Pathogenic/likely pathogenic mutations identified in Vietnamese children diagnosed with autism spectrum disorder using high-resolution SNP genotyping platform.

Among the most prevalent neurodevelopmental disorders, Autism Spectrum Disorder (ASD) is highly diverse showing a broad phenotypic spectrum. ASD also couples with a broad range of mutations, both de novo and inherited. In this study, we used a proprietary SNP genotyping chip to analyze the genomic DNA of 250 Vietnamese children diagnosed with ASD. Our Single Nucleotide Polymorphism (SNP) genotyping chip directly targets more than 800 thousand SNPs in the genome. Our primary focus was to identify pathogenic/likely pathogenic mutations that are potentially linked to more severe symptoms of autism. We identified and validated 23 pathogenic/likely pathogenic mutations in this initial study. The data shows that these mutations were detected in several cases spanning multiple biological pathways. Among the confirmed SNPs, mutations were identified in genes previously known to be strongly associated with ASD such as SLCO1B1, ACADSB, TCF4, HCP5, MOCOS, SRD5A2, MCCC2, DCC, and PRKN while several other mutations are known to associate with autistic traits or other neurodevelopmental disorders. Some mutations were found in multiple patients and some patients carried multiple pathogenic/likely pathogenic mutations. These findings contribute to the identification of potential targets for therapeutic solutions in what is considered a genetically heterogeneous neurodevelopmental disorder.

Improving the diagnosis of pulmonary tuberculosis in HIV-infected individuals in Ho Chi Minh City, Viet Nam.

SETTING: District 6, An Hoa Clinic in Ho Chi Minh City (HCMC), Viet Nam. OBJECTIVE: To evaluate the performance of various algorithms in tuberculosis (TB) screening and diagnosis in a human immunodeficiency virus (HIV) infected population in HCMC, Viet Nam. DESIGN: A cross-sectional study of 397 consecutive HIV-infected patients seeking care at the An Hoa Clinic from August 2009 to June 2010. Data on participant demographics, clinical status, chest radiography (CXR) and laboratory results were collected. A multiple logistic regression model was developed to assess the association of covariates and pulmonary TB (PTB). RESULTS: The prevalence of sputum culture-confirmed PTB, acid-fast bacilli (AFB) positive TB, and multidrugresistant TB among the 397 HIV-infected patients was respectively 7%, 2%, and 0.3%. Adjusted odds ratios for low CD4+ cell count, positive sputum smear, and CXR to positive sputum culture were respectively 3.17, 32.04 and 4.28. Clinical findings alone had poor sensitivity, but combining CD4+ cell count, AFB sputum smear and CXR had a more accurate diagnostic performance. CONCLUSION: Results suggest that symptom screening had poor clinical performance, and support the routine use of sputum culture to improve the detection of TB disease in HIV-infected individuals in Viet Nam. However, when routine sputum culture is not available, an algorithm combining CD4+ cell count, AFB sputum smear and CXR is recommended for diagnosing PTB.

Treatment of falciparum malaria in Vietnamese children: the need for combination therapy and optimized dosage regimens.

To assess the in vivo sensitivity of Plasmodium falciparum to mefloquine and artesunate in a hyperendemic area of southern Viet Nam, we studied 41 children and 21 adults from a remote commune who had uncomplicated falciparum malaria without previous treatment. Patients were randomly allocated to artesunate (4 mg/kg on day 0 and 2 mg/kg on days 1-4) or mefloquine (10 mg/kg followed by 5 mg/kg at 6 h). Serial assessments were performed over 28 days. Of 31 patients allocated artesunate, nine (29%) redeveloped parasitaemia during follow-up compared with 23% (seven of 30) who received mefloquine. Of the 41 children, 15 (37%) had recrudescence/re-infection compared with only one of 20 adults (5%; p < 0.001). Significantly more children than adults failed on mefloquine treatment (37% vs 0%; p = 0.021) and one case showed RIII resistance. There was no significant difference in the case of artesunate. In regression analysis, parasitaemia was an independent predictor of recrudescence/re-infection after mefloquine (p = 0.02). These data support the use of combination therapy such as artesunate plus mefloquine for falciparum malaria in a hyperendemic area of Viet Nam. Primarily because of their greater parasite densities, children should be given higher doses of mefloquine (e.g. 25 mg/kg).

Risk factors of HIV infection and needle sharing among injecting drug users in Ho Chi Minh City, Vietnam.

OBJECTIVE: We sought to identify risk factors for needle sharing and HIV infection among injecting drug users (IDUs) in Ho Chi Minh City (HCMC), Vietnam. METHODS: Three cross-sectional surveys among IDUs, both on the street (in 11 urban districts) and in the rehabilitation center for IDUs in HCMC, were carried out in April of 1995, 1997, and 1998. Outreach workers interviewed IDUs about socio-demographic characteristics, drug use and sexual practices, and HIV knowledge and perceptions. The IDUs were also tested for seropositivity to HIV. Independent predictors for HIV positivity and needle sharing were determined by univariate and multivariate logistic regression for the study sample within the rehabilitation center in 1997 and for that on the street in 1998. RESULTS: The HIV prevalence in 1998 among IDUs was 44% for those on the street and 38.5% for those in the rehabilitation center. Independent predictors for HIV infection in IDUs were being injected by drug dealers (for the 1997 sample), injecting on the street, and sharing the drug pots (for the 1998 sample). The reported rate of needle sharing was low and decreased significantly from 20% in 1995 to 12% in 1998 for the sample of IDUs at the street. In the multivariate analysis, predictors for needle sharing for both study samples were injecting on the street, injecting at shooting galleries, and having shared needles in the past. Adequate and easy access to sterile needles and syringes, and a supportive environment of behavior change, especially in street and shooting gallery could reduce risks of virus transmission in the Vietnamese IDU community.

The social context of HIV risk behaviour by drug injectors in Ho Chi Minh City, Vietnam.

A combined research approach with both quantitative and qualitative methods was used to contextualize risk behaviour among injecting drug users (IDUs) in Ho chi Minh City (HCMC), Vietnam, in April 1997. A total of 630 IDUs (330 inside and 300 outside the rehabilitation centre) were recruited to the study. Very high-risk injecting behaviour among IDUs in the past, including sharing needles, syringes and drug solutions from the same drug pot in shooting galleries, may explain why HIV prevalence among IDUs in HCM has been growing rapidly. IDUs who had in the past injected on the street, used syringes from shooting galleries, were injected by drug dealers and/or joined in needle sharing were more likely to be sharing needles and syringes currently. Condom use was low, and was mainly with female sex workers but not with regular partners. Both IDUs who continue to use shooting galleries and shooting gallery owners should be educated on the necessity of using clean injecting equipment and on how to clean it properly. Co-ordination between ministries and agencies involved in HIV/AIDS and drugs programmes is needed to create policies for supportive environments to bring about changes in both drug use and HIV risk behaviours.

Rising HIV infection rates in Ho Chi Minh City herald emerging AIDS epidemic in Vietnam.

OBJECTIVE: To describe the epidemiology of HIV in Ho Chi Minh City in the context of current surveillance data from Vietnam. METHODS: Since the late 1980s, HIV surveillance data have been collected in Ho Chi Minh City from centers for the treatment of venereal disease and tuberculosis, centers for the rehabilitation of injecting drug users and sex workers, prenatal clinics, blood banks and other sites. RESULTS: The first case of HIV infection in Vietnam was identified in 1990 in Ho Chi Minh City. The cumulative number of reported HIV infections in this city at the end of 1996 was 2774, about half of the number of cases in the country; 86% of infections were among men, 86% among injecting drug users, 2.5% among patients with sexually transmitted diseases and 2.5% among sex workers. The first HIV infection among antenatal women was detected in 1994. The prevalence of HIV among injecting drug users rose dramatically from 1% in 1992 to 39% in 1996, compared with 1.2% among sex workers, 0.3% among blood donors and 1.3% among tuberculosis patients in 1996. The populations of injecting drug users and sex workers in Ho Chi Minh City are estimated to be 30000 and 80000, respectively, and rates of sexually transmitted diseases are 2-3 per 1000 persons per year. By the end of December 1996, 42 out of 53 provinces had reported HIV infections, and border areas near China and Cambodia began identifying large numbers of HIV-seropositive people. CONCLUSIONS: Ho Chi Minh City is at the forefront of a new HIV epidemic in Vietnam. This epidemic shows similarities to that in Thailand nearly a decade ago, with rapidly rising HIV rates among injecting drug users and infection already established among sex workers. Prevention efforts should include the targeting of injecting drug users and sex workers outside rehabilitation centers, the availability of sterile needles and condoms, the establishment of anonymous testing sites, the control of sexually transmitted diseases and the coordination of programs within southeast Asia.

PIP: An analysis of annual sentinel surveillance data from Viet Nam indicates that Ho Chi Minh City is at the forefront of a new HIV epidemic. Since 1990, data on HIV cases have been collected from prenatal clinics, blood banks, centers for the treatment of sexually transmitted diseases (STDs) and tuberculosis, and rehabilitation centers for injecting drug users and commercial sex workers. The first HIV case in Viet Nam was reported in 1990 in Ho Chi Minh City. By the end of 1996, a cumulative total of 4961 HIV cases had been documented in Viet Nam, 2774 of which were in Ho Chi Minh City. In Ho Chi Minh City, 86.5% of cumulative HIV infections involved men. The distribution of total HIV cases by group has been: injecting drug users, 86.0%; tuberculosis patients, 3.3%; sex workers, 2.5%; STD patients, 2.5%; and pregnant women, 0.6%. By 1996, 42 of Viet Nam's 53 provinces had reported HIV cases and infection rates are rising dramatically in border areas near China and Cambodia. The pattern documented in this analysis resembles that observed in Thailand a decade ago: rapidly rising HIV rates among injecting drug users and infection already established among sex workers, without dissemination to the general population. The necessary infrastructure and resources for control of the epidemic are far more limited in Viet Nam than Thailand, however. Recommended, to prevent the further spread of HIV in Viet Nam, are educational activities targeted at injecting drug users and sex workers outside of rehabilitation centers, the availability of condoms and sterile needles, establishment of anonymous testing sites, control of STDs, and the coordination of programs within southeast Asia.