Randomised primary health center based interventions to improve the diagnosis and treatment of undifferentiated fever and dengue in Vietnam.

BACKGROUND: Fever is a common reason for attending primary health facilities in Vietnam. Response of health care providers to patients with fever commonly consists of making a presumptive diagnosis and proposing corresponding treatment. In Vietnam, where malaria was brought under control, viral infections, notably dengue, are the main causes of undifferentiated fever but they are often misdiagnosed and inappropriately treated with antibiotics.This study investigate if educating primary health center (PHC) staff or introducing rapid diagnostic tests (RDTs) improve diagnostic resolution and accuracy for acute undifferentiated fever (AUF) and reduce prescription of antibiotics and costs for patients. METHODS: In a PHC randomized intervention study in southern Vietnam, the presumptive diagnoses for AUF patients were recorded and confirmed by serology on paired (acute and convalescence) sera. After one year, PHCs were randomized to four intervention arms: training on infectious diseases (A), the provision of RDTs (B), the combination (AB) and control (C). The intervention lasted from 2002 until 2006. RESULTS: The frequency of the non-etiologic diagnosis "undifferentiated fever" decreased in group AB, and - with some delay- also in group B. The diagnosis "dengue" increased in group AB, but only temporarily, although dengue was the most common cause of fever. A correct diagnosis for dengue initially increased in groups AB and B but only for AB this was sustained. Antibiotics prescriptions increased in group C. During intervention it initially declined in AB with a tendency to increase afterwards; in B it gradually declined. There was a substantial increase of patients' costs in B. CONCLUSIONS: The introduction of RDTs for infectious diseases such as dengue, through free market principles, does improve the quality of the diagnosis and decreases the prescription of antibiotics at the PHC level. However, the effect is more sustainable in combination with training; without it RDTs lead to an excess of costs.

Viral respiratory tract infections among patients with acute undifferentiated fever in Vietnam.

To investigate the proportion of viral respiratory tract infections among acute undifferentiated fevers (AUFs) at primary health facilities in southern Vietnam during 2001-2005, patients with AUF not caused by malaria were enrolled at twelve primary health facilities and a clinic for malaria control program. Serum was collected on first presentation (t0) and after 3 weeks (t3) for serology. After exclusion of acute dengue infection, acute and convalescent serum samples from 606 patients were using enzyme-linked immunoassays to detect IgA, as well as IgM and IgG antibodies against common respiratory viruses. Paired sera showed the following infections: human parainfluenza virus (HPIV, 4.7%), influenza B virus (FLUBV, 2.2%), influenza A virus (FLUAV, 1.9%) and human respiratory syncytial virus (HRSV, 0.6%). There was no association between type of infection and age, sex or seasonality; some inter-annual differences were observed for influenza. Antibody prevalence, indicative of previous infections, was relatively low: HPV, 56.8%, FLUBV, 12.1%; FLUAV, 5.9% and HRSV, 6.8%.

Dengue as a cause of acute undifferentiated fever in Vietnam.

BACKGROUND: Dengue is a common cause of fever in the tropics but its contribution to the total burden of febrile illnesses that is presented to primary health facilities in endemic regions such as Vietnam, is largely unknown. We aimed to report the frequency of dengue as a cause of fever in Binh Thuan Province, to describe the characteristics of dengue patients, and analyze the diagnostic accuracy of the health care workers and the determinants of the diagnostic process. METHODS: All patients presenting with acute undifferentiated fever at twelve community health posts and one clinic at the provincial malaria station, Binh Thuan Province, a dengue endemic province in southern Vietnam, were included. Record forms were used to fill in patient and diseases characteristics, pre-referral treatment, signs and symptoms, provisional diagnosis and prescribed treatment, referral and final outcome. Serum samples were collected at first presentation and after 3 weeks for serologic diagnosis. RESULTS: 2096 patients were included from April 2001 to March 2002. All 697 patients with paired serum samples were tested for dengue virus IgM and IgG. Acute dengue was found in 33.6% cases and past dengue virus infections were found in 57.1% cases. Acute primary infections were more common among children under 15 years old than among adults (7.7% vs. 3.5%, p value < 0.001). Younger age significantly predicted acute dengue (RR per increasing year of age (95 % CI): 0.986 (0.975-0.997, p value = 0.014). 48.9% of cases with clinical diagnosis of acute dengue were serologically confirmed and 32.5% of cases without clinical diagnosis of acute dengue were positive by serology after all (OR = 1.981, p value 0.025, 95% CI: 1.079-3.635). Tourniquet test was not a predictor for dengue diagnosis. CONCLUSION: Dengue is responsible for one third of the fevers presented to the public primary health services in Binh Thuan, southern Vietnam. It presents as a highly unspecific illness and is hardly recognized as a clinical entity by primary physicians.

Effects of infection control measures on acquisition of five antimicrobial drug-resistant microorganisms in a tetanus intensive care unit in Vietnam.

PURPOSE: To quantify the effects of barrier precautions and antibiotic mixing on prevalence and acquisition of five drug-resistant microorganisms within a single tetanus intensive care unit at a tertiary referral hospital in Ho Chi Minh City, Vietnam. METHODS: All patients admitted within the study period were included. After a 1-year baseline period, barrier precautions were implemented and the single empirical treatment ceftazidime was changed to mixing (per consecutive patient) of three different regimens (ceftazidime, ciprofloxacin, piperacillin-tazobactam). Markov chain modeling and genotyping were used to determine the effects of interventions on prevalence levels and the relative importance of cross-transmission and antibiotic-associated selection. RESULTS: A total of 190 patients were included in year 1 (2,708 patient days, 17,260 cultures) and 167 patients in year 2 (3,384 patient days, 20,580 cultures). In year 1, average daily prevalence rates for methicillin-resistant Staphylococcus aureus (MRSA), extended spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae (excluding Klebsiella pneumoniae), Pseudomonas aeruginosa, gentamicin-resistant K. pneumoniae, and amikacin-resistant Acinetobacter species were 34.0, 61.3, 53.4, 65.7 and 57.1 %. After intervention, ceftazidime usage decreased by 53 %; the use of piperacillin-tazobactam and ciprofloxacin increased 7.2-fold and 4.5-fold, respectively. Adherence to hand hygiene after patient contact was 54 %. These measures were associated with a reduction of MRSA prevalence by 69.8 % (to 10.3 %), mainly because of less cross-transmission (88 % reduction), and of ESBL-producing Enterobacteriaceae prevalence by 10.3 % (non-significantly). In contrast, prevalence levels of the other three pathogens remained unaffected. CONCLUSION: The combination of simple infection control measures and antibiotic mixing was highly effective in reducing the prevalence of MRSA, but not of Gram-negative microorganisms.

Internally controlled, generic real-time PCR for quantification and multiplex real-time PCR with serotype-specific probes for serotyping of dengue virus infections.

Dengue has become a global public health problem and a sensitive diagnostic test for early phase detection can be life saving. An internally controlled, generic real-time PCR was developed and validated by testing serial dilutions of a DENV positive control RNA in the presence of a fixed amount of IC with results showing a good linearity (R(2) = 0.9967) and a LOD of at least 1.95 × 10(4) copies/mL. Application of the generic PCR on 136 patient samples revealed a sensitivity of 95.8% and specificity of 100%. A newly developed multiplex real-time PCR with serotype-specific probes allowed the serotyping of DENV for 80 out of 92 (87%) generic real-time PCR positive patients. Combined these real-time PCRs offer a convenient diagnostic tool for the sensitive and specific quantification of DENV in clinical specimens with the possibility for serotyping.

Detection of dengue nonstructural 1 (NS1) protein in Vietnamese patients with fever.

Diagnosing dengue in febrile patients is challenging. Of a total of 459 patients with acute undifferentiated fever, randomly selected from 12 primary health facilities and 1 clinic of the provincial malaria station in southern Vietnam, dengue-specific antibody (Ab) and NS1Ag enzyme-linked immunosorbent assay (ELISA) (Platelia, Bio-Rad Laboratories, Hercules, CA 94547, US) were performed on acute (t0) and convalescent (t3 weeks) sera. Polymerase chain reaction (PCR) was used for confirmation. Based on a composite of the NS1Ag-ELISA, Ab-ELISA, and PCR results, 54 (12%) patients had acute dengue. Positive and negative predictive values were 65% and 98% for the Ab-based diagnosis and 91% and 92% for NS1Ag, respectively. The agreement between Ab- and NS1Ag-based diagnosis was poor (kappa value, 0.2). Two patients without dengue had detectable NS1Ag on t0 and t3, 1 just above the cutoff value and 1 with very high values. For 5 dengue patients, NS1Ag was still detectable at very high levels at t3. Dengue NS1Ag can be used for early diagnosis of dengue; infrequent false-positive results need further clarification.

Brucellosis is not a major cause of febrile illness in patients at public health care facilities in Binh Thuan Province, Vietnam.

OBJECTIVE: To determine the presence of brucellosis among patients with acute febrile illness at health care facilities in Binh Thuan province, Vietnam. METHOD: A retrospective seroepidemiological study on serum samples collected at 13 not adjacent health care facilities using the Rose Bengal test as a rapid screening test and the Brucella IgM/IgG flow assay as a simple confirmatory test. RESULT: The seroprevalence in the Rose Bengal test among 406 patients presented with acute undifferentiated fever was 14.8%. Seven of the 64 Rose Bengal test positive samples reacted weakly (1+) positive in the Brucella IgM/IgG flow assay. No seroconversion was observed. CONCLUSIONS: Brucellosis is not a major cause of morbidity in Binh Thuan province.