fever of unknown origin (dhf;puo) study, 1979 · fever pyrexia of unknown origin (dhf;puo) study,...

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FEVER PYREXIA OF UNKNOWN ORIGIN (DHF;PUO) STUDY, 1979 Principal Investigators : Donald S, Burke, LTC, MC Ananda Nisalak, M.D, Suchitra Nimmannitya, M,D, U-Sa Titsayakarn, M.D. Douglas M. Watts, Ph.D. OBJECTIVES : To i d e n t i f y and obtain .historical, clinical and laboratory data from children with dengue Femorrhagic fever (DHP), dengue fever (DF),,and other febrile illnesses (non-dengue Pyrexia :,of' undetermined origin, NDPUO) from a single hospital, in order to obtain comparisons of these groups of children re- garding : 1. Racial and socioeconomic background 2. Nutritional statug 3, Serologic evidence of previous flaviviruS infection 4, Infecting dengue virus type. BACKGROUND : A heated debate persists regarding the importance of sequential infections in determiag the severity of dengue virus infections. Data previous- ly reported from Thailand showing an association of DHF with secondary type anti- body responses have been criticised on the basis that controf population were inadequately defined, and studies from aaer countries have not shown such an association, We therefore undertook a study of children with DHF, DF, and NDPUOts pre- senting to a single hospital in Bangkok. The study was :designed so that viro- logical factors (evidence af preyious flavivirus exposure, infecting virus type) could be compared between these three groups where a l l clinical diagnoses and grading were made and reviewed without knowledge of serologic or isolation results. History, =a1 examinat ion, and clinical laboratory : Data sheet : Por a l l DHF and PUO patients a data sheet was completed by specially trained Department of Virology Nurses who interviewed and measured the patient, 'interviewed the pgtient's parents, and extracted the physicians physi- cal examination data from the patPenfts cha%t. Serologic diagnosis of dengqe infections : An attempt was made to obtain acute and 2 to 4 week convalescent serum samples from all patients, This was done by giving the patient an appointment for a follow-up visit; if the patient failed to keep the appointment, then a phone call or more often a letter was sent to the patient as a reminder, and a second appointment made. If the pa- tient still did not return, then one of the department of Virology nurses visited the patienw's home. (Approximately 70% of patients returned for follow-up on the appointed day; an additional 10-15% in response to a letter reminder, and

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Page 1: FEVER OF UNKNOWN ORIGIN (DHF;PUO) STUDY, 1979 · FEVER PYREXIA OF UNKNOWN ORIGIN (DHF;PUO) STUDY, 1979 Principal Investigators : Donald S, Burke, LTC, MC Ananda Nisalak, M.D, Suchitra

FEVER PYREXIA OF UNKNOWN ORIGIN (DHF;PUO) STUDY, 1979

P r i n c i p a l Inves t iga to r s : Donald S, Burke, LTC, MC Ananda Nisalak, M.D, Suchi t ra Nimmannitya, M,D, U-Sa Titsayakarn, M.D. Douglas M. Watts, Ph.D.

OBJECTIVES : To i d e n t i f y and obtain . h i s t o r i c a l , c l i n i c a l and labora tory da ta from ch i ld ren wi th dengue Femorrhagic fever (DHP), dengue fever (DF),,and o t h e r f e b r i l e i l l n e s s e s (non-dengue Pyrexia :,of' undetermined o r i g i n , NDPUO) from a s i n g l e hosp i t a l , i n order t o obta in comparisons of these groups of chi ldren re- garding :

1. Racial and socioeconomic background 2. Nut r i t iona l s t a t u g 3, Serologic evidence of previous f l av iv i ruS i n f e c t i o n 4 , In fec t ing dengue v i r u s type.

BACKGROUND : A heated debate p e r s i s t s regarding t h e importance of sequent ia l in fec t ions i n determiag t h e sever i ty of dengue v i r u s in fec t ions . Data previous- l y repor ted from Thailand showing an assoc ia t ion of DHF with secondary type a n t i - body responses have been c r i t i c i s e d on the b a s i s t h a t controf populat ion were inadequately defined, and s t u d i e s from a a e r countr ies have not shown such an assoc ia t ion ,

W e t he re fo re undertook a study of chi ldren with DHF, DF, and NDPUOts pre- sent ing t o a s i n g l e h o s p i t a l i n Bangkok. The study w a s :designed so t h a t v i ro- l o g i c a l f a c t o r s (evidence af preyious f l a v i v i r u s exposure, i n f e c t i n g v i r u s type) could be compared between these t h r e e groups where a l l c l i n i c a l diagnoses and grading were made and reviewed without knowledge of se ro log ic o r i s o l a t i o n r e s u l t s .

History, =a1 examinat ion, and c l i n i c a l labora tory :

Data sheet : Por a l l DHF and PUO p a t i e n t s a d a t a sheet was completed by s p e c i a l l y t r a i n e d Department of Virology Nurses who interviewed and measured t h e p a t i e n t , 'interviewed t h e pg t i en t ' s parents , and ext rac ted t h e physic ians physi- cal examination d a t a from t h e patPenf ts cha%t.

Serologic d iagnosis of dengqe in fec t ions : An attempt was made t o obta in acu te and 2 t o 4 week convalescent serum samples from a l l p a t i e n t s , This was done by giving t h e pa t i en t an appointment f o r a follow-up v i s i t ; i f t h e p a t i e n t f a i l e d t o keep t h e appointment, then a phone c a l l o r more o f t en a le t te r was s e n t t o t h e pa t i en t a s a reminder, and a second appointment made. I f the pa- t i e n t s t i l l d id n o t r e t u r n , then one of t h e department of Virology nurses v i s i t e d t h e patienw's home. (Approximately 70% of p a t i e n t s re turned f o r follow-up on t h e appointed day; an a d d i t i o n a l 10-15% i n response t o a l e t t e r reminder, and

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