Circulating immune complexes and G6PD deficiency predict readmissions for blackwater fever and severe anemia in children with severe malaria in Eastern Uganda.

BACKGROUND: Recently, there has been an unexplained increase in the incidence of blackwater fever (BWF) in Eastern Uganda. In this study, we evaluate the association between immune complexes, glucose-6-phosphate dehydrogenase (G6PD) deficiency, and the occurrence and recurrence of BWF in children with severe malaria (SM). METHODS: Between 2014 and 2017, children aged six months to <4 years hospitalized with SM and community children (CC) were recruited at two hospitals in Central and Eastern Uganda. We measured serum circulating immune complexes (cIC) and their relationship to SM complications and post-discharge outcomes and evaluated effect mediation through G6PD deficiency. RESULTS: 557 children with SM and 101 CC were enrolled. The mean age of children was 2.1 years. Children with SM had higher cIC levels than CC, p<0.001. After controlling for age, sex, and site, cIC were associated with severe anemia, jaundice, and BWF (adjusted odds ratio, 95% confidence interval: 7.33 (3.45, 15.58), p<0.0001; 4.31 (1.68, 11.08), p=0.002; and 5.21 (2.06, 13.18), p<0.0001), respectively. cIC predicted readmissions for SM, severe anemia, and BWF (adjusted incidence rate ratios (95% confidence interval): 2.11 (1.33, 3.34), p=0.001; 8.62 (2.80, 26.59), p<0.0001; and 7.66 (2.62, 22.45), p<0.0001), respectively. The relationship was most evident in males where the frequency of the G6PD African allele (A-) was 16.8%. G6PD deficiency was associated with increases in cIC in males (p=0.01) and mediation analysis suggested G6PD deficiency contributes to recurrent severe anemia and BWF via increased cIC. CONCLUSIONS: Immune complexes are associated with hemolytic complications and predict recurrences in SM survivors.

Blackwater Fever Treated with Steroids in Nonimmune Patient, Italy.

Causes of blackwater fever, a complication of malaria treatment, are not completely clear, and immune mechanisms might be involved. Clinical management is not standardized. We describe an episode of blackwater fever in a nonimmune 12-year-old girl in Italy who was treated with steroids, resulting in a rapid clinical resolution.

Blackwater fever and acute kidney injury in children hospitalized with an acute febrile illness: pathophysiology and prognostic significance.

BACKGROUND: Acute kidney injury (AKI) and blackwater fever (BWF) are related but distinct renal complications of acute febrile illness in East Africa. The pathogenesis and prognostic significance of BWF and AKI are not well understood. METHODS: A prospective observational cohort study was conducted to evaluate the association between BWF and AKI in children hospitalized with an acute febrile illness. Secondary objectives were to examine the association of AKI and BWF with (i) host response biomarkers and (ii) mortality. AKI was defined using the Kidney Disease: Improving Global Outcomes criteria and BWF was based on parental report of tea-colored urine. Host markers of immune and endothelial activation were quantified on admission plasma samples. The relationships between BWF and AKI and clinical and biologic factors were evaluated using multivariable regression. RESULTS: We evaluated BWF and AKI in 999 children with acute febrile illness (mean age 1.7 years (standard deviation 1.06), 55.7% male). At enrollment, 8.2% of children had a history of BWF, 49.5% had AKI, and 11.1% had severe AKI. A history of BWF was independently associated with 2.18-fold increased odds of AKI (95% CI 1.15 to 4.16). When examining host response, severe AKI was associated with increased immune and endothelial activation (increased CHI3L1, sTNFR1, sTREM-1, IL-8, Angpt-2, sFlt-1) while BWF was predominantly associated with endothelial activation (increased Angpt-2 and sFlt-1, decreased Angpt-1). The presence of severe AKI, not BWF, was associated with increased risk of in-hospital death (RR, 2.17 95% CI 1.01 to 4.64) adjusting for age, sex, and disease severity. CONCLUSIONS: BWF is associated with severe AKI in children hospitalized with a severe febrile illness. Increased awareness of AKI in the setting of BWF, and improved access to AKI diagnostics, is needed to reduce disease progression and in-hospital mortality in this high-risk group of children through early implementation of kidney-protective measures.

Mystery of blackwater fever from an Australian perspective.

Blackwater fever is a haemolytic syndrome associated with malaria that coincided with the use of quinine chemoprophylaxis. Once quinine was no longer chronically used to prevent malaria, blackwater fever largely disappeared and its aetiology remains poorly understood. Blackwater fever is representative of classical tropical medicine and its history was reflected in Australia's colonial development of Papua New Guinea particularly as reported in the Australian medical literature.

Blackwater Fever in Ugandan Children With Severe Anemia is Associated With Poor Postdischarge Outcomes: A Prospective Cohort Study.

BACKGROUND: Blackwater fever (BWF), one of the complications of severe malaria, has recently re-emerged as a cause of severe anemia (SA) in African children. However, postdischarge morbidity in children with BWF has previously not been described. METHODS: This was a descriptive cohort study in which children, aged 0-5 years, admitted to Jinja Regional Referral Hospital with acute episodes of SA (hemoglobin ≤5.0 g/dL) were followed up for 6 months after hospitalization. Incidence of readmissions or deaths during the follow-up period was compared between SA children with BWF and those without BWF. RESULTS: A total of 279 children with SA including those with BWF (n = 92) and no BWF (n = 187) were followed for the duration of the study. Overall, 128 (45.9%) of the study participants were readmitted at least once while 22 (7.9%) died during the follow-up period. After adjusting for age, sex, nutritional status, and parasitemia, SA children with BWF had higher risk of readmissions (hazard ratio [HR], 1.68; 95% confidence interval [CI], 1.1-2.5) and a greater risk of death (HR. 3.37; 95% CI, 1.3-8.5) compared with those without BWF. Malaria and recurrence of SA were the most common reasons for readmissions. CONCLUSIONS: There is a high rate of readmissions and deaths in the immediate 6 months after initial hospitalization among SA children in the Jinja hospital. SA children with BWF had increased risk of readmissions and deaths in the postdischarge period. Postdischarge malaria chemoprophylaxis should be considered for SA children living in malaria endemic areas.

Exploring association between MBL2 gene polymorphisms and the occurrence of clinical blackwater fever through a case-control study in Congolese children.

BACKGROUND: Blackwater fever (BWF), one of the most severe and life-threatening forms of falciparum malaria, is characterized by acute massive intravascular haemolysis, often leading to acute renal failure. Thus far, the genetics of the underlying susceptibility to develop BWF is not fully elucidated. Deficiency in the MBL protein, an important component of the innate immune system, has previously been suggested to be a susceptibility factor for the development of severe malaria. This study aimed to evaluate the association between MBL2 gene polymorphisms, known to affect the MBL protein level/activity, and the occurrence of BWF among Congolese children. METHODS: This is a case-control study. Cases were patients with BWF, whereas controls, matched for gender and age, had uncomplicated malaria (UM). Dried blood spot was collected for genotyping. RESULTS: A total of 129 children were screened, including 43 BWF and 86 UM. The common allele in BWF and UM was A, with a frequency of 76.7 and 61.0%, respectively (OR: 2.67 (0.87-829) and p = 0.079). The frequency of the C allele was 18.6 and 29.1% in BWF and UM groups, respectively, with p = 0.858. Not a single D allele was encountered. Genotype AA was at higher risk for BWF whereas genotypes A0 (AB and AC) were over-represented in UM group (OR: 0.21 (0.06-0.78)) with p = 0.019. Nine haplotypes were observed in this study: 3 high MBL expression haplotypes and 6 low MBL expression haplotype. One new haplotype HYPC was observed in this study. None of these haplotypes was significantly associated with BWF. CONCLUSION: This pilot study is a preliminary research on MBL2 gene and infectious diseases in DRC. The study results show a higher risk for BWF in AA. This suggests that future studies on BWF should further investigate the contribution of a strong immune response to the occurrence of BWF.

Malaria and acute kidney injury.

Malaria is a parasitic infection transmitted by mosquitos, resulting in significant morbidity and mortality. It affects 212 million worldwide, causing death in up to 303,000 children annually. In the USA, up to 1700 people are affected yearly. Although the prevalence in developed countries is less than in developing countries, travelers from low transmission areas, and those from endemic areas who later return, are very susceptible to malaria and its complications. Severe malaria can cause significant multiorgan dysfunction including acute kidney injury (AKI). The pathogenesis is not clearly understood but proposed mechanisms include acute tubular necrosis (ATN) due to impediments in renal microcirculation, infection-triggered proinflammatory reactions within the kidney, and metabolic disturbances. Providers must consider malarial infection in cases of AKI in someone with a travel history, as early recognition and treatment are crucial to improving outcomes. This article will review malaria-induced AKI in order to provide a better understanding of this infection's effect on the kidneys.

A case of blackwater fever with persistent Plasmodium falciparum parasitaemia detected by PCR after artemether-lumefantrine treatment.

BACKGROUND: Blackwater fever is a complication of malaria infection consisting of a syndrome of febrile intra-vascular haemolysis with severe anaemia and intermittent passage of dark-red to black colour urine. Despite numerous reports and studies of this condition, its pathogenesis remains incompletely understood. CASE PRESENTATION: This report describes a case of classic blackwater fever in a returning traveller, without prior history of malaria infection nor usage of anti-malarial prophylaxis, treated with two courses of oral artemether-lumefantrine combination therapy. Unusual persistence of submicroscopic Plasmodium falciparum parasitaemia was detected by PCR for 18 days after initiation of treatment. CONCLUSION: To the authors' knowledge this is the first reported occurrence of a case of blackwater fever associated with prolonged submicroscopic parasitaemia. This unusual case challenges the current knowledge of the pathogenesis of this condition and opens questions that may have important diagnostic and treatment implications.

Severe delayed haemolytic anaemia associated with artemether-lumefantrine treatment of malaria in a Japanese traveller.

Delayed haemolytic anaemia has been reported in association with intravenous artesunate treatment in patients with severe Plasmodium falciparum malaria, and furthermore, oral artemisinin-based combination therapies including artemether-lumefantrine (AL) have also been incriminated. However, definite cases of delayed haemolytic anaemia associated with AL appear to be scarce, as reported cases were often treated concomitantly with other anti-malarials. In this study, we report a severe case of delayed haemolytic anaemia following AL alone in a Japanese traveller with severe parasitaemia caused by numerous P. falciparum parasites and a few P. vivax parasites. We also stress the need by further studies to differentiate between delayed haemolytic anaemia and blackwater fever, the latter being another malaria-related haemolytic condition, more clearly than they are now.

High Frequency of Blackwater Fever Among Children Presenting to Hospital With Severe Febrile Illnesses in Eastern Uganda.

BACKGROUND: In the Fluid Expansion as a Supportive Treatment (FEAST) trial, an unexpectedly high proportion of participants from eastern Uganda presented with blackwater fever (BWF). METHODS: We describe the prevalence and outcome of BWF among trial participants and compare the prevalence of 3 malaria-protective red blood cell polymorphisms in BWF cases vs both trial (non-BWF) and population controls. RESULTS: Of 3170 trial participants, 394 (12.4%) had BWF. The majority (318 [81.0%]) presented in eastern Uganda and were the subjects of further analysis. BWF cases typically presented with both clinical jaundice (254/318 [80%]) and severe anemia (hemoglobin level <5 g/dL) (238/310 [77%]). Plasmodium falciparum parasitemia was less frequent than in non-BWF controls, but a higher proportion were positive for P. falciparum histidine rich protein 2 (192/246 [78.0%]) vs 811/1154 [70.3%]; P = .014), suggesting recent antimalarial treatment. Overall, 282 of 318 (88.7%) received transfusions, with 94 of 282 (33.3%) and 9 of 282 (3.4%) receiving 2 or 3 transfusions, respectively. By day 28, 39 of 318 (12.3%) BWF cases and 154 of 1554 (9.9%) non-BWF controls had died (P = .21), and 7 of 255 (3.0%) vs 13/1212 (1%), respectively, had severe anemia (P = .036). We found no association with G6PD deficiency. The prevalence of both the sickle cell trait (10/218 [4.6%]) and homozygous α+thalassemia (8/216 [3.7%]) were significantly lower among cases than among population controls (334/2123 [15.7%] and 141/2114 [6.6%], respectively), providing further support for the role of malaria. CONCLUSIONS: We report the emergence of BWF in eastern Uganda, a condition that, according to local investigators, was rare until the last 7 years. We speculate that this might relate to the introduction of artemisinin-based combination therapies. Further studies investigating this possibility are urgently required.

Intravascular haemolysis with haemoglobinuria in a splenectomized patient with severe Plasmodium knowlesi malaria.

BACKGROUND: Haemoglobinuria is an uncommon complication of severe malaria, reflecting acute intravascular haemolysis and potentially leading to acute kidney injury. It can occur early in the course of infection as a consequence of a high parasite burden, or may occur following commencement of anti-malarial treatment. Treatment with quinine has been described as a risk factor; however the syndrome may also occur following treatment with intravenous artesunate. In Malaysia, Plasmodium knowlesi is the most common cause of severe malaria, often associated with high parasitaemia. Asplenic patients may be at additional increased risk of intravascular haemolysis. CASE PRESENTATION: A 61 years old asplenic man was admitted to a tertiary referral hospital in Sabah, Malaysia, with severe knowlesi malaria characterized by hyperparasitaemia (7.9 %), jaundice, respiratory distress, metabolic acidosis, and acute kidney injury. He was commenced on intravenous artesunate, but1 day later developed haemoglobinuria, associated with a 22 % reduction in admission haemoglobin. Additional investigations, including a cell-free haemoglobin of 10.2 × 10(5) ng/mL and an undetectable haptoglobin, confirmed intravascular haemolysis. The patient continued on intravenous artesunate for a total of 48 h prior to substitution with artemether-lumefantrine, and made a good recovery with resolution of his haemoglobinuria and improvement of his kidney function by day 3. CONCLUSIONS: An asplenic patient with hyperparasitaemic severe knowlesi malaria developed haemoglobinuria after treatment with intravenous artesunate. There are plausible mechanisms for increased haemolysis with hyperparasitaemia, and following both splenectomy and artesunate. Although in this case the patient made a rapid recovery, knowlesi malaria patients with this unusual complication should be closely monitored for potential deterioration.

Blood Trials: Transfusions, Injections, and Experiments in Africa, 1890-1920.

From about 1880 to 1920, a culture of medical experimentation promoted blood transfusion as a therapy for severe anemia in Europe, which was applied in German East Africa in 1892 for a case of blackwater fever, a complication of malaria afflicting mainly Europeans. This first case of blood transfusion in Africa, in which an African's blood was transfused into a German official, complicates the dominant narrative that blood transfusions in Africa came only after World War I. Medical researchers moreover experimented with blood serum therapies on human and animal subjects in Europe and Africa, injecting blood of different species, "races" and ethnicities into others to demonstrate parasite transmissibility and to discover vaccines for diseases such as malaria, sleeping sickness, and yellow fever. While research in German colonies is highlighted here, this was a transnational medical culture that crossed borders and oceans. This research is of interest as a possible early pathway for the epidemic spread of HIV and other zoonoses in Africa and the world, which biomedical researchers have identified as emerging in West-Central Africa sometime around the turn of the twentieth century.

Severe malaria in children: A descriptive report from Kinshasa, the Democratic Republic of Congo.

The decline of susceptibility of Plasmodium falciparum to chloroquine and sulfadoxine-pyrimethamine resulted in the change of drug policy. This policy has probably changed the facies of the severe form of malaria. A prospective study was conducted in Kinshasa, the Democratic Republic of Congo. Data on children aged ≤13 years, diagnosed with severe malaria were analyzed. In total, 378 children were included with an overall median age of 8 years (age range: 1-13 years). Dark urine was seen in 25.1% of cases. Metabolic acidosis (85.2%), hypoglycemia (62.2%) and hemoglobin ≤5 g/dl (39.1%) were the common laboratories features. Severe malaria anemia, cerebral malaria and Blackwater fever (BWF) were found in 39.1, 30.1 and 25.4%, respectively. Mortality rate was 4%. BWF emerges as a frequent form of severe malaria in our midst. Availing artemisin-based combination treatments in the health care system is a priority to reduce the incidence of BWF in our environment.

Physiopathology and clinical management of blackwater fever: a scoping review.

BACKGROUND: Blackwater fever (BWF) is a severe syndrome occurring in patients with malaria upon antimalarial treatment, characterized by massive intravascular haemolysis and haemoglobinuria. BWF is a neglected condition and management recommendations are unavailable. OBJECTIVES: We performed a scoping review to appraise available data on clinical picture, treatment and physiopathology of BWF, which could guide rationally its clinical management. METHODS: MEDLINE, EMBASE, LILACS, Web of Science, and Scopus databases, and the reference list of relevant publications, were searched. Papers reporting original data on BWF cases or investigating the physiopathology of BWF were eligible. Data regarding case characteristics, trigger event, clinical management and outcome were extracted. For papers investigating the physiopathology of BWF, study design and principal findings were extracted. No quality assessment was performed. Data are presented as numbers and percentages, and summary of findings, grouped by paper focus (clinical description or physiopathology). RESULTS: 101 papers were included. The majority of BWF cases were observed in autochthonous children (75.7%) and adults (15.3%), in contrast with historical perception that BWF patients were typically expatriates. Clinical management was described for 794 cases; corticosteroids were used in 23. Outcome was reported for 535 patients, with 18.1% mortality. The trigger was reported for 552 (47.5%) cases; in 70.4% identified as quinine. However, two RCT comparing artesunate and quinine for falciparum malaria treatment did not find significant difference in BWF occurrence after their administration. Two case-control studies did not find significant difference in G6PDH deficiency between malaria patients with and without BWF. CONCLUSIONS: The physiopathology and optimal treatment of BWF remain similarly unknown as they were over a century ago. Empirical supporting treatment approach seems reasonable, while change of antimalarial drug and use of corticosteroids remain object of debate.

Malaria Tropica: An Autopsy Case Report With a Discussion on the Presence of Malaria in Bulgaria.

Malaria is an infectious disease caused by several types of parasitic plasmodia and transmitted to humans through Anopheles mosquitoes. The disease has long been widespread and has caused a significant number of deaths and decreased life quality from sequelae worldwide. As understanding of the disease increased immensely at the beginning of the 20th century, eradication plans were implemented to decrease disease transmission. This led to the successful eradication of malaria across predominantly industrialized countries, with multiple geographic areas remaining malaria endemic zones to this day. With climate changes and migration, the risk of reintroduction of malaria to malaria-free zones has risen due to relatively easy travel to endemic zones and importation of cases. On the one hand, this is a significant public health risk and, on the other, a challenge to the medical system, as healthcare workers in malaria-free zones are often ill-prepared to recognize, diagnose, and treat malaria cases. Herein, we present an autopsy and histopathology case report of tropical (falciparum) malaria, complicated with blackwater fever (malignant malaria) with prevalent gross and histopathological changes, including hemomelanin deposition in the spline, liver, and bone marrow; visible parasitic forms in the remaining red blood cells; Durk's granulomas, sludge, and petechial hemorrhages in the central nervous system; and hemoglobin casts within the renal tubular structures. We also discuss the history and risk of reintroducing malaria into a malaria-free zone - Bulgaria.

Successful Oral Antimalarial Therapy in A 14-Year-Old Child with Blackwater Fever: A Case in a Rural Area of Asmat Regency of Papua, Indonesia: Successful Oral Antimalarial in Blackwater Fever.

Background: Blackwater fever (BWF) is one of the severe forms of malaria manifested by hemoglobinuria that causes dark-colored urine, fever, anemia, jaundice and acute kidney injury. BWF is most commonly associated with Plasmodium falciparum infection and its treatment. Parenteral antimalarial therapy is recommended as the treatment of choice for BWF. Here we present the first case of successful oral antimalarial therapy in BWF to the best of our knowledge. Case Presentation: A 14-year-old boy was hospitalized with BWF as the primary diagnosis based on the presence of fever, jaundice and "coca-cola"-colored urine, along with laboratory results which showed Plasmodium falciparum infection, anemia, and impaired kidney function. Uncomplicated malaria manifestations had been appearing for seven days before admission, but the syndrome of BWF developed several hours following the first dose of dihydroartemisinin-piperaquine (DHP). Treatment with a 3-day course of DHP was continued because parenteral antimalarials were unavailable at that time. Remarkable improvements were seen following the second and third doses of DHP along with adequate supportive medical care. Conclusion: The unavailability of parenteral antimalarials makes oral antimalarials a possible alternative treatment for BWF. In addition, close monitoring and supportive medical care are critical in the treatment of BWF.

Predictors of prolonged hospitalisation and mortality among children admitted with blackwater fever in eastern Uganda.

Our study aimed at determining clinical factors associated with prolonged hospitalisation and death among children admitted with blackwater fever (BWF). We analysed 920 eligible records for the period January - December 2018 from Mbale and Soroti Regional Referral Hospitals in Eastern Uganda. The median hospitalisation was 3 (IQR: 2-5 days) days. Prolonged hospitalisation was in 251/920 (27.3%). Clinical features independently associated with prolonged hospitalisation included abdominal tenderness, body pain and mild fever. 29/920 (3.2%) died, of these 20 (69.0%) within 48 h of admission. Features of severity associated with mortality were noisy or interrupted breathing, tachypnoea, chest pain, convulsions, delayed capillary refill time (≥3 s), severe pallor, high fever (>38.5°C), altered level of consciousness, prostration and acidotic breathing.

Autoimmune Dysfunction Due to Severe Malaria.

Despite advances in treatment and prevention, malaria still carries significant morbidity and mortality. Cases of malaria in the United States are rare and cases of severe malaria, mostly attributable to Plasmodium falciparum, are even more uncommon. With the coronavirus disease 2019 (COVID-19) pandemic, there have been distractions in evaluation and diagnosis leading to a rise in cases and deaths. We present a case of autoimmune dysregulation and blackwater fever secondary to severe malaria, requiring multiple courses of antimalarial therapy. Careful travel history and prompt recognition and treatment facilitates improved patient survival and recovery.

Acute kidney injury, persistent kidney disease, and post-discharge morbidity and mortality in severe malaria in children: A prospective cohort study.

BACKGROUND: Globally, 85% of acute kidney injury (AKI) cases occur in low-and-middle-income countries. There is limited information on persistent kidney disease (acute kidney disease [AKD]) following severe malaria-associated AKI. METHODS: Between March 28, 2014, and April 18, 2017, 598 children with severe malaria and 118 community children were enrolled in a two-site prospective cohort study in Uganda and followed up for 12 months. The Kidney Disease: Improving Global Outcomes (KDIGO) criteria were used to define AKI (primary exposure) and AKD at 1-month follow-up (primary outcome). Plasma neutrophil gelatinase-associated lipocalin (NGAL) was assessed as a structural biomarker of AKI. FINDINGS: The prevalence of AKI was 45·3% with 21·5% of children having unresolved AKI at 24 h. AKI was more common in Eastern Uganda. In-hospital mortality increased across AKI stages from 1·8% in children without AKI to 26·5% with Stage 3 AKI (p < 0·0001). Children with a high-risk plasma NGAL test were more likely to have unresolved AKI (OR, 7·00 95% CI 4·16 to 11·76) and die in hospital (OR, 6·02 95% CI 2·83 to 12·81). AKD prevalence was 15·6% at 1-month follow-up with most AKD occurring in Eastern Uganda. Risk factors for AKD included severe/unresolved AKI, blackwater fever, and a high-risk NGAL test (adjusted p < 0·05). Paracetamol use during hospitalization was associated with reduced AKD (p < 0·0001). Survivors with AKD post-AKI had higher post-discharge mortality (17·5%) compared with children without AKD (3·7%). INTERPRETATION: Children with severe malaria-associated AKI are at risk of AKD and post-discharge mortality. FUNDING: This work was supported by the National Institutes of Health National Institute of Neurological Disorders and Stroke (R01NS055349 to CCJ) and the Fogarty International Center (D43 TW010928 to CCJ), and a Ralph W. and Grace M. Showalter Young Investigator Award to ALC.

Blackwater Fever in Pregnancy With Severe Falciparum Malaria: A Case of Imported Malaria From Nigeria to the United Kingdom During the COVID-19 Pandemic.

We present the case of imported malaria in pregnancy to the United Kingdom (UK) from Nigeria, where a 28-year-old primigravida presented to our maternity assessment unit (MAU) with complaints of pyrexia, rigors and passing dark coloured urine. She gave a travel history of recent migration from Nigeria 10 days before presenting to our emergency department. She initially became unwell five days after her arrival with general malaise and myalgia. On day six, she developed lower abdominal pain and observed that her urine was dark in colour. This prompted her to contact her general practitioner (GP). Treatment for a urinary tract infection was initiated by the GP after a phone consultation in keeping with COVID-19 contingency guidance, and the patient was prescribed antibiotics for three days. She presented to the emergency department two days after completing the course of antibiotics where she complained of worsening pelvic pain, reduced foetal movements and passing black urine. She was treated as suspected COVID-19 and red flag sepsis. Obstetric review led to investigation and diagnosis of severe malaria in pregnancy, which was accompanied by blackwater fever (BWF). The patient recovered after three doses of artesunate. An ultrasound scan of the foetus revealed a congenital cardiac anomaly, which had not been detected in an earlier scan. There was no evidence of congenital malaria in the neonate after delivery. There are several novel aspects in this case as maternal mortality in severe Plasmodium falciparum can be significantly high. Those who survive the disease in pregnancy are also known to develop several complications such as intrauterine death and preterm labour. There was also the component of blackwater fever, which is a rare event associated with severe malaria, and it also has a mortality rate. Significant in her medical history was a diagnosis of the sickle cell trait, and we postulate that this feature gave an added protection from the complications of severe malaria in pregnancy as well as blackwater fever.