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Biomedical subjects

R H Guderian

Publications and source records attributed to R H Guderian.

At least 19 recordsLinked to original sources
PubMed2001

Early human infection with Onchocerca volvulus is associated with an enhanced parasite-specific cellular immune response.

The immune response after early exposure to or infection with Onchocerca volvulus was investigated in an autochthonous focus caused by the migration of infected persons to a previously unaffected area in Ecuador. Peripheral blood mononuclear cell (PBMC) proliferative and cytokine responses (interferon [IFN]-gamma and interleukin [IL]-5) to filarial antigens were measured in 14 subjects with serologic evidence of exposure and in 7 subjects with evidence of dermal microfilarial DNA and were compared with responses in 43 subjects with chronic O. volvulus infections. PBMC proliferative and cytokine responses (IFN-gamma and IL-5) to parasite antigens were elevated in the early exposure/infection group, compared with those in the chronic infection group. Addition of an IL-10-neutralizing antibody to filaria antigen-stimulated cultures resulted in significantly elevated proliferative responses in the chronic infection group. The findings suggest that early exposure and early parasite patency are associated with a vigorous cellular response, but, as infections become chronic, the cellular response becomes down-regulated, partly through an IL-10-dependent mechanism.

Adolescent↗
PubMed2000

Albendazole treatment of children with ascariasis enhances the vibriocidal antibody response to the live attenuated oral cholera vaccine CVD 103-HgR.

Because concurrent infections with geohelminth parasites might impair the immune response to oral vaccines, we studied the vibriocidal antibody response to the oral cholera vaccine CVD 103-HgR in children infected with Ascaris lumbricoides and investigated the effect of albendazole pretreatment on the postvaccination response. Children with ascariasis were randomized to receive either 2 sequential doses of 400 mg of albendazole or placebo. After the second dose, CVD 103-HgR was given, and serum vibriocidal antibody levels were measured before and 10 days after vaccination. Postvaccination rates of seroconversion were greater in the treatment group that received albendazole (P=.06). Significantly greater rates of seroconversion and geometric mean titer were observed in the albendazole group in subjects with non-O ABO blood groups. A significant association was observed between vibriocidal seroconversion rates and treatment group, suggesting that A. lumbricoides infections impair the immune response to oral cholera vaccine, particularly in subjects of non-O blood groups.

Adolescent↗
PubMed2000

Eotaxin and RANTES expression by the dermal endothelium is associated with eosinophil infiltration after ivermectin treatment of onchocerciasis.

The roles of eotaxin, RANTES, and MCP-3 expression in eosinophil recruitment to the site of parasite killing that occurs following ivermectin treatment of onchocerciasis were assessed in the skin of 13 Onchocerca volvulus-infected subjects and two noninfected controls before and after ivermectin treatment. Adverse reactions in infected subjects were associated with the appearance of eosinophils in the dermis as part of a perivascular inflammatory infiltrate. Although no expression of RANTES and eotaxin was seen in dermal vascular endothelial cells in biopsies taken before treatment (nor at any time in the skin of uninfected controls), endothelial expression of both eotaxin and RANTES was noted by 24 h following treatment. While RANTES expression was transient, eotaxin expression increased in parallel with increasing eosinophil recruitment up to 60 h posttreatment. These observations indicate that endothelial expression of eotaxin and RANTES may have an important role in eosinophil recruitment into the skin during helminth-killing reactions.

Adult↗
PubMed1999

Human onchocerciasis and tetanus vaccination: impact on the postvaccination antitetanus antibody response.

To investigate whether helminth infections may affect the efficacy of vaccines by impairing the immune response to nonparasite vaccine antigens, we compared the antibody responses to tetanus toxoid (TT) after tetanus vaccination in 193 subjects with Onchocerca volvulus infection with 85 comparable noninfected controls. After vaccination, the proportions of subjects in each group attaining protective levels of antitetanus antibodies were similar (96.9% infected versus 97.6% noninfected). Postvaccination increases in antitetanus immunoglobulin G (IgG) and the predominant IgG isotype, IgG1, were equivalent in both groups, as were increases in specific IgG4 and IgE; however, significantly greater increases in specific IgG2 (P < 0.05) and IgG3 (P < 0.001) were observed in the noninfected group. Stratification of the O. volvulus-infected group into two groups representing light and heavy infections revealed a significantly impaired antitetanus IgG response in those with heavy infections compared to those with light infections (P < 0.01) or no infection (P < 0.05). The impact of concurrent intestinal helminth infections on the antitetanus response was also examined; an increased IgG4/IgE ratio was seen in those infected with Strongyloides stercoralis (P < 0.05) and when all helminth infections were combined as a single group (P < 0.05). These findings indicate that concurrent infection with O. volvulus does not prevent the development of a protective antitetanus response, although heavier O. volvulus infections are able to alter the magnitude of this response, and concurrent helminth infections (O. volvulus and intestinal helminths) may alter TT-specific antibody isotype responses.

Adolescent↗
PubMed1998

Impaired tetanus-specific cellular and humoral responses following tetanus vaccination in human onchocerciasis: a possible role for interleukin-10.

Onchocerca volvulus infection has been associated with impaired cellular responses to parasite antigens, an impairment that may also extend to nonparasite antigens. To investigate the mechanism of this impaired immune response, the effect of concurrent O. volvulus infection on the immune response to tetanus toxoid (TT) following tetanus vaccination was studied. The proliferative, cytokine, and antibody response to TT of O. volvulus-infected subjects (n = 19) and comparable noninfected controls (n = 20) were studied before and 6 months after vaccination with TT. Following vaccination, antibody levels, proliferative responses, and levels of interferon-gamma were significantly greater in noninfected subjects (P < .05, .001, and .05, respectively); however, infected subjects produced interleukin-10, but noninfected controls did not (P < .001). These studies indicate that concurrent infection with O. volvulus can diminish the immune response to an unrelated antigen (TT) by a mechanism that is likely to involve interleukin-10.

Adolescent↗
PubMed1998

Current status of onchocerciasis in Colombia.

To assess the current epidemiologic status of onchocerciasis in Colombia two surveys were undertaken in 1995 in a suspected new focus on the border between Colombia and Ecuador and in the known focus located on the Micay River. No new focus was found along the Colombia-Ecuador border. In the known focus, communities along the upper Micay River and its tributaries were surveyed; 655 adults underwent physical examinations and skin biopsies. Infected individuals were found almost exclusively in the community of Naiciona, where prevalence of infection was 40% (36 of 91). Polymerase chain reaction detection of onchocercal DNA in skin snips correlated with the skin-snip biopsy results. The prevalence of punctate keratitis, the only ocular manifestation found, was 33%. A rapid entomologic assessment demonstrated Simulium exiguum infected with Onchocerca volvulus. This is the first finding in Colombia of naturally infected black flies and confirms S. exiguum as a vector species. These data will be used for implementing a control program using periodic ivermectin distribution.

Adolescent↗
PubMed1997

The pathogenesis of chorioretinal disease in onchocerciasis.

The pathogenesis of onchocercal chorioretinopathy is poorly understood. In this article, Philip Cooper, Ronald Guderian, Roberto Proaño and David Taylor discuss the important clinical, histological and epidemiological features of the resulting lesions that cause blindness, and review the numerous mechanisins that have been put forward to explain its pathogenesis. The pathogenesis of anterior segment disease, particulary sclerosing keratitis, has been reviewed in depth previously(1) and will not be discussed here.

Journal Article↗
PubMed1997

Successful control of onchocerciasis with community-based ivermectin distribution in the Rio Santiago focus in Ecuador.

Onchocerciasis is a major blinding disease in equatorial Africa and Central and South America. Ivermectin is a safe and effective drug in the treatment of this disease and now forms the basis of disease control in most endemic areas. We report the findings of long-term control of this infection in the Río Santiago focus in Ecuador, between January 1990 and December 1996, using a strategy of giving ivermectin treatments biannually in hyperendemic communities and annually in meso- and hypoendemic communities. Ivermectin was administered by local health workers from each community. A high level of compliance to ivermectin was achieved, with 81.9% to 98.0% of those eligible receiving the drug at each treatment instance. The impact of ivermectin therapy was monitored using a cohort of 120 randomly selected infected individuals from 8 hyperendemic communities. The geometric mean microfilarial density of this group declined from 19.3 to 0 mf/mg over the 84-month observation period. Ivermectin had a significant impact on anterior segment ocular disease, acute onchodermatitis and sowda. The rate of infection of blackflies declined from 1.1% in 1989-0.08% in 1996, which is below the vectorial capacity of the Simulium vector and, as no new nodules were detected after 1994 and no children under 5 became infected over the observation period, it is likely that the transmission of this infection was interrupted in the study area.

Animals↗
PubMed1996

RANTES in onchocerciasis: changes with ivermectin treatment.

Adverse reactions are seen relatively frequently after treatment of onchocerciasis patients with ivermectin. The chemokines RANTES and IL-8, which have both chemotactic and activation properties for eosinophils and neutrophils, respectively, may have a role in the pathogenesis of post-treatment reactions. Circulating levels of the chemokines and the cytokines tumour necrosis factor-alpha (TNF-alpha) and IL-6 were measured in the plasma of 22 Onchocerca volvulus-infected subjects. Peaks of mean circulating levels of RANTES and TNF-alpha were seen at 6 h after ivermectin administration. Peripheral eosinophil counts declined at 36 h post-treatment and an early peak in RANTES levels was associated with a delay in peripheral eosinopenia. RANTES levels were negatively correlated with severity of rash (P < 0.001) and lymphoedema (P < 0.05), suggesting that high circulating levels of RANTES may inhibit eosinophil sequestration. No changes in circulating levels of IL-8 were seen. These findings suggest a possible role of circulating RANTES in modulating eosinophil sequestration in vivo.

Adolescent↗
PubMed1996

Polymerase chain reaction-based assessment after macrofilaricidal therapy in Onchocerca volvulus infection.

A recently developed polymerase chain reaction (PCR)-based assay is significantly more sensitive than current methods for diagnosing Onchocerca volvulus infection, and it overcomes many difficulties in identifying active onchocerciasis. Since chemotherapy is widely used to treat onchocerciasis, the utility of PCR in assessing responses to treatment and in predicting recrudescence is important. Twenty-eight patients who had skin snips positive for microfilariae (Mf) were studied 120 days after receiving amocarzine, when each was negative for Mf: 16 (57%) were positive for O. volvulus DNA in the PCR-based assay. Of these, 14 (88%) were Mf positive when reassessed parasitologically on day 240, and all were Mf positive on day 365. Equally important was the finding that 12 patients had cleared both Mf and Mf DNA; only 1 was Mf positive at day 240. This suggest that the PCR-based assay provides a sensitive means assessing infection status after macrofilaricidal chemotherapy and is an early predictor of persons likely to have a recurrence of Mf.

Animals↗
PubMed1996

In utero exposure to Onchocerca volvulus: relationship to subsequent infection intensity and cellular immune responsiveness.

Afro-Ecuadorian individuals from an area where Onchocerca volvulus is hyperendemic have been monitored for infection over the past 16 years. To determine whether in utero exposure to O. volvulus biases a child's subsequent immune responses, children (9 to 16 years old) for whom the mother's infection status was known were chosen for study. Children of infected mothers (n = 19) had significantly higher levels of skin microfilariae than children of uninfected mothers (n = 13; P = 0.021). While the serum levels of O. volvulus-specific immunoglobulin G (IgG), IgG subclasses, and IgE showed no significant differences between the two groups of children, peripheral blood mononuclear cells of children of infected mothers produced higher levels of Th2-type cytokines to several parasite antigens and lower levels of Th1-type cytokines to nonparasite antigens than those of children of uninfected mothers. Thus, in utero exposure to O. volvulus has a long-term effect on the child's subsequent cellular immune response that may render the child more susceptible to O. volvulus infection postnatally.

Adolescent↗
PubMed1996

Onchocerciasis in Ecuador: evolution of chorioretinopathy after amocarzine treatment.

AIMS: To investigate the impact of the macrofilaricidal drug, amocarzine, on the evolution of chorioretinopathy in onchocerciasis. METHODS: A prospective uncontrolled cohort study was performed using subjects infected with Onchocerca volvulus in a hyperendemic onchocerciasis focus in Esmeraldas Province in Ecuador. Study subjects were recruited into four cohorts in which ophthalmic and parasitological data were collected for 2, 3, 4, and 5 years respectively. RESULTS: Complete ophthalmic follow up was obtained for 294 individuals in the four cohorts. The incidence of retinal pigment epithelial atrophy tended to remain constant between cohorts while that of chorioretinal scarring with a greater observation period. The incidence rate of cases with new or extending chorioretinal lesions was greater with an increasing period of follow up. An association was seen between the cumulative microfilarial loads in the skin and the development of new chorioretinal lesions (p < 0.05). No relation was noted between cumulative microfilarial loads and the progression of existing disease. CONCLUSION: Amocarzine therapy did not prevent the natural evolution of chorioretinal disease. It was suggested that ocular microfilariae were necessary for the induction of chorioretinopathy in previously unaffected eyes and that extension of existing disease might also be related to the presence of ocular microfilariae or to other immunological mechanisms.

Adolescent↗
PubMed1996

Absence of cellular responses to a putative autoantigen in onchocercal chorioretinopathy. Cellular autoimmunity in onchocercal chorioretinopathy.

PURPOSE: Onchocerciasis is a major cause of blindness in the developing world. An autoimmune pathogenesis for onchocercal chorioretinopathy was proposed after the identification of a recombinant Onchocerca volvulus antigen (designated Ov39) demonstrated immunologic crossreactivity with a component of the retinal pigment epithelium and other ocular tissues. The aim of this study was to determine whether patients with onchocercal chorioretinopathy have enhanced lymphoproliferative responses to Ov39 compared to those without chorioretinal disease. METHODS: Lymphocyte blastogenic assays were performed using peripheral blood mononuclear cells (PBMCs) from patients with and without evidence of chorioretinopathy. PBMCs were cultured with Ov39, and supernatant fluids from Ov39-stimulated PBMCs were used to determine levels of the cytokines, interferon-gamma, and interleukin-5. RESULTS: Lymphoproliferative responses to Ov39 were not enhanced in patients with onchocercal chorioretinopathy compared to those without clinical evidence of chorioretinal disease. CONCLUSIONS: A role for Ov39-specific cellular autoreactivity in the pathogenesis of onchocercal chorioretinopathy could not be demonstrated.

Adolescent↗
PubMed1995

Immunity to onchocerciasis: putative immune persons produce a Th1-like response to Onchocerca volvulus.

Immunity to Onchocerca volvulus (Ov) infection is suggested by the presence of putatively immune (PI) subjects in a region of Ecuador in which Ov is endemic. PI subjects were identified by traditional diagnostic methods combined with a polymerase chain reaction-based assay for Ov DNA in skin snips. Responses of peripheral blood mononuclear cells (PBMC) from the PI group (n = 16) were compared with those of persons with active infection (microfiladermic [MF] subjects; n = 51). PBMC of PI subjects proliferated significantly more to Ov antigen (OvAg; P < .009) than did PBMC of MF persons but less to streptolysin-O (P < .001). Cytokine analysis of PBMC culture supernatants revealed that PI subjects (n = 11) produced significantly more interferon-gamma to OvAg than did those in the MF group (n = 18; P = .018), less interleukin (IL)-5 to nonparasite antigen (P = .003) and mitogen (P = .012), and less IL-10 spontaneously (P = .016). Thus, immunity to Ov may in part be mediated by an antigen-specific Th1-type response.

Adolescent↗
PubMed1995

Onchocerciasis in Ecuador: ocular findings in Onchocerca volvulus infected individuals.

Little is known of the epidemiology and clinical picture of ocular onchocerciasis in South America. A survey of onchocercal eye disease was performed in the hyperendemic area of a rain forest focus of onchocerciasis in Esmeraldas Province in Ecuador. A total of 785 skin snip positive individuals from black and Chachi Amerindian communities were examined. The blindness rate attributable to onchocerciasis was 0.4%, and 8.2% were visually impaired. Onchocercal ocular lesions were seen in a high proportion of the study group: 33.6% had punctate keratitis, microfilariae in the anterior chamber and cornea were seen in 28.9% and 33.5% respectively, iridocyclitis was seen in 1.5%, optic atrophy in 5.1%, and chorioretinopathy in 28.0%. Sclerosing keratitis was not seen. The prevalence of all ocular lesions increased with age. Punctate keratitis was strongly associated with microfilarial counts in the cornea and chorioretinopathy was correlated with infection intensities in the cornea and anterior chamber. Chachi Amerindians had higher anterior chamber microfilarial counts and a greater prevalence of punctate keratitis than blacks though blacks had a greater prevalence of iridocyclitis and optic nerve disease. The pattern of ocular disease resembled rain forest onchocerciasis in west Africa with few severe ocular lesions in the anterior segment and all blinding lesions attributable to posterior segment disease.

Adolescent↗
PubMed1995

Yaws in Ecuador: impact of control measures on the disease in the Province of Esmeraldas.

OBJECTIVES: To determine the impact of a community-based programme of yaws control in Esmeraldas province in Ecuador. METHODS: Community health workers provided mass treatment and subsequent surveillance for the detection and treatment of new cases and their contacts over the period 1988 to 1993. Clinical and serological surveys were performed in the study area in 1988 and 1993. RESULTS: Over the 5 year observation period, the number of communities with active infections had decreased by 75%, from 20 communities in 1988 to 5 in 1993. In 1993, 4 communities were found free of clinical infections as well as latent infections. There was a corresponding decrease of 94.6% in the prevalence of dermal lesions (from 11.2% to 0.6%), and a reduction of 97.3% in latent infections (from 93.6% to 2.5%). CONCLUSIONS: The control of yaws using existing community-based health workers has proved very effective in Ecuador.

Adolescent↗