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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.

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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.

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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.

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Tumor necrosis factor (TNF)-alpha has been implicated as a key factor in inflammatory processes occurring in erythema nodosum leprosum (ENL). In the present study, the roles of soluble factors and contact-mediated interaction in the induction of enhanced TNF-alpha secretion in leprosy have been investigated. In vitro studies have demonstrated that Mycobacterium leprae per se is a poor stimulus for TNF-alpha production by purified monocytes obtained from normal subjects, although this could be enhanced by either exogenous interferon-gamma or cell contact with fixed activated T lymphocytes. Further investigations demonstrated that monocyte-T cell contact enhanced M. leprae-induced TNF-alpha production by peripheral blood mononuclear cells of ENL patients and was modulated by blocking antibodies to CD40L, CD69, and CD18. These results suggest that physical contact with T cells isolated from patients in a particular disease state (ENL) modulates monocyte function and may contribute to the secretion of proinflammatory cytokines described in ENL.

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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.

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OBJECTIVE: Tuberculosis (TB) is the commonest HIV-related opportunistic infection in many developing countries and is thought to be a frequent underlying cause of HIV-associated wasting. We have used reference water dilution methods to examine the body composition changes associated with TB and to assess the severity and pattern of wasting. METHODS: The study was conducted at a charitable support house for poor and homeless HIV-infected people in Rio de Janeiro, Brazil. Male patients who were HIV-positive and receiving treatment for active TB (HIVTB+) and HIV-infected controls without TB (HIVTB-) were studied. Total body water (TBW) and extracellular water (ECW) were measured by giving oral doses of deuterium oxide and sodium bromide, respectively, and determining enrichment in plasma after 4 hours. Intracellular water (ICW), body cell mass (BCM), lean body mass (LBM) and fat mass were calculated from these parameters using standard equations. RESULTS: HIVTB+ (n = 11) and HIVTB- (n = 12) groups were similar in age, height, CD4 count and HIV risk factors. HIVTB+ men had significantly lower mean ICW (13.2 versus 16.6 kg; p = .02) and BCM (18.4 versus 23.0 kg; p = .02), a relative expansion of ECW (35.0 versus 30.0 L/kg body weight; p = .04), and small and nonsignificant reductions in total body weight (58.0 versus 62.1 kg; p = .26), LBM (45.5 versus 47.7 kg; p = .33) and fat mass (12.5 versus 14.4 kg; p = .51) compared with HIVTB- controls. BCM in the HIVTB+ group was similar to reference values for severe malnutrition. The relative depletion of BCM appeared excessive in comparison with reference values for uncomplicated starvation. CONCLUSION: The nutritional status of HIVTB+ patients was significantly worse than HIVTB- patients. Body weight and LBM underestimated the nutritional deficit, and measurement of BCM is therefore necessary to appreciate the extent of malnutrition in such patients. Malnutrition in HIVTB+ patients is severe and may therefore contribute to decreased survival. Hypermetabolism appears to play a role in the wasting process in patients coinfected with HIV and TB.

PIP: This paper examines the impact of tuberculosis (TB) on the body composition of HIV-positive men with treatment for active TB (HIV/TB+) and HIV-infected men without TB (HIV/TB-) in Brazil. Total body water (TBW) and extracellular water (ECW) were measured by giving oral doses of deuterium oxide and sodium bromide, respectively, and determining the enrichment in plasma after 4 hours. Calculated from these parameters are the intracellular water (ICW), body cell mass (BCM), lean body mass (LBM) and fat mass. Age, height, CD4 count and HIV risk factors were similar among HIV/TB+ (n = 11) and HIV/TB- (n = 12). HIV/TB+ patients had significantly lower mean ICW (13.2 vs. 16.6 kg) and BCM (18.4 vs. 23 kg), a relative expansion of ECW (35 vs. 30 l/kg body weight, nonsignificant reductions in TBW (58 vs. 62.1 kg), LBM (45.5 vs. 47.7 kg) and fat mass (12.5 vs. 14.4 kg) compared with HIV/TB- men. Nutritional status was found to be significantly worse among HIV+ patients. Malnutrition was also severe in HIV/TB+ patients, which contributed to a decreased life span. Hypermetabolism appears to play a role in the wasting process of patients with HIV and TB. To improve physical function, quality of life, and survival among HIV-infected patients with TB, optimization of nutritional status should be at the core of treatment.

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OBJECTIVE: Constant antigenic stimulation of the large immune cell population contained within gut-associated lymphoid tissue during HIV infection may contribute to patients' total viral load. The aim of this investigation was to evaluate the effect of a mucosal antigenic challenge on HIV replication. DESIGN: Prospective clinical study. METHODS: Twelve HIV-1-infected men (mean age, 42.3 years) from the Casa de Apoio Santo Antonio, Rio de Janeiro, Brazil, were immunized with combined whole cell-toxin B subunit oral cholera vaccine. Blood was collected on days 0, 2, 4, 6, 10 and 15 after immunization and plasma was tested for cholera toxin-specific antibody response (IgG and IgA), beta2-microglobulin, and plasma viral load. CD4 lymphocyte counts were performed within 1 week before immunization. Five HIV-infected non-immunized individuals were studied as controls. RESULTS: There were no adverse effects following immunization and no deterioration in clinical outcome during 3 months of follow-up. A transient increase in viral load that ranged from twofold to 60-fold was observed in all cases and was statistically significant on days 2, 6 and 10 (P = 0.017, P = 0.025, P = 0.021, respectively). There was no correlation with CD4 cell counts. None of the non-immunized subjects demonstrated the pattern of viraemia observed after immunization (P > 0.10 on all days). CONCLUSIONS: Our data indicate that mucosal immunization with oral cholera vaccine induces a transient increase in HIV viraemia, regardless of clinical stage of infection and CD4 cell counts. These findings suggest that mucosal stimulation of HIV-infected patients enhances HIV replication.

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We report an outbreak of human bartonellosis in Zamora Chinchipe Province in Ecuador, which occurred in 1995-1996. Nineteen cases were seen, of which 18 presented with classical oroya fever (fever and profound anaemia) and one with verruga peruana; 11 of the cases (58%) had positive blood films containing Bartonella bacilliformis. The houses of cases and neighbouring controls were visited; blood samples for thin films and cultures were collected from members of each house and a questionnaire was administered to investigate possible risk factors for disease transmission. In none of those sampled was B. bacilliformis bacteriologically demonstrable. All case houses were located in isolated areas at the margin of forest and the presence of dead rodents was reported only in case houses (P < 0.05). We suggest that human bartonellosis is a zoonosis with a natural rodent reservoir and that migrant humans infected in this way may become a temporary reservoir host in populated areas.

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The mucosa associated lymphoid tissue regulates and coordinates immune responses against mucosal pathogens. Mucosal tissues are the major targets exposed to HIV during transmission. In this paper we describe in vitro models of HIV mucosal infection using human explants to investigate target cells within this tissue.

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The gut associated lymphoid tissue is responsible for specific responses to intestinal antigens. During HIV infection, mucosal immune deficiency may account for the gastrointestinal infections. In this review we describe the humoral and cellular mucosal immune responses in normal and HIV-infected subjects.

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The mucosa associated lymphoid tissue regulates and coordinates immune responses against mucosal pathogens. Mucosal tissues are the major targets exposed to HIV during transmission. In this paper we describe in vitro models of HIV mucosal infection using human explants to investigate target cells within this tissue.

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The gut associated lymphoid tissue is responsible for specific responses to intestinal antigens. During HIV infection, mucosal immune deficiency may account for the gastrointestinal infections. In this review we describe the humoral and cellular mucosal immune responses in normal and HIV-infected subjects.

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Human bartonellosis was investigated in the Ecuadorian province of Zamora Chinchipe; 17 cases were identified retrospectively from hospital records over the period 1984-1995, mostly from 6 communities in the provincial district of Zumba. A questionnaire concerning risk factors for disease transmission was administered in these 6 communities. Blood samples were taken from individuals with current febrile illnesses or skin lesions suggestive of bartonellosis. Samples for detection of Bartonella bacilliformis were also taken from all school-age children in communities where historical cases had been identified by questionnaire. No bacteriologically positive case was identified and no evidence of asymptomatic infection was detected. Risk factors for disease transmission, identified by the questionnaire, included the presence of sick or dying chickens and guinea-pigs. It was suggested that bartonellosis is a zoonosis with wild animals, probably rodents, as the reservoir. The widespread use of residual insecticides and the easy availability of antibiotics is likely to have modified the epidemiology of this disease over the last decade.

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1. Cytokine production in vitro was assessed in 16 malnourished children, before and after nutritional recovery. 2. Tumour necrosis factor-alpha and interleukin-6 were measured in whole blood after lipopolysaccharide stimulation. 3. The total amount of both cytokines was significantly less after 24 h incubation among malnourished children when compared with the same children after nutritional rehabilitation. 4. Cytokine production in vitro is impaired in severely malnourished children.

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1. The responses of plasma levels of C-reactive protein and serum amyloid A were assessed in two groups of malnourished children. 2. Sixty-six severely malnourished children were studied at admission. Fifty of these had clinical and/or laboratory evidence of infection. C-reactive protein was not elevated in 23 (46%) and serum amyloid A was not raised in 29 (58%) of these 50 children. 3. Surviving children (n = 62) received two doses of diphtheria-pertussis-tetanus vaccine, to which the C-reactive protein and serum amyloid A responses were measured. The first was given early in recovery, the second after nutritional rehabilitation. Ten mildly malnourished children acted as controls, receiving a single dose of diphtheria-pertussis-tetanus vaccine. 4. The responses of both C-reactive protein and serum amyloid A to diphtheria-pertussis-tetanus vaccine were significantly less in early recovery than after nutritional recovery. The response of the mildly malnourished group was no different from that of the severely malnourished group in early recovery, but was less than their response on discharge. 5. The acute-phase protein response of malnourished children is impaired. This may have prognostic implications as the response plays a central role in promoting healing.

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The reponse of plasma levels of C-reactive protein and serum amyloid A were assessed in two groups of malnourished children. Sixty-six severely malnourished children were studied at admission. Fifty of these had clinical and/or laboratory evidence of infection. C-reactive protein was not elevated in 23 (46 percent) and serum amyloid A was not raised in 29 (58 percent) of these 50 children. Surviving children(n=62) received two doses of diphtheria-pertussis-tetanus vaccine, to which the C-reactive protein and serum amyloid A responses were measured. The first was given early in recovery, the second after nutritional rehabilitation. Ten mildly malnourished children acted as controls, receiving a single dose of diphtheria-pertussis-tetanus vaccine. The responses of both C-reactive protein and serum amyloid A to diphtheria-pertussis-tetanus vaccine were significantly less in early recovery than after nutritional recovery. The response of the midly malnourished group was no different from that of the severely malnourished group in early recovery, but was less than their response on discharge. The acute-phase protein response of malnourished children is impaired. This may have prognostic implications as the reponse plays a central role in promoting healing. (Summary)

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Ultrasonographic, blinded assessment was made of the extent of hepatic steatosis in 55 children with severe malnutrition: undernutrition (n = 6), marasmus (n = 18), marasmickwashiorkor (n = 17), and kwashiorkor (n = 14). The children were examined on admission, in early recovery (considered as baseline), and again at discharge. Eleven healthy control children and eight of the previously malnourished children were studied as comparison groups. Both oedematous and non-oedematous malnourished children had significantly more steatosis than the comparison groups at each time. Children with oedematous malnutrition had significantly greater steatosis than non-oedematous children at admission. Half of the non-oedematous malnourished children had appreciable hepatic steatosis at both admission and at baseline. Hepatic fat was only slowly mobilised. The rate constant was 1.4 +/- 0.3%/day. One quarter of the children did not change steatosis grades during the period they were in hospital. There was no overall correlation between the extent of steatosis and liver size. Hepatic steatosis in childhood malnutrition is not confined to oedematous children: it is frequently present in marasmic and undernourished children. Its extent is not necessarily related to the degree of hepatomegaly and accumulated lipid is only slowly mobilised.

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Ultrasonographic, blinded assessment was made of the extent of hepatic steatosis in 55 children with severe malnutrition: undernutrion (n=6), marasmus (n=18), marasmic-kwashiorkor (n=17), and kwashiorkor (n=14). The children were examined on admission, in early recovery (considered as baseline), and again discharge. Eleven healthy control children and eight of the previously malnourished children were studied as comparison groups. Both oedematous and non-oedematous malnourished children had significantly more steatosis than the comparison groups at each time. Children with oedematous malnutrition had significantly greater steatosis than non-oedematous children at admission, Half of the non-oedematous malnourished children had appreciable hepatic steatosis at both admission and at baseline. Hepatic fat was only slowly mobilised. The rate constant was 1.4 ñ 0.3 percent/day. One quarter of the children did not change steatosis grades during the period they were in hospital. There was no overall correlation between the extent of steatosis and liver size. Hepatic steatosis in childhood malnutrition is not confined to oedematous children: it is frequently present in marasmic and under-nourished children. Its extent is not necessarily related to the degree of hepatomegaly and accumulated lipid is only slowly mobilised (AU)

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The acute phase response is a non-specific reaction to tissue injury, in which the liver plays a central role. We examined the acute phase response in 52 severely malnourished children by measuring the serum levels of C-Reactive Protein (CRP) and Serum Amyloid A (SAA), using an ELISA technique. Blood was taken both at admission and following a controlled stress, namely, Triple (DPT) Vaccine. Four children died. The surviving children received DPT either at admission (n=16) or early in recovery (time B) (n=32). All the children received a second vaccination with DPT once they had regained > 90 percent weight-for-height (discharge) (n=48). Both acute phase proteins responded in tandem. The admission values were elevated in only 44 percent of the children for CRP and 20 percent for SAA, despite clinical evidence of infection. The magnitude of the response of both acute phase proteins to DPT given at admission or at time B was significantly less than at discharge (p < 0.05). Even at discharge, approximately 20 percent of the children did not have the expected response. Children with oedematous malnutrition were less likely to respond than non-oedematous children. We suggest that, firstly, severly malnourished children are unable to mount an effective acute phase response, which may have functional implications. Secondly, that the inability to synthesize acute phase proteins represents one manifestation of the hepatic dysfunction that occurs in severe malnutrition (AU)

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Low levels of red cell glutathione (a scavenger of free radicals) have been previously shown to correlate well with the presence of oedema in malnourished children. We addressed the possibility that they may also correlate with the extent of hepatic steatosis. Thirty-three children were studied on three occasions - on admission, in early weight gain and at discharge. Ultrasonography was used to assess hepatic fat. The oedematous children had significantly more hepatic fat on admission than the non-oedmatous (p<0.01), but no child had a normal ultrasound. We found a significant inverse relationship (r = -0.53, p<0.001) between hepatic fat and the level of red cell glutathione that disappeared over time. We conclude that, firstly, hepatic steatosis occurs commmonly in even non-oedematous malnourished children. Secondly, this is associated with low levels of glutathione which may have aetiological implications (AU)

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