Asymptomatic Plasmodium falciparum carriage at the end of the dry season is associated with subsequent infection and clinical malaria in Eastern Gambia.

BACKGROUND: Chronic carriage of asymptomatic low-density Plasmodium falciparum parasitaemia in the dry season may support maintenance of acquired immunity that protects against clinical malaria. However, the relationship between chronic low-density infections and subsequent risk of clinical malaria episodes remains unclear. METHODS: In a 2-years study (December 2014 to December 2016) in eastern Gambia, nine cross-sectional surveys using molecular parasite detection were performed in the dry and wet season. During the 2016 malaria transmission season, passive case detection identified episodes of clinical malaria. RESULTS: Among the 5256 samples collected, 444 (8.4%) were positive for P. falciparum. A multivariate model identified village of residence, male sex, age ≥ 5 years old, anaemia, and fever as independent factors associated with P. falciparum parasite carriage. Infections did not cluster over time within the same households or recurred among neighbouring households. Asymptomatic parasite carriage at the end of dry season was associated with a higher risk of infection (Hazard Ratio, HR = 3.0, p < 0.0001) and clinical malaria (HR = 1.561, p = 0.057) during the following transmission season. Age and village of residence were additional predictors of infection and clinical malaria during the transmission season. CONCLUSION: Chronic parasite carriage during the dry season is associated with an increased risk of malaria infection and clinical malaria. It is unclear whether this is due to environmental exposure or to other factors.

Evidence for exposure dependent carriage of malaria parasites across the dry season: modelling analysis of longitudinal data.

BACKGROUND: In malaria endemic regions, transmission of Plasmodium falciparum parasites is often seasonal with very low transmission during the dry season and high transmission in the wet season. Parasites survive the dry season within some individuals who experience prolonged carriage of parasites and are thought to 'seed' infection in the next transmission season. METHODS: Dry season carriers and their role in the subsequent transmission season are characterized using a combination of mathematical simulations and data analysis of previously described data from a longitudinal study in Mali of individuals aged 3 months-12 years (n = 579). RESULTS: Simulating the life-history of individuals experiencing repeated exposure to infection predicts that dry season carriage is more likely in the oldest, most exposed and most immune individuals. This hypothesis is supported by the data from Mali, which shows that carriers are significantly older, experience a higher biting rate at the beginning of the transmission season and develop clinical malaria later than non-carriers. Further, since the most exposed individuals in a community are most likely to be dry season carriers, this is predicted to enable a more than twofold faster spread of parasites into the mosquito population at the start of the subsequent wet season. CONCLUSIONS: Carriage of malaria parasites over the months-long dry season in Mali is most likely in the older, more exposed and more immune children. These children may act as super-spreaders facilitating the fast spread of parasites at the beginning of the next transmission season.

Schistosoma Transmission in a Dynamic Seasonal Environment and its Impact on the Effectiveness of Disease Control.

BACKGROUND: A seasonal transmission environment including seasonal variation of snail population density and human-snail contact patterns can affect the dynamics of Schistosoma infection and the success of control interventions. In projecting control outcomes, conventional modeling approaches have often ignored seasonality by using simplified intermediate-host modeling, or by restricting seasonal effects through use of yearly averaging. METHODS: We used mathematical analysis and numerical simulation to estimate the impact of seasonality on disease dynamics and control outcomes, and to evaluate whether seasonal averaging or intermediate-host reduction can provide reliable predictions of control outcomes. We also examined whether seasonality could be used as leverage in creation of effective control strategies. RESULTS: We found models that used seasonal averaging could grossly overestimate infection burden and underestimate control outcomes in highly seasonal environments. We showed that proper intraseasonal timing of control measures could make marked improvement on the long-term burden reduction for Schistosoma transmission control, and we identified the optimal timing for each intervention. Seasonal snail control, implemented alone, was less effective than mass drug administration, but could provide additive impact in reaching control and elimination targets. CONCLUSIONS: Seasonal variation makes Schistosoma transmission less sustainable and easier to control than predicted by earlier modeling studies.

Effectiveness of Four Different Interventions Against Schistosoma haematobium in a Seasonal Transmission Setting of Côte d'Ivoire: A Cluster Randomized Trial.

BACKGROUND: Annual mass drug administration (MDA) using praziquantel is the cornerstone of schistosomiasis morbidity control but is not sufficient to interrupt transmission. We implemented a cluster-randomized trial to compare the effectiveness of 4 different intervention packages to interrupt transmission of Schistosoma haematobium in a seasonal transmission setting of Côte d'Ivoire. METHODS: Sixty-four localities with a S. haematobium prevalence in school children aged 13-14 years above 4% were randomly assigned to 1 of 4 intervention arms over a 3-year period: (1) the current standard strategy consisting of annual MDA before peak of transmission, (2) annual MDA after peak of transmission, (3) biannual MDA, and (4) standard MDA combined with snail control. The primary outcome was prevalence and intensity of S. haematobium infection in children aged 9-12 years 1 year after the final intervention, using urine filtration performed by experienced microscopists. RESULTS: By study end, we observed the lowest S. haematobium prevalence in the biannual MDA, compared to the standard treatment arm (0.6% vs 7.5%; odds ratio [OR] = 0.07, 95% confidence interval [CI] = .02 to .24). The prevalence in arms 2 and 4 was about 3.5%, which was not statistically significantly different from the standard strategy (both ORs 0.4, 95% CI = .1 to ~1.8). New cases of infection were still observed in all arms at study end. CONCLUSIONS: Biannual MDA was the only regimen that outperformed the standard treatment. All strategies resulted in decreased prevalence of infection; however, none of them was able to interrupt transmission of S. haematobium within a 3-year period. CLINICAL TRIALS REGISTRATION: ISRCTN10926858.

Mass campaigns combining antimalarial drugs and anti-infective vaccines as seasonal interventions for malaria control, elimination and prevention of resurgence: a modelling study.

BACKGROUND: The only licensed malaria vaccine, RTS,S/AS01, has been developed for morbidity-control in young children. The potential impact on transmission of deploying such anti-infective vaccines to wider age ranges, possibly with co-administration of antimalarial treatment, is unknown. Combinations of existing malaria interventions is becoming increasingly important as evidence mounts that progress on reducing malaria incidence is stalling and threatened by resistance. METHODS: Malaria transmission and intervention dynamics were simulated using OpenMalaria, an individual-based simulation model of malaria transmission, by considering a seasonal transmission setting and by varying epidemiological and setting parameters such as transmission intensity, case management, intervention types and intervention coverages. Chemopreventive drugs and anti-infective vaccine efficacy profiles were based on previous studies in which model parameters were fitted to clinical trial data. These intervention properties were used to evaluate the potential of seasonal mass applications of preventative anti-infective malaria vaccines, alone or in combination with chemoprevention, to reduce malaria transmission, prevent resurgence, and/or reach transmission interruption. RESULTS: Deploying a vaccine to all ages on its own is a less effective intervention strategy compared to chemoprevention alone. However, vaccines combined with drugs are likely to achieve dramatic prevalence reductions and in few settings, transmission interruption. The combined mass intervention will result in lower prevalence following the intervention compared to chemoprevention alone and will increase chances of interruption of transmission resulting from a synergistic effect between both interventions. The combination of vaccine and drug increases the time before transmission resurges after mass interventions cease compared to mass treatment alone. Deploying vaccines and drugs together requires fewer rounds of mass intervention and fewer years of intervention to achieve the same public health impact as chemoprevention alone. CONCLUSIONS: Through simulations we identified a previously unidentified value of deploying vaccines with drugs, namely the greatest benefit will be in preventing and delaying transmission resurgence for longer periods than with other human targeted interventions. This is suggesting a potential role for deploying vaccines alongside drugs in transmission foci as part of surveillance-response strategies.

Interrupting seasonal transmission of Schistosoma haematobium and control of soil-transmitted helminthiasis in northern and central Côte d'Ivoire: a SCORE study protocol.

BACKGROUND: To achieve a world free of schistosomiasis, the objective is to scale up control and elimination efforts in all endemic countries. Where interruption of transmission is considered feasible, countries are encouraged to implement a comprehensive intervention package, including preventive chemotherapy, information, education and communication (IEC), water, sanitation and hygiene (WASH), and snail control. In northern and central Côte d'Ivoire, transmission of Schistosoma haematobium is seasonal and elimination might be achieved. In a cluster-randomised trial, we will assess different treatment schemes to interrupt S. haematobium transmission and control soil-transmitted helminthiasis over a 3-year period. We will compare the impact of (i) arm A: annual mass drug administration (MDA) with praziquantel and albendazole before the peak schistosomiasis transmission season; (ii) arm B: annual MDA after the peak schistosomiasis transmission season; (iii) arm C: two yearly treatments before and after peak schistosomiasis transmission; and (iv) arm D: annual MDA before peak schistosomiasis transmission, coupled with chemical snail control using niclosamide. METHODS/DESIGN: The prevalence and intensity of S. haematobium and soil-transmitted helminth infections will be assessed using urine filtration and Kato-Katz thick smears, respectively, in six administrative regions in northern and central parts of Côte d'Ivoire. Once a year, urine and stool samples will be collected and examined from 50 children aged 5-8 years, 100 children aged 9-12 years and 50 adults aged 20-55 years in each of 60 selected villages. Changes in S. haematobium and soil-transmitted helminth prevalence and intensity will be assessed between years and stratified by intervention arm. In the 15 villages randomly assigned to intervention arm D, intermediate host snails will be collected three times per year, before niclosamide is applied to the selected freshwater bodies. The snail abundance and infection rates over time will allow drawing inference on the force of transmission. DISCUSSION: This cluster-randomised intervention trial will elucidate whether in an area with seasonal transmission, the four different treatment schemes can interrupt S. haematobium transmission and control soil-transmitted helminthiasis. Lessons learned will help to guide schistosomiasis control and elimination programmes elsewhere in Africa. TRIAL REGISTRATION: ISRCTN ISRCTN10926858 . Registered 21 December 2016. Retrospectively registered.

Detecting signals of chronic shedding to explain pathogen persistence: Leptospira interrogans in California sea lions.

Identifying mechanisms driving pathogen persistence is a vital component of wildlife disease ecology and control. Asymptomatic, chronically infected individuals are an oft-cited potential reservoir of infection, but demonstrations of the importance of chronic shedding to pathogen persistence at the population-level remain scarce. Studying chronic shedding using commonly collected disease data is hampered by numerous challenges, including short-term surveillance that focuses on single epidemics and acutely ill individuals, the subtle dynamical influence of chronic shedding relative to more obvious epidemic drivers, and poor ability to differentiate between the effects of population prevalence of chronic shedding vs. intensity and duration of chronic shedding in individuals. We use chronic shedding of Leptospira interrogans serovar Pomona in California sea lions (Zalophus californianus) as a case study to illustrate how these challenges can be addressed. Using leptospirosis-induced strands as a measure of disease incidence, we fit models with and without chronic shedding, and with different seasonal drivers, to determine the time-scale over which chronic shedding is detectable and the interactions between chronic shedding and seasonal drivers needed to explain persistence and outbreak patterns. Chronic shedding can enable persistence of L. interrogans within the sea lion population. However, the importance of chronic shedding was only apparent when surveillance data included at least two outbreaks and the intervening inter-epidemic trough during which fadeout of transmission was most likely. Seasonal transmission, as opposed to seasonal recruitment of susceptibles, was the dominant driver of seasonality in this system, and both seasonal factors had limited impact on long-term pathogen persistence. We show that the temporal extent of surveillance data can have a dramatic impact on inferences about population processes, where the failure to identify both short- and long-term ecological drivers can have cascading impacts on understanding higher order ecological phenomena, such as pathogen persistence.

Utility of plasma anti-gSG6-P1 IgG levels in determining changes in Anopheles gambiae bite rates in a rural area of Cameroon.

The applicability of the specific human IgG antibody response to Anopheles gambiae salivary Gland Protein-6 peptide 1 (gSG6-P1 salivary peptide) as a biomarker able to distinguish the level of exposure to mosquito bites according to seasonal variations has not yet been evaluated in Central African regions. The study aimed to provide the first reliable data on the IgG anti-gSG6-P1 response in rural area in Cameroon according to the dry- and rainy-season. Between May and December 2020, dry blood samples were collected from people living in the Bankeng village in the forest area of the Centre region of Cameroon. Malaria infection was determined by thick-blood smear microscopy and multiplex PCR. The level of IgG anti-gSG6-P1 response, was assessed by enzyme-linked immunosorbent assay. Anopheles density and aggressiveness were assessed using human landing catches. The prevalence of malaria infection remains significantly higher in the rainy season than in the dry season (77.57% vs 61.44%; p = 0.0001). The specific anti-gSG6-P1 IgG response could be detected in individuals exposed to few mosquito bites and showed inter-individual heterogeneity even when living in the same exposure area. In both seasons, the level of anti-gSG6-P1 IgG response was not significantly different between Plasmodium infected and non-infected individuals. Mosquito bites were more aggressive in the rainy season compared to the dry season (human biting rate-HBR of 15.05 b/p/n vs 1.5 b/p/n) where mosquito density was very low. Infected mosquitoes were found only during the rainy season (sporozoite rate = 10.63% and entomological inoculation rate-EIR = 1.42 ib/p/n). The level of IgG anti-gSG6-P1 response was significantly higher in the rainy season and correlated with HBR (p ˂ 0.0001). This study highlights the high heterogeneity of individual's exposure to the Anopheles gambiae s.l vector bites depending on the transmission season in the same area. These findings reinforce the usefulness of the anti-gSG6-P1 IgG response as an accurate immunological biomarker for detecting individual exposure to Anopheles gambiae s.l. bites during the low risk period of malaria transmission in rural areas and for the differentiating the level of exposure to mosquitoes.

Seasonal Patterns of Zoonotic Cutaneous Leishmaniasis Caused by L. major and Transmitted by Phlebotomus papatasi in the North Africa Region, a Systematic Review and a Meta-Analysis

BACKGROUND: In North African countries, zoonotic cutaneous leishmaniasis (ZCL) is a seasonal disease linked to Phlebotomus papatasi, Scopoli, 1786, the primary proven vector of L. major dynamics. Even if the disease is of public health importance, studies of P. papatasi seasonal dynamics are often local and dispersed in space and time. Therefore, a detailed picture of the biology and behavior of the vector linked with climatic factors and the framework of ZCL outbreaks is still lacking at the North African countries' level. Our study aims to fill this gap via a systematic review and meta-analysis of the seasonal incidence of ZCL and the activity of P. papatasi in North African countries. We address the relationship between the seasonal number of declared ZCL cases, the seasonal dynamic of P. papatasi, and climatic variables at the North African region scale. METHODS: We selected 585 publications, dissertations, and archives data published from 1990 to July 2022. The monthly incidence data of ZCL were extracted from 15 documents and those on the seasonal dynamic of P. papatasi from 11 publications from four North African countries. RESULTS: Our analysis disclosed that for most studied sites, the highest ZCL incidence is recorded from October to February (the hibernal season of the vector), while the P. papatasi density peaks primarily during the hot season of June to September. Overall, at the North African region scale, two to four months laps are present before the apparition of the scars reminiscent of infection by L. major. CONCLUSIONS: Such analysis is of interest to regional decision-makers for planning control of ZCL in North African countries. They can also be a rationale on which future field studies combining ZCL disease incidence, vector activity, and climatic data can be built.

Baseline and Impact of First-Year Intervention on Schistosoma haematobium Infection in Seasonal Transmission Foci in the Northern and Central Parts of Côte d'Ivoire.

In order to assess the impact of different control strategies against Schistosoma haematobium in seasonal transmission foci in Côte d'Ivoire, a three-year cluster randomized trial was implemented. The decrease in S. haematobium prevalence among children aged 9-12 years was the primary outcome. In the first step, an eligibility survey was conducted, subjecting 50 children aged 13-14 years to a single urine filtration. Sixty-four villages with a prevalence of S. haematobium of ≥4% were selected and randomly assigned to four intervention arms consisting of annual mass drug administration (MDA) before (arm 1) and after (arm 2) the peak transmission, biannual treatment with praziquantel before and after the peak transmission season (arm 3), and annual MDA before the peak transmission season, coupled with focal chemical snail control using molluscicides (arm 4). At baseline, we observed a prevalence of 24.8%, 10.1%, 13.9%, and 15.9% in study arms 1, 2, 3, and 4, respectively. One year after the first intervention, the prevalence decreased in all study arms by about two-thirds or more. The prevalence in arm 2 was lower than in arm 1 (3.5% vs. 8.1%), but the difference was not statistically significant (odds ratio (OR) = 0.42, 95% confidence interval (CI) = 0.10-1.80). After adjusting for baseline prevalence, arms 1 and 2 performed roughly similarly (adjusted odds ratio (aOR) = 1.03, 95% CI = 0.34-3.07). The prevalence in arms 3 and 4 (1.9% and 2.2%) were significantly lower compared to arm 1 in the unadjusted and the adjusted models (arm 3 vs. arm 1, OR = 0.22, 95% CI = 0.05-0.95, aOR = 0.19, 95% CI = 0.08-0.48; arm 4 vs. arm 1, OR = 0.26, 95% CI = 0.08-0.85, aOR = 0.23, 95% CI = 0.06-0.87). The initial intervention showed a significant impact on the prevalence of S. haematobium. It will be interesting to monitor the comparative impact of the different intervention arms and to determine whether the interruption of seasonal transmission of S. haematobium can be achieved in this epidemiological setting within three years.

Seasonal Distribution of Phlebotomus papatasi, Vector of Zoonotic Cutaneous Leishmaniasis.

PURPOSE: The activity of Phlebotomus papatasi Scopoli, a vector of cutaneous leishmaniasis, is known to be seasonal, but the information describing these patterns is sparse in time and space. The purpose of his paper is to conduct a meta-analysis to depict the seasonality of P. papatasi at the global scale. METHODS: The current paper uses data from a collection of 1200 scientific papers, where 300 are about the vector and 36 include monthly data (of 61 sites) of the P. papatasi from 15 countries published from 1994 to 2017. RESULTS: The activity peaked mainly in dry periods in all explored sites. A map of seasonal distribution depicted a peak activity in August, followed by September. Geographically (geographic preference), August and September at the latitude 33° showed the highest abundance at a global scale. Concerning the latitude P. papatasi distribution, the high number is localized between 27° and 35°. However, the high number of this species according to the longitude is localized between - 4° and 58°, which shows a high interval of activity. Locally, for the habitat preference, the findings show a preference of this vector to indoor than to outdoor. CONCLUSIONS: All these results can be helpful in identifying the period and sites of a future potential risk of leishmaniasis. This is the first attempt at the update of the vector activity both at global and local scale.

An investigation of the combined effect of an annual mass gathering event and seasonal infectiousness on disease outbreak.

In this paper, we investigate the effects of recurring mass gathering event on the spread of an epidemic. Mass gatherings take place when a large number of people from different locations visit a particular region during a short time period. Such activity plays a crucial role in the epidemic spread as traveling facilitates the spread of an epidemic between disparate locations and crowded conditions can accelerate the disease transmission. An additional component that affects disease spread is the seasonality in transmission. In this paper, we study the interplay between the periodic natures of seasonal transmission and of an annual mass gathering event. We find that the timing of the gathering relative to the peak in transmissibility can have a profound impact on the likelihood of an outbreak.

Prevalence and seasonal transmission of Schistosoma haematobium infection among school-aged children in Kaedi town, southern Mauritania.

BACKGROUND: Mauritania is at the fringe of transmission of human schistosomiasis, which mainly occurs in the southern and southeastern parts of the country. This study aimed to assess the influence of rainfall seasonality on the prevalence of Schistosoma haematobium infection among school-aged children in Kaedi, southern Mauritania. METHODS: Cross-sectional surveys (i.e. parasitological, malacological and observations on water-related human activities) were carried out in Kaedi between September 2014 and May 2015, during both the wet and dry seasons. A total of 2162 children aged 5-15 years provided a single urine sample that was subjected to S. haematobium diagnosis. Snails were sampled and checked for cercarial shedding. Water contact patterns of the local population were recorded by direct observation. RESULTS: The prevalence of S. haematobium was 4.0% (86/2162, 95% confidence interval (CI): 3.2-4.9%) with a geometric mean egg count per 10 ml of urine of 3.7 (95% CI: 2.8-4.3). Being male (adjusted odds ratio (aOR) 1.78, 95% CI: 1.13-2.80), being at primary school (aOR 1.73, 95% CI: 1.04-2.87) and dry season (aOR 0.56, 95% CI: 0.35-0.89) were significantly associated with S. haematobium. Among 284 potential intermediate host snail specimens collected over the rainy and dry seasons, three species were identified: Bulinus senegalensis (n = 13) and B. forskalii (n = 161) in the rainy season, and B. truncatus (n = 157) in the wet season. No snail was shedding cercariae. On average, seven human water contacts were recorded per hour per observer over a 28-day observation period. Twelve types of water contact activities were identified among which, swimming/bathing was predominant (n = 3788, 36.9%), followed by washing clothes (n = 2016, 19.7%) and washing dishes (n = 1322, 12.9%). Females (n = 5270, 51.4%) were slightly more in contact with water than males (n = 4983, 48.6%). The average time spent in the water per person per day was 14.2 min (95% CI: 13.8-14.6 min). The frequency and duration of water contact followed a seasonal pattern. CONCLUSION: Our findings demonstrate a low prevalence and intensity of S. haematobium among school-aged children in Kaedi. Appropriate integrated control measures, including health education among at-risk communities and snail control may help to interrupt transmission of S. haematobium in Kaedi.

Malaria parasites prepare for flight.

Life in seasonal environments often means facing extreme environmental fluctuations. Many multicellular organisms have evolved strategies to cope with this lifestyle. Single-celled malaria parasites are no different. An elegant experiment reveals that they respond to the availability of mosquitoes to make the most of seasonal transmission opportunities.

Malaria control under unstable dynamics: reactive vs. climate-based strategies.

In areas of the world where malaria prevails under unstable conditions, attacking the adult vector population through insecticide-based Indoor Residual Spraying (IRS) is the most common method for controlling epidemics. Defined in policy guidance, the use of Annual Parasitic Incidence (API) is an important tool for assessing the effectiveness of control and for planning new interventions. To investigate the consequences that a policy based on API in previous seasons might have on the population dynamics of the disease and on control itself in regions of low and seasonal transmission, we formulate a mathematical malaria model that couples epidemiologic and vector dynamics with IRS intervention. This model is parameterized for a low transmission and semi-arid region in northwest India, where epidemics are driven by high rainfall variability. We show that this type of feedback mechanism in control strategies can generate transient cycles in malaria even in the absence of environmental variability, and that this tendency to cycle can in turn limit the effectiveness of control in the presence of such variability. Specifically, for realistic rainfall conditions and over a range of control intensities, the effectiveness of such 'reactive' intervention is compared to that of an alternative strategy based on rainfall and therefore vector variability. Results show that the efficacy of intervention is strongly influenced by rainfall variability and the type of policy implemented. In particular, under an API 'reactive' policy, high vector populations can coincide more frequently with low control coverage, and in so doing generate large unexpected epidemics and decrease the likelihood of elimination. These results highlight the importance of incorporating information on climate variability, rather than previous incidence, in planning IRS interventions in regions of unstable malaria. These findings are discussed in the more general context of elimination and other low transmission regions such as highlands.