PROPOSAL ON MELIODOSIS SURVEILLANCE SYSTEM IN VIETNAM

Among main endemic areas of Melioidosis disease, extreme northern and northeastern Thailand are the two hotspots of the disease, with an annual incidence up to 50 /100,000 population (Figure 1). Melioidosis disease (MD) is the third leading cause of death due to infectious diseases in northeastern Thailand. Malaysia, Singapore, Vietnam, Cambodia, and Laos, are endemic areas of the disease as well. Case reports were also found in Indian subcontinents, southern China, Hong Kong, Taiwan, various islands of the Pacific and Indian oceans, and several areas of the Latin America. Sporadic cases have been reported from Nigeria, Gambia, Kenya, and Uganda, but the scope of the disease in Africa have still not been ascertained.

PROPOSAL ON MELIODOSIS SURVEILLANCE SYSTEM IN VIETNAM

1 Background

1.1 Melioidosis situation worldwide

Among main endemic areas of Melioidosis disease, extreme northern and northeasternThailand are the two hotspots of the disease, with an annual incidence up to 50 /100,000population (Figure 1) Melioidosis disease (MD) is the third leading cause of death due toinfectious diseases in northeastern Thailand Malaysia, Singapore, Vietnam, Cambodia, andLaos, are endemic areas of the disease as well Case reports were also found in Indiansubcontinents, southern China, Hong Kong, Taiwan, various islands of the Pacific and Indianoceans, and several areas of the Latin America Sporadic cases have been reported fromNigeria, Gambia, Kenya, and Uganda, but the scope of the disease in Africa have still notbeen ascertained.

Figure 1 Geographical distribution of Melioidosis disease

1.2 Melioidosis situation in Vietnam

1.2.1 Incidence of Melioidosis in Vietnam

The first case of Melioidosis in Vietnam described by Pons and Advier in 1925 was ayoung woman living in a suburb area of Saigon (now Ho Chi Minh City) The patient died of

sepsis and Whitmore bacilli was detected in the blood sample of the patient B pseudomallei

bacteria were first documented by Vaucel in Hanoi and Chambon (Saigon Pasteur Institute)confirmed Vaucel’s results later During Vietnamese war, numerous French and American

soldiers had exposed to environment contaminated with B pseudomallei and their clinical and

subclinical characteristics had been recorded Most of cases were found from 40s to 70s At

least 100 French soldiers stationing in Vietnam had been infected by B pseudomallei from

1948 to 1954; in 1973 343 cases were recorded by Moore Many other cases were alsorecorded including veterans who joined in Vietnamese war, Vietnamese migrants, and foreigntourists come back from Vietnam Parry et al in their work revealed that the proportion of

isolated B pseudomallei in cultured blood samples from 1992 to 1998 was 0.25% (9/3,653),and that no pathogenic strains of B pseudomallei were isolated from environments

surrounding Ho Chi Minh City A report in the North of Vietnam showed that during theperiod of 1997-2005, there were 54 patients identified as Melioidosis infection with cultured

blood or body fluids samples positive with B pseudomallei; all of them lived in 18 northern

provinces surrounding Ha Noi According to a report of Cho Ray Hospital in 2006, it isestimated that about 20 cases of Melioidosis disease were diagnosed and treated annually.Another report of Tropical Diseases Hopital in Ho Chi Minh City in 2013 revealed that about10 to 15 cases of Melioidosis disease per year were treated at the hospital.

A recent report of National Tropical Diseases Hospital in 2014-2016 showed a total of

23 cases of MD were tested positively with B pseudomallei In National Hospital of Hue anumber of 5 positive cases with B pseudomallei was reported Pasteur Institute of Ho Chi

Minh City in 2014 recorded over 239 blood samples from patients with suspected typhoid of

which 1 sample (0.4%) cultured positively with B pseudomallei bacteria In 2016, theInstitute also reported 3 samples (5%) positive with B pseudomallei among 60 sputum /blood

samples of pneumonia patients In Cho Ray hospital a total of 84 cases of MD were detectedduring the period 2013-2015

Table 1 Number of MD were reported by National Tropical Diseases Hospital, NationalChildren Hospital, Hue National Hospital of Hue, and Cho Ray Hospital

National Tropical DiseasesHospital

National Children HospitalHueNationalHospitalof Hue

Cho Ray Hospital

1 2011

2 2012

3 2013

4 2014

5 2015

6 2016

1.2.2 Epidemiology characteristics of Melioidosis Disease in Vietnam

In the northern region, a report of National Tropical Diseases Hospital showed thatMelioidosis cases from 2014-2016 commonly occurred in the Northeast region (9 cases) andthe North Central region (11 cases) The report of National Hospital of Hue showed that 1case of MD lived in Ha Tinh, 1 case in Hue and 3 cases in Quang Binh The report of theNational Children's Hospital also found that the majority of MD cases occurred in Northeastregion (Hanoi: 3; Bac Ninh: 3) and North Central region (Nghe An: 9) In the south region, astudy of Le Viet Nhiem on 58 MD patients visiting Tropical Diseases Hospital of Ho ChiMinh City showed that a large portion of MD patient lived in the Southeast region (6.3%), ofthose 15 lived in HCMC, 7 in Tay Ninh, 6 in Binh Duong, and 5 in Binh Phuoc A report ofCho Ray Hospital also found that most MD cases occurred in the Southeastern region (43/84cases, yielding 51.2%)

Table 2 Geographical distribution of MD cases in northern region from 2014 to 2016

MaleFemale MaleFemale MaleFemale

Northeastern region (Bắc Giang, Phú Thọ, Vĩnh Phúc, Quảng Ninh, Hà Nội, Ninh Bình)

North Central region (Thanh Hóa, Nghệ An, Hà Tĩnh)

Central region (Quảng Bình) 1

In the northern region, the report of National Tropical Diseases showed that MDcommonly occurs in the autumn period (July to September) with 12 cases detected during thisperiod In the southern region, the study of Le Viet Nhiem showed that the majority of MDcases (67.2%) occurred during the rainy season in which August (middle time of the rainyseason) have highest cases of 12 (20.7%), followed by June with 9 cases (15.5%) The reportof Cho Ray Hospital also recorded 69% of MD cases occurred during the rainy season Thus,it may suggest that MD in Vietnam frequently occur from July to September The seasonalityof MD in Vietnam is in accompany with that in other countries in which 75%-81% of MDcases occur during the rainy season

Table 3 Seasonality of MD cases in northern region from 2014 to 2016

In terms of gender, studies and reports in Vietnam showed that the disease occurs morefrequent in men than women The report of National Hospital of Hue recorded that 4 of 5 MD

cases (80%) were male The report of National Tropical Diseases Hospital showed that 18 of23 MD cases (78.3%) were male The study of Le Viet Nhiem noted that male was dominantamong MD cases (86%) with the ratio of male: female was 6: 1 The report of Children'sHospital showed that 51.86% children patients were male and 48.14% were female Thatdisease commonly occurs in men is probably due to the fact that men often expose tocontaminated soil and water more than women, so the risk of MD infection among men is alsohigher

In terms of occupation, the report of National Hospital of Hue showed that 1 case was afamer, 1 case was a retired man, 2 cases were chiefs, and 1 case was a young child The studyof Le Viet Nhiem revealed that there were 9 cases (32.8%) were famers and the rest did nothave occupations related to soil or water (officers, waitress, bus drivers, garment workers).The report of Cho Ray Hospital recorded 36.9% of MD patients employed in agriculture,26.2% were unemployed or homemaker Therefore, famers is likely to be a risk factor of theMD in Vietnam.

About medical history, the report of National Hospital of Hue showed that 1 patient hada history of rheumatism, 1 case with benign prostatic hyperplasia, 2 cases with diabetes type 2and history of malaria since childhood, and 1 case had a history of healthy conditions Thestudy of Le Viet Nhiem showed that diabetes mellitus was the most common underlyingdisease among MD patients, accounted for 39/58 cases (67.2%), followed by chronic liverdisease (7.3%), of those 6 cases were detected during hospitalization and 4 cases acquiredbefore hospitalization There were 8 patients (13.8%) without underlying diseases or otherconditions The report of Cho Ray Hospital recorded 54.8% of MD patients had a history ofdiabetes, 10.7% had a history of chronic diseases, and 7.1% had prolonged corticosteroidtreatment Therefore, it may conclude that diabetes is a risk factor of MD in Vietnam.

1.2.3 Clinical characteristics of Melioidosis in Vietnam

The report of Cho Ray Hospital recorded that clinical symptoms of MD patients variedincluding 45.4% of patients had fever with different types of fever such as fever or fever withchills, prolonged fever The average number of days of fever before admission of MD patientswas 14 days The report of National Hospital of Hue showed that 1 case had sepsis, 1 case hadurinary infection, 2 cases had hepatic and spleen abscess, 1 case had abscess of salivaryglands The study of Le Viet Nhiem revealed that the most common clinical symptoms of MDpatients was sepsis (63.8%), followed by systematic infection (24.1%) and the least commonsymptoms was localized infection (12.1%) The mortality rate was highest in patients withdisseminated infection (42.9%), followed by septicemia (21.6%) and localized infections

(14.3%) Organ lesions significant varied with the most common symptom was pneumonia(58.7%), of those primary pneumonia was predominant (76%) Septic shock occurred in oneof four MD case with extremely high mortality rate (86.7%) The report of Cho Ray Hospitalrecorded 66.7% of MD patients with sepsis, 17.6% with pneumonia and 3.4% with liverabscess, 24.4% with pus skin, and 16.8 % with osteoarthritis pain.

The study of Le Viet Nhiem also showed that number of leukocytes in peripheral bloodwas normal in half of MD cases; the rest had lightly increased leukocytes Other biomarkerssuch as CRP, PCT also increased in cases of sepsis or systematic infection The majority ofMD cases were diagnosed based on identification of bacteria, only about 1/5 of cases werediagnosed with MD prior to lab results confirmed

1.2.4 Treatment of Melioidosis in Vietnam

To date there are not any consensus on treatment of MD worldwide The same situationcould be found in Vietnam The National Tropical Disease Hospital suggested a therapy toMD with two phases including intensive phase and consolidative phase; however that therapy

was just applied in hospital setting The study of Le Viet Nhiem noted that B pseudomallei

are still sensitive with all antibiotics applied in intensive phase (Ceftazidime, Imipenem,Meropenem) and consolidative phase (TMP-SMX, Doxycycline) The report of Cho Ray

Hospital showed that B pseudomallei are still sensitive to antibiotics in intensive phase.

However, only 66.7% of MD cases are sensitive to TMP/SMX, with 23% to Ticarcillin /clavulanic acid, 27.5%, to Ciprofloxacin, and 20.8% to Cefepime.