Early pandemic influenza (2009 H1N1) in Ho Chi Minh City, Vietnam: a clinical virological and epidemiological analysis

Abstract

Background: To date, little is known about the initial spread and response to the 2009 pandemic of novel influenza A ("2009 H1N1") in tropical countries. Here, we analyse the early progression of the epidemic from 26 May 2009 until the establishment of community transmission in the second half of July 2009 in Ho Chi Minh City (HCMC), Vietnam. In addition, we present detailed systematic viral clearance data on 292 isolated and treated patients and the first three cases of selection of resistant virus during treatment in Vietnam.

Methods and findings: Data sources included all available health reports from the Ministry of Health and relevant health authorities as well as clinical and laboratory data from the first confirmed cases isolated at the Hospital for Tropical Diseases in HCMC. Extensive reverse transcription (RT)-PCR diagnostics on serial samples, viral culture, neuraminidase-inhibition testing, and sequencing were performed on a subset of 2009 H1N1 confirmed cases. Virological (PCR status, shedding) and epidemiological (incidence, isolation, discharge) data were combined to reconstruct the initial outbreak and the establishment of community transmission. From 27 April to 24 July 2009, approximately 760,000 passengers who entered HCMC on international flights were screened at the airport by a body temperature scan and symptom questionnaire. Approximately 0.15% of incoming passengers were intercepted, 200 of whom tested positive for 2009 H1N1 by RT-PCR. An additional 121 out of 169 nontravelers tested positive after self-reporting or contact tracing. These 321 patients spent 79% of their PCR-positive days in isolation; 60% of PCR-positive days were spent treated and in isolation. Influenza-like illness was noted in 61% of patients and no patients experienced pneumonia or severe outcomes. Viral clearance times were similar among patient groups with differing time intervals from illness onset to treatment, with estimated median clearance times between 2.6 and 2.8 d post-treatment for illness-to-treatment intervals of 1-4 d, and 2.0 d (95% confidence interval 1.5-2.5) when treatment was started on the first day of illness.

Conclusions: The patients described here represent a cross-section of infected individuals that were identified by temperature screening and symptom questionnaires at the airport, as well as mildly symptomatic to moderately ill patients who self-reported to hospitals. Data are observational and, although they are suggestive, it is not possible to be certain whether the containment efforts delayed community transmission in Vietnam. Viral clearance data assessed by RT-PCR showed a rapid therapeutic response to oseltamivir.

Figure 1. New cases as reported by the Ministry of Health and Hospital for Tropical Diseases.

Day-by-day comparison of official H1N1 confirmations in southern Vietnam as reported by the Ministry of Health in Vietnam (dark gray bars) and by the surveillance and diagnostics laboratories of HTD/Oxford University Clinical Research Unit (OUCRU) and the HCMC Health Services (red bars) during the initial epidemic phase in HCMC. Overall, 321 H1N1 confirmations were captured by HTD, OUCRU, and the HCMC Health Services, out of a total of 424 reported for southern Vietnam during the period from 31 May to 25 July 2009. HTD confirmations are a subset of Ministry of Health confirmations; reporting dates for individual cases can differ.

Figure 2. Status of confirmed new cases in HCMC.

321 PCR-confirmed 2009 H1N1 cases and 298 PCR-negative suspected 2009 H1N1 cases admitted to hospitals in HCMC between early May 2009 and 20 July 2009. All 619 individuals are classified either as travelers (those who recently entered HCMC on a commercial flight from a foreign country) or residents; travelers are shown above the axis and residents below the axis. Graph is organized in a stacked fashion, so that the height of each colored area corresponds to the number of patients of a particular status (e.g., circulating, isolated) on a particular day. Graph is cut off on 20 July 2009 as the data were more sparse after this date.

Figure 3. RT-PCR and culture results related to day of illness or treatment.

(A and B) PCR status for 932 individual samples by day of illness (A) and day of treatment (B), with the vertical axis extending to 292, the number of patients from whom samples were taken. (C and D) 108 (C) and 111 samples (D) of a total of 115 with which viral culture was attempted. Day one of treatment is the day of treatment initiation. Day zero of treatment is 1 d before treatment is initiated. Three culture-positive samples were PCR-negative: two taken on fourth day of illness (second day of treatment), and one taken on sixth day of illness (fourth day of treatment).

Figure 4. Per patient analysis of RT-PCR results shown by day of illness and day of treatment.

Time to PCR negativity and its dependence on illness-to-treatment interval. (A) Gray lines show the minimum and maximum number of patients who were PCR-negative after a certain number of days of illness, on the basis of patients' last positive PCR result and first negative PCR result, which could be separated by a gap of as many as 4 d. Red line shows the ML-fit (see Methods) of time to PCR negativity, and dashed lines are 95% confidence bands. (B) as (A), related to days of treatment. (C, D) Minimum and maximum durations of PCR positivity for patient subgroups corresponding to the length of illness-to-treatment interval. (E, F) ML-curves describing time to PCR-negativity for patient subgroups. Curves for patients who started treatment on the day of illness onset (illness-to-treatment interval = 0, 11 patients), and patients who started treatment 5 d postillness (illness-to-treatment interval = 5, 10 patients) are shown in gray as they differ qualitatively from the other four curves. Legend in (D) applies to (C–F). Data from 278 patients with both negative and positive PCRs were used to make these graphs.