Standard growth and diarrhea‐associated growth faltering in captive infant rhesus macaques (Macaca mulatta)

Abstract

Reference growth studies of captive rhesus macaque infants have not accounted for diarrhea and the potential for growth stunting or growth faltering. Healthy infants without diarrhea could be used to build a standard growth chart and a tool used to detect growth faltering associated with diarrhea. We hypothesized infants who develop diarrhea during the first year of life would experience decreased linear weight gain compared to healthy infants, and we used healthy infants to establish standard growth of male and female infants. We hypothesized the lower 3rd percentile of standard growth would be cut-off criteria used in screening for diarrhea-associated growth faltering. Using a retrospective cohort of 6510 infant weight records in a multiple linear regression, daily weight gain through the first year of life was determined by sex, housing type, and health status. Male standard growth was 4.1 g/day (95% CI: 4.0 – 4.2 g/day) in corrals and 4.7 g/day (95% CI: 4.5 – 4.8 g/day) in shelter housing. Female standard growth was 4.0 g/day (95% CI: 3.8 – 4.2 g/day) in corrals and 4.4 g/day (95% CI: 4.0 – 4.7 g/day) in shelter housing. Diarrhea was significantly associated with decreased linear weight gain by up to 34% during the first year of life. Odds of growth faltering of infants, defined as those falling below the 3rd percentile of standard growth, were at least 8.9 higher given a history of diarrhea compared to healthy. The growth faltering cut-off criteria had a sensitivity of at least 53% for males and females to screen for diarrhea in infants between 6 and 12 months in shelters housing. Interinstitutional collaborations of infant rhesus macaque weight records would refine the standard growth charts and cut-off criteria, and additional morphometric data would provide a more nuanced picture of growth stunting

Maturation of the infant rhesus macaque gut microbiome and its role in the development of diarrheal disease

“…As recently reported in an independent cohort [56], diarrhea was associated with physical growth faltering as these 15 infants weighed significantly less than infants that remained asymptomatic at 6 and 8 months of age (Fig. 4a).…”

“…In this study, we leveraged the infant rhesus macaque animal model to investigate the role of the microbiome in mediating susceptibility to diarrheal diseases. Here we define the maturation of the infant rhesus macaque gut microbiome through the first 8 months of life, the window during which infant macaques are at the highest risk of developing chronic diarrhea [45, 56]. Additionally, we used shotgun metagenomics to functionally characterize the microbial communities in animals that developed diarrhea versus those that remained asymptomatic before disease onset in order to identify potential biomarkers of susceptibility.…”

Growth faltering regardless of chronic diarrhea is associated with mucosal immune dysfunction and microbial dysbiosis in the gut lumen

“…Rhesus macaques housed at the Oregon National Primate Research Center (ONPRC) and California National Primate Research Center (CNPRC) naturally develop the diarrheal disease at a predictable yearly rate with Campylobacter and Shigella being the primary pathogens isolated at clinic admission 36 – 38 . In addition, infant macaques that experience diarrhea suffer growth faltering 37 . Rhesus macaques also display a high pathogen burden even in the absence of diarrheal disease, as described in infants 19 .…”

Vaccine-mediated protection against Campylobacter -associated enteric disease

“…Given the burden of diarrhea observed in shelter-housed animals ( Fig. 1A) and the substantial negative impact of diarrheal disease on animal health (7,8), we initiated a vaccine development program with an initial focus on C. coli (i.e., H 2 O 2 -Campy C ) since it represented the most common enteric pathogen encountered among hospitalized RM cases (Fig. 1B).…”

“…Here, we explored an environmental exposure model of Campylobacter infection in rhesus macaques (RMs) to test the efficacy of potential vaccine candidates. Outdoorhoused RM at the Oregon National Primate Research Center (ONPRC) experience a spectrum of acute and recurrent C. jejuni-and C. coliassociated diarrheal disease that mimics several aspects of Campylobacterassociated disease found among human populations that suffer from conditions of poor sanitation and hygiene, including (i) dysbiotic microbiomes, (ii) symptomatic and asymptomatic carriage, and (iii) higher disease incidence rates among infants with a concomitant increase in disease severity compared with adults (7,8).…”