Massimo Fabiani

'Killer' canines : the morbidity and mortality of ebino in northern Uganda

Summary In northern Uganda, unerupted primary canine teeth are commonly extracted because they are believed to cause diarrhoea, vomiting, and fever. This practice, known as ebino, is performed under very crude conditions often using unclean tools. To evaluate the morbidity and mortality of complications related to ebino, we retrospectively analysed discharge records from the paediatric ward of Lacor Hospital, Gulu. In the period 1992–98, ebino‐related complications, mainly sepsis and anaemia, were among the leading causes of admission (n = 740) and hospital death (n = 156, case fatality rate = 21.1%, proportional mortality rate = 3.3%). Discouraging the adoption of deeply rooted traditional practices that are potentially hazardous to health should be a public health priority in northern Uganda. This could be done by educating not only the general public, but also traditional healers and community and religious leaders, who could convey the knowledge to their people.

Ebola Hemorrhagic Fever Transmission and Risk Factors of Contacts, Uganda

From August 2000 through January 2001, a large epidemic of Ebola hemorrhagic fever occurred in Uganda, with 425 cases and 224 deaths. Starting from three laboratory-confirmed cases, we traced the chains of transmission for three generations, until we reached the primary case-patients (i.e., persons with an unidentified source of infection). We then prospectively identified the other contacts in whom the disease had developed. To identify the risk factors associated with transmission, we interviewed both healthy and ill contacts (or their proxies) who had been reported by the case-patients (or their proxies) and who met the criteria set for contact tracing during surveillance. The patterns of exposure of 24 case-patients and 65 healthy contacts were defined, and crude and adjusted prevalence proportion ratios (PPR) were estimated for different types of exposure. Contact with the patient’s body fluids (PPR = 4.61%, 95% confidence interval 1.73 to 12.29) was the strongest risk factor, although transmission through fomites also seems possible.

Immune activation in Africa is environmentally-driven and is associated with upregulation of CCR5.

BackgroundHIV infection in Africa is associated with immune activation and a cytokine profile that stimulates CCR5 expression. We investigated whether this immune activation is environmentally driven; if a dominant expression of CCR5 could indeed be detected in African individuals; and if R5 HIV strains would be prevalent in this population. MethodsFreshly drawn peripheral blood mononuclear cells from HIV-uninfected African and Italian individuals living in rural Africa, from HIV-uninfected Africans and Italians living in Italy, and from HIV-infected African and Italian patients were analysed. Determinations of HIV coreceptor-specific mRNAs and immunophenotype analyses were performed in all samples. Virological analyses included virus isolation and characterization of plasma neutralizing activity. FindingsResults showed that: immune activation is detected both in Italian and African HIV-uninfected individuals living in Africa but not in African subjects living in Italy; CCR5-specific mRNA is augmented and the surface expression of CCR5 is increased in African compared with Italian residents (CXCR4-specific mRNA is comparable); R5-HIV strains are isolated prevalently from lymphocytes of African HIV-infected patients; and plasma neutralizing activity in HIV-infected African patients is mostly specific for R5 strains. ConclusionsImmune activation in African residents is environmentally driven and not genetically predetermined. This immune activation results in a skewing of the CCR5 : CXCR4 ratio which is associated with a prevalent isolation of R5 viruses. These data suggest that the selection of the predominant virus strain within the population could be influenced by an immunologically driven pattern of HIV co receptor expression.

Immunohistochemical evidence of cytokine networks during progression of human melanocytic lesions

Melanoma cells in culture express a variety of growth factors and cytokines and some of their autocrine and paracrine roles have been investigated. However, less information is available on the potential dynamic changes in expression of these molecules on cells during melanoma development and progression in situ. Using immunohistochemistry, we tested 40 nevi and primary and metastatic melanoma lesions for the expression of 10 growth factors and cytokines and the respective receptors representing 10 cell surface molecules. Nevi and thin (< 1 mm) primary melanomas showed little expression of ligands except weak reactivity of tumor necrosis factor‐α (TNF‐α), transforming growth factor‐β (TGF‐β), interleukin‐8 (IL‐8) and reactivity of TGF‐βR and c‐kit. Marked up‐regulation of growth factors, cytokines and receptor expression was observed in thick (> 1 mm) primary melanomas, which were stained with polyclonal or monoclonal antibodies (MAbs) for IL‐1α, IL‐1β, IL‐6, IL‐8, TNF‐α, TGF‐β, granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) and stem cell factor (SCF), but not IL‐2. Metastases showed similar expression patterns except that SCF was absent. Co‐expression of ligand and receptor was observed for TGF‐β, GM‐CSF and IL‐6, suggesting an autocrine role for these ligands. TNF‐α appears to be a marker of benign lesions; IL‐6 and IL‐8 expression is associated with biologically early malignancy; TGF‐β, GM‐CSF and IL‐1α are highly expressed in biologically late lesions; and TNF‐β is an apparent marker of metastatic dissemination. Our results indicate that melanoma cells utilize cascades of growth factors and cytokines for their progression. Int. J. Cancer (Pred. Oncol.) 84:160–168, 1999.

Immunological activation markers in the serum of African and European HIV-seropositive and seronegative individuals.

Objective: The concentration of type 1 and type 2 cytokines and fibroblast‐associated apoptosis‐1 soluble receptor (sAPO‐1/Fas) was analysed in the sera of Ugandan and Italian HIV‐1‐seropositive and seronegative individualls. The data were compared to determine whether the immunological status of these groups was different. Methods: Sixty‐seven Ugandan and 30 Italian HIV‐positive patients were analysed and stratified according to CD4 counts (group 1, > 500×106/l; group 2, 200–500×106/l; group 3, < 200×106/l). Sera from 15 Ugandan and 11 Italian HIV‐negative blood donors were also analysed. Serum concentration of type 1 cytokines [interleu‐kin (IL)‐2, IL‐12, and interferon (IFN)‐&ggr;] and type 2 cytokines (IL‐4 and IL‐10), and sAPO‐1/Fas were measured by enzyme‐linked immunosorbent assay. Results: Serum levels of IL‐2, IFN‐&ggr; and IL‐10, but not of IL‐4 and IL‐12, were elevated in HIV‐positive group 1 and 2 Africans compared with HIV‐positive Italian individuals. IL‐4 was mildly augmented in HIV‐positive group 3 African patients. Serum concentration of sAPO‐1/Fas was reduced in HIV‐positive Africans compared with HIV‐positive Italian individuals. Finally, serum levels of IL‐2 and IL‐10 were increased and sAPO‐1/Fas reduced when sera of HIV‐negative African healthy controls were compared with their Italian counterparts. The ratio of type 1/type 2 cytokines was roughly 1.0 in HIV‐negative African controls, and much greater than 1.0 in HIV‐negative Italian controls. Conclusions: These preliminary findings indicate that immune activation is present in African HIV infection. Furthermore, these data raise the possibility that abnormal immune activation and increased susceptibility to antigen‐induced cell death is present even in HIV‐negative African controls.

Immune activation in Hiv-infected African individuals

Objective:Immune activation induced by chronic infections, dietary limitations, and poor hygienic conditions is suggested to be present in African HIV infection and is at the basis of the hypothesis that HIV infection in Africa could be prevalently associated with immunopathogenetic mechanisms. Very limited data are nevertheless available supporting this theory, and in particular no data are reported on functional and phenotypic analyses performed on fresh peripheral blood mononuclear cells (PBMC) of African HIV-infected patients living in Africa. Design:Immunological and virological parameters were analysed in fresh PBMC of HIV-infected African and Italian patients with advanced HIV disease and comparable CD4 and CD8 counts, sex, and age. Both functional (antigen- and mitogen-stimulated cytokine production) and phenotypic (activation markers; markers preferentially expressed by T helper (Th) type 2 cells or by memory and naive cells) analyses were performed. Results were compared with those of HIV-seronegative African and Italian controls. HIV plasma viraemia was analysed by competitive polymerase chain reaction (PCR) and branched DNA techniques. Results:(1) The production of mitogen-stimulated IFN-γ and TNF-α as well as the production of env peptide-stimulated IFN-γ, TNF-α, and IL-10 are increased in African HIV infection; (2) the expression of activation and Th2-associated markers is augmented in African HIV infection as is the memory/naive ratio; (3) mitogen-stimulated IFN-γ and IL-10 production, as well as the expression of activation and Th2-associated markers and the memory/naive ratio, are augmented in African compared with Italian controls; and (4) plasma viraemia is reduced in African compared with Italian HIV-infected individuals. Conclusions:These results, which are the first to be reported on fresh material from African HIV-infected patients living in Africa, indicate that HIV disease is associated with an abnormal immune hyperactivation and may be accompanied in these patients by lower loads of virus, and show that such activation is present even in HIV-seronegative controls.

HIV, malaria parasites, and acute febrile episodes in Ugandan adults: a case-control study.

BackgroundIn sub-Saharan Africa, co-infection with HIV and malaria is probably very common. Although an interaction between the two infections is biologically plausible, it has not been investigated thoroughly. ObjectivesTo evaluate the association firstly between co-infection with HIV and malaria parasites and the occurrence of acute fever, and secondly between HIV infection and clinical malaria, defined as the presence of acute fever and malaria parasites. MethodsA hospital-based case–control study was conducted in Gulu District (northern Uganda), an area endemic for malaria and with a high HIV prevalence. HIV testing and malaria parasite quantification were performed on 167 consecutive adult out-patients with acute fever and no signs or symptoms of localized infection, and on 134 consecutive adult in-patients without fever who were admitted for non-HIV-related trauma or elective surgery. ResultsNo significant association with acute fever was observed for single infection with either malaria parasites [adjusted odds ratio (AOR), 1.75; 95% confidence interval (CI), 0.73–4.21] or HIV (AOR, 1.01; 95% CI, 0.51–2.03), whereas a significant association was observed for co-infection (AOR, 9.75; 95% CI, 1.19–80.00). An association was found between HIV infection and clinical malaria (AOR, 2.34; 95% CI, 0.89–6.17); the association became statistically significant when the definition of clinical malaria included a cut-off for parasite density (50th percentile; i.e., 586 parasites/μl; AOR, 3.61; 95% CI, 1.04–12.52). ConclusionsDespite the limited statistical power, the results of our study show an association between HIV infection and clinical malaria; if confirmed, this finding could be important for public health in sub-Saharan Africa.

Screening for Infectious Diseases among Newly Arrived Migrants in EU/EEA Countries—Varying Practices but Consensus on the Utility of Screening

Screening is one possible tool for monitoring infectious diseases among migrants. However, there is limited information on screening programmes targeted for newly arrived migrants in EU/EEA countries. Our aim was to investigate the implementation, practices and usefulness of these programmes. We conducted a survey among country experts from EU/EEA countries and Switzerland, asking whether their countries had implemented screening programmes. We also estimated the association between the implementation of these programmes and the rate of asylum-seekers in the population. Of the countries, 16 (59%) had implemented screening programmes and 15 (56%) had national guidelines. The rate of asylum-seekers was associated with implementation of screening programmes (p = 0.014). Screening was performed most often for tuberculosis; most commonly on holding level, and was targeted to specific migrant groups in over half of the countries performing screening. Twenty-five of all the country experts (96%) considered screening among migrants useful, and 24 (92%) would welcome EU level guidelines for screening. The implementation of screening programmes varied, and the practices were different among countries. Our survey suggests, that establishing EU level guidelines for screening would be useful, although they would have to take into account differences between individual countries.

Trend in HIV-1 prevalence in an antenatal clinic in North Uganda and adjusted rates for the general female population

ObjectivesTo estimate HIV-1 prevalence among women attending an antenatal clinic in the Gulu District (North Uganda) and, based on these data, among the districts female population. MethodsAnonymous HIV-1 screening was performed for 8555 antenatal clinic attendees aged 15–39 years in the period 1993–1997. The results were used to estimate the prevalence among the districts female population, accounting for differences in fertility rates by HIV-1 serostatus. ResultsAmong antenatal clinic attendees, HIV-1 prevalence showed a significant linear decrease (P < 0.001), from 26.0% in 1993 [95% confidence Interval (CI), 23.2–29.0%] to 16.1% in 1997 (95% CI, 14.8–17.5%). This decrease was mostly due to a marked decrease until 1995 (14.3%; 95% CI, 12.7–16.0%) and was more pronounced among women aged under 30 years (P < 0.001), from both urban and rural areas (P < 0.001). The risk of being infected was higher among women from urban areas (Gulu Municipality), both over the entire period (adjusted prevalence proportion ratio = 1.54; 95% CI, 1.40–1.68) and by individual year. The estimated prevalence for the 15–39-year-old female population, standardized by age and area of residence, decreased from 25.4% in 1993–1994 to 17.8% in 1996–1997; these rates were 1.22 and 1.28 times higher, respectively, than those among antenatal clinic attendees. ConclusionsThe trend of decrease among young women, for whom changes in HIV-1 prevalence more closely reflect incidence, could be partially due to a reduction in risk behaviour and a consequent decreasing incidence. Differences in fertility rates by HIV-1 serostatus should be addressed when using antenatal clinic data to estimate prevalence among the general female population.

Investigating factors associated with uptake of HIV voluntary counselling and testing among pregnant women living in North Uganda

Abstract We investigated factors potentially associated with the uptake of HIV voluntary counselling and testing (VCT), which is the first step in acceding to programmes for the prevention of mother-to-child transmission of HIV infection. For the period 2001–2003, we estimated the VCT uptake among the 12,252 first-time attendees of the Antenatal Clinic (ANC) at Lacor Hospital (Gulu District, North Uganda). Associations between VCT uptake and socio-demographic characteristics and reproductive history were evaluated using log binomial regression models. VCT uptake was 55.6% for the overall study period; it increased from 51.0% in 2001 to 58.6% in 2002 and 57.7% in 2003 (P <0.001). Having some education [primary versus none, adjusted prevalence proportion ratio (PPR) =1.05, 95% confidence intervals (CI): 1.00–1.10] and being unmarried (cohabitating, PPR =1.07, 95% CI: 1.03–1.10; single/widowed/divorced, PPR =1.10, 95% CI: 1.03–1.18) were significantly associated with VCT uptake. Associations of borderline significance were found for: recent change of residence, having a partner with a modern occupation, and past use of contraceptives. VCT uptake is still low in this district of North Uganda. Although some socio-demographic factors were found to have been associated with uptake, the associations were weak and not of public-health significance.