Clinical Presentation, Risk Factors, and Comparison of Laboratory Diagnostics for Seasonal Influenza Virus Among Cambodians From 2007 to 2020.

Background: Despite its global significance, challenges associated with understanding the epidemiology and accurately detecting, measuring, and characterizing the true burden of seasonal influenza remain in many resource-poor settings. Methods: A prospective observational study was conducted in Cambodia at 28 health facilities between 2007 and 2020 utilizing passive surveillance data of patients presenting with acute undifferentiated febrile illness (AUFI) to describe the prevalence of influenza A and B and characterize associated risk factors and symptoms using a questionnaire. A comparison of rapid influenza diagnostic tests (RIDTs) and real-time reverse transcription polymerase chain reaction (rRT-PCR) results was also conducted. Results: Of 30 586 total participants, 5634 (18.4%) tested positive for either influenza A or B, with 3557 (11.6%) positive for influenza A and 2288 (7.5%) positive for influenza B during the study. Influenza A and B were strongly associated with the rainy season (odds ratio [OR], 2.30; P < .001) and being from an urban area (OR, 1.45; P < .001). Analysis of individual symptoms identified cough (OR, 2.8; P < .001), chills (OR, 1.4; P < .001), and sore throat (OR, 1.4; P < .001) as having the strongest positive associations with influenza among patients with AUFI. Analysis comparing RIDTs and rRT-PCR calculated the overall sensitivity of rapid tests to be 0.492 (95% CI, 0.479-0.505) and specificity to be 0.993 (95% CI, 0.992-0.994) for both influenza type A and B. Conclusions: Findings from this 14-year study include describing the epidemiology of seasonal influenza over a prolonged time period and identifying key risk factors and clinical symptoms associated with infection; we also demonstrate the poor sensitivity of RIDTs in Cambodia.

Etiology and risk factors for diarrheal disease amongst rural and peri-urban populations in Cambodia, 2012-2018.

Diarrheal diseases are a leading cause of mortality and morbidity, disproportionally affecting persons residing in low and middle-income countries. Accessing high-resolution surveillance data to understand community-level etiology and risk remains challenging, particularly in remote and resource limited populations. A multi-year prospective cohort study was conducted in two rural and two peri-urban villages in Cambodia from 2012 to 2018 to describe the epidemiology and etiology of acute diarrheal diseases within the population. Suspected diarrheal episodes among participants were self-reported or detected via routine weekly household visits. Fresh stool and fecal swabs were tested, and acute-illness and follow-up participant questionnaires collected. Of 5027 enrolled participants, 1450 (28.8%) reported at least one diarrheal incident. A total of 4266 individual diarrhea case events were recorded. Diarrhea incidence rate was calculated to be 281.5 persons per 1000 population per year, with an event rate of 664.3 individual diarrhea events occurring per 1000 population per year. Pathogenic Escherichia coli, Aeromonas spp., and Plesiomonas shigelloides were the most prevalent bacterial infections identified. Hookworm and Strongyloides stercoralis were the predominant helminth species, while Blastocystis hominis and Giardia lamblia were the predominant protozoan species found. Norovirus genotype 2 was the predominant virus identified. Mixed infections of two or more pathogens were detected in 36.2% of positive cases. Risk analyses identified unemployed status increased diarrhea risk by 63% (HR = 1.63 [95% CI 1.46, 1.83]). Individuals without access to protected water sources or sanitation facilities were 59% (HR = 1.59 [95% CI 1.49, 1.69]) and 19% (HR = 1.19 [95% CI 1.12, 1.28]) greater risk of contracting diarrhea, respectively. Patient-level surveillance data captured in this long-term study has generated a unique spatiotemporal profile of diarrheal disease in Cambodia. Understanding etiologies, together with associated epidemiological and community-level risk, provides valuable public health insight to support effective planning and delivery of appropriate local population-targeted interventions.

Understanding the epidemiology, clinical characteristics, knowledge and barriers to treatment and prevention of malaria among returning international laborers in northern Vietnam: a mixed-methods study.

BACKGROUND: With the decline in local malaria transmission in Vietnam as a result of the National Malaria Control Program (NMCP) elimination activities, a greater focus on the importation and potential reintroduction of transmission are essential to support malaria elimination objectives. METHODS: We conducted a multi-method assessment of the demographics, epidemiology, and clinical characteristics of imported malaria among international laborers returning from African or Southeast Asian countries to Vietnam. Firstly, we conducted a retrospective review of hospital records of patients from January 2014 to December 2016. Secondly, we conducted a mixed-methods prospective study for malaria patients admitted to the study sites from January 2017 to May 2018 using a structured survey with blood sample collection for PCR analysis and in-depth interviews. Data triangulation of the qualitative and quantitative data was used during analysis. RESULTS: International laborers were young (median age 33.0 years IQR 28.0-39.5 years), predominantly male (92%) adults returning mostly from the African continent (84%) who stayed abroad for prolonged periods (median time 13.5 months; IQR 6.0-331.5 months) and were involved in occupations that exposed them to a higher risk of malaria infection. Epidemiological trends were also similar amongst study strands and included the importation of Plasmodium falciparum primarily from African countries and P. vivax from Southeast Asian countries. Of 11 P. malariae and P. ovale infections across two study strands, 10 were imported from the African continent. Participants in the qualitative arm demonstrated limited knowledge about malaria prior to travelling abroad, but reported knowledge transformation through personal or co-worker's experience while abroad. Interestingly, those who had a greater understanding of the severity of malaria presented to the hospital for treatment sooner than those who did not; median of 3 days (IQR 2.0-7.0 days) versus 5 days (IQR 4.0-9.5 days) respectively. CONCLUSION: To address the challenges to malaria elimination raised by a growing Vietnamese international labor force, consideration should be given to appropriately targeted interventions and malaria prevention strategies that cover key stages of migration including pre-departure education and awareness, in-country prevention and prophylaxis, and malaria screening upon return.

Risk factors for malaria in high incidence areas of Viet Nam: a case-control study.

BACKGROUND: A key step to advancing the goal of malaria elimination in Viet Nam by 2030 is focusing limited resources for treatment and prevention to groups most at risk for malaria transmission. METHODS: To better understand risk factors for malaria transmission in central Viet Nam, a survey of 1000 malaria positive cases and 1000 malaria negative controls was conducted. Cases and controls were matched for age and gender and self-presented at commune health stations (CHS) in Binh Phuoc, Dak Nong and Dak Lak Provinces. Diagnoses were confirmed with microscopy, rapid diagnostic test and PCR. Participants were interviewed about 50 potential risk factors for malaria, which included information about occupation, forest visitation, travel, healthcare-seeking behaviour and prior use of anti-malaria interventions. Participants were enrolled by trained government health workers and the samples were analysed in Vietnamese government laboratories. Data were analysed by univariable, block-wise and multivariable logistic regression. RESULTS: Among cases, 61.8% had Plasmodium falciparum, 35.2% Plasmodium vivax and 3% mixed species infections. Median (IQR) age was 27 (21-36) years and 91.2% were male. Twenty-five risk factors were associated with being a case and eleven with being a control. Multivariable analysis found that malaria cases correlated with forest workers, recent forest visitation, longer duration of illness, having a recorded fever, number of malaria infections in the past year, having had prior malaria treatment and having previously visited a clinic. CONCLUSIONS: This study demonstrates the benefits of increased statistical power from matched controls in malaria surveillance studies, which allows identification of additional independent risk factors. It also illustrates an example of research partnership between academia and government to collect high quality data relevant to planning malaria elimination activities. Modifiable risk factors and implications of the findings for malaria elimination strategy are presented.

Results from a malaria indicator survey highlight the importance of routine data capture in high-risk forest and farm transmission sites in Vietnam to tailor location-specific malaria elimination interventions.

In-line with the World Health Organization's (WHO) Global Technical Strategy for Malaria (2016-2030), Vietnam is striving to eliminate malaria by 2030. Targeting appropriate interventions in high-risk populations such as forest and forest-fringe communities is a critical component of malaria elimination efforts in Vietnam. In 2016, a household-level malaria indicator survey was conducted in Phu Yen Province, Vietnam with the aim of assessing the knowledge, behaviors and associated risks of malaria infection among priority mobile and migrant populations (MMPs) working and sleeping in forests and on farms. A total of 4211 people were included in the survey, comprised of 1074 heads of households and 3137 associated household members. Of the 1074 head-of-household respondents, 472 slept in a forest, 92 slept on a farm, 132 slept in both forests and farms, and 378 slept at their villages within the last 12 months. Age, literacy, and occupation were significantly different among those who slept in a forest versus on a farm. Of 301 respondents who answered questions about malaria risk factors at sleeping sites, 35% were somewhat aware of malaria prevention practices, but only 4% could recall at least four malaria prevention messages. Among the same group of 301 respondents, only 29% used nets and only 11% used treated nets. Ownership and use of nets among forest-goers was significantly lower than those who slept on a farm or in their village. Huts without walls were significantly prominent forest sleeping site locations (POR = 10.3; 95% CI 4.67-22.7). All respondents who slept in a forest requested standby malaria drugs and one-third of them self-treated without blood testing. Results from this study highlight the importance of capturing relevant location-specific data among priority populations such as remote forest and farm going mobile and migrant populations in Vietnam. Data regarding behavioral practices, knowledge, preventative measures, and intervention coverage at remote-area transmission sites must be routinely captured to effectively monitor progress and refine targeted intervention strategies accordingly.

Mosquito Net Ownership, Utilization, and Preferences among Mobile and Migrant Populations Sleeping in Forests and Farms in Central Vietnam: A Cross-Sectional Study.

Strengthening vector control measures among mobile and migrant populations (MMPs) is crucial to malaria elimination, particularly in areas with multidrug-resistant malaria. Although a global priority, providing access and ensuring high coverage of available tools such as long-lasting insecticidal nets (LLINs) among these vulnerable groups remains a significant challenge. We assessed mosquito net ownership, utilization, and preference among individuals who slept in a forest and/or on a farm against those residing only in village "home" settings in a priority malaria elimination area of Vietnam. Proportions of respondents owning bed nets were similar among forest, farm, and home sleeping sites, ranging between 96% and 98%. The proportion of respondents owning hammock nets was higher for the forest group (92%), whereas ownership of hammocks in general was significantly lower for the home group (55%). Most respondents (97%) preferred to bring hammock nets to their remote sleeping site, whereas a smaller proportion (25%) also considered bed nets as an option. Respondent preferences included thick hammock nets with zippers (53%), hammocks with a flip cover (17%), and thin hammock nets with zippers (15%), with none choosing polyethylene (hard) LLINs. Although there is high coverage and access to nets for this high-priority MMP group, there was a noted gap between coverage and net use, potentially undermining the effectiveness of net-related interventions that could impact malaria prevention and elimination efforts in Vietnam. The design and material of nets are important factors for user preferences that appear to drive net use.

Targeting high risk forest goers for malaria elimination: a novel approach for investigating forest malaria to inform program intervention in Vietnam.

BACKGROUND: Individuals that work and sleep in remote forest and farm locations in the Greater Mekong Subregion continue to remain at high risk of both acquiring and transmitting malaria. These difficult-to-access population groups largely fall outside the reach of traditional village-centered interventions, presenting operational challenges for malaria programs. In Vietnam, over 60% of malaria cases are thought to be individuals who sleep in forests or on farms. New malaria elimination strategies are needed in countries where mobile and migrant workers frequently sleep outside of their homes. The aim of this study was to apply targeted surveillance-response based investigative approaches to gather location-specific data on confirmed malaria cases, with an objective to identify associated malaria prevention, treatment and risk behaviors of individuals sleeping in remote forest and farms sites in Vietnam. METHODS: A cross-sectional study using novel targeted reactive investigative approaches at remote area sleeping sites was conducted in three mountainous communes in Phu Yen province in 2016. Index cases were defined as individuals routinely sleeping in forests or farms who had tested positive for malaria. Index cases and non-infected neighbors from forest and farm huts within 500 m of the established sleeping locations of index cases were interviewed at their remote-area sleeping sites. RESULTS: A total of 307 participants, 110 index cases and 197 neighbors, were enrolled. Among 93 participants who slept in the forest, index cases were more likely to make > 5 trips to the forest per year (prevalence odds ratio (POR) 7.41, 95% confidence interval (CI) 2.66-20.63), sleep in huts without walls (POR 44.00, 95% CI 13.05-148.33), sleep without mosquito nets (POR 2.95, 95% CI 1.26-6.92), and work after dark (POR 5.48, 95% CI 1.84-16.35). Of the 204 farm-based respondents, a significantly higher proportion of index cases were involved in non-farming activities (logging) (POR 2.74, 95% CI 1.27-5.91). CONCLUSION: Investigative approaches employed in this study allowed for the effective recruitment and characterization of high-priority individuals frequently sleeping in remote forest and farm locations, providing relevant population and site-specific data that decision makers can use to design and implement targeted interventions to support malaria elimination.

Spatial and Temporal Patterns of Malaria in Phu Yen Province, Vietnam, from 2005 to 2016.

Malaria in Vietnam has become focal to a few provinces, including Phu Yen. This study aimed to assess correlations between intervention (population proportion protected by insecticide-treated nets and indoor residual spraying) and climatic variables with malaria incidence in Phu Yen Province. The Vietnam National Institute of Malariology, Parasitology, and Entomology provided incidence data for Plasmodium falciparum and Plasmodium vivax for 104 communes of Phu Yen Province from January 2005 to December 2016. A multivariable, zero-inflated Poisson regression model was developed with a conditional autoregressive prior structure to identify the underlying spatial structure of the data and quantify associations with covariates. There were a total of 2,778 P. falciparum and 1,770 P. vivax cases during the study period. Plasmodium falciparum and P. vivax incidence increased by 5.4% (95% credible interval [CrI] 5.1%, 5.7%) and 3.2% (95% CrI 2.9%, 3.5%) for a 10-mm increase in precipitation without lag, respectively. Plasmodium falciparum and P. vivax incidence decreased by 7.7% (95% CrI 5.6%, 9.7%) and 10.5% (95% CrI 8.3%, 12.6%) for a 1°C increase in minimum temperature without lag, respectively. There was a > 95% probability of a higher than provincial average trend of P. falciparum and P. vivax in Song Cau and Song Hoa districts. There was a > 95% probability of a lower than provincial average trend in Tuy Dong Xuan and Hoa districts for both species. Targeted distribution of resources, including intensified interventions, in this part of the province will be required for local malaria elimination.

Risk factor assessment for clinical malaria among forest-goers in a pre-elimination setting in Phu Yen Province, Vietnam.

BACKGROUND: The transition from malaria control to elimination requires understanding and targeting interventions among high-risk populations. In Vietnam, forest-goers are often difficult to test, treat and follow-up for malaria because they are highly mobile. If undiagnosed, forest-goers can maintain parasite reservoirs and contribute to ongoing malaria transmission. METHODS: A case-control study was conducted to identify malaria risk factors associated with forest-goers in three communes in Phu Yen Province, Vietnam. Cases (n = 81) were residents from the study area diagnosed with malaria and known to frequent forest areas. Controls (n = 94) were randomly selected forest-going residents from within the study area with no identified malaria infection. Participants were interviewed face-to-face using a standard questionnaire to identify malaria risk factors. Logistic regression was used to calculate odds ratios (ORs) and 95% CI for risk factors after adjusting for socio-demographic characteristics. RESULTS: Among the cases, malaria infection varied by species: 66.7% were positive for Plasmodium falciparum, 29.6% for Plasmodium vivax, and 3.7% were diagnosed as mixed infection. Cases were less likely than controls to use treated nets (aOR = 0.31; 95% CI 0.12-0.80), work after dark (aOR = 2.93; 95% CI 1.35, 6.34), bath in a stream after dark (aOR = 2.44; 95% CI 1.02-5.88), and collect water after dark (aOR = 1.99; 95% CI 1.02-3.90). CONCLUSIONS: As Vietnam moves toward malaria elimination, these findings can inform behaviour change communication and malaria prevention strategies, incorporating the risk of after-dark and water-related activities, in this priority and difficult-to-access population group.

Analysis of clinical malaria disease patterns and trends in Vietnam 2009-2015.

BACKGROUND: Viet Nam has made tremendous progress towards reducing mortality and morbidity associated with malaria in recent years. Despite the success in malaria control, there has been a recent increase in cases in some provinces. In order to understand the changing malaria dynamics in Viet Nam and measure progress towards elimination, the aim of this study was to describe and quantify spatial and temporal trends of malaria by species at district level across the country. METHODS: Malaria case reports at the Viet Nam National Institute of Malariology, Parasitology, and Entomology were reviewed for the period of January 2009 to December 2015. The population of each district was obtained from the Population and Housing Census-2009. A multivariate (insecticide-treated mosquito nets [ITN], indoor residual spraying [IRS], maximum temperature), zero-inflated, Poisson regression model was developed with spatial and spatiotemporal random effects modelled using a conditional autoregressive prior structure, and with posterior parameters estimated using Bayesian Markov chain Monte Carlo simulation with Gibbs sampling. Covariates included in the models were coverage of intervention (ITN and IRS) and maximum temperature. RESULTS: There was a total of 57,713 Plasmodium falciparum and 32,386 Plasmodium vivax cases during the study period. The ratio of P. falciparum to P. vivax decreased from 4.3 (81.0% P. falciparum; 11,121 cases) in 2009 to 0.8 (45.0% P. falciparum; 3325 cases) in 2015. Coverage of ITN was associated with decreased P. falciparum incidence, with a 1.1% (95% credible interval [CrI] 0.009%, 1.2%) decrease in incidence for 1% increase in the ITN coverage, but this was not the case for P. vivax, nor was it the case for IRS coverage. Maximum temperature was associated with increased incidence of both species, with a 4% (95% CrI 3.5%, 4.3%) and 1.6% (95% CrI 0.9%, 2.0%) increase in P. falciparum and P. vivax incidence for a temperature increase of 1 °C, respectively. Temporal trends of P. falciparum and P. vivax incidence were significantly higher than the national average in Central and Central-Southern districts. CONCLUSION: Interventions (ITN distribution) and environmental factors (increased temperature) were associated with incidence of P. falciparum and P. vivax during the study period. The factors reviewed were not exhaustive, however the data suggest distribution of resources can be targeted to areas and times of increased malaria transmission. Additionally, changing distribution of the two predominant malaria species in Viet Nam will require different programmatic approaches for control and elimination.