Mass Relapse Prevention to Reduce Transmission of Plasmodium vivax- A Systematic Review.

Several temperate countries have used mass chemoprevention interventions with medicines of the 8-aminoquinoline class that prevent relapses from Plasmodium vivax before peak transmission to reduce transmission of malaria. The WHO commissioned a systematic review of the literature and evidence synthesis to inform development of recommendations regarding this intervention referred to as "mass relapse prevention" (MRP). Electronic databases were searched, 866 articles screened, and 25 assessed for eligibility after a full-text review. Two nonrandomized studies were included, one from the Democratic People's Republic of Korea (391,357 participants) and the second from the Azerbaijan Soviet Socialist Republic (∼30,000 participants). The two studies administered a single round of primaquine over 14 days (0.25 mg/kg per day). From 1 to 3 months after the treatment round, the incidence of P. vivax infections was significantly lower in areas that received MRP than those that did not (pooled rate ratio [RR] 0.08, 95% CI 0.07-0.08). At 4 to 12 months after the treatment round, the prevalence of P. vivax infection was significantly lower in MRP villages than non-MRP villages (odds ratio 0.12, 95% CI 0.03-0.52). No severe adverse events were found. The certainty of evidence for all outcomes was very low and no conclusions as to the effectiveness or safety of MRP could be drawn. However, it is not likely that this intervention will be needed in the future as most temperate countries where P. vivax is transmitted are nearing or have already eliminated malaria.

Development of WHO Recommendations for the Final Phase of Elimination and Prevention of Re-Establishment of Malaria.

The WHO recommends that all affected countries work toward the elimination of malaria, even those still experiencing a high burden of disease. However, malaria programs in the final phase of elimination or those working to prevent re-establishment of transmission after elimination could benefit from specific evidence-based recommendations for these settings as part of comprehensive and quality-controlled malaria guidelines. The WHO convened an external guideline development group to formulate recommendations for interventions to reduce or prevent malaria transmission in areas with very low- to low-transmission levels and those that have eliminated malaria. In addition, several interventions that could be deployed in higher burden areas to accelerate elimination, such as mass drug administration, were reviewed. Systematic reviews were conducted that synthesized and evaluated evidence for the benefits and harms of public health interventions and summarized critical contextual factors from a health systems perspective. A total of 12 recommendations were developed, with five related to mass interventions that could be deployed at higher transmission levels and seven that would be most appropriate for programs in areas close to elimination or those working to prevent re-establishment of transmission. Four chemoprevention, two active case detection, and one vector control interventions were positively recommended, whereas two chemoprevention and three active case detection interventions were not recommended by the WHO. None of the recommendations were classified as strong given the limited and low-quality evidence base. Approaches to conducting higher quality research in very low- to low-transmission settings to improve the strength of WHO recommendations are discussed.

Impact of Intermittent Mass Testing and Treatment on Incidence of Malaria Infection in a High Transmission Area of Western Kenya.

Progress with malaria control in western Kenya has stagnated since 2007. Additional interventions to reduce the high burden of malaria in this region are urgently needed. We conducted a two-arm, community-based, cluster-randomized, controlled trial of active case detection and treatment of malaria infections in all residents mass testing and treatment (MTaT) of 10 village clusters (intervention clusters) for two consecutive years to measure differences in the incidence of clinical malaria disease and malaria infections compared with 20 control clusters where MTaT was not implemented. All residents of intervention clusters, irrespective of history of fever or other malaria-related symptoms, were tested three times per year before the peak malaria season using malaria rapid diagnostic tests. All positive cases were treated with dihydroartemisinin-piperaquine. The incidence of clinical malaria was measured through passive surveillance, whereas the cumulative incidence of malaria infection was measured using active surveillance in a cohort comprising randomly selected residents. The incidence of clinical malaria was 0.19 cases/person-year (p-y, 95% CI: 0.13-0.28) in the intervention arm and 0.24 cases/p-y (95% CI: 0.15-0.39) in the control arm (incidence rate ratio [IRR] 0.79, 95% CI: 0.61-1.02). The cumulative incidence of malaria infections was similar between the intervention (2.08 infections/p-y, 95% CI: 1.93-2.26) and control arms (2.19 infections/p-y, 95% CI: 2.02-2.37) with a crude IRR of 0.95 (95% CI: 0.87-1.04). Six rounds of MTaT over 2 years did not have a significant impact on the incidence of clinical malaria or the cumulative incidence of malaria infection in this area of high malaria transmission.

Community-based intermittent mass testing and treatment for malaria in an area of high transmission intensity, western Kenya: development of study site infrastructure and lessons learned.

BACKGROUND: Malaria transmission is high in western Kenya and the asymptomatic infected population plays a significant role in driving the transmission. Mathematical modelling and simulation programs suggest that interventions targeting asymptomatic infections through mass testing and treatment (MTaT) or mass drug administration (MDA) have the potential to reduce malaria transmission when combined with existing interventions. OBJECTIVE: This paper describes the study site, capacity development efforts required, and lessons learned for implementing a multi-year community-based cluster-randomized controlled trial to evaluate the impact of MTaT for malaria transmission reduction in an area of high transmission in western Kenya. METHODS: The study partnered with Kenya's Ministry of Health (MOH) and other organizations on community sensitization and engagement to mobilize, train and deploy community health volunteers (CHVs) to deliver MTaT in the community. Within the health facilities, the study availed staff, medical and laboratory supplies and strengthened health information management system to monitor progress and evaluate impact of intervention. RESULTS: More than 80 Kenya MOH CHVs, 13 clinical officers, field workers, data and logistical staff were trained to carry out MTaT three times a year for 2 years in a population of approximately 90,000 individuals. A supply chain management was adapted to meet daily demands for large volumes of commodities despite the limitation of few MOH facilities having ideal storage conditions. Modern technology was adapted more to meet the needs of the high daily volume of collected data. CONCLUSIONS: In resource-constrained settings, large interventions require capacity building and logistical planning. This study found that investing in relationships with the communities, local governments, and other partners, and identifying and equipping the appropriate staff with the skills and technology to perform tasks are important factors for success in delivering an intervention like MTaT.

Viral etiologies of influenza-like illness and severe acute respiratory infections in Thailand.

BACKGROUND: Information on the burden, characteristics and seasonality of non-influenza respiratory viruses is limited in tropical countries. OBJECTIVES: Describe the epidemiology of selected non-influenza respiratory viruses in Thailand between June 2010 and May 2014 using a sentinel surveillance platform established for influenza. METHODS: Patients with influenza-like illness (ILI; history of fever or documented temperature ≥38°C, cough, not requiring hospitalization) or severe acute respiratory infection (SARI; history of fever or documented temperature ≥38°C, cough, onset <10 days, requiring hospitalization) were enrolled from 10 sites. Throat swabs were tested for influenza viruses, respiratory syncytial virus (RSV), metapneumovirus (MPV), parainfluenza viruses (PIV) 1-3, and adenoviruses by polymerase chain reaction (PCR) or real-time reverse transcriptase-PCR. RESULTS: We screened 15 369 persons with acute respiratory infections and enrolled 8106 cases of ILI (5069 cases <15 years old) and 1754 cases of SARI (1404 cases <15 years old). Among ILI cases <15 years old, influenza viruses (1173, 23%), RSV (447, 9%), and adenoviruses (430, 8%) were the most frequently identified respiratory viruses tested, while for SARI cases <15 years old, RSV (196, 14%) influenza (157, 11%) and adenoviruses (90, 6%) were the most common. The RSV season significantly overlapped the larger influenza season from July to November in Thailand. CONCLUSIONS: The global expansion of influenza sentinel surveillance provides an opportunity to gather information on the characteristics of cases positive for non-influenza respiratory viruses, particularly seasonality, although adjustments to case definitions may be required.

Community-based intermittent mass testing and treatment for malaria in an area of high transmission intensity, western Kenya: study design and methodology for a cluster randomized controlled trial.

Most human Plasmodium infections in western Kenya are asymptomatic and are believed to contribute importantly to malaria transmission. Elimination of asymptomatic infections requires active treatment approaches, such as mass testing and treatment (MTaT) or mass drug administration (MDA), as infected persons do not seek care for their infection. Evaluations of community-based approaches that are designed to reduce malaria transmission require careful attention to study design to ensure that important effects can be measured accurately. This manuscript describes the study design and methodology of a cluster-randomized controlled trial to evaluate a MTaT approach for malaria transmission reduction in an area of high malaria transmission. Ten health facilities in western Kenya were purposively selected for inclusion. The communities within 3 km of each health facility were divided into three clusters of approximately equal population size. Two clusters around each health facility were randomly assigned to the control arm, and one to the intervention arm. Three times per year for 2 years, after the long and short rains, and again before the long rains, teams of community health volunteers visited every household within the intervention arm, tested all consenting individuals with malaria rapid diagnostic tests, and treated all positive individuals with an effective anti-malarial. The effect of mass testing and treatment on malaria transmission was measured through population-based longitudinal cohorts, outpatient visits for clinical malaria, periodic population-based cross-sectional surveys, and entomological indices.

Bat rabies in Guatemala.

Rabies in bats is considered enzootic throughout the New World, but few comparative data are available for most countries in the region. As part of a larger pathogen detection program, enhanced bat rabies surveillance was conducted in Guatemala, between 2009 and 2011. A total of 672 bats of 31 species were sampled and tested for rabies. The prevalence of rabies virus (RABV) detection among all collected bats was low (0.3%). Viral antigens were detected and infectious virus was isolated from the brains of two common vampire bats (Desmodus rotundus). RABV was also isolated from oral swabs, lungs and kidneys of both bats, whereas viral RNA was detected in all of the tissues examined by hemi-nested RT-PCR except for the liver of one bat. Sequencing of the nucleoprotein gene showed that both viruses were 100% identical, whereas sequencing of the glycoprotein gene revealed one non-synonymous substitution (302T,S). The two vampire bat RABV isolates in this study were phylogenetically related to viruses associated with vampire bats in the eastern states of Mexico and El Salvador. Additionally, 7% of sera collected from 398 bats demonstrated RABV neutralizing antibody. The proportion of seropositive bats varied significantly across trophic guilds, suggestive of complex intraspecific compartmentalization of RABV perpetuation.

Surveillance for hospitalized acute respiratory infection in Guatemala.

Acute respiratory infections (ARI) are an important cause of illness and death worldwide, yet data on the etiology of ARI and the population-level burden in developing countries are limited. Surveillance for ARI was conducted at two hospitals in Guatemala. Patients admitted with at least one sign of acute infection and one sign or symptom of respiratory illness met the criteria for a case of hospitalized ARI. Nasopharyngeal/oropharyngeal swabs were collected and tested by polymerase chain reaction for adenovirus, parainfluenza virus types 1,2 and 3, respiratory syncytial virus, influenza A and B viruses, human metapneumovirus, Chlamydia pneumioniae, and Mycoplasma pneumoniae. Urine specimens were tested for Streptococcus pneumoniae antigen. Blood culture and chest radiograph were done at the discretion of the treating physician. Between November 2007 and December 2011, 3,964 case-patients were enrolled. While cases occurred among all age groups, 2,396 (60.4%) cases occurred in children <5 years old and 463 (11.7%) among adults ≥65 years old. Viruses were found in 52.6% of all case-patients and 71.8% of those aged <1 year old; the most frequently detected was respiratory syncytial virus, affecting 26.4% of case-patients. Urine antigen testing for Streptococcus pneumoniae performed for case-patients ≥15 years old was positive in 15.1% of those tested. Among 2,364 (59.6%) of case-patients with a radiograph, 907 (40.0%) had findings suggestive of bacterial pneumonia. Overall, 230 (5.9%) case-patients died during the hospitalization. Using population denominators, the observed hospitalized ARI incidence was 128 cases per 100,000, with the highest rates seen among children <1 year old (1,703 per 100,000), followed by adults ≥65 years old (292 per 100,000). These data, which demonstrate a substantial burden of hospitalized ARI in Guatemala due to a variety of pathogens, can help guide public health policies aimed at reducing the burden of illness and death due to respiratory infections.

Discovery of diverse polyomaviruses in bats and the evolutionary history of the Polyomaviridae.

Polyomaviruses (PyVs) have been identified in a wide range of avian and mammalian species. However, little is known about their occurrence, genetic diversity and evolutionary history in bats, even though bats are important reservoirs for many emerging viral pathogens. This study screened 380 specimens from 35 bat species from Kenya and Guatemala for the presence of PyVs by semi-nested pan-PyV PCR assays. PyV DNA was detected in 24 of the 380 bat specimens. Phylogenetic analysis revealed that the bat PyV sequences formed 12 distinct lineages. Full-genome sequences were obtained for seven representative lineages and possessed similar genomic features to known PyVs. Strikingly, this evolutionary analysis revealed that the bat PyVs were paraphyletic, suggestive of multiple species jumps between bats and other mammalian species, such that the theory of virus-host co-divergence for mammalian PyVs as a whole could be rejected. In addition, evidence was found for strong heterogeneity in evolutionary rate and potential recombination in a number of PyV complete genomes, which complicates both phylogenetic analysis and virus classification. In summary, this study revealed that bats are important reservoirs of PyVs and that these viruses have a complex evolutionary history.