The clinical and epidemiological features of childhood malaria in a moderately endemic area of Sri Lanka

This study describes some clinical and epidemiological features of childhood malaria in a moderately endemic area of southern Sri Lanka. Six hundred and sixty-two children, who experienced 1,138 attacks of malaria, and 172 children, who experienced 202 attacks of acute non-malarial fever, were followed over a period of two years. Of the 1,138 malaria infections followed, 776 were due to P. vivax, 359 were due to P. falciparum, and 3 were mixed infections. The majority of children presented within the first three days of the onset of symptoms. Headache (96%), feeling cold (81%) and arthralgia (77%) were the commonest presenting symptoms. Two hundred and sixty-four children experienced more than one attack of malaria. The clinical and epidemiological features of childhood malaria that have important implications for the planning and targeting of preventive measures are discussed.     

Prevalence of malaria in Aligarh

In Aligarh Plasmodium vivax and Plasmodium falciparum infections during 1998 and 1999 were 69.6% and 62.2%, and 30.4% and 37.8%, respectively. Peak transmission of malaria with highest slide positivity rates (38-44.6%) and slide P. falciparum rates (13 to 16%) were recorded during the months of September and October. About 7.5 to 10% cases showed resistance to chloroquine in P. falciparum infections while 11.3 to 16% P. vivax cases relapsed after getting required doses of chloroquine. About 75% of relapsing cases were of short-term type. Patients who were given both chloroquine and primaquine also relapsed but frequency was less (3.17%). A few chloroquine resistant cases were recorded in patients suffering from vivax malaria.     

Cross-reactive cellular immune response to circumsporozoite proteins of Plasmodium vivax and P. falciparum in malaria-exposed individuals

Acquired immunity against the recombinant circumsporozoite protein of P. falciparum (rPfCS) or P. vivax (rPvCS) was studied in two malarious areas of the Brazilian Amazon. Cellular responsiveness, evaluated by proliferative assays, was detected in about 45% of individuals who had recovered from recent acute malaria infections. Peripheral blood mononuclear cells of individuals whose last malaria infection was by P. vivax responded more to the rCS proteins than those who had P. falciparum . Since in P. vivax infections hypnozoites in the liver retain CS antigen, this stage may have contributed to the increased cellular response. The unexpected result was that in primoinfections by P. falciparum or P. vivax the proliferative response did not correspond to the rPfCS and rPvCS, respectively. Furthermore, among the malaria-exposed individuals, there was a positive correlation between the intensity of the responses to the two rCS proteins. Our results suggest that cross-reactive epitopes exist in the CS protein of P. falciparum and P. vivax . In the areas studied, the frequency of antibodies against rPvCS and/or rPfCS ranged from 43% to 11%. Species-specific antibodies against the CS protein were detected in the primoinfected individuals. Some individuals living in the endemic area but with no clinical history of malaria were positive by serology (8%) or by in vitro proliferation (21%). However, antibodies and cellular responses against rCS were detected only in malaria-exposed individuals, since those living outside the endemic area were all negative.     

Malaria in Leicester 1983-1988: a review of 114 cases

We have reviewed 114 episodes of malaria in 110 patients who were admitted to the Infectious Diseases Unit in Leicester during the 5 year period from February 1983-January 1988. There were 71 episodes of vivax malaria (62%), 33 episodes of falciparum malaria (29%), four patients with mixed infection and six patients with negative blood films who were diagnosed on clinical suspicion alone. Most patients presented in the summer months, 68% were aged under 40 years, 39% were born in the Indian subcontinent, 23% in East Africa and 23% in Britain. Eighty-two per cent of patients with falciparum malaria had recently returned from Africa whereas 82% with vivax malaria had visited Asia. Thirty six per cent had been given antimalarial chemoprophylaxis but only half of these took medication correctly. Seventy five per cent of episodes of falciparum malaria presented within 2 weeks of arrival in Britain, however vivax malaria could present at any time and 49% of cases occurred over 3 months after exposure. Presenting symptoms and signs were often non-specific. Twenty nine per cent of patients had been treated with antibiotics and 11% received antimalarials prior to admission. Vivax malaria was generally a mild infection but falciparum malaria was often severe with 39% of patients experiencing complications including one death. Although Plasmodium vivax and P. falciparum are morphologically similar the diseases caused by the two species of parasite are quite distinct. Physicians must ensure that malaria is excluded in anyone who has travelled to an endemic area.     

The malaria situation in the WHO eastern Mediterranean region

About 45% of the population of the Eastern Mediterranean Region live under the risk of both falciparum and vivax malaria, and additional 15% under the risk of P. vivax alone. The estimated annual number of malaria cases is about 14 million, out of which 95% occur in four countries: Afghanistan, Somalia, Sudan and Yemen. In Afghanistan malaria is endemic throughout the country at altitude below 1500 m. About 80-90% of malaria cases belong to P. vivax, the rest to P. falciparum (the latter is prevalent mostly in the South and in Badakhshan). In Islamic Republic of Iran 16% of the population live in initially non-malarious areas, 66% in areas freed from malaria, 12% in areas with sporadic transmission, mostly of P. vivax, and only 6% in areas of continuous transmission with a high proportion of P. falciparum. As much as 77% of the recorded cases belong to the latter territories. Iraq. After the Gulf war, the situation deteriorated in the three north-eastern governorates, and malaria spread outside this area and rooted in the south (Basra). Syria. Transmission of P. vivax still occurs, mostly along the western part of the border with Turkey and in the north-eastern corner of the country. At present, there are three areas that causes concern along borders between the European and Eastern Mediterranean Regions: Afghanistan is a source of importation of malaria to all its neighbours; areas on the borders between Iran, Azerbaijan and, to some extent, Armenia; 4 northern governorates of Iraq and parts of southeastern Turkey, with repercussions in Syria and, to a Lesser extent in Iran, along its western border. To some extent, Cyprus is also threatened, since importation of malaria to the northern part of the island from Turkey has been documented. In practical terms, there is a need for co-ordination of antivectorial activities and standardization of control methods between the countries with strong programmes and relatively intense transmission in border areas, i.e. between Iran, and Azerbaijan, Iraq and Turkey, Syria and Turkey.     

Impact of single round of indoor residual spray with lambda-cyhalotrin 10% WP on Plasmodium falciparum infection in Akola district, Maharashtra State.

Lambda-cyhalothrin 10% WP (ICON 10WP) was sprayed from 5th November 1997 at a dose of 25 mg/m2 as indoor residual spray in 74 high risk villages. The spray was completed within 10 days in most of the villages. The monthly entomological monitoring showed nil density of Anopheles culicifacies and Aedes and very low density of non-vector Anopheles and Culex. The impact of Lambda-cyhalothrin spray was discernible right in the month of November 1997 showing 52% reduction in P. falciparum cases as compared to the same month of preceding year. The reduction of P. falciparum cases in three months post-spray period was 77% (from 47 cases to 11 cases) as compared to similar months of preceding year and overall reduction of total malaria cases was 50% during the same period. Since the major part of transmission of P. vivax infection was over by the time Lambda-cyhalothrin spray was taken up, obviously the impact on P. vivax infection was not markedly high as compared to P. falciparum infection. Neither cerebral malaria cases nor deaths due to malaria were recorded in the sprayed villages.     

Field trial of the RTM dipstick method for the rapid diagnosis of malaria based on the detection of Plasmodium falciparum HRP-2 antigen in whole blood

The performance of the Quorum RapidTest Malaria (RTM) dipstick method that detects Plasmodium falciparum histidine-rich protein-2 (PfHRP-2) antigen in whole blood was evaluated in a malaria endemic area. Results were compared with conventional Giemsa-stained blood films. Of 306 people tested 37.9% (116/306) were found to be parasitaemic; of these 66.4% (77/116) were P. vivax and 32.8% (38/116) were P. falciparum infections. There was only one (0.9%) mixed P. falciparum plus P. vivax infection.The RTM test was positive in 35/36 patients with P. falciparum identified on blood smear examination, resulting in a sensitivity of 97.2% [95% confidence interval (CI): 91.6-102.8%]. Specificity was 96.3% (95% CI: 93.9-98.6%).The RTM test had a positive predictive value of 77.8% (95% CI: 65.7-89.9%) and a negative predictive value of 99.6% (95% CI: 98.4-100.8%). Of the 10 false positives, seven reported recent malaria episode and treatment, indicating persistence of antigenaemia. If these were assumed truly infected, the positive predictive value is increased to 93.3% (95% CI: 85.8-100.8%).The RTM test was positive in all seven P. falciparum infections with gametocytes and one mixed infection, but was negative in all falciparum gametocytes and relapsing fever cases. All but one P. vivax infection gave negative result on the RTM test.The RTM test missed one patient with parasitaemia. The test is highly sensitive and specific requiring no instrument or trained personnel. It appears to be a very useful tool for rapid diagnosis of malaria, especially in the rural health institutions with limited diagnostic facilities.     

Chloroquine or sulfadoxine-pyrimethamine for the treatment of uncomplicated,Plasmodium falciparum malaria during an epidemic in Central Java,Indonesia

A recent malaria epidemic in the Menoreh Hills of Central Java has increased concern about the re-emergence of endemic malaria on Java, which threatens the island's 120 million residents. A 28-day, in-vivo test of the efficacy of treatment of malaria with antimalarial drugs was conducted among 167 villagers in the Menoreh Hills. The treatments investigated, chloroquine (CQ) and sulfadoxine-pyrimethamine (SP), constitute, respectively, the first- and second-line treatments for uncomplicated malaria in Indonesia. The prevalence of malaria among 1389 residents screened prior to enrollment was 33%. Treatment outcomes were assessed by microscopical diagnoses, PCR-based confirmation of the diagnoses, measurement of the whole-blood concentrations of CQ and desethylchloroquine (DCQ), and identification of the Plasmodium falciparum genotypes. The 28-day cumulative incidences of therapeutic failure for CQ and SP were, respectively, 47% (N = 36) and 22% (N = 50) in the treatment of P. falciparum, and 18% (N = 77) and 67% (N = 6) in the treatment of P. vivax. Chloroquine was thus an ineffective therapy for P. falciparum malaria, and the presence of CQ-resistant P. vivax and SP-resistant P. falciparum will further compromise efforts to control resurgent malaria on Java.     

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.     

Diagnosis of imported malaria by Plasmodium lactate dehydrogenase (pLDH) and histidine-rich protein 2 (PfHRP-2)-based immunocapture assays.

This study was conducted to evaluate the performance of two rapid non-microscopic assays: Plasmodium lactate dehydrogenase (pLDH) assay (OptiMAL) and Plasmodium falciparum histidine-rich protein 2 (PfHRP-2) assay (ICT Malaria). The assays were used to detect malaria infection in 515 immigrants living in Kuwait. The performance of both assays was compared to that of microscopy of Giemsa-stained thick blood films and to each other. Of the 515 patients tested, 163 were positive for malaria parasites by microscopy of thick blood film. Of these, 87 were infected with Plasmodium vivax parasites, 63 with P. falciparum, 1 with Plasmodium malariae, and 12 had mixed infections of P. falciparum and P. vivax. The PfHRP-2 assay detected 53 P. falciparum infections and, as expected, failed to detect all but one case of P. vivax. Three cases of mixed infections were also not detected by this assay. The pLDH assay detected 56 P. falciparum cases and 77 P. vivax infections but failed to detect 4 cases of mixed infections. Compared to microscopy, the performance of both the assays to diagnose P. falciparum infection was comparable. The sensitivity for the PfHRP-2 assay was 82% with a specificity of 99.0% and for the pLDH assay the sensitivity was 89% with a specificity of 99.5%. The PfHRP-2 assay detected 4 false positive cases, 2 of which were also detected by the pLDH assay. These patients reported treatment with chloroquine in the last 2-5 weeks. Though the immunocapture diagnostic assays may be helpful in certain situations, microscopy of thick blood film is still the method of choice in diagnosing imported malaria.     

The malaria situation in Afghanistan

Malaria is endemic throughout the country at altitude below 1500 m. About 80-90% of malaria cases belongs to P. vivax, the rest to P. falciparum. Malaria has gone out of control in Afghanistan in the past 20 years. The annual number of cases is estimated at 2-3 million, the number of officially reported was 288,070 in 1998. Out of the 20.5 million population of Afghanistan (1998 estimates), more than 12 million are to be living in malaria endemic areas. A field study to evaluate the susceptibility of P. vivax and P. falciparum to chloroquine was conducted in four sites of the eastern region. The study revealed 100% susceptibility of P. vivax while P. falciparum indicated an alarming degree of resistance.     

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.     

Resistant falciparum malaria in an endemic area of Allahabad (U.P.).

Over the last three decades the problems of resistance in P. falciparum malaria to chloroquine have emerged in many parts of the world including India. The present study was carried out at PHC, Jasra, an endemic area for malaria in Allahabad distt. to ascertain the level of resistance to chloroquine in P. falciparum in selected villages according to WHO extended 28-day field test. One hundred one (58.4%) cases were positive for malaria. Amongst the positive cases, 92 (91.1%) showed P. falciparum and 9 (8.9%) P. vivax infection. Of the 92 cases, 31 (33.7%) showed resistance to chloroquine and 61 (66.3%) were sensitive to the standard dose of chloroquine. Out of the 31 resistant cases, 19 (61.3%) showed resistance at RI level and 12 (38.7%) at RII level.     

Anti-neutrophil cytoplasmic antibodies (ANCA) in malaria

Various autoantibodies like anti-nuclear antibodies (ANA), anti-double stranded DNA (anti-dsDNA), anti-histone antibodies (AHA), anti-neutrophil cytoplasmic antibodies (ANCA), anti-myeloperoxidase (anti-MPO), anti-proteinase3 (anti-PR3) and anti-lactoferrin (anti-LF) antibodies were studied in 173 acute hospitalised patients suffering from malaria of which 160 patients had P. falciparum and remaining 13 had P. vivax infection. Standard methods like indirect immunofluorescence (IIF) microscopy along with Confocal microscopy and ELISA were used for identifying and quantifying the autoantibodies and IIF patterns on PMN and HL-60 cells were studied for ANCA classification. Also HEp-2 cells were used for ANA detection, while estimation of anti-dsDNA, AHA, anti-MPO, anti-PR3 and anti-LF were tested using ELISA. Sera from malaria patients showed prominent immunofluorescence staining patterns where 23.8% cases had ANA in P. falciparum group as compared to 15.4% in P. vivax group and ANCA was found to be present in 20% in P. falciparum and 15.4% in P. vivax group. An interesting observation was that, of the total ANCA positives, 59% had p-ANCA, 5.9% had c-ANCA and 44.1% of the cases showed the 'atypical' or X-ANCA pattern. When p-ANCA positivity was compared with c-ANCA positivity among these patients, a good statistical correlation was noted with OR = 16, chi 2 = 16.43, EF = 0.46 and p-value = 5.037E 0.5. ELISA showed 31.2% anti-MPO and 6.2% anti-PR3 in P. falciparum cases while the two ANCA positive cases in P. vivax had anti-MPO. Anti-LF was found to be present in 40.6% cases. Neither the P. falciparum nor P. vivax contained autoantibodies with specificities similar to the characteristic lupus autoantibodies such as double stranded DNA (dsDNA). ANCA positivity develops in some types of malarial infection also with the presence of various autoantibodies which is important from a clinical point of view and should be carefully evaluated in those geographic areas where malaria is endemic. It also alerts us to the fact, whether in cases of repeated malarial infections in susceptible individuals, vasculitic disorders, which through ANCA pathways develop, could lead to renal and other complications.     

Characteristics of malaria transmission in Kataragama, Sri Lanka: a focus for immuno-epidemiological studies

Parasitological and entomological parameters of malaria transmission were monitored for 17 months in 3,625 residents in a Plasmodium vivax malaria endemic region in southern Sri Lanka; the study area consisted of 7 contiguous villages where routine national malaria control operations were being conducted. Malaria was monitored in every resident; fever patients were screened and 4 periodical mass blood surveys were conducted. An annual malaria incidence rate of 23.1% was reported during the period: 9.3% was due to P. vivax and 13.8% was due to P. falciparum; there had been a recent epidemic of the latter in this region, whereas the P. falciparum incidence rate in the previous 10 years had been negligible. There was a wide seasonal fluctuation in the malaria incidence, with the peak incidence closely following the monsoon rains. The prevalence of malaria due to both species detected at the 4 mass blood surveys ranged from 0.98% (at low transmission) to 2.35% (at peak transmission periods). Adults and children developed acute clinical manifestations of malaria. Entomological measurements confirmed a low degree of endemicity with estimated inoculation rates of 0.0029 and 0.0109 (infectious bites/man/night) for P. vivax and P. falciparum, respectively. Several anopheline species contributed to the transmission, and the overall man biting rates (MBR) showed a marked seasonal variation. Malaria at Kataragama, typical of endemic areas of Sri Lanka, thus presents characteristics of "unstable" transmission. Malaria was clustered in the population. There was a low clinical tolerance to P. falciparum malaria, to which most had only been at risk, compared to P. vivax, to which most had had a life-long exposure.     

Therapeutic responses of Plasmodium vivax and P. falciparum to chloroquine, in an area of western India where P. vivax predominates

In 2003-2005, following an increase in the local incidence of human malaria, the therapeutic efficacy of chloroquine (CQ) in the treatment of Plasmodium vivax and P. falciparum malaria was evaluated in the Anand district of Gujarat state, in western India. After oral administration of CQ, clinical and parasitological responses were measured over a follow-up period of 28 days, following the standard protocol of the World Health Organization. Most of the recurrent infections were checked, by genotyping, to see whether they were the result of treatment failure or re-infection during the follow-up. At the primary health centre (PHC) in Deva, all 57 P. vivax cases included in the study responded to CQ within 3 days. At the Pansora PHC, however, only 59 [90.8%, with a 95% confidence interval (CI) of 83.7%-97.8%] of the 65 P. vivax cases appeared to respond completely, recurrent infections being observed in the other six cases (9.2%; CI=2.2%-16.3%). Of the four recurrent infections checked by genotyping, however, only two appeared to be the result of true treatment failure. Twenty-seven (81.8%; CI=67.2%-94.4%) of the 33 P. falciparum cases who were enrolled in the study, all from Pansora PHC also showed apparent treatment failure, with one early failure, 17 late clinical failures and nine late parasitological failures. All 23 P. falciparum cases that showed apparent treatment failure and were investigated by genotyping appeared to be true cases of failure, none showing any evidence of re-infection during follow-up. The mean parasite-clearance times for those infected with P. falciparum, both those considered CQ-sensitive and the treatment failures, exceeded 2 days. These results indicate the presence of CQ-resistant P. vivax and P. falciparum in Anand district. The high frequency of CQ failure against P. falciparum observed in this study led to a change in the drug policy at the Pansora PHC, with artemisinin-based combination therapy now being used for the first-line treatment of P. falciparum malaria. Chloroquine remains the recommended first-line treatment for P. vivax infections in the area but the treatment failure seen in at least two P. vivax cases indicates a need for further monitoring of the therapeutic efficacy of CQ against such infections, in central Gujarat and elsewhere.     

Malaria-attributable morbidity in Assam, north-eastern India.

Malaria is endemic in the Indian state of Assam and transmission of the causative parasites is perennial and persistent. The available data on malaria-related morbidity and mortality in the state for the years 1991-1999 have been reviewed. Over this period, Plasmodium falciparum was the predominant parasite, causing 58%-68% of the malaria cases; all other cases were attributed to P. vivax. All malaria-related deaths were attributed to P. falciparum infection, and the numbers of such deaths were correlated with the numbers of cases of P. falciparum malaria. The deaths occurred mostly in the rainy season (April-September) and among all age-groups of both sexes. The factors responsible for focal outbreaks of malaria across the state are discussed in relation to the existing health infrastructure.     

Malaria in a cohort of Javanese migrants to Indonesian Papua

The epidemiology of infection by Plasmodium falciparum and P. vivax was investigated among Javanese migrants to an endemic region of Papua, Indonesia. A cohort of 243 migrants from Java was followed for malaria in a new settlement village in the endemic Armopa area of north-eastern Papua, beginning on the day each migrant arrived in the village. The subjects were monitored during home visits (three/week) and by the twice-monthly production of bloodsmears that were checked for malarial parasites. At the end of 33 months, 159 (65%) of the subjects remained under follow-up. The prevalence of parasitaemia in the village declined from 16% among those already living there when the study began in August 1996, to 5% when the study finished in June 1999. Over this period, 596 infections by P. falciparum and 723 by P. vivax occurred in the cohort, 22 and 27 of the subjects each experiencing at least six infections by P. falciparum and P. vivax, respectively. The incidence of malarial infection was higher during the first and second years post-migration (3.2 and 2.7 infections/person-year) than during the third (1.2 infections/person-year). Although the geometric mean parasite counts for P. falciparum increased over time (1209, 1478, and 1830 parasites/microl in the first, second and third years, respectively), the corresponding values for P. vivax (497, 535 and 490 parasites/microl) showed no such trend. Only one of the nine subjects who developed severe malaria (requiring intravenous quinine therapy) was a child, giving an odds ratio for a case of severe malaria being in an adult of 6.1 (P=0.08).