Juan J. Calva

Rotavirus Infection in Infants as Protection against Subsequent Infections

BACKGROUND Rotavirus is the leading cause of severe diarrhea in infants. To provide a base line for assessing the efficacy of rotavirus vaccines, we evaluated the protection that is conferred by natural rotavirus infection. METHODS We monitored 200 Mexican infants from birth to two years of age by weekly home visits and stool collections. A physician assessed the severity of any episodes of diarrhea and collected additional stool specimens for testing by enzyme immunoassay and typing of strains. Serum collected during the first week of life and every four months thereafter was tested for antirotavirus IgA and IgG. RESULTS A total of 316 rotavirus infections were detected on the basis of the fecal excretion of virus (56 percent) or a serologic response (77 percent), of which 52 percent were first and 48 percent repeated infections. Children with one, two, or three previous infections had progressively lower risks of both subsequent rotavirus infection (adjusted relative risk, 0.62, 0.40, and 0.34, respectively) and diarrhea (adjusted relative risk, 0.23, 0.17, and 0.08) than children who had no previous infections. No child had moderate-to-severe diarrhea after two infections, whether symptomatic or asymptomatic. Subsequent infections were significantly less severe than first infections (P=0.024), and second infections were more likely to be caused by another G type (P=0.054). CONCLUSION In infants, natural rotavirus infection confers protection against subsequent infection. This protection increases with each new infection and reduces the severity of the diarrhea.

Efficacy of home-based peer counselling to promote exclusive breastfeeding: a randomised controlled trial.

BACKGROUND Exclusive breastfeeding is recommended worldwide but not commonly practised. We undertook a randomised controlled study of the efficacy of home-based peer counselling to increase the proportion of exclusive breastfeeding among mothers and infants residing in periurban Mexico City. METHODS Two intervention groups with different counselling frequencies, six visits (44) and three visits (52), were compared with a control group (34) that had no intervention. From March, 1995, to September, 1996, 170 pregnant women were identified by census and invited to participate in the study. Home visits were made during pregnancy and early post partum by peer counsellors recruited from the same community and trained by La Leche League. Data were collected by independent interview. Exclusive breastfeeding was defined by WHO criteria. FINDINGS 130 women participated in the study. Only 12 women refused participation. Study groups did not differ in baseline factors. At 3 months post partum, exclusive breastfeeding was practised by 67% of six-visit, 50% of three-visit, and 12% of control mothers (intervention groups vs controls, p<0.001; six-visit vs three-visit, p=0.02). Duration of breastfeeding was significantly (p=0.02) longer in intervention groups than in controls, and fewer intervention than control infants had an episode of diarrhoea (12% vs 26%, p=0.03). INTERPRETATION This is the first reported community-based randomised trial of breastfeeding promotion. Early and repeated contact with peer counsellors was associated with a significant increase in breastfeeding exclusivity and duration. The two-fold decrease in diarrhoea demonstrates the importance of breastfeeding promotion to infant health.

Serum Antibody as a Marker of Protection against Natural Rotavirus Infection and Disease

To determine whether naturally acquired serum IgA and IgG antibodies were associated with protection against rotavirus infection and illness, a cohort of 200 Mexican infants was monitored weekly for rotavirus excretion and diarrhea from birth to age 2 years. Serum samples collected during the first week after birth and every 4 months were tested for anti-rotavirus IgA and IgG. Children with an IgA titer >1:800 had a lower risk of rotavirus infection (adjusted relative risk [aRR], 0.21; P<.001) and diarrhea (aRR, 0. 16; P=.01) and were protected completely against moderate-to-severe diarrhea. However, children with an IgG titer >1:6400 were protected against rotavirus infection (aRR, 0.51; P<.001) but not against rotavirus diarrhea. Protective antibody titers were achieved after 2 consecutive symptomatic or asymptomatic rotavirus infections. These findings indicate that serum anti-rotavirus antibody, especially IgA, was a marker of protection against rotavirus infection and moderate-to-severe diarrhea.

Protection of breast-fed infants against Campylobacter diarrhea by antibodies in human milk

To investigate the role of breast-feeding in preventing diarrhea caused by Campylobacter jejuni , we followed 98 Mexican children prospectively for 2 years beginning at their birth. Attack rates of diarrhea in children less than 6 months of age who were not fed human milk were 2.3 times greater than those in children of the same age who were fed human milk. Breast-fed children remained free of diarrhea for a longer time than non-breast-fed children ( p C. jejuni for non-breast-fed infants was significantly greater ( p C. jejuni were high in colostrum, decreased during the first month of breast-feeding, and generally persisted throughout lactation. Human milk consumed by children in whom Campylobacter diarrhea developed did not contain secretory IgA antibodies to the glycine acid-extractable common antigen of Campylobacter . This study shows an association between Campylobacter antibodies in human milk and prevention of diarrhea caused by Campylobacter .

A prospective study of astrovirus diarrhea of infancy in Mexico City

AIM To describe the epidemiologic and clinical characteristics of astrovirus-associated diarrhea in a cohort of young children from a periurban community in Mexico City. METHODS From November, 1988, through December, 1991, a total of 214 children were enrolled in a longitudinal study of diarrhea and monitored from birth to 18 months of age. A stool specimen was collected during each episode of diarrhea. Specimens from a total of 510 diarrhea episodes were tested for astrovirus by enzyme immunoassay and examined for other enteric pathogens. The antigenic types of astrovirus were determined by a typing enzyme immunoassay. RESULTS Astrovirus was detected in 26 (5%) of 510 diarrhea episodes, with an incidence rate of 0.1 episode/child year; the highest rate was in children 13 to 18 months of age. Astrovirus-associated diarrhea was characterized by a median of 4 stools (range, 2 to 10) during the first 24 h, a median duration of 3 days (range, 1 to 21), vomiting (20%), and fever (7%). No cases of dehydration or repeat symptomatic infections were observed. Coinfection with another pathogen was detected in 11 of the 26 episodes (42%). Serotype 2 (35%) was most common, followed by serotypes 4 (15%), 3 (11%), and 1 and 5 (4% each); 31% were nontypable. Astrovirus-associated diarrhea was less severe, as measured by the number of stools (4.3 +/- 1.9), than diarrhea caused by rotavirus (7.1 +/- 2.8) or when coinfections occurred (5.5 +/- 1.6; P = 0.008). CONCLUSIONS Astrovirus was associated with 5% of the episodes of diarrhea in this cohort of young Mexican children and presented as a mild secretory diarrhea. Five predominant antigenic types were detected with type 2 being the most common.

Polymerase chain reaction for the detection of Mycobacterium tuberculosis DNA in tissue and assessment of its utility in the diagnosis of hepatic granulomas.

A polymerase chain reaction (PCR) assay for the rapid identification of Mycobacterium tuberculosis, based on amplification of the IS6110 insertion sequences, was tested in paraffin-embedded tissue from 64 biopsy samples with either positive or negative cultures for Mycobacterium tuberculosis. The utility of this PCR assay in the diagnosis of tuberculosis among patients with hepatic granulomas (HGs) was then tested by examining 43 liver biopsy samples. They were classified as either having definitive or probable tuberculosis or as being of nontuberculous origin, on the basis of clinical and microbiologic data and on their response to antituberculous treatment. PCR was 100% sensitive in the diagnosis of culture-positive M. tuberculosis infection in the lymph node, lung, and liver. The sensitivity of the PCR in the diagnosis of HG of definitive tuberculous origin was 58%, and the specificity was 96%. PCR is a valuable test for the demonstration of mycobacterial DNA in tissues. Although it is not highly sensitive, the DNA amplification method may also be more sensitive than culture in the diagnosis of M. tuberculosis-associated HG.

Mycobacterium bovis BCG Substrains Confer Different Levels of Protection against Mycobacterium tuberculosis Infection in a BALB/c Model of Progressive Pulmonary Tuberculosis

ABSTRACT Mycobacterium bovis BCG is the only available vaccine against tuberculosis. Reasons for why diverse BCG substrains induce different levels of protection in clinical trials remain unclear. The aim of this study was to compare the effectiveness of 10 BCG substrains in a mouse model of pulmonary tuberculosis. BALB/c mice were subcutaneously vaccinated and 2 months later were challenged with Mycobacterium tuberculosis H37Rv by intratracheal injection. Two and 4 months after challenge, delayed-type hypersensitivity (DTH) response, lung tissue affected by pneumonia, CFU, T-cell counts, and cytokine expression (interleukin-2 [IL-2], IL-4, IL-10, and gamma interferon) were determined. A differential protective effect of the diverse BCG substrains was found. BCG Phipps led to the largest and most persistent reduction of CFU counts and of the area of pneumonia at 2 and 4 months after challenge. This protection was accompanied by reduced IL-10-producing T cells. Contemporary BCG substrains induce a wide range of protection in this animal model. These data can help in the selection of the best vaccine for human immunization and for the development of novel recombinant BCG-based vaccine.

Prevalence and Genetic Diversity of Human Astroviruses in Mexican Children with Symptomatic and Asymptomatic Infections

ABSTRACT The prevalence and type diversity of human astroviruses (HAstV) in children with symptomatic and asymptomatic infections were determined in five localities of Mexico. HAstV were detected in 4.6 (24 of 522) and 2.6% (11 of 428) of children with and without diarrhea, respectively. Genotyping of the detected strains showed that at least seven (types 1 to 4 and 6 to 8) of the eight known HAstV types circulated in Mexico between October 1994 and March 1995. HAstV types 1 and 3 were the most prevalent in children with diarrhea, although they were not found in all localities studied. HAstV type 8 was found in Mexico City, Monterrey, and Mérida; in the last it was as prevalent (40%) as type 1 viruses, indicating that this astrovirus type is more common than previously recognized. A correlation between the HAstV infecting type and the presence or absence of diarrheic symptoms was not observed. Enteric adenoviruses were also studied, and they were found to be present in 2.3 (12 of 522) and 1.4% (6 of 428) of symptomatic and asymptomatic children, respectively.

Integrated Food Chain Surveillance System for Salmonella spp. in Mexico 1

This system effectively identified major public health priorities.

Asymptomatic Shigella infections in a cohort of Mexican children younger than two years of age.

The proportion of Shigella infections that occur asymptomatically in young children has not been established. A community-based cohort study of 367 infants was followed prospectively by weekly home visits from January, 1990, through December, 1991. Stool samples were collected weekly and when diarrhea occurred and were tested for Shigella and other enteropathogens. There were 2925 child months of observation and 65 episodes of Shigella infection. There were 3.1 episodes/100 child months during the warm season (May through September) and 0.97 episode/100 child months during the cold season. Shigella infections were rare during the first 6 months of life but increased with age (P < 0.0001). Overall 55% of detected infections were asymptomatic. The proportion of infections that were asymptomatic increased as age increased (P < 0.01). Symptom status was not significantly associated with Shigella species or season. All isolates from symptomatic and asymptomatic children had the 120- to 140-megadalton virulence plasmid. We conclude that infections with virulent strains of Shigella are commonly asymptomatic in Mexican children during the first 2 years of life.