David Shwe

Immunogenicity and safety of the candidate RTS,S/AS01 vaccine in young Nigerian children: a randomized, double-blind, lot-to-lot consistency trial.

BACKGROUND For regulatory approval, consistency in manufacturing of vaccine lots is expected to be demonstrated in confirmatory immunogenicity studies using two-sided equivalence trials. This randomized, double-blind study (NCT01323972) assessed consistency of three RTS,S/AS01 malaria vaccine batches formulated from commercial-scale purified antigen bulk lots in terms of anti-CS-responses induced. METHODS Healthy children aged 5-17 months were randomized (1:1:1:1) to receive RTS,S/AS01 at 0-1-2 months from one of three commercial-scale purified antigen bulk lots (1600 litres-fermentation scale; commercial-scale lots), or a comparator vaccine batch made from pilot-scale purified antigen bulk lot (20 litres-fermentation scale; pilot-scale lot). The co-primary objectives were to first demonstrate consistency of antibody responses against circumsporozoite (CS) protein at one month post-dose 3 for the three commercial-scale lots and second demonstrate non-inferiority of anti-CS antibody responses at one month post-dose 3 for the commercial-scale lots compared to the pilot-scale lot. Safety and reactogenicity were evaluated as secondary endpoints. RESULTS One month post-dose-3, anti-CS antibody geometric mean titres (GMT) for the 3 commercial scale lots were 319.6 EU/ml (95% confidence interval (CI): 268.9-379.8), 241.4 EU/ml (207.6-280.7), and 302.3 EU/ml (259.4-352.3). Consistency for the RTS,S/AS01 commercial-scale lots was demonstrated as the two-sided 95% CI of the anti-CS antibody GMT ratio between each pair of lots was within the range of 0.5-2.0. GMT of the pooled commercial-scale lots (285.8 EU/ml (260.7-313.3)) was non-inferior to the pilot-scale lot (271.7 EU/ml (228.5-323.1)). Each RTS,S/AS01 lot had an acceptable tolerability profile, with infrequent reports of grade 3 solicited symptoms. No safety signals were identified and no serious adverse events were considered related to vaccination. CONCLUSIONS RTS,S/AS01 lots formulated from commercial-scale purified antigen bulk batches induced a consistent anti-CS antibody response, and the anti-CS GMT of pooled commercial-scale lots was non-inferior to that of a lot formulated from a pilot-scale antigen bulk batch.

Factors associated with antiretroviral treatment interruption in human immunodeficiency virus (HIV)-1-infected children attending the Jos University Teaching Hospital, Jos, Nigeria

Background: Interrupting anti-retroviral therapy (ART) for any number of reasons is an indication of a compromised adherence to ART. Several factors, including the pill burden from other drugs used in treating co-infections in children with human immunodeficiency virus (HIV), may influence ART adherence. The aim of this study was to identify the factors associated with ART interruption in HIV-1-infected children. Materials and Methods: A retrospective cohort study analysing data on 580 children consecutively enrolled on ART between February 2006 and December 2010 at the paediatric HIV clinic of Jos University Teaching Hospital (JUTH), Jos. Subjects were children aged 2 months - 15 years diagnosed with HIV-1 infection and on first-line ART. Cotrimoxazole prophylaxis was usually commenced at diagnosis while awaiting ART commencement. Children diagnosed with tuberculosis (TB) were also placed on multiple individual anti-TB drugs. Statistical analysis used: A comparison of the data on children with and without ART interruption was made. Variables associated with ART interruption in a univariate analysis were fit in a multivariate logistic model to determine the factors that were associated with ART interruption. Results: Children on anti-TB drugs were twice more likely to interrupt ART compared to those who were not, (adjusted odds ratio, AOR = 1.84 (1.03-3.28); P = 0.04). But children on cotrimoxazole prophylaxis had a 57% reduction in the odds of interrupting ART compared to those who were not, (AOR = 0.43 (0.20-0.93); P = 0.03). Conclusion: Children on ART and also taking multiple individual anti-TB drugs should be monitored closely for ART adherence. Cotrimoxazole prophylaxis should be encouraged in children diagnosed with HIV while awaiting ART commencement as this may prime them for a better ART adherence.

Factors influencing irradiance of locally fabricated phototherapy devices in Jos, north-central Nigeria

Locally fabricated phototherapy devices (LFPDs) are widely used in Nigeria for the treatment of neonatal jaundice. Ours was a cross-sectional observational study of all LFPDs in major hospitals in Jos between January and March 2015. We evaluated a total of 24 LFPDs. The irradiance at the level of the baby was in the range of 2–23.9 µW/cm2/nm. Fourteen devices had the recommended irradiance of ≥10 µW/cm2/nm and none had irradiance in the intensive range. Decreasing distance from the baby, presence of reflectors and increasing number of flourecent tubes significantly contributed to higher irradiance. A combination of six tubes, presence of reflectors and a distance of 10 cm from the baby produced a mean irradiance of 23.40 µW/cm2/nm. The irradiance of LFPDs varies widely and can be improved by simple modifications.

Pathogenesis, diagnostic challenges and treatment of zika virus disease in resource-limited settings

The association of Zika virus (ZIKV) infection with congenital malformation and neurological sequelae has brought significant global concern. Consequently, the World Health Organization (WHO) declared it “a public health emergency of International concern” on 1 February, 2016. A critical review of its pathogenesis would lead to a better understanding of the clinical features and the neurological complications. This review is based on literature search in PubMed/Medline, Google Scholar and the WHO, http://www.who.int. This include all relevant articles written in English published through June 2018, with subject heading and keywords such as Zika, ZIKV, Zika pathogenesis, diagnosis of Zika, Zika Nigeria, Zika Africa and Zika resource-limited settings. Following ZIKV infection, viraemia ensues targeting primarily the monocytes for both the Asian and African strains. ZIKV infection by an African strain appears to be more pathogenic, in early pregnancy tends to result in spontaneous abortion. Whereas an Asian strain tends to be less pathogenic and more chronic, this allows the pregnancy to continue, ultimately resulting in congenital malformations. There is no routine laboratory diagnosis of ZIKV infection in resource-constrained countries. Serologic tests should be interpreted with caution since there can be cross-reactivity with other flaviviruses, especially in Africa where the burden of infection with flaviviruses is comparatively high. There is a paucity of well-equipped laboratories for comprehensive ZIKV diagnosis. It is imperative to strengthen the health systems, improve health workforce and diagnostic capacity of such settings.

Low Zika virus seroprevalence among pregnant women in North Central Nigeria, 2016

BACKGROUND Zika virus (ZIKV) has been known for decades in Africa but contemporary data is lacking at large. OBJECTIVES To describe the seroepidemiology of ZIKV in North Central Nigeria. STUDY DESIGN We performed a cross-sectional study at six health care facilities in North Central Nigeria from January to December 2016. Detection of ZIKV antibodies was done using an anti-ZIKV recombinant non-structural protein 1 (NS1)-based ELISA. A colorimetric assay to detect ZIKV neutralizing antibodies was used on ELISA reactive and randomly selected ELISA non-reactive samples. ZIKV real-time RT-PCR was done on a subset of samples. RESULTS A total of 468 individual samples were included with almost 60% from pregnant women. Using NS1-based ELISA, an anti-ZIKV positive rate of 6% for IgM and 4% for IgG was found. Pregnant women showed anti-ZIKV positive rates of 4% for IgM and 3% for IgG. None of the ZIKV antibody positive samples tested ZIKV RT-PCR positive. An association with male sex was found for anti-ZIKV IgG ELISA positivity (prevalence ratio 3.49; 95% confidence interval: 1.48-8.25; p = .004). No association with pregnancy, yellow fever vaccination or malaria was found for anti-ZIKV IgM or IgG positivity. ZIKV neutralizing antibodies were detected in 17/18 (94%) anti-ZIKV NS1 positive/borderline samples and in one sample without detectable ZIKV NS1 antibodies. Partial ZIKV E gene sequence was retrieved in one sample without ZIKV antibodies, which clustered within the West African ZIKV lineage. CONCLUSIONS Our results show a largely ZIKV immunologically naïve population and reinforce the importance of ZIKV surveillance in Africa.

Maternal and neonatal characteristics of babies admitted with congenital CNS anomalies in a tertiary hospital in North Central Nigeria

Background: CNS anomalies are an important group of largely preventable congenital anomalies. Knowledge of maternal and neonatal sociodemographic characteristics could identify a pattern of population at risk in order to target preventive interventions. Methods: This was a 3-year retrospective review of health records of all neonates admitted with CNS anomalies in Jos University Teaching Hospital (JUTH), Jos, central-Nigeria. Results: Out of a total of 27 neonates with congenital CNS anomalies reviewed, 25 had neural tube defects, 1 hydrocephalos and 1 anencephaly. The peak age group of mothers were 20-29years (44.4%) and 30-39 years (44.4%). Twenty-two (81.5%) mothers had antenatal care (ANC). No mother booked in the 1 month and only 7 (25.9%) booked in the first trimester. Twenty-four (88.9%) mothers took folic acid during pregnancy. No mother had periconceptional folic acid use. There were 11(40.7%) home births with 14(87.5%) of the 16 hospital births taking place in lower tier health facilities. Twenty-six (96.3%) mothers had vaginal delivery. An obstetric ultrasound scan was reported by one (3.7%) mother and did not detect the anomaly. Five (18.5%) of the mothers had HIV infection. Twenty-six were term with a male: female ratio of 1.1:1. The median age at presentation was 2 (interquartile range 1, 8) days. Conclusions: Neonates with congenital CNS anomalies in JUTH frequently had mothers aged <35 years who did not receive preventive care before and during delivery. We therefore recommend interventions to improve the efficiency of health care delivery to cater for this gap.

Paediatric Morbidity and Mortality in a Suburban Hospital in Jos, North -Central Nigeria

Background: Even though there has been some decline in childhood mortality, figures still remain high in subSaharan Africa. The pattern of morbidity and mortality in health care institutions may be a reflection of the disease burden of the community which it serves and will facilitate prevention/ control strategies. This study was conducted to determine the pattern of paediatric morbidity and mortality in a secondary level hospital in a sub – urban area in Jos, North – central Nigeria. Materials and Methods: This retrospective study is a review of paediatric admissions into the Vom Christian Hospital. Relevant data on all children who were admitted into the Vom Christian Hospital Original Research Article Toma et al.; IJTDH, 5(2): 156-164, 2015; Article no.IJTDH.2015.016 157 between May 2012 and April 2013 with medical conditions were retrieved from the admissions records. Data were entered into excel spread sheet and analyzed using Epi info 7. A p< 0.05 was considered statistically significant. Results: A total of 334 children aged between one day and 15 years were admitted during the period, out of which 235 (70.4%) were children less than 5 years old. Infections (221, 66.2%) were the major causes of morbidity. Out of all the 334 admissions, 304(91%) were discharged, 7 (2.1%) left against medical advice, 6(1.8%) were referred, while 17 (5.1%) died. Malaria was the commonest cause of morbidity (102, 30.5%) and mortality (6, 35.3%). Severe protein energy malnutrition had the highest case fatality rate (25%). Conclusion: The burden of paediatric morbidity and mortality is in children under 5 years and are mainly preventable. An emphasis on malaria eradication and child survival strategies will help to reduce childhood morbidity and mortality.