Human African Trypanosomiasis Cases Research Articles

Integration of Traditional Healers in Human African Trypanosomiasis Case Finding in Central Africa: A Quasi-Experimental Study.

Background: Based on the premise that Africans in rural areas seek health care from traditional healers, this study investigated a collaborative model between traditional healers and the national Human African Trypanosomiasis (HAT) programs across seven endemic foci in seven central African countries by measuring the model’s contribution to HAT case finding. Method: Traditional healers were recruited and trained by health professionals to identify HAT suspects based on its basics signs and symptoms and to refer them to the National Sleeping Sickness Control Program (NSSCP) for testing and confirmatory diagnosis. Results: 35 traditional healers were recruited and trained, 28 finally participated in this study (80%) and referred 278 HAT suspects, of which 20 (7.19%) were CATT positive for the disease. Most cases originated from Bandundu (45%) in the Democratic Republic of Congo and from Ngabe (35%) in Congo. Twelve (4.32%) patients had confirmatory diagnosis. Although a statistically significant difference was not shown in terms of case finding (p = 0.56), traditional healers were able to refer confirmed HAT cases that were ultimately cared for by NCSSPs. Conclusion: Integrating traditional healers in the control program of HAT will likely enhance the detection of cases, thereby, eventually contributing to the elimination of HAT in the most affected communities.

SNPs in IL4 and IFNG show no protective associations with human African trypanosomiasis in the Democratic Republic of the Congo: a case-control study

Background: Human African trypanosomiasis (HAT) is a protozoal disease transmitted by tsetse flies. Infection with trypanosomes can lead directly to active HAT or latent infection with no detectable parasites, which may progress to active HAT or to spontaneous self-cure. Genetic variation could explain these differences in the outcome of infection. To test this hypothesis, polymorphisms in 17 candidate genes were tested ( APOL1 [ G1 and G2], CFH, HLA-A, HPR, HP, IL1B, IL12B, IL12RB1, IL10, IL4R, MIF, TNFA , IL6, IL4, IL8, IFNG, and HLA-G). Methods: Samples were collected in Democratic Republic of the Congo. 233 samples were genotyped: 100 active HAT cases, 33 from subjects with latent infections and 100 negative controls. Commercial service providers genotyped polymorphisms at 96 single nucleotide polymorphisms (SNPs) on 17 genes. Data were analyzed using Plink V1.9 software and R. Loci, with suggestive associations (uncorrected p < 0.05) validated using an additional 594 individuals, including 164 cases and 430 controls. Results: After quality control, 87 SNPs remained in the analysis. Two SNPs in IL4 and two in IFNG were suggestively associated (uncorrected p<0.05) with a differential risk of developing a Trypanosoma brucei gambiense infection in the Congolese population. The IFNG minor allele (rs2430561, rs2069718) SNPs were protective in comparison between latent infections and controls. Carriers of the rs2243258_T and rs2243279_A alleles of IL4 and the rs2069728_T allele of IFNG had a reduced risk of developing illness or latent infection, respectively. None of these associations were significant after Bonferroni correction for multiple testing. A validation study using more samples was run to determine if the absence of significant association was due to lack of power. Conclusions: This study showed no evidence of an association of HAT with IL4 and IFNG SNPs or with APOL1 G1 and G2 alleles, which have been found to be protective in other studies.

SNPs in IL4 and IFNG show no protective associations with human African trypanosomiasis in the Democratic Republic of the Congo: a case-control study.

Background: Human African trypanosomiasis (HAT) is a protozoal disease transmitted by tsetse flies. Infection with trypanosomes can lead directly to active HAT or latent infection with no detectable parasites, which may progress to active HAT or to spontaneous self-cure. Genetic variation could explain these differences in the outcome of infection. To test this hypothesis, polymorphisms in 17 candidate genes were tested ( APOL1 [ G1 and G2], CFH, HLA-A, HPR, HP, IL1B, IL12B, IL12RB1, IL10, IL4R, MIF, TNFA , IL6, IL4, IL8, IFNG, and HLA-G). Methods: Samples were collected in Democratic Republic of the Congo. 233 samples were genotyped: 100 active HAT cases, 33 from subjects with latent infections and 100 negative controls. Commercial service providers genotyped polymorphisms at 96 single nucleotide polymorphisms (SNPs) on 17 genes. Data were analyzed using Plink V1.9 software and R. Loci, with suggestive associations (uncorrected p < 0.05) validated using an additional 594 individuals, including 164 cases and 430 controls. Results: After quality control, 87 SNPs remained in the analysis. Two SNPs in IL4 and two in IFNG were suggestively associated (uncorrected p<0.05) with a differential risk of developing a Trypanosoma brucei gambiense infection in the Congolese population. The IFNG minor allele (rs2430561, rs2069718) SNPs were protective in comparison between latent infections and controls. Carriers of the rs2243258_T and rs2243279_A alleles of IL4 and the rs2069728_T allele of IFNG had a reduced risk of developing illness or latent infection, respectively. None of these associations were significant after Bonferroni correction for multiple testing. A validation study using more samples was run to determine if the absence of significant association was due to lack of power. Conclusions: This study showed no evidence of an association of HAT with IL4 and IFNG SNPs or with APOL1 G1 and G2 alleles, which have been found to be protective in other studies.

An Active Follow-up Strategy for Serological Suspects of Human African Trypanosomiasis with Negative Parasitology Set up by a Health Zone Team in the Democratic Republic of Congo.

Background: The World Health Organization aims for the elimination of Human African Trypanosomiasis (HAT) as a public health problem by 2020 and for full elimination (absence of new cases) by 2030. One of strategies to achieve this is the active follow-up of all HAT serological suspects found during passive screening who have never been re-tested for parasitology. This is important because these cases can maintain HAT transmission and may be responsible for reemergence of the disease. Methods: In order to improve case finding at low cost in the targeted population, a general recall was transmitted to aparasitemic serological suspects about the availability of confirmation services at the general referral hospital. Transport was facilitated for re-testing. The initial examinations were carried out in Health Centers from Bagata Health Zone (HZ) in the Democratic Republic of the Congo between January 2017 and April 2019. This strategy of using a HZ team has not been previously documented. Results: From a total sample of 74 serological suspects listed by the health centers, 36 cases were re-examined at the general reference hospital; 19% (7/36) self-presented and 81% (29/36) were actively followed up by HZ personnel. Of those re-examined at the general reference hospital, 39% (14/36) resulted in a parasitologically confirmed case. Of the 14 people diagnosed with HAT, 14% (2/14) self-presented and the remaining 86% (12/14) were diagnosed in suspects who were actively followed up. This new strategy of facilitating transport from the villages added value by contributing to the detection of 12 HAT cases, compared to the passive approach, waiting for self-reference, which resulted in the detection of 2 new HAT cases. The cost per detected patient was 70 USD from the group of 7 suspects who self-presented for testing at the hospital and 346 USD per detected case for the group of 29 patients who were actively followed up by health zone staff. Conclusion: Targeted active follow-up of aparasitemic serological suspects by HZ teams is a cost-effective and promising approach to identifying additional cases of HAT in areas of very low prevalence, which would contribute to the HAT elimination goal set by the World Health Organization.

Plasma cytokine profiles associated with rhodesiense sleeping sickness and falciparum malaria co-infection in North Eastern Uganda

BackgroundImmunological Human African Trypanosomiasis (HAT) studies often exclude malaria, although both infections overlap in specific endemic areas. During this co-infection, it is not known whether this parasitic interaction induces synergistic or antagonistic cytokine response among humans. This study determined prevalence of Plasmodium falciparum malaria among Trypanosoma brucei rhodesiense HAT and plasma cytokine profile levels associated with HAT and/or malaria infections.MethodsParticipants were recruited at Lwala hospital in north eastern Uganda: healthy controls (30), malaria (28), HAT (17), HAT and malaria (15) diagnosed by microscopy and PCR was carried out for parasite species identification. Plasma cytokine levels of Interferon-gamma (IFN-γ), Tumour Necrosis Factor-alpha (TNF-α), Interleukin (IL)-6, IL-10 and Transforming Growth Factor-beta (TGF-β) were measured by sandwich Enzyme-Linked Immuno Sorbent Assay and data statistically analysed using Graphpad Prism 6.0.ResultsThe prevalence of P. falciparum malaria among T. rhodesiense HAT cases was high (46.8%). Malaria and/or HAT cases presented significant higher plasma cytokine levels of IFN-γ, TNF-α, IL-6, IL-10 and TGF-β than healthy controls (P < 0.05). Levels of IFN-γ, IL-6 and IL-10 were significantly elevated in HAT over malaria (P < 0.05) but no significant difference in TNF-α and TGF-β between HAT and malaria (P > 0.05). Co-infection expressed significantly higher plasma IFN-γ, IL-6, and IL-10 levels than malaria (P < 0.05) but no significant difference with HAT mono-infection (P > 0.05). The TNF-α level was significantly elevated in co-infection over HAT or malaria mono-infections (P < 0.05) unlike TGF-β level. Significant positive correlations were identified between IFN-γ verses TNF-α and IL-6 verses IL-10 in co-infection (Spearman’s P < 0.05).ConclusionsThe T. b. rhodesiense significantly induced the cytokine response more than P. falciparum infections. Co-infection led to synergistic stimulation of pro-inflammatory (IFN-γ, TNF-α), and anti-inflammatory (IL-6, and IL-10) cytokine responses relative to malaria mono-infection. Level of TNF-α partially indicates the effect induced by T. b. rhodesiense and P. falciparum mono-infections or a synergistic interaction of co-infections which may have adverse effects on pathogenesis, prognosis and resolution of the infections.Trial registration VCD-IRC/021, 26/08/2011; HS 1089, 16/01/2012

Integration of Human African Trypanosomiasis Control Activities into Primary Healthcare Services: A Scoping Review.

.Human African trypanosomiasis (HAT) also known as sleeping sickness is targeted for elimination as a public health problem by 2020 and elimination of infection by 2030. Although the number of reported cases is decreasing globally, integration of HAT control activities into primary healthcare services is endorsed to expand surveillance and control. However, this integration process faces several challenges in the field. This literature review analyzes what is known about integrated HAT control to guide the integration process in an era of HAT elimination. We carried out a scoping review by searching PubMed and Google Scholar data bases as well as gray literature documents resulting in 25 documents included for analysis. The main reasons in favor to integrate HAT control were related to coverage, cost, quality of service, or sustainability. There were three categories of factors influencing the integration process: 1) the clinical evolution of HAT, 2) the organization of health services, and 3) the diagnostic and therapeutic tools. There is a consensus that both active and passive approaches to HAT case detection and surveillance need to be combined, in a context-sensitive way. However, apart from some documentation about the constraints faced by local health services, there is little evidence on how this synergy is best achieved.

PO 8473 IMPACT OF EBOLA ON SLEEPING SICKNESS IN COASTAL GUINEA: A RETROSPECTIVE ANALYSIS (2012–2017) FROM THE GUINEAN NATIONAL CONTROL PROGRAMME

BackgroundCoastal Guinea harbours the most active human African trypanosomiasis (HAT) foci in West Africa. The Guinean government and its partners are conducting HAT control activities to reduce the burden of this neglected tropical disease and, as set-up by WHO, to eliminate it as a public health problem by 2020. Unfortunately, control efforts were deeply impaired during the Ebola outbreak that struck the country in 2014–2015. The aim of the study was to evaluate the impact of this unprecedented outbreak on HAT screening and care activities and more generally on T. brucei gambiense transmission.MethodsA retrospective analysis of the data collected by the HAT-NCP between 2012 and 2013 (pre-Ebola period) and 2014–2015 (Ebola outbreak) has shown an interruption of active HAT screening activities and a rapid decrease of passive HAT screening activities as the Ebola outbreak was spreading. During the Ebola epidemic, HAT patients were also diagnosed in a later stage of the disease and attendance to post-treatment control visits was also severely affected.ResultsOnly 59 HAT patients were diagnosed and treated during the Ebola outbreak (January 2014–October 2015) as compared to 154 before the outbreak (February 2012–December 2013). This potentially large undiagnosed human reservoir of trypanosomes may have contributed to increased transmission levels. After Guinea was declared free of Ebola virus disease, screening activities (both passive and active) were progressively resumed. In 2016 and 2017, Guinea reported 107 and 140 HAT cases, respectively (almost twice as much as during the pre-Ebola period) and became the second most affected country after the Democratic Republic of the Congo.ConclusionA major lesson taken from the Ebola outbreak is that disruption of medical care may lead to a quick HAT burst in areas of high transmission. Current HAT control measures combining screening and tsetse control interventions will help to stay on course for the elimination goal.

Identification of sinensetin and nobiletin as major antitrypanosomal factors in a citrus cultivar

Cases of human African trypanosomiasis caused by infection with a protozoan parasite, Trypanosoma brucei, are decreasing due to enhanced surveillance and control. However, effective and safe treatments for this disease are still needed. In this study, we investigated the antitrypanosomal activity of citrus fruit peel. When 19 citrus cultivars were examined for activity against T. brucei in vitro, significant activities were observed in four closely related cultivars and a distantly related one. Among these five cultivars, “Setoka” was selected for identification of its active components due to exhibiting the highest activity. Solvent extraction and gel filtration followed by preparative thin-layer chromatography succeeded in isolating two compounds exhibiting IC50s of 4.8 and 2.4 μg/mL, respectively. The spectral data of these two compounds were well consistent with those of sinensetin and nobiletin belonging to the class of polymethoxyflavones. Authentic compounds also showed similar IC50s. These results indicate that the two polymethoxyflavones are the major active components involved in the inhibition of T. brucei proliferation and are abundant in Setoka cultivar peel compared with the levels in the other cultivars. Setoka peel and the naturally occurring polymethoxyflavones might serve as dietary components imparting resistance to T. brucei.

Sleeping sickness in the historical focus of forested Guinea: update using a geographically based method.

In 2017, 1447 new cases of Human African Trypanosomiasis (HAT) were reported, which reflects considerable progress towards the World Health Organisation’s target of eliminating HAT as a public health problem by 2020. However, current epidemiological data are still lacking for a number of areas, including historical HAT foci. In order to update the HAT situation in the historical focus of forested Guinea, we implemented a geographically based methodology: Identification of Villages at Risk (IVR). The methodology is based on three sequential steps: Desk-based IVR (IVR-D), which selects villages at risk of HAT on the basis of HAT archives and geographical items; Field-based IVR (IVR-F), which consists in collecting additional epidemiological and geographical information in the field in villages at risk; and to be Medically surveyed IVR (IVR-M), a field data analysis through a Geographic Information System (GIS), to compile a list of the villages most at risk of HAT, suitable to guide active screening and passive surveillance. In an area of 2385 km2 with 1420,530 inhabitants distributed in 1884 settlements, 14 villages with a population of 11,236 inhabitants were identified as most at risk of HAT and selected for active screening. Although no HAT cases could be confirmed, subjects that had come into contact with Trypanosoma brucei gambiense were identified and two sentinel sites were chosen to implement passive surveillance. IVR, which could be applied to any gambiense areas where the situation needs to be clarified, could help to reach the objective of HAT elimination.

HLA-G 3’UTR 14 bp Insertion Is Associated with a Decreased Risk of Developing Human African Trypanosomiasis in the C&amp;#244;te d’Ivoire Population

Human African trypanosomiasis (HAT), or sleeping sickness, caused by Trypanosoma brucei gambiense, is associated with diverse clinical outcomes. Host’s genetic factors involved in immunity are potential factors that can regulate infection. Genetic polymorphisms within HLA-G could influence the level of HLA-G expression and therefore play a critical role in infection outcomes. The goal of our study was to investigate the association of 14 bp Indel HLA-G polymorphism with the susceptibility/resistance to HAT. DNA samples were collected from 119 cases, 221 controls and 43 seropositive individuals living in Ivorian HAT foci. The 14 bp Indel polymorphism was determined by PCR. Homozygous individuals for 14 bp insertion had a lower risk of progressing to active HAT (p = 0.012, OR = 0.27, 95% CI: 0.09 - 0.8). Moreover, the frequency of 14 bp insertion homozygous genotype was higher in the seropositive group (11%) than in the HAT cases group (3%) (p = 0.043, OR = 0.27, 95% CI: 0.07 - 0.99), which suggested a protective effect of 14 bp insertion homozygous genotype. Genetic polymorphisms in HLA-G may be associated with a variable risk to develop HAT. The 14 bp insertion appears to favour the occurrence of long-lasting T. b. gambiense latent infections.

Monitoring the elimination of human African trypanosomiasis: Update to 2016.

BackgroundHuman African trypanosomiasis (HAT) is a neglected tropical disease targeted for elimination ‘as a public health problem’ by 2020. The indicators to monitor progress towards the target are based on the number of reported cases, the related areas and populations exposed at various levels of risk, and the coverage of surveillance activities. Based on data provided by the National Sleeping Sickness Control Programmes (NSSCP), Non-Governmental Organizations (NGOs) and research institutions—and assembled in the Atlas of HAT—the World Health Organization (WHO) provides here an update to 2016 for these indicators, as well as an analysis of the epidemiological situation.ResultsTrends for the two primary indicators of elimination are on track for the 2020 goal: 2,164 cases of HAT were reported in 2016 (as compared to the milestone of 4,000 cases), and for the period 2012–2016 280,000 km2 are estimated to be at moderate risk or higher (i.e. ≥ 1 case/10,000 people/year), as compared to the milestone of 230,000 km2. These figures correspond to reductions of 92% and 61% as compared to the respective baselines (i.e. 26,550 HAT cases in the year 2000, and 709,000 km2 exposed at various levels of risk for the period 2000–2004). Among the secondary indicators, an overall improvement in the coverage of at risk populations by surveillance activities was observed. Regarding passive surveillance, the number of fixed health facilities providing gambiense HAT diagnosis or treatment expanded, with 1,338 enumerated in endemic countries in 2017 (+52% as compared to the survey completed only sixteen months earlier). Concerning rhodesiense HAT, 124 health facilities currently provide diagnosis or treatment. The broadening of passive surveillance is occurring in a context of fairly stable intensity of active case finding, with between 1.8 million and 2.4 million people screened per year over the period 2012–2016.DiscussionElimination of HAT as a public health problem by 2020 seems within reach, as the epidemiological trends observed in previous years are confirmed in this latest 2016 monitoring update. However, looking beyond 2020, and in particular to the 2030 goal of elimination of transmission as zero cases for the gambiense form of the disease only, there is no room for complacency. Challenges still abound, including ensuring the effective integration of HAT control activities in the health system, sustaining the commitment of donors and HAT endemic countries, and clarifying the extent of the threat posed by cryptic reservoirs (e.g. human asymptomatic carriers and the possible animal reservoirs in gambiense HAT epidemiology). WHO provides through the network for HAT elimination the essential coordination of the wide range of stakeholders to ensure synergy of efforts.

Knowledge, attitudes and practices about human African trypanosomiasis and their implications in designing intervention strategies for Yei county, South Sudan.

BackgroundA clear understanding of the knowledge, attitudes and practices (KAP) of a particular community is necessary in order to improve control of human African trypanosomiasis (HAT).New screening and diagnostic tools and strategies were introduced into South Sudan, as part of integrated delivery of primary healthcare. Knowledge and awareness on HAT, its new/improved screening and diagnostic tools, the places and processes of getting a confirmatory diagnosis and treatment are crucial to the success of this strategy.MethodologyA KAP survey was carried out in Yei County, South Sudan, to identify gaps in community KAP and determine the preferred channels and sources of information on the disease. The cross-sectional KAP survey utilized questionnaires, complemented with key informant interviews and a focus group discussion to elicit communal as well as individual KAP on HAT.FindingsMost (90%) of the respondents had general knowledge on HAT. Lower levels of education, gender and geographic locations without a history of HAT interventions were associated with incorrect knowledge and/or negative perceptions about the treatability of HAT. Symptoms appearing in the late stage were best known. A majority (97.2%) would seek treatment for HAT only in a health centre. However, qualitative data indicates that existing myths circulating in the popular imagination could influence people’s practices. Seventy-one percent of the respondents said they would offer social support to patients with HAT but qualitative data highlights that stigma still exists. Misconceptions and stigma can negatively influence the health seeking behaviour of HAT cases. In relation to communication, the top preferred and effective source of communication was radio (24%).ConclusionGaps in relation to KAP on HAT still exist in the community. Perceptions on HAT, specifically myths and stigma, were key gaps that need to be bridged through effective education and communication strategies for HAT control alongside other interventions.

The impact of passive case detection on the transmission dynamics of gambiense Human African Trypanosomiasis.

Gambiense Human African Trypanosomiasis (HAT), or sleeping sickness, is a vector-borne disease affecting largely rural populations in Western and Central Africa. The main method for detecting and treating cases of gambiense HAT are active screening through mobile teams and passive detection through self-referral of patients to dedicated treatment centres or hospitals. Strategies based on active case finding and treatment have drastically reduced the global incidence of the disease over recent decades. However, little is known about the coverage and transmission impact of passive case detection. We used a mathematical model to analyse data from the period between active screening sessions in hundreds of villages that were monitored as part of three HAT control projects run by Médecins Sans Frontières in Southern Sudan and Uganda in the late 1990s and early 2000s. We found heterogeneity in incidence across villages, with a small minority of villages found to have much higher transmission rates and burdens than the majority. We further found that only a minority of prevalent cases in the first, haemo-lymphatic stage of the disease were detected passively (maximum likelihood estimate <30% in all three settings), whereas around 50% of patients in the second, meningo-encephalitic were detected. We estimated that passive case detection reduced transmission in affected areas by between 30 and 50%, suggesting that there is great potential value in improving rates of passive case detection. As gambiense HAT is driven towards elimination, it will be important to establish good systems of passive screening, and estimates such as the ones here will be of value in assessing the expected impact of moving from a primarily active to a more passive screening regime.

Epidemiological Situation of the Human African Trypanosomiasis in the Bilolo Municipality of Central African Republic

The Human African Trypanosomiasis (HAT) is a disabling and fatal disease caused by a vector-borne parasite still impacting in residual hotbeds. The aim of our study was to update the epidemiological data of HAT in one of Central African Republic foci after the (2012-2014) period of conflict. The survey was carried out in 24 villages in the Bilolo's municipality where 4788 persons were examined by the CATT (Card Agglutination Trypanosomiasis Test) technique. The identified cases were submitted to a serological titration test followed by parasitological testing for confirmation. The cytorachia technique was used for clinical phase determination. The CATT has identified 221 persons, of which 54 were confirmed by serological titration test, giving a seroprevalence of 1.12%. Parasitological confirmation was obtained for 15 patients. Our study showed the abundance of Trypanosoma parasites in the Bilolo municipality. However, since 2007, no case of HAT had been diagnosed in this focus after screening, treatment and vector control.

Neural Damage in Experimental Trypanosoma brucei gambiense Infection: Hypothalamic Peptidergic Sleep and Wake-Regulatory Neurons.

Neuron populations of the lateral hypothalamus which synthesize the orexin (OX)/hypocretin or melanin-concentrating hormone (MCH) peptides play crucial, reciprocal roles in regulating wake stability and sleep. The disease human African trypanosomiasis (HAT), also called sleeping sickness, caused by extracellular Trypanosoma brucei (T. b.) parasites, leads to characteristic sleep-wake cycle disruption and narcoleptic-like alterations of the sleep structure. Previous studies have revealed damage of OX and MCH neurons during systemic infection of laboratory rodents with the non-human pathogenic T. b. brucei subspecies. No information is available, however, on these peptidergic neurons after systemic infection with T. b. gambiense, the etiological agent of 97% of HAT cases. The present study was aimed at the investigation of immunohistochemically characterized OX and MCH neurons after T. b. gambiense or T. b. brucei infection of a susceptible rodent, the multimammate mouse, Mastomys natalensis. Cell counts and evaluation of OX fiber density were performed at 4 and 8 weeks post-infection, when parasites had entered the brain parenchyma from the periphery. A significant decrease of OX neurons (about 44% reduction) and MCH neurons (about 54% reduction) was found in the lateral hypothalamus and perifornical area at 8 weeks in T. b. gambiense-infected M. natalensis. A moderate decrease (21% and 24% reduction, respectively), which did not reach statistical significance, was found after T. b. brucei infection. In two key targets of diencephalic orexinergic innervation, the peri-suprachiasmatic nucleus (SCN) region and the thalamic paraventricular nucleus (PVT), densitometric analyses showed a significant progressive decrease in the density of orexinergic fibers in both infection paradigms, and especially during T. b. gambiense infection. Altogether the findings provide novel information showing that OX and MCH neurons are highly vulnerable to chronic neuroinflammatory signaling caused by the infection of human-pathogenic African trypanosomes.

Neural Damage in Experimental Trypanosoma brucei gambiense Infection: The Suprachiasmatic Nucleus.

Trypanosoma brucei (T. b.) gambiense is the parasite subspecies responsible for most reported cases of human African trypanosomiasis (HAT) or sleeping sickness. This severe infection leads to characteristic disruption of the sleep-wake cycle, recalling attention on the circadian timing system. Most animal models of the disease have been hitherto based on infection of laboratory rodents with the T. b. brucei subspecies, which is not infectious to humans. In these animal models, functional, rather than structural, alterations of the master circadian pacemaker, the hypothalamic suprachiasmatic nucleus (SCN), have been reported. Information on the SCN after infection with the human pathogenic T. b. gambiense is instead lacking. The present study was aimed at the examination of the SCN after T. b. gambiense infection of a susceptible rodent, the multimammate mouse, Mastomys natalensis, compared with T. b. brucei infection of the same host species. The animals were examined at 4 and 8 weeks post-infection, when parasites (T. b. gambiense or T. b. brucei) were detected in the brain parenchyma, indicating that the disease was in the encephalitic stage. Neuron and astrocyte changes were examined with Nissl staining, immunophenotyping and quantitative analyses. Interestingly, significant neuronal loss (about 30% reduction) was documented in the SCN during the progression of T. b. gambiense infection. No significant neuronal density changes were found in the SCN of T. b. brucei-infected animals. Neuronal cell counts in the hippocampal dentate gyrus of T. b. gambiense-infected M. natalensis did not point out significant changes, indicating that no widespread neuron loss had occurred in the brain. Marked activation of astrocytes was detected in the SCN after both T. b. gambiense and T. b. brucei infections. Altogether the findings reveal that neurons of the biological clock are highly susceptible to the infection caused by human pathogenic African trypanosomes, which have the capacity to cause permanent partial damage of this structure.

Mass Survey of Human African Trypanosomiasis in Ukwani and Ethiope East Local Government Areas, Delta State, Nigeria

This study was intended to update the epidemiological status of Human African Trypanosomiasis (HAT), also known as sleeping sickness in Ukwuani and Ethope East Local Government Areas (LGAs) Delta State, Nigeria, and to establish a HAT control programme. In 2012, 1979 people from 26 villages were serologically screened for Trypanosomabruceigambiense, the causative agent of HAT. In 2012, surveys were carried out in villages where HAT cases had been identified. 119individuals were screened using the card agglutination Trypanosomiasis test (CATT), and then parasitologically examined for the presence of the parasite. CATT- positive individuals in whom the presence of the parasite could not be confirmed were further tested with the CATT using serum dilutions, and those with a positive antibody titer of 1 – in – 4or above were followed-up. Patients with 10 white cells and no trypanosomes in their cerebrospinal fluid (CSF) were classified as being in the second stage of the disease. Vector control was also considered necessary.In this survey, of the 1979 people screened, consisting of 7(0.57%) out of 1220 females and 4(0.53%) out of 759 males with no difference in sex – specificincidences. The positive cases occurred in Umutu and Umuebu communities in Ukuwani LGA, and in Ovu and Okpara inland communities in Ethiope- East LGA.

A Phase III Diagnostic Accuracy Study of a Rapid Diagnostic Test for Diagnosis of Second-Stage Human African Trypanosomiasis in the Democratic Republic of the Congo

ObjectivesTo estimate the diagnostic accuracy of HAT Sero K-SeT for the field diagnosis of second-stage human African trypanosomiasis (HAT). DesignA phase III diagnostic accuracy design. Consecutive patients with symptoms clinically suggestive of HAT were prospectively enrolled. We compared results of the index test HAT Sero K-SeT with those of a composite reference standard: demonstration of trypanosomes in cerebrospinal fluid (CSF), or trypanosomes detected in any other body fluid AND white blood cell count in CSF >5/μl. SettingRural hospital in the Democratic Republic of the Congo. ParticipantsAll patients above five years old presenting at Mosango hospital with a neurological problem of recent onset at the exclusion of trauma. Interventionsn.a. Main Outcome MeasuresSensitivity and specificity of HAT Sero K-SeT test. ResultsThe sensitivity of the HAT Sero K-SeT was 8/8 or 100.0% (95% confidence interval: 67.6 to 100.0%) and the specificity was 258/266 or 97.0% (94.2% to 98.5%). ConclusionThe high sensitivity of the HAT Sero K-SeT is in line with previously published estimates, though the sample of HAT cases in this study was small. The specificity estimate was very high and precise. This test, when negative, allows the clinician to rule out HAT in a clinical suspect in a hospital setting in this endemic region.

Impact of the Ebola outbreak on Trypanosoma brucei gambiense infection medical activities in coastal Guinea, 2014-2015: A retrospective analysis from the Guinean national Human African Trypanosomiasis control program.

BackgroundThe 2014–2015 Ebola outbreak massively hit Guinea. The coastal districts of Boffa, Dubreka and Forecariah, three major foci of Human African Trypanosomiasis (HAT), were particularly affected. We aimed to assess the impact of this epidemic on sleeping sickness screening and caring activities.Methodology/Principal findingsWe used preexisting data from the Guinean sleeping sickness control program, collected between 2012 and 2015. We described monthly: the number of persons (i) screened actively; (ii) or passively; (iii) treated for HAT; (iv) attending post-treatment follow-up visits. We compared clinical data, treatment characteristics and Disability Adjusted Life-Years (DALYs) before (February 2012 to December 2013) and during (January 2014 to October 2015) the Ebola outbreak period according to available data. Whereas 32,221 persons were actively screened from February 2012 to December 2013, before the official declaration of the first Ebola case in Guinea, no active screening campaigns could be performed during the Ebola outbreak. Following the reinforcement and extension of HAT passive surveillance system early in 2014, the number of persons tested passively by month increased from 7 to 286 between April and September 2014 and then abruptly decreased to 180 until January 2015 and to none after March 2015. 213 patients initiated HAT treatment, 154 (72%) before Ebola and 59 (28%) during the Ebola outbreak. Those initiating HAT therapy during Ebola outbreak were recruited through passive screening and diagnosed at a later stage 2 of the disease (96% vs. 55% before Ebola, p<0.0001). The proportion of patients attending the 3 months and 6 months post-treatment follow-up visits decreased from 44% to 10% (p <0.0001) and from 16% to 3% (p = 0.017) respectively. The DALYs generated before the Ebola outbreak were estimated to 48.7 (46.7–51.5) and increased up to 168.7 (162.7–174.7), 284.9 (277.1–292.8) and 466.3 (455.7–477.0) during Ebola assuming case fatality rates of 2%, 5% and 10% respectively among under-reported HAT cases.Conclusions/SignificanceThe 2014–2015 Ebola outbreak deeply impacted HAT screening activities in Guinea. Active screening campaigns were stopped. Passive screening dramatically decreased during the Ebola period, but trends could not be compared with pre-Ebola period (data not available). Few patients were diagnosed with more advanced HAT during the Ebola period and retention rates in follow-up were lowered. The drop in newly diagnosed HAT cases during Ebola epidemic is unlikely due to a fall in HAT incidence. Even if we were unable to demonstrate it directly, it is much more probably the consequence of hampered screening activities and of the fear of the population on subsequent confirmation and linkage to care. Reinforced program monitoring, alternative control strategies and sustainable financial and human resources allocation are mandatory during post Ebola period to reduce HAT burden in Guinea.

Candidate genes-based investigation of susceptibility to Human African Trypanosomiasis in Côte d'Ivoire.

Human African Trypanosomiasis (HAT) or sleeping sickness is a Neglected Tropical Disease. Long regarded as an invariably fatal disease, there is increasing evidence that infection by T. b. gambiense can result in a wide range of clinical outcomes, including latent infections, which are long lasting infections with no parasites detectable by microscopy. The determinants of this clinical diversity are not well understood but could be due in part to parasite or host genetic diversity in multiple genes, or their interactions. A candidate gene association study was conducted in Côte d’Ivoire using a case-control design which included a total of 233 subjects (100 active HAT cases, 100 controls and 33 latent infections). All three possible pairwise comparisons between the three phenotypes were tested using 96 SNPs in16 candidate genes (IL1, IL4, IL4R, IL6, IL8, IL10, IL12, IL12R, TNFA, INFG, MIF, APOL1, HPR, CFH, HLA-A and HLA-G). Data from 77 SNPs passed quality control. There were suggestive associations at three loci in IL6 and TNFA in the comparison between active cases and controls, one SNP in each of APOL1, MIF and IL6 in the comparison between latent infections and active cases and seven SNP in IL4, HLA-G and TNFA between latent infections and controls. No associations remained significant after Bonferroni correction, but the Benjamini Hochberg false discovery rate test indicated that there were strong probabilities that at least some of the associations were genuine. The excess of associations with latent infections despite the small number of samples available suggests that these subjects form a distinct genetic cluster different from active HAT cases and controls, although no clustering by phenotype was observed by principle component analysis. This underlines the complexity of the interactions existing between host genetic polymorphisms and parasite diversity.