SlideShare a Scribd company logo
1 of 3
Download to read offline
Short Report
Outbreak of beriberi in the
state of Maranha‹ o, Brazil:
revisiting the mycotoxin
aetiologic hypothesis
Helena Cristina Alves
Vieira Lima DDS MSc*
Eucilene Alves Santana Porto BS*
Jose´ Ricardo Pio Marins MD§
Rejane Maria Alves RN†
Rosaˆngela Rosa Machado MDV‡
Karla Neves Laranjeira Braga BS MS‡
Francisca Bernardes de Paiva SW**
Greice Madeleine
Ikeda Carmo MDV MS†
Ana Carolina Faria Silva
e Santelli MD MSc*
Jeremy Sobel MD MPH*††
*Brazilian Field Epidemiology Training Program, Secretariat
of Health Surveillance, Ministry of Health, Brasilia;
†
Foodborne and Waterborne Diseases Branch; ‡
Laboratory
Coordination Branch; §
Secretariat of Health Surveillance,
Ministry of Health, Brasilia, DF; **Secretariat of Health
Minas Gerais State, Brazil; ††
Centers for Disease Control and
Prevention, Atlanta, GA, USA
Correspondence to: Helena Cristina Alves Vieira Lima,
Centro de Pesquisa Gonc¸alo Moniz – CPqGM,
Rua Waldemar Falca˜o 121, Candeal – Salvador,
Bahia, Brazil, CEP: 40296-710
Email: helencris2006@gmail.com
TROPICAL DOCTOR 2010; 40: 95–97
DOI: 10.1258/td.2009.090439
SUMMARY Beriberi is caused by thiamine deficiency.
Early 20th century epidemics inJapan were attributed to
rice contaminated by citreoviridin mycotoxin. Our investi-
gation of an outbreak of beriberi in Brazil showed an
association of beriberi with the consumption of poor
quality subsistence farming rice, although, unlike other
investigators of this outbreak, we did not identify citreo-
viridin producing fungi in the implicated rice.
Introduction
Beriberi is a syndrome caused by thiamine deficiency.
Thiamine requirements may be increased by physical
exertion, hot climate, pregnancy, thyroid abnormalities,
infection, alcohol consumption or a diet of simple
carbohydrates.1
Beriberi manifests with peripheral neurologic symptoms of
paresthesias, pain, weakness or paralysis, and, centrally, the
Wernicke-Korsakoff syndrome of horizontal nystagmus,
ophthalmoplegia, ataxia and memory loss. Cardiovascular
involvement entails a high output cardiac failure due to pro-
found vasodilatation; the Japanese literature describes fulmi-
nant cardiac failure as ‘shoshin’.2
Japan experienced a massive epidemic of beriberi at the turn
of the 20th century. The epidemic coincided with rapid urbaniz-
ation and a shift to a diet predominantly consisting of polished
rice, often visibly contaminated with molds.3
Implementation
of rigorous rice quality control measures was followed by a
precipitous decline in the illness.3
Subsequently, Japanese
investigators suggested that this epidemic was caused by myco-
toxin citreoviridin, produced by Penicillum citreonigrum,
Aspergillus terreus and Eupenicillium ochrosalmoneum.
Citreoviridin produces a striking cardiac beriberi-like syndrome
in rodents.4–7
An outbreak of beriberi occurred in a poor, rural area of
Maranha˜o state, Brazil, in 2006. A substantial proportion of
rice consumed by the population is locally grown bysubsistence
farmers. This rice is dried on the ground and then polished in
small local unregulated rice establishments, where it is stored
in precarious conditions (Figure 1). In 2007 rice samples were
collected from local rice-polishing facilities; these yielded
citreoviridin-producing P. citreonigrun; citreoviridin was
present in the rice samples.8
Cases of beriberi continued into 2007. We conducted an
investigation to test the hypothesis that this persistent out-
break of beriberi was due to the contamination of rice with
citreoviridin mycotoxin.
Patients and methods
We conducted a 1:1 matched case control study. A case was a
person reported as having beriberi by Maranha˜o State
between January and June 2007. A control was a neighbour
residing to the right of the case-patient’s residence, who
did not have beriberi and did not consume thiamine sup-
plements. Data were collected by standard questionnaire.
We used McNemar Chi-square, Kruskal-Wallis and Student
t-tests. Analysis was conducted in EpiInfo 3.5.2. Serum
was collected for determination of thiamine levels (by high
performance liquid chromatography9
), transaminase, cre-
atine, kinase and creatine kinase-BB.
One kilogram of rice was collected from each case and
each control household. Rice was defined as commercial
(subject to sanitary inspection) or subsistence farming rice
(locally grown and polished in unregulated facilities). At
the Instituto de Tecnologia de Alimentos, Brazil, samples
were cultured and tested for the presence of mycotoxins,
including aflotoxins, ocratoxin, citrinine and citreoviridin.10
Tropical Doctor April 2010, 40 95
Results
In 2006 and 2007, 471 cases of beriberi were reported;
142 (30.0%) had onset symptoms in 2007. Of these, 52
(37.0%) were excluded because of incomplete addresses or a
different final diagnosis. We enrolled 90 cases and 90 controls.
Of the 90 cases, 73 (80.0%) were men, the median age was
31 years (range 14–55) and median schooling was four years
(range 0–11). Among the controls, 45 (50.0%) were men, the
median age was 25 years (1–86) and median schooling was
three years (range 0–11). The median monthly income of
the cases was US $131 (range US $0–539) and for the con-
trols it was US $185 (US $0–777). For 45 (50.0%) cases the
principal employment was field labour and for 43 (45.0%)
controls it was homemaking. Cases and controls had a low
calculated thiamine intake on a 24-hour food history –
0.7 mg/day (range 0.0–6.0 mg/day) and 0.6 mg/day
Figure 1 Drying, polishing and storage of rice from the region of beriberi outbreak, Maranha˜o
State, Brazil, 2007. (a) Drying the rice; (b) polishing and storing the rice
Table 1 Results of univariate and multivariate analysis of exposures and beriberi, Maranha˜o, Brazil, 2007
Exposures Cases n (%) Controls n (%) mOR 95% CI P value
Univariate analysis
Male 73 (81) 44 (49) 3.8 1.9–8.6 ,0.01
Alcohol consumption 50 (53) 10 (11) 8.8 3.5–28.4 ,0.01
Smoking 33 (36) 12 (13) 6.0 2.1–23.8 ,0.01
Intense physical activity 79 (88) 66 (73) 2.6 1.1–6.9 ,0.05
Mainly consumes subsistence farming rice 40 (44) 22 (24) 3.1 1.4–8.0 ,0.05
Consumes fermented mandioca flour 55 (61) 50 (55) 1.5 0.6–3.5 0.37
Consumes dry mandioca flour 9 (10) 16 (17) 0.5 0.2–1.3 0.12
Exposures mOR 95% CI P value
Multivariate analysis by conditional logistic regression
Alcohol consumption 7.8 3.2–19.0 ,0.01
Intense physical activity 4.2 1.5–11.9 ,0.01
Mainly consumes subsistence farming rice 3.2 1.5–7.1 ,0.01
Concurrent hypertension or diabetes 2.7 1.1–6.5 0.03
Male sex 2.4 1.0–5.6 0.04
Years of schooling 1.1 0.9–1.2 0.24
Thiamine intake 1.0 0.50–1.9 1.00
OR, odds ratio; CI, confidence interval
Short Report
96 Tropical Doctor April 2010, 40
(range 0.0–5.2 mg/day), respectively (recommended daily
intake is 1.2 mg/day).
Cases reported symptoms of paresthesia (77.0%); oedema
(75.0%) and calf pain (63.0%); 22 (24.0%) were hospital-
ized. At the time of interview, 64 (70.0%) were being
treated with thiamine and 51 (56.0%) were still symptomatic.
On univariate analysis, beriberi was associated with male
sex, the consumption of alcohol, smoking, physical activity
and consumption of subsistence farming rice. On multi-
variate analysis, independently associated factors were: the
consumption of alcohol; intense physical activity; consump-
tion of subsistence farming rice; co-morbidity; and male sex
(Table 1).
Serum was collected from case-patients a median of 63
days after thiamine replacement therapy. For case-patients
and controls, serum thiamine, transaminase and creatine
kinase levels were within normal limits.
Eighty-one rice samples were collected: 44 (55%) from
case households and 37 (45%) from control households.
Fifty-eight (72%) were of polished rice and 23 (28%)
samples were paddy.
Culture yielded xerophilic growth in 28 (64%) case and 21
(57%) control samples, including Aspergillus penicilioides
and A. versicolor. Additionally, fungi producing aflotoxin
(A. flavus, A. parasiticus), citrinine (P. citrinum) and ocra-
toxin A (A. niger) were isolated. No citreviridin-producing
fungi were cultured.
Conclusions
Cases of beriberi, initially detected in 2006, continue to be
reported in Maranha˜o State. In addition to the established
risk factors for the disease, we showed that there is an inde-
pendent association of illness with the consumption of unin-
spected subsistence agricultural rice, as opposed to
commercially processed and government inspected rice.
The main purpose of our study was to determine whether
citreoviridin mycotoxin was present in rice from case-patient
homes, given the extensive body of historical and toxicologi-
cal research from Japan supporting a role for this mycotoxin
in the pathogenesis of beriberi. However, no citreoviridin-
producing fungi were identified in rice samples from case-
patient or control homes. Accordingly, we cannot conclude
that this mycotoxin played a role in this protracted outbreak.
The limitations of this study include the obtainment of rice
samples weeks to months after the onset of the illness.
Samples may not have been from the same stock as that con-
sumed before onset of the illness, or may have been of the
same stock but, perhaps, had been subjected to conditions
that may have modified the fungal flora over time.
Additionally, most rice samples were of polished rice. Rice
polishing heats rice grains, which could have altered the
fungal flora while leaving mycotoxin intact. As no
citreoviridin-producing fungi were encountered, we did not
test directly for the presence of the toxin.
We recommend that the active surveillance and timely
treatment of case-patients, thiamine supplementation for the
population and quality and safety standards for transpor-
tation, storage and processing of subsistence farming rice
should be continued.
Acknowledgments
We thank the officials of the state and the municipal sec-
retaries of health in the state of Maranha˜o, Brazil, and col-
leagues of the Secretariat of Health Surveillance of the
Ministry of Health and the colleagues of Field
Epidemiology Training Program of Brazil.
References
1 Lonsdale D. A review of the biochemistry, metabolism and clini-
cal benefits of thiamin(e) and its derivatives. Evid Based
Complement Alternat Med 2006;3:49–59
2 Hoyumpa AM. Mechanism of vitamin deficiencies in alcoholism.
Alcohol Clin Exp Res 1986;10:572–81
3 Uraguchi K. Micotoxic origin of cardiac beriberi. J Stored Prod
Res 1969;5:27–36
4 Ueno Y, Ueno I. Isolation and acute toxicity of citreoviridin,
a neurotoxic micotoxin of Penicillium Citreo-Viride Biourge.
Jap J Exp Med 1972;42:91–105
5 Ohtsubo K. Mycotoxins in foodstuffs and their biological action
on mammals. Beitr Pathol Bd 1973;148:213–20
6 Murphy PA, Hendrich S, Landgren C, Bryant C. Food mycotox-
ins: an update. J Food Sci Chicago 2006;71:51–65
7 Smith JE, Henderson RS. Mycotoxins and Animal Foods.
London: CRC Press, 1991
8 Rosa CA, Keller KM, Oliveira AA, et al. Production of citreovir-
idin by Penicillium citreonigrum strains associated with rice con-
sumption and beriberi cases in the Maranhao State, Brazil. Food
Addit Contam Part A Chem Anal Control Expo Risk Assess
2009;29:1–8
9 Chatzimichalakis PF, Samanidou VF, Verpoorte R. Development
of a validated HPLC method for the determination of B-complex
vitamins in pharmaceuticals and biological fluids after solid
phase extraction. J Sep Sci 2004;27:181–8
10 Pitt JI, Hocking AD. Fungi and Food Spoilage. 2nd edn. London:
Blackie Academic & Professional, 1997: 593
Short Report
Tropical Doctor April 2010, 40 97

More Related Content

What's hot (7)

Unravelling fungal immunity through primary immune deficiencies
Unravelling fungal immunity through primary immune deficienciesUnravelling fungal immunity through primary immune deficiencies
Unravelling fungal immunity through primary immune deficiencies
 
Anil k. tyagi
Anil k. tyagiAnil k. tyagi
Anil k. tyagi
 
Holscher-JNutr2015
Holscher-JNutr2015Holscher-JNutr2015
Holscher-JNutr2015
 
Food protein induced enterocolitis syndrome (FPIES)
Food protein induced enterocolitis  syndrome (FPIES)Food protein induced enterocolitis  syndrome (FPIES)
Food protein induced enterocolitis syndrome (FPIES)
 
Atopic dermatitis: work in progress
Atopic dermatitis: work in progressAtopic dermatitis: work in progress
Atopic dermatitis: work in progress
 
Effect of crude oil pollution on phytochemical and anti diabetic potentials o...
Effect of crude oil pollution on phytochemical and anti diabetic potentials o...Effect of crude oil pollution on phytochemical and anti diabetic potentials o...
Effect of crude oil pollution on phytochemical and anti diabetic potentials o...
 
Luisetto m, behzad n a, ghulam r m. relapses and recurrent chronic bacteric p...
Luisetto m, behzad n a, ghulam r m. relapses and recurrent chronic bacteric p...Luisetto m, behzad n a, ghulam r m. relapses and recurrent chronic bacteric p...
Luisetto m, behzad n a, ghulam r m. relapses and recurrent chronic bacteric p...
 

Viewers also liked (14)

Beri beri
Beri beriBeri beri
Beri beri
 
Vitamina B1 - (Tiamina)
Vitamina B1 - (Tiamina)Vitamina B1 - (Tiamina)
Vitamina B1 - (Tiamina)
 
Vitamina b1
Vitamina b1 Vitamina b1
Vitamina b1
 
Beri beri
Beri beriBeri beri
Beri beri
 
El beriberi
El beriberiEl beriberi
El beriberi
 
Tiamina
TiaminaTiamina
Tiamina
 
Vitamina B1
Vitamina B1Vitamina B1
Vitamina B1
 
Vitamina b1 e b2 (complexo b)
Vitamina b1 e b2 (complexo b)Vitamina b1 e b2 (complexo b)
Vitamina b1 e b2 (complexo b)
 
Beri beri
Beri beriBeri beri
Beri beri
 
Thiamine
ThiamineThiamine
Thiamine
 
Seizures lecture
Seizures lectureSeizures lecture
Seizures lecture
 
Epilepsy.ppt
Epilepsy.pptEpilepsy.ppt
Epilepsy.ppt
 
Vitamina B1(tiamina)
Vitamina B1(tiamina)Vitamina B1(tiamina)
Vitamina B1(tiamina)
 
Vitaminas (apresentação 2)
Vitaminas (apresentação 2)Vitaminas (apresentação 2)
Vitaminas (apresentação 2)
 

Similar to Beriberi

Short Communication: Natural Prophylaxis to the Control of Swine Coccidiosis
Short Communication: Natural Prophylaxis to the Control of Swine CoccidiosisShort Communication: Natural Prophylaxis to the Control of Swine Coccidiosis
Short Communication: Natural Prophylaxis to the Control of Swine CoccidiosisAgriculture Journal IJOEAR
 
STUDY OF ASCITIC FLUID FOR DIAGNOSIS OF SPONTANEOUS BACTERIAL PERITONITIS (SB...
STUDY OF ASCITIC FLUID FOR DIAGNOSIS OF SPONTANEOUS BACTERIAL PERITONITIS (SB...STUDY OF ASCITIC FLUID FOR DIAGNOSIS OF SPONTANEOUS BACTERIAL PERITONITIS (SB...
STUDY OF ASCITIC FLUID FOR DIAGNOSIS OF SPONTANEOUS BACTERIAL PERITONITIS (SB...Earthjournal Publisher
 
Listeria monocytogenes: An emerging foodborne pathogen in Ghana?
Listeria monocytogenes: An emerging foodborne pathogen in Ghana? Listeria monocytogenes: An emerging foodborne pathogen in Ghana?
Listeria monocytogenes: An emerging foodborne pathogen in Ghana? ILRI
 
Mastitis in dairy cows a case study of public health hazard in Sau Pharsatik...
Mastitis in dairy cows  a case study of public health hazard in Sau Pharsatik...Mastitis in dairy cows  a case study of public health hazard in Sau Pharsatik...
Mastitis in dairy cows a case study of public health hazard in Sau Pharsatik...Bijay Khanal
 
Austin publishing group - Oral kefir grains supplementation improves metaboli...
Austin publishing group - Oral kefir grains supplementation improves metaboli...Austin publishing group - Oral kefir grains supplementation improves metaboli...
Austin publishing group - Oral kefir grains supplementation improves metaboli...Austin Publishing Group
 
Nutritional assessment by Dr. Rajan Bikram Rayamajhi
Nutritional assessment by Dr. Rajan Bikram RayamajhiNutritional assessment by Dr. Rajan Bikram Rayamajhi
Nutritional assessment by Dr. Rajan Bikram Rayamajhiwrigveda
 
2007 List SKIN PROTEOMICS
2007 List SKIN PROTEOMICS2007 List SKIN PROTEOMICS
2007 List SKIN PROTEOMICSEdward List
 
Biochemical changes associated with protein energy malnutrition among pregnan...
Biochemical changes associated with protein energy malnutrition among pregnan...Biochemical changes associated with protein energy malnutrition among pregnan...
Biochemical changes associated with protein energy malnutrition among pregnan...Alexander Decker
 
Doctor's Data Inc GI Pathogen Reference Guide
Doctor's Data Inc GI Pathogen Reference GuideDoctor's Data Inc GI Pathogen Reference Guide
Doctor's Data Inc GI Pathogen Reference GuideBonnieReynolds4
 
Final E poster WASET June 2014 Initial Examination of Facility and Meat Micro...
Final E poster WASET June 2014 Initial Examination of Facility and Meat Micro...Final E poster WASET June 2014 Initial Examination of Facility and Meat Micro...
Final E poster WASET June 2014 Initial Examination of Facility and Meat Micro...Susan Prattis VMD, Ph.D., MS, Dipl. ACLAM
 
Living microorganisms in therapy
Living microorganisms in therapyLiving microorganisms in therapy
Living microorganisms in therapyCSN Vittal
 
Better Milk Quality from Better Mastitis Therapy Decisions- Dr. Ron Erskine
Better Milk Quality from Better Mastitis Therapy Decisions- Dr. Ron ErskineBetter Milk Quality from Better Mastitis Therapy Decisions- Dr. Ron Erskine
Better Milk Quality from Better Mastitis Therapy Decisions- Dr. Ron ErskineDAIReXNET
 
Eubioflor aplicado en recién nacidos para regular la flora intestinal Scerbacova
Eubioflor aplicado en recién nacidos para regular la flora intestinal ScerbacovaEubioflor aplicado en recién nacidos para regular la flora intestinal Scerbacova
Eubioflor aplicado en recién nacidos para regular la flora intestinal ScerbacovaNaturpharma (Medicina Biológica)
 

Similar to Beriberi (20)

Short Communication: Natural Prophylaxis to the Control of Swine Coccidiosis
Short Communication: Natural Prophylaxis to the Control of Swine CoccidiosisShort Communication: Natural Prophylaxis to the Control of Swine Coccidiosis
Short Communication: Natural Prophylaxis to the Control of Swine Coccidiosis
 
STUDY OF ASCITIC FLUID FOR DIAGNOSIS OF SPONTANEOUS BACTERIAL PERITONITIS (SB...
STUDY OF ASCITIC FLUID FOR DIAGNOSIS OF SPONTANEOUS BACTERIAL PERITONITIS (SB...STUDY OF ASCITIC FLUID FOR DIAGNOSIS OF SPONTANEOUS BACTERIAL PERITONITIS (SB...
STUDY OF ASCITIC FLUID FOR DIAGNOSIS OF SPONTANEOUS BACTERIAL PERITONITIS (SB...
 
Listeria monocytogenes: An emerging foodborne pathogen in Ghana?
Listeria monocytogenes: An emerging foodborne pathogen in Ghana? Listeria monocytogenes: An emerging foodborne pathogen in Ghana?
Listeria monocytogenes: An emerging foodborne pathogen in Ghana?
 
Mastitis in dairy cows a case study of public health hazard in Sau Pharsatik...
Mastitis in dairy cows  a case study of public health hazard in Sau Pharsatik...Mastitis in dairy cows  a case study of public health hazard in Sau Pharsatik...
Mastitis in dairy cows a case study of public health hazard in Sau Pharsatik...
 
Austin publishing group - Oral kefir grains supplementation improves metaboli...
Austin publishing group - Oral kefir grains supplementation improves metaboli...Austin publishing group - Oral kefir grains supplementation improves metaboli...
Austin publishing group - Oral kefir grains supplementation improves metaboli...
 
Kidney health
Kidney healthKidney health
Kidney health
 
Kidney health
Kidney health Kidney health
Kidney health
 
Wips
WipsWips
Wips
 
Probiotics in Pediatric Practice
Probiotics in Pediatric PracticeProbiotics in Pediatric Practice
Probiotics in Pediatric Practice
 
Nutritional assessment by Dr. Rajan Bikram Rayamajhi
Nutritional assessment by Dr. Rajan Bikram RayamajhiNutritional assessment by Dr. Rajan Bikram Rayamajhi
Nutritional assessment by Dr. Rajan Bikram Rayamajhi
 
2007 List SKIN PROTEOMICS
2007 List SKIN PROTEOMICS2007 List SKIN PROTEOMICS
2007 List SKIN PROTEOMICS
 
Biochemical changes associated with protein energy malnutrition among pregnan...
Biochemical changes associated with protein energy malnutrition among pregnan...Biochemical changes associated with protein energy malnutrition among pregnan...
Biochemical changes associated with protein energy malnutrition among pregnan...
 
Doctor's Data Inc GI Pathogen Reference Guide
Doctor's Data Inc GI Pathogen Reference GuideDoctor's Data Inc GI Pathogen Reference Guide
Doctor's Data Inc GI Pathogen Reference Guide
 
Bovine mastitis at kari naivasha kampala presentation by dr. peter ndirangu
Bovine mastitis at kari naivasha kampala presentation by dr. peter ndiranguBovine mastitis at kari naivasha kampala presentation by dr. peter ndirangu
Bovine mastitis at kari naivasha kampala presentation by dr. peter ndirangu
 
Final E poster WASET June 2014 Initial Examination of Facility and Meat Micro...
Final E poster WASET June 2014 Initial Examination of Facility and Meat Micro...Final E poster WASET June 2014 Initial Examination of Facility and Meat Micro...
Final E poster WASET June 2014 Initial Examination of Facility and Meat Micro...
 
Living microorganisms in therapy
Living microorganisms in therapyLiving microorganisms in therapy
Living microorganisms in therapy
 
Probiotics
ProbioticsProbiotics
Probiotics
 
Better Milk Quality from Better Mastitis Therapy Decisions- Dr. Ron Erskine
Better Milk Quality from Better Mastitis Therapy Decisions- Dr. Ron ErskineBetter Milk Quality from Better Mastitis Therapy Decisions- Dr. Ron Erskine
Better Milk Quality from Better Mastitis Therapy Decisions- Dr. Ron Erskine
 
Eubioflor aplicado en recién nacidos para regular la flora intestinal Scerbacova
Eubioflor aplicado en recién nacidos para regular la flora intestinal ScerbacovaEubioflor aplicado en recién nacidos para regular la flora intestinal Scerbacova
Eubioflor aplicado en recién nacidos para regular la flora intestinal Scerbacova
 
09e414fb4d39590e0f000000
09e414fb4d39590e0f00000009e414fb4d39590e0f000000
09e414fb4d39590e0f000000
 

Recently uploaded

Male Infertility Panel Discussion by Dr Sujoy Dasgupta
Male Infertility Panel Discussion by Dr Sujoy DasguptaMale Infertility Panel Discussion by Dr Sujoy Dasgupta
Male Infertility Panel Discussion by Dr Sujoy DasguptaSujoy Dasgupta
 
PAIN/CLASSIFICATION AND MANAGEMENT OF PAIN.pdf
PAIN/CLASSIFICATION AND MANAGEMENT OF PAIN.pdfPAIN/CLASSIFICATION AND MANAGEMENT OF PAIN.pdf
PAIN/CLASSIFICATION AND MANAGEMENT OF PAIN.pdfDolisha Warbi
 
Bulimia nervosa ( Eating Disorders) Mental Health Nursing.
Bulimia nervosa ( Eating Disorders) Mental Health Nursing.Bulimia nervosa ( Eating Disorders) Mental Health Nursing.
Bulimia nervosa ( Eating Disorders) Mental Health Nursing.aarjukhadka22
 
Trustworthiness of AI based predictions Aachen 2024
Trustworthiness of AI based predictions Aachen 2024Trustworthiness of AI based predictions Aachen 2024
Trustworthiness of AI based predictions Aachen 2024EwoutSteyerberg1
 
BENIGN BREAST DISEASE
BENIGN BREAST DISEASE BENIGN BREAST DISEASE
BENIGN BREAST DISEASE Mamatha Lakka
 
Neurological history taking (2024) .
Neurological  history  taking  (2024)  .Neurological  history  taking  (2024)  .
Neurological history taking (2024) .Mohamed Rizk Khodair
 
historyofpsychiatryinindia. Senthil Thirusangu
historyofpsychiatryinindia. Senthil Thirusanguhistoryofpsychiatryinindia. Senthil Thirusangu
historyofpsychiatryinindia. Senthil Thirusangu Medical University
 
Female Reproductive Physiology Before Pregnancy
Female Reproductive Physiology Before PregnancyFemale Reproductive Physiology Before Pregnancy
Female Reproductive Physiology Before PregnancyMedicoseAcademics
 
Physiology of Smooth Muscles -Mechanics of contraction and relaxation
Physiology of Smooth Muscles -Mechanics of contraction and relaxationPhysiology of Smooth Muscles -Mechanics of contraction and relaxation
Physiology of Smooth Muscles -Mechanics of contraction and relaxationMedicoseAcademics
 
Unit I herbs as raw materials, biodynamic agriculture.ppt
Unit I herbs as raw materials, biodynamic agriculture.pptUnit I herbs as raw materials, biodynamic agriculture.ppt
Unit I herbs as raw materials, biodynamic agriculture.pptPradnya Wadekar
 
High-Performance Thin-Layer Chromatography (HPTLC)
High-Performance Thin-Layer Chromatography (HPTLC)High-Performance Thin-Layer Chromatography (HPTLC)
High-Performance Thin-Layer Chromatography (HPTLC)kishan singh tomar
 
SGK RỐI LOẠN TOAN KIỀM ĐHYHN RẤT HAY VÀ ĐẶC SẮC.pdf
SGK RỐI LOẠN TOAN KIỀM ĐHYHN RẤT HAY VÀ ĐẶC SẮC.pdfSGK RỐI LOẠN TOAN KIỀM ĐHYHN RẤT HAY VÀ ĐẶC SẮC.pdf
SGK RỐI LOẠN TOAN KIỀM ĐHYHN RẤT HAY VÀ ĐẶC SẮC.pdfHongBiThi1
 
Clinical Research Informatics Year-in-Review 2024
Clinical Research Informatics Year-in-Review 2024Clinical Research Informatics Year-in-Review 2024
Clinical Research Informatics Year-in-Review 2024Peter Embi
 
ANATOMICAL FAETURES OF BONES FOR NURSING STUDENTS .pptx
ANATOMICAL FAETURES OF BONES  FOR NURSING STUDENTS .pptxANATOMICAL FAETURES OF BONES  FOR NURSING STUDENTS .pptx
ANATOMICAL FAETURES OF BONES FOR NURSING STUDENTS .pptxWINCY THIRUMURUGAN
 
DNA nucleotides Blast in NCBI and Phylogeny using MEGA Xi.pptx
DNA nucleotides Blast in NCBI and Phylogeny using MEGA Xi.pptxDNA nucleotides Blast in NCBI and Phylogeny using MEGA Xi.pptx
DNA nucleotides Blast in NCBI and Phylogeny using MEGA Xi.pptxMAsifAhmad
 
CPR.nursingoutlook.pdf , Bsc nursing student
CPR.nursingoutlook.pdf , Bsc nursing studentCPR.nursingoutlook.pdf , Bsc nursing student
CPR.nursingoutlook.pdf , Bsc nursing studentsaileshpanda05
 
power point presentation of Clinical evaluation of strabismus
power point presentation of Clinical evaluation  of strabismuspower point presentation of Clinical evaluation  of strabismus
power point presentation of Clinical evaluation of strabismusChandrasekar Reddy
 

Recently uploaded (20)

Male Infertility Panel Discussion by Dr Sujoy Dasgupta
Male Infertility Panel Discussion by Dr Sujoy DasguptaMale Infertility Panel Discussion by Dr Sujoy Dasgupta
Male Infertility Panel Discussion by Dr Sujoy Dasgupta
 
PAIN/CLASSIFICATION AND MANAGEMENT OF PAIN.pdf
PAIN/CLASSIFICATION AND MANAGEMENT OF PAIN.pdfPAIN/CLASSIFICATION AND MANAGEMENT OF PAIN.pdf
PAIN/CLASSIFICATION AND MANAGEMENT OF PAIN.pdf
 
Bulimia nervosa ( Eating Disorders) Mental Health Nursing.
Bulimia nervosa ( Eating Disorders) Mental Health Nursing.Bulimia nervosa ( Eating Disorders) Mental Health Nursing.
Bulimia nervosa ( Eating Disorders) Mental Health Nursing.
 
Trustworthiness of AI based predictions Aachen 2024
Trustworthiness of AI based predictions Aachen 2024Trustworthiness of AI based predictions Aachen 2024
Trustworthiness of AI based predictions Aachen 2024
 
BENIGN BREAST DISEASE
BENIGN BREAST DISEASE BENIGN BREAST DISEASE
BENIGN BREAST DISEASE
 
Immune labs basics part 1 acute phase reactants ESR, CRP Ahmed Yehia Ismaeel,...
Immune labs basics part 1 acute phase reactants ESR, CRP Ahmed Yehia Ismaeel,...Immune labs basics part 1 acute phase reactants ESR, CRP Ahmed Yehia Ismaeel,...
Immune labs basics part 1 acute phase reactants ESR, CRP Ahmed Yehia Ismaeel,...
 
American College of physicians ACP high value care recommendations in rheumat...
American College of physicians ACP high value care recommendations in rheumat...American College of physicians ACP high value care recommendations in rheumat...
American College of physicians ACP high value care recommendations in rheumat...
 
Neurological history taking (2024) .
Neurological  history  taking  (2024)  .Neurological  history  taking  (2024)  .
Neurological history taking (2024) .
 
historyofpsychiatryinindia. Senthil Thirusangu
historyofpsychiatryinindia. Senthil Thirusanguhistoryofpsychiatryinindia. Senthil Thirusangu
historyofpsychiatryinindia. Senthil Thirusangu
 
Female Reproductive Physiology Before Pregnancy
Female Reproductive Physiology Before PregnancyFemale Reproductive Physiology Before Pregnancy
Female Reproductive Physiology Before Pregnancy
 
Physiology of Smooth Muscles -Mechanics of contraction and relaxation
Physiology of Smooth Muscles -Mechanics of contraction and relaxationPhysiology of Smooth Muscles -Mechanics of contraction and relaxation
Physiology of Smooth Muscles -Mechanics of contraction and relaxation
 
Unit I herbs as raw materials, biodynamic agriculture.ppt
Unit I herbs as raw materials, biodynamic agriculture.pptUnit I herbs as raw materials, biodynamic agriculture.ppt
Unit I herbs as raw materials, biodynamic agriculture.ppt
 
High-Performance Thin-Layer Chromatography (HPTLC)
High-Performance Thin-Layer Chromatography (HPTLC)High-Performance Thin-Layer Chromatography (HPTLC)
High-Performance Thin-Layer Chromatography (HPTLC)
 
SGK RỐI LOẠN TOAN KIỀM ĐHYHN RẤT HAY VÀ ĐẶC SẮC.pdf
SGK RỐI LOẠN TOAN KIỀM ĐHYHN RẤT HAY VÀ ĐẶC SẮC.pdfSGK RỐI LOẠN TOAN KIỀM ĐHYHN RẤT HAY VÀ ĐẶC SẮC.pdf
SGK RỐI LOẠN TOAN KIỀM ĐHYHN RẤT HAY VÀ ĐẶC SẮC.pdf
 
Clinical Research Informatics Year-in-Review 2024
Clinical Research Informatics Year-in-Review 2024Clinical Research Informatics Year-in-Review 2024
Clinical Research Informatics Year-in-Review 2024
 
ANATOMICAL FAETURES OF BONES FOR NURSING STUDENTS .pptx
ANATOMICAL FAETURES OF BONES  FOR NURSING STUDENTS .pptxANATOMICAL FAETURES OF BONES  FOR NURSING STUDENTS .pptx
ANATOMICAL FAETURES OF BONES FOR NURSING STUDENTS .pptx
 
DNA nucleotides Blast in NCBI and Phylogeny using MEGA Xi.pptx
DNA nucleotides Blast in NCBI and Phylogeny using MEGA Xi.pptxDNA nucleotides Blast in NCBI and Phylogeny using MEGA Xi.pptx
DNA nucleotides Blast in NCBI and Phylogeny using MEGA Xi.pptx
 
Biologic therapy ice breaking in rheumatology, Case based approach with appli...
Biologic therapy ice breaking in rheumatology, Case based approach with appli...Biologic therapy ice breaking in rheumatology, Case based approach with appli...
Biologic therapy ice breaking in rheumatology, Case based approach with appli...
 
CPR.nursingoutlook.pdf , Bsc nursing student
CPR.nursingoutlook.pdf , Bsc nursing studentCPR.nursingoutlook.pdf , Bsc nursing student
CPR.nursingoutlook.pdf , Bsc nursing student
 
power point presentation of Clinical evaluation of strabismus
power point presentation of Clinical evaluation  of strabismuspower point presentation of Clinical evaluation  of strabismus
power point presentation of Clinical evaluation of strabismus
 

Beriberi

  • 1. Short Report Outbreak of beriberi in the state of Maranha‹ o, Brazil: revisiting the mycotoxin aetiologic hypothesis Helena Cristina Alves Vieira Lima DDS MSc* Eucilene Alves Santana Porto BS* Jose´ Ricardo Pio Marins MD§ Rejane Maria Alves RN† Rosaˆngela Rosa Machado MDV‡ Karla Neves Laranjeira Braga BS MS‡ Francisca Bernardes de Paiva SW** Greice Madeleine Ikeda Carmo MDV MS† Ana Carolina Faria Silva e Santelli MD MSc* Jeremy Sobel MD MPH*†† *Brazilian Field Epidemiology Training Program, Secretariat of Health Surveillance, Ministry of Health, Brasilia; † Foodborne and Waterborne Diseases Branch; ‡ Laboratory Coordination Branch; § Secretariat of Health Surveillance, Ministry of Health, Brasilia, DF; **Secretariat of Health Minas Gerais State, Brazil; †† Centers for Disease Control and Prevention, Atlanta, GA, USA Correspondence to: Helena Cristina Alves Vieira Lima, Centro de Pesquisa Gonc¸alo Moniz – CPqGM, Rua Waldemar Falca˜o 121, Candeal – Salvador, Bahia, Brazil, CEP: 40296-710 Email: helencris2006@gmail.com TROPICAL DOCTOR 2010; 40: 95–97 DOI: 10.1258/td.2009.090439 SUMMARY Beriberi is caused by thiamine deficiency. Early 20th century epidemics inJapan were attributed to rice contaminated by citreoviridin mycotoxin. Our investi- gation of an outbreak of beriberi in Brazil showed an association of beriberi with the consumption of poor quality subsistence farming rice, although, unlike other investigators of this outbreak, we did not identify citreo- viridin producing fungi in the implicated rice. Introduction Beriberi is a syndrome caused by thiamine deficiency. Thiamine requirements may be increased by physical exertion, hot climate, pregnancy, thyroid abnormalities, infection, alcohol consumption or a diet of simple carbohydrates.1 Beriberi manifests with peripheral neurologic symptoms of paresthesias, pain, weakness or paralysis, and, centrally, the Wernicke-Korsakoff syndrome of horizontal nystagmus, ophthalmoplegia, ataxia and memory loss. Cardiovascular involvement entails a high output cardiac failure due to pro- found vasodilatation; the Japanese literature describes fulmi- nant cardiac failure as ‘shoshin’.2 Japan experienced a massive epidemic of beriberi at the turn of the 20th century. The epidemic coincided with rapid urbaniz- ation and a shift to a diet predominantly consisting of polished rice, often visibly contaminated with molds.3 Implementation of rigorous rice quality control measures was followed by a precipitous decline in the illness.3 Subsequently, Japanese investigators suggested that this epidemic was caused by myco- toxin citreoviridin, produced by Penicillum citreonigrum, Aspergillus terreus and Eupenicillium ochrosalmoneum. Citreoviridin produces a striking cardiac beriberi-like syndrome in rodents.4–7 An outbreak of beriberi occurred in a poor, rural area of Maranha˜o state, Brazil, in 2006. A substantial proportion of rice consumed by the population is locally grown bysubsistence farmers. This rice is dried on the ground and then polished in small local unregulated rice establishments, where it is stored in precarious conditions (Figure 1). In 2007 rice samples were collected from local rice-polishing facilities; these yielded citreoviridin-producing P. citreonigrun; citreoviridin was present in the rice samples.8 Cases of beriberi continued into 2007. We conducted an investigation to test the hypothesis that this persistent out- break of beriberi was due to the contamination of rice with citreoviridin mycotoxin. Patients and methods We conducted a 1:1 matched case control study. A case was a person reported as having beriberi by Maranha˜o State between January and June 2007. A control was a neighbour residing to the right of the case-patient’s residence, who did not have beriberi and did not consume thiamine sup- plements. Data were collected by standard questionnaire. We used McNemar Chi-square, Kruskal-Wallis and Student t-tests. Analysis was conducted in EpiInfo 3.5.2. Serum was collected for determination of thiamine levels (by high performance liquid chromatography9 ), transaminase, cre- atine, kinase and creatine kinase-BB. One kilogram of rice was collected from each case and each control household. Rice was defined as commercial (subject to sanitary inspection) or subsistence farming rice (locally grown and polished in unregulated facilities). At the Instituto de Tecnologia de Alimentos, Brazil, samples were cultured and tested for the presence of mycotoxins, including aflotoxins, ocratoxin, citrinine and citreoviridin.10 Tropical Doctor April 2010, 40 95
  • 2. Results In 2006 and 2007, 471 cases of beriberi were reported; 142 (30.0%) had onset symptoms in 2007. Of these, 52 (37.0%) were excluded because of incomplete addresses or a different final diagnosis. We enrolled 90 cases and 90 controls. Of the 90 cases, 73 (80.0%) were men, the median age was 31 years (range 14–55) and median schooling was four years (range 0–11). Among the controls, 45 (50.0%) were men, the median age was 25 years (1–86) and median schooling was three years (range 0–11). The median monthly income of the cases was US $131 (range US $0–539) and for the con- trols it was US $185 (US $0–777). For 45 (50.0%) cases the principal employment was field labour and for 43 (45.0%) controls it was homemaking. Cases and controls had a low calculated thiamine intake on a 24-hour food history – 0.7 mg/day (range 0.0–6.0 mg/day) and 0.6 mg/day Figure 1 Drying, polishing and storage of rice from the region of beriberi outbreak, Maranha˜o State, Brazil, 2007. (a) Drying the rice; (b) polishing and storing the rice Table 1 Results of univariate and multivariate analysis of exposures and beriberi, Maranha˜o, Brazil, 2007 Exposures Cases n (%) Controls n (%) mOR 95% CI P value Univariate analysis Male 73 (81) 44 (49) 3.8 1.9–8.6 ,0.01 Alcohol consumption 50 (53) 10 (11) 8.8 3.5–28.4 ,0.01 Smoking 33 (36) 12 (13) 6.0 2.1–23.8 ,0.01 Intense physical activity 79 (88) 66 (73) 2.6 1.1–6.9 ,0.05 Mainly consumes subsistence farming rice 40 (44) 22 (24) 3.1 1.4–8.0 ,0.05 Consumes fermented mandioca flour 55 (61) 50 (55) 1.5 0.6–3.5 0.37 Consumes dry mandioca flour 9 (10) 16 (17) 0.5 0.2–1.3 0.12 Exposures mOR 95% CI P value Multivariate analysis by conditional logistic regression Alcohol consumption 7.8 3.2–19.0 ,0.01 Intense physical activity 4.2 1.5–11.9 ,0.01 Mainly consumes subsistence farming rice 3.2 1.5–7.1 ,0.01 Concurrent hypertension or diabetes 2.7 1.1–6.5 0.03 Male sex 2.4 1.0–5.6 0.04 Years of schooling 1.1 0.9–1.2 0.24 Thiamine intake 1.0 0.50–1.9 1.00 OR, odds ratio; CI, confidence interval Short Report 96 Tropical Doctor April 2010, 40
  • 3. (range 0.0–5.2 mg/day), respectively (recommended daily intake is 1.2 mg/day). Cases reported symptoms of paresthesia (77.0%); oedema (75.0%) and calf pain (63.0%); 22 (24.0%) were hospital- ized. At the time of interview, 64 (70.0%) were being treated with thiamine and 51 (56.0%) were still symptomatic. On univariate analysis, beriberi was associated with male sex, the consumption of alcohol, smoking, physical activity and consumption of subsistence farming rice. On multi- variate analysis, independently associated factors were: the consumption of alcohol; intense physical activity; consump- tion of subsistence farming rice; co-morbidity; and male sex (Table 1). Serum was collected from case-patients a median of 63 days after thiamine replacement therapy. For case-patients and controls, serum thiamine, transaminase and creatine kinase levels were within normal limits. Eighty-one rice samples were collected: 44 (55%) from case households and 37 (45%) from control households. Fifty-eight (72%) were of polished rice and 23 (28%) samples were paddy. Culture yielded xerophilic growth in 28 (64%) case and 21 (57%) control samples, including Aspergillus penicilioides and A. versicolor. Additionally, fungi producing aflotoxin (A. flavus, A. parasiticus), citrinine (P. citrinum) and ocra- toxin A (A. niger) were isolated. No citreviridin-producing fungi were cultured. Conclusions Cases of beriberi, initially detected in 2006, continue to be reported in Maranha˜o State. In addition to the established risk factors for the disease, we showed that there is an inde- pendent association of illness with the consumption of unin- spected subsistence agricultural rice, as opposed to commercially processed and government inspected rice. The main purpose of our study was to determine whether citreoviridin mycotoxin was present in rice from case-patient homes, given the extensive body of historical and toxicologi- cal research from Japan supporting a role for this mycotoxin in the pathogenesis of beriberi. However, no citreoviridin- producing fungi were identified in rice samples from case- patient or control homes. Accordingly, we cannot conclude that this mycotoxin played a role in this protracted outbreak. The limitations of this study include the obtainment of rice samples weeks to months after the onset of the illness. Samples may not have been from the same stock as that con- sumed before onset of the illness, or may have been of the same stock but, perhaps, had been subjected to conditions that may have modified the fungal flora over time. Additionally, most rice samples were of polished rice. Rice polishing heats rice grains, which could have altered the fungal flora while leaving mycotoxin intact. As no citreoviridin-producing fungi were encountered, we did not test directly for the presence of the toxin. We recommend that the active surveillance and timely treatment of case-patients, thiamine supplementation for the population and quality and safety standards for transpor- tation, storage and processing of subsistence farming rice should be continued. Acknowledgments We thank the officials of the state and the municipal sec- retaries of health in the state of Maranha˜o, Brazil, and col- leagues of the Secretariat of Health Surveillance of the Ministry of Health and the colleagues of Field Epidemiology Training Program of Brazil. References 1 Lonsdale D. A review of the biochemistry, metabolism and clini- cal benefits of thiamin(e) and its derivatives. Evid Based Complement Alternat Med 2006;3:49–59 2 Hoyumpa AM. Mechanism of vitamin deficiencies in alcoholism. Alcohol Clin Exp Res 1986;10:572–81 3 Uraguchi K. Micotoxic origin of cardiac beriberi. J Stored Prod Res 1969;5:27–36 4 Ueno Y, Ueno I. Isolation and acute toxicity of citreoviridin, a neurotoxic micotoxin of Penicillium Citreo-Viride Biourge. Jap J Exp Med 1972;42:91–105 5 Ohtsubo K. Mycotoxins in foodstuffs and their biological action on mammals. Beitr Pathol Bd 1973;148:213–20 6 Murphy PA, Hendrich S, Landgren C, Bryant C. Food mycotox- ins: an update. J Food Sci Chicago 2006;71:51–65 7 Smith JE, Henderson RS. Mycotoxins and Animal Foods. London: CRC Press, 1991 8 Rosa CA, Keller KM, Oliveira AA, et al. Production of citreovir- idin by Penicillium citreonigrum strains associated with rice con- sumption and beriberi cases in the Maranhao State, Brazil. Food Addit Contam Part A Chem Anal Control Expo Risk Assess 2009;29:1–8 9 Chatzimichalakis PF, Samanidou VF, Verpoorte R. Development of a validated HPLC method for the determination of B-complex vitamins in pharmaceuticals and biological fluids after solid phase extraction. J Sep Sci 2004;27:181–8 10 Pitt JI, Hocking AD. Fungi and Food Spoilage. 2nd edn. London: Blackie Academic & Professional, 1997: 593 Short Report Tropical Doctor April 2010, 40 97