Thomson Lakwo

Transmission of Onchocerciasis in Wadelai Focus of Northwestern Uganda Has Been Interrupted and the Disease Eliminated

Wadelai, an isolated focus for onchocerciasis in northwest Uganda, was selected for piloting an onchocerciasis elimination strategy that was ultimately the precursor for countrywide onchocerciasis elimination policy. The Wadelai focus strategy was to increase ivermectin treatments from annual to semiannual frequency and expand geographic area in order to include communities with nodule rate of less than 20%. These communities had not been covered by the previous policy that sought to control onchocerciasis only as a public health problem. From 2006 to 2010, Wadelai program successfully attained ultimate treatment goal (UTG), treatment coverage of ≥90%, despite expanding from 19 to 34 communities and from 5,600 annual treatments to over 29,000 semiannual treatments. Evaluations in 2009 showed no microfilaria in skin snips of over 500 persons examined, and only 1 of 3011 children was IgG4 antibody positive to the OV16 recombinant antigen. No Simulium vectors were found, and their disappearance could have sped up interruption of transmission. Although twice-per-year treatment had an unclear role in interruption of transmission, the experience demonstrated that twice-per-year treatment is feasible in the Ugandan setting. The monitoring data support the conclusion that onchocerciasis has been eliminated from the Wadelai focus of Uganda.

Serosurveillance to Monitor Onchocerciasis Elimination: The Ugandan Experience

Uganda is the only African country whose onchocerciasis elimination program uses a two-pronged approach of vector control and mass drug distribution. The Ugandan program relies heavily upon the use of serosurveys of children to monitor progress toward elimination. The program has tested over 39,000 individuals from 11 foci for Onchocerca volvulus exposure, using the Ov16 ELISA test. The data show that the Ov16 ELISA is a useful operational tool to monitor onchocerciasis transmission interruption in Africa at the World Health Organization (WHO) recommended threshold of < 0.1% in children. The Ugandan experience has also resulted in a re-examination of the statistical methods used to estimate the boundary of the upper 95% confidence interval for the WHO prevalence threshold when all samples tested are negative. This has resulted in the development of Bayesian and hypergeometric statistical methods that reduce the number of individuals who must be tested to meet the WHO criterion.

The Imaramagambo Onchocerciasis Focus in Southwestern Uganda: Interruption of Transmission After Disappearance of the Vector Simulium neavei and Its Associated Freshwater Crabs

It was not until early 1990s that, when the Imaramagambo focus of southwest Uganda was mapped, mass treatment with a single annual dose of ivermectin for onchocerciaisis control commenced. However, comprehensive investigations on its transmission were launched after a nationwide policy for onchocerciasis elimination in 2007. Entomological surveys throughout the focus from 2007 to 2015 have yielded few or no freshwater crabs (Potamonautes aloysiisabaudiae), which serve as the obligate phoretic host of the larvae and pupae of the vector Simulium neavei. No S. neavei flies have been observed or collected since 2007. Skin snips (microscopy) from 294 individuals in 2008 were negative for skin microfilariae, and of the 462 persons analyzed by polymerase chain reaction skin snip poolscreen in 2009, only five (1.08%) persons were indicated as infected with onchocerciasis. All five of the positive persons were at least 40 years old. Serosurvey results showed negative exposure among 3,332 children in 2012 and 3,108 children in 2015. Both were within the upper bound of the 95% confidence interval of the prevalence estimate of 0.06%, which confirmed the elimination of onchocerciasis. Treatment coverage in Imaramagambo was generally poor, and transmission interruption of onchocerciasis could not be attributed solely to annual mass treatment with ivermectin. There was sufficient evidence to believe that the possible disappearance of the S. neavei flies, presumed to have been the main vector, may have hastened the demise of onchocerciasis in this focus.

After 70 years of fighting an age-old scourge, onchocerciasis in Uganda, the end is in sight.

Onchocerciasis causes severe itching, serious skin disease and ocular damage leading to visual impairment or permanent blindness. It is associated with hanging groin, epilepsy, Nakalanga dwarfism and, most recently, nodding disease. This disease affected communities in 17 transmission foci in 37 districts of Uganda, where about 6.7 million people are once at risk. The efforts against onchocerciasis in Uganda commenced in the late 1940s, when vector control was launched using dichlorodiphenyltrichloroethane; by 1973, Simulium damnosum had been eliminated in the Victoria focus. Success outside of the Victoria focus was short-lived due to changes in government priorities and the political upheavals of the 1970s and 1980s. With the return of political stability, annual treatment with ivermectin through mass drug administration was launched in the early 1990s. Control of the disease has been successful, but there has been failure in interrupting transmission after more than 15 years. In 2007 Uganda launched a nationwide transmission elimination policy based on twice-per-year treatment and vector control/elimination, with a goal of eliminating river blindness nationwide by 2020. By 2017, 1 157 303 people from six foci had been freed from river blindness. This is the largest population ever declared free under World Health Organization elimination guidelines, providing evidence that elimination of river blindness in Africa is possible.

Substantiating freedom from parasitic infection by combining transmission model predictions with disease surveys

Stopping interventions is a critical decision for parasite elimination programmes. Quantifying the probability that elimination has occurred due to interventions can be facilitated by combining infection status information from parasitological surveys with extinction thresholds predicted by parasite transmission models. Here we demonstrate how the integrated use of these two pieces of information derived from infection monitoring data can be used to develop an analytic framework for guiding the making of defensible decisions to stop interventions. We present a computational tool to perform these probability calculations and demonstrate its practical utility for supporting intervention cessation decisions by applying the framework to infection data from programmes aiming to eliminate onchocerciasis and lymphatic filariasis in Uganda and Nigeria, respectively. We highlight a possible method for validating the results in the field, and discuss further refinements and extensions required to deploy this predictive tool for guiding decision making by programme managers.The decision when to stop an intervention is a critical component of parasite elimination programmes, but reliance on surveillance data alone can be inaccurate. Here, Michael et al. combine parasite transmission model predictions with disease survey data to more reliably determine when interventions can be stopped.

“Cross-border collaboration in onchocerciasis elimination in Uganda: progress, challenges and opportunities from 2008 to 2013”

BackgroundUntil recently onchocerciasis was prevalent in 37 out of 112 districts of Uganda with at least 3.8 million people at risk of contracting the disease, but following the launching of community-directed treatment with ivermectin (CDTI) in 1996 and the adoption of an onchocerciasis elimination policy in 2007, the country has made significant progress in combating the disease. By 2015, interruption of transmission had been achieved in ten of the 17 onchocerciasis foci, but cross-border foci remained particularly problematic, and therefore within the onchocerciasis elimination framework, Uganda embarked upon addressing these issues with its neighbouring countries, namely the Democratic Republic of Congo (DRC) and South Sudan. This paper summarises the experience of Uganda in addressing cross-border issues on onchocerciasis elimination with DRC.Main achievements and lessons learnedThe key achievements comprise of the adoption of an elimination policy by the Government of Uganda, cross-border meetings, training DRC technical staff and entomological/ epidemiological surveys. The first strategy meeting was held in Kampala in 2008, but the second strategy meeting was not held in Kinshasa until 2013. The involvement of the high-level officials from the Ministry of Health of DRC was critical for the success of the second strategy meeting, and was precipitated by collaboration to control an outbreak of Ebola Virus. Both meetings demonstrated the political commitment of endemic countries and allowed the implementation of a joint action plan. Important steps in establishing a mutually respected elimination targets was agreed on during cross border meetings.The African Programme for Onchocerciasis Control facilitated and funded these initial meetings, thus overcoming some political and financial challenges faced by both countries. This highlighted the need for multilateral organisations such as the Expanded Special Project for the Elimination of Neglected Tropical Diseases in cross-border activities for other Neglected Tropical Diseases.The collaboration between both countries facilitated the training of technical staff from DRC in entomology which facilitated joint cross-border activities to update the epidemiological understanding of onchocerciasis in Beni and Mahagi districts in North Kivu and Ituri Provinces respectively. In Nebbi district, Uganda, 23.7% of crabs were infested by the vector Simulium neavei compared with 6.3% in Mahagi district, DRC. Rapid Epidemiological Assessment (REA) revealed nodule prevalence of 3.2% and onchodermatitis at 26.4% from five villages in DRC.ConclusionPolitical commitment of both countries and the support from APOC allowed two cross-border meetings which were critical for the implementation of initial cross border activities for onchocerciasis elimination.

Molecular Identification of Onchocerca spp. Larvae in Simulium damnosum sensu lato Collected in Northern Uganda

Previous studies have demonstrated that the presence of larvae of other filarial species in Simulium damnosum sensu lato can distort estimates of transmission potential for Onchocerca volvulus in West Africa. However, studies conducted in foci of onchocerciasis in West Central Uganda indicated that larvae other thanO. volvuluswere not common in vectors collected there. Recent data collected in Northern Uganda revealed a striking discordance between estimates of the prevalence of flies carrying O. volvulus infective larvae obtained from molecular pool screening and dissection methods. To resolve this discrepancy, sequences from three mitochondrially encoded genes were analyzed from the larvae collected by dissection. All larvae analyzed were Onchocerca ochengi v. Siisa, a parasite of cattle, or Onchocerca ramachandrini, a parasite of warthogs. These results suggest that nonhuman parasite larvae are common in vectors in Northern Uganda, underscoring the necessity for molecular identification methods to accurately estimate O. volvulus transmission. In 2007, Uganda announced a program to eliminate onchocerciasis in all 17 foci in the country, becoming the first country in Africa to make complete elimination of onchocerciasis a national goal. The strategic plan of the Uganda Onchocerciasis Elimination Program was based on twice per year mass drug administration of Mectizan (ivermectin) to the afflicted communities supplemented with localized vector control measures where appropriate. In 2008, the Uganda Ministry of Health established an advisory committee, known as the Uganda Onchocerciasis Elimination Expert Advisory Committee (UOEEAC) to provide technical guidance to the elimination program. One of the first actions of the UOEEAC was to consult with the Ugandan Ministry of Health to develop a set of guidelines for the program to use for verifying the suppression and eventual elimination of transmission of Onchocerca volvulus. These guidelines were based on the guidelines for the elimination of onchocerciasis published by theWorld Health Organization in 2001 and updated in 2016. The guidelines rely on a combination of serological indicators of transmission (development of antibodies against the parasite specific antigen Ov16 in children) and entomological indicators (presence of infective stage larvae in the black fly vectors of the parasite) to confirm suppression of transmission. Detection of infective larvae in the vector black flies has advantageswhen used tomonitor transmission ofO. volvulus. Most importantly, it provides the most timely and accurate measure of transmission. Traditionally, detection of infective larvae in vectors has been accomplished through dissection of vector black flies. However, there are some disadvantages associated with the method. First, in the face of an effective control or elimination program, flies carrying infective larvae become increasingly rare. This means that large numbers of flies need to be examined to detect the rare infectious fly, which is laborious and expensive. Second, in West Africa, it has long been known that Simulium damnosum s.l., the most important vector throughout Africa also serves as the vector for a number of Onchocerca species associated with domestic or wild ungulate hosts (e.g., bovids, suids). These larvae are difficult or impossible to distinguish from O. volvulus morphologically, confounding accurate measurement of the prevalence of flies carrying infective larvae of the human parasite. Molecular methods involving polymerase chain reaction (PCR) amplification of O. volvulus specific DNA sequences in DNA prepared from pools of flies or from individual larvae have been developed to overcome these difficulties. When molecular identifications were performed on infective larvae identified by dissection inWest Africa, it was found that about half of the larvae provisionally identified as O. volvulus by field dissection teams were ungulate-associated Onchocerca. By contrast, one report applying molecular identificationmethods to larvae collected from Kabarole and Kasese districts in West Central Uganda suggested that all were O. volvulus, suggesting that ungulate-associatedOnchocerca might pose less of a problem in East Africa. Onchocerciasis elimination efforts inNorthernUgandawere hindered by political unrest in the area for several years. However, after the restoration of peace to this area, elimination efforts accelerated in 2012. These efforts included both serosurveys of children to measure exposure to the parasite, aswell as entomological surveys, inwhich a portion of the flies collected were screened in pools using molecular methods, whereas a portion were screened using traditional dissection. In 2015, significantly larger numbers of flies carrying infective larvae were detected by the field dissection teams than were found by PCR pool screening. To further investigate the reason for this discrepancy, the larvae collected by the dissection teams were subjected to a detailed molecular analysis. Simulium damnosum females were collected using standard methods from several sites in the Madi-Mid North onchocerciasis focus of Northern Uganda (Figure 1). Flies were collected from the districts of Nwoya, Amuru (Elegu), and Moyo, as part of routine surveillance activities conducted by *Address correspondence to Thomas R. Unnasch, Global Health Infectious Disease Research, 3720 Spectrum Boulevard Suite 304, Tampa, FL 33612. E-mail: tunnasch@health.usf.edu

Characterizing Reactivity to Onchocerca volvulus Antigens in Multiplex Bead Assays

Multiplex bead assays (MBAs) may provide a powerful integrated tool for monitoring, evaluation, and post-elimination surveillance of onchocerciasis and co-endemic diseases; however, the specificity and sensitivity of Onchocerca volvulus antigens have not been characterized within this context. An MBA was developed to evaluate three antigens (OV-16, OV-17, and OV-33) for onchocerciasis. Receiver operating characteristics (ROC) analyses were used to characterize antigen performance using a panel of 610 specimens: 109 O. volvulus-positive specimens, 426 non-onchocerciasis controls with filarial and other confirmed parasitic infection, and 75 sera from patients with no other parasitic infection. The IgG and IgG4 assays for OV-16 demonstrated sensitivities of 95.4% and 96.3%, and specificities of 99.4% and 99.8%, respectively. The OV-17 IgG and IgG4 assays had sensitivities of 86.2% and 76.1% and specificities of 79.2% and 82.8%. For OV-33, the IgG and IgG4 assays had sensitivities of 90.8% and 96.3%, and specificities of 96.8% and 98.6%. The OV-16 IgG4-based MBA had the best assay characteristics, followed by OV-33 IgG4. The OV-16 IgG4 assay would be useful for monitoring and evaluation using the MBA platform. Further evaluations are needed to review the potential use of OV-33 as a confirmatory test in the context of program evaluations.

Ecogeographically and Non-Ecogeographically Forecasting Discontinuous Canopied Simulium damnosum s.l. Habitats by Interpolating Metrizable Sub-Mixel Mean Solar Exoatmospheric Quantum Scalar Irradiance

We interpolated a geospectrally decomposed 5 meter (m) RapidEye™,Red Edge, Normalized Difference Vegetation Index (NDVI), unmixed, endmember, biosignature of a georeferenced, larval habitat of Similium damnosum s.l.,a black fly vector of onchocerciasis. We did so to identify unknown, unsampled, prolific, habitats in African riverine environments. The S. damnosum s.l.larval habitat was initially geosampled in a riverine village in Burkina Faso and overlaid onto the 5m resolution data. The Band Mathfunction of ENVI 4.8TM was employed to calculate the RedEdge NDVI. Before applying the spectral index to the imagery raw mixel (“mixed pixel”) values, digital numbers(DN)] were converted into physically meaningful units to differentiate absorption reflectance spectra and immature Similium productivity based on habitat size.Linear regression was used to equate and quantitate band data to DN and the reflectance values which in the geospectral,sub-mixel, risk analysis was equivalent to removing the solar irradiance and the atmospheric path radiance in the object-based classifier. A radiometric calibration tool then calibrated the spaceborne sensor data to radiance and top-of-atmosphere (ToA) reflectance.Additionally,Fast Line-of-sight Atmospheric Analysis of Spectral Hypercubes (FLAASH®)removed the effects of multiscattering in the scene.We calculated the internal relative reflectance which normalized the image to a scene average spectrum. ENVI’s Log Residuals Correction Tool removed the instrument gain, topographic effects, and albedo effects from the reflectance, transmittance, wavelength emissitivities. The instantaneous fraction of direct beam radiation intercepted by the habitat canopy was calculated and described as fPAR = 1 - exp (-k (leaf area index)/cosθs) where the extinction coefficient k was a function of leaf angle distribution.We employed a successive progressive algorithm, a two stream radiative atmospheric transfer analyses, a geometric-optical model and a bidirectional reflectance distribution function to unmix the S. damnosum s.l., larval habitat,canopied endmembers.The non-parametric, residual, explanatorial, decomposed, sub-mixel estimators derived from the RapidEye™data were then used to construct a Boolean model.Therefater,the imaged larval habitat and its geospatially, ecohydrological, within-canopy pigments (e.g., chorophyll, zeathinins) were defined and a Red Edge,NDVI, endmember biosignature was decomposed in ENVI. An autocorrelation uncertainty matrix was deconvolved into combinations of the unmixed canopied endmembers.Subsequently, the NDVI, endmember biosignature, decomposed, canopied endmembers with its multiple ToA noise-adjusted coefficients were kriged in Geospatial Analyst of ArcGIS 10.3®to identify unknown, unsampled, prolific, S. damnosum s.l., georeferencable, larval habitats along a northern Ugandan riverine ecosystem. Of the forecasted prolific, shaded, larval habitats by the canopy model, 72% were found to contain S. damnosum s.l. larvae when field verified. The sensitivity of the test was 78.26 while the specifity was 100.