Paul E Simonsen

National Institute for Medical Research (NIMR), Dar es Salaam, Dar es Salaam Region, Tanzania

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Publications (28)86.52 Total impact

  • Article: Change in composition of the Anopheles gambiae complex and its possible implications for the transmission of malaria and lymphatic filariasis in north-eastern Tanzania.
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    ABSTRACT: 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. 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. 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. 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.
    Malaria Journal 06/2012; 11:188. · 3.19 Impact Factor
  • Article: A 22 year follow-up study on lymphatic filariasis in Tanzania: analysis of immunological responsiveness in relation to long-term infection pattern.
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    ABSTRACT: Seventy-one individuals who had been examined for Wuchereria bancrofti microfilaraemia in 1975, some of whom had been offered mass treatment with diethylcarbamazine (DEC) in subsequent years, were re-identified in 1996 and examined for microfilaraemia, circulating filarial antigenemia and cellular and humoral immunoresponsiveness to crude antigen homogenates prepared from Brugia pahangi parasite material. 85.9% of the study individuals had the same infection status in 1975 and 1996, suggesting strong predisposition to infection over extended periods of time. IL-4, IL-5 and IFNγ responses were associated with being infection negative in 1996 whereas IL-10 responses were associated with being infection positive. Similarly, specific IgG3 and IgE were strongly associated with being infection negative in 1996 whereas specific IgG4, and thus high IgG4/IgE ratios, were strongly associated with being infection positive. Intermediary levels of mainly IL-5, IFNγ and PBMC stimulation indices were observed for study individuals who changed from being infection positive in 1975 to infection negative in 1996, or vice versa, suggesting a transition in cellular immunoresponsiveness associated with changing infection status. The findings suggest that some people are more disposed to infection with bancroftian filariasis than others and that this is largely unaffected by treatment with DEC. The findings also suggest that specific cellular and antibody responses are more related to current than past infection status, and that IL-4, IL-5, IFNγ, specific IgG3 and IgE are associated with parasite clearance, whereas IL-10 and specific IgG4 are associated with parasite protection.
    Acta tropica 09/2011; 120(3):258-67. · 2.22 Impact Factor
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    Article: Bayesian geostatistical modelling of malaria and lymphatic filariasis infections in Uganda: predictors of risk and geographical patterns of co-endemicity.
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    ABSTRACT: 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. 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. 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. 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.
    Malaria Journal 01/2011; 10:298. · 3.19 Impact Factor
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    Article: Is the current decline in malaria burden in sub-Saharan Africa due to a decrease in vector population?
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    ABSTRACT: 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. 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. 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. 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.
    Malaria Journal 01/2011; 10:188. · 3.19 Impact Factor
  • Article: Mansonella perstans filariasis in Africa.
    Paul E Simonsen, Ambrose W Onapa, Santa Maria Asio
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    ABSTRACT: Mansonella perstans is a vector-borne human filarial nematode, transmitted by tiny blood-sucking flies (biting midges). It is widespread in many parts of Sub-Saharan Africa and also occurs in parts of Central and South America. Despite the commonness of this parasite very few studies have been carried out on its epidemiology and on the morbidity resulting from it, and only few thorough drug trials have been conducted to look for effective and suitable drugs and drug regimens for treatment and control. Here, we review currently available knowledge on M. perstans infections in Africa, including documented aspects of biology, vectors, transmission, diagnosis, epidemiology, morbidity and treatment. It is concluded that there is an urgent need for more research on this widespread but greatly neglected infection in order to properly assess its public health significance and as a background for identifying and recommending optimal means and strategies for treatment and control.
    Acta tropica 02/2010; 120 Suppl 1:S109-20. · 2.22 Impact Factor
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    Article: Lymphatic filariasis control in Tanzania: effect of repeated mass drug administration with ivermectin and albendazole on infection and transmission.
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    ABSTRACT: In most countries of sub-Saharan Africa the control of lymphatic filariasis (LF) is based on annual mass drug administration (MDA) with a combination of ivermectin and albendazole, in order to interrupt transmission. Here we present the first detailed study on the effect of 3 repeated MDAs with this drug combination, as implemented by the Tanzanian National Lymphatic Filariasis Elimination Programme (NLFEP). Infection and transmission was monitored during a five-year period (one pre-intervention and four post-intervention years) in a highly endemic community (Kirare village) in north-eastern Tanzania. The vectors were Anopheles gambiae, An. funestus and Cx. quinquefasciatus. After start of intervention, human microfilaraemia initially decreased rapidly and statistically significant (prevalence by 21.2% and 40.4%, and mean intensity by 48.4% and 73.7%, compared to pre-treatment values after the first and second MDA, respectively), but thereafter the effect levelled off. The initial decrease in microfilaraemia led to significant decreases in vector infection and vector infectivity rates and thus to a considerable reduction in transmission (by 74.3% and 91.3% compared to pre-treatment level after first and second MDA, respectively). However, the decrease in infection and infectivity rates subsequently also levelled off, and low-level transmission was still noted after the third MDA. The MDAs had limited effect on circulating filarial antigens and antibody response to Bm14. Critical issues that may potentially explain the observed waning effect of the MDAs in the later study period include the long intervals between MDAs and a lower than optimal treatment coverage. The findings highlight the importance of ongoing surveillance for monitoring the progress of LF control programmes, and it calls for more research into the long-term effect of repeated ivermectin/albendazole MDAs (including the significance of treatment intervals and compliance), in order to optimize efforts to control LF in sub-Saharan Africa.
    PLoS Neglected Tropical Diseases 01/2010; 4(6):e696. · 4.69 Impact Factor
  • Article: Association between mannose-binding lectin polymorphisms and Wuchereria bancrofti infection in two communities in North-Eastern Tanzania.
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    ABSTRACT: The association between selected mannose-binding lectin (MBL) genotype polymorphisms and Wuchereria bancrofti infection status was assessed among individuals whose infection status had been monitored for three decades. Blood samples were collected in 2006 and examined for polymorphisms in the mbl-2 gene and for W. bancrofti-specific circulating filarial antigen (CFA) status. Logistic regression analysis showed a significant association between MBL genotype and CFA status, with low-expression MBL genotype individuals being almost three times more likely to be CFA positive than high-expression MBL genotype individuals (odds ratio [OR] = 2.90). When individuals' filarial infection (microfilaria) status in 1975 was included in the analyses, the gain of new infections between the two examination points was almost 10 times higher among individuals with low than among those with high MBL expression genotype (OR = 9.51). The susceptibility to W. bancrofti infection thus appears to be significantly affected by the MBL expression genotype of the host.
    The American journal of tropical medicine and hygiene 01/2010; 82(1):115-20. · 2.59 Impact Factor
  • Article: The effect of HIV on filarial-specific antibody response before and after treatment with diethylcarbamazine in Wuchereria bancrofti infected individuals.
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    ABSTRACT: The effect of HIV on filarial-specific antibody response before and after treatment with diethylcarbamazine (DEC) was analysed by comparing two groups of Wuchereria bancrofti-infected adult individuals (positive for circulating filarial antigen) who were positive (n=15) or negative (n=21) for HIV co-infection. Prior to DEC treatment there was no significant difference in filarial-specific IgG1, IgG2, IgG4 and IgE antibody response between the HIV negative and the HIV positive group, while a five times (statistically significant) higher filarial-specific IgG3 response was observed in the HIV positive than in the HIV negative group. At 12 weeks after treatment with DEC, a significant decrease in filarial-specific IgG4 was observed in the HIV positive but not in the HIV negative group, indicating that DEC treatment had a stronger antifilarial effect in individuals co-infected with HIV. DEC treatment had no significant effect on the other classes of filarial specific antibodies, neither in the HIV negative or the HIV positive group.
    Parasitology International 02/2009; 58(2):141-4. · 2.13 Impact Factor
  • Article: A randomised, double-blind field trial of ivermectin alone and in combination with albendazole for the treatment of Mansonella perstans infections in Uganda.
    Santa Maria Asio, Paul E Simonsen, Ambrose W Onapa
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    ABSTRACT: The effect of a single dose of ivermectin alone (150-200microg/kg body weight) or in combination with albendazole (total of 400mg) in Mansonella perstans infection was assessed in a randomised, double-blind field trial in two endemic communities in Mukono and Luwero districts of Uganda. No side effects were observed or reported during the first 7 days after treatment. The effect on microfilaraemia was analysed among individuals with >or=20 microfilariae (mf) per 100mul of blood at baseline, who took the treatment and who attended follow-up examinations at 6 months and 12 months after treatment (48 and 46 in Mukono and 48 and 40 in Luwero for the ivermectin and combination treatment, respectively). In both communities, the combination treatment appeared slightly more effective than ivermectin alone, but the difference was not statistically significant. Both drug regimens were more effective in Luwero than in Mukono, probably owing to different diets in the two areas. However, in general both treatment regimens in both communities had limited effect on microfilarial intensities, and only one individual (given combination treatment in Luwero) was mf-negative at 6 months and 12 months after treatment. [ClinicalTrials.gov identifier: NCT00215280].
    Transactions of the Royal Society of Tropical Medicine and Hygiene 12/2008; 103(3):274-9. · 2.16 Impact Factor
  • Article: Micronutrient status indicators in individuals single- or double-infected with HIV and Wuchereria bancrofti before and after DEC treatment.
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    ABSTRACT: 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. 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. 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. 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.
    Tropical Medicine & International Health 12/2008; 14(1):44-53. · 2.80 Impact Factor
  • Article: Mansonella perstans filariasis in Uganda: patterns of microfilaraemia and clinical manifestations in two endemic communities.
    Santa Maria Asio, Paul E Simonsen, Ambrose W Onapa
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    ABSTRACT: Surveys for Mansonella perstans infection and potentially related clinical manifestations were undertaken in two endemic communities in Mukono and Luwero districts of Uganda where no other human filarial infections are transmitted. A sensitive and accurate counting chamber method was used for quantifying microfilaraemia in 100microl of finger-prick blood. Among 575 and 991 examined individuals aged >or=1 year in the two communities, the overall microfilariae (mf) prevalence was significantly higher in Mukono (76.5%) than in Luwero (57.7%). As early as age 1-4 years, 40.6% and 20.5% of the children were mf-positive. Prevalences increased rapidly with increasing age to reach 89.2% and 81.4% in the 15-19 years age group and then remained high in subsequent age groups. The geometric mean mf intensity among mf-positive individuals was slightly higher in the Mukono community (32.4mf/100microl) than in the Luwero community (29.9mf/100microl), and this parameter increased with age in both communities. No obvious associations were observed between various clinical parameters and M. perstans microfilaraemia in any of the study communities. The observed patterns of microfilaraemia and the lack of obvious visible clinical manifestations suggest that the host's regulatory responses are downregulated in M. perstans infections. [ClinicalTrials.gov identifier: NCT00215280].
    Transactions of the Royal Society of Tropical Medicine and Hygiene 09/2008; 103(3):266-73. · 2.16 Impact Factor
  • Article: Immunoepidemiology of Wuchereria bancrofti infection in two East African communities: antibodies to the microfilarial sheath and their role in regulating host microfilaraemia.
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    ABSTRACT: 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.
    Acta Tropica 07/2008; 106(3):200-6. · 2.72 Impact Factor
  • Article: Immunoepidemiology of Wuchereria bancrofti infection: parasite transmission intensity, filaria-specific antibodies, and host immunity in two East African communities.
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    ABSTRACT: 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.
    Infection and immunity 01/2008; 75(12):5651-62. · 4.21 Impact Factor
  • Article: 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.
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    ABSTRACT: 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.
    The American journal of tropical medicine and hygiene 10/2007; 77(3):507-13. · 2.59 Impact Factor
  • Article: A role for Mansonia uniformis mosquitoes in the transmission of lymphatic filariasis in Uganda?
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    ABSTRACT: 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.
    Acta Tropica 03/2007; 101(2):159-68. · 2.72 Impact Factor
  • Article: Filarial-specific antibody response in East African bancroftian filariasis: effects of host infection, clinical disease, and filarial endemicity.
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    ABSTRACT: 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.
    The American journal of tropical medicine and hygiene 08/2006; 75(1):97-107. · 2.59 Impact Factor
  • Article: The effect of eight half-yearly single-dose treatments with DEC on Wuchereria bancrofti circulating antigenaemia.
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    ABSTRACT: The effect of eight half-yearly treatment rounds with diethylcarbamazine (DEC; 6mg/kg bodyweight) on Wuchereria bancrofti-specific circulating filarial antigen (CFA), a marker of adult worm infection, was followed in 79 individuals who were CFA-positive before start of treatment. Half of these were also microfilariae (mf)-positive. Microfilaraemia decreased rapidly after onset of treatment and became undetectable after four treatments. Circulating antigenaemia also decreased progressively, but at a much slower rate. After two, four and eight treatment rounds, the mean CFA intensity was reduced by 81, 94 and 98%, and the prevalence of CFA positivity was 85, 66 and 57%, compared with pre-treatment, respectively. CFA clearance rates were negatively related to pre-treatment CFA intensities, and were higher among pre-treatment mf-negative individuals than among pre-treatment mf-positive individuals. Even among patients who had pre-treatment CFA intensities above the upper measuring level (32000antigen units), and who continued to have intensities above this level after treatment, a decrease in post-treatment CFA intensities was obvious from a continuous decrease in ELISA optical density values. Repeated DEC therapy thus appears to have a slow but profound and persistent macrofilaricidal effect, which in the long run may be beneficial to populations undergoing DEC-based control interventions by reducing the probability of future morbidity development.
    Transactions of the Royal Society of Tropical Medicine and Hygiene 08/2005; 99(7):541-7. · 2.16 Impact Factor
  • Article: Long-term effect of three different strategies for mass diethylcarbamazine administration in bancroftian filariasis: follow-up at 10 years after treatment.
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    ABSTRACT: The long-term effect of three different strategies for mass diethylcarbamazine (DEC) administration in bancroftian filariasis was assessed 10 years after start of treatment in three endemic communities in Tanzania. The strategies were the standard 12 day treatment (strategy I); a semi-annual single-dose treatment (strategy II); and a monthly low-dose treatment (strategy III). Treatment was given only during the first year. Following reductions immediately after treatment, overall community microfilaraemia levels were approaching pre-treatment levels in all three communities, 10 years later. In individuals who were microfilaria-positive and treated at baseline, the treatment had a long-term effect on microfilarial intensities, with geometric mean intensities being only 11%, 13% and 2% of pre-treatment levels 10 years later for strategies I, II and III, respectively. This suppressive effect was most pronounced for strategy III, which also cleared microfilaraemia and circulating filarial antigenaemia in a larger proportion of treated individuals than the other strategies. Most of the follow-up individuals who developed microfilaraemia between 2 and 10 years after start of treatment had also been microfilaraemic before treatment, suggesting that reappearance of microfilaraemia may be due to surviving female worms and/or that previously microfilaraemic individuals have a higher chance of reinfection than previously amicrofilaraemic individuals.
    Transactions of the Royal Society of Tropical Medicine and Hygiene 12/2004; 98(11):627-34. · 2.16 Impact Factor
  • Article: Observations on false positive reactions in the rapid NOW Filariasis card test.
    Paul E Simonsen, Stephen M Magesa
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    ABSTRACT: The NOW Filariasis card test is a useful tool for rapid field diagnosis of Wuchereria bancrofti infection, based on detection of specific circulating filarial antigen (CFA) in the patients' blood. Concern has been raised that a high proportion of infection negative individuals develop false positive reactions in these tests when the test cards are left for a prolonged period before being examined. We carried out a survey in an endemic Tanzanian village to investigate this phenomenon. Individuals who were positive in the NOW Filariasis test at 10 min after specimen application were also positive in the TropBio ELISA for CFA, and thus appeared to be truly positive. Many of the test cards that were negative at 10 min developed a positive line later, but these lines appeared to be falsely positive when the TropBio test was used as the gold standard. Close examination revealed that true and false positivity lines could be distinguished on their shape and colour. The study thus reaffirmed that test cards should be read after 10 min to avoid false positives, but it also indicated that experienced test card users should be able to make a correct diagnosis even at a later time.
    Tropical Medicine & International Health 12/2004; 9(11):1200-2. · 2.80 Impact Factor
  • Article: Short Communication: Observations on false positive reactions in the rapid NOW® Filariasis card test
    Paul E. Simonsen, Stephen M. Magesa
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    ABSTRACT: The NOW® Filariasis card test is a useful tool for rapid field diagnosis of Wuchereria bancrofti infection, based on detection of specific circulating filarial antigen (CFA) in the patients’ blood. Concern has been raised that a high proportion of infection negative individuals develop false positive reactions in these tests when the test cards are left for a prolonged period before being examined. We carried out a survey in an endemic Tanzanian village to investigate this phenomenon. Individuals who were positive in the NOW® Filariasis test at 10 min after specimen application were also positive in the TropBio ELISA for CFA, and thus appeared to be truly positive. Many of the test cards that were negative at 10 min developed a positive line later, but these lines appeared to be falsely positive when the TropBio test was used as the gold standard. Close examination revealed that true and false positivity lines could be distinguished on their shape and colour. The study thus reaffirmed that test cards should be read after 10 min to avoid false positives, but it also indicated that experienced test card users should be able to make a correct diagnosis even at a later time.
    Tropical Medicine & International Health 10/2004; 9(11):1200 - 1202. · 2.80 Impact Factor