Haematological profiles of the people of rural southern Malawi: an overview.

An integrative review of the results of two published and two unpublished studies of anaemia in children, adolescent females, pregnant women and adults living in southern Malawi is presented. Anaemia was universally present in all age-groups, with the higher prevalences in infants (100%) and adolescent primigravidae (93.8%). Nutritional deficits of iron and vitamin A were major contributory factors but chronic malarial haemolysis also significantly contributed to the anaemia. Among boys, anaemia was more common among those with glucose-6-phosphate-dehydrogenase (G6PD) deficiency than in those without this deficiency (P<0.002). This enzymopathy, which occurred in 23.5% [95% confidence interval (CI)=16.7%-30.1%] of the male and 30% (CI=17.3%-42.7%) of the female infants examined, was also associated with neonatal jaundice. The overall prevalences of the-alpha(3.7)/alphaalpha and -alpha(3.7)/-alpha(3.7) thalassaemia genotypes were estimated at 41.0% (CI=28.3%-53.7%) and 8.7% (CI=1.5%-15.9%), respectively. Haemoglobin AS was present in 18.1% (CI=12.8%-23.4%) of the infants and haemoglobin SS in 2.5% (CI=1.4%-3.6%). As the prevalence of infection with Plasmodium falciparum was significantly higher in infants with haemoglobin AS than in those with AA (21.4% v. 6.7%; P<0.001), an increased risk of early-onset moderate parasitaemias in young infants probably stimulates the development of immunity, protecting older heterozygotes from severe malarial infection. Innovative community approaches are required to break the cycle of ill health that anaemia supports in those living in rural areas of southern Malawi. Interventions in adolescent girls could be of particular importance, as they could break the cycle in both pregnant women and their infants.

CO2 production during acute infection in malnourished Malawian children.

OBJECTIVE: This study tested the hypotheses that the rate of CO2 production is less in marasmic children with acute infection when compared to well-nourished children, but greater when compared to uninfected marasmic children. DESIGN: A descriptive comparison of children aged 12-60 months who had their rates of CO2 production measured using a stable isotope tracer dilution method while receiving feedings. Body mass index (BMI) was the best measure of lean body mass available in this study. SETTING: Queen Elizabeth Central Hospital, Blantyre, Malawi. SUBJECTS: A total of 56 children were studied, 28 with marasmus and acute infection, 16 with marasmus, and 12 well nourished with acute infection. Those with acute infection had malaria, pneumonia, or sepsis. RESULTS: Well-nourished children with acute infection produced more CO2 than marasmic children (344+/-60 vs 225+/-65 mmol CO2/h, mean+/-s.d., P<0.001; 24.2+/-4.6 vs 18.4+/-5.4 mmol CO2/BMI h, P=0.001). However, the rate of CO2 production in marasmic children with acute infection was not greater than in uninfected marasmic children (225+/-65 vs 228+/-61 mmol CO2/h). The observed rate of CO2 production was greater than that which could be produced from the dietary intake alone (29.6 vs. 25.8 mmol CO2/kg h). CONCLUSIONS: Marasmic children do not increase energy expenditure in response to acute infection, as well-nourished children do. Dietary energy provided to marasmic children should be at least 420 kJ/kg day.

Risk factors for fetal anaemia in a malarious area of Malawi.

The prevalence of infants born with low cord haemoglobin (fetal anaemia) is high in areas where malaria and iron deficiency anaemia in pregnancy are common. The objective of the present study was to determine risk factors for fetal anaemia in an area of high malaria transmission in southern Malawi. A case control study was undertaken with fetal anaemia defined as cord haemoglobin (Hb) < 12.5 g/dl. Between March 1993 and July 1994, pregnant women attending the study hospitals for the first time in that pregnancy were enrolled. Data on socio-economic status, anthropometry, previous obstetric history and current pregnancy were collected. Malaria parasitaemia, Hb levels and iron status were measured in maternal blood at recruitment and delivery and in umbilical venous blood. Fetal anaemia occurred in 23.4% of babies. Mean (SD) cord Hb was 13.6 g/dl (1.83). Factors associated with fetal anaemia were: birth in the rainy season [adjusted odds ratio (AOR) 2.33, 95% CI 1.73-3.14], pre-term delivery (AOR 1.60, 1.03-2.49), infant Hb < 14 g/dl at 24 hours (AOR 2.35, 1.20-4.59), maternal Hb at delivery < 8 g/dl (AOR 1.61, 1.10-2.42) or <11 g/dl (AOR 1.60, 1.10-2.31). A higher prevalence of fetal anaemia occurred with increasing peripheral Plasmodium falciparum parasite density (p=0.03) and geometric mean placental parasite densities were higher in babies with fetal anaemia than in those without (3331 vs 2152 parasites/microl, p=0.07). Interventions should aim to reduce fetal anaemia by improving malaria and anaemia control in pregnancy and by addressing the determinants of pre-term delivery.

Teaching tuberculosis control to medical undergraduates: the Malawi experience.

SETTING: National Tuberculosis (TB) Control Programme (NTP) and College of Medicine (COM), Malawi. OBJECTIVES: To develop a TB/HIV module, incorporating TB control and the DOTS strategy, for 4th year medical undergraduates. To describe 1) the way in which the module was developed, 2) the contents and structure of the module, 3) the experience of teaching the module from 2000-2002, and d) the financial costs to the NTP. DESIGN: A descriptive study. RESULTS: The TB/HIV module, including the teaching manual, resource materials and undergraduate assessments, was developed between June and December 1999 by NTP, College of Medicine, interested stakeholders and an external consultant. The module was well received by medical undergraduates. Student knowledge, based on pre-module and post-module assessments, increased to satisfactory levels. Novel aspects of teaching, which included reading chapters in class followed by student-led knowledge reviews, modular assessments and using NTP staff as facilitators, were highly rated. The cost of developing the module was 14,070 US dollars, and the recurrent annual cost of teaching the module was 900 US dollars. CONCLUSION: The results show that a national tuberculosis control programme can work effectively with an academic medical institution in teaching medical undergraduates the important principles of country-wide TB control.

Epidemiology of measles in Blantyre, Malawi: analyses of passive surveillance data from 1996 to 1998.

Measles surveillance data in Blantyre, Malawi were reviewed for 1996-8 to describe the epidemiology of infection and to estimate vaccine efficacy (VE) by the screening method. A total of 674 measles cases were reported to the Blantyre District Health Office during this period. Age distribution showed that 108 (16.1%) of the cases were aged less than 1 year. The median age was 5 years. Eighty percent of the cases between 1 and 19 years had been previously vaccinated. VE was 68.6% (95% CI, 527-792) for children 12-23 months of age and 67.3% (95% CI, 48.3-79.3) for infants 9-11 months of age. Reasons for this low vaccine efficacy are discussed. Previous vaccination history was negatively associated with the risk for developing cough during measles infection (odds ratio (OR), 0.30; 95% CI, 0.09-0.91), diarrhoea (OR, 0.64; CI, 0.44-0.95) and pneumonia (OR, 0.40; CI, 0.25-0.62). Logistic regression analysis showed that pneumonia in adults was negatively associated with vaccination history. The passive surveillance system for measles in Malawi was useful to describe the epidemiology of measles.

Childhood tuberculosis in Malawi: nationwide case-finding and treatment outcomes.

SETTING: All 43 non-private hospitals (three central, 22 [corrected] district and 18 [corrected] mission) in Malawi that register and treat adult and paediatric TB cases. OBJECTIVE: To assess the rate, pattern and treatment outcome of childhood TB case notifications in Malawi in 1998. DESIGN: Retrospective data collection using TB registers, treatment cards and information from health centre registers. Information was collected on number of cases, types of TB and treatment outcomes using standardised definitions. RESULTS: There were 22,982 cases of TB registered in Malawi in 1998, of whom 2,739 (11.9%) were children. Children accounted for 1.3% of all case notifications with smear-positive pulmonary TB (PTB), 21.3% with smear-negative PTB and 15.9% with extra-pulmonary TB (EPTB). Estimated rates of TB in children were 78/ 100,000 in those aged less than one year, 83/100,000 in those aged 1-4 years and 33/100,000 in those aged 5-14 years. A significantly higher proportion of TB cases was diagnosed in central hospitals. Only 45% of children completed treatment. There were high rates of death (17%), default (13%) and unknown treatment outcomes (21%). Treatment outcomes were worse in younger children and in children with smear-negative PTB. Treatment completion was best (76%) and death rates lowest (11%) for the 127 children with smear-positive PTB. CONCLUSION: Childhood TB is common in Malawi and treatment outcomes are poor. Research should be directed towards improved diagnosis and follow-up of children with TB, and the National TB Programme should support appropriate management of childhood contacts of smear positive PTB cases.

Detection and characterization of rotaviruses in hospitalized neonates in Blantyre, Malawi.

In five separate fecal collections spanning three years, group A rotaviruses were detected by enzyme-linked immunosorbent assay in 35 (25%) of 142 specimens obtained from nondiarrheic, hospitalized neonates in Blantyre, Malawi. Molecular characterization of each strain identified, for the first time in neonates, a short electropherotype, genotype P[6], G8 strain type, similar to the dominant, cocirculating community strain detected in symptomatic infants in Blantyre. Partial sequence analysis of the VP4 and NSP4 genes of neonatal and community strains failed to identify changes which could explain the differences in clinical outcome. Neonatal serotype G8 rotaviruses should be considered as potential rotavirus vaccine candidates for use in Malawi.

Detection of group C rotavirus in children with acute gastroenteritis in Blantyre, Malawi.

Among 606 children who were treated for acute gastroenteritis at the Queen Elizabeth Central Hospital in Blantyre, Malawi, Group C rotavirus (Gp C RV) was detected by enzyme-linked immunosorbent assay in fecal specimens from 16 (3.9%) of 408 inpatients and in 4 (2.0%) of 198 outpatients. Thirteen (65%) children excreting Gp C RV were coinfected with Group A rotavirus.

Plasma HIV burden in Malawian children co-infected with rotavirus.

Fifty-eight HIV-infected children with acute rotavirus diarrhea were tested for plasma HIV RNA. There was no difference between acute and convalescent mean viral loads, and little change in CD4 cell counts. Compared with the 16 children who died within 4 weeks, 31 survivors had slightly lower viral loads at presentation and significantly higher CD4 cell counts. Low CD4 cell counts, but not HIV-1-RNA concentrations, were predictive of Death. Local, enteric rotavirus infection did not appear to affect blood HIV viral load or CD4 cell counts in this small group of children.

Effect of concomitant HIV infection on presentation and outcome of rotavirus gastroenteritis in Malawian children.

BACKGROUND: Rotaviruses represent important causes of severe diarrhoea in early childhood. We examined the effect of HIV infection on the presentation and outcome of rotavirus gastroenteritis in Malawian children. METHODS: Children younger than 5 years who were treated for acute gastroenteritis at the Queen Elizabeth Central Hospital in Blantyre from July, 1997, to June, 1999, were enrolled. Children with rotavirus diarrhoea, with and without HIV infection, were followed up for up to 4 weeks after hospital discharge. Rotavirus disease severity (assessed with a 20-point score), duration of rotavirus shedding, and seroresponse to rotavirus were compared between HIV-infected and HIV-uninfected children. FINDINGS: 786 inpatients (median age 8 months, 271 [34%] of whom were HIV-1-infected) and 400 outpatients (median age 9 months, 65 [16%] of whom were HIV-infected) were enrolled. Rotavirus was detected less frequently among HIV-infected children (102 of 336 [30%]) than among HIV-uninfected children (348 of 850 [41%], (relative risk 0.71 [95% CI 0.53-0.87], p=0.0007). There were no differences in rotavirus disease severity for hospitalised children with and without HIV infection, but HIV-infected children were more likely to die during follow-up (11/50 [22%]) than HIV-uninfected children (0/61, p<0.0001). Of 29 HIV-infected and 45 HIV-uninfected children who completed follow-up, six (21%) HIV-infected children shed rotavirus, compared with two (4%) HIV-uninfected children (4.66 [1.01-21.51], p=0.05), but shedding was not associated with diarrhoea. Three-quarters of children exhibited a four-fold rise of serum IgG or IgA to rotavirus, which did not vary by HIV status. INTERPRETATION: Malawian children with concomitant HIV infection resolved acute rotavirus infections. Rotavirus vaccine safety and immunogenicity in HIV-infected infants should now be determined.

The Australian contribution towards medical training in Malawi.

Malawi opened its only medical school in April 1991, despite opposition from some who believed that the venture was a waste of precious resources. From 1986, selected Malawi students had done preclinical training in Australia, the United Kingdom and South Africa, returning to Malawi for the clinical phase of their training. From 1994, Malawi students have been able to do the whole undergraduate medical course in their own country. Twenty Malawi medical students attended the medical schools of the University of Adelaide and Flinders University in South Australia between 1991 and 1996. All but three of those students are now qualified doctors working in various capacities in healthcare delivery service in Malawi.

An analysis of intra-uterine growth retardation in rural Malawi.

OBJECTIVE: (1) To describe the sex-specific, birth weight distribution by gestational age of babies born in a malaria endemic, rural area with high maternal HIV prevalence; (2) to assess the contribution of maternal health, nutritional status and obstetric history on intra-uterine growth retardation (IUGR) and prematurity. METHODS: Information was collected on all women attending antenatal services in two hospitals in Chikwawa District, Malawi, and at delivery if at the hospital facilities. Newborns were weighed and gestational age was assessed through post-natal examination (modified Ballard). Sex-specific growth curves were calculated using the LMS method and compared with international reference curves. RESULTS: A total of 1423 live-born singleton babies were enrolled; 14.9% had a birth weight <2500 g, 17.3% were premature (<37 weeks) and 20.3% had IUGR. A fall-off in Malawian growth percentile values occurred between 34 and 37 weeks gestation. Significantly associated with increased IUGR risk were primiparity relative risk (RR) 1.9; 95% CI 1.4--2.6), short maternal stature (RR 1.6; 95% CI 1.0--2.4), anaemia (Hb<8 g/dl) at first antenatal visit (RR 1.6; 95% CI 1.2--2.2) and malaria at delivery (RR 1.4; 95% CI 1.0--1.9). Prematurity risk was associated with primiparity (RR 1.7; 95% CI 1.3--2.4), number of antenatal visits (RR 2.2; 95% CI 1.6--2.9) and arm circumference <23 cm (RR 1.9; 95% CI 1.4--2.5). HIV infection was not associated with IUGR or prematurity. CONCLUSION: The birth-weight-for-gestational-age, sex-specific growth curves should facilitate improved growth monitoring of newborns in African areas where low birth weight and IUGR are common. The prevention of IUGR requires improved malaria control, possibly until late in pregnancy, and reduction of anaemia.

African Burkitt's lymphoma: a new perspective.

High titres of antibody to Epstein-Barr virus (EBV) late genes identify individuals at risk of developing endemic Burkitt's lymphoma (eBL). Viral lytic cycle early and intermediate-early gene expression in BL is associated with a favourable tumour response to chemotherapy. Our study investigated whether serological data identifying antibody expression to zta, a viral function that activates lytic-cycle gene expression, correlate with expression of its gene in tumours, and could have prognostic value. Studies on 10 Malawian patients, with presumed BL on clinical grounds, showed good correlations, suggesting that serum antibody responses might predict treatment responsiveness. The results with 1 patient were particularly striking. When admitted in January 1998, prognosis was poor as he was unable to walk, and had tumour cells, characteristic of stage IV disease, in his bone marrow. Laboratory investigations showed particularly high levels both of serum zta antibodies and of gene expression in his tumour. Follow-up confirmed him alive 6 months after hospital discharge. Among the EBV-positive cases, 2 were ultimately diagnosed as rhabdomyosarcoma, a tumour not previously associated with this virus. The findings from this small study, if confirmed, should have value for future BL management in resource-poor parts of the world.

The first decade of the Malawi College of Medicine: a critical appraisal.

The College of Medicine of the University of Malawi was opened in April 1991. Over almost a decade it has flourished in the face of economic and political constraints, as well as a change in the philosophy of donor support. We review the past, assess the present and look to the future.

Rotavirus strain diversity in Blantyre, Malawi, from 1997 to 1999.

In a 2-year study of viral gastroenteritis in children in Blantyre, Malawi, the diversity of rotavirus strains was investigated by using electropherotyping, reverse transcription-PCR amplification of the VP7 and VP4 genes (G and P genotyping), and nucleotide sequencing. Of 414 rotavirus strains characterized, the following strain types were identified: P[8], G1 (n = 111; 26.8%); P[6], G8 (n = 110; 26.6%); P[8], G3 (n = 93; 22.5%); P[4], G8 (n = 31; 7.5%); P[8], G4 (n = 21; 5.1%); P[6], G3 (n = 12; 2.9%); P[6], G1 (n = 7; 1.7%); P[6], G9 (n = 3; 0.7%); P[6], G4 (n = 3; 0.7%); P[4], G3 (n = 1; 0.2%); and mixed (n = 15; 3.6%). While all strains could be assigned a G type, seven strains (1.7%) remained P nontypeable. The majority of serotype G8 strains and all serotype G9 strains had short electropherotype profiles. All remaining typeable strains had long electropherotypes. Divergent serotype G1 rotaviruses, which contained multiple base substitutions in the 9T-1 primer binding site, were commonly identified in the second year of surveillance. Serotype G2 was not identified. Overall, G8 was the most frequently identified VP7 serotype (n = 144; 34.8%) and P[8] was the most frequently detected VP4 genotype (n = 227; 54.8%). Partial sequence analysis of the VP4 gene of genotype P[8] rotaviruses identified three distinct clusters, which predominantly (but not exclusively) comprised strains belonging to a distinct VP7 serotype (G1, G3, or G4). As a result of mutations in the 1T-1 primer binding site, strains belonging to each cluster required a separate primer for efficient typing. One cluster, represented by P[8], G4 strain OP354, was highly divergent from the established Wa and F45 VP4 P[8] lineages. As is the case for some other countries, the diversity of rotaviruses in Malawi implies that rotavirus vaccines in development will need to protect against a wider panel of serotypes than originally envisioned.

A Medical Curriculum for all seasons - a dialogue.

Ten years have now passed since the College of Medicine of the University of Malawi was opened. The College's Curriculum is firmly based on community needs. We describe the genesis and implementation of the curriculum of the College of Medicine and how it has persisted over the past ten years. The challenges that have so far been met are outlined.

Dietary phytate reduction improves zinc absorption in Malawian children recovering from tuberculosis but not in well children.

High dietary phytate content that compromises zinc nutriture is thought to be a major problem among children of the developing world. Zinc stable isotope techniques permit the quantitative assessment of the effect of phytate reduction on zinc homeostasis. We tested the hypothesis that zinc absorption would be increased in Malawian children fed a reduced-phytate corn-plus-soy diet compared with a standard high phytate diet. Twenty-three children hospitalized in Blantyre, Malawi, were enrolled. Children were selected from those recovering from tuberculosis and from well children (those with minor injuries, those awaiting elective surgery or healthy siblings). Children received a diet of corn-plus-soy porridge (either low phytate or high phytate) for a period of 3-7 d and then participated in a zinc stable isotope study. The study included the administration of oral and intravenous zinc stable isotopes and 7-d collections of urine and stool. The diet was maintained throughout the duration of specimen collection. Zinc isotopic enrichments in urine and stool were measured, and zinc fractional absorption, total zinc absorption, endogenous fecal zinc, net zinc retention and size of the exchangeable zinc pool were calculated. Among the 14 children recovering from tuberculosis, dietary phytate reduction resulted in higher fractional absorption (0.41 +/- 0.14 versus 0.24 +/- 0.09, mean +/- SD, P: < 0.05) and total zinc absorption (169 +/- 55 versus 100 +/- 46 microg/(kg. d), P: < 0.05). No effect of phytate reduction was seen in the well children (n = 9). Phytate reduction did not decrease the absolute endogenous fecal zinc, but it did decrease it relative to total absorbed zinc. These preliminary results indicate that phytate reduction may be beneficial in improving zinc nutriture in groups with increased zinc requirements who consume a cereal-based diet.

Lack of protection against vertical transmission of HIV-1 by interferons produced during pregnancy in a cohort from East African republic of Malawi.

Interferons (IFNs) associated with pregnancy were studied for their possible role in inhibition of vertical transmission of the human immunodeficiency virus type 1 (HIV-1). A study group was composed of 43 HIV-1-positive mothers, of whom 15 transmitted the virus to the offspring and 28 did not. The control group included 48 HIV-1-negative mother-infant pairs. The IFN-alpha was detected only sporadically in the maternal sera from the groups of transmitters (27%), nontransmitters (21%), and controls (19%). The average levels of IFN-alpha were low, 16.3 +/- 2.5 pg/ml, 21.4 +/- 9.9 pg/ml, and 21.3 +/- 9.4 pg/ml among the transmitters, nontransmitters, and control subjects, respectively. In the cord blood, IFN-alpha was detected only on two occasions among transmitters, and on a single occasion in the control group. IFN-beta was absent from both maternal and cord blood in the study group, and found to be present in one case in the control group simultaneously in the maternal and fetal sera. In the placentas, on the other hand, both type I and II IFNs were expressed universally in the villous trophoblast, and IFN-alpha and -beta in the stromal macrophages as well. In one case among transmitters, no IFNs were detected; nevertheless, no significant difference with respect to nontransmitters could be confirmed. Our data suggest that although the placental IFNs have an antiviral potential, they are not sufficient to suppress transmission of HIV from mother to infant.

Association of HIV-1 load and CD4 lymphocyte count with mortality among untreated African children over one year of age.

OBJECTIVE: To examine the association of viral load and CD4 lymphocyte count with mortality among HIV-infected children over one year of age. DESIGN: A prospective study. HIV-infected children were enrolled during the first year of life and followed for more than 2 years at the Queen Elizabeth Central Hospital in Blantyre, Malawi (southeast Africa). METHODS: Morbidity and mortality information was collected every 3 months, and physical examination and blood testing (for viral level and CD4 cell percentage) were performed every 6 months. Kaplan-Meier analyses and proportional hazards models were used to estimate survival and to examine the association of primary predictors with mortality. RESULTS: Of 155 HIV-infected children originally enrolled, 115 (74%) had viral load testing and 82 (53%) had both viral load and CD4 cell percentage testing after their first year. Among children over one year of age, significant associations were found between mortality and the log10 viral load and CD4 cell percentage in both univariate and multivariate models. Independent of the CD4 cell value, a one unit log10 increase in HIV RNA level increased the hazard of child mortality by more than twofold. Children with low CD4 cell counts (< 15%) and high viral loads (> or = 250,000 copies/ml median value) had the worst survival; children with high CD4 cell counts (> or = 15%) and low viral loads (< 250,000 copies/ml) had the best survival. CONCLUSION: As in developed countries, viral load and CD4 cell count are the main predictors of mortality among African children. Making these tests available adds to the challenges to be considered if antiviral therapies were to be adopted in these countries.

Plasma urea appearance rate is lower when children with kwashiorkor and infection are fed egg white-tryptophan rather than milk protein.

In kwashiorkor, there is less endogenous proteolysis in response to acute infection than in a well-nourished state. Thus the amino acid composition of dietary protein may be more important in facilitating the acute phase response in kwashiorkor. This study tested the hypothesis that during the treatment of kwashiorkor with infection, there is a lower rate of urea appearance when the dietary intake of amino acids more closely resembles the amino acid composition of acute phase proteins. Thirty children in Malawi with kwashiorkor and acute infection were fed isoenergetic, isonitrogenous meals containing either egg white-tryptophan or milk as a protein source. After 24 h, the rates of urea appearance and whole-body protein breakdown and synthesis were measured with the use of 1-13C-leucine and 15N2-urea tracers. Plasma concentrations of seven acute phase proteins, interleukin 6 and tumor necrosis factor-alpha were measured on admission, and at 24 and 48 h. The 16 children who received egg white-tryptophan had lower rates of urea appearance than those who received milk [57+/-30 vs. 87+/-36 micromol/(kg x h), mean +/- SD, P<0.02]. No significant differences were found in the rates of whole-body protein turnover or in the concentration of any of the acute phase proteins or cytokines. The concentration of interleukin 6 was consistent with an appropriate proinflammatory response and correlated directly with the concentrations of C-reactive protein (r = 0.67, P<0.01) and alpha1-antitrypsin (r = 0.40, P<0.05). The findings suggest that egg white-tryptophan is associated with less amino acid oxidation in kwashiorkor and acute infection than is milk.