Density Of Microfilariae Research Articles

Single dose moxidectin versus ivermectin for Onchocerca volvulus infection in Ghana, Liberia, and the Democratic Republic of the Congo: a randomised, controlled, double-blind phase 3 trial

SummaryBackgroundThe morbidity and socioeconomic effects of onchocerciasis, a parasitic disease that is primarily endemic in sub-Saharan Africa, have motivated large morbidity and transmission control programmes. Annual community-directed ivermectin treatment has substantially reduced prevalence. Elimination requires intensified efforts, including more efficacious treatments. We compared parasitological efficacy and safety of moxidectin and ivermectin.MethodsThis double-blind, parallel group, superiority trial was done in four sites in Ghana, Liberia, and the Democratic Republic of the Congo. We enrolled participants (aged ≥12 years) with at least 10 Onchocerca volvulus microfilariae per mg skin who were not co-infected with Loa loa or lymphatic filariasis microfilaraemic. Participants were randomly allocated, stratified by sex and level of infection, to receive a single oral dose of 8 mg moxidectin or 150 μg/kg ivermectin as overencapsulated oral tablets. The primary efficacy outcome was skin microfilariae density 12 months post treatment. We used a mixed-effects model to test the hypothesis that the primary efficacy outcome in the moxidectin group was 50% or less than that in the ivermectin group. The primary efficacy analysis population were all participants who received the study drug and completed 12-month follow-up (modified intention to treat). This study is registered with ClinicalTrials.gov, number NCT00790998.FindingsBetween April 22, 2009, and Jan 23, 2011, we enrolled and allocated 998 participants to moxidectin and 501 participants to ivermectin. 978 received moxidectin and 494 ivermectin, of which 947 and 480 were included in primary efficacy outcome analyses. At 12 months, skin microfilarial density (microfilariae per mg of skin) was lower in the moxidectin group (adjusted geometric mean 0·6 [95% CI 0·3–1·0]) than in the ivermectin group (4·5 [3·5–5·9]; difference 3·9 [3·2–4·9], p<0·0001; treatment difference 86%). Mazzotti (ie, efficacy-related) reactions occurred in 967 (99%) of 978 moxidectin-treated participants and in 478 (97%) of 494 ivermectin-treated participants, including ocular reactions (moxidectin 113 [12%] participants and ivermectin 47 [10%] participants), laboratory reactions (788 [81%] and 415 [84%]), and clinical reactions (944 [97%] and 446 [90%]). No serious adverse events were considered to be related to treatment.InterpretationSkin microfilarial loads (ie, parasite transmission reservoir) are lower after moxidectin treatment than after ivermectin treatment. Moxidectin would therefore be expected to reduce parasite transmission between treatment rounds more than ivermectin could, thus accelerating progress towards elimination.FundingUNICEF/UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases.

Comparing antibody responses to &lt;i&gt;Onchocerca volvulus&lt;/i&gt; and non-parasite antigens in placebo-controlled and ivermectin-treated onchocerciasis patients

Serum antibodies to parasite-specific and non-parasite antigens were evaluated using enzyme-linked immunosorbent assay (ELISA). Out of the 470 sera collected, 409 were from residents of an onchocerciasis hyper-endemic area, 55 non-endemic and 6 European normal sera served as control. The patients’ age, sex, skin microfilaria densities, dermal and ocular clinical manifestations (colour of optic disc) have been well characterised. The study population had participated in a placebocontrolled (n=191) trial of ivermectin (Mectizan®) treatment (n=218). The parasite antigens are phosphate buffered saline crude extract of adult worms of Onchocerca volvulus, a recombinant antigen (Ov1.9) and a monoclonal antibody purified antigen (Cam 1). The non-parasite antigens are deoxycholate citrate extract of optic nerve (nerve-DOC) and commercially available IgA, IgM and IgG were used to assay for rheumatoid factor (Rh-F) auto-antibodies. Generally, antibodies to parasite antigens in onchocerciasis patients were remarkably higher than control group (p&lt;0.05) using exact F-test. There was no significant difference (p&gt;0.05) in antibodies to nerve-DOC and Rh-F in patients compared to control. Antibodies increased with increasing skin snip microfilaria load from 0.69±0.28 with 0mf/mg (n=54) as against 0.80±0.26 for those with 4-20mf/mg. Observed slight negative correlation in IgG antibody levels and severity of disc colour with mean OD values of 0.26±0.22 in those graded as having no optic nerve disease (OND) (disc 1, n=86) and 0.17±0.19 for those with severe changes (disc 3, n=49) was not statistically significant (P&gt;0.05). An age dependent significant decrease (P&lt;0.05) in antibodies were observed with 0.64±0.34 for 15-30yr old (n=48) compared to 0.48±0.35 for those 50yr (n=50) for PBS with a similar trend for IgG to Ov1.9 and Cam1. In conclusion, serum parasite-specific and non-parasite antibodies may not be responsible for the pathology of optic nerve disease. Onchocerciasis patients were apparently not at higher risk of developing rheumatoid arthritis than the control.Keywords: Onchocerciasis; Antibodies; Antigens; Immune responses; Ivermectin.

Bancroftian filariasis in four slums of Bankura, West Bengal, India

ObjectiveTo assess the prevalence of disease and microfilaremia in four slums of Bankura, West Bengal, India. MethodsData on age and sex-specific of all the respondents were collected and compared with microfilaria rate and density (20 mm3 blood was collected by finger prick) to examine the relationship between the dynamics of Wuchereria bancrofti. Screening of the population for the main signs and symptoms of lymphatic filariasis (LF) in both sexes and hydrocele in men, was performed in a health facility setting (health center/health post) by physicians/trained nurses. Disease rate and endemicity rate were also calculated. Aspects related to vectors were also studied by regular collection and dissection of mosquitoes. ResultsMicrofilaria rate, mean microfilarial density, disease rate and endemicity rate were 5.04%, 7.03%, 13.83% and 18.37%, respectively. Causative parasite was identified as Wuchereria bancrofti and Culex quinquefasciatus was recorded as vector. Per man hour density, infection and infectivity rates of the vector Culex quinquefasciatus were found to be 14.12%, 5.98% and 0.87%, respectively. ConclusionsUsing these baseline data would be useful in planning for the elimination of LF in slums of Bankura, West Bengal, India as per World Health Organization goal to eliminate LF by 2020.

Kondisi Filariasis Pasca Pengobatan Massal di Kelurahan Pabean Kecamatan Pekalongan Utara Kota Pekalongan

Pekalongan city is endemic for filariasis. Filariasis Mass Drug Administration (MDA) implemented to decrease filariasis endemicity in Pekalongan and was started in 2011, but especially the Pabean Village has started implementing in 2009. The study aimed to determine the post-filariasis MDA by measuring filariasis endemicity parameters include the distribution of patients, microfilariae rate, microfilariae density, microfilariae species and adherence of the people. A descriptive study with cross sectional design was conducted in Pabean village, Pekalongan city. Finger Blood Filariasis slide and medication status of those who had Filariasis MDA in 2011-2013 were examined. Finger Blood Filariasis slide of 519 respondents examined found 7 (Mf rate 1.35%) microfilariae positive, decreased from 2007, accounted for 3.4% and spread almost evenly throughout the village. Microfilariae density accounted for 229.02 per ml of blood and only one species of filarial worms found as Wuchereria brancrofti. Respondents who received the drug in 2011, 2012, and 2013 increased (80.02%, 90.75%, 92.68% respectively), but respondents who were taking medication decreased (63.01% 60.89%, and 55, 88% respectively). From this findings, filariasis endemicity parameters showed that filariasis MDA for 5 years have not been able to eliminate filariasis endemicity despite of the drop parameter. Key words : filariasis, microfilariae, mass drug administration

Familial Aggregation and Heritability of Wuchereria bancrofti Infection.

The familial recurrence risk of lymphatic filariasis (LF) is unknown. This case study aimed to evaluate the familial susceptibility to infection with Wuchereria bancrofti and to microfilaremia in a village of the Republic of Congo. The heritability and intrafamilial correlation coefficients were assessed for both W. bancrofti infection and microfilaremia by controlling for individual risk factors, environmental influence, and household effects. Pedigree charts were constructed for 829 individuals, including 143 individuals with a diagnosis of W. bancrofti circulating filarial antigens (CFAs) and 44 who also had microfilariae (MF). There was no intrafamilial correlation regarding CFA levels. However, the presence of MF (ρ = 0.45) and microfilarial density (ρ = 0.44) were significantly correlated among parent-offspring pairs. Heritability estimates for CFA positivity and intensity were 0.23 and 0.18, respectively. Heritability estimates were high for microfilarial positivity (h(2) = 0.74) and microfilarial density traits (h(2) = 0.81). Our study suggests that the acquisition of LF is mainly driven by environmental factors and habits and that genetic factors are moderately involved in the regulation of infection. By contrast, genetic factors play a major role in both the presence and intensity of microfilaremia.

Mapping of Bancroftian Filariasis in Cameroon: Prospects for Elimination.

BackgroundLymphatic filariasis (LF) is one of the most debilitating neglected tropical diseases (NTDs). It still presents as an important public health problem in many countries in the tropics. In Cameroon, where many NTDs are endemic, only scant data describing the situation regarding LF epidemiology was available. The aim of this study was to describe the current situation regarding LF infection in Cameroon, and to map this infection and accurately delineate areas where mass drug administration (MDA) was required.MethodologyThe endemicity status and distribution of LF was assessed in eight of the ten Regions of Cameroon by a rapid-format card test for detection of W. bancrofti antigen (immunochromatographic test, ICT). The baseline data required to monitor the effectiveness of MDA was collected by assessing microfilariaemia in nocturnal calibrated thick blood smears in sentinel sites selected in the health districts where ICT positivity rate was ≥ 1%.Principal findingsAmong the 120 health districts visited in the eight Regions during ICT survey, 106 (88.3%) were found to be endemic for LF (i.e. had ICT positivity rate ≥ 1%), with infection rate from 1.0% (95% CI: 0.2–5.5) to 20.0% (95% CI: 10–30). The overall infection rate during the night blood survey was 0.11% (95% CI: 0.08–0.16) in 11 health districts out of the 106 surveyed; the arithmetic mean for microfilaria density was 1.19 mf/ml (95% CI: 0.13–2.26) for the total population examined.Conclusion/significanceICT card test results showed that LF was endemic in all the Regions and in about 90% of the health districts surveyed. All of these health districts qualified for MDA (i.e. ICT positivity rate ≥ 1%). Microfilariaemia data collected as part of this study provided the national program with baseline data (sentinel sites) necessary to measure the impact of MDA on the endemicity level and transmission of LF important for the 2020 deadline for global elimination.

Nodding Syndrome May Be Only the Ears of the Hippo.

Nodding Syndrome (NS) is a neurological disorder of unknown etiology and pathogenesis, reported to occur mainly in the Western Equatoria State in South Sudan, in several districts in northern Uganda, and in Mahenge district in Tanzania [1]. The characteristic clinical feature of NS is a paroxysmal spell where the head nods forward repeatedly, 5–20 times per minute, in a seemingly unresponsive affected child. These nodding episodes represent an atonic form of epilepsy during which generalized electrodecrement is seen on electroencephalography and paraspinal dropout on electromyography [2]. During these episodes, children exhibit differing levels of decreased awareness, confusion, and unresponsiveness to commands [1]. Children with NS develop varying degrees of mental retardation, and in some, there is considerable stunting of growth and failure to develop secondary sexual characteristics. The syndrome generally appears between the ages of five and 18. Affected children are generally reported to be healthy until the nodding episodes begin. The natural history is not well known but has been described as starting with nodding and often progressing to generalized tonic-clonic seizures with accumulated sequelae. No proven effective specific treatment is available, and many children have died as a result of uncontrolled seizures that led to drowning or burning [1]. Recent studies, however, show that children with NS who receive adequate care—including anti-epileptic treatment, nutritional and emotional support, and physical rehabilitation—may substantially improve clinically [3]. NS is characterized by temporal, geographical, and familial clustering in villages in some onchocerciasis-endemic areas. The extent of the outbreaks in South Sudan and northern Uganda has made NS a major public health problem in these countries. In contrast, in Tanzania, the prevalence of NS is low and stable [4]. NS, like other forms of epilepsy, is associated with social stigma and can have severe socioeconomic consequences for families and communities. Various infectious, toxic, nutritional, psychosocial, and genetic causes for NS have been proposed, but none have been confirmed [5]. Cerebrospinal fluid (CSF) total protein, cells, and glucose are generally normal [2]. In a study in Uganda of 19 patients with NS, brain MRIs without contrast, performed using a 0.5 Tesla machine, showed different degrees of cortical and cerebral atrophy but no focal changes [6]. However, in a study of 12 patients with NS in Tanzania, using an MRI machine with better resolution (1.5 Tesla), five had gliotic lesions and five had changes in the hippocampus [7]. A weak association between Onchocerca volvulus (OV) skin PCR positivity and lesions on MRI was reported [7]. No autopsy or brain biopsy data for NS patients has been published. Epidemiological studies suggest a strong association between NS and onchocerciasis [8]. NS is only known to occur in onchocerciasis-endemic areas, and case-control studies have demonstrated a statistically significant higher prevalence of onchocerciasis in individuals with NS than in controls [7,9,10]. It is, however, unclear how onchocerciasis might cause NS because microfilariae (mf) and adult OV worms are not generally considered able to invade the central nervous system. In 1976, Duke et al., however, noted the presence of small numbers of OV microfilariae in the CSF ( 100 mf/mg skin) onchocerciasis patients. During diethylcarbamazine treatment, in 10 of 11 heavily infected patients presenting with an ocular form of onchocerciasis, the numbers of OV microfilariae in the CSF increased even up to 8–31 mf/ml [11]. However, more recently, a Tanzanian study of patients with onchocerciasis and epilepsy did not have microfilariae in the CSF, and PCR of CSF of patients with NS failed to identify OV DNA [7,10,12]. The latter results are difficult to interpret, as it was unclear how many participants had been previously treated with ivermectin and how frequently [13]. Most of the patients (60.8%) had visible microfilariae on microscopic examination of the skin biopsies, but the mean microfilariae density was low, 3.6 mf/mg, potentially because of prior ivermectin treatment [12].

A lymphatic dwelling filarioid nematode, Rumenfilaria andersoni (Filarioidea; Splendidofilariinae), is an emerging parasite in Finnish cervids.

BackgroundRecent studies revealed expansion of filarioid nematodes into northern Finland. In addition to Setaria tundra, an abundant filarioid, Rumenfilaria andersoni, was found inhabiting the lymphatic vessels of reindeer. Our study explores the dynamics of the rapid geographic expansion of R. andersoni, defining prevalence and density of microfilariae among 4 new cervid host species in Finland while developing a context for host-parasite ecology in Fennoscandia and more broadly in the Arctic and boreal regions.MethodsBlood samples were evaluated for presence of microfilariae from 1576 semi-domesticated reindeer, 8 captive reindeer, and free-ranging cervids including 105 wild forest reindeer, 862 moose, 114 white tailed deer and 73 roe deer in 2003–2006 (−2010). Additionally, the prepatent period and the efficacy of ivermectin treatment were investigated.ResultsRumenfilaria andersoni was found to be a common and abundant parasite in reindeer (0-90%) and wild forest reindeer (41-100%). Also moose (0-12%), white-tailed deer (15-22%) and roe deer (3%) were revealed as definitive hosts. Ivermectin was not effective against adult parasites. The prepatent period was estimated to be about five months.ConclusionsRumenfilaria andersoni was identified in 3 endemic cervid species and the introduced white-tailed deer, all constituting previously unrecognized host species in the Palearctic. Among moose, the prevalence and intensity were substantially lower than levels observed among subspecies of reindeer. White-tailed deer had a relatively high prevalence and density of R. andersoni microfilariae (rmf), whereas our limited data for roe deer indicated that the nematode may not have been abundant. Density and prevalence of rmf in moose and white tailed deer suggests the nematode may be adapted to these species, and that these cervids may be among the primary hosts of R. andersoni and reservoirs for transmission in Finland. Our current data suggest that R. andersoni became established in Finland recently, coincidental with introduction of white-tailed deer from North America in 1935; subsequent invasion and emergence in the past 70–80 years appears driven by climate-related factors. An alternative hypothesis for a temporally deeper occurrence for R. andersoni in Fennoscandia, representing post-Pleistocene range expansion with moose tracking deglaciation, is not firmly supported.

Reproductive biology of Onchocerca ochengi, a nodule forming filarial nematode in zebu cattle

Onchocerca ochengi is a nodule-forming filarial nematode parasite of cattle in tropical Africa and closely related to the human pathogen Onchocerca volvulus. The adult worms reside in intradermal nodules. While females are sedentary, males may move between nodules. The first stage larvae (microfilariae) disperse in the skin of the host waiting to be taken up by the intermediate host. The density of microfilariae in the skin is largely independent of the number of adult worms present indicating some form of density dependent control. Recently, Onchocerca sp. Siisa, a form of Onchocerca distinguishable from O. ochengi by mitochondrial DNA sequences but not by morphology, was described to occur in cattle. This raised the question if Onchocerca sp. Siisa represents a different mitochondrial clade of O. ochengi or a new species. In order to study the reproductive biology and to understand this self-control of the off-spring population we systematically analyzed all Onchocerca nodules from the skin of one zebu cow and we examined a sample of microfilariae from a skin biopsy. We identified 87 O. ochengi females and 146 males. 56 (64.4%) of the females contained developing embryos. In order to assign the progeny to their respective parents we determined the genotypes at six nuclear and two mitochondrial molecular genetic markers in the adult worms, in a fraction of the progeny present in the uteri of the females and in the skin microfilariae. The 121 skin microfilariae we analyzed originated from at least 17 different mothers, which contributed rather differently to the total. Forty-five larvae (37.2%) were the progeny of a single female. Of the adult worms 16.7% were of the type Onchocerca sp. Siisa. These worms appeared to interbreed freely with the rest of the O. ochengi population and therefore belong to the same species.

Editorial: Nodding Disease or syndrome: What is the way forward?

Nodding disease or syndrome is one of those conditions that recently appeared to be of public health concern in some countries in Africa. The disease has been reported to occur in South Sudan, Tanzania, northern Uganda and Liberia. In South Sudan the disease is mainly concentrated along Yei River1, 2. Nodding syndrome is a mentally and physically disabling disease that affects children3, typically between the ages of 5 and 15. The disease is characterized by episodes of repetitive nodding of the head, with progression to generalized tonic-clonic seizures, mental deterioration and physical incapacity1, 3. During seizures the children lose consciousness and they may fall into fire or hurt themselves. They usually drop out of school because of deterioration in cognitive function and inability to cope with the school environment. A disease similar to nodding syndrome was first reported in Uganda by Raper 4 in 1950. This disease was called ‘nakalanga’ because of the pathological dwarfism and the affected persons were incapable of procreation. It occurred among the dwellers of Mabira forest near the source of the Nile in Uganda. The forest was heavily infested by the black fly. The disease occurred among any of the tribes living in the area provided they had lived in the forested area for a sufficient number of years. The children born by uneventful pregnancies became thin, weak and listless around the time of weaning with progressive mental and physical retardation with maximal severity occurring around 8 to 15 years. The local inhabitants, who had long recognized the disease, had incriminated the bites of the black fly. Similarly, a high number of patients with epilepsy and retarded growth was reported in an endemic area for onchocerciasis in western Uganda5. However, a study that evaluated the role of Onchocerca volvulus in the development of epilepsy in rural Tanzania reported no difference in microfilaria density between participants with epilepsy and those without6. Since 2009, about 4000 cases of nodding disease have been reported in northern Uganda. For over 20 years northern Uganda was a conflict area and most people lived in camps for the internally displaced. Following a cease-fire in 2006, most of the people have returned to their villages and this period has coincided with increased numbers of nodding disease, with some families reporting more than two cases7. In this issue of African Health Sciences, Tumwine and others8 report clinical and epidemiological characteristics of nodding syndrome in Mundri county, South Sudan. The study was carried out in poor rural communities that had been characterised by several displacements between 1994 and 1997. The prevalence of Nodding Syndrome in the study areas was 2.1% and 4.6% in the endemic communities. Similar to the epidemic in northern Uganda, some families have more than one affected child. The ratio of male to female cases was 1.2. The age at onset of suspected cases ranged from 2 to 18 years, with a median of 12 years, and the mean duration of illness had been reported to be 3.0 years. Previous case-control studies had shown a positive association between cases and infestation with Onchocerca volvulus microfilaria, evidenced by positive skin snips. The nodding was reported to be worse during meals or upon walking up in the morning, and on the traditional carbohydrate based diet compared to the western style diet. For some children, head nodding did not disrupt eating or the ability to follow commands. Episodes of abnormal behaviour associated with shouting, screaming or running were reported. Physical examination revealed stunting of growth, dwarfism, mental retardation, and poor development of secondary sexual characteristics. Electroencephalographic examination was consistent with progressive epileptic encephalopathy. The authors concluded that Nodding Syndrome was strongly associated with Onchocerca volvulus. There was no evidence to suggest an environmental pollutant, chemical agent, or other toxic factor. The authors recommend larger studies to elucidate the etiology and optimal treatment for these children. It has been proven that symptomatic treatment with anticonvulsants and other supportive measures such as nutrition rehabilitation improves the quality of life, though not a cure. On going studies in northern Uganda speculate that the disease is associated with vitamin B6 deficiency and probably high doses of vitamin B6 may be beneficial to these children. The disease seems to be more prevalent in the poor communities. Improved social economic status, environmental control measures for microfilaria will go along way to reduce morbidity due to nodding syndrome.

Bancroftiasis among the mumuye of Northeastern Nigeria: Parasitological and clinical studies in Northern Taraba State

The study reports the prevalence of bancroftiasis in three Local Government Areas (LGAs) of Taraba State, Nigeria. Night blood samples collected from one thousand and thirty one individuals were stained with haematoxylin and examined microscopically for the presence of Wu-chereria bancrofti. The overall prevalence of infection in the study area was high (21.2%) but mean microfilaria densities were generally low. Statistically, prevalence rate differed significantly (χ2d.f.2 = 10.498; P χ2d.f.1 = 1.385; P > 0.05) between sexes. Infection also did not statistically differ between age groups (χ2d.f.5 = 13.219; P > 0.05) even though infection rate increased steadily with age and reaching a peak at the 40 - 49 year age group. Lymphoe-dema was the commonest (M = 12.4%, F = 19.2%) clinical manifestation of bancroftian morbidity encountered in the survey. Overall, the findings indicate that bancroftian filariasis is a public health problem in Taraba state and there is an urgent need to establish an elimination programme with a view of halting transmission in the area.

Assessment of microfilaria prevalence in Karimnagar and Chittoor Districts of Andhra Pradesh, India

Objective To assess the prevalence of disease and microfilaraemia in villages of Karimnagar and Chittoor districts. Methods Data on age and sex of all the respondents were collected and compared with the microfilaria rate (mf) and density (20 μL of peripheral blood by using finger prick method) to examines the relationship between the dynamics of Wuchereria bancrofti among the population. Results Microfilaraemia prevalence was found among all the age groups and its occurrence was more prevalent especially above 30 years age groups. Similarly, the microfilaraemia and disease rates were found significantly higher in males compared to females. Conclusions Using these baseline data would be useful in planning for the elimination of lymphatic filariasis in Andhra Pradesh as per the WHO goal to eliminate lymphatic filariasis by 2020.

Elimination of lymphatic filariasis in the Republic of Korea: an epidemiological survey of formerly endemic areas, 2002–2006

To determine the current status of lymphatic filariasis (LF) in Korea. Epidemiological surveys between 2002 and 2006 in areas where LF was previously endemic: remote and coastal areas Jeollanam-do, Gyeongsangnam-do, and Jeju-do, and inland Gyeongsangbuk-do. We took night blood smears from 9426 people for microfilaria testing and assayed samples from 3049 children (10- to 13-year-olds) and 1526 adults for Brugia malayi antibodies. We found two cases (0.01%) with low microfilaria density in their peripheral blood (1-2/20 mul) on the remote island of Jeollanam-do in the southern part of the Korean peninsula. These patients, males over 60-years old, were treated with diethylcarbamazine (DEC). None of the 4575 people surveyed tested positive for specific B. malayi antibodies. Lymphatic filariasis appears to have been eliminated in Korea.

Protective efficacy of a filarial surface antigen in experimental filariasis

A water-insoluble, detergent-soluble, surface-associated glycoprotein, designated as Dssd1, was found to induce microfilaria clearance in Mastomys coucha implanted with Setaria digitata. Intraperitoneal implantation of adult female worms of S. digitata in M. coucha could induce microfilaraemia lasting about 165 days in circulation. Immunization of M. coucha with Dssd1 antigen either before or after implantation of worms resulted in a significant reduction in microfilaria density. Complete clearance of circulating microfilaria was achieved by immunization (before and after implantation) in animals by 95 and 105 days post-implantation, respectively, indicating the efficacy of Dssd1 antigen in the clearance of microfilaraemia in infected M. coucha.

Blood Parasites of Two Costa Rican Amphibians with Comments on Detection and Microfilaria Density Associated with Adult Filarial Worm Intensity

The 2 objectives of this study were: (1) to compare parasite detectability in blood smears obtained from toe-clips versus the heart from amphibian hosts; and (2) to test whether microfilariae density is correlated with adult filarial worm intensity. We examined blood parasites of 2 species of amphibians, Rana vaillanti (n = 45) and Eleutherodactylus fitzingeri (n = 36), from Costa Rica collected during the summer of 2003. Separate blood smears were obtained from toe-clips and the heart during necrospy. Eight species of blood parasites were identified from R. vaillanti and 1 from E. fitzingeri. Each parasite species was counted in a 2 x 2.2-cm2 area on each blood smear, and the density of host red blood cells (RBCs) was estimated using a sub-sampling approach, allowing parasite infections to be expressed as individuals per RBC. The detection failure rate for toe-cut smears ranged from 71-100% (x = 92.3%) and from 0-9% (x = 2.4%) for heart smears, depending on parasite species. The density of RBCs was significantly higher in smears produced from heart samples and may explain the differences in detectability. Foleyellides striatus microfilariae densities (per RBC) were significantly correlated with adult female worm intensity (R2 = 0.32, P = 0.011).

Ivermectin-facilitated immunity in onchocerciasis; activation of parasite-specific Th1-type responses with subclinical Onchocerca volvulus infection.

The present study examined the quantitative and qualitative changes registered in the parasite-specific antibody response, cellular reactivity and cytokine production profile in onchocerciasis patients repeatedly treated with ivermectin over a period of 8 years. The densities of Onchocerca volvulus microfilariae (mf) in treated patients remained significantly reduced, whereas the number of permanently amicrofilaridermic patients (subclinical infection) increased with repeated treatments. In vitro cellular responses to O. volvulus antigen (OvAg) were highest (P < 0.01) in untreated control individuals exposed to infection, but negative for mf of O. volvulus (endemic normals). Cellular reactivity in repeatedly treated patients was higher at 84 than at 36 months post initial treatment (p.i.t); furthermore, the proliferative responses to OvAg, mycobacterial purified protein derivative (PPD) and streptococcal SL-O were greater (P < 0.05) at 84 months p.i.t. in amicrofilaridermic than in microfilaria-positive onchocerciasis patients. In amicrofilaridermic patients such reactivity approached the magnitude observed in endemic normals. Peripheral blood mononuclear cells (PBMC) from patients and endemic normals produced equivalent amounts of IL-2, IL-4 and interferon-gamma (IFN-gamma) in response to mitogenic stimulation with phytohaemagglutinin (PHA); in response to OvAg, however, significantly more IL-2 and IFN-gamma were produced by PBMC from subclinical amicrofilaridermic patients or endemic normals than by mf-positive patients. OvAg-specific production of IL-4 by PBMC from treated patients was lower at 84 than at 36 months p.i.t. At three months p.i.t. the titres of circulating OvAg-specific IgG1-3 had increased (P < 0.05), but they then continuously declined with repeated treatments. Only IgG1 and IgG4 bound to OvAg of mol. wt 2-12 kD at 1 month p.i.t., while recognition of OvAg of mol. wt 10-200 kD by IgG1, IgG2 and IgG4 reached a maximum intensity at 3-6 months p.i.t., with the overall intensity of binding to OvAg gradually weakening thereafter. These results suggest that onchocerciasis-associated immunosuppression is reversible following ivermectin-induced permanent clearance of microfilariae from the skin; and that a vigorous parasite-specific cellular reactivity and a sustained production of IL-2 and IFN-gamma in amicrofilaridermic individuals may contribute to controlling O. volvulus infection.

Vector competence of Culex quinquefasciatus Say, 1823 exposed to different densities of microfilariae of Dirofilaria immitis (Leidy, 1856)

The metropolitan region of Recife, Brazil is endemic for Dirofilaria immitis and has an environment favorable to the development of Culex quinquefasciatus. The goal of this study was to evaluate the vector competence of the Cx. quinquefasciatus RECIFE population for D. immitis transmission. A total of 2,104 females of Cx. quinquefasciatus RECIFE population were exposed to different densities of D. immitis microfilariae blood meals, ranging from 1,820 to 2,900 mf/ml of blood, in a natural membrane apparatus. The results showed a variation between 92.3% and 98.8% of females fed. The exposure of the Cx. quinquefasciatus RECIFE population to different densities of microfilariae did not influence the mortality of the mosquitoes. Infective larvae from D. immitis were observed in the Malpighian tubules beginning on the 12th day, whereas larvae were observed in the head and proboscis beginning on the 13th day following infection. The vector efficiency index (VEI) presented by the mosquitoes ranged from 7.8 to 56.5. The data demonstrates that the Cx. quinquefasciatus RECIFE population has great potential for the transmission of D. immitis, as it allowed the development of the filarid until the infectious stage at the different densities of microfilariae to which it was exposed.

Diethylcarbamazine (DEC)-medicated salt for community-based control of lymphatic filariasis

Mass treatment with diethylcarbamazine (DEC)-medicated salt has been used in a number of places as a control measure for lymphatic filariasis. We sought reliable evidence about its effect on lymphatic filariasis transmission. To evaluate the effects of DEC-medicated salt on infection with lymphatic nematodes in studies of individuals and communities. In August 2006, we searched the Cochrane Infectious Disease Group Specialized Register, CENTRAL (The Cochrane Library 2006, Issue 3), MEDLINE, EMBASE, and LILACS. We also checked reference lists. Studies of DEC-medicated salt in endemic populations or microfilaraemic individuals that reported on some measure of human infection before and after the intervention. Two authors assessed study eligibility and methodological quality. We calculated the percentage change in microfilariae prevalence and density, adult worm prevalence, disease rates, and vector infection and infectivity. We carried out meta-regression to explore the variability in percentage reduction in microfilariae prevalence between studies. Twenty-one studies were included; two compared DEC-medicated salt with other forms of DEC, five had some control group, and 14 were before-and-after studies. Five were efficacy and safety studies of individuals who were all microfilaraemic at baseline; the rest studied endemic communities. Percentage reductions in microfilariae prevalence were large (43% to 100%) and consistent in most studies with high levels of coverage. Large reductions in microfilariae density were also observed, though most studies reported changes in microfilariae density only for people with microfilaraemia at baseline. Vector infection and infectivity also declined, but the samples were usually small. Changes in disease prevalence were inconclusive as most studies were not powered for this outcome. Adverse events seemed mild. Only two studies compared DEC-medicated salt with other forms of DEC (such as annual or standard 12-day dose), but in both performance of DEC-medicated salt was better.A few studies included longer term follow up (two to 19 years). Reductions in microfilariae prevalence, density, and vector infectivity were maintained over time. The DEC concentration in the salt and the duration of intervention were significant factors influencing the percentage reduction in microfilariae prevalence in these studies. DEC-medicated salt is an effective intervention when maintained with levels of coverage of at least 90% for at least six months. Further studies are required to assess the effects of continuous low-dose, DEC-medicated salt on adult worms, disease prevalence, and development of drug resistance.

Wuchereria bancrofti Filariasis Control in Samoa before PacELF (Pacific Programme to Eliminate Lymphatic Filariasis)

BackgroundSamoa was formerly highly endemic for Wuchereria bancrofti filariasis transmitted by Aedes mosquitoes. Previous control efforts including sporadic mass drug administration (MDA) campaigns have reduced the prevalence to low levels but have not succeeded in eliminating the disease. To effectively plan, model and evaluate the worldwide elimination effort, the Global Programme to Eliminate Lymphatic Filariasis (GPFLF) needs data on filariasis epidemiology (including age and sex-specific prevalence and the density of microfilariae (Mf)) and estimates of the number of years of MDA required for elimination. The five-year nationwide MDA campaign carried out in Samoa before the start of the Pacific Programme to Eliminate Lymphatic Filariasis (PacELF) generated extensive data on these issues.Methodology⁄Principal FindingsMDA campaigns were conducted in Samoa with diethylcarbamazine (DEC) in 1993 to 1995 and DEC plus ivermectin in 1996 to 1997 for all persons aged 2 years and above. Coverage of the MDA, as assessed from the campaign village register books, ranged from 62% to 97% depending on the year, and was over 80% in three out of five years. Village based surveys showed that prevalence of Mf declined from 4.3% in 1993 (N=10,256) to 1.1% in 1998 (N=4,054) (Pχ2=94.4, p<0.001). Males had a three- to five-fold higher prevalence than females, and this difference remained consistent over the five-year period. Transmission was still occurring over the period as shown by the occurrence of new infections in 3 children less than 5 years old out of 5,691 tested (five-year cumulative incidence of 0.53 per thousand children for the period 1993 to 1998). There was a statistically significant reduction in the geometric mean number of Mf per 60 μl in positive cases between 1993 (11.8) and 1998 (6.9) (t=2.61; p<0.01). The proportion of people with a high density of Mf - over 60 Mf per 60 μl (1000 per ml) - declined from to 19.4% to 4.0% (Pχ2=5.6, p=0.018).Conclusions⁄SignificanceFive years of sustained MDA with DEC (3 years) and DEC plus ivermectin (2 years) reduced the prevalence of Mf of W.bancrofti in Samoa by 74%. Density of Mf in infected individuals was also significantly reduced. Males had a three to five-fold higher prevalence than women. New infections in children less than five years old still occurred at a low level, suggesting that transmission was not completely interrupted. These findings helped to prepare a sound monitoring and evaluation plan for PacELF.

CONSEQUENCES OF VECTOR BEHAVIOR IN EPIDEMIOLOGY OF ONCHOCERCIASIS ON THE FIRESTONE RUBBER PLANTATION IN LIBERIA

In the current study, we have assessed the distribution of black fly vectors and the occurrence of onchocerciasis among residents of the Firestone Rubber Plantation (FRP) in Liberia. The degree of endemicity of onchocerciasis on the FRP is correlated with the breeding of Simulium yahense on the Du River and Simulium soubrense on the Farmington River, as well as with the feeding behavior of these black fly vectors. S. yahense is highly anthropophilic and highly susceptible to Onchocerca volvulus, thus, it is apparently the primary vector of O. volvulus on the plantation. S. soubrense is predominantly zoophilic; consequently, it has a low capacity for transmitting of O. volvulus to humans. The prevalence of the disease is hyperendemic in the divisional camps near the Du River, affecting 77.6% to 94.4% of males and 64.9% to 88.9% of females. In the camps along the Farmington River, the disease is hypoendemic, affecting 26.1% to 49.2% of males and 25.6% to 35.1% of females. The mean intensity of infection in the camps near the Du River was 14.1 microfilariae (mf)/mg of skin in males and 13.7 mf/mg of skin in females. The density of microfilariae in people in the camps along the Farmington River was 4.8 mf/mg of skin in males and 1.9 mf/mg of skin in females. The age-specific infection in camps along both rivers substantially increased after the ages 21-30, reaching a maximum at ages 41-50. The mean density of mf/mg of skin in three anatomic locations (calf, hip, and shoulder) was 28.0, 24.5, and 14.1 mf/mg of skin, respectively, for those living on the Du River, and 10.2, 7.6, and 5.8 mf/mg of skin, respectively, for those on the Farmington River.