The effectiveness of non-pyrethroid insecticide-treated durable wall lining to control malaria in rural Tanzania: study protocol for a two-armed cluster randomized trial.

BACKGROUND: Despite considerable reductions in malaria achieved by scaling-up long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS), maintaining sustained community protection remains operationally challenging. Increasing insecticide resistance also threatens to jeopardize the future of both strategies. Non-pyrethroid insecticide-treated wall lining (ITWL) may represent an alternate or complementary control method and a potential tool to manage insecticide resistance. To date no study has demonstrated whether ITWL can reduce malaria transmission nor provide additional protection beyond the current best practice of universal coverage (UC) of LLINs and prompt case management. METHODS/DESIGN: A two-arm cluster randomized controlled trial will be conducted in rural Tanzania to assess whether non-pyrethroid ITWL and UC of LLINs provide added protection against malaria infection in children, compared to UC of LLINs alone. Stratified randomization based on malaria prevalence will be used to select 22 village clusters per arm. All 44 clusters will receive LLINs and half will also have ITWL installed on interior house walls. Study children, aged 6 months to 11 years old, will be enrolled from each cluster and followed monthly to estimate cumulative incidence of malaria parasitaemia (primary endpoint), time to first malaria episode and prevalence of anaemia before and after intervention. Entomological inoculation rate will be estimated using indoor CDC light traps and outdoor tent traps followed by detection of Anopheles gambiae species, sporozoite infection, insecticide resistance and blood meal source. ITWL bioefficacy and durability will be monitored using WHO cone bioassays and household surveys, respectively. Social and cultural factors influencing community and household ITWL acceptability will be explored through focus-group discussions and in-depth interviews. Cost-effectiveness, compared between study arms, will be estimated per malaria case averted. DISCUSSION: This protocol describes the large-scale evaluation of a novel vector control product, designed to overcome some of the known limitations of existing methods. If ITWL is proven to be effective and durable under field conditions, it may warrant consideration for programmatic implementation, particularly in areas with long transmission seasons and where pyrethroid-resistant vectors predominate. Trial findings will provide crucial information for policy makers in Tanzania and other malaria-endemic countries to guide resource allocations for future control efforts. TRIAL REGISTRATION: NCT02533336 registered on 13 July 2014.

Two Decades of Wildlife Pathogen Surveillance: Case Study of Choclo orthohantavirus and Its Wild Reservoir Oligoryzomys costaricensis.

The Costa Rican pygmy rice rat (Oligoryzomys costaricensis) is the primary reservoir of Choclo orthohantavirus (CHOV), the causal agent of hantavirus disease, pulmonary syndrome, and fever in humans in Panama. Since the emergence of CHOV in early 2000, we have systematically sampled and archived rodents from >150 sites across Panama to establish a baseline understanding of the host and virus, producing a permanent archive of holistic specimens that we are now probing in greater detail. We summarize these collections and explore preliminary habitat/virus associations to guide future wildlife surveillance and public health efforts related to CHOV and other zoonotic pathogens. Host sequences of the mitochondrial cytochrome b gene form a single monophyletic clade in Panama, despite wide distribution across Panama. Seropositive samples were concentrated in the central region of western Panama, consistent with the ecology of this agricultural commensal and the higher incidence of CHOV in humans in that region. Hantavirus seroprevalence in the pygmy rice rat was >15% overall, with the highest prevalence in agricultural areas (21%) and the lowest prevalence in shrublands (11%). Host-pathogen distribution, transmission dynamics, genomic evolution, and habitat affinities can be derived from the preserved samples, which include frozen tissues, and now provide a foundation for expanded investigations of orthohantaviruses in Panama.

Factors related to human-vector contact that modify the likelihood of malaria transmission during a contained Plasmodium falciparum outbreak in Praia, Cabo Verde.

Background: Determining the reproductive rate and how it varies over time and space (RT) provides important insight to understand transmission of a given disease and inform optimal strategies for controlling or eliminating it. Estimating RT for malaria is difficult partly due to the widespread use of interventions and immunity to disease masking incident infections. A malaria outbreak in Praia, Cabo Verde in 2017 provided a unique opportunity to estimate RT directly, providing a proxy for the intensity of vector-human contact and measure the impact of vector control measures. Methods: Out of 442 confirmed malaria cases reported in 2017 in Praia, 321 (73%) were geolocated and informed this analysis. RT was calculated using the joint likelihood of transmission between two cases, based on the time (serial interval) and physical distance (spatial interval) between them. Log-linear regression was used to estimate factors associated with changes in RT, including the impact of vector control interventions. A geostatistical model was developed to highlight areas receptive to transmission where vector control activities could be focused in future to prevent or interrupt transmission. Results: The RT from individual cases ranged between 0 and 11 with a median serial- and spatial-interval of 34 days [interquartile range (IQR): 17-52] and 1,347 m (IQR: 832-1,985 m), respectively. The number of households receiving indoor residual spraying (IRS) 4 weeks prior was associated with a reduction in RT by 0.84 [95% confidence interval (CI) 0.80-0.89; p-value <0.001] in the peak-and post-epidemic compared to the pre-epidemic period. Conclusions: Identifying the effect of reduced human-vector contact through IRS is essential to determining optimal intervention strategies that modify the likelihood of malaria transmission and can inform optimal intervention strategies to accelerate time to elimination. The distance within which two cases are plausibly linked is important for the potential scale of any reactive interventions as well as classifying infections as imported or introduced and confirming malaria elimination.

Case-control study of an acute aflatoxicosis outbreak, Kenya, 2004.

OBJECTIVES: During January-June 2004, an aflatoxicosis outbreak in eastern Kenya resulted in 317 cases and 125 deaths. We conducted a case-control study to identify risk factors for contamination of implicated maize and, for the first time, quantitated biomarkers associated with acute aflatoxicosis. DESIGN: We administered questionnaires regarding maize storage and consumption and obtained maize and blood samples from participants. PARTICIPANTS: We recruited 40 case-patients with aflatoxicosis and 80 randomly selected controls to participate in this study. EVALUATIONS/MEASUREMENTS: We analyzed maize for total aflatoxins and serum for aflatoxin B1-lysine albumin adducts and hepatitis B surface antigen. We used regression and survival analyses to explore the relationship between aflatoxins, maize consumption, hepatitis B surface antigen, and case status. RESULTS: Homegrown (not commercial) maize kernels from case households had higher concentrations of aflatoxins than did kernels from control households [geometric mean (GM) = 354.53 ppb vs. 44.14 ppb; p = 0.04]. Serum adduct concentrations were associated with time from jaundice to death [adjusted hazard ratio = 1.3; 95% confidence interval (CI), 1.04-1.6]. Case patients had positive hepatitis B titers [odds ratio (OR) = 9.8; 95% CI, 1.5-63.1] more often than controls. Case patients stored wet maize (OR = 3.5; 95% CI, 1.2-10.3) inside their homes (OR = 12.0; 95% CI, 1.5-95.7) rather than in granaries more often than did controls. CONCLUSION: Aflatoxin concentrations in maize, serum aflatoxin B1-lysine adduct concentrations, and positive hepatitis B surface antigen titers were all associated with case status. RELEVANCE: The novel methods and risk factors described may help health officials prevent future outbreaks of aflatoxicosis.

Age-specific malaria mortality rates in the KEMRI/CDC health and demographic surveillance system in western Kenya, 2003-2010.

Recent global malaria burden modeling efforts have produced significantly different estimates, particularly in adult malaria mortality. To measure malaria control progress, accurate malaria burden estimates across age groups are necessary. We determined age-specific malaria mortality rates in western Kenya to compare with recent global estimates. We collected data from 148,000 persons in a health and demographic surveillance system from 2003-2010. Standardized verbal autopsies were conducted for all deaths; probable cause of death was assigned using the InterVA-4 model. Annual malaria mortality rates per 1,000 person-years were generated by age group. Trends were analyzed using Poisson regression. From 2003-2010, in children <5 years the malaria mortality rate decreased from 13.2 to 3.7 per 1,000 person-years; the declines were greatest in the first three years of life. In children 5-14 years, the malaria mortality rate remained stable at 0.5 per 1,000 person-years. In persons ≥15 years, the malaria mortality rate decreased from 1.5 to 0.4 per 1,000 person-years. The malaria mortality rates in young children and persons aged ≥15 years decreased dramatically from 2003-2010 in western Kenya, but rates in older children have not declined. Sharp declines in some age groups likely reflect the national scale up of malaria control interventions and rapid expansion of HIV prevention services. These data highlight the importance of age-specific malaria mortality ascertainment and support current strategies to include all age groups in malaria control interventions.

Profile: the KEMRI/CDC Health and Demographic Surveillance System--Western Kenya.

The KEMRI/Centers for Disease Control and Prevention (CDC) Health and Demographic Surveillance System (HDSS) is located in Rarieda, Siaya and Gem Districts (Siaya County), lying northeast of Lake Victoria in Nyanza Province, western Kenya. The KEMRI/CDC HDSS, with approximately 220 000 inhabitants, has been the foundation for a variety of studies, including evaluations of insecticide-treated bed nets, burden of diarrhoeal disease and tuberculosis, malaria parasitaemia and anaemia, treatment strategies and immunological correlates of malaria infection, and numerous HIV, tuberculosis, malaria and diarrhoeal disease treatment and vaccine efficacy and effectiveness trials for more than a decade. Current studies include operations research to measure the uptake and effectiveness of the programmatic implementation of integrated malaria control strategies, HIV services, newly introduced vaccines and clinical trials. The HDSS provides general demographic and health information (such as population age structure and density, fertility rates, birth and death rates, in- and out-migrations, patterns of health care access and utilization and the local economics of health care) as well as disease- or intervention-specific information. The HDSS also collects verbal autopsy information on all deaths. Studies take advantage of the sampling frame inherent in the HDSS, whether at individual, household/compound or neighbourhood level.

Short report: Molecular insights for Giardia, Cryptosporidium, and soil-transmitted helminths from a facility-based surveillance system in Guatemala.

We molecularly characterized samples with Giardia, Cryptosporidium, and soil-transmitted helminths from a facility-based surveillance system for diarrhea in Santa Rosa, Guatemala. The DNA sequence analysis determined the presence of Giardia assemblages A (N = 7) and B (N = 12) and, Cryptosporidium hominis (N = 2) and Cryptosporidium parvum (N = 2), suggestive of different transmission cycles. All 41 samples with soil-transmitted helminths did not have the ß-tubulin mutation described for benzimidazole resistance, suggesting potential usefulness in mass drug administration campaigns.