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Статті в журналах з теми "Pneumonia Prevention; Pneumonia Papua New Guinea"

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Автор: Grafiati

Опубліковано: 10 грудня 2022

Оновлено: 29 січня 2023

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1

Barnes, D. J., S. Naraqi, and J. D. Igo. "Community-Acquired Acinetobacter Pneumonia in Adults in Papua New Guinea." Clinical Infectious Diseases 10, no. 3 (May 1, 1988): 636–39. http://dx.doi.org/10.1093/clinids/10.3.636.

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2

SHANN, FRANK, DONALD MACGREGOR, JOHN RICHENS, and JOHN COAKLEY. "Cardiac failure in children with pneumonia in Papua New Guinea." Pediatric Infectious Disease Journal 17, no. 12 (December 1998): 1141–43. http://dx.doi.org/10.1097/00006454-199812000-00008.

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3

Witt, C. S., and M. P. Alpers. "Immune function in adult highland Papua New Guinea patients with pneumonia." Transactions of the Royal Society of Tropical Medicine and Hygiene 83, no. 2 (March 1989): 269–74. http://dx.doi.org/10.1016/0035-9203(89)90677-9.

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4

Groves, V. J., D. Lehmann, and G. L. Gilbert. "Seroepidemiology of cryptosporidiosis in children in Papua New Guinea and Australia." Epidemiology and Infection 113, no. 3 (December 1994): 491–99. http://dx.doi.org/10.1017/s0950268800068503.

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SUMMARYEnzyme immunoassays (EIA) were used to measure serum antibodies to Cryptosporidium in four immunocompetent adults with recent proven cryptosporidial infection, 379 healthy children and 73 adult volunteers in Melbourne, Australia, and 205 children in Papua New Guinea (PNG) (47 healthy children; 158 with pneumonia). Antibodies peaked 3–6 weeks after infection and fell to baseline within a few months. A high level (5000 EIA units/ml) or a significant change between paired sera, of IgG or IgM, were taken as evidence of recent infection and found in 24% of PNG children and in 8% of children and 5% of adults in Melbourne. Among PNG children with pneumonia who had high cryptosporidial antibody levels, those with measles (6/8) were significantly more likely (P = 0·002) to have diarrhoea than the remainder (4/28). Symptomatic cryptosporidiosis may be associated with transient immune suppression due to viral infection. This study indicates that serological surveys can contribute to an understanding of the epidemiology of cryptosporidosis.

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5

Pomat, W. S., T. A. Smith, R. C. Sanders, C. S. Witt, J. Montgomery, D. Lehmann, and M. P. Alpers. "Levels of anti-pneumococcal antibodies in young children in Papua New Guinea." Epidemiology and Infection 111, no. 1 (August 1993): 109–19. http://dx.doi.org/10.1017/s0950268800056739.

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SummaryAnti-pneumococcal polysaccharide antibody (anti-PPS) levels were measured in 153 serum samples collected from children aged between 2 and 47 months living in the highlands of Papua New Guinea (PNG). Fifty-seven of the samples were collected during acute episodes of lower respiratory tract infection (ALRI). Total IgA and IgG increased steadily with age; however, no association was found between the levels of these antibodies and the health status of the child. Total IgM levels showed little relationship to the age of the child but under 12 months of age levels were somewhat higher on average in children with pneumonia. For most of eight pneumococcal serotypes tested, specific IgG levels were found to decline rapidly in the first 6–8 months, reaching a minimum at approximately 12 months of age. Serotype 3 was exceptional in having very low titres in the youngest children. A separate analysis of 24 cord sera suggested that antibodies to this serotype do not usually cross the placenta in PNG. Children with pneumonia tended to have lower levels of specific IgG than healthy controls of the same age. Specific anti-PPS IgA levels were found to increase steadily with age, but were not associated with health status.

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6

Duke, Trevor, Francis Wandi, Merilyn Jonathan, Sens Matai, Magdalene Kaupa, Martin Saavu, Rami Subhi, and David Peel. "Improved oxygen systems for childhood pneumonia: a multihospital effectiveness study in Papua New Guinea." Lancet 372, no. 9646 (October 2008): 1328–33. http://dx.doi.org/10.1016/s0140-6736(08)61164-2.

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7

Walker, Emma C., Rashmi Ramani, Sarah Javati, Elizabeth Todd, Pallavi Chandra, John-Paul Matlam, Edgar Anaya, William Pomat, and Sharon Celeste Morley. "A novel variant in ubiquinone biosynthesis highly prevalent in Papua New Guinea children increases mortality following bacterial pneumonia." Journal of Immunology 204, no. 1_Supplement (May 1, 2020): 231.5. http://dx.doi.org/10.4049/jimmunol.204.supp.231.5.

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Abstract To identify immune variants predisposing to severe pneumonia, we performed whole exome sequencing in a pediatric population highly susceptible to acute lower respiratory infections, identifying a candidate novel variant in the ubiquinone (CoQ10) biosynthetic pathway. To evaluate the effect of this variant on immune function during bacterial pneumonia, we generated a mouse line using CRISPR-Cas9 that expresses the homologous aspartate to tyrosine variant in the enzyme COQ6. Intra-tracheal S. pneumoniae infection leads to increased bacteremia and mortality in mice homozygous for the variant despite similar numbers of immune cells in the lung. Mechanistic studies show that macrophages expressing the variant have decreased mitochondrial activity at the ubiquinone-dependent reduction of cytochrome c by complex III, as well as decreased maximum respiratory capacity in response to acute stimulation. Variant-expressing macrophages also exhibit impaired generation of mitochondrial reactive oxygen species (mROS) causing a direct, intrinsic defect in intracellular killing of internalized bacteria. Thus, the novel variant in CoQ10 biosynthesis leads to changes in macrophage mitochondria and an intrinsic inability to kill internalized bacteria. As alveolar macrophages are the first responders in the lung to bacterial challenge, the inability of these macrophages to mount a sufficient immune response can explain the observed increase in mortality following bacterial pneumonia. Because variants in CoQ10 biosynthesis can be supplemented with CoQ10, a readily available therapy may be able to correct this defect and improve survival in children with this variant

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8

Kim, Jinseob, Jong-Hun Kim, Hae-Kwan Cheong, Ho Kim, Yasushi Honda, Mina Ha, Masahiro Hashizume, Joel Kolam, and Kasis Inape. "Effect of Climate Factors on the Childhood Pneumonia in Papua New Guinea: A Time-Series Analysis." International Journal of Environmental Research and Public Health 13, no. 2 (February 15, 2016): 213. http://dx.doi.org/10.3390/ijerph13020213.

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9

Spooner, V., J. Barker, S. Tulloch, D. Lehmann, T. F. d. C. Marshall, M. Kajoi, and M. P. Alpers. "Clinical Signs and Risk Factors Associated with Pneumonia in Children Admitted to Goroka Hospital, Papua New Guinea." Journal of Tropical Pediatrics 35, no. 6 (December 1, 1989): 295–300. http://dx.doi.org/10.1093/tropej/35.6.295.

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10

Anga, G., J. D. Vince, and M. Kaupa. "Early Introduction of Solids and Pneumonia in Young Infants in Papua New Guinea: A Case Control Study." Journal of Tropical Pediatrics 54, no. 3 (October 15, 2007): 192–95. http://dx.doi.org/10.1093/tropej/fmm102.

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11

WITT, C. S., W. POMAT, D. LEHMANN, and M. P. ALPERS. "Antibodies to pneumococcal polysaccharides in pneumonia and response to pneumococcal vaccination in young children in Papua New Guinea." Clinical & Experimental Immunology 83, no. 2 (June 28, 2008): 219–24. http://dx.doi.org/10.1111/j.1365-2249.1991.tb05618.x.

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12

Kim, Jinseob, Hae-Kwan Cheong, Ho Kim, Yasushi Honda, Mina Ha, Hashizume Masahiro, and Kasis Inape. "The Impact of Local and Oceanic Climate Variability on the Incidence of Childhood Pneumonia in Papua New Guinea." ISEE Conference Abstracts 2013, no. 1 (September 19, 2013): 4350. http://dx.doi.org/10.1289/isee.2013.p-1-12-30.

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13

Pulsan, Francis, Kone Sobi, and Trevor Duke. "Continuous positive airway pressure in children with severe pneumonia and hypoxaemia in Papua New Guinea: an evaluation of implementation." Acta Paediatrica 108, no. 10 (April 11, 2019): 1887–95. http://dx.doi.org/10.1111/apa.14796.

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14

Shann, F., S. Walters, L. L. Pifer, D. M. Graham, I. Jack, E. Uren, D. Birch, and N. D. Stallman. "Pneumonia associated with infection with pneumocystis, respiratory syncytial virus, chlamydia, mycoplasma, and cytomegalovirus in children in Papua New Guinea." BMJ 292, no. 6516 (February 1, 1986): 314–17. http://dx.doi.org/10.1136/bmj.292.6516.314.

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15

Duke, Trevor, Harry Poka, Frank Dale, Audrey Michael, Joyce Mgone, and Tilda Wal. "Chloramphenicol versus benzylpenicillin and gentamicin for the treatment of severe pneumonia in children in Papua New Guinea: a randomised trial." Lancet 359, no. 9305 (February 2002): 474–80. http://dx.doi.org/10.1016/s0140-6736(02)07677-8.

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16

Unger, Holger W., Celestine Aho, Maria Ome-Kaius, Regina A. Wangnapi, Alexandra J. Umbers, Wanda Jack, Alice Lafana, et al. "Impact of Intermittent Preventive Treatment in Pregnancy with Azithromycin-Containing Regimens on Maternal Nasopharyngeal Carriage and Antibiotic Sensitivity of Streptococcus pneumoniae, Haemophilus influenzae, and Staphylococcus aureus: a Cross-Sectional Survey at Delivery." Journal of Clinical Microbiology 53, no. 4 (February 11, 2015): 1317–23. http://dx.doi.org/10.1128/jcm.03570-14.

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Sulfadoxine-pyrimethamine (SP) plus azithromycin (AZ) (SPAZ) has the potential for intermittent preventive treatment of malaria in pregnancy (IPTp), but its use could increase circulation of antibiotic-resistant bacteria associated with severe pediatric infections. We evaluated the effect of monthly SPAZ-IPTp compared to a single course of SP plus chloroquine (SPCQ) on maternal nasopharyngeal carriage and antibiotic susceptibility ofStreptococcus pneumoniae,Haemophilus influenzae, andStaphylococcus aureusat delivery among 854 women participating in a randomized controlled trial in Papua New Guinea. Serotyping was performed, and antibiotic susceptibility was evaluated by disk diffusion and Etest. Potential risk factors for carriage were examined. Nasopharyngeal carriage at delivery ofS. pneumoniae(SPAZ, 7.2% [30/418], versus SPCQ, 19.3% [84/436];P< 0.001) andH. influenzae(2.9% [12/418] versus 6.0% [26/436],P= 0.028), but notS. aureus, was significantly reduced among women who had received SPAZ-IPTp. The number of macrolide-resistant pneumococcal isolates was small but increased in the SPAZ group (13.3% [4/30], versus SPCQ, 2.2% [2/91];P= 0.033). The proportions of isolates with serotypes covered by the 13-valent pneumococcal conjugate vaccine were similar (SPAZ, 10.3% [3/29], versus SPCQ, 17.6% [16/91];P= 0.352). Although macrolide-resistant isolates were rare, they were more commonly detected in women who had received SPAZ-IPTp, despite the significant reduction of maternal carriage ofS. pneumoniaeandH. influenzaeobserved in this group. Future studies on SPAZ-IPTp should evaluate carriage and persistence of macrolide-resistantS. pneumoniaeand other pathogenic bacteria in both mothers and infants and assess the clinical significance of their circulation.

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17

Barker, J., M. Gratten, I. Riley, D. Lehmann, J. Montgomery, M. Kajoi, H. Gratten, D. Smith, T. F. De C. Marshall, and M. P. Alpers. "Pneumonia in Children in the Eastern Highlands of Papua New Guinea: A Bacteriologic Study of Patients Selected by Standard Clinical Criteria." Journal of Infectious Diseases 159, no. 2 (February 1, 1989): 348–52. http://dx.doi.org/10.1093/infdis/159.2.348.

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18

Morre, Rose, Kone Sobi, Wendy Pameh, Paulus Ripa, John D. Vince, and Trevor Duke. "Safety, Effectiveness and Feasibility of Outpatient Management of Children with Pneumonia with Chest Indrawing at Port Moresby General Hospital, Papua New Guinea." Journal of Tropical Pediatrics 65, no. 1 (April 6, 2018): 71–77. http://dx.doi.org/10.1093/tropej/fmy013.

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19

Blyth, Christopher C., Kathryn J. Britton, Cattram D. Nguyen, Joycelyn Sapura, John Kave, Birunu Nivio, Jocelyn Chan, et al. "Effectiveness of 13-valent pneumococcal conjugate vaccine against hypoxic pneumonia and hospitalisation in Eastern Highlands Province, Papua New Guinea: An observational cohort study." Lancet Regional Health - Western Pacific 22 (May 2022): 100432. http://dx.doi.org/10.1016/j.lanwpc.2022.100432.

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20

Pukai, Gordon, and Trevor Duke. "Nebulised normal saline in moderate acute bronchiolitis and pneumonia in a low- to middle-income country: a randomised trial in Papua New Guinea." Paediatrics and International Child Health 40, no. 3 (February 17, 2020): 171–76. http://dx.doi.org/10.1080/20469047.2020.1725338.

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21

Walker, Emma C., Elizabeth Todd, Rashmi Ramani, Edgar Anaya, Sarah Javati, John-Paul Matlam, William Pomat, and S. Celeste Morley. "A novel function for the CoQ10 biosynthetic complex in anti-pneumococcal macrophage function." Journal of Immunology 208, no. 1_Supplement (May 1, 2022): 50.27. http://dx.doi.org/10.4049/jimmunol.208.supp.50.27.

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Abstract Despite the recent introduction of pneumococcal polysaccharide and conjugate vaccines, Streptococcus pneumoniae infection remains a leading cause of illness and death worldwide. In particular, infants in Papua New Guinea are at increased risk of severe pneumococcal pneumonia compared to infants in similar countries. We sought to determine if a novel genetic variant could explain this increased susceptibility. Whole exome sequencing revealed a single nucleotide variant (D308Y) in the gene encoding COQ6 (COQ6DY), a monooxygenase required for CoQ10 biosynthesis. We have utilized both a Saccharomyces cerevisiae model and a mouse model of COQ6DY to show that despite adequate production of CoQ10, this variant directly causes increased susceptibility to S. pneumoniae. This variant represents a previously unknown function of the CoQ10 biosynthetic complex that does not exert its effects through CoQ10 deficiency but rather through alterations of mitochondrial function and metabolism. These mitochondrial deficits in COQ6DY macrophages are sufficient to abrogate macrophage killing of S. pneumoniae and alter the coordination of the downstream immune response. In conclusion, we have identified a novel susceptibility allele to S. pneumoniae infection that exerts its effects via alterations in macrophage mitochondrial function. Supported by NIH (R21 AI142723), SLCH Children's Discovery Institute (PD-II-2018-742)

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22

Witt, Campbell S., Janet M. Montgomery, WUliam Pomat, Deborah Lehmann, and Michael P. Alpers. "Detection of Streptococcus pneumoniae and Haemophilus influenzae Type b Antigens in the Serum and Urine of Patients with Pneumonia in Papua New Guinea: Comparison of Latex Agglutination and Counterimmunoelectrophoresis." Clinical Infectious Diseases 12, Supplement_8 (November 1, 1990): S1001—SI005. http://dx.doi.org/10.1093/clinids/12.supplement_8.s1001.

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23

Blanc, Julien, Isabella Locatelli, Patricia Rarau, Ivo Mueller, Blaise Genton, Noémie Boillat-Blanco, Mario Gehri, and Nicolas Senn. "Retrospective study on the usefulness of pulse oximetry for the identification of young children with severe illnesses and severe pneumonia in a rural outpatient clinic of Papua New Guinea." PLOS ONE 14, no. 4 (April 15, 2019): e0213937. http://dx.doi.org/10.1371/journal.pone.0213937.

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24

Nguyen, Cattram, Rupert Weaver, Christopher Blyth, Claire von Mollendorf, Kate Britton, Jocelyn Chan, David A. B. Dance, et al. "383Pneumococcal conjugate vaccine is effective against hypoxic pneumonia in Laos, Mongolia and Papua New Guinea." International Journal of Epidemiology 50, Supplement_1 (September 1, 2021). http://dx.doi.org/10.1093/ije/dyab168.481.

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Abstract Background We describe a novel approach to determine PCV13 effectiveness (VE) against hypoxic pneumonia in children admitted with pneumonia in Lao People’s Democratic Republic (Laos), Mongolia and Papua New Guinea (PNG). Methods A 3-5 year prospective hospital-based observational study of children < =59 months admitted with pneumonia was undertaken. Pneumonia was defined using the 2013 WHO definition. Hypoxia was defined as an oxygen saturation <90% in room air or requiring oxygen supplementation during hospitalisation. PCV13 status was determined by written record. VE was calculated using logistic regression comparing the odds of hypoxia between vaccinated and under-vaccinated pneumonia cases. To handle potential confounding, a propensity score (PS) analysis using inverse probability of treatment weighting (IPW) was used. In Laos, multiple imputation (MI) analysis was undertaken for missing data. Results The VE against hypoxic pneumonia were: in Laos, unadjusted 23% (95% CI: -9, 46%; p = 0·14), IPW adjusted 37% (6, 57%; p = 0.02), MI and IPW adjusted 35% (7, 55%; p = 0.02); in Mongolia, unadjusted 33% (26, 40%; p < 0.001), IPW adjusted 33% (16, 47%; p < 0.001); and in PNG, unadjusted 6% (-15, 24%; p = 0.53), IPW adjusted 36% (17, 51%; p = 0.001). Conclusions Our novel approach shows that PCV13 is effective against hypoxic pneumonia. PCV13 will contribute to reducing child mortality. Key messages We describe a novel, single hospital-based approach for determining VE that can be applied to other similar settings. This is one of the first studies showing PCV13 to be effective against hypoxic pneumonia in children in Asia.

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Britton, Kathryn, William Pomat, Rebecca Ford, Joycelyn Sapura, John Kave, Birunu Nivio, Clinical Deborah Lehmann, Jocelyn Chan, Fiona Russell, and Clinical Christopher Blyth. "997Childhood pneumonia in the Eastern Highlands Province, Papua New Guinea: clinical predictors of severe disease." International Journal of Epidemiology 50, Supplement_1 (September 1, 2021). http://dx.doi.org/10.1093/ije/dyab168.098.

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Abstract Background Pneumonia is the leading cause of death in young children globally and is prevalent in the highlands of Papua New Guinea (PNG). We investigated clinical predictors of severe pneumonia to inform local treatment guidelines in this resource-limited setting. Methods Between 2013 and 2020, prospective studies were undertaken enrolling children <5 years presenting with pneumonia to health-care facilities in Goroka Town, Eastern Highlands Province. Physical examination findings and blood cultures were collected. Logistic regression analyses were performed to determine predictors of hypoxaemia (oxygen saturation <90% on presentation), bacteraemia and death. Results There were 2067 cases of pneumonia, hypoxaemia was detected in 36.1%. Bacteraemia was identified in 47/1943 (2.4%) blood cultures. Of 1444 children followed up, 18 (1.2%) died. Central cyanosis (odds ratio 3.82, 95% CI 2.55-5.71) and reduced breath sounds (2.77, 2.17-3.53) independently predicted hypoxaemia; altered consciousness (21.44, 3.91-117.48), bronchial breathing (10.49, 2.01-54.63) and apnoea (2.54, 1.26-5.14) independently predicted bacteraemia; and altered consciousness (20.95, 2.32-189.00), reduced skin turgor (14.43 (4.79-43.49) and central cyanosis (5.96, 2.13-16.66) independently predicted death. Conclusions In children with pneumonia in the PNG highlands, those with central cyanosis, apnoea, bronchial breathing, altered consciousness or reduced skin turgor are at greatest risk of severe outcomes. Ongoing training of health care workers is essential to ensure these signs are recognised and appropriate management promptly instituted. Key messages Prompt recognition of signs of severity is likely to lead to better outcomes for children in PNG with pneumonia. These findings will inform future modifications to local treatment guidelines.

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Duke, Trevor, Francis Pulsan, Doreen Panauwe, Ilomo Hwaihwanje, Martin Sa'avu, Magdalynn Kaupa, Jonah Karubi, et al. "Solar-powered oxygen, quality improvement and child pneumonia deaths: a large-scale effectiveness study." Archives of Disease in Childhood, October 16, 2020, archdischild—2020–320107. http://dx.doi.org/10.1136/archdischild-2020-320107.

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BackgroundPneumonia is the largest cause of child deaths in low-income countries. Lack of availability of oxygen in small rural hospitals results in avoidable deaths and unnecessary and unsafe referrals.MethodWe evaluated a programme for improving reliable oxygen therapy using oxygen concentrators, pulse oximeters and sustainable solar power in 38 remote health facilities in nine provinces in Papua New Guinea. The programme included a quality improvement approach with training, identification of gaps, problem solving and corrective measures. Admissions and deaths from pneumonia and overall paediatric admissions, deaths and referrals were recorded using routine health information data for 2–4 years prior to the intervention and 2–4 years after. Using Poisson regression we calculated incidence rates (IRs) preintervention and postintervention, and incidence rate ratios (IRR).ResultsThere were 18 933 pneumonia admissions and 530 pneumonia deaths. Pneumonia admission numbers were significantly lower in the postintervention era than in the preintervention era. The IRs for pneumonia deaths preintervention and postintervention were 2.83 (1.98–4.06) and 1.17 (0.48–1.86) per 100 pneumonia admissions: the IRR for pneumonia deaths was 0.41 (0.24–0.71, p<0.005). There were 58 324 paediatric admissions and 2259 paediatric deaths. The IR for child deaths preintervention and postintervention were 3.22 (2.42–4.28) and 1.94 (1.23–2.65) per 100 paediatric admissions: IRR 0.60 (0.45–0.81, p<0.005). In the years postintervention period, an estimated 348 lives were saved, at a cost of US$6435 per life saved and over 1500 referrals were avoided.ConclusionsSolar-powered oxygen systems supported by continuous quality improvement can be achieved at large scale in rural and remote hospitals and health care facilities, and was associated with reduced child deaths and reduced referrals. Variability of effectiveness in different contexts calls for strengthening of quality improvement in rural health facilities.Trial registration numberACTRN12616001469404.

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Blyth, Christopher C., Rebecca Ford, Joycelyn Sapura, Tonny Kumani, Geraldine Masiria, John Kave, Lapule Yuasi, et al. "Childhood pneumonia and meningitis in the Eastern Highlands Province, Papua New Guinea in the era of conjugate vaccines: study methods and challenges." Pneumonia 9, no. 1 (March 5, 2017). http://dx.doi.org/10.1186/s41479-017-0029-y.

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Pulsan, Francis, and Trevor Duke. "Response to oxygen therapy using oxygen concentrators run off solar power in children with respiratory distress in remote primary health facilities in Papua New Guinea." Tropical Doctor, August 17, 2020, 004947552094788. http://dx.doi.org/10.1177/0049475520947886.

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Oxygen therapy reduces mortality and morbidity from hypoxaemia in children. There are no published studies assessing individual patient responses to oxygen when delivered by oxygen concentrators in primary healthcare facilities. Ours was a prospective observational study in remote health facilities over three years. A data recording form was used for children who required oxygen. Oxygen saturation (SpO2) was recorded before administration of oxygen, at 30 min and then daily. We assessed the primary diagnosis and the outcome. The common primary diagnoses needing oxygen were pneumonia: moderate (39%) and severe (37%). The median SpO2 before administration of oxygen in 913 patients was 80% (interquartile range [IQR] 66%–88%), and by five days, for the 121 patients who were recorded, SpO2 was 97% (IQR 93%–98%). Of the 745 patients with a recorded outcome, 99% had an uneventful recovery. We conclude that oxygen concentrators are effective in treating children in rural health facilities in Papua New Guinea.

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Mukap, Mispah, Corin Sprod, Nakapi Tefuarani, Moses Laman, Madhu Page-Sharp, Sam Salman, Brioni R. Moore, Kevin T. Batty, Timothy M. E. Davis, and Laurens Manning. "Validation of a Dried Blood Spot Ceftriaxone Assay in Papua New Guinean Children with Severe Bacterial Infections." Antimicrobial Agents and Chemotherapy 62, no. 10 (July 16, 2018). http://dx.doi.org/10.1128/aac.00940-18.

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ABSTRACT Dried blood spot (DBS) antibiotic assays can facilitate pharmacokinetic (PK) studies in situations where venous blood sampling is logistically and/or ethically challenging. In this study, we aimed to demonstrate the validity of a DBS ceftriaxone assay in a PK study of children with severe illness from Papua New Guinea (PNG), a setting in which health care resources are limited and anemia is common. Using a previously validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay, serial plasma and DBS ceftriaxone concentrations were measured in PNG children aged 5 to 10 years with acute bacterial meningitis or severe pneumonia. The concentration-time data were incorporated into population PK models. Ten children were recruited with an admission hematocrit of 0.22 to 0.52. Raw data demonstrated good correlation between plasma and DBS concentrations (Spearman's rank correlation coefficient [rs] = 0.94 [95% confidence interval, 0.91 to 0.97], P < 0.0001). A marked systematic hematocrit bias was observed, with lower hematocrits resulting in underestimation of DBS-predicted plasma concentration. After adjustment for red cell partitioning and hematocrit bias, a population PK model comparing plasma and DBS-predicted plasma concentrations did not differ in terms of key PK parameters, including clearance, volume of distribution, and residual variability. The performance of the ceftriaxone DBS assay is robust and provides reassurance that this platform can be used as a surrogate for plasma concentrations to provide valid PK and PK/pharmacodynamic studies of severely unwell children hospitalized in a resource-limited setting. It highlights the importance of hematocrit bias in validation studies of DBS assays.

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Martinovich, Kelly M., Elke J. Seppanen, Amy S. Bleakley, Sharon L. Clark, Ross M. Andrews, Peter C. Richmond, Michael J. Binks, Ruth B. Thornton, and Lea-Ann S. Kirkham. "Evidence of maternal transfer of antigen-specific antibodies in serum and breast milk to infants at high-risk of S. pneumoniae and H. influenzae disease." Frontiers in Immunology 13 (September 21, 2022). http://dx.doi.org/10.3389/fimmu.2022.1005344.

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IntroductionChildren in low-mid income countries, and First Nations children in high-income countries, experience disproportionately high rates of Streptococcus pneumoniae and Haemophilus influenzae infections and diseases including pneumonia and otitis media. We previously observed that infants from Papua New Guinea had no evidence of waning maternal immunity for H. influenzae-specific antibodies. In this study, we assessed S. pneumoniae and H. influenzae antibody titres in Australian First Nation mothers and infants to determine antigen-specific antibody ontogenies and whether H. influenzae antibody titres in infants were due to low maternal antibody titres or lack of placental transfer.MethodsBreast milk, infant nasopharyngeal swabs and ear assessment data were collected 1-, 2-, 7-months post-birth as well as maternal, cord and 7-month-old infant sera, from 85 Australian Aboriginal and Torres Strait Islander mother-infant pairs. Serum IgG and breast milk IgG and IgA antibody titres to S. pneumoniae antigens (PspA1, PspA2, CbpA, Ply) and H. influenzae antigens (PD, ChimV4, OMP26, rsPilA) were measured.ResultsIgG titres in maternal and cord sera were similar for all antigens, except Ply (higher in cord; p=0.004). Sera IgG titres at 7-months of age were lower than cord sera IgG titres for all S. pneumoniae antigens (p<0.001). Infant sera IgG titres were higher than cord sera for H. influenzae PD (p=0.029), similar for OMP26 (p=0.817) and rsPilA (p=0.290), and lower for ChimV4 (p=0.004). Breast milk titres were similar for all antigens at 1, 2 and 7-months except OMP26 IgA (lower at 7-months than 1-month; p=0.035), PspA2 IgG (p=0.012) and Ply IgG that increased by 7-months (p=0.032). One third of infants carried nontypeable Haemophilus influenzae (NTHi), 45% carried S. pneumoniae and 52% had otitis media (OM) observed at least once over the 7-months. 73% of infants who carried either S. pneumoniae or NTHi, also had otitis media observed.ConclusionsSimilarities between maternal and cord IgG titres, and absence of waning, support a lack of maternal H. influenzae IgG antibodies available for cross-placental transfer. Increased maternal anti-PD IgG could offer some protection from early carriage with NTHi, and maternal immunisation strategies should be considered for passive-active immunisation of infants to protect against S. pneumoniae and H. influenzae diseases.Trial registrationClinicalTrials.gov NCT00714064 and NCT00310349.

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