Gentamicin concentration and acute kidney injury in term neonates treated for neonatal sepsis with gentamicin and ampicillin-cloxacillin combination.

Gentamicin is widely used to treat neonatal infections caused by both Gram-negative and Gram-positive bacteria, and the WHO recommends its use while monitoring serum creatinine and gentamicin concentrations to avoid drug-induced nephrotoxicity and ototoxicity. Yet in some resource-limited settings, the drug is used without monitoring. A population pharmacokinetics study involving term neonates with neonatal infection admitted to a neonatal unit. Participants were started on intravenous gentamicin 5 mg/kg once a day in combination with ampicilin-cloxacillin. Blood samples for serum gentamicin concentration were taken at 0.25, 0.5, 1, 2, 3, 5, 6, 8, 10, 12, 14, 16, 18, 20, 23, and 24 hours after the initial dose, each participant contributing two samples to the 24 hour sampling schedule. An additional sample for trough concentration was taken from each participant just before the third gentamicin dose while serum creatinine concentration was measured before and after treatment. Twenty-four participants were enrolled into the study and included in the final analysis. Mean (SD) peak and trough serum gentamicin concentrations were 16.66 (0.64) µg/mL and 3.28 (0.70) µg/mL, respectively. Gentamicin clearance (CL) was 0.40 mL min-1 kg-1 and volume of distribution (VD) was 0.31 L kg-1. Mean (SD) serum creatinine level after treatment was 209.7 (70.4) µmol/L compared to 103.3 (23.6) µmol/L before treatment [mean difference (106.4 ± 67.1; 95% confidence interval (CI): 78.1; 134.7 µmol/L; t (23) = 7.77; P < 0.001]. All participants fulfilled the Kidney Disease Improving Global Outcomes (KDIGO) criteria for acute kidney injury after treatment. Treatment of neonatal infection with antimicrobial regimen containing gentamicin, without renal function and gentamicin concentration monitoring, carries a significant risk for drug-induced acute kidney injury.

Polymicrobial bloodstream infections a risk factor for mortality in neonates at the national hospital, Tanzania: A case-control study.

BACKGROUND: Polymicrobial bloodstream infections (BSI) are difficult to treat since empiric antibiotics treatment are frequently less effective against multiple pathogens. The study aimed to compare outcomes in patients with polymicrobial and monomicrobial BSIs. METHODS: The study was a retrospective case-control design conducted at Muhimbili National Hospital for data processed between July 2021 and June 2022. Cases were patients with polymicrobial BSI, and controls had monomicrobial BSI. Each case was matched to three controls by age, admitting ward, and duration of admission. Logistic regression was performed to determine independent risk factors for in-hospital and 30-day mortality. RESULTS: Fifty patients with polymicrobial BSI and 150 with monomicrobial BSI were compared: the two arms had no significant differences in sex and comorbidities. The most frequent bacteria in polymicrobial BSI were Klebsiella pneumoniae 17% (17/100) and Enterobacter species 15% (15/100). In monomicrobial BSI, S. aureus 17.33% (26/150), Klebsiella pneumoniae 16.67% (25/150), and Acinetobacter species 15% (15/150) were more prevalent. Overall, isolates were frequently resistant to multiple antibiotics tested, and 52% (130/250) were multidrug resistance. The 30-day and in-hospital mortality were 33.5% (67/200) and 36% (72/200), respectively. On multivariable analysis, polymicrobial BSIs were independent risk factors for both in-hospital mortality (aOR 2.37, 95%CI 1.20-4.69, p = 0.01) and 30-day mortality (aOR 2.05, 95%CI 1.03-4.08), p = 0.04). In sub-analyses involving only neonates, polymicrobial BSI was an independent risk factor for both 30-day mortality (aOR 3.13, 95%CI 1.07-9.10, p = 0.04) and in-hospital mortality (aOR 5.08, 95%CI 1.60-16.14, p = 0.006). Overall, the median length of hospital stay post-BSIs was numerically longer in patients with polymicrobial BSIs. CONCLUSION: Overall, polymicrobial BSI was a significant risk for mortality. Patients with polymicrobial BSI stay longer at the hospital than those with monomicrobial BSI. These findings call for clinicians to be more aggressive in managing polymicrobial BSI.

Long-term retention on antiretroviral treatment after enrolment in prevention of vertical HIV transmission services: a prospective cohort study in Dar es Salaam, Tanzania.

INTRODUCTION: To prevent vertical HIV transmission and ensure healthy mothers and children, pregnant women with HIV must remain on antiretroviral treatment (ART) for life. However, motivation to remain on ART may decline beyond the standard 2-year breastfeeding/postpartum period. We assessed attrition and retention in ART care among women with HIV up to 6 years since enrolment in vertical transmission prevention services in Dar es Salaam, Tanzania. METHODS: A prospective cohort of 22,631 pregnant women with HIV were enrolled in vertical transmission prevention services between January 2015 and December 2017 in routine healthcare settings and followed-up to July 2021. Kaplan-Meier was used to estimate time to ART attrition (died, stopped ART or was lost to follow-up [no show ≥90 days since scheduled appointment]) and the proportion retained in care. Cox proportional hazard models were used to estimate adjusted hazard ratios (aHR) of ART attrition in relation to predictors. RESULTS: Participants were followed-up to 6 years for a median of 3 years (IQR: 0.1-4). The overall ART attrition rate was 13.8 per 100 person-years (95% CI: 13.5-14.1), highest in the first year of enrolment at 27.1 (26.3-27.9), thereafter declined to 9.5 (8.9-10.1) in year 3 and 2.7 (2.1-3.5) in year 6. The proportion of women retained in care were 78%, 69%, 63%, 60%, 57% and 56% at 1, 2, 3, 4, 5 and 6 years, respectively. ART attrition was higher in young women aged <20 years (aHR 1.63, 95% CI: 1.38-1.92) as compared to 30-39 year-olds and women enrolled late in the third versus first trimester (aHR 1.29, 95% CI: 1.16-1.44). In contrast, attrition was lower in older women ≥40 years, women who initiated ART before versus during the index pregnancy and women attending higher-level health facilities. CONCLUSIONS: ART attrition among women with HIV remains highest in the first year of enrolment in vertical transmission prevention services and declines markedly following a transition to chronic HIV care. Targeted interventions to improve ART continuity among women with HIV during and beyond prevention of vertical transmission are vital to ending paediatric HIV and keeping women and children alive and healthy.

Drug resistant epilepsy and associated factors among children with epilepsies in tanzania: a cross-sectional study.

BACKGROUND: Epilepsy contributes to high morbidity among children and adolescents in developing countries. A quarter of all children with epilepsy will be resistant to anti-seizure medications (ASMs), with associated neurocognitive impairments and risk of higher mortality. This study aimed to estimate and characterize drug-resistant epilepsy (DRE) (defined as failure to achieve sustained remission after adequate trials of two tolerated and appropriately chosen ASMs) and its associated factors among children and adolescents with epilepsies attending the pediatric neurology clinic at Muhimbili National Hospital (MNH), Dar es Salaam Tanzania. METHODS: This cross-sectional study was conducted from June 2020 to June 2021. Children with epilepsies and who had been treated with ASMs for at least 3 months were eligible for inclusion. Exclusion criteria included children whose caregivers denied consent and those who exhibited acute medical conditions necessitating admission on the scheduled visit day. Data on demographic characteristics, perinatal history, detailed history of the seizures semiology, drug history, magnetic resonance imaging (MRI), and electroencephalography (EEG) results were obtained from caregivers and medical records available during recruitment. Seizures and epilepsies were classified using the 2017 International League Against Epilepsy (ILAE) classification. Logistic regression was used to determine factors associated with DRE. RESULTS: A total of 236 children and adolescents aged between 4 months and 15 years (Median age 72 months (IQR = 42-78)) were enrolled in this study. We found the proportion of DRE to be 14.8% in this cohort. Of the thirty-five patients with DRE, 60% had generalized epilepsy and almost 25% had a diagnosis of an epilepsy syndrome, the most common being Lennox-Gastaut syndrome (LGS). Structural abnormalities on brain MRI were seen in almost 80% of all patients with DRE, the most prevalent being cystic encephalomalacia, which was observed in 34% of patients. Patients using both ASMs and alternative therapies accounted for 9% of this cohort. The onset of seizures during the first month of life (aOR = 1.99; 95%CI 1.7-4.6; p = 0.031) and high initial seizure frequency (aOR = 3.6; 95%CI 1.6-8;p = 0.002) were found to be independently associated with DRE. CONCLUSION: The proportion of DRE in Tanzania is high. Patients with neonatal onset seizures and high initial seizure frequency should be followed up closely to ensure early diagnosis of DRE.

Prevalence of anaemia and associated factors among preterm infants at six weeks chronological age at Muhimbili National Hospital, Dar es Salaam, Tanzania: a cross-sectional study.

Introduction: preterm infants are vulnerable to several medical complications including anaemia, a significant public health problem with consequences on neurodevelopment. This study looked at the magnitude of anaemia and its associated factors among preterm infants at 6 weeks chronological age in a paediatric clinic of Muhimbili National Hospital (MNH). Methods: this was a hospital based cross-sectional study conducted among preterm infants at 6 weeks chronological age attending follow-up clinic at MNH from October 2019 to March 2020. Parental interviews, medical records reviews and haemoglobin assessment was done during the clinic visits. Logistic regression was used to determine the association between studied factors and anaemia. Results: the proportion of preterm infants with anaemia at 6 weeks chronological age was 38.4% (142/370) with 74% of these infants having moderate anaemia. Morphological types of anaemia were normocytic (56.3%) and microcytic anaemia (4.9%). Two-thirds of preterm infants (62%) were on haematinics supplementation. Moderate preterm born at gestation age 32 to <34 weeks (OR=2.21, 95% CI 1.15-4.25, p=0.017), two or less phlebotomies (OR=2.3; 95% CI 1.23-4.30; P=0.010) and more than two phlebotomies (OR=7.2, 95% CI 3.62-14.16, p≤0.001) were significantly associated with anaemia. Conclusion: the proportion of preterm infants with anaemia at 6 weeks chronological age is high despite two-thirds being on haematinics supplementation. Moderate preterm and multiple phlebotomies significantly contributed to the occurrence of anaemia. Screening preterm infants for anaemia, appropriate management, and close follow-up are recommended to reduce its burden.

Effect on neonatal sepsis following immediate kangaroo mother care in a newborn intensive care unit: a post-hoc analysis of a multicentre, open-label, randomised controlled trial.

Background: To implement the immediate Kangaroo mother care (iKMC) intervention in the previous multicentre, open-label, randomised controlled trial, the mother or a surrogate caregiver and neonate needed to be together continuously, which led to the concept of the Mother-Newborn Care Unit (MNCU). Health-care providers and administrators were concerned of the potential increase in infections caused by the continuous presence of mothers or surrogates in the MNCU. We aimed to assess the incidence of neonatal sepsis in sub-groups and the bacterial profile among intervention and control neonates in the study population. Methods: This is a post-hoc analysis of the previous iKMC trial, which was conducted in five level 2 Newborn Intensive Care Units (NICUs) one each in Ghana, India, Malawi, Nigeria, and Tanzania, in neonates with birth weight 1 to <1.8 kg. The intervention was KMC initiated immediately after birth and continued until discharge and compared to conventional care with KMC initiated after meeting stability criteria. The primary outcomes of this report were the incidence of neonatal sepsis in sub-groups, sepsis-related mortality and bacterial profile of isolates during hospital stay. The original trial is registered with the Australia and New Zealand Clinical Trials Registry (ACTRN12618001880235) and the Clinical Trials Registry-India (CTRI/2018/08/01536). Findings: Between November 30, 2017, and January 20, 2020, 1609 newborns in the intervention group and in the control group 1602 newborns were enrolled in iKMC study. 1575 newborns in the intervention group and 1561 in the control group were clinically evaluated for sepsis. Suspected sepsis was 14% lower in intervention group in sub-group of neonates with birth weight 1.0-<1.5 kg; RR 0.86 (CI 0.75, 0.99). Among neonates with birth weight 1.5-<1.8 kg, suspected sepsis was reduced by 24%; RR 0.76 (CI 0.62, 0.93). Suspected sepsis rates were lower in intervention group than in the control group across all sites. Sepsis related mortality was 37% less in intervention group than the control group; RR 0.63 (CI 0.47-0.85) which was statistically significant. The intervention group had fewer cases of Gram-negative isolates (n = 9) than Gram positive isolates (n = 16). The control group had more cases of Gram-negative isolates (n = 18) than Gram positive (n = 12). Interpretation: Immediate Kangaroo Mother care is an effective intervention to prevent neonatal sepsis and sepsis related mortality. Funding: The original trial was funded by the Bill and Melinda Gates Foundation through a grant to the World Health Organization (grant No. OPP1151718).

Immediate skin-to-skin contact for low birth weight infants is safe in terms of cardiorespiratory stability in limited-resource settings.

Aim: To investigate the safety of skin-to-skin contact initiated immediately after birth on cardiorespiratory parameters in unstable low birth weight infants. Methods: A randomized clinical trial was conducted in tertiary newborn units in Ghana, India, Malawi, Nigeria and Tanzania in 2017-2020, in infants with birth weight 1.0-1.799 kg. The intervention was Kangaroo mother care initiated immediately after birth and continued until discharge compared to conventional care with Kangaroo mother care initiated after meeting stability criteria. The results of the primary study showed that immediate Kangaroo mother care reduced neonatal mortality by 25% and the results have been published previously. The post-hoc outcomes of this study were mean heart rate, respiratory rate, oxygen saturation during the first four days and the need of respiratory support. Results: 1,602 infants were allocated to control and 1,609 to intervention. Mean birth weight was 1.5 kg (SD 0.2) and mean gestational age was 32.6 weeks (SD 2.9). Infants in the control group had a mean heart rate 1.4 beats per minute higher (95% CI -0.3-3.1, p = 0.097), a mean respiratory rate 0.4 breaths per minute higher (-0.7-1.5, p = 0.48) and a mean oxygen saturation 0.3% higher (95% CI -0.1-0.7, p = 0.14) than infants in the intervention group. Conclusion: There were no significant differences in cardiorespiratory parameters during the first four postnatal days. Skin-to-skin contact starting immediately after birth is safe in low birth weight infants in limited-resource settings.

ePOCT+ and the medAL-suite: Development of an electronic clinical decision support algorithm and digital platform for pediatric outpatients in low- and middle-income countries.

Electronic clinical decision support algorithms (CDSAs) have been developed to address high childhood mortality and inappropriate antibiotic prescription by helping clinicians adhere to guidelines. Previously identified challenges of CDSAs include their limited scope, usability, and outdated clinical content. To address these challenges we developed ePOCT+, a CDSA for the care of pediatric outpatients in low- and middle-income settings, and the medical algorithm suite (medAL-suite), a software for the creation and execution of CDSAs. Following the principles of digital development, we aim to describe the process and lessons learnt from the development of ePOCT+ and the medAL-suite. In particular, this work outlines the systematic integrative development process in the design and implementation of these tools required to meet the needs of clinicians to improve uptake and quality of care. We considered the feasibility, acceptability and reliability of clinical signs and symptoms, as well as the diagnostic and prognostic performance of predictors. To assure clinical validity, and appropriateness for the country of implementation the algorithm underwent numerous reviews by clinical experts and health authorities from the implementing countries. The digitalization process involved the creation of medAL-creator, a digital platform which allows clinicians without IT programming skills to easily create the algorithms, and medAL-reader the mobile health (mHealth) application used by clinicians during the consultation. Extensive feasibility tests were done with feedback from end-users of multiple countries to improve the clinical algorithm and medAL-reader software. We hope that the development framework used for developing ePOCT+ will help support the development of other CDSAs, and that the open-source medAL-suite will enable others to easily and independently implement them. Further clinical validation studies are underway in Tanzania, Rwanda, Kenya, Senegal, and India.

Vertical HIV transmission within 18 months post partum among women on lifelong antiretroviral therapy for HIV in Dar es Salaam, Tanzania: a prospective cohort study.

BACKGROUND: The UNAIDS estimate of vertical HIV transmission in Tanzania is high (11%), despite 84% uptake of antiretroviral therapy (ART) among pregnant women with HIV. We aimed to evaluate vertical transmission and its determinants by 18 months post partum among women on lifelong ART in routine health-care settings in Tanzania. METHODS: We conducted a prospective cohort study in 226 health facitilies across Dar-es-Salaam, Tanzania. Eligible participants were pregnant women of any age with HIV, and later their infants, who enrolled in routine health-care services for the prevention of vertical transmission. We prospectively followed up mother-infant pairs at routine monthly visits until 18 months post partum and extracted data from the care and treatment clinic (CTC2) database, a national electronic database that stores patient-level HIV care and treatment clinic data. The primary outcome was time from birth to HIV diagnosis, defined as a positive infant HIV DNA PCR or antibody test from age 18 months. We used the Kaplan-Meier method to estimate cumulative risk of vertical transmission by 18 months post partum and Cox proportional hazards regression with shared frailties to account for potential clustering in health facilities to evaluate predictors of transmission. FINDINGS: Between Jan 1, 2015, and Dec 31, 2017, 22 930 pregnant women with HIV (median age 30 years, IQR 25-34) enrolled on a care programme. After excluding 9140 (39·9%) women and 539 (2·4%) infants with missing outcome data, 13 251 (59·0%) mother-infant pairs were analysed, of whom 6072 (45·8%) women were already on ART before pregnancy. By 18 months post partum, 159 (1·2%) of 13 251 infants were diagnosed with HIV, equivalent to a risk of vertical transmission of 1·4% (95% CI 1·2-1·6). In the complete case analysis, the rates of vertical transmission were higher among women who enrolled in the third trimester of pregnancy than among those who enrolled in the first trimester (adjusted hazard ratio 3·01, 95% CI 1·59-5·70; p=0·0003), among women with advanced HIV disease than among those with early-stage disease (1·89, 1·22-2·93; p=0·0046), and among women who were on a second-line ART regimen than among those on a first-line regimen (3·58, 1·08-11·82; p=0·037). By contrast, the rate of vertical transmission was lower among women who were already on ART at enrolment than among those starting ART at enrolment (0·39, 0·25-0·60; p<0·0001) as well as among women in high-volume clinics than among those in low-volume clinics (0·46 (0·24-0·90; p<0·0097). INTERPRETATION: Provision of ART for life (WHO's option B+ recommendation) has reduced the risk of vertical transmission to less than 2% among pregnant women with HIV in routine care settings in urban Tanzania. There is still a need to improve timely HIV diagnosis and ART uptake, and to optimise follow-up for the prevention of vertical transmission and the uptake of infant HIV testing. FUNDING: Swedish International Development Cooperation Agency.

The impact of a community health worker intervention on uptake of antenatal care: a cluster-randomized pragmatic trial in Dar es Salaam.

The provision of high-quality antenatal care (ANC) is important for preventing maternal and newborn mortality and morbidity, but only around half of pregnant women in Tanzania attended four or more ANC visits in 2019. Although there is emerging evidence on the benefit of community health worker (CHW) interventions on ANC uptake, few large-scale pragmatic trials have been conducted. This pragmatic cluster-randomized trial, implemented directly through the public sector health system, assessed the impact of an intervention that trained public sector CHWs to promote the uptake of ANC. We randomized 60 administrative wards in Dar es Salaam to either a targeted CHW intervention or a standard of care. The impact of the intervention was assessed using generalized estimating equations with an independent working correlation matrix to account for clustering within wards. A total of 243 908 women were included in the analysis of our primary outcome of four or more ANC visits. The intervention significantly increased the likelihood of attending four or more ANC visits [relative risk (RR): 1.42; 95% confidence interval (CI): 1.05, 1.92] and had a modest beneficial effect on the total number of ANC visits (percent change: 7.7%; 95% CI: 0.2%, 15.5%). While slightly more women in the intervention arm attended ANC in their first trimester compared with the standard-of-care arm (19% vs 18.7%), the difference was not significant (RR: 1.02; 95% CI: 0.84, 1.22). Our findings suggest that trained CHWs can increase attendance of ANC visits in Dar es Salaam and similar settings. However, additional interventions appear necessary to promote the early initiation of ANC. This study demonstrates that routine health system data can be leveraged for outcome assessment in trials and programme evaluation and that the results are likely superior, both in terms of bias and precision, to data that are collected specifically for science.

Limited resources restrict the provision of adequate neonatal respiratory care in the countries of Africa.

AIM: Over two thirds of newborn deaths occur in Africa and South Asia, and respiratory failure is a major contributor of these deaths. The exact availability of continuous positive airway pressure (CPAP) and surfactant in Africa is unknown. The aim of this study was to describe the availability of newborn respiratory care treatments in the countries of Africa. METHODS: Surveys, in English, French and Portuguese, were sent to neonatal leaders in all 48 continental countries and the two islands with populations over 1 million. RESULTS: Forty-nine (98%) countries responded. Twenty-one countries reported less than 50 paediatricians, and 12 countries had no neonatologists. Speciality neonatal nursing was recognised in 57% of countries. Most units were able to provide supplemental oxygen. CPAP was available in 63% and 67% of the most well-equipped government and private hospitals. Surfactant was available in 33% and 39% of the most well-equipped public and private hospitals, respectively. Availability of CPAP and surfactant was greatly reduced in smaller cities. Continuous oxygen saturation monitoring was only available in 33% of countries. CONCLUSION: The availability of proven life-saving interventions in Africa is inadequate. There is a need to sustainably improve availability and use of these interventions.

Effect of peer-mother interactive programme on prevention of mother-to-child HIV transmission outcomes among pregnant women on anti-retroviral treatment in routine healthcare in Dar es Salaam, Tanzania.

Peer support services are increasingly being integrated in programmes for the prevention of mother-to-child HIV transmission (PMTCT). We aimed to evaluate the effect of a peer-mother interactive programme on PMTCT outcomes among pregnant women on anti-retroviral treatment (ART) in routine healthcare in Dar es Salaam, Tanzania. Twenty-three health facilities were cluster-randomized to a peer-mother intervention and 24 to a control arm. We trained 92 ART experienced women with HIV to offer peer education, adherence and psychosocial support to women enrolling in PMTCT care at the intervention facilities. All pregnant women who enrolled in PMTCT care at the 47 facilities from 1st January 2018 to 31st December 2019 were identified and followed up to 31st July 2021. The primary outcome was time to ART attrition (no show >90 days since the scheduled appointment, excluding transfers) and any difference in one-year retention in PMTCT and ART care between intervention and control facilities. Secondary outcomes were maternal viral suppression (<400 viral copies/mL) and mother-to-child HIV transmission (MTCT) by ≥12 months post-partum. Analyses were done using Kaplan Meier and Cox regression (ART retention/attrition), generalized estimating equations (viral suppression) and random effects logistic regression (MTCT); reporting rates, proportions and 95% confidence intervals (CI). There were 1957 women in the peer-mother and 1384 in the control facilities who enrolled in routine PMTCT care during 2018-2019 and were followed for a median [interquartile range (IQR)] of 23 [10, 31] months. Women in both groups had similar median age of 30 [IQR 25, 35] years, but differed slightly with regard to proportions in the third pregnancy trimester (14% versus 19%); advanced HIV (22% versus 27%); and ART naïve (55% versus 47%). Peer-mother facilities had a significantly lower attrition rate per 1000 person months (95%CI) of 14 (13, 16) versus 18 (16, 19) and significantly higher one-year ART retention (95%CI) of 78% (76, 80) versus 74% (71, 76) in un-adjusted analyses, however in adjusted analyses the effect size was not statistically significant [adjusted hazard ratio of attrition (95%CI) = 0.85 (0.67, 1.08)]. Viral suppression (95%CI) was similar in both groups [92% (91, 93) versus 91% (90, 92)], but significantly higher among ART naïve women in peer-mother [91% (89, 92)] versus control [88% (86, 90)] facilities. MTCT (95%CI) was similar in both groups [2.2% (1.4, 3.4) versus 1.5% (0.7, 2.8)]. In conclusion, we learned that integration of peer-mother services in routine PMTCT care improved ART retention among all women and viral suppression among ART naïve women but had no significant influence on MTCT.

Poor weight gain and its predictors among preterm neonates admitted at Muhimbili National Hospital in Dar-es-salaam, Tanzania: a prospective cohort study.

BACKGROUND: Preterm delivery is among the major public health problems worldwide and the leading cause of morbidity and mortality among neonates. Postnatal poor weight gain, which can contribute to mortality, can be influenced by feeding practices, medical complications and quality of care that is provided to these high-risk neonates. This study aimed to investigate the proportion and predictors of poor weight gain among preterm neonates at Muhimbili National Hospital (MNH), from September 2018 to February 2019. METHODS: A hospital-based prospective cohort study involving preterm neonates with Gestation age (GA) < 37 weeks receiving care at MNH. Eligible preterm, were consecutively recruited at admission and followed up until discharge, death or end of neonatal period. Poor weight gain was defined as weight gain less than 15 g per kg per day. The risk factors associated with poor weight gain were evaluated. Predictors of poor weight gain were evaluated using a multivariate analysis. Results were considered statistically significant if P -value was < 0.05 and 95% confidence interval (CI) did not include 1. RESULTS: A total of 227 preterm neonates < 37 weeks GA, with male to female ratio of 1:1.2 were enrolled in the study. The overall proportion of preterm with poor weight gain was 197/227 (86.8%). Proportion of poor weight gain among the early and late preterm babies, were 100/113 (88.5%) and 97/114 (85.1%) respectively. Predictors of poor weight gain were low level of maternal education (AOR = 2.58; 95%Cl: 1.02-6.53), cup feeding as the initial method of feeding (AOR = 8.65; 95%Cl: 1.59-16.24) and delayed initiation of the first feed more than 48 h (AOR = 10.06; 95%Cl: 4.14-24.43). A previous history of preterm delivery was protective against poor weight gain (AOR = 0.33; 95% Cl: 0.11-0.79). CONCLUSION AND RECOMMENDATION: Poor weight gain was a significant problem among preterm neonates receiving care at MNH. This can be addressed by emphasizing on early initiation of feed and tube feeding for neonates who are not able to breastfeed. Health education and counselling to mothers focusing on feeding practices as well as close supervision of feeding especially for mothers experiencing difficulties in feeding their preterm will potentially minimize risk of growth failure.

Health care costs associated with clinic visits for prevention of mother-to-child transmission of HIV in Dar es Salaam, Tanzania.

ABSTRACT: Early and appropriate antenatal care (ANC) is key for the effectiveness of prevention of mother-to-child transmission (PMTCT) of human immunodeficiency virus (HIV). We evaluated the importance of ANC visits and related service costs for women receiving option B+ to prevent mother-to-child transmission (MTCT) of HIV in Tanzania.A cost analysis from a health care sector perspective was conducted using routine data of 2224 pregnant women newly diagnosed with HIV who gave birth between August 2014 and May 2016 in Dar es Salaam, Tanzania. We evaluated risk of infant HIV infection at 12 weeks postnatally in relation to ANC visits (<4 vs ≥4 visits). Costs for service utilisation were estimated through empirical observations and the World Health Organisation Global Price Reporting Mechanism.Mean gestational age at first ANC visit was 22 (±7) weeks. The average number of ANC/prevention of MTCT visits among the 2224 pregnant women in our sample was 3.6 (95% confidence interval [CI] 3.6-3.7), and 57.3% made ≥4 visits. At 12 weeks postnatally, 2.7% (95% CI 2.2-3.6) of HIV exposed infants had been infected. The risk of MTCT decreased with the number of ANC visits: 4.8% (95% CI 3.6-6.4) if the mother had <4 visits, and 1.0% (95% CI 0.5-1.7) at ≥4. The adjusted MTCT rates decreased by 51% (odds ratio 0.49, 95% CI 0.31-0.77) for each additional ANC visit made. The potential cost-saving was 2.2 US$ per woman at ≥4 visits (84.8 US$) compared to <4 visits (87.0 US$), mainly due to less defaulter tracing.Most pregnant women living with HIV in Dar es Salaam initiated ANC late and >40% failed to adhere to the recommended minimum of 4 visits. Improved ANC attendance would likely lead to fewer HIV-infected infants and reduce both short and long-term health care costs due to less spending on defaulter tracing and future treatment costs for the children.

Peripheral neuropathy in HIV-infected children attending care and treatment clinic, at Muhimbili National Hospital, Dar es Salaam: a cross sectional study.

BACKGROUND: Peripheral neuropathy (PN) is a neurological complication of untreated Human Immunodeficiency Virus (HIV) infection or exposure to certain antiretroviral drugs. In Tanzania where HIV is a major public health problem, the burden of HIV associated peripheral neuropathy has not yet been well defined in children.Thisstudy investigated the prevalence and associated factors for peripheral neuropathy among children living with HIV, attending Care and Treatment Clinic (CTC) at Muhimbili National Hospital (MNH). MATERIALS AND METHODS: A cross-sectional study was conducted among 383 HIV positive children aged 5 to 18 years at MNH, CTC in Dar es Salaam between October to December 2019. All participants provided written assent/consent. Structured questionnaires designed for this study was used to collect data and screening for peripheral neuropathy was done on each participant using the Pediatric modified Total Neuropathy Score (Ped m TNS) that includes subjective and objective assessment. A score of 5 or greater on the Ped m TNS was used to define peripheral neuropathy. Data analysis was done using SPSS Version 23. RESULTS: The prevalence of peripheral neuropathy among HIV infected children was 14.1 % (95 % CI (10.8 - 18 %). Common neuropathic symptoms were numbness, tingling sensation, reduced ankle reflexes and reduced sensation to light touch and pain that was limited to the toes. Low CD4 cell count (OR = 12.21; 95 % CI3.75-39.66; p = 0.0001), high viral load (OR = 10.54; 95 % CI 3.19-34.77; p = 0.0001), ART regime containing NRTI plus PI (OR = 3.93; 95 % CI 1.43- 10.74; p = 0.01) and the last exposure to isoniazid more than 6 months ago (OR = 3.71; 95 % CI 1.57-8.77; p = 0.003) were independent predictors for peripheral neuropathy. CONCLUSION: Peripheral neuropathy is common among HIV infected children attending CTC at MNH and its frequency increases with advanced disease. The choice of ART regimen and other drugs for treating comorbid conditions should carefully be evaluated.

Immediate "Kangaroo Mother Care" and Survival of Infants with Low Birth Weight.

BACKGROUND: "Kangaroo mother care," a type of newborn care involving skin-to-skin contact with the mother or other caregiver, reduces mortality in infants with low birth weight (<2.0 kg) when initiated after stabilization, but the majority of deaths occur before stabilization. The safety and efficacy of kangaroo mother care initiated soon after birth among infants with low birth weight are uncertain. METHODS: We conducted a randomized, controlled trial in five hospitals in Ghana, India, Malawi, Nigeria, and Tanzania involving infants with a birth weight between 1.0 and 1.799 kg who were assigned to receive immediate kangaroo mother care (intervention) or conventional care in an incubator or a radiant warmer until their condition stabilized and kangaroo mother care thereafter (control). The primary outcomes were death in the neonatal period (the first 28 days of life) and in the first 72 hours of life. RESULTS: A total of 3211 infants and their mothers were randomly assigned to the intervention group (1609 infants with their mothers) or the control group (1602 infants with their mothers). The median daily duration of skin-to-skin contact in the neonatal intensive care unit was 16.9 hours (interquartile range, 13.0 to 19.7) in the intervention group and 1.5 hours (interquartile range, 0.3 to 3.3) in the control group. Neonatal death occurred in the first 28 days in 191 infants in the intervention group (12.0%) and in 249 infants in the control group (15.7%) (relative risk of death, 0.75; 95% confidence interval [CI], 0.64 to 0.89; P = 0.001); neonatal death in the first 72 hours of life occurred in 74 infants in the intervention group (4.6%) and in 92 infants in the control group (5.8%) (relative risk of death, 0.77; 95% CI, 0.58 to 1.04; P = 0.09). The trial was stopped early on the recommendation of the data and safety monitoring board owing to the finding of reduced mortality among infants receiving immediate kangaroo mother care. CONCLUSIONS: Among infants with a birth weight between 1.0 and 1.799 kg, those who received immediate kangaroo mother care had lower mortality at 28 days than those who received conventional care with kangaroo mother care initiated after stabilization; the between-group difference favoring immediate kangaroo mother care at 72 hours was not significant. (Funded by the Bill and Melinda Gates Foundation; Australian New Zealand Clinical Trials Registry number, ACTRN12618001880235; Clinical Trials Registry-India number, CTRI/2018/08/015369.).

Small and sick newborn care during the COVID-19 pandemic: global survey and thematic analysis of healthcare providers' voices and experiences.

INTRODUCTION: The COVID-19 pandemic is disrupting health systems globally. Maternity care disruptions have been surveyed, but not those related to vulnerable small newborns. We aimed to survey reported disruptions to small and sick newborn care worldwide and undertake thematic analysis of healthcare providers' experiences and proposed mitigation strategies. METHODS: Using a widely disseminated online survey in three languages, we reached out to neonatal healthcare providers. We collected data on COVID-19 preparedness, effects on health personnel and on newborn care services, including kangaroo mother care (KMC), as well as disruptors and solutions. RESULTS: We analysed 1120 responses from 62 countries, mainly low and middle-income countries (LMICs). Preparedness for COVID-19 was suboptimal in terms of guidelines and availability of personal protective equipment. One-third reported routine testing of all pregnant women, but 13% had no testing capacity at all. More than 85% of health personnel feared for their own health and 89% had increased stress. Newborn care practices were disrupted both due to reduced care-seeking and a compromised workforce. More than half reported that evidence-based interventions such as KMC were discontinued or discouraged. Separation of the mother-baby dyad was reported for both COVID-positive mothers (50%) and those with unknown status (16%). Follow-up care was disrupted primarily due to families' fear of visiting hospitals (~73%). CONCLUSION: Newborn care providers are stressed and there is lack clarity and guidelines regarding care of small newborns during the pandemic. There is an urgent need to protect life-saving interventions, such as KMC, threatened by the pandemic, and to be ready to recover and build back better.

Long-term virological outcomes in women who started option B+ care during pregnancy for prevention of mother-to-child transmission of HIV in Dar es Salaam, Tanzania: a cohort study.

BACKGROUND: Option B+ marked a milestone in prevention of mother-to-child transmission (PMTCT) of HIV by recommending lifelong antiretroviral therapy (ART) for all pregnant women with HIV. Nevertheless, concerns remain regarding long-term outcomes in settings with a high HIV burden. We analysed long-term virological outcomes in women enrolled on option B+ in Tanzania. METHODS: In this prospective cohort study, we extracted data for pregnant women with HIV starting PMTCT care between Oct 1, 2014, and Sept 30, 2016, in routine health-care settings in Dar es Salaam, Tanzania, from national HIV and district health information system databases. We then excluded women who exited study sites before 6 months of ART follow-up and women who did not have a viral load test. Women were followed up until March 8, 2019. We used Poisson generalised estimating equations to examine trends in HIV viral suppression (<400 copies per mL) and virological failure (≥400 copies per mL), reporting relative risks (RRs) and 95% CIs adjusted for maternal age, gestational age, and several clinical characteristics. FINDINGS: We identified 15 586 pregnant women with HIV, of whom 10 161 were eligible for follow-up. Women were followed up for a median of 37 months (IQR 31-45) and a maximum of 53 months. The median age at PMTCT initiation was 31 years (IQR 27-35). At PMTCT enrolment, 1245 (17·0%) of 7318 women with available data were in their third trimester, 4901 (48·2%) of 10 161 women started ART at least 1 month before PMTCT enrolment, and 3380 (33·4%) of 10 131 women with available data had advanced HIV. Overall, a viral suppression rate of 88·2% (95% CI 87·8-88·7) was observed over the entire follow-up period, ranging from 85·1% (84·3-85·9) in viral load tests done at 0-11 months to 90·6% (89·7-91·4) at 36 months or longer since PMTCT enrolment. In a complete-case analysis (ie, including patients with <30% missing data; n=7306), the risk of virological failure among women who remained in HIV care decreased over time (adjusted RR 0·87 [95% CI 0·80-0·95] at 12-23 months since PMTCT enrolment; 0·65 [0·59-0·72] at 24-35 months; and 0·63 [0·55-0·71] at ≥36 months vs at 0-11 months). Younger women (aged <20 years: 1·76 [1·40-2·23] vs aged 30-39 years) and those starting PMTCT late in pregnancy (third trimester: 1·28 [1·10-1·50] vs first trimester) or with advanced HIV (1·33 [1·16-1·51] vs without advanced HIV) had increased risk of virological failure. Women who attended an antenatal care facility where more than 50% of attendees received couples HIV testing had a decreased risk of virological failure (adjusted RR 0·81 [0·65-0·99] vs <50% having couples testing). INTERPRETATION: High rates of viral suppression among women starting option B+ who remain in HIV care are sustainable, and might increase, at least up to 53 months. This rate might be further improved by addressing challenges of adolescent mothers, late presenters, and couples HIV testing at antenatal care. FUNDING: Swedish International Development Agency.

Pfeiffer Syndrome type 2; A case report of cranio-orbitofaciostenosis with bilateral choanal atresia at Muhimbili National Hospital, Tanzania.

Pfeiffer syndrome is a rare genetic disorder with heterogenous phenotype and prognosis. Due to its diverse clinical presentation, it can easily be misdiagnosed. Where genetic testing still remains a challenge, antenatal sonogram can aid in early diagnosis. The cranioorbito-faciostenosis demands aggressive management to permit survival instead of uniform early demise.

Vitamin D-Resistant Rickets Diagnostics and Treatment Challenges at Muhimbili National Hospital, Tanzania.

Introduction. Rickets is softening of bones caused by defective mineralization of the cartilage in the epiphyseal growth plate, causing widening of the ends of long bones, growth retardation, and skeletal deformities in children. It can be classified into calciopenic and phosphopenic, each type with various subclasses. Case Presentations. We presented 2 cases, first of a 1 year and 4-month-old male, with a history of recurrent episodes of cough for 8 months and bowing of the legs 6 months prior to admission. Clinical and laboratory investigation was suggestive of vitamin D-dependent rickets, and he started vitamin D treatment with minimal response. The second case is of a 4 years and 7-month-old male who presented with developmental delay, poor weight gain, and recurrent chest infection and worsening of bone pain since 9 months of age. Laboratory investigation was suggestive of phosphopenic rickets, and he was started on treatment at 9 months of age with little improvement and at 4 years, he sustained multiple fractures and succumbed to severe respiratory tract infection and died at 4 years and 7 months of age. CONCLUSION: Rickets pose a diagnostic and treatment challenge in resource-limited countries, and clinical judgment and early initiation of treatment are important.