community study ͉ developing country ͉ diarrheal disease ͉ environment ͉ humans

This review of the safety of the co-administration regimens to be used in programmes to eliminate lymphatic filariasis (albendazole + ivermectin or albendazole + diethylcarbamazine [DEC]) is based on 17 studies conducted in Sri Lanka, India, Haiti, Ghana, Tanzania, Kenya, Ecuador, the Philippines, Gabon, Papua New Guinea, and Bangladesh. The total data set comprises 90,635 subject exposures and includes individuals of all ages and both genders. Results are presented for hospital-based studies, laboratory studies, active surveillance of microfilaria-positive and microfilaria-negative individuals, and passive monitoring in both community-based studies and mass treatment programmes of individuals treated with albendazole (n = 1538), ivermectin (9822), DEC (576), albendazole + ivermectin (7470), albendazole + DEC (69,020), or placebo (1144). The most rigorous monitoring, which includes haematological and biochemical laboratory parameters pre- and post-treatment, provides no evidence that consistent changes are induced by any treatment; the majority of abnormalities appear to be sporadic, and the addition of albendazole to either ivermectin or DEC does not increase the frequency of abnormalities. Both DEC and ivermectin show, as expected, an adverse event profile compatible with the destruction of microfilariae. The addition of albendazole to either single-drug treatment regimen does not appear to increase the frequency or intensity of events seen with these microfilaricidal drugs when used alone. Direct observations indicated that the level of adverse events, both frequency and intensity, was correlated with the level of microfilaraemia. In non microfilaraemic individuals, who form 80-90% of the 'at risk' populations to be treated in most national public health programmes to eliminate lymphatic filariasis (LF), the event profile with the compounds alone or in combination does not differ significantly from that of placebo. Data on the use of ivermectin + albendazole in areas either of double infection (onchocerciasis and LF), or of loiais (with or without concurrent LF) are still inadequate and further studies are needed. Additional data are also recommended for populations infected with Brugia malayi, since most data thus far derive from populations infected with Wuchereria bancrofti.

A new group of chiral monodentate diamidophosphite ligands (2 P-N/1 P-O bond) based on diazaphospholidine backbones derived from N,N 0 -dibenzylcyclohexane-1,2-diamine (7) and N, N 0 -dimethylcyclohexane-1,2-diamine (8), and diazaphosphepine backbones derived from N, N 0 -dimethyl-[1,1 0 -binaphthyl]-2,2 0 -diamine (9) and various chiral alkoxy groups (coming from phenylethanol a, borneol b, methyllactate c, allylic alcohol d, and methanol e) were prepared. The ligands have a highly modular structure, which is well suited to the synthesis of a small library. Preparation was readily accomplished by the successive addition of pure enantiomeric substituted diamine and pure enantiomeric alcohol to phosphorus trichloride. The corresponding diamidophosphite selenides Se(7-9) were prepared and the J PSe was calculated in order to evaluate the σ-donor ability of the new ligands. The reaction of [Pd(μ-Cl)(η 3 -2-CH 3 C 3 H 4 )] 2 with the new diamidophosphite ligands (7-9) led to the monomeric allylic neutral complexes 11-13. Two isomers appeared in solution due to the R-or S-geometry around the palladium atom. The molecular structure determined by X-ray diffraction of the neutral complex [PdCl(η 3 -2-CH 3 C 3 H 4 )(7a)] (11a-(S,S,S al )) showed a nonsymmetric coordination of the allyl moiety due to the greater trans influence of the phosphorus atom. The asymmetric hydrovinylation reaction between styrene and ethylene was tested using filtered CH 2 Cl 2 solutions of [PdCl(η 3 -2-CH 3 C 3 H 4 )L] complexes and AgBF 4 as catalytic precursors. The reaction performed at 15 °C and 15 bar of ethylene starting pressure led to good selectivities and moderate to good activities of 3-phenyl-1-butene. The best results were obtained when the cationic catalytic precursor contained the 9b-(R,S al ) diamidophosphite with a binaphthyl backbone and bornyloxy as the third substituent. With this system the TOF reached 595 h -1 of 3-phenyl-1-butene, whereas the ee was 90% toward the R-isomer.

The immune response after early exposure to or infection with Onchocerca volvulus was investigated in an autochthonous focus caused by the migration of infected persons to a previously unaffected area in Ecuador. Peripheral blood mononuclear cell (PBMC) proliferative and cytokine responses (interferon [IFN]-gamma and interleukin [IL]-5) to filarial antigens were measured in 14 subjects with serologic evidence of exposure and in 7 subjects with evidence of dermal microfilarial DNA and were compared with responses in 43 subjects with chronic O. volvulus infections. PBMC proliferative and cytokine responses (IFN-gamma and IL-5) to parasite antigens were elevated in the early exposure/infection group, compared with those in the chronic infection group. Addition of an IL-10-neutralizing antibody to filaria antigen-stimulated cultures resulted in significantly elevated proliferative responses in the chronic infection group. The findings suggest that early exposure and early parasite patency are associated with a vigorous cellular response, but, as infections become chronic, the cellular response becomes down-regulated, partly through an IL-10-dependent mechanism.

Summary Onchocerciasis is a major blinding disease in equatorial Africa and Central and South America. Ivermectin is a safe and effective drug in the treatment of this disease and now forms the basis of disease control in most endemic areas. We report the findings of long‐term control of this infection in the Rio Santiago focus in Ecuador, between January 1990 and December 1996, using a strategy of giving ivermectin treatments biannually in hyperendemic communities and annually in mesoand hypoendemic communities. Ivermectin was administered by local health workers from each community. A high level of compliance to ivermectin was achieved, with 81.9% to 98.0% of those eligible receiving the drug at each treatment instance. The impact of ivermectin therapy was monitored using a cohort of 120 randomly selected infected individuals from 8 hyperendemic communities. The geometric mean microfilarial density of this group declined from 19.3 to 0 mf/mg over the 84‐month observation period. Ivermectin had a significant impact on anterior segment ocular disease, acute onchodermatitis and sowda. The rate of infection of blackflies declined from 1.1% in 1989–0.08% in 1996, which is below the vectorial capacity of the Simulium vector and, as no new nodules were detected after 1994 and no children under 5 became infected over the observation period, it is likely that the transmission of this infection was interrupted in the study area.