Browsing by Author "Mturi, Neema"

Now showing 1 - 2 of 2
  • Thumbnail Image
    Item
    Dosing of Ceftriaxone and Metronidazole for Children With Severe Acute Malnutrition
    (Clinical Pharmacology & Therapeutics, 2018) Standing, Joseph F.; Ongas, Martin O.; Ogwang, Caroline; Kagwanja, Nancy; Murunga, Sheila; Mwaringa, Shalton; Ali, Rehema; Mturi, Neema; Timbwa, Moline; Manyasi, Christine; Mwalekwa, Laura; Bandika, Victor L.; Ogutu, Bernhards; Waichungo, Joseph; Kipper, Karin; Berkley, James A.
    Infants and young children with severe acute malnutrition (SAM) are treated with empiric broad-spectrumantimicrobials. Parenteral ceftriaxone is currently a second-line agent for invasive infection. Oral metronidazole principally targets small intestinal bacterial overgrowth. Children with SAM may have altered drug absorption, distribution, metabolism, and elimination. Population pharmacokinetics of ceftriaxone and metronidazole were studied, with the aimof recommending optimal dosing. Eighty-one patients with SAM (aged 2–45 months) provided 234 postdose pharmacokinetic samples for total ceftriaxone, metronidazole, and hydroxymetronidazole. Ceftriaxone protein binding was alsomeasured in 190 of these samples. A three-compartment model adequately described free ceftriaxone, with a Michaelis–Menten model for concentration and albumin-dependent protein binding. A one-compartment model was used for both metronidazole and hydroxymetronidazole, with only 1% of hydroxymetronidazole predicted to be formed during first-pass. Simulations showed 80mg/kg once daily of ceftriaxone and 12.5mg/kg twice daily ofmetronidazole were sufficient to reach therapeutic targets.
  • Thumbnail Image
    Item
    Malaria hospitalisation in East Africa: age, phenotype and transmission intensity
    (BMC medicine, 2022) Kamau, Alice; Paton, Robert S.; Akech, Samuel; Mpimbaza, Arthur; Khazenzi, Cynthia; Ogero, Morris; Mumo, Eda; Alegana, Victor A.; Agweyu, Ambrose; Mturi, Neema; Mohammed, Shebe; Bigogo, Godfrey; Audi, Allan; Kapisi, James; Sserwanga, Asadu; Namuganga, Jane F.; Kariuki, Simon; Otieno, Nancy A.; Nyawanda, Bryan O.; Olotu, Ally; Salim, Nahya; Athuman, Thabit; Abdulla, Salim; Mohamed, Amina F.; Mtove, George; Reyburn, Hugh; Gupta, Sunetra; Lourenço, José; Bejon, Philip; Snow, Robert W.
    Understanding the age patterns of disease is necessary to target interventions to maximise costeffective impact. New malaria chemoprevention and vaccine initiatives target young children attending routine immunisation services. Here we explore the relationships between age and severity of malaria hospitalisation versus malaria transmission intensity. Methods: Clinical data from 21 surveillance hospitals in East Africa were reviewed. Malaria admissions aged 1 month to 14 years from discrete administrative areas since 2006 were identified. Each site-time period was matched to a model estimated community-based age-corrected parasite prevalence to provide predictions of prevalence in childhood (PfPR2–10). Admission with all-cause malaria, severe malaria anaemia (SMA), respiratory distress (RD) and cerebral malaria (CM) were analysed as means and predicted probabilities from Bayesian generalised mixed models. Results: 52,684 malaria admissions aged 1 month to 14 years were described at 21 hospitals from 49 site-time locations where PfPR2–10 varied from < 1 to 48.7%. Twelve site-time periods were described as low transmission (PfPR2–10 < 5%), five low-moderate transmission (PfPR2–10 5–9%), 20 moderate transmission (PfPR2–10 10–29%) and 12 high transmission (PfPR2–10 ≥ 30%). The majority of malaria admissions were below 5 years of age (69–85%) and rare among children aged 10–14 years (0.7–5.4%) across all transmission settings. The mean age of all-cause malaria hospitalisation was 49.5 months (95% CI 45.1, 55.4) under low transmission compared with 34.1 months (95% CI 30.4, 38.3) at high transmission, with similar trends for each severe malaria phenotype. CM presented among older children at a mean of 48.7 months compared with 39.0 months and 33.7 months for SMA and RD, respectively. In moderate and high transmission settings, 34% and 42% of the children were aged between 2 and 23 months and so within the age range targeted by chemoprevention or vaccines. Conclusions: Targeting chemoprevention or vaccination programmes to areas where community-based parasite prevalence is ≥10% is likely to match the age ranges covered by interventions (e.g. intermittent presumptive treatment in infancy to children aged 2–23 months and current vaccine age eligibility and duration of efficacy) and the age ranges of highest disease burden.