Background Trials done in infants with low birthweight in west Africa suggest that BCG vaccination reduces all-cause mortality in the neonatal period, probably because of heterologous protection against non-tuberculous infections. This study investigated whether BCG alters all-cause infectious disease morbidity in healthy infants in a different high-mortality setting, and explored whether the changes are mediated via trained innate immunity.Methods This was an investigator-blind, randomised, controlled trial done at one hospital in Entebbe, Uganda. Infants who were born unwell (ie, those who were not well enough to be discharged directly home from the labour ward because they required medical intervention), with major congenital malformations, to mothers with HIV, into families with known or suspected tuberculosis, or for whom cord blood samples could not be taken, were excluded from the study. Any other infant well enough to be discharged directly from the labour ward was eligible for inclusion, with no limitation on gestational age or birthweight. Participants were recruited at birth and randomly assigned (1:1) to receive standard dose BCG 1331 (BCG-Danish) on the day of birth or at age 6 weeks (computer-generated randomisation, block sizes of 24, stratified by sex). Investigators and clinicians were masked to group assignment; parents were not masked. Participants were clinically followed up to age 10 weeks and contributed blood samples to one of three immunological substudies. The primary clinical outcome was physician-diagnosed non-tuberculous infectious disease incidence. Primary immunological outcomes were histone trimethylation at the promoter region of TNF, IL6, and IL1B; ex-vivo production of TNF, IL-6, IL-1β, IL-10, and IFNγ after heterologous stimulation; and transferrin saturation and hepcidin levels. All outcomes were analysed in the modified intention-to-treat population of all randomly assigned participants except those whose for whom consent was withdrawn. This trial is registered with the International Standard Randomised Controlled Trial Number registry (#59683017).

Background Helminth infection may influence cardiometabolic risk through effects on inflammation and metabolism. We hypothesised that helminths are protective and their treatment detrimental to metabolic outcomes. Methods We conducted a cluster-randomised trial in 26 fishing communities, Lake Victoria, Uganda. We investigated effects of community-wide intensive (quarterly single-dose praziquantel, triple dose albendazole) versus standard (annual single-dose praziquantel, six-monthly single-dose albendazole) anthelminthic treatment on metabolic outcomes, and observational associations between helminth infection and metabolic outcomes. The primary outcome, homeostatic model assessment of insulin resistance (HOMA-IR) and secondary outcomes (including blood pressure, fasting blood glucose and lipids) were assessed in a survey conducted after four years of intervention among individuals ≥10 years. Results We analysed 1898 participants. The intervention had no effect on HOMA-IR (adjusted geometric mean ratio [95%CI] 0.96 [0.86,1.07] p=0.42) but resulted in higher mean LDL-cholesterol in the intensive arm (2.86 vs 2.60 mmol/L, adjusted mean difference [95%CI] 0.26 [-0.03,0.56] p=0.08). Lower LDL-cholesterol levels were observed in S. mansoni (2.37 vs 2.80 mmol/L, -0.25 [-0.49,-0.02] p=0.04) and Strongyloides infected (2.34 vs 2.69mmol/L, -0.32 [-0.53,-0.12] p=0.003) participants compared with uninfected. S. mansoni infection was associated with lower total cholesterol levels (4.24 vs 4.64 mmol/L, -0.25 [-0.44,-0.07] p=0.01). Participants with moderate to heavy S. mansoni infection had lower triglycerides, LDL-cholesterol and diastolic blood pressure levels. Conclusions Helminth infections improve lipid profiles and may lower blood pressure. Further studies to confirm causality and investigate mechanisms will contribute to understanding the epidemiological transition and may suggest new approaches to prevent cardiometabolic disease. Clinical trials registration ISRCTN47196031

Despite reductions in S. mansoni intensity and hookworm prevalence, intensive MDA had no effect on atopy, allergy-related disease or helminth-related pathology. This could be due to sustained low-intensity infections, thus a causal link between helminths and allergy outcomes cannot be discounted. Intensive community-based MDA has limited impact in high-schistosomiasis-transmission fishing communities, in the absence of other interventions.

OBJECTIVESRecent reports suggest that Schistosoma infection may increase the risk of acquiring human immunodeficiency virus (HIV). We used data from a large cross-sectional study to investigate whether Schistosoma mansoni infection is associated with increased HIV prevalence.METHODSWe conducted a household survey of residents in island fishing communities in Mukono district, Uganda, between October 2012 and July 2013. HIV status was assessed using rapid test kits. Kato-Katz (KK) stool tests and urine-circulating cathodic antigen (CCA) were used to test for Schistosoma infection. Multivariable logistic regression, allowing for the survey design, was used to investigate the association between S. mansoni infection and HIV infection.RESULTSData from 1412 participants aged 13 years and older were analysed (mean age 30.3 years, 45% female). The prevalence of HIV was 17.3%. Using the stool Kato-Katz technique on a single sample, S. mansoni infection was detected in 57.2% (719/1257) of participants; urine CCA was positive in 73.8% (478/650) of those tested. S. mansoni infection was not associated with HIV infection. [KK (aOR = 1.04; 95% CI: 0.74–1.47, P = 0.81), CCA (aOR = 1.53; 95% CI: 0.78–3.00, P = 0.19)]. The median S. mansoni egg count per gram was lower in the HIV-positive participants (P = 0.005).CONCLUSIONSThese results add to the evidence that S. mansoni has little effect on HIV transmission, but may influence egg excretion.

Summary Background It is proposed that helminth exposure protects against allergy‐related disease, by mechanisms that include disconnecting risk factors (such as atopy) from effector responses. Objective We aimed to assess how helminth exposure influences rural‐urban differences in risk factors for allergy‐related outcomes in tropical low‐ and middle‐income countries. Methods In cross‐sectional surveys in Ugandan rural Schistosoma mansoni (Sm)‐endemic islands, and in nearby mainland urban communities with lower helminth exposure, we assessed risk factors for atopy (allergen‐specific skin prick test [SPT] reactivity and IgE [asIgE] sensitization) and clinical allergy‐related outcomes (wheeze, urticaria, rhinitis and visible flexural dermatitis), and effect modification by Sm exposure. Results Dermatitis and SPT reactivity were more prevalent among urban participants, urticaria and asIgE sensitization among rural participants. Pairwise associations between clinical outcomes, and between atopy and clinical outcomes, were stronger in the urban survey. In the rural survey, SPT positivity was inversely associated with bathing in lakewater, Schistosoma‐specific IgG4 and Sm infection. In the urban survey, SPT positivity was positively associated with age, non‐Ugandan maternal tribe, being born in a city/town, BCG scar and light Sm infection. Setting (rural vs urban) was an effect modifier for risk factors including Sm‐ and Schistosoma‐specific IgG4. In both surveys, the dominant risk factors for asIgE sensitization were Schistosoma‐specific antibody levels and helminth infections. Handwashing and recent malaria treatment reduced odds of asIgE sensitization among rural but not urban participants. Risk factors for clinical outcomes also differed by setting. Despite suggestive trends, we did not find sufficient evidence to conclude that helminth (Sm) exposure explained rural‐urban differences in risk factors. Conclusions and clinical relevance Risk factors for allergy‐related outcomes differ between rural and urban communities in Uganda but helminth exposure is unlikely to be the sole mechanism of the observed effect modification between the two settings. Other environmental exposures may contribute significantly.