Mass Drug Administration With Dihydroartemisinin-piperaquine and Malaria Transmission Dynamics in The Gambia: A Prospective Cohort Study

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Incidence of Postpartum Infection, Outcomes and Associated Risk Factors at Mbarara Regional Referral Hospital in Uganda

Background: There is a paucity of recent prospective data on the incidence of postpartum infections and associated risk factors in sub-Saharan Africa. Retrospective studies estimate that puerperal sepsis causes approximately 10% of maternal deaths in Africa. Methods: We enrolled 4231 women presenting to a Ugandan regional referral hospital for delivery or postpartum care into a prospective cohort and measured vital signs postpartum. Women developing fever (\u3e 38.0 °C) or hypothermia (\u3c 36.0 °C) underwent symptom questionnaire, structured physical exam, malaria testing, blood, and urine cultures. Demographic, treatment, and post-discharge outcomes data were collected from febrile/hypothermic women and a random sample of 1708 normothermic women. The primary outcome was in-hospital postpartum infection. Multivariable logistic regression was used to determine factors independently associated with postpartum fever/ hypothermia and with confirmed infection. Results: Overall, 4176/4231 (99%) had ≥1 temperature measured and 205/4231 (5%) were febrile or hypothermic. An additional 1708 normothermic women were randomly selected for additional data collection, for a total sample size of 1913 participants, 1730 (90%) of whom had complete data. The mean age was 25 years, 214 (12%) were HIV-infected, 874 (51%) delivered by cesarean and 662 (38%) were primigravidae. Among febrile/hypothermic participants, 174/205 (85%) underwent full clinical and microbiological evaluation for infection, and an additional 24 (12%) had a partial evaluation. Overall, 84/4231 (2%) of participants met criteria for one or more in-hospital postpartum infections. Endometritis was the most common, identified in 76/193 (39%) of women evaluated clinically. Twenty-five of 175 (14%) participants with urinalysis and urine culture results met criteria for urinary tract infection. Bloodstream infection was diagnosed in 5/185 (3%) participants with blood culture results. Another 5/186 (3%) tested positive for malaria. Cesarean delivery was independently associated with incident, in-hospital postpartum infection (aOR 3.9, 95% CI 1.5– 10.3, P = 0.006), while antenatal clinic attendance was associated with reduced odds (aOR 0.4, 95% CI 0.2–0.9, P = 0.02). There was no difference in in-hospital maternal deaths between the febrile/hypothermic (1, 0.5%) and normothermic groups (0, P = 0.11)

The impact of HIV-1 on the malaria parasite biomass in adults in sub-Saharan Africa contributes to the emergence of antimalarial drug resistance

Background. HIV-related immune-suppression increases the risk of malaria (infection, disease and treatment failure) and probably the circulating parasite biomass, favoring the emergence of drug resistance parasites. Methods. The additional malaria parasite biomass related to HIV-1 co-infection in sub-Saharan Africa was estimated by a mathematical model. Parasite biomass was computed as the incidence rate of clinical malaria episodes multiplied by the number of parasites circulating in the peripheral blood of patients at the time symptoms appear. A mathematical model estimated the influence of HIV-1 infection on parasite density in clinical malaria by country and by age group, malaria transmission intensity and urban/rural area. In a multivariate sensitivity analysis, 95% confidence intervals (CIs) were calculated using the Monte Carlo simulation. Results. The model shows that in 2005 HIV-1 increased the overall malaria parasite biomass by 18.0% (95%CI: 11.6-26.9). The largest relative increase (134.9-243.9%) was found in southern Africa where HIV-1 prevalence is the highest and malaria transmission unstable. The largest absolute increase was found in Zambia, Malawi, the Central African Republic and Mozambique, where both malaria and HIV are highly endemic. A univariate sensitivity analysis shows that estimates are sensitive to the magnitude of the impact of HIV-1 infection on the malaria incidence rates and associated parasite densities. Conclusion. The HIV-1 epidemic by increasing the malaria parasite biomass in sub-Saharan Africa may also increase the emergence of antimalarial drug resistance, potentially affecting the health of the whole population in countries endemic for both HIV-1 and malaria

Insecticide-Treated Nets for the Prevention of Malaria in Pregnancy: A Systematic Review of Randomised Controlled Trials

BACKGROUND: Protection from malaria with insecticide-treated bednets (ITNs) during pregnancy is widely advocated, but evidence of benefit has been inconsistent. We undertook a systematic review of randomised trials. METHODS AND FINDINGS: Three cluster-randomised and two individually randomised trials met the inclusion criteria; four from Africa (n = 6,418) and one from Thailand (n = 223). In Africa, ITNs compared to no nets increased mean birth weight by 55 g (95% confidence interval [CI] 21–88), reduced low birth weight by 23% (relative risk [RR] 0.77, 95% CI 0.61–0.98), and reduced miscarriages/stillbirths by 33% (RR 0.67, 0.47–0.97) in the first few pregnancies. Placental parasitaemia was reduced by 23% in all gravidae (RR 0.77, 0.66–0.90). The effects were apparent in the cluster-randomised trials and the one individually randomised trial in Africa. The trial in Thailand, which randomised individuals to ITNs or untreated nets, showed reductions in anaemia and fetal loss in all gravidae, but not reductions in clinical malaria or low birth weight. CONCLUSIONS: ITNs used throughout pregnancy or from mid-pregnancy onwards have a beneficial impact on pregnancy outcome in malaria-endemic Africa in the first few pregnancies. The potential impact of ITNs in pregnant women and their newborns in malaria regions outside Africa requires further research

Human immunodeficiency virus infection and cerebral malaria in children in Uganda: a case-control study

<p>Abstract</p> <p>Background</p> <p>Human immunodeficiency virus (HIV)-1 infection increases the burden of malaria by increasing susceptibility to infection and decreasing the response to malarial treatment. HIV-1 has also been found to suppress the immune system and predispose to severe forms of malaria in adults. There is still a paucity of data on the association between HIV-1 infection and cerebral malaria in children. The aim of this study was to determine whether HIV-1 infection is a risk factor for cerebral malaria in children.</p> <p>Method</p> <p>We conducted an unmatched case-control study, in which 100 children with cerebral malaria were compared with 132 with uncomplicated malaria and 120 with no malaria. In stratified analyses we estimated odds ratios (ORs) and 95% confidence intervals (CIs) adjusted for age.</p> <p>Results</p> <p>HIV-1 infection was present in 9% of children with cerebral malaria compared to 2.3% in uncomplicated malaria (age-adjusted odds ratio (aOR) 5.94 (95% confidence interval (CI) 1.36-25.94, p = 0.012); and 2.5% in children with no malaria (aOR 3.85 (95% CI0.99-14.93, p = 0.037). The age-adjusted odds of being HIV-positive among children with cerebral malaria compared to the control groups (children with uncomplicated malaria and no malaria) was 4.98 (95% CI 1.54-16.07), p-value = 0.003.</p> <p>Conclusions</p> <p>HIV-1 infection is associated with clinical presentation of cerebral malaria in children. Clinicians should ensure that children diagnosed with HIV infection are initiated on cotrimoxazole prophylaxis as soon as the diagnosis is made and caretakers counselled on the importance of adherence to the cotrimoxazole towards reducing the risk of acquiring <it>P.falciparum </it>malaria and associated complications such as cerebral malaria. Other malaria preventive measures such as use of insecticide-treated mosquito nets should also be emphasized during counselling sessions.</p

Implementation research of a cluster randomized trial evaluating the implementation and effectiveness of intermittent preventive treatment for malaria using dihydroartemisinin-piperaquine on reducing malaria burden in school-aged children in Tanzania: methodology, challenges, and mitigation

BACKGROUND: It has been more than 20 years since the malaria epidemiologic shift to school-aged children was noted. In the meantime, school-aged children (5-15 years) have become increasingly more vulnerable with asymptomatic malaria prevalence reaching up to 70%, making them reservoirs for subsequent transmission of malaria in the endemic communities. Intermittent Preventive Treatment of malaria in schoolchildren (IPTsc) has proven to be an effective tool to shrink this reservoir. As of 3(rd) June 2022, the World Health Organization recommends IPTsc in moderate and high endemic areas. Even so, for decision-makers, the adoption of scientific research recommendations has been stifled by real-world implementation challenges. This study presents methodology, challenges faced, and mitigations used in the evaluation of the implementation of IPTsc using dihydroartemisinin-piperaquine (DP) in three councils (Handeni District Council (DC), Handeni Town Council (TC) and Kilindi DC) of Tanga Region, Tanzania so as to understand the operational feasibility and effectiveness of IPTsc on malaria parasitaemia and clinical malaria incidence. METHODS: The study deployed an effectiveness-implementation hybrid design to assess feasibility and effectiveness of IPTsc using DP, the interventional drug, against standard of care (control). Wards in the three study councils were the randomization unit (clusters). Each ward was randomized to implement IPTsc or not (control). In all wards in the IPTsc arm, DP was given to schoolchildren three times a year in four-month intervals. In each council, 24 randomly selected wards (12 per study arm, one school per ward) were chosen as representatives for intervention impact evaluation. Mixed design methods were used to assess the feasibility and acceptability of implementing IPTsc as part of a more comprehensive health package for schoolchildren. The study reimagined an existing school health programme for Neglected Tropical Diseases (NTD) control include IPTsc implementation. RESULTS: The study shows IPTsc can feasibly be implemented by integrating it into existing school health and education systems, paving the way for sustainable programme adoption in a cost-effective manner. CONCLUSIONS: Through this article other interested countries may realise a feasible plan for IPTsc implementation. Mitigation to any challenge can be customized based on local circumstances without jeopardising the gains expected from an IPTsc programme. Trial registration clinicaltrials.gov, NCT04245033. Registered 28 January 2020, https://clinicaltrials.gov/ct2/show/NCT04245033

Imported Plasmodium falciparum malaria in HIV-infected patients: a report of two cases

As HIV becomes a chronic infection, an increasing number of HIV-infected patients are travelling to malaria-endemic areas. Association of malaria with HIV/AIDS can be clinically severe. Severe falciparum malaria is a medical emergency that is associated with a high mortality, even when treated in an Intensive Care Unit. This article describes two cases of HIV-positive patients, who returned from malaria-endemic areas and presented a parasitaemia > 5% of erythrocytes and clinical signs of severe falciparum malaria, both with > 350 CD4 cell count/μl, absence of chemoprophylaxis and successful response. Factors like drug interactions and the possible implication of anti-malarial therapy bioavailability are all especially interesting in HIV-malaria co-infections

Falciparum malaria and HIV-1 in hospitalized adults in Maputo, Mozambique: does HIV-infection obscure the malaria diagnosis?

<p>Abstract</p> <p>Background</p> <p>The potential impact of HIV-1 on falciparum malaria has been difficult to determine because of diagnostic problems and insufficient epidemiological data.</p> <p>Methods</p> <p>In a prospective, cross-sectional study, clinical and laboratory data was registered consecutively for all adults admitted to a medical ward in the Central Hospital of Maputo, Mozambique, during two months from 28^thOctober 2006. Risk factors for fatal outcome were analysed. The impact of HIV on the accuracy of malaria diagnosis was assessed, comparing "Presumptive malaria", a diagnosis assigned by the ward clinicians based on fever and symptoms suggestive of malaria in the absence of signs of other infections, and "Verified malaria", a malaria diagnosis that was not rejected during retrospective review of all available data.</p> <p>Results</p> <p>Among 333 included patients, fifteen percent (51/333) had "presumptive malaria", ten percent (28 of 285 tested persons) had positive malaria blood slides, while 69.1% (188/272) were HIV positive. Seven percent (n = 23) had "verified malaria", after the diagnosis was rejected in patients with neck stiffness or symptom duration longer than 2 weeks (n = 5) and persons with negative (n = 19) or unknown malaria blood slide (n = 4). Clinical stage of HIV infection (CDC), hypotension and hypoglycaemia was associated with fatal outcome. The "presumptive malaria" diagnosis was rejected more frequently in HIV positive (20/31) than in HIV negative patients (2/10, p = 0.023).</p> <p>Conclusion</p> <p>The study suggests that the fraction of febrile illness attributable to malaria is lower in HIV positive adults. HIV testing should be considered early in evaluation of patients with suspected malaria.</p

Placental Plasmodium falciparum malaria infection: Operational accuracy of HRP2 rapid diagnostic tests in a malaria endemic setting

<p>Abstract</p> <p>Background</p> <p>Malaria has a negative effect on the outcome of pregnancy. Pregnant women are at high risk of severe malaria and severe haemolytic anaemia, which contribute 60-70% of foetal and perinatal losses. Peripheral blood smear microscopy under-estimates sequestered placental infections, therefore malaria rapid diagnostic tests (RDTs) detecting histidine rich protein-2 antigen (HRP-2) in peripheral blood are a potential alternative.</p> <p>Methods</p> <p>HRP-2 RDTs accuracy in detecting malaria in pregnancy (MIP >28 weeks gestation) and placental <it>Plasmodium falciparum </it>malaria (after childbirth) were conducted using Giemsa microscopy and placental histopathology respectively as the reference standard. The study was conducted in Mbale Hospital, using the midwives to perform and interpret the RDT results. Discordant results samples were spot checked using PCR techniques.</p> <p>Results</p> <p>Among 433 febrile women tested, RDTs had a sensitivity of 96.8% (95% CI 92-98.8), specificity of 73.5% (95% CI 67.8-78.6), a positive predictive value (PPV) of 68.0% (95% CI 61.4-73.9), and negative predictive value (NPV) of 97.5% (95% CI 94.0-99.0) in detecting peripheral <it>P. falciparum </it>malaria during pregnancy. At delivery, in non-symptomatic women, RDTs had a 80.9% sensitivity (95% CI 57.4-93.7) and a 87.5% specificity (95%CI 80.9-92.1), PPV of 47.2% (95% CI 30.7-64.2) and NPV of 97.1% (95% CI 92.2-99.1) in detecting placental <it>P. falciparum </it>infections among 173 samples. At delivery, 41% of peripheral infections were detected by microscopy without concurrent placental infection. The combination of RDTs and microscopy improved the sensitivity to 90.5% and the specificity to 98.4% for detecting placental malaria infection (McNemar's <it>X </it>²> 3.84). RDTs were not superior to microscopy in detecting placental infection (McNemar's <it>X </it>²< 3.84). Presence of malaria in pregnancy and active placental malaria infection were 38% and 12% respectively. Placental infections were associated with poor pregnancy outcome [pre-term, still birth and low birth weight] (aOR = 37.9) and late pregnancy malaria infection (aOR = 20.9). Mosquito net use (aOR 2.1) and increasing parity (aOR 2.7) were associated with lower risk for malaria in pregnancy.</p> <p>Conclusion</p> <p>Use of HRP-2 RDTs to detect malaria in pregnancy in symptomatic women was accurate when performed by midwives. A combination of RDTs and microscopy provided the best means of detecting placental malaria. RDTs were not superior to microscopy in detecting placental infection. With a high sensitivity and specificity, RDTs could be a useful tool for assessing malaria in pregnancy, with further (cost-) effectiveness studies.</p