Honorati Masanja

Randomised trial of efficacy of SPf66 vaccine against Plasmodium falciparum malaria in children in southern Tanzania

Effective, safe antimalarial vaccines have proved elusive. The synthetic polypeptide SPf66 vaccine is based on preerythrocytic and asexual blood-stage proteins of Plasmodium falciparum. We report here a randomised double-blind placebo-controlled trial of the efficacy of the SPf66 vaccine against clinical P falciparum malaria in idete, southern Tanzania, an area of intense perennial malaria transmission. 586 children aged 1-5 years received three doses of vaccine (n = 274) or placebo (n = 312). The incidence and density of parasitaemia were assessed through repeated cross-sectional surveys on subgroups of children. Morbidity was monitored over a 1 year period through passive case detection in all children plus active case detection in a subgroup of 191. An episode of clinical malaria was defined as measured fever (> or = 37.5 degrees C) and parasite density > 20,000/microL. No severe side-effects were seen and the frequency of mild side-effects after the third dose was less than 6%. The vaccine was highly immunogenic and after three doses all vaccine recipients had detectable anti-SPf66 antibodies: the geometric mean index of response was 8.3 in the vaccine group and 0.7 in the placebo group. The incidence of parasitaemia was similar in both groups. 123 children had at least one episode of clinical malaria during the follow-up period after the third dose and annual incidence rates were 0.25 in the vaccine group and 0.35 in the placebo group. Estimated vaccine efficacy was 31% (95% confidence interval 0-52%; p = 0.046). After the third dose there were 6 deaths among the study cohort (1 vaccine, 5 placebo). This study confirms that SPf66 is safe, immunogenic and reduces the risk of clinical malaria among children exposed to intense P falciparum transmission.

Effectiveness and cost of facility-based Integrated Management of Childhood Illness (IMCI) in Tanzania

BACKGROUND The Integrated Management of Childhood Illness (IMCI) strategy is designed to address major causes of child mortality at the levels of community, health facility, and health system. We assessed the effectiveness of facility-based IMCI in rural Tanzania. METHODS We compared two districts with facility-based IMCI and two neighbouring comparison districts without IMCI, from 1997 to 2002, in a non-randomised study. We assessed quality of case-management for childrens illness, drug and vaccine availability, and supervision involving case-management, through a health-facility survey in 2000. Household surveys were used to assess child-health indicators in 1999 and 2002. Survival of children was tracked through demographic surveillance over a predefined 2-year period from mid 2000. Further information on contextual factors was gathered through interviews and record review. The economic cost of health care for children in IMCI and comparison districts was estimated through interviews and record review at national, district, facility, and household levels. FINDINGS During the IMCI phase-in period, mortality rates in children under 5 years old were almost identical in IMCI and comparison districts. Over the next 2 years, the mortality rate was 13% lower in IMCI than in comparison districts (95% CI -7 to 30 or 5 to 21, depending on how adjustment is made for district-level clustering), with a rate difference of 3.8 fewer deaths per 1000 child-years. Contextual factors, such as use of mosquito nets, all favoured the comparison districts. Costs of childrens health care with IMCI were similar to or lower than those for case-management without IMCI. INTERPRETATION Our findings indicate that facility-based IMCI is good value for money, and support widespread implementation in the context of health-sector reform, basket funding, good facility access, and high utilisation of health facilities.

Cause-specific mortality rates in sub-Saharan Africa and Bangladesh.

OBJECTIVE To provide internationally comparable data on the frequencies of different causes of death. METHODS We analysed verbal autopsies obtained during 1999 -2002 from 12 demographic surveillance sites in sub-Saharan Africa and Bangladesh to find cause-specific and age-specific mortality rates. The cause-of-death codes used by the sites were harmonized to conform to the ICD-10 system, and summarized with the classification system of the Global Burden of Disease 2000 (Version 2). FINDINGS Causes of death in the African sites differ strongly from those in Bangladesh, where there is some evidence of a health transition from communicable to noncommunicable diseases, and little malaria. HIV dominates in causes of mortality in the South African sites, which contrast with those in highly malaria endemic sites elsewhere in sub-Saharan Africa (even in neighbouring Mozambique). The contributions of measles and diarrhoeal diseases to mortality in sub-Saharan Africa are lower than has been previously suggested, while malaria is of relatively greater importance. CONCLUSION The different patterns of mortality we identified may be a result of recent changes in the availability and effectiveness of health interventions against childhood cluster diseases.

Child survival gains in Tanzania: Analysis of data from demographic and health surveys.

BACKGROUND A recent national survey in Tanzania reported that mortality in children younger than 5 years dropped by 24% over the 5 years between 2000 and 2004. We aimed to investigate yearly changes to identify what might have contributed to this reduction and to investigate the prospects for meeting the Millennium Development Goal for child survival (MDG 4). METHODS We analysed data from the four demographic and health surveys done in Tanzania since 1990 to generate estimates of mortality in children younger than 5 years for every 1-year period before each survey back to 1990. We estimated trends in mortality between 1990 and 2004 by fitting Lowess regression, and forecasted trends in mortality in 2005 to 2015. We aimed to investigate contextual factors, whether part of Tanzanias health system or not, that could have affected child mortality. FINDINGS Disaggregated estimates of mortality showed a sharp acceleration in the reduction in mortality in children younger than 5 years in Tanzania between 2000 and 2004. In 1990, the point estimate of mortality was 141.5 (95% CI 141.5-141.5) deaths per 1000 livebirths. This was reduced by 40%, to reach a point estimate of 83.2 (95% CI 70.1-96.3) deaths per 1000 livebirths in 2004. The change in absolute risk was 58.4 (95% CI 32.7-83.8; p<0.0001). Between 1999 and 2004 we noted important improvements in Tanzanias health system, including doubled public expenditure on health; decentralisation and sector-wide basket funding; and increased coverage of key child-survival interventions, such as integrated management of childhood illness, insecticide-treated nets, vitamin A supplementation, immunisation, and exclusive breastfeeding. Other determinants of child survival that are not related to the health system did not change between 1999 and 2004, except for a slow increase in the HIV/AIDS burden. INTERPRETATION Tanzania could attain MDG 4 if this trend of improved child survival were to be sustained. Investment in health systems and scaling up interventions can produce rapid gains in child survival.

Prevalence of active convulsive epilepsy in sub-Saharan Africa and associated risk factors: Cross-sectional and case-control studies

Summary Background The prevalence of epilepsy in sub-Saharan Africa seems to be higher than in other parts of the world, but estimates vary substantially for unknown reasons. We assessed the prevalence and risk factors of active convulsive epilepsy across five centres in this region. Methods We did large population-based cross-sectional and case-control studies in five Health and Demographic Surveillance System centres: Kilifi, Kenya (Dec 3, 2007–July 31, 2008); Agincourt, South Africa (Aug 4, 2008–Feb 27, 2009); Iganga-Mayuge, Uganda (Feb 2, 2009–Oct 30, 2009); Ifakara, Tanzania (May 4, 2009–Dec 31, 2009); and Kintampo, Ghana (Aug 2, 2010–April 29, 2011). We used a three-stage screening process to identify people with active convulsive epilepsy. Prevalence was estimated as the ratio of confirmed cases to the population screened and was adjusted for sensitivity and attrition between stages. For each case, an age-matched control individual was randomly selected from the relevant centres census database. Fieldworkers masked to the status of the person they were interviewing administered questionnaires to individuals with active convulsive epilepsy and control individuals to assess sociodemographic variables and historical risk factors (perinatal events, head injuries, and diet). Blood samples were taken from a randomly selected subgroup of 300 participants with epilepsy and 300 control individuals from each centre and were screened for antibodies to Toxocara canis, Toxoplasma gondii, Onchocerca volvulus, Plasmodium falciparum, Taenia solium, and HIV. We estimated odds ratios (ORs) with logistic regression, adjusted for age, sex, education, employment, and marital status. Results 586 607 residents in the study areas were screened in stage one, of whom 1711 were diagnosed as having active convulsive epilepsy. Prevalence adjusted for attrition and sensitivity varied between sites: 7·8 per 1000 people (95% CI 7·5–8·2) in Kilifi, 7·0 (6·2–7·4) in Agincourt, 10·3 (9·5–11·1) in Iganga-Mayuge, 14·8 (13·8–15·4) in Ifakara, and 10·1 (9·5–10·7) in Kintampo. The 1711 individuals with the disorder and 2032 control individuals were given questionnaires. In children (aged <18 years), the greatest relative increases in prevalence were associated with difficulties feeding, crying, or breathing after birth (OR 10·23, 95% CI 5·85–17·88; p<0·0001); abnormal antenatal periods (2·15, 1·53–3·02; p<0·0001); and head injury (1·97, 1·28–3·03; p=0·002). In adults (aged ≥18 years), the disorder was significantly associated with admission to hospital with malaria or fever (2·28, 1·06–4·92; p=0·036), exposure to T canis (1·74, 1·27–2·40; p=0·0006), exposure to T gondii (1·39, 1·05–1·84; p=0·021), and exposure to O volvulus (2·23, 1·56–3·19; p<0·0001). Hypertension (2·13, 1·08–4·20; p=0·029) and exposure to T solium (7·03, 2·06–24·00; p=0·002) were risk factors for adult-onset disease. Interpretation The prevalence of active convulsive epilepsy varies in sub-Saharan Africa and that the variation is probably a result of differences in risk factors. Programmes to control parasitic diseases and interventions to improve antenatal and perinatal care could substantially reduce the prevalence of epilepsy in this region. Funding Wellcome Trust, University of the Witwatersrand, and South African Medical Research Council.

Plasmodium falciparum malaria in the first year of life in an area of intense and perennial transmission

A longitudinal study of Plasmodium falciparum malaria in infants in Idete village, south‐eastern Tanzania, was conducted over a period of 14 months in order to determine the incidence of P. falciparum infection and clinical malaria in the first year of life. Of 1356 blood slides from cross‐sectional surveys, 52.1% were positive for asexual stages of P. falciparum. There were marked increases in P. falciparum prevalence, parasite densities, overall fever incidence and the incidence of malaria fevers with age for the first 6 months of life. The average attack rate, estimated from a reversible catalytic model, was 0.029 per day with a slight increase with age but there was no initial period of protection against infection in neonates. Estimated average duration of infections was 64 days, with infections in older infants lasting much longer than those contracted during the first 2 months of life.

Revising the WHO verbal autopsy instrument to facilitate routine cause-of-death monitoring

Objective Verbal autopsy (VA) is a systematic approach for determining causes of death (CoD) in populations without routine medical certification. It has mainly been used in research contexts and involved relatively lengthy interviews. Our objective here is to describe the process used to shorten, simplify, and standardise the VA process to make it feasible for application on a larger scale such as in routine civil registration and vital statistics (CRVS) systems. Methods A literature review of existing VA instruments was undertaken. The World Health Organization (WHO) then facilitated an international consultation process to review experiences with existing VA instruments, including those from WHO, the Demographic Evaluation of Populations and their Health in Developing Countries (INDEPTH) Network, InterVA, and the Population Health Metrics Research Consortium (PHMRC). In an expert meeting, consideration was given to formulating a workable VA CoD list [with mapping to the International Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) CoD] and to the viability and utility of existing VA interview questions, with a view to undertaking systematic simplification. Findings A revised VA CoD list was compiled enabling mapping of all ICD-10 CoD onto 62 VA cause categories, chosen on the grounds of public health significance as well as potential for ascertainment from VA. A set of 221 indicators for inclusion in the revised VA instrument was developed on the basis of accumulated experience, with appropriate skip patterns for various population sub-groups. The duration of a VA interview was reduced by about 40% with this new approach. Conclusions The revised VA instrument resulting from this consultation process is presented here as a means of making it available for widespread use and evaluation. It is envisaged that this will be used in conjunction with automated models for assigning CoD from VA data, rather than involving physicians.Objective Verbal autopsy (VA) is a systematic approach for determining causes of death (CoD) in populations without routine medical certification. It has mainly been used in research contexts and involved relatively lengthy interviews. Our objective here is to describe the process used to shorten, simplify, and standardise the VA process to make it feasible for application on a larger scale such as in routine civil registration and vital statistics (CRVS) systems. Methods A literature review of existing VA instruments was undertaken. The World Health Organization (WHO) then facilitated an international consultation process to review experiences with existing VA instruments, including those from WHO, the Demographic Evaluation of Populations and their Health in Developing Countries (INDEPTH) Network, InterVA, and the Population Health Metrics Research Consortium (PHMRC). In an expert meeting, consideration was given to formulating a workable VA CoD list [with mapping to the International Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) CoD] and to the viability and utility of existing VA interview questions, with a view to undertaking systematic simplification. Findings A revised VA CoD list was compiled enabling mapping of all ICD-10 CoD onto 62 VA cause categories, chosen on the grounds of public health significance as well as potential for ascertainment from VA. A set of 221 indicators for inclusion in the revised VA instrument was developed on the basis of accumulated experience, with appropriate skip patterns for various population sub-groups. The duration of a VA interview was reduced by about 40% with this new approach. Conclusions The revised VA instrument resulting from this consultation process is presented here as a means of making it available for widespread use and evaluation. It is envisaged that this will be used in conjunction with automated models for assigning CoD from VA data, rather than involving physicians.

The role of low level Plasmodium falciparum parasitaemia in anaemia among infants living in an area of intense and perennial transmission

Summary Children under one year of age in an area of intense and perennial Plasmodium falciparum transmission were followed up for one year to establish to what extent chronic, low parasitaemia was associated with severe anaemia. There was a significant increase in the prevalence of anaemia (PCV ≥ 25%) with increase in parasite density. PCV levels were related not only to concurrent parasite density but also decreased with densities measured one month previously. At any point in time, the mean PCV level in infants with low parasitaemia (<1000 parasites/μ1) was higher than that of infants with intermediate (1000–9999/μ1) and high parasite densities (≥10 000/μl). After the age of 7 months, infants with low parasite densities tend to recover, probably as a result of developing immunity. At the age of 12 months, they have similar PCV levels to infants with no detectable parasitaemia by microscopy. The maintenance of low parasite density appears crucial to the survival of infants in malaria endemic areas. The findings suggest that interventions which lower parasite densities in areas of intense transmission reduce the development of severe malarial anaemia and thus malaria‐related mortality and morbidity in infants.

Patterns of Age-Specific Mortality in Children in Endemic Areas of Sub-Saharan Africa

Cutaneous leishmaniasis (CL) treatment is painful, and cosmetic results are often unsatisfying. Azithromycin has been reported to be effective in treatment of CL caused by Leishmania viannia braziliensis. The efficacy of azithromycin was compared with Glucantime in treatment of Old World leishmaniasis. Of 49 patients, 22 received 500 mg/day azithromycin for 5 days/month. Treatment cycles were repeated monthly to a maximum of 4 months; 27 patients received 60 mg/kg intramuscular meglumine antimoniate for 20 days. Both groups were followed up for 16 weeks. In the azithromycin group, 2 patients withdrew because of GI symptoms. The response rates of 20 patients (29 lesions) were as follows: full improvement, 10.3%; partial improvement, 27.6%; and 62.1%, no response. In the glucantime group with 27 patients (58 lesions), these rates were 34.4%, 13.8%, and 51.7%, respectively (P = 0.036). Azithromycin was determined to be not as effective as Glucantime in treatment of Old World CL.

Mosquito nets and the poor: can social marketing redress inequities in access?

Treated mosquito nets are a practical malaria control tool. However, implementation of efficient delivery mechanisms remains a challenge. We investigated whether social marketing of treated mosquito nets results in decreased equity in rural Tanzania, through household surveys before the start of a social marketing programme and 3 years later. About 12 000 household heads were asked about ownership of nets and other assets including a tin roof, radio, or bicycle. A socio‐economic status score was developed for each household. Net ownership was calculated for households in each quintile of this score, from poorest to least poor. In 1997, about 20% of the poorest households and over 60% of the least poor households owned a mosquito net. Three years later, more than half of the poorest households owned a net, as did over 90% of the least poor: the ratio of net ownership among the poorest to least poor increased from 0.3 in 1997 to 0.6 in 2000. Social marketing in the presence of an active private sector for nets was associated with increased equity.