Anthony K. Mbonye

Introducing malaria rapid diagnostic tests at registered drug shops in Uganda: limitations of diagnostic testing in the reality of diagnosis.

In Uganda, around two thirds of medicines are procured from the private sector, mostly from drug shops. The introduction of malaria rapid diagnostic tests (RDTs) at drug shops therefore has the potential to make a significant contribution to targeting antimalarial drugs to those with malaria parasites. We undertook formative research in a district in Uganda in preparation for a randomised trial of RDTs in drug shops. In May to July 2009, we interviewed 9 drug shop workers, 5 health workers and 4 district health officials and carried out 10 focus group discussions with a total of 75 community members to investigate the role of drug shops and the potential for implementation of RDTs at these health care outlets. Drug shops were seen to provide an important service to community members, the nature of which is determined by responsiveness to client demands. However, drug shops hold a liminal status: in the eyes of different actors, these outlets are at once a shop and clinic; legitimate and illegitimate; and trusted and distrusted. Malaria treatment was found to be synonymous with diagnosis. Diagnostic testing was deemed useful in theory, and community members were curious about the results, with the expectation that a test would decrease uncertainty and help secure an end to illness. However, whether testing would be sought as a routine step in treatment decisions in practice is uncertain, since the appeal of the tests waned in light of their costs and potential for results to conflict with presumed diagnosis. Interventions that increase awareness of multiple causes and management of malaria-like illness will be needed to support the new rationalisation for malaria treatment represented by parasitological diagnosis.

The feasibility of introducing rapid diagnostic tests for malaria in drug shops in Uganda

BackgroundNational malaria control programmes and international agencies are keen to scale-up the use of effective rapid diagnostic tests (RDTs) for malaria. The high proportion of the Ugandan population seeking care at drug shops makes these outlets attractive as providers of malaria RDTs. However, there is no precedent for blood testing at drug shops and little is known about how such tests might be perceived and used. Understanding use of drug shops by communities in Uganda is essential to inform the design of interventions to introduce RDTs.MethodsWe conducted a qualitative study, with 10 community focus group discussions, and 18 in-depth interviews with drug shop attendants, health workers and district health officials. The formative study was carried out in Mukono district, central Uganda an area of high malaria endemicity from May-July 2009.ResultsDrug shops were perceived by the community as important in treating malaria and there was awareness among most drug sellers and the community that not all febrile illnesses were malaria. The idea of introducing RDTs for malaria diagnosis in drug shops was attractive to most respondents. It was anticipated that RDTs would improve access to effective treatment of malaria, offset high costs associated with poor treatment, and avoid irrational drug use. However, communities did express fear that drug shops would overprice RDTs, raising the overall treatment cost for malaria. Other fears included poor adherence to the RDT result, reuse of RDTs leading to infections and fear that RDTs would be used to test for human immune deficiency virus (HIV). All drug shops visited had no record on patient data and referral of cases to health units was noted to be poor.ConclusionThese results not only provide useful lessons for implementing the intervention study but have wide implications for scaling up malaria treatment in drug shops.

BARRIERS TO PREVENTION OF MOTHER-TO-CHILD TRANSMISSION OF HIV SERVICES IN UGANDA

Understanding care-seeking practices and barriers to prevention of mother-to-child transmission (PMTCT) of HIV is necessary in designing effective programmes to address the high disease burden due to HIV/AIDS in Uganda. This study explored perceptions, care-seeking practices and barriers to PMTCT among young and HIV-positive women. A household survey (10,706 women aged 14-49 years), twelve focus group discussions and 66 key informant interviews were carried out between January and April 2009 in Wakiso district, central Uganda. Results show that access to PMTCT services (family planning, HIV counselling and testing and delivery at health units) was poor. Decision making was an important factor in accessing PMTCT services. Socioeconomic factors (wealth quintile, age, education level) and institutional practices also influenced access to PMTCT. Overall, having had an HIV test was highest when both men and women made decisions together or when women were empowered to make their own decisions. This was significant across wealth quintiles (p=0.0001), age groups (p=0.0001) and education levels (p=0.0001). The least level of HIV testing was when men made decisions for their spouses; and this was the case with family planning and deliveries at health units. Other barriers to PMTCT were fear of women and male spouses to have an HIV test and the perception that HIV testing is compulsory in antenatal clinics. In conclusion, to increase access to PMTCT among women, especially the young, poor and least educated, there is a need to empower them to make decisions on health seeking, and also to empower men to support their spouses to make good decisions. Other barriers like fear of having an HIV test should be addressed through appropriate counselling of clients.

Treatment-seeking practices for malaria in pregnancy among rural women in mukono district, uganda

Understanding treatment-seeking practices for malaria in pregnancy is necessary in designing effective programmes to address the high malaria morbidity in pregnancy. This study assessed womens perceptions on malaria in pregnancy, recognition of early signs of pregnancy and of malaria, and the cultural context in which treatment seeking takes place in Mukono District. Focus group discussions (FGD) and key informant interviews were conducted among pregnant women, non-pregnant women, adolescents and men. The results showed that malaria, locally known as omusujja, was perceived as the most common cause of ill health among pregnant women. Although malaria commonly presents with fever, some pregnant women feel hot in the womb with or without signs of fever and this illness, locally known as nabuguma, may lead to progressive weakness and occasionally to miscarriage and few respondents associated it with malaria. Primigravidae, adolescents and men were not considered at risk of omusujja or nabuguma. Similarly anaemia and low birth weight were not associated with malaria; in fact paleness was described as a normal sign of pregnancy. There are cultural and social pressures on married women to get pregnant and this forces them to conceal symptoms like feeling feverishness, backache, nausea, general weakness, loss of appetite and vomiting until they are sure these are due to pregnancy. Most women, however, could not differentiate symptoms of malaria from those of early pregnancy. There is a belief that omusujja is a normal sign of pregnancy and this is coupled with a strong cultural practice of using herbs and clays as a first resort to treat pregnancy ailments including malaria. The cultural beliefs and practices regarding delivery of twin and first births, coupled with the high cost of care, prevent women from delivering and using other services at health units.

Treatment of fevers prior to introducing rapid diagnostic tests for malaria in registered drug shops in Uganda

BackgroundSince drug shops play an important role in treatment of fever, introducing rapid diagnostic tests (RDTs) for malaria at drug shops may have the potential of targeting anti-malarial drugs to those with malaria parasites and improve rational drug use. As part of a cluster randomized trial to examine impact on appropriate treatment of malaria in drug shops in Uganda and adherence to current malaria treatment policy guidelines, a survey was conducted to estimate baseline prevalence of, and factors associated with, appropriate treatment of malaria to enable effective design and implementation of the cluster randomized trial.MethodsA survey was conducted within 20 geographical clusters of drug shops from May to September 2010 in Mukono district, central Uganda. A cluster was defined as a parish representing a cluster of drug shops. Data was collected using two structured questionnaires: a provider questionnaire to capture data on drug shops (n=65) including provider characteristics, knowledge on treatment of malaria, previous training received, type of drugs stocked, reported drug sales, and record keeping practices; and a patient questionnaire to capture data from febrile patients (n=540) exiting drug shops on presenting symptoms, the consultation process, treatment received, and malaria diagnoses. Malaria diagnosis made by drug shop vendors were confirmed by the study team through microscopy examination of a blood slide to ascertain whether appropriate treatment was received.ResultsAmong febrile patients seen at drug shops, 35% had a positive RDT result and 27% had a positive blood slide. Many patients (55%) had previously sought care from another drug shop prior to this consultation. Three quarters (73%) of all febrile patients seen at drug shops received an anti-malarial, of whom 39% received an ACT and 33% received quinine. The rest received another non-artemisinin monotherapy. Only one third (32%) of patients with a positive blood slide had received treatment with Coartem® while 34% of those with a negative blood slide had not received an anti-malarial. Overall appropriate treatment was 34 (95% CI: 28 – 40) with substantial between-cluster variation, ranging from 1% to 55%.ConclusionIn this setting, the proportion of malaria patients receiving appropriate ACT treatment at drug shops was low. This was due to the practice of presumptive treatment, inadequate training on malaria management and lack of knowledge that Coartem® was the recommended first-line treatment for malaria. There is urgent need for interventions to improve treatment of malaria at these outlets.

A Cluster Randomised Trial Introducing Rapid Diagnostic Tests into Registered Drug Shops in Uganda: Impact on Appropriate Treatment of Malaria

Background Inappropriate treatment of malaria is widely reported particularly in areas where there is poor access to health facilities and self-treatment of fevers with anti-malarial drugs bought in shops is the most common form of care-seeking. The main objective of the study was to examine the impact of introducing rapid diagnostic tests for malaria (mRDTs) in registered drug shops in Uganda, with the aim to increase appropriate treatment of malaria with artemisinin-based combination therapy (ACT) in patients seeking treatment for fever in drug shops. Methods A cluster-randomized trial of introducing mRDTs in registered drug shops was implemented in 20 geographical clusters of drug shops in Mukono district, central Uganda. Ten clusters were randomly allocated to the intervention (diagnostic confirmation of malaria by mRDT followed by ACT) and ten clusters to the control arm (presumptive treatment of fevers with ACT). Treatment decisions by providers were validated by microscopy on a reference blood slide collected at the time of consultation. The primary outcome was the proportion of febrile patients receiving appropriate treatment with ACT defined as: malaria patients with microscopically-confirmed presence of parasites in a peripheral blood smear receiving ACT or rectal artesunate, and patients with no malaria parasites not given ACT. Findings A total of 15,517 eligible patients (8672 intervention and 6845 control) received treatment for fever between January-December 2011. The proportion of febrile patients who received appropriate ACT treatment was 72·9% versus 33·7% in the control arm; a difference of 36·1% (95% CI: 21·3 – 50·9), p<0·001. The majority of patients with fever in the intervention arm accepted to purchase an mRDT (97·8%), of whom 58·5% tested mRDT-positive. Drug shop vendors adhered to the mRDT results, reducing over-treatment of malaria by 72·6% (95% CI: 46·7– 98·4), p<0·001) compared to drug shop vendors using presumptive diagnosis (control arm). Conclusion Diagnostic testing with mRDTs compared to presumptive treatment of fevers implemented in registered drug shops substantially improved appropriate treatment of malaria with ACT. Trial Registration ClinicalTrials.gov NCT01194557.

Epidemiology of HPV genotypes in Uganda and the role of the current preventive vaccines: A systematic review

BackgroundLimited data are available on the distribution of human papillomavirus (HPV) genotypes in the general population and in invasive cervical cancer (ICC) in Uganda. Yet, with the advent of preventive HPV vaccines that target HPV 16 and 18 responsible for causing about 70% of ICC cases in the world, such information is crucial to predict how vaccination and HPV-based screening will influence prevention of ICC.MethodsTo review the distribution of HPV infection and prevalent genotypes, electronic databases (e.g. PubMed/MEDLINE and HINARI) were searched for peer reviewed English articles on HPV infection up to November 30, 2010. Eligible studies were selected according to the following criteria: DNA-confirmed cervical or male genital HPV prevalence and genotypes, HPV incidence estimates and HPV seroprevalence among participants.ResultsTwenty studies were included in the review. Among HIV negative adult women, the prevalence of HR-HPV infections ranged from 10.2% -40.0% compared to 37.0% -100.0% among HIV positive women. Among HIV positive young women aged below 25 years, the prevalence of HR-HPV genotypes ranged from 41.6% -75.0% compared to 23.7% -67.1% among HIV negative women. Multiple infections with non vaccine HR-HPV genotypes were frequent in both HIV positive and HIV negative women. The main risk factors for prevalent HPV infections were age, lifetime number of sexual partners and HIV infection. Incident infections with HR-HPV genotypes were more frequent among adult HIV positive than HIV negative women estimated at 17.3 and 7.0 per 100 person-years, respectively. Similarly, incident HR-HPV among young women aged below 25 years were more frequent among HIV positive (40.0 per 100 person-years) than HIV negative women (20.3 per 100 person-years) women. The main risk factor for incident infection was HIV infection. HPV 16 and 18 were the most common genotypes in ICC with HPV 16/18 contributing up to 73.5% of cases with single infections.Among uncircumcised adult HIV positive males, HR-HPV prevalence ranged from 55.3% -76.6% compared to 38.6% -47.6% in HIV negative males. Incident and multiple HR-HPV infections were frequent in HIV positive males. Being uncircumcised was the main risk factor for both prevalent and incident HPV infection.ConclusionInfections with HR-HPV genotypes were very common particularly among HIV positive individuals and young women irrespective of HIV status. Given the high prevalence of HIV infection, HPV-associated conditions represent a major public health burden in Uganda. However, although the most common HPV genotypes in ICC cases in Uganda were those targeted by current preventive vaccines, there were a large number of individuals infected with other HR-HPV genotypes. Technology allowing, these other HR-HPV types should be considered in the development of the next generation of vaccines.

A lab-on-chip for malaria diagnosis and surveillance

BackgroundAccess to timely and accurate diagnostic tests has a significant impact in the management of diseases of global concern such as malaria. While molecular diagnostics satisfy this need effectively in developed countries, barriers in technology, reagent storage, cost and expertise have hampered the introduction of these methods in developing countries. In this study a simple, lab-on-chip PCR diagnostic was created for malaria that overcomes these challenges.MethodsThe platform consists of a disposable plastic chip and a low-cost, portable, real-time PCR machine. The chip contains a desiccated hydrogel with reagents needed for Plasmodium specific PCR. Chips can be stored at room temperature and used on demand by rehydrating the gel with unprocessed blood, avoiding the need for sample preparation. These chips were run on a custom-built instrument containing a Peltier element for thermal cycling and a laser/camera setup for amplicon detection.ResultsThis diagnostic was capable of detecting all Plasmodium species with a limit of detection for Plasmodium falciparum of 2 parasites/μL of blood. This exceeds the sensitivity of microscopy, the current standard for diagnosis in the field, by ten to fifty-fold. In a blind panel of 188 patient samples from a hyper-endemic region of malaria transmission in Uganda, the diagnostic had high sensitivity (97.4%) and specificity (93.8%) versus conventional real-time PCR. The test also distinguished the two most prevalent malaria species in mixed infections, P. falciparum and Plasmodium vivax. A second blind panel of 38 patient samples was tested on a streamlined instrument with LED-based excitation, achieving a sensitivity of 96.7% and a specificity of 100%.ConclusionsThese results describe the development of a lab-on-chip PCR diagnostic from initial concept to ready-for-manufacture design. This platform will be useful in front-line malaria diagnosis, elimination programmes, and clinical trials. Furthermore, test chips can be adapted to detect other pathogens for a differential diagnosis in the field. The flexibility, reliability, and robustness of this technology hold much promise for its use as a novel molecular diagnostic platform in developing countries.

Intermittent preventive treatment of malaria in pregnancy: a new delivery system and its effect on maternal health and pregnancy outcomes in Uganda

OBJECTIVE To assess whether traditional birth attendants, drug-shop vendors, community reproductive-health workers, or adolescent peer mobilizers could administer intermittent preventive treatment (IPTp) for malaria with sulfadoxine-pyrimethamine to pregnant women. METHODS A non-randomized community trial was implemented in 21 community clusters (intervention) and four clusters where health units provided routine IPTp (control). The primary outcome measures were access and adherence to IPTp, number of malaria episodes, prevalence of anaemia, and birth weight. Numbers of live births, abortions, still births, and maternal and child deaths were secondary endpoints. FINDINGS 1404 (67.5%) of 2081 with the new delivery system received two doses of sulfadoxine-pyrimethamine versus 281 (39.9%) of 704 with health units (P < 0.0001). The prevalence of malaria episodes decreased from 906 (49.5%) of 1830 to 160 (17.6%) of 909 (P < 0.001) with the new delivery system and from 161 (39.1%) of 412 to 13 (13.1%) of 99 (P < 0.001) with health units. Anaemia was significantly less prevalent in both arms. There was a lower proportion of low birth weight 6.0% with the new delivery system versus 8.3% with health units (P < 0.03). Few abortions and stillbirths were recorded in either arm. Fewer children and women who accessed IPTp with health units died than in the intervention group. CONCLUSION The new approaches were associated with early access and increased adherence to IPTp. Health units were, however, more effective in reducing parasitaemia and malaria episodes. We recommend further studies to assess programming modalities linking the new approaches and health units.

Epidemiological and laboratory characterization of a yellow fever outbreak in northern Uganda, October 2010-January 2011

BACKGROUND In November 2010, following reports of an outbreak of a fatal, febrile, hemorrhagic illness in northern Uganda, the Uganda Ministry of Health established multisector teams to respond to the outbreak. METHODS This was a case-series investigation in which the response teams conducted epidemiological and laboratory investigations on suspect cases. The cases identified were line-listed and a data analysis was undertaken regularly to guide the outbreak response. RESULTS Overall, 181 cases met the yellow fever (YF) suspected case definition; there were 45 deaths (case fatality rate 24.9%). Only 13 (7.5%) of the suspected YF cases were laboratory confirmed, and molecular sequencing revealed 92% homology to the YF virus strain Couma (Ethiopia), East African genotype. Suspected YF cases had fever (100%) and unexplained bleeding (97.8%), but jaundice was rare (11.6%). The overall attack rate was 13 cases/100000 population, and the attack rate was higher for males than females and increased with age. The index clusters were linked to economic activities undertaken by males around forests. CONCLUSIONS This was the largest YF outbreak ever reported in Uganda. The wide geographical case dispersion as well as the male and older age preponderance suggests transmission during the outbreak was largely sylvatic and related to occupational activities around forests.