Do hotspots fuel malaria transmission: a village-scale spatio-temporal analysis of a 2-year cohort study in The Gambia.

BACKGROUND: Despite the biological plausibility of hotspots fueling malaria transmission, the evidence to support this concept has been mixed. If transmission spreads from high burden to low burden households in a consistent manner, then this could have important implications for control and elimination program development. METHODS: Data from a longitudinal cohort in The Gambia was analyzed. All consenting individuals residing in 12 villages across the country were sampled monthly from June (dry season) to December 2013 (wet season), in April 2014 (mid dry season), and monthly from June to December 2014. A study nurse stationed within each village recorded passively detected malaria episodes between visits. Plasmodium falciparum infections were determined by polymerase chain reaction and analyzed using a geostatistical model. RESULTS: Household-level observed monthly incidence ranged from 0 to 0.50 infection per person (interquartile range = 0.02-0.10) across the sampling months, and high burden households exist across all study villages. There was limited evidence of a spatio-temporal pattern at the monthly timescale irrespective of transmission intensity. Within-household transmission was the most plausible hypothesis examined to explain the observed heterogeneity in infections. CONCLUSIONS: Within-village malaria transmission patterns are concentrated in a small proportion of high burden households, but patterns are stochastic regardless of endemicity. Our findings support the notion of transmission occurring at the household and village scales but not the use of a targeted approach to interrupt spreading of infections from high to low burden areas within villages in this setting.

Heterogeneous malaria transmission in long-term Afghan refugee populations: a cross-sectional study in five refugee camps in northern Pakistan.

BACKGROUND: Afghan refugees in northern Pakistan have been resident for over 30 years and current information on malaria in this population is sparse. Understanding malaria risk and distribution in refugee camps is important for effective management both in camps and on return to Afghanistan. METHODS: Cross-sectional malariometric surveys were conducted in five Afghan refugee camps to determine infection and exposure to both Plasmodium falciparum and Plasmodium vivax. Factors associated with malaria infection and exposure were analysed using logistic regression, and spatial heterogeneity within camps was investigated with SatScan. RESULTS: In this low-transmission setting, prevalence of infection in the five camps ranged from 0-0.2 to 0.4-9 % by rapid diagnostic test and 0-1.39 and 5-15 % by polymerase chain reaction for P. falciparum and P. vivax, respectively. Prevalence of anti-malarial antibodies to P. falciparum antigens was 3-11 and 17-45 % for P. vivax antigens. Significant foci of P. vivax infection and exposure were detected in three of the five camps. Hotspots of P. falciparum were also detected in three camps, only one of which also showed evidence of P. vivax hotspots. CONCLUSIONS: There is low and spatially heterogeneous malaria transmission in the refugee camps in northern Pakistan. Understanding malaria risk in refugee camps is important so the malaria risk faced by these populations in the camps and upon their return to Afghanistan can be effectively managed.

Focal Screening to Identify the Subpatent Parasite Reservoir in an Area of Low and Heterogeneous Transmission in the Kenya Highlands.

BACKGROUND: Mass screening and treatment currently fails to identify a considerable fraction of low parasite density infections, while mass treatment exposes many uninfected individuals to antimalarial drugs. Here we test a hybrid approach to screen a sentinel population to identify clusters of subpatent infections in the Kenya highlands with low, heterogeneous malaria transmission. METHODS: Two thousand eighty-two inhabitants were screened for parasitemia by nested polymerase chain reaction (nPCR). Children aged ≤ 15 years and febrile adults were also tested for malaria by rapid diagnostic test (RDT) and served as sentinel members to identify subpatent infections within the household. All parasitemic individuals were assessed for multiplicity of infections by nPCR and gametocyte carriage by nucleic acid sequence-based amplification. RESULTS: Households with RDT-positive individuals in the sentinel population were more likely to have nPCR-positive individuals (odds ratio: 1.71, 95% confidence interval, 1.60-1.84). The sentinel population identified 64.5% (locality range: 31.6%-81.2%) of nPCR-positive households and 77.3% (locality range: 24.2%-91.0%) of nPCR-positive individuals. The sensitivity of the sentinel screening approach was positively associated with transmission intensity (P = .037). CONCLUSIONS: In this low endemic area, a focal screening approach with RDTs prior to the high transmission season was able to identify the majority of the subpatent parasite reservoirs.

Use of different transmission metrics to describe malaria epidemiology in the highlands of western Kenya.

BACKGROUND: Monitoring and evaluation of malaria programmes may require a combination of approaches to detect any effects of control. This is particularly true at lower transmission levels where detecting both infection and exposure to infection will provide additional evidence of any change. This paper describes use of three transmission metrics to explore the malaria epidemiology in the highlands of western Kenya. METHODS: A malariometric survey was conducted in June 2009 in two highland districts, Kisii and Rachuonyo South, Nyanza Province, Kenya using a cluster design. Enumeration areas were used to sample 46 clusters from which 12 compounds were randomly sampled. Individuals provided a finger-blood sample to assess malaria infection (rapid diagnostic test, PCR) and exposure (anti-Plasmodium falciparum MSP-1 antibodies) and a questionnaire was administered to record household factors and assess use of vector control interventions. RESULTS: Malaria prevalence infection rates were 3.0 % (95 % CI 2.2-4.2 %) by rapid diagnostic test (RDT) and 8.5 % (95 % CI 7.0-10.4 %) by PCR and these ranged from 0-13.1 to 0-14.8 % between clusters for RDT and PCR, respectively. Seroprevalence was 36.8 % (95 % CI 33.9-39.8) ranging from 18.6 to 65.8 %. Both RDT and PCR prevalences were highest in children aged 5-10 years but the proportion of infections that were sub-patent was highest in those between 15 and 20 years of age (78.1 %, 95 % CI 63.0-93.3 %) and those greater than 20 years (73.3 %, 95 % CI 64.5-81.9 %). Those reporting both indoor residual spraying (IRS) in their home and use of bed nets had lower exposure to malaria compared to those who reported using IRS or bed nets alone. CONCLUSIONS: In this highland site in western Kenya malaria transmission was low, but highly heterogeneous. To accurately characterize the true extent of malaria transmission, more sensitive and complementary metrics such as PCR or serology are required in addition to the standard microscopy and/or RDTs that are routinely used. This is likely to be the case in other low endemicity settings.

A method of active case detection to target reservoirs of asymptomatic malaria and gametocyte carriers in a rural area in Southern Province, Zambia.

BACKGROUND: Asymptomatic reservoirs of malaria parasites are common yet are difficult to detect, posing a problem for malaria control. If control programmes focus on mosquito control and treatment of symptomatic individuals only, malaria can quickly resurge if interventions are scaled back. Foci of parasite populations must be identified and treated. Therefore, an active case detection system that facilitates detection of asymptomatic parasitaemia and gametocyte carriers was developed and tested in the Macha region in southern Zambia. METHODS: Each week, nurses at participating rural health centres (RHC) communicated the number of rapid diagnostic test (RDT) positive malaria cases to a central research team. During the dry season when malaria transmission was lowest, the research team followed up each positive case reported by the RHC by a visit to the homestead. The coordinates of the location were obtained by GPS and all consenting residents completed a questionnaire and were screened for malaria using thick blood film, RDT, nested-PCR, and RT-PCR for asexual and sexual stage parasites. Persons who tested positive by RDT were treated with artemether/lumefantrine (Coartem). Data were compared with a community-based study of randomly selected households to assess the prevalence of asymptomatic parasitaemia in the same localities in September 2009. RESULTS: In total, 186 and 141 participants residing in 23 case and 24 control homesteads, respectively, were screened. In the case homesteads for which a control population was available (10 of the 23), household members of clinically diagnosed cases had a 8.0% prevalence of malaria using PCR compared to 0.7% PCR positive individuals in the control group (p = 0.006). The case and control groups had a gametocyte prevalence of 2.3% and 0%, respectively but the difference was not significant (p = 0.145). CONCLUSIONS: This pilot project showed that active case detection is feasible and can identify reservoirs of asymptomatic infection. A larger sample size, data over multiple low transmission seasons, and in areas with different transmission dynamics are needed to further validate this approach.

Impact of metric and sample size on determining malaria hotspot boundaries.

The spatial heterogeneity of malaria suggests that interventions may be targeted for maximum impact. It is unclear to what extent different metrics lead to consistent delineation of hotspot boundaries. Using data from a large community-based malaria survey in the western Kenyan highlands, we assessed the agreement between a model-based geostatistical (MBG) approach to detect hotspots using Plasmodium falciparum parasite prevalence and serological evidence for exposure. Malaria transmission was widespread and highly heterogeneous with one third of the total population living in hotspots regardless of metric tested. Moderate agreement (Kappa = 0.424) was observed between hotspots defined based on parasite prevalence by polymerase chain reaction (PCR)- and the prevalence of antibodies to two P. falciparum antigens (MSP-1, AMA-1). While numerous biologically plausible hotspots were identified, their detection strongly relied on the proportion of the population sampled. When only 3% of the population was sampled, no PCR derived hotspots were reliably detected and at least 21% of the population was needed for reliable results. Similar results were observed for hotspots of seroprevalence. Hotspot boundaries are driven by the malaria diagnostic and sample size used to inform the model. These findings warn against the simplistic use of spatial analysis on available data to target malaria interventions in areas where hotspot boundaries are uncertain.

High levels of asymptomatic and subpatent Plasmodium falciparum parasite carriage at health facilities in an area of heterogeneous malaria transmission intensity in the Kenyan highlands.

In endemic settings, health facility surveys provide a convenient approach to estimating malaria transmission intensity. Typically, testing for malaria at facilities is performed on symptomatic attendees, but asymptomatic infections comprise a considerable proportion of the parasite reservoir. We sampled individuals attending five health facilities in the western Kenyan highlands. Malaria prevalence by rapid diagnostic test (RDT) was 8.6-32.9% in the health facilities. Of all polymerase chain reaction-positive participants, 46.4% (95% confidence interval [95% CI] = 42.6-50.2%) of participants had infections that were RDT-negative and asymptomatic, and 55.9% of those infections consisted of multiple parasite clones as assessed by merozoite surface protein-2 genotyping. Subpatent infections were more common in individuals reporting the use of non-artemisinin-based antimalarials in the 2 weeks preceding the survey (odds ratio = 2.49, 95% CI = 1.04-5.92) compared with individuals not reporting previous use of antimalarials. We observed a large and genetically complex pool of subpatent parasitemia in the Kenya highlands that must be considered in malaria interventions.

Reliability of school surveys in estimating geographic variation in malaria transmission in the western Kenyan highlands.

BACKGROUND: School surveys provide an operational approach to assess malaria transmission through parasite prevalence. There is limited evidence on the comparability of prevalence estimates obtained from school and community surveys carried out at the same locality. METHODS: Concurrent school and community cross-sectional surveys were conducted in 46 school/community clusters in the western Kenyan highlands and households of school children were geolocated. Malaria was assessed by rapid diagnostic test (RDT) and combined seroprevalence of antibodies to bloodstage Plasmodium falciparum antigens. RESULTS: RDT prevalence in school and community populations was 25.7% (95% CI: 24.4-26.8) and 15.5% (95% CI: 14.4-16.7), respectively. Seroprevalence in the school and community populations was 51.9% (95% CI: 50.5-53.3) and 51.5% (95% CI: 49.5-52.9), respectively. RDT prevalence in schools could differentiate between low (<7%, 95% CI: 0-19%) and high (>39%, 95% CI: 25-49%) transmission areas in the community and, after a simple adjustment, were concordant with the community estimates. CONCLUSIONS: Estimates of malaria prevalence from school surveys were consistently higher than those from community surveys and were strongly correlated. School-based estimates can be used as a reliable indicator of malaria transmission intensity in the wider community and may provide a basis for identifying priority areas for malaria control.

Beyond temperature and precipitation: ecological risk factors that modify malaria transmission.

Being able to identify the ecological factors that impact risk for malaria would confer important predictive capacity to target malaria control interventions in a community. Temperature and water available for breeding habitats have been shown to be important primary ecological factors that impact the distribution of the malaria vectors and the rate at which the mosquito and parasite develop. However, to this point, studies focusing on the local level have been met with many inconsistent results when assessing malaria risk using both temperature and precipitation. This paper reviewed existing literature to determine if other ecological factors beyond temperature and water are present that may be modifying any associations present between ecological factors and malaria risk. It was found that the ability for water to pool and persist, water quality, elevation, deforestation, and agriculture have all been associated with malaria and may be modifying risk. Using the primary and modifying ecological variables, identifying the interactions between these factors and specific thresholds for increased malaria risk is critical: filling this knowledge gap would enable communities to develop tailored malaria control interventions targeted to their specific circumstances.