Aetiology and outcome of neonatal sepsis and meningitis in Malawi

In Malawi there has been significant progress in reducing post-neonatal and under-5 deaths over the past decade but very little progress in reducing neonatal deaths. The major causes of neonatal deaths in Malawi are prematurity, infections and birth asphyxia. Neonatal sepsis has been shown to have long term complications ranging from motor deficits to cognitive impairment, epilepsy and behavioural disorders in preterm very low birth weight infants in the developed setting. Contrary to the epidemiology in the developed setting where neonatal sepsis is predominantly seen in preterm low birth weight infants, in the developing setting neonatal sepsis is also common among term babies. However, very little is known on the long term outcome of neonatal sepsis in the resource restrained setting. In this thesis the aetiology and outcome of neonatal sepsis and meningitis is investigated. METHODOLOGY This was study had 2 components; a cross sectional arm and a prospective cohort arm. The cross sectional study was looking at the aetiology, resistance pattern and in hospital outcome of severe neonatal infection cases presenting at QECH in Blantyre. The prospective cohort arm involved participants who were recruited in the cross sectional arm at QECH and were residing within Blantyre urban and infants that never had an episode of severe neonatal infection were recruited from Zingwangwa health Centre. The infants from Zingwangwa acted as controls. The participants in the prospective cohort arm were followed up to the age of 1 year where neurodevelopmental outcomes were assessed using the Bayley’s assessment tool. These participants also had detailed neurologic examination during the follow up visits at 6 and 12 months of age. A comparison between the cases and controls was made to ascertain the impact of neonatal infection outcome. RESULTS During the study a total of 412 cases were enrolled in the cross sectional arm. 75% of the cases had late onset disease. GBS was the commonest organism grown in blood culture 17/42(40%) and CSF culture 16/33(48%). 44% had abnormal serum sodium levels on admission and hypernatraemia was independently associated with an increased risk of dying in hospital (8.34[95% CI 1.95-35.7]). 51% of the gram negative organisms were multidrug resistant. In the long term outcome neonatal sepsis without overt meningitis was associated with an up to 6.6 –fold {95% CI (2.38-18.4} increased risk of developmental delay at 1 year of age. Meningitis was associated with a 17-fold {95% CI 4.89- 61.7} increased risk of developmental delay at 1 year of age. Positive blood or CSF culture and being HIV exposed were independent predictors of delay at I year of age. CONCLUSION GBS is a significant cause of neonatal infections in Malawi. The magnitude of developmental delay observed in infants who had neonatal sepsis without meningitis is worrying up to 35% of these infants were delayed. It is therefore important to employ measures that can prevent neonatal infections. Follow up is recommended in infants who had an episode of severe neonatal infection

AutoSyP: A Low-Cost, Low-Power Syringe Pump for Use in Low-Resource Settings

This article describes the design and evaluation of AutoSyP, a low-cost, low-power syringe pump intended to deliver intravenous (IV) infusions in low-resource hospitals. A constant-force spring within the device provides mechanical energy to depress the syringe plunger. As a result, the device can run on rechargeable battery power for 66 hours, a critical feature for low-resource settings where the power grid may be unreliable. The device is designed to be used with 5- to 60-mL syringes and can deliver fluids at flow rates ranging from 3 to 60 mL/hour. The cost of goods to build one AutoSyP device is approximately $500. AutoSyP was tested in a laboratory setting and in a pilot clinical study. Laboratory accuracy was within 4% of the programmed flow rate. The device was used to deliver fluid to 10 healthy adult volunteers and 30 infants requiring IV fluid therapy at Queen Elizabeth Central Hospital in Blantyre, Malawi. The device delivered fluid with an average mean flow rate error of −2.3% ± 1.9% for flow rates ranging from 3 to 60 mL/hour. AutoSyP has the potential to improve the accuracy and safety of IV fluid delivery in low-resource settings

The Treatment of Possible Severe Infection in Infants: An Open Randomized Safety Trial of Parenteral Benzylpenicillin and Gentamicin Versus Ceftriaxone in Infants <60 days of Age in Malawi

Background - The World Health Organization recommends benzylpenicillin and gentamicin as antimicrobial treatment of infants with sepsis in low income settings (LICs), and ceftriaxone or cefotaxime as an alternative. In a meta-analysis from 13 LICs, Staphylococcus aureus, Klebsiella spp. and E.coli accounted for 55% of infants with sepsis. In a review of bacterial meningitis, resistance to third generation cephalosporins was >50% of all isolates, and 44% of Gram-negative isolates were gentamicin resistant. However, ceftriaxone may cause neonatal jaundice and gentamicin may cause deafness. Therefore, we compared parenteral benzylpenicillin plus gentamicin to ceftriaxone as first line treatment, assessing outcome and adverse events. Methods - This was an open randomized trial carried out in the Queen Elizabeth Central Hospital, Blantyre, Malawi from 2010 to 2013. Infants < 60 days of age with possible severe sepsis received either benzylpenicillin and gentamicin or ceftriaxone. Adverse events and outcomes were recorded until 6 months post discharge. Results - 348 infants were included in analyses. Outcome in the benzylpenicillin and gentamicin or ceftriaxone groups was similar; deaths were 13.7% and 16.5% and sequelae 14.5% and 11.2% respectively. More infants in the penicillin/gentamicin group required phototherapy: 15% v 5%, p=0.03. Thirteen (6%) survivors had bilateral hearing loss. There was no difference between the treatment groups. By 6 months post discharge 11 more infants had died and 17 more children were found to have sequelae. Conclusions - Ceftriaxone and gentamicin are safe for infants in our setting. Infants should receive long term follow up as many poor outcomes occurred after hospital discharge

Association of Neonatal Hypothermia with Morbidity and Mortality in a Tertiary Hospital in Malawi.

OBJECTIVES To evaluate associations with neonatal hypothermia in a tertiary-level neonatal unit (NU) in Malawi. METHODS Neonates with a birth weight >1000 g were recruited and temperatures were recorded 5 min after birth, on admission and 4 h thereafter. Clinical course and outcome were reviewed. Data were analysed using Stata v.15 and p < 0.05 was considered statistically significant. RESULTS Between August 2018 to March 2019, 120 neonates were enrolled, and 112 were included in the data analysis. Hypothermia at 5 min after birth was noted in 74%, 77% on admission to the NU and 38% at 24 h. Neonates who had hypothermia 5 min after birth were more likely to have hypothermia on admission to the NU compared with normothermic subjects (p < 0.01). All neonates with hypothermia on admission to the NU died (100 vs.72%, p = 0.02), but hypothermia at 5 min nor at 24 h were not associated with mortality. After adjusting for potential confounders, the odds ratio of hypothermia at 5 min for hypothermia on admission to NU was 13.31 (95% CI 4.17-42.54). DISCUSSION A large proportion of hospitalized neonates is hypothermic on admission and has associated morbidity and mortality. Our findings suggest that a strong predictor of mortality is neonatal hypothermia on admission to the NU, and that early intervention in the immediate period after delivery could decrease the incidence of hypothermia and reduce associated morbidity and mortality

Postpartum Depression and HIV Infection Among Women in Malawi

HIV-infected women face several risk factors for postpartum depression (PPD). We aimed to describe the prevalence and cumulative incidence of PPD in the low-income setting of Malawi, and to determine the association between maternal and infant HIV and PPD

Early Antiretroviral Therapy Initiation and Mortality Among Infants Diagnosed With HIV in the First 12 Weeks of Life: Experiences From Kinshasa, DR Congo and Blantyre, Malawi

AB Background: Based on clinical trial results, the WHO recommends infant HIV testing at age 4-6 weeks and immediate antiretroviral therapy (ART) initiation in all HIV-infected infants. Little is known about the outcomes of HIV infected infants diagnosed with HIV in the first weeks of life in resource-limited settings. We assessed ART initiation and mortality in the first year of life among infants diagnosed with HIV by 12 weeks of age. Methods: Cohort of HIV-infected infants in Kinshasa and Blantyre diagnosed before 12 weeks to estimate 12-month cumulative incidences of ART initiation and mortality, accounting for competing risks. Multivariate models were used to estimate associations between infant characteristics and timing of ART initiation. Results: 121 infants were diagnosed at a median age of 7 weeks (interquartile range 6-8). The cumulative incidence of ART initiation was 46% (95% CI: 36%, 55%) at 6 months and 70% (95% CI: 60%, 78%) at 12 months. Only age at HIV diagnosis was associated with ART initiation by age 6 months, with a subdistribution hazard ratio of 0.70 (95% CI: 0.52, 0.91) for each week increase in age at DNA PCR test. The 12-month cumulative incidence of mortality was 20% (95% CI: 13%, 28%). Conclusions: Despite early diagnosis of HIV, ART initiation was slow and mortality remained high, underscoring the complexity in translating clinical trial findings and WHO guidance into real-life practice. Novel and creative health system interventions will be required to ensure that all HIV infected infants achieve optimal treatment outcomes under routine care settings

“They Have Already Thrown Away Their Chicken”: barriers affecting participation by HIV-infected women in care and treatment programs for their infants in Blantyre, Malawi

HIV-infected infants and young children are at high risk of serious illness and death. Morbidity and mortality can be greatly reduced through early infant diagnosis (EID) of HIV and timely initiation of antiretroviral therapy (ART). Despite global efforts to scale-up of EID and infant ART, uptake of these services in resource poor, high HIV burden countries remains low. We conducted a qualitative study of 59 HIV-infected women to identify and explore barriers women face in accessing HIV testing and care for their infants. To capture different perspectives, we included mothers whose infants were known positive (n=9) or known negative (n=14), mothers of infants with unknown HIV status (n=13), and pregnant HIV-infected women (n=20). Five important themes emerged: lack of knowledge regarding EID and infant ART, the perception of health care workers as authority figures, fear of disclosure of own and/or child’s HIV status, lack of psychosocial support, and intent to shorten the life of the child. A complex array of cultural, economic and psychosocial factors creates barriers for HIV-infected women to participate in early infant HIV testing and care programs. For optimal impact of EID and infant ART, reasons for poor uptake should be better understood and addressed in a culturally sensitive manner

Mathematical Modeling to Assess the Drivers of the Recent Emergence of Typhoid Fever in Blantyre, Malawi

Background. Multiyear epidemics of Salmonella enterica serovar Typhi have been reported from countries across eastern and southern Africa in recent years. In Blantyre, Malawi, a dramatic increase in typhoid fever cases has recently occurred, and may be linked to the emergence of the H58 haplotype. Strains belonging to the H58 haplotype often exhibit multidrug resistance and may have a fitness advantage relative to other Salmonella Typhi strains. Methods. To explore hypotheses for the increased number of typhoid fever cases in Blantyre, we fit a mathematical model to culture-confirmed cases of Salmonella enterica infections at Queen Elizabeth Central Hospital, Blantyre. We explored 4 hypotheses: (1) an increase in the basic reproductive number (R(0)) in response to increasing population density; (2) a decrease in the incidence of cross-immunizing infection with Salmonella Enteritidis; (3) an increase in the duration of infectiousness due to failure to respond to first-line antibiotics; and (4) an increase in the transmission rate following the emergence of the H58 haplotype. Results. Increasing population density or decreasing cross-immunity could not fully explain the observed pattern of typhoid emergence in Blantyre, whereas models allowing for an increase in the duration of infectiousness and/or the transmission rate of typhoid following the emergence of the H58 haplotype provided a good fit to the data. Conclusions. Our results suggest that an increase in the transmissibility of typhoid due to the emergence of drug resistance associated with the H58 haplotype may help to explain recent outbreaks of typhoid in Malawi and similar settings in Africa

Timing of HIV Seroreversion Among HIV-Exposed, Breastfed Infants in Malawi: Type of HIV Rapid Test Matters

Introduction Rapid HIV serological tests are a cost-effective, point-of-care test among HIV exposed infants but cannot distinguish between maternal and infant antibodies. The lack of data on the timing of decay of maternal antibodies in young infants hinders the potential use of rapid tests in exposed infants. We aimed to determine the time to seroreversion for two commonly used rapid tests in a prospective cohort of HIV-exposed breastfeeding infants ages 3-18 months of life. Methods We collected data on the performance of two commonly used rapid tests (Determine and Unigold) in Malawi between 2008 and 2012 or at the University of North Carolina between 2014 and 2015. Time to seroreversion was estimated for both rapid tests using the Kaplan-Meier product limit estimator which allows for interval censored data. Results At 3 months of age, 3 % of infants had seroreverted according to Determine and 7 % had seroreverted according to Unigold. About one in four infants had achieved seroreversion by 4 months using Unigold, but only about one in twelve infants by 4 months when using Determine. More than 95 % of all infants had seroverted by 7 months according to Unigold and by 12 months according to the Determine assay. Discussion We show that the time of seroreversion depends greatly on the type of test used. Our results highlight the need for recommendations to specify the timing and type of test used in the context of infant HIV detection in resource-poor settings, and base the interpretation of test result on knowledge of time to seroreversion of the selected test