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

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

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

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

Variable effect of co-infection on the HIV infectivity: Within-host dynamics and epidemiological significance

<p>Abstract</p> <p>Background</p> <p>Recent studies have implicated viral characteristics in accounting for the variation in the HIV set-point viral load (spVL) observed among individuals. These studies have suggested that the spVL might be a heritable factor. The spVL, however, is not in an absolute equilibrium state; it is frequently perturbed by immune activations generated by co-infections, resulting in a significant amplification of the HIV viral load (VL). Here, we postulated that if the HIV replication capacity were an important determinant of the spVL, it would also determine the effect of co-infection on the VL. Then, we hypothesized that viral factors contribute to the variation of the effect of co-infection and introduce variation among individuals.</p> <p>Methods</p> <p>We developed a within-host deterministic differential equation model to describe the dynamics of HIV and malaria infections, and evaluated the effect of variations in the viral replicative capacity on the VL burden generated by co-infection. These variations were then evaluated at population level by implementing a between-host model in which the relationship between VL and the probability of HIV transmission per sexual contact was used as the within-host and between-host interface.</p> <p>Results</p> <p>Our within-host results indicated that the combination of parameters generating low spVL were unable to produce a substantial increase in the VL in response to co-infection. Conversely, larger spVL were associated with substantially larger increments in the VL. In accordance, the between-host model indicated that co-infection had a negligible impact in populations where the virus had low replicative capacity, reflected in low spVL. Similarly, the impact of co-infection increased as the spVL of the population increased.</p> <p>Conclusion</p> <p>Our results indicated that variations in the viral replicative capacity would influence the effect of co-infection on the VL. Therefore, viral factors could play an important role driving several virus-related processes such as the increment of the VL induced by co-infections. These results raise the possibility that biological differences could alter the effect of co-infection and underscore the importance of identifying these factors for the implementation of control interventions focused on co-infection.</p

Causes of Perinatal Death at a Tertiary Care Hospital in Northern Tanzania 2000-2010: A Registry Based Study.

Perinatal mortality reflects maternal health as well as antenatal, intrapartum and newborn care, and is an important health indicator. This study aimed at classifying causes of perinatal death in order to identify categories of potentially preventable deaths. We studied a total of 1958 stillbirths and early neonatal deaths above 500 g between July 2000 and October 2010 registered in the Medical Birth Registry and neonatal registry at Kilimanjaro Christian Medical Centre (KCMC) in Northern Tanzania. The deaths were classified according to the Neonatal and Intrauterine deaths Classification according to Etiology (NICE). Overall perinatal mortality was 57.7/1000 (1958 out of 33 929), of which 1219 (35.9/1000) were stillbirths and 739 (21.8/1000) were early neonatal deaths. Major causes of perinatal mortality were unexplained asphyxia (n=425, 12.5/1000), obstetric complications (n=303, 8.9/1000), maternal disease (n=287, 8.5/1000), unexplained antepartum stillbirths after 37 weeks of gestation (n= 219, 6.5/1000), and unexplained antepartum stillbirths before 37 weeks of gestation (n=184, 5.4/1000). Obstructed/prolonged labour was the leading condition (251/303, 82.8%) among the obstetric complications. Preeclampsia/eclampsia was the leading cause (253/287, 88.2%) among the maternal conditions. When we excluded women who were referred for delivery at KCMC due to medical reasons (19.1% of all births and 36.0% of all deaths), perinatal mortality was reduced to 45.6/1000. This reduction was mainly due to fewer deaths from obstetric complications (from 8.9 to 2.1/1000) and maternal conditions (from 8.5 to 5.5/1000). The distribution of causes of death in this population suggests a great potential for prevention. Early identification of mothers at risk of pregnancy complications through antenatal care screening, teaching pregnant women to recognize signs of pregnancy complications, timely access to obstetric care, monitoring of labour for fetal distress, and proper newborn resuscitation may reduce some of the categories of deaths

Placental Malaria is associated with reduced early life weight development of affected children independent of low birth weight

<p>Abstract</p> <p>Background</p> <p>Infection with <it>Plasmodium falciparum </it>during pregnancy contributes substantially to the disease burden in both mothers and offspring. Placental malaria may lead to intrauterine growth restriction or preterm delivery resulting in low birth weight (LBW), which, in general, is associated with increased infant morbidity and mortality. However, little is known about the possible direct impact of the specific disease processes occurring in PM on longer term outcomes such as subsequent retarded growth development independent of LBW.</p> <p>Methods</p> <p>In an existing West-African cohort, 783 healthy infants with a birth weight of at least 2,000 g were followed up during their first year of life. The aim of the study was to investigate if <it>Plasmodium falciparum </it>infection of the placenta, assessed by placental histology, has an impact on several anthropometric parameters, measured at birth and after three, six and 12 months using generalized estimating equations models adjusting for moderate low birth weight.</p> <p>Results</p> <p>Independent of LBW, first to third born infants who were exposed to either past, chronic or acute placental malaria during pregnancy had significantly lower weight-for-age (-0.43, 95% CI: -0.80;-0.07), weight-for-length (-0.47, 95% CI: -0.84; -0.10) and BMI-for-age z-scores (-0.57, 95% CI: -0.84; -0.10) compared to infants born to mothers who were not diagnosed with placental malaria (p = 0.019, 0.013, and 0.012, respectively). Interestingly, the longitudinal data on histology-based diagnosis of PM also document a sharp decline of PM prevalence in the Sukuta cohort from 16.5% in 2002 to 5.4% in 2004.</p> <p>Conclusions</p> <p>It was demonstrated that PM has a negative impact on the infant's subsequent weight development that is independent of LBW, suggesting that the longer term effects of PM have been underestimated, even in areas where malaria transmission is declining.</p