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?相似文献   

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?×?10(3)/mm(3) 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?相似文献   

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.     

Differential perpetuation of malaria species among Amazonian Yanomami Amerindians.

To determine whether malaria perpetuates within isolated Amerindian villages in the Venezuelan Amazon, we surveyed malaria infection and disease among 1,311 Yanomami in three communities during a 16-month period. Plasmodium vivax was generally present in each of these small, isolated villages; asymptomatic infection was frequent, and clinical disease was most evident among children less than five years of age (odds ratio [OR] = 6.3, 95% confidence interval [CI] = 1.4-29.2) and among persons experiencing parasitemias > or = 1,000 parasites/mm3 of blood (OR = 45.0, 95% CI = 5.5-370.7). Plasmodium falciparum, in contrast, was less prevalent, except during an abrupt outbreak in which 72 infections resulted in symptoms in all age groups and at all levels of parasitemia, and occasionally were life-threatening. The observed endemic pattern of P. vivax infection may derive from the capacity of this pathogen to relapse, while the epidemic pattern of P. falciparum infection may reflect occasional introductions of strains carried by immigrants or residents of distant villages and the subsequent disappearance of this non-relapsing pathogen.     

Malaria prophylaxis using azithromycin: a double-blind, placebo-controlled trial in Irian Jaya, Indonesia.

New drugs are needed for preventing drug-resistant Plasmodium falciparum malaria. The prophylactic efficacy of azithromycin against P. falciparum in malaria-immune Kenyans was 83%. We conducted a double-blind, placebo-controlled trial to determine the prophylactic efficacy of azithromycin against multidrug-resistant P. falciparum malaria and chloroquine-resistant Plasmodium vivax malaria in Indonesian adults with limited immunity. After radical cure therapy, 300 randomized subjects received azithromycin (148 subjects, 750-mg loading dose followed by 250 mg/d), placebo (77), or doxycycline (75, 100 mg/d). The end point was slide-proven parasitemia. There were 58 P. falciparum and 29 P. vivax prophylaxis failures over 20 weeks. Using incidence rates, the protective efficacy of azithromycin relative to placebo was 71.6% (95% confidence interval [CI], 50.3-83.8) against P. falciparum malaria and 98.9% (95% CI, 93.1-99.9) against P. vivax malaria. Corresponding figures for doxycycline were 96.3% (95% CI, 85.4-99.6) and 98% (95% CI, 88.0-99.9), respectively. Daily azithromycin offered excellent protection against P. vivax malaria but modest protection against P. falciparum malaria.     

Epidemiology of malaria in an area of low transmission in central India

A longitudinal study on malaria was carried out from 2003 to 2005 in an area of unstable malaria in the Panna district in central India. Both Plasmodium vivax and P. falciparum were prevalent; however, the risk of P. falciparum malaria was 31.6% (95% confidence interval [CI] = 29.6-33.6%), which is four times higher compared with that of P. vivax malaria (7.8%, 95% CI = 6.7-9%). An increasing trend was recorded in malaria prevalence from 30.2% in 2003 to 46.6% in 2004 (odds ratio [OR] = 2.0, 95% CI = 1.6-2.5) that increased to 58.6% in 2005 (OR = 1.6, 95% CI = 1.2-2.1). This increase was statistically significant (chi(2) = 120.5, degrees of freedom = 2, P < 0.0001). Anopheles culicifacies was the dominant vector of malaria and showed partial (< 50%) resistance to DDT, which indicated that DDT can still be used. Improved access to treatment facilities, combination therapy, and vector control appears to be the most promising method for controlling malaria in this region.     

Risk factors for presentation to hospital with severe anaemia in Tanzanian children: a case-control study

In malaria endemic areas anaemia is a usually silent condition that nevertheless places a considerable burden on health services. Cases of severe anaemia often require hospitalization and blood transfusions. The objective of this study was to assess risk factors for admission with anaemia to facilitate the design of anaemia control programmes. We conducted a prospective case-control study of children aged 2-59 months admitted to a district hospital in southern Tanzania. There were 216 cases of severe anaemia [packed cell volume (PCV) < 25%] and 234 age-matched controls (PCV > or = 25%). Most cases [55.6% (n = 120)] were < 1 year of age. Anaemia was significantly associated with the educational level of parents, type of accommodation, health-seeking behaviour, the child's nutritional status and recent and current medical history. Of these, the single most important factor was Plasmodium falciparum parasitaemia [OR 4.3, 95% confidence interval (CI) 2.9-6.5, P < 0.001]. Multivariate analysis showed that increased recent health expenditure [OR 2.2 (95% CI 1.3-3.9), P = 0.005], malnutrition [OR 2.4 (95%CI 1.3-4.3), P < 0.001], living > 10 km from the hospital [OR 3.0 (95% CI 1.9-4.9), P < 0.001], a history of previous blood transfusion [OR 3.8 (95% CI 1.7-9.1), P < 0.001] and P. falciparum parasitaemia [OR 9.5 (95% CI 4.3-21.3), P < 0.001] were independently related to risk of being admitted with anaemia. These findings are considered in terms of the pathophysiological pathway leading to anaemia. The concentration of anaemia in infants and problems of access to health services and adequate case management underline the need for targeted preventive strategies for anaemia control.     

Chloroquine/doxycycline combination versus chloroquine alone, and doxycycline alone for the treatment of Plasmodium falciparum and Plasmodium vivax malaria in northeastern Irian Jaya, Indonesia.

Combination therapy is one method of overcoming the global challenge of drug-resistant Plasmodium falciparum malaria. We conducted a hospital-based 28-day in vivo test comparing chloroquine/doxycycline to chloroquine or doxycycline alone for treating P. falciparum and Plasmodium vivax malaria in Irian Jaya, Indonesia. Eighty-nine patients with uncomplicated falciparum malaria were randomized to standard dose chloroquine (n = 30), doxycycline (100 mg every 12 hours [7 days], n = 20), or chloroquine with doxycycline (n = 39); corresponding numbers for vivax malaria (n = 63) were 23, 16, 24. Endpoints were parasite sensitivity (S) or resistance (RI/RII/RIII). Of the 105 evaluable patients, chloroquine/doxycycline cured (S) 20/22 (90.9% [95% CI 78.9-100%]) patients with P. falciparum malaria; 2/22 (9.1% [0-21%]) were RIII resistant. Doxycycline cured 11/17 (64.7% [42.0-87.4%]) patients, and chloroquine 4/20 (20% [2.5-37.5%]). Against P. vivax, chloroquine/doxycycline cured (S) 12/17 (70.6% [48.9-92.2%]) patients, doxycycline 4/12 (33.3% [6.6-59.9%]), and chloroquine 5/17 (29.4% [7.7-51.1%]). Chloroquine/doxycycline was effective against P. falciparum but only modestly effective against P. vivax. These findings support the use of chloroquine/doxycycline as an inexpensive alternative to mefloquine for treating chloroquine-resistant P. falciparum but not chloroquine-resistant P. vivax in this setting.     

Alpha(+)-thalassemia protects African children from severe malaria

The high frequency of alpha(+)-thalassemia in malaria-endemic regions may reflect natural selection due to protection from potentially fatal severe malaria. In Africa, bearing 90% of global malaria morbidity and mortality, this has not yet been observed. We tested this hypothesis in an unmatched case-control study among 301 Ghanaian children with severe malaria and 2107 controls (62% parasitemic). In control children, alpha(+)-thalassemia affected neither prevalence nor density of Plasmodium falciparum. However, heterozygous alpha(+)-thalassemia was observed in 32.6% of controls but in only 26.2% of cases (odds ratio [OR], 0.74; 95% confidence interval [CI], 0.56-0.98). Protection against severe malaria was found to be pronounced comparing severe malaria patients with parasitemic controls (adjusted OR in children < 5 years of age, 0.52; 95% CI, 0.34-0.78) and to wane with age. No protective effect was discernible for homozygous children. Our findings provide evidence for natural selection of alpha(+)-thalassemia in Africa due to protection from severe malaria.     

Factors contributing to anemia after uncomplicated falciparum malaria.

The factors contributing to anemia in falciparum malaria were characterized in 4,007 prospectively studied patients on the western border of Thailand. Of these, 727 patients (18%) presented with anemia (haematocrit < 30%), and 1% (55 of 5,253) required blood transfusion. The following were found to be independent risk factors for anemia at admission: age < 5 years, a palpable spleen, a palpable liver, recrudescent infections, being female, a prolonged history of illness (> 2 days) before admission, and pure Plasmodium falciparum infections rather than mixed P. falciparum and Plasmodium vivax infections. The mean maximum fractional fall in hematocrit after antimalarial treatment was 14.1% of the baseline value (95% confidence interval [CI], 13.6-14.6). This reduction was significantly greater in young children (aged < 5 years) and in patients with a prolonged illness, high parasitemia, or delayed parasite clearance. Loss of parasitized erythrocytes accounted for < 10% of overall red blood cell loss. Hematological recovery was usually complete within 6 weeks, but it was slower in patients who were anemic at admission (adjusted hazards ratio [AHR], 1.9, 95% CI, 1.5-2.3), and those whose infections recrudesced (AHR, 1.2, 95% CI, 1.01-1.5). Half the patients with treatment failure were anemic at 6 weeks compared with 19% of successfully treated patients (relative risk, 2.8, 95% CI, 2.0-3.8). Patients coinfected with P. vivax (16% of the total) were 1.8 (95% CI, 1.2-2.6) times less likely to become anemic and recovered 1.3 (95% CI, 1.0-1.5) times faster than those with P. falciparum only. Anemia is related to drug resistance and treatment failure in uncomplicated malaria. Children aged < 5 years of age were more likely than older children or adults to become anemic. Coinfection with P. vivax attenuates the anemia of falciparum malaria, presumably by modifying the severity of the infection.     

Prognostic value of thrombocytopenia in African children with falciparum malaria

Thrombocytopenia is a common finding in malaria, but its prognostic value has not been addressed in children. The relationship between thrombocytopenia (platelet count < 100,000/mm3 on admission) and severity and outcome was investigated prospectively in children hospitalized with falciparum malaria in Dakar, Senegal, an area that is hypoendemic for malaria. Of 288 falciparum cases, 215 matched the 2000 World Health Organization definition of severe malaria. Median platelet counts were lower (98,000/mm3 versus 139,000/mm3; P < 0.02) among severe cases than in mild cases, and in children who died than among those who recovered (68,500/mm3 versus 109,000/mm3; P < 0.002). In severe cases, children presenting with a platelet count < 100,000/mm3 were more likely to die (odds ratio [OR] = 6.31, 95% confidence interval [CI] = 2.0-26.0). Moreover, multivariate analysis identified thrombocytopenia as an independent predictor of death (OR = 13.3, 95% CI = 3.2-55.1). Our data show an association between thrombocytopenia and either severity or prognosis in childhood falciparum malaria.     

Efficacy of monthly tafenoquine for prophylaxis of Plasmodium vivax and multidrug-resistant P. falciparum malaria

We assessed monthly doses of tafenoquine for preventing Plasmodium vivax and multidrug-resistant P. falciparum malaria. In a randomized, double-blind, placebo-controlled study, 205 Thai soldiers received either a loading dose of tafenoquine 400 mg (base) daily for 3 days, followed by single monthly 400-mg doses (n = 104), or placebo (n = 101), for up to 5 consecutive months. In volunteers completing follow-up (96 tafenoquine and 91 placebo recipients), there were 22 P. vivax, 8 P. falciparum, and 1 mixed infection. All infections except 1 P. vivax occurred in placebo recipients, giving tafenoquine a protective efficacy of 97% for all malaria (95% confidence interval [CI], 82%-99%), 96% for P. vivax malaria (95% CI, 76%-99%), and 100% for P. falciparum malaria (95% CI, 60%-100%). Monthly tafenoquine was safe, well tolerated, and highly effective in preventing P. vivax and multidrug-resistant P. falciparum malaria in Thai soldiers during 6 months of prophylaxis.     

Double-blind, randomized, placebo-controlled assessment of chloroquine/primaquine prophylaxis for malaria in nonimmune Colombian soldiers.

To improve upon the efficacy of primaquine prophylaxis for malaria (94%, Plasmodium falciparum malaria; 85%, Plasmodium vivax malaria), we administered chloroquine (300 mg weekly) in combination with primaquine (30 mg daily) to nonimmune Colombian soldiers during 16 weeks of patrol in a region of endemicity and for a further 1 week in base camp. The occurrence of symptomatic parasitemia was determined during those 17 weeks and during a further 3 weeks in base camp. The protective efficacy for the chloroquine/primaquine treatment group of 100 subjects, compared with that for the placebo treatment group of 51 subjects, was 88% (95% confidence interval [CI], 76-94) against all types of malaria, 89% (95% CI, 61-97) against P. falciparum malaria, and 88% (95% CI, 58-93) against P. vivax malaria. Two chloroquine/primaquine recipients had severe gastrointestinal distress. Comparison of these data with data from a previous study indicates that the addition of chloroquine did not increase the prophylactic efficacy of primaquine.     

Both heterozygous and homozygous alpha+ thalassemias protect against severe and fatal Plasmodium falciparum malaria on the coast of Kenya

Although the alpha+ thalassemias almost certainly confer protection against death from malaria, this has not been formally documented. We have conducted a study involving 655 case patients with rigorously defined severe malaria and 648 controls, frequency matched on area of residence and ethnic group. The prevalence of both heterozygous and homozygous alpha+ thalassemia was reduced in both case patients with severe malaria (adjusted odds ratios [ORs], 0.73 and 0.57; 95% confidence intervals [95% CIs], 0.57-0.94 and 0.40-0.81; P = .013 and P = .002, respectively, compared with controls) and among the subgroup of children who died after admission with severe malaria (OR, 0.60 and 0.37; 95% CI, 0.37-1.00 and 0.16-0.87; P = .05 and P = .02, respectively, compared with surviving case patients). The lowest ORs were seen for the forms of malaria associated with the highest mortality-coma and severe anemia complicated by deep, acidotic breathing. Our study supports the conclusion that both heterozygotes and homozygotes enjoy a selective advantage against death from Plasmodium falciparum malaria.     

Travel histories as risk factors in the analysis of urban malaria in Colombia

Self-reported travel histories were used in a case-control study to determine whether movement of local residents to neighboring endemic areas was a risk factor for malaria in the town of Quibdo, Colombia. Multivariate analyses showed that among residents of Quibdo, traveling to an endemic area 8-14 days before disease onset was the strongest risk factor for both Plasmodium falciparum (adjusted odds ratio [OR] = 28.96, 95% confidence interval [CI] = 13.9-60.32) and P. vivax (adjusted OR = 14.24, 95% CI = 5.27-38.46) malaria. For P. falciparum, individuals who did not travel outside Quibdo during the 8-14 days before disease onset, but who reported traveling 1-7, 15-21, or 22-30 days before disease onset also had an increased risk of malaria. Conversely, use of protection against mosquitoes was negatively associated with P. falciparum. These results highlight the need for malaria control measures that target mobile populations. A definition of imported malaria that allows distinction of imported from autochthonous cases in Quibdo town is proposed.     

The risk of malarial infections and disease in Papua New Guinean children

In a treatment re-infection study of 206 Papua New Guinean school children, we examined risk of reinfection and symptomatic malaria caused by different Plasmodium species. Although children acquired a similar number of polymerase chain reaction-detectable Plasmodium falciparum and P. vivax infections in six months of active follow-up (P. falciparum = 5.00, P. vivax = 5.28), they were 21 times more likely to develop symptomatic P. falciparum malaria (1.17/year) than P. vivax malaria (0.06/year). Children greater than nine years of age had a reduced risk of acquiring P. vivax infections of low-to-moderate (>150/microL) density (adjusted hazard rate [AHR] = 0.65 and 0.42), whereas similar reductions in risk with age of P. falciparum infection was only seen for parasitemias > 5,000/microL (AHR = 0.49) and symptomatic episodes (AHR = 0.51). Infection and symptomatic episodes with P. malariae and P. ovale were rare. By nine years of age, children have thus acquired almost complete clinical immunity to P. vivax characterized by a very tight control of parasite density, whereas the acquisition of immunity to symptomatic P. falciparum malaria remained incomplete. These observations suggest that different mechanisms of immunity may be important for protection from these malaria species.     

Demographic risk factors for severe and fatal vivax and falciparum malaria among hospital admissions in northeastern Indonesian Papua

Between January 1998 and December 2000, the Jayapura Provincial Public Hospital in northeastern Indonesian New Guinea (Papua) admitted 5,936 patients with a diagnosis of malaria. The microscopic diagnosis at admission was Plasmodium falciparum (3,976, 67%), Plasmodium vivax (1,135, 19%), Plasmodium malariae (8, < 1%), and mixed species infections (817, 14%). Approximately 9% (367) of patients were classified as having severe malaria (277 P. falciparum, 36 P. vivax, 53 mixed infections, and 1 P. malariae) and 88 died (79 P. falciparum/mixed infections and 9 P. vivax). Risk of fatal outcomes among severe malaria patients was indistinguishable between those with falciparum versus vivax malaria (OR = 0.89; P = 0.771). Compared with non-pregnant women, pregnant women showed no higher risk of severe malaria (P = 0.643) or death caused by severe malaria (P = 0.748). This study compares admissions per population (based on census data), parasitemia, morbidity, and mortality among children versus adults, pregnant versus non-pregnant women, and urban/suburban versus rural residents.     

Malaria prevalence and associated risk factors in Eritrea

A parasitological cross-sectional survey was undertaken from September 2000 through February 2001 to estimate the prevalence of malaria parasitemia in Eritrea. A total of 12,937 individuals from 176 villages were screened for both Plasmodium falciparum and Plasmodium vivax parasite species using the OptiMal Rapid Diagnostic Test. Malaria prevalence was generally low but highly focal and variable with the proportion of parasitemia at 2.2% (range: 0.4% to 6.5%). Despite no significant differences in age or sex-specific prevalence rates, 7% of households accounted for the positive cases and 90% of these were P. falciparum. Multivariate regression analyses revealed that mud walls were positively associated with malaria infection (OR [odds ratio] = 1.6 [95% CI: 1.2, 2.2], P < 0.008). For countries with low and seasonal malaria transmission, such information can help programs design improved strategic interventions.     

Serious and fatal illness associated with falciparum and vivax malaria among patients admitted to hospital at West Sumba in eastern Indonesia

Records of 3,449 patients admitted to Karitas Hospital at Waitabula in eastern Indonesia with microscopy-confirmed malaria through 2008 and 2009 were systematically reviewed. Falciparum, vivax, and mixed species malaria occurred among 1,541, 1,837, and 71 admissions, respectively. Among these, 400 (26%), 199 (11%), and 15 (21%) had serious illness. Fatalities occurred in 46 (12%), 18 (9%), and 2 (13%) of these patients, respectively. Although patients with a diagnosis of falciparum malaria were more likely to have serious illness compared with those with vivax malaria (odds ratio [OR] = 2.9; 95% confidence interval [CI]: 2.4-3.5), this diagnosis nonetheless was associated with 32% of serious illness and 27% of fatalities. Among the seriously ill with a diagnosis of falciparum or vivax malaria, no significant difference in risk of death occurred (OR = 1.3; 95% CI: 0.7-2.5). Serious and fatal illness was predominantly anemia or altered mental state syndromes among patients with either of the species diagnoses. Plasmodium vivax was associated with a substantial share of the burden of morbidity and mortality caused by malaria in this hypo- to meso-endemic community.     

Age-dependent impairment of IgG responses to glycosylphosphatidylinositol with equal exposure to Plasmodium falciparum among Javanese migrants to Papua,Indonesia

Immune responses directed at glycosylphosphatidylinositol (GPI) anchors of Plasmodium falciparum may offer protection against symptomatic malaria. To independently explore the effect of age on generation of the anti-GPI IgG response, we measured serum anti-GPI IgGs in a longitudinal cohort of migrant Javanese children (6-12 years old) and adults (> or = 20 years old) with equivalent numbers of exposures to P. falciparum in Papua, Indonesia. While the peak response in adults was achieved after a single infection, comparable responses in children required > or = 3-4 infections. Significantly fewer children (16%) than adults (41%) showed a high (optical density > 0.44) anti-GPI IgG response (odds ratio [OR] = 3.8, 95% confidence interval [CI] = 2.3-6.3, P < 0.0001), and adults were more likely to show a persistently high response (OR = 5.5, 95% CI = 1.0-56.8, P = 0.03). However, the minority of children showing a strong response were significantly less likely to experience symptoms with subsequent parasitemia compared with those with a weak response (OR = 4.0, 95% CI = 1.1-13.8, P = 0.02). This effect was not seen among high- and low-responding adults (OR = 1.2, 95% CI = 0.5-2.8, P = 0.60). Host age, independent of cumulative exposure, apparently represents a key determinant of the quantitative and qualitative nature of the IgG response to P. falciparum GPI.