Abhishek Kochar

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.

Thrombocytopenia in Plasmodium falciparum, Plasmodium vivax and mixed infection malaria: A study from Bikaner (Northwestern India)

The occurrence, relation and magnitude of thrombocytopenia in different species of malaria are not clearly defined. This study included 1,064 patients admitted with malaria to study thrombocytopenia (platelet count <150,000 /cumm) in Plasmodium falciparum (Pf) and Plasmodium vivax (Pv) mono infection and mixed infection (Pf + Pv). The species diagnosis was done by peripheral blood film (PBF) and rapid diagnostic test (RDT). Validation by polymerase chain reaction (PCR) was done only in patients with severe thrombocytopenia (platelet count <20,000 /cumm). The breakup of patients was 525 (49.34%) Pf, 460 (43.23%) Pv and 79 (7.42%) mixed malaria (Pf + Pv). Thrombocytopenia was observed in 24.6% (262/1064) patients. The risk was greatest in the mixed infections in comparison to monoinfection individually (43.04% [34/79]; mixed vs Pv monoinfection: Odds Ratio [OR] = 1.675 [95% Confidence Interval (CI) 1.029–2.726], p < 0.0366; mixed vs Pf monoinfection: OR=3.911 [95% CI 2.367–6.463], p < 0.0001). Pv monoinfection (31.09% [143/460]) had greater risk compared to Pf monoinfection (16.19% [85/525]; OR = 2.335 [95% CI 1.722–3.167], p < 0.0001). The occurrence of severe thrombocytopenia was also higher in Pv monoinfection (18.18% [26/143]) in comparison to either Pf monoinfection (10.59% [9/85], OR = 1.877 (95% CI 0.834–4.223)) or mixed infection (11.76% [4/34]; OR = 1.667 (95% CI 0.540–5.142) but this association was statistically not significant. Six patients (3 Pv, 2 Pf and 1 mixed) developed severe epistaxis requiring platelet transfusion. There was no relation between parasite density and platelet count as many patients with severe thrombocytopenia had parasite density similar to patients without thrombocytopenia. We found that the association of thrombocytopenia was statistically more significant with P. vivax monoinfection as compared to P. falciparum.

Clinical profiles of 13 children with Plasmodium vivax cerebral malaria

Abstract Background: Bikaner region is endemic for both P. vivax and P. falciparum malaria. Usually, cerebral malaria is caused by P. falciparum but it has been reported recently also in P. vivax mono-infection. Epidemiologic studies and clinical descriptions of P. vivax cerebral malaria in children are rare. Aims: To describe the clinical features of PCR-confirmed cerebral malaria owing to P. vivax mono-infection and its clinico-laboratory profile in Bikaner, Northwest India. Methods: This observational prospective study was based on detailed clinical and laboratory investigation of children admitted with cerebral malaria owing to P. vivax between November 2008 and December 2010. Cerebral malaria was categorised according to the WHO (2000) criteria for P. falciparum and the diagnosis of P. vivax mono-infection was established by peripheral blood film and rapid diagnostic tests and confirmed by polymerase chain reaction. The possibility of other diseases/infections causing similar illness were investigated thoroughly. Results: Thirteen children with P. vivax cerebral malaria were studied, eight of whom (61·5%) had multi-organ (two or more organs) dysfunction. Other associated severe manifestations included severe anaemia (7), hepatic dysfunction (2), renal dysfunction (2), bleeding manifestation (2), respiratory distress (2), metabolic acidosis (2) and shock (one). Hypoglycaemia was not observed in any patient. There was no evidence of neurological sequelae. All the children were managed according to WHO guidelines using intravenous artisunate. Thrombocytopenia was detected in five and hyponatraemia in four children. Conclusion: P. vivax mono-infection can cause cerebral malaria and multi-organ dysfunction.

An unexpected cause of fever and seizures

In June, 2007, a 27-year-old man was brought to our emergency department by ambulance, having regained consciousness after a generalised tonic-clonic seizure. He had been having fever, chills, and rigors, on alternate days, for the previous 8 days. He had no past history of convulsions, head injury, febrile convulsions during infancy, birth trauma, meningitis, encephalitis, or psychiatric illness. There was no other past medical history of note. Until he fell ill, he had been working in a jewellery shop in Surat, Gujarat—a city where both falciparum and vivax malaria are endemic. On examination, nothing abnormal was found. The patient’s full blood count was normal; biochemistry tests, including a blood glucose measurement, also gave unremarkable results. Electrocardiography, ophthalmoscopy, examination of the cerebrospinal fl uid, and CT of the head all showed nothing of note. However, examination of the blood fi lm showed trophozoites of Plasmodium vivax, at a density of 16 200 per μL (fi gure). A rapid diagnostic test (FalciVax, Zephyr Biomedical Systems, Goa, India) indicated the presence of parasite lactate dehydrogenase, specifi c to P vivax, and the absence of histidine-rich protein 2, specifi c to P falciparum. 6 h after he arrived, the patient had another generalised seizure. He was immediately given intravenous quinine, as per the WHO guidelines for severe vivax malaria; in addition, anticonvulsant drugs were given. Over the next 12 h, the patient had a total of eight generalised seizures, with intervals of 30–120 min, without regaining full consciousness. 48 h after treatment began, the fever subsided, and the patient became fully conscious. Further blood tests—for dengue fever, leptospirosis, and HIV—gave negative results; repeat CT of the head, and electroencephalography, showed nothing remarkable. PCR, which was done as described by Kochar and colleagues, confi rmed that the patient had been infected by P vivax, but not P falciparum. The patient was discharged 8 days after his arrival. When last seen, in August, 2007, he was entirely well. P falciparum is known to cause cerebral malaria, which can manifest with seizures. The parasite multiplies in red blood cells, which adhere to the walls of small blood vessels, causing reduced cerebral blood fl ow. P vivax is less likely than P falciparum to cause severe illness— indeed, the typical 48 h interval between fevers, and benign course, have led to vivax malaria being termed “benign tertian malaria”. Classically, P vivax has not been thought to cause cerebral malaria. However, it is now known that severe P vivax infection can cause cerebral malaria—although, to our knowledge, this is the fi rst case in which the cause of seizures has been confi rmed as P vivax alone. How P vivax causes cerebral malaria is unclear, but recent studies indicate that the mechanism may be similar to that triggered by P falciparum. Other causes of seizures in malaria include hypoglycaemia, hyponatraemia, lactic acidosis—and other illnesses, such as epilepsy.

Thrombocytopenia in childhood malaria with special reference to P. vivax monoinfection: A study from Bikaner (Northwestern India)

Thrombocytopenia is commonly seen in Plasmodium vivax malaria, but its prognostic value has not been addressed in children. This prospective study included 676 admitted children of malaria [Plasmodium falciparum (Pf) monoinfection 262, Plasmodium vivax (Pv) monoinfection 380, and mixed (Pf + Pv) infection 34], in which thrombocytopenia (platelet count <150 × 103/mm3 on admission) was found in 442 (65.38%) children [Pf monoinfection 55.3% (145/262), Pv monoinfection 73.16% (278/380), and mixed infection 55.88% (19/34)]. The association of thrombocytopenia was statistically significant with Pv monoinfection [73.16% (278/380)] in comparison to either Pf monoinfection [55.34% (145/262); odds ratio (OR) = 2.199 (95% confidence interval (CI) 1.577–3.068), p < 0.0001] or mixed infection [55.88% (19/34); OR = 2.152 (95%CI 1.054–4.394), p = 0.032]. In Pv monoinfection, thrombocytopenia was highest in 0–5 years age group and subsequently decreased with advancing age, whereas in Pf monoinfection it was reverse. Severe thrombocytopenia (platelet count <20 × 103/mm3) was present in 16.52% (73/442) children [Pv monoinfection 21.58% (60/278) and Pf monoinfection 8.97% (13/145)]. The risk of developing severe thrombocytopenia was also highest in Pv monoinfection [15.79% (60/380)] in comparison to Pf monoinfection [10.59% (13/262); OR = 3.591 (95%CI 1.928–6.690), p < 0.0001]. Bleeding manifestations were associated in 21.27% (94/442) children [Pf monoinfection 9.92% (26/262), Pv monoinfection 16.58% (63/380), and mixed malaria 14.71% (5/34)]. All the children having bleeding manifestations had thrombocytopenia but low platelet counts were not always associated with abnormal bleeding. The association of severe malaria was significantly more among children having Pv monoinfection with platelet counts <20 × 103/mm3 [OR = 2.569 (95%CI 1.196–5.517), p < 0.014] with specificity of 88.3% and positive predictive value of 85%. Till today, thrombocytopenia is not included in severe malaria criterion described by WHO, but when platelet counts <20 × 103/mm3, we advocate it to include as one of the severe malaria criteria.

Comparative evaluation of microscopy,OptiMAL~(?) and 18S rRNA gene based multiplex PCR for detection of Plasmodium falciparum & Plasmodium vivax from field isolates of Bikaner,India

OBJECTIVE To evaluate microscopy, OptiMAL(®) and multiplex PCR for the identification of Plasmodium falciparumm (P. falciparum) and Plasmodium vivax (P. vivax) from the field isolates of Bikaner, Rajasthan (Northwest India). METHODS In this study, a multiplex PCR (P. falciparum and P. vivax) was further developed with the incorporation of Plasmodium malariae (P. malariae) specific primer and also a positive control. The performance of microscopy, plasmodium lactate dehydrogenase (pLDH) based malaria rapid diagnostic test OptiMAL(®) and 18S rRNA gene based multiplex PCR for the diagnosis of P. falciparum and P. vivax was compared. RESULTS The three species multiplex PCR (P. falciparum, P. vivax and P. malariae) with an inbuilt positive control was developed and evaluated. In comparison with multiplex PCR, which showed the sensitivity and specificity of 99.36% (95%CI, 98.11%-100.00%) and 100.00% (95%CI, 100.00%-100.00%), the sensitivity and specificity of microscopy was 90.44% (95%CI, 88.84%-95.04%) and 99.22% (95%CI, 97.71%-100.00%), and OptiMAL(®) was 93.58% (95%CI, 89.75%-97.42%) and 97.69% (95%CI, 95.10%-100.00%). The efficiencies were 99.65%, 95.10% and 95.45% for multiplex PCR, microscopy and OptiMAL(®), respectively. CONCLUSIONS Our results raise concerns over the overall sensitivities of microscopy and OptiMAL(®), when compared to the multiplex PCR and thus stress the need for new molecular interventions in the accurate detection of the malarial parasites. This further highlights the fact that further developments are needed to improve the performance of rapid diagnostic tests at field level.

Association between erectile dysfunction and cardiovascular risk in individuals with type-2 diabetes without overt cardiovascular disease

Background: Erectile dysfunction in type-2 diabetes may be an independent marker for coronary artery disease. Present study was undertaken to investigate whether type-2 diabetic patients with erectile dysfunction without having overt cardiovascular disease had increased cardiovascular risk. Aim: To find out correlation between ED and cardiovascular risk in diabetic patients. Methods: Fifty type-2 diabetic patients were assessed for erectile dysfunction using international index of erectile dysfunction (IIEF-5), which include questionnaire and cardiovascular risk assessment by multiparameter cardiovascular analysis device (periscope). Results: The prevalence of erectile dysfunction in type-2 diabetics was very high (78%), mild, moderate and severe ED was present in 6, 36 and 36%, respectively. The total cardiovascular risk was more in patients with ED in comparison to patients without ED (34.87 ± 18.82 vs 20.91 ± 11.03 p = 0.002). The mean 10-years coronary risk and cardiac risk was 12.00 + 9.60 and 22.23 + 14.14 (p = 0.029) and 13.36 ± 1.22 and 28.85 ± 4.13 (p 0.002) in patients without ED and with ED respectively. The mean vascular and atherosclerosis risk was 28.73 ± 13.94 and 39.38 ± 19.51 (p > 0.05) and 26.18 ± 10.31 and 33.92 ± 13.40 (p > 0.05) in patients without ED and with ED, respectively. Total cardiovascular risk was found to increase with age, duration of diabetes and HbA1c levels. Conclusion: The total cardiovascular risk increases with increasing severity of erectile dysfunction in type-2 diabetic patients without having overt cardiovascular disease.

Acute intermittent porphyria presenting with neurological emergency: review of six cases.

Acute intermittent porphyria presenting with short duration of gastrointestinal symptoms followed by rapidly progressive fulminant neurological syndrome during first attack is relatively uncommon. It is a neurological emergency and mimics many other psychiatric and medical disorders and can be fatal if it remains undiagnosed and untreated. Further, specific treatment in the form of Heme arginate is not universally available and very costly, so high clinical suspicion and early diagnosis and management of acute attack and prevention of further attacks are very important. We report a series of six cases who presented with convulsion and/or polyneuropathy early in the course of disease to highlight this fact.