• View in gallery

    (A) Map of the Abu Hamed focus showing black fly collection sites and some serology collection sites in 2014/2015. Also shown is the flooded portion of the focus and some displaced communities. (B) Timeline of onchocerciasis history in Abu Hamed from discovery to elimination.

  • 1.

    Crump A, Morel CM, Omura S, 2012. The onchocerciasis chronicle: from the beginning to the end? Trends Parasitol 28: 208288.

  • 2.

    World Health Organization, 2011. African Programme for Onchocerciasis Control: meeting of national onchocerciasis task forces. Wkly Epidemiol Rec 86: 541549.

    • Search Google Scholar
    • Export Citation
  • 3.

    Morgan H, 1958. Onchocerciasis in northern Sudan. J Trop Med Hyg 61: 145147.

  • 4.

    Williams JF, Abu Yousif AH, Ballard M, Awad R, el Tayeb M, Rasheed M, 1985a. Onchocerciasis in Sudan: the Abu Hamed focus. Trans R Soc Trop Med Hyg 79: 464468.

    • Search Google Scholar
    • Export Citation
  • 5.

    Higazi TB, Boakye DA, Wilson MD, Mahmoud BM, Baraka OZ, Mukhtar MM, Unnasch TR, 2000. Cytotaxonomic and molecular analysis of Simulium (Edwardsellum) damnosum sensu lato (Diptera: Simuliidae) from Abu Hamed, Sudan. J Med Entomol 37: 547553.

    • Search Google Scholar
    • Export Citation
  • 6.

    Higazi TB, Katholi CR, Mahmoud BM, Baraka OZ, Mukhtar MM, Qubati YA, Unnasch TR, 2001. Onchocerca volvulus: genetic diversity of parasite isolates from Sudan. Exp Parasitol 97: 2434.

    • Search Google Scholar
    • Export Citation
  • 7.

    Zarroug IMA, Elaagib A, Mohamed HA, Elmmubark WA, Osman KH, Deran TCM, Aziz N, Nugud A, 2014. Plants associated with aquatic stages of onchocerciasis vector Simulium damnosum sensu lato in Abu Hamed and Galabat foci in Sudan. Sud J Pub Hlth 9: 3841.

    • Search Google Scholar
    • Export Citation
  • 8.

    Zarroug IMA, Hashim K, Elaagip AH, Samy AM, Frah EA, ElMubarak WA, Mohamed HA, Deran TC, Aziz N, Higazi TB, 2016. Seasonal variation in biting rates of Simulium damnosum sensu lato, vector of Onchocerca volvulus, in two Sudanese foci. PLoS One 11: e0150309.

    • Search Google Scholar
    • Export Citation
  • 9.

    World Health Organization, 2013. Progress towards eliminating onchocerciasis in the WHO Region of the Americas: verification by WHO of elimination of transmission in Columbia. Wkly Epidemiol Rec 88: 381388.

    • Search Google Scholar
    • Export Citation
  • 10.

    World Health Organization, 2014. Progress towards eliminating onchocerciasis in the WHO Region of the Americas: Ecuador's progress towards verification of elimination. Wkly Epidemiol Rec 89: 401408.

    • Search Google Scholar
    • Export Citation
  • 11.

    World Health Organization, 2015. Progress towards eliminating onchocerciasis in the WHO Region of the Americas: verification by WHO of elimination of transmission in Mexico. Wkly Epidemiol Rec 90: 577581.

    • Search Google Scholar
    • Export Citation
  • 12.

    World Health Organization, 2001. Certification of Elimination of Human Onchocerciasis: Criteria and Procedures. Geneva, Switzerland: World Health Organization, 136.

    • Search Google Scholar
    • Export Citation
  • 13.

    Higazi TB, Zarroug I, Mohamed HA, Mohamed WA, Deran TC, Aziz N, Katabarwa M, Hassan HK, Unnasch TR, Mackenzie CD, Richards F, 2011. Polymerase chain reaction pool screening used to compare prevalence of infective black flies in two onchocerciasis foci in northern Sudan. Am J Trop Med Hyg 84: 753756.

    • Search Google Scholar
    • Export Citation
  • 14.

    Higazi TB, Zarroug I, Mohamed HA, Elmubarak WA, Deran T, Aziz N, Katabarwa M, Hassan HK, Unnasch T, Mackenzie C, Richards F, Hashim K, 2013. Interruption of Onchocerca volvulus transmission in the Abu Hamed focus, Sudan. Am J Trop Med Hyg 89: 5157.

    • Search Google Scholar
    • Export Citation
  • 15.

    Zarroug IMA, Elaagib A, Abuelmaali SA, Mohamed HA, Elmubarak WA, Hashim K, Deran TCM, Aziz N, Higazi T, 2014. The impact of Merowe dam on Simulium hamedense vector of onchocerciasis in Abu Hamed focus: northern Sudan. Parasit Vectors 7: 168172.

    • Search Google Scholar
    • Export Citation
  • 16.

    World Health Organization, 2016. Guidelines for Stopping Mass Drug Administration and Verifying Elimination of Human Onchocerciasis: Criteria and Procedures. Geneva, Switzerland: World Health Organization, 136.

    • Search Google Scholar
    • Export Citation
  • 17.

    Katabarwa M, Richards F, 2014. Twice-yearly ivermectin for onchocerciasis: the time is now. Lancet 14: 373374.

 

 

 

 

The First Confirmed Elimination of an Onchocerciasis Focus in Africa: Abu Hamed, Sudan

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  • 1 Ministry of Health, Khartoum, Sudan.
  • 2 The Carter Center, Khartoum, Sudan.
  • 3 The Carter Center, Atlanta, Georgia.
  • 4 Global Health Infectious Disease Research Program, College of Public Health, University of South Florida, Tampa, Florida.
  • 5 Michigan State University, Lancing, Michigan.
  • 6 Ohio University, Zanesville, Ohio.

Mass treatment with ivermectin for onchocerciasis was stopped in 2012 in Abu Hamed, an isolated focus on the River Nile in northern Sudan. A 3-year posttreatment surveillance (PTS) ensued, at the end of which an evaluation was conducted in 2015 following the current World Health Organization guidelines for verification of onchocerciasis elimination. Vector black flies were collected from sentinel breeding sites and finger-prick bloodspots were collected from children ≤ 10 years of age resident in 35 communities within the focus. Polymerase chain reaction (PCR) screening of 19,191 flies from four sites for the O-150 parasite-specific marker found no flies carrying Onchocerca volvulus larvae (0%, 95% upper confidence limit [UCL] = 0.16), and serological testing of 5,266 children identified only one Ov16 seropositive child (0.019%, 95% UCL = 0.074); whose skin snips were negative when tested by O-150 PCR assay. These results indicate that for the first time in Africa, onchocerciasis elimination has been verified after a successful PTS in Abu Hamed.

Onchocerciasis or river blindness is a major tropical disease currently endemic in Venezuela, Brazil, Yemen, and importantly in 31 African countries where 99% of the estimated 123 million individuals at risk reside.1 Onchocerciasis is caused by the parasitic filarial nematode Onchocerca volvulus, and is transmitted by black flies of the genus Simulium that breed in fast-flowing rivers and streams. The disease is manifested in debilitating skin lesions and ocular pathology that can lead to blindness.

Sudan is one of 20 African countries within the former African Program for Onchocerciasis Control (APOC) that covered > 102 million people at risk of this infection.2 Currently, the disease remains endemic in four foci located in the north, east, southeast, and in the southwest of the country. The Abu Hamed focus, the northernmost focus in the world, is an isolated site associated with active Simulium breeding in the River Nile as it winds through the rocks and sands within the Nubian Desert to the north and east (Figure 1A). The focus is at least 600 km away from the closest existing onchocerciasis focus in Galabat, east Sudan. First reported in 1958,3 the Abu Hamed onchocerciasis focus has been described at times of having infection rates of up to 37%4 (Figure 1B), and presenting a nonblinding form of the disease predominated by severe dermal disease, including the characteristic “sowda” form of acute reactive onchodermatitis.4 Molecular and cytogenetic studies have identified the presence of unique forms of the parasite and Simulium damnosum s.l. vector5,6 in this focus and the characteristics of black fly breeding sites and biting in Abu Hamed have been described.7,8

Figure 1.
Figure 1.

(A) Map of the Abu Hamed focus showing black fly collection sites and some serology collection sites in 2014/2015. Also shown is the flooded portion of the focus and some displaced communities. (B) Timeline of onchocerciasis history in Abu Hamed from discovery to elimination.

Citation: The American Society of Tropical Medicine and Hygiene 95, 5; 10.4269/ajtmh.16-0274

The Abu Hamed focus was the first in the country to undergo rapid epidemiological mapping of onchocerciasis and to begin a control program under auspices of APOC using a mass drug administration (MDA) strategy employing annual community-directed treatment with ivermectin (CDTI) in 1998 (Figure 1B). The isolated nature and the mesoendemic disease status of the Abu Hamed focus led the government of Sudan to declare an official elimination strategy for the first time in Africa in December 2006 (Figure 1B). As onchocerciasis elimination has now been achieved in Colombia,9 Ecuador,10 and Mexico11 by using a semiannual or quarterly ivermectin treatment regimen, a switch to semiannual CDTI in the Abu Hamed focus was used with the new elimination approach, and detailed parasitological, entomological, and serological assessments of the disease were carried out. The 2007 entomological assessment of more than 29,000 flies by O-150 polymerase chain reaction (PCR)–based enzyme-linked immunosorbent assay showed 0.17 (95% confidence interval [CI] = 0.097–1.88) L3 larvae per 2,000 black flies indicating (according to World Health Organization [WHO] guidelines requiring < 1 L3/2,00012) ongoing transmission of infection despite 10 years of annual MDA.13

To focus on elimination, the treatment coverage of the target population of about 120,000 in this focus was improved and a second assessment of the disease status was performed in 2011/2012, 5 years after the switch to semiannual CDTI14 (Figure 1B). In this assessment, no infection was found in > 17,000 black flies screened by O-150 PCR, no antibodies to Ov16 antigen in 6,756 children ≤ 10 years of age, and no signs of infection in 536 adult individuals from seven communities within the focus.14 This assessment indicated that the disease transmission has been interrupted in Abu Hamed based on the WHO 2001 guidelines for interruption of onchocerciasis transmission.11 Review of these findings prompted the government of Sudan to declare interruption of the parasite transmission, halting mass treatment activities, and beginning a 3-year posttreatment surveillance (PTS) phase in May 2012 (Figure 1B). The PTS period has been marked and celebrated by extensive health education and community mobilization campaigns throughout the focus in 2013 and 2014, led by state ministries of health (MOHs) and community partners, to educate the local population about the cessation of the disease transmission, the stoppage of treatment, and the next steps toward successful elimination of this infection.

Both the 2012 and the assessments described in the present report have taken into consideration some of the important recent environmental developments in the area. The Merowe hydroelectric dam, about 30 km downstream of the western limit of the Abu Hamed focus (Figure 1A), was built and activated in 2009. The artificial reservoir filling as a result of the completion of the dam has gradually flooded a considerable portion of the western part of the focus and displaced some island and shore communities to new locations within and near the focus (Figure 1A).1315 Thus, a new breeding site near Al Sarsaf village west of the flooded area was added to the PTS assessment protocol. In addition, Hamdab Island, downstream of Merowe dam, was also monitored for the possible introduction of new black fly breeding sites due to favorable conditions created by the dam, and two displaced communities were screened in their new locations for any exposure to the infection.

The Abu Hamed PTS assessment followed the criteria and procedures of the 2016 WHO guidelines for stopping MDA and verifying elimination of human onchocerciasis.16 Black flies were collected from four sentinel breeding sites within the focus (Figure 1A) from November 2014 to June 2015 following standard procedures.14 Finger-prick sampled blood was also collected on filter papers from children ≤ 10 years of age from 39 schools representing 35 communities within and around the focus including flooded and displaced communities (Figure 1A) in July 2015. Black flies and sera extracted from filter paper were processed and tested for O. volvulus infection using the O-150 pool screening PCR and the Ov16 serological assays, respectively, as previously described.14 All communities included in the study were informed of the purpose and procedures of the monitoring process and necessary ethical approvals were obtained from federal and state MOHs, and all individuals involved in the study, or their guardians/headmasters. In addition, the study protocols were reviewed by the Emory University Institutional Review Board, which classified them as nonresearch routine program evaluation.

PCR screening of 19,191 black fly bodies collected from four sites throughout the focus in the 2014/2015 breeding season showed no parasite-specific DNA (point prevalence of flies carrying O. volvulus of 0%, with an upper limit of the 95% CI = 0.16/2,000 flies) (Table 1). No flies were detected in the Hamdab Island site downstream of the Merowe dam (Table 1). Testing black fly bodies allows for detection of all larval stages of the parasite rather than only L3 larvae that are detected in black fly heads. Screening of blood spots from 5,266 children ≤ 10 years of age from 33 communities within the focus and residing in two displaced communities, showed one child positive for Ov16 IgG4 antibodies (0.019% prevalence; 95% CI = 0.00003–0.074) (Table 2). As soon the Ov16 serological test results became known, the assessment team conducted an epidemiological investigation. The child was a 9-year-old female from the Kurgus community who had no history of travel or clinical history or symptoms of onchocerciasis infection. Two skin snips obtained from the left and right posterior superior iliac crest tested negative for parasite-specific DNA by the O-150 PCR assay. The number of samples collected and screened in this study complies with the limits set by WHO guidelines of at least 6,000 black flies and 2,000 blood spots per transmission zone.16

Table 1

Prevalence of Onchocerca volvulus–infected black flies in Abu Hamed from November 2014 to June 2015 based on O-150 pool screening polymerase chain reaction

Breeding siteNo. of flies/pools analyzedNo. infectedPrevalence of flies carrying O. volvulus (any stage) per 2,000 flies*
Kelsakel5,664/5800 (0–0.72)
Nady3,550/3800 (0–1.12)
Karny2,245/2400 (0–1.6)
AlSarsaf7,732/8200 (0–0.52)
Hamdab Island0N/AN/A
Abu Hamed total19,191/20200 (0–0.16)

N/A = not applicable.

Upper number represents the estimated point pervalence (95% confidence interval).

Table 2

Prevalence of Ov16 IgG4 antibodies in school children ≤ 10 years of age in Abu Hamed focus on July 2015

Site (no. of communities)No. examinedNo. positive (prevalence %)95% CI (%)
Within focus (33)4,9871* (0.02)0.00003–0.075
Displaced (2)2790 (0)0–0.68
Abu Hamed total5,2661* (0.019)0.00003–0.074

CI = confidence interval.

O-150 polymerase chain reaction on skin snips showed no current infection.

Previously we reported the first evidence of interruption of O. volvulus transmission in Africa achieved with annual and semiannual ivermectin mass treatment alone in Abu Hamed in 2012,14 and now provide evidence for the first elimination of onchocerciasis after PTS in Africa following the new WHO guidelines for verification of onchocerciasis transmission interruption and elimination16; these guidelines are based on the successes in South America.911 Our data meets the major recommendation of < 1% upper limit 95% CI of infection where no black flies screened by the O-150 PCR assay are infected, as well as the upper limit of the 95% CI of 0.1% for the prevalence of infection in children ≤ 10 years of age. In addition, the absence of positive bodies in the flies is strong evidence for the absence of available microfilaria in the human population. Finally, O-150 PCR confirmed the absence of current active infection in skin snips from the single Ov16 seropositive child as recommended in the guidelines. This positive reaction may have been due to a false positive, an exposure without patent infection, or a prepatent infection. The child will be followed up on a later date to determine the latter. Other factors that assisted in the decision to stop treatment in 2012 and achievement of elimination status are the absence of lymphatic filariasis and the negligible chance of infected vectors or people migration into the Abu Hamed area due to its unique location and nature.14

The onchocerciasis elimination activities in Abu Hamed had its share of challenges represented by displacement of communities impacted by Merowe dam and the potential for creation of new and perennial vector breeding sites in the spillway downstream of the dam. In this and a previous study, we have screened an 8-km area along the River Nile to verify absence of adult and aquatic stages of black flies. The area upstream of the dam was also screened to identify the westernmost breeding sites beyond the flooding impact of the artificial reservoir. Overall, Merowe Dam appears to have had a positive impact on onchocerciasis and its black fly vectors in Abu Hamed focus.15 This study shows the importance of monitoring the impact of hydropower dams and other environment changes on onchocerciasis elimination activities. It also shows that elimination efforts must face and tackle the unique characteristics of each onchocerciasis transmission zone. The history of the onchocerciasis control and elimination activities in Abu Hamed also highlights the impact of the switch from annual to semiannual mass treatment in completing the interruption of transmission14,17 and ultimate achievement of the disease elimination.

The Abu Hamed success story is an example of sustained commitment and successful collaboration of state governments, international organization, non-governmental organizations, pharmaceutical companies, and the local affected communities to realize the vision of elimination of a major tropical disease in Africa. The PTS assessment data presented here was reviewed in a meeting of the national onchocerciasis elimination program partners in Khartoum, Sudan, in October 2015, at which time the government of Sudan declared elimination of onchocerciasis from Abu Hamed. We presented assessment data for the first PTS and verification of elimination of the disease in Africa based on the 2016 WHO guidelines. Lessons and experience learned from these activities should assist in elimination efforts in the rest of the country and across the continent.

ACKNOWLEDGMENTS

We thank the affected communities for their cooperation and support. We acknowledge the contributions Tong C. M. Deran in the earlier stages of the elimination program. The Lions Clubs SightFirst Program and The Carter Center funded treatment activities from 2004 to 2011 as well as the fieldwork and laboratory analysis associated with monitoring and evaluation activities. The former African Program for Onchocerciasis Control supported the ivermectin treatment program in Abu Hamed from 1998 to 2003. Ivermectin (Mectizan®) was donated by Merck.

  • 1.

    Crump A, Morel CM, Omura S, 2012. The onchocerciasis chronicle: from the beginning to the end? Trends Parasitol 28: 208288.

  • 2.

    World Health Organization, 2011. African Programme for Onchocerciasis Control: meeting of national onchocerciasis task forces. Wkly Epidemiol Rec 86: 541549.

    • Search Google Scholar
    • Export Citation
  • 3.

    Morgan H, 1958. Onchocerciasis in northern Sudan. J Trop Med Hyg 61: 145147.

  • 4.

    Williams JF, Abu Yousif AH, Ballard M, Awad R, el Tayeb M, Rasheed M, 1985a. Onchocerciasis in Sudan: the Abu Hamed focus. Trans R Soc Trop Med Hyg 79: 464468.

    • Search Google Scholar
    • Export Citation
  • 5.

    Higazi TB, Boakye DA, Wilson MD, Mahmoud BM, Baraka OZ, Mukhtar MM, Unnasch TR, 2000. Cytotaxonomic and molecular analysis of Simulium (Edwardsellum) damnosum sensu lato (Diptera: Simuliidae) from Abu Hamed, Sudan. J Med Entomol 37: 547553.

    • Search Google Scholar
    • Export Citation
  • 6.

    Higazi TB, Katholi CR, Mahmoud BM, Baraka OZ, Mukhtar MM, Qubati YA, Unnasch TR, 2001. Onchocerca volvulus: genetic diversity of parasite isolates from Sudan. Exp Parasitol 97: 2434.

    • Search Google Scholar
    • Export Citation
  • 7.

    Zarroug IMA, Elaagib A, Mohamed HA, Elmmubark WA, Osman KH, Deran TCM, Aziz N, Nugud A, 2014. Plants associated with aquatic stages of onchocerciasis vector Simulium damnosum sensu lato in Abu Hamed and Galabat foci in Sudan. Sud J Pub Hlth 9: 3841.

    • Search Google Scholar
    • Export Citation
  • 8.

    Zarroug IMA, Hashim K, Elaagip AH, Samy AM, Frah EA, ElMubarak WA, Mohamed HA, Deran TC, Aziz N, Higazi TB, 2016. Seasonal variation in biting rates of Simulium damnosum sensu lato, vector of Onchocerca volvulus, in two Sudanese foci. PLoS One 11: e0150309.

    • Search Google Scholar
    • Export Citation
  • 9.

    World Health Organization, 2013. Progress towards eliminating onchocerciasis in the WHO Region of the Americas: verification by WHO of elimination of transmission in Columbia. Wkly Epidemiol Rec 88: 381388.

    • Search Google Scholar
    • Export Citation
  • 10.

    World Health Organization, 2014. Progress towards eliminating onchocerciasis in the WHO Region of the Americas: Ecuador's progress towards verification of elimination. Wkly Epidemiol Rec 89: 401408.

    • Search Google Scholar
    • Export Citation
  • 11.

    World Health Organization, 2015. Progress towards eliminating onchocerciasis in the WHO Region of the Americas: verification by WHO of elimination of transmission in Mexico. Wkly Epidemiol Rec 90: 577581.

    • Search Google Scholar
    • Export Citation
  • 12.

    World Health Organization, 2001. Certification of Elimination of Human Onchocerciasis: Criteria and Procedures. Geneva, Switzerland: World Health Organization, 136.

    • Search Google Scholar
    • Export Citation
  • 13.

    Higazi TB, Zarroug I, Mohamed HA, Mohamed WA, Deran TC, Aziz N, Katabarwa M, Hassan HK, Unnasch TR, Mackenzie CD, Richards F, 2011. Polymerase chain reaction pool screening used to compare prevalence of infective black flies in two onchocerciasis foci in northern Sudan. Am J Trop Med Hyg 84: 753756.

    • Search Google Scholar
    • Export Citation
  • 14.

    Higazi TB, Zarroug I, Mohamed HA, Elmubarak WA, Deran T, Aziz N, Katabarwa M, Hassan HK, Unnasch T, Mackenzie C, Richards F, Hashim K, 2013. Interruption of Onchocerca volvulus transmission in the Abu Hamed focus, Sudan. Am J Trop Med Hyg 89: 5157.

    • Search Google Scholar
    • Export Citation
  • 15.

    Zarroug IMA, Elaagib A, Abuelmaali SA, Mohamed HA, Elmubarak WA, Hashim K, Deran TCM, Aziz N, Higazi T, 2014. The impact of Merowe dam on Simulium hamedense vector of onchocerciasis in Abu Hamed focus: northern Sudan. Parasit Vectors 7: 168172.

    • Search Google Scholar
    • Export Citation
  • 16.

    World Health Organization, 2016. Guidelines for Stopping Mass Drug Administration and Verifying Elimination of Human Onchocerciasis: Criteria and Procedures. Geneva, Switzerland: World Health Organization, 136.

    • Search Google Scholar
    • Export Citation
  • 17.

    Katabarwa M, Richards F, 2014. Twice-yearly ivermectin for onchocerciasis: the time is now. Lancet 14: 373374.

Author Notes

* Address correspondence to Tarig B. Higazi, Department of Biological Sciences, Ohio University, 249 Elson Hall, 1425 Newark Road, Zanesville, OH 43701. E-mail: higazi@ohio.edu

Authors' addresses: Isam M. A. Zarroug, Entomology, Ministry of Health, Khartoum, Sudan, E-mail: imazarroug@gmail.com. Kamal Hashim, Ophthalmology, Ministry of Health, Khartoum, Sudan, E-mail: kamalbinnawi@yahoo.com. Wigdan A. ElMubark, Zainab A. I. Shumo, Kawthar A. M. Salih, Nuha A. A. ElNojomi, and Huda A. Awad, Parasitology, Ministry of Health, Khartoum, Sudan, E-mails: wigdanelmubark@yahoo.com, shumo@yahoo.com, kawthar@yahoo.com, elnojomi@yahoo.com, and hudaaawad@hotmail.com. Nabil Aziz, The Carter Center, Khartoum, Sudan, E-mail: nabilazizm@hotmail.com. Moses Katabarwa and Frank Richards, The Carter Center, Emory University, Atlanta, GA, E-mails: mkataba@emory.edu and frank.richards@cartercenter.org. Hassan K. Hassan and Thomas R. Unnasch, Department of Global Health, University of South Florida, Tampa, FL, E-mails: hhassan@health.usf.edu and tunnasch@health.usf.edu. Charles D. Mackenzie, Department of Pathobiology, Michigan State University, East Lansing, MI, E-mail: mackenz8@msu.edu. Tarig B. Higazi, Department of Biological Sciences, Ohio University Zanesville, Zanesville, OH, E-mail: higazi@ohio.edu.

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