Browsing by Author "Achan, Jane"

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    Antiretroviral Agents and Prevention of Malaria in HIV-Infected Ugandan Children
    (The New England Journal of Medicine, 2012) Achan, Jane; Kakuru, Abel; Ikilezi, Gloria; Ruel, Theodore; Clark, Tamara D.; Nsanzabana, Christian; Charlebois, Edwin; Aweeka, Francesca; Dorsey, Grant; Rosenthal, Philip J.; Havlir, Diane; Kamya, Moses R
    Human immunodeficiency virus (HIV) protease inhibitors show activity against Plasmodium falciparum in vitro. We hypothesized that the incidence of malaria in HIV infected children would be lower among children receiving lopinavir–ritonavir– based antiretroviral therapy (ART) than among those receiving nonnucleosidereverse transcriptase inhibitor (NNRTI)–based ART.
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    Artemisinin-Based Combination Therapies Are Efficacious and Safe for Treatment of Uncomplicated Malaria in HIV-Infected Ugandan Children
    (Clinical infectious diseases, 2014) Kakuru, Abel; Achan, Jane; Muhindo, Mary K.; Ikilezi, Gloria; Arinaitwe, Emmanuel; Mwangwa, Florence; Ruel, Theodore; Clark, Tamara D.; Charlebois, Edwin; Kamya, Moses R.; Tappero, Jordan W.; Dorsey, Grant
    Artemisinin-based combination therapies (ACTs) are highly efficacious and safe, but data from human immunodeficiency virus (HIV)–infected children concurrently receiving antiretroviral therapy (ART) and ACTs are limited. We evaluated 28-day outcomes following malaria treatment with artemether-lumefantrine (AL) or dihydroartemisinin-piperaquine (DP) in 2 cohorts of HIV-infected Ugandan children taking various ART regimens. In one cohort, children <6 years of age were randomized to lopinavir/ritonavir (LPV/r) or nonnucleoside reverse transcriptase inhibitor–based ART and treated with AL for uncomplicated malaria. In another cohort, children <12 months of age were started on nevirapine-based ART if they were eligible, and randomized to AL or DP for the treatment of their first and all subsequent uncomplicated malaria episodes. There were 773 and 165 treatments for malaria with AL and DP, respectively. Initial response to therapy was excellent, with 99% clearance of parasites and <1% risk of repeat therapy within 3 days. Recurrent parasitemia within 28 days was common following AL treatment. The risk of recurrent parasitemia was significantly lower among children taking LPV/r-based ART compared with children taking nevirapine-based ART following AL treatment (15.3% vs 35.5%, P = .009), and those treated with DP compared with AL (8.6% vs 36.2%, P < .001). Both ACT regimens were safe and well tolerated. Treatment of uncomplicated malaria with AL or DP was efficacious and safe in HIV-infected children taking ART. However, there was a high risk of recurrent parasitemia following AL treatment, which was significantly lower in children taking LPV/r-based ART compared with nevirapine-based ART.
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    Bacteremia among Febrile Ugandan Children Treated with Antimalarials Despite a Negative Malaria Test
    (The American journal of tropical medicine and hygiene, 2015) Kibuuka, Afizi; Byakika-Kibwika, Pauline; Achan, Jane; Yeka, Adoke; Nalyazi, Joan N.; Mpimbaza, Arthur; Rosenthal, Philip J.; Kamya, Moses R.
    Bacteremia may be inappropriately treated as malaria in children admitted with a febrile illness in Africa. We determined the prevalence, clinical features, and spectrum of bacteremia among febrile children younger than 5 years of age admitted with a negative malaria test, but prescribed antimalarials at a referral hospital in Jinja, Uganda. After initial evaluation, a blood sample was drawn from 250 children for a complete blood count and bacterial culture. Of 250 samples cultured, 15 grew organisms presumed to be skin contaminants, and of the remaining 235 samples, 45 (19.1%) had bacteremia. Staphylococcus aureus (42%), non-typhoidal Salmonella (24%), Pseudomonas aeruginosa (11%), and Streptococcus pneumoniae (9%) were the most common bacterial isolates. On multivariate analysis, history of weight loss (odds ratio [OR] = 2.75; 95% confidence interval [CI] = 1.27–5.95), presence of pulmonary crackles (OR = 3.63; 95% CI = 1.40–9.45), and leukocytosis (OR = 2.21; 95% CI = 1.09–4.47) were independent predictors of bacteremia. At a hospital in Uganda, bacteremia was a remarkably common finding in children with febrile illness who were treated for malaria despite negative malaria test results.
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    Challenges and Strategies for Conducting Clinical Research During the COVID-19 Pandemic: Experiences from Resource Limited Settings
    (European Journal of Clinical Medicine, 2021) Achan, Jane; Serwanga, Asadu; Aanyu, Hellen.T; Opigo, Jimmy; Kyagulanyi, Tonny; Nuwa, Anthony; Magumba, Godfrey; Nakwagala, Fredrick; Marasciulo, Madeleine; Hamade, Prudence; Tibenderana, James
    As COVID-19 disease surges across much of the world, researchers in different settings have a unique opportunity to address the various research priorities that have been identified. The challenges that containment and mitigation strategies present for research, especially in resource limited settings, could be significant and negatively impact the essential contribution of these settings to COVID-19 research.To describe experiences of conducting research during this pandemic, discuss challenges faced and present strategies implemented to address these challenges.Malaria Consortium recently initiated an observational case series study to assess the magnitude and clinical consequences of co-infection of COVID-19, malaria, and other common infections. This study is being conducted in eight COVID-19 treatment centres in Uganda. Qualitative methods including observations and interviews were utilized to document experiences and mitigating strategies for identified challenges. The main outcomes were a descriptive narrative of experiences conducting this research, discussion of challenges faced, and presentation of strategies implemented to address these challenges.Expedited ethical review and approval facilitated timely initiation of research activities. The primary clinical care teams at each treatment centre performed all study procedures to minimize infection. Given concerns about fomite transmission, considerations arose on how best to handle consent forms that had been signed or thumb-printed by patients to ensure that both hospital and research staff were not exposed to infection. Consenting severely ill or mentally impaired patients was also a challenge, especially when the next of kin was not available. Patient compensation was done through a mobile money/digital platform to avoid potential risks associated with cash. Patients, health care workers and study staff faced significant psychosocial challenges and anxiety that needed to be addressed.These experiences demonstrate that more adaptable and innovative approaches may be needed to support the implementation of research activities during this COVID-19 pandemic. This pandemic should also spur institutional review boards and investigators to respond to emerging challenges by updating policies and procedures around research review and approvals, and modifications in research methods.
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    Current malaria infection, previous malaria exposure, and clinical profiles and outcomes of COVID-19 in a setting of high malaria transmission: an exploratory cohort study in Uganda
    (Global Technical Team, Malaria Consortium, London, UK, 2022) Achan, Jane
    Background The potential effects of SARS-CoV-2 and Plasmodium falciparum co-infection on host susceptibility and pathogenesis remain unknown. We aimed to establish the prevalence of malaria and describe the clinical characteristics of SARS-CoV-2 and P falciparum co-infection in a high-burden malaria setting. Methods This was an exploratory prospective, cohort study of patients with COVID-19 who were admitted to hospital in Uganda. Patients of all ages with a PCR-confirmed diagnosis of SARS-CoV-2 infection who had provided informed consent or assent were consecutively enrolled from treatment centres in eight hospitals across the country and followed up until discharge or death. Clinical assessments and blood sampling were done at admission for all patients. Malaria diagnosis in all patients was done by rapid diagnostic tests, microscopy, and molecular methods. Previous P falciparum exposure was determined with serological responses to a panel of P falciparum antigens assessed using a multiplex bead assay. Additional evaluations included complete blood count, markers of inflammation, and serum biochemistries. The main outcome was overall prevalence of malaria infection and malaria prevalence by age (including age categories of 0–20 years, 21–40 years, 41–60 years, and >60 years). The frequency of symptoms was compared between patients with COVID-19 with P falciparum infection versus those without P falciparum infection. The frequency of comorbidities and COVID-19 clinical severity and outcomes was compared between patients with low previous exposure to P falciparum versus those with high previous exposure to P falciparum. The effect of previous exposure to P falciparum on COVID-19 clinical severity and outcomes was also assessed among patients with and those without comorbidities. Findings Of 600 people with PCR-confirmed SARS-CoV-2 infection enrolled from April 15, to Oct 30, 2020, 597 (>99%) had complete information and were included in our analyses. The majority (502 [84%] of 597) were male individuals with a median age of 36 years (IQR 28–47). Overall prevalence of P falciparum infection was 12% (95% CI 9·4–14·6; 70 of 597 participants), with highest prevalence in the age groups of 0–20 years (22%, 8·7–44·8; five of 23 patients) and older than 60 years (20%, 10·2–34·1; nine of 46 patients). Confusion (four [6%] of 70 patients vs eight [2%] of 527 patients; p=0·040) and vomiting (four [6%] of 70 patients vs five [1%] of 527 patients; p=0·014] were more frequent among patients with P falciparum infection than those without. Patients with low versus those with high previous P falciparum exposure had a increased frequency of severe or critical COVID-19 clinical presentation (16 [30%] of 53 patients vs three [5%] of 56 patients; p=0·0010) and a higher burden of comorbidities, including diabetes (12 [23%] of 53 patients vs two [4%] of 56 patients; p=0·0010) and heart disease (seven [13%] of 53 patients vs zero [0%] of 56 patients; p=0·0030). Among patients with no comorbidities, those with low previous P falciparum exposure still had a higher proportion of cases of severe or critical COVID-19 than did those with high P falciparum exposure (six [18%] of 33 patients vs one [2%] of 49 patients; p=0·015). Multivariate analysis showed higher odds of unfavourable outcomes in patients who were older than 60 years (adjusted OR 8·7, 95% CI 1·0–75·5; p=0·049).Interpretation Although patients with COVID-19 with P falciparum co-infection had a higher frequency of confusion and vomiting, co-infection did not seem deleterious. The association between low previous malaria exposure and severe or critical COVID-19 and other adverse outcomes will require further study. These preliminary descriptive observations highlight the importance of understanding the potential clinical and therapeutic implications of overlapping co-infections. Funding Malaria Consortium (USA).
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    The effect of HIV on malaria in the context of the current standard of care for HIV-infected populations in Africa
    (Future virology, 2012) Kamya, Moses R.; Byakika-Kibwika, Pauline; Gasasira, Anne F.; Havlir, Diane; Rosenthal, Philip J.; Dorsey, Grant; Achan, Jane
    HIV infection affects the clinical pattern of malaria. There is emerging evidence to suggest that previously documented interactions may be modified by recently scaled-up HIV and malaria interventions. Prophylaxis with trimethoprim– sulfamethoxazole (TS) in combination with use of insecticide-treated nets can markedly decrease the incidence of malaria in HIV-infected pregnant and nonpregnant adults and children even in the setting of antifolate resistanceconferring mutations that are currently common in Africa. Nonetheless, additional interventions are needed to protect HIV-infected people that reside in highmalaria- transmission areas. Artemether–lumefantrine and dihydroartemisinin– piperaquine are highly efficacious and safe for the treatment of uncomplicated malaria in HIV-infected persons. Coadministration of antiretroviral and antimalarial drugs creates the potential for pharmacokinetic drug interactions that may increase (causing enhancement of malaria treatment efficacy and posttreatment prophylaxis and/or unanticipated toxicity) or reduce (creating risk for treatment failure) antimalarial drug exposure. Further studies are needed to elucidate potentially important pharmacokinetic interactions between commonly used antimalarials, antiretrovirals and TS and their clinical implications. Data on the benefits of long-term TS prophylaxis among HIV patients on antiretroviral therapy who have achieved immune-reconstitution are limited. Studies to address these questions are ongoing or planned, and the results should provide the evidence base required to guide the prevention and treatment of malaria in HIV-infected patients.
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    Effectiveness of quinine versus artemether-lumefantrine for treating uncomplicated falciparum malaria in Ugandan children: randomised trial
    (Bmj, 2009) Achan, Jane; Tibenderana, James K.; Kyabayinze, Daniel; Wabwire Mangen, Fred; Kamya, Moses R.; Dorsey, Grant; D’Alessandro, Umberto; Rosenthal, Philip J.; Talisuna, Ambrose O.
    Objective To compare the effectiveness of oral quininewith that of artemether-lumefantrine in treatinguncomplicated malaria in children.Design Randomised, open label effectiveness study.Setting Outpatient clinic of Uganda’s national referral hospital in Kampala.Participants 175 children aged 6 to 59 months withuncomplicated malaria.Interventions Participants were randomised to receiveoral quinine or artemether-lumefantrine administered bycare givers at home.Main outcome measures Primary outcomes wereparasitological cure rates after 28 days of follow-upunadjusted and adjusted by genotyping to distinguishrecrudescence from new infections. Secondary outcomeswere adherence to study drug, presence of gametocytes, recovery of haemoglobin concentration from baseline at day 28, and safety profiles.Results Using survival analysis the cure rate unadjustedby genotyping was 96% for the artemether-lumefantrinegroup compared with 64% for the quinine group (hazardratio10.7, 95% confidence interval 3.3 to 35.5, P=0.001).In the quinine group 69% (18/26) of parasitologicalfailures were due to recrudescence compared with none inthe artemether-lumefantrine group. The mean adherenceto artemether-lumefantrine was 94.5% compared with85.4% to quinine (P=0.0008). Having adherence levels of80% or more was associated with a decreased risk oftreatment failure (0.44, 0.19 to 1.02, P=0.06). Adverseevents did not differ between the two groups.ConclusionsThe effectiveness of a seven day course ofquinine for the treatment of uncomplicated malariainUgandanchildren was significantly lower than that ofartemether-lumefantrine. These findings question theadvisability of the recommendation for quinine therapyfor uncomplicated malaria in Africa.Trial registration ClinicalTrials.gov NCT00540202.
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    Efficacy and Safety of Three Regimens for the Prevention of Malaria in Young HIV-Exposed Ugandan Children: A Randomized Controlled Trial
    (AIDS, 2014) Kamya, Moses R.; Kapisi, James; Bigira, Victor; Tamara, D. Clark; Kinara, Stephen; Mwangwa, Florence; Muhindo, Mary K.; Kakuru, Abel; Aweeka, Francesca T.; Achan, Jane; Havlir, Diane V.; Rosenthal, Philip J.; Dorsey, Grant
    Trimethoprim-sulfamethoxazole (TS) prophylaxis is recommended for HIV-exposed infants until breastfeeding ends and HIV infection has been excluded. Extending prophylaxis with a focus on preventing malaria may be beneficial in high transmission areas. We investigated three regimens for the prevention of malaria in young HIV-exposed children. Tororo, Uganda, a rural area with intense, year-round, malaria transmission. 200 infants aged 4-5 months enrolled and 186 randomized after cessation of breastfeeding and confirmed to be HIV uninfected (median 10 months of age). No chemoprevention, monthly sulfadoxine-pyrimethamine (SP), daily TS, or monthly dihydroartemisinin-piperaquine (DP) given from randomization to 24 months of age. The primary outcome was the incidence of malaria during the intervention period. Secondary outcomes included the incidence of hospitalization, diarrheal illness, or respiratory tract infection; prevalence of anemia and asymptomatic parasitemia; measures of safety; and incidence of malaria over 1 year after the intervention was stopped. During the intervention, the incidence of malaria in the no chemoprevention group was 6.28 episodes per person-year at risk. Protective efficacy was 69% (95% CI, 53-80%, p<0.001) for DP, 49% (95% CI, 23-66%, p=0.001) for TS, and 9% for SP (95% CI, −35 to 38%, p=0.65). There were no significant differences in any secondary outcomes, with the exception of a lower prevalence of asymptomatic parasitemia in the DP arm. Monthly chemoprevention with DP was safe and associated with a significant reduction in malaria in young HIV-exposed children.
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    Growth Recovery Among HIV-Infected Children Randomized to Lopinavir/Ritonavir or NNRTI-Based Antiretroviral Therapy
    (The Pediatric infectious disease journal, 2016) Achan, Jane; Kakuru, Abel; Ikilezi, Gloria; Mwangwa, Florence; Charlebois, Edwin; Young, Sera; Havlir, Diane; Kamya, Moses; Ruel, Theodore
    Diminished growth is highly prevalent among HIV-infected children and might be improved by antiretroviral therapy (ART). We examined growth recovery in a rural Ugandan cohort of HIV-infected children randomized to lopinavir/ritonavir or non-nucleoside-reverse-transcription-inhibitor-based ART. HIV-infected children 2 months to 6 years of age were randomized to Lopinavir/ritonavir- or non-nucleoside-reverse-transcription-inhibitor-based ART. Changes in weight-for-age (WAZ), height-for-age (HAZ), and weight-for-height (WHZ) Z-scores for 24 months were evaluated using generalized linear repeated-measures models. Recovery from being underweight (WAZ<−2), stunted (HAZ<−2) and wasted (WHZ<−2) to Z-scores > −2 was also compared by arm using Kaplan-Meier survival and Cox proportional hazard modeling. A total of 129 children with median age of 3 years initiated therapy; 64 received Lopinavir/ritonavir-based and 65 non-nucleoside-reverse-transcription-inhibitor-based ART (nevirapine: 36 and efavirenz: 29). The median (IQR) difference in growth measures between baseline and 24 months for Lopinavir/ritonavir (n= 45) vs. non-nucleoside-reverse-transcription-inhibitor-based therapy (n=40) were as follows, WAZ: 0.47 (0.10, 1.62) vs. 0.53 (0.03, 1.14) (p=0.59) and HAZ: median 1.55 (0.78, 1.86) vs. 1.19 (0.62, 1.65) (p=0.23), respectively. ART regimen was not predictive of change in WAZ (beta: −0.02, 95%CI: −0.25, 0.20) or HAZ (beta: 0.05, 95%CI: −0.10, 0.19). Presence of confirmed virologic failure was not associated with growth. Most ART-naive children experienced recovery of both WAZ and HAZ over the 24 months following ART-initiation, with no significant difference between those receiving Lopinavir/ritonavir vs. non-nucleoside-reverse-transcriptase-inhibitor-based ART. However, the persistence of median Z-scores below zero underscores the need for additional strategies to improve growth outcomes in HIV+ African children.
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    High Risk of Neutropenia in HIV-Infected Children following Treatment with Artesunate plus Amodiaquine for Uncomplicated Malaria in Uganda
    (Clinical infectious diseases, 2008) Gasasira, Anne F.; Kamya, Moses R.; Achan, Jane; Mebrahtu, Tsedal; Kalyango, Joan N.; Ruel, Theodore; Charlebois, Edwin; Staedke, Sarah G.; Kekitiinwa, Adeodata; Rosenthal, Philip J.; Havlir, Diane; Dorsey, Grant
    Artemisinin-based combination therapies are rapidly being adopted for the treatment of malaria in Africa; however, there are limited data on their safety and efficacy among human immunodeficiency virus (HIV)–infected populations. Methods. We compared malaria treatment outcomes between cohorts of HIV-infected and HIV-uninfected children in Uganda who were observed for 18 and 29 months, respectively. Malaria was treated with artesunate plus amodiaquine, and outcomes were assessed using standardized guidelines. HIV-infected children received trimethoprim-sulfamethoxazole prophylaxis and antiretroviral therapy in accordance with current guidelines. Results. Twenty-six HIV-infected participants experiencing 35 episodes of malaria and 134 HIV-uninfected children experiencing 258 episodes of malaria were included in the study. Twelve HIV-infected children were receiving antiretroviral therapy, 11 of whom were receiving zidovudine. Malaria treatment was highly efficacious in both the HIV-infected and HIV-uninfected cohorts (28-day risk of recrudescence, 0% and 3.6%, respectively); however, there was a trend towards increased risk of recurrent malaria among the HIV-uninfected children (2.9% vs. 13.2%; Pp.08). Importantly, the risk of neutropenia 14 days after initiation of treatment with artesunate plus amodiaquine was higher among HIV-infected children than among HIV-uninfected children (45% vs. 6%; P ! .001). The severity of all episodes of neutropenia in HIV-uninfected children was mild to moderate, and 16% of episodes of neutropenia in the HIV-infected cohort were severe or life-threatening (neutrophil count, !750 cells/ mm3). In the HIV-infected cohort, the risk of neutropenia was significantly higher among children who received antiretroviral therapy than among those who did not receive antiretroviral therapy (75% vs. 26%; Pp.001). Conclusions. Artesunate plus amodiaquine was highly efficacious for malaria treatment in HIV-infected children but was associated with a high risk of neutropenia, especially in the context of concurrent antiretroviral use. Our findings highlight an urgent need for evaluation of alternative antimalarial therapies for HIV-infected individuals.
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    Impact of Current Malaria Infection and Previous Malaria Exposure on the Clinical Profiles and Outcome of COVID-19 in a High Malaria Transmission Setting
    (Lancet, 2021) Achan, Jane
    Background: Our understanding of the potential impact of SARS-CoV-2 and malaria co-infection on host susceptibility and pathogenesis remains unclear. We determined the prevalence of malaria and describe the consequences of SARS-CoV-2 and malaria co-infection in a high burden malaria setting. Methods: This was a prospective cohort study of hospitalized Covid-19 patients in Uganda. Malaria diagnosis was done using rapid diagnostic tests, microcopy and molecular methods. Previous P. falciparum exposure was assessed using serologic responses to a panel of P. falciparum antigens using a multiplex bead assay. Additional evaluations included complete blood count, markers of inflammation and serum biochemistries. Findings: Of 597 PCR confirmed Covid-19 cases enrolled between 16th April and 30th October 2020, 500 (84.1%) were male and median age (1QR) was 36 (28-47) years. Overall prevalence of P. falciparum infection was 11.7% (70/597, 95% CI 9.4 to 14.6), with highest prevalence in the 0- 20 years (21.7%, 5/23, 95% CI 8.7-44.8) and > 60 years (19.6%, 9/46, 95% CI 10.2-34.1) age groups. Confusion [5.7% (4/70) vs. 1.5%, (8/527), p=0.04] and vomiting [5.7% (5/70) vs.1.0%, 5/527), p=0.007] were more frequent among patients with P. falciparum infection. Patients with low previous P. falciparum exposure had a higher frequency of severe/critical Covid-19 cases (30.2%, 16/53, p=0.001), a higher burden of comorbidities [hypertension (30.2%, 16/53, p=0.02) and diabetes (22.6%, 12/53, p=0.003)] and more deaths (3.8%, 2/53, p=0.01). Among patients with no comorbidities, those with low previous exposure still had a higher proportion of severe/critical Covid-19 cases (18.2%, 6/53 vs. 2.0%, 1/56, p=0.01) compared to those with high exposure. Interpretation: Prevalence of P. falciparum infection among Covid-19 patients was relatively high. Though Covid-19 patients with P. falciparum infection had a higher frequency of confusion and vomiting, co-infection with malaria did not seem deleterious. Low previous malaria exposure was associated with severe/critical Covid-19 and adverse outcomes. Funding: Funding: Grant from Malaria Consortium, US Declaration of Interest: HA and FN are members of the Mulago Hospital Research and Ethics but did not participate in decisions pertaining this study. All other authors declare no competing interests. Ethical Approval: The study was approved by the Mulago National Referral Hospital Research and Ethics committee and the Uganda National Council for Science and Technology.
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    Improving the quality of neonatal data capture and clinical care at a tertiary-care hospital in Uganda through enhanced surveillance, training and mentorship
    (Paediatrics and International Child Health, 2020) Achan, Jane; Wanzira, Humphrey; Mpimbaza, Arthur; Tumwine, Daniel; Namasopo, Sophie; Nambuya, Harriet; Serwanga, Asadu; Nantanda, Rebecca
    Accurate documentation of neonatal morbidity and mortality is limited in many countries in sub-Saharan Africa. This project aimed to establish a surveillance system for neonatal conditions as an approach to improving the quality of neonatal care. Methods: A systematic data capture and surveillance system was established at Jinja Regional Referral Hospital, Uganda using a standardised neonatal medical record form which collected detailed individual patient level data. Additionally, training and mentorship were conducted and basic equipment was provided. Results: A total of 4178 neonates were hospitalised from July 2014 to December 2016. Median (IQR) age on admission was one day (1–3) and 48.0% (1851/3859) were male. Median (IQR) duration of hospitalisation was 17 days (IQR 10–40) and the longest duration of hospitalisation was 47 days (IQR 41–58). The majority were referrals from government health facilities (54.4%, 2012/3699), though 30.6% (1123/3669) presented as self-referrals. Septicaemia (44.9%, 1962/4371), prematurity (21.0%, 917/4371) and birth asphyxia (19.1%, 833/4371) were the most common diagnoses. The overall mortality was 13.8% (577/4178) and the commonest causes of death included septicaemia (26.9%, 155/577), prematurity (24.3%, 140/577), birth asphyxia (21.0%, 121/577), hypothermia (9.9%, 57/577) and respiratory distress (8.0%, 46/577). The majority of deaths (51.5%, 297/577) occurred within the first 24 h of hospitalisation although a significant proportion of deaths also occurred after 7 days of hospitalisation (24.1%, 139/577). A modest decrease in mortality and improvement in clinical outcome were observed. Conclusion: Improvement in neonatal data capture and quality of care was observed following establishment of an enhanced surveillance system, training and mentorship.
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    Intravenous artesunate plus Artemisnin based Combination Therapy (ACT) or intravenous quinine plus ACT for treatment of severe malaria in Ugandan children: a randomized controlled clinical trial
    (BMC infectious diseases, 2017) Byakika-Kibwika, Pauline; Achan, Jane; Lamorde, Mohammed; Karera-Gonahasa, Carine; Kiragga, Agnes N.; Mayanja-Kizza, Harriet; Kiwanuka, Noah; Nsobya, Sam; Talisuna, Ambrose O.; Merry, Concepta
    Severe malaria is a medical emergency associated with high mortality. Adequate treatment requires initial parenteral therapy for fast parasite clearance followed by longer acting oral antimalarial drugs for cure and prevention of recrudescence. In a randomized controlled clinical trial, we evaluated the 42-day parasitological outcomes of severe malaria treatment with intravenous artesunate (AS) or intravenous quinine (QNN) followed by oral arte
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    Neurocognitive and Motor Deficits in HIV-Infected Ugandan Children With High CD4 Cell Counts
    (Clinical Infectious Diseases, 2012) Ruel,Theodore D.; Boivin, Michael J.; Boal, Hannah E.; Bangirana, Paul; Charlebois,Edwin; Havlir, Diane V.; Rosenthal, Philip J.; Dorsey,Grant; Achan, Jane; Akello, Carolyne; Kamya, Moses R.; Wong, Joseph K.
    Background. Human immunodeficiency virus (HIV) infection causes neurocognitive or motor function deficits in children with advanced disease, but it is unclear whether children with CD4 cell measures above the World health Organization (WHO) thresholds for antiretroviral therapy (ART) initiation suffer significant impairment
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    Parasite-based malaria diagnosis: Are Health Systems in Uganda equipped enough to implement the policy?
    (BMC Public Health, 2012) Kyabayinze, Daniel J.; Achan, Jane; Nakanjako, Damalie; Mpeka, Betty; Mawejje, Henry; Mugizi, Rukaaka; Kalyango, Joan N.; D’Alessandro, Umberto; Talisuna, Ambrose; Jean-Pierre, Van geertruyden
    Malaria case management is a key strategy for malaria control. Effective coverage of parasite-based malaria diagnosis (PMD) remains limited in malaria endemic countries. This study assessed the health system's capacity to absorb PMD at primary health care facilities in Uganda. Methods: In a cross sectional survey, using multi-stage cluster sampling, lower level health facilities (LLHF) in 11 districts in Uganda were assessed for 1) tools, 2) skills, 3) staff and infrastructure, and 4) structures, systems and roles necessary for the implementing of PMD. Results: Tools for PMD (microscopy and/or RDTs) were available at 30 (24%) of the 125 LLHF. All LLHF had patient registers and 15% had functional in-patient facilities. Three months’ long stock-out periods were reported for oral and parenteral quinine at 39% and 47% of LLHF respectively. Out of 131 health workers interviewed, 86 (66%) were nursing assistants; 56 (43%) had received on-job training on malaria case management and 47 (36%) had adequate knowledge in malaria case management. Overall, only 18% (131/730) Ministry of Health approved staff positions were filled by qualified personnel and 12% were recruited or transferred within six months preceding the survey. Of 186 patients that received referrals from LLHF, 130(70%) had received pre-referral anti-malarial drugs, none received pre-referral rectal artesunate and 35% had been referred due to poor response to antimalarial drugs. Conclusion: Primary health care facilities had inadequate human and infrastructural capacity to effectively implement universal parasite-based malaria diagnosis. The priority capacity building needs identified were: 1) recruitment and retention of qualified staff, 2) comprehensive training of health workers in fever management, 3) malaria diagnosis quality control systems and 4) strengthening of supply chain, stock management and referral systems.
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    Protective Efficacy and Safety of Three Antimalarial Regimens for the Prevention of Malaria in Young Ugandan Children: A Randomized Controlled Trial doi:10.1371/journal.pmed.1001689
    (PLoS medicine, 2014) Bigira, Victor; Kapisi, James; Clark, Tamara D.; Kinara, Stephen; Mwangwa, Stephen; Muhindo, Mary K.; Osterbauer, Beth; Aweeka, Francesca T.; Huang, Liusheng; Achan, Jane; Havlir, Diane V.; Rosenthal, Philip J.; Kamya, Moses R.; Dorsey, Grant
    Chemoprevention offers a promising strategy for prevention of malaria in African children. However, the optimal chemoprevention drug and dosing strategy is unclear in areas of year-round transmission and resistance to many antimalarial drugs. To compare three available regimens, we conducted an open-label randomized controlled trial of chemoprevention in Ugandan children. Methods and Findings: This study was conducted between June 28, 2010, and September 25, 2013. 400 infants were enrolled and 393 randomized at 6 mo of age to no chemoprevention, monthly sulfadoxine-pyrimethamine (SP), daily trimethoprim-sulfamethoxazole (TS), or monthly dihydroartemisinin-piperaquine (DP). Study drugs were administered at home without supervision. Piperaquine (PQ) levels were used as a measure of compliance in the DP arm. Participants were given insecticide-treated bednets, and caregivers were encouraged to bring their child to a study clinic whenever they were Chemoprevention was stopped at 24 mo of age, and participants followed-up an additional year. Primary outcome was the incidence of malaria during the intervention period. During the intervention, the incidence of malaria in the no chemoprevention arm was 6.95 episodes per person-year at risk. Protective efficacy was 58% (95% CI, 45%–67%, p,0.001) for DP, 28% (95% CI, 7%–44%, p = 0.01) for TS, and 7% for SP (95% CI, 219% to 28%, p = 0.57). PQ levels were below the detection limit 52% of the time when malaria was diagnosed in the DP arm, suggesting non-adherence. There were no differences between the study arms in the incidence of serious adverse events during the intervention and the incidence of malaria during the 1-y period after the intervention was stopped.Conclusions: For preventing malaria in children living in an area of high transmission intensity, monthly DP was the mostefficacious and safe, although adherence may pose a problem.Monthly SP and daily TS may not be appropriate in areas with high transmission intensity and frequent resistance to antifolates.
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    Quinine monotherapy for treating uncomplicated malaria in the era of artemisinin-based combination therapy: an appropriate public health policy?
    (The Lancet infectious diseases, 2009) Yeka, Adoke; Achan, Jane; D’Alessandro, Umberto; Talisuna, Ambrose O.
    Several African countries that have adopted artemisinin-based combination therapy (ACT) as fi rst-line treatment of uncomplicated Plasmodium falciparum malaria also use quinine monotherapy as second-line therapy. This policy goes against WHO recommendations for combination therapy and could be considered an inappropriate public health policy. Adherence to a 7-day quinine treatment schedule is likely to be poor and may increase the risk of selecting resistant parasites. Furthermore, because quinine has limited post-treatment prophylaxis, it will not prevent, in areas of intense transmission, recurrent malaria infections, which can lead to additional morbidity, including anaemia. Therefore, ACTs and not quinine should be used as second-line treatment, because these are well tolerated, highly effi cacious, and have the advantage of reducing gametocyte carriage and consequently malaria transmissibility, particularly in areas of less intense transmission.
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    Quinine, an old anti-malarial drug in a Modern world: role in the treatment of Malaria
    (Malaria journal, 2011) Achan, Jane; Talisuna, Ambrose O.; Erhart, Annette; Yeka, Adoke; Tibenderana, James K.; Baliraine, Frederick N.; Rosenthal, Philip J.; D’Alessandro, Umberto;
    Quinine remains an important anti-malarial drug almost 400 years after its effectiveness was first documented.However, itscontinued use is challenged by its poor tolerability, poor compliance with complex dosing regimens,and the availability of more efficacious anti-malarial drugs. This article reviews the historical role of quinine,considers its current usage and provides insight into its appropriate future use in the treatment of malaria. In lightof recent research findings intravenous artesunate should be thefirst-line drug for severe malaria, with quinine asan alternative. The role of rectal quinine as pre-referral treatment for severe malaria has not been fully explored,but it remains a promising intervention. In pregnancy, quinine continues to play a critical role in the managementof malaria, especially in the first trimester, and it will remain a mainstay of treatment until safer alternatives becomeavailable. For uncomplicated malaria, artemisinin-based combination therapy (ACT) offers a better option thanquinine though the difficulty of maintaining a steady supply of ACT in resource-limited settings renders the rapidwithdrawal of quinine for uncomplicated malaria cases risky. The best approach would be to identify solutions toACT stock-outs, maintain quinine in case ofACT stock-outs, and evaluate strategies for improving quininetreatment outcomes by combining it with antibiotics. In HIV andTB infected populations, concerns about potentialinteractions between quinine and antiretroviral and antituberculosis drugs exist, andthese will need furtherresearch and pharmacovigilance.
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    Reliability and validity of the center for epidemiologic studies-depression scaleinscreening for depression among HIV-infected and -uninfected pregnant women attending antenatal services in northern Uganda: a cross-sectional study
    (BMC Psychiatry, 2014) Natamba, Barnabas K.; Achan, Jane; Arbach, Angela; Oyok, Thomas O.; Ghosh, Shibani; Mehta, Saurabh; Stoltzfus, Rebecca J.; Griffiths, Jeffrey K.; Young, Sera L.
    Background: There are limited data on the prevalence and approaches to screening for depression among pregnant women living in resource poor settings with high HIV burden. Methods: We studied the reliability and accuracy of the Center for Epidemiologic Studies Depression (CES-D) scale in 123 (36 HIV-infected and 87 -uninfected) pregnant women receiving antenatal care at Gulu Regional Referral Hospital, Uganda. CES-D scores were compared to results from the psychiatrist-administered Mini-International Neuropsychiatric Interview (MINI) for current major depressive disorder (MDD), a “gold standard” for assessingdepression. We employed measures of internal consistency (Cronbach’s alpha), and criterion validity [Area Underthe Receiver Operating Characteristic Curve (AUROC), sensitivity (Se), specificity (Sp), and positive predictive value(PPV)] to evaluate the reliability and validity of the CES-D scale. Results: 35.8% of respondents were currently experiencing an MDD, as defined from outputs of the MINI-depression module. The CES-D had high internal consistency (Cronbach’s alpha = 0.92) and good discriminatory ability in detecting MINI-defined current MDDs (AUROC = 0.82). The optimum CES-D cutoff score for the identification of probable MDD was between 16 and 17. A CES-D cutoff score of 17, corresponding to Se, Sp, and PPV values of 72.7%, 78.5%, and 76.5%, is proposed for adoption in this population and performs well for HIV-infected and -uninfected women. Afteradjusting for baseline differences between the HIV subgroups (maternal age and marital status), HIV-infectedpregnant women scored 6.2 points higher on the CES-D than HIV-uninfected women (p = 0.032).Conclusions: The CES-D is a suitable instrument for screening for probable major depression among pregnant womenof mixed HIV status attending antenatal services in northern Uganda.
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    Short-Term Risk of HIV-Disease Progression and Death in Ugandan Children Not Eligible for Antiretroviral Therapy
    (Journal of acquired immune deficiency syndromes, 2010) Charlebois, Edwin D; Ruel, Theodore D; Gasasira, Anne F.; Achan, Jane; Kateera, Frederick; Akello, Caroline; Cao, Huyen; Dorsey, Grant; Rosenthal, Philip J; Ssewanyana, Isaac; Kamya, Moses R; Havlir, Diane V
    Background—Increasing numbers of HIV-infected children not yet eligible for antiretroviral therapy (ART) are entering health care in Africa. We sought to characterize the risk of short-term disease progression in this population. Methods—In a cohort of HIV-infected ART-naive and -ineligible Ugandan children >1 year old, the rates of clinical/immunologic progression within 2 years were assessed using Kaplan–Meier survival analysis and multivariate Cox proportional-hazards modeling. Results—Among 192 children (mean age: 6.4 years, CD4%:25), 19% progressed within 2 years by WHO-stage 3/4 event(n=22), death (n=3), or WHO-defined CD4 threshold for ARTinitiation( n=12). Significant univariate predictors were CD4%(HR=2.0 per 10% decrease, p=0.005), HIV-RNA level(HR=2.4 per log10 increase, p=0.002), male gender (HR:2.0, p=0.04), age < 3 years (HR=3.7, p=0.001), CD4-activation [%CD4+CD38+HLADR+] (HR=1.6 per 10% increase, p=0.05) and CD8-activation [%CD8+CD38+HLADR+](HR=1.3 per 10% increase, p=0.05] (HR=1.3, p=0.5). In multivariate analysis, CD4%(HR=2.0, p=0.034), HIV-RNA level(HR=1.8, p=0.013) and age < 3 years (HR:3.0, p=0.008) were independently predictive. Children with HIV-RNA >105 copies/ml and CD4% <25 had progression rates of 29% (1 year) and 34% (2 years). Conclusions—Even with frequent CD4 monitoring, HIV-infected Ugandan children experienced significant clinical events while ineligible for ART. Alternate strategies for monitoring or ART-initiation may be needed to improve outcomes