High failure rates of melarsoprol for sleeping sickness, Democratic Republic of Congo

A retrospective chart review of 4,925 human African trypanosomiasis patients treated with melarsoprol in 2001-2003 in Equateur Nord Province of the Democratic Republic of Congo showed a treatment failure rate of 19.5%. This rate increased over the 3 years. Relapse rates were highest in the central part of the province.     

External quality assessment of Giemsa-stained blood film microscopy for the diagnosis of malaria and sleeping sickness in the Democratic Republic of the Congo

Objective

To report the findings of a second external quality assessment of Giemsa-stained blood film microscopy in the Democratic Republic of the Congo, performed one year after the first.

Methods

A panel of four slides was delivered to diagnostic laboratories in all provinces of the country. The slides contained: (i) Plasmodium falciparum gametocytes; (ii) P. falciparum trophozoites (reference density: 113 530 per µl); (iii) Trypanosoma brucei subspecies; and (iv) no parasites.

Findings

Of 356 laboratories contacted, 277 (77.8%) responded. Overall, 35.0% of the laboratories reported all four slides correctly but 14.1% reported correct results for 1 or 0 slides. Major errors included not diagnosing trypanosomiasis (50.4%), not recognizing P. falciparum gametocytes (17.5%) and diagnosing malaria from the slide with no parasites (19.0%). The frequency of serious errors in assessing parasite density and in reporting false-positive results was lower than in the previous external quality assessment: 17.2% and 52.3%, respectively, (P < 0.001) for parasite density and 19.0% and 33.3%, respectively, (P < 0.001) for false-positive results. Laboratories that participated in the previous quality assessment performed better than first-time participants and laboratories in provinces with a high number of sleeping sickness cases recognized trypanosomes more frequently (57.0% versus 31.2%, P < 0.001). Malaria rapid diagnostic tests were used by 44.3% of laboratories, almost double the proportion observed in the previous quality assessment.

Conclusion

The overall quality of blood film microscopy was poor but was improved by participation in external quality assessments. The failure to recognize trypanosomes in a country where sleeping sickness is endemic is a concern.     

Population genetics of Trypanosoma brucei gambiense in sleeping sickness patients with treatment failures in the focus of Mbuji-Mayi,Democratic Republic of the Congo

Human African trypanosomiasis (HAT) in the Democratic Republic of the Congo (DRC) is caused by the protozoan Trypanosoma brucei gambiense. Until recently, all patients in the second or neurological stage of the disease were treated with melarsoprol. At the end of the past and the beginning of the present century, alarmingly high relapse rates in patients treated with melarsoprol were reported in isolated HAT foci. In the Mbuji-Mayi focus of DRC, a particular mutation that confers cross resistance for pentamidine and melarsoprol was recently found for all strains studied. Nevertheless, treatment successfully cured a significant proportion of patients. To check for the existence of other possible genetic factors of the parasites, we genotyped trypanosomes isolated from patients before and after treatment (relapsing patients) with eight microsatellite markers. We found no evidence of any genetic correlation between parasite genotype and treatment outcome and we concluded that relapse or cure probably depend more on patients’ factors such as disease progression, nutritional or immunological status or co-infections with other pathogens. The existence of a melarsoprol and pentamidine resistance associated mutation at such high rates highlights an increasing problem, even for other drugs, especially those using the same transporters as melarsoprol and pentamidine.     

间接免疫荧光技术应用于狂犬病抗体IgG检测研究

目的：研究间接免疫荧光技术在狂犬病抗体中的应用。方法：由本中心研制狂犬抗原片和荧光血清,比较间接免疫荧光技术与酶标方法的效果。结果：间接免疫荧光技术检测狂犬病抗体特异性、稳定性良好、变异系数CV＝4．9％。间接免疫荧光技术与ELISA同时检测,间接免疫荧光法阳性率为82．89％,ELISA法阳性率为40．48％。结论：间接免疫荧光法测定狂犬病抗体特异性、稳定性好。狂犬疫苗免疫后应用该技术检测抗体,确保免疫效果。     

Serodiagnosis of Sudanese visceral and mucosal leishmaniasis: comparison of ELISA--immunofluorescence and indirect haemagglutination

Two established immunodiagnostic techniques, immunofluorescence and indirect haemagglutination, were compared with ELISA (enzyme-linked immunosorbent assay) using intact promastigotes as antigen for the detection of specific antibodies against Leishmania in the serum of patients with visceral or mucosal leishmaniasis from the Sudan. The ELISA was found to be more sensitive and more specific than either of the other two tests.     

间接免疫荧光技术检测狂犬病毒感染性滴度的可行性研究

目的研究间接免疫荧光技术在定量检测狂犬病毒感染性滴度中的应用。方法建立并优化用于定量检测狂犬病毒滴度的间接免疫荧光技术,并将其检测结果与传统滴定法——小白鼠颅内接种法进行比较,研究间接免疫荧光技术定量检测狂犬病毒感染性滴度的灵敏度、特异性和重复性。结果此法的检测结果是特异的;其重复性良好,相同样品多次检测的滴度相近;其灵敏度与小白鼠颅内接种法相似。结论此法具有特异、灵敏、省时和操作简便等优点,可应用于狂犬病毒感染性滴度检测。     

Antibody detection tests for Onchocerca volvulus: comparison of the sensitivity of a cocktail of recombinant antigens used in the indirect enzyme-linked immunosorbent assay with a rapid-format antibody card test

There is a need for a specific, sensitive, and practical diagnostic test to monitor onchocerciasis elimination campaigns. In April 2001, an enzyme-linked immunosorbent assay (ELISA) using 3 recombinant antigens and a rapid-format antibody card test (immunochromatographic test; ICT) using an individual antigen were compared in a Mexican population with onchocerciasis. The sensitivity of the ELISA and ICT was 97% and 86%, respectively.     

Surgical care for the direct and indirect victims of violence in the eastern Democratic Republic of Congo

Background  

The provision of surgical assistance in conflict is often associated with care for victims of violence. However, there is an increasing appreciation that surgical care is needed for non-traumatic morbidities. In this paper we report on surgical interventions carried out by Médecins sans Frontières in Masisi, North Kivu, Democratic Republic of Congo to contribute to the scarce evidence base on surgical needs in conflict.     

Outbreak of cholera in the Republic of Congo and the Democratic Republic of Congo, and cholera worldwide

Cholera is an acute intestinal disease caused by infection of the Vibrio cholerae bacterium. Often manifested as a constant diarrhoeal disease, Cholera is associated with significant mortality as well as economic loss due to the strain on health care. Cholera often affects nations with lower economic status. The recent outbreak of cholera in the Republic of Congo and the Democratic Republic of Congo has affected thousands of people. Here we review the past cholera epidemiology, molecular mechanisms of the bacterium, and the political and environmental aspects that affect the treatment and eradication of this disease.     

New concepts in the epidemiology of Rhodesian sleeping sickness

The results from recent studies of a number of outbreaks of T. rhodesiense sleeping sickness have enabled workers in this field to reconsider the epidemiology of the disease.     

Further progress in the control of sleeping sickness in Nigeria

Three types of sleeping sickness are described as occurring in Nigeria— the mild type, the toxic and the nervous. The great majority of the cases found at sleeping sickness surveys belong to the first group. Patients suffer from occasional attacks of headache and fever and from some weakness, very little else. It is their increased susceptibility to intercurrent diseases which often caused the depopulation found in some of the more heavily infected areas. In the second group, which is much more rare, toxaemia is the salient feature. In the third, there are signs of progressive nervous involvement. The proportion of patients suffering from the three types varies. Even in the more virulent epidemics the mild form is common.In Northern Nigeria there is a striking correlation between the areas of infection and the lines of communication, railways, roads, and mining areas. The main zone is confined to the central part of the country. Peripheral areas, though heavily infested with tsetse-fly, are still practically free from infection.Nigerian policy is to establish convenient permanent treatment centres once a full survey of the whole population has been followed by mass treatment. The information obtained at the survey makes the planning of effective protective measures possible. The work of the sleeping sickness teams, dispensaries and the control of mines labour is described.From 1931 to 1943 a total of 3,148,069 people were examined in new areas and 306,322 cases found, an infection rate of 9·7 per cent. In the worst areas 913,718 people were re-examined and an infection rate of 2·2 per cent. found. During the first 5 years of this period the disease was still increasing. The average infection rate was 13·6 per cent. In the next 5 years the spread had been stopped though the infection rate was still high in the remaining new areas. From 1941 onwards the new areas discovered had a low infection rate. The rate for resurveys of what were formerly some of the worst areas was 2·5 per cent. Taking Northern Nigeria as a whole, it is doubtful if there is much more than a tenth of the old amount of infection.The sleeping sickness dispensary system has been expanded during the last few years. Some 80,704 cases of sleeping sickness have been treated. Practically all were voluntary attendances. The general medical and health work also has been improved.With the 43,674 cases treated at general medical stations, a total of 450,451 cases have been treated in the last 13 years. Of these about 400,000 were new cases, the remainder relapses. 'The control of the disease by communal clearing campaigns is described. So far about 240,400 people have been protected from any serious risk of contracting sleeping sickness.A brief account is also given of the Zaria sleeping sickness settlement scheme. So much attention has been paid to all aspects of rural planning and development in the settlement area that it has come to be regarded as a model of rural development.The changes in population figures, particularly in Zaria Emirate, give a striking indication of what has been accomplished. In the period 1923–1933, when the disease was increasing, the population fell by about 12 per cent. At the survey of the whole Emirate 78,000 cases were diagnosed and treated, an infection rate of 20 per cent. There was direct evidence of correlation between infection rates and mortality. With the decrease in sleeping sickness consequent on treatment and control, depopulation stopped. Since 1933 the total population has increased about 24 per cent. It is not claimed that results of treatment have been as valuable in the milder area where there was no sign of the disease causing immediate loss of population.The general position is much more satisfactory throughout the country though constant vigilance is necessary if this relative improvement is to be maintained.     

Standardization of the indirect fluorescent antibody test for malaria.

Methods are described whereby results of malarial immunofluorescence tests can be evaluated objectively. The IFA test was quantitated by standardizing the physical system against a fluorescent standard and preparation of biological standards of malarial antisera and fluorescein labelled conjugates. Using these known standards the reactivity of antigens was characterized. It was found that antigen preparations are best when they include mature schizonts, and keep best when they are stored in a dry condition at or below -20 degree C. However, even under carefully controlled conditions of storage, antigens showed considerable variation of reactivity between individual batches.     

A history of Rhodesian sleeping sickness in the Lambwe Valley

The main events in the spread of Rhodesian sleeping sickness around the eastern shores of Lake Victoria during the 1930s and 1940s are summarized and the history of the disease in the Lambwe Valley area of western Kenya is described since its appearance there in 1959. The area was very receptive to the introduction and dispersal of T. rhodesiense on account of a close association between human communities and their domestic livestock, a large tsetse (Glossina pallidipes) population, and game animals. The possible origins of the first Lambwe Valley disease focus and the epidemiological significance of the main elements of the Lambwe environment (man, tsetse, game animals) are discussed in relation to the consolidation and spread of the disease throughout the area.     

A comparison of enzyme-linked immunosorbent assay and indirect fluorescent antibody test in the sero-diagnosis of cutaneous and visceral leishmaniasis in Iran.

ELISA AND IFAT have been applied to the sero-diagnosis of cutaneous and visceral leishmaniasis and the levels of leishmanial antibody detected by Leishmania donovani antigens in both tests have been compared. From the results it appears that ELISA is a little more sensitive than IFAT, but IFAT seems to be more specific in detecting leishmanial antibodies. In both tests reactions between leishmanial antigen and some other infections, such as malaria and typhoid, were observed. These non-specific reactions reduce the validity of both tests, especially ELISA, in the sero-diagnosis of cutaneous leishmaniasis but, in visceral leishmaniasis, the leishmanial antibody levels were high enough to be unaffected by non-specific reactions. In general, ELISA is as good as IFAT and more practical in the sero-diagnosis and mass screening surveys for kala-azar.     

Antigenic activity in adult Dipetalonema viteae in the indirect immunofluorescent test against sera from filariasis patients--the immunofluorescent histological search for "pure" antigen.

Using IFAT, it has been shown that isolated egg-shells and uterine fluid of Dipetalonema viteae are the most potent antigens in heterologous systems using human sera from patients infected with Wuchereria bancrofti, Onchocerca volvulus and Loa loa, as well as in homologous systems using sera from animals infected with D. viteae. It is suggested that these antigens are unlikely to be highly species-specific, and that anatomical isolation of antigens is a necessary prerequisite to immunochemical analysis aimed at the preparation of a "pure" antigen.