Endemic malaria in four villages of the Pakistani province of Punjab

The prevalence of malaria in 4 villages 60 km south of Lahore, Punjab, where Anopheles culicifacies is the vector was estimated from blood films made during three mass malaria surveys (MS) and at 204 clinics (CS) held over 18 consecutive months. The highest parasite rate occurred during October 1984 when 43% of the CS population had parasitaemias. Plasmodium vivax predominated early in the major transmission season (23% and 15% vivax parasitaemias in August 1983 and 1984 respectively) whereas P. falciparum was the most common species later in the transmission season (an average falciparum prevalence of 37% in October and November 1984) and following the transmission season through March. Despite the proximity and habitat similarity of the 4 villages, both total and species malaria prevalence rates showed inter-village differences. Asexual stage and gametocyte parasite rates in children were 2 to 5 times higher than in adults. No increased mortality due to malaria was detected among the 4000 study population. Malaria was stable and endemic, albeit seasonally transmitted, in these 4 villages during 1983 and 1984.     

Attributable fraction estimates and case definitions for malaria in endemic

Asymptomatic carriage of malaria parasites occurs frequently in endemic areas and the detection of parasites in a blood film from a febrile individual does not necessarily indicate clinical malaria. In areas of low and moderate endemicity the parasite prevalence in fever cases can be compared with that in community controls to estimate the fraction of cases which are attributable to malaria. In areas of very high transmission such estimates of the attributable fraction may be imprecise because very few individuals are without parasites. Furthermore, non-malarial fevers appear to suppress low levels of parasitaemia resulting in biased estimates of the attributable fraction. Alternative estimation techniques were therefore explored using data collected during 1989-1991 from a highly endemic area of Tanzania, where over 80 per cent of young children are parasitaemic. Logistic regression methods which model fever risk as a continuous function of parasite density give more precise estimates than simple analyses of parasite prevalence and overcome problems of bias caused by the effects of non-malarial fevers. Such models can be used to estimate the probability that any individual episode is malaria-attributable and can be extended to allow for covariates. A case definition for symptomatic malaria that is used widely in endemic areas requires fever together with a parasite density above a specific cutoff. The choice of a cutoff value can be assisted by using the probabilities derived from the logistic model to estimate the sensitivity and specificity of the case definition.     

A cohort study of Plasmodium falciparum diversity during the dry season in Ndiop, a Senegalese village with seasonal, mesoendemic malaria

Prolonged carriage of Plasmodium falciparum in humans during the dry season is critical for parasite survival, as the infected subjects constitute a major reservoir in the absence of transmission. Yet, very little is known about the host/parasite interactions contributing to parasite persistence. In order to study the characteristics of P. falciparum infections during the dry season, we have genotyped parasites collected from untreated, asymptomatic individuals during 3 cross-sectional surveys conducted during the dry season in Ndiop, a Senegalese village with seasonal, mesoendemic malaria. Monthly entomological surveillance did not detect any transmission during that period. Parasite prevalence decreased markedly in the children aged < 7 years after 7 months of undetected transmission, but was stable in older children and adults throughout the dry season. In all chronically infected individuals, infection complexity remained stable, but there were substantial fluctuations of individual genotype(s), reflecting complex dynamics of multiple-clone infections during chronic asymptomatic parasite carriage. This fluctuation resulted in changes in the msp1 and msp2 allelic distribution within the cohort after 7 months of undetected transmission, contrasting with the stability observed during the preceding rainy season in that village.     

Risk of malaria attacks in Gambian children is greater away from malaria vector breeding sites

The causes of local variation in the prevalence of malaria were investigated in rural Gambia. Cross-sectional prevalence surveys were carried out among 1184 young children (aged 6 months-5 years) in 48 villages, at the end of the transmission season in 1996. Villages were categorized according to distance from the nearest vector breeding sites, and the patterns of malaria transmission, infection and disease compared. Children living in villages within 3 km of breeding sites experienced more infective bites, and higher prevalences of parasitaemia and spleen enlargement than less-exposed children living further away. Clinical illness, in contrast, was more common among infected children who were less exposed. Infected children living 3 km or more from breeding sites were more likely to have high-density parasitaemia (odds ratio [OR] = 1.98), fever (OR = 2.60) and high-density parasitaemia together with fever (OR = 3.17). Clinical attacks did not decline in older children, as seen amongst children who were more exposed. These findings show that significant differences in the risk of infection and clinical attacks can occur over very short distances. The age at which protective immunity is acquired may be delayed in villages where transmission intensity is lower, thus increasing the risk of a clinical attack following infection. Communities with the lowest vector densities may be those at greatest risk of disease.     

Associations of peak shifts in age--prevalence for human malarias with bednet coverage

Effects of bednet coverage (C) on prevalence of malaria were analysed using data from 1990-92 from 9 Papua New Guinean villages. Effects of coverage varied by age, resulting in a shift in age of peak prevalence from 4.7 (C = 0%) to 11.6 (C = 100%) years for Plasmodium falciparum, from 3.4 to 4.9 years for P. vivax and from 11.0 to 16.8 years for P. malariae. In small areas with no bednets the age distribution of P. falciparum parasitaemia was like that of a holoendemic area. Where coverage was complete the pattern corresponded to mesoendemicity. Thus, protracted use of bednets can result in profound changes in the endemicity of malaria even when coverage is incomplete and without insecticide treatment. Average entomological inoculation rates (EIRs) estimated from indoor landing rates on individuals without bednets were 35, 12 and 10 infectious bites per person per annum for P. falciparum, P. vivax and P. malariae, respectively. Logistic regression analyses indicated that the EIR estimate for P. falciparum was related to prevalence of this species independently of effects of bednet coverage. However, the recent EIR still accounted for much less variation than did the bednets. A similar pattern was seen for P. malariae, while there were no significant relationships between the recent EIR and the parasite positivity for P. vivax. It is concluded that short-term variations in inoculation rate are not important determinants of parasite prevalence in this population.     

Anopheline ecology and malaria transmission at a new irrigation project area (Bargi Dam) in Jabalpur (Central India)

Anopheline ecology and malaria transmission were studied in a newly irrigated area of the Bargi Project, District Jabalpur, Madhya Pradesh, Central India. Observations were made for 2 years (1993-95) in 10 villages along the Bargi irrigation canal, which are situated between 44 km (head end of canal) and 78 km (tail end of canal) from the dam site. Anopheles annularis was the predominant species in the head-end villages and its abundance was directly related to the opening of the canal, whereas Anopheles culicifacies was the most abundant species in tail-end villages, where irrigation is limited. Anopheles culicifacies showed 2 typical peaks not related to canal irrigation. Site-related differences in species prevalence were significant in both immatures and adults. Malaria infection was due to Plasmodium vivax and Plasmodium falciparum. The annual parasite incidence in children and adults was significantly higher in head-end villages (>4-fold) as compared to that in tail-end villages. However, seasonal trends in the prevalence of P. falciparum and P. vivax were the same in each group, with some fluctuations. In this study, preliminary results of the investigation are presented, demonstrating the trends in anopheline ecology and parasite prevalence in relation to the dynamics of irrigation development.     

Morbidity from malaria and immune responses to defined Plasmodium falciparum antigens in children with sickle cell trait in The Gambia.

Morbidity from Plasmodium falciparum malaria and humoral and in vitro cellular immune responses to defined malaria antigens were measured in rural Gambian children with haemoglobin phenotype AS (HbAS) and in those with a normal haemoglobin (HbAA). In a survey undertaken during the dry season, HbAS children had a higher parasite rate than HbAA children but a lower prevalence of parasitaemia at a level of 500/microliters or greater. Malariometric indices measured during a rainy season survey were similar in the 2 groups of children. During the rainy season, the incidence of infection with P. falciparum did not vary with haemoglobin phenotype. However, in children aged 6 years or less, a significantly smaller proportion of HbAS children who acquired infection developed clinical symptoms than did HbAA children. During both the dry season and rainy season surveys, humoral and in vitro cellular immune responses to defined antigens from the sporozoite and merozoite stages of P. falciparum were similar in the 2 groups of children. Thus, despite the differences in parasite indices and morbidity from malaria between the 2 groups of children, we found no evidence of an enhanced immune response to malaria infection amongst HbAS children compared with normal children.     

Criteria for diagnosing clinical malaria among a semi-immune population exposed to intense and perennial transmission

In highly malaria-endemic areas, thick smears are usually positive regardless of the clinical context. Therefore the simple positivity or negativity of the thick smear is not an adequate criterion for distinguishing malaria from other causes of fever. In order to define simple parasitological and clinical criteria for diagnosing clinical malaria with a small risk of error, a study was undertaken in a rural area in the Congo where malaria transmission is intense and perennial. Results of the systematic determination of the parasite density of 1562 samples from persons of all ages considered representative of the population of the studied area are compared to those from 327 febrile patients, 204 patients detected during medical consultations held in the villages and 123 febrile schoolchildren detected during surveys for fever. The analysis of the clinical data and the parasitological results clearly demonstrates the importance of the parasite density determination for the diagnosis of clinical malaria. Clinical Plasmodium falciparum malaria is unlikely to occur in children under 15 years if the parasite/leucocyte ratio is less than 1.5. On the contrary this diagnosis is very probable if the parasite/leucocyte ratio is higher than 2. Clinical criteria were too non-specific to serve as useful diagnostic criteria.     

Variation in malaria endemicity in relation to microenvironmental conditions in the Admiralty Islands,Papua New Guinea

For 197 adults and adolescents in four villages of three small islands in the Admiralty Islands, Papua New Guinea, antimalarial antibody titers were examined using the indirect fluorescent antibody test (IFAT) and malaria parasites were detected by the microtiter plate hybridisation (MPH) method using polymerase chain reaction (PCR) technique. The parasite rate (either Plasmodium falciparum or P. vivax, or both) averaged 39.2%, varying from 31.1% to 44.8% among the four villages due to natural and artificial microenvironmental conditions related to breeding sites of mosquitoes (Anopheles farauti). The lack of flat zones owing to geomorphological formation contributed to the lowest parasite rate in the extremely small island. However, human-modified environments such as a wet-land (naturally formed but artificially reformed) and an open well played significant roles in other inter-village differences. The present findings imply significant roles of microenvironment in diversified malaria prevalence and suggest some ways of mitigation of malarial hazards.     

Evaluation of the antibody response to Anopheles salivary antigens as a potential marker of risk of malaria

The evaluation of human immune responses to arthropod bites may be a useful marker of exposure to vector-borne diseases, with applications to malaria, the most serious parasitic infection in humans. The specific antibody (Ab) IgG response to saliva obtained from Anopheles gambiae mosquitoes was evaluated in young children from an area of seasonal malaria transmission in Senegal. Specific IgG was higher in children who developed clinical Plasmodium falciparum malaria within the 3 months that followed than in those who did not (P<0.05), and it increased significantly (P<0.0001) with the level of Anopheles exposure, as evaluated by conventional entomological methods. These results suggest that evaluation of antisalivary Ab responses could be a useful approach for identifying a marker for the risk of malaria transmission.     

Epidemiology of malaria transmission in forest and plain ecotype villages in Sundargarh District, Orissa, India

A study of the epidemiology of malaria transmission was undertaken in 13 tribal villages located in forest and plain areas of Sundargarh District of Orissa state, India, from January 2001 to December 2003. In forest areas, intense transmission of malaria is attributed to the highly anthropophagic vector Anopheles fluviatilis sibling species S and is complemented by A. culicifacies sibling species C. In plain areas, A. culicifacies sibling species C is responsible for malaria transmission. The entomological inoculation rate in the forest and plain areas was 0.311 and 0.014 infective bites/person/night, respectively, during 2003. Malaria transmission is perennial both in forest and plain areas but is markedly low in the plain area compared with the forest area. Plasmodium falciparum accounted for 85.0% of the total malaria cases during the study period. In forest and plain areas, the number of P. falciparum cases per 1000 population per year was 284.1 and 31.2, respectively, whereas the parasite rate was 14.0% and 1.7%, respectively. In forest areas, clinical malaria occurs more frequently in children aged 0-5 years and declines gradually with increasing age. The study showed that villages in forest and plain areas separated by short geographical distances have distinct epidemiology of malaria transmission.     

Evaluating a malaria intervention strategy using knowledge, practices and coverage surveys in rural Bolifamba, southwest Cameroon

We evaluated the impact of a malaria intervention in Bolifamba in rural Cameroon. The intervention consisted of educating the community on management of malaria and provision of a dispensary for early diagnosis and treatment. In July 2001, prior to the intervention, a questionnaire was used to obtain information on knowledge of and practices toward childhood malaria of 185 mothers of children aged 0-5 years. The same questionnaire was administered to 120 of the 185 mothers, one-year post-intervention. Clinical and laboratory investigations were carried out on children whose mothers were interviewed. A comparison of pre- and post-intervention data indicated significant changes in (i) the use of appropriate malaria treatment (from 50% to 81.7%); (ii) recognition of splenomegaly as a feature of malaria (from 18.4% to 80.8%); (iii) prevalence of splenomegaly (from 26.5% to 13.3%); (iv) prevalence of fever (from 27.8% to 13.3%); (v) parasite prevalence (from 60.5% to 44.2%) and (vi) severe malaria anaemia (from 2.6% to 0.0%). These findings revealed that proper education of villagers, particularly mothers, on malaria and the presence of health facilities, where treatment is readily available at affordable cost, close to villages, are important strategies that would reduce malaria morbidity and mortality significantly.     

Unstable malaria in Sudan: the influence of the dry season. Clone multiplicity of Plasmodium falciparum infections in individuals exposed to variable levels of disease transmission.

Studies of infection and immunity to malaria often take little account of the fact that the amount of infectious challenge individuals receive is very variable. Classic studies in areas of holoendemic transmission showed that clinical immunity develops quite rapidly during childhood, although the processes through which increasing levels of resistance to infection are acquired are still not understood. However, holoendemic transmission is one end of the spectrum of malaria epidemiology and the development of clinical immunity is also affected by factors such as the infection rate and the local parasite species composition. An exceptionally simple type of malaria transmission occurs during the short, autumnal malaria outbreaks of the Sudanese sahel-savannah belt, where a sparse 200-500 mm of rain falls in 2-3 summer months, Plasmodium falciparum causes > 95% of malaria cases in most areas, and the entomological inoculation rate (EIR) is very low by African standards; thus the population dynamics of malaria parasites are less affected by super-infection. A comparison of certain features of parasite genetic diversity, particularly the average number of parasite clones present in infections in the Sudanese sahel and in malaria study sites with different levels of transmission, is presented. It is proposed that increasing EIRs are associated with progressively smaller increases in the average number of malaria parasite clones per host and the implications of this relationship for studies on malaria infection and immunity are discussed.     

Reduction in incidence and prevalence of Plasmodium falciparum in under-5-year-old children by permethrin impregnation of mosquito nets

The malaria incidence and prevalence rates among children who slept under permethrin-impregnated mosquito nets in four villages near Madang, Papua New Guinea, were compared with the rates among children who slept under unimpregnated nets in four paired control villages. Immediately following a parasitological survey in the eight villages, malaria parasites were cleared from the children with chemotherapy, and the mosquito nets in the four experimental villages were impregnated with permethrin. Follow-up parasitological surveys were performed 4 and 10 weeks later. Sporozoite rates in female mosquitos of the Anopheles punctulatus complex decreased significantly in two of the experimental villages after impregnation. Also, the incidence of Plasmodium falciparum between the 4-week and 10-week surveys was significantly lower among the 0-4-year olds in villages with impregnated nets than in those with unimpregnated nets, leading to reduced prevalence of P. falciparum in this age group. Use of permethrin-impregnated nets had no effect on the incidence or prevalence of P. falciparum among 5-9-year olds or on that of P. vivax among the 0-4- or 5-9-year olds.     

Low-dose daily iron supplementation for 12 months does not increase the prevalence of malarial infection or density of parasites in young Zanzibari children

Conflicting evidence exists on the possible role of iron supplementation in the predisposition to malaria infection or the enhancement of its clinical severity. Where anemia prevalence is >40%, current guidelines are to provide low-dose daily iron to young children for up to 18 mo. Earlier studies used doses higher than the current guidelines, intermittent doses, or have supplemented for durations < or = 4 mo. We aimed to assess the effect of low-dose, long-term iron supplementation on malaria infection using a double-blind, placebo-controlled, randomized design, and to examine possible subgroup effects by season and child age. The study was conducted in Pemba Island, Zanzibar, where Plasmodium falciparum malaria has year-round high transmission. A community-based sample of 614 children 4-71 mo old was randomly allocated to 10 mg/d iron or placebo for 12 mo. Outcome measures were the prevalence and density of malaria infection, which was assessed by blood films at monthly intervals. At baseline, 94.4% were anemic (hemoglobin < 110 g/L), 48.1% were stunted (height-for-age Z-score less than -2) and >80% had malaria-positive blood films. No significant differences in malariometric indices were observed between children in the iron-supplemented and placebo groups. Parasite density was higher in certain months and in younger children, but iron supplementation was not associated with any malarial infection outcome in any season or age subgroup. We conclude that in this environment of high malaria transmission, daily oral low-dose supplementation of iron for 12 mo did not affect the prevalence of malaria infection or parasite density.     

Malaria and Anemia among Children in a Low Resource Setting In Nigeria

Background

This study aimed at determining the prevalence of malaria and anemia among children in rural community of Okada, Edo State Nigeria, as well as to assess the level of use of Insecticide treated bed nets and its impact on prevalence of malaria and anemia among study population.

Methods

Thick blood films from 226 children with signs and symptoms of malaria in Okada community were stained and examined for presence of malaria parasites. Hemoglobin concentration of all children was also determined using standard method.

Result

A total of 185 (81.9%) children were infected with malaria parasite. Malaria parasitaemia was significantly affected by age (P =0.003). A significantly higher number of positive cases of malaria and anemia was observed in rainy season as compared to dry season (P<0.05). The prevalence of anemia in children was 47.3%. Malaria was a risk factor for development of anemia in children (OR=2.551; 95% CI=1.227, 5.305; P=0.015). Use of insecticide treated bed nets was recorded in 11(4.9%) of children studied, and did not significantly reduce the prevalence of malaria and anemia. However among malaria parasite infected children, its use significantly reduced the prevalence of anemia (OR=0.126; 95%CI=0.015, 1.047; P=0.031).

Conclusion

Malaria and anemia among children was high malaria intervention progammes by relevant agencies is strongly advocated.     

Cross-sectional study of specific antibodies to a polymorphic Plasmodium falciparum antigen and of parasite antigen genotypes in school children on the slope of Mount Cameroon

To investigate relationships between Plasmodium falciparum parasitaemia, parasite genotypes, and specific anti-parasite antibodies, 244 school children (aged 4 to 16 years) were studied in April/May 2002, the peak malaria transmission season in Buea, Cameroon. Antibody reactivities were analysed by ELISA using an array of recombinant antigens representing different sequences from the polymorphic block 2 region of the merozoite surface protein 1 (MSP1), and the blood samples that were slide-positive for P. falciparum were genotyped for msp1 block 2 alleles. The prevalence of antibodies to the specific MSP1 block 2 antigens was significantly higher in children at one particular school (situated at the lowest altitude) compared to the others, although the prevalence of infection or particular parasite genotypes did not differ. Thus, at a population level, the prevalence of these antibodies does not simply reflect prevalence of parasites, but rather may be due to differences in the incidence of past infections. However, there were weak positive associations between specific antibody reactivity and the presence of the corresponding allele in the blood of individuals (statistically significant for the MAD20-type allele of block 2), indicating that antibody specificities are to some extent determined by current parasite infections.     

Treatment uptake by individuals infected with Plasmodium falciparum in rural Gambia,West Africa

OBJECTIVE: To find out what proportion of Plasmodium falciparum infections are treated in rural Gambia. METHODS: Subjects from four villages in the Gambia were followed over nine months through visits to village health workers. Monthly cross-sectional malaria surveys measured the prevalence of P. falciparum infection. Linked databases were searched for treatment requests. Treated cases were individuals with parasitaemia who requested treatment during narrow or extended periods (14 or 28 days, respectively) before or after a positive blood film was obtained. FINDINGS: Parasite prevalence peaked in November 1998, when 399/653 (61%) individuals had parasitaemia. Parasite prevalence was highest throughout the study in children aged 5-10 years. Although access to treatment was better than in most of sub-Saharan Africa, only 20% of infected individuals sought medical treatment up to 14 days before or after a positive blood film. Within two months of a positive blood film, 199/726 (27%) individuals with parasitaemia requested treatment. Despite easy access to health care, less than half (42%) of those with parasite densities consistent with malaria attacks (5000/ l) requested treatment. High parasite density and infection during October-November were associated with more frequent treatment requests. Self-treatment was infrequent in study villages: in 3/120 (2.5%) households antimalarial drugs had been used in the preceding malaria season. CONCLUSION: Many P. falciparum infections may be untreated because of their subclinical nature. Intermittent presumptive treatment may reduce morbidity and mortality. It is likely that not all untreated infections were asymptomatic. Qualitative research should explore barriers to treatment uptake, to allow educational interventions to be planned.     

The efficiency of sporozoite transmission in the human malarias, Plasmodium falciparum and P. vivax

Reported are malaria sporozoite and inoculation rates over a 1-year period in eight epidemiologically defined villages of different endemicity in Madang Province, Papua New Guinea. In the study, more than 41 000 wild-caught mosquitos were analysed for Plasmodium falciparum and P. vivax sporozoites by ELISA. In a given village the entomological inoculation rates correlated strongly with the prevalences of both these malarial parasites in children. However, the prevalence of P. falciparum infections in children was much higher than that of P. vivax, despite similar inoculation rates for the two species. These data suggest that in Papua New Guinea P. falciparum is more efficiently transmitted than P. vivax from mosquito to man. The increased efficiency of transmission of P. falciparum may be due to the heavier sporozoite densities in wild-caught mosquitos naturally infected with P. falciparum sporozoites that were tenfold greater than the sporozoite densities in mosquitos infected with P. vivax.     

Differential antibody response of Gambian donors to soluble Plasmodium falciparum antigens

A seroepidemiological and clinical study was performed in an area of West Africa (The Gambia) where Plasmodium falciparum is endemic with seasonal transmission. Plasma samples were tested by intermediate gel immunoelectrophoresis for antibodies against 7 soluble P. falciparum antigens. There were marked differences in the age-related pattern of antibody response to the different antigens. Antibodies to 4 of the antigens were acquired slowly with a maximum prevalence reached after 25-35 years of age. Antibodies against the 3 remaining antigens, including the endotoxin-like antigen, Ag7, were acquired earlier with a plateau of maximum prevalence reached after 5-11 years, i.e. at the time when morbidity due to malaria decreased. Children who had not appeared to be infected with malaria during the preceding transmission season had lower levels of antibodies to soluble antigens than did children who had had a documented attack of clinical malaria or parasitaemia. There was no difference in antibody profiles to soluble antigens between children with sickle cell trait and children with normal haemoglobin.