Author: Walker, P F
Date published: March 25, 2011
Since 2008, approximately 30,000 Bhutanese refugees have been resettled in the United States. Routine medical examinations of refugees after arrival in resettlement states indicated hematologic and neurologic disorders caused by vitamin B 12 deficiency These cases were reported by examining physicians and state health departments to CDC, which initiated an investigation. This report summarizes the results ofthat investigation. Sera from overseas medical examinations, postarrivai examinations in three state health departments (Minnesota, Utah, and Texas), and medical records and interviews at a health clinic in St. Paul, Minnesota, were evaluated. Vitamin B 1 2 deficiency, defined as serum vitamin B 1 2 concentration <203 pg/mL, was found in 64% (63 of 99) of overseas specimens, 27% (17 of 64) of postarrivai medical screenings, and 32% (19 of 60) of Bhutanese refugees screened for vitamin Bl 2 deficiency at the St. Paul clinic. Although the deficiencies might be multifactorial, the main cause is thought to be the diet consumed by these refugees for nearly two decades in Nepal, which lacked meat, eggs, and dairy products, the major dietary sources of vitamin B 12. Additionally, infection with Helicobacter pylori might play a role. Clinicians should be aware of the risk for vitamin B 12 deficiency in Bhutanese refugees. All Bhutanese refugees should be given nutrition advice and should receive supplemental vitamin B 12 upon arrival in the United States. In addition, refugees with clinical manifestations suggestive of deficiency should be tested for adequate serum vitamin B 12 concentrations and, if found to have a Bl 2 deficiency, screened for underlying causes, treated with parenteral vitamin B12 or high-dose oral supplements, and evaluated for response to therapy.
Approximately 108,000 ethnic Nepalis were forced from their longstanding homes in Bhutan in the early 1990s and have since been living in Nepal. Since March 2008, approximately 30,000 Bhutanese refugees have arrived in the United States, with many more expected. In the Nepalese camps, rations provided by the World Food Programme and the United Nations High Commissioner for Refugees consist of rice, lentils, chickpeas, vegetable oil, sugar, salt, and fresh vegetables (I). Only certain refugees, including young and malnourished children, pregnant and lactating women, and active tuberculosis patients, receive additional rations and multivitamin supplements. A locally made, fortified, blended food containing vitamin B 12 and other micronutrients is available in Nepalese camps but might not be consumed regularly by all refugees. Other micronutrient deficiencies, including vitamin B2 (riboflavin), have been identified in this population (2).
This investigation examined three sources of data: 1) test results from sera collected during overseas medical examinations, 2) results of postarrivai examinations collected by three state health departments, and 3) medical records and interviews at a health clinic in St. Paul. CDCs Migrant Serum Bank contains de-identified surplus serum specimens collected during mandatory overseas medical screening examinations for refugees. Serum vitamin B12 concentrations were tested in 99 randomly selected specimens from adult Bhutanese refugees collected during December 2007-November 2008. Total serum vitamin B 12 was measured using the Roche E- 170 automated electrochemiluminescence immunoassay. Vitamin Bl 2 deficiency, defined as a serum concentration of <203 pg/mL (150 pmol/L) (3), was detected in 63 (64%) refugees, including 28 (60%) females and 35 (67%) males (Table 1).
Serum vitamin B12 concentrations were measured during the postarrivai medical screening examinations for all resettled refugees in three states during September 2010- January 2011. The 326 refugees screened came from 12 countries of origin, including Bhutan (Table 2). Of the Bhutanese tested, 32% (17 of 53) of persons aged >1 5 years were B12 deficient. None of the 13 children aged <15 years were Bl 2 deficient, and the median level decreased with increasing age group. Other than the Bhutanese, only the Somali population had any B 1 2-deficient persons (10 [12%] of 82 screened).
Medical records were reviewed for 141 Bhutanese refugees seen at a health clinic in St. Paul during June 2009- January 201 1; 60 had serum vitamin Bl 2 levels tested, and 19 (32%) were B 12 deficient. Only one (7%) of 14 children aged <15 years was B12 deficient. None of the 19 Bl 2-deficient patients were anemic; however, four (21%) had macrocytosis, and two (11%) had peripheral neuropathy (Table 3). Of six B 1 2-deficient patients tested for antibodies to H pylori, a potential cause of vitamin B12 deficiency, five were positive, whereas only one of four nondeficient patients was positive.
Vitamin B 12, or cobalamin, is obtained naturally only from products of animal origin, including meat, eggs, and dairy products, but also is supplied in Western diets by fortified cereals. The recommended dietary allowance for adults is 2.4 /¿g/day* Vitamin Bl 2 deficiencies lead to delayed DNA synthesis resulting in megaloblastic anemia, peripheral neuropathy, and other neurologic signs 4,5). The deficiency commonly is caused by low dietary intake or food-cobalamin malabsorption disorder, which usually is associated with atrophic gastritis, with or without H. pylori infection (4). The deficiency also can be caused by an inherited or acquired lack of the intrinsic factor required for absorption of vitamin B 12, a condition known as pernicious anemia. A recent World Health Organization Technical Consultation recommends a threshold of <203 pg/mL (150 pmol/L) for describing population-level deficiencies; however, clinical deficiencies occasionally can be observed at higher serum levels (3). In the United States, the prevalence of deficiency is low (<1%- 6%) (6). In the developing world, deficiencies are more common because of limited access to products of animal origin (7). In a survey of pregnant Nepali women conducted during 1994-1995, 49% demonstrated dietary Bl 2 deficiency, with serum Bl 2 concentrations <1 50 pmol/L (8).
Analysis of the three data sources described in this report suggests prevalent vitamin B12 deficiency in the Bhutanese refugee population. The highest proportion of Bl 2 deficiencies (64%) was observed in the testing results from serum collected in overseas screening examinations during 2007-2008. Lower proportions (27% and 32%) were observed in samples collected in the United States during 2009-201 1 . This might be explained by possible recent improvement in nutrition in the camps (although no official ration changes were made) or a higher proportion of children aged <15 years in the domestic samples from 2009 to 201 1 (approximately 5-10 years are required for body stores of vitamin B12 to become depleted) (4). Of concern in this population is the unusually high proportion of young and middle-aged adults affected; breast-fed infants of mothers who have vitamin Bl 2 deficiency can develop permanent neurologic damage (9). The most likely cause of the deficiency in this population is inadequate dietary intake; however, other secondary causes, such as chronic gastritis, potentially caused by H. pylori infection, cannot be ruled out. Infection with H. pylori was more prevalent among Bl 2-deficient patients in a small group that was tested. Further investigations will seek the underlying cause and determine the prevalence of other micronutrient deficiencies in this population.
The findings in this report are subject to at least three limitations. First, the three-state postarrivai screening data sample was incomplete. Only one clinic in Texas participated, although numerous clinics conduct refugee screening in that state. In Minnesota, vitamin B 12 concentrations were returned for only 49% (231 of 476) of refugees screened during the investigation period because of delayed reporting. Second, the limited screening data available for Bhutanese children aged <1 5 years make drawing conclusions about vitamin Bl 2 deficiency in this age group difficult. However, because children and nursing mothers receive micronutrient supplementation in the camps (1) and deficiency takes years to develop, children might be less likely to be deficient. Finally, because refugees are at risk for serious health problems other than micronutrient deficiencies that are a priority for clinicians during screening examinations, underscreening or underrecording in the St. Paul medical records of any potential clinical manifestations of vitamin B 1 2 deficiency might have occurred. The prevalence of the signs and symptoms of vitamin B12 deficiency most likely is underestimated in this report.
The results of this investigation suggest that all Bhutanese refugees should be provided with nutrition advice that emphasizes consumption of foods containing vitamin Bl 2 and should receive oral supplementation for a minimum of 30 days upon arrival in the United States. Although no specific guidelines exist, two recent studies indicate that the lowest dose of oral cyanocobalamin needed to normalize metabolites in subclinical vitamin B 12 deficiency is 500-1,000 /¿g daily' During postarrivai medical screening and follow-up examinations, this population should be screened for clinical signs and symptoms of the deficiency, such as megaloblastic anemia, peripheral neuropathy, and other neurologic disorders (4,5). Those exhibiting these conditions should be tested for adequate serum vitamin Bl 2 concentrations and underlying causes of vitamin B12 deficiency (e.g., H pylori). Bl 2-deficient patients should be treated with parenteral or high-dose oral vitamin B 12, given appropriate treatments for underlying causes, and carefully monitored to assess response to therapy (10). In addition, clinicians should consider that other nutritional deficiencies are a concern in Bhutanese and other refugee populations.
This report is based, in part, on contributions by C Conner, HealthPartners Center for International Health, St. Paul; G Plotnikoff, Allina Center for Health Care Innovation, Minneapolis; M Abassi, U Jongwutiwes, S Lee, W Stauffer, Univ of Minnesota; G Dowdle, Utah Dept of Health; L Buxton, A Reyes, A Suton, Refugee Health Screening Clinic, Austin/Travis County Health and Human Svcs, Austin; J Montour, Texas Dept of State Health Sycs; and D Lee, Y Liu, Z Wang, M Weinberg, T Mitchell, H Burke, C Brown, Div of Global Migration and Quarantine; JJ Sejvar, Div of High- Consequence Pathogens and Pathology and Div of VectorBorne Infectious Diseases, National Center for Emerging and Zoonotic Infectious Diseases; M Ser dula, MD, K Scanion, PhD, Div of Nutrition, Physical Activity, and Obesity, National Center for Chronic Disease Prevention and Health Promotion; DJ LaVoie, DJ Rabinowitz, HP Chen, and C Dodson, Div of Laboratory Sciences, National Center for Environmental Health, CDC.
* Additional information available at http://ods.od.nih.gov/factsheets/vitaminb12.
[dagger] Additional information available at http://www.cdc.gov/ncbddd/bl2/documents/b12-030910.pdf.
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PF Walker, MD, HealthPartners Center for International Health, St. Paul; A OTallon, MA, K Nelson, MPH, B Mamo, MPH, S Dicker, MS, MPH, S Chute, MPP, R Lynfield, MD, Minnesota Dept of Health. P Swoboda, MD, M Rabin, MD, Salt Lake Family Health Center, Salt Lake City, Utah. S Householder, MPH, Texas Dept of State Health Sv cs. J Painter, DVM, W Zhou, MD, PhD, Div of Global Migration and Quarantine, National Center for Emerging and Zoonotic Infectious Diseases; CM Pfeiffer, PhD , Div of Laboratory Sciences, National Center for Environmental Health; SE Dunkle, DVM, JL Foltz, MD, EIS officers, CDC.