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Background Despite a non-decreasing HIV epidemic, international donors are soon expected to withdraw funding from Kazakhstan. Here we analyze how allocative, implementation, and technical efficiencies could strengthen the national HIV response under assumptions of future budget levels. Methodology We used the Optima model to project future scenarios of the HIV epidemic in Kazakhstan that varied in future antiretroviral treatment unit costs and management expenditure—two areas identified for potential cost-reductions. We determined optimal allocations across HIV programs to satisfy either national targets or ambitious targets. For each scenario, we considered two cases of future HIV financing: the 2014 national budget maintained into the future and the 2014 budget without current international investment. Findings Kazakhstan can achieve its national HIV targets with the current budget by (1) optimally re-allocating resources across programs and (2) either securing a 35% [30%–39%] reduction in antiretroviral treatment drug costs or reducing management costs by 44% [36%–58%] of 2014 levels. Alternatively, a combination of antiretroviral treatment and management cost-reductions could be sufficient. Furthermore, Kazakhstan can achieve ambitious targets of halving new infections and AIDS-related deaths by 2020 compared to 2014 levels by attaining a 67% reduction in antiretroviral treatment costs, a 19% [14%–27%] reduction in management costs, and allocating resources optimally. Significance With Kazakhstan facing impending donor withdrawal, it is important for the HIV response to achieve more with available resources. This analysis can help to guide HIV response planners in directing available funding to achieve the greatest yield from investments. The key changes recommended were considered realistic by Kazakhstan country representatives.

Summary The lytic effect of complement activated through the alternative pathway (AP) was studied on pathogenic and nonpathogenic Entamoeba histolytica recently isolated from stool samples. Recent nonpathogenic isolates were nearly unaffected by exposure to AP whereas recent pathogenic stool isolates were highly susceptible to AP dependent complement-mediated lysis. Complement susceptible pathogenic stool isolates developed complement resistance in vivo during hamster liver passage and in vitro during cultivation in the presence of increasing concentrations of normal human serum (NHS). Since a clone of pathogenic HM-l.IMSS which initially was highly susceptible also acquired complement resistance during cultivation in the presence of NHS, it is concluded that complement resistance was caused by induction rather than by selection alone. Because cultivation in the presence of heat-inactivated NHS did not affect complement susceptibility of the cloned HM-l.IMSS, complement activation itself might induce complement resistance in pathogenic E. histolytica.

Objective To evaluate HIV and syphilis prevalence among men who have sex with men (MSM) in Nigeria, and assess their HIV-related risk behaviours and exposure to HIV prevention interventions. Methods Cross-sectional study using respondent-driven sampling conducted in Lagos, Kano and Cross River states, Nigeria, between July and September 2007. Results A total of 879 MSM participated, 293 from each state. Eight participants (1.1%, CI 0.1% to 2.2%) in Cross River, 27 (9.3%, CI 5.7% to 15.4%) in Kano and 74 (17.4%, CI 12.3% to 23.2%) in Lagos tested positive for HIV. No syphilis was detected. The median age was 22 years. MSM reported an average of 4.2 male anal sex partners in the past 6 months. Between 24.4% (Lagos) and 36.0% (Kano) of MSM reported selling sex to other men. Up to 49.7% of MSM reported sex with a girlfriend and ≤6.5% purchased sex from female sex workers. Consistent condom use in commercial sex with other men over the past 6 months ranged from 28.0% (Cross River) to 34.3% (Kano), in contrast to between 23.9% (Kano) and 45.8% (Lagos) for non-commercial sex. Associations with HIV positivity included age in the three states, having been the receptive partner in anal sex in the past 6 months in Lagos and in Lagos and Kano feeling at risk of HIV. Conclusion Large differentials in HIV prevalence between states together with high mobility, inconsistent condom use and behavioural links with female sex partners, have the potential for further HIV transmission within MSM networks, and between MSM and the general population.

Objective: To measure changes in service utilization of a model integrating family planning with HIV counselling and testing (HCT) antiretroviral therapy (ART) and prevention of mother-to-child transmission (PMTCT) in the Nigerian public health facilities. Design: It is a retrospective survey of attendance and family planning commodity uptake in 71 health facilities in Nigeria that analyzes the preintegration and postintegration periods between March 2007 and January 2009. Methods: A prepost retrospective comparison of mean attendance at family planning clinics and couple-years of protection (CYP) compared 6 months preintegration with 9 months postintegration period. An analysis of service ratios was conducted relating completed referrals at family planning clinics to service utilization at the referring HIV clinics. Results: Mean attendance at family planning clinics increased significantly from 67.6 in preintegration to 87.0 in postintegration. Themean CYP increased significantly from32.3 preintegration to 38.2 postintegration. Service ratio of referrals from each of the HIV clinics was low but increased in the postintegration period by 4 34 and 42 per 1000 clients from HCT ART and PMTCT clinics respectively. Service ratios were higher in primary healthcare settings than in secondary or tertiary hospitals. Attendance by men at family planning clinics was significantly higher among clients referred from HIV clinics. Conclusion: Family planning-HIV integration using the referral model improved family planning service utilization by clients accessing HIV services but further improvement is possible. Male utilization of family planning services also improved. The government of Nigeria should review the family planning user fee policy and scale up the integration in primary healthcare facilities.

Summary Background Of 18 million people world-wide who are infested with the tissue nematode Onchocerca volvulus, more than 30% are considered to have skin lesions, the pathomechanisms of which are poorly understood. Objectives To relate skin changes associated with onchocerciasis to parasitological findings and systemic cellular immune responses. Methods In the course of a genetic study, 691 members of 241 families exposed to hyperendemic O. volvulus transmission and free of other filarial or schistosomal infestations were studied clinically, by counting palpable Onchocerca nodules and skin microfilariae, by measuring peripheral blood cell (PBC) counts and total serum IgE, and by determining PBC in vitro proliferation and cytokine secretion in response to O. volvulus antigen. Results Of 691 individuals studied, 219 presented with onchocerciasis-associated skin changes. The groups of individuals with and without skin lesions neither differed in prevalences nor in average numbers of microfilariae. Compared with individuals without skin lesions, pronounced systemic T-helper (Th) 2-type responses were found with a trend of increasing intensity in the order of depigmentation, papular dermatitis, atrophy and lichenified dermatitis. Differences between the groups were most pronounced for serum IgE, less so for eosinophilia, and relatively weak for PBC proliferation and interleukin-5 secretion. Conclusions Skin lesions in onchocerciasis are associated with a spectrum of increasing generalized Th2-type responses ranging from low reactivities in cases of depigmentation alone to strong reactivities in cases of lichenification.

The cellular immune response to Onchocerca volvulus antigen (OvAg) was studied in 551 persons exposed to O. volvulus transmission in a hyperendemic area of Ghana, West Africa. A whole-blood assay showed that, in response to a soluble O. volvulus extract, cell proliferation, as well as interleukin (IL)-5 and IL-13 concentrations in the supernatants, were high in cultures of blood from microfilaria (mf)-negative persons and significantly decreased with increasing mf counts of the donors. Only background concentrations of interferon (IFN)-gamma were found, and these did not correlate with mf counts. In response to a mitogen, cells from all persons strongly reacted with proliferation and secretion of all 3 cytokines studied. These findings show that the response of human peripheral blood cells to OvAg does not include significant IFN-gamma production; that mf negativity is associated with IL-5 and IL-13 production but not, as previously suggested, with IFN-gamma production; and that IL-5 and IL-13 production decreases with increasing mf density.

Pathogenic forms of the protozoan parasite Entamoeba histolytica were reported previously to resist the cytolytic effect of the alternative complement pathway (AP) only temporarily during exposure to complement. In contrast, nonpathogenic forms of E. histolytica had been found to show AP resistance as a stable property. We studied the mechanisms of AP resistance of the two forms. Upon exposure to AP activity, resistant pathogenic or nonpathogenic forms bound significantly less C3 products than complement-sensitive pathogenic amebae, indicating that the two resistant forms both inhibited AP amplification. Various enzymatic treatments and inhibition of membrane mobility by cytochalasin B and glutaraldehyde fixation showed that the mechanisms of AP inhibition differed between pathogenic and nonpathogenic forms; in contrast to nonpathogenic forms, pathogenic amebae required intact membrane mobility and a trypsin-sensitive surface component(s) to inhibit AP activation.

Summary The effect of nonimmune human serum on Entamoeba histolytica trophozoites was studied: (a) using whole serum in the presence of Ca and Mg ions allowing complement activation via both the alternative and classical pathways or in the presence of MgEGTA permitting alternative pathway activation only; (b) using different E. histolytica isolates; (c) varying serum and trophozoite concentrations and the time of incubation; and (d) using three different methods to quantify lysis, i.e., microscopic inspection, flow cytometry and 111In release. All three methods yielded similar results, with flow cytometry being most sensitive in identifying membrane damage and 111In release being most valid in determining cell death. Microscopic analysis was reliable only when a chamber was used to calculate the number of complement treated cells in relation to the initial cell count. E. histolytica isolates were classified into three groups according to their susceptibility to lysis by complement: (i) pathogenic isolates after long term cultivation in vitro were susceptible; (ii) pathogenic isolates after recent in vivo passage were less susceptible; and (iii) nonpathogenic isolates were nearly unaffected by exposure to the alternative pathway alone. The extent of lysis of the various isolates correlated with the degree of complement consumption in the serum samples, suggesting that unlysed isolates did not activate complement under the conditions employed. In general, lysis of susceptible trophozoites increased with the serum concentration and with the time of incubation. However, when the trophozoite concentration was 106/ml or higher, lysis no longer reflected complement susceptibility because of exhaustion of the complement supply.