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Background: Culex mosquitoes are vectors for a variety of pathogens of public health concern. New indicators of exposure to Culex bites are needed to evaluate the risk of transmission of associated pathogens and to assess the efficacy of vector control strategies. An alternative to entomological indices is the serological measure of antibodies specific to mosquito salivary antigens. This study investigated whether the human IgG response to both the salivary gland extract and the 30 kDa salivary protein of Culex quinquefasciatus may represent a proxy of human exposure to Culex bites., Methodology/principal Findings: A multidisciplinary survey was conducted with children aged 1 to 14 years living in neighborhoods with varying exposure to Culex quinquefasciatus in the city of Bouaké, Côte d'Ivoire. Children living in sites with high exposure to Cx quinquefasciatus had a significantly higher IgG response to both salivary antigens compared with children living in the control site where only very few Culex were recorded. Moreover, children from any Culex-high exposed sites had significantly higher IgG responses only to the salivary gland extract compared with children from the control village, whereas no difference was noted in the anti-30 kDa IgG response. No significant differences were noted in the specific IgG responses between age and gender. Sites and the use of a bed net were associated with the level of IgG response to the salivary gland extract and to the 30 kDa antigen, respectively., Conclusions/significance: These findings suggest that the IgG response to Culex salivary gland extracts is suitable as proxy of exposure; however, the specificity to the Culex genus needs further investigation. The lower antigenicity of the 30 kDa recombinant protein represents a limitation to its use. The high specificity of this protein to the Culex genus makes it an attractive candidate and other specific antibody responses might be more relevant as a biomarker of exposure. These epidemiological observations may form a starting point for additional work on developing serological biomarkers of Culex exposure., Competing Interests: The authors have declared that no competing interests exist.

Background: Envenomation by the South American Lonomia saturniid caterpillars, named lonomism, constitutes an emerging and somewhat neglected public health issue in Argentina and neighboring countries. Considering that there is an intricate relationship between environment and human health in such cases, this study aimed to analyze the eco-epidemiological profile of 40 accidents and 33 occurrences of Lonomia spp. in Misiones (Argentina) between January 2014 and May 2020., Methodology/principal Findings: We described the eco-epidemiological variables and characterized the abiotic scenario of such cases. Additionally, we obtained a density map that shows the punctual intensity of Lonomia records throughout Misiones. Most of the accidents occurred in the Department of Guaraní and involved male victims younger than 20 years old. The accidental/occasional occurrence of Lonomia spp. (considering both adult and caterpillar stages together) was significantly higher in the rural area, whereas only adult specimens were found in urban areas. We determined that the presence of this insect in Misiones is positively related to higher temperatures and solar radiation, and larger precipitation and evapotranspiration throughout the year., Conclusion/significance: This study represents an initial step towards the global understanding of lonomism as a public health problem in Argentina. It provides a map of the risk level for this envenomation in Misiones, which could help authorities address public health policy efforts to implement sustainable strategies for prevention and response to this threat in Northeastern Argentina and neighboring regions., Competing Interests: The authors have declared that no competing interests exist.

Background: The existence of locations with low but stable onchocerciasis prevalence is not well understood. An often suggested yet poorly investigated explanation is that the infection spills over from neighbouring locations with higher infection densities., Methodology: We adapted the stochastic individual based model ONCHOSIM to enable the simulation of multiple villages, with separate blackfly (intermediate host) and human populations, which are connected through the regular movement of the villagers and/or the flies. With this model we explore the impact of the type, direction and degree of connectedness, and of the impact of localized or full-area mass drug administration (MDA) over a range of connected village settings., Principal Findings: In settings with annual fly biting rates (ABR) below the threshold needed for stable local transmission, persistence of onchocerciasis prevalence can well be explained by regular human traffic and/or fly movement from locations with higher ABR. Elimination of onchocerciasis will then theoretically be reached by only implementing MDA in the higher prevalence area, although lingering infection in the low prevalence location can trigger resurgence of transmission in the total region when MDA is stopped too soon. Expanding MDA implementation to the lower ABR location can therefore shorten the duration of MDA needed. For example, when prevalence spill-over is due to human traffic, and both locations have about equal populations, then the MDA duration can be shortened by up to three years. If the lower ABR location has twice as many inhabitants, the reduction can even be up to six years, but if spill-over is due to fly movement, the expected reduction is less than a year., Conclusions/significance: Although MDA implementation might not always be necessary in locations with stable low onchocerciasis prevalence, in many circumstances it is recommended to accelerate achieving elimination in the wider area., Competing Interests: The authors have declared that no competing interests exist.

Leishmaniasis is a neglected tropical disease which kills an estimated 50,000 people each year, with its deadly impact confined mainly to lower to middle income countries. Leishmania parasites are transmitted to human hosts by sand fly vectors during blood feeding. Recent experimental work shows that transmission is modulated by the patchy landscape of infection in the host's skin, and the parasite population dynamics within the vector. Here we assimilate these new findings into a simple probabilistic model for disease transmission which replicates recent experimental results, and assesses their relative importance. The results of subsequent simulations, describing random parasite uptake and dynamics across multiple blood meals, show that skin heterogeneity is important for transmission by short-lived flies, but that for longer-lived flies with multiple bites the population dynamics within the vector dominate transmission probability. Our results indicate that efforts to reduce fly lifespan beneath a threshold of around two weeks may be especially helpful in reducing disease transmission., Competing Interests: The authors have declared that no competing interests exist.

Trypanosoma rangeli is a non-pathogenic protozoan parasite that infects mammals, including humans, in Chagas disease-endemic areas of South and Central America. The parasite is transmitted to a mammalian host when an infected triatomine injects metacyclic trypomastigotes into the host's skin during a bloodmeal. Infected mammals behave as parasite reservoirs for several months and despite intensive research, some major aspects of T. rangeli-vertebrate interactions are still poorly understood. In particular, many questions still remain unanswered, e.g. parasite survival and development inside vertebrates, as no parasite multiplication sites have yet been identified. The present study used an insect bite transmission strategy to investigate whether the vector inoculation spot in the skin behave as a parasite-replication site. Histological data from the skin identified extracellular parasites in the dermis and hypodermis of infected mice in the first 24 hours post-infection, as well as the presence of inflammatory infiltrates in a period of up to 7 days. However, qPCR analyses demonstrated that T. rangeli is eliminated from the skin after 7 days of infection despite being still consistently found on circulating blood and secondary lymphoid tissues for up to 30 days post-infection. Interestingly, significant numbers of parasites were found in the spleen and mesenteric lymph nodes of infected mice during different periods of infection and steady basal numbers of flagellates are maintained in the host's bloodstream, which might behave as a transmission source to insect vectors. The presence of parasites in the spleen was confirmed by fluorescent photomicrography of free and cell-associated T. rangeli forms. Altogether our results suggest that this organ could possibly behave as a T. rangeli maintenance hotspot in vertebrates., Competing Interests: The authors have declared that no competing interests exist.

Background: Phlebotomus orientalis is a vector of Leishmania donovani, the causative agent of life threatening visceral leishmaniasis spread in Eastern Africa. During blood-feeding, sand fly females salivate into the skin of the host. Sand fly saliva contains a large variety of proteins, some of which elicit specific antibody responses in the bitten hosts. To evaluate the exposure to sand fly bites in human populations from disease endemic areas, we tested the antibody reactions of volunteers' sera against recombinant P. orientalis salivary antigens., Methodology/principal Findings: Recombinant proteins derived from sequence data on P. orientalis secreted salivary proteins, were produced using either bacterial (five proteins) or mammalian (four proteins) expression systems and tested as antigens applicable for detection of anti-P. orientalis IgG in human sera. Using these recombinant proteins, human sera from Sudan and Ethiopia, countries endemic for visceral leishmaniasis, were screened by ELISA and immunoblotting to identify the potential markers of exposure to P. orientalis bites. Two recombinant proteins; mAG5 and mYEL1, were identified as the most promising antigens showing high correlation coefficients as well as good specificity in comparison to the whole sand fly salivary gland homogenate. Combination of both proteins led to a further increase of correlation coefficients as well as both positive and negative predictive values of P. orientalis exposure., Conclusions/significance: This is the first report of screening human sera for anti-P. orientalis antibodies using recombinant salivary proteins. The recombinant salivary proteins mYEL1 and mAG5 proved to be valid antigens for screening human sera from both Sudan and Ethiopia for exposure to P. orientalis bites. The utilization of equal amounts of these two proteins significantly increased the capability to detect anti-P. orientalis antibody responses., Competing Interests: The authors have declared that no competing interests exist.

Background: Aedes mosquitoes severely affect the health and wellbeing of human populations by transmitting infectious diseases. In French Polynesia, Aedes aegypti is the main vector of dengue, chikungunya and Zika, and Aedes polynesiensis the primary vector of Bancroftian filariasis and a secondary vector of arboviruses. Tools for assessing the risk of disease transmission or for measuring the efficacy of vector control programmes are scarce. A promising approach to quantify the human-vector contact relies on the detection and the quantification of antibodies directed against mosquito salivary proteins., Methodology/principal Findings: An ELISA test was developed to detect and quantify the presence of immunoglobulin G (IgG) directed against proteins from salivary gland extracts (SGE) of Ae. aegypti and Ae. polynesiensis in human populations exposed to either species, through a cross-sectional study. In Tahiti and Moorea islands where Ae. aegypti and Ae. polynesiensis are present, the test revealed that 98% and 68% of individuals have developed IgG directed against Ae. aegypti and Ae. polynesiensis SGE, respectively. By comparison, ELISA tests conducted on a cohort of people from metropolitan France, not exposed to these Aedes mosquitoes, indicated that 97% of individuals had no IgG directed against SGE of either mosquito species. The analysis of additional cohorts representing different entomological Aedes contexts showed no ELISA IgG cross-reactivity between Ae. aegypti and Ae. polynesiensis SGE., Conclusions/significance: The IgG response to salivary gland extracts seems to be a valid and specific biomarker of human exposure to the bites of Ae. aegypti and Ae. polynesiensis. This new immuno-epidemiological tool will enhance our understanding of people exposure to mosquito bites, facilitate the identification of areas where disease transmission risk is high and permit to evaluate the efficacy of novel vector control strategies in Pacific islands and other tropical settings., Competing Interests: The authors have declared that no competing interests exist.

Mosquito saliva is a very complex concoction of >100 proteins, many of which have unknown functions. The effects of mosquito saliva proteins injected into our skin during blood feeding have been studied mainly in mouse models of injection or biting, with many of these systems producing results that may not be relevant to human disease. Here, we describe the numerous effects that mosquito bites have on human immune cells in mice engrafted with human hematopoietic stem cells. We used flow cytometry and multiplex cytokine bead array assays, with detailed statistical analyses, to detect small but significant variations in immune cell functions after 4 mosquitoes fed on humanized mice footpads. After preliminary analyses, at different early times after biting, we focused on assessing innate immune and subsequent cellular responses at 6 hours, 24 hours and 7 days after mosquito bites. We detected both Th1 and Th2 human immune responses, and delayed effects on cytokine levels in the blood, and immune cell compositions in the skin and bone marrow, up to 7 days post-bites. These are the first measurements of this kind, with human immune responses in whole animals, bitten by living mosquitoes, versus previous studies using incomplete mouse models and salivary gland extracts or needle injected saliva. The results have major implications for the study of hematophagous insect saliva, its effects on the human immune system, with or without pathogen transmission, and the possibility of determining which of these proteins to target for vaccination, in attempts to block transmission of numerous tropical diseases., Competing Interests: The authors have declared that no competing interests exist.

Visceral leishmaniasis (VL) is a deadly neglected tropical disease that poses a serious problem in various countries all over the world. Implementation of various intervention strategies fail in controlling the spread of this disease due to issues of parasite drug resistance and resistance of sandfly vectors to insecticide sprays. Due to this, policy makers need to develop novel strategies or resort to a combination of multiple intervention strategies to control the spread of the disease. To address this issue, we propose an extensive SIR-type model for anthroponotic visceral leishmaniasis transmission with seasonal fluctuations modeled in the form of periodic sandfly biting rate. Fitting the model for real data reported in South Sudan, we estimate the model parameters and compare the model predictions with known VL cases. Using optimal control theory, we study the effects of popular control strategies namely, drug-based treatment of symptomatic and PKDL-infected individuals, insecticide treated bednets and spray of insecticides on the dynamics of infected human and vector populations. We propose that the strategies remain ineffective in curbing the disease individually, as opposed to the use of optimal combinations of the mentioned strategies. Testing the model for different optimal combinations while considering periodic seasonal fluctuations, we find that the optimal combination of treatment of individuals and insecticide sprays perform well in controlling the disease for the time period of intervention introduced. Performing a cost-effective analysis we identify that the same strategy also proves to be efficacious and cost-effective. Finally, we suggest that our model would be helpful for policy makers to predict the best intervention strategies for specific time periods and their appropriate implementation for elimination of visceral leishmaniasis.

Background: Arboviral diseases are an important public health concerns. Vector control remains the sole strategy to fight against these diseases. Because of the important limits of methods currently used to assess human exposure to Aedes mosquito bites, much effort is being devoted to develop new indicators. Recent studies have reported that human antibody (Ab) responses to Aedes aegypti Nterm-34kDa salivary peptide represent a promising biomarker tool to evaluate the human-Aedes contact. The present study aims investigate whether such biomarker could be used for assessing the efficacy of vector control against Aedes., Methodology/principal Findings: Specific human IgG response to the Nterm-34kDa peptide was assessed from 102 individuals living in urban area of Saint-Denis at La Reunion Island, Indian Ocean, before and after the implementation of vector control against Aedes mosquitoes. IgG response decreased after 2 weeks (P < 0.0001), and remained low for 4 weeks post-intervention (P = 0.0002). The specific IgG decrease was associated with the decline of Aedes mosquito density, as estimated by entomological parameters and closely correlated to vector control implementation and was not associated with the use of individual protection, daily commuting outside of the house, sex and age. Our findings indicate a probable short-term decrease of human exposure to Aedes bites just after vector control implementation., Conclusion/significance: Results provided in the present study indicate that IgG Ab response to Aedes aegypti Nterm-34kDa salivary peptide could be a relevant short-time indicator for evaluating the efficacy of vector control interventions against Aedes species., Competing Interests: The authors have declared that no competing interests exist.

Historically the western sahelian dry regions of Mali are known to be highly endemic for cutaneous leishmaniasis (CL) caused by Leishmania major, while cases are rarely reported from the Southern savanna forest of the country. Here, we report baseline prevalence of CL infection in 3 ecologically distinct districts of Mali (dry sahelian, north savanna and southern savanna forest areas). We screened 195 to 250 subjects from 50 to 60 randomly selected households in each of the 6 villages (four from the western sahelian district of Diema in Kayes region, one from the central district of Kolokani and one from the southern savanna district of Kolodieba, region of Sikasso). The screening consisted of: 1] A Leishmanin Skin Test (LST) for detection of exposure to Leishmania parasites; 2] clinical examination of suspected lesions, followed by validation with PCR and 3] finger prick blood sample to determine antibody levels to sand fly saliva. LST positivity was higher in the western district of Diema (49.9%) than in Kolokani (24.9%) and was much lower in Kolondieba (2.6%). LST positivity increased with age rising from 13.8% to 88% in Diema for age groups 2-5 years and 41-65 years, respectively. All eight PCR-confirmed L. major CL cases were diagnosed in subjects below 18 years of age and all were residents of the district of Diema. Exposure to sand fly bites, measured by anti-saliva antibody titers, was comparable in individuals living in all three districts. However, antibody titers were significantly higher in LST positive individuals (P<0.0001). In conclusion, CL transmission remains active in the western region of Mali where lesions were mainly prevalent among children under 18 years old. LST positivity correlated to higher levels of antibodies to sand fly salivary proteins, suggesting their potential as a risk marker for CL acquisition in Mali., Competing Interests: The authors have declared that no competing interests exist.

Background: The sandfly Phlebotomus papatasi is the vector of Leishmania major, the main causative agent of Old World cutaneous leishmaniasis (CL) in Saudi Arabia. Sandflies inject saliva while feeding and the salivary protein PpSP32 was previously shown to be a biomarker for bite exposure. Here we used recombinant PpSP32 to evaluate human exposure to Ph. papatasi bites, and study the association between antibody response to saliva and CL in endemic areas in Saudi Arabia., Methodology/principal Findings: In this observational study, anti-PpSP32 antibodies, as indicators of exposure to sandfly bites, were measured in sera from healthy individuals and patients from endemic regions in Saudi Arabia with active and cured CL. Ph. papatasi was identified as the primary CL vector in the study area. Anti-PpSP32 antibody levels were significantly higher in CL patients presenting active infections from all geographical regions compared to CL cured and healthy individuals. Furthermore, higher anti-PpSP32 antibody levels correlated with the prevalence and type of CL lesions (nodular vs. papular) observed in patients, especially non-local construction workers., Conclusions: Our findings suggest a possible correlation between the type of immunity generated by the exposure to sandfly bites and disease outcome.

A shift towards early morning biting behavior of the major malaria vector Anopheles funestus have been observed in two villages in south Benin following distribution of long-lasting insecticidal nets (LLINs), but the impact of these changes on the personal protection efficacy of LLINs was not evaluated. Data from human and An. funestus behavioral surveys were used to measure the human exposure to An. funestus bites through previously described mathematical models. We estimated the personal protection efficacy provided by LLINs and the proportions of exposure to bite occurring indoors and/or in the early morning. Average personal protection provided by using of LLIN was high (≥80% of the total exposure to bite), but for LLIN users, a large part of remaining exposure occurred outdoors (45.1% in Tokoli-V and 68.7% in Lokohoué) and/or in the early morning (38.5% in Tokoli-V and 69.4% in Lokohoué). This study highlights the crucial role of LLIN use and the possible need to develop new vector control strategies targeting malaria vectors with outdoor and early morning biting behavior. This multidisciplinary approach that supplements entomology with social science and mathematical modeling illustrates just how important it is to assess where and when humans are actually exposed to malaria vectors before vector control program managers, policy-makers and funders conclude what entomological observations imply.

Classic vector control strategies target mosquitoes indoors as the main transmitters of malaria are indoor-biting and -resting mosquitoes. However, the intensive use of insecticide-treated bed-nets (ITNs) and indoor residual spraying have put selective pressure on mosquitoes to adapt in order to obtain human blood meals. Thus, early-evening and outdoor vector activity is becoming an increasing concern. This study assessed the effect of a deltamethrin-treated net (100 mg/m(2)) attached to a one-meter high fence around outdoor cattle enclosures on the number of mosquitoes landing on humans. Mosquitoes were collected from four cattle enclosures: Pen A - with cattle and no net; B - with cattle and protected by an untreated net; C - with cattle and protected by a deltamethrin-treated net; D - no cattle and no net. A total of 3217 culicines and 1017 anophelines were collected, of which 388 were Anopheles gambiae and 629 An. ziemanni. In the absence of cattle nearly 3 times more An. gambiae (p<0.0001) landed on humans. The deltamethrin-treated net significantly reduced (nearly three-fold, p<0.0001) culicine landings inside enclosures. The sporozoite rate of the zoophilic An. ziemanni, known to be a secondary malaria vector, was as high as that of the most competent vector An. gambiae; raising the potential of zoophilic species as secondary malaria vectors. After deployment of the ITNs a deltamethrin persistence of 9 months was observed despite exposure to African weather conditions. The outdoor use of ITNs resulted in a significant reduction of host-seeking culicines inside enclosures. Further studies investigating the effectiveness and spatial repellence of ITNs around other outdoor sites, such as bars and cooking areas, as well as their direct effect on vector-borne disease transmission are needed to evaluate its potential as an appropriate outdoor vector control tool for rural Africa.

We performed a longitudinal study of adult survival of Anopheles darlingi, the most important vector in the Amazon, in a malarigenous frontier zone of Brazil. Survival rates were determined from both parous rates and multiparous dissections. Anopheles darlingi human biting rates, daily survival rates and expectation of life where higher in the dry season, as compared to the rainy season, and were correlated with malaria incidence. The biting density of mosquitoes that had survived long enough for completing at least one sporogonic cycle was related with the number of malaria cases by linear regression. Survival rates were the limiting factor explaining longitudinal variations in Plasmodium vivax malaria incidence and the association between adult mosquito survival and malaria was statistically significant by logistic regression (P<0.05). Survival rates were better correlated with malaria incidence than adult mosquito biting density. Mathematical modeling showed that P. falciparum and P. malariae were more vulnerable to changes in mosquito survival rates because of longer sporogonic cycle duration, as compared to P. vivax, which could account for the low prevalence of the former parasites observed in the study area. Population modeling also showed that the observed decreases in human biting rates in the wet season could be entirely explained by decreases in survival rates, suggesting that decreased breeding did not occur in the wet season, at the sites where adult mosquitoes were collected. For the first time in the literature, multivariate methods detected a statistically significant inverse relation (P<0.05) between the number of rainy days per month and daily survival rates, suggesting that rainfall may cause adult mortality.

Occurrence of intraspecific variation in parasite virulence, a prerequisite for coevolution of hosts and parasites, has largely been reported. However, surprisingly little is known of the molecular bases of this variation in eukaryotic parasites, with the exception of the antigenic variation used by immune-evading parasites of mammals. The present work aims to address this question in immune suppressive eukaryotic parasites. In Leptopilina boulardi, a parasitic wasp of Drosophila melanogaster, well-defined virulent and avirulent strains have been characterized. The success of virulent females is due to a major immune suppressive factor, LbGAP, a RacGAP protein present in the venom and injected into the host at oviposition. Here, we show that an homologous protein, named LbGAPy, is present in the venom of the avirulent strain. We then question whether the difference in virulence between strains originates from qualitative or quantitative differences in LbGAP and LbGAPy proteins. Results show that the recombinant LbGAPy protein has an in vitro GAP activity equivalent to that of recombinant LbGAP and similarly targets Drosophila Rac1 and Rac2 GTPases. In contrast, a much higher level of both mRNA and protein is found in venom-producing tissues of virulent parasitoids. The F1 offspring between virulent and avirulent strains show an intermediate level of LbGAP in their venom but a full success of parasitism. Interestingly, they express almost exclusively the virulent LbGAP allele in venom-producing tissues. Altogether, our results demonstrate that the major virulence factor in the wasp L. boulardi differs only quantitatively between virulent and avirulent strains, and suggest the existence of a threshold effect of this molecule on parasitoid virulence. We propose that regulation of gene expression might be a major mechanism at the origin of intraspecific variation of virulence in immune suppressive eukaryotic parasites. Understanding this variation would improve our knowledge of the mechanisms of transcriptional evolution currently under active investigation.

The impact of climate on the vector behaviour of the worldwide dog tick Rhipicephalus sanguineus is a cause of concern. This tick is a vector for life-threatening organisms including Rickettsia rickettsii, the agent of Rocky Mountain spotted fever, R. conorii, the agent of Mediterranean spotted fever, and the ubiquitous emerging pathogen R. massiliae. A focus of spotted fever was investigated in France in May 2007. Blood and tissue samples from two patients were tested. An entomological survey was organised with the study of climatic conditions. An experimental model was designed to test the affinity of Rh. sanguineus for biting humans in variable temperature conditions. Serological and/or molecular tools confirmed that one patient was infected by R. conorii, whereas the other was infected by R. massiliae. Dense populations of Rh. sanguineus were found. They were infected with new genotypes of clonal populations of either R. conorii (24/133; 18%) or R. massiliae (13/133; 10%). April 2007 was the warmest since 1950, with summer-like temperatures. We show herein that the human affinity of Rh. sanguineus was increased in warmer temperatures. In addition to the originality of theses cases (ophthalmic involvements, the second reported case of R. massiliae infection), we provide evidence that this cluster of cases was related to a warming-mediated increase in the aggressiveness of Rh. sanguineus, leading to increased human attacks. From a global perspective, we predict that as a result of globalisation and warming, more pathogens transmitted by the brown dog tick may emerge in the future.

We have investigated the pathogenicity of tsetse (Glossina pallidipes)-transmitted cloned strains of Trypanosoma brucei rhodesiense in vervet monkeys. Tsetse flies were confirmed to have mature trypanosome infections by xenodiagnosis, after which nine monkeys were infected via the bite of a single infected fly. Chancres developed in five of the nine (55.6%) monkeys within 4 to 8 days post infection (dpi). All nine individuals were successfully infected, with a median pre-patent period of 4 (range = 4-10) days, indicating that trypanosomes migrated from the site of fly bite to the systemic circulation rapidly and independently of the development of the chancre. The time lag to detection of parasites in cerebrospinal fluid (CSF) was a median 16 (range = 8-40) days, marking the onset of central nervous system (CNS, late) stage disease. Subsequently, CSF white cell numbers increased above the pre-infection median count of 2 (range = 0-9) cells/microl, with a positive linear association between their numbers and that of CSF trypanosomes. Haematological changes showed that the monkeys experienced an early microcytic-hypochromic anaemia and severe progressive thrombocytopaenia. Despite a 3-fold increase in granulocyte numbers by 4 dpi, leucopaenia occurred early (8 dpi) in the monkey infection, determined mainly by reductions in lymphocyte numbers. Terminally, leucocytosis was observed in three of nine (33%) individuals. The duration of infection was a median of 68 (range = 22-120) days. Strain and individual differences were observed in the severity of the clinical and clinical pathology findings, with two strains (KETRI 3741 and 3801) producing a more acute disease than the other two (KETRI 3804 and 3928). The study shows that the fly-transmitted model accurately mimics the human disease and is therefore a suitable gateway to understanding human African trypanosomiasis (HAT; sleeping sickness).