Nidia Rizzo

Successful Interruption of Transmission of Onchocerca volvulus in the Escuintla-Guatemala Focus, Guatemala

Background Elimination of onchocerciasis (river blindness) through mass administration of ivermectin in the six countries in Latin America where it is endemic is considered feasible due to the relatively small size and geographic isolation of endemic foci. We evaluated whether transmission of onchocerciasis has been interrupted in the endemic focus of Escuintla-Guatemala in Guatemala, based on World Health Organization criteria for the certification of elimination of onchocerciasis. Methodology/Principal Findings We conducted evaluations of ocular morbidity and past exposure to Onchocerca volvulus in the human population, while potential vectors (Simulium ochraceum) were captured and tested for O. volvulus DNA; all of the evaluations were carried out in potentially endemic communities (PEC; those with a history of actual or suspected transmission or those currently under semiannual mass treatment with ivermectin) within the focus. The prevalence of microfilariae in the anterior segment of the eye in 329 individuals (≥7 years old, resident in the PEC for at least 5 years) was 0% (one-sided 95% confidence interval [CI] 0–0.9%). The prevalence of antibodies to a recombinant O. volvulus antigen (Ov-16) in 6,432 school children (aged 6 to 12 years old) was 0% (one-sided 95% IC 0–0.05%). Out of a total of 14,099 S. ochraceum tested for O. volvulus DNA, none was positive (95% CI 0–0.01%). The seasonal transmission potential was, therefore, 0 infective stage larvae per person per season. Conclusions/Significance Based on these evaluations, transmission of onchocerciasis in the Escuintla-Guatemala focus has been successfully interrupted. Although this is the second onchocerciasis focus in Latin America to have demonstrated interruption of transmission, it is the first focus with a well-documented history of intense transmission to have eliminated O. volvulus.

Dengue vector management using insecticide treated materials and targeted interventions on productive breeding-sites in Guatemala.

BackgroundIn view of the epidemiological expansion of dengue worldwide and the availability of new tools and strategies particularly for controlling the primary dengue vector Aedes aegypti, an intervention study was set up to test the efficacy, cost and feasibility of a combined approach of insecticide treated materials (ITMs) alone and in combination with appropriate targeted interventions of the most productive vector breeding-sites.MethodsThe study was conducted as a cluster randomized community trial using “reduction of the vector population” as the main outcome variable. The trial had two arms: 10 intervention clusters (neighborhoods) and 10 control clusters in the town of Poptun Guatemala. Activities included entomological assessments (characteristics of breeding-sites, pupal productivity, Stegomyia indices) at baseline, 6 weeks after the first intervention (coverage of window and exterior doorways made of PermaNet 2.0 netting, factory treated with deltamethrin at 55 mg/m2, and of 200 L drums with similar treated material) and 6 weeks after the second intervention (combination of treated materials and other suitable interventions targeting productive breeding-sites i.e larviciding with Temephos, elimination etc.). The second intervention took place 17 months after the first intervention. The insecticide residual activity and the insecticidal content were also studied at different intervals. Additionally, information about demographic characteristics, cost of the intervention, coverage of houses protected and satisfaction in the population with the interventions was collected.ResultsAt baseline (during the dry season) a variety of productive container types for Aedes pupae were identified: various container types holding >20 L, 200 L drums, washbasins and buckets (producing 83.7% of all pupae). After covering 100% of windows and exterior doorways and a small number of drums (where the commercial cover could be fixed) in 970 study households, tropical rains occurred in the area and lead to an increase of the vector population, more pronounced (but statistically not significant) in the control arm than in the intervention arm. In the second intervention (17 months later and six weeks after implementing the second intervention) the combined approach of ITMs and a combination of appropriate interventions against productive containers (Temephos in >200 L water drums, elimination of small discarded tins and bottles) lead to significant differences on reductions of the total number of pupae (P = 0.04) and the House index (P = 0.01) between intervention and control clusters, and to borderline differences on reductions of the Pupae per Person and Breteau indices (P = 0.05). The insecticide residual activity on treated curtains was high until month 18 but the chemical concentration showed a high variability. The cost per house protected with treated curtains and drum covers and targeting productive breeding-sites of the dengue vector was

Chemotherapy of cutaneous leishmaniasis: a review

5.31 USD. The acceptance of the measure was generally high, particularly in families who had experienced dengue.ConclusionEven under difficult environmental conditions (open houses, tropical rainfall, challenging container types mainly in the peridomestic environment) the combination of insecticide treated curtains and to a less extent drum covers and interventions targeting the productive container types can reduce the dengue vector population significantly.

One Hundred Years After Its Discovery in Guatemala by Rodolfo Robles, Onchocerca volvulus Transmission Has Been Eliminated from the Central Endemic Zone

Abstract. A wide variety of treatment modalities have been employed for cutaneous leishmaniasis (CL); however, none has been demonstrated to be good enough to be used as the first-line drug to treat patients in all the CL epidemiological scenarios. Although pentavalent antimonials remain a drug widely used in the treatment of all forms of leishmaniasis, they are far from being satisfactory. A great variety of topical treatments have been used to treat CL. However, the majority of these modalities have been tested in non-controlled studies, with only few subjects and the interpretation of results is usually difficult due to the lack of a standard and well-accepted cure definition. Several oral drugs, such as ketoconazole and itraconazole, have also been tested for CL, but results obtained were not completely satisfactory. As of today, miltefosine, originally developed as an oral antineoplastic agent, seems, from the preliminary results obtained in different phase II clinical studies, to be the most promising oral drug developed during the last decade.

The domestic dog, a potential reservoir for Leishmania in the Peten region of Guatemala

We report the elimination of Onchocerca volvulus transmission from the Central Endemic Zone (CEZ) of onchocerciasis in Guatemala, the largest focus of this disease in the Americas and the first to be discovered in this hemisphere by Rodolfo Robles Valverde in 1915. Mass drug administration (MDA) with ivermectin was launched in 1988, with semiannual MDA coverage reaching at least 85% of the eligible population in > 95% of treatment rounds during the 12-year period, 2000-2011. Serial parasitological testing to monitor MDA impact in sentinel villages showed a decrease in microfilaria skin prevalence from 70% to 0%, and polymerase chain reaction (PCR)-based entomological assessments of the principal vector Simulium ochraceum s.l. showed transmission interruption by 2007. These assessments, together with a 2010 serological survey in children 9-69 months of age that showed Ov16 IgG4 antibody prevalence to be < 0.1%, meeting World Health Organization (WHO) guidelines for stopping MDA, and treatment was halted after 2011. After 3 years an entomological assessment showed no evidence of vector infection or recrudescence of transmission. In 2015, 100 years after the discovery of its presence, the Ministry of Health of Guatemala declared onchocerciasis transmission as having been eliminated from the CEZ.

Elimination of Onchocerca volvulus Transmission in the Huehuetenango Focus of Guatemala

In the present study, domestic dogs in a Leishmania endemic area in the Peten Region of Guatemala were sampled to determine if they are a potential reservoir for Leishmania parasites. Blood from 100 dogs from six villages was tested with two different antibody-capture assays for Leishmania-specific antibodies and a 28% seroprevalence was determined. Tissue scrapings from six dogs presenting with chronic lesions characteristic of Leishmania infection were sampled and four dogs were positive by a genus-specific fluorogenic PCR assay. Histopathology by giemsa stain confirmed the presence of amastigotes in one of these dogs. These findings support the hypothesis that dogs may play an important role in the transmission of Leishmania in a region where no mammal has ever been implicated as a reservoir.

A Knowledge, Attitudes and Practices Survey Conducted Three Years after Halting Ivermectin Mass Treatment for Onchocerciasis in Guatemala

In Latin America, onchocerciasis is targeted for elimination by 2012 through twice-yearly mass treatment of the eligible population with ivermectin. In Guatemala, two of the four historical endemic foci have demonstrated elimination of transmission, following World Health Organization guidelines. Using established guidelines ophthalmological, serological, and entomological evaluations were conducted in 2007-8 to determine the transmission status of onchocerciasis in the Huehuetenango focus. The prevalence of Onchocerca volvulus microfilariae in the anterior segment of the eye in 365 residents was 0% (95% confidence interval [CI] 0–0.8%), the prevalence of infection of O. volvulus in Simulium ochraceum among 8252 flies collected between November 2007 and April 2008 was 0% (95% CI 0–0.02%), and the prevalence of antibodies to a recombinant O. volvulus antigen in 3118 school age children was 0% (95% CI 0–0.1%). These results showed transmission interruption; thus, in 2009 mass treatment was halted and posttreatment surveillance began. To verify for potential recrudescence an entomological evaluation (from December 2010 to April 2011) was conducted during the 2nd and 3rd year of posttreatment surveillance. A total of 4587 S. ochraceum were collected, and the prevalence of infection of O. volvulus was 0% (95% CI 0–0.04%). Transmission of onchocerciasis in the Huehuetenango focus has been eliminated.

Evaluation of a standardized leishmanin skin test in Guatemala.

Background Mass drug administration (MDA) with ivermectin for onchocerciasis was provided in Guatemala’s Central Endemic Zone (CEZ) over a 24 year period (1988–2011). Elimination of Onchocerca volvulus transmission was declared in 2015 after a three year post MDA surveillance period (2012–2014) showed no evidence of recrudescence. The purpose of the present study was to evaluate the knowledge, attitudes and practices (KAP) towards onchocerciasis and ivermectin among residents in the post endemic CEZ. A major interest in this study was to determine what community residents thought about the end of the ivermectin MDA program. Methodology/Principal Findings A total of 148 interviews were conducted in November 2014 in four formerly hyperendemic communities using a standard questionnaire on smart phones. The majority (69%) of respondents knew that the MDA program had ended because the disease was no longer present in their communities, but a slight majority (53%) was personally unsure that onchocerciasis had really been eliminated. Sixty-three percent wanted to continue to receive ivermectin because of this uncertainty, or because ivermectin is effective against intestinal worms. Eighty-nine percent of respondents said that they would seek medical attention immediately if a family member had symptoms of onchocerciasis (especially the presence of a nodule), which is a finding very important for ongoing surveillance. Conclusions/Significance Many respondents wanted to continue receive ivermectin and more than half did not believe onchocerciasis had been eliminated. The ministry of health outreach services should be prepared to address ongoing concerns about onchocerciasis in the post endemic CEZ.

Operational Performance of the Onchocerca volvulus “OEPA” Ov16 ELISA Serological Assay in Mapping, Guiding Decisions to Stop Mass Drug Administration, and Posttreatment Surveillance Surveys

Before recommending the skin-test use at national level in Guatemala of an antigen prepared from Leishmania major (a Leishmania species not found in the New World), we conducted a study in 100 Guatemalans to determine its sensitivity and specificity. The antigen consisted of 0.1 mL of a solution that contained 5 x 10(6) promastigotes of L. major (MRHO/IR/75/VAX). Positive leishmanin skin test (LST) reactions at 48 h were observed in 16 (80%) of 20 patients with proven active cutaneous leishmaniasis (CL), 18 (90%) of 20 with previously treated proven CL, and in 18 (90%) of 20 with a history and compatible scan of previously suspected but unconfirmed CL. None of 20 healthy controls or 20 patients with skin lesions due to causes other than CL had positive reactions to the LST, giving a sensitivity of 85% and specificity of 100%. There were no statistically significant differences in ethnic group, age, duration of the lesion, lesion size or Leishmania species between the 34 persons with true positive reactions. Even though it will be necessary to test this antigen on a larger number of patients, these preliminary results show that this antigen is specific and reasonably sensitive in identifying current or past CL and that it is a reasonable choice for epidemiological studies on CL in Guatemala.

Randomized, controlled, double-blind trial of topical treatment of cutaneous leishmaniasis with paromomycin plus methylbenzethonium chloride ointment in Guatemala

Onchocerciasis is a neglected tropical disease targeted for elimination. The World Health Organization (WHO) has developed guidelines for the verification of onchocerciasis elimination that include entomological and epidemiological criteria. The latter require demonstrating with statistical confidence that the infection prevalence in children is less than 0.1%, necessitating an assay with a high degree of specificity. We present an analysis of the performance of the Onchocerciasis Elimination Program for the Americas (OEPA) version of the Ov16 enzyme-linked immunosorbant assay (ELISA) when used under operational conditions. In Africa and Latin America, the assay demonstrated 99.98% specificity in 69,888 children in 20 foci where transmission was believed to be interrupted. The assay produced a prevalence estimate equal to that of skin snip microscopy when applied in putatively hypo-endemic zones of Ethiopia. The OEPA Ov16 ELISA demonstrated the specificity required to be effectively deployed to verify transmission elimination under the WHO guidelines, while exhibiting a sensitivity equivalent to skin snip microscopy to identify hypo-endemic areas.