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 B(1)–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 B(1)–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

Effect of Transmission Reduction by Insecticide-Treated Bednets (ITNs) on Antimalarial Drug Resistance in Western Kenya

Despite the clear public health benefit of insecticide-treated bednets (ITNs), the impact of malaria transmission-reduction by vector control on the spread of drug resistance is not well understood. In the present study, the effect of sustained transmission reduction by ITNs on the prevalence of Plasmodium falciparum gene mutations associated with resistance to the antimalarial drugs sulfadoxine-pyrimethamine (SP) and chloroquine (CQ) in children under the age of five years was investigated during an ITN trial in Asembo area, western Kenya. During the ITN trial, the national first line antimalarial treatment changed from CQ to SP. Smear-positive samples collected from cross sectional surveys prior to ITN introduction (baseline, n = 250) and five years post-ITN intervention (year 5 survey, n = 242) were genotyped for single nucleotide polymorphisms (SNPs) at dhfr-51, 59, 108, 164 and dhps-437, 540 (SP resistance), and pfcrt-76 and pfmdr1-86 (CQ resistance). The association between the drug resistance mutations and epidemiological variables was evaluated. There were significant increases in the prevalence of SP dhps mutations and the dhfr/dhps quintuple mutant, and a significant reduction in the proportion of mixed infections detected at dhfr-51, 59 and dhps-437, 540 SNPs from baseline to the year 5 survey. There was no change in the high prevalence of pfcrt-76 and pfmdr1-86 mutations. Multivariable regression analysis further showed that current antifolate use and year of survey were significantly associated with more SP drug resistance mutations. These results suggest that increased antifolate drug use due to drug policy change likely led to the high prevalence of SP mutations 5 years post-ITN intervention and reduced transmission had no apparent effect on the existing high prevalence of CQ mutations. There is no evidence from the current study that sustained transmission reduction by ITNs reduces the prevalence of genes associated with malaria drug resistance

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

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.

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. 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. 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

Predicting highland malaria epidemics: Associations with weather variability and land -use change in southwestern Uganda.

African highlands, once considered refuges from the death and disability caused by malaria in the rest of sub-Saharan Africa, are apparently experiencing a resurgence of disease. Because of the infrequent transmission of malaria in these cooler areas, the human population has a corresponding lower immunity to the parasite. When transmission does occur, epidemics occur explosively affecting a large segment of the population. The objectives of the research presented in this dissertation were to improve understanding of the environmental factors which influence highland malaria transmission and to identify strategies which may provide early warning of highland malaria epidemics. Our results indicated that, during the 8-month study period from December, 1997, through July, 1998, rainfall anomaly was correlated with mosquito density at a one month lag (r = 0.55, P P P = 0.0001), and in multivariate analyses, mean minimum temperature was significantly associated with mosquito density. Therefore, it appeared that change in natural swamp vegetation led to increased temperatures which may have been responsible for elevated malaria transmission risk in areas bordering cultivated swamps. We compared three sampling strategies which could be used to determine whether household mosquito density had reached levels associated with epidemic risk. Our results indicated that while calculation of mean mosquito density with satisfactory precision would require too many sampling units, a minimum sample size or sequential sampling approach could provide sufficient information on mosquito density with minimal sampling effort. It is hoped that the results of this dissertation will eventually contribute to the control of highland malaria epidemics.Ph.D.Health and Environmental SciencesPublic healthUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/132187/2/9959808.pd

Zoonotic malaria requires new policy approaches to malaria elimination

Increasing numbers of human zoonotic malaria cases are reported globally. Current malaria control measures cannot eliminate transmission from wildlife reservoirs, leaving many countries with no pathway to malaria elimination certification. New policies are needed to redefine elimination goals and certification

Is there evidence of sustained human-mosquito-human transmission of the zoonotic malaria Plasmodium knowlesi? A systematic literature review.

BACKGROUND: The zoonotic malaria parasite Plasmodium knowlesi has emerged across Southeast Asia and is now the main cause of malaria in humans in Malaysia. A critical priority for P. knowlesi surveillance and control is understanding whether transmission is entirely zoonotic or is also occurring through human-mosquito-human transmission. METHODS: A systematic literature review was performed to evaluate existing evidence which refutes or supports the occurrence of sustained human-mosquito-human transmission of P. knowlesi. Possible evidence categories and study types which would support or refute non-zoonotic transmission were identified and ranked. A literature search was conducted on Medline, EMBASE and Web of Science using a broad search strategy to identify any possible published literature. Results were synthesized using the Synthesis Without Meta-analysis (SWiM) framework, using vote counting to combine the evidence within specific categories. RESULTS: Of an initial 7,299 studies screened, 131 studies were included within this review: 87 studies of P. knowlesi prevalence in humans, 14 studies in non-human primates, 13 studies in mosquitoes, and 29 studies with direct evidence refuting or supporting non-zoonotic transmission. Overall, the evidence showed that human-mosquito-human transmission is biologically possible, but there is limited evidence of widespread occurrence in endemic areas. Specific areas of research were identified that require further attention, notably quantitative analyses of potential transmission dynamics, epidemiological and entomological surveys, and ecological studies into the sylvatic cycle of the disease. CONCLUSION: There are key questions about P. knowlesi that remain within the areas of research that require more attention. These questions have significant implications for malaria elimination and eradication programs. This paper considers limited but varied research and provides a methodological framework for assessing the likelihood of different transmission patterns for emerging zoonotic diseases

Additional file 3 of Is there evidence of sustained human-mosquito-human transmission of the zoonotic malaria Plasmodium knowlesi? A systematic literature review

Dataset containing information on human cases of P. knowles

Is there evidence of sustained human-mosquito-human transmission of the zoonotic malaria Plasmodium knowlesi? A systematic literature review

The zoonotic malaria parasite Plasmodium knowlesi has emerged across Southeast Asia and is now the main cause of malaria in humans in Malaysia. A critical priority for P. knowlesi surveillance and control is understanding whether transmission is entirely zoonotic or is also occurring through human-mosquito-human transmission