Loiasis is endemic in the Ndikinimeki Health District (Centre Region, Cameroon) but does not represent a hindrance to onchocerciasis elimination.

Community-Directed Treatment with Ivermectin (CDTI) is the strategy of choice to fight onchocerciasis in Africa. In areas where loiasis is endemic, onchocerciasis control and/or elimination is hindered by severe adverse events (SAEs) occurring after ivermectin mass treatments. This study aimed at (i) investigating the impact of two decades of CDTI on L. loa clinical and parasitological indicators in the Ndikinimeki Health District, and (ii) assessing the risk of SAEs after this long-term preventive chemotherapy. A cluster-based cross-sectional survey was conducted in the six Health Areas of the Ndikinimeki Health District. All volunteers underwent day-time calibrated thick blood smears to search for L. loa microfilariae, as well as an interview to assess the history of migration of eye worm and Calabar swelling. The overall prevalence of L. loa microfilaraemia was 2.2 % (95% CI: 1.3-3.7%), and the proportions of individuals who had already experienced eye worm and/or Calabar swelling were 1.0% and 0.5%, respectively. The mean microfilarial density was 63.55 (SD: 559.17; maximum: 9220.0) mf/mL. These findings indicate that (i) the long-term ivermectin-based preventive chemotherapy against onchocerciasis significantly reduced L. loa clinical and parasitological indicators, and (ii) the risk of developing neurologic and potentially fatal SAE after ivermectin mass treatment is zero in the Ndikinimeki Health District.

A Test-and-Not-Treat Strategy for Onchocerciasis Elimination in Loa loa-coendemic Areas: Cost Analysis of a Pilot in the Soa Health District, Cameroon.

BACKGROUND: Severe adverse events after treatment with ivermectin in individuals with high levels of Loa loa microfilariae in the blood preclude onchocerciasis elimination through community-directed treatment with ivermectin (CDTI) in Central Africa. We measured the cost of a community-based pilot using a test-and-not-treat (TaNT) strategy in the Soa health district in Cameroon. METHODS: Based on actual expenditures, we empirically estimated the economic cost of the Soa TaNT campaign, including financial costs and opportunity costs that will likely be borne by control programs and stakeholders in the future. In addition to the empirical analyses, we estimated base-case, less intensive, and more intensive resource use scenarios to explore how costs might differ if TaNT were implemented programmatically. RESULTS: The total costs of US$283 938 divided by total population, people tested, and people treated with 42% coverage were US$4.0, US$9.2, and US$9.5, respectively. In programmatic implementation, these costs (base-case estimates with less and more intensive scenarios) could be US$2.2 ($1.9-$3.6), US$5.2 ($4.5-$8.3), and US$5.4 ($4.6-$8.6), respectively. CONCLUSIONS: TaNT clearly provides a safe strategy for large-scale ivermectin treatment and overcomes a major obstacle to the elimination of onchocerciasis in areas coendemic for Loa loa. Although it is more expensive than standard CDTI, costs vary depending on the setting, the implementation choices made by the institutions involved, and the community participation rate. Research on the required duration of TaNT is needed to improve the affordability assessment, and more experience is needed to understand how to implement TaNT optimally.

The Population Biology and Transmission Dynamics of Loa loa.

Endemic to Central Africa, loiasis - or African eye worm (caused by the filarial nematode Loa loa) - affects more than 10 million people. Despite causing ocular and systemic symptoms, it has typically been considered a benign condition, only of public health relevance because it impedes mass drug administration-based interventions against onchocerciasis and lymphatic filariasis in co-endemic areas. Recent research has challenged this conception, demonstrating excess mortality associated with high levels of infection, implying that loiasis warrants attention as an intrinsic public health problem. This review summarises available information on the key parasitological, entomological, and epidemiological characteristics of the infection and argues for the mobilisation of resources to control the disease, and the development of a mathematical transmission model to guide deployment of interventions.

Potential Role for Flubendazole in Limiting Filariasis Transmission: Observations of Microfilarial Sensitivity.

Flubendazole (FLBZ) is a potent and efficacious macrofilaricide after parenteral administration. Studies in animal models and one trial in patients infected with Onchocerca volvulus revealed that FLBZ elicits minimal effects on microfilariae (mf). Severe complications after ivermectin (IVM) treatment of patients with high Loa loa microfilaraemia are of great concern. We examined the potential of FLBZ to rapidly kill L. loa mf, the phenomenon proposed to underlie the complications. Mf of L. loa were exposed to FLBZ, its reduced metabolite, albendazole, or IVM in vitro. Viability of L. loa mf was unaffected by FLBZ (10 µM, 72 hours); similar results were obtained with mf of Brugia malayi. We also measured the effects of FLBZ on transmission of mf. Aedes aegypti were fed FLBZ-exposed B. malayi mf and dissected 24 hours or 14 days postfeeding to count mf that crossed the midgut and developed to infective L3. FLBZ impaired the ability of mf to cross the midgut, regardless of duration of exposure (≥ 2 hours). FLBZ also prevented the development of mf to L3s, irrespective of duration of exposure or concentration. FLBZ is not microfilaricidal under these conditions; however, it blocks transmission. These results support the possibility that FLBZ may be a useful macrofilaricide in loiasis regions and may limit transmission from treated individuals.

Loa loa vectors Chrysops spp.: perspectives on research, distribution, bionomics, and implications for elimination of lymphatic filariasis and onchocerciasis.

BACKGROUND: Loiasis is a filarial disease caused Loa loa. The main vectors are Chrysops silacea and C. dimidiata which are confined to the tropical rainforests of Central and West Africa. Loiasis is a mild disease, but individuals with high microfilaria loads may suffer from severe adverse events if treated with ivermectin during mass drug administration campaigns for the elimination of lymphatic filariasis and onchocerciasis. This poses significant challenges for elimination programmes and alternative interventions are required in L. loa co-endemic areas. The control of Chrysops has not been considered as a viable cost-effective intervention; we reviewed the current knowledge of Chrysops vectors to assess the potential for control as well as identified areas for future research. RESULTS: We identified 89 primary published documents on the two main L. loa vectors C. silacea and C dimidiata. These were collated into a database summarising the publication, field and laboratory procedures, species distributions, ecology, habitats and methods of vector control. The majority of articles were from the 1950-1960s. Field studies conducted in Cameroon, Democratic Republic of Congo, Equatorial Guinea, Nigeria and Sudan highlighted that C. silacea is the most important and widespread vector. This species breeds in muddy streams or swampy areas of forests or plantations, descends from forest canopies to feed on humans during the day, is more readily adapted to human dwellings and attracted to wood fires. Main vector targeted measures proposed to impact on L. loa transmission included personal repellents, household screening, indoor residual spraying, community-based environmental management, adulticiding and larviciding. CONCLUSIONS: This is the first comprehensive review of the major L. loa vectors for several decades. It highlights key vector transmission characteristics that may be targeted for vector control providing insights into the potential for integrated vector management, with multiple diseases being targeted simultaneously, with shared human and financial resources and multiple impact. Integrated vector management programmes for filarial infections, especially in low transmission areas of onchocerciasis, require innovative approaches and alternative strategies if the elimination targets established by the World Health Organization are to be achieved.

A Step Toward Eradication of Human Filariases in Areas Where Loa Is Endemic.

Mass drug administration (MDA) programs have achieved remarkable success in limiting the pathology and transmission of the human parasitic infections onchocerciasis and lymphatic filariasis. The full implementation of MDA campaigns for filariasis elimination has been stymied by the unacceptable incidence of severe adverse events observed following drug treatment of a subset of individuals who harbor high loads of Loa loa microfilaria. Extending MDA strategies to regions where loiasis is coendemic could be done confidently if a simple, inexpensive, and rapid diagnostic method was available that could accurately identify individuals who have L. loa microfilarial loads above the risk threshold and could thus be excluded from treatment. A recent paper in mBio reports the discovery of an antigen unique to L. loa microfilaria that can be detected in blood and urine and may form the basis for such an assay. Further work will reveal whether this discovery will smooth the path to achieve filariasis eradication.

Impact of Anti-Retroviral Treatment and Cotrimoxazole Prophylaxis on Helminth Infections in HIV-Infected Patients in Lambaréné, Gabon.

BACKGROUND: Foci of the HIV epidemic and helminthic infections largely overlap geographically. Treatment options for helminth infections are limited, and there is a paucity of drug-development research in this area. Limited evidence suggests that antiretroviral therapy (ART) reduces prevalence of helminth infections in HIV-infected individuals. We investigated whether ART exposure and cotrimoxazole preventive therapy (CTX-P) is associated with a reduced prevalence of helminth infections. METHODOLOGY AND PRINCIPAL FINDINGS: This cross-sectional study was conducted at a primary HIV-clinic in Lambaréné, Gabon. HIV-infected adults who were ART-naïve or exposed to ART for at least 3 months submitted one blood sample and stool and urine samples on 3 consecutive days. Outcome was helminth infection with intestinal helminths, Schistosoma haematobium, Loa loa or Mansonella perstans. Multivariable logistic regression was used to assess associations between ART or CTX-P and helminth infection. In total, 408 patients were enrolled. Helminth infection was common (77/252 [30.5%]). Filarial infections were most prevalent (55/310 [17.7%]), followed by infection with intestinal helminths (35/296 [11.8%]) and S. haematobium (19/323 [5.9%]). Patients on CTX-P had a reduced risk of Loa loa microfilaremia (adjusted odds ratio (aOR) 0.47, 95% CI 0.23-0.97, P = 0.04), also in the subgroup of patients on ART (aOR 0.36, 95% CI 0.13-0.96, P = 0.04). There was no effect of ART exposure on helminth infection prevalence. CONCLUSIONS/SIGNIFICANCE: CTX-P use was associated with a decreased risk of Loa loa infection, suggesting an anthelminthic effect of antifolate drugs. No relation between ART use and helminth infections was established.

Impact of repeated ivermectin treatments against onchocerciasis on the transmission of loiasis: an entomologic evaluation in central Cameroon.

BACKGROUND: Annual community-directed treatment with ivermectin (CDTI) have been carried out since 1999 in the Lekie division (central region of Cameroon where most cases of Loa-related post ivermectin severe adverse events were reported) as part of the joined activities of the African Programme for Onchocerciasis Control (APOC) and Mectizan® Donation Program (MDP). As large-scale administration of ivermetine was demonstrated to be an efficient means to control loiasis transmission, it was hypothesized that CDTI would have lowered or halted the transmission of Loa loa in the Lekie division after 13 years of annual drug administration, indicating a possible reduction in the occurrence of Loa-related post-ivermectin severe adverse events. METHODS: A 4-month entomologic study was carried out from March to June 2012 in the Lekie division to evaluate the impact of 13 years of CDTI on the transmission of L. loa whose baseline data were recorded in 1999-2000. RESULTS: There was a significant reduction in the infection rate for Chrysops silacea and C. dimidiata from 6.8 and 9% in 1999-2000 to 3 and 3.6% in 2012, respectively. The differences in the infective rate (IR) (percentage of flies harboring head L3 larvae), potential infective rate (PIR) (percentage of flies bearing L3 larvae), mean head L3 larvae load (MHL3) (average L3 per infective fly) and mean fly L3 larvae load (MFL3) (average L3 per potentially infective fly) for both C. silacea and C. dimidiata were not significantly different between the two investigation periods. The biting density (BD) was almost three-fold higher in 2012 for C. silacea but not for C. dimidiata. The transmission potential (TP) which is a function of the BD, was higher in the present study than in the baseline investigation for each species. CONCLUSION: The infection rate remaining high, the high TP and the stability observed in the IR, PIR, MHL3 and MFL3 after 13 years of CDTI suggest that transmission of L. loa is still active. This is an indication that the risk of occurrence of severe adverse events such as fatal encephalopathies is still present, especially for heavily microfilaria-loaded people taken ivermectin for the first time.

Rapid assessment procedure for loiasis and mapping lymphatic filariasis: two perfect illustrations of "to be in English or not to be".

Interest in filariasis has found a new impetus now that neglected tropical diseases have their own journal. However, some of the advances published in renowned international journals have completely ignored previous publications on the subject, particularly those in languages other than English. The rapid assessment procedure for loiasis and the mapping of lymphatic filariasis provide two perfect illustrations of this. This problem may seem a bit outdated, given that all "good authors" now publish exclusively in English. It certainly is outdated for most areas of medicine. But, surely, this should not be the case for neglected tropical diseases, for which certain long-standing findings are every bit as important as what may be presented as new discoveries. One possibility would be for certain journals, such as PLOS Neglected Tropical Diseases, to include a specific heading permitting the publication in English of older studies that initially appeared in a language other than English. The texts would be English versions respecting the entirety of the original text. Submission should be accompanied by a presentation of the problem, with details and explanatory comments, with submission at the initiative of the authors of the former article in question or their students or sympathizers.

Integrated rapid mapping of onchocerciasis and loiasis in the Democratic Republic of Congo: impact on control strategies.

BACKGROUND: Onchocerciasis can be effectively controlled by annual mass treatment with ivermectin in endemic communities. However, in communities that are endemic for loiasis there may be significant risk of severe adverse reactions after ivermectin treatment. Planning of control requires therefore mapping of these two infections using rapid assessment tools developed for each disease. These tools were initially implemented independently till the feasibility of combining them was demonstrated. This paper reports the results of integrated mapping in four epidemiological zones in the Democratic Republic of Congo and its implications on operational decision-making on ivermectin treatment. METHODS: Rapid assessment surveys were conducted between 2004 and 2005 using both rapid epidemiological mapping of onchocerciasis (REMO) and rapid assessment procedure for loiasis (RAPLOA). The survey results were subjected to a spatial analysis in order to generate for each of the two diseases maps of the estimated prevalence of infection throughout the four zones. RESULTS: Surveys were undertaken in 788 villages where 25,754 males were examined for palpable onchocercal nodules and 62,407 people were interviewed for history of eye worm. The results showed major differences in the geographic distribution of the two diseases. Loiasis was highly endemic in some areas, where special precautions were required, but not in others where routine ivermectin treatment could proceed. CONCLUSION: Integrated rapid mapping of onchocerciasis and loiasis reduces both time and cost of surveys and greatly facilitates operational decision-making on ivermectin treatment in areas where loiasis might be co-endemic.

Preliminary examination of integrated vector management in a tropical rainforest area of Cameroon.

In the tropical rainforest area of Cameroon, people are affected by blackflies (Simulium spp.) and mosquitoes (Anopheles spp). Use of insecticide-treated bed nets (ITNs) has been promoted to protect vulnerable groups from mosquito bites, whereas historically indoor residual spraying (IRS) was the primary intervention. In a malaria-endemic area, a pilot study examined different mosquito control interventions applied to entire villages to assess their impact on vectors, malaria incidence and the quality of life of the communities. The Sanaga River near these villages was treated with insecticide to kill blackfly larvae. A medical survey of the six villages had shown that 20% of the population suffered from malaria, while 50% were infected with onchocerciasis and 5% with Loa loa. IRS+ITN using ICON CS (lambda-cyhalothrin capsule suspension formulation) or improved screening of houses combined with outdoor misting reduced the numbers of mosquitoes collected from exit traps compared to the other treatments. More sporozoites were detected in mosquitoes sampled in exit traps in the untreated village than in the treated villages. Malaria incidence several months after treatments was not significantly different from pre-treatment levels. Blackfly adult populations were reduced for several weeks following larvicide application but recovered when treatment was halted.

Filaria control and elimination: diagnostic, monitoring and surveillance needs.

Gold standard diagnosis using blood films or skin snips has dimished relevance as mass drug distribution programmes for control of filaria infections expand. The view of 'diagnosis' and its relevance at the individual level has changed, as it has been recognised that the spectrum of programmatic processes (mapping, mass drug interventions, monitoring and evaluation, and surveillance) require different approaches as different questions are asked at each stage. The feasibility and relevance of skin biopsy or blood film examination is challenged when mass drug distribution seeks to treat all eligibles in communities. The need to expand programmes rapidly by identifying the highest risk communities has seen the development of rapid assessment methods, such as rapid epidemiological mapping of onchocerciasis (REMO) and rapid epidemiological assessment (REA) for onchocerciasis, immunochromatographic test (ICT)-based mapping for lymphatic filariasis (LF), and Rapid Assessment Procedure for Loiasis (RAPLOA) for Loa, to reduce the risk of serious adverse events and to guide projects in high-risk communities. As programmes reduce the prevalence through mass drug distribution, more sensitive techniques are required to define endpoints, for LF in particular where the programmatic goal is elimination; for onchocerciasis, sensitive surveillance tools are required particularly in those areas where such risks of recrudescence are high. Whilst much progress has been made in the development and deployment of rapid methods, there are still specific needs for antigen detection in onchocerciasis, whilst standardisation of a panel of tools for LF will allow the definition of endpoint parameters so that countries can decide when mass drug administration (MDA) can be stopped and have a sensitive post-MDA surveillance system.

Adverse reactions from community directed treatment with ivermectin (CDTI ) for onchocerciasis and loiasis in Ondo State, Nigeria

Onchocerciasis is an endemic disease in Ondo state, Nigeria. Community directed distribution of ivermectin is currently on-going in some local government areas of the state. Randomly selected persons (2 331 males and 2 469 females) were interviewed using a modified rapid assessment procedure for Loa loa (RAPLOA) to assess community directed treatment with ivermectin. The retrospective study evaluated the coverage, impacts and adverse reactions to the drug treatment. A questionnaire was administered by house-to-house visit in six local government areas, implementing community directed treatment with ivermectin (CDTI) in this bioclimatic zone. A total of 2,398 respondents were reported to have participated in the treatment. The overall ivermectin coverage of 49.96% was recorded (range 0 - 52% in different communities). Adverse reactions from ivermectin administration were experienced in 38% of individuals. Diverse adverse reactions experienced included predominantly itching (18.50%); oedema, especially of the face and the limbs (8.2%); rashes (3.4%) and body weakness (2.4%). Expulsion of intestinal worms occurred in 0.96% of the respondents. The occurrence of adverse reactions in relation to age categories was statistically significant. Neither fatal nor severe adverse reactions were reported by respondents. Significantly, despite experienced adverse reactions, continued participation, acceptability and compliance to ivermectin treatment was expressed by the various communities. This attitude is in consonance with the African Programme for Onchocerciasis Control (APOC) objectives. Rev. Biol. Trop. 56 (4): 1635-1643. Epub 2008 December 12.

La oncocercosis es endémica en el estado Ondo, Nigeria. Se seleccionaron 4 800 personas al azar para evaluar con encuesta retrospectiva la cobertura, efectos y reacciones al tratamiento farmacológico con ivermectina administrado por la misma comunidad. La cobertura global de ivermectina fue 50 % con reacciones adversas en 38 % de los individuos. Estas fueron comezón picazón (18%), edema, especialmente de la cara y las extremidades (8%), erupciones cutáneas (3%) y debilidad (2%); dependieron de la edad y no hubo reacciones más graves. La expulsión de las lombrices intestinales se produjo en 96% de los encuestados. A pesar de las reacciones adversas, hubo continuidad, aceptación y cumplimiento del tratamiento con ivermectina, en consonancia con los objetivos del Programa Africano para el Control de Oncocercosis (APOC).

Loiasis: African eye worm.

The filarial parasite Loa loa is transmitted by Chrysops fly bites. Loiasis is endemic in rainforest areas of West and Central Africa, and sporadic cases have also been diagnosed in travellers and migrants. Whilst many infected persons are asymptomatic, microfilariae may be detected in the blood or adult worms may be seen under the skin or the sclera of the eye. Mass treatment programmes for onchocerciasis have raised concern about the risk of severe adverse effects when ivermectin is distributed in areas co-endemic for onchocerciasis and loiasis.

Adverse reactions from community directed treatment with ivermectin (CDTI) for onchocerciasis and loiasis in Ondo State, Nigeria.

Onchocerciasis is an endemic disease in Ondo state, Nigeria. Community directed distribution of ivermectin is currently on-going in some local government areas of the state. Randomly selected persons (2331 males and 2469 females) were interviewed using a modified rapid assessment procedure for Loa loa (RAPLOA) to assess community directed treatment with ivermectin. The retrospective study evaluated the coverage, impacts and adverse reactions to the drug treatment. A questionnaire was administered by house-to-house visit in six local government areas, implementing community directed treatment with ivermectin (CDTI) in this bioclimatic zone. A total of 2,398 respondents were reported to have participated in the treatment. The overall ivermectin coverage of 49.96% was recorded (range 0-52% in different communities). Adverse reactions from ivermectin administration were experienced in 38% of individuals. Diverse adverse reactions experienced included predominantly itching (18.50%); oedema, especially of the face and the limbs (8.2%); rashes (3.4%) and body weakness (2.4%). Expulsion of intestinal worms occurred in 0.96% of the respondents. The occurrence of adverse reactions in relation to age categories was statistically significant. Neither fatal nor severe adverse reactions were reported by respondents. Significantly, despite experienced adverse reactions, continued participation, acceptability and compliance to ivermectin treatment was expressed by the various communities. This attitude is in consonance with the African Programme for Onchocerciasis Control (APOC) objectives. Rev. Biol.