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ABSTRACT |
 TOP ABSTRACT INTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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Because onchocerciasis in the Americas is generally transmitted by less efficient vectors than those found in Africa and endemic foci are geographically isolated, it is believed that interruption of transmission to the point of regional eradication of the parasite is possible.2 Elimination of new ocular morbidity attributable to onchocerciasis and, wherever possible, transmission of the disease is the goal of the Onchocerciasis Elimination Program of the Americas (OEPA).3 The OEPA initiative, which was launched in response to a 1991 resolution by the Pan American Health Organization’s (PAHO) XXXV Directing Council, works with national Ministries of Health to provide ivermectin twice annually to 100% of endemic communities, attempting to reaching at least 85% of the eligible population in each community, a coverage rate that has been shown to suppress transmission of onchocerciasis.4
For the Americas overall, Guatemala is home to 39% of the regional population at risk residing in four geographically isolated endemic foci. Endemic communities are associated mainly with coffee plantations located between 500- and 1,500-m elevation along the slopes of several of the many volcanoes in the country.5 The numerous small streams flowing down the volcanic ridge are excellent breeding sites for several species of Simulium, especially S. ochraceum, which has been shown to be the primary vector of O. volvulus in the country.6 One of the foci of transmission (the central endemic focus, Departments of Suchitepéquez, Sololá, and Chimaltenango) is considered hyperendemic (i.e., historical nodule rates > 39%), and the other three foci (the Escuintla-Guatemala, Santa Rosa, and Huehuetenango foci) are considered hypoendemic (i.e., historical nodule rates < 20%). Treatment with ivermectin has been underway in Guatemala since 1996, with semiannual coverage rates > 85% of the eligible population reported from all four endemic foci of the country since 2000.
To verify the elimination of morbidity and transmission, and therefore to help guide decisions on when to halt semi-annual treatment of the eligible population at risk with ivermectin, WHO established a set of measurable epidemiologic and entomologic criteria (Table 1
).7 Based on these guidelines, we undertook three evaluations (entomologic, serologic, and ophthalmologic) in the Department of Santa Rosa to verify absence of morbidity and transmission of onchocerciasis. Our goal was to determine whether a recommendation could be made to the Ministry of Public Health and Social Welfare (MSPAS, in the Spanish acronym) to stop ivermectin treatments in Santa Rosa. This report includes the results of those surveys and a discussion of the challenges we had in applying the current WHO certification criteria guidelines.
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MATERIALS AND METHODS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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), has a population of 305,436 in an area of 3,164 km2.8 Elevation ranges from sea level on the Pacific Coast to 1,945 m at the top of the volcano Tecuamburro. Serial epidemiologic studies on onchocerciasis (primarily based on onchocercal nodule prevalence determined by palpation) were conducted here between 1940 and 1990 by the MSPAS. In the 1940s, 32 communities in the municipios (analogous to counties) of Barberena, Chiquimulilla, Taxisco, Guazacapán, and Pueblo Nuevo Viñas were found to have nodule prevalences > 3% (with only one community having a prevalence > 40%).5 This number had decreased to only six communities by the 1970s, with no communities reporting a prevalence > 5%, leading to its classification as a hypoendemic focus.5 In the 1980s, a MSPAS survey of 2,302 people in Santa Rosa found only 4 (0.2%) with microfilariae in skin biopsies and 13 (0.6%) with nodules; in 1990, 377 individuals were examined and no one with microfilariae or nodules was found (MSPAS, unpublished data). Annual ivermectin mass treatments began in 1996 and were increased in 2000 to semiannual treatment rounds that reached at least 94% of the eligible population in each round to date (Figure 2).9 The number of individuals who were targeted for semiannual ivermectin treatment in the Department of Santa Rosa in 2006 is 9,818.
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). These communities formed the basis for sample selection for the three assessments reported below. Ophthalmologic assessment. The prevalence of microfilariae in the anterior segment (MFAS) of the eye was measured in a sample of residents of Santa Rosa.
Site selection.
To maximize the possibility of finding morbidity related to onchocerciasis, all PECs with nodule prevalence > 0% in any of the last three MSPAS surveys (1983, 1987, and 1990) and elevation > 800 m were identified. There were four communities fitting these criteria that were currently inhabited (Comayagua, Danilandia, El Pacayal, and Joya Grande) and two that had been abandoned (Santa Clara and Santa Ana). These latter were replaced by the next two closest communities (La Palmira and El Manacal, respectively; Figure 1).
Recruitment of participants.
All six communities were censused to determine the number of residents eligible for eye examination (defined as those 
7 years of age who had resided in the community for at least 5 years). All eligible residents were invited to attend the ophthalmologic survey on the appointed day.
Sample size.
The WHO criteria require documentation of a 5-year cumulative incidence rate of onchocercal anterior segment reversible lesions (microfilaria in the anterior chamber [MFAC] and punctate keratitis) to be < 1 new case per 1,000 (Table 1). A recent study performed in Guatemala noted that punctate keratitis had the lowest specificity for onchocerciasis and recommended that, for the purposes of elimination certification, ocular examinations should focus on finding of MFAS of the eye (e.g., in the anterior chamber or cornea).10,11 We had no baseline data or cohort from which to measure a cumulative incidence rate, so we decided to measure the point prevalence of MFAS. The sample size required to calculate a one-sided 95% CI for a prevalence that excludes 0.1% is 3,000; examining this number of individuals was considered prohibitively expensive and time-consuming, and we therefore aimed to show a prevalence of reversible lesions < 1%, requiring a sample size of 300.
Procedures. A trained ophthalmologist (OO) with previous experience conducting assessments of ocular morbidity associated with onchocerciasis11 examined all participants in a darkened area with a slit lamp after they had sat with their head between their knees for at least 5 minutes.12 Based on results from a previous study of the specificity and reliability of indicators of onchocercal eye disease in Guatemala, MFAS were graded as follows: Grade 1, presence of live or coiled microfilaria without inflammation in the cornea of at least one of the two eyes; Grade 2, presence of dead or straightened microfilariae without inflammation in the cornea of at least one of the two eyes and/or MFAC.11 Visual acuity was measured with a Snellen chart.
Data management and analysis.
Data were recorded on forms and entered into a Microsoft Access database. The confidence interval (CI) for the prevalence was calculated as exact one-sided 95% CIs using the FREQ procedure of SAS (Version 9; SAS Institute, Cary, NC) with the EXACT statement, BINOMIAL option and an 
level of 0.10.
Entomologic assessment. We collected black flies from selected sites within Santa Rosa from December 2004 through April 2005 and analyzed them with polymerase chain reaction (PCR) to determine the proportion of infective flies.
Characteristics of transmission of O. volvulus in Guatemala. Transmission of O. volvulus in Guatemala occurs annually between October and July, with the highest vector biting rates occurring towards the beginning of the transmission season and the highest infection rates occurring toward the middle.13 The main vector in Guatemala is S. ochraceum. In areas where S. ochraceum maintains high microfilarial skin densities, S. metallicum may also transmit O. volvulus.13 However, because of the extremely low transmission rates in Santa Rosa, S. metallicum was not considered a vector but was captured and tested as a xenodiagnostic tool.
Site selection.
Seven fincas or communities were purposively selected from among the PECs after initial screening of several sites likely to have high vector densities. Criteria for inclusion in the sample included verification of the presence of S. ochraceum, the willingness of the finca owner or community members to participate, and the presence of appropriate capture sites near the housing area (casco) and the coffee-growing area (cafetal). One of the fincas was large enough to serve as two collection sites, resulting in eight collection localities (Figure 1).
Collection procedures.
We used standard methods to assess the biting rate and collect specimens of S. ochraceum.13 Four teams consisting of collector and paid attractant (male resident of the finca 18 years old) rotated between the eight localities, each containing two collection sites (one near the casco and the other near the cafetal), twice per month, for a total of 32 collection-days per month from December 2004 through April 2005. This period is responsible for ~65% of the number of L3 larvae transmitted annually.14
Black fly collections began at 8:00 AM for 50 minutes each hour and continued until 5:00 PM with a 1-hour break for lunch. Flies were collected by aspiration before they had a chance to bite. Collected flies were stored in 80% ethanol in tubes labeled with the hour, date, site, and community. At the end of each day, female flies were separated according to species using a stereoscope. The numbers of S. ochraceum collected were recorded for each hour along with the number of S. metallicum and other Simulium species. Specimens of S. metallicum were tested as a xenodiagnostic to detect infection. S. ochraceum and S. metallicum were pooled separately in vials containing 100% ethanol such that no pool had > 50 flies, but collection sites and months of collection remained separate.
Laboratory analysis. The heads and bodies of the flies were separated using standard procedures;15 one half of the S. metallicum was sent to a reference laboratory (University of Alabama at Birmingham [UAB]) for comparison and the remainder of the S. metallicum and all of the S. ochraceum were analyzed at the Universidad del Valle de Guatemala (UVG) by PCR to detect O. volvulus DNA.16,17 The algorithm used in testing was to analyze body pools first; if any body pools tested positive, it was confirmed by repeat testing. If a body pool was confirmed positive, body pool testing was suspended, and all of the head pools were analyzed. As part of a process to standardize this procedure, positive controls were obtained from UAB.
Data analysis. The geometric mean number of S. ochraceum caught per hour was calculated as
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where x + 1 is the number of flies caught in a 50-minute collection period plus 1 [to avoid log(0)], n is the number of collection periods, and 0.833 is the conversion factor to convert a 50-minute collection period into 1 hour. This geometric mean hourly landing rate (which approximates the biting rate, as it will be called hereafter) was calculated for S. ochraceum over the capture period (December 2004–April 2005). The total biting density for this period (called the seasonal biting density [SBD]) was calculated as the geometric mean hourly biting rate multiplied by 10 potential hours of biting per day and the number of days in the season. Additionally, the arithmetic average daily biting rate was calculated for comparisons with model estimates of the minimum daily biting rate required to sustain transmission.
The Poolscreen program version 2.0,18 which uses a statistical model to calculate the probability of infection of an individual black fly from the number of positive pools and the size of the pools, was used to calculate the proportion of infective flies with 95% CI computed using the Bayesian method.16,17
The seasonal transmission potential (STP) was calculated as the product of the SBD (December 2004–April 2005; number of bites/person/season), the proportion of flies with infective-stage O. volvulus larvae, and the mean number of infective larvae per infective fly (assumed to be one in an area of low transmission).19 The STP may be equal to, or slightly less than, the annual transmission potential (ATP).
Serologic assessment. We measured the prevalence of IgG4 antibodies to OV-16,20,21 a recombinant antigen of O. volvulus, in schoolchildren 6–12 years of age in the Department of Santa Rosa.
Site selection. All schools (both official public schools and those of the National Program for Self-Managed Education, or PRONADE in the Spanish acronym) located in the PECs were identified, and the number of eligible children was estimated. The estimated number of participants was below the targeted sample size; therefore, we expanded to include all 43 schools located within a 2-km buffer zone around each PEC (buffers created in ArcView GIS 3.2; Environmental Systems Research Institute, Redlands, CA).
Recruitment. Meetings were held with the directors, teachers, and parents of each of the selected schools to explain the purpose of the evaluation. Teachers were requested to prepare complete lists of all enrolled children for the day of the survey.
Sample size. WHO guidelines call for demonstration of a 5-year cumulative incidence rate < 0.1%. We considered the prevalence of antibodies to OV-16 to be equivalent to the cumulative incidence rate. A sample size of at least 3,000 schoolchildren is needed to calculate a prevalence rate with a one-sided 95% CI < 0.1% if zero positives are found.
Procedures. Participants were interviewed to determine their age and the length of time they had been resident in the community or finca. Sterile procedures were used to prick the fingers of all participants, and four to six drops of blood were absorbed onto Whatman No. 2 filter paper. Participants were provided with a bottle of multivitamins for their participation. All sick children were followed to their homes, where we requested their participation in the evaluation.
The filter paper blood samples were dried, separated by sheets of paper, and bundled and stored in plastic bags in a cooler until they were returned to the laboratory at the UVG and stored at 4°C until processed, within 1 month of collection.
Laboratory analysis. Two 6-mm punches of saturated filter paper were placed in a phosphate-buffered saline (PBS)-Tween 0.05% and bovine serum albumin (BSA) 5% buffer and eluted overnight at 4°C. The elution was run in duplicate in a standard enzyme-linked immunosorbent assay (ELISA) to detect IgG4 antibodies against the OV-16 recombinant antigen. We used a standard curve on each plate to identify positive samples and permit comparisons between plates and over days. The cut-off value was determined after analyzing OV-16 negative (~300 individuals from a region of Guatemala free of onchocerciasis) and OV-16 positive samples (from 10 parasitologically confirmed O. volvulus positive individuals). The cut-off was chosen as 40 arbitrary units by identifying the value that optimized both sensitivity and specificity. Any positive results were repeated before being reported as positive.
Data management and analysis. Demographic data and sample identification numbers with check digits were recorded on scannable forms (Cardiff Teleforms, Vista, CA) and scanned into a Microsoft Access (Microsoft Corp., Redmond, WA) database. Exact one-sided 95% CIs were calculated as described earlier.
Human subjects. The protocols for these evaluations received appropriate review at the Centers for Disease Control and Prevention (Atlanta, GA) and the Universidad del Valle de Guatemala (Guatemala City, Guatemala). The evaluation was approved by the Guatemalan MSPAS. Written, informed consent was obtained from all adult participants. Written, informed consent was obtained from the parents or guardians of all children < 18 years of age, who also were read and signed or marked assent forms. The paid attractants in the entomologic evaluation signed informed consent forms and received ivermectin before and after collections and had OV-16 blood tests taken to determine their infection status at the start and end of collections.
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RESULTS |
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7 years of age who had lived at least 5 years in the six selected communities and recruited 363 (89%) to participate in the evaluation; 50% were women, 28% were < 15 years old, and the majority (61%) had lived their entire lifetime in the community. Visual acuity was good, with 96% testing between 20/20 and 20/70, and no case of blindness was encountered. We found no cases of MFAS; the one-sided 95% CI for the prevalence of MFAS was 0–0.8%.
Entomologic evaluation.
We conducted 1,004 hours of capture in eight localities over a 4-month period and captured 2,727 S. ochraceum and 22,180 S. metallicum (Table 2). The number of S. ochraceum captured per month was highest in December and January and relatively constant throughout the remaining collection period. Geometric mean hourly biting rates were highest in December (4.2 bites/person/h) and dropped to < 1 bite/person/h after January. The SBD was estimated as 2,380 bites/person (95% CI, 2,162–2,611). The arithmetic average daily biting rate for S. ochraceum was 33 bites/person/d (95% CI, 29–36).
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Because the proportion of S. ochraceum with O. volvulus larvae was zero, the STP for the Department of Santa Rosa during the transmission season of 2005 was 0 L3 larvae/person. The maximum STP was calculated using the upper boundary of the 95% CI for the infection rate (i.e., 0.086%) and, assuming one infective larva per infective fly, was estimated as 2.0 L3/person/season.
Serologic evaluation. A total of 4,127 children 6–12 years of age were enrolled in the 43 schools located in the 2-km buffer around each PEC, and 3,241 (79%) participated in the study. Inadequate samples were taken from 9 participants, leaving 3,232 participants (78%) for analysis. No child was found seropositive for OV-16. The one-sided 95% exact CI for the percentage positive was 0–0.09%.
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DISCUSSION |
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Semiannual coverage with ivermectin has reached at least 85% of the eligible population at risk in the Department of Santa Rosa since 2000, resulting in 10 complete rounds of treatment before the evaluations we conducted in 2005 and 14 rounds to date (Figure 2). Historic data suggest that transmission of O. volvulus in Santa Rosa was in major or even permanent decline well before semiannual ivermectin mass treatments began.5 The reasons for the decline in transmission before the initiation of treatment are unclear. The collapse of the traditional highland coffee market caused many fincas to reduce their coffee harvests and therefore their work force. This resulted in outmigration from the area, which, coupled with increasing deforestation and pollution that have reduced the number of S. ochraceum breeding sites, probably contributed to a decrease in transmission before onchocerciasis control activities were initiated in 1996. However, we still found the arithmetic mean daily biting rate of S. ochraceum (33 bites/person/d) above the estimated minimum (between 16 and 23 bites/person/d) needed to maintain transmission (although our calculation covered the peak biting season and therefore may be an overestimate).19,22,23 Therefore, the 10 effective rounds of ivermectin treatment before this evaluation were likely important in ensuring elimination of transmission.
To our knowledge, this is the first attempt to operationalize the 2001 WHO criteria for certification of elimination of onchocerciasis transmission, and in doing so, we identified difficulties not foreseen in the drafting of these guidelines. The remainder of this discussion will be directed at several aspects that need to be addressed in future revisions of the criteria.
First, the criteria call for measuring a 5-year cumulative incidence of reversible eye lesions of < 0.1%. Because microfilariae persist in the eye for ~18–24 months, in areas of low to nonexistent transmission of O. volvulus, this condition could not persist for 5 years, particularly if ivermectin treatment is being administered.24 Because cumulative incidence cannot be calculated from a point measure because of the short duration of this condition, to achieve the criterion as written, multiple examinations over a period of 5 years of at least 3,000 individuals originally free of disease would be needed; this is beyond the means of OEPA and national programs. Results of epidemiologic surveys in the hyperendemic focus of Guatemala in the late 1970s found the prevalence of MFAC between 3.7% in the finca with the lowest level of transmission and > 30% in the hyperendemic fincas.25 Because MFAS includes both MFAC and microfilariae in the cornea, the prevalence of MFAS was higher (but cannot be determined from the historic data). We therefore used a point prevalence of < 1% MFAS to indicate absence of morbidity caused by O. volvulus.
Second, the criterion related to the entomologic evidence specifies the required sample size (minimum 10,000 flies) but does not clearly specify the threshold prevalence of infection (absence or near absence of infection; Table 1). The criteria used by the former Onchocerciasis Control Program of West Africa (OCP) was a prevalence of infective flies < 0.1% in parous flies or < 0.05% in all flies (assuming a parity rate of 50%). The sample size needed to exclude a prevalence of infective flies of 0.05% in all flies at a 95% confidence level, given that no infective fly is found, is 6,000.
We were unable to meet either the minimum sample size of 10,000 flies specified in the WHO criteria or the sample size of 6,000 flies needed to meet the former OCP criterion. Despite conducting > 125 collection-days over a 5-month period, we collected only 2,727 S. ochraceum, a seasonal biting density of 2,380 bites/person. Therefore, despite finding no flies positive for parasite DNA, the one-sided 95% CI around the estimate of the prevalence of infective flies (0–0.086%) does not exclude either 0.01% (WHO criterion) or 0.05% (former OCP criterion). An OEPA-convened meeting of entomologists in September 2006 recommended the use of ATP or STP to assess the status of onchocerciasis transmission, because both of these measurements take into account the biting rate (which was particularly low in Santa Rosa) and the prevalence of infective flies. If ATP or STP are to become the new criteria for assessing whether transmission has been interrupted, it is particularly important that they represent the exposure of the population being assessed through an adequate and representative sampling plan.
The ATP or STP below which the effective reproduction ratio of the parasite is < 1, i.e., the threshold transmission potential that indicates the system is moving towards eradication, has yet to be identified and is likely to vary according to characteristics of the vector species. Eventually, the data collected in Santa Rosa and other foci in Guatemala may help to inform the work being conducted to find the threshold transmission potential for S. ochraceum. However, the maximum value calculated in Santa Rosa (2.0 L3 larvae/person/season) is actually lower than all of the ATP estimates that have been postulated to correspond to cessation of transmission: estimates of this threshold transmission potential have ranged from 5 to 54 L3 larvae/person/yr using mathematical models22,23 and from 7.6 to 18 using field observations.7,19 The transmission potential in Santa Rosa is considerably lower than these estimates, and therefore, is probably well below the threshold transmission potential in this area.
Third, the criterion that relates to absence of detectable infection in untreated children reaching the age of 5 years will be difficult to operationalize in Guatemala and in many other endemic countries in the Americas. Children younger than school age are hard to locate, and parents are understandably reluctant to let very young children submit to blood letting, even if a finger stick. This is not the case with school children, whose population is also larger that that of children younger than 5 years, resulting in it being more likely to recruit the 3,000 children necessary to show a prevalence < 0.1%. Additionally, epidemiologic data suggest that the school-aged group may be the best indicator of transmission. Model data show that acquisition of infection rises fastest between 5 and 20 years of age.26 In Guatemala, villages with relatively lower infection rates had few children < 5 years old with microfilariae in skin snips.25 Adults would not be a good indicator age group for serology studies because of the possibility of persistent antibodies caused by exposure to pre-control parasite transmission levels. Therefore, beause younger children are difficult to access and unlikely to be infected in low transmission settings, adults are likely to have antibody from previously active infection, and because the rate of seroconversion is likely to rise most rapidly from 5 to 20 years of age, we believe school children provide the best information on recent transmission events in Guatemala.
Fourth, we did not attempt to satisfy the last criterion related to new, untreated residents because it would have been extremely difficult, if not impossible, to easily identify and single out new residents in Santa Rosa. This may, however, be possible in other areas.
Last, the measurement of an incidence rate of new infection of < 0.1% is problematic diagnostically in onchocerciasis for the following reasons: onchocercal nodules do not always develop in infected individuals, or may not be palpable, and do not appear for 1–3 years after infection; microfilariae in skin snips appear more quickly, but this test is relatively invasive and taking skin snips from 3,000 children would be considerably problematic; and onchocerciasis has no rapid diagnostic test or antigen test to detect viable parasites. The most practical approach is the IgG4 antibody based serologic test that we used.27 However, we do not know for how long IgG4 antibodies to this recombinant antigen persist in the body; there is some indication from a similar test developed for lymphatic filariasis that 50% of antibody-positive individuals become negative within 4 years.28 We are undertaking more analysis and testing to understand better the duration of antibody response in this important assay.
In conclusion, after adapting and operationalizing the WHO criteria presented in Certification of Elimination of Human Onchocerciasis: Criteria and Procedures,7 we found no evidence of recent transmission of O. volvulus in the Santa Rosa focus of Guatemala. In 2007, the Minister of Public Health and Social Welfare of Guatemala will suspend ivermectin treatment in Santa Rosa, which will result in the first of the 13 foci of onchocerciasis in the Americas to have treatment suspended. This represents a significant success for the OEPA initiative. The next challenge will be to establish an appropriate monitoring approach in Santa Rosa to identify any potential recrudescence of disease.
Received January 22, 2007. Accepted for publication March 19, 2007.
Acknowledgments: This work would not have been possible without the guidance and assistance of Dr. Robert Klein, retired director of the CDC Regional Office for Central America and Panama. We are grateful to Estuardo Barrios for assistance with mapping, Mayari Hengstermann for support on the ophthalmological survey, Carlos Mendoza for support on the serological survey, and Adria Prosser for her initial attempts in organizing the serology survey. We are grateful to Mynor Lopez, Jorge Sincal, Jose Humberto Miguel, and Rodrigo Gramajo for assisting with the field and laboratory work. We thank the Director of the Santa Rosa Health Area and her team, and in particular Gérman Rosales, for their support and assistance with this project. We are grateful for the willing participation of the residents of Santa Rosa. Without the administrative support of the Centro de Estudios en Salud of the Universidad del Valle de Guatemala this project would not have been possible. This work was presented in part at the 15th Annual Interamerican Conference on Onchocerciasis (IACO), Caracas, Venezuela, November 13–18, 2005, at the 54th Annual Meeting of the American Society of Tropical Medicine and Hygiene, Washington, DC, December 11–15, 2005 (abstract 533), and to the Mectizan Expert Committee, London, January 2006. The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the Centers for Disease Control and Prevention.
Financial support: These studies were funded by the Centers for Disease Control and Prevention (Atlanta, GA) and the Onchocerciasis Elimination Program of the Americas (Guatemala City, Guatemala). The OEPA funds were provided through a grant by the Bill and Melinda Gates Foundation (Seattle, WA) to The Carter Center (Atlanta, GA).
* Address correspondence to Kim A. Lindblade, Regional Office for Central America and Panama, Centers for Disease Control and Prevention, Universidad del Valle de Guatemala, 18 Avenida 11-95, Zona 15 VH III, Apartado Postal No. 82, Guatemala City, Guatemala. E-mail: kil2{at}cdc.gov 
Authors’ addresses: Kim A. Lindblade, Regional Office for Central America and Panama, Centers for Disease Control and Prevention, Universidad del Valle de Guatemala, 18 Avenida 11-95, Zona 15 VH III, Apartado Postal No. 82, Guatemala City, Guatemala, Telephone: 502-2364-0336, extension 513, Fax: 502-2369-7539, E-mail: kil2{at}cdc.gov. Byron Arana, Nidia Rizzo, Nancy Cruz-Ortiz, and Jane Richards, Centro de Estudios en Salud, Universidad del Valle de Guatemala, 18 Avenida 11-95, Zona 15 VH III, Apartado Postal No. 82, Guatemala City, Guatemala, Telephone: 502-2364-0336, extension 513, Fax: 502-2369-7539, E-mails: baaz{at}cdc.gov, nrrz{at}cdc.gov, ncoz{at}cdc.gov, and jane.e.richards{at}uth.tmc.edu. Guillermo Zea-Flores, Alfredo Dominguez, Mauricio Sauerbrey, and Orlando Oliva, Onchocerciasis Elimination Program of the Americas, 14 Calle 3-51, Oficina 14-01 Zona 10, Guatemala City 01010 Guatemala, Telephone: 502-2366-6109, Fax: 502-2366-6127, E-mails: gzea{at}oepa.net, adominguez{at}oepa.net, oepa{at}oepa.net, and centrovisual{at}intelnett.com. Charles H. Porter, Division of Parasitic Diseases, National Center for Zoonotic, Vector-Borne and Enteric Diseases, Centers for Disease Control and Prevention, 4770 Buford Highway, MS F-22, Atlanta, GA 30341-3724, Telephone: 770-488-4838, Fax: 770-488-7761, E-mail: chp1{at}cdc.gov. Thomas R. Unnasch, Gorgas Center of Geographic Medicine, Division of Infectious Diseases, BBRB 538, 1530 3rd Ave. South, Birmingham, AL 35294-2170, Telephone: 205-975-7601, Fax: 205-934-5600, E-mail: tunnasch{at}uab.edu. George A. Punkosdy, National Institute of Allergies and Infectious Diseases, National Institutes of Health, Building 10 - Magnuson, CC Room 11N315, 10 Center Dr., Bethesda, MD, Telephone: 301-496-5046, E-mail: punkosdyg{at}mail.nih.gov. Julio Castro and Eduard Catú, Programa de Enfermedades Transmitidas por Vectores, Ministerio de Salud y Asistencia Publica, 5a Avenida 11-40, Zona 11, Guatemala, Guatemala, Telephone/Fax: 502-2472-0128, E-mail: pvectores{at}intelnett.com. Frank O. Richards, Jr., The Carter Center, One Copenhill, 453 Freedom Parkway, Atlanta, GA 30307, Telephone: 404-420-5100, E-mail: fxr1{at}cdc.gov.
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