Emergent canine visceral leishmaniasis in Argentina: Comparative diagnostics and relevance to proliferation of human disease.

Background: Visceral leishmaniasis (VL) is a zoonotic protozoal vector-borne disease that is a major public health challenge. In Argentina, canine (CVL) and human visceral leishmaniasis (HVL) have recently emerged. There is a lack of standardised diagnostic tests for CVL, which hinders control of CVL and HVL.

Epidemiological and molecular investigation of resurgent cutaneous leishmaniasis in Sudan.

Objectives: Local health personnel have drawn attention to an apparent increase in incidence and severity of cutaneous leishmaniasis (CL) in Sudan. The objective of this study was to investigate CL burden and surveillance.

Methods: Surveillance data were compiled from the KalaCORE programme, Leishmania coordinators in Northern Kordofan and Southern Darfur, and Khartoum Dermatology Hospital.

Outbreak science: recent progress in the detection and response to outbreaks of infectious diseases.

The frequency of reported outbreaks of infectious diseases has increased over the past 3 decades, with predictions that this rise will continue. Outbreak response continues to follow nine basic principles: establish the presence of an outbreak, verify the diagnosis, make a case definition, find cases and contacts, conduct basic epidemiology, test hypotheses, institute control measures, communicate the situation and establish ongoing surveillance. Within each of these areas, significant advances have been made over the past 5 years using progress in digital, laboratory, epidemiology and anthropological equipment or techniques.

Effect of single-dose anthelmintic treatment during pregnancy on an infant's response to immunisation and on susceptibility to infectious diseases in infancy: a randomised, double-blind, placebo-controlled trial.

Background: Helminth infections affect the human immune response. We investigated whether prenatal exposure to and treatment of maternal helminth infections affects development of an infant's immune response to immunisations and unrelated infections.

Methods: In this randomised, double-blind, placebo-controlled trial, we enrolled 2507 women in the second or third trimester of pregnancy who were planning to deliver in Entebbe General Hospital, Entebbe, Uganda.

Effects of maternal and infant co-infections, and of maternal immunisation, on the infant response to BCG and tetanus immunisation.

Some vaccines show poor efficacy in tropical countries. Within a birth cohort in Uganda, we investigated factors that might influence responses to BCG and tetanus immunisation. Whole blood assay responses to crude culture filtrate proteins of Mycobacterium tuberculosis (cCFP)) and tetanus toxoid (TT) were examined among 1506 and 1433 one-year-olds, respectively.

Identifying sub-optimal responses to ivermectin in the treatment of River Blindness.

Identification of drug resistance before it becomes a public health concern requires a clear distinction between what constitutes a normal and a suboptimal treatment response. A novel method of analyzing drug efficacy studies in human helminthiases is proposed and used to investigate recent claims of atypical responses to ivermectin in the treatment of River Blindness. The variability in the rate at which Onchocerca volvulus microfilariae repopulate host's skin following ivermectin treatment is quantified using an individual-based onchocerciasis mathematical model.

The impact of helminths on the response to immunization and on the incidence of infection and disease in childhood in Uganda: design of a randomized, double-blind, placebo-controlled, factorial trial of deworming interventions delivered in pregnancy and early childhood [ISRCTN32849447].

Background: Helminths have profound effects on the immune response, allowing long-term survival of parasites with minimal damage to the host. Some of these effects "spill-over", altering responses to non-helminth antigens or allergens. It is suggested that this may lead to impaired responses to immunizations and infections, while conferring benefits against inflammatory responses in allergic and autoimmune disease.

Relation between chemokine receptor use, disease stage, and HIV-1 subtypes A and D: results from a rural Ugandan cohort.

Objectives: To determine whether there are differences in coreceptor use in subjects infected with HIV-1 envelope subtypes A and D that could explain the differences in progression rates between these subtypes in a rural Ugandan cohort.

Methods: HIV-1 was subtyped in env by V3 sequencing or heteroduplex mobility assay. Coreceptor use was determined by the ability of the isolates to replicate in U87 CD4 cells expressing different coreceptors.

The role of vertical transmission and health care-related factors in HIV infection of children: a community study in rural Uganda.

Objectives: To determine the probable route of transmission of HIV to children aged 12 years or younger in a rural area of Uganda from 1999 through 2000 and to examine associations between HIV infection and health care-related variables.

Methods: The HIV infections status for 6991 children was determined from 1 round of an ongoing population surveillance system, and the reported numbers of injections in the past year and blood transfusions were determined for 5922 of these children based on a medical questionnaire. Data from the surveillance system and from an additional survey were used to assess the potential for vertical infection from a mother to her child.

A polymorphism that reduces RANTES expression is associated with protection from death in HIV-seropositive Ugandans with advanced disease.

We investigated the effect of RANTES polymorphisms on human immunodeficiency virus type 1 (HIV-1) disease progression in an urban population of Uganda. HIV-positive individuals homozygous for the INT1.1C polymorphism, which had been associated previously with low RANTES expression, were less likely to die than were those with other genotypes (hazard ratio, 0.

Schistosoma mansoni, nematode infections, and progression to active tuberculosis among HIV-1-infected Ugandans.

Rates of tuberculosis (TB) in Africa are highest among people infected with HIV. Searching for additional risk factors in a cohort of HIV-infected Ugandan adults, we previously found that a type 2 cytokine bias and eosinophilia were associated with progression to active TB. A possible role for helminth infection was assessed in this study.

A randomised controlled trial of the effects of albendazole in pregnancy on maternal responses to mycobacterial antigens and infant responses to Bacille Calmette-Guérin (BCG) immunisation [ISRCTN32849447].

Background: Maternal schistosomiasis and filariasis have been shown to influence infant responses to neonatal bacille Calmette-Guérin (BCG) immunisation but the effects of maternal hookworm, and of de-worming in pregnancy, are unknown.

Methods: In Entebbe, Uganda, we conducted a randomised, double-blind, placebo-controlled trial of a single dose of 400 mg of albendazole in the second trimester of pregnancy. Neonates received BCG.

Herpes simplex virus 2 infection increases HIV acquisition in men and women: systematic review and meta-analysis of longitudinal studies.

Objective: To estimate the sex-specific effect of herpes simplex virus type 2 (HSV-2) on the acquisition of HIV infection.

Background: The increased number of longitudinal studies available since the last meta-analysis was published allows for the calculation of age- and sexual behaviour-adjusted relative risks (RR) separately for men and women.

Design: Systematic review and meta-analysis of longitudinal studies.

A randomized controlled safety and acceptability trial of dextrin sulphate vaginal microbicide gel in sexually active women in Uganda.

Objective: To assess the safety of dextrin sulphate (DS) gel compared to placebo gel in terms of local and systemic adverse events, and to determine the acceptability of dextrin sulphate gel.

Design: A 4-week randomized trial of DS intra-vaginal gel, partially blinded, with placebo and observation control arms. Participants were randomized to use DS gel twice daily, placebo gel twice daily, DS gel pre-sex, or into an observation only arm.

Conjugate pneumococcal vaccine in HIV-infected Ugandans and the effect of past receipt of polysaccharide vaccine.

We investigated the immunogenicity of a 7-valent conjugate pneumococcal vaccine (CPV) in human immunodeficiency virus-infected Ugandan adults and measured the effect of past pneumococcal polysaccharide vaccine (PPV) receipt given as part of a controlled trial. Two doses of CPV, 4 weeks apart, were given to 54 past PPV recipients and 55 past placebo recipients (84% female; median CD4 cell count, 251 cells/ microL [range, 1-936 cells/ microL]). Postvaccination anticapsular immunoglobulin G (IgG) concentrations were directly correlated with CD4 cell count (P < .

The effect of malaria on mortality in a cohort of HIV-infected Ugandan adults.

Objectives: To investigate the effects of malaria parasitaemia and clinical malaria on mortality in HIV seropositive and seronegative adults.

Methods: A cohort of adults in rural Uganda were followed from 1990 to 1998. Participants attended routine clinic visits every 3 months and also when sick (interim visits).

HIV risk perception and prevalence in a program for prevention of mother-to-child HIV transmission: comparison of women who accept voluntary counseling and testing and those tested anonymously.

Objective: To determine whether data from voluntary counseling and testing (VCT)/prevention of mother-to-child transmission (PMTCT) programs can be used for HIV surveillance.

Methods: Women attending an antenatal clinic at the district hospital in Entebbe, Uganda, from May 2002 to April 2003 were offered counseling and HIV testing with same-day results (VCT) and nevirapine for PMTCT was provided for HIV-positive women and their babies. Those who declined VCT were tested for HIV anonymously.

Treatment of Schistosoma mansoni infection increases helminth-specific type 2 cytokine responses and HIV-1 loads in coinfected Ugandan adults.

Background: Studies showing that helminths stimulate type 2 cytokine responses and influence responses to unrelated antigens suggest that helminths may accelerate human immunodeficiency virus type 1 (HIV-1) disease progression in coinfected individuals and that antihelminthic therapy may be beneficial. By the same logic, however, the increase in type 2 cytokines occurring immediately after antischistosomal treatment might increase viral replication and be detrimental.

Methods: To assess the effect of antischistosomal therapy on immune responses and HIV-1 replication, a cohort of 163 Ugandans coinfected with Schistosoma mansoni and HIV-1 was treated with praziquantel.

Can population differences explain the contrasting results of the Mwanza, Rakai, and Masaka HIV/sexually transmitted disease intervention trials?: A modeling study.

Objective: To determine whether population differences can explain the contrasting impacts on HIV observed in the Mwanza trial of sexually transmitted disease (STD) syndromic treatment (ST), the Rakai trial of STD mass treatment (MT), and the Masaka trial of information, education, and communication (IEC) with and without ST as well as to predict the effectiveness of each intervention strategy in each population.

Methods: Stochastic modeling of the transmission of HIV and 6 STDs was used with parameters fitted to demographic, sexual behavior, and epidemiological data from the trials and general review of STD/HIV biology.

Results: The baseline trial populations could be simulated by assuming higher risk behavior in Uganda compared with Mwanza in the 1980s, followed by reductions in risk behavior in Uganda preceding the trials.

The impact of attending a behavioural intervention on HIV incidence in Masaka, Uganda.

Objective: Changing behaviour is an important method for preventing HIV infection. We examined why a community randomized trial of a behavioural intervention found no significant effect of this on HIV incidence in rural Uganda.

Design: An individual-level analysis of a community randomized trial.

Why does HIV infection not lead to disseminated strongyloidiasis?

We investigated the hypothesis that host immunosuppression due to advancing human immunodeficiency virus (HIV) disease favors the direct development of infective larvae of Strongyloides stercoralis, which may facilitate hyperinfection and, hence, disseminated strongyloidiasis. To do this, we sought correlations between the immune status of the subjects and the development of S. stercoralis infections.

Helminth infection is not associated with faster progression of HIV disease in coinfected adults in Uganda.

Background: We studied a cohort of human immunodeficiency virus (HIV)-infected adults in Uganda who were not receiving antiretroviral therapy, to explore the impact of helminths on HIV progression in areas where antiretrovirals are not available.

Methods: A total of 663 patients were screened for helminths, treated presumptively with albendazole and selectively with praziquantel, and monitored for 6 months. Blood samples were analyzed for CD4+ cell count and HIV-1 RNA.