for S. haematobium eggs and haematuria, stool was examined for STH eggs, peripheral blood was examined for eosinophilia and haemoglobin level, the urinary tract was ultrasound-examined for S. haematobium-related pathology, and the height and weight was measured and used to calculate the body mass index (BMI). RESULTS: Prevalences of S. haematobium, hookworm, T. trichiura and A. lumbricoides infection were 94, 81, 88 and 46 %, respectively. There was no significant association between S. haematobium and STH infection but intensity of hookworm infection significantly increased with that of T. trichiura. Lower BMI scores were associated with high intensity of S. haematobium (difference =-0.48, p > 0.05) and A. lumbricoides (difference =-0.67, p < 0.05). Haematuria (both macro and micro) was common and associated with S. haematobium infection, while anaemia was associated with high intensity of S. haematobium (OR = 2.08, p < 0.05) and high hookworm infections OR = 4.75; p < 0.001). The majority of children had eosinophilia, which was significantly associated with high intensity of hookworm infection (OR = 5.34, p < 0.05). Overall 38 % of the children had ultrasound-detectable urinary tract morbidity, which was associated with high intensity of S. haematobium infection (OR = 3.13, p < 0.05). CONCLUSION: Prevalences of S. haematobium and STH infections among the primary school children were high and the parasites were responsible for significant morbidity. A clear synergistic interaction was observed between hookworm and T. trichiura infections. Increased coverage in administration of praziquantel and albendazole in the area is recommended to control morbidity due to these infections.

Ecological Drivers of Mansonella perstans Infection in Uganda and Patterns of Co-endemicity with Lymphatic Filariasis and Malaria.

BACKGROUND: Mansonella perstans is a widespread, but relatively unknown human filarial parasite transmitted by Culicoides biting midges. Although it is found in many parts of sub-Saharan Africa, only few studies have been carried out to deepen the understanding of its ecology, epidemiology, and health consequences. Hence, knowledge about ecological drivers of the vector and parasite distribution, integral to develop spatially explicit models for disease prevention, control, and elimination strategies, is limited. METHODOLOGY: We analyzed data from a comprehensive nationwide survey of M. perstans infection conducted in 76 schools across Uganda in 2000-2003, to identify environmental drivers. A suite of Bayesian geostatistical regression models was fitted, and the best fitting model based on the deviance information criterion was utilized to predict M. perstans infection risk for all of Uganda. Additionally, we investigated co-infection rates and co-distribution with Wuchereria bancrofti and Plasmodium spp. infections observed at the same survey by mapping geographically overlapping areas. PRINCIPAL FINDINGS: Several bioclimatic factors were significantly associated with M. perstans infection levels. A spatial Bayesian regression model showed the best fit, with diurnal temperature range, normalized difference vegetation index, and cattle densities identified as significant covariates. This model was employed to predict M. perstans infection risk at non-sampled locations. The level of co-infection with W. bancrofti was low (0.3%), due to limited geographic overlap. However, where the two infections did overlap geographically, a positive association was found. CONCLUSIONS/SIGNIFICANCE: This study presents the first geostatistical risk map for M. perstans in Uganda. We confirmed a widespread distribution of M. perstans, and identified important potential drivers of risk. The results provide new insight about the ecologic preferences of this otherwise poorly known filarial parasite and its Culicoides vector species in Uganda, which might be relevant for other settings in sub-Saharan Africa.

COMMUNITY MEMBERS' PERCEPTIONS OF MASS DRUG ADMINISTRATION FOR CONTROL OF LYMPHATIC FILARIASIS IN RURAL AND URBAN TANZANIA.

Lymphatic filariasis is one of several neglected tropical diseases with severely disabling and stigmatizing manifestations that are referred to as 'neglected diseases of poverty'. It is a mosquito-borne disease found endemically and exclusively in low-income contexts where, concomitantly, general public health care is often deeply troubled and fails to meet the basic health needs of impoverished populations. This presents particular challenges for the implementation of mass drug administration (MDA), which currently is the principal means of control and eventual elimination. Several MDA programmes face the dilemma that they are unable to attain and maintain the required drug coverage across target groups. In recognition of this, a qualitative study was conducted in the Morogoro and Lindi regions of Tanzania to gain an understanding of community experiences with, and perceptions of, the MDA campaign implemented in 2011 by the National Lymphatic Filariasis Elimination Programme. The study revealed a wide variation of perceptions and experiences regarding the aim, rationale and justification of MDA. There were positive sentiments about the usefulness of the drugs, but many study participants were sceptical about the manner in which MDA is implemented. People were particularly disappointed with the limited attempts by implementers to share information and mobilize residents. In addition, negative sentiments towards MDA for lymphatic filariasis reflected a general feeling of desertion and marginalization by the health care system and political authorities. However, the results suggest that if the communities are brought on board with genuine respect for their integrity and informed self-determination, there is scope for major improvements in community support for MDA-based control activities.

Filarial infections in domestic dogs in Lusaka, Zambia.

Filariae are common parasites of dogs in many parts of the world, but little is known about the status of these infections in sub-Saharan Africa. A study was carried out to determine the occurrence and species of filariae among 272 dogs in Lusaka, Zambia. Giemsa stained blood smear and Knott's concentration methods revealed microfilariae in 16 (5.9%) of the dogs. PCR confirmed that most of these dogs had Acanthocheilonema reconditum infection. Ten (4.0%) of the examined dogs were positive for Dirofilaria immitis circulating antigen (by DiroCHEK(®) test), but D. immitis microfilariae were not identified in any of the dogs and the status of this infection remains unclear. Further studies are needed to explore the occurrence of filariae in Zambian dogs and the zoonotic potential for humans.

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.

Differential effect of human ivermectin treatment on blood feeding Anopheles gambiae and Culex quinquefasciatus.

BACKGROUND: Widespread and large scale use of ivermectin in humans and domestic animals can have unexpected effects on non-target organisms. As a search for a possible explanation for an observed longitudinal decline in density of anopheline vector mosquitoes, but not in Culex quinquefasciatus, in an area of north-eastern Tanzania which has been exposed to ivermectin mass drug administration, this study assessed and compared the effect of human ivermectin treatment on blood feeding Anopheles gambiae and Cx. quinquefasciatus. METHODS: Consenting adult volunteers were randomized into two groups to receive either ivermectin or placebo. Twenty four hours after treatment, one volunteer from each group was concurrently exposed to 50 laboratory reared An. gambiae on one arm and 50 laboratory reared Cx. quinquefasciatus on the other arm for 15-30 minutes. Engorged mosquitoes were maintained on 10% glucose solution for 12 days and observed for survival and fecundity. The experiment was repeated 15 times. RESULTS: Two days after the blood meals, nearly half (average 47.7% for the 15 experiments) of the blood fed An. gambiae in the ivermectin group had died while almost all in the placebo group were alive (97.2%), and the difference in survival between these two groups continued to widen on the following days. There was no clear effect of ivermectin on Cx. quinquefasciatus, which had high survival in both ivermectin and placebo group on day 2 (95.7% and 98.4%, respectively) as well as on the following days. Ivermectin completely inhibited egg laying in An. gambiae, while egg laying and subsequent development of immature stages appeared normal in the other three groups. CONCLUSION: Blood meals taken on ivermectin treated volunteers significantly reduced survival and halted fecundity of An. gambiae but had only limited or no effect on Cx. quinquefasciatus. The result suggests that widespread use of ivermectin may have contributed to the observed decline in density of An. gambiae, without similar decrease in Cx. quinquefasciatus, in north-eastern Tanzania.

Lymphatic filariasis control in Tanga Region, Tanzania: status after eight rounds of mass drug administration.

BACKGROUND: Lymphatic filariasis (LF) control started in Tanga Region of Tanzania in 2004, with annual ivermectin/albendazole mass drug administration (MDA). Since then, the current project has monitored the effect in communities and schools in rural areas of Tanga District. In 2013, after 8 rounds of MDA, spot check surveys were added in the other 7 districts of Tanga Region, to assess the regional LF status. METHODS: LF vector and transmission surveillance, and human cross sectional surveys in communities and schools, continued in Tanga District as previously reported. In each of the other 7 districts, 2-3 spot check sites were selected and about 200 schoolchildren were examined for circulating filarial antigens (CFA). At 1-2 of the sites in each district, additional about 200 community volunteers were examined for CFA and chronic LF disease, and the CFA positives were re-examined for microfilariae (mf). RESULTS: The downward trend in LF transmission and human infection previously reported for Tanga District continued, with prevalences after MDA 8 reaching 15.5% and 3.5% for CFA and mf in communities (decrease by 75.5% and 89.6% from baseline) and 2.3% for CFA in schoolchildren (decrease by 90.9% from baseline). Surprisingly, the prevalence of chronic LF morbidity after MDA 8 was less than half of baseline records. No infective vector mosquitoes were detected after MDA 7. Spot checks in the other districts after MDA 8 showed relatively high LF burdens in the coastal districts. LF burdens gradually decreased when moving to districts further inland and with higher altitudes. CONCLUSION: LF was still widespread in many parts of Tanga Region after MDA 8, in particular in the coastal areas. This calls for intensified control, which should include increased MDA treatment coverage, strengthening of bed net usage, and more male focus in LF health information dissemination. The low LF burdens observed in some inland districts suggest that MDA in these could be stepped down to provide more resources for upscale of control in the coastal areas. Monitoring should continue to guide the programme to ensure that the current major achievements will ultimately lead to successful LF elimination.

Factors influencing drug uptake during mass drug administration for control of lymphatic filariasis in rural and urban Tanzania.

BACKGROUND: In most countries of Sub-Saharan Africa, control of lymphatic filariasis (LF) is based on annual mass drug administration (MDA) with a combination of ivermectin and albendazole. Treatment coverages are however often suboptimal for programmes to reach the goal of transmission interruption within reasonable time. The present study aimed to identify predictors and barriers to individual drug uptake during MDA implementation by the National LF Elimination Programme in Tanzania. METHODS: A questionnaire based cross sectional household survey was carried out in two rural and two urban districts in Lindi and Morogoro regions shortly after the 2011 MDA. 3279 adults (≥15 years) were interviewed about personal characteristics, socio-economic status, MDA drug uptake among themselves and their children, reasons for taking/not taking drugs, and participation in previous MDA activities for LF control. FINDINGS: The overall drug uptake rate was 55.1% (range of 44.5-75.6% between districts). There was no overall major difference between children (54.8%) and adults (55.2%) or between females (54.9%) and males (55.8%), but the role of these and other predictors varied to some extent between study sites. Major overall predictors of drug uptake among the interviewed adults were increasing age and history of previous drug uptake. Being absent from home during drug distribution was the main reason for not taking the drugs (50.2%) followed by clinical contraindications to treatment (10.8%), missing household visits of drug distributors (10.6%), and households not being informed about the distribution (9.0%). CONCLUSION: Drug uptake relied more on easily modifiable provider-related factors than on individual perceptions and practices in the target population. Limited investments in appropriate timing, dissemination of accurate timing information to recipients and motivation of drug distributors to visit all households (repeatedly when residents are absent) are likely to have considerable potential for increasing drug uptake, in support of successful LF transmission elimination.

Urinary cytokines in Schistosoma haematobium-infected schoolchildren from Tana Delta District of Kenya.

BACKGROUND: Pathological changes due to infection with Schistosoma haematobium include cytokine-mediated urinary tract inflammation. The involved cytokines may be excreted in urine and their presence in urine may therefore reflect S. haematobium-related urinary tract pathology. The present study, for the first time, reports on the relationship between selected cytokines in urine and infection with S. haematobium in children from an area highly affected by this parasite. METHODS: Children aged 5-12 years from two primary schools in Tana Delta District of Kenya were examined for S. haematobium eggs using urine filtration technique, for haematuria using dipstix and for eosinophil cationic protein (ECP), IL-6, IFN- γ, TNF-α and IL-10 levels using ELISA, and for S. haematobium-related urinary tract pathology using ultrasonography. In addition, venous blood was examined for serum IL-6, IFN- γ, TNF-α and IL-10 levels using ELISA. RESULTS: There was no significant correlation between urinary and serum levels of IL-6, IFN- γ, TNF-α or IL-10. There was no significant difference in geometric mean intensity (GMI) in any of the serum cytokines, or in urinary TNF-α or IFN-γ, between children with light and heavy S. haematobium infections. However, children with heavy S. haematobium infections had significantly higher GMI of urinary IL-6 (p < 0.001) and lower GMI of urinary IL-10 (p = 0.002) than children with light infections. There was also a significant positive correlation between urinary IL-6 and urinary ECP (p < 0.001) and a significant negative correlation between urinary IL-10 and urinary ECP (p = 0.012). CONCLUSION: Urinary IL-6 was positively correlated to and IL-10 was negatively correlated to infection intensity and urinary tract inflammation in S. haematobium-infected children. Urinary IL-6 and IL-10 ELISA may be a useful non-invasive tool to complement the already available tools for studying S. haematobium-related urinary tract pathology in children.

Mapping the geographical distribution of lymphatic filariasis in Zambia.

BACKGROUND: Past case reports have indicated that lymphatic filariasis (LF) occurs in Zambia, but knowledge about its geographical distribution and prevalence pattern, and the underlying potential environmental drivers, has been limited. As a background for planning and implementation of control, a country-wide mapping survey was undertaken between 2003 and 2011. Here the mapping activities are outlined, the findings across the numerous survey sites are presented, and the ecological requirements of the LF distribution are explored. METHODOLOGY/PRINCIPAL FINDINGS: Approximately 10,000 adult volunteers from 108 geo-referenced survey sites across Zambia were examined for circulating filarial antigens (CFA) with rapid format ICT cards, and a map indicating the distribution of CFA prevalences in Zambia was prepared. 78% of survey sites had CFA positive cases, with prevalences ranging between 1% and 54%. Most positive survey sites had low prevalence, but six foci with more than 15% prevalence were identified. The observed geographical variation in prevalence pattern was examined in more detail using a species distribution modeling approach to explore environmental requirements for parasite presence, and to predict potential suitable habitats over unsurveyed areas. Of note, areas associated with human modification of the landscape appeared to play an important role for the general presence of LF, whereas temperature (measured as averaged seasonal land surface temperature) seemed to be an important determinant of medium-high prevalence levels. CONCLUSIONS/SIGNIFICANCE: LF was found to be surprisingly widespread in Zambia, although in most places with low prevalence. The produced maps and the identified environmental correlates of LF infection will provide useful guidance for planning and start-up of geographically targeted and cost-effective LF control in Zambia.

Urban schistosomiasis and soil transmitted helminthiases in young school children in Dar es Salaam and Tanga, Tanzania, after a decade of anthelminthic intervention.

Rapid urbanization in resource poor countries often results in expansion of unplanned settlements with overcrowding and inadequate sanitation. These conditions potentially support transmission of schistosomiasis and soil transmitted helminths (STH), but knowledge on the occurrence, transmission and control of these infections in urban settings is limited. The present study assessed the status of urinary schistosomiasis and STH across two different-sized cities in Tanzania - Dar es Salaam and Tanga - after a decade of anthelminthic intervention. Primary school children were examined for parasite eggs in urine and stool. Questionnaires were administered to the children, and observations were made on the urban environments. The burden of urinary schistosomiasis and STH was found to be low in both cities (overall 1.2% in Dar es Salaam and 0.3% in Tanga for urinary schistosomiasis; overall <1% in Dar es Salaam and 1-2% in Tanga for each STH infection), and the identified cases showed no clear pattern of spatial distribution. The findings indicated that a marked decrease in prevalence of these infections had occurred in the two cities during recent years. The observed promising developments appeared to have been accomplished by implementation of drug based intervention programs, in combination with environmental change (fewer snail habitats) and generally improved levels of hygiene. Continued efforts, including anthelminthic treatment and health education, are important to maintain these positive achievements.

PREVALENCE OF LYMPHATIC FILARIASIS, MALARIA AND SOIL TRANSMITTED HELMINTHIASIS IN A COMMUNITY OF BARDIYA DISTRICT, WESTERN NEPAL.

Lymphatic filariasis (LF), malaria and soil transmitted helminthiasis (STH) cause major health problems in Nepal, but in spite of this very few stud- ies have been carried out on these parasitic infections in Nepal. A cross sectional survey of all three categories of parasitic infections was carried out in Deuda- kala Village of Bardiya District, western Nepal. A total of 510 individuals aged 5 years and above were examined from finger prick blood for circulating filarial antigen (CFA), malaria antigen using a rapid diagnostic test (RDT), and malaria DNA using a PCR-based assay. In addition, 317 individuals were examined for soil-transmitted helminth (STH) eggs by the Kato-Katz technique. Prevalence of LF, malaria (antigen) and STH infection was 25.1%, 0.6% and 18.3%, respectively. PCR analysis did not detect any additional malaria cases. The prevalence of LF and STH infections differ significantly among different age groups and ethnic communities. The high prevalence of LF in the community studied indicates an immediate need for implementing a mass drug administration program for its control in this particular geographical area of Nepal.

Urban lymphatic filariasis in the metropolis of Dar es Salaam, Tanzania.

BACKGROUND: The last decades have seen a considerable increase in urbanization in Sub-Saharan Africa, and it is estimated that over 50% of the population will live in urban areas by 2040. Rapid growth of cities combined with limited economic resources often result in informal settlements and slums with favorable conditions for proliferation of vectors of lymphatic filariasis (LF). In Dar es Salaam, which has grown more than 30 times in population during the past 55 years (4.4 million inhabitants in 2012), previous surveys have indicated high prevalences of LF. This study investigated epidemiological aspects of LF in Dar es Salaam, as a background for planning and implementation of control. METHODS: Six sites with varying distance from the city center (3-30 km) and covering different population densities, socioeconomic characteristics, and water, sewerage and sanitary facilities were selected for the study. Pupils from one public primary school at each site were screened for circulating filarial antigen (CFA; marker of adult worm infection) and antibodies to Bm14 (marker of exposure to transmission). Community members were examined for CFA, microfilariae and chronic manifestations. Structured questionnaires were administered to pupils and heads of community households, and vector surveys were carried out in selected households. RESULTS: The study indicated that a tremendous decrease in the burden of LF infection had occurred, despite haphazard urbanisation. Contributing factors may be urban malaria control targeting Anopheles vectors, short survival time of the numerous Culex quinquefasciatus vectors in the urban environment, widespread use of bed nets and other mosquito proofing measures, and mass drug administration (MDA) in 2006 and 2007. Although the level of ongoing transmission was low, the burden of chronic LF disease was still high. CONCLUSIONS: The development has so far been promising, but continued efforts are necessary to ensure elimination of LF as a public health problem. These will include improving the awareness of people about the role of mosquitoes in transmission of LF, more thorough implementation of environmental sanitation to reduce Cx. quinquefasciatus breeding, continued MDA to high-risk areas, and set-up of programmes for management of chronic LF disease.

Transmission assessment surveys (TAS) to define endpoints for lymphatic filariasis mass drug administration: a multicenter evaluation.

BACKGROUND: Lymphatic filariasis (LF) is targeted for global elimination through treatment of entire at-risk populations with repeated annual mass drug administration (MDA). Essential for program success is defining and confirming the appropriate endpoint for MDA when transmission is presumed to have reached a level low enough that it cannot be sustained even in the absence of drug intervention. Guidelines advanced by WHO call for a transmission assessment survey (TAS) to determine if MDA can be stopped within an LF evaluation unit (EU) after at least five effective rounds of annual treatment. To test the value and practicality of these guidelines, a multicenter operational research trial was undertaken in 11 countries covering various geographic and epidemiological settings. METHODOLOGY: The TAS was conducted twice in each EU with TAS-1 and TAS-2 approximately 24 months apart. Lot quality assurance sampling (LQAS) formed the basis of the TAS survey design but specific EU characteristics defined the survey site (school or community), eligible population (6-7 year olds or 1(st)-2(nd) graders), survey type (systematic or cluster-sampling), target sample size, and critical cutoff (a statistically powered threshold below which transmission is expected to be no longer sustainable). The primary diagnostic tools were the immunochromatographic (ICT) test for W. bancrofti EUs and the BmR1 test (Brugia Rapid or PanLF) for Brugia spp. EUs. PRINCIPAL FINDINGS/CONCLUSIONS: In 10 of 11 EUs, the number of TAS-1 positive cases was below the critical cutoff, indicating that MDA could be stopped. The same results were found in the follow-up TAS-2, therefore, confirming the previous decision outcome. Sample sizes were highly sex and age-representative and closely matched the target value after factoring in estimates of non-participation. The TAS was determined to be a practical and effective evaluation tool for stopping MDA although its validity for longer-term post-MDA surveillance requires further investigation.

Urban lymphatic filariasis in the city of Tanga, Tanzania, after seven rounds of mass drug administration.

Urban lymphatic filariasis (LF) has been listed among the challenges to the ongoing global efforts to eliminate LF. This is partly because the control strategies developed for rural areas - where most LF occurs - do not easily comply with human organization and behaviour in urban areas, and partly because the urban vectors thrive and proliferate in poorly planned urban settlements. This study investigated LF infection, disease and transmission in the medium-sized city of Tanga (approx. 300,000 inhabitants), Tanzania, after seven rounds of mass drug administration (MDA). Three representative sites with varying distance from the city centre were selected for the study. Pupils from one public primary school at each site were screened for circulating filarial antigens (CFA; marker of adult worm infection) and antibodies to Bm14 (marker of exposure to transmission). Community members were examined for CFA, microfilariae and chronic manifestations. Questionnaires were administered to pupils and heads of community households, and vector surveys were carried out in selected households. Although there was evidence of considerable reduction in infection and transmission, there was still LF in the city, with mf and CFA prevalences well above the cut-off levels for stopping MDA. In this respect, the LF situation resembled that seen in nearby rural areas outside the city. The study emphasizes the importance of motivating the urban individuals to engage and comply with the full range of LF intervention measures (MDAs, use of mosquito proofing measures including bed nets, environmental sanitation to prevent vector breeding) in order to reach successful LF control in the city. The high LF disease burden noted, despite the reduction in infection and transmission, moreover emphasizes the importance of allocating resources for morbidity management, to ensure true elimination of LF as a public health problem.

Lymphatic filariasis control in Tanzania: effect of six rounds of mass drug administration with ivermectin and albendazole on infection and transmission.

BACKGROUND: Control of lymphatic filariasis (LF) in most countries of sub-Saharan Africa is based on annual mass drug administration (MDA) with a combination of ivermectin and albendazole, in order to interrupt transmission. We present findings from a detailed study on the effect of six rounds of MDA with this drug combination as implemented by the National Lymphatic Filariasis Elimination Programme (NLFEP) in a highly endemic rural area of north-eastern Tanzania. METHODS: The effect of treatment on transmission and human infection was monitored in a community- and a school-based study during an 8-year period (one pre-intervention and 7 post-intervention years) from 2003 to 2011. RESULTS: Before intervention, 24.5% of the community population had microfilariae (mf) in the blood, 53.3% had circulating filarial antigens (CFA) and 78.9% had specific antibodies to the recombinant filarial antigen Bm14. One year after the sixth MDA, these values had decreased considerably to 2.7%, 19.6% and 27.5%, respectively. During the same period, the CFA prevalence among new intakes of Standard 1 pupils in 10 primary schools decreased from 25.2% to 5.6%. In line with this, transmission by the three vectors (Anopheles gambiae, An. funestus and Culex quinquefasciatus) as determined by dissection declined sharply (overall vector infectivity rate by 99.3% and mean monthly transmission potential by 99.2% between pre-intervention and fifth post-intervention period). A major shift in vector species composition, from predominantly anopheline to almost exclusively culicine was observed over the years. This may be largely unrelated to the MDAs but may have important implications for the epidemiology of LF in the area. CONCLUSIONS: Six MDAs caused considerable decrease in all the measured indices for transmission and human infection. In spite of this, indices were still relatively high in the late period of the study, and it may take a long time to reach the recommended cut-off levels for interruption of transmission unless extra efforts are made. These should include increased engagement of the target population in the control activities, to ensure higher treatment coverage. It is expected that the recent initiative to distribute insecticide impregnated bed nets to every household in the area will also contribute towards reaching the goal of successful LF elimination.