RESUMO
Africa contains more human genetic variation than any other continent, but the majority of the population-scale analyses of the African peoples have focused on just two of the four major linguistic groups, the Niger-Congo and Afro-Asiatic, leaving the Nilo-Saharan and Khoisan populations under-represented. In order to assess genetic variation and signatures of selection within a Nilo-Saharan population and between the Nilo-Saharan and Niger-Congo and Afro-Asiatic, we sequenced 50 genomes from the Nilo-Saharan Lugbara population of North-West Uganda and 250 genomes from 6 previously unsequenced Niger-Congo populations. We compared these data to data from a further 16 Eurasian and African populations including the Gumuz, another putative Nilo-Saharan population from Ethiopia. Of the 21 million variants identified in the Nilo-Saharan population, 3.57 million (17%) were not represented in dbSNP and included predicted non-synonymous mutations with possible phenotypic effects. We found greater genetic differentiation between the Nilo-Saharan Lugbara and Gumuz populations than between any two Afro-Asiatic or Niger-Congo populations. F3 tests showed that Gumuz contributed a genetic component to most Niger-Congo B populations whereas Lugabara did not. We scanned the genomes of the Lugbara for evidence of selective sweeps. We found selective sweeps at four loci (SLC24A5, SNX13, TYRP1, and UVRAG) associated with skin pigmentation, three of which already have been reported to be under selection. These selective sweeps point toward adaptations to the intense UV radiation of the Sahel.
Assuntos
Adaptação Fisiológica/genética , Variação Genética/genética , Seleção Genética/genética , Pigmentação da Pele/genética , Antiporters/genética , População Negra/genética , Gerenciamento de Dados , Etiópia/epidemiologia , Feminino , Genética Populacional , Genoma Humano/genética , Haplótipos/genética , Humanos , Masculino , Glicoproteínas de Membrana/genética , Oxirredutases/genética , Polimorfismo de Nucleotídeo Único/genética , Nexinas de Classificação/genética , Proteínas Supressoras de Tumor/genética , Uganda/epidemiologiaRESUMO
BACKGROUND: Copy number variation is an important class of genomic variation that has been reported in 75% of the human genome. However, it is underreported in African populations. Copy number variants (CNVs) could have important impacts on disease susceptibility and environmental adaptation. To describe CNVs and their possible impacts in Africans, we sequenced genomes of 232 individuals from three major African ethno-linguistic groups: (1) Niger Congo A from Guinea and Côte d'Ivoire, (2) Niger Congo B from Uganda and the Democratic Republic of Congo and (3) Nilo-Saharans from Uganda. We used GenomeSTRiP and cn.MOPS to identify copy number variant regions (CNVRs). RESULTS: We detected 7608 CNVRs, of which 2172 were only deletions, 2384 were only insertions and 3052 had both. We detected 224 previously un-described CNVRs. The majority of novel CNVRs were present at low frequency and were not shared between populations. We tested for evidence of selection associated with CNVs and also for population structure. Signatures of selection identified previously, using SNPs from the same populations, were overrepresented in CNVRs. When CNVs were tagged with SNP haplotypes to identify SNPs that could predict the presence of CNVs, we identified haplotypes tagging 3096 CNVRs, 372 CNVRs had SNPs with evidence of selection (iHS > 3) and 222 CNVRs had both. This was more than expected (p < 0.0001) and included loci where CNVs have previously been associated with HIV, Rhesus D and preeclampsia. When integrated with 1000 Genomes CNV data, we replicated their observation of population stratification by continent but no clustering by populations within Africa, despite inclusion of Nilo-Saharans and Niger-Congo populations within our dataset. CONCLUSIONS: Novel CNVRs in the current study increase representation of African diversity in the database of genomic variants. Over-representation of CNVRs in SNP signatures of selection and an excess of SNPs that both tag CNVs and are subject to selection show that CNVs may be the actual targets of selection at some loci. However, unlike SNPs, CNVs alone do not resolve African ethno-linguistic groups. Tag haplotypes for CNVs identified may be useful in predicting African CNVs in future studies where only SNP data is available.
Assuntos
População Negra/genética , Variações do Número de Cópias de DNA , Genômica/métodos , África/etnologia , Bases de Dados Genéticas , Predisposição Genética para Doença , Genética Populacional , Genoma Humano , Haplótipos , HumanosRESUMO
Mammalian teeth exhibit incremental structures representing successive forming fronts of enamel at varying time scales, including a short daily increment called a cross striation and a long period called a stria of Retzius, the latter of which, in humans, occurs on average every 8-9 days. The number of daily increments between striae is called the repeat interval, which is the same period as that required to form one increment of bone, i.e. the lamella, the fundamental - if not archetypal - unit of bone. Lamellae of known formation time nevertheless vary in width, and thus their measures provide time-calibrated growth rate variability. We measured growth rate variability for as many as 6 years of continuously forming primary incremental lamellar bone from midshaft femur histological sections of sub-Saharan Africans of Bantu origin and known life history. We observed periodic growth rate variability in approximately 6- to 8-week intervals, and in some cases annual rhythms were visible. Endogenous biological periodicities, cycles manifest in the external environment, and/or perturbations of development are all potentially contained within growth rate variability studies of lamellar incremental patterns. Because lamellae are formed within defined periods of time, quantitative measures of widths of individual lamellae provide time-resolved growth rate variability that may reveal rhythms in human bone growth heretofore unknown.
Assuntos
Esmalte Dentário/crescimento & desenvolvimento , Fêmur/crescimento & desenvolvimento , Calibragem , Feminino , Fêmur/anatomia & histologia , Humanos , Masculino , Fatores de TempoRESUMO
Introduction: Trypanosoma brucei (T.b.) rhodesiense is the cause of the acute form of human African trypanosomiasis (HAT) in eastern and southern African countries, including Malawi. For a long time, untreated HAT infections were believed to be 100% fatal. However, recent studies show that infection by T.b. rhodesiense can result in a wide range of clinical outcomes in its human host. Apart from other factors such as parasite diversity, cytokines have been strongly implicated to play a major role in the outcome of T.b. rhodesiense infections.In this study, we quantify the levels of three cytokines Interleukin-8 (IL-8), Tumor Necrotic Factor alpha (TNF-α) and Interleukin -10 (IL-10) in plasma amongst HAT cases (treated and untreated) and controls recruited during medical survey. Methods: Two-hundred and thirty-three plasma samples (HAT cases and controls) from Rumphi, one of the endemic areas in Malawi were used. Blood collected was centrifuged, plasma extracted and stored in cryovials at -80°C until processing. Plasma cytokine concentration was measured using ELISA. Results: Plasma samples for 233 individuals, 76 HAT cases and 157 controls were quantified. Among the cases, nine had their plasma collected before treatment (untreated) and the rest were treated before blood for plasma analysis was collected. Controls had significantly higher mean plasmatic levels of TNF-α (94.5 ±474.12 pg/ml) and IL-8 (2258.6 ±5227.4 pg/ml) than cases TNF-α (29.35±181.58 pg/ml) and IL-8 (1191.3±4236.09 pg/ml). Controls and cases had similar mean levels of IL-10 in plasma. Only IL-8 had statistically significant higher median levels in the untreated than treated HAT cases P=0.006. Conclusion: Our data suggest that cytokines could be considered as biomarkers of HAT infection and treatment. Further studies with a larger cohort of cases and additional cytokines which are known to be associated with HAT infection outcomes will be required to evaluate these cytokines further.
Assuntos
Trypanosoma brucei rhodesiense , Tripanossomíase Africana , Animais , Estudos de Coortes , Citocinas , Humanos , Malaui , Tripanossomíase Africana/epidemiologiaRESUMO
Background: Trypanosomes are protozoan flagellates that cause human African trypanosomiasis (HAT) and African animal trypanosomiasis (AAT). HAT is caused by Trypanosoma brucei rhodesiense in East and Central Africa and T.b. gambiense in West Africa, whereas AAT is caused by a number of trypanosome species, including T. brucei brucei, T. evansi, T. vivax, T. congolense, T. godfreyi and T. simiae. The aim of this study was to establish if tsetse flies at Liwonde Wild Life Reserve (LWLR) are infected with these trypanosomes and thus pose a risk to both humans and animals within and surrounding the LWLR. Methods: A total of 150 tsetse flies were caught. Of these, 82 remained alive after capture and were dissected such that the mid-gut could be examined microscopically for trypanosomes. DNA extractions were performed from both mid-guts and the 68 dead flies using a Qiagen Kit. Amplification techniques involved the Internal Transcriber Spacer 1 (ITS 1) conventional polymerase chain reaction (PCR) with primers designed to identify trypanosome species, and Repetitive Insertion Mobile Element - Loop Mediated Isothermal Amplification (RIME LAMP), a sequence specific to T. brucei. Results: Analysis showed that 79/82 (96.3%) of the mid-guts examined microscopically were positive for trypanosomes and that 75/150 (50%) of the DNA extracts (from the mid-gut, and tsetse fly carcasses) were positive for T. brucei, as determined by the RIME LAMP method. ITS1 PCR further showed that 87/150 (58.0%) flies were positive for trypanosomes, of which 56/87 (64.4%) were T. brucei, 9/87 (10.3%) were T. vivax; 7/87 (8.1%) were T. simiae; 6/87 (6.9%) were T. congolense, and 6/87 (6.9%) were T. godfreyi. Ten samples had a mixture of infections. Conclusion: Our analysis demonstrated a mixture of infections from trypanosome species in tsetse flies at LWLR, and that T. brucei, the species that causes HAT, was the most common. Our study successfully used molecular techniques to demonstrate the presence of T. b. rhodesiense at LWLR, a species that causes HAT in both East and Central Africa.
Assuntos
Insetos Vetores/parasitologia , Reação em Cadeia da Polimerase/métodos , Trypanosoma/classificação , Trypanosoma/genética , Moscas Tsé-Tsé/parasitologia , Animais , DNA Ribossômico/genética , DNA Espaçador Ribossômico/genética , Humanos , Malaui , Epidemiologia Molecular , Dados de Sequência Molecular , Trypanosoma/isolamento & purificação , Tripanossomíase Africana/epidemiologia , Tripanossomíase Africana/parasitologia , Tripanossomíase Africana/transmissãoRESUMO
Trypanosoma brucei (T.b.) rhodesiense is the cause of the acute form of human African trypanosomiasis (HAT) in eastern and southern African countries. There is some evidence that there is diversity in the disease progression of T.b. rhodesiense in different countries. HAT in Malawi is associated with a chronic haemo-lymphatic stage infection compared to other countries, such as Uganda, where the disease is acute with more marked neurological impairment. This has raised the question of the role of host genetic factors in infection outcomes. A candidate gene association study was conducted in the northern region of Malawi. This was a case-control study involving 202 subjects, 70 cases and 132 controls. All individuals were from one area; born in the area and had been exposed to the risk of infection since birth. Ninety-six markers were genotyped from 17 genes: IL10, IL8, IL4, HLA-G, TNFA, IL6, IFNG, MIF, APOL, HLA-A, IL1B, IL4R, IL12B, IL12R, HP, HPR, and CFH. There was a strong significant association with APOL1 G2 allele (p = 0.0000105, OR = 0.14, CI95 = [0.05-0.41], BONF = 0.00068) indicating that carriers of the G2 allele were protected against T.b. rhodesiense HAT. SNP rs2069845 in IL6 had raw p < 0.05, but did not remain significant after Bonferroni correction. There were no associations found with the other 15 candidate genes. Our finding confirms results from other studies that the G2 variant of APOL1 is associated with protection against T.b. rhodesiense HAT.
Assuntos
Alelos , Apolipoproteína L1/genética , Predisposição Genética para Doença/genética , Nefropatias/complicações , Nefropatias/genética , Tripanossomíase Africana/complicações , Adulto , Estudos de Casos e Controles , Citocinas/genética , Progressão da Doença , Feminino , Estudos de Associação Genética , Marcadores Genéticos/genética , Genótipo , Humanos , Nefropatias/epidemiologia , Malaui , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Trypanosoma brucei rhodesiense , Tripanossomíase Africana/epidemiologia , Uganda/epidemiologiaRESUMO
The tsetse fly, Glossina morsitans morsitans, is a significant problem in Zambia and Malawi. It is the vector for the human infective parasite Trypanosoma brucei rhodesiense, which causes human African trypanosomiasis, and various Trypanosoma species, which cause African animal trypanosomiasis. Understanding the genetic diversity and population structure of G. m. morsitans is the basis of elucidating the connectivity of the tsetse fly populations, information that is essential in implementing successful tsetse fly control activities. This study conducted a population genetic study using partial mitochondrial cytochrome oxidase gene 1 (CO1) and 10 microsatellite loci to investigate the genetic diversity and population structure of G. m. morsitans captured in the major HAT foci in Zambia and Malawi. We have included 108 and 99 G. m. morsitans samples for CO1 and microsatellite analyses respectively. Our results suggest the presence of two different genetic clusters of G. m. morsitans, existing East and West of the escarpment of the Great Rift Valley. We have also revealed genetic similarity between the G. m. morsitans in Kasungu National Park and those in the Luangwa river basin in Zambia, indicating that this population should also be included in this historical tsetse belt. Although further investigation is necessary to illustrate the whole picture in East and Southern Africa, this study has extended our knowledge of the population structure of G. m. morsitans in Southern Africa.
Assuntos
Variação Genética , Tripanossomíase Africana/parasitologia , Moscas Tsé-Tsé/genética , Animais , Complexo IV da Cadeia de Transporte de Elétrons/genética , Feminino , Genética Populacional , Haplótipos , Humanos , Insetos Vetores/genética , Malaui , Masculino , Repetições de Microssatélites , Filogeografia , Moscas Tsé-Tsé/enzimologia , ZâmbiaRESUMO
Xenomonitoring is an important approach in assessing the progress of trypanosomiasis control as well as in estimating the endemicity of trypanosomes in affected areas. One of the major challenges in this approach is the unavailability of sensitive and easy to use xenomonitoring tools that can be used in the remote areas where the disease occurs. One tool that has been used successfully in detecting the parasites in tsetse flies is the repetitive insertion mobile element loop-mediated isothermal amplification (RIME LAMP). This tool has recently been modified from the liquid form to dry form for use in remote areas; however, uptake for use in the field has been slow. Field-collected tsetse flies were used to evaluate the performance of dry RIME LAMP over the conventional liquid RIME LAMP. All the samples were also subjected to internal transcribed spacer 1 (ITS1) ribosomal deoxyribonucleic acid (DNA) polymerase chain reaction (PCR) as a standard. ITS1-PCR-positive samples were further sequenced for confirmation of the species. A total of 86 wild tsetse flies were left to dry at room temperature for 3 months and DNA was extracted subsequently. All 86 flies were Glossina morsitans morsitans. From these, dry RIME LAMP detected 16.3% while liquid RIME LAMP detected 11.6% as infected with trypanosomes. Ten positive samples on ITS1-PCR were sequenced and all were shown to be trypanosomes. The use of dry RIME LAMP in the field for xenomonitoring of trypanosomes in tsetse flies will greatly contribute towards control of this neglected tropical disease as it provides the cheapest, fastest and simplest way to estimate possible human infective trypanosome infection rates in the tsetse fly vectors.
Assuntos
Técnicas de Amplificação de Ácido Nucleico/veterinária , Trypanosoma/isolamento & purificação , Moscas Tsé-Tsé/parasitologia , Animais , Malaui , Técnicas de Amplificação de Ácido Nucleico/métodos , Vigilância da População , Moscas Tsé-Tsé/classificaçãoRESUMO
Background: Anaemia commonly results from destruction of erythrocytes in the peripheral blood and failure of the bone marrow haematopoietic cells to replenish the erythrocytes. The mechanisms involved in trypanosoma-induced anaemia, including the role of the bone marrow haematopoietic cells are incompletely understood. We studied the responses of a tetrapeptide, AcSDKP, and IL-10, and their association with bone marrow nucleated cells in a Trypanosoma brucei brucei GVR35 experimental infection model. Methods: Mouse infection was done intraperitoneally with 1 × 103 trypanosomes/mL. Mice were either infected or left uninfected (N = 100). At days 0, 9, 16, 23, 30, 37, and 44 post-infection, mice were euthanised and blood was collected by cardiac puncture to examine for parasitaemia and packed cell volume (PCV) and then centrifuged for plasma, which was used for cytokine ELISA. The mice's femurs were also dissected and bone marrow was collected for femur cellularity. Results: PCV dropped from 39.6% to 27% in infected animals by day 9 and remained low (relative to uninfected mice) for the duration of the experiment. AcSDKP levels decreased from day 0 (11.5 × 104 pg/mL) to day 16 (10 × 104), and increased by day 30 (12.6 × 104). There was a significant difference at day 16 (P = 0.023) between the infected and uninfected groups. By contrast, expression of IL-10 markedly increased between day 0 (18.6 pg/mL) and day 16 (145 pg/mL) and decreased by day 30 (42.8 pg/mL). There was also a significant difference in IL-10 expression between infected and uninfected mice at day 16 (P < 0.001). Bone marrow nucleated cells were significantly reduced during periods of low plasma AcSDKP and high plasma IL-10 concentrations (5.4 × 106 infected vs 6.2 × 106 on day 0 and 4.9 × 106 infected vs 10 × 106 uninfected on day 16). Conclusions: These data unravel a possible negative feedback interaction between AcSDKP and IL-10 in trypanosome infection. More importantly, this study implicates an IL-10/AcSDKP cytokine network in the regulation of bone marrow nucleated cells and provides a new potential mechanism in the pathogenesis of trypanosoma-induced anaemia. Further mechanistic blocking experiments on AcSDKP and IL-10 are recommended to further clarify understanding of the interaction.
Assuntos
Interleucina-10/sangue , Oligopeptídeos/sangue , Trypanosoma brucei brucei/fisiologia , Tripanossomíase Africana/complicações , Tripanossomíase Africana/veterinária , Anemia/sangue , Anemia/etiologia , Animais , Contagem de Eritrócitos/veterinária , Hematócrito/veterinária , Camundongos , Oligopeptídeos/genética , Tripanossomíase Africana/sangue , Tripanossomíase Africana/imunologiaRESUMO
BACKGROUND: Trypanosoma brucei rhodesiense is the causative agent of acute human African trypanosomiasis. Identification of T. b. rhodesiense in tsetse populations is essential for understanding transmission dynamics, assessng human disease risk, and monitoring spatiotemporal trends and impact of control interventions. Accurate detection and characterisation of trypanosomes in vectors relies on molecular techniques. For the first time in Malawi, a molecular technique has been used to detect trypanosomes in tsetse flies in Nkhotakota Wildlife Reserve. METHODS: A polymerase chain reaction (PCR) technique was used to identify the serum resistance associated (SRA) gene of T. b. rhodesiense in tsetse flies. Of 257 tsetse flies that were randomly caught, 42 flies were dissected for microscopic examination. The midguts of 206 flies were positive and were individually put in eppendorf tubes containing phosphate-buffered saline (PBS buffer) for DNA extraction. Internal transcribed spacer (ITS)-PCR was first used to isolate all trypanosome species from the flies. TBR PCR was then used to isolate the Trypanozoon group. T. brucei-positive samples were further evaluated by SRA PCR for the presence of the SRA gene. RESULTS: Of 257 flies caught, 185 (72%) were Glossina morsitans morsitans and 72 (28%) were Glossina pallidipes. Three were tenerals and 242 were mature live flies. Of the 242 flies dissected, 206 were positive, representing an 85.1% infection rate. From 206 infected flies, 106 (51.5%) were positive using ITS-PCR, 68 (33.0%) being mixed infections, 18 (8.7%) T. brucei, 9 (4.4%) Trypanosoma vivax, 4 (1.9%) Trypanosoma godfrey, 3 (1.5%) Trypanosoma congolense savanna, 3 (1.5%) Trypanosoma simae, and 1 (0.4%) Trypanosoma simaetsavo. When subjected to TBR PCR, 107(51.9%) were positive for T. brucei. Of the 107 T. brucei-positive samples, 5 (4.7%) were found to have the SRA gene. CONCLUSIONS: These results suggest that wild tsetse flies in Malawi are infected with human-infective trypanosomes that put communities around wildlife reserves at risk of human African trypanosomiasis outbreaks. Further studies need to be done to identify sources of blood meals for the flies and for surveillance of communities around wildlife reserves.
Assuntos
Insetos Vetores/parasitologia , Glicoproteínas de Membrana/genética , Reação em Cadeia da Polimerase/métodos , Proteínas de Protozoários/genética , Trypanosoma brucei rhodesiense/genética , Tripanossomíase Africana/prevenção & controle , Moscas Tsé-Tsé/parasitologia , Animais , DNA Ribossômico/química , DNA Ribossômico/genética , DNA Espaçador Ribossômico/química , DNA Espaçador Ribossômico/genética , Malaui , Microscopia , Análise de Sequência de DNA , Trypanosoma brucei rhodesiense/isolamento & purificaçãoRESUMO
Arm span and standing height were measured in 289 boys and 337 girls aged 6-15 years who were free from physical deformities which can affect stature or arm span. The arm span exceeded height in all age groups of boys and in older girls. At the age of 7, 11 and 12 years girls were significantly taller than the boys and had longer arm span while at the age of 15 years, the trend was opposite. The mean difference between the two anthropometric parameters for boys was 5.45 +/- 4.21 cm (t = 3.556, p < 0.001) and for girls was 4.94 +/- 4.96 cm (t = 3.542, p < 0.001). Correlation coefficient between height and arm span measurements for Malawian boys was 0.983 and for girls was 0.986. Height, arm span and height-arm span difference increased with age of children while height to arm span ratio decreased. The gender difference in height-arm span differences was only significant at the age of 15 years. Multiple regression and cross validation were performed. Height of Malawian children of both sexes can be estimated from equation: Height (cm) = 15.756 + (0.168 x age) + (0.839 x arm span) (SEE = 0.760, R2 = 0.988).
Assuntos
Antropometria/métodos , Braço/anatomia & histologia , Estatura , Adolescente , Criança , Desenvolvimento Infantil , Feminino , Humanos , Modelos Lineares , Malaui , Masculino , Análise Multivariada , Reprodutibilidade dos TestesAssuntos
Bancos de Espécimes Biológicos , Tripanossomíase Africana/genética , Tripanossomíase Africana/prevenção & controle , Adolescente , Adulto , África Subsaariana/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Envelhecimento , Bancos de Espécimes Biológicos/ética , Bancos de Espécimes Biológicos/normas , DNA/genética , Erradicação de Doenças , Predisposição Genética para Doença , Humanos , Pessoa de Meia-Idade , Plasma , Tripanossomíase Africana/epidemiologia , Adulto JovemRESUMO
BACKGROUND: Cytosine arabinoside (Ara-C) is an S-phase specific cytotoxic drug used in the treatment of malignancies. It is converted to Cytosine Arabinoside triphosphate (Ara-CTP) in the cell. Cytosine Arabinoside triphosphate, reversibly displaces deoxy cytidine triphosphate from DNA polymerase for incorporation into DNA. This process leads to cell death. OBJECTIVE: To investigate the in vivo effects of Ara-C on the Granulocyte Macrophage Colony Forming Cells (GM-CFC) and High Proliferative Potential Colony Forming Cells (HPP-CFC) respectively in mice. METHODOLOGY: Ara-C (150mg/kg) was administered intraperitoneally (i.p) once to mice and bone marrow cells sampled on days 1, 3 and 6. RESULTS: Ara-C reduced the numbers of both GM-CFC and HPP-CFC in the bone marrow. HPP-CFCs were initially more sensitive to Ara-C treatment than GM-CFCs. In the six days after treatment the effect on GM-CFC persisted, while there was a partial recovery in the number of HPP-CFCs. CONCLUSION: It is possible that Ara-C disturbs the stem cells niche by damaging the stromal cells of the bone marrow microenvironment. This would result in derangement of HPP-CFC proliferation.
Assuntos
Células da Medula Óssea/efeitos dos fármacos , Citarabina/efeitos adversos , Granulócitos/efeitos dos fármacos , Imunossupressores/efeitos adversos , Macrófagos/efeitos dos fármacos , Células-Tronco/efeitos dos fármacos , Animais , Células da Medula Óssea/citologia , Contagem de Células , Linhagem Celular , Células Cultivadas , Citarabina/administração & dosagem , Relação Dose-Resposta a Droga , Granulócitos/citologia , Imunossupressores/administração & dosagem , Injeções Intraperitoneais , Macrófagos/citologia , Camundongos , Células-Tronco/citologiaRESUMO
Human African Trypanosomiasis (HAT) is a neglected tropical disease (NTD). Surveillance in many of the endemic areas is often inadequate. Up to date information on the HAT situation in Malawi, where the disease is endemic in some districts, provides opportunity to raise the profile of the disease and interest in prevention and control. A retrospective study was conducted in three Malawian districts: Nkhotakota, Rumphi and Kasungu to describe the prevalence of HAT. Hospital laboratory registers from January 2000 to December 2006 were used. The calculated annual district prevalence of Trypanosomiasis ranged from 0.29 cases per 100,000 population in 2000, to 0.58 cases per 100,000 population in 2003. Nkhotakota District had the highest case detection rate of trypanosomiasis of 16.56 cases per 100,000 in 2002 and the lowest rate in 2004 of 5.23 cases per 100,000. From 2004 onwards a decline in cases detected was observed. In Rumphi district the highest number of cases (17.67 cases per 100,000 population) was identified in 2003 and the lowest rate of 1.29 cases per 100,000 in 2001. The rate (17.67 cases per 100,000) found in 2003 represented a 5-fold increase of 2002 (3.02 cases per 100,000). In Kasungu the detection rate ranged from 0 per 100,000 in 2001, 2003 and 2004 to 0.99 cases per 100,000 in 2005. The number of cases in this district has remained low including in 2006, when a detection rate of 0.16 cases per 100,000 was observed. HAT is endemic in selected districts of Malawi. There is need to explore the feasibility of active disease surveillance and the establishment of permanent preventive and control measures.
Assuntos
Tripanossomíase Africana/epidemiologia , Humanos , Malaui/epidemiologia , Prevalência , Estudos RetrospectivosRESUMO
BACKGROUND: Diverse clinical features have been reported in human African trypanosomiasis (HAT) foci caused by Trypanosoma brucei rhodesiense (T.b.rhodesiense) giving rise to the hypothesis that HAT manifests as a chronic disease in South-East African countries and increased in virulence towards the North. Such variation in disease severity suggests there are differences in host susceptibility to trypanosome infection and/or genetic variation in trypanosome virulence. Our molecular tools allow us to study the role of host and parasite genotypes, but obtaining matched extensive clinical data from a large cohort of HAT patients has previously proved problematic. METHODS/PRINCIPAL FINDINGS: We present a retrospective cohort study providing detailed clinical profiles of 275 HAT patients recruited in two northern foci (Uganda) and one southern focus (Malawi) in East Africa. Characteristic clinical signs and symptoms of T.b.rhodesiense infection were recorded and the degree of neurological dysfunction determined on admission. Clinical observations were mapped by patient estimated post-infection time. We have identified common presenting symptoms in T.b.rhodesiense infection; however, marked differences in disease progression and severity were identified between foci. HAT was characterised as a chronic haemo-lymphatic stage infection in Malawi, and as an acute disease with marked neurological impairment in Uganda. Within Uganda, a more rapid progression to meningo-encephaltic stage of infection was observed in one focus (Soroti) where HAT was characterised by early onset neurodysfunction; however, severe neuropathology was more frequently observed in patients in a second focus (Tororo). CONCLUSIONS/SIGNIFICANCE: We have established focus-specific HAT clinical phenotypes showing dramatic variations in disease severity and rate of stage progression both between northern and southern East African foci and between Ugandan foci. Understanding the contribution of host and parasite factors in causing such clinical diversity in T.b.rhodesiense HAT has much relevance for both improvement of disease management and the identification of new drug therapy.
Assuntos
Trypanosoma brucei rhodesiense/isolamento & purificação , Trypanosoma brucei rhodesiense/patogenicidade , Tripanossomíase Africana/epidemiologia , Tripanossomíase Africana/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Estudos de Coortes , Progressão da Doença , Feminino , Geografia , Humanos , Lactente , Malaui/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Índice de Gravidade de Doença , Tripanossomíase Africana/parasitologia , Uganda/epidemiologia , Adulto JovemRESUMO
BACKGROUND: Human African Trypanosomiasis (HAT) is caused by two species of the tsetse fly vectored protozoan hemoflagellates belonging to Trypanosma brucei, namely T.b gambiense which predominates in Western Africa and follows a chronic disease course and T.b rhodensiense which is more prevalent in Southern and Eastern Africa, Malawi included, and follows a more acute and aggressive disease course. Previous studies in the Democratic Republic of Congo, Angola, Uganda and Sudan have demonstrated that the prevalence rates of T.b rhodensiense infection have reached epidemic proportions. OBJECTIVES: To describe the epidemiology of Trypanosomiasis in Rumphi District over the past ten years. METHODOLOGY: A total of 163 records from January 2000 to December 2006 were retrospectively studied. RESULTS: There were more males than females (121 vs. 40) with the 20 - 29 years age bracket having the highest number of cases (26.3%, n = 160). Stage 2 HAT was the commonest stage at presentation (58.2%, n = 158) with the patients in the same being 3.5 times more likely to die than those with stage 1 HAT. Case fatality rates for late and early stage disease were 21.5% (n = 92) and 7.2% (n = 66) respectively with 84.6% having been cured (n = 162). Convulsions were associated with fatal disease outcome and the majority of cases (97.2%, n = 103) lived within 5 kilometres of the Vwaza game reserve boundary. CONCLUSION: More men have been infected than women, with a high involvement in the 20 - 29 age brackets. A dramatic increase with active case finding indicates a high under-detection of the disease with late stage HAT being predominant at presentation. Though it has been found that cases with late stage disease have an increased likelihood of dying compared to those in early stage HAT, the high proportion of successful treatment indicates that the disease still carries a high degree of favourable outcome with treatment. It has also been demonstrated in this study that more than 95% of trypanosomiasis cases live within 5 km of game reserve boundary. Disease interventions should be implemented in areas within 5 km of marshland game reserve boundary as priority areas.
Assuntos
Surtos de Doenças , Trypanosoma brucei rhodesiense , Tripanossomíase Africana/epidemiologia , Adolescente , Adulto , Distribuição por Idade , Animais , Área Programática de Saúde , Criança , Pré-Escolar , Feminino , Hospitais de Distrito , Humanos , Lactente , Malaui , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Saúde da População Rural , Distribuição por Sexo , Tripanossomíase Africana/diagnóstico , Tripanossomíase Africana/terapia , Adulto JovemRESUMO
Given that oesophageal cancer (OC) is common in Malawi and its outcome is so dismal, would it be pragmatic to promptly mitigate the effects of smoking, alcohol and aflatoxins rather than seek a higher degree of local evidence for their role in OC? We retrospectively analysed a total of 13,217 OC and Kaposi's sarcoma (KS) cases as recorded in the Malawi National Cancer Registry from 1985 to February, 2006. We found no OC clustering to suggest a role for culturally variable habits like smoking, alcohol, maize use and maize storage in the country. It may be that drinking and eating hot foods physically damages the oesophageal mucosa, this is in line with work recently reported from Asia. We also found that OC numbers have risen in line with KS (and HIV) suggesting a link between these conditions.
Assuntos
Carcinoma de Células Escamosas/epidemiologia , Neoplasias Esofágicas/epidemiologia , Sarcoma de Kaposi/epidemiologia , Distribuição por Idade , Carcinoma de Células Escamosas/patologia , Neoplasias Esofágicas/patologia , Feminino , Humanos , Malaui/epidemiologia , Masculino , Sistema de Registros , Estudos Retrospectivos , Fatores de Risco , Sarcoma de Kaposi/patologiaRESUMO
Cancer is causing a lot of suffering and death in Africa but is not considered a major health problem in Africa. This needs to change. Cancer should be given equal emphasis to HIV/AIDS, tuberculosis (TB) and Malaria. A national cancer policy is required in Malawi to develop and improve evidence-based cancer prevention, early diagnosis, curative and palliative therapy. A national cancer policy is crucial to ensure a priotised, clear, coordinated and sustained fight against cancer. When no policy exists, events are likely to be random, stakeholders and practitioners in the fight against cancer may not agree on how to proceed, may duplicate efforts or may neglect areas that would have greater nationwide impact resulting in poor quality activities and haphazard development.
Assuntos
Política de Saúde , Avaliação das Necessidades/organização & administração , Neoplasias , Humanos , Incidência , Malaui , Programas Nacionais de Saúde/organização & administração , Neoplasias/diagnóstico , Neoplasias/epidemiologia , Neoplasias/prevenção & controle , Neoplasias/terapia , Qualidade da Assistência à SaúdeRESUMO
Infectious diseases remain a major health and socioeconomic problem in many low-income countries, particularly in sub-Saharan Africa. For many years, the three most devastating diseases, HIV/AIDS, malaria, and tuberculosis (TB) have received most of the world's attention. However, in rural and impoverished urban areas, a number of infectious diseases remain neglected and cause massive suffering. It has been calculated that a group of 13 neglected infectious diseases affects over one billion people, corresponding to a sixth of the world's population. These diseases include infections with different types of worms and parasites, cholera, and sleeping sickness, and can cause significant mortality and severe disabilities in low-income countries. For most of these diseases, vaccines are either not available, poorly effective, or too expensive. Moreover, these neglected diseases often occur in individuals who are also affected by HIV/AIDS, malaria, or TB, making the problem even more serious and indicating that co-infections are the rule rather than the exception in many geographical areas. To address the importance of combating co-infections, scientists from 14 different countries in Africa and Europe met in Addis Ababa, Ethiopia, on September 9-11, 2007. The message coming from these scientists is that the only possibility for winning the fight against infections in low-income countries is by studying, in the most global way possible, the complex interaction between different infections and conditions of malnourishment. The new scientific and technical tools of the post-genomic era can allow us to reach this goal. However, a concomitant effort in improving education and social conditions will be needed to make the scientific findings effective.