M. K. Bhan

Typhoid and paratyphoid fever

Typhoid fever is estimated to have caused 21.6 million illnesses and 216,500 deaths globally in 2000, affecting all ages. There is also one case of paratyphoid fever for every four of typhoid. The global emergence of multidrug-resistant strains and of strains with reduced susceptibility to fluoroquinolones is of great concern. We discuss the occurrence of poor clinical response to fluoroquinolones despite disc sensitivity. Developments are being made in our understanding of the molecular pathogenesis, and genomic and proteomic studies reveal the possibility of new targets for diagnosis and treatment. Further, we review guidelines for use of diagnostic tests and for selection of antimicrobials in varying clinical situations. The importance of safe water, sanitation, and immunisation in the presence of increasing antibiotic resistance is paramount. Routine immunisation of school-age children with Vi or Ty21a vaccine is recommended for countries endemic for typhoid. Vi vaccine should be used for 2-5 year-old children in highly endemic settings.

Plasma zinc as a predictor of diarrheal and respiratory morbidity in children in an urban slum setting.

The association between low initial plasma zinc concentration and risk of morbidity over the subsequent 3 mo was examined in a cohort of 116 children aged 12-59 mo recovering from acute diarrhea. Children with low initial plasma zinc (< or = 8.4 micromol/L) had more episodes of diarrhea [risk ratio (RR): 1.47; 95% CI: 1.03, 2.49) and severe diarrhea, defined as passage of > or = 5 liquid stools in a 24-h period, (RR: 1.70; 95% CI: 1.06, 2.72) than did children with normal plasma zinc (> 8.4 micromol/L). The mean prevalence rate of diarrhea associated with fever was 4 times higher in the zinc-deficient group (P = 0.01). Overall, the difference in the number of episodes of acute lower respiratory tract infections (ALRIs) between the two groups was not statistically significant (RR: 1.76; 95% CI: 0.88-3.53) but the mean prevalence rate of ALRIs was 3.5 times higher in children with low plasma zinc (P = 0.05). The increased risk of diarrhea and ALRIs episodes in zinc-deficient children was larger in boys than in girls. These results show that children with low plasma zinc concentrations are at risk for increased diarrheal and respiratory morbidity.

Incidence of severe rotavirus diarrhea in New Delhi, India, and G and P types of the infecting rotavirus strains.

A total of 62,475 children <5 years old from a defined population of approximately 500,000 children and adults from slums in New Delhi, India, were assessed for 1 year by means of passive surveillance, to identify children who were hospitalized for diarrhea. The incidence of severe rotavirus diarrhea was estimated, and the G and P types of the infecting rotavirus strains were determined and were correlated with the clinical severity of diarrhea. Of 584 children who were hospitalized with diarrhea, 137 (23.5%) had rotavirus detected in stool specimens (incidence of rotavirus diarrhea-associated hospitalizations, 337 hospitalizations/100,000 children <5 years of age). Most cases of diarrhea (98%) occurred during the first 2 years of life, peaking at 9-11 months of age. Rotavirus-associated diarrhea occurred year-round but was predominant in winter. Among the strains that could be G-typed, G1 was the most common serotype, followed by G9 and G2; 10% of cases of diarrhea were due to mixed G-type infections. Common strains identified in the present surveillance study were P[8]G1, P[4]G2, P[8]G9, P[6]G1, P[6]G9, and P[6]G3. Children infected with G1 strains had a greater risk of developing more-severe cases of diarrhea than did children infected with other rotavirus strains (odds ratio, 2.95; 95% confidence interval, 1.3-6.67).

Emergence of G12 Rotavirus Strains in Delhi, India, in 2000 to 2007

ABSTRACT The prospect that rotavirus diarrhea in children may soon be prevented by vaccines has placed a new priority on understanding the diversity of rotavirus strains and the mechanism by which these strains evolve over time. We have characterized a total of 465 rotavirus strains collected in North India from 2000 to 2007 for G and P types by reverse transcription-PCR and sequencing. The novel G12 rotavirus strains recently detected in other countries were first detected in India in 2001 and have emerged as the predominant strains in Delhi, India, during 2005 to 2007. While the VP7 sequence was highly homologous among G12 strains isolated in Delhi, suggesting recent emergence from a common ancestor, the strains had a diverse constellation of other gene segments, demonstrating substantial reassortment. For the entire period, the common rotavirus G types G1 (26%), G2 (25%), and G9 (14%) comprised 65% of the strains, and common P types, P[4] (19%), P[6] (22%), and P[8] (35%), comprised 76% of the total P types. Of note, we detected a high percentage of unusual (17%) strains and fecal specimens with mixed (12% G and 15% P) rotavirus infections having a variety of genomic constellations. For the first time, we identified two novel rotavirus strains with unusual G/P combinations, G2P[11] and G3P[11], in patients with diarrhea. The study highlights the great diversity among rotaviruses isolated from Indian children, the opportunity for genetic reassortment between strains, and the emergence of a novel G12 strain in our country. Due to the demonstrated effect of antigenic diversity on rotavirus vaccines, it will be important to continue careful monitoring of these strains as rotavirus vaccine programs are implemented in India.

Quantitative Evaluation of Rotaviral Antigenemia in Children with Acute Rotaviral Diarrhea

BACKGROUND Rotaviral antigen and RNA have recently been identified in the serum of patients with rotaviral gastroenteritis, but the roles they play in disease remains undetermined. METHODS Rotaviral antigen and RNA were quantified by enzyme-linked immunosorbant assay and by quantitative reverse-transcription polymerase chain reaction in stool and serum specimens from children with rotaviral diarrhea (n=102), children with nonrotaviral diarrhea (n=40), and nondiarrheal control children (n=30). RESULTS Rotaviral antigenemia was detected in 64%, 3%, and 0% of the children with rotaviral diarrhea, the children with nonrotaviral diarrhea, and the nondiarrheal control children, respectively. The level of rotaviral antigen in serum was approximately 2x10(2) -fold lower than that in stool, and a moderate correlation was observed between the 2 levels. Rotaviral RNA was detected in 93% of the antigen-positive serum specimens. The median number of RNA copies in serum was approximately 1 x 10(5) -fold lower than that in stool, and no correlation was observed between the 2 levels. Serum levels of both antigen and RNA were inversely associated with baseline titers of rotaviral serum immunoglobulin G (P<.01). Antigenemia was also associated with G1 serotype. CONCLUSIONS Rotaviral antigenemia and viremia were common in children with rotaviral diarrhea, but antigen and RNA levels in serum were substantially lower than those in stool. Antigenemia was associated with infection with G1 strains and with low baseline titers of rotaviral serum antibody.

Mortality associated with acute watery diarrhea dysentery and persistent diarrhea in rural North India.

Mortality associated with diarrhea was investigated in a longitudinally followed cohort of children under six years of age in rural North India. During the follow‐up, 1663 episodes of diarrhea and 23 diarrhea related deaths were recorded in 1467 children followed up for 20 months. The case fatality rate was 0.56% for acute watery diarrhea, 4.27% for dysentery and 11.94% for non‐dysenteric persistent diarrhea. Most of the episodes lasted less than a week; 5.2% became persistent (duration > 14 days). The case fatality rate was similar in episodes of one and two weeks’duration (0.64% and 0.8%) and increased to 13.95% for persistent episodes. Of the total 86 persistent episodes, 22.1% were dysenteric; the case fatality rate for such dysenteric persistent episodes was 21.1% and for watery persistent diarrhea 11.4%. Diarrheal attack rates were similar among different nutritional groups, but diarrheal case fatality rates progressively increased with increasing severity of malnutrition, these were 24 times higher in children with severe malnutrition (7.48%) compared to those normally nourished (0.31%). With availability and use of oral rehydration therapy, dysentery and persistent diarrhea emerge as major causes of diarrhea related mortality, with underlying malnutrition as a key associated factor.

High prevalence of rotavirus infection among neonates born at hospitals in Delhi, India: predisposition of newborns for infection with unusual rotavirus.

Although rotavirus is the most common cause of diarrhea in children older than 3 months of age, neonatal infections, which are asymptomatic, have rarely been surveyed and have been identified in only a few discrete nosocomial outbreaks. After such a nosocomial outbreak of rotavirus infection among newborns at a hospital in Delhi, we screened infants born at five other nurseries in the immediate area to assess the prevalence of neonatal infections and to determine whether the unique neonatal rotavirus strain, 116E, previously identified in Delhi, was present in other settings. Infection was documented in 43 to 78% of hospitalized infants between 4 and 6 days of life born at five of the six hospitals. Infection with strains related to 116E were the most common, but other unusual strains and no strains common in the community were detected. In addition a shift in genotype was observed among specimens collected from two of these hospitals during a 2-year period. Our observation that neonatal rotavirus infections are more common than recognized previously would encourage the administration of rotavirus vaccines during the newborn period and suggests that the low efficacy of vaccines observed during trials in developing countries may be caused by early natural exposure of infants before immunization. The extraordinary predisposition of neonates for unusual rotavirus strains not commonly found in the community should encourage others to screen neonates for this infection, characterize the strains more fully and attempt to understand at a molecular level the unique relationship between the infecting strain type and the age of the host.

Treating sick young infants in urban slum setting

This editorial disputes the advice of the World Health Organization (WHO) on treatment of sick infants within the first two months of life. WHO recommends that infants with acute lower respiratory infection suspected septicemia or other serious infections be admitted to hospitals. Evidence is cited in this editorial that indicates that in the slums of northern India outpatient care should be provided to those families that find hospitalization not feasible. In the study hospitalization was recommended for 273 children. 66 children or 24.2% received hospitalization. 59.1% refused hospitalization because there was no one to accompany the mother or to care for other siblings. 27.3% sought medicine from other physicians and 3.5% tried home remedies. 6.7% had unpleasant hospital experiences. 28.6% decided to wait. The case fatality rate of children who needed hospitalization was a low of 3.3%. Deaths occurred primarily among those children with severe malnutrition. The children who were advised to be hospitalized were followed up with a visit at 24 hours one week later and four weeks after referral. Revisits stressed the need for hospitalization. The low case fatality among children with outpatient treatment instead of hospitalization is attributed to parental compliance with the treatment regime and drug effectiveness. The author acknowledges that there may have been problems with assessment but this is not accepted as a valid criticism because physicians in the study were well trained.

Increased diarrhoeal and respiratory morbidity in association with zinc deficiency--a preliminary report.

Plasma zinc levels, in a cohort of 116 children aged 12–59 months recently recovered from an episode of acute diarrhoea attending a community health clinic in an urban slum, were related to diarrhoeal and respiratory morbidity in the 3 month period following recovery. Children with low plasma zinc levels (< 60 μg dl−1) spent a significantly greater number of days with watery diarrhoea (rate ratio 1.69 (95% confidence intervals 1.03‐2.78)), diarrhoea associated with fever (rate ratio 1.88 (95% confidence intervals 1.05‐3.34)), and acute lower respiratory tract infections (rate ratio 2.69 (95% confidence intervals 1.64‐4.38)).

Efficacy of mung bean (lentil) and pop rice based rehydration solutions in comparison with the standard glucose electrolyte solution.

Children with acute diarrhea and moderate dehydration between 3 months and 5 years of age were randomly assigned to receive treatment with standard WHO oral rehydration solution (ORS) (n = 33) and two other solutions in which the 20 g/L glucose was substituted by 50 g/L of pop rice (n = 31) and 60 g/L of mung bean (lentil) powder (n = 29). Satisfactory oral rehydration, as assessed clinically and by changes in PCV and total serum solids (TSS), was achieved in 90.9% with WHO ORS, 96.8% with pop rice, and 96.6% in the mung bean ORS treated group (p > 0.05). The purging rates (ml/kg/h) until recovery were 2.49 ± 1.5 (pop rice); 2.91 ± 2.0 (WHO), and 3.41 ± 1.7 in the mung bean group (p > 0.05). The percentage of patients recovering from diarrhea within the 72 h study period was 58.0 (pop rice), 48.4 (WHO), and 44.8 for mung bean group (p > 0.05). Though differences in stool volumes and duration in the three groups were not statistically different, there was a trend toward improvement in efficacy with the pop rice ORS in several parameters: greater weight gain, higher percentage decline in TSS, higher urine output despite lower ORS intake, and lower purging rates. The intake of semisolids in the 24–72 h study period was also higher in the pop rice group as compared to the other two groups (p < 0.05). The number of breast feeds and intake of artificial milk was however similar in all groups (p > 0.05).