Low seroprevalence of COVID-19 in Lao PDR, late 2020.

BACKGROUND: In 2020 Lao PDR had low reported COVID-19 cases but it was unclear whether this masked silent transmission. A seroprevalence study was done August - September 2020 to determine SARS-CoV-2 exposure. METHODS: Participants were from the general community (n=2433) or healthcare workers (n=666) in five provinces and bat/wildlife contacts (n=74) were from Vientiane province. ELISAs detected anti- SARS-CoV-2 Nucleoprotein (N; n=3173 tested) and Spike (S; n=1417 tested) antibodies. Double-positive samples were checked by IgM/IgG rapid tests. Controls were confirmed COVID-19 cases (n=15) and pre-COVID-19 samples (n=265). Seroprevalence for the general community was weighted to account for complex survey sample design, age and sex. FINDINGS: In pre-COVID-19 samples, 5·3%, [95% CI=3·1-8·7%] were anti-N antibody single-positive and 1·1% [0·3-3·5%] were anti-S antibody single positive. None were double positive. Anti-N and anti-S antibodies were detected in 5·2% [4·2-6·5%] and 2·1% [1·1-3·9%] of the general community, 2·0% [1·1-3·3%] and 1·4% [0·5-3·7%] of healthcare workers and 20·3% [12·6-31·0%] and 6·8% [2·8-15·3%] of bat/wildlife contacts. 0·1% [0·02-0·3%] were double positive for anti-N and anti-S antibodies (rapid test negative). INTERPRETATION: We find no evidence for significant SARS-CoV-2 circulation in Lao PDR before September 2020. This likely results from early decisive measures taken by the government, social behavior, and low population density. High anti-N /low anti-S seroprevalence in bat/wildlife contacts may indicate exposure to cross-reactive animal coronaviruses with threat of emerging novel viruses. FUNDING: Agence Française de Développement. Additional; Institut Pasteur du Laos, Institute Pasteur, Paris and Luxembourg Ministry of Foreign and European Affairs ("PaReCIDS II").

Varicella zoster and fever rash surveillance in Lao People's Democratic Republic.

BACKGROUND: In Lao PDR, the epidemiology of varicella infection is uncertain, since it is not a notifiable disease and VZV outbreaks are rarely reported as fever/rash (F/R) diseases. METHODS: We estimated the seroprevalence of VZV (IgG ELISA) in different age cohorts (9 months to 46 years; N = 3139) and investigated VZV and 6 other viruses in patients during F/R outbreaks and in an ad hoc sentinel site in the context of the national reporting system (IgM ELISA, PCR). RESULTS: At least 80% of the sampled population had evidence of VZV infection before the age of 15. The largest increase in seroprevalence occurred between the age groups 1 to 5 and 6 to 7 year-olds. A VZV outbreak (clade 2) also occurred in this age group mostly during the first year of primary school (median age 6 years, interquartile range 4.0-7.5). During a dengue outbreak, 6% had varicella. At our F/R sentinel site, 14% of children with viral etiology were laboratory diagnosed as varicella and among others, a sizeable number of measles (N = 12) and rubella cases (N = 25) was detected compared to those reported for the whole country (N = 56 and 45), highlighting nationwide a large challenge of underreporting or misdiagnosis of these notifiable diseases because of lack of diagnostic laboratory capacity. CONCLUSION: We recommend strengthening the clinical and laboratory diagnosis of VZV, measles and rubella, the surveillance and reporting of notifiable F/R diseases by retraining of healthcare workers and by setting up sentinel sites and enhancing laboratory capacity.

Chikungunya virus emergence in the Lao PDR, 2012-2013.

In May 2012, the first authenticated cases of active chikungunya virus infection were detected in Champasak Province, Southern Laos. Analysis of series of human samples and mosquito specimens collected during the outbreak and over the year that followed the emergence enabled the drawing up of a map of the progression of CHIKV and the establishment of a full genetic characterization of the virus.

The Lao Experience in Deploying Influenza A(H1N1)pdm09 Vaccine: Lessons Made Relevant in Preparing for Present Day Pandemic Threats.

The Lao PDR, as did most countries of the Mekong Region, embarked on a pandemic vaccine initiative to counter the threat posed by influenza A(H1N1)pdm09. Overall, estimated vaccine coverage of the Lao population was 14%, with uptake in targeted health care workers and pregnant women 99% and 41%, respectively. Adverse Events Following Immunization accounted for only 6% of survey driven, reported vaccination experiences, with no severe consequences or deaths. Public acceptability of the vaccine campaign was high (98%). Challenges to vaccine deployment included: 1) no previous experience in fielding a seasonal influenza vaccine, 2) safety and efficacy concerns, and 3) late arrival of vaccine 10 months into the pandemic. The Lao success in surmounting these hurdles was in large measure attributed to the oversight assigned the National Immunization Program, and national sensitivities in responding to the avian influenza A(H5N1) crisis in the years leading up to the pandemic. The Lao "lessons learned" from pandemic vaccine deployment are made even more relevant four years on, given the many avian influenza strains circulating in the region, all with pandemic potential.

Influenza seasonality and vaccination timing in tropical and subtropical areas of southern and south-eastern Asia.

OBJECTIVE: To characterize influenza seasonality and identify the best time of the year for vaccination against influenza in tropical and subtropical countries of southern and south-eastern Asia that lie north of the equator. METHODS: Weekly influenza surveillance data for 2006 to 2011 were obtained from Bangladesh, Cambodia, India, Indonesia, the Lao People's Democratic Republic, Malaysia, the Philippines, Singapore, Thailand and Viet Nam. Weekly rates of influenza activity were based on the percentage of all nasopharyngeal samples collected during the year that tested positive for influenza virus or viral nucleic acid on any given week. Monthly positivity rates were then calculated to define annual peaks of influenza activity in each country and across countries. FINDINGS: Influenza activity peaked between June/July and October in seven countries, three of which showed a second peak in December to February. Countries closer to the equator had year-round circulation without discrete peaks. Viral types and subtypes varied from year to year but not across countries in a given year. The cumulative proportion of specimens that tested positive from June to November was > 60% in Bangladesh, Cambodia, India, the Lao People's Democratic Republic, the Philippines, Thailand and Viet Nam. Thus, these tropical and subtropical countries exhibited earlier influenza activity peaks than temperate climate countries north of the equator. CONCLUSION: Most southern and south-eastern Asian countries lying north of the equator should consider vaccinating against influenza from April to June; countries near the equator without a distinct peak in influenza activity can base vaccination timing on local factors.

National dengue surveillance in the Lao People's Democratic Republic, 2006-2012: epidemiological and laboratory findings.

Although dengue has been a public health problem for several decades in the Lao People's Democratic Republic, the magnitude of the disease burden and epidemiological trends remain poorly understood. We analysed national dengue surveillance and laboratory data from 2006 to 2012 by person, place and time. Between 2006 and 2012, the annual dengue notification rate ranged between 62 and 367 cases per 100 000 population with an apparent geographical expansion of transmission throughout the country in recent years and concurrent co-circulation of all four dengue virus subtypes. An electronic database, called Lao People's Democratic Republic Early Warning Alert and Response Network, was introduced in 2008 to provide automated early warning for outbreaks and epidemics. Village outbreaks continue to be notified primarily through event-based surveillance, whereas the weekly indicator-based system provides systematic assessment of annual epidemic cycles. The dengue case data indicate a high and increasing burden of disease. Efforts now need to focus on using available data to prompt more effective outbreak response and to guide the design and implementation of intervention strategies.

Chronic hepatitis B prevalence among children and mothers: results from a nationwide, population-based survey in Lao People's Democratic Republic.

BACKGROUND: Hepatitis B is regarded as a serious public health issue in Lao People's Democratic Republic (Lao PDR), a Southeast Asian country. However, disease epidemiology among the general population is not well known, and thus a nationwide cross-sectional survey for hepatitis B surface antigen (HBsAg) prevalence in children and their mothers was conducted. METHODS AND FINDINGS: We applied three-stage cluster sampling using probability proportionate to size. After randomly selecting child (5 to 9 years old) and mother (15 to 45 years old) pairs from the selected villages, questionnaires and HBsAg rapid tests were conducted. Data from 965 child and mother pairs were analyzed. Multivariate logistic regression analyses were used to investigate the independent association of individual background characteristics for the odds of being HBsAg positive. In total, 17 children and 27 mothers were HBsAg positive. HBsAg prevalence was estimated to be 1.7% (95% confidence interval: 0.8%-2.6%) in children, and 2.9% (95% confidence interval: 1.7%-4.2%) in their mothers after taking sampling design and weight of each sample into account. Mother's infection status was positively associated with HBsAg positivity in children (p<0.001), whereas other potential risk factors, such as ethnicity, proximity to health centers, and history of surgery, were not. There were no significant associations between mother's HBsAg status and history of surgery, and other sociodemographic factors. CONCLUSIONS: Despite the slow implementation of the hepatitis B vaccination program, HBsAg prevalence among children and their mothers was not high in Lao PDR compared to reports from neighboring countries. The reasons for the differences in prevalence among these countries are unclear. We recommend that prevalence surveys be conducted in populations born before and after the implementation of a hepatitis B vaccination program to better understand the epidemiology of hepatitis B.

National dengue surveillance in the Lao People's Democratic Republic, 2006–2012: epidemiological and laboratory findings

Although dengue has been a public health problem for several decades in the Lao People's Democratic Republic, the magnitude of the disease burden and epidemiological trends remain poorly understood. We analysed national dengue surveillance and laboratory data from 2006 to 2012 by person, place and time. Between 2006 and 2012, the annual dengue notification rate ranged between 62 and 367 cases per 100 000 population with an apparent geographical expansion of transmission throughout the country in recent years and concurrent co-circulation of all four dengue virus subtypes. An electronic database, called Lao People's Democratic Republic Early Warning Alert and Response Network, was introduced in 2008 to provide automated early warning for outbreaks and epidemics. Village outbreaks continue to be notified primarily through event-based surveillance, whereas the weekly indicator-based system provides systematic assessment of annual epidemic cycles. The dengue case data indicate a high and increasing burden of disease. Efforts now need to focus on using available data to prompt more effective outbreak response and to guide the design and implementation of intervention strategies.

Emergence of chikungunya in Moonlapamok and Khong Districts, Champassak Province,the Lao People's Democratic Republic, May to September 2012.

INTRODUCTION: Chikungunya is a vector-borne disease transmitted to humans by Aedes mosquitoes, which are widespread in the Lao People's Democratic Republic. However, chikungunya virus (CHIKV) had not been detected in the country before outbreaks reported in July 2012. The first outbreaks were detected through health care worker event-based surveillance. METHODS: The case definition for the outbreaks was defined as a person with acute onset of fever (≥ 38 °C) and severe arthralgia (joint pain) or arthritis from 1 May 2012 in Champassak Province. Rapid response teams conducted active case finding, performed an environmental assessment including an entomological survey and implemented control measures. Descriptive analysis was undertaken in Microsoft Excel. RESULTS: There were 197 cases (attack rate 3.4%) of suspected chikungunya reported from 10 villages in Moonlapamok and Khong Districts of Champassak Province. All age groups (age range: seven months-74 years) were affected with slightly more female (56%) than male cases. Thirty-one per cent (16 of 52) of serum samples tested positive for CHIKV by polymerase chain reaction. The environmental assessment found poor water storage practices and high entomological indices. DISCUSSION: These outbreaks show the effectiveness of health care worker event-based surveillance and the importance of sharing of information across borders for detecting emerging diseases. Public health education is an important measure to prevent epidemics of chikungunya. Information about chikungunya should be supplied to health care workers in the region so they are alert to the potential spread and are able to implement control measures for this disease.

Respiratory virus infections in hospitalized children and adults in Lao PDR.

BACKGROUND: Acute respiratory infections are an important cause of morbidity and mortality worldwide, with a major burden of disease in developing countries. The relative contribution of viruses in acute lower respiratory infections (ALRI) is, however, poorly documented in Lao PDR. OBJECTIVE: The objective of this study is to investigate the etiology of ALRI in patients of all ages in two hospitals of Laos. METHODS: Multiplex PCR/RT-PCR methods were used to target 18 major common respiratory viruses. Between August 2009 and October 2010, samples from 292 patients presenting with ALRI were collected. RESULTS AND CONCLUSION: Viruses were detected in 162 (55%) samples. In 48% (140/292) of the total ALRI cases, a single virus was detected while coinfections were observed in 8% (22/292) of the samples. The most frequent viruses were rhinovirus/enterovirus (35%), human respiratory syncytial virus (26%), and influenza viruses (13%). Parainfluenza viruses were detected in 9%, adenovirus in 6%, human metapneumovirus in 4%, coronaviruses (229E, NL63, OC43, HKU1) in 4%, and bocavirus in 3% of ALRI specimens. Most viral infections occurred in patients below 5 years of age. The distribution of viruses varied according to age-groups. No significant correlation was observed between the severity of the disease and the age of patients or the virus species. This study provides the description of viral etiology among patients presenting with ALRI in Lao PDR. Additional investigations are required to better understand the clinical role of the different viruses and their seasonality in Laos.

Causes of non-malarial fever in Laos: a prospective study.

BACKGROUND: Because of reductions in the incidence of Plasmodium falciparum malaria in Laos, identification of the causes of fever in people without malaria, and discussion of the best empirical treatment options, are urgently needed. We aimed to identify the causes of non-malarial acute fever in patients in rural Laos. METHODS: For this prospective study, we recruited 1938 febrile patients, between May, 2008, and December, 2010, at Luang Namtha provincial hospital in northwest Laos (n=1390), and between September, 2008, and December, 2010, at Salavan provincial hospital in southern Laos (n=548). Eligible participants were aged 5-49 years with fever (≥38°C) lasting 8 days or less and were eligible for malaria testing by national guidelines. FINDINGS: With conservative definitions of cause, we assigned 799 (41%) patients a diagnosis. With exclusion of influenza, the top five diagnoses when only one aetiological agent per patient was identified were dengue (156 [8%] of 1927 patients), scrub typhus (122 [7%] of 1871), Japanese encephalitis virus (112 [6%] of 1924), leptospirosis (109 [6%] of 1934), and bacteraemia (43 [2%] of 1938). 115 (32%) of 358 patients at Luang Namtha hospital tested influenza PCR-positive between June and December, 2010, of which influenza B was the most frequently detected strain (n=121 [87%]). Disease frequency differed significantly between the two sites: Japanese encephalitis virus infection (p=0·04), typhoid (p=0·006), and leptospirosis (p=0·001) were more common at Luang Namtha, whereas dengue and malaria were more common at Salavan (all p<0·0001). With use of evidence from southeast Asia when possible, we estimated that azithromycin, doxycycline, ceftriaxone, and ofloxacin would have had significant efficacy for 258 (13%), 240 (12%), 154 (8%), and 41 (2%) of patients, respectively. INTERPRETATION: Our findings suggest that a wide range of treatable or preventable pathogens are implicated in non-malarial febrile illness in Laos. Empirical treatment with doxycycline for patients with undifferentiated fever and negative rapid diagnostic tests for malaria and dengue could be an appropriate strategy for rural health workers in Laos. FUNDING: Wellcome Trust, WHO-Western Pacific Region, Foundation for Innovative New Diagnostics, US Centers for Disease Control and Prevention

Epidemiological and virological characteristics of seasonal and pandemic influenza in Lao PDR, 2008-2010.

BACKGROUND: Information on influenza virology and epidemiology from Lao PDR is limited and the seasonal patterns of influenza have not been previously described. OBJECTIVES: To describe epidemiological and virologic characteristics of influenza in Lao PDR to recommend public health interventions, including improvements in surveillance and response. PATIENTS/METHODS: We performed a descriptive analysis of samples taken from patients with influenza-like-illness (ILI) (fever >38°C with cough and/or sore throat) presenting at seven sentinel hospitals in three regions of Lao PDR, January 2008-December 2010. A nasopharyngeal (NP) swab or combined nasal with oropharyngeal swab was collected from patients with ILI. Samples were tested for influenza by either Luminex RVP, conventional reverse transcriptase PCR (RT-PCR) (January 2008-2009), or by real-time PCR (rRT-PCR) using US CDC reagents (February 2009 onward). RESULTS: Of 2346 samples tested from patients with ILI, 523 (22%) were positive for influenza. The median age of those positive was 12 years (range, <1-60 year). The percentage of samples that were influenza positive was similar over the 3 years (20-23%). Each year 3-4 types/subtypes cocirculated with differing predominant type/subtype. Influenza was detected year-round with the highest proportion of positive specimens in the 3rd and 4th quarter. CONCLUSIONS: Similar to other countries in the region, we found that influenza is present year-round and has a peak activity from July to December. Dominant types or subtypes vary by year. A large proportion of patients with ILI are not influenza positive. ILI surveillance is critical for weighing disease burden, both morbidity and mortality, against the costs of advancing influenza vaccine delivery strategy.

Emergence of chikungunya in Moonlapamok and Khong Districts, Champassak Province,the Lao People's Democratic Republic, May to September 2012

Introduction: Chikungunya is a vector-borne disease transmitted to humans by Aedes mosquitoes, which are widespread in the Lao People’s Democratic Republic. However, chikungunya virus (CHIKV) had not been detected in the country before outbreaks reported in July 2012. The first outbreaks were detected through health care worker event-based surveillance. Methods: The case definition for the outbreaks was defined as a person with acute onset of fever (> 38 °C) and severe arthralgia (joint pain) or arthritis from 1 May 2012 in Champassak Province. Rapid response teams conducted active case finding, performed an environmental assessment including an entomological survey and implemented control measures. Descriptive analysis was undertaken in Microsoft Excel. Results: There were 197 cases (attack rate 3.4%) of suspected chikungunya reported from 10 villages in Moonlapamok and Khong Districts of Champassak Province. All age groups (age range: seven months–74 years) were affected with slightly more female (56%) than male cases. Thirty-one per cent (16 of 52) of serum samples tested positive for CHIKV by polymerase chain reaction. The environmental assessment found poor water storage practices and high entomological indices. Discussion: These outbreaks show the effectiveness of health care worker event-based surveillance and the importance of sharing of information across borders for detecting emerging diseases. Public health education is an important measure to prevent epidemics of chikungunya. Information about chikungunya should be supplied to health care workers in the region so they are alert to the potential spread and are able to implement control measures for this disease.

Capacity building in response to pandemic influenza threats: Lao PDR case study.

The Lao People's Democratic Republic (PDR) committed to pandemic detection and response preparations when faced with the threat of avian influenza. Since 2006, the National Center for Laboratory and Epidemiology of Lao PDR has developed credible laboratory, surveillance, and epidemiological (human) capacity and as a result was designated a World Health Organization National Influenza Center in 2010. The Lao PDR experience in building influenza capacities provides a case study of the considerable crossover effect of such investments to augment the capacity to combat emerging and re-emerging diseases other than influenza.

An early report from newly established laboratory-based influenza surveillance in Lao PDR.

BACKGROUND: Prior to 2007, little information was available about the burden of influenza in Laos. We report data from the first laboratory-based influenza surveillance system established in the Lao People's Democratic Republic. METHODS: Three hospitals in the capital city of Vientiane began surveillance for influenza-like illness (ILI) in outpatients in 2007 and expanded to include hospitalized pneumonia patients in 2008. Nasal/throat swab specimens were collected and tested for influenza and other respiratory viruses by multiplex ID-Tag respiratory viral panel (RVP) assay on a Luminex 100x MAP IS instrument (Qiagen, Singapore). RESULTS: During January 2007 to December 2008, 287 of 526 (54.6%) outpatients with ILI were positive for at least one respiratory virus. Influenza was most commonly identified, with 63 (12.0%) influenza A and 92 (17.5%) influenza B positive patients identified. In 2008, six of 79 (7.6%) hospitalized pneumonia patients were positive for influenza A and four (5.1%) were positive for influenza B. Children <5 years represented 19% of viral infections in outpatients and 38% of pneumonia inpatients. CONCLUSION: Our results provide the first documentation of influenza burden among patients with febrile respiratory illness and pneumonia requiring hospitalization in Laos. Implementing laboratory-based influenza surveillance requires substantial investments in infrastructure and training. However, continuing outbreaks of avian influenza A/H5N1 in poultry and emergence of the 2009 influenza A(H1N1) pandemic strain further underscore the importance of establishing and maintaining influenza surveillance in developing countries.