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.

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.

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.

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.

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.

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.

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.

Urban lymphatic filariasis.

Lymphatic filariasis (LF) is a disabling and disfiguring disease resulting from a mosquito-borne parasitic infection. It is a major public health problem in many countries with a warm climate. Research and control activities have mainly focused on LF in rural areas where it also has its major impact. However, with rapid and unplanned growth of cities in the developing world, there is a need also to consider LF transmission and control in urban settings. Here, we review currently available knowledge on urban LF and the environmental and socio-economic basis for its occurrence. Among the three parasite species causing LF in humans, only Wuchereria bancrofti has been documented to have a significant potential for urban transmission. This is primarily because one of its vectors, Culex quinquefasciatus, thrives and proliferates excessively in crowded city areas with poor sanitary, sewerage and drainage facilities. For this reason, urban LF also often shows a marked focality in distribution, with most cases clustered in areas inhabited by the less privileged city populations. More knowledge on urban LF is needed, in particular on its socio-economic and human behavioural context, on the potential for transmission in regions where other LF vector species predominate, and on rapid methods for identification and mapping of risk areas, to provide a strong evidence base for its control.

Change in composition of the Anopheles gambiae complex and its possible implications for the transmission of malaria and lymphatic filariasis in north-eastern Tanzania.

BACKGROUND: A dramatic decline in the incidence of malaria due to Plasmodium falciparum infection in coastal East Africa has recently been reported to be paralleled (or even preceded) by an equally dramatic decline in malaria vector density, despite absence of organized vector control. As part of investigations into possible causes for the change in vector population density, the present study analysed the Anopheles gambiae s.l. sibling species composition in north-eastern Tanzania. METHODS: The study was in two parts. The first compared current species complex composition in freshly caught An. gambiae s.l. complex from three villages to the composition reported from previous studies carried out 2-4 decades ago in the same villages. The second took advantage of a sample of archived dried An. gambiae s.l. complex specimens collected regularly from a fourth study village since 2005. Both fresh and archived dried specimens were identified to sibling species of the An. gambiae s.l. complex by PCR. The same specimens were moreover examined for Plasmodium falciparum and Wuchereria bancrofti infection by PCR. RESULTS: As in earlier studies, An. gambiae s.s., Anopheles merus and Anopheles arabiensis were identified as sibling species found in the area. However, both study parts indicated a marked change in sibling species composition over time. From being by far the most abundant in the past An. gambiae s.s. was now the most rare, whereas An. arabiensis had changed from being the most rare to the most common. P. falciparum infection was rarely detected in the examined specimens (and only in An. arabiensis) whereas W. bancrofti infection was prevalent and detected in all three sibling species. CONCLUSION: The study indicates that a major shift in An. gambiae s.l. sibling species composition has taken place in the study area in recent years. Combined with the earlier reported decline in overall malaria vector density, the study suggests that this decline has been most marked for An. gambiae s.s., and least for An. arabiensis, leading to current predominance of the latter. Due to differences in biology and vectorial capacity of the An. gambiae s.l. complex the change in sibling species composition will have important implications for the epidemiology and control of malaria and lymphatic filariasis in the study area.

Bayesian geostatistical modelling of malaria and lymphatic filariasis infections in Uganda: predictors of risk and geographical patterns of co-endemicity.

BACKGROUND: In Uganda, malaria and lymphatic filariasis (causative agent Wuchereria bancrofti) are transmitted by the same vector species of Anopheles mosquitoes, and thus are likely to share common environmental risk factors and overlap in geographical space. In a comprehensive nationwide survey in 2000-2003 the geographical distribution of W. bancrofti was assessed by screening school-aged children for circulating filarial antigens (CFA). Concurrently, blood smears were examined for malaria parasites. In this study, the resultant malariological data are analysed for the first time and the CFA data re-analysed in order to identify risk factors, produce age-stratified prevalence maps for each infection, and to define the geographical patterns of Plasmodium sp. and W. bancrofti co-endemicity. METHODS: Logistic regression models were fitted separately for Plasmodium sp. and W. bancrofti within a Bayesian framework. Models contained covariates representing individual-level demographic effects, school-level environmental effects and location-based random effects. Several models were fitted assuming different random effects to allow for spatial structuring and to capture potential non-linearity in the malaria- and filariasis-environment relation. Model-based risk predictions at unobserved locations were obtained via Bayesian predictive distributions for the best fitting models. Maps of predicted hyper-endemic malaria and filariasis were furthermore overlaid in order to define areas of co-endemicity. RESULTS: Plasmodium sp. parasitaemia was found to be highly endemic in most of Uganda, with an overall population adjusted parasitaemia risk of 47.2% in the highest risk age-sex group (boys 5-9 years). High W. bancrofti prevalence was predicted for a much more confined area in northern Uganda, with an overall population adjusted infection risk of 7.2% in the highest risk age-group (14-19 year olds). Observed overall prevalence of individual co-infection was 1.1%, and the two infections overlap geographically with an estimated number of 212,975 children aged 5 - 9 years living in hyper-co-endemic transmission areas. CONCLUSIONS: The empirical map of malaria parasitaemia risk for Uganda presented in this paper is the first based on coherent, national survey data, and can serve as a baseline to guide and evaluate the continuous implementation of control activities. Furthermore, geographical areas of overlap with hyper-endemic W. bancrofti transmission have been identified to help provide a better informed platform for integrated control.

Is the current decline in malaria burden in sub-Saharan Africa due to a decrease in vector population?

BACKGROUND: In sub-Saharan Africa (SSA), malaria caused by Plasmodium falciparum has historically been a major contributor to morbidity and mortality. Recent reports indicate a pronounced decline in infection and disease rates which are commonly ascribed to large-scale bed net programmes and improved case management. However, the decline has also occurred in areas with limited or no intervention. The present study assessed temporal changes in Anopheline populations in two highly malaria-endemic communities of NE Tanzania during the period 1998-2009. METHODS: Between 1998 and 2001 (1st period) and between 2003 and 2009 (2nd period), mosquitoes were collected weekly in 50 households using CDC light traps. Data on rainfall were obtained from the nearby climate station and were used to analyze the association between monthly rainfall and malaria mosquito populations. RESULTS: The average number of Anopheles gambiae and Anopheles funestus per trap decreased by 76.8% and 55.3%, respectively over the 1st period, and by 99.7% and 99.8% over the 2nd period. During the last year of sampling (2009), the use of 2368 traps produced a total of only 14 Anopheline mosquitoes. With the exception of the decline in An. gambiae during the 1st period, the results did not reveal any statistical association between mean trend in monthly rainfall and declining malaria vector populations. CONCLUSION: A longitudinal decline in the density of malaria mosquito vectors was seen during both study periods despite the absence of organized vector control. Part of the decline could be associated with changes in the pattern of monthly rainfall, but other factors may also contribute to the dramatic downward trend. A similar decline in malaria vector densities could contribute to the decrease in levels of malaria infection reported from many parts of SSA.

Micronutrient status indicators in individuals single- or double-infected with HIV and Wuchereria bancrofti before and after DEC treatment.

OBJECTIVE: To identify possible associations between selected micronutrient status indicators (serum ferritin, retinol, beta-carotene, alpha-tocopherol, and the acute phase reactant alpha-1 antichymotrypsin) and infection with human immunodeficiency virus (HIV) or Wuchereria bancrofti, and to assess the effect of the antifilarial drug diethylcarbamazine (DEC) on the micronutrient status indicators in individuals positive for one or both of the two infections. METHODS: Serum concentrations of ferritin, retinol, beta-carotene, alpha-tocopherol and the acute phase reactant alpha-1 antichymotrypsin were examined in 59 individuals with HIV, W. bancrofti infection, or both, in Tanga Region, Tanzania, before and 12 weeks after treatment with DEC. RESULTS: HIV infection, but not W. bancrofti infection, was associated with higher serum ferritin concentrations and lower beta-carotene and alpha-tocopherol. Neither HIV infection nor W. bancrofti infection was associated with serum retinol. The four micronutrient status indicators and alpha-1 antichymotrypsin were generally lower at 12 weeks after treatment both in the DEC and the placebo groups. CONCLUSIONS: The negative association between HIV infection and the antioxidant vitamins beta-carotene and alpha-tocopherol may be due to infection-induced oxidative stress, whereas W. bancrofti infection seemed not to be associated with oxidative stress. The drop in antioxidant vitamin concentrations after treatment may be due to oxidative stress induced by HIV progression (HIV infected) and inflammation around dead adult worms and microfilariae (W. bancrofti infected) rather than to an effect of DEC.

Immunoepidemiology of Wuchereria bancrofti infection in two East African communities: antibodies to the microfilarial sheath and their role in regulating host microfilaraemia.

The response pattern of specific antibodies to the microfilarial sheath (sheath-Ab) of the mosquito-borne filarial parasite Wuchereria bancrofti was investigated in individuals from two East African communities with different levels of endemicity. Individuals from both communities presented a strong inverse relationship between positivity for sheath-Ab and being positive for microfilariae (mf) and circulating filarial antigens (CFA). The prevalence of sheath-Ab positivity was highest in young individuals, but peaked at a younger age in the high (1-14 years) than the low (15-19 years) endemicity community. IgG1, IgG2, IgG3 and IgE intensities to a crude adult filarial worm antigen were higher, and IgG4 intensities were lower, in sheath-Ab positive than in sheath-Ab negative individuals, probably reflecting the infection status of individuals. From the study it appears that individuals become sheath-Ab positive before mf and/or CFA can be detected in the peripheral blood, and only after later disappearance of sheath-Ab from the circulation can CFA and mf be diagnosed. In light of the findings, possible roles of the distinct sheath-Ab in the host-parasite relationship are discussed, and a hypothesis is proposed which suggests that sheath-Ab play an important role in the regulation of host microfilaraemia.

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.

Immunoepidemiology of Wuchereria bancrofti infection: parasite transmission intensity, filaria-specific antibodies, and host immunity in two East African communities.

We compared the age profiles of infection and specific antibody intensities in two communities with different transmission levels in East Africa to examine the contribution of humoral responses to human immunity to the vector-borne helminth Wuchereria bancrofti. The worm intensities were higher and exhibited a nonlinear age pattern in a high-transmission community, Masaika, in contrast to the low but linearly increasing age infection profile observed for a low-transmission community, Kingwede. The mean levels of specific immunoglobulin G1 (IgG1), IgG2, IgG4, and IgE were also higher in Masaika, but intriguingly, the IgG3 response was higher in Kingwede. The age-antibody patterns differed in the two communities but in a manner apparently contrary to a role in acquired immunity when the data were assessed using simple correlation methods. By contrast, multivariate analyses showed that the antibody response to infection may be classified into three types and that two of these types, a IgG3-type response and a response measuring a trade-off in host production of IgG4 and IgG3 versus production of IgG1, IgG2, and IgE, had a negative effect on Wuchereria circulating antigen levels in a manner that supported a role for these responses in the generation of acquired immunity to infection. Mathematical modeling supported the conclusions drawn from empirical data analyses that variations in both transmission and worm intensity can explain community differences in the age profiles and impacts of these antibody response types. This study showed that parasite-specific antibody responses may be associated with the generation of acquired immunity to human filarial infection but in a form which is dependent on worm transmission intensity and interactions between immune components.

Effect of diethylcarbamazine on HIV load, CD4%, and CD4/CD8 ratio in HIV-infected adult Tanzanians with or without lymphatic filariasis: randomized double-blind and placebo-controlled cross-over trial.

We assessed the effect of anti-filarial treatment (diethylcarbamazine, DEC) on HIV load, CD4%, and CD4/CD8 ratio in HIV-positive individuals with and without infection with the filarial parasite Wuchereria bancrofti in a randomized, double-blind, placebo-controlled cross-over trial. The study was conducted in Tanga Region, Tanzania, in 2002 and involved 27 adults. A significant decrease in HIV load (54%) and an insignificant increase in CD4% were observed in the HIV-positive individuals with filarial co-infection at 12 weeks after treatment. HIV load and CD4% both increased, although not statistically significantly, in the HIV-positive individuals without filarial infection. The findings suggest that DEC affected HIV load through its effect on the filarial infection rather than through a direct (pharmacodynamic) effect on HIV. Global efforts to control lymphatic filariasis by annual mass treatment with DEC may have a beneficial effect on the HIV/AIDS epidemic in areas where HIV and lymphatic filariasis co-exist.

A role for Mansonia uniformis mosquitoes in the transmission of lymphatic filariasis in Uganda?

The possible role of Mansonia uniformis mosquitoes in the transmission of lymphatic filariasis was assessed in an endemic area of Uganda, by examining their diurnal biting cycle, host preference and ability to support the development of experimental and natural Wuchereria bancrofti infections. Anopheles gambiae s.l. served as controls. Human landing catches revealed that outdoor biting peaked early in the evening (19:00-20:00h), while indoor biting peaked around midnight (23:00-24:00h). By far the majority of indoor collected M. uniformis had derived their blood meals from humans. Both biting and feeding behaviour were therefore compatible with a potential for transmission. In experimentally fed M. uniformis (total of 1915), the microfilariae were seen to ex-sheath and to start migration, but the L1s accumulated in the thorax and only few developed further. In dissections from Day 11 onwards, 4.6% (43/932) of M. uniformis had L2 larvae and 0.7% (7/932) had L3 larvae of W. bancrofti. The corresponding figures for An. gambiae s.l. were 13.4% and 4.6%, respectively. Dissection of wild caught M. uniformis (total of 6823) did not reveal any natural infections with W. bancrofti infective larvae, whereas wild caught An. gambiae s.l. had an infective rate of 1.3%. Other filarial species, and mermithids, were common in M. uniformis. It is concluded that M. uniformis has a limited potential to support development of W. bancrofti to the infective stage, and it does not appear to play a role as a vector under natural conditions.

Filarial-specific antibody response in East African bancroftian filariasis: effects of host infection, clinical disease, and filarial endemicity.

The effect of host infection, chronic clinical disease, and transmission intensity on the patterns of specific antibody responses in Bancroftian filariasis was assessed by analyzing specific IgG1, IgG2, IgG3, IgG4, and IgE profiles among adults from two communities with high and low Wuchereria bancrofti endemicity. In the high endemicity community, intensities of the measured antibodies were significantly associated with infection status. IgG1, IgG2, and IgE were negatively associated with microfilaria (MF) status, IgG3 was negatively associated with circulating filarial antigen (CFA) status, and IgG4 was positively associated with CFA status. None of the associations were significantly influenced by chronic lymphatic disease status. In contrast, IgG1, IgG2, and IgG4 responses were less vigorous in the low endemicity community and, except for IgG4, did not show any significant associations with MF or CFA status. The IgG3 responses were considerably more vigorous in the low endemicity community than in the high endemicity one. Only IgG4 responses exhibited a rather similar pattern in the two communities, being significantly positively associated with CFA status in both communities. The IgG4:IgE ratios were higher in infection-positive individuals than in infection-negative ones, and higher in the high endemicity community than in the low endemicity one. Overall, these results indicate that specific antibody responses in Bancroftian filariasis are more related to infection status than to chronic lymphatic disease status. They also suggest that community transmission intensity play a dominant but subtle role in shaping the observed response patterns.

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.

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.