Publications

Chronic osteomyelitis is a considerable healthcare burden in many developing countries, but this burden is poorly quantified. To estimate the clinical burden of osteomyelitis we systematically sampled the medical records of orthopaedic clinics at five hospitals in Uganda. To estimate the surgical burden of osteomyelitis we reviewed the diagnosis in 9354 operations conducted during a 1 year period at the same five hospitals. Of 1844 outpatients with a documented diagnosis sampled over 1 year, 187 (10%) had osteomyelitis. Only 20% of those with osteomyelitis were older than 20 years, whereas this age group accounted for 52% of patients with another orthopaedic diagnosis or no diagnosis (P<0.001). Osteomyelitis was diagnosed in 325 (3.5%) of the surgical operations; in 32% of these operations the patients were children aged between 10 and 14 years. The tibia was the bone most frequently involved (31%), and sequestrectomy was the most frequent surgical procedure (60%). These findings suggest that osteomyelitis disproportionately affects the young, and is a burden on both clinical and surgical services. To decrease this burden in populations with limited resources, improved diagnosis and more timely treatment of acute osteomyelitis is needed.

BACKGROUND

Artesunate and amodiaquine (AS&AQ) is at present the world's second most widely used artemisinin-based combination therapy (ACT). It was necessary to evaluate the efficacy of ACT, recently adopted by the World Health Organization (WHO) and deployed over 80 countries, in order to make an evidence-based drug policy.

METHODS

An individual patient data (IPD) analysis was conducted on efficacy outcomes in 26 clinical studies in sub-Saharan Africa using the WHO protocol with similar primary and secondary endpoints.

RESULTS

A total of 11,700 patients (75% under 5 years old), from 33 different sites in 16 countries were followed for 28 days. Loss to follow-up was 4.9% (575/11,700). AS&AQ was given to 5,897 patients. Of these, 82% (4,826/5,897) were included in randomized comparative trials with polymerase chain reaction (PCR) genotyping results and compared to 5,413 patients (half receiving an ACT). AS&AQ and other ACT comparators resulted in rapid clearance of fever and parasitaemia, superior to non-ACT. Using survival analysis on a modified intent-to-treat population, the Day 28 PCR-adjusted efficacy of AS&AQ was greater than 90% (the WHO cut-off) in 11/16 countries. In randomized comparative trials (n = 22), the crude efficacy of AS&AQ was 75.9% (95% CI 74.6-77.1) and the PCR-adjusted efficacy was 93.9% (95% CI 93.2-94.5). The risk (weighted by site) of failure PCR-adjusted of AS&AQ was significantly inferior to non-ACT, superior to dihydroartemisinin-piperaquine (DP, in one Ugandan site), and not different from AS+SP or AL (artemether-lumefantrine). The risk of gametocyte appearance and the carriage rate of AS&AQ was only greater in one Ugandan site compared to AL and DP, and lower compared to non-ACT (p = 0.001, for all comparisons). Anaemia recovery was not different than comparator groups, except in one site in Rwanda where the patients in the DP group had a slower recovery.

CONCLUSION

AS&AQ compares well to other treatments and meets the WHO efficacy criteria for use against falciparum malaria in many, but not all, the sub-Saharan African countries where it was studied. Efficacy varies between and within countries. An IPD analysis can inform general and local treatment policies. Ongoing monitoring evaluation is required.