The Role of the Maridi Dam in Causing an Onchocerciasis-Associated Epilepsy Epidemic in Maridi, South Sudan: An Epidemiological, Sociological, and Entomological Study.

Background: An epilepsy prevalence of 4.4% was documented in onchocerciasis-endemic villages close to the Maridi River in South Sudan. We investigated the role of the Maridi dam in causing an onchocerciasis-associated epilepsy epidemic in these villages. Methods: Affected communities were visited in November 2019 to conduct focus group discussions with village elders and assess the OV16 seroprevalence in 3- to 9-year-old children. Entomological assessments to map blackfly breeding sites and determine biting rates around the Maridi River were conducted. Historical data regarding various activities at the Maridi dam were obtained from the administrative authorities. Results: The Maridi dam was constructed in 1954-1955. Village elders reported an increasing number of children developing epilepsy, including nodding syndrome, from the early 1990s. Kazana 2 (the village closest to the dam; epilepsy prevalence 11.9%) had the highest OV16 seroprevalence: 40.0% among children 3-6 years old and 66.7% among children 7-9 years old. The Maridi dam spillway was found to be the only Simulium damnosum breeding site along the river, with biting rates reaching 202 flies/man/h. Conclusion: Onchocerciasis transmission rates are high in Maridi. Suitable breeding conditions at the Maridi dam, coupled with suboptimal onchocerciasis control measures, have probably played a major role in causing an epilepsy (including nodding syndrome) epidemic in the Maridi area.

Interruption of the transmission of Onchocerca volvulus in the Kashoya-Kitomi focus, western Uganda by long-term ivermectin treatment and elimination of the vector Simulium neavei by larviciding.

Uganda is the only country in sub-Saharan Africa whose onchocerciasis elimination programme extensively uses vector control and biannual treatment with ivermectin. The purpose of this study was to assess the impact of combined strategies on interrupting onchocerciasis transmission in the Kashoya-Kitomi focus. Mass Drug Administration annually (13 years) followed by biannual treatments (6 years) and ground larviciding (36 cycles in 3 years) with temephos (Abate®, EC500) against Simulium neavei were conducted. Routine fly catches were conducted for over seven years in six catching sites and freshwater crabs Potamonautes aloysiisabaudiae were examined for immature stages of Simulium neavei. Epidemiological assessments by skin snip were performed in 2004 and 2013. Collection of dry blood spots (DBS) from children <10 years for IgG4 antibodies analysis were done in 2010 and 2013. Treatment coverage with ivermectin improved with introduction of biannual treatment strategy. Microfilaria prevalence reduced from 85% in 1991 to 62% in 2004; and to only 0.5% in 2013. Crab infestation reduced from 59% in 2007 to 0% in 2013 following ground larviciding. Comparison of total fly catches before and after ground larviciding revealed a drop from 5334 flies in 2007 to 0 flies in 2009. Serological assays conducted among 1,362 children in 2010 revealed 11 positive cases (0.8%; 95% CI: 0.4%-1.2%). However, assessment conducted on 3246 children in 2013 revealed five positives, giving point prevalence of 0.15%; 95% CI: 0.02%-0.28%. Four of the five children subjected to O-150 PCR proved negative. The data show that transmission of onchocerciasis has been interrupted based on national and WHO Guidelines of 2012 and 2016, respectively.

Nodding syndrome since 2012: recent progress, challenges and recommendations for future research.

We aim to review the current epidemiology of nodding syndrome (NS) and discuss relevant gaps in research. NS and convulsive epilepsy of unknown aetiology are clustered within the same villages and families in onchocerciasis-endemic areas. They are therefore potentially different clinical expressions of the same disease. It has been difficult to perform full autopsies on NS patients who die in remote villages. Adequate fixation of tissue immediately after death is critical for the examination of brain tissue. Therefore, post-mortem transsphenoidal brain biopsies, performed immediately after death by trained nurses, will provide the best option for obtaining tissue for analysis. We suspect that certain blackflies in onchocerciasis-endemic areas may transmit a novel pathogen that could cause NS and epilepsy. This is supported by a recent drop in the number of new NS cases coinciding with vector control activities aimed at reducing blackfly populations in northern Uganda. We propose that metagenomic studies of human samples, blackflies and microfilariae are conducted to screen for pathogens, and that a clinical trial is planned to evaluate the impact of larviciding against NS and epilepsy epidemics.

The disappearance of onchocerciasis from the Itwara focus, western Uganda after elimination of the vector Simulium neavei and 19 years of annual ivermectin treatments.

The Itwara onchocerciasis focus is located around the Itwara forest reserve in western Uganda. In 1991, annual treatments with ivermectin started in the focus. They were supplemented in 1995 by the control of the vector Simulium neavei, which was subsequently eliminated from the focus. The impact of the two interventions on the disease was assessed in 2010 by nodule palpations, examinations of skin snips by microscopy and PCR, and Ov16 recombinant ELISA. There was no evidence of any microfilaria in 688 skin snips and only 2 (0.06%) of 3316 children examined for IgG4 were slightly above the arbitrary cut off of 40. A follow up of the same children 21 months later in 2012 confirmed that both were negative for diagnostic antigen Ov-16, skin snip microscopy and PCR. Based on the World Health Organization (WHO) elimination criteria of 2001 and the Uganda onchocerciasis certification guidelines, it was concluded that the disease has disappeared from the Itwara focus after 19 years of ivermectin treatments and the elimination of the vector around 2001. Ivermectin treatments were recommended to be halted.

Evaluation of schistosoma mansoni morbidity one year after praziquantel treatment in rhino cAMP and obongi in west nile, Uganda.

An evaluation study on reversibility of Schistosoma mansoni induced periportal fibrosis (PF) morbidity following treatment with praziquantel, 40mg/kg body weight after one year, was carried out in Rhino Camp and Obongi all are West Nile districts in northern Uganda. To assess the reversibility of Schistosoma (S) mansoni induced PFs morbidity following treatment with praziquantel, 40mg/kg body weight after one year. The design was a Prospective cohorts study; and the setting was a busy canoe landing sites along Albert Nile in Schistosoma (S) mansoni hyperendemic areas of Rhino Camp and Obongi fishing village were selected for the study. Previously in 2005, 1562 people including fishermen and women, school pupils, teachers, and civil servants were studied in both fishing villages for S. mansoni using Kato/Katz stool smear method. Abdominal ultrasonography and sonomorphological abnormalities of periportal fibrosis were performed with Aloka portable ultrasound machine (Hellige, Freiburg, Germany) fitted with a convex probe of 3.5 mega Hertz was also performed in the field clinic on all patients who had S. mansoni eggs in their faeces. The sonomorphological abnormalities of periportal fibrosis were categorised and organomorphometry of liver and spleen was done. One thousand two hundred and seventy three 1273 (81.5%) patients in Rhino Camp and Obongi fishing villages were found to be excreting from 100 to ≥ 500 eggs per gram (epg) of faeces of S. mansoni eggs. Two hundred and eighty nine (18.5%) did not have eggs of S.mansoni in their faeces. All the 1273 patients secreting eggs of S.mansoni in their stool in Rhino Camp and Obongi fishing villages had abdominal ultrasonography and sonomorphological abnormalities of periportal fibrosis. Eight hundred and forty 840 (66%) although excreted S. mansoni eggs in their stool had Pf (0); Pf grade (I), n=259 (20.3%); Pf grade (II) n =147 (11.5%); and Pf grade (III) n=27 (2.1%) were observed.

The elimination of the vector Simulium neavei from the Itwara onchocerciasis focus in Uganda by ground larviciding.

The Itwara focus of onchocerciasis covers an area of approximately 600 km(2) in western Uganda about 20 km north of Fort Portal. The vector is Simulium neavei, whose larvae and pupae live in a phoretic association on freshwater crabs. The phoretic host in the Itwara focus is the crab Potamonautes aloysiisabaudiae. Before any onchocerciasis control, ATPs were estimated to reach between 4500 and 6500 infective larvae per person per year. S. neavei was found to be a very efficient vector with 40% of parous flies harbouring developing larvae of Onchocerca volvulus. After 4 years of community-based distribution of ivermectin transmission was still considerable and in 1995 monthly treatment of streams with the larvicide temephos commenced in the first of three sub-foci, and was gradually extended to the whole focus. Biting S. neavei disappeared from the first sub-focus (Itwara main) in June 1996, and the last infested crab was caught in November 1996. In the second sub-focus (Siisa) treatment commenced towards the end of 1995, and the last biting fly was caught in March 1997, but a deterioration in the security situation interrupted the programme (after only three treatments in the third sub-focus). Monthly treatments restarted in the second and third sub-foci (Aswa) in September 1998, and when the situation was reassessed in 2003 no biting flies were found anywhere, and the flies had not reinvaded the first sub-focus, but infected crabs were found in the second and third sub-foci. The last treatments were carried out in April-June 2003, and since then no infested crabs have been found. In summary, no S. neavei-infested crabs have been found anywhere in the focus since June 2003 and the vector is considered eliminated from that date. However, transmission had already been halted since February 2001, when the last biting flies had been collected. The parasite reservoir should die out in the human population by 2016.

Progress towards the elimination of onchocerciasis as a public-health problem in Uganda: opportunities, challenges and the way forward.

The national onchocerciasis-control programme in Uganda successfully eliminated Simulium neavei s.s. from the Itwara focus in 1997, by monthly ground spraying with larvicidal temophos (Abate). Since then, no vectors have been caught in the main Itwara focus or two secondary foci in the same area. After 4 years of intervention, S. neavei s.s. has also been nearly eliminated from the Mpamba-Nkusi focus, and the elimination of this vector from two more foci (West Nile and Wambabya-Rwamarongo) appears quite feasible. There are, however, four isolated foci in Uganda (Budongo, Kashoya-Kitomi, Mount Elgon and Kigezi-Bwindi) which are probably too large and inaccessible to make the elimination of S. neavei s.s. by ground spraying a realistic possibility. Encouragingly, >70% of Ugandans have received an annual dose of ivermectin for at least 10 years, and the national programme of community-directed treatment with ivermectin (CDTI) is thought to be progressing towards sustainability. Despite the good treatment coverages, however, many potential vectors are still found infected with Onchocerca volvulus and many Ugandans have O. volvulus in their skin. There is now evidence that adult O. volvulus can be eliminated, within a period of about 6 years, through semiannual treatment with ivermectin. Together, the isolated foci where vector elimination is not considered feasible have a human population of about 700,000, most of whom (595,000) are eligible to receive ivermectin treatment. The estimated cost of each treatment, via the Ugandan CDTI, is U.S.$0.78 if the salaries of the government-employed personnel and the working time lost by the volunteers who act as community-directed drug distributors (CDD) are taken into account. If these 'expenses' are ignored, however, the cost falls to just U.S.$0.17/treatment, and the total costs for the four isolated foci where vector control is not likely to be successful become about U.S.$101,150/year for annual treatment (for an indefinite period of time) or approximately U.S.$202,300/year for semi-annual treatment (for the 6 years needed to eliminate adult O. volvulus), which would be the more cost-effective option. With the necessary financial support and the continued free supply of ivermectin from Merck, the national onchocerciasis-control programme could eliminate human onchocerciasis from Uganda, through a combination of semi-annual treatment with ivermectin in the isolated foci where S. neavei s.s. elimination is not feasible, and vector elimination in all the other foci.

Non-adherence to community directed treatment with ivermectin for onchocerciasis control in Rungwe district, southwest Tanzania.

BACKGROUND: Community directed treatment with ivermectin (CDTI) for onchocerciasis control was developed as a strategy for achieving sustained high coverage in endemic communities. This strategy for over a short period of time has radically altered the consequences of infection with Onchocerca volvulus. The present challenge is maintaining the high therapeutic coverage especially in some of the impoverished endemic countries. One of these challenges is non-adherence to ivermectin treatment and this provides compelling reason for data collection at community level. OBJECTIVE: To describe the factors associated with non-adherence to CDTI. DESIGN: Cross-sectional descriptive study. SETTING: Communities participating in CDTI activities in Ndubi village, Rungwe district, southwest Tanzania. RESULTS: A high proportion (66%) of respondents were aware of onchocerciasis, and this was more significant in males than females (X2 = 9.17; p< 0.002). Knowledge on causes of the disease was low, only 29.3% associated it with the bite of Simulium fly, 17% associated it with mosquitoes, 17.1% to houseflies, and 30% had completely no idea. Knowledge on signs and symptoms of onchocerciasis was also observed to be equally low (20.4%) among the respondents. Similarly, only 35.4% of the respondents knew itching, swelling of the body, diarrhoea and vomiting as associated side effects of ivermectin. There was, however, no sex difference in knowledge levels (X2 = 0.01; p>0.939). Low knowledge levels on causes of the disease, signs and symptoms and side effects of ivermectin were attributed to inadequate health education in the communities. However, some other factors associated with non-adherence were local beliefs and the lifestyle of alcoholism. CONCLUSIONS: Factors identified to affect programme implementation and associated with non-adherence were inadequate knowledge on causes of the disease and sign/symptoms, side effects of ivermectin, local beliefs and lifestyle of alcoholism in the communities.

Transmission of Onchocerca volvulus and prospects for the elimination of its vector, the blackfly Simulium neavei in the Mpamba-Nkusi focus in Western Uganda.

The transmission of Onchocerca volvulus Leuckart (Spirudida: Onchocercidae) and the prospects of Simulium neavei Roubaud (Diptera: Simuliidae) vector elimination through ground larviciding were investigated in the Mpamba-Nkusi focus, western Uganda. Transmission levels and the initiated vector elimination activities were assessed to supplement the ongoing ivermectin mass distribution programme. Searches for breeding sites, adult fly catches, dissection of flies, river treatment with temephos (Abate) and a review of annual ivermectin treatment data were conducted. High levels of crab infestation with S. neavei sensu stricto immature stages were recorded; 57.9% and 100% for the Mpamba and Nyabugando river systems, respectively. The mean numbers of larvae/pupae per crab were 3.6 +/- 0.5 in the Mpamba and 20.6 +/- 1.8 in the Nyabugando systems. Pre-intervention mean biting densities were 39 and 32 flies/(man day) in 2001 and 2002, respectively, and an annual biting rate in 2001 of > 14 000. The bimodal biting pattern of S. neavei s.s. consisted of two peaks; one in the morning (09.00-10.00 hours) and one in the afternoon (14.00-15.00 hours) with a mid-day lull in biting. The infection/infective rates were 13.3%/2.8% and 16.6%/2.9% in the dissected parous flies from the Mpamba and Nyabugando river systems, respectively. Out of approximately 1000 parous flies, 129 and 109 were found to be harbouring infective larvae of Onchocerca volvulus in their heads from the Mpamba and Nyabugando river systems, respectively. In spite of the > 10 years of ivermectin treatment, at a mean coverage of 71.3%, infection remained relatively high. Ground larviciding with temephos (Abate) initiated in June and October 2002 had a significant impact. In the Mpamba river system there was a significant (P < 0.001) reduction in positive crabs from 57.9% in 2001 to 0.06% in 2003 and a decrease in the mean number of larvae/pupae per crab from 3.6 +/- 0.5 in 2001 to 0.0007 +/- 0.0001 (P < 0.002) in 2003. Similarly, in the Nyabugando river system, a significant (P < 0.001) reduction in crab infestation from 100% in 2001 to 0.06% in 2003 and a decrease in the mean number of larvae/pupae per crab from 20.6 +/- 1.8 in 2001 to 0.06 +/- 0.03 in 2003. Drastic reductions were observed in the mean number of biting flies from 3 flies/h in 2001 to 0 flies/h in 2003 and the annual biting rates fell from 14,235 flies/year in 2001 to only 730 flies/year in 2003. These data suggest that substantial progress towards the goal of S. neavei s.s. vector elimination has been made and this will enhance the ongoing ivermectin treatment in this isolated focus.

Preliminary studies on the biting activity and transmission of Onchocerca volvulus by Simulium neavei (diptera: simuliidae) in Kashoya-Kitomi focus, Western Uganda.

OBJECTIVE: To determine the biting activity and onchocerciasis transmission in Kashoya-Kitomi focus, Western Uganda. DESIGN: Cross-sectional survey in randomly selected sites. SETTING: Three districts in Western Uganda. METHOD: Crab trapping and examination for immature stages of Simulium neavei and full day human bait catches and dissections were conducted at three sites. RESULTS: A total of 338 crabs were caught and out of this 372 (95.9%) were positive with immature stages of S. neavei with mean S. neavei/crab of 6.9. High biting density of S. neavei was observed in the two sites in Kabarole and Mbarara districts whereas an extremely low density was observed at a site in Bushenyi. Diurnal biting pattern revealed two peaks in the morning (09:00-10:00 hours.) and in the late afternoon (14:00-15:00 hours.) with a mid-day lull. The infection/infective rates were 53.3/11.0%, 30.7% to 7.8% and 20.0/0% for sites in Mbarara, Kabarole and Bushenyi districts, respectively. Monthly biting rates/ Transmission potentials for Mbarara, Kabarole and Bushenyi districts were 6231/5437, 9244/2916 and 247/0. CONCLUSION: There was high transmission of onchocerciasis observed in Kashoya-Kitomi focus despite the ongoing ivermectin treatment. The need for improved chemotherapeutic coverage and instituting other control measures may be necessary.

Evidence for a long-term effect of a single dose of praziquantel on Schistosoma mansoni-induced hepatosplenic lesions in northern Uganda.

Treatment with praziquantel reduces the prevalence and intensity of Schistosoma mansoni infection. However, reversibility of periportal fibrosis of the liver, which potentially leads to fatal complications, is not unequivocally substantiated. In the Nile District of Uganda, 460 patients were parasitologically (Kato-Katz method) and ultrasonographically examined during October 1991, October 1992, and May 1994. Treatment with praziquantel at a dosage of 40 mg per kilogram of body weight was given in October 1991 and October 1992 to 460 individuals (group A). Another 192 patients were seen during the baseline study in October 1991 and missed the follow-up in October 1992 but took part in the second follow-up in May 1994. Thus, they received praziquantel only once in October 1991 (group B) and had an interval of 2.7 years until the next investigation in May 1994. Periportal thickening (PT) of the liver was assessed by ultrasound at each time point. Praziquantel therapy reduced the prevalence of S. mansoni in group A from 84% in 1991 to 31% in 1992 and 30% in 1994. The respective intensities of infection (geometric means of egg output) were 81 eggs per gram (epg) of stool in 1991, 31 epg in 1992, and 30 epg in 1994. Periportal thickening was found in 46% of patients in 1991, 32% of patients in 1992, and 35% of patients in 1994. Reversibility of PT was influenced by age (markedly lower reversibility in individuals older than 30 years) and sex (women and girls responded less favorably than did men and boys). Surprisingly, no significant difference was detected between group A and group B with respect to reversibility of PT The outcome between the 2 groups did not differ significantly. This may indicate that a single dose of praziquantel (as given to group B) may have a longer lasting effect than previously thought, that is, more than 2.5 years.

Integrated control trial of schistosomiasis at Nakiwogo fishing village near Entebbe, Uganda.

Using the Kato Katz technique, 600 people living in Nakiwogo fishing village at Lake Victoria, Uganda, were examined for Schistosoma mansoni infection. The total population of this village was estimated between 1,000 and 1,500 mainly consisting of migrants from western Uganda. Of the 600 individuals in the study group, 328 people (54.7%) were found to be infected with S. mansoni. The geometric mean egg count was 422 eggs per gramme of stool. A survey of the snail intermediate hosts for S. mansoni and S. haematobium at Nakiwogo was carried out. The collected snails were tested for cercariae shedding. A significant decrease in the number of Biomphalaria choanomphala and Biomphalaria pfeifferi (52%) which both still shed cercariae and Bulinus tropicus (52.5%) could be observed. There was a lower none-significant decrease of 13.3% of the Bulinus globosus population. With a combined approach including community participation in control measures in the form of health education, sanitation, environmental management and chemotherapy, the prevalence of S. mansoni infection was reduced from 54.7% to 14.6% in the period of one year.

Schistosoma mansoni along Lake Albert, Kibale District, Western Uganda.

Four hundred and fifty one human strata living in the three fishing villages of Ndiaga, Kabukanga and Rwabikongoro along Lake Albert shore in Kibale District were examined for S. mansoni infection using Kato/Katz method. Of the 451 people, 409 (90.7%) were found infected with S. mansoni with geometric mean egg count of 561.3 eggs per gram (epg) faeces. Males had significantly higher mean egg counts than females, 608.3 epg and 415.6 epg respectively. All S. mansoni infected individuals were treated with praziquantel at 40 mg/kg body weight. Other common parasites observed were Asaris lumbricoides, Trichuris trichiura and hookworms. These were treated with mebendazole. Snail infection rate among the 115 Biomphalaria sudanica and the 56 B. stanleyi were 5.2% and 3.6% respectively. All the 66 Bulinus (B) tropicus found, were negative for cercariae shedding. The main pulmonate snails were 250 Lymnae natalensis, 500 Pila ovata and 375 Bellamya spp were the commonest prosobranchs followed by Bivalves (101).

Intergrated control trial of schistosomiasis at Nakiwogo fishing village near Entebbe; Uganda

Using the Kato katzi technique; 600 people living in Nakiwogo fishing village at Lake Victoria; Uganda; were examined for schistosoma mansoni infection. The total population of this village was estimated between 1;00 and 1;500 mainly consisting of migrants from Western Uganda. Of the 600 individuals in the study group; 328 people (54.7) were found to be infected with S. mansoni. The geometric mean egg count was 422 eggs per gramme of stool. a survey of the snail intermediate hosts for S. mansoni and S. haematobium at Nakiwogo was carried out. The collected snails were tested for cercariae shedding. A significant decrease in the number of Biomphalaria choanomphala and Biomphalaria pfeifferi (52) which both still shed cercariae and Bulinus (52.5) could be observed. There was a lower none-significant decrease of 13.3of the Bulinus globosus population. With a combined approach including community participation in control measures in the form of health education; sanitation; environmental management and chemotherapy; the prevalence of S. mansoni infection was reduced from 54.7to 14.6 in the period of one year

Schistosoma mansoni along Lake Alibert; Kibale district; Western Uganda

Four hundred and fifty one human strata living in the three fishing villages of Ndiaga; kabukanga and Rwabikongoro along Lake Albert shore in Kibale District were examined for S. mansoni infection using Kata/Katz method. Of the 451 people; 409(90.7) were found infected with S. mansoni with geometric mean egg count of 561.3 eggs per gram (epg) faeces. Males had significantly higher mean egg counts than females; 608.e epg and 415.6 epg respectively. All S. mansoni infected individuals were treated with praziquantel at 40mg/kg body weight. Other common parasites observed were Ascaris lumbricoides; Trichuris trichiura and hookworms. These were treated with mebandazole. Snail infection rate among the 115 Biomphalaria sudanica and the 56 B. stanleyi were 5.2and 3.6respectively. All the 66 Bulinus (B) tropicus found; were negative for cercariae shedding. The main pulmonate snails were 250 Lymnae natalensis; 500 Pila ovata and 375 Bellamya spp were the commonest prosobranchs followed by Bivalves (101)

Urban Schistosoma mansoni near Enyau river in Arua town, Uganda.

Using the Kato Katz method for quantification of parasitic eggs in faeces, 500 individuals aged between 4 and 50 years, living along River Enyau, half a kilometre from Arua town, were studied to assess the prevalence of Schistosoma mansoni in the population. The overall prevalence of Schistosoma mansoni infection was 62%. The infection was highest among school children (71.1%, i.e. 199 out of 280). Villagers who lived along the immediate vicinity of the river had a 62.8% prevalence of infection (98 out of 156). School teachers and the members of their families had the lowest infection rate (20.3% i.e. 13 out of 64). The geometric mean egg output for males and females in the community studied was 203 and 179 eggs per gram of stool, respectively. 206 (41%) out of 500 individuals had mixed infections of S. mansoni and hookworms. The rate of orally transmitted intestinal helminths like Trichuris trichiura was very low (0.8%). Ascaris lumbricoides eggs were not found.

Evidence for the occurrence of Schistosoma intercalatum at Albert Nile in northern Uganda.

During a field investigation in Rhino Camp at Albert Nile in northern Uganda, 77.8% of 636 persons excreted Schistosoma mansoni ova that were detected by the Kato-Katz method. Six patients, 8-17 years of age, had terminally spined schistosome eggs in their stools. These findings were confirmed when preserved specimens were examined at the Institute of Medical Parasitology in Bonn using a concentration technique. The mean +/- SD length of 36 terminally spined eggs was 156 +/- 6 microns and the mean +/- SD width was 59 +/- 3.6 microns. Urine filtration in the study patients revealed no schistosome eggs in the urine. It is concluded that these findings provide evidence for the occurrence of S. intercalatum at Albert Nile in northern Uganda.