The Kiss of Death

^aA: Health center laboratories located in areas at risk ofvectorial and nonvectorial transmission (the infrastructure is that from the first level of medical care upwards). B: Specialized laboratories for parasitological diagnosis. A and B laboratories are found at MSSP and IBBA in La Paz, MSSP in Cochabamba, and MSSP in Santa Cruz. Since 1991 USAID has helped improve these laboratories for chagas diagnosis. Sucre lacks an adequately equipped B laboratory.

^bAs compared to xenodiagnosis for the acute stage of the infection and to serological diagnosis for the chronic stage.

Relatively few Latin Americans are tested for T. cruzi due to a combination of factors including cost, pain, and a fatalistic attitude that, if they test positive, medications are prohibitively priced and only partially effective, with the probability that they will be again be parasitized. There is also the social cost of being ostracized, although this is less true in Bolivia than in some other places. Epidemic diseases frequently lead to old and new prejudices surfacing that lead to ostracism of the victims (see Foege 1988, and Lederberg 1988, in regard to AIDS in the United States). It would not be a very popular decision for immigrants to the United States to let others know they are seropositive for T. cruzi.

Table 4

SEROLOGICAL METHODS FOR DIAGNOSIS OF CHAGAS AND ANTIGENS USED

(WHO 1991:40)

Complement-fixation test (CFT). Aqueous or methanol extracts of whole T. cruzi have been widely used but have been replaced by purified fractions of the parasite in an attempt to standardize the sensitivity and specificity measures.

Indirect immunofluorescent antibody test (IFAT). Formol-fixed epimastigotes are stable antigens. The IFAT has the advantage that it can be used for differentiating IgM from IgG antibodies.

Indirect haemagglutination test (IHA). The antigens are polysaccharide or glycoprotein fractions from epimastigotes. Red cells sensitized with those antigens can be stored lyophilized or in suspension.

Direct agglutination test (DA and 2-MEDA). The antigen consists of whole epimastigotes treated with trypsin, and fixed with formaldehyde and filtered to prevent autoagglutination. The test can be used for detection of IgG or IgM antibodies.

ELISA. The antigen consists of peroxidase, or phosphatase-labeled conjugates or fractions of T. cruzi adsorbed to polyvinyl plates or other materials, and is stable. The test can be used for detection of IgG or IgM antibodies.

Latex agglutination. Polystyrene particles absorbed with T. cruzi extracts are used.

APPENDIX 13 Chemotherapy

The first chemical solutions against Chagas’ disease with sufficient activity to justify clinical trials, the bisquinaldines, were not discovered until 1937 (Jensch 1937), and it was not until 1972 that the first drug to combat the disease, nifurtimox, was announced and launched by Bayer for use in some countries of Latin America in 1976 (Bock et al. 1972). (Bayer has discontinued producing the drug as of 1997). Nifurtimox is a 5-nitrofuran derivative (synonyms: Bayer 2502, Lampit) with antiprotozoal activity, and it is also used to treat leishmaniasis and African trypanosomiasis (Reynolds 1986:673; see Figure 32).

^{Figure 32.}

^{Nifurtimox. (From W.E. Gutteridge, Existing Chemotherapy and Its Limitations, 1985.)}

Nifurtimox is administered as a yellow powder that a patient is to dissolve in water and drink three times a day after meals for sixty to ninety days at a daily dose of 8-10 mg per kg for adults, 15-20 mg per kg for children aged one to ten years, and 12.5-15 mg per kg for children aged eleven to sixteen years. Dosages may be as large as 25 mg/kg for severe complications such as acute meningoencephalitis (WHO 1991). Children tolerate the drug better than do adults. Nifurtimox is readily absorbed and rapidly metabolized, with a peak plasma concentration at one to three hours, which declines to zero by twenty-four hours. Some doctors prefer to stagger the treatment in two-month intervals (Jauregui, interview 6/22/91). Although the usual treatment extends for 120 days, it can be effective when given for sixty days (Macedo 1982).

The earlier the diagnosis is made and treatment initiated, the greater is the chance that the patient will be parasitologically cured (Cancado and Brener 1979). Drug therapy is highly recommended to minimize parasitic invasion of vital tissues (McGreevy and Marsden 1986:117). Good results are achieved early in treatment, as indicated by the disappearance of circulating trypanosomes, remission of disease signs and symptoms, and occasional reversion to a serologically negative condition. Serological tests tend to become negative from six to eight months after treatment, and the cure is considered successful when both parasitemia and serological tests become negative and remain so for at least a year after the end of treatment.

Nifurtimox does have side effects, including nausea, skin rashes, peripheral neuritis, bone-marrow depression, loss of weight, loss of memory, and sleeping disorders, which may lead to depression and general malaise to such a degree that few patients actually complete the treatment period (Gutteridge 1985). When nifurtimox was given to animals in high doses, it produced cancer; but no such effects have been described in human patients (McGreevy and Marsden 1986:117). In one study using nifurtimox in Brazil, all treated patients had weight loss, 70 percent had anorexia, and 33 percent had peripheral neuritis during treatment at 7-8 mg/kg per day for sixty days (McGreevy and Marsden 1986:117). Peripheral neuritis and psychosis depend on dosages of nifurtimox and usually occur at the end of high-dose treatment (15-20 mg/kg per day). Nifurtimox will cause hemolytic anemia in glucose 6-phosphate dehydrogenase (G6PD)-deficient individuals.

The efficacy of nifurtimox varies in different geographical areas. Cure rates appear to decrease going from south to north in Latin America, and this is probably due in part to variation in the sensitivity of different strains of T. cruzi (see Appendix 2: Strains of T. cruzi ). Studies of both acute and chronic Chagas’ disease show that patients from central Brazil are relatively unresponsive to nifurtimox as compared with patients from Argentina, Bolivia, and Chile (Cancado and Brener 1979, Brener 1979). The cure rate is about 92 percent in Argentina, Chile, Bolivia, and southern Brazil, and about 53 percent in central Brazil. Low concentrations of circulating parasites are difficult to detect, and monthly xenodiagnosis or blood culture is required.