Brian Faragher

Liverpool School of Tropical Medicine · Department of Clinical Sciences

Objectives Induction of labour (IOL), or starting labour artificially, can be a lifesaving intervention for pregnant women and their babies, and rates are rising significantly globally. As rates increase, it becomes increasingly important to fully evaluate all available data, especially that from low income settings where the potential benefits and...

Background Every year approximately 30,000 women die from hypertensive disease in pregnancy. Magnesium sulphate and anti-hypertensives reduce morbidity, but delivery is the only cure. Low dose oral misoprostol, a prostaglandin E1 analogue, is a highly effective method for labour induction. Usually, once active labour has commenced, the misoprostol...

Background: Plasmodium falciparum and Plasmodium vivax infections are important causes of adverse pregnancy outcomes in the Asia-Pacific region. We hypothesised that monthly intermittent preventive treatment (IPT) or intermittent screening and treatment (IST) with dihydroartemisinin-piperaquine is more effective in reducing malaria in pregnancy th...

The live attenuated Japanese encephalitis (JE) vaccine SA14-14-2 has been used in Nepal for catch-up campaigns and is now included in the routine immunisation schedule. Previous studies have shown good vaccine efficacy after one dose in districts with a high incidence of JE. The first well-documented dengue outbreak occurred in Nepal in 2006 with o...

Evidence of specific DENV serotype circulation. (A) DENV neutralising antibody (NAb) titres in participants positive (PRNT50 ≥ 1:10) for only one DENV serotype. (B) DENV neutralising antibody titres in participants positive (PRNT50 ≥ 1:10) for only one DENV serotype, who are also JEV NAb negative. (C) JEV NAb titres in participants positive for one...

Frequency distribution histogram of ages of participants in the three districts sampled. Histogram bins are 5 years wide, the x axis indicates the central value of each bin. (PDF)

Rationale: In the context of rapid antiretroviral therapy rollout and an increasing burden of noncommunicable diseases, there are few contemporary data describing the etiology and outcome of community-acquired pneumonia (CAP) in sub-Saharan Africa.Objectives: To describe the current etiology of CAP in Malawi and identify risk factors for mortality....

Between 62,000 and 77,000 women die annually from pre-eclampsia/eclampsia. Prompt delivery, preferably by the vaginal route, is vital for good maternal and neonatal outcomes. Two low cost interventions -low dose oral misoprostol tablets and transcervical Foley catheterisation- are already used in low resource settings. In this open label, parallel...

Background: Substantial reductions in malaria incidence in sub-Saharan Africa have been achieved with massive deployment of long-lasting insecticidal nets (LLINs), but pyrethroid resistance threatens control. Burkina Faso is an area with intense malaria transmission and highly pyrethroid-resistant vectors. We assessed the effectiveness of bednets...

Background: Maternal and Child Health Aides are the largest nursing cadre in Sierra Leone providing maternal and child health care at primary level. Poor healthcare infrastructure and persistent shortage of suitably qualified health care workers have contributed to high maternal and newborn morbidity and mortality. In 2012, 50% of the MCHAides coh...

Objective: To determine the effectiveness and economic impact of two methods for induction of labour in hypertensive women, in low-resource settings. Design: Cost-consequence analysis of a previously reported multi-centre, parallel, open-label randomized trial. Setting & population: 602 women with a live fetus, aged>18 years requiring delivery...

Background Between 62 000 and 77 000 women die annually from pre-eclampsia and eclampsia. Prompt delivery, preferably by the vaginal route, is vital for good maternal and neonatal outcomes. Two low-cost interventions—low-dose oral misoprostol tablets and transcervical Foley catheterisation—are already used in low-resource settings. We aimed to comp...

Methods: We derived a nomogram using mortality predictors derived from a logistic regression model of a discovery database of adult Malawian ABM patients (n=523, 65% CSF culture positive). We validated the nomogram internally using a bootstrapped procedure and subsequently used the nomogram scores to further interpret the effects of adjunctive dex...

Objectives Conduct a feasibility study on the effect of menstrual hygiene on schoolgirls' school and health (reproductive/sexual) outcomes. Design 3-arm single-site open cluster randomised controlled pilot study. Setting 30 primary schools in rural western Kenya, within a Health and Demographic Surveillance System. Participants Primary schoolgir...

Background In Africa, most plasmodium infections during pregnancy remain asymptomatic, yet are associated with maternal anemia and low birthweight. WHO recommends intermittent preventive therapy in pregnancy with sulfadoxine-pyrimethamine (IPTp-SP). However, sulfadoxine-pyrimethamine (SP) efficacy is threatened by high-level parasite resistance. We...

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Baseline characteristics comparing women that contributed to the primary endpoint versus those that did not (missing). (DOCX)

Intention to treat analysis population: covariate-adjusted analysis of primary endpoint, with and without imputation for missing variables. (DOCX)

Effect of ISTp-DP versus IPTp-SP on mean maternal hemoglobin, birthweight, gestational age, and birthweight-for-gestational age Z-score (crude analysis). (DOCX)

Fetal loss and perinatal and infant death among DP recipients and non-recipients in the ISTp-DP arm, compared with the IPTp-SP arm (post hoc analysis). (DOCX)

Study protocol. (PDF)

Trial registration. (PDF)

Maternal patent and subpatent plasmodium infection at delivery by microscopy, RDT, or PCR. *Patent infection defined as PCR-positive and RDT- or microscopy-positive; subpatent infection defined as PCR-positive and RDT- or microscopy-negative. RDTs detected 44.9% of the PCR-positive infections in paucigravidae and 29.2% in multigravidae. The p-value...

Incidence of infant morbidity by the end of follow-up at 6?8 wk. Data in columns on the left represent the number of infants with an event, the number of events/person-time of follow-up, and, in parentheses, the incidence rate per 100 person-years. *p-Value by Fisher?s exact test. The p-value for the interaction term depicts the p-value for differe...

Per protocol analysis population: unadjusted and covariate-adjusted analysis of primary endpoint, with missing values for covariates imputed. (DOCX)

Subgroup analysis of the effect of ISTp-DP versus IPTp-SP on the composite primary outcome of small for gestational age, low birthweight, or preterm birth. Hb, hemoglobin; RR, relative risk. Season was defined by ranking the average rainfall in the 6 mo prior to delivery. (TIF)

Placental plasmodium infection by microscopy, RDT, PCR, and placental histology. *p-Value by Fisher?s exact test. #PCR-positive or histology-positive (active infection) and RDT- or microscopy-positive (patent) or RDT- or microscopy-negative (subpatent). The p-value for the interaction term depicts the p-value for differences in effect size between...

Adherence to follow-up visit schedule and number of courses received by pregnant women (intention to treat population). (DOCX)

Mutant allele frequencies in Plasmodium falciparum parasites collected at study enrollment by study site and overall. (DOCX)

Prespecified statistical analysis plan. (PDF)

French translation of the Abstract and Author Summary. (DOCX)

Subgroup analysis of the effect of ISTp-DP versus IPTp-SP on the primary outcome maternal or placental plasmodium infection at delivery. Hb, hemoglobin; RR, relative risk. Season was defined by ranking the average rainfall in the 6 mo prior to delivery. The p-value for the interaction term comparing the treatment effect for maternal or placental pl...

Proportion of women with missing data for the primary outcomes, by treatment arm. (DOCX)

Sensitivity analysis to determine the effect of the use of corrected versus uncorrected birthweight, using the intention to treat analysis population. (DOCX)

Adherence and tolerance of study drugs and regimen by pregnant women. (DOCX)

Supplementary methods. (DOCX)

Background: Severe anemia is a major cause of sickness and death in African children, yet the causes of anemia in this population have been inadequately studied. Methods: We conducted a case-control study of 381 preschool children with severe anemia (hemoglobin concentration, <5.0 g per deciliter) and 757 preschool children without severe anemia...

Background Missing outcomes can seriously impair the ability to make correct inferences from randomized controlled trials (RCTs). Complete case (CC) analysis is commonly used, but it reduces sample size and is perceived to lead to reduced statistical efficiency of estimates while increasing the potential for bias. As multiple imputation (MI) method...

INTRODUCTION: Between 40,000 and 80,000 women die annually from pre-eclampsia/eclampsia. Prompt delivery, preferably by vaginal route, is vital for good maternal and neonatal outcomes. Two low cost interventions-oral misoprostol tablets and transcervical Foley catheterization-are already used in low resource settings, but their relative risks and b...

Background: Oral vaccination with live-attenuated S. Typhi (Ty21a) is modestly efficacious, however the mechanisms of protection are currently unknown. While humoral and cellular immune responses are well-described in peripheral blood, the cellular response at the intestinal mucosa has never been directly assessed. Methods: We vaccinated healthy...

Background Risk Difference (RD) is becoming the measure of choice for estimating effect size in antimalarial drug efficacy trials. Calculating RD using binomial regression is prone to model nonconvergence. Cheung’s modified ordinary least squares (OLS) method is a proven technique for handling non-convergence when estimating RD. Other promising met...

Objective: To investigate HIV, its treatment, and hypertension as stroke risk factors in Malawian adults. Methods: We performed a case-control study of 222 adults with acute stroke, confirmed by MRI in 86%, and 503 population controls, frequency-matched for age, sex, and place of residence, using Global Positioning System for random selection. M...

Recent reductions in malaria in sub-Saharan Africa have been associated with increased coverage with long-lasting insecticidal nets (LLINs). Pyrethroids are currently the only insecticide class used for treating nets, and the rapid increase in resistance to pyrethroids in vector mosquitoes may jeopardise future vector control. Nets containing a nov...

Pneumonia is the 2nd leading cause of years of life lost worldwide and is a common cause of adult admissions to hospital in sub-Saharan Africa. Risk factors for adult pneumonia are well characterised in developed countries, but are less well described in sub-Saharan Africa where HIV is a major contributing factor. Exposure to indoor and outdoor air...

Background. The Malawi Liverpool Wellcome Trust Clinical Research Programme (MLW) has routinely collected specimens for blood culture from febrile patients, and cerebrospinal fluid from patients with suspected meningitis, presenting to Queen Elizabeth Central Hospital (QECH), Blantyre, Malawi, since 1998. Methods. We present bloodstream infection (...

Streptococcus pneumoniae is a nasopharyngeal commensal that occasionally invades normally sterile sites to cause bloodstream infection and meningitis. Although the pneumococcal population structure and evolutionary genetics are well defined, it is not clear whether pneumococci that cause meningitis are genetically distinct from those that do not. H...

Background: Chronic suppurative otitis media (CSOM) is one of the leading causes of preventable disabling hearing impairment (DHI) in developing countries. Early detection and management complements advances made in other survival programs, improves work capacity, and enhances learning opportunities for school children. We aimed to determine the p...

600 mcg of oral misoprostol reduces the incidence of postpartum haemorrhage (PPH), but in previous research this medication has been administered by health workers. It is unclear whether it is also safe and effective when self-administered by women. This placebo-controlled, double-blind randomised trial enrolled consenting women of at least 34 week...

There are limited published data on the characteristics of blood transfusion recipients in sub-Saharan Africa. This study describes the demographic characteristics of blood transfusion recipients and patterns of blood and blood component use in Zimbabwe. Data on the characteristics of the blood transfusion recipients (age, sex, blood group), blood...

The inaccessibility of the brain poses a problem for neuroscience. Scientists have traditionally responded by developing biomarkers for brain physiology and disease. The retina is an attractive source of biomarkers since it shares many features with the brain. Some even describe the retina as a 'window' to the brain, implying that retinal signs are...

Nontyphoidal Salmonellae (NTS) are responsible for a huge burden of bloodstream infection in Sub-Saharan African children. Recent reports of a decline in invasive NTS (iNTS) disease from Kenya and The Gambia have emphasised an association with malaria control. Following a similar decline in iNTS disease in Malawi, we have used 9 years of continuous...

The effectiveness of pyrethroid-treated bednets for malaria control in sub-Saharan Africa is under threat because of high levels of resistance to pyrethroid insecticides in the vectors. Here we assess the durability of polyethylene nets with a novel combination of permethrin, a pyrethroid, with pyriproxyfen, an insect juvenile mimic (PPF-LLIN), in...

Background: Japanese encephalitis (JE) virus (JEV) is a mosquito-borne flavivirus found across Asia that is closely related to West Nile virus. There is no known antiviral treatment for any flavivirus. Results from in vitro studies and animal models suggest intravenous immunoglobulin (IVIG) containing virus-specific neutralizing antibody may be ef...

In developing countries like Malawi, further investigation is rare after patients with chronic cough test negative for tuberculosis. Chronic airways disease has presentations that overlap with tuberculosis. However, chronic airways disease is often unrecognised due to a lack of diagnostic services. Within developing countries, referral systems at p...

Objective To document the prevalence of multidrug resistance among people newly diagnosed with – and those retreated for – tuberculosis in Malawi. Methods We conducted a nationally representative survey of people with sputum-smear-positive tuberculosis between 2010 and 2011. For all consenting participants, we collected demographic and clinical da...

Background: Acute bacterial meningitis (ABM) in sub-Saharan African adults occurs in young, HIV co-infected people, is predominately caused by S. pneumoniae, and mortality exceeds 50%. We tested if nurse-led Early Goal Directed Therapy (EGDT) was feasible for ABM in a resource-limited hospital in Malawi. Methods: We prospectively recruited pa...

Objective We investigated HIV, its treatment and other risk factors for stroke in Malawi. Methods We performed a prospective case-control study of 222 adults with acute stroke, confirmed by MRI in 86%, and 503 population controls, frequency-matched for age, sex and place of residence. Multivariate logistic regression models were used for case–contr...