Effects of poor hygiene on cytokine phenotypes in children in the tropics.

We describe immune phenotypes (innate and adaptive cytokines) according to environmental exposure using latent class analysis. A total of 310 schoolchildren living in Ecuador were assayed for spontaneous cytokine production as well as mitogen (SEB)-stimulated cytokines in whole blood cultures. We collected data on environmental exposures by questionnaire and on intestinal parasites by examination of stool samples. Latent class analysis (LCA) was used to group children according to their innate (IL-6, IL-8, IL-10 and TNF-α) and adaptive (IL-5, IL-13, IL-17, IFN-γ and IL-10) cytokine profile. We also conducted multiple-group LCA and LCA with covariates to evaluate the effect of predictors on profile membership. We identified both hyporesponsive and Th2-modified immune phenotypes produced by peripheral blood leukocytes (PBLs) that were associated with intestinal worms and birth order, providing insights into how poor hygiene mediates immunologic effects on immune-mediated diseases.

Effect of urban vs. rural residence on the association between atopy and wheeze in Latin America: findings from a case-control analysis.

BACKGROUND: The association between atopy and asthma is attenuated in non-affluent populations, an effect that may be explained by childhood infections such as geohelminths. OBJECTIVE: To investigate the association between atopy and wheeze in schoolchildren living in urban and rural areas of Ecuador and examine the effects of geohelminths on this association. METHODS: We performed nested case-control studies among comparable populations of schoolchildren living in rural communities and urban neighbourhoods in the Province of Esmeraldas, Ecuador. We detected geohelminths in stool samples, measured recent wheeze and environmental exposures by parental questionnaire, and atopy by specific IgE (sIgE) and skin prick test (SPT) reactivity to aeroallergens. RESULTS: Atopy, particularly sIgE to house dust mite (HDM), was more strongly associated with recent wheeze in urban than rural schoolchildren: (urban, adj. OR 5.19, 95% CI 3.37-8.00, P < 0.0001; rural, adj. OR 1.81, 95%CI 1.09-2.99, P = 0.02; interaction, P < 0.001). The population fractions of wheeze attributable to atopy were approximately two-fold greater in urban schoolchildren: SPT to any allergen (urban 23.5% vs. rural 10.1%), SPT to HDM (urban 18.5% vs. rural 9.6%), and anti-HDM IgE (urban 26.5% vs. rural 10.5%), while anti-Ascaris IgE was related to wheeze in a high proportion of rural (49.7%) and urban (35.4%) children. The association between atopy and recent wheeze was attenuated by markers of geohelminth infections. CONCLUSIONS: Our data suggest that urban residence modifies the association between HDM atopy and recent wheeze, and this effect is explained partly by geohelminth infections.

Effects of geohelminth infection and age on the associations between allergen-specific IgE, skin test reactivity and wheeze: a case-control study.

BACKGROUND: Most childhood asthma in poor populations in Latin America is not associated with aeroallergen sensitization, an observation that could be explained by the attenuation of atopy by chronic helminth infections or effects of age. OBJECTIVE: To explore the effects of geohelminth infections and age on atopy, wheeze, and the association between atopy and wheeze. METHODS: A case-control study was done in 376 subjects (149 cases and 227 controls) aged 7-19 years living in rural communities in Ecuador. Wheeze cases, identified from a large cross-sectional survey, had recent wheeze and controls were a random sample of those without wheeze. Atopy was measured by the presence of allergen-specific IgE (asIgE) and skin prick test (SPT) responses to house dust mite and cockroach. Geohelminth infections were measured in stools and anti-Ascaris IgE in plasma. RESULTS: The fraction of recent wheeze attributable to anti-Ascaris IgE was 45.9%, while those for SPT and asIgE were 10.0% and 10.5% respectively. The association between atopy and wheeze was greater in adolescents than children. Although Anti-Ascaris IgE was strongly associated with wheeze (adj. OR 2.24 (95% CI 1.33-3.78, P = 0.003) and with asIgE (adj. OR 5.34, 95% CI 2.49-11.45, P < 0.001), the association with wheeze was independent of asIgE. There was some evidence that the association between atopy and wheeze was greater in uninfected subjects compared with those with active geohelminth infections. CONCLUSIONS AND CLINICAL RELEVANCE: Atopy to house dust mite and cockroach explained few wheeze cases in our study population, while the presence of anti-Ascaris IgE was an important risk factor. Our data provided only limited evidence that active geohelminth infections attenuated the association between atopy and wheeze in endemic areas or that age modified this association. The role of allergic sensitization to Ascaris in the development of wheeze, independent of atopy, requires further investigation.

Long-term periodic anthelmintic treatments are associated with increased allergen skin reactivity.

BACKGROUND: The low prevalence of allergic disease in the rural tropics has been attributed to the protective effects of chronic helminth infections. There is concern that treatment-based control programmes for these parasites may lead to an increase in the prevalence of allergic diseases. OBJECTIVE: We measured the impact of 15-17 years of anthelmintic treatment with ivermectin on the prevalence of allergen skin test reactivity and allergic symptoms in school-age children. METHODS: The prevalence of allergen skin test reactivity, exercise-induced bronchospasm and allergic symptoms was compared between school-age children living in communities that had received community-based treatments with ivermectin (for onchocerciasis control) for a period of 15-17 years with those living in geographically adjacent communities that had received no ivermectin. RESULTS: The prevalence of allergen skin test reactivity was double in children living in treated communities compared with those in untreated communities (16.7% vs. 8.7%, adjusted OR 2.10, 95% CI 1.50-2.94, P<0.0001), and the effect was mediated partly by a reduced prevalence of Trichuris trichiura among treated children. Ivermectin treatments were associated with an increased prevalence of recent eczema symptoms (adjusted OR 2.24, 95% CI 1.05-4.78, P=0.04) but not symptoms of asthma or rhino-conjunctivitis. The effect on eczema symptoms was not associated with reductions in geohelminth infections. CONCLUSION: Long-term periodic treatments with ivermectin were associated with an increased prevalence of allergen skin test reactivity. There was some evidence that treatment was associated with an increased prevalence of recent eczema symptoms but not those of asthma or rhino-conjunctivitis.

High prevalence of bacterial vaginosis in adolescent girls in a tropical area of Ecuador.

Bacterial vaginosis (BV) is a common clinical syndrome, but data are scarce on the BV prevalence in tropical regions among sexually active and virgin adolescents. To estimate the prevalence of BV among adolescent girls in an Ecuadorian coastal town, girls were asked to complete a questionnaire on risk factors for BV and vaginal samples were examined. Bacterial vaginosis was present in 31.5% of 213 girls, and the prevalence was similar in self-reported virgin and sexually active girls (OR 1.06, 95% CI, 0.51-2.21, P = 0.88), although the power of this analysis was limited. The prevalence of BV was high among Ecuadorian adolescent girls, and did not appear to be associated with sexual activity.

Risk factors for atopy among school children in a rural area of Latin America.

BACKGROUND: Infection with common childhood infectious diseases including geohelminth infections may provide protection against the development of atopy and allergic disease. Few studies have investigated risk factors for atopy among children living in rural areas of Latin America. OBJECTIVE: To identify risk factors associated with atopy among school-age children in a rural area of Latin America. METHODS: Analytic cross-sectional study of school-age children conducted in seven rural schools in Pichincha Province in Ecuador. Detailed risk factor information was obtained by questionnaire, stool samples were collected for identification of geohelminth parasites, and Mantoux testing was performed to determine tuberculin sensitization. RESULTS: A total of 1002 children from seven rural schools were recruited. The prevalence of geohelminth infections was high (70.1% were infected with at least one geohelminth parasite) and the prevalence of allergic sensitization was high (20.0% had evidence of aeroallergen sensitization). Factors associated with significant protection against atopy in multivariate analyses were the presence of overcrowding in the child's home, low socio-economic level, and infection with geohelminth parasites, and the protective effects of the three factors were statistically independent. CONCLUSION: Low socio-economic level, overcrowding and geohelminth infection, are independently protective against atopy among school-age children living in a rural area of Latin America.

Geohelminth infections protect against severe inflammatory diarrhoea in children.

We investigated the risk of severe inflammatory diarrhoea associated with geohelminth parasites in 1746 children attending a rural hospital in Ecuador from December 2000 to July 2002. Infections with geohelminths were strongly protective against the risk of severe inflammatory diarrhoea. Our findings suggest that geohelminth infections have important protective effects against enteroinvasive infections in young children.

Relationship between bacille Calmette-Guérin vaccination, Mantoux test positivity, and geohelminth infection.

To investigate the potential protective effects of Bacille Calmette-Guerin (BCG) vaccination scar and sensitization to tuberculin against geohelminth infections, we conducted a cross-sectional study among school age children in rural communities in Pichincha Province in Ecuador where BCG vaccination is routinely given at birth. A total of 944 children aged 8-14 years were evaluated for the presence of BCG scars and sensitization to tuberculin, and underwent faecal examination for geohelminth parasites. BCG scars were present in 88.2% of children and positive Mantoux tests were observed in 19.1% of children. Geohelminth prevalence was high with 70.3% infected with any parasite, 52.1% with Ascaris lumbricoides, 52.3% with Trichuris trichiura, 7.6% with Ancylostoma duodenale, and 3.0% with Strongyloides stercoralis. In multivariate analyses, the presence of BCG vaccine scars was not significantly associated with infections with any geohelminth parasite (adjusted odds ratio [AOR] = 0.74, 95% CI 0.43-1.28, P = 0.28), but an inverse association was observed for infections with S. stercoralis that was of borderline statistical significance (AOR = 0.38, 95% CI 0.15-1.00, P = 0.05). There were no associations between sensitization to tuberculin and infection with geohelminth parasites. The data provide little support for an important protective role of neonatal BCG vaccination or current mycobacterial sensitization against geohelminth infections.

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.

Human infection with Ascaris lumbricoides is associated with a polarized cytokine response.

To define the cytokine response to Ascaris lumbricoides infection, the cellular immune response to adult and larval-stage Ascaris antigens in young adults with moderate infection intensities (n=73) was compared with that of a group of uninfected control subjects (n=40). A. lumbricoides-infected subjects had significantly greater lymphoproliferative responses to adult and larval-stage antigens, compared with uninfected control subjects (P<.01). The frequencies of parasite antigen-stimulated peripheral blood mononuclear cell (PBMC)-expressing interleukin (IL)-4 and IL-5 were significantly greater in the infected group (P<.001), whereas the frequencies of IL-10- and interferon-gamma-expressing PBMC were similar in the 2 groups studied. The ratios of Th2 to Th1 cytokine frequencies were significantly elevated in the infected group, compared with those in uninfected subjects, as was IL-5 protein production by PBMC stimulated with adult (P<.05) and L3/L4 stage (P<.001) antigens. Analysis of these data indicates that A. lumbricoides infections in endemic regions are associated with a highly polarized type 2 cytokine response.

Macrofilaricidal effects of chloroquine on adult Onchocerca volvulus by local infiltration of palpable onchocercal nodules

O efeito macrofilaricida da infiltração local, com uma alta concentração de cloroquina, dentro da cápsula do nódulo oncocercótico sobre o verme adulto de Onchocerca volvulus foi determinado. Seis semanas depois da infiltração, estudos histopatológicos de nódulos simple demonstraram todos os vermes adultos mortos. Em conglomerados de nódulos a ação da cloroquina foi só sobre os vermes adultos do nódulo infiltrado, não acontecendo a difusão da droga aos nódulos adjacentes. A infiltração de cloroquina a nódulos novos ou de recente formação reduz a carga de vermes adultos dos indivíduos parasitados e pode ser uma alternativa para os altos custos das nodulectomias.

The macrofilaricidal effects of local infiltration of high concentrations of chloroquine into the capsule of onchocercal nodules on adult worms of Onchocerca volvulus was determined. Six weeks post infiltration, histological examination of single nodules showed all adult worms to be dead. With nodule conglomerates, there was localized action of chloroquine only on the adult worms in the infiltrated nodule, with no diffusion of the drug to adjacent nodules. Chloroquine infiltration of young, recently formed nodules to reduce the adult worm load of infected individuals may be an alternative method to costly nodulectomy.

Macrofilaricidal effects of chloroquine on adult Onchocerca volvulus by local infiltration of palpable onchocercal nodules.

The macrofilaricidal effects of local infiltration of high concentrations of chloroquine into the capsule of onchocercal nodules on adult worms of Onchocerca volvulus was determined. Six weeks post infiltration, histological examination of single nodules showed all adult worms to be dead. With nodule conglomerates, there was localized action of chloroquine only on the adult worms in the infiltrated nodule, with no diffusion of the drug to adjacent nodules. Chloroquine infiltration of young, recently formed nodules to reduce the adult worm load of infected individuals may be an alternative method to costly nodulectomy.

Evaluation of a direct immunofluorescent antibody (DIFMA) test using Leishmania genus-specific monoclonal antibody in the routine diagnosis of cutaneous leishmaniasis.

A direct immunofluorescent antibody (DIFMA) test using a Leishmania genus-specific monoclonal antibody was evaluated in the routine diagnosis of cutaneous leishmaniasis (CL) in Ecuador. This test was compared with the standard diagnostic techniques of scrapings, culture and histology. Diagnostic samples were taken from a total of 90 active dermal ulcers from patients from areas of Ecuador known to be endemic for cutaneous leishmaniasis. DIFMA was positive in all lesions. It was shown to be significantly superior to standard diagnostic methods either alone or in combination. The sensitivity of DIFMA did not diminish with chronicity of lesions. This test proved to be extremely useful in the routine diagnosis of CL because it is highly sensitive, is easy to use and produces rapid results.

Placebo controlled treatment of Ecuadorian cutaneous leishmaniasis.

Pentavalent antimony has been considered to be the standard treatment for leishmaniasis, but more recently, the orally administrable agent allopurinol ribonucleoside has been the subject of several clinical trials. In this study, these two agents were evaluated in patients with Ecuadorian cutaneous leishmaniasis. Patients were randomly assigned to the two treatment groups. The mean reduction in lesion size for the 28 patients treated with Pentostam (20 mg Sb/kg/day intramuscularly for 20 days) was 61%, 23%, and 11% after one, two, and three weeks, respectively. There was a wide range in the individual values, and some lesions markedly enlarged in the first week of therapy. An initially healed lesion was defined as one that had greater than 80% re-epithelialized by the 1.5-month post-treatment followup. All Pentostam patients demonstrated this degree of lesion resolution (100% initial healing rate), but one patient showed evidence of relapse at the three month followup resulting in a 96% complete healing rate for the 12 month observation period. Patients in the untreated control group demonstrated a strikingly high rate of healing with 9 of 12 patients having re-epithelialized all lesions after 1.5 months observation (75% initial healing rate). The mean reduction in lesion size for the untreated patients was 56%, 29%, and 25% after one, two, and three weeks, respectively. Twenty-one patients received allopurinol ribonucleoside (1,500 mg QID) plus probenecid (500 mg QID) for 28 days. Lesions in nine of these patients were healed at the time of the 1.5 month followup (41% healing rate).(ABSTRACT TRUNCATED AT 250 WORDS)

Chagas disease in Ecuador: a sylvatic focus in the Amazon region.

A sylvatic focus of Chagas disease is reported in the Amazon region of Ecuador (provinces of Napo and Sucumbios). During 1987-1989, 10 cases of acute infection were diagnosed by direct visualization of Trypanosoma cruzi in peripheral blood smears during routine malaria checks. Also in that region, three triatomine bugs, Rhodnius pictipes, Rhodnius robustus and Panstrongylus geniculatus were found naturally infected with T. cruzi suggesting that the human cases represent an autochthonous focus of active transmission.

Human cutaneous leishmaniasis in Ecuador: identification of parasites by enzyme electrophoresis.

Twenty-six strains of Leishmania were isolated from cutaneous lesions in humans in 3 different geographical areas of Ecuador. The species were identified by enzyme electrophoresis as Leishmania braziliensis, L. panamensis, L. guyanensis, L. mexicana, and L. amazonensis.