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Vaccine Reports

Rotavirus Infection, Illness, and Vaccine Performance in Malnourished Children: A Review of the Literature

Burnett, Eleanor BSN, MPH; Parashar, Umesh D. MBBS, MPH; Tate, Jacqueline E. PhD

Author Information
The Pediatric Infectious Disease Journal: October 2021 - Volume 40 - Issue 10 - p 930-936
doi: 10.1097/INF.0000000000003206

Abstract

Despite the availability of rotavirus vaccines since 2006, rotavirus is estimated to cause approximately 200,000 deaths worldwide among children <5 years old.1,2 In 2009, the World Health Organization expanded the recommendation for 2 live, oral rotavirus vaccines (Rotarix [GlaxoSmithKline Biologicals, Rixensart, Belgium] and RotaTeq (Merck & Co., West Point, PA)] to all countries1 and 2 additional live, oral rotavirus vaccines, Rotasiil (Serum Institute of India Pvt. Ltd., Pune, India) and ROTAVAC (Bharat Biotech International Ltd., Hyderabad, India) were prequalified in 2017.3 To date, >100 countries have introduced a rotavirus vaccine into their routine, infant immunization schedule.4 In observational studies and clinical trials, a difference of about 20 percentage points in Rotarix and RotaTeq performance by a country’s <5-year-old child mortality level has been documented.5,6 Although there are several hypotheses for lower rotavirus vaccine performance in higher mortality countries, including interference by oral polio vaccine, differences in the gut microbiome and prevalence of malnutrition, the contribution to reduced effectiveness by these possible factors is unknown.7,8

Malnutrition in children has a high burden of disability and mortality and long-term malnutrition before a child’s second birthday has irreversible lifelong impacts.9–12 Though child malnutrition has been declining worldwide, progress has been uneven and more than 1 in 3 children in Sub-Saharan African and South Asia have chronic malnutrition.9,13 There are 3 common anthropometric indicators of malnutrition in children: length-for-age (stunting), weight-for-length (wasting) and weight-for-age (a combination of wasting and stunting). Low length-for-age, that is length-for-age with a Z-score of <−2, is considered a measure of long-term malnutrition while low weight-for-length suggests acute malnutrition.14 Additionally, malnutrition can be characterized by deficiencies in micronutrients, such as zinc, vitamin A and iron, and can be measured by serum levels of these micronutrients.10,13,15 Related to malnutrition, environmental enteric dysfunction (EED) is an asymptomatic condition characterized by malabsorption, increased permeability and increased inflammation in the small intestine possibly due to frequent enteropathogen infections.11,16 EED can be measured with fecal and serum biomarkers and has been linked to poor weight gain and stunting.11,16–19 Malnutrition is associated with increased susceptibility to disease and there is limited evidence that it also impairs oral and parenteral vaccine performance.8,20,21 There is insufficient evidence from a limited number of evaluations to determine if EED impairs oral vaccine performance, including oral rotavirus vaccine performance.22

In this review of the literature, we aim to summarize the available evidence of natural rotavirus infection and illness by nutritional status and quantify rotavirus vaccine performance among well-nourished and malnourished children <5 years old.

METHODS

Literature Search Methods and Inclusion Criteria

The literature search was conducted in 3 parts and completed on October 2, 2020. First, we reviewed articles identified as part of a systematic review of rotavirus vaccine post-licensure effectiveness for any analyses that stratified vaccine effectiveness (VE) by well-nourished and malnourished children <5 years old.5 Detailed methods and exclusion criteria for the initial search have been previously described.5 We completed a second PubMed search of abstracts including “rotavirus” and the terms “*nutrition,” “*nourished” or “environmental enter*” to identify articles on rotavirus prevalence or rotavirus vaccine efficacy (VE) or immunogenicity in clinical trials. Finally, we reviewed the references and citing articles of key publications because analyses of natural rotavirus infection stratified by nutritional status were often secondary objectives or rotavirus was one of many enteropathogens tested and both were not always indicated in the title or abstract.

We included articles that had a laboratory-confirmed rotavirus endpoint and categorized malnutrition among children <5 years old using anthropometric indicators (Z-score <-2). Laboratory-confirmed rotavirus endpoints included rotavirus-positive diarrhea of any severity, rotavirus-positive stool specimens (rotavirus infection), presence of rotavirus antibodies in serum specimens (seropositivity) and an increase in the concentration of rotavirus antibodies in serum specimens (seroconversion). Articles were excluded if nutritional status was defined by feeding method only, for example, exclusively breast-fed or duration of breast-feeding. Among evaluations of natural rotavirus infection prevalence, we excluded articles where the relationship being investigated was diarrhea as the cause of malnutrition or malnutrition as a predictor diarrhea illness outcomes. We limited VE articles to those published in 2006 or later; we did not limit articles about natural infection by date of publication.

Finally, articles that measured vaccine performance by EED status were excluded as we determined no additional analyses were published since the publication of another recent literature review and that the variation in methods limited our ability to meaningfully aggregate the results.22 Two rotavirus prevalence articles that otherwise met our inclusion criteria used the same dataset, with 1 year of overlap in the data collection period; however, the earlier article included more types of anthropometric indicators of malnutrition, so we chose to include both articles.23,24 For a multi-country study of malnutrition and intestinal infections in children in low-income countries (the Etiology, Risk Factors and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development or MAL-ED study), we chose to include overall results, rather than published findings from any individual country.

Analytic Methods

We divided the articles into 2 groups: rotavirus prevalence and performance of rotavirus vaccines; we further categorized vaccine performance evaluations by VE and immunogenicity. For each group, we describe the study population, design and analytic methods as well as summarize key, common findings across studies. The range of VE point estimates with medians is presented by study design. Data were abstracted using a Microsoft Excel database, analyzed using R v.6.3.1, and figures generated using the ggplot2 package.25

RESULTS

Results of our literature searches are detailed in Supplemental Digital Content 1, http://links.lww.com/INF/E404 (Figure; http://links.lww.com/INF/E404).

Vaccine Efficacy and Effectiveness by Nutritional Status

We identified 7 analyses from 11 countries published from 2007 to 2019 that stratified rotavirus VE or vaccine effectiveness by malnutrition status using anthropometric indicators (Table 1). Five studies used Rotarix and 1 used RotaTeq, which included separate analyses for 2 groups of countries. One Rotarix and both RotaTeq analyses were post-hoc VE analyses of clinical trial data, which measured malnutrition at the time of receipt of the first rotavirus vaccine dose; the 4 case-control VE evaluations of Rotarix measured malnutrition at the time of the child’s diarrhea illness. Overall, among well-nourished children, the VE point estimates ranged from 71% to 84% (median: 77%) for observational studies and 26% to 61% (median: 32%) for clinical trials (Fig. 1). Among malnourished children, the VE point estimates ranged from −28% to 45% (median: 20%) for observational studies and −3% to 61% (median: 21%) for clinical trials. The range of relative difference between VE in well-nourished and malnourished children was 37%–64% (median: 61%) in the 4 studies that classified malnutrition by length-for-age, 0%–107% (median: 62%) in the 4 studies that classified malnutrition by weight-for-age and −65%–137% (median: 111%) in the 3 studies that classified malnutrition by weight-for-height (Fig. 2). The post-hoc clinical trial analyses found a smaller relative difference between malnourished and well-nourished children than the case-control evaluations of rotavirus vaccine under conditions of routine use.

TABLE 1. - Rotavirus Vaccine Efficacy and Effectiveness Evaluations Stratified by Nutritional Status, 2006–2020
Vaccine Type of Study Year of Publication Country Age Group Recruitment Setting Rotavirus Endpoint Indicator of Malnutrition Malnourished VE (95% CI) Well-nourished VE (95% CI) Reference
Rotarix Randomized trial 2007 Brazil, Mexico, Venezuela <12 months Community Rotavirus positive diarrhea Weight-for-age 61 (10 to 83) 61 (37 to 75) 26
Rotarix Case-control 2016 Botswana 4–59 months Emergency department, inpatient Rotavirus positive diarrhea Weight-for-length −28 (−309 to 60) 75 (41 to 89) 27
Rotarix Case-control 2016 Malawi <32 months Emergency department, inpatient Rotavirus positive diarrhea Length-for-age 28 (−100 to 74) 78 (6 to 95) 28
Rotarix Case-control 2019 Kenya 1–32 months Inpatient Rotavirus positive diarrhea Weight-for-age 10 (−134 to 66) 84 (62 to 93) 29
Length-for-age 28 (−118 to 76) 75 (48 to 88)
Weight-for-length −9 (−224 to 63) 84 (64 to 93)
Rotarix Case-control 2019 Zimbabwe 6–11 months Emergency department, inpatient Rotavirus positive diarrhea Length-for-age 45 (−148 to 88) 71 (29 to 88) 30
RotaTeq Randomized trial 2017 Bangladesh, Vietnam <24 months Community Rotavirus positive diarrhea Weight-for-age −3 (−256 to 70) 45 (24 to 60) 31
RotaTeq Randomized trial 2017 Ghana, Kenya, Mali <24 months Community Rotavirus positive diarrhea Weight-for-age 21 (−34 to 53) 32 (17 to 43) 31
Length-for-age 13 (−58 to 52) 32 (18 to 44)
Weight-for-length 43 (15 to 62) 26 (10 to 40)

FIGURE 1.
FIGURE 1.:
Vaccine efficacy and effectiveness estimates for well-nourished and malnourished children by study design and anthropometric indicator of malnutrition. VE indicates vaccine efficacy.
FIGURE 2.
FIGURE 2.:
Relative difference in rotavirus vaccine efficacy or effectiveness estimates between well-nourished and malnourished children by anthropometric indicator of malnutrition, study design and rotavirus vaccine. RTC, randomized control trial.

We identified 2 additional clinical trials that measured immunogenicity after vaccination with Rotarix (Table 2). One found that normal length-for-age was predictive of anti-rotavirus IgA seroconversion and seropositivity. The other found no association between anti-rotavirus IgA seroconversion and any anthropometric indicator of malnutrition. The age groups for these 2 studies were quite different, making any summary measures a challenge.

TABLE 2. - Anti-rotavirus Immunogenicity Evaluations Including Nutritional Status as a Predictor, 2006–2020
Vaccine Type of Study Year of Publication Country Age Group Study Setting Rotavirus Endpoint Indicator of Malnutrition Key Finding Reference
Rotarix Randomized trial 2016 Bangladesh <6 months Community IgA (seroconversion) Length-for-age No association 32
Weight-for-length No association
Rotarix Randomized trial 2020 Zimbabwe <18 months Community IgA (seroconversion) Weight-for-age No association 33
Length-for-age Well-nourished associated with seroconversion
Weight-for-length No association
IgA (seropositivity) Weight-for-age Well-nourished associated with seroconversion in univariate model only
Length-for-age Well-nourished associated with seroconversion
Weight-for-length No association

Rotavirus Prevalence by Nutritional Status

We identified 3 cohort and 6 cross-sectional studies comparing natural rotavirus infection and illness in well-nourished and malnourished children published 1990–2019 (Table 3). In one of the 9 studies, data were collected in 8 countries and rotavirus vaccine was available in half of the countries during part or all of the data collection period; in all other studies, rotavirus vaccines were not available through the national immunization program at the time of data collection. Overall, of the 12 countries that are represented, 11 are low-income or middle-income countries. Study populations and design were variable in these evaluations; malnutrition was assessed at different timepoints relative to testing for rotavirus, making comparisons across studies challenging. In 2 studies that considered rotavirus infection as the endpoint, there was no association found with length-for-age, weight-for-age or weight-for-length. In the 7 studies where rotavirus illness was the outcome of interest, 4 found malnourished children were less likely to have rotavirus diarrhea than well-nourished children and 3 found no association. Finally, 1 study in a prevaccine setting found lower IgG titers in weight-for-age malnourished children than well-nourished children and no differences in IgM titers by anthropometric indicators of malnutrition. Overall, none of the articles found malnourished children were more likely to have rotavirus than well-nourished children.

TABLE 3. - Scientific Articles Showing Prevalence of Rotavirus Stratified by Nutritional Status
Vaccine Type of Study Year of Publication Country Age Group Recruitment Setting Rotavirus Endpoint Indicator of Malnutrition Key Finding Reference
Rotarix (4 countries)/none (4 countries) Cohort 2017 Bangladesh, Brazil, India, Nepal, Peru, Pakistan, South Africa, Tanzania <24 months old Community Rotavirus positive diarrhea, rotavirus infection Length-for-age, weight-for-age, weight-for-length No association 34
None Cohort 2016 Bangladesh <3 years old Community Rotavirus positive diarrhea Length-for-age, weight-for-age, weight-for-length Associated with better nourishment 35
None Cohort 2019 Malawi 6–18 months old Community Rotavirus infection Length-for-age (excluded children with wasting) No association 36
None Cross-sectional 1990 Israel <3 years old Outpatient Rotavirus positive diarrhea Weight-for-length No association 37
None Cross-sectional 1995 Ecuador 12–59 months Community IgM, IgG titers Length-for-age, weight-for-age, weight-for-length, Zinc, Hemoglobin, Vitamin A Higher IgG associated with normal weight-for-age 38
None Cross-sectional 1998 Bangladesh <5 years old Inpatient Rotavirus positive diarrhea Length-for-age, weight-for-age, weight-for-length Associated with better nourishment 23
None Cross-sectional 2011 Burkina Faso <5 years old Outpatient, inpatient Rotavirus positive diarrhea Length-for-age, weight-for-age, weight-for-length Associated with better nourishment 39
None Cross-sectional 2013 Bangladesh <5 years old Inpatient Rotavirus positive diarrhea Weight-for-age Associated with better nourishment 24
None Cross-sectional 2017 Tanzania <5 years old Outpatient Rotavirus positive diarrhea Weight-for-length No association 40

DISCUSSION

We found in 9 of 11 analyses that the rotavirus VE point estimate was lower among malnourished children compared with well-nourished children. The VE among well-nourished children was remarkably consistent across studies, with a range of <20 percentage points for each vaccine and were slightly higher than those found by a meta-analysis of post-introduction VE,5 which included both well-nourished and malnourished children. Overall, rotavirus VE among malnourished children was consistently lower than for well-nourished children in studies that measured malnutrition at the time of the child’s illness and mostly lower in the clinical trials, where malnutrition was measured at the time of vaccination (~6 weeks of age). However, unlike well-nourished children, there was a wide range of VE estimates among malnourished children, even among studies using the same anthropometric indicators of malnutrition, though the overall medians were similar between observational and trial data. Although we did not formally include sample size in this evaluation due to inconsistent reporting of subpopulation sample sizes, fewer children were malnourished than well-nourished, likely making the VE estimates for malnourished children less precise and more unstable. We chose not to do a formal meta-analysis because of the small sample size and variation in study design, measurement of malnutrition and timing of malnutrition assessment, as well as age groups and child mortality level of the study setting, which have been associated with variation in VE.

The relative difference between VE among chronically malnourished (low length-for-age) and well-nourished children was consistent; this relative difference was considerably more variable when using other indicators of malnutrition which relied on the child’s weight, though the median percent differences in length-for-age and weight-for-age were similar. As rotavirus diarrhea is dehydrating, weight at the time of illness, which was used in several of the case-control evaluations, may be especially susceptible to misclassification. The 2 studies that presented VE for all 3 measures of malnutrition found variation between anthropometric indicators of malnutrition, and the trends in this variation were not consistent. There was also no obvious pattern in these findings by anthropometric indicators of malnutrition in the articles showing natural rotavirus infection and illness. More generally, anthropometric indicators of malnutrition may be caused by an array of conditions.13,41 Studies included in this literature review also varied in when illness occurred relative to when malnutrition was measured and anthropometric indicators of malnutrition at 6 weeks of age including low birth weight and prematurity are correlated with, but distinct from, malnutrition later in infancy or in the second year of life.13 Future research evaluating rotavirus vaccine performance should carefully consider which indicators of malnutrition and when they are measured.

While the findings from studies of prevalence rotavirus infection and illness stratified by nutritional status were mixed, none of the studies reported malnourished children were more likely to have rotavirus than well-nourished children and several studies reported that malnourished children were less likely to have rotavirus than well-nourished children. This is a noteworthy finding because malnourished children have been found to be more susceptible to other enteropathogens20,41,42 and it is unlikely that this finding is due to a difference in exposure to rotavirus among well-nourished and malnourished children. Additional research could help better understand possible mechanisms for differences in susceptibility to natural rotavirus infection and disease, as it may help our understanding of live, oral rotavirus vaccine performance in malnourished children. It is plausible that as the same mechanism that may make malnourished children less susceptible to rotavirus disease, despite probably being exposed at a similar level as well-nourished children, could also impair malnourished children from mounting an immune response after exposure to the live, oral vaccines. If malnourished children are less susceptible to rotavirus infection and illness, this would also have important implications for rotavirus vaccine research design, for example, in estimating appropriate sample size for stratified analyses to evaluate vaccine performance. Nonetheless, protection from rotavirus, which includes high vaccination coverage, is important for malnourished children, because if infected, malnourished children are more likely to have prolonged diarrhea and generally worse outcomes than well-nourished children.13,39

This literature review has several limitations. First, none of these studies were specifically powered to look at differences in VE among well-nourished and malnourished children. Thus, while the consistency of the findings of the lower point estimate of VE among malnourished infants in most studies supports that this is a real phenomenon, the overlap in VE confidence intervals between the 2 groups preclude firm conclusions. Second, while we intended to be as comprehensive as possible, analyses of the association of rotavirus infection and illness with malnutrition were often secondary and we used PubMed as our only search engine. It is possible we did not identify all published articles. However because the original VE literature review was extensive,5 we are confident all post-introduction VE articles stratified by nutritional status were included here. Third, there were a limited number of articles overall and no post-introduction VE evaluations of RotaTeq, Rotasiil or ROTAVAC stratified by nutritional status. Finally, sample sizes of subpopulations were not well documented, making it challenging to assess the quality and provide appropriate comparisons. Confidence intervals are quite wide and the sample sizes available indicate that these studies may have been underpowered for these analyses.

In this literature review, we found that rotavirus vaccines may offer less protection to children with malnutrition than well-nourished children, though they likely offer some protection. As malnourished children often have worse outcomes from diarrhea, better understanding of oral rotavirus vaccine performance in this population is important.

REFERENCES

1. WHO. Rotavirus vaccines WHO position paper. Weekly Epidemiological Record. 2013;88:49–64.
2. Tate JE, Burton AH, Boschi-Pinto C, et al.; World Health Organization-Coordinated Global Rotavirus Surveillance Network. Global, regional, and national estimates of rotavirus mortality in children <5 years of age, 2000-2013. Clin Infect Dis. 2016;62(suppl 2):S96–S105.
3. Burke RM, Tate JE, Kirkwood CD, et al. Current and new rotavirus vaccines. Curr Opin Infect Dis. 2019;32:435–444.
4. Department of Immunization, Vaccines and Biologicals. Vaccine in National Immunization Programme Update. In: Immunization Analysis and Insights. World Health Organization; 2020. Available at: https://www.who.int/immunization/monitoring_surveillance/en/.
5. Burnett E, Parashar UD, Tate JE. Real-world effectiveness of rotavirus vaccines, 2006-19: a literature review and meta-analysis. Lancet Glob Health. 2020;8:e1195–e1202.
6. Clark A, van Zandvoort K, Flasche S, et al. Efficacy of live oral rotavirus vaccines by duration of follow-up: a meta-regression of randomised controlled trials. Lancet Infect Dis. 2019;19:717–727.
7. Velasquez DE, Parashar U, Jiang B. Decreased performance of live attenuated, oral rotavirus vaccines in low-income settings: causes and contributing factors. Expert Rev Vaccines. 2018;17:145–161.
8. Parker EP, Ramani S, Lopman BA, et al. Causes of impaired oral vaccine efficacy in developing countries. Future Microbiol. 2018;13:97–118.
9. UNICEF. Malnutrition March 2020. 2020. Available at: https://data.unicef.org/topic/nutrition/malnutrition/. Accessed September 15, 2020.
10. Haiti: WHO and UNICEF coverage estimates of immunization coverage: 2019 revision. World Health Organization; 2020. Available at: https://www.who.int/immunization/monitoring_surveillance/data/hti.pdf.
11. Korpe PS, Petri WA Jr. Environmental enteropathy: critical implications of a poorly understood condition. Trends Mol Med. 2012;18:328–336.
12. Adair LS, Fall CH, Osmond C, et al.; COHORTS group. Associations of linear growth and relative weight gain during early life with adult health and human capital in countries of low and middle income: findings from five birth cohort studies. Lancet. 2013;382:525–534.
13. Black RE, Victora CG, Walker SP, et al.; Maternal and Child Nutrition Study Group. Maternal and child undernutrition and overweight in low-income and middle-income countries. Lancet. 2013;382:427–451.
14. Blossner M, de Onis M. Malnutrition: Quantifying the health impact at national and local levels. In: Annette PÜ, Diarmid CL, Carlos C, Alistair W, eds. Nutrition for Health and Development WHO. World Health Organization; 2005.
15. Caulfield LE, Bose A, Chandyo RK, et al.; MAL-ED Network Investigators. Infant feeding practices, dietary adequacy, and micronutrient status measures in the MAL-ED study. Clin Infect Dis. 2014;59(suppl 4):S248–S254.
16. Harper KM, Mutasa M, Prendergast AJ, et al. Environmental enteric dysfunction pathways and child stunting: a systematic review. PLoS Negl Trop Dis. 2018;12:e0006205.
17. Petri WA Jr, Naylor C, Haque R. Environmental enteropathy and malnutrition: do we know enough to intervene? BMC Med. 2014;12:187.
18. Prendergast A, Kelly P. Enteropathies in the developing world: neglected effects on global health. Am J Trop Med Hyg. 2012;86:756–763.
19. Hoke MK, McCabe KA, Miller AA, et al. Validation of endotoxin-core antibodies in dried blood spots as a measure of environmental enteropathy and intestinal permeability. Am J Hum Biol. 2018;30:e23120.
20. Ibrahim MK, Zambruni M, Melby CL, et al. Impact of childhood malnutrition on host defense and infection. Clin Microbiol Rev. 2017;30:919–971.
21. Prendergast AJ. Malnutrition and vaccination in developing countries. Philos Trans R Soc Lond B Biol Sci. 2015;370:20140141.
22. Church JA, Parker EP, Kosek MN, et al. Exploring the relationship between environmental enteric dysfunction and oral vaccine responses. Future Microbiol. 2018;13:1055–1070.
23. Dewan N, Faruque AS, Fuchs GJ. Nutritional status and diarrhoeal pathogen in hospitalized children in Bangladesh. Acta Paediatr. 1998;87:627–630.
24. Das SK, Chisti MJ, Huq S, et al. Clinical characteristics, etiology and antimicrobial susceptibility among overweight and obese individuals with diarrhea: observed at a large diarrheal disease hospital, Bangladesh. PLoS One. 2013;8:e70402.
25. Wickham H. ggplot2: Elegant Graphics for Data Analysis. Springer International Publishing; 2016.
26. Perez-Schael I, Salinas B, Tomat M, et al. Efficacy of the human rotavirus vaccine RIX4414 in malnourished children. J Infect Dis. 2007;196:537–540.
27. Gastañaduy PA, Steenhoff AP, Mokomane M, et al. Effectiveness of monovalent rotavirus vaccine after programmatic implementation in Botswana: a multisite prospective case-control study. Clin Infect Dis. 2016;62 Suppl 2:S161–S167.
28. Bar-Zeev N, Jere KC, Bennett A, et al.; Vaccine Effectiveness and Disease Surveillance Programme, Malawi (VACSURV) Consortium. Population impact and effectiveness of monovalent rotavirus vaccination in urban Malawian children 3 years after vaccine introduction: ecological and case-control analyses. Clin Infect Dis. 2016;62 Suppl 2:S213–S219.
29. Khagayi S, Omore R, Otieno GP, et al. Effectiveness of monovalent rotavirus vaccine against hospitalization with acute rotavirus gastroenteritis in Kenyan children. Clin Infect Dis. 2020;70:2298–2305.
30. Mujuru HA, Burnett E, Nathoo KJ, et al. Monovalent rotavirus vaccine effectiveness against rotavirus hospitalizations among children in Zimbabwe. Clin Infect Dis. 2019;69:1339–1344.
31. Gruber JF, Hille DA, Liu GF, et al. Heterogeneity of rotavirus vaccine efficacy among infants in developing countries. Pediatr Infect Dis J. 2017;36:72–78.
32. Emperador DM, Velasquez DE, Estivariz CF, et al. Interference of monovalent, bivalent, and trivalent oral poliovirus vaccines on monovalent rotavirus vaccine immunogenicity in Rural Bangladesh. Clin Infect Dis. 2016;62:150–156.
33. Church JA, Chasekwa B, Rukobo S, et al. Predictors of oral rotavirus vaccine immunogenicity in rural Zimbabwean infants. Vaccine. 2020;38:2870–2878.
34. Mohan VR, Karthikeyan R, Babji S, et al.; Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED) Network Investigators. Rotavirus infection and disease in a multisite birth cohort: results from the MAL-ED Study. J Infect Dis. 2017;216:305–316.
35. Verkerke H, Sobuz S, Ma JZ, et al. Malnutrition is associated with protection from rotavirus diarrhea: evidence from a Longitudinal Birth Cohort Study in Bangladesh. J Clin Microbiol. 2016;54:2568–2574.
36. Lehto KM, Fan YM, Oikarinen S, et al. Presence of Giardia lamblia in stools of six- to 18-month old asymptomatic Malawians is associated with children’s growth failure. Acta Paediatr. 2019;108:1833–1840.
37. Dagan R, Bar-David Y, Sarov B, et al. Rotavirus diarrhea in Jewish and Bedouin children in the Negev region of Israel: epidemiology, clinical aspects and possible role of malnutrition in severity of illness. Pediatr Infect Dis J. 1990;9:314–321.
38. Brüssow H, Sidoti J, Dirren H, et al. Effect of malnutrition in Ecuadorian children on titers of serum antibodies to various microbial antigens. Clin Diagn Lab Immunol. 1995;2:62–68.
39. Nitiema LW, Nordgren J, Ouermi D, et al. Burden of rotavirus and other enteropathogens among children with diarrhea in Burkina Faso. Int J Infect Dis. 2011;15:e646–e652.
40. Andersson ME, Elfving K, Shakely D, et al. Rapid clearance and frequent reinfection with enteric pathogens among children with acute diarrhea in Zanzibar. Clin Infect Dis. 2017;65:1371–1377.
41. Walson JL, Berkley JA. The impact of malnutrition on childhood infections. Curr Opin Infect Dis. 2018;31:231–236.
42. Platts-Mills JA, Taniuchi M, Uddin MJ, et al. Association between enteropathogens and malnutrition in children aged 6-23 mo in Bangladesh: a case-control study. Am J Clin Nutr. 2017;105:1132–1138.
Keywords:

Rotavirus; rotavirus vaccine; vaccine effectiveness; literature review; malnutrition

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