Therapeutic Efficacy and Effects of Artesunate-Mefloquine and Mefloquine Alone on Malaria-Associated Anemia in Children with Uncomplicated Plasmodium falciparum Malaria in Southwest Nigeria

The treatment efficacy and effects of artesunate-mefloquine (AMQ) and mefloquine (MQ) on malariaassociated anemia (MAA) were evaluated in 342 children ≤ 10 years of age with uncomplicated Plasmodium falciparum malaria randomized to receive either drug/drug combination. All children recovered clinically. Fever clearance times were similar. Parasite clearance was significantly faster with AMQ (mean ± SD = 1.4 ± 0.6 days, 95% confidence interval [CI] = 1.3–1.5, P < 0.0001), but polymerase chain reaction–corrected cure rates were similar (97% versus 94%). Gametocyte carriage rates and the drug-attributable fall in hematocrit were significantly lower with AMQ (mean ± SD = 4.8 ± 3.8%, 95% CI = 3.6–6.0, P = 0.03), but the rates of resolution of MAA were similar. Both regimens were well tolerated. AMQ clears parasitemia and reduces gametocyte carriage more rapidly and causes lesser fall in hematocrit than MQ, but both regimens are effective treatment of uncomplicated P. falciparum malaria in Nigerian children

Use of area under the curve to evaluate the effects of antimalarial drugs on malaria associated anemia after treatment

To evaluate the effects of antimalarial drugs on Plasmodium falciparum malaria associated anemia (MAA), we use the area under curve (AUC) of anemia levels after treatment as an approach to combine their duration and magnitude. The method involves numerical estimation, by trapezoidal rule, of AUC from a plot of deficit in hematocrit levels from 30% (the lower threshold of normal) versus time in anemic children. Using the method, we evaluated, in randomized trials, the effects of artesunate-mefloquine (AMQ) versus mefloquine alone (MQ), and artemether-lumefantrine (AL) versus amodiaquine-artesunate (AA) on the time-course of recovery from MAA in 109 children. Anemia resolution times were similar (10.9 ± 6.2 [SD] vs 13.3 ± 8.9 d, P = 0.2) but mean AUC was significantly lower in AMQ- compared to MQ- treated children (35.5 ± 7.1 [SEM] vs 49.8 ± 11.3 %.h, P = 0.02) indicating larger exposure to anemia in MQ-treated children. In ALand AA- treated children, both anemia resolution times (8.6 ± 5.3 [SD] vs 8.6 ± 4.8 d, P = 0.98) and mean AUC (57.1 ± 12.9 [SEM] vs 46.3 ± 8.7 %.h, P = 0.74) were similar. Estimation of AUC appears more robust than estimation of anemia resolution time in evaluating antimalarial drug effects and can be used in both observational studies and clinical trials assessing the effects of therapies on MAA

Early variations in plasmodium falciparum dynamics in Nigerian children after treatment with two artemisinin-based combinations: implications on delayed parasite clearance

<p>Abstract</p> <p>Background</p> <p>Combination treatments, preferably containing an artemisinin derivative, are recommended to improve efficacy and prevent <it>Plasmodium falciparum </it>drug resistance. Artemether-lumefantrine (AL) and artesunate-amodiaquine (AA) are efficacious regimens that have been widely adopted in sub-Saharan Africa. However, most study designs ignore the effects of these regimens on peripheral parasitaemia in the first 24 hours of therapy. The study protocol was designed to evaluate more closely the early effects and the standard measures of efficacies of these two regimens.</p> <p>Methods</p> <p>In an open label, randomized controlled clinical trial, children aged 12 months to 132 months were randomized to receive AL (5-14 kg, one tablet; 15-24 kg, two tablets and 25-34 kg, three tablets twice daily) or artesunate (4 mg/kg daily) plus amodiaquine (10 mg/kg daily) for three days. Peripheral blood smears were made hourly in the first 4 hours, 8 h, 16 h, 24 h, and daily on days 2-7, and on days 7, 14, 21, 28, 35, and 42 for microscopic identification and quantification of <it>Plasmodium falciparum</it>.</p> <p>Results</p> <p>A total of 193 children were randomized to receive either AL (97) or AA (96). In children that received both medications, early response of peripheral parasitaemia showed that 42% of children who received AL and 36.7% of those who received AA had an immediate rise in peripheral parasitaemia (0-4 h after treatment) followed by a rapid fall. The rise in parasitaemia was significant and seems to suggest a mobilization of asexual parasites from the deep tissues to the periphery. Days 3, 7, 14, 28, and 42 cure rates in the per protocol (PP) population were > 90% in both groups of children. Both drug combinations were well tolerated with minimal side effects.</p> <p>Conclusion</p> <p>The study showed the high efficacy of AL and AA in Nigerian children. In addition the study demonstrated the mobilisation of asexual parasites from the deep to the periphery in the early hours of commencing ACT treatment in a subset of patients in both study groups. It is unclear whether the early parasite dynamics discovered in this study play any role in the development of drug resistance and thus it is important to further evaluate this discovery. It may be useful for studies investigating delay in parasite clearance of artemisinin derivatives as a way of monitoring the development of resistance to artemisinin to assess the early effects of the drugs on the parasites.</p

Plasmodium falciparum gametocyte carriage, emergence, clearance and population sex ratios in anaemic and non-anaemic malarious children

Anaemia in falciparum malaria is associated with an increased risk of gametocyte carriage, but its effects on transmission have not been extensively evaluated in malarious children. Plasmodium falciparum gametocyte carriage, emergence, clearance, population sex ratios (SR) (defined as the proportion of gametocytes that are male), inbreeding rates and temporal changes in SR were evaluated in 840 malarious children. Gametocyte carriage pre-treatment was at a level of 8.1%. Anaemia at enrolment was an independent risk factor for gametocyte carriage post-treatment. The emergence of gametocytes seven days post-treatment was significantly more frequent in anaemic children (7/106 vs. 10/696, p = 0.002). In the initially detected gametocytes, the proportion of children with a male-biased SR (MBSR) (> 0.5) was significantly higher in anaemic children (6/7 vs. 3/10, p = 0.027). Pre-treatment SR and estimated inbreeding rates (proportion of a mother’s daughters fertilised by her sons) were similar in anaemic and non-anaemic children. Pre-treatment SR became more female-biased in non-anaemic children following treatment. However, in anaemic children, SR became male-biased. Anaemia was shown to significantly increase gametocyte emergence and may significantly alter the SR of emerging gametocytes. If MBSR is more infective to mosquitoes at low gametocytaemia, then these findings may have significant implications for malaria control efforts in endemic settings where malaria-associated anaemia is common

Therapeutic Efficacy and Effects of Artemether-Lumefantrine and Artesunate-Amodiaquine Coformulated or Copackaged on Malaria-Associated Anemia in Children with Uncomplicated Plasmodium falciparum Malaria in Southwest Nigeria

The therapeutic efficacy and effects of artemether-lumefantrine (AL) and artesunate-amodiaquine coformulated (AAcf) or co-packaged (AAcp) on malaria-associated anemia (MAA) were evaluated in 285 children < 12 years of age with uncomplicated Plasmodium falciparum malaria randomized to receive one of the three drug combinations. Fever and parasite clearance times were similar in all treatment groups. Mean drug-attributable fall in hematocrit (DAFH), defined as difference between hematocrit values pre- and 3 d post- initiation of treatment, was low (< 4.5%) and rates of recovery from MAA were similar with all treatments. Mean areas under curve (AUCs) of the plot of deficit in hematocrit levels from 30% versus time in anemic children were similar in all groups. All regimens were well tolerated. AL, AAcf and AAcp cleared fever and parasitemia rapidly and had similar rates of resolution of MAA after treatment in malarious Nigerian children. * Address corresp

Amodiaquine-Associated Asthenia: A Case Based Review and Gaps in Literature

Introduction: Amodiaquine is a partner drug in the artemisinin-based combination therapy artesunate-amodiaquine. Reports of the adverse drug reaction known as amodiaquine-associated asthenia are scarce, and this adverse reaction needs to be investigated in detail. This article presents and reviews a case of amodiaquine-associated asthenia. A literature search for the characteristics of this adverse reaction highlighted gaps in the literature. Methods: A case of probable amodiaquine asthenia was described and discussed under the sub-headings of epidemiology, clinical features, laboratory features, aetiopathogenesis, and management. A literature search limited to Medline Health Databases (Medline and PubMed Central, PMC) using the search terms and was conducted on 10 March 2015. Retrieved literature on the subject was closely scrutinized for relevant details of adverse drug reactions to amodiaquine when used in the management or prophylaxis of malaria. Cited literature within retrieved manuscripts was examined manually for other relevant literature. Papers retrieved from the search were used to describe the existing knowledge and gaps in it of the adverse drug reaction under sub-categories of incidence, clinical features, laboratory features, aetiopathogenesis, and management.  Results: Thirty-nine manuscripts were retrieved; 20 had content relevant to the objectives of this review. The frequency of amodiaquine-associated asthenia in different populations ranged from 12–36%. There is a paucity of reports, and no detailed study of this adverse reaction has been published in popular English medical literature. Conclusion: With the use of amodiaquine as a partner drug in antimalarial combination therapies being scaled up, well-structured studies are needed on adverse reactions to amodiaquine and to investigate amodiaquine-associated asthenia. In addition, approaches to elucidating this adverse reaction more effectively in children need to be developed

Factors contributing to delay in parasite clearance in uncomplicated falciparum malaria in children

Background: Drug resistance in Plasmodium falciparum is common in many endemic and other settings but there is no clear recommendation on when to change therapy when there is delay in parasite clearance after initiation of therapy in African children. Methods: The factors contributing to delay in parasite clearance, defined as a clearance time > 2 d, in falciparum malaria were characterized in 2,752 prospectively studied children treated with anti-malarial drugs between 1996 and 2008. Results: 1,237 of 2,752 children (45%) had delay in parasite clearance. Overall 211 children (17%) with delay in clearance subsequently failed therapy and they constituted 72% of those who had drug failure, i.e., 211 of 291 children. The following were independent risk factors for delay in parasite clearance at enrolment: age less than or equal to 2 years (Adjusted odds ratio [AOR] = 2.13, 95% confidence interval [CI]1.44-3.15, P < 0.0001), presence of fever (AOR = 1.33, 95% CI = 1.04-1.69, P = 0.019), parasitaemia >50,000/ul (AOR = 2.21, 95% CI = 1.77-2.75, P < 0.0001), and enrolment before year 2000 (AOR= 1.55, 95% CI = 1.22-1.96, P < 0.0001). Following treatment, a body temperature ≥ 38°C and parasitaemia > 20000/μl a day after treatment began, were independent risk factors for delay in clearance. Non-artemisinin monotherapies were associated with delay in clearance and treatment failures, and in those treated with chloroquine or amodiaquine, with pfmdr 1/pfcrt mutants. Delay in clearance significantly increased gametocyte carriage (P < 0.0001). Conclusion: Delay in parasite clearance is multifactorial, is related to drug resistance and treatment failure in uncomplicated malaria and has implications for malaria control efforts in sub-Saharan Africa

Demographic and epidemiological characteristics of HIV opportunistic infections among older adults in Nigeria

Background: In view of the maturing HIV epidemic in sub-Saharan Africa, better understanding of its epidemiology among older adults is necessary in order to design appropriate care and treatment programmes for them.Objectives: To describe the demographic and epidemiological characteristics of HIV opportunistic infections among newly enrolled patients aged 50 years and above in Ibadan, South-West Nigeria.Methods: Analysis of data extracted from electronic records of 17, 312 subjects enrolled for HIV/AIDS care and treatment between January 2006 and December 2014 at the ART clinic, University College Hospital, Ibadan.Results: Age of the patients ranged from 18 to 90 years with a mean of 36.4 years (SD= 10.3) with older adults constituting 12.0% (2075). Among older adults, about half (52.9%) were females. Majority (59.1%) were currently married while 25.9% were widowed. Prevalence of opportunistic infections was 46.6%. The commonest opportunistic infections (OIs) were: oral candidiasis (27.6%), chronic diarrhoea (23.5% and peripheral neuropathy (14.8%). Significant factors associated with opportunistic infections in older adults were: CD4 count less than 350 (OR=3.12, CI: 2.29-4.25) and hepatitis C virus co-infection (OR=2.17, CI: 1.14-4.13).Conclusion: There is need for prompt response to the peculiar challenges associated with the emerging shift in the epidemiology of HIV and associated infections in sub-Saharan Africa.Keywords: HIV/AIDS, older adults, epidemiological characteristics, opportunistic infections, Nigeri

Community Acquired Bacteremia in Young Children from Central Nigeria- A Pilot Study

<p>Abstract</p> <p>Background</p> <p>Reports of the etiology of bacteremia in children from Nigeria are sparse and have been confounded by wide spread non-prescription antibiotic use and suboptimal laboratory culture techniques. We aimed to determine causative agents and underlying predisposing conditions of bacteremia in Nigerian children using data arising during the introduction of an automated blood culture system accessed by 7 hospitals and clinics in the Abuja area.</p> <p>Methods</p> <p>Between September 2008 and November 2009, we enrolled children with clinically suspected bacteremia at rural and urban clinical facilities in Abuja or within the Federal Capital Territory of Nigeria. Blood was cultured using an automated system with antibiotic removing device. We documented clinical features in all children and tested for prior antibiotic use in a random sample of sera from children from each site.</p> <p>Results</p> <p>969 children aged 2 months-5 years were evaluated. Mean age was 21 ± 15.2 months. All children were not systematically screened but there were 59 (6%) children with established diagnosis of sickle cell disease and 42 (4.3%) with HIV infection. Overall, 212 (20.7%) had a positive blood culture but in only 105 (10.8%) were these considered to be clinically significant. Three agents, <it>Staphylococcus aureus </it>(20.9%), <it>Salmonella typhi </it>(20.9%) and Acinetobacter (12.3%) accounted for over half of the positive cultures. <it>Streptococcus pneumoniae and non-typhi Salmonellae </it>each accounted for 7.6%. Although not the leading cause of bacteremia, <it>Streptococcus pneumoniae </it>was the single leading cause of all deaths that occurred during hospitalization and after hospital discharge.</p> <p>Conclusion</p> <p><it>S. typhi </it>is a significant cause of vaccine-preventable morbidity while <it>S. pneumoniae </it>may be a leading cause of mortality in this setting. This observation contrasts with reports from most other African countries where non-typhi Salmonellae are predominant in young children. Expanded surveillance is required to confirm the preliminary observations from this pilot study to inform implementation of appropriate public health control measures.</p

Demographic and epidemiological characteristics of HIV opportunistic infections among older adults in Nigeria.

Background: In view of the maturing HIV epidemic in sub-Saharan Africa, better understanding of its epidemiology among older adults is necessary in order to design appropriate care and treatment programmes for them. Objectives: To describe the demographic and epidemiological characteristics of HIV opportunistic infections among newly enrolled patients aged 50 years and above in Ibadan, South-West Nigeria. Methods: Analysis of data extracted from electronic records of 17, 312 subjects enrolled for HIV/AIDS care and treatment between January 2006 and December 2014 at the ART clinic, University College Hospital, Ibadan. Results: Age of the patients ranged from 18 to 90 years with a mean of 36.4 years (SD= 10.3) with older adults constituting 12.0% (2075). Among older adults, about half (52.9%) were females. Majority (59.1%) were currently married while 25.9% were widowed. Prevalence of opportunistic infections was 46.6%. The commonest opportunistic infections (OIs) were: oral candidiasis (27.6%), chronic diarrhoea (23.5% and peripheral neuropathy (14.8%). Significant factors associated with opportunistic infections in older adults were: CD4 count less than 350 (OR=3.12, CI: 2.29-4.25) and hepatitis C virus co-infection (OR=2.17, CI: 1.14-4.13). Conclusion: There is need for prompt response to the peculiar challenges associated with the emerging shift in the epidemiology of HIV and associated infections in sub-Saharan Africa