Invasive non-typhoidal Salmonella in Mozambican children

Objective  To describe the epidemiology and clinical presentation of invasive non-typhoidal Salmonella (NTS) in Mozambique.
Methodology  We analysed the epidemiology, clinical presentation and serotype distribution of invasive NTS among Mozambican children admitted to the Manhiça District Hospital between May 2001 and April 2006.
Results  A total of 401 NTS cases were analysed; the median age was 16 months [interquartile range (IQR): 10–24]. Fever, cough and increased respiratory rate were the most common symptoms reported, while diarrhoea was present in only 29%. In the univariate analysis, invasive NTS was associated with age, fever, diarrhoea, increased respiratory rate, splenomegaly, hepatomegaly, severe malnutrition, and severe anaemia. Young age, severe malnutrition, diarrhoea and pneumonia were independent risk factors of death. S. typhimurium (66%), and S. enteritidis (25%) were the most frequent serotypes, with incidence rates of 240.4 and 108.6 per 100 000 child years among infants for S. typhimurium and S. enteritidis , respectively; and no significant differences were found regarding their clinical presentation. Resistance to ampicillin, chloramphenicol and trimethoprim-sulfamethoxazole was high for both S. typhimurium and S. enteritidis .
Conclusions  Clinical presentation of invasive NTS was non-specific and similar to that of other infections, with some factors being associated with NTS. Antibiotic resistance was very common to currently recommended and available antibiotics for suspected sepsis.     

Severe anaemia in children living in a malaria endemic area of Kenya

Severe anaemia is an important cause of morbidity and mortality in African children, but the causes, particularly falciparum malaria, are difficult to determine. We assessed the contribution of falciparum malaria to anaemia in Kenyan children by clinical examination and measurement of parasitaemia and haemoglobin (Hb) concentration in 559 children in the community and in 2412 children admitted to Kilifi district hospital during a 2‐year period. We also attempted to characterize severe malarial anaemia by examining the causes and pathophysiology of anaemia in 101 children admitted with Hb concentration 50 g/l during a 1‐year period. Plasmodium falciparum infection was associated with reduced Hb concentration in children in the community and in those admitted to hospital irrespective of diagnosis. Falciparum malaria was the primary cause in 46 cases (46%) of severe anaemia admitted to hospital. There was no difference in the frequency of haemolysis or dyserythropoiesis in the children with malarial anaemia and those with anaemia from other causes, such as iron deficiency or sickle cell disease. The mortality rate in the children with severe malarial anaemia was 8.6% compared with 3.6% in children with severe anaemia due to other causes. Falciparum malaria does not present with a characteristic clinical or haematological picture, but is a major cause of the morbidity and mortality in children with severe anaemia who live on the Kenyan coast, a malaria endemic area.     

Severe anaemia in Zambian children with Plasmodium falciparum malaria

BACKGROUND: Severe anaemia and cerebral malaria are highly prevalent complications of Plasmodium falciparum malaria among African children. The mechanisms of severe malarial anaemia, and the relative importance of this condition in comparison to cerebral malaria, are not known for many regions of Africa. METHODS We reviewed the records of 6200 children up to 6 years of age admitted to one rural Zambian hospital between 1994 and 1996. Severe malarial anaemia was defined as an haemoglobin concentration < 5.0 g/dl in a patient with asexual forms of P. falciparum in the peripheral blood. Cerebral malaria was defined as impaired consciousness (Blantyre coma score < 5) not attributable to any other cause in a patient with a positive malaria smear. RESULTS Severe malarial anaemia was found in 590 children (9.5% of paediatric admissions) and strictly defined cerebral malaria occurred in 286 children (4.6% of paediatric admissions); 98 of these patients had the combination of both complications. Severe malarial anaemia correlated strongly with the degree of parasitaemia, with malnutrition as indicated by low weight for age, with absence of fever and with presentation late in the malaria season. In comparison, patients with cerebral malaria were more often febrile and presented earlier in the malaria season. The case fatality rate of severe malarial anaemia (0.088) was about half that of cerebral malaria (0.189), but because severe malarial anaemia was more common, these two forms of complicated malaria were implicated in similar numbers of in-hospital paediatric deaths. CONCLUSION Severe anaemia is a more common complication of P. falciparum malaria in hospitalized Zambian children than cerebral malaria and is associated with a similar number of deaths. Malnutrition and changes in immune response patterns due to prolonged exposure to P. falciparum may contribute to the development of this complication.     

Non-typhoidal salmonella bacteraemia--an under-recognized feature of AIDS in African adults

Non-typhoidal salmonella (NTS) infections are severe, invasive and recurrent in the HIV-infected adult, and NTS are the commonest cause of hospital admission with bacteraemia in sub-Saharan Africa. NTS bacteraemia typically presents in patients with HIV/AIDS once the CD4 count falls below 200 cells/microL. In-patient mortality is 35%-60%, and is highest in patients with confusion or severe anaemia. Among survivors, 25%-45% may have single or multiple recurrences of NTS bacteraemia 1-6 months after the first illness, requiring retreatment. Diagnosis relies on blood culture, so in many areas this disease cannot be definitively diagnosed, and must be empirically treated. Treatment is guided by local antibiotic sensitivities; fluoroquinolones are particularly useful for initial treatment if there is multidrug reistance to other agents, and may result in lower recurrence rates than other agents. Where possible, long-term secondary chemoprophylaxis to prevent recurrence is advisable. Successful ARV treatment also prevents recurrence. There is inadequate knowledge about the epidemiology of carriage and transmission among at-risk populations.     

Bacteraemia and mortality among adult medical admissions in Malawi--predominance of non-typhi salmonellae and Streptococcus pneumoniae

OBJECTIVES: The high seroprevalence of HIV in Malawi might be expected to alter the pattern of pathogens isolated from bacteraemic patients. We aimed to describe the frequency and seasonal pattern of bacterial isolates from blood, their antibiotic susceptibility, and patient outcome, in order to provide data on which to base empirical antibiotic therapy and further studies of pathogenesis. METHODS: Over a 12-month period, blood cultures were taken from all febrile adult medical admissions to Queen Elizabeth Central Hospital, Blantyre. RESULTS: A total of 2789 out of 9298 adult general medical admissions had blood culture performed, of whom 449 (16.1%) grew significant pathogens. Non-typhi salmonellae (NTS) (37%) and Streptococcus pneumoniae (30%) were the two commonest isolates. Mortality was 18% among general medical admissions and 38% among bacteraemic patients. Mortality for individual pathogens was: NTS 33%; S. pneumoniae 36%; Escherichia coli 54%; Klebsiella spp. 58%; Neisseria meningitidis 44%; Salmonella typhi 17%. Despite an overwhelming association between the major pathogens and HIV infection (95% of S. pneumoniae cases and 92% of NTS cases were seropositive for HIV), a seasonal pattern was preserved. Streptococcus pneumoniae was more frequently isolated in the cold dry months, while STM isolates increased following a rise in temperature. A case of bacteraemia with Vibrio cholerae (serotype 01) was detected during a cholera outbreak in the rainy season. Although S. pneumoniae isolates were relatively susceptible to penicillin (88%) and chloramphenicol (74%), S. typhimurium isolates were fully susceptible only to chloramphenicol. CONCLUSIONS: This large study confirms the dominance of NTS and S. pneumoniae in bacteraemia in an area affected by HIV-1 and allows comparison of mortality by individual pathogens. It demonstrates a preserved seasonal pattern of bacteraemia for these major pathogens, despite an overwhelming association with HIV infection.     

Bacteremia in Malawian children with severe malaria: prevalence, etiology, HIV coinfection, and outcome

BACKGROUND: Previous prospective studies of bacteremia in African children with severe malaria have mainly included children with cerebral malaria, and no study has examined the impact of human immunodeficiency virus (HIV) infection. We examined the prevalence and etiology of bacteremia and the impact of HIV infection on bacteremia in Malawian children with severe malaria, as well as the impact of bacteremia and HIV infection on outcome. METHODS: From 1996 until 2005, blood for culture was obtained on admission from all children admitted with severe malaria during the rainy season to the Paediatric Research Ward at the Queen Elizabeth Central Hospital in Blantyre, Malawi. HIV testing was performed prospectively from 2001 to 2005 and retrospectively for those admitted from 1996 to 2000. Multivariate regression analysis examined independent risk factors for bacteremia and death. RESULTS: Sixty-four (4.6%) of 1388 children with severe malaria had bacteremia; nontyphoidal Salmonellae (NTS) accounted for 58% of all bacteremias. The prevalence of any bacteremia and of NTS bacteremia was highest in children with severe malarial anemia (11.7% and 7.6%), compared with the prevalence in children with cerebral malaria and severe anemia (4.7% and 3.8%) and in those with cerebral malaria alone (3.0% and 0.9%). HIV infection status was determined in 1119 patients. HIV prevalence was 16% (and was highest in those with severe malaria anemia, at 20.4%), but HIV infection was not significantly associated with bacteremia. Neither bacteremia nor HIV infection was associated with death. CONCLUSIONS: Antibiotics are not routinely indicated for children with severe malaria in this region, in which HIV is endemic. However, antibiotic therapy should be used to treat NTS infection if bacteremia is suspected in children with severe malarial anemia.     

Intermittent preventive treatment using artemisinin-based combination therapy reduces malaria morbidity among school-aged children in Mali

Objective  To assess the efficacy of intermittent preventive treatment (IPT) against malaria in school-aged children.
Methods  This was an open randomized controlled trial of seasonal IPT among school children (IPTsc) aged 6–13 years in Kollé, Mali. The study began in September 2007 and completed follow-up in May 2008. Students were randomized to one of three study arms: Sulfadoxine–pyrimethamine plus artesunate (SP/AS), amodiaquine plus artesunate (AQ/AS) or vitamin C. All students received two full treatment doses, given 2 months apart during the season of high transmission from September to December. Groups were compared with respect to incidence of clinical malaria, asymptomatic parasitemia and haemoglobin concentration.
Results  A total of 296 students were randomized, and retention in the study was 99.3%. Clinical malaria incidence in the SP/AS and AQ/AS arms was reduced by 66.6% and 46.5%, respectively, vs . vitamin C ( P  < 0.001). There were fewer clinic visits for any cause among the children receiving SP/AS or AQ/AS ( P  = 0.024). The prevalence of asymptomatic parasitemia was fivefold higher in the vitamin C arm than either SP/AS or AQ/AS at each post-treatment evaluation ( P  < 0.001). At the end of the transmission period, children treated with IPT had lower rates of anaemia (SP/AS, 17.7%; AQ/AS, 16.0%; vitamin C, 29.6%; P  = 0.039).
Conclusion  IPT among school children reduced the rates of clinical malaria, all-cause acute clinic visits, asymptomatic parasitemia and anaemia among school-aged children.     

Bacteraemia in adult patients presenting with malaria in India

Severe falciparum malaria is a major health problem in Odisha, India, contributing to high mortality. Multi organ dysfunction is a predominant manifestation of severe disease in Odisha, unlike in Africa, where cerebral malaria and anaemia are common. There are several studies implicating bacteraemia with severe malaria in African children while there are no reports in adults in India. This study has addressed this issue by enrolling 67 P. falciparum infected adult patients categorized into severe and uncomplicated malaria. Blood culture failed to confirm bacteraemia in any sample with the exception of one case of uncomplicated malaria. Study is inconclusive with regard to use of antibiotics in adult patients.     

Changes in white blood cells and platelets in children with falciparum malaria: relationship to disease outcome

Little is known about the changes in white blood cells and platelets in children with falciparum malaria in endemic areas. We measured the white cell count (WCC) and platelets of 230 healthy children from the community, 1369 children admitted to hospital with symptomatic malaria, and 1461 children with other medical conditions. Children with malaria had a higher WCC compared with community controls, and leucocytosis was strongly associated with younger age, deep breathing, severe anaemia, thrombocytopenia and death. The WCC was not associated with a positive blood culture. In children with malaria, high lymphocyte and low monocyte counts were independently associated with mortality. A platelet count of less than 150 x 109/l was found in 56.7% of children with malaria, and was associated with age, prostration and parasite density, but not with bleeding problems or mortality. The mean platelet volume was also higher in children with malaria compared with other medical conditions. This may reflect early release from the bone marrow in response to peripheral platelet destruction. Thus, leucocytosis was associated with both severity and mortality in children with falciparum malaria, irrespective of bacteraemia, whereas thrombocytopenia, although very common, was not associated with adverse outcome.     

Community-acquired bacterial bloodstream infections in developing countries in south and southeast Asia: a systematic review

Information about community-acquired bacteraemia in developing countries in south and southeast Asia is scarce. We aimed to establish the case fraction of bacteraemia in febrile patients admitted to hospital. We searched four databases and identified studies of south and southeast Asia published between 1990 and 2010 that prospectively assessed patients admitted to hospital and from whom a blood culture was taken. We reviewed 17 eligible studies describing 40,644 patients. Pathogenic organisms were isolated from 3506 patients (9%; range 1-51%); 1784 (12%) of 14,386 adults and 1722 (7%) of 26,258 children. Salmonella enterica serotype Typhi was the most common bacterial pathogen, accounting for 532 of 1798 (30%) isolates in adults and 432 of 1723 (25%) in children. Other commonly isolated organisms in adults were Staphylococcus aureus, Escherichia coli, and other gram-negative organisms, and in children were Streptococcus pneumoniae and Haemophilus influenzae. A substantial case fraction of bacteraemia occurs in patients admitted to hospital with fever in this region. Management could be improved if diagnostic microbiology facilities were more widely available. The prevailing organisms causing bacteraemia and their susceptibility patterns could inform empirical treatment regimens and prevention strategies.     

Differences in presentation of severe malaria in urban and rural Gabon

There are rare comparative studies of the clinical and laboratory features of severe and moderate malaria, including predictors of poor outcome, in rural and urban areas for regions of high malaria transmission. We therefore studied 2,235 children hospitalized for malaria in a rural (Lambaréné) and an urban (Libreville) area in Gabon between January 2001 and December 2002. From children screened, 33% and 48% were hospitalized for malaria in Libreville and Lambaréné, respectively (P < 0.001). Two malaria clinical groups were identified according to the World Health Organization 2000 classification of severe malaria. In both areas, severe malaria was characterized by a high proportion of severe anemia. The case fatality rate was 5-fold lower in Lambaréné than in Libreville (1% versus 5%; P < 0.0001). In both sites, cerebral malaria associated with respiratory distress was the most important predictor of fatal malaria (odds ratio = 10.7, 95% confidence interval = 4.8-23.8 P < 0.0001).     

The epidemiology of malaria among pregnant women attending antenatal clinics in an area with intense and highly seasonal malaria transmission in northern Ghana

Objective  To describe the factors associated with malaria infection and anaemia in pregnancy in northern Ghana.
Method  We studied 3642 pregnant women of all gravidities and gestational age of 18–32 weeks who attended an antenatal clinic in the Kassena-Nankana district of Ghana between June 2004 and July 2006. Blood samples were examined for haemoglobin concentrations and parasitaemia, and we obtained socio-demographic data, an obstetric history, information on their past and current state of health and bed net use.
Results  The overall prevalence of malaria parasitaemia during pregnancy was 47%. Older age [adjusted odds ratio (AOR) 0.65, 95% CI 0.54–0.78], multigravidity (AOR 0.51, 95% CI 0.42–0.61) and third trimester of pregnancy (AOR 0.85, 95% CI 0.73–0.99) were associated with a decreased risk of parasitaemia. Enrolment during the rainy or post-rainy season was associated with an increased risk of parasitaemia (AOR 2.59, 95% CI 2.20–3.04 and AOR 3.12, 95% CI, 2.60–3.74 respectively). Malaria infection was associated with an increased risk of anaemia among young women. The prevalences of anaemia (Hb<11.0 g/dl) and severe anaemia (Hb<7.0 g/dl) during pregnancy were 72% and 2% respectively. The risk of anaemia was lower in older women (AOR 0.79, 95% CI, 0.64–0.97), multigravidae (AOR 0.67, 95% CI 0.55–0.83) and in educated women (AOR 0.81, 0.68–0.98).
Conclusion  The prevalence of malaria parasitaemia and anaemia among pregnant women in Kassena-Nankana district is high with marked seasonal variation. Targeting of interventions to the high transmission season and to paucigravidae may be appropriate in this setting.     

Prolonged macrophage activation and persistent anaemia in children with complicated malaria

objective   To determine if prolonged immune activation may be associated with the persistence of anaemia after treatment for severe malaria, we measured serum concentrations of neopterin and interleukin-4 during one week of antimalarial therapy and determined haemoglobin levels one month later. Neopterin is a clinically valuable marker for monitoring activation of macrophages by gamma-interferon and thus reflects the TH-1 immune response. Interleukin-4 is a major cytokine that tends to be inhibited by TH-1 activity. method   The study population consisted of 26 Zambian children <6 years of age who presented with cerebral malaria to a rural hospital in 1994 and who were treated with quinine for seven days. Six children (23%) were anaemic (haemoglobin < 11 g/dl) one month after completing antimalarial therapy. results   On admission, concentrations of neopterin were markedly elevated in all patients. During the seven days of anti-malarial therapy, neopterin levels remained elevated in the 6 children who proved to have persistent anaemia one month after finishing treatment but declined significantly ( P = 0.008) in the 20 children who corrected their haemoglobin levels by that time. Conversely, interleukin-4 levels declined in the children with persistent anaemia ( P = 0.043) but not in the other children. conclusion   Persistence of the TH-1 mediated immune response and associated activation of macrophages may be involved in the pathogenesis of lingering anaemia after treatment of malaria.     

Case fatality of SARS in mainland China and associated risk factors

Objective To analyse the case fatality ratio (CFR) and its risk factors for severe acute respiratory syndrome (SARS) in mainland China by using a comprehensive dataset of all probable cases.
Methods The data of all probable SARS cases were derived from the Infectious Disease Reporting System of the Center of Diseases Control and Hospital Information Systems, during the 2003 epidemic in mainland China. The definition of probable SARS case was consistent with the definition for clinically confirmed SARS issued by the Ministry of Health of the People's Republic of China. We performed univariate and multivariate logistic regression analysis to determine the association of CFR with age, sex, residence location, occupation, the period of the epidemic and the duration from symptom onset to admission into hospital.
Results The overall CFR was 6.4% among 5327 probable SARS cases in mainland China. Old age, being a patient during the early period of a local outbreak, and being from Tianjin led to a relatively higher CFR than young age, late stage of a local outbreak and cases from Beijing. Guangdong Province resulted in an even lower CFR compared with Beijing.
Conclusions Because of their deteriorated health status and apparent complications, SARS patients aged >60 years had a much higher risk of dying than younger patients. At the early stage of local outbreaks, lack of experience in patient care and perhaps treatment also led to a relatively higher CFR. The Tianjin SARS outbreak happened mainly within a hospital, leading to a high impact of co-morbidity. The relatively young age of the cases partly explains the low CFR in mainland China compared with other countries and areas affected by SARS.     

Hepcidin regulation in Kenyan children with severe malaria and non-typhoidal Salmonella bacteremia

Malaria and invasive non-typhoidal Salmonella (NTS) are life-threatening infections that often co-exist in African children. The iron-regulatory hormone hepcidin is highly upregulated during malaria and controls the availability of iron, a critical nutrient for bacterial growth. We investigated the relationship between Plasmodium falciparum malaria and NTS bacteremia in all pediatric admissions aged <5 years between August 1998 and October 2019 (n=75,034). We then assayed hepcidin and measures of iron status in five groups: (1) children with concomitant severe malarial anemia (SMA) and NTS (SMA+NTS, n=16); and in matched children with (2) SMA (n=33); (3) NTS (n=33); (4) cerebral malaria (CM, n=34); and (5) community-based children. SMA and severe anemia without malaria were associated with a 2-fold or more increased risk of NTS bacteremia, while other malaria phenotypes were not associated with increased NTS risk. Children with SMA had lower hepcidin/ferritin ratios (0.10; interquartile range [IQR]: 0.03-0.19) than those with CM (0.24; IQR: 0.14-0.69; P=0.006) or asymptomatic malaria (0.19; IQR: 0.09-0.46; P=0.01) indicating suppressed hepcidin levels. Children with SMA+NTS had lower hepcidin levels (9.3 ng/mL; IQR: 4.7-49.8) and hepcidin/ferritin ratios (0.03; IQR: 0.01-0.22) than those with NTS alone (105.8 ng/mL; IQR: 17.3-233.3; P=0.02 and 0.31; IQR: 0.06-0.66; P=0.007, respectively). Since hepcidin degrades ferroportin on the Salmonella-containing vacuole, we hypothesize that reduced hepcidin in children with SMA might contribute to NTS growth by modulating iron availability for bacterial growth. Further studies are needed to understand how the hepcidin-ferroportin axis might mediate susceptibility to NTS in severely anemic children.     

Extraintestinal focal infections in adults with nontyphoid Salmonella bacteraemia: predisposing factors and clinical outcome

BACKGROUND: Nontyphoid Salmonella (NTS) isolates lead to not only self-limited, acute gastrointestinal infections, but also bacteraemia with or without extraintestinal focal infections (EFIs). The risk factors associated with EFIs in adults with NTS bacteraemia were not clearly elucidated. METHODS: In a medical center in southern Taiwan, patients aged > or = 18 years with NTS bacteraemia between January 1999 and June 2005 were included for analysis. RESULTS: Of 129 patients, 51 (39.5%) were complicated with EFIs. The most common EFI was mycotic aneurysm, followed by pleuropulmonary infections and spinal osteomyelitis. Compared to patients with primary bacteraemia, those with EFIs had higher leucocyte counts (P = 0.004) and higher serum levels of C-reactive protein (P < 0.0001). The development of EFIs was associated with a higher mortality, more severe septic manifestations, longer hospital stays and duration of antimicrobial therapy. Univariate analysis revealed that diabetes mellitus (P = 0.02), hypertension (P = 0.02) and chronic lung disease (P = 0.006) were significantly associated with EFIs. However, patients with malignancy (P = 0.01) and immunosuppressive therapy (P = 0.03) were less likely to develop EFIs. On the basis of multivariate analysis, an independent factor for the occurrence of EFIs was age [adjusted odds ratio (aOR) 1.05; 95% confidence interval (CI) 1.02-1.07; P < 0.0001], whilst malignancy was negatively associated with EFIs (aOR 0.16; 95% CI 0.14-0.78; P = 0.01). CONCLUSION: Amongst patients with NTS bacteraemia, EFIs often occurred in the aged, and were associated with a higher mortality and morbidity. Recognition of specific host factors is essential for identification of EFIs which often demand early surgical interventions and prolonged antimicrobial therapy.     

Trends in malaria-attributable morbidity and mortality among young children admitted to Ugandan hospitals, for the period 1990-2001

A retrospective study based on paediatric ward registers was conducted in the Ugandan districts of Hoima and Kabale, which are areas of stable and unstable malaria transmission, respectively. The records of Hoima hospital from 1990 to 2001 and of Kabale hospital from 1994 to 2000 were reviewed and the initial diagnoses for all young children (i.e. those aged <5 years) were noted. Admissions for malaria and for anaemia were significantly more common among the young children admitted to Hoima hospital than among those admitted to Kabale hospital (P<0.0001 for each). Over the study periods, there were significant linear increases in the numbers of young children admitted with malaria or anaemia, at both Hoima hospital (with chi2 values of 25.6 and 191.5, respectively; P<0.0001 for each) and at Kabale hospital (with chi2 values of 31.6 and 29.0, respectively; P<0.0001 for each). Anaemia was not an important cause of mortality at Kabale hospital during the period reviewed. As in other sites in the East African highlands, the increasing malaria-related morbidity and mortality at Kabale hospital between 1994 and 2000 could be explained by the general increase in air temperatures over the same period. This increase may have made the local climate more conducive to mosquito survival and to parasite development in the vector, leading to increases in the intensity of transmission. At Hoima hospital, however, the increasing numbers of admissions for anaemia or malaria between 1990 and 2001 seem more likely to be the result of increased resistance to chloroquine (CQ) and sulfadoxine-pyrimethamine (SP) in the parasites and to changes in treatment seeking behaviour. With the recent change in the national drug policy, from the use of CQ alone as the first-line treatment of uncomplicated malaria to the use of a combination of CQ with SP, and the abolition of user charges at government health facilities, a reversal of these worrying trends might be anticipated. Although it may be not be appropriate to extrapolate the conclusions of studies based on hospital records to the communities at risk of malaria, such conclusions do allow the health services to monitor general trends in the morbidity and mortality associated with malaria and anaemia.     

Clinical features of children hospitalized with malaria--a study from Bikaner, northwest India

Severe Plasmodium vivax malaria in adults has been reported from Bikaner (northwestern India) but the reports on children are scanty. This prospective study was done on 303 admitted children of malaria. The diagnosis was done by peripheral blood smear and rapid diagnostic test. Further confirmation of severe P. vivax monoinfection was done by polymerase chain reaction (PCR). The proportion of P. falciparum, P. vivax, and mixed (P. falciparum and P. vivax) infection was 61.01%, 33.99%, and 4.95%, respectively. Severe disease was present in 49.5% (150/303) children with malaria, with the risk greatest among P. vivax monoinfection (63.1% [65/103]) compared with P. falciparum, either alone (42.7% [79/185]; odds ratio [OR] = 2.3 [95% confidence interval (CI) = 1.40-3.76], P = 0.001) or mixed infections (40% [6/15]; OR = 2.57 [95% CI = 0.88-7.48]). In children < 5 years of age, the proportion of severe malaria attributable to P. vivax rose to 67.4% (31/46) compared with 30.4% (14/46) of P. falciparum (OR = 4.7 [95% CI = 2.6-8.6], P < 0.0001) and 2.2% (1/46) of mixed infection (OR = 92 [95% CI = 24.6-339.9], P < 0.0001). The proportion of patients having severe manifestations, which included severe anemia, thrombocytopenia, cerebral malaria, acute respiratory distress syndrome, hepatic dysfunction, renal dysfunction, abnormal bleeding was significantly high in association with P. vivax monoinfection in 0-5 year age group, while the same was significantly high in association with P. falciparum monoinfection in 5-10 year age group. Similarly P. vivax monoinfection had greatest propensity to cause multiorgan dysfunction in 0-5 year age group (34.1% [17/41], P < 0.0001) in comparison to P. falciparum monoinfection, which had similar propensity in 5-10 year age group (36.8% [35/95], P = 0.039). Plasmodium vivax monoinfection was almost equally serious to cause significant mortality in comparison to P. falciparum (case fatality rate of severe P. vivax was 3.9% versus 3.2% of severe P. falciparum malaria; P = 1.0). This study reaffirms the evidence of severe P. vivax malaria in children in Bikaner.     

The influence of hyperbilirubinaemia on malaria-related mortality: an analysis of 1103 patients

The influence of hyperbilirubinaemia on malaria-related mortality was explored among 1103 cases of acute, Plasmodium falciparum malaria at a referral hospital in Orissa, India. Most (64.3%) of the subjects investigated had > 1.2 mg bilirubin/dl serum and were therefore considered hyperbilirubinaemic. Compared with the other patients, those with hyperbilirubinaemia were much more likely to have cerebral malaria (24.1% v. 9.4%; P < 0.0001) or acute renal failure (9.5% v. 2.3%; P < 0.0001), but not severe anaemia (5.9% v. 4.3%; P < 0.22). Mortality was 7.9% among the patients with hyperbilirubinaemia (all the deaths being attributable to cerebral malaria, acute renal failure and/or severe anaemia) but only 1% among the non-hyperbilirubinaemics. There were no deaths, however, among the 506 hyperbilirubinaemics who did not have cerebral malaria, acute renal failure or severe anaemia, even among those with high serum concentrations of bilirubin. It therefore appears that, in acute, Plasmodium falciparum malaria, hyperbilirubinaemia is not in itself a severe complication, and only appears linked with mortality when associated with at least one other complication.