Concurrence of dermatological and ophthalmological morbidity in onchocerciasis.

Prevalence of skin and eye disorders in African onchocerciasis (river blindness) is well documented. However, less is known about their joint occurrence. Information on concurrence may improve our understanding of disease pathogenesis and is required to estimate the disease burden of onchocerciasis. We analysed data from 765 individuals from forest villages in the Kumba and Ngambe Health districts, Cameroon. These data were collected in 1998, as baseline data for the evaluation of the African Programme for Onchocerciasis Control. Concurrence of symptoms was assessed using logistic regression. Onchocerciasis was highly endemic in the study population (63% nodule prevalence among males aged ≥20). Considerable overall prevalences of onchocercal visual impairment (low vision or blindness: 4%), troublesome itch (15%), reactive skin disease (19%), and skin depigmentation (25%) were observed. The association between onchocercal visual impairment and skin depigmentation (OR 9.0, 95% CI 3.9-20.8) was partly explained by age and exposure to infection (OR 3.0, 95% CI 1.2-7.7). The association between troublesome itch and reactive skin disease was hardly affected by adjustment (adjusted OR 6.9, 95% CI 4.2-11.1). Concluding, there is significant concurrence of morbidities within onchocerciasis. Our results suggest a possible role of host characteristics in the pathogenesis of depigmentation and visual impairment. Further, we propose a method to deal with concurrence when estimating the burden of disease.

Individual exposure to Simulium bites and intensity of Onchocerca volvulus infection.

BACKGROUND: Onchocerca volvulus, the causative agent of river blindness, is transmitted through the black fly Simulium damnosum s.l., which breeds in turbulent river waters. To date, the number of flies attacking humans has only been determined by standard fly collectors near the river or the village. In our study, we counted the actual number of attacking and successfully feeding S. damnosum s.l. flies landing on individual villagers during their routine day-time activities in two villages of the Sudan-savannah and rainforest of Cameroon. We compared these numbers to the number of flies caught by a standard vector-collector, one positioned near the particular villager during his/her daily activity and the other sitting at the nearest Simulium breeding site. RESULTS: Using these data obtained by the two vector-collectors, we were able to calculate the Actual Index of Exposure (AIE). While the AIE in the savannah was on average 6,3%, it was 34% in the rainforest. The Effective Annual Transmission Potential (EATP) for individual villagers was about 20 fold higher in the rainforest compared to the savannah. CONCLUSIONS: Here we show for the first time that it is possible to determine the EATP. Further studies with more subjects are needed in the future. These data are important for the development of future treatment strategies.

Elephantiasis of non-filarial origin (podoconiosis) in the highlands of north-western Cameroon.

Lymphoedema, a condition of localized fluid retention, results from a compromised lymphatic system. Although one common cause in the tropics is infection with filarial worms, non-filarial lymphoedema, also known as podoconiosis, has been reported among barefoot farmers in volcanic highland zones of Africa, Central and South America and north-western India. There are conflicting reports on the causes of lymphoedema in the highland regions of Cameroon, where the condition is of great public-health importance. To characterise the focus of lymphoedema in the highlands of the North West province of Cameroon and investigate its real causes, a cross-sectional study was carried out on the adults (aged > or =15 years) living in the communities that fall within the Ndop and Tubah health districts. The subjects, who had to have lived in the study area for at least 10 years, were interviewed, examined clinically, and, when possible, checked for microfilaraemia. The cases of lymphoedema confirmed by ultrasonography and a random sample of the other subjects were also tested for filarial antigenaemia. The interviews, which explored knowledge, attitudes and perceptions (KAP) relating to lymphoedema, revealed that the condition was well known, with each study community having a local name for it. Of the 834 individuals examined clinically, 66 (8.1%) had lymphoedema of the lower limb, with all the clinical stages of this condition represented. None of the 792 individuals examined parasitologically, however, had microfilariae of W. bancrofti (or any other filarial parasite) in their peripheral blood, and only one (0.25%) of the 399 individuals tested for the circulating antigens of W. bancrofti gave a positive result. In addition, none of the 504 mosquitoes caught landing on human bait in the study area and dissected was found to harbour any stage of W. bancrofti. These findings indicate that the elephantiasis seen in the North West province of Cameroon is of non-filarial origin.

Spatial modelling and the prediction of Loa loa risk: decision making under uncertainty.

Health decision-makers working in Africa often need to act for millions of people over large geographical areas on little and uncertain information. Spatial statistical modelling and Bayesian inference have now been used to quantify the uncertainty in the predictions of a regional, environmental risk map for Loa loa (a map that is currently being used as an essential decision tool by the African Programme for Onchocerciasis Control). The methodology allows the expression of the probability that, given the data, a particular location does or does not exceed a predefined high-risk threshold for which a change in strategy for the delivery of the antihelmintic ivermectin is required.

[African programme for onchocerciasis control (APOC): entomological aspects of Onchocerca volvulus transmission by Simulium neavei in the Basin of Sankuru (Eastern Kasai, Democratic Republic of Congo)]. / Aspects entomologiques de la transmission d'Onchocerca volvulus par Simulium neavei dans le bassin du Sankuru (Kasaï oriental, République Démocratique du Congo).

As part of a study to evaluate the long-term impact of community-directed treatment with ivermectin (CDTI), baseline entomological data on the transmission of onchocerciasis in the forest zone of the Eastern Kasai Province were collected from July 1998 to January 1999. Species of the Simulium neavei complex were the only vectors found in the site during the study. Nuisance activity was low with a mean biting rate of only 32.5 bites/man/day. The mean parturity rate was 29.4%, the mean rate of infected females was 14.5% and the mean number of infective Onchocerca larvae per 1000 parous flies was 659. These findings clearly show that the S. neavei population at the study site has high vector capability and constitutes a large microfilarial reservoir. The entomological features found in the study area are consistent with a hyper-endemic zone.

Successful vaccination against Onchocerca ochengi infestation in cattle using live Onchocerca volvulus infective larvae.

Epidemiological evidence has led to the hypothesis that the concurrent and predominant transmission of Onchocerca ochengi by Simulium damnosum s.l. in sub-Saharan Africa could lead to the protection of humans against onchocerciasis caused by Onchocerca volvulus (zooprophylaxis). To gain support for this hypothesis, we investigated whether exposure to O. volvulus could protect cattle from O. ochengi. Gudali calves were vaccinated with live O. volvulus-infective larvae and subsequently challenged with O. ochengi-infective larvae whilst raised in a fly-proof house. Post-challenge adult parasite and microfilaria development, IgG1 and lgG2 subclass antibodies response to Ov10/Ov11 recombinant Onchocerca antigens, and peripheral blood lymphocyte proliferative responses to O. ochengi crude antigens were studied over a 1-year period. The vaccinated-challenged animals had 83-87% less adult O. ochengi parasites than non-vaccinated-challenged animals. IgG1 and lgG2 antibodies to Ov10/Ov11 recombinant Onchocerca antigens were invoked by non-vaccinated-challenged animals but not by most (80%) of the vaccinated-challenged animals. These findings support the idea of cross-protection (zooprophylaxis) due to inoculation of humans with O. ochengi-infective larvae under natural transmission conditions in endemic areas.

[Onchocerciasis in the area of Lastourville, Gabon. Clinical and entomological aspects]. / L'onchocercose dans la région de Lastourville, Gabon. Aspects cliniques et entomologiques.

The African Programme for Onchocerciasis Control (APOC) has implemented a series of surveys aimed at evaluating the long-term impact of its activities. The region of Lastourville (Gabon) is one of the selected sites for this study. A total of 886 persons was examined for skin lesions, and 459 out of them participated in detailed ocular examinations. Blackflies were collected during one year and dissected. Although the focus was found to be hypoendemic (prevalence of nodules: 7.7%), the frequency of onchodermatitis was relatively high. The lesions of the anterior segment of the eye were rare, but the prevalence of optic nerve disease, and of choroido-retinal lesions reached 5.2 and 2.7%, respectively. The annual transmission potential (2,171 infective larvae per man) was high, when compared with the results recorded in the human population. This may be due to the presence of Onchocerca spp. of animal origin in the blackflies. These results indicate that in the area of Lastourville, though regarded as the main focus of onchocerciasis in Gabon, the disease is relatively mild.

[African Programme for Onchocerdasis Control (APOC): Onchocerca Simulium squamosum in two regions in the Republic of Cameroon]. / Programme africain de lutte contre l'onchocercose (APOC): intensité de la transmission d'Onchocerca volvulus par Simulium squamosum dans deux régions de la République du Cameroun.

In 1998, the African Programme for Onchocerciasis Control (APOC) decided to launch a long-term impact assessment of its operations. This paper reports the baseline entomological data collected throughout a whole year in two sites of Cameroon (Kahn and Bolo). The Simulium populations of the two study sites were characterized by parous rates of 7.2% and 33.5% respectively and infectivity by O. volvulus of 31 and 190 infective larvae per 1000 parous flies respectively The Annual Transmission Potentials (ATP) were respectively 523 and 9972 infective larvae per man and per year in Kahn and in Bolo. The Simulium populations studied in both sites, even though the ATP in Kahn is 19 times lower than that of Bolo, showed a pattern of an onchocerciasis hyperendemic zone in terms of vector capacities and entomological indices.

[African Program for Onchocerciasis Control (APOC): Onchocerca volvulus transmission by Simulium damnosum s. l. in two regions of the Central African Republic]. / Programme africain de lutte contre l'onchocercose (APOC): transmission d'Onchocerca volvulus par Simulium damnosum s. l. dans deux régions de la République Centrafricaine.

Entomological baseline data were collected in the villages of Zinga and Boali-Falls in Central African Republic (CAR) in view of the long term impact assessment of community-directed treatment with ivermectin (CDTI). Morphological determinations revealed that flies caught in both sites belong to the sub-group Sou/Sq. In Boali, the nuisance was relatively high with biting rates averaging 243 bites/man/day, with a parous rate of 61.6% and a crude annual transmission potential (ATP) of 8,259 infective larvae/man/year; and the average number of infective larvae per 1,000 parous flies was 177. In Zinga, the mean biting rate was 191 bites/man/day, with a parous rate of 51.6%, a crude ATP of 3,422, and 86 infective larvae per 1,000 porous flies. In conclusion, the vectorial capacity and the entomological indices recorded are characteristic of high onchocerciasis transmission zones. However, some of the infective larvae found, maybe of animal origin, need identification to better determine the real level of endemicity.

A new cytotype of Simulium squamosum from south-west Cameroon.

A new cytotype of Simulium squamosum Enderlein (Diptera: Simuliidae) (here named S. squamosum'D') is described from around Mount Cameroon in south-west Cameroon on the basis of sex-chromosome differences on the short arm of chromosome I. Two polymorphic inversions, IS-To (a new inversion) and IS-2, are partially Y linked. These inversions usually occur together, although IS-To has a higher frequency and is more strongly Y linked than IS-2. This sex-chromosome system has not been previously described and the occurrence and evolution of sex-chromosome systems in S. squamosum is discussed.

Experimental studies on the transmission of Onchocerca volvulus by its vector in the Sanaga valley (Cameroon): Simulium squamosum B. Intake of microfilariae and their migration to the haemocoel of the vector.

As large-scale ivermectin distribution is becoming the mainstay of onchocerciasis control in Africa, the issue of its impact on local transmission is increasing in importance. The vector competence of Simulium squamosum B in the severe focus of the Sanaga valley, Cameroon, was therefore investigated, by feeding 1320 flies on 14 carriers of Onchocerca volvulus microfilariae (mff). The results enabled the relationships between skin microfilarial load, microfilarial intake by the flies, the proportion and mean number of ingested mff that succeed in reaching the fly's haemocoel, and the frequency distribution of the ingested mff to be described, as functions of time post-engorgement (p.e.) and parasite density (while taking account of possible measurement error in the predictor variable). The proportion of flies with haemocoelic mff and the mean number of mff/fly increased up to 3 h p.e. The proportion of flies with ingested mff was non-linearly related to mean intake, via the negative-binomial distribution, with the overdispersion parameter k best described as an increasing (power) function of the mean. Approximately one in every three ingested mff escaped imprisonment by the peritrophic matrix, irrespective of the skin microfilarial load or the intake of mff. The relationship between successful and input mff is nearly linear (indicating proportionality) in S. squamosum B. These results are compared with those from O. volvulus-S. damnosum s.l. combinations in other West African foci.

Cytotaxonomy, morphology and molecular systematics of the Bioko form of Simulium yahense (Diptera: Simuliidae).

Cytotaxonomic analysis of the polytene chromosomes from larvae of the Simulium damnosum Theobald complex from the island of Bioko in Equatorial Guinea is reported, and a new endemic cytoform is described. Chromosomally this cytoform is close to both S. squamosum (Enderlein) and S. yahense Vajime & Dunbar, but is not identical to either. However, it is morphologically and enzymatically identical to S. yahense. The Bioko form was also found to differ from other cytoforms of the S. damnosum complex in West Africa in the copy number or RFLP pattern of several different repetitive DNA sequences. It is clear that the Bioko form is genetically distinct from other populations of the S. damnosum complex, and whilst it is closest to S. yahense, it shows features that suggest a high degree of geographical and genetic isolation. Such isolation is an important consideration in the assessment of the potential for onchocerciasis vector eradication on Bioko.

Epidemiology of concomitant infections due to Loa loa, Mansonella perstans, and Onchocerca volvulus in rain forest villages of Cameroon.

An epidemiological survey was conducted in 16 remote villages of the rain forest of southern Cameroon to ascertain the prevalence and intensity of three species of filariae: Loa loa, Onchocerca volvulus, and Mansonella perstans. We examined 1458 individuals for blood-dwelling microfilariae and 1255 of these were also for the presence of palpable nodules. All the villages surveyed were found highly endemic for onchocerciasis and mansonellosis with prevalence ranging from 28.44% to 87.17% for O. volvulus and 52.48% to 100% for M. perstans. The intensities of infection were also found high for M. perstans with arithmetic means of microfilaremia ranging from 280.94 to 4947.57 mf/ml. The loiasis prevalence was relatively low with value from 2.22% to 19.23%. Males were found more infected than females for the three species of filariae, and the prevalence and intensities of microfilaremia vary differently in males and females at different ages. The three species of filariae displayed different degrees of association in the inhabitants with a low prevalence of co-occurrence between L. loa/O. volvulus and between L. loa/M. perstans. In contrast, there was a high prevalence of co-occurrence between M. perstans and O. volvulus. The implications of the co-occurrence of the three species of filariae in the populations of these remote villages on the intervention programs based on mass treatment with mectizan are discussed.

Rapid epidemiological mapping of onchocerciasis (REMO): its application by the African Programme for Onchocerciasis Control (APOC).

One of the fundamental challenges that the African Programme for Onchocerciasis Control (APOC) has had to face is how to identify the endemic communities where its mass ivermectin-treatment operations are to be carried out in conformity with its stated objective of targetting the most highly endemic, affected and at-risk populations. This it has done by adopting a technique, known as the rapid epidemiological mapping of onchocerciasis (REMO), that provides data on the distribution and prevalence of onchocerciasis. Integration of the REMO data into a geographical information system (GIS) enables delineation of zones of various levels of endemicity, and this is an important step in the planning process for onchocerciasis control. Zones are included in (or excluded from) the APOC-funded programme of community-directed treatment with ivermectin (CDTI), depending on whether or not their levels of onchocercal endemicity reach the threshold set by APOC. This review describes the application of the REMO/GIS technique by APOC in its operations, and identifies the remaining related challenges.

The migration and localization of Loa loa infective and fourth-stage larvae in normal and immunosuppressed rodents.

The migration and localization of the human filarial parasite Loa loa in laboratory mice (BALB/c and Swiss) and jirds (Meriones unguiculatus) was investigated. The rodents, either left immunocompetent or immunosuppressed with hydrocortisone, were each inoculated subcutaneously or intraperitoneally with 50 or 200 infective, third-stage larvae (L(3)) of L. loa. Groups of the rodents were killed at various times post-infection, up to day 40, to enable histological studies and permit developing larvae to be recovered. Larvae survived and developed for only 1 week in the immunocompetent rodents but for a mean of 3 weeks in the immunosuppressed. Most of the larvae were found in the subcutaneous tissues (81.9%), peritoneal cavity (14.9%), pleural cavity (1.8%) or the lungs and heart (1.3%) and none was detected in the spleen, kidney, intestine, liver or pancreas. Localization of the larvae appeared unaffected by the site of inoculation, the rodent species or strain, or the dose of L(3) used. The recovery of larvae (as a percentage of the number inoculated) was better among the rodents inoculated with 50 L(3) each than among those given four times as many L(3). The results of the histological studies not only confirmed the presence of larvae in the subcutaneous tissue (72.5%), muscles (11.7%) and peritoneal and pleural cavities (7.8%) of the infected rodents but also revealed worms in the lymphatic vessels of the mesentery and spinal cord (7.3%). These results indicate that most L. loa L(3) inoculated into a mammalian host localize in the cutaneous sites and that only a small proportion of them might migrate, using the lymphatic system, into the internal organs. The observation of migrating L. loa larvae in the lymphatic vessel of the meningeal envelope of the spinal cord, albeit in an experimental host, may explain why, in areas where human loiasis is endemic, neurological manifestations occasionally occur in those with L. loa infections.

Antibody responses in onchocerciasis as a function of age and infection intensity.

Onchocerciasis is caused by the filarial nematode Onchocerca volvulus and is a major public health problem in West and Central Africa. With only partial and long-term treatment currently available, there is a need to develop a suitable vaccine. We analysed the antibody response to infective L3 larvae because this stage is thought to be associated with host protective immunity. In addition, we have related our findings to the age, gender and current infection intensity of our participants: variables that may significantly influence antibody production. Interestingly, whilst 90% of our study group were seropositive for adult specific immunoglobulin (Ig)E, only 23% produced L3 specific IgE. This is in contrast to IgG4 where seropositivity was comparable at 96% and 92%, respectively. Furthermore, IgG levels were significantly affected by age and the intensity of infection but unaffected by host gender. This finding is independent for the IgG subclass (IgG1, IgG2, IgG3 and IgG4) and its specificity (L3 versus adult antigen). In summary, we show that L3 larvae induce little specific IgE and the antibody response shows a different isotype balance than that against adult antigens. Both host and parasite variables can influence antibody production in this disease.

Co-endemicity of loiasis and onchocerciasis in the South West Province of Cameroon: implications for mass treatment with ivermectin.

Encephalopathy has been reported in Cameroon in individuals heavily infected with Loa loa microfilariae who were treated with ivermectin against onchocerciasis. Prior to the initiation of the community-directed treatment of onchocerciasis with ivermectin (CDTI) in the South West Province of Cameroon, an epidemiological survey of loiasis was conducted (in July 1998-July 1999) to ascertain the intensity of the disease. Thick blood films were made from 1228 blood samples collected during the day. Rapid epidemiological assessment (REA) of onchocerciasis was conducted among 614 individuals in the Upper Bayang area. Sixteen percent of the population examined were carriers of L. loa microfilariae. More males (20.1%) than females (12.4%) were infected. The community mean microfilaraemias of the different villages were low (< 1100 mf/mL). However, 1 person was found harbouring 174,000 mf/mL of blood and 1% of the study population (12) had microfilaraemia > 8100 mf/mL. Results of the REA of onchocerciasis show that 31.3% of the population investigated in the Upper Bayang area have this disease. These findings show that loiasis and onchocerciasis are co-endemic in the area, but the risk of developing encephalopathy after taking ivermectin is small.