The journey towards elimination of gambiense human African trypanosomiasis: not far, nor easy.

Considering the epidemic situation of gambiense human African trypanosomiasis (HAT) at the end of the twentieth century, the World Health Organization (WHO) and partners strengthened disease control and surveillance. Over the last 15 years, the activities implemented through the National Control Programmes have brought gambiense HAT under control and now its elimination is deemed as an achievable goal. In 2012, WHO targeted gambiense HAT for elimination as a public health problem by 2020. The final goal will be the sustainable disease elimination by 2030, defined as the interruption of the transmission of gambiense HAT. The elimination is considered feasible, because of the epidemiological vulnerability of the disease, the current state of control, the availability of strategies and tools and international commitment and political will. Integration of activities in the health system is needed to ensure the sustainability of the elimination. The development of user-friendly diagnostic and treatment tools will facilitate the integration process. Adequate funding is needed to implement activities, but also to support research that will make the elimination sustainable. A long-term commitment by donors is needed and ownership of the process by endemic countries is critical.

Mapping sleeping sickness in Western Africa in a context of demographic transition and climate change.

Human population growth, climate change and economic development are causing major environmental modifications in Western Africa, which will have important repercussions on the epidemiology of sleeping sickness. A new initiative, the Atlas of human African trypanosomiasis (HAT), aims at assembling and geo-referencing all epidemiological data derived from both active screening activities and passive surveillance. A geographic database enables to generate up-to-date disease maps at a range of scales and of unprecedented spatial accuracy. We present preliminary results for seven West African countries (Benin, Burkina Faso, Côte d'Ivoire, Ghana, Guinea, Mali and Togo) and briefly discuss the relevance of the Atlas for future monitoring, control and research activities.

Supplementation of glutamine and vitamin E on the morphometry of the intestinal mucosa in broiler chickens.

The objective of this experiment was to evaluate the influence of Gln and vitamin E (VE) supplementation in the diet of broiler chickens (Cobb-Vantress) on the morphometry of the intestinal mucosa. The design was completely randomized in a 2 x 3 (VE x periods of administering Gln) factorial arrangement. The levels of VE used were 10 and 500 mg/kg of diet and 3 periods of administering (1%) Gln-supplemented starter diet (for the first 7 or 14 d of life or for no added Gln), totaling 6 treatments with 5 replicates of 50 birds per experimental unit. In the growth period (d 22 to 41 posthatch), the treatments consisted only in the respective levels of VE. On d 7, 14, 21, and 41 posthatch, 2 birds per replicate were killed, and samples of the duodenum, jejunum, and ileum were subsequently removed, fixed in Bouin solution, and later embedded in paraffin and stained with hematoxylin-eosin. The parameters analyzed were villus height and crypt depth. An ANOVA was applied to the obtained data, and the means were compared using Tukey's test (5% significance level). Greater development was observed in the duodenum, followed by the jejunum and ileum. On 41 d of life, diets with 10 mg of VE/kg supplemented with Gln (for the first 7 d of life) provided better development of the intestinal mucosa in broiler chickens.

Study of resistance to anti-tuberculosis drugs in five districts of Equatorial Guinea: rates, risk factors, genotyping of gene mutations and molecular epidemiology.

SETTING: Five districts in Equatorial Guinea, March 1999 to February 2001. OBJECTIVES: To determine tuberculosis drug resistance among new and previously treated cases, the risk factors associated with resistance, and the mutations associated with isoniazid and rifampicin (katG, inhA and rpoB genes) resistance, and to genotype resistant strains. RESULTS: A positive culture identified as Mycobacterium tuberculosis complex was obtained in 240/499 patients. Susceptibility testing was performed in 236 strains. The overall resistance rate in new cases was 16.9% compared to 41.6% in previously treated cases. Isoniazid resistance was the most frequent (respectively 12.5% and 16.6%) in the two groups, while multidrug resistance was observed in 1.7% and 25% of new and previously treated cases, respectively. Female sex was statistically associated with resistance in new cases. Of 41 isoniazid-resistant strains, 33 (80.5%) had mutations in the inhA gene; none had mutations in the katG gene and eight had no mutations in either gene. All strains had low-level isoniazid resistance. Of eight strains resistant to rifampicin, six had mutations in the rpoB gene. Genotyping defined seven clusters. CONCLUSIONS: Moderate resistance was found in new cases. Low-level isoniazid resistance predominated among mutations in the inhA gene, with a high percentage of clustering in resistant strains.

Molecular epidemiology of tuberculosis in the Bata and Malabo districts of Equatorial Guinea.

SETTING: Bata and Malabo districts, Equatorial Guinea, 1 March 1999 to 28 February 2001. OBJECTIVE: To study the molecular epidemiology of tuberculosis (TB). RESULTS: During the study period, 429 patients were diagnosed with TB in the Bata and Malabo districts. A positive culture was obtained in 206 (48%) TB patients, with RFLP analysis being performed in 185 (89.8%). Ninety-two different patterns were identified. Single patterns were found in 71 strains (38.3%) and the remaining 114 strains (61.6%) were classified into 21 clusters (of 2 to 25 patients). In addition, 37 of the typing strains were resistant to one or more anti-tuberculosis drugs, and 30 were included in clusters (81%), with 21 low level isoniazid (MIC < or = 1 microg/ml) resistance strains in the same cluster. Statistical analysis showed that resistance to anti-tuberculosis drugs (OR 3.1; 95% CI 1.2-7.6; P = 0.014), and positive smear results (4+ grade smear) (OR 4.3; 95% CI 1.5-12; P = 0.005), were significantly more frequent among patients with clustered strains. No epidemiological links were related to clustering. CONCLUSIONS: The level of clustering (61.6%) observed suggests a high degree of recent transmission and a predominance of determined patterns of Mycobacterium tuberculosis strains among the population of Equatorial Guinea.

[Has the focus of human African trypanosomiasis in Luba, Equatorial Guinea been eradicated?]. / Le foyer de trypanosomiase humaine africaine de Luba en Guinée Equatoriale a-t-il été éradique?

Human African trypanosomiasis was considered a major public health problem in Luba, Equatorial Guinea in 1985. Because of the lack of qualified personnel, the emergency response consisted of a simple control strategy based on serological screening without parasitological confirmation and staging by lumbar puncture. This strategy was highly effective since the outbreak seems to have stopped. The authors discuss implications of this strategy which raises the risk of misdiagnosis and unwarranted treatment of trypanosomiasis. Other points of discussion in this article include the concept of sterilization of the disease area and need for continued low-grade surveillance.

[Cost of a national program to control human African trypanosomiasis in the high Mbomou region, Central African Republic]. / Cout d'un projet d'appui au programme national de lutte contre la trypanosomiase humaine africaine dans le foyer du Haut Mbomou, Republique Centrafricaine.

An outbreak of human African trypanosiaisis is ongoing in the High Mbomou area of the Central African Republic. This area is located on the Sudanese border approximately 1,100 kilometers from the capital city of Bangui. According to current estimates, the cost of implementing the National Human African Trypanosomiasis Program is 754,000 United States Dollars, i.e., 4.1 dollars per protected inhabitant. However actual conditions in the field suggest that this estimate should be revised. Special field conditions include constant refugee movement across the border, lack of accurate epidemiological data concerning neighboring Haut Zaire, and low participation of village residents in mass screening operations (less than 50%). In response to these problems, the authors recommend the organization of more exploratory missions to allow better targeting of screening and therapy. In the initial plan, exploratory missions were to account for 1% of the total cost. This proportion will probably require upward adjustment.

Diversity of human African trypanosomiasis epidemiological settings requires fine-tuning control strategies to facilitate disease elimination.

In 2001, the World Health Organization (WHO) established a public-private partnership to fight human African trypanosomiasis (HAT). As a result of this continuous collaboration, and in addition to the coordination with nongovernmental organizations and bilateral cooperation agencies, the number of new cases of HAT annually reported by the WHO has strikingly decreased. In 2012, HAT was included in WHO's roadmap on neglected tropical diseases with a 2020 target date for elimination. Although the prevalence of HAT is decreasing and its elimination is targeted, control approaches must be adapted to the different epidemiological patterns in order to adopt the most adequate strategies to maintain their cost-effectiveness. These strategies must be flexible and dynamic in order to be adapted to the disease progression, as well as to the changes affecting the existing health facilities in transmission areas, including their accessibility, their capabilities, and their involvement in the elimination process. Considering the different patterns of transmission (Trypanosoma brucei (T.b.) rhodesiense HAT) and transmission intensity (T.b. gambiense HAT), different settings have been defined. In the case of T.b. rhodesiense, this form exists primarily where wild animals are the main parasite reservoir, and where the main parasite reservoir is cattle. In T.b. gambiense, this form exists in areas with high intensity transmission, areas with moderate intensity transmission, and areas with low intensity transmission. Criteria and indicators must be established to monitor and evaluate the actions implemented toward the elimination of HAT.

The elimination of Trypanosoma brucei gambiense sleeping sickness in the focus of Luba, Bioko Island, Equatorial Guinea.

After the resurgence of sleeping sickness in Luba, Equatorial Guinea, a major campaign to control the disease was established in 1985. The campaign comprised no vector control, but intensive active and passive surveillance using serology for screening, and treatment of all parasitological and suspected serological cases. Total prevalence was used to classify villages as endemic, at risk, anecdotal and non-endemic which also allowed defining the geographic extent of the focus. Active case-finding was implemented from 1985 to 2004. The frequency of surveys was based on parasitological prevalence: twice a year during intensified control, once a year during ordinary control and once every 2 years during the control consolidation phase, when the parasitological prevalence in the whole focus fell to 0.1%. From 1985 to 1999, the indirect immunofluorescent antibody test (IFAT) was used as an initial screening tool, followed by parasitological confirmation of IFAT positive cases, and the Card Agglutination Trypanosomiasis Test (CATT) if necessary. In 2000, the IFAT was replaced by the CATT. Serum-positive individuals without parasitological confirmation were subsequently tested on serial dilution. All cases underwent lumbar puncture to determine the stage of the disease. First-stage cases were treated with pentamidine and second-stage cases with melarsoprol. A few relapses and very advanced cases were treated with eflornithine. The last sleeping sickness case was identified and treated in 1995.

Attitude towards CATT-positive individuals without parasitological confirmation in the African Trypanosomiasis (T.b. gambiense) focus of Quiçama (Angola).

Serologically positive individuals without parasitological confirmation constitute an important problem for trypanosomiasis control programmes because of epidemiological and therapeutical consequences. In July 1997, in the focus of Quiçama (Angola), 4753 individuals were screened using CATT/T.b.gambiense on whole blood. In CATT-positive but parasite-negative individuals, CATT titration on serum was performed. Sixteen individuals showing an end-titre lower than 1/4 were considered noninfected according to the results of a previous study of serological status of parasitologically confirmed cases; 86 individuals with end titres >/= 1/4 were considered suspected of trypanosomiasis and were followed-up from July 1997 to July 1998 with controls every three months. After one year, 32 individuals whose antibody titres dropped < 1/4 were considered noninfected, 22 were confirmed by demonstration of parasites, 17 were further followed-up because antibody titres remained >/= 1/8 but parasites could not be found. Fifteen individuals did not show up for testing. Following the usual criterion, only parasitologically confirmed cases were treated. However, if it had been decided to treat parasite-negative individuals with a CATT end-titre > 1/8, 22 initially unconfirmed but infected individuals would have been treated earlier, whereas 5 noninfected individuals would have been treated unnecessarily. CATT titration on diluted serum or plasma is useful for making therapeutical decisions.

Increased trypanolytic activity in sera of sleeping sickness patients after chemotherapy.

We tested sera from patients previously treated for human African trypanosomiasis, from patients infected with trypanosomes, and from individuals never diagnosed with African trypanosomiasis living in the Trypanosoma brucei gambiense sleeping sickness focus of Mbini in Equatorial Guinea for their trypanolytic activity against bloodstream forms of T. b. rhodesiense expressing a metacyclic and bloodstream variant surface glycoprotein (VSG). Nearly 80% of the sera from treated patients showed high trypanolytic activity against trypanosomes expressing a metacyclic VSG. The trypanolytic activity of part of these sera was mediated by IgM while that of the other part was antibody-independent. On the other hand, only 40% of the sera exhibited high trypanolytic activity against trypanosomes expressing a bloodstream VSG which also was almost completely abolished by heat-inactivation. In contrast, most sera from infected and negative individuals displayed only low to moderate trypanolytic activity against either trypanosomes expressing a metacyclic or a bloodstream VSG. These results suggest that trypanolytic activity of sera increases after African sleeping sickness and is directed against trypanosomes expressing metacyclic VSG.

Detection of Trypanosoma brucei gambiense in sleeping sickness suspects by PCR amplification of expression-site-associated genes 6 and 7.

We have developed a sensitive and specific method to identify Trypanosoma brucei ssp. using PCR to amplify conserved expression-site-associated gene 6 and 7 DNA target sequences. Amplification of 10% of the DNA in a single trypanosome produced sufficient PCR product to be visible as a band in an agarose gel stained with ethidium bromide. We analysed 59 blood samples of serologically positive cases of sleeping sickness by PCR, and directed parasitological examination of tissue fluids. The PCR test detected 87% of the parasitologically positive cases, with a specificity of 97%. In 5 cases, the parasite was demonstrated by the PCR test 4-6 months prior to parasitological detection. This result shows the potential of the assay in early diagnosis of actual T. b. gambiense infections in apparently aparasitaemic sleeping sickness patients.

Endometriosis apendicular. Informe de un caso. / Apendicceal endometriosis.Report of a case

La endometriosis apendicular tiene una frecuencia menor de 1 por ciento de las endometriosis pelvicas. Su diagnostico en la mayor parte de las ocasiones es incidental. Se informa un caso de endometriosis apendicular en una mujer en la cuarta decada de la vida, con antecedentes de esterilidad primaria, que ingreso con cuadro doloroso abdominal en cuadrante inferior derecho sin otros datos clinicos, radiologicos e do laboratorio que sugirieran el diagnostico. Se intervino con diagnostico preoperatorio de apendicitis aguda y se el realizo apendicectomia. El estudio histopatologico demostro focos endometrioides en la serosa apendicular sin datos de apendicitis aguda. La endometriosis debe considerarse entre las posibilidades diagnosticas en mujeres con cuadros "apendiculares" en los dias premenstruales y menstruales