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Biomedical subjects

Mathuram Santosham

Publications and source records attributed to Mathuram Santosham.

At least 19 recordsLinked to original sources

Incidence of invasive group A streptococcal infections and comparison of emm types from invasive infections, pharyngitis, and throat carriage in American Indian communities in the Southwest United States.

BACKGROUND: American Indian/Alaska Native (AI/AN) communities in the US have high rates of group A streptococcal (GAS) infections. We determined the incidence of invasive infections in AI communities in the Southwest and compared emm types from invasive infections, pharyngitis, and throat carriage. METHODS: Activities conducted in the White Mountain Apache Tribal lands (WMA) and Navajo Nation (NN) included active, laboratory-based surveillance for invasive GAS infections (WMA: 2019─2024; NN: 2023─2024; all ages); surveillance for GAS pharyngitis (2023-2024; children 0─17 years); and culture for GAS from oropharyngeal carriage samples (2019 and 2022─2023; children 0─14 years). Emm types were determined by whole-genome sequencing. Annual incidence rates were calculated using Poisson regression. RESULTS: In WMA, age-standardized rates of invasive infections ranged from 80-270/100,000 persons between 2019-2024. Predominant emm types varied (n=74 isolates): 91 (59%) and 49 (32%) in 2019-2020, and 43 (40%) and 53 (30%) in 2023. In NN, rates were 40-60/100,000 persons in 2023-2024; common emm types (n=51) were 53 (28%), 101 (18%), and 12 (16%). In WMA and NN, emm types 1, 12, and 53 predominated in pharyngitis (n=190), and 1, 12, and 91 in throat carriage (n=119). CONCLUSIONS: Rates of invasive GAS infections in these communities were 3-35 times higher than the national US average (12.2/100,000 in 2024). Emm types varied over time with limited overlap in strains from throat carriage or pharyngitis isolates and those from invasive infections. Findings support continuing GAS surveillance and engaging AI/AN communities throughout vaccine development and evaluation.

Indigenous health↗

Contributions of Native Americans to the global control of infectious diseases.

For over a half of a century, Native American populations have participated in numerous studies regarding the epidemiology, prevention and treatment of infectious diseases. These studies have resulted in measures to prevent morbidity and mortality from many infectious diseases. The lessons learned from these studies and their resultant prevention or treatment interventions have been applied around the world, and have had a major impact in the reduction of global childhood morbidity and mortality.

Humans↗

Effect of community-wide conjugate pneumococcal vaccine use in infancy on nasopharyngeal carriage through 3 years of age: a cross-sectional study in a high-risk population.

BACKGROUND: A 7-valent pneumococcal conjugate vaccine (PnCRM7) has been shown to be highly effective in preventing invasive pneumococcal disease. Pneumococcal conjugate vaccines also protect against nasopharyngeal carriage of vaccine serotypes, but the duration of protection against nasopharyngeal carriage is not known. METHODS: A group-randomized efficacy trial of PnCRM7 (vaccine serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F) was conducted on the Navajo and White Mountain Apache reservations from April 1997 to October 2000. A group C meningococcal conjugate vaccine was used as the control vaccine. Infants enrolled between 6 weeks and 7 months of age received 3 doses of vaccine 2 months apart and a fourth dose at 12-15 months of age. Vaccinees were enrolled in a nasopharyngeal carriage study from February 2001 to January 2002 to assess the duration of protection against pneumococcal carriage induced by PnCRM7. RESULTS: We included 749 children in the analysis, including 468 children vaccinated with PnCRM7 and 281 children vaccinated with group C meningococcal conjugate vaccine. The median age was 3.3 years (range, 1-7 years), and the median time since last dose of study vaccine was 27 months (range, 12-48 months). Frequencies of overall pneumococcal carriage were similar among PnCRM7 and group C meningococcal conjugate vaccine recipients (63.9% vs. 60.5%, respectively). The absolute frequency of vaccine-type pneumococcal carriage was lower among PnCRM7 recipients (10.3%) than among controls (17.1%; P = .01). This reduction was offset by an increase of nonvaccine-type pneumococcal carriage among PnCRM7 recipients (39.2% vs. 29.8%; P = .01). CONCLUSION: Community-wide PnCRM7 vaccination in infancy reduces the prevalence of vaccine-type carriage and increases the prevalence of nonvaccine-type carriage through at least 3 years of age.

Carrier State↗

The effect of zinc supplementation during pregnancy on immune response to Hib and BCG vaccines in Bangladesh.

An essential role for zinc in development of the fetal immune system has been documented. However, the effect of antenatal zinc supplementation on infants' postnatal immune response to vaccinations is unknown. The objective of this study was to evaluate the effect of zinc supplementation during pregnancy on immune response to the Bacillus Calmette-Guerin (BCG) vaccine and the Haemophilus influenzae type b (Hib) component of the combined diphtheria, tetanus toxoid and pertussis (DTP)-Haemophilus influenzae type-b (Hib)- conjugate vaccine in poor Bangladeshi infants. We immunized 405 infants whose mothers were supplemented daily with 30 mg elemental zinc or placebo beginning at 12-16 weeks gestation with the standard BCG vaccine at birth. A subcohort of 203 infants were in addition immunized at 1-month intervals with three doses of DTP-Hib vaccine starting at 9 weeks of age. The delayed hypersensitivity (PPD) skin test was performed in 345 infants at 24 weeks of age. Hib polysaccharide (PRP) antibodies were assessed for 91 infants at 4 and 24 weeks of age. In infants born with low birth weight (LBW) a lower proportion of negative responses to PPD skin test were observed in the zinc (66.2%) compared to placebo (78.5%) group (p = 0.07). No differences were observed in normal birth weight infants. There were no differences in proportion of infants above the protective thresholds for anti-PRP antibodies between zinc (81%) and placebo (89%) group. Geometric mean PRP antibody titres at 4 and 24 weeks of age were not different between groups. Zinc supplementation during pregnancy did not enhance immune response to Hib-conjugate vaccine but there was a suggestion of improved delayed hypersensitivity immune responses to BCG-vaccine in Bangladeshi LBW infants.

Antibodies, Bacterial↗

Safety and efficacy of a pentavalent human-bovine (WC3) reassortant rotavirus vaccine.

BACKGROUND: Rotavirus is a leading cause of childhood gastroenteritis and death worldwide. METHODS: We studied healthy infants approximately 6 to 12 weeks old who were randomly assigned to receive three oral doses of live pentavalent human-bovine (WC3 strain) reassortant rotavirus vaccine containing human serotypes G1, G2, G3, G4, and P[8] or placebo at 4-to-10-week intervals in a blinded fashion. Active surveillance was used to identify subjects with serious adverse and other events. RESULTS: The 34,035 infants in the vaccine group and 34,003 in the placebo group were monitored for serious adverse events. Intussusception occurred in 12 vaccine recipients and 15 placebo recipients within one year after the first dose including six vaccine recipients and five placebo recipients within 42 days after any dose (relative risk, 1.6; 95 percent confidence interval, 0.4 to 6.4). The vaccine reduced hospitalizations and emergency department visits related to G1-G4 rotavirus gastroenteritis occurring 14 or more days after the third dose by 94.5 percent (95 percent confidence interval, 91.2 to 96.6 percent). In a nested substudy, efficacy against any G1-G4 rotavirus gastroenteritis through the first full rotavirus season after vaccination was 74.0 percent (95 percent confidence interval, 66.8 to 79.9 percent); efficacy against severe gastroenteritis was 98.0 percent (95 percent confidence interval, 88.3 to 100 percent). The vaccine reduced clinic visits for G1-G4 rotavirus gastroenteritis by 86.0 percent (95 percent confidence interval, 73.9 to 92.5 percent). CONCLUSIONS: This vaccine was efficacious in preventing rotavirus gastroenteritis, decreasing severe disease and health care contacts. The risk of intussusception was similar in vaccine and placebo recipients. (ClinicalTrials.gov number, NCT00090233.)

Administration, Oral↗

Home-visiting intervention to improve child care among American Indian adolescent mothers: a randomized trial.

OBJECTIVE: To assess the impact of a paraprofessional-delivered home-visiting intervention to promote child care knowledge, skills, and involvement among pregnant American Indian adolescents. DESIGN: Randomized controlled trial comparing a family-strengthening intervention with a breastfeeding education program. SETTING: One Apache and 3 Navajo communities. PARTICIPANTS: Fifty-three pregnant American Indian adolescents were randomly assigned to intervention (n = 28) or control (n = 25) groups. Follow-up data were available for 19 intervention and 22 control participants. Intervention Paraprofessionals delivered 41 prenatal and infant care lessons in participants' homes from 28 weeks' gestation to 6 months post partum. MAIN OUTCOME MEASURES: Child care knowledge, skills, and involvement. RESULTS: Mothers in the intervention compared with the control group had significantly higher parent knowledge scores at 2 months (adjusted mean difference [AMD], +14.9 [95% confidence interval (CI), +7.5 to +22.4]) and 6 months post partum (AMD, +15.3 [95% CI, +5.9 to +24.7]). Intervention group mothers scored significantly higher on maternal involvement scales at 2 months post partum (AMD, +1.5 [95% CI, -0.02 to +3.02]), and scores approached significance at 6 months post partum (AMD, +1.1 [95% CI, -0.06 to +2.2]). No between-group differences were found for child care skills. CONCLUSIONS: A paraprofessional-delivered, family-strengthening home-visiting program significantly increased mothers' child care knowledge and involvement. A longer and larger trial is needed to understand the intervention's potential to improve adolescent parenting and related child outcomes in American Indian communities.

Adolescent↗

Efficacy of zinc in the treatment of severe pneumonia in hospitalized children <2 y old.

BACKGROUND: Severe pneumonia remains a leading cause of morbidity and mortality in undernourished young children in developing countries. OBJECTIVE: This study evaluated the effect of adjuvant zinc therapy on recovery from severe pneumonia by hospitalized children in southern India who were receiving standard antibiotic therapy. DESIGN: This randomized, double-blind, placebo-controlled clinical trial was conducted at the Christian Medical College Hospital, an 1800-bed teaching hospital in Tamilnadu, India. Enrollment and follow-up occurred between September 2003 and August 2004. Children aged 2-23 mo (n = 299) who were hospitalized with severe pneumonia were randomly assigned to receive 10-mg tablets of zinc sulfate or placebo twice a day during hospitalization, along with standard therapy for severe pneumonia. All clinical signs and symptoms of pneumonia were assessed and recorded at 8-h intervals. RESULTS: There were no clinical or statistically significant differences in the duration of tachypnea, hypoxia, chest indrawing, inability to feed, lethargy, severe illness, or hospitalization. Zinc supplementation was associated with a significantly longer duration of pneumonia in the hot season (P = 0.015). CONCLUSIONS: Zinc supplementation had no overall effect on the duration of hospitalization or of clinical signs associated with severe infection in young children hospitalized for severe pneumonia in southern India. This finding differs from the results of 2 previously reported trials wherein zinc supplementation was associated with a shorter period of recovery from severe pneumonia. Given the conflicting results, further research in representative settings is required to help clarify the role of zinc in the treatment of severe pneumonia.

Dietary Supplements↗

Molecular basis of resistance displayed by highly ciprofloxacin-resistant Salmonella enterica serovar Typhi in Bangladesh.

Highly ciprofloxacin-resistant (MIC, 512 microg/ml) strains of Salmonella enterica serovar Typhi were isolated from the blood of typhoid patients in Dhaka, Bangladesh. The strains were indistinguishable by their antibiograms, biotypes, and variable-number tandem repeat types and had matching point mutations at positions 83 and 87 of the gyrA gene. The isolation of these strains in an area of high endemicity indicates the need for continuous surveillance of antibiotic resistance of S. enterica serovar Typhi and for the rationalized use of ciprofloxacin.

Anti-Bacterial Agents↗

Detection of antigenuria for diagnosis of invasive Haemophilus influenzae type b disease.

BACKGROUND: Haemophilus influenzae type b (Hib) diseases are responsible for an estimated 400,000 childhood deaths, mostly in developing countries. OBJECTIVES: To determine the value of the Wellcogen quantitative latex agglutination test (LA) in urine for the diagnosis of Hib pneumonia and meningitis. METHODS: Healthy and sick children aged <5 y were enrolled in Dhaka Shishu (Children's) Hospital. Boiled and non-concentrated urine specimens underwent LA testing. In vaccinated subjects, urine was tested by LA at 24 h, 4-6 and 7-10 d after vaccination. RESULTS: Of 1302 enrolled cases, 201 were healthy (90 Hib vaccine recipients and 111 provided NP) and 1101 were sick with either pneumonia (n=974) or meningitis (n=127). Among the healthy children enrolled, 41 (41/111, 37%) were colonised with Hib and two (2/41, 5%) were positive by LA test. Hib antigenuria among the children who had received Hib vaccination was mainly detected only on day 1 (7/90, 8%) of vaccination. Among the sick children, LA test for Hib antigen was positive for all confirmed cases of Hib pneumonia (10) and meningitis (35). In contrast, none of the urine specimens from the cases with a known aetiology other than Hib (n=104) was positive. Quantitative analysis of antigenuria of sick children showed that it is positive at least up to 1:8 and 1:16 dilutions for pneumonia and meningitis, respectively, in contrast with or=1:8 dilutions. CONCLUSIONS: The Wellcogen LA test for Hib using boiled and non-concentrated urine is more sensitive than blood culture alone and is highly specific.

Antigens, Bacterial↗

Could a single dose of pneumococcal conjugate vaccine in children be effective? Modeling the optimal age of vaccination.

Using incidence rates from CDC's Active Bacterial Core surveillance and immunogenicity data from the Navajo/Apache trial of pneumococcal conjugate vaccine (PCV), we used Markov modeling to predict the optimal age to give a single dose of PCV. Antibody concentration thresholds of 0.35 and 1.0 mcg/ml were considered protective. Our outcome was vaccine serotype-specific invasive pneumococcal disease (IPD) incidence at 24 months. The models predicted the optimal age to vaccinate is 5-7 months with vaccine-induced immunologic memory and 8-10 months without memory. IPD reduction ranged from 15 to 62%, depending on model parameters. A single PCV dose in infants could prevent substantial IPD.

Adolescent↗

Delivering pneumococcal vaccine to a high risk population: the Navajo experience.

High rates of preventable diseases such as pneumococcal disease occur among the Navajo despite their universal health insurance through the Indian Health Service. The objective of this study was to determine the proportion of Navajo adults vaccinated with pneumococcal polysaccharide vaccine and to examine key features of vaccination programs of the Navajo Indian Health Service. For this cross-sectional study, medical charts of Navajo patients with vaccine indications were randomly selected and reviewed to determine who had been vaccinated as of January 1, 1999. Among 480 Navajo>or=65 years old, 73% were vaccinated (95% confidence interval [CI]: 69%-77%). Among 111 Navajo 18-64 years old with vaccine indications, 54% were vaccinated (95% CI: 45% -63%). Vaccination programs utilized extensive public health nursing, home visits, standing orders, and "express lane" clinics. In spite of excellent delivery systems and universal healthcare, the proportion of Navajo persons vaccinated was still below the goals for Healthy People 2010 of having 90% of persons>or=65 years old vaccinated and 60% of high-risk persons 18-64 years old vaccinated.

Adolescent↗

Epidemiology of invasive Haemophilus influenzae type A disease among Navajo and White Mountain Apache children, 1988-2003.

BACKGROUND: Before the introduction of Haemophilus influenzae type b (Hib) conjugate vaccines, rates of H. influenzae disease among Navajo and White Mountain Apache (WMA) children were among the highest reported worldwide. Routine Hib vaccination has significantly reduced rates of Hib disease in these populations. As Hib disease rates decrease to very low levels, there are concerns that non-type b strains of H. influenzae may emerge as more prevalent causes of invasive disease in children. METHODS: We reviewed population-based, active laboratory surveillance data from the period of 1988-2003 for invasive H. influenzae type a (Hia) disease among Navajo and WMA children aged <5 years. Clinical information on cases was collected by chart review. A sample of Hia isolates from Navajo children was typed by pulsed-field gel electrophoresis (PFGE). RESULTS: During 1988-2003, a total of 76 reported cases of invasive Hia disease occurred among Navajo and WMA children. The overall annual incidence was 20.2 cases per 100,000 population aged <5 years. There was no increase in Hia disease rates after Hib vaccination was introduced. The median age of patients was 12 months. Meningitis (50% of cases) was the most common presentation, followed by pneumonia (27.6%). Two children with Hia disease died. PFGE analysis revealed a limited genetic diversity of Hia strains in this population. CONCLUSIONS: Active surveillance data showed high rates of invasive Hia disease among Navajo and WMA children but no increase in the incidence after Hib vaccination was introduced. The presentation of Hia disease is similar to that of Hib disease in the prevaccine era.

Arizona↗

Invasive Haemophilus influenzae type B diseases in Bangladesh, with increased resistance to antibiotics.

OBJECTIVE: To determine the prevalence, age-group distribution, serotype, and antibiotic susceptibility patterns of invasive Haemophilus influenzae type b (Hib) isolates in Bangladeshi children because data regarding Hib diseases in developing countries are scarce, which has led to delay of the introduction of Hib vaccine in these countries. METHODS: Children diagnosed with meningitis (n = 1412) and pneumonia (n = 2434) were enrolled in this surveillance study for Hib invasive diseases. Cerebrospinal fluid (CSF) and blood specimens, and the subsequent isolates, were processed using standard procedures. RESULTS: During 1993 to 2003, 455 H influenzae strains were isolated from patients with meningitis (n = 425) and pneumonia (n = 30), and an additional 68 Hib meningitis cases were detected by latex agglutination (LA) testing. Overall, 35% of pyogenic meningitis cases were a result of H influenzae, 97.1% of which were Hib. Most (91.4%) cases occurred during the first year of life. Resistance to ampicillin, chloramphenicol, and cotrimoxazole was 32.5%, 21.5%, and 49.2%, respectively. There was a trend toward increasing resistance for all three drugs. Resistance to ampicillin and chloramphenicol was almost universally coexistent and was associated with increased sequelae compared with the patients infected with susceptible strains (31% [23/75] vs 11% [21/183]; P <.001). CONCLUSION: Hib is the most predominant cause of meningitis in young Bangladeshi children. Resistance to ampicillin and chloramphenicol and the high cost of third-generation cephalosporin highlight the importance of disease prevention through vaccination against Hib.

Age Factors↗

Infection control practices reduce nosocomial infections and mortality in preterm infants in Bangladesh.

OBJECTIVE: The skin is a potential source for invasive infections in neonates from developing countries such as Bangladesh, where the level of environmental contamination is exceedingly high. A randomized controlled trial was conducted from 1998 to 2003 in the Special Care Nursery of a tertiary hospital in Bangladesh to test the effectiveness of topical emollient therapy in enhancing the skin barrier of preterm neonates less than 33 weeks of gestational age. In the initial months of the study, the infection and mortality rates were noted to be unacceptably high. Therefore, an infection control program was introduced early in the trial to reduce the rate of nosocomial infections. STUDY DESIGN: After a comprehensive review of neonatal care practices and equipment to identify sources of nosocomial infections, a simple but comprehensive infection control program was introduced that emphasized education of staff and caregivers about measures to decrease risk of contamination, particularly hand-washing, proper disposal of infectious waste, and strict asepsis during procedures, as well as prudent use of antibiotics. RESULTS: Infection control efforts resulted in declines in episodes of suspected sepsis (47%), cases of culture-proven (61%) sepsis, patients with a clinical diagnosis of sepsis (79%), and deaths with clinical (82%) or culture-proven sepsis (50%). CONCLUSION: The infection control program was shown to be a simple, low-cost, low-technology intervention to reduce substantially the incidence of septicemia and mortality in the nursery.

Bangladesh↗

Efficacy of zinc in young infants with acute watery diarrhea.

BACKGROUND: Recent studies reported that zinc significantly reduced the duration and volume of acute watery diarrhea in children aged > or = 4 mo, but there were no data specifically on infants aged < 6 mo. OBJECTIVE: This study investigated the effect of zinc on the duration of illness and the stool quantity in acute watery diarrhea of infants aged 1-6 mo by comparing a 20 mg Zn/d dose with a 5 mg Zn/d dose. DESIGN: Infants hospitalized with at least some dehydration (by World Health Organization classification) were enrolled in a double-blind, randomized, placebo-controlled trial. Infants were randomly assigned to receive 20 mg Zn (acetate)/d, 5 mg Zn/d, or placebo for the duration of illness. RESULTS: Two hundred seventy-five infants were enrolled between 20 September 1998 and 18 December 2000. Neither diarrhea duration nor mean stool volume differed between groups. There were no significant differences in fluid intake, the need for unscheduled intravenous fluid, weight gain, or vomiting rates between the groups. CONCLUSIONS: Zinc supplementation did not affect diarrhea duration or stool volume in young infants. Young infants tolerated both zinc doses. A beneficial effect on subsequent illness cannot be ruled out.

Acute Disease↗