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 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

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 a young 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 also recorded including veterans who joined in Vietnamese war, Vietnamese migrants, and foreign tourists 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 the period 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 is estimated 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 about

10 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 a number 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, the Institute 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 detected during the period 2013-2015

Table 1 Number of MD were reported by National Tropical Diseases Hospital, National

Children Hospital, Hue National Hospital of Hue, and Cho Ray Hospital

o

Ye

ar

National Tropical Diseases

Hospital

National Children Hospital Hue

National Hospital

of Hue

Cho Ray Hospital

Morbidi

ty Mortali ty Positiv e Morbidit y Mortalit y Positiv e Morbidit y Morbidit y Mortalit y

1 201

1

2 201

2

3 201

3

4 201

4

5 201

5

6 201

6

Tot

al

1.2.2 Epidemiology characteristics of Melioidosis Disease in Vietnam

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

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

Male Female Male Female Male Female

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 MD commonly occurs in the autumn period (July to September) with 12 cases detected during this period In the southern region, the study of Le Viet Nhiem showed that the majority of MD cases (67.2%) occurred during the rainy season in which August (middle time of the rainy season) have highest cases of 12 (20.7%), followed by June with 9 cases (15.5%) The report

of 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 seasonality

of MD in Vietnam is in accompany with that in other countries in which 75%-81% of MD cases occur during the rainy season

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

Male Female Male Female Male Female

In terms of age, the report of National Hospital of Hue showed among 5 cases detected

in 2016, one was 3-year-old, 2 were 40 years of age, 1 was 39 years and 1 was 80 years The report of National Tropical Diseases Hospital recorded 8 MD cases aged 16-45 and 7 cases of 45-60 years old The study of Le Viet Nhiem showed that the min age of patients was 21 and the maximum age was 79, and most of patients aged from 40-60, yielding 53.5% The report

of Children's Hospital showed that 59.26% of MD cases were children aged 1-5 years From these studies, it may conclude that two age groups frequently suffer from MD are 1-5 group and 40 and older group This has also been noted in the literature in which the incidence of

MD was highest at the age group of 40-60 and school age children

In terms of gender, studies and reports in Vietnam showed that the disease occurs more frequent 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 of

23 MD cases (78.3%) were male The study of Le Viet Nhiem noted that male was dominant among MD cases (86%) with the ratio of male: female was 6: 1 The report of Children's Hospital showed that 51.86% children patients were male and 48.14% were female That disease commonly occurs in men is probably due to the fact that men often expose to contaminated soil and water more than women, so the risk of MD infection among men is also higher

In terms of occupation, the report of National Hospital of Hue showed that 1 case was a famer, 1 case was a retired man, 2 cases were chiefs, and 1 case was a young child The study

of Le Viet Nhiem revealed that there were 9 cases (32.8%) were famers and the rest did not have 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 the

MD in Vietnam

About medical history, the report of National Hospital of Hue showed that 1 patient had

a history of rheumatism, 1 case with benign prostatic hyperplasia, 2 cases with diabetes type 2 and history of malaria since childhood, and 1 case had a history of healthy conditions The study of Le Viet Nhiem showed that diabetes mellitus was the most common underlying disease among MD patients, accounted for 39/58 cases (67.2%), followed by chronic liver disease (7.3%), of those 6 cases were detected during hospitalization and 4 cases acquired before hospitalization There were 8 patients (13.8%) without underlying diseases or other conditions The report of Cho Ray Hospital recorded 54.8% of MD patients had a history of diabetes, 10.7% had a history of chronic diseases, and 7.1% had prolonged corticosteroid treatment 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 varied including 45.4% of patients had fever with different types of fever such as fever or fever with chills, prolonged fever The average number of days of fever before admission of MD patients was 14 days The report of National Hospital of Hue showed that 1 case had sepsis, 1 case had urinary infection, 2 cases had hepatic and spleen abscess, 1 case had abscess of salivary glands The study of Le Viet Nhiem revealed that the most common clinical symptoms of MD patients was sepsis (63.8%), followed by systematic infection (24.1%) and the least common symptoms was localized infection (12.1%) The mortality rate was highest in patients with disseminated 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 one

of four MD case with extremely high mortality rate (86.7%) The report of Cho Ray Hospital recorded 66.7% of MD patients with sepsis, 17.6% with pneumonia and 3.4% with liver abscess, 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 blood was normal in half of MD cases; the rest had lightly increased leukocytes Other biomarkers such as CRP, PCT also increased in cases of sepsis or systematic infection The majority of

MD cases were diagnosed based on identification of bacteria, only about 1/5 of cases were diagnosed 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 situation could be found in Vietnam The National Tropical Disease Hospital suggested a therapy to

MD 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