Failed attempts at experimental transplantation and transmission of nocturnally-periodic simian Loa from monkey to man

This paper describes unsuccessful attempts to induce a nocturnally-periodic infection with simian Loa in a human volunteer (the author of this paper) by means of 1. Transplanting adult simian Loa worms from a wild drill (Mandrillus leucophaeus) to man; and 2. Infecting the same volunteer by sub-cutaneous inoculation with infective larvae of simian Loa from a laboratory-bred, experimentally infected Chrysops silacea

Criteria for the differentiation between young and old Onchocerca volvulus filariae

Drugs exist that show long-lasting inhibition of embryogenesis and microfilaria production or macrofilaricidal activity against Onchocerca volvulus. Therefore, the patients have to be followed-up for several years. Clinical drug trials have to be performed in areas with ongoing transmission to assess the efficacy on younger worms. In addition, future vaccine trials may also require demonstrating efficacy against establishment of new worms. For the evaluation of the efficacy, it is necessary to differentiate between older worms, which were exposed to the drug, and younger worms newly acquired after drug treatment or vaccination. Here, we describe criteria for the differentiation between young and old filariae based on histological studies of worms with a known age from travellers, or from children, or patients living in areas with interrupted transmission in Burkina Faso, Ghana or Uganda. Older worms were larger and presented degenerated tissues. Gomori's iron stain showed that the worms accumulated more iron with increasing age, first in the gut and later in other organs. Using an antibody against O. volvulus lysosomal aspartic protease, the gut of young worms was stained only weakly; whereas, it was stronger labelled in older worms, accompanied by additional staining of hypodermis and epithelia. Using morphological and immunohistological criteria, it was possible to differentiate young (1–3 years old) from older females and to identify young males

Phenotypic Evidence of Emerging Ivermectin Resistance in Onchocerca volvulus

Onchocerciasis, commonly known as river blindness, is caused by the filarial nematode Onchocerca volvulus and is transmitted by a blackfly vector. Over 37 million people are thought to be infected, with over 90 million at risk. Infection predominantly occurs in sub-Saharan Africa. Foci also exist in the Arabian Peninsula and Central and South America. Ivermectin, the sole pharmaceutical available for mass chemotherapy, has been used on a community basis for annual or semi-annual treatment since 1987. Multiple treatments with ivermectin kill the microfilariae that are responsible for the pathology of onchocerciasis. More importantly, ivermectin suppresses the reproductive activity of the adult female worms, thus delaying or preventing the repopulation of the skin with new microfilariae and thereby reducing transmission. This study extends earlier reports of sub-optimal responses to ivermectin by examining repopulation levels of microfilaria one year after treatment, worm burdens per nodule, the age structure of adult female worms recovered from nodules, and the reproductive status of adult female worms 90 days after ivermectin treatment. In some communities which have shown a pattern of sub-optimal response to treatment, the data is consistent with an emergence of ivermectin non response or resistance manifested by a loss of the effect of ivermectin on the suppression of parasite reproduction

Strong expression of TGF-beta in human host tissues around subcutaneous Dirofilaria repens

Dirofilaria repens and other Dirofilaria species are widely distributed parasitic nematodes of carnivores, which occasionally are transmitted to men, causing subcutaneous nodules. In humans, it usually occurs only as single male or female filariae without production of microfilariae. The non-productive living or dead Dirofilaria worms in subcutaneous biopsies from 15 human patients permitted us to study the role of the pleiotropic and immunoregulatory cytokine transforming growth factor beta (TGF-beta) independent from the influence of microfilariae. Antiserum against latent TGF-beta 1 was used for an immunohistological examination. In the infiltrates around female and male filariae, there occurred strongly TGF-beta-positive macrophages, mast cells, endothelial cells, fibrocytes, and giant cells adjacent to dead worms. In one nodule, secondary lymph follicles were observed with clearly TGF-beta-positive B cells in the mantle zone and weakly positive macrophages and B cells in the germinal centre. A network of CD35-positive follicular dendritic cells was observed in the germinal centre. All Dirofilaria contained Wolbachia endobacteria, which probably had attracted the numerous TGF-beta-negative neutrophils near to the worm. Wolbachia were phagocytosed by neutrophils adjacent to dead filariae. Macrophages and lymphocytes expressed the MHC class II molecule HLA-DR in small accumulations of immune cells in the outer zone of the infiltrate and the mantle zone and germinal centre of secondary lymph follicles. It is concluded that single non-productive Dirofilaria worms elicit a strong expression of TGF-beta. This result is in accordance with observations on Onchocerca volvulus from patients with the hyporeactive (generalised) form

Macrofilaricides and onchocerciasis control, mathematical modelling of the prospects for elimination

BACKGROUND: In most endemic parts of the world, onchocerciasis (river blindness) control relies, or will soon rely, exclusively on mass treatment with the microfilaricide ivermectin. Worldwide eradication of the parasite by means of this drug is unlikely. Macrofilaricidal drugs are currently being developed for human use. METHODS: We used ONCHOSIM, a microsimulation mathematical model of the dynamics of onchocerciasis transmission, to explore the potentials of a hypothetical macrofilaricidal drug for the elimination of onchocerciasis under different epidemiological conditions, as characterized by previous intervention strategies, vectorial capacity and levels of coverage. RESULTS: With a high vector biting rate and poor coverage, a very effective macrofilaricide would appear to have a substantially higher potential for achieving elimination of the parasite than does ivermectin. CONCLUSIONS: Macrofilaricides have a substantially higher potential for achieving onchocerciasis elimination than ivermectin, but high coverage levels are still key. When these drugs become available, onchocerciasis elimination strategies should be reconsidered. In view of the impact of control efforts preceding the introduction of macrofilaricides on the success of elimination, it is important to sustain current control efforts

Onchocerciasis transmission in Ghana: Persistence under different control strategies and the role of the simuliid vectors

Background: The World Health Organization (WHO) aims at eliminating onchocerciasis by 2020 in selected African countries. Current control focuses on community-directed treatment with ivermectin (CDTI). In Ghana, persistent transmission has been reported despite long-term control. We present spatial and temporal patterns of onchocerciasis transmission in relation to ivermectin treatment history. Methodology/Principal Findings: Host-seeking and ovipositing blackflies were collected from seven villages in four regions of Ghana with 3–24 years of CDTI at the time of sampling. A total of 16,443 flies was analysed for infection; 5,812 (35.3%) were dissected for parity (26.9% parous). Heads and thoraces of 12,196 flies were dissected for Onchocerca spp. and DNA from 11,122 abdomens was amplified using Onchocerca primers. A total of 463 larvae (0.03 larvae/fly) from 97 (0.6%) infected and 62 (0.4%) infective flies was recorded; 258 abdomens (2.3%) were positive for Onchocerca DNA. Infections (all were O. volvulus) were more likely to be detected in ovipositing flies. Transmission occurred, mostly in the wet season, at Gyankobaa and Bosomase, with transmission potentials of, respectively, 86 and 422 L3/person/month after 3 and 6 years of CDTI. The numbers of L3/1,000 parous flies at these villages were over 100times the WHO threshold of one L3/1,000 for transmission control. Vector species influenced transmission parameters. At Asubende, the number of L3/1,000 ovipositing flies (1.4, 95% CI = 0–4) also just exceeded the threshold despite extensive vector control and 24 years of ivermectin distribution, but there were no infective larvae in host-seeking flies. Conclusions/Significance: Despite repeated ivermectin treatment, evidence of O. volvulus transmission was documented in all seven villages and above the WHO threshold in two. Vector species influences transmission through biting and parous rates and vector competence, and should be included in transmission models. Oviposition traps could augment vector collector methods for monitoring and surveillance

Relationship between oral declaration on adherence to ivermectin treatment and parasitological indicators of onchocerciasis in an area of persistent transmission despite a decade of mass drug administration in Cameroon

BACKGROUND: Onchocerciasis control for years has been based on mass drug administration (MDA) with ivermectin (IVM). Adherence to IVM repeated treatment has recently been shown to be a confounding factor for onchocerciasis elimination precisely in rain forest areas where transmission continues and Loa loa co-exists with Onchocerca volvulus. In this study, participants’ oral declarations were used as proxy to determine the relationship between adherence to IVM treatment and parasitological indicators of onchocerciasis in the rain forest area of Cameroon with more than a decade of MDA. METHODS: Participants were recruited based on their IVM intake profile with the aid of a semi-structured questionnaire. Parasitological examinations (skin sniping and nodule palpation) were done on eligible candidates. Parasitological indicators were calculated and correlated to IVM intake profile. RESULTS: Of 2,364 people examined, 15.5 % had never taken IVM. The majority (40.4 %) had taken the drug 1–3 times while only 18 % had taken ≥ 7 times. Mf and nodule prevalence rates were still high at 47 %, 95 % CI [44.9–49.0 %] and 36.4 %, 95 % CI [34.4–38.3 %] respectively. There was a treatment-dependent reduction in microfilaria prevalence (r(s) =−0.986, P = 0.01) and intensity (r(s) =−0.96, P = 0.01). The highest mf prevalence (59.7 %) was found in the zero treatment group and the lowest (33.9 %) in the ≥ 7 times treatment group (OR = 2.8; 95 % CI [2.09–3.74]; P < 0.001). Adults with ≥ 7 times IVM intake were 2.99 times more likely to have individuals with no microfilaria compared to the zero treatment group (OR = 2.99; 95 % CI [2.19–4.08], P < 0.0001). There was no clear correlation between treatment and nodule prevalence and intensity. CONCLUSION: Adherence to ivermectin treatment is not adequate in this rain forest area where L. loa co-exists with O. volvulus. The prevalence and intensity of onchocerciasis remained high in individuals with zero IVM intake after more than a decade of MDA. Our findings show that using parasitological indicators, reduction in prevalence is IVM intake-dependent and that participants’ oral declaration of treatment adherence could be relied upon for impact studies. The findings are discussed in the context of challenges for the elimination of onchocerciasis in this rain forest area

Lymphatic filariasis in the Democratic Republic of Congo; micro-stratification overlap mapping (MOM) as a prerequisite for control and surveillance

<p>Abstract</p> <p>Background</p> <p>The Democratic Republic of Congo (DRC) has a significant burden of lymphatic filariasis (LF) caused by the parasite <it>Wuchereria bancrofti</it>. A major impediment to the expansion of the LF elimination programme is the risk of serious adverse events (SAEs) associated with the use of ivermectin in areas co-endemic for onchocerciasis and loiasis. It is important to analyse these and other factors, such as soil transmitted helminths (STH) and malaria co-endemicity, which will impact on LF elimination.</p> <p>Results</p> <p>We analysed maps of onchocerciasis community-directed treatment with ivermectin (CDTi) from the African Programme for Onchocerciasis Control (APOC); maps of predicted prevalence of <it>Loa loa</it>; planned STH control maps of albendazole (and mebendazole) from the Global Atlas of Helminth Infections (GAHI); and bed nets and insecticide treated nets (ITNs) distribution from Demographic and Health Surveys (DHS) as well as published historic data which were incorporated into overlay maps. We developed an approach we designate as micro-stratification overlap mapping (MOM) to identify areas that will assist the implementation of LF elimination in the DRC. The historic data on LF was found through an extensive review of the literature as no recently published information was available.</p> <p>Conclusions</p> <p>This paper identifies an approach that takes account of the various factors that will influence not only country strategies, but suggests that country plans will require a finer resolution mapping than usual, before implementation of LF activities can be efficiently deployed. This is because 1) distribution of ivermectin through APOC projects will already have had an impact of LF intensity and prevalence 2) DRC has been up scaling bed net distribution which will impact over time on transmission of <it>W. bancrofti </it>and 3) recently available predictive maps of <it>L. loa </it>allow higher risk areas to be identified, which allow LF implementation to be initiated with reduced risk where <it>L. loa </it>is considered non-endemic. We believe that using the proposed MOM approach is essential for planning the expanded distribution of drugs for LF programmes in countries co-endemic for filarial infections.</p