Prevalence of enteric infections among hospitalized patients in two referral hospitals in Ghana.

BACKGROUND: Diarrhea is an important cause of morbidity and mortality worldwide. In Africa and Ghana in particular, it is estimated to contribute directly to 19 and 25% of pediatric mortality among children under 5 years, respectively. METHODS: Surveillance for hospitalized acute diarrheal illness was initiated in November 2010 through October 2012 in a referral hospital in southern Ghana, and a teaching hospital in northern Ghana. Consenting hospitalized patients who met a standardized case definition for acute diarrheal illness provided demographic and epidemiologic data. Stool samples were collected and tested by culture for bacteria and by enzyme immunoassays for a panel of viruses and parasites. RESULTS: A total of 429 patients were enrolled; 216 (50.3%) were under 5 years, and 221 (51.5%) were females. Stool samples were received from 153 patients. Culture isolates included Shigella sp., Salmonella spp., Plesiomonas sp. and Vibrio cholerae. Of 147 samples tested for viruses, 41 (27.9%) were positive for rotaviruses, 11 (7.5%) for astroviruses, 10 (6.8%) for noroviruses, and 8 (5.4%) for adenoviruses. Of 116 samples tested for parasitic infections; 4 (3.4%) were positive for Cryptosporidium sp. and 3 (2.6%) for Giardia lamblia. Of the enrolled patients, 78.8% had taken antibiotics prior to sample collection. CONCLUSIONS: Diarrheal pathogens were identified across all ages, however, predominantly (81%) in the children under 5 years of age. This study also detected high antibiotic use which has the potential of increasing antibiotic resistance. The most common enteric pathogen detected (49.4%) was rotavirus.

Spatio-Temporal Distribution of Mycobacterium tuberculosis Complex Strains in Ghana.

BACKGROUND: There is a perception that genomic differences in the species/lineages of the nine species making the Mycobacterium tuberculosis complex (MTBC) may affect the efficacy of distinct control tools in certain geographical areas. We therefore analyzed the prevalence and spatial distribution of MTBC species and lineages among isolates from pulmonary TB cases over an 8-year period, 2007-2014. METHODOLOGY: Mycobacterial species isolated by culture from consecutively recruited pulmonary tuberculosis patients presenting at selected district/sub-district health facilities were confirmed as MTBC by IS6110 and rpoß PCR and further assigned lineages and sub lineages by spoligotyping and large sequence polymorphism PCR (RDs 4, 9, 12, 702, 711) assays. Patient characteristics, residency, and risks were obtained with a structured questionnaire. We used SaTScan and ArcMap analyses to identify significantly clustered MTBC lineages within selected districts and spatial display, respectively. RESULTS: Among 2,551 isolates, 2,019 (79.1%), 516 (20.2%) and 16 (0.6%) were identified as M. tuberculosis sensu stricto (MTBss), M. africanum (Maf), 15 M. bovis and 1 M. caprae, respectively. The proportions of MTBss and Maf were fairly constant within the study period. Maf spoligotypes were dominated by Spoligotype International Type (SIT) 331 (25.42%), SIT 326 (15.25%) and SIT 181 (14.12%). We found M. bovis to be significantly higher in Northern Ghana (1.9% of 212) than Southern Ghana (0.5% of 2339) (p = 0.020). Using the purely spatial and space-time analysis, seven significant MTBC lineage clusters (p< 0.05) were identified. Notable among the clusters were Ghana and Cameroon sub-lineages found to be associated with north and south, respectively. CONCLUSION: This study demonstrated that overall, 79.1% of TB in Ghana is caused by MTBss and 20% by M. africanum. Unlike some West African Countries, we did not observe a decline of Maf prevalence in Ghana.

Detection and characterization of drug-resistant conferring genes in Mycobacterium tuberculosis complex strains: A prospective study in two distant regions of Ghana.

We spoligotyped and screened 1490 clinical Mycobacterium tuberculosis complex strains from Northern and Greater Accra regions of Ghana against INH and RIF using the microplate alamar blue phenotypic assay. Specific drug resistance associated genetic elements of drug resistant strains were analyzed for mutations. A total of 111 (7.5%), 10 (0.7%) and 40 (2.6%) were mono-resistant to INH, RIF, and MDR, respectively. We found the Ghana spoligotype to be associated with drug resistance (INH: 22.1%; p = 0.0000, RIF: 6.2%; p = 0.0103, MDR: 4.6%; p = 0.0240) as compared to the Cameroon spoligotype (INH: 6.7%, RIF: 2.4%, MDR: 1.6%). The propensity for an isolate to harbour katG S315T mutation was higher in M. tuberculosis (75.8%) than Mycobacterium africanum (51.7%) (p = 0.0000) whereas the opposite was true for inhApro mutations; MAF (48.3%) compared to MTBSS (26.7%) (p = 0.0419). We identified possible novel compensatory INH resistance mutations in inhA (G204D) and ahpCpro (-88G/A and -142G/A) and a novel ndh mutation K32R. We detected two possible rpoC mutations (G332R and V483G), which occurred independently with rpoB S450L, respectively. The study provides the first evidence that associate the Ghana spoligotype with DR-TB and calls for further genome analyses for proper classification of this spoligotype and to explore for fitness implications and mechanisms underlying this observation.

Antiplasmodial activity of extracts of Tridax procumbens and Phyllanthus amarus in in vitro Plasmodium falciparum culture systems.

BACKGROUND: Aqueous extracts of Tridax procumbens (TP) (Compositae) and Phyllanthus amarus (PA) (Euphorbiaceae) are used in traditional medicine in Ghana to treat malaria. Previous studies have demonstrated the anti-trypanosoma, anti-bacterial and anti-HIV effects of TP and PA. OBJECTIVE: To assess the antiplasmodial activity of extracts of TP and PA. METHOD: Aqueous extracts of TP and PA were prepared. A portion of each was freeze-dried and the remaining extracted sequentially with ethyl acetate and chloroform. Ethanolic extracts were also prepared. The antiplasmodial activity of the extracts was assessed with the 3H-hypoxanthine assay using chloroquine-resistant (Dd2) Plasmodium falciparum parasites. Chloroquine was used as the reference drug. The modified tetrazolium-based colorimetric assay was also used to evaluate the red blood cell (RBC)-protective/antiplasmodial activities and cytotoxicities of the extracts. RESULTS: Results showed that TP and PA have antiplasmodial activities. The aqueous and ethanolic extracts of PA were the most active, yielding EC50 values of 34.9 µg/ml and 31.2 µg/ml, respectively in the tetrazolium-based assay. The TP and PA produced and IC50 values of 24.8 µg/ml and 11.7 µg/ml, respectively in the hypoxanthine assay. Protection of human RBCs against P. falciparum damage by the extracts highly correlated with their antiplasmodial activities. None of the extracts, within the concentration range (1.9-500 µg/ml) studied produced any overt toxicity to human RBCs. CONCLUSION: The results indicate that both PA and TP have activities against chloroquine-resistant P. falciparum (Dd2) parasites. The antiplasmodial principles extracted into water and ethanol but not chloroform or ethyl acetate.

A randomized, comparative study of supervised and unsupervised artesunate-amodiaquine, for the treatment of uncomplicated malaria in Ghana.

Although the use of artesunate-amodiaquine treatment is growing in Africa, data on its effectiveness are limited. In only the second published comparison of supervised and unsupervised treatments with this combination, Ghanaian children with uncomplicated malaria have recently been investigated in an open-label, randomized, comparative study. Children aged 6-120 months attending the Navrongo War Memorial hospital between November 2005 and December 2006 were enrolled if they had uncomplicated Plasmodium falciparum malaria and at least one of their parents/guardians gave their informed consent. Overall, 638 patients were screened, 357 were found to have P. falciparum infection, and 308 of these satisfied the other selection criteria and were enrolled. The subjects were divided randomly into two treatment arms. All the children were scheduled to receive 10 mg amodiaquine/kg and 4 mg artesunate/kg daily for 3 days but only 154 (the 'supervised') were given all their treatments in hospital, with each dose directly observed. Although the other 154 children (the 'unsupervised') were given their first dose in hospital, under supervision, they were then sent home with the tablets they required to complete treatment. Study participation lasted for 28 days, with follow-up on days 3, 7, 14, 21 and 28. During follow-up, axillary temperatures, any emergent signs and symptoms, and concomitant drug consumption were recorded and haemoglobin concentrations and malarial parasitaemias and gametocytaemias were measured. All but seven of the 308 subjects completed the study. At enrolment the subjects had a mean age of 45.0 months, a mean weight of 14.8 kg, a mean axillary temperature of 37.9 degrees C and a geometric mean parasitaemia of 11,367 asexual stages/microl. About 55% of the children investigated were girls. There were no significant baseline difference between the two treatment arms. Although there was also no difference in the clearance of fever and parasitaemia between the two arms by day 14, a supervised child was significantly more likely to show an adequate clinical and parasitological response, by day 21 (91.3% v. 84.1%; P= 0.05) or day 28 (80.0% v. 64.9%; P<0.01), than an unsupervised child. The reported adverse effects following treatment and the trend in haemoglobin recovery were, however, similar in the two arms. Although artesunate-amodiaquine appeared very effective in the treatment of uncomplicated P. falciparum malaria in children, whether supervised or not, it appears that supervised treatment provided stronger prevention against re-infection and recrudescence. At least in the present study, treatment at home, without medical supervision, probably led to relatively poor compliance.

The in-vitro susceptibilities of Ghanaian Plasmodium falciparum to antimalarial drugs.

In Ghana in 2004 (when choroquine was still the nationally recommended drug for the first-line treatment of malaria), the sensitivities, to chloroquine, amodiaquine, quinine, mefloquine, artesunate and halofantrine, of 60 Plasmodium falciparum isolates from two ecologically distinct areas of the country were assessed in vitro. The aim was to make available, to policy-makers, the field-based evidence needed to review the national strategy for malaria treatment. Drug susceptibilities were explored using the standardized protocol of the Antimalarial Drug Resistance Network. Although 32 of the P. falciparum isolates evaluated (56.1% of the 57 isolates successfully investigated for their susceptibility to choroquine) showed resistance to chloroquine and two showed slightly reduced sensitivity to amodiaquine, all the isolates were sensitive to mefloquine, artesunate, quinine and halofantrine. The median inhibitory concentrations (IC(50)) of chloroquine were positively correlated with those of quinine (r=0.4528; P=0.0008) but not those of any of the other drugs investigated. The IC(50) of amodiaquine and artesunate were also positively correlated (r=0.3703; P=0.0067). These results provide evidence of the presence, in Ghana, of P. falciparum isolates that are highly resistant to chloroquine but generally sensitive to most of the other antimalarial drugs commonly used in the country. Partly in consequence of these observations, the recommended first-line treatment for malaria in Ghana was changed to an amodiaquine-artesunate combination in January 2005.

When is "malaria" malaria? The different burdens of malaria infection, malaria disease, and malaria-like illnesses.

In this review we discuss the different meanings of the term 'malaria' and urge writers and readers to distinguish accurately between them. The distinction is important in clinical practice, clinical trials, epidemiology, and the evaluation of control programs. Both over- and underdiagnosis of malaria as the cause of a disease episode are inevitable; overdiagnosis is common in high-transmission areas and underdiagnosis is common in areas with little or no transmission. Parasite density thresholds, attributable fractions, and clinical algorithms have played important but only partial roles in strengthening diagnosis. Methods by which malaria infection could be confidently identified as the cause, rather than an irrelevant accompaniment, of an illness, are important targets for research. One such 'signature' is a distinctive retinopathy that occurs in severe malaria and not in clinically similar diseases. Other indicators of a malarial etiology of clinical disease are needed to strengthen clinical and scientific approaches to the control of malaria.

Population Based Reference Intervals for Common Blood Haematological and Biochemical Parameters in the Akuapen North District

Objectives : To estimate the reference intervals for commonly used blood haematology and biochemical parameters in an adult (18-55yrs) population of residents of Mampong Akuapem. Design: This was a population based cross sectional study of a randomly selected sample of the adult population of Mampong. The sample was selected from an updated census list of the Mampong area. Results: Median values (95 range) for measured parameters were established as follows: Haemoglobin; (males) 14.2 g/dl (females) 12.0 g/dl Alanine aminotransferase (ALT); (female) 19.6 U/L (males) 26.1 U/L and Creatinine; (males) 108 mmol/L (females) 93 mmol/L. Conclusion: In comparison to reference values that are commonly used in Ghana; the haemoglobulin levels from this study were lower; and liver function parameters higher. This could be a result of genetic or environmental differences and calls for the need to establish site specific reference values applicable to our population

Termination of pregnancy in South Tyneside.

We evaluated prospectively, compliance with the Royal College of Obstetricians and Gynaecologists (RCOG) guidelines on termination of pregnancy (TOP) in a cohort of 340 women referred for termination of pregnancy in 2003 at South Tyneside Foundation Trust. The number of referrals represented one-fifth of all births in our unit during the study period. Teenagers were the largest single group of women requesting termination of pregnancy and the majority were nulliparous. There were 85 women who were seeking a repeat termination of pregnancy. The RCOG minimum referral standard was met in 80% of cases. A good number of women were unsure of their menstrual dates and only 5% had used emergency contraception. A total of 96% were either not using contraception, using condoms or taking oral contraceptives irregularly. A total of 50% of the women attended hospital without a Certificate A being completed by the referring practitioner. Surgical termination was preferred over medical termination in the cohort of women who could exercise a choice. It is possible to comply with the RCOG Termination of Pregnancy guidelines to a large extent in a District General Hospital, with some innovation. Close liaison between General Practitioners, Family Planning Clinics and Acute Hospitals is required. The adoption of agreed referral requirements and pathways would help in the delivery of a high quality service as advocated by the guideline.

Antimalarial prescribing practices: a challenge to malaria control in Ghana.

OBJECTIVE: The study was conducted to determine antimalarial prescribing practices among prescribers in 2 of the 6 sentinel sites established to document antimalarial drug efficacy in Ghana in order to provide some explanation underlying chloroquine treatment failures in the country. SUBJECTS AND METHODS: The study was descriptive combining both qualitative and quantitative designs. The qualitative design involved in-depth interviews of general prescribers in the Wassa West and Kassena Nankana districts using an interview guide. The quantitative design involved a review of Outpatient Department prescriptions of 100 patients clinically diagnosed as having malaria within the year 2000 in each of the 7 selected health care facilities. RESULTS: The overall number of drugs prescribed per patient encounter was 4.3 in the Wassa West district and 3.0 in the Kassena Nankana district. The number of drugs per patient encounter was 5.4 and 3.7 in private and government health care facilities, respectively. The commonly prescribed antimalarial drug in all the health care facilities visited was chloroquine. However, only 9.8% of prescriptions in private health care facilities contained correct doses of chloroquine compared to 54% in government health care facilities (p = 0.000). Prescriptions containing chloroquine injections were least likely to have correct doses of chloroquine. CONCLUSION: The findings indicate that although chloroquine remained the first-line drug in the treatment of uncomplicated malaria in the two districts, the level of appropriateness of doses prescribed was generally low. Inappropriate doses of chloroquine prescribed were more prevalent in private than government health care facilities, and among prescriptions containing injections.

Does apolipoprotein E polymorphism influence susceptibility to malaria?

Outcome of infection varies greatly among people, and in the case of three very different viruses, it is determined by apolipoprotein E (APOE) genotype. APOE might affect outcome of malaria infection also, since apoE protein and the protozoon (like the viruses) share cell entry mediators (heparan sulphate proteoglycans and/or specific apoE receptors). APOE polymorphisms give rise to protein variants that differ in binding strength to these mediators; thus, the extent of competition between apoE and protozoon for cell entry, and hence magnitude of protozoan damage, might depend on apoE isoform. Genotypes of infants infected with malaria were examined. It was found that APOE epsilon 2 homozygotes became infected at an earlier age than those carrying the other genotypes, the difference being statistically significant. Parasite densities, all of which were low, did not differ significantly. This effect, although based on small numbers, suggests that APOE epsilon 2 may be a risk factor for early infection.

Absolute levels and ratios of proinflammatory and anti-inflammatory cytokine production in vitro predict clinical immunity to Plasmodium falciparum malaria.

The relationship between malaria-related outcomes and cytokine production in whole blood cultures associated with cellular immune responses and immunity to Plasmodium falciparum malaria was examined in a study in southern Ghana. Production of malaria-specific interferon (IFN)-gamma was associated with reduced risk of fever and clinical malaria. Protective IFN-gamma responses were induced by live schizonts but not by dead parasites. Production of malaria-specific tumor necrosis factor (TNF)-alpha was associated with reduced risk of fever during follow-up. Baseline levels of TNF-alpha and phytohemagglutinin (PHA)-induced interleukin (IL)-10 were positively associated with hemoglobin concentration. IL-12 production was associated with reduced risk of parasitemia. PHA-induced transforming growth factor-beta production was associated with reduced risk of fever during follow-up. High ratios of proinflammatory to anti-inflammatory cytokines were associated with increased risk of fever and higher hemoglobin concentrations. Thus, absolute levels and ratios of proinflammatory and anti-inflammatory cytokines influence susceptibility to infection, clinical disease, and anemia. These data contradict data from cross-sectional clinical studies and indicate a need for detailed analysis of the relationship between cellular immunity to malaria and resistance to disease.

Antibody response to 17D yellow fever vaccine in Ghanaian infants.

OBJECTIVES: To assess the seroresponses to yellow fever vaccination at 6 and 9 months of age; assess any possible adverse effects of immunization with the 17D yellow fever vaccine in infants, particularly at 6 months of age. METHODS: Four hundred and twenty infants who had completed BCG, OPV and DPT immunizations were randomized to receive yellow fever immunization at either 6 or 9 months. A single dose of 0.5 ml of the reconstituted vaccine was administered to each infant by subcutaneous injection. To determine the yellow fever antibody levels of the infants, each donated 1 ml whole blood prior to immunization and 3 months post-immunization. Each serum sample was titred on Vero cells against the vaccine virus. FINDINGS: The most common adverse reactions reported were fever, cough, diarrhoea and mild reactions at the inoculation site. The incidences of adverse reactions were not statistically different in both groups. None of the pre-immunization sera in both age groups had detectable yellow fever antibodies. Infants immunized at 6 months recorded seroconversion of 98.6% and those immunized at 9 months recorded 98% seroconversion. The GMT of their antibodies were 158.5 and 129.8, respectively. CONCLUSIONS: The results indicate that seroresponses to yellow fever immunization at 6 and 9 months as determined by seroconversion and GMTs of antibodies are similar. The findings of good seroresponses at 6 months without significant adverse effects would suggest that the 17D yellow fever vaccine could be recommended for use in children at 6 months in outbreak situations or in high risk endemic areas.

Incidence of symptomatic and asymptomatic Plasmodium falciparum infection following curative therapy in adult residents of northern Ghana.

Adult residents of holoendemic malaria regions in Africa have a naturally acquired immunity (NAI) to malaria that renders them more resistant to new infections, limits parasitemia, and reduces the frequency and severity of illness. Given such attributes, it is not clear how one might evaluate drug or vaccine efficacy in adults without serious confounding. To determine symptomatic and asymptomatic malaria attack rates in adults of northern Ghana, 197 men and women underwent curative therapy for any pre-existing malaria infections at the start of the high transmission (wet) season. They were monitored for first parasitemia and first clinical episode of infection by Plasmodium falciparum over a 20-week period (May-October 1996). The cumulative incidence of primary infection by P. falciparum was 0.98 and incidence density of infection was calculated to be 7.0 cases/person-year. Symptoms were reported by 19.5% of the individuals at the time of first recurrent parasitemia. Incidence of infection, parasite density, and the frequency of symptoms were comparable in males and females. The results suggest that NAI did not provide these adults with significant defense against rapid re-infection and suggest that this population-infection design could serve to demonstrate the efficacy of a drug or vaccine in preventing parasitemia.

Novel Plasmodium falciparum clones and rising clone multiplicities are associated with the increase in malaria morbidity in Ghanaian children during the transition into the high transmission season.

A survey of Plasmodium falciparum infection and clone multiplicity in Ghanaian children was carried out to study the effect of the onset of the malaria transmission season on disease incidence. Fortnightly blood samples were collected from 40 children living in the rural town of Dodowa, between February and August 1998. P. falciparum parasite densities were calculated and PCR genotyping was carried out using the polymorphic MSP-1 and MSP-2 genes as target loci for the estimation of the number of parasite clones in each sample. The average clone number was estimated using maximum likelihood techniques and the minimum number of clones per patient was analysed for the effects of age, sex, season, minimum number of clones per child, level of parasitaemia and parasite genotype. The statistical analysis indicated that the more clones a child carried, the more likely they were to have a clinical malaria episode. This was true after adjusting for age and season effects and for the measured circulating parasitaemia. The probability of clinical disease also increased if the MSP-1 MAD 20 and the MSP-2 FC 27 alleles were present. This longitudinal analysis thus indicates that the probability of a Ghanaian child having a symptomatic malaria episode is positively associated with both increasing numbers and novel types of P. falciparum clones.

Selection of glutamate-rich protein long synthetic peptides for vaccine development: antigenicity and relationship with clinical protection and immunogenicity.

Antibodies against three long synthetic peptides (LSPs) derived from the glutamate-rich protein (GLURP) of Plasmodium falciparum were analyzed in three cohorts from Liberia, Ghana, and Senegal. Two overlapping LSPs, LR67 and LR68, are derived from the relatively conserved N-terminal nonrepeat region (R0), and the third, LR70, is derived from the R2 repeat region. A high prevalence of antibody responses to each LSP was observed in all three areas of endemic infection. Levels of cytophilic immunoglobulin G (IgG) antibodies against both GLURP regions were significantly correlated with protection from clinical P. falciparum malaria. Protected children from the Ghana cohort possessed predominantly IgG1 antibodies against the nonrepeat epitope and IgG3 antibodies against the repeat epitope. T-cell proliferation responses, studied in the cohort from Senegal, revealed that T-helper-cell epitopes were confined to the nonrepeat region. When used as immunogens, the LR67 and LR68 peptides elicited strong IgG responses in outbred mice and LR67 also induced antibodies in mice of different H-2 haplotypes, confirming the presence of T-helper-cell epitopes in these constructs. Mouse antipeptide antisera recognized parasite proteins as determined by immunofluorescence and immunoblotting. This indicates that synthetic peptides derived from relatively conserved epitopes of GLURP might serve as useful immunogens for vaccination against P. falciparum malaria.

Antibodies to variant antigens on the surfaces of infected erythrocytes are associated with protection from malaria in Ghanaian children.

Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) is a variant antigen expressed on the surface of infected erythrocytes. Each parasite genome contains about 40 PfEMP1 genes, but only 1 PfEMP1 gene is expressed at a given time. PfEMP1 serves as a parasite-sequestering ligand to endothelial cells and enables the parasites to avoid splenic passage. PfEMP1 antibodies may protect from disease by inhibiting sequestration, thus facilitating the destruction of infected erythrocytes in the spleen. In this study, we have measured antibodies in Ghanaian children to a conserved region of PfEMP1 by enzyme-linked immunosorbent assay and antibodies to variant molecules on erythrocytes infected with field isolates of P. falciparum by flow cytometry. Based on close clinical monitoring, the children were grouped into those who did (susceptible) and those who did not (protected) have malaria during the season. The prevalences of antibodies to both the conserved PfEMP1 peptide and the variant epitopes were greater than 50%, and the levels of immunoglobulin G (IgG) correlated with age. The levels of antibodies to both the conserved peptide and the variant epitopes were higher in protected than in susceptible children. After correcting for the effect of age, the levels of IgG to variant antigens on a Sudanese and a Ghanaian parasite isolate remained significantly higher in protected than in susceptible children. Thus, the levels of IgG to variant antigens expressed on the surface of infected erythrocytes correlated with protection from clinical malaria. In contrast, the levels of IgG to a peptide derived from a conserved part of PfEMP1 did not correlate with protection from malaria.

Do maternally acquired antibodies protect infants from malaria infection?

Neonates and infants are relatively protected from clinical malaria, but the mechanism of this protection is not well understood. Maternally derived antibodies are commonly believed to provide protection against many infectious diseases, including malaria, for periods of up to 6-9 months but several recent epidemiological studies have produced conflicting results regarding a protective role of passively acquired antimalarial antibodies. In this article, we review the epidemiological evidence for resistance of young infants to malaria, summarize the data on antimalarial antibody levels and specificity and their association with protection from malaria infection or clinical disease, and explore alternative explanations for resistance to malaria in infants.

Frequent and persistent, asymptomatic Plasmodium falciparum infections in African infants, characterized by multilocus genotyping.

To determine the duration and complexity of naturally acquired Plasmodium falciparum infections in small children, a longitudinal cohort study of 143 newborns was conducted in coastal Ghana. On average, children experienced 2 episodes of infection in their first 2 years of life, the median duration of an asymptomatic infection was <4 weeks, and estimates of the mean number of parasite genotypes per infection were 1.15-2.28. Nevertheless, 40% of the children experienced infections lasting 5 months old. The ability of very young children to clear or control malaria infections indicates the presence of effective innate or immune antiparasite mechanisms.