Clinical trial NCT03847870: Rickettsiae in Myanmar
Official title: Background Seroprevalence of Rickettsial Infections in Myanmar
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Rickettsiae Infections
Keywords: rickettsiae
seroprevalence
Lead sponsor: Myanmar Oxford Clinical Research Unit
Sponsor class: OTHER
Collaborators: name: National Health Laboratory, Myanmar
name: Magway General Hospital, Magway
name: Monywa Hospital, Sagaing
name: Mandalay General Hospital and University of Medicine, Mandalay
name: University of Medicine, Magway
name: Mahidol Oxford Tropical Medicine Research Unit
name: Medical Action Myanmar
First posted: 2019-02-20
Enrollment: 700
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: OTHER
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The population investigated will be patients who had a leftover samples from routine clinical blood draw when attending seven different Medical Action Myanmar (MAM) clinics and hospitals in different regions of Myanmar with each site including approximately 100 patients.

Brief summary: Rickettsial infections have been found to be the second most common cause of non-malarial febrile illness in Southeast Asia, just after dengue, and are largely neglected treatable causes of morbidity and mortality. The rickettsiae can be divided into three major groups: the scrub typhus group (STG), the typhus group (TG) and the spotted fever group (SFG). Rickettsial infections typically present with an acute fever and are difficult to diagnose due to the many different causes of undifferentiated fever in Southeast Asia. Rickettsial IgG seroprevalence, reflecting past infection, will give an estimate of the burden of rickettsial infections in the population. Background seroprevalence studies in countries around Myanmar have found high rates of rickettsial infections. Yet, in Myanmar there have been no prevalence studies on rickettsial infections since the Second World War. We plan to determine IgG levels to the three different groups of rickettsial infections in leftover blood samples in several clinics and hospitals in different regions of Myanmar.

Detailed description: Rickettsial infections have been found to be the second most common cause of non-malarial febrile illness in Southeast Asia, just after dengue, and are largely neglected treatable causes of morbidity and mortality. The rickettsiae can be divided into three major groups: the scrub typhus group (STG), the typhus group (TG) and the spotted fever group (SFG). Rickettsial infections typically present with an acute fever and are difficult to diagnose due to the many different causes of undifferentiated fever in Southeast Asia. Rickettsial IgG seroprevalence, reflecting past infection, will give an estimate of the burden of rickettsial infections in the population. The current best test for IgG serological diagnosis of previous rickettsial infections is the indirect immunofluorescence assay (IFA). IFA has several limitations

in that it is difficult to standardize due to operator subjectivity, it needs appropriate local diagnostic cut- offs and requires improvement in terms of standardization and ease of use. An alternative serological test that is cheaper and is easier to use is the enzyme-linked immunosorbent assay (ELISA), which is more suited to screen for the burden of rickettsial diseases in low-resource countries. Background seroprevalence studies in countries around Myanmar have found high rates of rickettsial infections. Yet, in Myanmar there have been no prevalence studies on rickettsial infections since the Second World War. We plan to determine IgG levels to the three different groups of rickettsial infections in leftover blood samples in several clinics and hospitals in different regions of Myanmar. Participants with leftover blood samples after having undergone a blood draw for any clinical reason or a blood donation will be requested to participate in the study. The participant will be informed about the study and requested to provide informed consent when agreeing to participate. The leftover sample will be anonymized and frozen. The gender, age and location of clinic/hospital of the participant will be recorded. All samples will be tested for IgG antibodies using an in-house ELISA test in the Mahidol Oxford Tropical Medicine Research Unit (MORU), Bangkok, Thailand for scrub typhus (Orientia tsutsugamushi strains Karp, Kato, Gilliam and TA716), murine typhus (Rickettsia typhi strain type Wilmington), and spotted fever rickettsioses (Rickettsia honei and Rickettsia conorii). If the sample tests positive for IgG antibodies, an IFA test will be performed as the gold standard reference test to confirm the finding. The anonymous samples will be discarded as soon as they are no longer needed for the study. The population investigated will be 700 patients attending seven different clinics and hospitals in different regions of Myanmar with each site including 100 patients.

We will include patients at the following study sites:

1. Himalaya general clinic, Puta-O, Kachin;
2. Lily general clinic, Thanbyuzayat, Mon;
3. Orchid general clinic, Hlaing Thar Yar, Yangon;
4. Winka general clinic, Winka, Kayin;
5. Monywa Hospital, Sagaing;
6. Mandalay General Hospital and University of Medicine, Mandalay;
7. Magway General Hospital, Magway This is a minimal risk study. The participants will not have to undergo any additional procedures, since we will be using leftover blood samples that have been collected for routine clinical tests to study the background levels of previous rickettsial infections. Participation in this study is voluntary. Subjects who decline to participate will have no impact on the care they receive at the hospital or clinic. There will be no incentives or compensation for study participation.

Eligibility criteria: Inclusion Criteria:

* Male and female, all age groups, requiring a blood draw for a routine clinical purpose

Exclusion Criteria:

* Leftover blood sample of less than 500μL

Primary outcomes:
measure: Positive ELISA confirmed by positive IFA
timeFrame: January, 2020
Secondary outcomes:
measure: Patient characteristics associated with rickettsial infections
timeFrame: January, 2020
Other outcomes:
Locations:
city: Yangon
country: Myanmar
facility: Myanmar Oxford Clinical Research Unit
Study officials:
affiliation: Myanmar Oxford Clinical Research Unit
name: Elizabeth Anne Ashley, Dr
role: PRINCIPAL_INVESTIGATOR
affiliation: Mahidol Oxford Tropical Medicine Research Unit
name: Stuart Blacksell, Prof
role: PRINCIPAL_INVESTIGATOR
affiliation: Myanmar Oxford Clinical Research Unit
name: Philip Elders, MSc
role: STUDY_DIRECTOR
affiliation: Myanmar Oxford Clinical Research Unit
name: Wei Yan Aung Htay, Dr
role: STUDY_DIRECTOR
affiliation: National Health Laboratory, Myanmar
name: Yin Yin Htwe, Dr
role: STUDY_DIRECTOR
affiliation: Magway General Hospital, Magway
name: Myat Myat Moe, Dr
role: STUDY_DIRECTOR
affiliation: Monywa Hospital, Sagaing
name: Wai Mon Kyaw, Dr
role: STUDY_DIRECTOR
affiliation: Mandalay General Hospital and University of Medicine, Mandalay
name: Ni Ni Zaw, Dr
role: STUDY_DIRECTOR
affiliation: Mandalay General Hospital and University of Medicine, Mandalay
name: Win May Thein, Prof
role: STUDY_DIRECTOR
affiliation: University of Medicine, Magway
name: Thin Thin Nwe, Prof
role: STUDY_DIRECTOR
affiliation: Myanmar Oxford Clinical Research Unit
name: Kyaw Soe, BSc
role: STUDY_DIRECTOR
affiliation: Mahidol Oxford Tropical Medicine Research Unit
name: Ampai Tanganuchitcharnchai, BSc
role: STUDY_DIRECTOR
affiliation: Myanmar Oxford Clinical Research Unit and Medical Action Myanmar
name: Ni Ni Tun, Dr
role: STUDY_DIRECTOR
affiliation: Myanmar Oxford Clinical Research Unit and Medical Action Myanmar
name: Frank Smithuis, Prof
role: STUDY_DIRECTOR
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